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Indian Journal for

the Practising Doctor

Executive Editor Editor-in-Chief

Bashir Gaash, MD, PhD, DCH Muzaffar Ahmad, MD, FACP, FIMSA

Medical Quiz: Diagnostic dilemma

Childhood Infections: Fever in childhood
Immunization: Cold chain maintenance
Student’s page: B cell development
Endemic Disease: Viral hepatitis
Surgical emergency: Reduction of rectal prolapse
Global threat: Influenza
Drug update: Cefixime in UTI
Pregnancy: Rh incompatibility
Rural surgery: Operating room etiquette
Heart Disease: Rheumatic Fever
Parent/patient education: Febrile child, asthma, osteoarthritis, cervical cancer
Haematology : Diagnosis of anaemia
Foods we take: Tea
A leaf from the history of Medicine: Joseph Lister
Hazardous waste: Healthcare waste – A Consideration
Special supplement: Drug Use in Hepatic Impairment

Vol I No. 4 (January 2005)


Indian J for Practising Doctor, Vol: 4


(A bimonthly journal for doctors working in


Editor-in-Chief Executive Editor

Dr Muzaffar Ahmad, MD, FACP, FIMSA Dr Bashir Gaash, MD, PhD, DCH.
Director Health Services, Kashmir. Principal, Regional Institute of
Health & Family Welfare, Kashmir.

Editorial Assistance:
Dr Rehana Kausar, MD, Dipl H&FW
Dr Manzoor Kadri, MBBS, PG Dipl HIV/AIDS
Dr Rohini Bhan, MBBS, PG Dipl RCH
Dr Farooq Fazilli, MD
Dr Rubina Shaheen, MD
Dr Shabnam Bashir, MBBS

Managing Editor:
Neelam Bashir, BCA, G.Tech

Editorial correspondence: P. O. Box: 673 (GPO), Srinagar, Kashmir

[Phones: 951954-255042; Email:]


Indian J for Practising Doctor, Vol: 4


• Medical Quiz IVI

• Diagnosis of Anaemia: role of CBC & PBF, 7 (Neha Dahiya)
• Torch Test – Need for Use as a Screening Test, 13 (Naveen Thapliyal, Getta Jain, &
Godavari Pandey)
• Torch Test: Test & Inference, 1??8 (S M Kadri)
• Patient education: Anaemia, 12; Influenza 25; Asthma, 62; Cervical Cancer 83;
Osteoarthritis 85.
• Influenza – A Reminder, 18 (Bashir Gaash)
• Cold Chain Maintenance, 27 (Rubina Shaheen)
• Operating Room Etiquette, 34 (W.H.O.)
• Pregnancy: Rh Incompatibility, 39 (Rehana Kausar)
• Fever in Children, 43 (Farooq Fazilli)
• Rheumatic Fever, 52 (Shabnam Bashir)
• Foods We Take: Tea (Neelam Bashir)
• Viral Hepatitis, 78. (Rohini Bhan & Arvind Bhan)
• Immunity: B-Lymphocyte Development, 79, (Gazala Shakoor)
• Role of Cefixime in Paedriatic UTI, ?? (Srividya Rao)
• A Leaf From the History Of Medicine: Joseph Lister, 90 (RIHFW)
• Waste From Health care activities, 91 (Muzaffar Ahmad)
• Reduction of Rectal Prolapse, 95 (Shabnam Bashir)
• Special Supplement: Drug use in Hepatic Impairment, 97 (WHO guidelines)

Indian J for Practising Doctor, Vol: 4


The first two issues of the IJPD met an expectedly warm response. The doctors practicing
in the field as well as medical students, both, have enthusiastically welcomed the issue. This has
encouraged all those involved in the publication of the journal.
The journal, as promised, carries articles of direct relevance to the practising doctor.
Anaemia is a common nutritional disorder particularly rampant in the developing world.
Classification & typing is generally based on the results of complete blood count and peripheral
blood smear. These parameters are easy to do and are within the reach of practitioners even in
the remote areas of the country. One article has been put to highlight the role of CBC 7 PBF in
diagnosis of anemia.
Pregnancy is a special occasion, where the mother’s condition directly affects the child.
The so-called TORCH infections are generally mild in the mother but can prove disastrous to the
ofetus & the neonate. Accordingly the fetus may abort or the neonate may get congenital
anomalies, rashes and CNS calcifications. Rh incompatibility between the mother and her foetus
is an important cause of mortality among the neonate, and at the same time is so easy to prevent.
One article on this not so infrequent condition has also been included. Als.
Cold chain maintenance is an area which is so crucial to the potency of vaccines yet is so
easily overlooked. We have discussed this important aspect of immunization is detail.
Influenza is a tricky infectio: it is one of the oldest scourges of mankind which runs the
danger of attaining pandemic proportions every few years. Why despite all efforts to curb its
epidemicity influenza virus still continues to baffle mankind has been fully dealt with. Viral
hepatitis is a common infection across the world, and new viruses are emerging with passage of
time. Some recent information on this hepatotrophic virus has been shared here.
Urinary tract infection in children is a common infection. Infants and younger children
require aggressive therapy because they are prone to get pyelonephritis with renal scarring.
Traditionally, patients of this tender age have been treated intravenously, but cefexime – a 3rd
generation oral cephalosporin - has made treatment very convenient and cheaper. The role of
cefexime in the treatment of urinary tract infection is discussed by our collague from Andhra.
Fever in children is one of the commonest symptoms, and may sometimes try the wits of any
doctor. Management of paedriatic fever is dealt in with reference to use of antipyretics.
Foods we use are not only nutritionally important sometimes have benefits which only
recently have been explored and documented. Our favourite beverage, tea, has been found to
contain antioxidats and ingredients which could prevent atherosclerosis, heart disease and even
In a series of essays on establishing and maintaining surgical facilities in remote areas,
we are carrying an article on surgery room etiquette. A surgical emergency, reduction of rectal
prolapse also has been included.
A special supplement on drug use in hepatic impairment has been given as the annexure.

January 2005.

(Executive Editor)

Indian J for Practising Doctor, Vol: 4


Neha Dahiya, DNB (Path), is Consultant Pathologist, & Director, K G Lab Services, Coimbatore,
Tamil Nadu.

Srividya Rao, MD, DCH, is a paedriatician from Guntur (Andhra Pradesh), currently working with
the Ministry of Health, Islamic Repu
blic of Iran. She is stationed at Turbat-e- Hyderiya, Khorasan.

Naveen Thapliyal, MD. is Assistant Professor, Pathology, STMFH & Medical College, Haldwani,

Geeta Jain, MD, is Assistant Professor, & Godavari Pandey, MD, Resident, Deptt of Obstetrics &
Gynaecology, STMF & Medical College, Haldwani, Uttaranchal.

Rehana Kausar, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate
from SK Institute of Medical Sciences, Soura, Srinagar. Before joining RIHFW she has had a stint
in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Manzoor A Kadri: Trainer at the Regional Institute of Health, Kashmir, was a teacher at the
Government Medical College, Srinagar (Department of Microbiology) before joining us.

Farooq Fazilli, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate
from the SK Institute of Medical Scinces, Soura, Srinagar. Before joining the RIHFW, the doctor
worked in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Rubina Shaheen, MD: Faculty member, Regional Institute of Health, Kashmir, is a postgraduate
in Microbiology. She taught at the SKIMS before her new appointment.

Gazala Shakoor, MD, is a private practitioner working in Srinagar.

Rohini Bhan is a trainer at the Regional Institute of Health, Kashmir.

Shabnam Bashir is a medical graduate from the Government Medical College, Srinagar.

Bashir Gaash; an International Fellow in Tropical Diseases, is a postgraduate in Social &

Preventive Medicine and Health Administration, and currently is the Principal, Regional Institute of
Health, Kashmir.

Muzaffar Ahmad; MD in general Medicine, has a Fellowship in Emergency Medicine from USA,
and currently is the Director Health Services, Kashmir.

Indian J for Practising Doctor, Vol: 4

Diagnostic dilemmas
Medical Quiz: III
A 10-year old boy presented with a history of lethargy and abnormal behaviour at school. He is
taking iron tablets for iron-deficiency anaemia, which was diagnosed by his doctor. The boy is the only
child in the family; they live in a 3-bedroomed old house. He is withdrawn and does not want to talk. He has
been described as a ‘violent child’ by his mother on several occasions in the last 3 months, and has been
expelled from a school club because of his behaviour. His best friends had left him because of his
argumentative nature. Sometimes he complains of headache, with fuzzy vision. His eyes were checked twice
by optometrist for refraction errors without detection of any abnormalities. The child has once threatened to
jump out from the window of his room where he passes most of his time. The child has started losing
weight. He wakes up at nights shouting and complaining of headache, which requires analgesics. The boy
looks withdrawn and makes no eye contact. He hates the school and does not want to go there.
All aspects of the systemic examination are normal. All cranial nerves are intact but he does not
like to have a light shone into his eyes. A fundus examination shows papilloedema but no other abnormality.
His BP is 120/75 mm, heart rate 70, and respiratory rate 20. X-ray abdomen suggested the presence of
ureteral stones and a calcified lesion in the bladder. His lab findings showed:

Hb 8.7 g/dl MCV 45fl

MCHC 25g/dl
Platelets 3.57 laks
Blood sugar 4.5 mmol/l
Urine shows Proteinuria & phosphaturia

After admission, he had a cranial MRI, which turned to be normal. After mid-night he started to
have generalized tonic-clonic seizures for 5 minutes, which stopped after rectal administration of diazepam.
There were no more seizures and an EEG was carried out which showed no epileptiform activity. His
behaviour fluctuated and a decision was made to treat him as having encephalitis.
1) At this juncture which single test should be carried out?
Abdominal ultrasound Barium swallow
Urine toxicology IVP
Cystoscopy Lumbar puncture
Ferritin level Lead level
Ammonia level Mantoux test

2) Which other two investigations should be carried out to reach at the diagnosis?
Blood film
Urinary copper level
Long-bone x-ray
Abdominal CT
Repeat EEG
3) What is the diagnosis?
The patient was treated and after 6 weeks another blood test was taken which showed that
he still had the same problem, even though there had been some improvement in his
behaviour and he had started to attend the school in the last 2 weeks.

4) What should the management plan be?

ƒ Admit to hospital until he finishes the course of treatment
ƒ Refer to the psychiatrist
ƒ Inform the social services/child protection team/police?
ƒ Start treatment again with strict supervision by the community care team.

Indian J for Practising Doctor, Vol: 4

………………………….. (Answers on pg 18)

Diagnosis of Anaemia: There are many types of anemia.

Primarily they can be classified into
Role of CBC & Peripheral 1) Anemia because of blood loss
Blood Smear 2) Anemia because of impaired red cell
3) Anemia due to increased destruction
of RBC (haemolytic anaemia)
Neha Dahiya*
_________________________________ Various steps for diagnosing
anaemia are:
Anaemia is less than normal 1) Clinical signs / symptoms
2) Physical Examination
number of red blood cells, measured as a
3) Laboratory investigations
decrease in the haemoglobin content of
the red blood cells. Anaemia leads to a
decrease in the oxygen carrying capacity
of blood.

Fig 1: CBC - Parameters considered while establishing & typifying anaemia:

Indian J for Practising Doctor, Vol: 4

Here focus is on the investigations useful - In some instances of aplastic

in diagnosing and classifying anaemia. anemia
The most basic of all the tests asked for - Myxoedema
is “CBC” – a Complete Blood Count,
which gives information regarding In all cases the red cell precursors in the
presence or absence of anaemia and also marrow are normal in morphology.
helps to classify the type of anaemia to
some extent. The CBC has to be seen in 2) Moderate increase in the MCV:
conjunction with a peripheral blood [MCV >105 and <110 fl]
smear examination. The automated CBC - Liver disease
encompasses a number of parameters,
which throw light on the aetiology of 3) Marked increase in the MCV:
anaemia. A CBC on a haematology cell [MCV > 110 fl]
counter with 5 part differential gives at - Megaloblastic due to the lack of
least 24 parameters as seen in Fig 1. vitamin B-12 or folic acid.

Table 1 The red cell distribution width - “RDW”-

RBC Total red blood cell count assesses the variation in volume of red
HGB Haemoglobin blood cells. This is equivalent to the
microscopic assessment of anisocytosis –
HCT / PCV Haematocrit / Packed cell
variation in cell size
Red Blood Cell Indices:
Increased RDW indicates the presence of
MCV Mean corpuscular volume more than one population of red blood
MCH Mean corpuscular cells.
MCHC Mean corpuscular The RDW expressed as CV
haemoglobin conc (coefficient of variation) has been found
RDW Red cell distribution width
to be of some value in the distinction
The red blood cell indices help in morphological between:
classification of anemia and aid in further
1) Iron deficiency anemia (RDW
investigational studies.
usually increased) and
The macrocytic anaemias can be thalassaemia trait (RDW usually
further divided according to MCV: normal).
2) Megaloblastic anemia (RDW
1) Slight increase in MCV: often increased) and other causes
[MCV >100 but <105 fl] of macrocytosis (RDW usually
- Due to the presence of normal)

Indian J for Practising Doctor, Vol: 4



Normocytic normochromic MCV: 76 to 98 fl ƒ Recent Bleeding
anaemia MCHC: 32 – 36% ƒ Haemolysis
ƒ Marrow
On Blood smear: replacememt
Normocytosis, Normochromia, Slight ƒ Marrow
Anisocytosis and Poikilocytosis (ie Depression
variation in size and shape of RBC

Macrocytic anaemia With MCV > 98 fl Pernicious anemia

"Megaloblastic" Marrow MCHC > 36%
On Blood smear:
Macrocytosis, Anisocytosis,
Poikilocytosis (Teardrop)

Macrocytic Without MCV > 98 fl Liver Disease

"Megaloblastic" Marrow MCHC > 32 - 36%
On Blood smear:
Macrocytosis, Target Cells

MCV: < 76 fl ƒ Iron deficiency

MCHC: 32 – 36% if sub-classified as anemia
MCHC < 30%, if sub-classified as ƒ Repeated
Microcytic Hypochromic pregnancy
On Blood Smear: ƒ Thalassemia
Microcytosis, Hypochromia,
ƒ Chronic Blood
Anisocytosis, Poikilocytosis
ƒ Vit. B 6

Indian J for Practising Doctor, Vol: 4

Indian J for Practising Doctor; Vol I; No. 4

Increased RDW indicates presence of Whenever a patient presents with

more than one population of red blood complaints of fatigue, weakness, mild
cells. dyspnoea on exertion, simple
The RDW expressed as CV (coefficient haemoglobin estimation is done and if
of variation) has been found to be of found to be decreased the patient is
some value in the distinction between: labelled as having anaemia. It is always
1) Iron deficiency anemia (RDW usually advisable to do a CBC along with a
increased) and thalassaemia trait (RDW peripheral smear, and sometimes a bone
usually normal). marrow examination.
2) Megaloblastic anemia (RDW often
increased) and other causes of
macrocytosis (RDW usually normal)
It must be remembered that
anaemia could be the result of a benign
CBC provides all this problem as deficiency of dietary iron or
information. On peripheral blood smear could be a feature of an underlying
one can confirm the same findings eg serious disease.We illustrate our point
one can see the presence of microcytes with two examples:
(small RBCs) / macrocytes (large RBCs)
/ schistocytes (fragmented RBC). A 25 year female presented with
easy fatigability, and low grade fever off
Thus, CBC and PBF and on. Haemoglobin was found to be
examination have a decisive role in 8.5 gm/dl and she was labelled as
diagnosis and classification of anaemia. having anaemia, and started on
Another investigation, which is of haematinics. This continued for two
importance, is the “Reticulocyte Count”. months without any significant
improvement. Finally she was referred
Reticulocyte count reflects to KG Hospital (Dept of Medicine),
erythropoietic activity of the bone where the consultant asked for a CBC
marrow and corresponds to the finding of and peripheral smear. Her Hb was low
polychromasia on a blood film. The with normal MCV indicating normocytic
normal range is 0.5 to 1.5% of the red anaemia. Her total WBC count was
cell population studied. Disease states 15,000/μl and platelets were mildly
with increased Reticulocyte counts are: decreased to 98,000/μl. The peripheral
1. Hemolytic Anaemias
blood smear revealed occasional blasts
suggestive of leukaemia and the bone
2. After acute hemorrhage marrow confirmed diagnosis of acute
myeloid leukaemia. Her anemaia was due
3. Pernicious Anaemia or iron to marrow replacement by leukemic blasts.
deficiency anaemia after treatment

Disease states with decreased In another case, a 60 year old

reticulocyte counts are: male was diagnosed to have anaemia
and tuberculous parotitis and was on
1. Aplastic Anaemia put on ATT , but there was no response
2. Iron Deficiency Anaemia before to the treatment. Patient developed
treatment swelling of legs with reduced appetite,
3. Pernicious anaemia before treatment nausea and vomiting and was found to
have renal failure. At this stage, the
patient was referred to the neprology

Indian J for Practising Doctor; Vol I; No. 4

department of the hospital. The only These two cases amply illustrate
positive findings were Hb 7.7gms%, the fact that a low Hb does indicate
urea and creatinine were 86 mg and 3.2 anaemia, but for a final diagnosis as to
mg respectively and the ESR was the underlying cause of anemia a panel
120mm/hr. Peripheral smear was of investigations is needed.
showing a normocytic normochromic
anaemia. No cause for renal failure The protocol followed in K. G
could be identified. Hence a bone Hospital, clinics & laboratory, is – CBC,
marrow was done. This revealed peripheral smear, reticulocyte count and
multiple myeloma. A renal biopsy was bone marrow aspiration. It helps to arrive
done which showed interstitial infiltrate at the correct diagnosis as early as
of myeloma cells in the kidney. Again the possible.
anemia was due to marrow replacement by

There is a tendency among the practitioners in peripheral areas to be content with

Hb estimation for diagnosis of anaemia and to put the patient on iron. Anaemia is a
disease of multiple causation and its scientific management requires an exact
classification which can be done only after a complete study of blood.
Fortunately, simple and economical tests are available for diagnosis, classification
and typing of anemia. Hb estimation merely detects the presence and severity of
anaemia. However, further tests are required to classify anaemia for appropriate
management. In any case of anaemia, therefore, it is not wise to begin treatment without
a CBC & PBF.
Nutritional anaemias may be from the deficiency a mononutrient (as iron) or a
combination of deficiencies ie iron, other minerals, B12 & folic acid. In the developing
world, at least two of them – iron & folic acid – are generally deficient in diet.
Pregnancy anaemia is multifactorial, including hypervolemia, need for the feotus,
& iron deficiency. It needs to be seen in that context.
In case of children, both preschool age & school age, presence of anaemia may be
due to nutritional deficiency generally exacerbated by roundworm or hookworm
infestation. Unless the child is rid of the underlying infections, he will not be benefited by
nutritional supplementation and therapeutic iron.
In smaller children, especially with pica, chronic lead poisoning may mimic iron-
deficiency anaemia which is refractory to treatment.
Very important causes of anaemia as chronic blood loss should always be borne
in mind: loss of blood may be gross and evident as in excessive menstrual loss or
incipient and overlooked as microscopic haematuria or blood in stools.
In older patient, possibility of a malignancy should never be forgotten. Anaemia
may also present as a prominent feature of connective tissue disorder or hypothyroidism.


Indian J for Practising Doctor; Vol I; No. 4

Patient Education  

Anaemia (Greek, “bloodlessness”) is a blood condition involving an abnormal

reduction in the number of red blood cells (erythrocytes) or in their haemoglobin content.
Red blood cells are the means by which oxygen is carried to the various parts of the body.
People who are anaemic develop symptoms caused by the inadequate delivery of oxygen
to their body tissues. The condition is far more common in women and children than in
men. Pregnant mothers and preschool children are especially prone to get anaemia. There
are three primary causes: (1) reduced production of red blood cells, which may result from
deficiency in nutrients or hormones, or from disease or other conditions; (2) excessive
destruction of red blood cells, often a hereditary problem; and (3) excessive blood loss,
such as that caused by gastrointestinal ulcers, heavy menstrual periods, or overdose of
aspirin. The most usual symptoms of anaemia are pallor, shortness of breath, low vitality,
dizziness, and digestive disorders.

The most common type of anaemia is iron-deficiency anaemia, which occurs when
the body’s need for iron increases, as during certain periods of childhood (during the first
5 years of life; again during adolescence) and in pregnancy, or when there is insufficient
iron in the diet. Pernicious anaemia, a chronic ailment that mostly affects people over 40,
is a result of vitamin B12 deficiency. Rather than a diet deficient in the vitamin, this is
usually caused by intestinal malabsorption, resulting in decreased B12 uptake. Sickle-cell
anaemia is the result of a hereditary defect in the synthesis of haemoglobin. Aplastic
anaemia occurs when there is severe reduction in red blood corpuscles, and when the bone
marrow is unable to regenerate them. Ionizing radiation is one possible cause.

Past treatment of the condition has included removal of the spleen, repeated
transfusions of blood, and a diet featuring beef or calf’s liver. Transfusions are still used in
cases of acute blood loss; iron supplements for iron-deficiency anaemia and injections of
vitamin B12 for pernicious anaemia are often effective. Synthetically manufactured
erythropoietin (normally produced by the human kidney) is now used to stimulate the
production and growth of red blood cells. Other therapy focuses on curing the underlying
causes of the nutritional or hormonal deficiency. There may be deficiency of folic acid
(which is derived from green leafy vegetables) which can cause anaemia which can be
diagnodsed from examination of blood and blood film. Blood transfusions and,
increasingly, bone marrow transplants, are necessary forms of treatment for aplastic
anaemia patients.

Balanced diet containing the required amounts of iron, folic acid and B-12
should be taken by the vulnerable population to prevent development of anaemia.

Indian J for Practising Doctor; Vol I; No. 4


Table: Complications of TORCH
Infections During Pregnancy
Naveen Thapliyal*, Geeta Jain**, ¾ Miscarriage .
Godavari Pandey*** ¾ Small-for-gestational-age, or SGA.
_______________________________ ¾ Congenital heart disease (heart defects
the child is born with)
Definition ¾ Cataract (clouding of the lens of the eye),
The ‘TORCH’ test is a group of blindness, or significant visual
antibody titre tests, which measures the
¾ Hearing impairment, including
presence of antibodies against a specific deafness.
group of infectious diseases and their ¾ Microcephaly (Small head size).
level of concentration in the blood. ¾ Mental retardation or other learning,
TORCH, an acronym for a special group behavioral, or emotional problems.
of infections, may be acquired by a ¾ Low blood counts (anemia).
woman during pregnancy with disastrous ¾ Liver or spleen enlargement.
consequences for the infant. All are ¾ Pneumonia.
grouped together because they can cause ¾ Skin rash - usually reddish-purple or
a cluster of symptomatic birth defects in brown.
¾ Involvement of the central nervous
newborns, collectively called the
system (encephalitis, calcium deposits in
TORCH syndrome. the brain tissue, and seizures).
¾ Jaundice.
"TORCH" group of infections includes ¾ In addition to these symptoms, each of
1. Toxoplasma infection, also called the TORCH infections has its own
toxoplasmosis. characteristic differentiating symptom
2. Other infections, such as hepatitis B,
cluster in newborns.
syphilis, and varicella-herpes zoster.
3. Rubella, the virus that causes German measles
4. Cytomegalovirus, or CMV, and.
5. Herpes simplex virus, the cause of genital Brief Description:
TORCH infections can affect any Toxoplasmosis is caused by
human; children, men, and non-pregnant Toxoplasma gondii, a parasite that the
women may also catch these infections. mother can acquire from handling
However, their importance lies in the fact infected cats, drinking un-pasteurized
that they can be they can be transmitted milk, or eating contaminated meat. The
to the fetus while it is in the womb. infection is carried transplacentally, and
When a mother is exposed during the may cause infection of the eyes or central
first 5 months of pregnancy, serious fetal nervous system. The organism can
complications may occur. (Table) invade brain or muscle tissue and form
tissue cysts. Contracted early in
_________________________________ pregnancy, toxoplasmosis is more likely
* Assistant Professor, Pathology, ** Assistant
Professor, Obstetric & Gynaecology, *** Senior
to cause a miscarriage or serious birth
Resident, Obstetric & Gynaecology, Dr.S.T.M. F.H. defects However, the later in pregnancy
& Medical College, Haldwani (UTTARANCHAL) the mother is infected, the higher the

Indian J for Practising Doctor; Vol I; No. 4

probability that the fetus will be infected. produces symptoms resembling those of
The incidence of toxoplasmosis in infectious mononucleosis. About 1-2.2%
newborns is 1 in 1,000 live births. of newborns are infected with CMV. Of
this group, 10% will have measurable
Syphilis symptoms. The mortality rate for these
Syphilis is caused by a spirochete symptomatic newborns is 20-30%.
(spiral- or coil-shaped bacterium), Surviving infants with CMV may suffer
Treponema pallidum. It is transmitted in from hearing problems (15%) or mental
the adult population by sexual retardation (30%). Newborns that acquire
intercourse. About 2-5% of children born CMV during the birth process or shortly
to mothers diagnosed with syphilis will after birth may develop pneumonia,
have the disease at birth. Syphilis was hepatitis, or various blood disorders.
added to the TORCH panel because of a
rapid increase in reported cases since Herpes simplex virus (HSV):
1990. Syphilis can cause early delivery, Herpesvirus infections are among
miscarriage, or stillbirth. The mortality the most common viral infections in
rate in infants infected with syphilis is man. They are spread by oral, as well as
about 54%. With widely available genital, contact. Estimatedly, between 1
antibiotic treatment, Syphilis is now in 1,000 and 1 in 5,000 infants are born
taking a back seat among the sexually- with HSV infections. About 80% of
transmitted infections. these infections are acquired during the
birth process itself; the virus enters the
Rubella : infant through its eyes, skin, mouth, and
Rubella is a virus that has a upper respiratory tract. Of the infants
seasonal pattern, with epidemics most born with HSV infection, about 20% will
likely in the spring. Between 0.1-2% of have localized infections of the eyes,
newborns will be infected with rubella. mouth, or skin and about 50% will
Birth defects are most likely (85%) in develop disease spread throughout the
infants infected during the first eight body (disseminated) within 9-11 days
weeks of pregnancy. Infants born with after birth. Disseminated herpes
rubella may already show signs of heart infections attack the liver and adrenal
disease, retarded growth, hearing loss, glands, as well as other body organs.
blood disorders, vision problems, or Without treatment, the mortality rate is
pneumonia. They may also develop 80%. Even with antiviral medication, the
problems later in childhood, including mortality rate is still 15-20%, with 40-
autism, hearing loss, brain syndromes, 55% of the survivors having long-term
immune system disorders, or thyroid damage to the central nervous system. It
disease. is critical for the doctor to diagnose HSV
infection in the newborn as soon as
Cytomegalovirus (CMV): possible, for effective treatment.
Cytomegalovirus belongs to the
herpesvirus group of viruses. It can be Who is a candidate for the test?
transmitted through body secretions, as Any pregnant woman who has
well as by sexual contact; some bad obestetric history or has been
newborns acquire CMV through the exposed to the above infections is a
mother's breast milk. In adults, it candidate for screening.

Indian J for Practising Doctor; Vol I; No. 4

How is the test performed? old one, is present. If an old infection is

A blood test measuring antibody- the cause of antibodies in the blood, the
titers is used to detect antibodies to any level of antibodies will not rise with the
the suspected TORCH organism. An second blood sample, as it does with a
antibody is a special protein made by the new infection. This is important, because
immune system that helps fight old infections usually do not result in
infections. The body makes specific harm to the fetus, except in the case of
antibodies in response to specific herpes. Only infections that are newly
infections. These antibodies are made in caught during the early part of
large amounts when an infection occurs. pregnancy usually put the fetus at risk.
When the initial sample of blood is taken
shortly after exposure, the body may not What do the test results mean?
have had enough time to start making A "negative" test means that the
antibodies yet. However, a woman can woman does not seem to have a new
have antibodies to the infection in her TORCH infection. A positive test means
blood because of an old infection or from that high or increasing levels of
a vaccine. A second sample of blood is antibodies were detected. This generally
usually taken 10 to 21 days later to see if means that the mother has caught a new
blood antibody levels or titers against the TORCH infection.
infection are rising. This generally
means that a new infection, instead of an


• TOxoplasmosis is a parasitic infection

that can be passed from mother to baby
TORCH Test through the placenta during pregnancy.
An infection with Toxoplasma gondii can
Manzoor Kadri cause eye and central nervous system
________________________________ infections as well as brain and muscle
cysts. If acquired during the pregnancy,
it may result in a miscarriage or cause
TORCH is an acronym for a birth defects, though this depends on
group of infectious diseases that, while the time during the pregnancy in which
infecting the pregnant women, may the infection was acquired by the
cause birth defects in their newborns. mother. Toxoplasmosis is acquired by
The test is a screen for the presence of ingesting the parasite when handling
any of the antibodies to these infections. the excrement of infected cats, drinking
Confirmation of an active infection may unpasteurized goat’s milk, and, most
require more specific tests. commonly, by eating contaminated
The following tests make up
the TORCH panel: • Rubella is the virus that causes
German measles. If contracted early in

Indian J for Practising Doctor; Vol I; No. 4

the pregnancy, the infant may develop congenital abnormalities suspected to be

heart disease, retarded growth, caused by an infection with one of the
hearing loss, blood disorders, vision diseases
problems, or pneumonia. Problems
that may develop during childhood Blood Collection
include autism, brain problems,
The TORCH panel requires a
immune disorders, or thyroid disease.
sample of the infant's blood. Samples
• Cytomegalovirus (CMV) is another from infants are usually obtained by the
viral infection that the mother may heel-stick procedure when only a small
have acquired. More than half of all quantity of blood is needed. The baby's
American adults have been infected foot is wrapped in a warm cloth for five
with CMV at some point in their life minutes, to make the blood flow more
and, in most cases, it does not cause easily. The foot is then wiped with an
severe illness. It may pass to the fetus alcohol swab and a lancet is used to stick
during the birth process but can also the baby's heel on one side. It is
infect newborns through breast milk. important to avoid the centre of the heel,
Infected infants may have severe in order to prevent an inflammation of
problems, such as hearing loss, mental the bone. No special preparation, other
retardation, pneumonia, hepatitis, or than sterile technique, is required. The
blood disorders. only complications associated with the
test are those resulting from the heel-
• Herpes simplex virus (HSV) is a stick technique itself (ie scarring,
common viral infection. The two most infection of the bone, cellulitis, small
common infections with HSV are “cold lumpy calcium deposits) and the
sores” affecting the lips and genital possibility of inaccurate test results.
herpes. Both of these infections can
recur. HSV is most commonly
Normal. The normal result
acquired through oral or genital
denotes normal levels of IgM in the
contact. Newborns who contract the
virus usually do so during travel
infant's blood. IgM is a specific class of
through the birth canal of a woman
antibodies that seeks out virus particles.
who has a genital HSV infection. The
In contrast to adults, IgM is the most
virus may spread throughout the
common type of immunoglobulin in
newborn’s body, attacking vital newborn children. It is, therefore, the
organs. Treatment with specific most useful indicator of the presence of a
antiviral medication should begin as TORCH infection.
soon as possible in the infected Abnormal results. The abnormal
newborn. Even if treated, surviving (positive) finding would be high levels of
babies may have permanent damage to IgM antibody. The test can be refined
the central nervous system. further for antibodies specific to given
disease agents. The TORCH screen,
TORCH test is performed to however, can produce both false-positive
screen for these infectious diseases that and false-negative findings. Doctors can
can cause birth defects in newborns and measure IgM levels in the infant's
illness in adults. The test is indicated cerebrospinal fluid, as well as in the
when the mother becomes ill while blood, if they want to confirm the
pregnant or if a baby is born with TORCH results.

Indian J for Practising Doctor; Vol I; No. 4

Usual Concerns of the mother

If I have a positive antibody test, does that 1) Lead level 2) Blood film; long-bone x-ray 3)
mean I am infected? Lead poisoning 4) Start treatment again with
strict supervision by the community care team.
A positive IgG antibody test is usually a sign
of past-exposure to the TORCH agent and is Chronic lead poisoning can occur
not a marker for current active infection. after chewing or sucking pain from old
Detection of IgM antibody is more difficult, windows or doors. Lead from burning
and false negative and false positive results batteries, lead shots for fishing, and old
may occur. Any positive results should be water pipes pose a similar risk. Children
confirmed with additional specific tests before from southeast Asia may get lead poisoning
the diagnosis is considered valid. If the doctor from using surma or kajal – eye make up
suspects that you or your newborn may have prepared from lead. Affected children may
have pica or a compulsive eating disorder.
one of these infections, even though the
Children working as papier mache workers
results were negative, other tests for the in Kashmir, who have a habit of mending
suspected infection should be done. their brushes with lips, run the risk of getting
lead poisoning as the base of most paints is
To make the diagnosis of an lead oxide. Patients are usually anaemic, are
active infection with one of the TORCH usually diagnosed as having iron-deficiency
agents, more specific confirmatory tests anaemia, but fail to respond to iron-therapy.
may be required. In a baby, cerebrospinal Shortly, other clinical features are
fluid testing (requiring a lumbar puncture superimposed on anaemia. They have
or “spinal tap”) is often used to confirm obstipation, abdominal pain, headache, and
toxoplasmosis, herpes and rubella; urine behavioural problems, along with a
may be cultured for cytomegalovirus; deteriorating school performance.
and skin lesions may be scraped and
When poisoning is severe, the child
cultured for herpes simplex virus. can have convulsions, irritability, loss of
Making the diagnosis of toxoplasmosis consciousness, which may lead to coma and
in the pregnant woman or the baby may death.
require additional blood samples, which
are sent to a reference laboratory that The lead level can be measured; the
specializes in such tests. blood film shows hypochromic, microcytic
red cells, and basophilic stippling. Gums
may show lead lines. The long-bones show
*************************************** lead-lines which affect mainly their ends.
Lead flakes which are radiopaque may be
Answers to Medical Quiz: 4 seen on abdominal x-ray.
Lead poisoning is one of the causes
of increased intracranial pressure, and thus
papilloedema is common.

Removal of the child from the

► affected environment is very helpful.

Chelating agents (D-penicillamine in

(from page 6) mild cases; Ethylene-diamine-tetra-acetic
acid or EDTA, in severe cases) are used.

Indian J for Practising Doctor; Vol I; No. 4

internal proteins make up the polymerase

enzyme system (functionally
transcriptase complex) which triggers
Influenza: A Reminder replication of virus in the infected host
Bashir Gaash
________________________________ The virus consists of a central core
(nucleocapsid) containing internal proteins and
the viral RNA. The major structural protein,
matrix protein (M1), integral to the nucleocapsid
Influenza has been known since is responsible for virion integrity. Glycoproteins,
antiquity, at least since 437 BC. The two which are needed for entering the host cell,
faintly remembered epidemics of history project as ‘spikes’ through the lipid envelope.
could have been the ‘English Sweat’ of Mature virus is spherical, measuring
1485 and 1551. Nevertheless, the first some 90-120 nm in diameter.
pandemic which brought the deadly virus
to the world stage was the ‘Spanish’ or Growth & Replication: The replication
‘swine’ influenza of 1918. cycle of the virus begins when it attaches
to specific receptors on epithelial cells
Influenza outbreaks occur lining the respiratory passages. These
frequently in all parts of the world specific receptors are the terminal sialic
including the developed ones. In the UK, (neuraminic) acid residues on the
for example, increased number of cases oligosaccharide side-chains of the
occur each winter with an annual susceptible cells. The virus enters the
mortality of 3000-4000. cell and gets uncoated so that the viral
nucleocapsid (containing RNA and
Influenza, known since 400 BC, is one of enzymes) is released in to the host cell
the last great uncontrolled ‘plagues’ of cytoplasm. Once the nucleocapsid
mankind. It will continue to strike reaches the nucleus, the viral RNA and
mankind off and on because of the enzymes direct the formation of mRNA
inherent survival techniques of the virus for manufacture of progeny RNA. The
RNA matures into nucleocapsid followed
The virus: Influenza virus has 3 by assembly and thus formation of new
different strains, A, B & C, which differ virus which leave the cell and infect
in their ribonucleo-protein moieties. The other susceptible cells.
virus produces 11 different proteins - 3
are surface proteins, while internal Epidemiologic and clinical behaviour:
proteins are needed for varied functions despite similar morphology, the 3 strains
including keeping the virus alive and show different epidemiologic and
virulent. The type A virus has a capacity clinical patterns.
to undergo consistent genetic changes of
their nucleic acids, resulting in annual Type A is associated with most of
phenotypic modifications and changes in the widespread epidemics and is the only
their surface antigens. Alterations in one to produce occasional pandemics.
antigenic structure help the virus to Clinically also the infection is severe
dodge the body’s natural and artificially- with an increased predisposition to
induced immune defences. Four of the secondary bacterial infections. The major

Indian J for Practising Doctor; Vol I; No. 4

2 surface proteins, Haemaglutinin (HA) Animal Reservoir: Many animals and

and neuraminidase (NA) undergo subtle, birds function as hosts to type A viruses
minor changes in structure almost which bear genetically similar but
annually, because of point mutations in antigenetically different versions of
viral RNA genes coding for them. (This surface haemaglutinin and neuraminidase
is because of the absence of a proof- antigens. Wild avian species are primary
reading mechanism to correct mistakes extra-human reservoirs of type A virus.
arising during replication of viral nucleic When humans are infected with these
acid). This annual variability of the type novel viruses, a localized outbreak may
A virus surface protein, the antigenic herald a global pandemic. This is
drift, is a major reason for their success because the new surface antigens are not
to evade human immune system, and recognized by the human immune
causing frequent outbreaks and defence system, thus the virus meets no
epidemics. resistance to spread at all.

Antigenic drift, which is an Type A is far more dangerous because of the

ongoing process, is greater for the HA antigenic drift, extra-human reservoir,
antigen, and leads to distinct alterations potential for pandemics, propensity to cause
in the reactivity of the surface proteins severe illness, and ability to predispose to
secondary bacterial pneumonia. The lower
every 2-3 years. These mutations can be
mutation rate and lack of mammalian or
detected in the laboratory. These avian reservoir for the type B makes it a
antigenic changes are responsible for the lesser clinical and epidemiologic problem.
reduced capacity of pre-existing
antibodies to previously experienced
Infectivity: The incubation period of
influenza virus. The failure of
type A influenza is 3 days and of type B
neutralization by existent antibodies
virus 4 days. Virus replication in the
helps in quicker and wider uptake and
respiratory tract in adults peaks 48 hours
dissemination of virus in the body.
after infection. Newly formed ‘progeny’
virions are shed in nasal secretions and
Type B generally causes milder saliva from 1-7 days after infection.
illness, but spectrum is broader, from Children start shedding the virus earlier,
common-cold like illness to typical ie from the first day, and much longer, ie
severe influenza. Type B infection is upto 13 days after infection. The main
commoner and more symptomatic in transmitters of influenza are preschoolers
children than adults; infection in adults is and school-going children.
milder or asymptomatic. The number of
patients requiring hospitalization is 1/4th Antigenic Shift: Emergence, in the type
of that with the type A. The mutation rate A virus, of an HA protein that is novel to
is lower than that in type A, therefore the population results in a large epidemic
antigenic variability is less. or pandemic. In the 20th century 5 such
pandemics have occurred. The deadliest
The type C virus is either of these, the ‘Spanish (Swine)’ influenza,
asymptomatic or causes only mild, lead to 20 million deaths, particularly
common-cold like mild symptoms (‘the among young adults. The last occurred in
touch of flu’). 1977 with reappearance of the HA

Indian J for Practising Doctor; Vol I; No. 4

Influenza elicits strong immune response, yet it continues to occur regularly in the
population. This virus causes epidemics of ‘flu’ annually and pandemics at frequent
intervals. This is because influenza virus is not only a human virus but has a complex
relationship that includes replication in several hosts. Thus influenza A virus infects not
only humans but also pigs, birds, horses, mink, and some aquatic mammals such as seals
and whales.

At least 14 subtypes of haemagglutinin (H) protein are present in viruses that

infect birds; 3 of these can infect human. Similarly there are 9 neuraminidase (N) surface
antigens. Viruses that cause worldwide infections (pandemics) can be classified according
to their H & N types. Each pandemic is characterized by a new combination (from

The 1918 pandemic was H1N1

The 1957 ‘Asian Flu’ was H2N2
The 1968 ‘Hong Kong Flu’ was H1Ni, and the 1977 flu was, again, H1N1.

These dramatic shifts of H & N serotypes result from the exchange of genome
segments by mammalian and avian influenza viruses. Although it is presumed that
viruses of one species (as birds) are not efficient at infecting another species (humans),
there is evidence of direct infection of human beings by an avian strain (H5N1) in 1997.
Since no man will have immunity against such a novel virus, large epidemics, even,
pandemics can potentially occur. The only consolation is that such alien viruses are
incapable of efficient spread in human beings, and the man proves the dead-end host.
There is no man-to-man transmission in such viruses.

Pigs provide very good hosts to both human and avian viruses – the lining of their
throats contains receptors for both types of viruses. Thus, pigs act as non-selective hosts
for mixed infections of both human and avian types, and thus a good medium for
reassortment of H & N of different species. This gives rise to new viruses which can lead
to reinfection of human population.

Because of the dense human population in southeast Asia, large number of people
come in daily contact with domesticated pigs, ducks, fowl, & geese. There is
epidemiological evidence that the 1957 and 1968 pandemics originated in China, and that
human N & H serotypes are circulating in wild-fowl population. The intermixing of large
numbers of human beings, migratory birds, and domesticated swine & birds provide a
continually expanding opportunity for recombinations and reassortments of different
influenza viruses and thus emergence of newer viruses.

Indian J for Practising Doctor; Vol I; No. 4

antigen similar to those of the 1918 and viruses have infected human beings, they
1933-34 pandemics. have not been able to lead to any major
outbreaks. This is because these viruses
Curiously all these sudden major could establish among human beings and
changes occurred in China. Most of them thus there was no man-to-man
arose from genetic re-assortment of transmission.
surface antigens between human and
mammalian/avian strains. Generally, one Immunity: Infection elicits both
sub-type of type A infects only a humoral and cellular immune response.
particular species, but when cross- Antibodies are protective whether
species transmission occurs, genetic re- systemic (in serum) or local (at various
assortment takes place between the mucosal surfaces as nose and other areas
transmitted subtype and type A virus in of the respiratory tract). Humoral
the recipient host. A new virus subtype is response could be life-long but for the
formed with surface proteins from either antigenic drift shown by the virus which
parent subtype. This virus has the leads to waning of protection over time.
capability to infect the 3rd host, the Virus-specific CMI (through cytolytic T-
human being. The 1957 ‘Asian’ cells) leads to destruction of virus-laden
influenza virus obtained 2 genes coding cells in the respiratory tract and thus
for its HA & NA surface proteins and helps in recovery from infection. The
one gene coding for its internal proteins cell-mediated immunity is more
from an avian subtype. The remaining 5 specific, less amenable to antigenic drift,
genes were derived from the pre-existing highly effective but does not take effect
strain in circulation since 1933-34 till 2-3 days after the initial infection,
pandemic. and is short-lived (lasts for only a few
15 different haemagglutinin (HA)
proteins [H1 to H15] and 9 different Protection from the virus is mainly through
neuraminidase (NA) proteins [N1 to N9] humoral response; role of the CMI in early
are found in influenza strains infecting stages is minimal. However, cellular
different hosts including man. However, responses take over later and play more
only 3 of the former (H1, H2, & H3) dominant part in limiting the already
hade been encountered in all type A established infection and in eliminating the
virus. Elimination of infection is
strains which had caused epidemics
accomplished by destruction the virus-laden,
among humans till 1997, when the first infected cells. Regeneration of the destroyed
evidence of direct infection of man from mucosa occurs 7-10 days after the start of
a virus with non-human HA antigen (H5 infection.
avian) appeared in Hong Kong. In 1999,
H9 avian got transmitted to humans, who Transmission: Influenza virus is
proved to be ‘dead-end’ hosts. transmitted from person-to-person
through droplets (in nasal secretions and
Since the pandemic of 1977 saliva during sneezing & coughing) as
(Russian flu), 2 type A viruses have been well as during the normal daily contact
circulating among humans: H1N1 among humans. Thus fomites are also
(Russian) and H3N2 (Hong Kong). important in spread of infection.
During the last 30 years, though avian

Indian J for Practising Doctor; Vol I; No. 4

Pathogenesis: The virus may infect

whole respiratory tract from nose down Bronchoscopy shows de-ciliated,
to lungs. Droplets are usually <2 mm, oedematous, and acutely inflamed
land in the lower respiratory tract, attach bronchi, trachea and larynx. This
to the epithelium and initiate infection. results in desquamation of cells.
Absence or gross deficiency of the type-
specific surface antibody (IgA) facilitates Local defences & recovery:
establishment of infection. 1) The virus triggers the interferon
The establishment of infection release very effectively which
depends on: coincides with onset of symptoms,
• Various non-specific and virus- levels peaking some 24 hours later.
specific host factors: Susceptibility Interferon plays an important role in
of the local mucosal columnar cells reducing replication of virus and in
makes adherence of virus easier. limiting spread of virus in the
Muco-ciliary mechanisms get rid of respiratory tract.
large quantity of virus in non-
The systemic features of malaise,
smokers. Antibodies to type B can
not protect from type A infection.
aching pain in back and joints, and
Similarly, previously acquired fever are associated with release of
antibodies to either type may not various pro-inflammatory cytokines
afford any protection to subsequent including interferon, interleulkin-6
infection. and tumour necrosis factor-α.
• Viral factors as quantity of virus
inhaled: Larger viral dose 2) Other nonspecific host factors are
overwhelms the local defences. soluble factors, such as lung
• The intrinsic virulence of the virus, surfactants, sialylglycoproteins and
which in turn depends on the type alveolar macrophages take up the
and subtype and changes with virus ands thus prevent it from
antigenic drift and shift. attaching to and invading the
susceptible epithelial cells.
Within 5-6 hours of establishment of
infection, progeny viruses are
3) In the first (primary) infection,
released to enter other susceptible
locally elicited antibody response is
cells. Lytic replication of the virus
important. IgA is secreted locally;
leads to almost total destruction of
IgG is derived from the transudate
the ciliated epithelial cells of the
spilling into the respiratory tract
respiratory tract.
secretions from the bloodstream as a
result of inflammation. Both these
Infection in the nasopharynx
prevent the virus from attaching to
leads to a loss of ciliated epithelium –
the epithelium or entering the cell, by
an important nonspecific respiratory
blocking the activities of
defence - in nasopharynx and
haemagglutinin proteins. In 80%
trachea, which paves way for
cases, a primary serum IgG response
secondary bacterial infection
is seen, which again has to reach the
(streptococcal, staphylococcal, H
respiratory mucosa for neutralizing
influenza) in the lower respiratory
the virus.
tract. Fatal pneumonia may ensue in
the elderly.

Indian J for Practising Doctor; Vol I; No. 4

Immunologic memory of the Children may exhibit more lower

local IgA which is specific for the respiratory tract involvement presenting
haemagglutinin and neuraminidase as croup or pneumonia. There may be
proteins of virus could ward off all extrapulmonary manifestations as
subsequent infections, provided there vomiting, abdominal pain and myositis.
were no antigenic drift or shift. Same
applies to the serum antibody, mainly Complications
IgG. In some cases influenza may be complicated
. by:
Clinical presentation 1) Myositis: This is commoner in type B
In temperate areas, infections infection, and in children recovering from
the illness but may occur during acute phase
usually occur in winter with a threat of
with direct viral invasion of muscle. It begins
outbreaks from December till March. with acute pain and tenderness in
However, cases occur throughout the gastrocnemius and soleus muscles leading to
year. In the UK, a weekly incidence of extremely painful walking. There is a
influenza-like illnesses greater than transient elevation of serum creatine
400/100,000 population is considered to phosphokinase. Very rarely heart muscle
constitute an infectious rate of epidemic may be involved with tachy-dysrhythmias,
proportions. and elevation of cardiac enzymes. Patients
may suffer myoglobinuria and renal failure.
In adults, influenza is an acute The majority recover within 3-4 days.
infection. with an incubation period of 2- 2) Reye’s syndrome: It occurs particularly in
paedriatic influenza patients receiving
3 days. Usual presentation, after an
aspirin. There is acute encephalopathy with
incubation period of 2-3 days, is an cerebral oedema, with fatty degeneration of
abrupt onset of rhinitis, sore-throat, non- the liver. The cerebrospinal fluid is normal
productive cough, with fever (38°-40°C), except for its raised pressure. Liver function
malaise, headache, chills and myalgia. tests are abnormal.
Clinical picture is of pharyngitis and 3) Pneumonia: Involvement of lung occurs
tracheo-bronchitis. Infection is more usually in those at high-risk of getting
severe in smokers. Majority of cases are influenza as the elderly, and those with
typical; a minority may be asymptomatic COPD and other cardiopulmonary diseases.
(sub-clinical) or present as simple However, in some pandemics (as the 1957
rihinitis and sore throat. Asian pandemic) 1/4th of all healthy persons
got it. The virus replicates in the alveolar
epithelial cells. The patient becomes
When uncomplicated, the acute overwhelmingly toxaemic and exhibits a
episode lasts for 3-7 days, though rapid respiratory rate, tachycardia, cyanosis,
weakness may last another week. high fever and hypothension. Chest x-ray
shows patchy consolidation in two or more
In children and adolescents, lobes; cavitation or pleural effusion implies
influenza is slightly milder and of a bacterial super-infection. Pathological
shorter duration. Subclinical and minor picture is shared by many viruses invading
infection is commoner in younger lower respiratory tract: thus, there is
children. However, there could be severe interstitial pneumonitis with severe
presentations with high fever and febrile hyperaemia and broadening of the alveolar
walls together and mononuclear cell
infiltration. The patient may die within 1-4
days. Such severe presentation is usual with

Indian J for Practising Doctor; Vol I; No. 4

type A infection. The survivors begin 2) At risk groups: These include the elderly
improving some 5-15 days after the start of (75 yr or above, the debilitated, persons with
pneumonia. Usually there are no sequelae. COPD (including asthma and bronchitis),
4) Secondary bacterial infections: diabetrics, ischaemic heart disease, or renal
Superinfection with pneumococcus, staph disease, immuno-compromised persons, and
areus and H influenza is common. This is residents of closed institutions where attack
probably because the viral neuraminidase-1 rate is very high. The majority of at-risk
induces apoptosis (programmed cell death) persons have some degree of immune-
in the invaded epithelial cells and leucocytes, compromise. For example, the elderly
which in turn permits bacterial overgrowth. suffering from thymus involution resulting in
There is already existent colonization with T-cell insufficiency. Mortality rate among
bacteria in cystic fibrosis and occasionally in the elderly with one or more risk-factors
COPD, excessive smoking and attributable to influenza among the elderly is
environmental pollution. Mortality is greatly 0.8% as compared to 0.02% in those under
increased with bacterial superinfection. 65. In obstructive and occupational
respiratory diseases, and among smokers,
Diagnosis is mainly clinical and difficult local epithelial defences (mucociliary
in absence of an outbreak. During an clearance) are weakened. Influenza
epidemic an adult with a diffuse exacerbates asthma in children. Congenital
interstitial pneumonia is likely to be disorders (cystic fibrosis), organ transplants,
and HIV infection increase risk of death
suffering from influenza virus
among young adults.
In ischaemic heart disease, hypoxia and
myocarditis both increase the mortality. HIV
Influenza in special categories: impairs T-cell response which in normal
1) Pregnancy & influenza: There is no individuals helps in getting rid of virus.
definitive proof of congenital anomalies or Elderly diabetics have a 6-fold increased risk
haemotoligical malignancies with influenza. of requiring hospitalization for ketoacidosis ,
However, in a pandemic caused by a novel with adverse outcome. The increased risk
virus, pregnant women may contract fatal among them is related to their cardiovascular
disease in 2nd or 3rd trimester. It was complications and deranged metabolic
observed in both the 1918 and 1957 control. ************

Further reading:
Bender BS, Small PA. Influenza: pathogenesis & host defences. Semin Respir Inf 1992; 7:38-45
Bush RM, Bender CA, Subbarao K. Predicting the evolution of human influenza A. Science 1999;
Couch, RB. Influenza: prospects for control. Amm Intern Med 2000; 133: 992-8
Das P. Flu experts feel countries are unprepared for a future pandemic. Lancet 2001; 357: 1419.
De Jong JC, Rimmelzwaan GF, Fouchier RAM. Influenza virus: A master of metamorphosis. J Infect 2000;
Ellis J, Joseph C, Zambon M. Fifty years of influenza surveillance. Commun Dis Public Health 1999; 2: 81-
Nguyen-Van-Tam JS. Epidemiology of influenza. In: Nicholson KG, Webster RG (ed)> Textbook of
nfluenza. Oxford: Blackwell, 1998.
Olviera EC, Marik PE, Colice G. Influenza Pneumonia: a descriptive study. Chest 2001; 119:1717.
Webster RG. Immunity to influenza in the elderly. Vaccine 2000; 18:1686-9
Potter CW. A history of influenza. J Appl Microbiol 2001; 91:572-9
Simonsen L. The global impact of influenza on morbidity and mortality. Vaccine 1999; 17 Suppl 1

Indian J for Practising Doctor; Vol I; No. 4

unique quality of periodically mutating

Patient Education to negate any immunity people may
Influenza develop. The problem has been met by
creating polyvalent vaccines: vaccine
against type B is combined with vaccines
against the subtypes of type A as they
Influenza is an acute, infectious, evolve. This has required a worldwide
contagious disease of the respiratory surveillance system to detect altered
tract, especially the trachea, colloquially virus forms as soon as they arise, so that
called flu or, less often, grippe. The adequate stocks of vaccine can be
symptoms of a simple attack include dry prepared in time. Because it would be
cough, sore throat, nasal obstruction and prohibitively expensive to prepare
discharge, and burning of the eyes; more vaccine for the entire population each
complex cases are characterized by chill, time the virus mutated, vaccine was for a
sudden onset of fever, headache, aching long time administered only to those
of muscles and joints, and occasional most susceptible to developing
gastrointestinal symptoms. In pneumonia when they contract influenza.
uncomplicated cases, symptoms fade and
temperature drops to normal in a few The different antigenic types of
days; the risk of death increases if the influenza virus appear in cycles; for
disease is accompanied or followed by instance, the variant appearing in the
viral or bacterial pneumonia. 1978-1979 season was identical to the
virus that was widespread during the
Since the 16th century, at least 31 early 1950s. Some evidence exists that
influenza pandemics (very widespread pandemics occurring 60 to 70 years apart
epidemics) have been described. The are caused by the same form of virus.
most destructive epidemic of modern Based on this theory, public health
times, that of 1918, is estimated to have officials expected in 1976 that the same
caused 40 million deaths. virus that caused the 1918 pandemic
would reappear. When this form of the
The three types of causative
organism (known colloquially as swine
virus, known as A, B, and C, were
flu) was isolated from army recruits in
isolated in 1933, 1940, and 1950,
Fort Dix, New Jersey, United States,
respectively; the first two are responsible
vaccine against it was prepared, and
for disease epidemics. In 1941 it was
mass inoculation was carried out in the
shown that influenza could be controlled
United States. No outbreak, however, of
by a vaccine containing virus. The
that form of influenza occurred.
problem of immunization is complicated,
because the different types are The drug amantadine
antigenically unrelated and so do not hydrochloride, which is taken orally, is
induce cross-immunity. It is also effective in preventing influenza caused
complicated because immunity to a by influenza A virus, and also
specific virus persists for less than a year moderately effective in treating influenza
and because these viruses exhibit the

Indian J for Practising Doctor; Vol I; No. 4

A after symptoms have appeared. and 1968, each of which also killed
Amantadine is used as an adjunct to millions around the world. Medical
immunization for high-risk patients, but experts now believe it is a question of
immunization is still considered the most when and not if another flu pandemic
effective way to combat the disease. causes infection on a global scale and
Human infection with avian influenza A maybe affects millions of people.
(H5N1) viruses were identified in Hong Potentially the situation is worse now
Kong in 1997. As of January 1998, a because of the explosion of international
total of 16 cases and three suspected travel in recent decades. However,
cases of this new type of influenza had improved communications and the
been confirmed. Individuals with high World Health Organization's monitoring
levels of exposure to infected poultry or work mean that a deadly strain could be
direct exposure to the virus in the isolated more quickly, allowing doctors
laboratory, or health-care workers, are more time to formulate a vaccination.
thought to be at most risk. Finally, antibiotics, while ineffective
against viruses, would be crucial for
Since the 1918 pandemic there tackling infections that many victims
have been two other pandemics, in 1957 would develop as a result of influenza.

Indian J for Practising Doctor; Vol I; No. 4

Cold Chain Maintenance will avoid artificial shortages created by

accumulation of large balance stocks at
places where the programme is not
functioning effectively.
Rubina Shaheen
_____________________________ Range Vaccines

A vaccine must have two Most sensitive BCG(after reconstitution)

characteristics, one is safety and other is OPV
potency. The potency of a vaccine is Hepatitis B
maintained by cold chain. The cold chain DPT
is a system of storing and transporting DT
the vaccines at recommended
temperatures from the point of Least sensitive BCG(before
manufacture to the point of use. The TT(Tetanus toxoid)
essential elements of the cold chain are: Vaccine Vaccines that can be
• Personnel to organize and manage damaged by frozen without harm
vaccine distribution. freezing
• Equipment for storage and DPT BCG(before
transport of vaccine. DT reconstitution)
• Transport facilities TT OPV
• Maintenance of equipment and Hepatitis B Measles(before
• Monitoring.

Why to maintain the cold chain? Storage temperature:

Maintenance of cold chain All vaccines are to be retained at
system is important because the temperatures between +2 to +8 0C. A
vaccines lose their potency if exposed break in the cold chain is indicated if
to adverse temperatures. The tables temperature rises above +80C or falls
below show the sensitivity of different below +20C in case of ILR & other
vaccines to heat and freezing. refrigerators.

Monitoring of Cold Chain: Potency tests

Monitoring of cold chain Vaccines produced by production
regularly is important if you expect it to unit are tested for potency before these
function effectively and efficiently. The are released in the market. However,
things you will need to monitor are: there is no guarantee that this vaccine
• Availability of equipment &its will remain potent till it is administered
working to the child; that dependents on a
• Supplies competent cold chain. To actually
• Storage temperature monitor vaccine potency in the field, one
• Potency tests has to send a random sample of oral
polio vaccines lifted from field to
Supplies: laboratory for testing potency. This
Arrange supplies according to activity is, in addition, and independent
demand and utilization so that there is a of production-testing.
regular and smooth flow of vaccines. It

Indian J for Practising Doctor; Vol I; No. 4

The concentration of live attenuated • Roll the polythene bag around the
polio virus shall constitute the parameter sample and secure it by a rubber
to measure potency. The titration is band.
performed on HEp-2 Cincinnati cells • Place the polythene bag containing
the sample in vaccine carriers
with passage level of <350.
containing enough ice packs.

Cases where potency of vaccine The samples so collected should

from field needs to be checked be rushed to the headquarters in vaccine
• When you suspect break in the cold
carrier observing cold chain, known as
• To monitor the efficiency of storage
the reverse cold chain. If delay is
in the field. anticipated in transmitting the sample for
• As a part of evaluation of testing, such samples should be kept in a
vaccination e.g.; sero-conversion deep freezer/ILR till they are sent to the
studies. testing laboratory.
Testing facilities are available at the:
• Central Research Institute, Kasauli General guidelines for testing OPV
(H.P). sample
• National Institute of Communicable • Total number of samples to be
Diseases, Delhi, collected from the state in a year is
prescribed. Roughly the number of
• Enterovirus Research Centre,
samples to be collected is the same
as the number of PHCs in the state.
• School of Tropical Medicine,
• Out of the total number of samples,
30 percent should be from out-reach
• S. K. Institute of Medical Sciences session PHCs, 15 percent from
Soura, Srinagar, Kashmir. district headquarters and 5 percent
from walk- in coolers.
OPV has been selected as • For samples collected from out-reach
“indicator” of cold chain as this vaccine sessions and PHCs, care sold be
is more heat-labile than other vaccines taken not to take more than one
and is easier to test. sample from one area/ institution in
a year.
• The team formed to collect samples
Collection of OPV sample for potency
should plan their visits in advance
testing and also be responsible for
• Select a used or unused vial of
maintenance of the reverse cold
OPV. The used vial must have at
least 2ml of vaccine.
• The storage point for vaccines
• Affix an adhesive label on the
should be codified; so that
bottom of the vial name of the
relationship between samples and
Primary Health Centre and date of
storage points can be easily
• Ensure that manufacturer’s label is
• Te samples collected should be
rushed to headquarters in a vaccine
• Place the labeled vial of OPV in a carrier observing cold chain (reverse
polythene bag and affix second cold chain.) and kept in the deep
label indicating the name of the freezer until they are sent for testing
Primary Health Centre on the in the laboratory.
polythene bag.

Indian J for Practising Doctor; Vol I; No. 4

• The VVM status of the sample is used for storing of OPV and measles
should be recorded at the time of vaccine and also for freezing ice packs.
collection of sample and the time of In case of power failure, it can maintain
receipt of vaccine in laboratory.
the cabinet temperature for 18 to 26
hours, if not opened. These are available
Cold chain equipments: in two models, having a capacity of 300
There are equipments of different litres and 140 litres. The chest freezers
capacity for storage of vaccines at are provided with special insulation,
different levels as under: which helps in maintaining inside
temperature, in case of electricity failure,
Walk-in-freezers: for much longer time. The 140 litre-chest
These are used for bulk storage of freezer can store 65000 doses of
OPV, measles vaccines and also to vaccines.
prepare frozen ice-packs at state stores. The 300 litre capacity freezer at
They maintain a temperature around district headquarters are to supplied for :
minus 20°C. They are available in sizes • Storage of OPV& measles
of 16.5 Cu. Mt. and 32 Cu. Mt. These are vaccines
provided with two identical cooling units • Preparations of ice packs.
and a standby generator sets. Bulk The 140 litre capacity freezer at PHC
quantities of ice packs are also made and headquarters are to be supplied for:
stored in the walk-in-freezers. • Storage of OPV& measles
Walk-in-coolers: • Preparations of ice packs.
These are used for bulk storage of
vaccines at State and Regional stores. The diluents should not be kept in
They maintain a temperature of +2°C to deep freezers. These should be stored at
+8°C. They are available in sizes of 16.5 a temperature between +2° to +8°C and
Cu. Mt. and 32 Cu. Mt, and are used for should be transported along with the
storage of large quantities of vaccines at concerned vaccine.
state and regional level. This is provided
with two identical cooling units and Preparation of Ice Packs:
standby generator sets with automatic • Fill the ice pack with water up to the
start and stop facilities. They are also mark and close the cap tightly.
provided with temperature recorder and • Prepare ice-pack by keeping the
alarm systems. Walk-in-coolers are water-filled container in freezer or in
the freezer compartment of
established at regional levels, which
refrigerator so that water freezes.
store vaccines for about 4-5 districts.
• Do not add salt to the water in the
Both, walk-in collers & walk-in-freezers ice pack while placing in the freezer,
store three months of requirement of it will lower the temperature to
vaccines + 25% buffer stock for the subzero level which is not
districts they cater. recommended for DPT, DT, TT and
Deep freezers: • Shake it and invert to check that it is
Deep freezers supplied under not leaking
immunization programme have a top • Place the ice packs on one side in the
freezer initially, placing 16-24 packs,
opening lid. The cabinet temperature is
maintained between -18° to -20°C. This

Indian J for Practising Doctor; Vol I; No. 4

and change to another on the next Conventional Refrigerators:

day. • This is to be used in case of
• For emergency requirement a PHC breakdown of ILR.
should have 50-60 frozen ice packs • Temperature in the ordinary
at a given time. chamber remains between 4 & 10
degrees. In the ice chamber the
temperature fluctuates between 0-
Ice Lined Refrigerators: 4 degrees centigrade. Overall
These type of refrigerators are speaking, the temperature in an
ordinary refrigerator ranges from
top-opening because they can hold the
+2 to +8°C.
cold air inside better than a refrigerator
• Measles and polio vaccines are kept
with a front-opening. An ILR can keep on the top shelf below the freezer.
vaccine safe with as little as 8 hours • Vaccines should not be frozen or
continuous electricity supply in a 24 hour thawed repeatedly as this will
period. It is available in two sizes decrease their potency.
• ILR-MK 300 of 300 litre capacity and • DPT, DT, TT, BCG and diluents are
• ILR-MK 140 of 140 litre capacity. kept in the middle shelf.
• Water bottles with coloured water
The MK-300 is supplied to (to serve as buffer in case of
district headquarters and MK 140 is electricity failure) are kept at the
supplied to PHC headquarters. bottom shelf and door.

Inside the ILR, there is a lining of Installation of the equipment:

water-containers fitted all around the No electric cold chain equipment
walls and held in place by frame. While should be installed without a voltage
the refrigerator is in operation, water in stabilizer. Before installation, one should
containers freezes and when the get familiar with various features of
electricity supply fails, then the ice lining Automatic Voltage Stabilizer.
keeps the inside temperature of the
refrigerator at a safe level for vaccines. Vaccine Transportation Equipments
In such a situation the temperature
remains within safe limits in ILR for Cold boxes
much longer than in deep freezers. Cold boxes are mainly used for
transportation of large quantities of
ILR has got two sections- the top vaccines. They can also be used to store
and the bottom. The bottom of the vaccines for transfer up to five days.
refrigerator is the coldest place. These are of two sizes 5 litres and 20
Therefore, DPT, DT TT and BCG litres with requisite number of ice packs.
vaccines should not be kept directly on The 5 litre cold box can transport about
the floor of the refrigerator as they can 1500 doses of vaccines; the 20 litre
freeze and get damaged. The top section boxes have enough space to transport
of the ILR maintains the temperature of about 6000 doses of vaccines. The ‘hold
+2° to +8°C. BCG, DPT, DT, and TT over time’ is more than 90 hrs for 5 L
vaccines are kept in this section in the and six days for 20L cold box. We may
baskets provided with the refrigerator. store vaccine in cold boxes in case of
breakdown of ILR. The vials of DPT, DT
and TT vaccines should not be placed in

Indian J for Practising Doctor; Vol I; No. 4

direct contact with frozen ice packs and Storage temperature:

should be surrounded by OPV vials. To measure the temperature
during storage/transport, different types
How to keep cold boxes in good of thermometers are used.
condition when not in use
• Clean and dry after use • Dial thermometers
• Examine inside and outside Dial thermometers have been
surface after every use for cracks. provided to record the temperature in the
• Check that the rubber seal around ILRs / Freezers. One dial thermometer
the lid is not broken; if broken, should be kept in every unit. A staff
replace immediately. member should be made responsible for
• Adjust the tension on the latches recording the temperature. The
so that the lid closes tightly temperature record should be used to
• Lubricate hinges and locks monitor and control the temperature and
routinely. to take follow up action as required.

Vaccine Carriers • Alcohol stem thermometers

Vaccine carriers are used for Alcohol thermometers are much
carrying small quantities of vaccines (16- sensitive and accurate than dial
20 vials) to the sub-centers or villages by thermometers. They can record
health workers. The vaccine carriers are temperatures from -50°C to +50°C
made of insulated material, the quality of and can be used for ILRs and deep
which determines the cold-life of the freezers.
carrier. These are containers with thick
walls and lids of material which does not Recording and monitoring of
allow heat to pass through it easily. storage temperature
The temperature in the ILR must
Fully frozen ice packs are used to be monitored twice daily (morning and
keep vaccines cold in the carrier. The evening). This is done in order to:
vials of DPT, DT and TT vaccines • Be sure that vaccines were not
should not be placed in direct contact exposed to temperature above +80
with the frozen packs. Do not leave the Celsius.
lid open and do not expose the carrier to • Check that the equipment is
the sun. Vaccines can be kept in the working properly.
carrier for 48 hrs. • We must be careful and ensure
that the temperature in the ILR
If more than one vaccine carrier does not rise above +8°C. Also
is being carried, keep the whole range of one must check that the
the vaccines required for the day in the temperature does not fall below
carrier so that only one carrier is opened -20°C as it damages the T series
at a time. Keep the vaccine carrier in (tetanus-containing) of
good condition when not in use. vaccines.
• Vaccines are damaged by heat
whether they are exposed to a lot

Indian J for Practising Doctor; Vol I; No. 4


Vaccines Storage temperature in 0C

0-8 22-25 35-37 Over 37

Tetanus and Stable for 3-7 years Stable for months Stable for at least 6 Stable for 2
diphtheria weeks weeks at 450C,
toxoid as loss of potency
monovalent after few ours at
vaccines or 60 to 650C
of vaccines
Pertussis Safe storage for 18-24 Stability varies. Some vaccines Stability varies. At 450c about
vaccine month although with stable for two weeks. Some vaccines loss 10% loss of
continuous slow 50% of potency after potency per day,
decrease of potency one week storage. rapid loss in
potency at 500C
Freeze-dried Stable for one year Stability varies. 20-30% loss of Stability varies. 20% Unstable. 50%
BCG vaccine viability after 3 month storage loss of viability after loss after 30
3-14 month storage minute exposure
to 700C
Reconstituted Reconstituted BCG vaccine should not be used beyond one working session (5-6 hours). This
BCG vaccine recommendation has two bases (1) concern over the risk of contamination, as BCG contains no
bacteriostatic agents, and (2) concern over the loss of potency.
Freeze-dried Stable for two years Retains satisfactory Retains satisfactory 50% loss of
Measles potency for one potency for at least potency after 2-
vaccine month one week. 3 day exposure
to 410c; 80%
loss in potency
after one day
Reconstituted Unstable-should be used in one Unstable-50% loss Very unstable; titer Inactivation
measles working session after one hour. 70% may be below within one hour
vaccine loss after 3 hours acceptable level after
OPV Stable for 6-12 months Unstable, 50% loss Very unstable loss of Very unstable.
after 20 days. Some satisfactory titers At 410c 50%
vaccines may retain after 1-3 days loss after one
satisfactory titers for day. At 500c
1-2 weeks loss of
titers after 1-3
Inactivated Stable for 1-4 years Decline of D-antigen Loss of D-antigen for Precise data
polio vaccine content for type 1 type1 after 20 days lacking
after 20 days in some vaccines but
no significant loss
after 4 weeks in

of heat in a short time or a small • A break in the cold chain is

amount of heat over a long indicated if temperature rises
period. above +8°C or falls below +2°C
• Maintaining the cold chain in the ILR; and above -18°C in
demands constant vigilance. the Deep Freezer.

Indian J for Practising Doctor; Vol I; No. 4

Shake test:
The “shake test” is a test to Supply of vaccines:
determine if a vaccine was frozen or not A health administrator’s major
at any time. Freezing can damage DPT, responsibility is to provide vaccines to
DT, tetanus toxoid (T-series of vaccines), health centres in time. Before making
typhoid and hepatitis vaccines. We can supplies, we must check the following
find out if any of these was frozen or not • Requirements of the PHC
by performing this test. (session wise)
• Utilization during the previous
Vaccines never frozen months. We can get this
• Smooth and cloudy. information from monthly
• It is clear with no sediment monitoring report
• Find out balance in hand.
Vaccines frozen • Arrange supplies according to
• Vaccines frozen contain granules,
demand & utilization.
and sediments are fond settled at the

Indian J for Practising Doctor; Vol I; No. 4

Operating Room Etiquette

(Reproduced from “Surgical Care at the District Hospital”, WHO, Geneva, 2003)

{This section is reproduced for the benefit of doctors and paramedics working in the District &
sub-district hospitals of India, particularly J & K State]


The operating theatre is a room enter the operating room,

specifically for use by the anaesthesia especially after an operation
and surgical teams and must not be used has started.
for other purposes. A treatment room has ƒ Keep the operating room
equipment similar to an operating uncluttered and easy to clean.
theatre, but on a smaller scale. Both ƒ Between cases, clean and
rooms require: disinfect the table and
instrument surfaces.
ƒ Goods lighting and ventilation ƒ At the end of each day, clean
ƒ Dedicated equipment for the operating room: start at
procedures the top and continue to the
ƒ Equipment top monitor patients, floor, including all furniture,
as required for the procedure overhead equipment and
ƒ Drugs and other consumables, lights; use a liquid
such as sutures, for routine and disinfectant at a dilution
emergency use. recommended by the
Ensure that procedures are ƒ Sterilize all surgical
established for the correct use of the instruments and supplies
operating room and that all staff are after use and store them
trained to follow them: protected and ready for the
next use.
ƒ Keep all doors to the ƒ Leave the operating room
operating room closed, ready for use in case of an
except as needed for passage emergency.
of equipment, personnel and
the patient. Sponge & Instrument Counts
ƒ Store some sutures and extra
instruments in the operating It is essential to keep track of the
room to decrease the need for materials being used in the operating
people to enter and leave the room and during any complicated
operating room during a procedure in order to avoid inadvertent
case. disposal or the potentially disastrous loss
ƒ Keep to a minimum the of sponges and instruments in the wound.
number of people allowed to

Indian J for Practising Doctor; Vol I; No. 4

It is standard practice to count of the instruments included in that tray

supplies (instruments, needles, & for future reference.
ƒ Before beginning a case Scrubbing & Gowning
ƒ Before final closure
ƒ On completing the procedure Before each operation, all members of
the surgical team – that is, those will
The aim is to ensure that touch the sterile surgical field, surgical
materials are not left behind or lost. Pay instruments or the wound – should scrub
special attention to small items and their hands and arms to the elbows.
sponges. Scrubbing can not completely sterilize
the skin, but will decrease the bacterial
Create and make copies of a load and risk of wound contamination
standard list of equipment for use as a from the hands.
checklist to check equipment as it is set
up for the case and then as counts are Each hospital should develop a
completed during the case. Include space written procedure for scrubbing that
for suture material and other specifies the length and type of scrub to
consumables added during the case. be undertaken. It is usual that the first
scrub of the day is longer (minimum 5
When trays are created with the minutes) than any subsequent scrub
instruments for a specific case, such as a between consecutive clean operations
(minimum 3 minutes).
Caesarean section, also make a checklist

Indian J for Practising Doctor; Vol I; No. 4

When scrubbing:
1. Remove all jewellery and trim the nails
2. Use soap, a brush (on the nails and finger tips) and running water to clean
thoroughly around and underneath the nails.
3. Scrub your hands and arms up to elbows
4. After scrubbing, hold up your arms to allow water to drip off your elbows
5. Turn off the tap with your elbow.

After scrubbing your hands:

1. Dry them with a sterile towel and make sure the towel does not become
2. Hold your hands and forearms away from your body and higher than your elbows
until you put on a sterile gown and sterile gloves.

Indian J for Practising Doctor; Vol I; No. 4

Surgical gloves prevent transmission of procedure. Shaving can damage the skin
HIV through contact with blood, but so clipping is better if hair removal is
there is always the possibility of required; it should be done in the
accidental injury and of a glove being operating room.
punctured. Promptly change a glove Just before the operation, wash
punctured during an operation and rinse the operation site and the area
your hand with antiseptic or re-scrub if surrounding it with soap and water.
the glove has leaked during the Prepare the skin with antiseptic solution,
puncture. Patient safety is of primary starting in the centre and moving to the
concern; do not compromise it. Change periphery. This area should be large
your gloves only when it is safe for the enough to include the entire incision and
patient. adjacent working area, so that you can
manoeuvre during the operation without
touching the unprepared skin.
Chlorhexidine gluconate and iodine are
Skin Preparation: preferable to alcohol and are less
irritating to the skin. The solution should
The patient should bathe the night remain wet on the skin for at least two
before an elective operation. Hair in the minutes.
operative site should not be removed
unless it will interfere with the surgical

Indian J for Practising Doctor; Vol I; No. 4

Draping: contamination. There are many

Scrub, gown and glove before covering approaches to draping, some of which
the patient with sterile drapes. Leave depend on the kind of drapes being used.
uncovered only the operative field and Do not place drapes until you are
those areas necessary for the gowned and gloved, so as to maintain the
maintenance of anaethesia. Secure the sterility of drapes. It is important to
drapes with towel clips at each corner. secure good exposure and a large sterile
Draping exposes the area of the area. When laying out the drapes, the
operative field and provides a sterile edges and folds (which hang below the
field for the operating staff to work. This operating table) are considered to be
is designed to maximize surgical non-sterile.
exposure and limit potential for

Pregnancy in the Rh-

Indian J for Practising Doctor; Vol I; No. 4

negative woman positive offspring; a heterozygous

partner will produce either Rh +ve or Rh
Rehana Kausar -ve offspring. Rh iso-immunization can
________________________________ occur only in that pregnancy in which a
Rh+ve foetus resides, and only that
foetus or subsequent Rh +ve foetuses
Isoimmunization (maternal will be affected by the maternally
blood-group immunization), a disease of produced Rh antibody.
genetic predisposition, has been a focus
of concern for obstetricians for centuries. B) Atypical antibodies: Antibodies
Fifty years ago, Landsteiner and Weiner directed against the c and E , and less
first described their classic experiment in commonly against e and C are also
which monkey red-cell antiserum was associated with hemolytic disease of the
mixed with blood samples from a newborn. These are called atypical
selected human population. Levine and antibodies. A number of other red cell
colleagues subsequently demonstrated antigens that are not part of the Rh
that the immune response in an Rh antigen complex are capable of
negative woman was the primary cause stimulating isoimmunization as well.
of hemolytic disease in the newborn. The Because of the efficacy with which Rh
identification of the rhesus antigen and immune globulin prophylaxis prevents
its description in these classic works are Rh isoimmunization, hemolytic disease
the cornerstone of modern immuno- caused by these antigens has become
hematology. The pregnant woman and relatively more important.
her caregiver now have the ability to
both avoid and treat this historically Etiology: Blood group isoimmunization
difficult problem. will occur from one of two pathogenic
mechanisms: incompatible blood
The incidence of Rh negativety in transfusion or foeto-maternal
Caucasian population is 15% to 16%. In hemorrhage.
India the incidence is about 5-8%.
Although the risk of Rh
Rh system incompatibility depends on the dose, a
small inoculum of 50-70 ml of Rh +
A) D antigen: The Rh complex consists blood is needed to produce
of three pairs of antigenic determinants immunization. The secondary response
(Dd, Cc, Ee). The presence of D antigen will require as little as 0.1 ml of red cells.
determines that the individual is Rh +ve.
Although the mother could be theoretically
The Rh +ve individual will be found to immunized if enough erythrocytes enter the
be homozygous for D (i.eDD) foetal circulation to elicit an immune response,
approximately 45% of the time. This isoimmunization is rare due to the following
results from having inherited the D reasons:
containing set of alleles from both 1) Varying rate of occurrence of
various red cell antigens.
partners. The remainder of Rh +ve
2) Their variable antigenicity.
individuals will be heterozygous for the 3) Insufficient transfer of antigen or
D locus. A homozygous partner (DD) of antibody.
a Rh-ve woman will produce only Rh

Indian J for Practising Doctor; Vol I; No. 4

4) Variability of the maternal immune Kleihauer-Betke (KB) test: The principle is

response to the antigen. that foetal erythrocytes contain hemoglobin
5) Protection from isoimmunization by F, which is more resistant to acid dissolution
ABO incompatibility of foetus and than hemoglobin A. After exposure to acid,
mother. This confers some protection only foetal hemoglobin remains. Fetal red
against D-isoimmunization because foetal cells can then be identified by uptake of a
red cells entering the mother usually are special stain and quantified on a peripheral
rapidly destroyed before they can smear. The presence of D-positive fetal red
elicit an immune response viz there is cells in maternal blood can also be
only a 2 % chance of D isoimmunization determined by the rosette test which is more
in all women by 6 months postpartum. sensitive than the Kleihaeur –Betke test.

RISK FACTORS Hydrops foetalis: This is the most serious

• 2% of women are at risk of becoming Rh form of Rh hemolytic disease. Excessive
immunized after having spontaneous or destruction of the foetal red cells leads to
therapeutic abortions. The risk grows by severe anemia, tissue anoxemia and
2.5 fold after 20 weeks. A blood sample metabolic acidosis. These have got adverse
should be taken from every woman at effects on the foetal heart and brain and on
her first antenatal visit for Rh blood the placenta. Hyperplasia of the placenta
grouping and antibody screening. occurs in an effort to increase oxygen
• Paternal antigen status: The Rh –ve delivery o the foetus but due to ongoing
gravida’s partner should be evaluated for hemolysis the foetal red cells are
ABO and Rh status. If the father is also progressively diminished. Damage to foetal
Rh –ve the conceptus will be Rh- liver causes hypo-proteinemia leading to
negative and the mother is not at risk for generalized edema (hydrops fetalis), ascites,
Rh immunization. As extramarital and hydrothorax. Foetal death occurs due to
pregnancies do occur, the patient should cardiac failure.
be made aware of the potential for Diagnostic features of hydrops :
catastrophic events should a father be ƒ Polyhydramnios
demonstrated antigen positive. ƒ Straight X ray abdomen shows
• Trauma to the abdomen poses a special ‘Buddha ‘position of the foetus with a
risk of immunization to the Rh negative halo, around the head due to
woman. The K-B test can detect the oedematous scalp.
amount of bleeding. Abruptio placentae ƒ At birth, the baby is pale, oedematous,
causing third trimester vaginal bleeding with an enlarged abdomen due to
and increased uterine irritability is ascites.
associated with transplacental bleeding ƒ Placenta is large, oedematous and
and should be evaluated with K-B test. pale. The placental weight is
The appropriate amount of RhIG should increased.
be given.
Icterus gravis neonatorum: This entity is
MANIFESTATIONS OF THE HEMOLYTIC due to a lesser degree of foetal hemolysis.
DISEASE The baby is not jaundiced at birth but
develops it within 24 hours of birth. If the
The haemolytic disease of newborn may serum bilirubin level crosses 20mg/dl, the
manifest as bilirubin crosses the blood–brain barrier
causing staining and damage to the basal
1. HYDROPS FETALIS nuclei and producing kernicterus.
NEWBORN Congenital anemia of the newborn: This is
the mildest form of the disease where the

Indian J for Practising Doctor; Vol I; No. 4

hemolysis is going on slowly. Although Amniotic fluid analysis: If the patient’s

anemia develops slowly within first few antibody titre is just at the critical level and
weeks of life, jaundice is not usually present. the patient has not had a baby with
The destruction of red cells continues up to 6 erythroblastosis, the initial amniocentesis
weeks, after which the antibodies are not can be done at 28 to 29 weeks’ gestation. If
available for hemolysis. the titre or history suggests that the
erythroblastosis foetalis may be more severe,
MANAGEMENT: then the amniocentesis may have to be done
) Antibody screening: At the first prenatal as early as 18 weeks gestation. In this way
visit, the patient’s blood group and Rh the course of management can be decided.
type should be determined, and antibody The amount of bilirubin in the amniotic fluid
screening performed. Maternal antibodies correlates roughly with the degree of
are identified by indirect Coomb’s test hemolysis and thus indirectly predicts the
and neonatal antibodies are evaluated by severity of foetal anemia. Since the
direct Coomb’s test. The absorbed concentration of bilirubin is so low, its
antibodies act as hemolysins, leading to concentration is measured by a continuously-
an accelerated rate of red cell destruction. recording spectrophotometer and is
If the patient is Rh negative, screening is demonstrable as a change in absorbance at
performed again at 28 weeks gestation. If 450nm, referred to as ∆OD450 on a graph
antibody is detected, it is identified and originated by Liley in 1961. In the presence
the titre measured Severe hemolytic of bilirubin there is a deviation bulge
disease of the newborn rarely occurs if peaking at 450nm wave length. The greater
the antibody titer is below 1:16. Patients the bulge, the more severe is the affection of
whose antibody titre is less than this level the baby. For any given gestational age, the
can be managed expectantly. Patients height of the deviation bulge at 450 nm falls
with antibody titre more than 1:16 ie the within one of the three zones when plotted in
critical titre, indicates the possibility of Liley’s chart.
severe hemolytic disease. The patient is
no longer a candidate for RhIG. Now an Interpretation
evaluation for presence of the
Erythroblastosis fetalis must be ) If it falls in zone I (low zone) the
undertaken. fetus is not affected.

When the maternal antibody titre exceeds ) If it falls in zone II (mid zone) the
the critical level, further evaluation is done fetus may require premature
by spectrophotometric analysis of the
termination beyond 34 weeks. In
amniotic fluid
lower zone 2, the expected Hb
concentration is between 11.0 and
Today the Rh–immunized
13.9 g/dl, whereas in upper zone 2
pregnancy may be evaluated by five
,the anticipated Hb is 8.0 to 10.9
complimentary modalities:
g/dl and without therapy death
• Measurement of antibody titers
within 7 to 10 days is expected.
• Amniotic fluid (AF) DNA Rh typing Repeat samples are taken at 1 to 2
• AF deviation in optical density at 450 week intervals to see the trend of
nm Eq samples. Pregnancies in the line
• Cordocentesis showing a rise towards zone 3
• Sonography require immediate evaluation.

Indian J for Practising Doctor; Vol I; No. 4

) If it falls in zone III (high zone) the PREVENTION

foetus is severely affected and Anti D immunoglobulin is a 7S immune
death is imminent. If the globulin G extracted by cold alcohol
pregnancy is beyond 34 weeks, fractionation from plasma containing
termination is done forthwith. If high-titer D –antibody. Each dose
pregnancy is less than 34 weeks, provides not less than 300μg of D-
intrauterine transfusion is done antibody. It is given to D-negative, non-
and repeated till such period when sensitized mothers to prevent the hazards
termination can be done safely. of sensitization.

DELIVERY: Vaginal delivery at or near Anti-D: Anti D globulin is

term is the goal of management. The provided to D-negative mothers after
pregnancy is usually closely monitored miscarriage, abortion, evacuation of a
with tests of foetal well-being performed. molar pregnancy or ectopic pregnancy. It
Gestational age is the most important is also administered when there is a
consideration in choosing which large foeto-maternal bleed like placental
treatment to pursue. With careful abruption, intrauterine manipulation,
monitoring and transfusions, when placenta previa. There is need for extra
appropriate, very preterm delivery can be Rh D immune globulin in these patients.
prevented. Labour can be initiated as A dose of 300μ will neutralize about 15
soon as pulmonary maturity is ml of red cells or 30 ml of foetal blood.
documented. A Kleihauer–Betke or rosette test is done
on all such women to know the accurate
EXCHANGE TRANSFUSION IN THE amount of anti-D required.
Cord blood analysis is carried ANTENATAL ADMINISTRATION OF Anti
immediately for any pregnancy in the D- D: With the concept that feto-maternal
negative mother. Cord blood is tested hemorrhage occurs throughout
for blood grouping and Rh typing of the pregnancy ,some centers advocate use of
baby. If the baby is Rh negative, then no anti-D during pregnancy.300 μg of anti
further treatment is needed. Cord blood D are administered at 28 weeks and
hemoglobin concentration and Direct again at 34 weeks and the routine dose
Coomb’s test are of considerable after delivery.Subsequently it was seen
importance when the infant is Rh that a single dose given antenatally at 28
positive. If the infant is overtly anaemic weeks is as effective as two doses
exchange transfusion is done antepartum.
immediately. Type O, D-negative red
blood cells, recently collected are used.
For infants who are not overtly anaemic,
the need for exchange transfusion is
determined by the rate of increase in
bilirubin concentration, the maturity of
infant, and the presence of other


feel more comfortable but it is not
possible, or desirable, to aim to
Fever in childhood normalize the temperature while
someone is fighting off an infection.
Farooq Fazilli Heat production associated with fever
_____________________________ increases the oxygen consumption,
carbon dioxide production, and cardiac
output. Thus, fever may exacerbate
Fever is defined as an elevation cardiac insufficiency in children with
of body temperature in response to any heart disease, chronic anemia, pulmonary
pathological stimulus. American college insufficiency and metabolic instability.
of Emergency Physicians has published a
clinical policy on febrile illness in It must be remembered that the
children that chooses a rectal temperature part of human brain that controls body
of ≥38◦c (100.4◦F) as the most widely temperature is not fully developed in
used definition of fever. children. This means that a child’s
temperature may rise and fall very
Fevers are a sign that the body is quickly and the child is sensitive to the
fighting an infection. The main reason to temperature of his or her surroundings.
treat the child is to make him or her feel
better. When the child is achy and fussy, One of the simplest and most
he/she may need some medicine effective ways to help a child with a
fever feel more comfortable is to take off
In normal circumstances, the some of the child's clothes so that heat
temperature of deep tissues of the body can escape from their body more easily.
(‘core temperature’) is kept at a very
even level by a range of automatic
adjustments. Increase in temperature What is a normal temperature?
increases the amount of blood flowing
A normal temperature is about
through the skin by opening up the tiny
98.6°F when taken orally (by mouth).
capillary blood vessels. This radiates
Temperatures taken rectally (by rectum)
away excess heat and sweating can
usually run 1° higher than those taken
further enhance this. Having too cold
orally. Rectal temperatures are the
temperature causes shut down of skin
closest to 'core' temperature and are
blood vessels and conserves heat within
about 0.5ºC (2ºF) higher than readings
the internal organs. If necessary more
taken from the mouth or ear. So a
heat can be generated by shivering. Fever
normal temperature is about 99.6°F when
is part of the body's defense mechanism
taken rectally. Many doctors define a
against pyrogens. The body tries to
fever as an oral temperature above
create extra heat so that the foreign
99.4°F or a rectal temperature above
organism cannot survive. Increasing the
temperature helps the body to fight
illness. Thus, fever is an adaptive
response and should be treated only in How to take child's temperature?
selected circumstances. Actions to A body temperature reading can be
reduce a fever can help make someone taken from the mouth, armpit, ear, skin surface or
the rectum. The most accurate way to take the
Indian J for Practising Doctor; Vol I; No. 4

temperature of a child is orally or rectally with a the child's forehead are popular but give
mercury or digital thermometer. In a child just a rough indication. Most of the time,
younger than 4 years, take the temperature
rectally. In an older child, take it orally. Although
the exact level of a child’s temperature is
a rectal temperature reading is the most accurate not particularly important, unless it is
and is quite often used in hospitals it is not very high (39ºC or over). In practical
necessary to be so precise when taking terms the temperature reading will be
temperature readings at home. Rectal enough to give an indication of whether a
temperature reading is therefore not
recommended for home use.
fever is present.
Ear temperature
ƒ A mercury thermometer should show a If affordable, an ear thermometer is a very
temperature lower than 98.6°F before quick method and will give a read-out in seconds. Ear
taking a temperature. This can be done thermometers rely on measuring infrared (heat)
by running cool water over the tapered radiation from the eardrum.
end to lower the reading. Some
thermometers must be shaken to lower
the reading. Other types of thermometer (such as the
probe type) are not suitable for taking ear readings and
ƒ Don't bundle the baby or child up too must never be placed within the ear canal. Some ear
tightly before taking the temperature. thermometers are adjustable so they can be made
suitable for adults or children.
ƒ Never leave the child alone while taking
his or her temperature.
ƒ To get a reliable temperature measurement
ƒ Be sure to use the right thermometer. from the ear, the thermometer must be used
Rectal thermometers are thicker than exactly as directed.
oral thermometers.

ƒ While taking the child's temperature ƒ Read the instructions carefully before you
rectally, coat the tip of the start.
thermometer with petroleum jelly ie
vaseline) and insert it half an inch into ƒ Especially with small children, ear
the rectum. Hold the thermometer still thermometers require a steady hand to find
for 2 minutes. Never let go off the the right spot.

ƒ While taking the child’s temperature ƒ The ear canal has a natural curve, so to
orally, place the end of the ensure that the thermometer is pointing
thermometer under the tongue and towards the eardrum it may be necessary to
leave it there for 2 minutes. Don't let pull the top part of the child's ear gently
the child bite on the thermometer. It upwards during the reading.
may injure his mouth or release the
toxic mercury into his the GIT.
ƒ If the child has been lying with his head on a
ƒ After using the thermometer, wash it in warm pillow, or has just come inside out of
cool, soapy the cold, you will need to wait 10 to 15
minutes before the ear can provide an
accurate measurement of body temperature.
We can take reading:
♦ From the child’s mouth
Under the armreadings from the
♦ In the ear

armpit are not very reliable and are about Short duration fevers
0.5ºC lower than mouth temperature. Most cases of short duration
Thermometer strips that are placed on fevers (less than two weeks) are because

Indian J for Practising Doctor; Vol I; No. 4

of infections due to viruses, bacteria, or ♦ Meningitis: Marked irritability with

protozoa. Many of these patients recover photophobia and headache, vomiting
completely even before a precise and neck stiffness should arouse the
diagnosis is made or treatment is given. suspicion of meningo-encephalitis.
The child may have neurological
Short duration fevers may be signs, convulsions, apathy, stupor,
present with or without localizing and coma apart from high grade
manifestations. Malaise, headache, fever. The diagnosis needs lumbar
nausea, vomiting and loss of appetite are puncture for the examination of
the nonspecific symptoms associated cerebrospinal fluid. Meningitis and
with most infective fevers in childhood. septicemia in first 4-6 months of life
Some common infections causing short usually have atypical presentation.
duration fevers are considered below: ♦ Exanthematous disorders: Careful
♦ Respiratory system: Common cold, search is required for detection of
pharyngitis, acute otitis media, exanthema or enanthem in all cases
mastoiditis and pneumonia are the of fever.
usual acute respiratory illnesses. ♦ Pyogenic infections: A meticulous
These are often viral in etiology. search should be made for the foci
Significantly, in viral infections a of infection in liver, perinephric and
number of mucosal surfaces are sub-diaphragmatic regions, bones
involved simultaneously or in quick and joints. Long bones should be
succession. In bacterial infections, palpated for any tenderness and even
the inflammatory process is usually X-ray may be sometimes required.
localized; regional lymph nodes are ♦ Malaria: It should always be
often involved. The rate of spread of considered in the differential
infection is slower in bacterial diagnosis of any short term-fever in
infections. Throat should always be endemic area. Although fever in
examined to exclude follicular malaria is classically intermittent
tonsillitis and diphtheria; other and relapsing, it may present in an
important area to be examined is ear, atypical manner especially in
where acute suppurative otitis media children in endemic areas.
is a common cause of fever among ♦ Typhoid fever: Typhoid fever is
children. endemic in most tropical and
♦ Urinary tract infection: Infections subtropical countries with poor
of urinary tract are equally common standards of sanitation and personal
in infancy among both sexes. After hygiene. Classical picture of enteric
infancy, girls are more prone to fever may not be present in some
develop such infections. Signs & cases. Mild splenomegaly may be
symptoms may, however, be present.
minimal or absent. The fever may be ♦ Other cause: Heat hyperpyrexia,
high and intermittent, at times dehydration, fever, allergy to drugs
associated with chills. Urine (drug fever), thrombo-embolic
analysis should be done for the phenomena and hemolytic crisis are
diagnosis of unexplained fever other less common causes of short-
especially in girls. term fever among children

Indian J for Practising Doctor; Vol I; No. 4

♦ Heat hyperpyrexia: This is not an 1 Infections

unusual cause of fever in tropical 2 Connective tissue disorders e.g.
rheumatoid arthritis and systemic
countries where ambient lupus erythematosus etc.
temperatures may go as high as 3 Neoplastic disorders e.g. lymphoma,
45°C. Heat hyperpyrexia may occur Hodgkin disease, leukemia etc.
even without direct exposure of the Less common causes
child to sunlight. The predisposing 1 Immune deficiency disorders
2 Hematological disorders e.g.
factors include high temperature and spherocytosis, agranulocytosis, and
humidity in the environment, hemolytic anemia.
unsuitable clothing, dehydration, 3 Neurological disorders e.g. familial
and debilitating illnesses as malaria, dysautonomia, hypothalamic and
third ventricular lesions.
pneumonia, measles and renal
4 Genetic disorders e.g. anhidrotic
disorders. Invariably heat ectodermal dysplasia.
hyperpyrexia is associated with 5 Miscellaneous causes e.g. drug
cessation of sweating. The onset of fever, periodic fever.
high fever may be sudden. The 6 Metabolic e.g. thyrotoxicosis,
diabetes insipidus.
rectal temperatures may exceed 42-
43°C. The skin appears dry and hot
(without sweating); tachycardia and A verbal child may complain of
tachypnea are present. Loss of feeling hot or cold, body aches, headache,
consciousness occurs early. The or have difficulty sleeping or sleep more
patient may develop peripheral
circulatory failure and hemorrhages.
Headache, faintness, abdominal Evaluation of fevers
discomfort and delirium are usually
Before starting to investigate it is
present. The liver and kidney failure
essential to document fever and observe the
may complicate heat hyperpyrexia. type of fever. The onset, type and character
of fever and the course of illness should be
Prolonged fever (more than two weeks) clinically evaluated to arrive at possible
Long duration of fever among diagnosis. In general, a single isolated fever
children is a difficult diagnostic problem spike is not associated with an infectious
and requires utmost clinical judgment disease (in infusion of blood & blood
and skill. Some causes of prolonged products, some drugs, some procedures, and
fever among children are given below: other manipulations); temperature in excess
of 41ºC are most often associated with a non
infectious cause. ( e.g. central fever resulting
Symptoms of Fever in Children from central nervous system dysfunction
involving hypothalamus, malignant
Signs and symptoms of fever may hyperthermia, malignant neuroleptic
be obvious or subtle. The younger the syndrome, drug fever, or heat stroke.)
child, the more subtle the symptoms are. Temperatures that are lower than normal
(<36ºC) can be associated with
The infant may be irritable, fussy, overwhelming sepsis but are more
lethargic, quiet, feel warm or hot, not feed
commonly related to cold exposure,
normally, cry, breathe rapidly, or exhibits
changes in sleeping or eating habits. hypothyroidism, or overuse of antipyretics.
Fever with chills and rigors suggest malaria,
Common causes of the prolonged fever. urinary tract infection, and abscess or
Relatively common causes nosocomial infection. Hodgkin disease has

Indian J for Practising Doctor; Vol I; No. 4

typical Pel-Ebstein type of fever (3-10 days Fever is a common manifestation

cycle of febrile and afebrile periods). of infectious disease but is not predictive
of severity. Viral fevers are usually
benign in normal hosts and respond well
Intermittent fever is an exaggerated to the supportive therapy. Other
circadian rhythm that includes a period of infections like; sepsis, meningitis,
normal temperatures on most days; pneumonia, osteoarthritis, pyelonephritis
extremely wide fluctuations may be termed if untreated may have significant
septic or hectic fever. Sustained fever is morbidity and mortality.
persistent and does not vary by more than
0.5ºC per 24 hours. Remittent fever is Fever without localizing signs or
persistent and varies by more than 0.5ºc symptoms usually of acute onset and
/24hr. Relapsing fever is characterized by present for less than one week is a
febrile periods that are separated by intervals common diagnostic dilemma. Young
of normal temperature; tertian fever occurs
infants demonstrate limited signs of
on the 1st and 3rd days (e.g. vivax malaria).
And Quartan fever occurs on 1st and 4th
infection, often making it difficult to
days (e.g. in plasmodium malaria). A distinguish clinically between serious
biphasic fever indicates a single illness with bacterial infections and self limiting viral
two distinctive periods of fever over one or illness.
more weeks (camel back fever pattern e.g. in
poliomyelitis, Leptospirosis, dengue fever, Infants younger than 3 months
yellow fever, tick fever, African
hemorrhagic fevers). Periodic fever is used An infectious agent usually viral
narrowly to describe fever syndromes with a is identified in 70% of infants younger
regular periodicity (e. g. cyclic neutropenia, than 3 months of age with fever. The
periodic fever, apthous stomatitis, etc.) remainder has usually undiagnosed self
limited viral infection. However fever in
The relationship between the an infant younger than 3 mo of age
patient’s pulse rate and temperature can be should be taken in the category of
informative. Relative tachycardia, when
serious illness like bacteremia. Serious
pulse rate is elevated out of proportion to the
temperature, is usually due to non-infectious
bacterial infections are present in 10-
causes in which a toxin is released to cause 15% of previously healthy term infants
the fever. Relative bradycardia presenting with rectal temperatures of
(temperature-pulse dissociation), when the 38ºC or greater. These infections include
pulse rate remains low in the presence of sepsis, meningitis, urinary tract infection,
fever, suggests typhoid fever, brucellosis, enteritis, and osteomyelitis and
Leptospirosis, or drug fever. There can also supparative arthritis. Bacteremia is
be some conduction defects associated with present in 5% of febrile infants younger
the fever. Administration of antimicrobial than 3 mo of age. Organisms responsible
agents can result in very rapid elimination of for bacteremia include B streptococcus
bacteria, if tissue injury has been active, the
and Listeria monocytogens (late onset
inflammatory response and fever can
continue for days after all microbes have
neonatal sepsis and meningitis) and
been eradicated. community acquired pathogens including
Salmonella (enteritis), Eschericia Coli
(Urinary tract infection), Neisseria
meningitides, streptococcus pneumonia,
Fever without focus and Hemophilus influenzae type B (sepsis

Indian J for Practising Doctor; Vol I; No. 4

and meningitis) and staphylococcus antigens present on encapsulated

aureus (osteoarticular infection). bacteria. S. pneumoniae accounts for
Pyelonephritis is more common in 90% of cases of occult bacteremia, with
uncircumcised infant boys, neonates and N. meningitidis and salmonella
infants with urinary tract anomalies, and accounting for most of the remaining
young girls. positive cultures.
Other bacterial diseases in this Common bacterial infections
age group include Otitis media, among children 3-36 mo of age that have
pneumonia, omphalitis, mastitis, and localizing signs include otitis media,
other skin and soft tissue infections. upper respiratory tract infection,
pneumonia, enteritis, urinary tract
Viral pathogens can be identified infection, osteomyelitis and meningitis.
in 40-60% of febrile illnesses younger In this age group, bacteremia is present
than 3 months of age. In contrast to in 11% of febrile children with
bacterial infections which have no pneumonia and 1.5% of febrile children
seasonal pattern, viral diseases have with otitis media or pharyngitis.
definitive seasonal pattern. Respiratory
syncytial virus and viral influenza-A Without treatment occult
virus infections are more common during bacteremia may subside spontaneously
the winters, whereas enterovirus with sequelae, may persist or may lead to
infections usually occur in the summer localized infections, such as meningitis,
and fall. pneumonia, cellulites, or suppurative
The approach to the febrile infant
younger than 3 mo should be on Fever with petechiae: Independent of
emergency lines and the infant need to be age, fever with petechiae, with or
hospitalized. Careful history and physical without, localizing signs indicates high
examination should be done. The child is risk for life-threatening bacterial
treated as sick child and evaluated infections such as bacteremia, sepsis, and
accordingly. meningitis. From 8%-20% of patients
with fever and petechiae have a serious
Children 3 mo -3 years of age. bacterial infection, and 7%-10% have
meningococcal sepsis or meningitis. H.
Approximately 30% of febrile influenzae type B disease can also be
children 3mo-3yrs of age have no present with fever and petechiae. All
localizing signs of infection. Occult such children need to be hospitalized for
bacteremia (bacteremia without an appropriate evaluation.
apparent infection) due to S.
pneumoniae, N. meningitides, and
salmonella occurs in approximately
1.5% of relatively well-appearing Hyperpyrexia (temperature > 41ºC) is
children between 3-36 mo of age with uncommon. Infants and children with
fever. The increased incidence of hyperpyrexia should be carefully
bacteremia among young children may evaluated as for all children withy fever.
be due to maturational immune
deficiency in the production of opsonic
IgG antibodies to the polysaccharide

Indian J for Practising Doctor; Vol I; No. 4

Treatment: dyspepsia, GI bleed, reduced renal blood

flow, and rarely aseptic meningitis, or
Fever and infection in children aplastic anemia.
are not synonymous; antimicrobial
agents should, therefore, not be used as Tepid sponge bathing in
antipyretics and empirical trails of lukewarm water (not alcohol) is another
medication should be avoided. recommended method for lowering the
Hospitalization may be required for temperatures in children because of
radiographic and laboratory studies that infection or heat stroke.
are un-available or impractical in an
ambulatory setting. After a complete _________________________________
evaluation antipyretics may be indicated
to control fever and latter on appropriate
antimicrobial therapy may be given to
the child when the evaluation has been The pathogens causing human
completed. disease have adapted to thrive optimally
at 37°C ie the normal body temperature.
Fever with temperatures less than Fever is body’s response to all
39º C in healthy children usually does microorganisms which aim to enter the
not require treatment. As temperatures body’s natural incubator to thrive and
become higher, patients tend to become multiply. Our body, in its own fight,
more uncomfortable and administration aims to deprive the microorganisms of
of antipyretics often makes the patient the optimal temperature by raising its
feel better. Other than providing temperature above the normal.
symptomatic relief antipyretics do not
change the course of the infectious Thus, it is not prudent to lower
disease. Hyperpyrexia (>41º C) indicates the body’s raised temperature just for the
greater risk of sever infection, sake of bringing it down. Body may be
hypothalamic disorders, or CNS helped to dissipate heat by evaporation
hemorrhage, and should always be by lukewarm sponging or bath.
treated with antipyretics. Antipyretics, which reduce body’s
temperature, should be employed only
Aspirin, acetaminophen and when the child is very restless, the
ibuprofen are inhibitors of hypothalamic temperature exceeds 104°F, or when
cyclo-oxigenase, thus inhibiting PGE2 there is previous history of febrile
synthesis. These all drugs are equally convulsions in the child.
effective antipyretics. Aspirin has been
associated with Reye syndrome in Practitioners should desist from
children and adolescents, its use is not prescribing antipyretics when the patient
recommended for the treatment of fever. is comfortable.
Acetaminophen 10-15 mg/kg orally When prescribed therapeutic dose
every 4 hours is not associated with should be given at the required intervals,
significant adverse affects, however for example 325 mg (or 650 mg)
prolonged use may be associated with paracetamol at 4 hourly intervals, or 200
renal injury and massive overdose may mg (400 mg) ibuprofen 6-8 hourly. (Ed)
be hepatotoxic. Ibuprofen, 5-10 mg /kg
orally every 6-8 hours may cause

Parent Education
(For the parent of a febrile child)

Tips on giving medicine

• Don't give more than 5 doses in 1 day.

• Don't give a baby younger than 4 months old medicine unless doctor tells to do so.

• Read labels carefully. Make sure you are giving the child, right amount of medicine.

• If using drops, fill the dropper to the line.

• For liquid elixir, use a liquid measuring device to make sure to give the right dose.

Other ways to help the child feel better

• Give the child plenty to drink to prevent dehydration (not enough fluid in the body) and
help the body cool itself.

• Keep the child still and quiet.

• Keep the room temperature at about 70°F to 74°F.

• Dress the child in light cotton pajamas so that body heat can escape.

• If the child is chilled, put on an extra blanket but remove it when the chills stop

Bath helps to lower child's fever

Used together, acetaminophen and a lukewarm bath may help lower a fever. Give
the acetaminophen before the bath. If the bath is given alone, the child may start
shivering as his or her body tries to raise its temperature again. This may make child feel
worse. Don't use alcohol or cold water for baths.

Need for consultation

If the child has any of the warning signs listed in the box below,
Under 1 month old. If the baby's temperature goes over 100.5°F rectally, even if he or she
doesn't seem sick, such babies need evaluation. Babies this young can get very sick very

One to 3 months old. If the baby has a temperature of 100.5°F (even if the baby doesn't
seem sick) or a temperature of 99.5°F that has lasted more than 24 hours.

Three months and older. If the child has a fever of 101.4°F, watch how he or she acts. If
the fever rises or lasts for more than 3 days & the children 3 months to 2 years of age, if
the temperature is 102°F, the child may seem to feel fine.
• The young child is less than 3 months
Need of consultation: if the child old, who runs a high fever.
has any of these warning signs
• Changes in behavior • The child cries and cries, without being
able to comfort them, and doesn't wake
• Constant vomiting or diarrhea up easily.

• Dry mouth • The child has a temperature over 38ºC

(101.3ºF) for more than three days.
• Earache or pulling at ears

• Fever comes and goes over several days • The child has just had an operation.

• High-pitched crying
• The child doesn't seem to be getting
• Irritable better.

• Not hungry If the child experiences any of the following

symptoms with a fever, they should be evaluated;
• Pale
• Stiff neck.
• Seizures

• Severe headache • Affected by bright light.

• Skin rash
• Hallucinations.
• Sore or swollen joints
• Red rash or blue/purple dots or patches.
• Sore throat

• Stiff neck • Trouble breathing.

• Stomach pain
• Cramps.
• Swelling of the soft spot on the head
• Continued vomiting or diarrhea.
• Unresponsive or limp

• Wheezing or problems breathing • Continued tonsillitis.

• Whimpering
• Pain when urinating, or urinating more
Critical fever than usual.

Look at the child and see • Other illnesses.

♦ Whether they look exhausted or ill? The Indian Journal of Practising Doctor is
distributed to all hospitals of the Kashmir
♦ Are they behaving differently? Province. Individuals can get their copies against
a payment of Rs 150/- per copy. However, the
undergraduate medical students may get a
♦ If the answer is yes, evaluation is necessary. subsidized subscription at the discretion of the
Indian J for Practising Doctor; Vol I; No. 4

Rheumatic Fever about infectious diseases, lack of

awareness about need for getting mild
infections like sore throat being getting
Shabnam Bashir treated, or non-availability of medical
_______________________________ facilities.
Cardiovascular diseases are very Of 12 million people currently
important cause of morbidity and affected by rheumatic fever and
mortality across the world. In the year rheumatic heart disease, 2/3rd are
2002, these diseases accounted for 16.7 children between 5 and 15 years of age.
million deaths globally. There are around 3 lakh deaths each
year, with 2 million people requiring
Rheumatic fever is one of the repeated hospitalization and one million
cardiovascular diseases especially likely to require surgery in the next 5 to
common in the developing world. It 20 years.
usually follows an untreated beta-
hemolytic streptococcal throat infection India, Pakistan, Bangladesh, China, &
in children. It can affect many parts of Indonesia top the list with the highest
the body, and may result in rheumatic number of deaths from rheumatic fever
heart disease, in which the valves are & rheumatic heart disease. Ignorance
permanently damaged, and which may about rheumatic fever & rheumatic heart
progress to heart failure, atrial fibrillation disease is widespread in these countries.
and embolic stroke.
Early treatment of streptococcal
No of cases in 5-14 yr olds (reported in
sore throat can preclude the development
of rheumatic fever. Regular long-term
S.No Region No of penicillin treatment can prevent
deaths rheumatic fever becoming rheumatic
1 Sub-Saharan Africa 1,008,207 heart disease, and can halt disease
2 South-Central Asia 7,34,786 progression in people whose heart valves
3 China 1,76,576 are already damaged by the disease. If
4 Eastern Mediterranean 1,53,679 treated 75% of people with rheumatic
& North Africa fever recover completely. In many
5 Latin America 1,36,971 developing countries, lack of awareness
6 Other parts of Asia 1,01,822 of these measures, coupled with shortage
7 Eastern Europe 40,366 of money and resources, are important
8 Pacific 7,744 barriers to the control of the disease.
9 Developed countries 33,330

Nowadays, rheumatic fever

mostly affects children in developing
countries, especially where poverty is
widespread. Up to 1% of all school
children in Africa, Asia, the Eastern
Mediterranean region and Latin America
show signs of disease. This has to do
with overcrowding, lack of awareness

Indian J for Practising Doctor; Vol I; No. 4

Patient Education: may still be present, bed rest, and

Rheumatic Fever administration of salicylates or
corticosteroids. It may take many weeks
or months before the attack runs its
____________________ course. Rheumatic fever has become
relatively rare, probably due at least in
Rheumatic Fever, once common part to the widespread use of antibiotics.
acute inflammatory disease,
characterized by fever and pain,
tenderness, redness, and swelling of the Endocarditis implies infection
and inflammation of the membrane
joints. Rheumatic fever can cause
lining the inner surface of the heart,
inflammation of the heart and damage to including the heart valves. The two
the heart valves (endocarditis). First major forms of the disease are the acute
attacks usually occur from the age of 7 to type, which appears suddenly and can be
12 or 14; recurrent attacks can occur fatal within a few days, and the subacute
throughout adult life. The mortality from type, which develops slowly and may
the acute attack is low, and most cases cause death within months.
subside spontaneously. Often, however,
inflammation of the heart leads to Subacute bacterial endocarditis
scarring and deformity, causing the usually results in fever, toxaemia, and
valves to malfunction. This strain on the lesions of the heart valves; particles
dislodged from these lesions often cause
heart muscle causes rheumatic heart
embolism. Infection of the heart valves
disease, which can cause death in middle
and lining, or endocardium, may come
or later life. from primary infections of the teeth,
tonsils, and sinuses. The disease is
Acute rheumatic fever is a
characterized by the formation of
complication of streptococcal infection,
bacterial or fungal growths on the valves
such as strep throat, scarlet fever, or and endocardium. It has its greatest
erysipelas. It sometimes develops after incidence in people between the ages of
infections so mild as to pass unnoticed. 30 and 50 years. Antibiotic therapy,
Rheumatic fever begins either when used in large doses for extended
insidiously or abruptly after a latent periods, is effective in curing the
period of two to six weeks following the bacterial infection of subacute bacterial
streptococcal infection. Aside from endocarditis, but damage done to the
fever, malaise, and migratory arthritis, heart by the bacteria cannot be repaired.
patients may develop nodules under the Routine use of penicillin and other
skin, skin rashes, abdominal pain, antibiotics during dental surgery and to
treat primary bacterial infections has
pleurisy, and chorea. The most serious
decreased the incidence of endocarditis.
aspect of the disease, however, is the
involvement of the heart.

Treatment involves the use of

penicillin to eradicate streptococci that

Indian J for Practising Doctor; Vol I; No. 4

Management of Rheumatic Fever • A shorter latency period

• Currently recommended therapies
Treatment of patients with acute for Group A beta-haemolytic
rheumatic fever is geberally directed streptococci pharyngitis have
toward decreasing acute inflammation, becomes inadequate for
decreasing fever & toxicity, controlling prevention of acute rheumatic
cardiac failure, preventing episodes of fever. This is the biggest worry
acute rheumatic fever after significant currently.
streptococcal upper respiratory tract
infections, and preventing rheumatic Approximately 1/3rd of patients
heart disease. who develop acute rheumatic fever have
streptrococcal infections which are either
The mainstay of treatment are subclinical or too mild to be brought to
salicylates and corticosteroids. However, medical attention. As a result they
neither of these drugs can prevent or receive no antimicrobial therapy for their
modify the development of rheumatic infection. Recent studies show that up to
heart disease. Patients clinically 75% of patients with acute rheumatic
diagnosed with acute rheumatic fever fever either have no history of a
who have not received antibiotic therapy preceding streptococcal infection or have
for a recent episode of Group A-beta an infection that was so mild they did not
hemolytic streptococci pharyngitis seek medical treatment. This fact
should receive a 10-day course of complicates prevention of acute
penicuillin. rheumatic fever

Primary prevention of acute Patients who develop acute

rheumatic fever depends on accurate rheumatic fever require continuous
diagnosis of a antecedent streptococcal prophylaxis to prevent intercurrent and
infection as well as adequate therapy. recurrent streptococcal infections and
Penicillin given orally for 10 days or recurrent episodes of acute rheumatic
intramusclularly one time has been fever. The preferred regimen consists of
shown effective in prevention of pencillin G benzathine (1.2 million units,
rheumatic fever. In penicillin-allergic IM every 4 weeks). The recurrence rate
patients, although erythromycin is with this regimen is reported to be 0.4
considered the drug of choice, it has not cases/100 patient yearsof observation.
been shown to prevent acute rheumatic
fever. Alternative therapies include oral
penicillin (250 mg, twice a day) or oral
Then there are patients who may sulfadiazine. Both these regimens are
develop acute rheumatic fever despite considered less effective than
receiving adequate therapy for Group A intramuscular benzathine penicillin,
beta-hemolytic streptococci pharyngitis. primarily because of non-compliance by
Various reasons for this ominous patients. Patients who are allergic to
situation could be: penicillin can be can be treated with
erythromycin (250 mg twice daily).
• Poor patient compliance (this is a
problem with both oral &
injectable penicillin)

Indian J for Practising Doctor; Vol I; No. 4

Duration of prophylaxis is Further Reading:

controversial. Previously investigators
recommended lifelong prophylaxis. Bisno AL. streptococcus pyogenes. In:
However, fortunately, the risk of Mandell, Bennett, Ed. Principles & practice
recurrences of acute rheumatic fever of infectious diseases. 4th ed, New York:
Churchill Livingstone, 1995; 1786-1810.
decreases with patient’s age and the
number of years since the last attack. In Congeni BL. The resurgence of acute
general, it is recommended that rheumatic fever in the United States. Pediatr
prophylaxis continue until patients are in Ann 1992; 21:816-20
their early twenties and at least 5 years
have passed since the most recent Dajani AS. Current status of non-suppurative
episode of acute rheumatic fever. complications of group A streptococci.
Pediatr Infec Dis J 1991; 10:S25-7
The American Heart Association
Committee on Rheumatic Fever & Dajani A, Taubert K (Committee on
Rheumatic fever, endocarditis, and Kawasaki
Endocarditis recommends that patients
disease). Treatment of acute streptococcal
who have rheumatic fever without pharyngitis and prevention of rheumatic
carditis should receive prophylaxis until fever: a statement for health professionals.
the age of 21 or until at least 5 years Pediatrics 1995;96:758-64.
have passed since their last attack.
Denny FW, Wannmaker LW, Brink WR.
Patients who had rheumatic fever with Prevention of rheumatic fever. Treatment of
carditis but no valvular disease should preceding streptococcal infection. J Am Med
receive prophylaxis until adulthood and assoc 1950;143:151-53
until at least 10 years have passed since
their last attack of acute rheumatic fever. Mackay J & Mensah GA. Rheumatic fever
and rheumatic heart disease. In: The Atlas of
Heart Disease & Stroke. World Health
Patients with valvular disease should Organization & Centre for Disease Control
receive prophylaxis until age 40 and until & Prevention, Georgia; 2004; pg 20-21
at least 10 years had passed since their
last attack. Gerber MA, Markowitz M. Streptococcal
pharyngitis: clearing up the controversies.
Contemp Pedriat 1992:118-31
Patients with residual valvular
Klein JO. Management of streptococcal
rheumatic disease must receive antibiotic
pharyngitis. Pediat Infec Dis J; 1994;13:572-
prophylaxis whenever they undergo a 73
surgical or dental procedure, thart may
have a potential of evoking bactermia. Pitetti RD, Stevens DP. Streptococcus
This is necessary to prevent occurrence pyogenes. In: Yu VL, Merigan TC, Barrier
of bacterial endocarditis. SL. Antimicrobial therapy & vaccines.1999;
Williams & Wilkins; pg 448-9
Shulmann ST. Evaluation of penicilins,
cephalosporins, and macrolides for therapy
of streptococcal pharyngitis. Pediatrics 1996;

Indian J for Practising Doctor; Vol I; No. 4

16th century. By 1619, Holland was trading

in tea with its European neighbours,
including Scandinavia and Britain. The first
British ships did not reach China until 1637.
By 1644 the British established themselves in
Amoy port, which became their principal
base in China for about a century. European
contact, through the British & Dutch East
India companies made tea an essential world
Neelam Bashir commodity.
_______________________________ In 1657 the first recorded sale of tea
in England appeared when Thomas Garway,
Tea, which is culturally and tobacconist and coffee-shopkeeper, served
economically the most significant non- and sold tea in Garraways Coffee House,
alcoholic beverage of the world, is a Exchange Alley, London. Other coffee
drink from the buds & leaves of the houses were quick to follow suit. Tea-
drinking in the coffee houses, the forerunner
Camellia sinensis plant.
of the gentlemen’s clubs, became the vogue.
In 1662 the Portuguese Infanta, Catherine of
Braganza, arrived in England to marry
I HISTORY Charles II. Chests of tea formed part of her
dowry and it was she who introduced tea-
Tea-drinking is first said to have
drinking “in the home”.
been recorded in China, c. 2737 BC, when the
Chinese emperor Shen Nung, while touring In the 17th century tea was
his empire, sat beneath a tree and ordered expensive, partly because it was still a
his servant to boil some water for drinking. relatively rare commodity, but mainly
A leaf from the tree fell into the water, and because of the imposition of duties and taxes
Shen Nung tried the brew and liked it. The on tea and other beverages. In 1773 the East
tree was the Camellia sinensis, now known as India Company gained the monopoly for
the tea plant. By the time of the Tang British trading with China as well as India,
Dynasty (618-907) tea was China’s national plus the import rights in the colonies. For
drink. Buddhist monks are reputed to have most of the 18th century the high cost of tea
spread the tea-drinking habit throughout the in Britain led to smuggling, adulteration of
Orient. They cultivated tea gardens in the tea leaves, and a thriving black market. By
grounds of monasteries and Chinese royal 1834 the reduction in the tax on tea and the
palaces. In the 8th century BC, they took tea end of the East India Company’s monopoly
to Japan, pioneering tea cultivation there and opened the way to free trade, and the
developing the Japanese tea ceremony. The foundations of Britain’s shipbuilding
Persian merchant Hajji Muhammad brought industry were laid with the advent of the tea
the first knowledge of tea to Europe. He told clipper. Tea, now much more accessibly
the Venetian author Giambattista Ramusio priced, replaced ale and gin as the drink of
of his travels in Cathay (China) and how tea the masses. More crockery and pottery were
was made and drunk by the locals, and also needed to cope with the demand for tea-
those in Persia and the country of the drinking, helping the growth of the British
Franks. Jesuit missionaries, travelling on the pottery industry.
Portuguese ships that pioneered the sea
routes to the Orient in the 16th century,
initially brought the tea-drinking habit back
to Europe. Dutch sailors opened up their
own trade routes with the Orient in the late

Indian J for Practising Doctor; Vol I; No. 4

CHARACTERISTICS OF THE Teas belong to the family Theaceae of

II FAMILY the order Theales. The genus to which
The tea family, with 250 tea belongs is Camellia. The tea plant is
species placed in 20 genera, is primarily classified as Camellia sinensis.
tropical and subtropical in distribution,
centred in south-eastern Asia, with few
temperate members. Most members are Tea varies in flavour and
evergreen trees with broad, simple, resin- characteristics according to the type of soil,
containing leaves, although a few climbers altitude, and climatic conditions of the area
and herbs occur. The flowers usually have in which it is grown. Processing methods
four or five free, or unfused, sepals (outer also affect the flavour and characteristics, as
floral whorls) and four or five petals (inner does the blending of different teas from
floral whorls) and are radially symmetrical. different areas.
The numerous stamens (male floral organs)
are fused either into a ring, as in the plants Today, tea is grown on small-
of the Camellia or tea genus, or into distinct holdings or estates. In smallholding tea
bundles. When the stamens are united into a areas, cooperatives are formed to build a tea-
ring, the petals are often joined to the ring, as processing factory central to a group of
in the plants of the tea genus. The ovary smallholders. The larger tea estate is a self-
(female floral organ) is superior—that is, the contained unit, often covering hundreds of
sepals, petals, and stamens are produced hectares, housing its own factory, tea-
from its base. growing area, and even staff houses.

Under modern cultivation the tea

bushes are maintained at waist height for
III THE TEA PLANT ease of plucking, and are grown from
The plant Camellia sinensis is cuttings or clones, which are carefully
considered the most important plant in the nurtured in nursery beds, and trained to
Camellia genus, particularly from a grow in a fan-shape until ready for planting
commercial point of view. It is indigenous to out. Young bushes are planted about 5 ft
both China (Camellia sinensis sinensis) and apart in rows approximately 3 ft apart. This
India (Camellia sinensis assamica), hence the allows easy access to the bushes for both
use of the tea trade terms “China jat” or pluckers and gardeners. In the higher
“Indian jat” to distinguish the origin of the altitudes these rows follow the contours of
original tea bushes on some of the older tea the hills or mountainsides to avoid soil
estates. Today, these two jats are considered erosion. On some of the higher estates and
the main varieties, of which there are many smallholdings terraces are built, again to
hybrids. In its wild state, the tea plant grows avoid soil erosion.
as a tree, reaching some 98 ft in height.
While coming to maturity, the
Cultivated tea is grown as a bush, about 3 ft
shape-training of tea plants continues, so
high, with continuous vegetative growth.
that after three to five years, the mature
Leaves of the tea bush are, generally,
bushes have a flat top, known as a plucking
serrated, shiny, and pointed. The China jat,
plateau. Before the first plucking, the bushes
classed as an erectophile (leaf angle less than
are severely pruned, known as “lung”
50 degrees), has a small leaf that is normally
pruning. The mature tea bushes are plucked
darker in colour than the larger, broader,
mostly by hand every 7 to 14 days. Altitude
and lighter green leaf of the Indian jat,
and climatic conditions of the growing
classed as a planophile (leaf angle less than
region are the two deciding factors with
70 degrees).
regard to this regrowth period. A tea plant
grown at sea level will replace itself more

Indian J for Practising Doctor; Vol I; No. 4

quickly than one grown at a higher altitude, into further categories as the leaf particles
where the air is often cooler. Only the top decline in size. Fannings and dust grades are
‘two leaves and a bud’ are plucked from the the two smallest particles. Other terms are
sprigs on the plucking plateau. Yields range used to describe the colour and content of
from 700 to 1800 kg per acre. the black tea leaf.

1. Black tea dominates the international

market. Grades of black tea conform to
Some 30-35 kg of plucked leaf guidelines that emerged from the British tea
makes some 7.5-9 kg of black tea, which industry in 19th-century India & Ceylon
(now Sri Lanka). Whole leaves produce the
is the type of tea that has the major share
best flavour and are classified by the size
of the market in terms of production, and the ways in which they are rolled.
sales, and consumption. Leaves that have been broken conform to
some of these qualities; the small pieces of
There are five stages in the tea- leaves (debris from the processing of whole
making process. Withering is the first & broken leaves) are called ‘dust’ and even
stage, in which the plucked leaf is spread smaller ones are termed ‘fannings’. These go
on vast trays or racks, and left to wither into teabags & brick tea. Black teas from
in air temperatures of 25-30° C for a India are collectively called Darjeeling teas.
period of 10-16 hours, depending on the Keemum is a black tea from northern China.
wetness of the leaf. As the leaf moisture Lapsang Souchongs is a large-leafed black
tea scented with pinewood smoke.
evaporates the leaves become flaccid. In
the next stage, the withered leaf is 2. Green tea: The teas drunk in China &
broken by machine, releasing the natural Japan are mostly green. In its preparation
leaf juices. During the fermentation fermentation stage is excluded, and the
stage, the broken leaf is spread on trays enzymes are destroyed by steam or pan
or put in troughs. On contact with the air, heating before the leaves are rolled and
the released enzymes (from the leaf fired. In North Africa, too, green tea is
juices) oxidize. The leaf is turned from preferred. Since the classic word
‘fermentation’ customarily applied to the
time to time until each tray or trough is
oxidation process is correlated with the
full of a rusty-brown coloured leaf. formation of alcohol, it was misunderstood
Drying, often called firing, is the next by Muslims and thus this stage of tea
stage. The fermented leaf is fed slowly preparation in Muslim countries was
through a warm air chamber, which omitted. The size of the leaves determines
extracts the moisture, emerging as a dark the grade of a green tea. Gunpowder, a
brown dried leaf, known as black tea. green tea, consists of the tight, small
During the final stage, known as sorting, balls of younger leaves. It is withered
the black tea is fed into a machine fitted then dried, steamed, rolled, and further
with a series of sieves and outlets. This dried, so that when brewed in hot water
sorts the grades into chests before its the complete leaf often unfurls.
onward journey to auctions, traders, or
blenders. In China, tea is sometimes 3. Oolong tea, semi-fermented, stands
between green & black tea; although it is
allowed to absorb the scent from various
fermented, this is done only for 30 minutes
flowers; jasmine is a particular favourite. after rolling. For other teas, it lasts for 1-2
There are two main grades—pekoe hours. Oolongs generally come from
and broken pekoe. Each grade is subdivided Taiwan.

Indian J for Practising Doctor; Vol I; No. 4

Before the tea is shipped, factory tea can be plucked throughout the year.
tea-tasters sample the finished make to The western and eastern sides of the
ensure no mistakes have been made island are divided roughly by the central
during manufacture. These tasters also mountain system, and because of the
send samples of the make to their natural climatic conditions of the region,
brokers, agents, and buyers. At the end the western side’s plucking season
of each make the factory is washed alternates with that of the eastern side.
thoroughly to ensure that the completed Ceylon teas span the complete spectrum
make does not contaminate the next. of low, medium, and high-grown teas,
which are drunk as speciality teas and
used for blending purposes.
Today’s major tea producers are
India, China, Sri Lanka, Indonesia, Although tea was widely used in
Kenya, Malawi, Zimbabwe, Papua New neighbouring China, it had not spread to
Guinea, Bangladesh, Mauritius, the India till European colonization. The
Democratic Republic of the Congo, and preferred beverages of India, instead,
Cameroon. Tea is also grown in South were milk & buttermilk. The first
America, Japan, Australasia, Eastern account of tea being eaten and drunk was
Europe, and the Middle and Far East, but given by a Dutch seafarer as late as 1598.
mainly for domestic consumption. Some Tea cultivation was begun by the British
teas are seasonal, others are not, in the 19th Century.
depending on the altitude, proximity to
India, a major tea producer, with
the equator, and climatic conditions of
more than 400,000 hectares under tea
the producer region. Yield per hectare
cultivation, produces approximately 30
also depends on these factors, plus good
per cent of the world’s tea, and accounts
husbandry by the producer. The harvest
for 14 per cent of the world tea exports.
weight of plucked leaves from an estate
Indian teas are seasonal, with plucking
in East Africa or Assam can fluctuate
undertaken from March through to
between 1,600 and 6,000 kg per hectare,
October. They range from the low-grown
but is less in high-grown regions, such as
indigenous Assam, discovered around
Darjeeling (700 kg). Tea plays an
1832 by the Bruce Brothers, to the high-
important role in the producer countries’
grown teas of Darjeeling, which were
economies as a foreign-exchange earner.
originally planted from seeds and
Sri Lanka is the world’s largest seedlings imported from China.
tea exporter, accounting for 21% of the
India is currently the leading producer of tea in
world tea exports. Teas from Sri Lanka the world with a yield of 715,000 tons annually.
retain the country’s old name “Ceylon”. However, since Indians average half a cup daily
Scotsman James Taylor is reputed to on a per capita basis, 70% of the produce is
have planted the first tea estate at consumed locally. Tea in India is generally spiced
Loolecondera in Kandy, and today is & served with milk. As a cup of tea with sugar &
known as the “father of tea” by the milk may contain up to 40 calories, this is also a
islanders. Ceylon teas have been arriving source of quick energy. In India, a skilled worker
for sale in the London auction since using hand shears harvests between 60-100 kg of
1876. Today, Sri Lanka has more than tea per day; the machine can raise the yield to
200,000 hectares under tea cultivation, 1000-2000kg but is used for low-grade teas
meant for teabags.
and, because of its geographical position,

Indian J for Practising Doctor; Vol I; No. 4

China is the second largest tea Over the millennia tea has maintained a
producer and exporter after India and Sri reputation for contributing to good health.
Buddhist monks in China & Japan who were
Lanka respectively. It retains the physicians used tea to help people through
majority of its tea produce for home illnesses. Even today tea is employed in ancillary
consumption, exporting about a quarter therapy for individuals who suffer from various
of its annual tea yield, which accounts infections, colds or chronic diseases. Tea is a
for 18 per cent of the world tea exports. diuyretic and produces both warmth (if it is
served hot) and coolness (because it promotes
In the United Kingdom tea accounts evaporation of water from the skin) in the body.
Moreover, steam of hot tea moisturizes the nose,
for about 42 per cent of the total drinks
mouth and throat. The caffeine in tea is also a
market. There is an average consumption of ‘pick-me-up’.
150,000 tonnes yearly, which is more than
North America and Europe combined. New Caffeine for soft drinks & medicine
Zealand and Australia also consume large is produced from the processed tea ‘fluff’ &
amounts. As a nation, the United Kingdom waste. Caffeine in tea was once called
imports about 16 per cent of the producer ‘theine’, but since it is chemically identical to
countries’ tea exports. caffeine in coffee, the separate term has been
abandoned. Depending on the type of tea, a
Tea is an aromatic stimulant, 150 ml cup may contain 30-50 mg of caffeine,
containing various polyphenols, essential only 1/3rd of that found in a cup of coffee.
oils, and the alkaloids caffeine and
theobromine. The concentration of Because of its origin in the East,
caffeine in tea ranges from 2.5 to 4.5 per maximum research on health benefits of tea has
cent, as contrasted to an average been conducted in the Eastern region. However,
since 1980s, laboratories in the USA & Canada
concentration of about 1.5 per cent in (and a few in Europe) have started showing
coffee. interest in research on relation between tea and
How to make good tea preventive or promotive health. Their findings
were summarized at the First International
Get fine tea (whole or bagged). Arrange
Conference on Tea & Health, held in New York
clean, cold water, that has no taste of its
in 1991. The research suggested that people who
own. For green tea, bring the water to a drink tea regularly have a lessened risk of
simmer; for black or Oolong, it must be at a coronary heart disease. This was also highlighted
rolling boil. Warm the vessel in which the that tea has a beneficial effect in warding off
tea is to be brewed by pouring boiling water cancers of the stomach, esophagus, and lung.
into and out of it, and add about 3 gm of tea New research suggests that the caffeine in tea
per cup to be brewed. Pour boiling water may play a role in such cancer prevention. Black
over the leaves and allow to steep for 3-5 tea & green tea had very similar (if not identical)
minutes, depending on the type of tea. preventive effects, and a few findings showed
Finally remove the leaves or teabags from delayed growth and even regression of cancers in
the vessel and pour the tea, adding sugar (or laboratory animals.
an artificial sweetener), milk, lemon, as
Encouraged by the research findings, the
role of tea in prevention of others diseases and
disorders is being probed all over the world.
Tea & health There are suggestions that the lower risk of lung
In modern times, tea is one of the cancer in Japanese men, who smoke many more
world’s least expensive beverages, and after cigarettes on per capita basis than their American
water is the most commonly used beverage. counterparts, may be attributable to their tea
Because it is made with boiled - & therefore drinking habit.
sterile water - tea is safe to consume in areas
where water quality may be less than satisfactory.

Indian J for Practising Doctor; Vol I; No. 4

The preventive effect of green & black tea is frequently in aging people who are regular
attributable to the presence of specific tea drinkers.
polyphenols that can act as powerful Ceffeine in tea is sufficient to
antioxidants. Research has shown that the account for its pleasant, slightly stimulating
risk of heart disease and many types of effect on mental function, and is the reason
cancer is lowered by the raised antioxidant for tea’s popularity as a morning beverage.
level in the bodies of those who drink tea At the same time the amount is low enough
and , conversely, the conditions promoting to preclude any overdosage.
these diseases involve abnormally low levels
of oxidation. Decaffeinated tea, prepared by solid
CO2 extraction, contains polyphenols but no
Tea polyphenols also modify caffeine. It retains the taste of tea and is
intestinal bacterial flora, leading to a beneficial to those who can’t take caffeine or
decrease in the levels of undesirable bacteria for the ones who want an evening cup
and contributing to the maintenance and without the attendant risk of insomnia.
increase of desirable bacteria. Tea is, in fact, Decaffeination can be done at home: Brew a
is the culture medium for kombucha (the tea- first infusion, discard it, & brew a second
fungus), which is a symbiotic bacterial from the same tea. Caffeine is extracted from
culture used in alternative medicine. Tea can tea in 1-2 minutes, and so a second infusion
have a specific anti-bacterial action and a will have a weaker taste & no caffeine.
limited effect against specific viruses.
Recent results suggest that
Alzheimer’s disease may occur less

Antioxidants prevent cellular damage caused by reactive oxygen species.

Flavonoids – a group of phenolic compounds – are known antioxidants. Approximately
30% of the tea solids in a typical infusion is composed of flavonoids, whereas about 5%
of the water soluble solid extract of tea is formed by flavonols like quercetin,
kaempferol, myricetin, and their glycosides. Catechins are highly potent flavonoids
present in tea and serve as the best dietary source of natural antioxidants. Of these
catechins, epigallocatechin gallate is present maximally in green tea – forms 10% of dry
weight. Methylxanthines, mainly in the form of caffeine, are present in a proportion of
1/3rd of its content. In addition tea contains theanine, an important aminoacid.
Interflavonoid linkages resulting in formation of proanthocyanidines are being studied
at present.
Antioxidants protect the body against the damaging effects of free radicals
generated in the body durng conversion of glucose and fat to energy, exercise, and by
the action of sunlight on skin. Oxidative stress induced by overproduction of reactive
oxygen species disrupts cellular function. They can interact to form reactive molecules.
These reactive molecules can be counteracted by antioxidants like vitamin C, tocopherol,
carotenoids and flavonoids.
Flavonoids found in tea are 20 times more powerful as antioxidants as vitamin C.
Polyphenols have been proven to inihibit lipid hydroperoxide formation. Their
scavenging properties have been demonstrated against many offensive oxidants
including superperoxide radicals, free radicals, and peroxinitrite. They are known
chemopreventors for protection, romotion and progression of various forms of tumour.
In this regard, epigallocatechin gallate with 5 polyphenol moieties is considered the
most potent tea antioxidant.

Indian J for Practising Doctor; Vol I; No. 4

Patient Education

Asthma is a chronic airway age of 10, boys are twice as likely as
disease that involves episodic attacks of girls to have asthma, but by the preteen
breathing difficulty, wheezing, years the numbers even out. By age 20,
coughing, or tightness in the chest. Just as well as throughout the remainder of
what triggers these attacks varies from life, women are about 3 times more
one person to another, but allergies likely than men to be diagnosed with
probably account for the majority of asthma. They are also more likely to be
symptoms in people with susceptible hospitalized for asthma and to die of an
airways. Other influences can include attack.
cold air, respiratory infections (including
colds), smoke and environmental Some of the differences in
pollutants, sudden changes in diagnoses are undoubtedly attributable to
temperature or humidity, and strenuous the greater propensity of women to seek
exercise. Only rarely is asthma attributed medical attention for any condition. The
to emotional or psychological distress, differences may also be related to the
although for many years this was fact that asthma in men is often
considered one of the prime triggers. misdiagnosed as some other respiratory
condition, such as chronic obstructive
During an asthma attack the lung disease or emphysema. Even so,
muscles tighten around the tubes inside there is now some intriguing evidence
and leading to the lungs (the bronchi), that at least some of the explanation for
and the lining of the tubes becomes women’s susceptibility lies in hormonal
swollen and inflamed. Often thick mucus differences. Also, women frequently
accumulates in the airways as well. In all have conditions (such as arthritis,
cases airflow is restricted, and emptying menstrual cramps, and headaches) that
the lungs of air becomes particularly lead them to use aspirin and other anti-
difficult. These attacks can last inflammatory drugs which, in rare cases,
anywhere from several minutes to may trigger asthma attacks. In addition,
several days. Although severely women may be exposed more frequently
restricted airflow can be life-threatening, than men to certain inhaled allergens,
in most cases the attacks are mild or such as the mites that grow in house dust
moderate. In fact, by avoiding triggers and other indoor pollutants. Despite the
and using appropriate medications, most many strides made in sharing household
people with asthma can lead active, duties, a woman allergic to dust mites
healthy lives. still is much more likely to be the one
who does the vacuuming than a man
Asthma has become increasingly with similar susceptibilities.
common in early childhood, affecting as
many as 10 percent of all children, There is no evidence that asthma
probably because of a rise in both attacks become more severe or more
outdoor and indoor pollution. Up to the frequent during pregnancy, but asthma

Indian J for Practising Doctor; Vol I; No. 4

can pose particular problems for a What are the symptoms?

woman expecting a baby. This is
because restricted airflow to the mother The classic symptoms of an
can potentially deprive the fetus of asthma attack are wheezing (noisy
oxygen. During pregnancy many women breathing), coughing (especially at
who do not have asthma notice changes night), tightness in the chest, shortness
in breathing patterns or difficulty of breath, and labored breathing.
breathing because the growing uterus Symptoms may begin upon exposure to
changes the shape of the chest cavity. In the offending trigger or may develop
pregnant women with asthma, these slowly over many hours. Often attacks
body changes can make asthma attacks develop in the middle of the night.
more difficult to control than normal.
Still, most women with asthma can In a severe attack breathing
expect to stay healthy and have healthy becomes rapid and shallow, heartbeat
babies if they continue to take their quickens, and the skin pales or takes on
medications under the supervision of a a bluish cast. It may be necessary to use
clinician who is aware of their accessory neck and abdominal muscles
pregnancy. in order to support breathing. Sometimes
a person with longstanding asthma
Who is likely to develop asthma? becomes barrel-chested as the chest
expands to accommodate enlarged lungs
The susceptibility to asthma -the body’s way of compensating for
appears to be inherited, and people with constricted airways.
allergies are particularly likely to
develop it at some point. Among the How is the condition evaluated?
allergens that trigger attacks in people
with susceptible airways are dust mites, Usually asthma is diagnosed by a
molds, pollens, animal dander, and clinician only after several attacks have
certain foods. As much as 8 percent of occurred. Various tests including
the population is also allergic to food pulmonary function tests can help
additives called sulfites (whitening differentiate asthma from other
agents), and they may experience an respiratory diseases. Once asthma has
almost immediate asthma attack after been diagnosed, the clinician may
eating foods containing these chemicals. suggest seeing an allergist, who can do
Sulfites are often found in dried fruits skin tests to see if there are any
and vegetables, wine, beer, potatoes, identifiable allergens underlying the
dehydrated seafood soups, baking mixes, attacks. The clinician may also suggest
fruit drinks, and certain soft drinks. keeping a diary to help determine if the
attacks can be linked to any particular
Susceptible people exposed to substances or situations.
large amounts of smoke (whether from
cigarettes or wood-burning stoves), How is asthma treated?
gasoline fumes, fresh paint, and other
environmental pollutants may have Active asthma attacks are usually
frequent attacks of asthma. treated with a short-acting
bronchodilator, such as albuterol, which

Indian J for Practising Doctor; Vol I; No. 4

opens the airways by relaxing smooth counter, the condition should be

muscle. Corticosteroid medication in an evaluated by a clinician before these are
inhaler or in oral form, such as tried.
prednisolone or prednisone, reduces
inflammation, which is a key mechanism Most asthma drugs are
of asthma attacks. Because it takes at considered safe for use during
least 6 hours for corticosteroids to take pregnancy. If antibiotics are prescribed
effect even if inhaled, bronchodilators to treat the upper respiratory infections
are used to provide immediate relief of that can trigger asthma, tetracycline or
symptoms. sulfa drugs should be avoided because of
adverse effects on the fetus.
Once the attack is under control, Corticosteroids used in inhaled form are
the physician may prescribe maintenance preferred over oral forms during
medications, such as cromolyn, which pregnancy, since relatively little drug
reduce the chances that the airways will can reach the fetus through this route.
become inflamed. Corticosteroids are But because severe asthma attacks can
usually continued on a maintenance be life-threatening to the pregnant
basis, in the inhalable form; long-term woman and so potentially damaging to
treatment with oral preparations is the fetus, systemic steroids are
avoided if possible because they are considered an appropriate tradeoff for
associated with adverse side effects. pregnant women with severe asthma,
even though their safety for the fetus has
Many asthma medications are not yet been proved or disproved.
available in aerosol form and can be
inhaled into the lungs in specific In the past, people with known
amounts through a device called a allergies received desensitization shots
metered-dose inhaler. The medications to reduce susceptibility to allergens.
are also available as tablets and syrups. Today, however, allergists often
The aerosol inhalers fit inside a purse advocate eliminating or reducing
and should be carried at all times to exposure to the allergen as a first course
stave off emergency attacks. of action, partly because desensitization
Bronchodilators are also available in a shots must be taken quite frequently, are
solution for use in an electric nebulizer, not always effective, and are
which produces a mist that the patient uncomfortable and expensive.
breathes through a hand-held inhaler
attached by tubing to the machine. The Anyone with asthma needs to be
mist may provide added relief at home under the regular care of a clinician. This
during prolonged attacks. is because it often takes a good deal of
Bronchodilators can also be taken trial and error before the right
systemically if necessary. Nose sprays combination of medications and
can help dry up the stuffy or runny nose preventive steps can be determined.
which often accompanies allergic
asthma. How can asthma be prevented?

Although some asthma Although the underlying physical

medications are available over the cause of asthma cannot be prevented,

Indian J for Practising Doctor; Vol I; No. 4

minimizing the frequency of asthma are willing or able to take these steps
attacks boils down to eliminating or (nor do they necessarily help). Perhaps a
reducing exposure to anything known to more practical alternative is to cover the
trigger them. This is not always easy and affected person’s mattress and
is sometimes impossible, in which case pillowcase with airtight rubber covers,
the only recourse is heavy reliance on wipe these down with water on a weekly
medications. The many asthma attacks basis, wash bedding frequently in very
that develop for no apparent reason hot water, and keep the bedroom in
obviously cannot be prevented either. particular as dust-free as possible. If
Anyone who suspects certain allergens there is a forced-air heating system in
or environmental sources can try one or the home (which disperses dust even
more of the following tactics. more than other heating systems), it
should be equipped with an effective air
Minimize dust and other household filter to trap offending particles.
Various steps can be taken
Ordinary household dust consists against specific allergens found in dust.
of a number of different materials that If dust mites are the problem, for
trigger asthma attacks, including the example, agents lethal to the mites,
feces of dust mites and cockroaches, pet called acaricides, can be applied to
dander, and microscopic fabric fibers. carpeting although these are probably
Frequent dusting and vacuuming can not safe for use in the home of a
minimize dust exposure over the long pregnant woman. A cockroach problem
run, but often these well-intentioned may be reduced by having the house or
efforts only stir some of the lighter- apartment fumigated regularly by an
weight particles into the air, where they exterminator. As for animal dander, the
are readily inhaled. For this reason, best solution is clearly to avoid owning a
someone other than the allergic person dog, cat, or other furry pet and to avoid
should be assigned these dust-busting long stays at homes inhabited by these
tasks and the allergic person should stay animals. If this is impossible, having
out of the room for at least half an hour someone who is not allergic wash the pet
after cleaning. on a weekly basis can be a significant
An alternative is to invest in a
double-filtered vacuum cleaner or, better Avoid molds and pollens
yet, a so-called high-efficiency
particulate arresting (HEPA) vacuum Because many of these
cleaner. HEPA air cleaners are a good substances are prevalent only during
investment for the bedroom, if not the certain seasons, the best tactic for those
whole house, because so much time is unable to exile themselves temporarily
spent in that room during sleep. Many to another climate may be to stay
allergists also recommend more extreme indoors as much as possible, preferably
measures such as ripping out carpeting, in a home, car, or office with air-
eliminating all stuffed and upholstered conditioned or filtered air. At all times of
furniture, and removing books and dust- the year, shampoos and skin creams
catching knickknacks, but not all people should be checked to make sure they do

Indian J for Practising Doctor; Vol I; No. 4

not contain extracts of cottonseed, Be wary of aspirin and other anti-

flaxseed, or other natural substances that inflammatory drugs
are sometimes allergenic. Those allergic
to mold and dust mites in particular may Because many drugs used to
want to invest in a dehumidifier, since reduce pain seem to promote asthma
humidity above 20 percent encourages attacks, anyone with asthma should use
the growth of these organisms. Adding a these drugs with caution until she is
few drops of chlorine bleach to cut certain they do not pose a problem for
flower arrangements and changing the her. Aspirin (acetylsalicylic acid), which
water daily can also help prevent mold. is sold under a variety of brand names, is
Also, because soil and water can foster a common culprit. Other analgesics that
the growth of molds, it is a good idea to often cause problems are ibuprofen and
keep indoor plants to a minimum. If other non-steroidal anti-inflammatory
there is a humidifier in the home, it drugs (NSAIDs).
needs to be cleaned regularly to prevent
the growth of molds and other allergens. Avoid smoke and other pollutants

Exercise with care Anyone with asthma should cut

out cigarettes and steer clear of other
Even though exercise often people’s smoke whether it is secondhand
triggers asthma attacks, there is no smoke from a cigarette or smoke from a
reason people with asthma should have woodstove, burning leaves, or an
to forgo an activity so important to industrial chimney. It is also advisable to
health and well-being. In fact, regular stay inside during pollution or ozone
exercise that develops lung capacity is alerts in urban areas and to avoid
generally recommended. Just what steps breathing fumes from fresh paint,
need to be taken to keep exercise safe, turpentine, insecticides, deodorants,
however, will vary with the individual. chlorine, cleaning fluid, and other
If exercise itself triggers attacks,
it is often sufficient to inhale a Eliminate foods that cause problems
bronchodilator before beginning the
exercise. If cold or rapid temperature If the problem is a solitary food
changes trigger attacks, it is best to such as peanuts, this is relatively easy to
restrict exercise to places with warm, avoid. It can be quite an ordeal,
humidified air (such as swimming pools however, when the allergy is to eggs,
or gymnasiums). If it is necessary to milk, or flour ingredients that are often
walk in the cold air, problems can be hidden in processed foods or foods
reduced by wearing a warm scarf or prepared in restaurants. Anyone who
mask around the mouth and nose and reacts to sulfites needs to be particularly
breathing through the nose in order to careful in restaurants and should
warm, filter, and humidify the air before routinely check all labels on packaged
it reaches the lungs. If pollen plays a role foods eaten at home. The Food and Drug
as well as exercise, it makes sense to Administration (FDA) recently banned
exercise indoors during allergy season. the use of these agents on fresh fruits
and vegetables and made it mandatory

Indian J for Practising Doctor; Vol I; No. 4

for manufacturers to include a notice on have a flu vaccination every year. Other
labels if detectable amounts of sulfites household members might also consider
are present in a food. getting shots, to minimize the chances
that they will bring an infection home.
Consider getting a flu shot Also, if at all possible, contact with
people who have viral infections
If asthma is triggered by (including colds) should be avoided.
respiratory infections, it is a good idea to

Viral Hepatitis: Recent disease they cause, the host's immunologic
reaction to the presence of virus in
Progress hepatocytes emerges as the dominant
mechanism of liver-cell damage and
inflammation1. Newer medications in the
Rohini Bhan & Arvind Bhan form of interferon-α and nucleoside
analogues have been added to the
armamentarium of chronic viral hepatitis.
Liver transplantation has been established
Viral hepatitis is still one of the most as an effective therapy for patients with end-
common causes of acute and chronic liver stage liver disease2 (Bzowej NH 1999). This
disease worldwide. Viral hepatitis is a review discusses the recent advances in our
subject of profound concern and results in knowledge of viral hepatitis A to E and viral
about 10,000 new papers each year, from hepatitis Non-A-to Non-E, focussing on the
molecular structure to newest treatments. literature of the past few years.
Major new advances have been made in our
knowledge of these diseases, many during
the past two years. A. New Agents of Viral Hepatitis
Non-A -To-Non-E Viral Hepatitis
Five hepatotropic viruses A to E are
now recognised and all are important public
health issues, although more so in some The list of potential hepatotropic
countries than others. Three additional viruses continues to grow, with the
viruses, Hepatitis G, TT virus, and SEN-V recent discovery of the GB virus-C, the
have been discovered recently, but have to TT virus, and the SEN virus. Prevalence
be proved to be hepatotropic and pathogenic rates of the GB virus-C have ranged
to liver. from 1.2% to 13% among healthy blood
It is evident that these viruses,
donors from all over the world. Higher
although similar in some respects, have a prevalence rates have been reported
number of intriguing differences. Most are among intravenous drug users. Similarly,
RNA viruses but Hepatitis B and TT virus the TT virus has a global distribution.
are DNA viruses. Each belongs to a different However, in spite of numerous reports of
virus family and, with the exception of the presence of both of these viruses in
Hepatitis D virus, has unique features that various kinds of liver diseases, definite
have resulted in being classified in a new evidence linking them to a specific
genus within family. Two viruses (Hepatitis disease, or illness is lacking. The SEN
B and C) are enveloped and two (Hepatitis virus is thought to be a novel viral agent
A and E) are not, whereas the Hepatitis D
that may be linked to cryptogenic
virus requires an envelope provided by the
surface-coat material of Hepatitis B virus
chronic hepatitis, but data are awaited.
for it to propagate. Only Hepatitis B virus
Hepatitis G
integrates into the host DNA. Two viruses
(Hepatitis A and E) are spread enterically The Hepatitis G virus (HGV) is a
and cause acute illness, whereas three single-stranded DNA virus that is
(Hepatitis B, C, D, G, TTV and SEN-V) are
included in the Flaviviridae family and
spread parenterally and Hepatitis B, C and
D cause chronic disease. Hepatitis G, TTV shares a 27% homology with HCV. The
and SEN-V are also thought to cause mild name HGV actually denotes 2
acute and chronic disease. Although viral independent viruses, HGV and GBV-C.
factor may contribute to the nature of the The HGV has not yet been isolated.
Indian J for Practising Doctor; Vol I; No. 4

Hepatitis G virus, was first isolated in 1995. The incubation period is not yet
Two lines of investigations led to its known. Currently, HGV infection can be
discovery: 1) an agent termed GBV-C was diagnosed only by identifying viral
recovered from a human following the genomes by using polymerase chain
identification of similar viral isolate, GBV-A
reaction (PCR) assay. No serologic test
and GBV-B, isolated from tamarinds
infected with serum from a surgeon (G.B.)
is available. In United States 1% to 2 %
with hepatitis, and 2) a blood-borne virus blood donors are viraemic as defined by
was isolated from plasma from a patient the presence of viral nucleic acid in their
with chronic hepatitis and designated blood.
Hepatitis G virus (HGV). These two human
isolates (GBV-C and HGV) are now TT Virus (TTV)
considered strains of the same virus and
have amino acid sequence homology of 95%. A group in Japan, in December
1997, reported yet another transfusion-
Although Hepatitis G virus (HGV) transmissible virus discovered via the
can cause chronic infection and use of cloning and DNA sequence
viraemia, it is a rare cause of hepatic analysis. This novel, single-stranded
inflammation and most infected persons linear DNA virus has been designated
are asymptomatic. Histologic evidence TT-virus or TTV after the initials of the
of HGV infection is rare, and serum first patient (TT) from whom the virus
aminotransferase concentrations usually was isolated. The virus is un-enveloped
are normal 3. Currently no conclusive and has been associated with biopsy-
evidence indicates that HGV causes proven, post-transfusion hepatitis of
fulminant - or chronic disease and co- unknown aetiology. TTV has a
infection does not seem to worsen the significant prevalence in the United
course of infection with Hepatitis B States, United Kingdom, Japan, Thailand
virus (HBV) or Hepatitis C virus (HCV). and Germany.

The HGV has been reported in Transaminase activity or liver

adults and children throughout the histological score is not significantly
world. Infection has been reported in increased among TTV positive patients4 .
10% to 20% of adults with chronic HBV The Hepatitis B infection (HBV) and
or HCV infection, indicating that co- Mediterranean origin are the risk factors
infection is a common occurrence. The associated with TTV infection. TTV is a
primary route of spread is through blood widely spread infectious agent with a
transfusions, but HGV also can be weak pathogenesity. TTV infection does
transmitted by organ transplantation. not impact on liver damage with HCV
Other important risk factors include infection. TTV infection also does not
injection drug use, haemodialysis, and affect the development and progression
homosexual and bisexual relationships, of hepatocellular carcinoma.
indicating that sexual transmission may Cryptogenic cirrhosis (one in which the
occur. Transplantation transmission cause of cirrhosis is not evident)
seems to be rare and has been associated accounts for 5% to 15% patients with
with high-titre maternal viraemia; when chronic liver diseases in the United
it occurs, infection usually becomes States, supporting that unidentified viral
persistent in infants. agents are associated with liver disease5 .

Indian J for Practising Doctor; Vol I; No. 4

TTV DNA is detected by PCR and most frequently reported vaccine

by phylogenetic analysis. (Phylogenesis preventable disease in the developed
is the evolutionary development of a world. The risk of Hepatitis A in patients
species, as distinguished from ontogeny, with chronic liver disease has been
development of the individual.) TTV confirmed and the efficacy of Hepatitis
strains can be divided into 6 genotypes A vaccine in these patients has been
using phylogenetc analysis. The majority proved7. The reduction in the incidence
of TTV-DNA sequences are related to of Hepatitis A in developed countries
genotypes 1 and 2 as described in will only be achieved by routine
Europe. childhood vaccination rather than by
targeted vaccination of high-risk group.
Hepatitis SEN-V Unlike Hepatitis B virus (HBV)
transmission by blood via parental routes
In July 1999, the Diasorin can occur but is unusual in Hepatitis A
Research Centre in Bresica, Italy, found infection.
that a novel virus, provisionally named
SEN-V, caused acute and chronic Hepatitis B
hepatitis, probably accounting for many
cases of Non A-to-G hepatitis. This virus The advances in molecular
is parenterally transmitted, and therefore, biology techniques in the past decade
appropriate screening of blood and blood have led to the clarification of Hepatitis
products could control its spread. In B viral DNA sequences. However, much
addition, this virus appears capable of remains to be established regarding the
co-infecting patients who have other emerging Hepatitis B mutants. Several
types of viral disease raising the putative forms of Hepatitis B virus have
possibility that it may aggravate their been isolated, but their epidemiology,
clinical course and/or their response to natural course of infection and clinical
treatment6. significance remain sketchy.
Compounding these problems are factors
Hepatitis F created by human interventions, such as
HBsAg mass immunization,
In 1994, French researchers chemotherapy of chronic HBV patients
reported the isolation of an enteric agent and HBIg prophylaxis of orthoptic liver
responsible for sporadic cases of Non-A- transplant (OLT) patients, which tend to
E hepatitis and named the virus Hepatitis encourage new mutants to emerge.
F (HFV), for hepatitis French virus.
However, their findings have not been Hepatitis B virus: A complex structure
confirmed by others and the term HFV is
currently unclaimed. Hepatitis B (HBV) is a
Hepadnavirus. It is a small enveloped
B. Hepatitis-A-To-E DNA virus containing 3.2 kb. The
Hepatitis A Hepatitis B virion consists of a surface
and a core. The core contains a DNA
Hepatitis A virus (HAV) is an polymerase and the e-antigen. The DNA
enterovirus in the family of structure is double-stranded and circular.
Picornaviridae. It has only one serotype. There are four major polypeptide
The genome is a single strand of reading frames (genes): the S (surface),
positive-sense RNA. Hepatitis A is the

Indian J for Practising Doctor; Vol I; No. 4

the C (core), the P (polymerase) and the found to be caused by pre-core and
X (transcriptional, transactivating). The surface mutants. If pre-core mutants
S gene consists of two regions, the pre- become a clinically important problem,
S1, pre-S2 and encodes the surface it will be important to incorporate them
proteins (HBsAg). Very rarely a into the next generation of Hepatitis B
mutation may occur in the S gene and vaccine8 . Although the efficacy of HBV
may abort the HBsAg with the result that immunization is well proven, cases of
a person may be HbsAg negative but vaccine failure leading to chronicity,
still have virus present as determined by acute self-limited symptomatic hepatitis
HBV DNA. The C gene is divided into and in some cases, fulminant hepatitis
two regions, the pre-core and the core, has been reported. In some of these
and codes two different proteins, the cases, anti-HBsAg neutralization-
Core antigen (HBcAg) and the E antigen resistant mutants or/naturally occurring
(HBeAg) escape mutants have been identified.
Vaccine escape mutants have also been
HBV Mutants identified in newborns from infected
mothers who had been vaccinated at
Because HBV uses a reverse
birth. Clearance of HBV infection results
transcription mechanism, mutations are
from complex immune mechanisms
fairly common. It is now known that
including TH1 cytokines significantly
HBV mutates far more frequently than
associated with HLA class II alleles.
the usual DNA virus but less than
Escape HBV mutants, especially pre-
rotaviruses. During the last 7 years a
core mutants influence the outcome.
series of HBV mutants have been
recognized. The most important of these To make it even more complex,
is the so-called pre-core mutation, in the HBsAg particles are antigenically
which there is a defect in the pre-core complex and these antigenic
region of HBV DNA. This mutation determinants have been identified. There
results in the failure to express HBeAg. is a single common determinant
The pro-core may stop production of designated a, and four sub-determinants
HBeAg and these persons will be designated d, y, w, and r. Thus, the four
HBsAg positive, HBV DNA positive, major determinants are: adr, ayw and
but HBeAg negative. The pre-core ayr.
mutation has been implicated in the
pathogenesis of fulminant hepatitis and Extra-hepatic Associations Although
may be responsible for severe uncommon, a number of conditions
exacerbations of chronic hepatitis associated with Hepatitis B antigen-
associated with HBV infection. In antibody complexes have been
general, patients with this mutant are recognised. These include: polyarteritis,
more likely to progress to cirrhosis and glomerulonephritis, polymyalgia
hepatic insufficiency, compared to rheumatica, Guillian-Barre syndrome,
infection with wild strains. myocarditis and essential mixed
cryoglobulinaemia - sometimes only a
A wide geographical variation test tube finding9
seems to emerge from pre-core mutants.
As high as 25% of chronic HBV Clinical Course Hepatitis B is
infections in patients in Delhi were transmited by parenteral, congenital and

Indian J for Practising Doctor; Vol I; No. 4

sexual routes. Fulminant disease carries immunologic or other precipitating

a 1.2% mortality. Up to 10% of patients factor and (3) a true causal relationship
develop a chronic hepatitis complicated between HB vaccination and MS or
by cirrhosis or hepatocellular carcinoma. other CNS demyelinating disease.
Congenital infection brings a high risk of
hepatocellular carcinoma. Evidence to support the first
hypothesis includes the fact that no
Treatment Lamivudine is a major statistically significant association was
advance in the therapy of chronic found between Hepatitis B vaccine and
Hepatitis B. Although drug resistant MS in the limited studies conducted to
mutants may be selected during therapy, date. Further the age and sex
additional nucleoside analogues distributions of MS cases reported
including adefovir are promising. through spontaneous reporting of MS
Aggressive combination therapy has reporting systems match the recognised
emerged as a promising strategy from age and sex distribution of MS cases that
chronic Hepatitis B and C. Liver preceded the use of the vaccine and are
transplantation has become routine for not correlated with vaccine
end stage Hepatitis B virus liver administration.
disease10. The spontaneous risk for viral
recurrence after transplantation is high, In support of hypothesis of an
but has been decreased effectively in increased risk of MS after HB
Hepatitis B-positive recipients with the vaccination seen as a precipitating factor
use of HBIG and lamivudine11. is that some studies have shown slightly
elevated odds ratios, although these were
Hepatitis B vaccine: Safety and efficacy not statistically significant. Evidence
inconsistent with this hypothesis is the
Concerns have been raised by observation that no increased risk was
reports of multiple sclerosis (MS) or found in another study.
other demyelinating diseases occurring
in adults who had recently received The data available to date, although
Hepatitis B vaccine. There are three limited, do not demonstrate a causal
hypotheses that could explain the association between HB vaccination and
observed cases of demyelinating CNS demyelinating diseases, including
diseases following HB vaccine: (1)
coincidence, because of the large
The present studies support the
number of HB vaccine doses
WHO recommendations that all
administered in the developed world,
countries should have universal infant
many of them in age groups where
and/or adolescent immunization
symptoms of MS first occur.
programmes and continue to immunize
(2)"triggering": an increased risk of
adults at increased risk of HB infection
symptomatic demyelination following
as appropriate.
HB vaccine, which would act as
"trigger" in individuals predisposed to Studies have shown that the
develop MS or CNS demyelinating vaccine is 95% effective in preventing
diseases - these individuals would have children and adults from developing
developed demyelination with or without chronic infection if they have not yet
an altered natural history after some been infected. In many countries where

Indian J for Practising Doctor; Vol I; No. 4

8% to 15% of children used to become transfusion settings. Intravenous drug

chronically infected with HBV, the rate abuse is currently the main risk but
of chronic infection has been reduced to nosocomial (hospital) infection is also a
less than 1% in immunized group of concern.
Nosocomial spread is potentially
Hepatitis C important and in some instances
preventable. It has been shown, for
Ten years have elapsed since example, that in many chronic
identification of Hepatitis C virus haemodialysis patients, there is 20% to
[HCV]) was first reported. This 30% prevalence of ant-HCV positivity in
remarkable achievement occurred after the absence of any clear parenteral risk
more than 20 years of intense efforts by factors.
investigators worldwide following
observation that at least one additional A recent Australian report has
viral agent, other than Hepatitis A and raised the possibility of HCV
Hepatitis B, was the major cause of post- transmission through contaminated
transfusion hepatitis13. anaesthetic equipment intra-operatively.
This is the first case report of patient-to-
The viral agent HCV is an enveloped, patient transmission of HCV.
positive-stranded RNA virus with a Transmission of HCV by endoscopy is
genome that consists of 10,000 also possible, as suggested by a French
nucleotides. The virus is a member of report that highlights the importance of
flavivirus family, which also includes meticulous cleaning of endoscopic
other parenterally spread viruses such as instruments, including biopsy channel.
yellow fever and dengue. At least 6
genotypes as well as a number of Injection-Associated Hepatitis C In Egypt
subtypes have been identified. A An increasing body of evidence suggest that
correlation seems to exist between the a large proportion of hepatitis infections in
genotype and clinical course of infection Egypt were caused by unsafe injection
practices during the last decades. In
and its treatment. For example,
particular, improperly sterilized needles
genotype1, which is common in the appear to have been used to treat
United States, seems to be most virulent schistosomiasis. Approximately 13% of the
of the genotypes and more resistant to Egyptian population is infected with
treatment. Unfortunately HCV is a very Hepatitis C virus leading to a high burden
mutagenic virus, a characteristic that of chronic liver disease, cirrhosis, and liver
enables it to survive the immune defence cancer as well as mortality resulting from
mechanisms of the host. As a result more these diseases. The tartaric emetic
than 75% of the adults acquiring acute intravenous injections were given twice a
week for 7 weeks to treat schistosomiasis.
infection go on to develop chronic
The tartaric emetic is an antimonial
Hepatitis C with continuing HCV compound. The use of injections to treat
infection14. schistosomiasis stopped about 15 years ago;
the current treatment for schistosomiasis is
Epidemiology Three per cent of the oral administration of praziquintel.
world population has been infected with Evidently, this practice has resulted in a
Hepatitis C virus (HCV). Epidemiology large reservoir of the virus that has
has shifted from transfusion to non- contributed to the spread of infection in the

Indian J for Practising Doctor; Vol I; No. 4

country. This is one of the historic events in of CD81 protein as one the HCV
which the introduction of a new modality or receptor candidates may help to
a new technique was considered initially of understand how chronic HCV infection
major credit to the patient but later,
may trigger a wide spectrum of clinical
unfortunately, turned out to be a virtual
catastrophe. Such events are not rare in the
manifestations, autoimmune or even
history of medicine. lymphoproliferative, through potent
continuous B cell activation in the
The UK researchers have found context of various host and/or
that delivering at-risk babies by environmental cofactors. Hepatitis C
caesarean section may protect the infants virus infection occurs with increased
from the Hepatitis C virus. frequency in patients with non-
Hodgkins's lymphoma. Evidence of prior
Pathology There is correlation infection with HCV is common in
between hepatitis quasi species and the patients with non-Hodgkin's
progression of liver disease. The quasi 16
lymphoma .
species hypothesis suggests that viruses,
particularly RNA viruses, circulate as Clinical course and treatment
mixed populations of closely related Infection may cause a mild acute
variants. Changing population dynamics hepatitis but many cases are
may lead to alterations in the relative asymptomatic: fulminant hepatitis is
dominance of one or more variants, and rare. HCV infection persists up to 80%
new variants emerge. Quasi species may of patients; up to 35% of these develop
have relevance for the capacity of a virus cirrhosis, liver failure and hepatocellular
to evade immune control. They have carcinoma between 10 and 30 years
been documented in Hepatitis C virus later. This occurs because frequent virus
infection, typically a chronic infection mutation results in immunologically
with a varying clinical impact amongst distinct quasi-species, allowing the
patients. organism to escape immunological
Three independent factors seem
associated with fibrosis progression in Among patients with chronic
HCV: age, daily alcohol consumption of Hepatitis C, 48 weeks of treatment with
50g or more and male gender. Median interferon/ ribavirin therapy produced a
duration of progression to cirrhosis is response rate of 28% among those with
about 30 years. At the cirrhotic stage, genotype 1 and 66% with other
about 3-5% of patients per year develop genotypes. Similar differences were
hepatocellular carcinoma. There is little found in combination therapy among
evidence that direct cyto-pathogenecity patients who had relapsed following
plays a significant role in the liver cell previous interferon (IFN) therapy. Viral
injury. The spontaneous Hepatitis C load prior to treatment has been clearly
virus clearance is determined by class II shown to be predictive of response to
antigens (mainly DQB10301) and interferon treatment, with increased viral
female sex, while viral genotype plays load associated with decreased rate of
no role15. HCV also infects extrahepatic response. In patients non-responsive to
cells which seem critical in the interferon, a second course of interferon
pathogenesis of any extrahepatic alone has non-beneficial effect whereas
manifestations9. The recent identification combination therapy may induce

Indian J for Practising Doctor; Vol I; No. 4

response in 25% of patients. The suggested that a dose higher than that
combination therapy is recommended in usually used for Hepatitis B infection
all situations. Viral eradication should may beneficial.
not be the only objective of the treatment
since histological improvement may be Hepatitis E
obtained despite persisting viral
Hepatitis E virus consists of small,
replication with prolonged maintenance
32 to 34 nm diameter, icosahedral, non-
of antiviral therapy17.
enveloped particles with a single-
Hepatitis D stranded, positive-sense, 7.5-kb RNA.
The virus has two main geographically
The Hepatitis D virus (also called distinct strains, Asian and Mexican;
delta virus) is a small circular RNA recently, novel isolates from non-
virus. The Hepatitis D virus is endemic areas and a genetically related
replication defective and therefore swine HEV have been described. HEV is
cannot propagate in the absence of responsible for large epidemics of acute
another virus. In humans, Hepatitis D hepatitis and a proportion of sporadic
virus infection only occurs in the hepatitis cases in the Indian
presence of Hepatitis B infection. subcontinent, Southeast and central Asia,
the Middle East, parts of Africa, and
A patient can acquire Hepatitis D Mexico19. Clinical illness is similar to
virus infection at the same time as s/he is other forms of acute viral hepatitis
infected with the Hepatitis B virus. This except for pregnant women, in whom
is called co-infection. A patient with illness is particularly severe with a high
Hepatitis B can be infected with mortality rate. Sub-clinical and
Hepatitis D virus at any time after acute unapparent infection may occur,
Hepatitis B virus infection. This is called however, chronic infection is unknown.
super-infection18. No specific treatment is available. Use
of clean water and proper sanitation is
Hepatitis virus super-infection
currently the most effective method of
should be suspected in a patient with
prevention. Passive immunization has
chronic Hepatitis B whose condition
not been proved to be effective, and
suddenly worsens. There is usually an
recombinant vaccines for travellers to
obvious history of continued exposure to
disease-endemic areas and for pregnant
blood or blood products (e.g. an active
women currently are being developed20.
intravenous drug user). A particularly
aggressive acute Hepatitis B infection Hepatitis E virus (HEV) is an
could suggest Hepatitis D co-infection. important cause of enterically-
Co-infection or super infection with transmitted acute viral hepatitis in
Hepatitis D virus in a patient with several less-developed countries and is
Hepatitis B is diagnosed by the presence transmitted by faecal-oral route. Data on
of antibodies against the Hepatitis D duration of viral excretion and viraemia
virus. IgM antibodies indicate acute during HEV infection are limited.
infection. Investigation of an outbreak of Hepatitis
E in Lucknow suggested that extended
Interferon-α is used to treat
viral excretion and viraemia, particularly
patients with chronic Hepatitis B and
those extending beyond the duration of
Hepatitis D infection. Some studies have

Indian J for Practising Doctor; Vol I; No. 4

biochemical hepatitis, are distinctly Hepatitis C virus related. Furthermore,

rare21. Thus, in disease-endemic areas, even in the presence of normal
individuals who have recovered from aminotranserase concentrations,
acute Hepatitis E are unlikely to serve as considerable liver pathology can be
a reservoir of HEV infection. found in 10% to 20% of HBsAg and anti
HBVe positive individuals. Such
pathology is not associated with the
C. Viral Hepatitis: Pathology And occurrence of pre-core stop codon
Pathogenesis mutations24.

The histological features of viral It is especially noteworthy to note

hepatitis have not changed and light the little-appreciated fact that half the
microscopic examination remains patients with hepatocellular carcinoma
essential for making diagnosis and who test negative for HBsAg have HBV
classification of chronic hepatitis and the DNA sequences in their tumours.
provision of objective parameters on
grading and staging22. However, new Cytokines play an important role
understanding and knowledge of viral in the defence against viral infections,
pathogenesis, host immune responses, both indirectly, through determination of
the biological behaviour of the causative the predominant pattern of host response
viral agents and, in particular, viral and directly, through inhibition of viral
interference in multiple hepatotropic replication. However, in the context of
viral infections must be taken into an inflammatory response against a
consideration in the interpretation of virus, cytokines may also lead to liver
histopathological and damage. The importance of this is best
immunopathological findings of liver illustrated in viral Hepatitis B (HBV). In
tissues. The study by Huang et al acute HBV infection, a vigorous
(1997)23 presents some histopathological polyclonal cellular immune response is
analyses on multiple hepatotropic viral critical; thus type 1 cytokine release is
infections. The diagnostic histological essential to initiate an effective immune
criteria for acute hepatitis remain response. The cytokines released by
applicable in such settings. However, the CD4+ and CD8+ cells also play an
cause of acute flare up in chronic important role in down regulation of
hepatitis could not be determined HBV replication, demonstrating that it is
without clinical, virological and possible to control a viral infection
serological information. Routine without the death of infected cells.
histopathology cannot distinguish a new However, if there is a defect in the acute
infection from an acute exacerbation due response, HBV becomes chronic; in that
to high level of viral replication or case, the presence of an ongoing sub-
mutant virus. A battery of immuno- optimal inflammatory reaction can
cytochemical stains for viral antigens is activate the process of hepatic fibrosis.
helpful, but caution must be exercised in In Hepatitis C infection, the role of
suggesting a specific viral aetiology due cellular immune responses and cytokines
the fact that suppression of pre-existing is less clear. Hepatitis C may be resistant
viral antigens can be pronounced when to inhibition by cytokines, so cytokines
the new or concurrent infection is may have a more prominent role in liver
damage than controlling viral

Indian J for Practising Doctor; Vol I; No. 4

replication. Both Hepatitis B and C may always is associated with the presence of
have specific mechanisms to inhibit IgM anti-HBc. IgG anti-HBc positivity
cytokine production, highlighting the indicates a resolving infection or chronic
critical role these molecules in recovery Hepatitis B. The presence of HBeAg
from infection25. indicates active viral replication and
high infectivity. Anti-HBe appears when
D. Laboratory Evaluation Of viral replication ceases. Resolved
Viral Hepatitis hepatitis B and lasting immunity either
Although they are referred to as from infection or immunization are
"liver function tests," elevation of serum associated with the presence of anti-
AST, ALT and GGT actually are HBs.
indicative of hepatocellular damage.
Slight elevations of AST and ALT do Hepatitis C virus cannot be
not always predict mild disease, and cultured. Hepatitis C is associated with
both can fall with end-stage liver failure. the detection of anti-HCV by enzyme-
The most useful indicator of hepatic linked immunosorbent assay, but this
synthetic function is the prothrombin test must be followed by supplemental
time (PT)26. In some cases of Hepatitis specificity tests to substantiate the
A, a falling aminotransferase level may diagnosis, including recombinant
predict a poor outcome if the decline immunoblot assay (RIBA) or
occurs in conjunction with rising measurement of HCV RNA by
bilirubin level and prolonged PT. This polymerase chain reaction (PCR).
combination of findings indicates that PCR assays for HCV infection are
massive hepatic injury has occurred, used commonly in clinical practice in the
resulting in few functioning hepatocytes. early diagnosis of infection, for
Acute Hepatitis A is diagnosed by a identifying infection early in life e.g.
positive IgM anti-HAV. The additional perinatal transmission when maternal
findings of IgG anti-HAV, in the serum antibody interferes with the
absence of IgM, indicates a resolved ability to detect antibody produced by
Hepatitis A infection with lasting the infant, and for monitoring patients
immunity. Patients who have been receiving antiviral therapy. A patient
immunized against Hepatitis A may with positive PCR result for Hepatitis C
have undetectable antibody titers by is infected with Hepatitis C virus even if
standard commercially available serologic markers for Hepatitis C are
laboratory assays. Diagnostic antibodies, negative. A negative PCR result for
anti-HAV IgM appear before jaundice Hepatitis C with positive result for
develops and persists for three months. serological markers 1) indicates past
Both acute and chronic hepatitis B Hepatitis C infection, 2) indicates acute
infections are diagnosed by the presence HCV infection with transitory negative
of HBsAg. HBsAg positivity warrants PCR phases, 3) may indicate a patient
investigation of Hepatitis D co-infection who has passively received anti-HCV
or super infection, as defined by the immunoglobulins during a blood
presence of IgM anti-HDV. Hepatitis D transfusion.
can occur only in the presence of HBsAg Radioimmuno assay and enzyme
positivity. Acute Hepatitis B infection immuno-assay for anti-HDV (Hepatitis

Indian J for Practising Doctor; Vol I; No. 4

D virus) are available commercially, at mutants are very important agents in

referral laboratories. Tests for IgM- cases of where Hepatitis B results AHF
specific ant-HDV antibody and HDAg in this country. Half of the patients with
are research procedures at present. If AHF are female, one quarter of whom
markers for HDV infection exist, co- are pregnant. Therefore, pregnant
infection with HBV usually can be females who contract viral hepatitis
differentiated from super-infection of an constitute a high-risk group for
established HBsAg carrier by testing for development of AHF. However, the
IgM Hepatitis B core (HBcIgM) outcome of AHF in this group is similar
antibody; absence of this core antibody to that in non-pregnant women and men.
suggests that the person is an HBsAg In AIIMS, Delhi, approximately one-
carrier. Methods for detection of HDV third of AHF patients survive with
RNA are available. aggressive conservative therapy,
whereas, two-thirds of deaths occur
Recombinant DNA technology within 72 hours of hospitalisation
has resulted in development of (Acharya SK et al 2000).
antibodies to Hepatitis E virus (HEV)
particles, and IgM and IgG assays are Hepatitis D is not uncommon in India. In
available to distinguish between acute a study reported from Bombay (Banker
and resolved infections. IgM antibody to 1992), out of 331 cases of Hepatitis B,
viral antigen becomes positive after 148 patients had an evidence of Hepatitis
about one week of illness. Viral RNA D as well. Fulminant hepatitis developed
can be detected in stool and serum by in 39 patients, 32 of whom had Hepatitis
PCR. Diagnosis of Hepatitis E is usually B and 20 of these (63%) also had
made by detection of specific IgM Hepatitis D. These findings indicate the
antibody, which disappears rapidly over extent of association of Hepatitis D with
a few months; IgG ant-HEV persists for Hepatitis B and the high-risk of fatal
at least a few years. fulminant hepatitis in these patients.
The only diagnostic tests for Hepatitis G *********************************
virus infection are PCR assays. They are
used to detect HGV RNA
E. Viral Hepatitis: Indian Scenario
Acute hepatic failure (AHF) in India
almost always presents with
encephalopathy within four weeks of the
onset of acute hepatitis. Viral hepatitis is
the cause in approximately 95-100% of
patients, who therefore constitute a more
homogeneous population than AHF
patients in the West. In India, Hepatitis
E (HEV) and Hepatitis B (HBV) viruses
are the most important causes of AHF;
these two viruses cause approximately
60% of cases. Hepatitis B virus core

distinct H and L chains. The pairing of H
Immunology Update and L chains in a quasi-random manner
further expands the number of distinct
B-Lymphocyte Ig molecules that can be formed.
Development The H-chain variable region
is initially expressed in association with
Gazala Shakoor
the product of the m-constant (C)-region
gene. Together these elements encode
the m IgH chain, which is used in
B-lymphocytes are derived
immunoglobulins of the IgM class. The
from haematopoietic stem cells by a
successful completion of the process of
complex set of differentiation events.
Ig gene rearrangement and the
Various molecular mechanisms which
expression of the resultant IgM on the
lead to maturation of the early B lineage
cell surface marks the transition between
cells into mature B-lymphocytes occur
the pre-B and B-cell states. The newly
in the foetal liver and, in adult life,
differentiated B cell initially expresses
principally in the bone marrow.
surface immunoglobulin solely of the
Interaction with specialized stromal cells
IgM class.
and their products, including cytokines
such as interleukin-7 (IL-7), are critical
The cell completes its
to the normal regulation of this process.
maturation process by expressing on its
surface a second class of
The key events in B-cell
immunoglobulins composed of the same
development occur in cells designated
L chain and the same H
pro-B cells and pre-B cells. They centre
chain variable region but of a different
about the assembly of the genetic
H-chain C region; this second Ig H chain
elements encoding the antigen-specific
is designated d, and the immunoglobulin
receptors of B cells, which are
to which it contributes is designated IgD.
immunoglobulin (Ig) molecules
specialized for expression on the cell
The differentiation process is
surface. Immunoglobulins are
controlled at several steps by a system of
heterodimeric molecules consisting of
checks that determines whether prior
heavy (H) and light (L) chains, both of
steps have been successfully completed.
which have variable (V) regions that
These checks depend on the expression
contribute to the binding of antigen and
on the surface of the cell of
that differ in sequence from one Ig
appropriately constructed Ig or Ig-like
molecule to another. In addition, the
molecules. Pre-B cells that fail to
heavy and light chains contain regions
express the preliminary complex do not
that are not variable but constant (C
move forward to future differentiation
states. That eliminates inefficient cells
from maturation process.
In pro-B and pre-B cells,
genetic elements encoding variable B-Lymphocyte Activation
portions of heavy & light chains are such A mature B cell can be
which add diversity so to result in the activated by an encounter with an
generation of a very large number of antigen expressing epitopes that are
Indian J for Practising Doctor; Vol I; No. 4

recognized by its cell-surface antigens are the capsular polysaccharides

Immunoglobulin. The activation process of many medically important
may be a direct one, dependent on cross- microorganisms such as pneumococci,
linkage of membrane Ig molecules by streptococci, and meningococci. Similar
the antigen (cross-linkage-dependent B- expression of multiple identical epitopes
cell activation), or an indirect one, on a single immunogenic particle is a
occurring most efficiently in the context property of many viruses because they
of an intimate interaction with a helper T express multiple copies of envelope
cell, in a process proteins on their surface. Cross-linkage-
often referred to as cognate help. dependent B-cell activation is a major
protective immune response mounted
Cross-lineage-dependent B-cell against these microbes. The binding of
activation: When B cells encounter antigens complement components to antigen or
that bear multiple copies of an epitope that antigen-antibody complexes can increase
can bind to their surface Ig, the resultant the magnitude of the cross-linkage-
cross-linkage stimulates biochemical signals
dependent B-cell activation due to the
within the cell leading to B-cell activation,
growth, and differentiation.
action of a receptor for complement,
Resting B cells can bind antigens which, together with other molecules,
that bear epitopes complementary to their increases the magnitude of a B-cell
cell-surface immunoglobulin (Ig). Even if response to limiting amounts of antigen.
the antigen cannot cross-link the receptor, it
will be endocytosed and enter late Cognate help allows B cells
endosomes and lysosomes where it will be to mount responses against antigens that
degraded to peptides. Some of these cannot cross-link receptors and, at the
peptides will be loaded into class II MHC
same time, provides co-stimulatory
molecules and brought to the cell surface,
where they can be recognized by CD4+ T
signals that rescue B cells from
cells that bear receptors specific for that inactivation when they are stimulated by
peptide/class II complex. This interaction weak cross-linkage events. Cognate help
allows an activation ligand on the T cells is dependent on the binding of antigen
(CD40 ligand) to bind to its receptor on B by the B cell’s membrane Ig, the
cells (CD40) and to signal B-cell activation. endocytosis of the antigen, and its
In addition, the T cells secrete several fragmentation into peptides within the
cytokines that regulate the growth and endosomal / lysosomal compartment of
differentiation of the stimulated B cell.
the cell. Some of the resultant peptides
In many instances, B-cell activation
events may result from both pathways of
are loaded into a groove in a specialized
stimulation. set of cell-surface proteins, the class II
major histocompatibility complex
Because each B cell bears (MHC) molecules. The resultant class II
membrane Ig molecules with identical /peptide complexes are expressed on the
variable regions, cross-linkage of the cell surface; these complexes are the
cell-surface receptors requires that the ligands for the antigen-specific receptors
antigen express more than one copy of of a set of T cells designated CD4+ T
an epitope complementary to the binding cells. CD4+ T cells that have receptors
site of the receptor. This requirement is specific for the class II/peptide complex
fulfilled by antigens with repetitive expressed on the B-cell surface
(multiple) epitopes. Among these recognize and interact with that B cell.

Indian J for Practising Doctor; Vol I; No. 4

That interaction results in the activation Division and differentiation

of the B cell through the agency of cell- of cells into antibody-secreting cells is
surface molecules expressed by the T largely controlled by the interaction of
cells (e.g., the CD40 ligand [CD154]) the activated B cells with T cells
and cytokines produced by the T cell. expressing CD154 and by their
The role of the B-cell receptor for stimulation by T-cell-derived cytokines.
antigen is to create
the T-cell ligand on the surface of The differentiation of
antigen-specific B cells; activation of the activated B cells into memory cells
B cell derives largely from the action of occurs in a specialized micro-
the T cell. However, in many environmental structure in the spleen
physiologic situations, receptor cross- and lymph nodes, the germinal centre.
linkage stimuli and cognate help The process through which increase in
synergize to yield more vigorous B-cell antibody affinity occurs also takes place
responses. within the germinal centre. The latter
process, designated affinity maturation,
B-Lymphocyte Differentiation is dependent on somatic hypermutation.
The survival of cells within the germinal
Activation of B cells centre depends on the capacity to bind
prepares them to divide and to antigen so that as antigen availability
differentiate either into antibody- diminishes, cells that have higher
secreting cells or into memory cells, so affinity receptors, either naturally or as a
that there are more cells specific for the result of the hypermutation process,
antigen used for immunization and these have a selective survival and growth
cells have new properties. Those cells advantage. Thus, such cells come to
that differentiate into antibody secreting dominate the population.
cells account for primary antibody
responses. Some of these antibody The process through which
secreting cells migrate to the bone a single H-chain V region can become
marrow where they may continue to expressed with genes encoding C
produce antibody for an extended period regions other than m and d is referred to
of time and may have lifetimes in excess as Ig class switching. It is dependent on
of 1 year. a gene translocation event through which
Memory B cells give rise to the C-region genes between the genetic
antibody-secreting cells upon re- elements encoding the V region and the
challenge of the individual. The newly expressed C gene are excised,
hallmark of the antibody response to re- resulting in the switched C gene being
challenge (a secondary response) is that located in the position that the Cm gene
it is of greater magnitude, occurs more formerly occupied (Fig. 3). This process
promptly, is composed of antibodies also occurs in germinal centres.
with higher affinity for the antigen, and
is dominated by immunoglobulins B1 or CD5+ B-Lymphocytes
expressing g, a, or e C regions (IgG,
IgA, or IgE) rather than by IgM, which A second population of B
is the dominant Ig of the primary cells (B1 cells) has been described that
response. differs from the dominant B-cell
population (sometimes designated B2

Indian J for Practising Doctor; Vol I; No. 4

cells or conventional B cells) in several the host’s own tissues. The mechanisms
important respects. These cells were ensuring this failure to respond to self-
initially recognized because some antigens are complex and involve a
express a cell-surface protein, CD5, not series of strategies. Chief among them is
generally found on other B cells. B1 B elimination of cells capable of self-
cells are quite numerous in foetal and reactivity or the inactivation of such
perinatal life, but scant and restricted in cells. The encounter of immature, naive
adult life. Whether B1 B cells derive B cells with antigens with repetitive
from a separate set of stem cells found in epitopes capable of cross-linking
the foetal liver but absent from (or membrane Ig can lead to elimination of
present only at low frequency in) the the B cells, particularly if no T-cell help
adult bone marrow is still a matter of is provided at the time of the encounter.
controversy. The alternative view is that This elimination of potentially self-
B1 B cells are derived from conventional reactive cells is often referred to as
B cells as a result of cross-linkage- clonal elimination. Some self-reactive
dependent B-cell activation. B1 B cells cells, rather than dying upon encounter
appear to be self-renewing, in contrast to with self-antigens, may re-express the
conventional B cells, in which division proteins needed for immunoglobulin
and memory are antigen driven. gene rearrangement and undergo a
further round of such rearrangement.
B1 B cells appear to be This process, referred to as receptor
responsible for the secretion of the editing, allows a self-reactive cell to
serum IgM that exists in non-immunized substitute a new receptor and therefore
animals, often referred to as natural IgM. to avoid elimination.
Among the antibodies found in such
"natural" IgM are molecules that can There are many self-antigens that
combine with phosphatidyl choline (a are not encountered by the developing
component of pneumococcal cell walls) B-cell population or that do not have the
and for lipopolysaccharide and influenza capacity to cross-link B-cell receptors to
virus. B1 B cells also produce a sufficient degree to elicit the clonal
autoantibodies, although they are elimination/receptor editing process.
generally of low affinity and in most Such cells, even when mature, may
cases not pathogenic. It is believed that nonetheless be inactivated through a
B1 B cells are important in resistance to process that involves cross-linkage of
several pathogens and may have a receptors without the receipt of critical
significant role in mucosal immunity. co-stimulatory signals. These
inactivated cells may be retained in the
B-Lymphocyte Tolerance body but are unresponsive to antigen and
are referred to as anergic. When
One of the central problems removed from the presence of the
facing the immune system is that of anergy-inducing stimulus, such cells
being able to mount highly effective may regain responsiveness.
immune responses to the antigens of ********************************
foreign, potentially pathogenic, agents
while ignoring antigens associated with

Indian J for Practising Doctor; Vol I; No. 4

Cervical Cancer

Manzoor Kadri

The cervix is the lower part of Gynecologists (similar to the American

the uterus that opens into the vagina. Cancer Society guidelines) advise that
Cervical cancer, accounting for 40% of
all cancer mortality, is the second most "All women who are or who
common cause of cancer death for have been sexually active or who have
women worldwide - surpassed only by reached age 18 should undergo an
breast cancer. At the same time it is a annual Pap test and pelvic examination.
disease that is almost 100 percent After a woman has had three or more
curable with accurate screening and consecutive, satisfactory annual
early detection. In India, it is the greatest examinations with normal findings, the
killer in women of the menopausal age. Pap test may be performed less
Early marriages, poor sexual hygiene frequently at the discretion of her
and growing extra-marital and pre- physician."
marital contacts make the occurrence of
this cancer increasingly common. Cervical cancer does not develop
Human papilloma virus (HPV) has been immediately from normal cervix cells.
implicated as the agent causing this The cervix goes through a "pre-
cancer. cancerous" phase where the cells grow
closer together first. This pre-cancerous
Traditional cervical screening stage is called "dysplasia". The
tests for the cancer include the Pap cancerous and pre-cancerous cell
smear and the pelvic exam. During a changes in the cervix can be detected by
pelvic exam, the physician will check for pap smear. It is also used to diagnose
abnormalities in the size or shape of the viral infections of the urogenital system
patient’s uterus, vagina, ovaries, like genital warts and herpes, and
fallopian tubes, bladder and rectum. sexually transmitted diseases.
Using a speculum, the upper portion of
the vagina and cervix will also be If the cells look normal, no
examined. During a Pap smear, the treatment is necessary. The Pap test may
physician collects cells sitting at the show that the patient has an infection.
surface of the cervix using a small The doctor may treat her for the
wooden spatula or a brush. These cells infection and suggest that she has
are smeared on a slide and sent to the another Pap test in several months. If the
laboratory for analysis under a cells look abnormal, more tests like
microscope. The procedure is painless. colposcopy and cervical conization may
be necessary. The doctor will discuss the
The guidelines of The American test results and advice for follow-up
College of Obstetricians and exam. A Pap test is not 100% accurate, it

Indian J for Practising Doctor; Vol I; No. 4

is a screening test. Nevertheless, it is a because of prevention, screening, and

simple, effective and low-cost early detection by the Pap smear. In the
technology for detecting cervical cancer United States, about 2-3 million
in its early stages, when it is treatable, abnormal Pap smear results are found
and has been available for over 30 years. each year. Most of them indicate the
The incidence of cancer and early stages of disease and need
deaths from cervical cancer has reasonable observation by doctor.
significantly declined over the years
incidence of cancer of the
cervix increases with age at
Risks factors for cancer of the cervix a time when women may be
less likely to get a Pap
smear. Most of these
cancers are diagnosed in
1. Multiple sexual partners (or women older than 50 years.
sexual partners who have had Even after menopause,
multiple partners) women should continue to
have regular Pap smears.
2. Starting sexual intercourse at
an early age 4 The National Cancer
Institute encourages women
3. Viral infection, such as HPV, aged 65 years and older to
human immunodeficiency get Pap smear at least every
virus (HIV), or herpes 2 years and every year if at
simplex virus (HSV) higher risk and advised by
their doctor. Many older
4. Weakened immune system
women believe they no
5. Previous cancer of the lower longer need Pap smears
genital tract (and think they are not at
risk for cervical cancer)
6. Smoking because of their age, or
because they may not be
sexually active, or because
they have had a
Screening for cervical cancer hysterectomy. That is not
1 Cervical cancer screening is correct. These women need
recommended yearly Pap smears because their
starting when women risk is higher.
are aged 18 years or they 5 If you have had your uterus
become sexually active, if removed, yearly screening
younger than 18 years. should be performed if there
2 Less frequent screening is is a history of abnormal Pap
done if the patient has a smear results or other lower
negative Pap smear result 3 genital tract cancer.
years in a row or if she is
not sexually active.

3 No upper age limit for

screening exists because the

Indian J for Practising Doctor; Vol I; No. 4

Patient Education
Osteoarthritis Treatment for osteoarthritis

Osteoarthiritis can’t be cured

(Rohini Bhan)
and, so far, doctors can’t reverse joint
degeneration. But many medications can
treat the pain, and some new therapies
Sometimes called degenerative show promise of slowing or stopping
joint disease, osteoarthritis results when cartilage destruction.
the cushioning cartilage in the joints
breaks down, causing pain and stiffness. Treatment focuses on relieving
It is the most common form of arthritis. pain, preventing the joints from further
It is perhaps the most common and damage, and helping you stay active.
oldest disease affecting humans. With Working with health professionals, the
the improvement in life expectancy from patient can learn to avoid stressing his
55 yrs to 70 yrs on an average, most joints, compensate for any loss of
persons past the age of 60 have flexibility or mobility, and strengthen
osteoarthritis to a certain degree. muscles to better support already
weakened joints.
Osteoarthritis is termed
primary osteoarthritis when it occurs in In cases of severe cartilage
the absence of a particular cause. loss, surgery can help. Total joint
Secondary osteoarthritis can be replacement is now commonplace,
attributed to an obvious underlying relieving pain and restoring mobility to
factor such as injury (previous fractures), many people who would be unable to
infections, hormonal disorders, or as a function otherwise. A note about
consequence of another type of arthritis medications: Many of the prescription
such as rheumatoid arthritis. Obesity drugs prescribed for osteoarthritis have
(overweight) may also lead to secondary side effects. Be sure to discuss treatment
osteoarthritis in the weight bearing benefits and risks with your doctor.
Weight Loss
Joint pain is the usual
symptom. Initially the pain comes on Extra stress on your joints wears
after overwork and is relieved by rest. out your cartilage faster. If you are
Later, as the disease progresses, pain overweight, your doctor will urge you to
occurs even while resting. Rarely is the trim down to a weight appropriate for
pain felt far from the affected joint. This your age and height. However, avoid
is known as referred pain in medical crash diets though. A combination of
parlance. Some people with exercise and diet works best.
osteoarthritis in their hips feel referred
pain in their knees. Painkillers

Creams, gels and lotions

containing various kinds of painkillers
are popular over – the – counter

Indian J for Practising Doctor; Vol I; No. 4

treatments. Rubbed onto the painful

joint, they work either by stimulating
sensations that distract the pain or by Surgery
blocking pain nerves.
The patient might benefit from
Counter irritants distract surgery if his osteoarthritis progresses to
the sensation of pain. Some contain the point where it seriously interferes
salicylates, which are aspirin and work with his ability to move easily, causes
as local pain relievers. severe pain or deforms hisr joints.

A cream or gel that

More common types of surgery for
contains capsaicin, which is found in osteoarthritis include
cayenne pepper, interrupts substance P, a
neuro - transmitter believed to carry pain
message to the brain. Debridement The surgeon smoothes
out irregular joint surfaces, and removes
Glucocorticoid injections loose bits of bone or cartilage that could
be contributing to inflammation.
Injection directly into or
around the joint are sometimes given to Osteotomy Doctors cut and re- set
relieve pain and swelling. People have bones to realign the joint. This procedure
different reactions. For some, it gives is most often performed on the knee
immediate relief that can last for a long joint.
time. Others don’t respond at all.
Doctors don’t like to give these
injections more than four times a year Arthrodesis
because of the risk of cartilage damage Also called “ joint fusion”, the doctor
may suggest this surgery when joints are
Assistive devices seriously damaged. It is usually done on
sections of the spine but may involve
Canes, splints, braces, and other ankles and other joints.
assistive devices that help support the
joints or relieve stress and pain can help Arthroplasty
the patient get around better and reduce This is another term for total
his risk of falling. If the patient has joint replacement; the damaged joint is
osteoarthritis in his hands or wrists, removed and replaced with a plastic or
specially designed kitchen tools, metal joint. Most often done on knee and
doorknobs, and other gadgets can ease hip joints, arthroplasty can be done on
the strain of day to day tasks. any joint except those of the spine.
However, artificial joints usually have to
Warm- water exercise be replaced after 10 to 20 years, which
Swimming and doing other aerobic means they are a last choice for a young
water exercises in a heated pool can help person who would require several
you exercise without putting pressure on replacements over time.
your joints.

Indian J for Practising Doctor; Vol I; No. 4

at least 3:1. After the first year, however,

there is a female preponderance.

Role of Cefexime in Bacteriologically, urinary tract infection is

detected by growth of a significant number
Paediatric UTI of organisms (>105/ml) of a single species of
bacteria in urine.

Srividya Rao
________________________________ Clinical features

Urinary tract infection (UTI) is It must be remembered that UTI

quite common and, among the is one of the most common bacterial
ambulatory patients, is exceeded in infection in infants and children. Rapid
frequency only by respiratory and gastro- evaluation and prompt appropriate
intestinal infections. Bacterial infections evaluation is needed to prevent renal
of the urinary tract are the commonest parenchymal damage which may lead to
cause of both community acquired and hypertension and chronic renal failure.
nosocomial infections in patients
admitted to American hospitals1. UTI Unlike adults, symptoms are
accounts for about 6% of new generally non-specific in the paedriatic
consultations in general practice in age group. Infants and younger children
Europe and Scandinavia2. Women are may present with irritability, fever, poor
especially prone; about 5-6% of all feeding, vomiting or diarrhoea. The
sexually active women have bacteriuria3, typical symptoms (dysuria, frequency of
which in them is associated with urination, and flank pain) become
increased mortality.4. The cumulative common with increasing age.
prevalence of asymptomatic bacteriuria
in female increases about 1% per decade Every child with a suspicion of
throughout life5, why more women UTI requires evaluation for presence of
acquire bacteriuria with increasing age is complications and the risk of
not known. In addition to causing recurrences. History should include
considerable discomfort and ill health voiding habits. This should include
UTI, overt as asymptomatic, can lead to general physical examination, blood
complications within and outside the pressure, abdominal examination,
urinary tract. In the developing countries, genitalia, perineal sensation and deep
particularly in rural areass, the problem tendon reflexes.
is compounded by the fact that patients
are late to seek treatment. At the same Urine analysis (for microscopic
time, because of lack of facilities, vast examination) can be used to start
majority of urinary infections are treated treatment, but UTI can be confirmed
empirically and only a small minority only by urine culture. Dipsticks tests (for
can get pre-therapy testing. leucocyte esterase and nitrite tests) are
not available in India.
The incidence of urinary tract
infection varies with age and sex. In the Diagnosis depends on
first year of life, the male:female ratio is Careful history
Urine analysis

Indian J for Practising Doctor; Vol I; No. 4

Urine culture

For culture a clean catch midstream sample is collected directly into a sterile container,
after cleaning urethral orifice with soap and water. If urethral sample is not possible, a
sample is collected by suprapubic aspiration or urethral catheterization.

Definitions in Urinary Tract Infection

Bacteriuria Presence of bacteria in the urine. Asymptomatic bacteriuria has at least 105
colony forming units (CFU)/ml – termed significant bacteriuria – on 2
successive cultures with or without pyuria in a patient without symptoms.

Cystitis Inflammation of bladder. Definition of acute cystitis includes dysuria, urgency

and/or frequency with only 102 CFU/ml in mid-stream specimen.
Acute Acute bacterial infection of kidney, characterized by chills and often high
pyelonephritis fever, flank pain as well as tenderness.
Re-infection An infection with a different strain or serological type after eradication of
previous infection
Relapse Consecutive urinary infection caused by the same strain or serotype of bacteria.
Persistence Continued presence of the micro-organisms isolsated at the beginning of the
Recurrent UTI Patients with at least 2 infections within 6 months or more than 3 during a
single year in which initial episode is resolved and is followed by another
Complicated The patient has conditions that predispose or promote the development or
Infection persistence of infection.

Treatment gentamicin combination or 3rd generation

cephalosporins as cefotaxime or
Children who are too toxic and ceftriaxone).
infants <3 months should be given Children older than 3 month, who are not
parenteral antibiotics (Ampicillin & toxic, may be given oral antibiotics.
hospitalization, and prevents nosocomial

Role of cefixime

Conventionally, a young, febrile Cefixime is a 3rd-generation oral

child with UTI would be hospitalized for cephalosporin that is highly active
intravenous antibiotics. However, with against a broad range of gram negative
the availability of potent oral agents, the and some gram positive aerobic bacteria.
consensus is shifting towards ambulatory It achieves a bactericidal concentration in
management. This decreases the cost of urine of children.
treatment, avoids inconvenience of

Indian J for Practising Doctor; Vol I; No. 4

Studies conducted to compare It is concluded that for

oral and combined oral and intravenous uncomplicated UTI, cefixime is equal to
therapy in young children (1 month to 2 or more effective than other usual
year of age) showed promising results treatments, and has a low rate of side
for former route of administration. Short- effects.
term clinical outcome (sterilization of the
urine and defervescence) and long-term Cefixime is a 3rd-generation oral
morbidity (incidence of re-infection, and cephalosporin that is highly effective against
incidence & extent of renal scarring at 6 a broad-range of gram –ve and some gram
months) were comparable. In addition to +ve bacteria. In uncomplicated UTIs, it is
equal to or more effective than other usual
convenience of administration, the cost
treatments, and has a low rate of side-effects.
of therapy was reduced by half. Results of various studies performed across
Cefixime was found to be the only oral the world have indicated that cefoxime can
antibiotic which could be used alone for be used as monotherapy or switch-therapy
serious forms of UTI like acute in uncomplicated UTI in children.
Role in prophylaxis: As UTIs occur
The drug is as a monotherapy, 8 mg/kg in frequently and recurrently in children,
single dose ot two divided 12-hourly doses prompt therapy is required to avoid renal
for 14 days; double dose on the first day.
damage. Prophylaxis of re-infection is
Alternatively, an IV antibiotic may be used
for first 3 days followed by oral cefixime for
equally important. Cefixime has been
the remaining 11 days (switch-therapy). shown to be very effective in longterm
prophylaxis of urinary infections
Plasma & urine concentrations of associated with urinary anomalies. Low-
the drug are well above the reported dose cefixime prophylaxis (2mg/kg
minimal & urinary concentrations for bodyweight) was found to be as effective
most common urinary tract pathogens for as other urinary prophylactics like
up to 12 and 24 hours after nitrofurantoin.********
administration respectively.

β-lactam antibiotics inhibit peptidoglycan synthesis. Thus, like penicillin, cephalosporins

act by inhibiting cell wall synthesis. Their targets are biosynthetic enzymes,
transpeptidases, carboxypeptidases, and endopeptidases. Penicillin-binding proteins,
PBPs (pencillin-sensitive enzymes) are found in different organisms sensitive to
cephalosporins, and each bacterial species possesses a characteristic set of PBPs, with
different affinity to β-lactams. The differences of activity between oral cephaloporins are
related to their affinity for PBPs. Moraxella catarrhalis has 9 PBPs. E. coli posseses 8
different PBPs; the major target for oral cephalosporins is PBP3. 3rd generation
cephalosporins show good affinity for PBP2,4 & 5 of H. influenzae. Anti-staphylococcal
activity requires inhibition of PBP 2 & 3. The lack of activity of cefixime against S. aureus
and coagulase-negative staphylococci is due to poor binding tp PBP2. (Ed)

Indian J for Practising Doctor; Vol I; No. 4

Further reading

• Bloomsfield P, Hodson EM, Craig JC. Antibiotics for acute pyelonephritis in Children.
Cochrane Database Syst Rev 2003; 3: CD003772.
• Bryskier, AJ & Belfiglio SR. Cephalosporins: Oral. In: Antimicrobial Therapy &
Vaccines, LuVL, Merington TC (ed), 1999, Williams & Wilkins, USA; pg 710
• Fanos V, Cataldi L. Cefixime in urinary tract infections with special reference to
pediatrics. Overview. J Chemothe 2001; 13: 112-27
• Hamilton-Miller J. Cefixime for switch therapy. Chemother 1998; 44: 24-7
• Hoberman A, Wald ER, Hickey RW. Oral versus initial intravenous therapy for UTI in
young, febrile children. Pediatrics 1999; 104: 79-86
• Mamzoridi K, Kasterridou N, Peonides A. Pharmakokinetics of cefixime in children with
UTI after a single dose oral dose. Pharmacol Toxicol 1996; 78: 417-20
• Shetty, GS. UTI management in children: Advantage cefixime. Antimicrobial Update.
2003; 8-10
• Shigi Y, Matsumoto Y, Kaizo M. Mechanism of action of the new orally active
cephalosporins. Jpn J Antibiot 1984; 37: 790-96

More than 100 brand preparations of cefixime trihydrate are available in the Indian market.
The formulation is available as 200 & 100 mg tablets, 50 mg dispersible tablets (DT), and 30-ml
dry syrup [50 mg/tsf].


Joseph Lister (1827-1912), was a

British surgeon, whose discovery of
antiseptics in 1865 greatly reduced the
number of deaths due to operating-room
infections. Born in Upton, Essex, and
educated at the Universities of London
and Edinburgh, Lister began to study the
coagulation of blood and the
inflammation that followed injuries and
surgical wounds. In 1861 he was
appointed surgeon of the Glasgow Royal
Infirmary in a new surgery unit designed
to reduce gangrene and other infections,
then thought to be caused by bad air.
Despite his efforts to keep surgical
instruments and rooms clean, the
mortality rate remained close to 50 per Joseph Lister


Indian J for Practising Doctor; Vol I; No. 4

About half of all patients recovering from surgery whose experiments revealed that
died of infections before British surgeon Joseph fermentation and putrefaction were
Lister’s discovery of antiseptics in 1865. Lister caused by micro-organisms brought in
found that mortality rates dropped to 15 percent contact with organic material. By
when he used carbolic acid in the operating applying carbolic acid to instruments and
environment and on patients’ wounds. directly to wounds and dressings, Lister
reduced surgical mortality to 15 per cent
Believing infection to be caused by 1869.
by airborne dust particles, Lister sprayed Lister's discoveries in antisepsis
the air with carbolic acid (now called met initial resistance, but by the 1880s
phenol), a chemical that was then being they had become widely accepted. In
used to treat foul-smelling sewers. In 1897 he was made a baron by Queen
1865 he came upon the germ theory of Victoria, who had been his patient.
the French bacteriologist Louis Pasteur,

Phenol, formerly called carbolic acid, is an aromatic organic compound, C6H5OH. It is

weakly acidic and resembles the alcohols in structure. The colourless, needlelike crystals
of purified phenol melt at 43° C (109° F) and boil at 182° C (360° F). During storage the
crystals become pink and finally reddish brown. Phenol is soluble in organic solvents
and slightly soluble in water at room temperature, but infinitely soluble above 66° C
(150.8° F). It is a constituent of coal tar.

Phenol was first used as a disinfectant in 1867 by the British surgeon Joseph Lister
for sterilizing wounds, surgical dressings, and instruments. Dilute solutions are useful
antiseptics, but strong solutions are caustic and scarring to tissue. Less irritating and
more efficient germicides have replaced phenol, but it is widely used in the manufacture
of resins, plastics, insecticides, explosives, dyes, and detergents, and as raw material for
the production of medicinal drugs such as aspirin.

A phenol derivative, phenolphthalein (C20H 14O4), is a chemical compound

prepared by a reaction between phenol and phthalic anhydride in the presence of
sulphuric acid; it is used as an indicator for acidity or alkalinity.

The term phenol is also used for any of a group of related acidic compounds that
are hydroxyl derivatives of aromatic hydrocarbons, such as methylphenols (cresols) and

Indian J for Practising Doctor; Vol I; No. 4

Wastes from Healthcare Activities

A Consideration.

_________________Muzaffar Ahmad_________________
Health-care activities - for instance,
Chemicals - for example solvents and
immunizations, diagnostic tests, medical
disinfectants; and
treatments, and laboratory examinations -
protect and restore health and save lives. Pharmaceuticals - expired, unused,
But what about the wastes and by- and contaminated; whether the drugs
products they generate? themselves (sometimes toxic and
powerful chemicals) or their metabolites,
From the total of wastes vaccines and sera. Chemicals and
generated by health-care activities, pharmaceuticals amount to about 3% of
almost 80% are general waste waste from health-care activities.
comparable to domestic waste. The
remaining approximate 20% of wastes
Genotoxic waste - highly hazardous,
are considered hazardous materials that
mutagenic, teratogenic1 or carcinogenic,
may be infectious, toxic or radioactive.
such as cytotoxic drugs used in cancer
The wastes and by-products cover a
treatment and their metabolites; and
diverse range of materials, as the
following list illustrates: Radioactive matter, such as glassware
contaminated with radioactive
Infectious wastes - cultures and
diagnostic material or radiotherapeutic
stocks of infectious agents, wastes from
infected patients, wastes contaminated
with blood and its derivatives, discarded Wastes with high heavy metal
diagnostic samples, infected animals content, such as broken mercury
from laboratories, and contaminated thermometers. Genotoxic waste,
materials (swabs, bandages) and radioactive matter and heavy metal
equipment (disposable medical devices content represent about 1% of the total
etc.); and waste from health-care activities.
Anatomic - recognizable body parts The major sources of health-care
and animal carcasses. Infectious and waste are hospitals and other health-care
anatomic wastes together represent the establishments, laboratories and research
majority of the hazardous waste, up to centres, mortuary and autopsy centres,
15% of the total waste from health-care animal research and testing laboratories,
activities. blood banks and collection services, and
nursing homes for the elderly.
Sharps - syringes, disposable scalpels
and blades etc. Sharps represent about High-income countries can
1% of the total waste from health-care generate up to 6 kg of hazardous waste
activities. per person per year. In the majority of

Indian J for Practising Doctor; Vol I; No. 4

low-income countries, health-care waste and needles for injections is particularly

is usually not separated into hazardous or common in certain African, Asian and
non-hazardous waste. In these countries, Central and Eastern European countries.
the total health-care waste per person per Regarding injection practices, public
year is anywhere from 0.5 to 3 kg. health authorities in West Bengal, have
recommended a shift to re-usable glass
syringes, as the disposal requirements for
HEALTH IMPACTS disposable syringes could not be
Health-care waste is a reservoir
of potentially harmful micro-organisms In developing countries, additional
which can infect hospital patients, hazards occur from scavenging on waste
health-care workers and the general disposal sites and manual sorting of the
public. Other potential infectious risks waste recuperated at the back doors of
include the spread of, sometimes health-care establishments. These
resistant, micro-organisms from health- practices are common in many regions of
care establishments into the environment. the world. The waste handlers are at
These risks have so far been only poorly immediate risk of needle-stick injuries
investigated. Wastes and by-products can and other exposures to toxic or infectious
also cause injuries, for example radiation materials.
burns or sharps-inflicted injuries;
poisoning and pollution, whether through
the release of pharmaceutical products, Vaccine waste
in particular, antibiotics and cytotoxic
drugs, through the waste water or by In June 2000, six children were
toxic elements or compounds such as diagnosed with a mild form of smallpox
mercury or dioxins. (vaccinia virus) after having played with
glass ampoules containing expired
smallpox vaccine at a garbage dump in
Vladivostok (Russia). Although the
Sharps infections were not life-threatening, the
vaccine ampoules should have been
Throughout the world every year
treated before being discarded.
an estimated 2 000 million injections are
administered. And not all needles and
syringes are properly disposed of,
generating a considerable risk for injury Radioactive wastes
and infection and opportunities for re-
use. The use of radiation sources in
medical and other applications is
Worldwide, 8-16 million hepatitis B, widespread throughout the world.
2.3 to 4.7 million hepatitis C and 80 Occasionally, the public is exposed to
000 to 160 000 HIV infections are radioactive waste, usually originating
estimated to occur yearly from re-use of from radiotherapy treatments, that has
syringe needles without sterilization. not been properly disposed of. Serious
Many of these infections could be accidents have been documented in
avoided if syringes were disposed of Goiânia, Brazil in 1988 in which four
safely. The re-use of disposable syringes people died from acute radiation

Indian J for Practising Doctor; Vol I; No. 4

syndrome and 28 suffered serious Only modern incinerators are able to

radiation burns. Similar accidents work at 800-1000°C, with special
happened in Mexico City in 1962, emission-cleaning equipment, can ensure
Algeria in 1978, Morocco in 1983 and that no dioxins and furans (or only
Ciudad Juárez in Mexico in 1983. insignificant amounts) are produced.
Smaller devices built with local materials
Risks associated with other and capable of operating at these high
fractions of health-care wastes, in temperatures are currently being field-
particular blood waste and chemicals, tested and implemented in a number of
have been relatively poorly assessed, and countries.
need to be strengthened. In the
meantime, precautionary measures need At present, there are practically no
to be taken. environmentally-friendly, low-cost
options for safe disposal of infectious
wastes. Incineration of wastes has been
RISKS ASSOCIATED WITH WASTE widely practised, but alternatives are
DISPOSAL becoming available, such as autoclaving,
chemical treatment and microwaving,
Although treatment and disposal and may be preferable under certain
of health-care wastes aim at reducing circumstances. Landfilling may also be a
risks, indirect health risks may occur viable solution for parts of the waste
through the release of toxic pollutants stream if practised safely. However,
into the environment through treatment action is necessary to prevent the
or disposal. important disease burden currently
Landfilling can potentially result in created by these wastes.
contamination of drinking water. In addition, perceived risks
Occupational risks may be associated related to health-care waste management
with the operation of certain disposal may be significant. In most cultures,
facilities. Inadequate incineration, or disposal of health-care wastes is a
incineration of materials unsuitable for sensitive issue and also has ethical
incineration can result in the release of dimensions.
pollutants into the air. The incineration
of materials containing chlorine can
generate dioxins and furans, which are
classified as possible human carcinogens FAILURE
and have been associated with a range of
adverse effects. Incineration of heavy The absence of waste
metals or materials with high metal management, lack of awareness about
contents (in particular lead, mercury and the health hazards, insufficient financial
cadmium) can lead to the spread of and human resources and poor control of
heavy metals in the environment. waste disposal are the most common
Dioxins, furans and metals are persistent problems connected with health-care
and accumulate in the environment. wastes. Many countries do not have
Materials containing chlorine or metal appropriate regulations, or do not enforce
should therefore not be incinerated. them. An essential issue is the clear
attribution of responsibility of
appropriate handling and disposal of

Indian J for Practising Doctor; Vol I; No. 4

waste. According to the ‘polluter pays’ Selection of safe and

principle, this responsibility lies with the environmental-friendly management
waste producer, usually being the health- options, to protect people from
care provider, or the establishment hazards when collecting, handling,
involved in related activities. storing, transporting, treating or
disposing of waste.
Government commitment and
support is needed to reach an overall and
Improvements in health-care waste long-term improvement of the situation,
management rely on the following key although immediate action can be taken
elements: locally.
The build-up of a comprehensive Health-care waste management is
system, addressing responsibilities, an integral part of health-care, and
resource allocation, handling and creating harm through inadequate waste
disposal. This is a long-term process, management reduces the overall benefits
sustained by gradual improvements; of health-care.
Awareness raising and training
about risks related to health-care
waste, and safe and sound practices;

provoking factor. Children with weak rectal
musculature such as those with
Reduction of rectal meningomyelocele, prune belly syndrome,
prolapse and extrophy of the bladder are predisposed
Shabnam Bashir to rectal prolapse. Procidentia in an older
______________________________ child warrants an investigation for disease
associated with this condition such as cystic
fibrosis, rectal polyps or illnesses associated
Rectal prolapse is a rare condition with ascites or a sustained cough.
characterized by an abnormal protrusion of
the rectum through anus. Partial prolapse Patients with rectal prolapse present
involves the mucosa and submucosa and is with a painless protrusion from the rectum
most common in children who are less than 3 that often resolves spontaneously, folds of
years of age. Peak incidence occurs in the 1 mucosa protruding through the anus. Full
to 2 year age group and may be a result of thickness rectal prolapse must be
recently acquired erect posture and voluntary differentiated from hemorrhoids, a prolapsed
control over defecation. Prolapse of entire rectal polyp, or an intussussception extruded
rectal wall is termed procidentia and occurs via the anus.
more often both in older children with
underlying disease and in debilitated elderly Indications of reduction
adults. Manual reduction of a rectal
prolapse that has not reduced spontaneously
In most cases of childhood rectal is always indicated. Reduction is also
prolapse, the cause is unknown. Diarrhoea or necessary if the prolapse is prolonged or if
straining with bowl movement is a common passive congestion or bleeding has occurred.

Indian J for Practising Doctor; Vol I; No. 4

Unlike with adults, simple mucocal prolapse examination to ensure that the reduction is
in the pediatric population does not require complete. Instruct the patient to lie on his or
surgical evaluation unless it is recurrent or her side after the procedure. If the prolapse
recalcitrant to routine management. Prolapse recurs immediately, tape the buttocks
as a complication of anorectal surgery temporarily.
requires specialized surgical procedures for
its correction. Surgery may be warranted if there is
no response to conservative management..
Contraindications to reduction Surgery includes peri-rectal injection of
There are no absolute sclerosing agents with which many authors
contraindications for the reduction of a rectal report an excellent success rate. Major
prolapse. If vascular compromise of the surgical procedures as performed on adults
prolapsed segment is evident, perform are rarely necessary in children.
reduction immediately. Admit these patients
to the hospital because they are at risk for Remarks
bowel perforation. In the case of acute rectal prolapse in
children, it is first necessary to ascertain the
Complications diagnosis by distinguishing it from
The rectal prolapse itself may be hemorrhoids, a prolapsed polyp, or extruded
complicated by bleeding or ulceration. intussusception. Hemorrhoids occur
Rarely, the prolapsed bowl can become primarily in adolescents, are purple in color,
gangrenous if the prolapse is prolonged. and are contiguous with one wall of the anal
Rupture of a vascularly compromised mucosa so that a palpating finger cannot
segment could occur during manual endfile?? the entire hemorrhoid. Prolapsed
reduction but has not been reported in the polyps often are palpable within the rectum
pediatric literature. as a small growth on stalk. Again they are
from a single wall of the rectum and not
Equipment from the entire circumference.
The only equipment required for reducing a Intussusception is a diagnosis suspected on
rectal prolapse are gloves, a lubricant and some
clinical grounds in a lethargic child who is
gauze pads. A sedative, that is appropriate for the
age of the patient and the level of anxiety, may be vomiting. On physical examination, the
necessary circular folds of the mucosa of the
intussusception may appear as a full
Techniques thickness rectal prolapse. The extent of the
Place the adequately sedated patient prolapse and the clinical history and
in a prose position over the parent’s lap or in examination lead to the diagnosis of
the knee chest position on the examination intussusception. After manual reduction, it
table. Use lubricated gloves to place 4x4 is of utmost importance to address the
gauze pads at the 3 and 9 o’ clock position of primary problem. Because straining with
the prolapse. Gauze improves grip on the stools is the most common inciting event for
mucosa. Apply firm, gentle pressure to rectal prolapse, prescribe stool softeners and
reduce the direction of the prolapse. Such lubricants such as mineral oil. In addition,
pressure can be achieved by pressing on the recommend a child toilet seat for toilet-
prolapse with both thumbs while stabilizing trained children to reduce the spreading of
the hands on the buttocks (fig 1); alternately, the gluteal folds during defecation. Patients
the index and middle fingers may be used to with recurrent prolapse require a workup for
compress the prolapse while an assistant cystic fibrosis and a barium enema to rule
holds the patient As such as 15 minutes of out rectal polyps or other lesions that may
pressure is often required to complete the act as a lead point for the prolapse.
reduction. Perform a digital rectal *************************************

Indian J for Practising Doctor; Vol I; No. 4

Special Supplement

Drug Use
in Hepatic Impairment*

*(based on WHO

Indian J for Practising Doctor; Vol I; No. 4

Drug use in Hepatic Impairment

Liver disease may alter the response to drugs. However, the hepatic reserve
appears to be large and liver disease has to be severe before important changes in drug
metabolism take place. The ability to eliminate a specific drug may or may not correlate
with liver' s synthetic capacity for substances such as albumin or clotting factors, which
tends to decrease as hepatic function declines. Unlike renal disease, where estimates of
renal function based on creatinine clearance correlate with parameters of drug elimination
such as clearance and half-life, routine liver function tests do not reflect actual liver
function but are rather markers of liver cellular damage.

The altered response to drugs in liver disease can include all or some of the following

• Impaired intrinsic hepatic eliminating (metabolizing) capacity due

to lack of or impaired function of hepatocytes.

• Impaired biliary elimination due to biliary obstruction or transport

abnormalities (for example, rifampicin is excreted in the bile
unchanged and may accumulate in patients with intrahepatic or
extrahepatic obstructive jaundice).

• Impaired hepatic blood flow due to surgical shunting, collateral

circulation or poor perfusion with cirrhosis and portal

• Altered volume of distribution of drugs due to increased

extracellular fluid (ascites, oedema) and decreased muscle mass.

• Decreased protein binding and increased toxicity of drugs highly

bound to proteins (for example phenytoin) due to impaired
albumin production.

• Increased bioavailability through decreased first-pass metabolism.

• Decreased bioavailability due to malabsorption of fats in

cholestatic liver disease.

In severe liver disease, increased sensitivity to the effects of some drugs can
further impair cerebral function and may precipitate hepatic encephalopathy (for example
morphine, pethidine). Oedema and ascites in chronic liver disease may be exacerbated by

Indian J for Practising Doctor; Vol I; No. 4

drugs that cause fluid retention (for example acetylsalicylic acid, ibuprofen, prednisolone,

Usually drugs are metabolized without injury to the liver. A few drugs cause dose-
related hepatotoxicity. However, most hepatotoxic reactions to drugs occur only in rare
persons and are unpredictable. In patients with impaired liver function the dose-related
hepatotoxic reaction may occur at lower doses whereas unpredictable reactions seem to
occur more frequently. Both should be avoided.

Information to help prescribing in hepatic impairment is included in the following

table. The table contains only those drugs that need dose adjustment. However, absence
from the table does not automatically imply safety as for many drugs data about safety are
absent; it is therefore important to also to refer to the individual drug entries.

Table of drugs to be avoided or used with caution in liver disease

Drug Comment

Abacavir No dosage adjustment required in mild hepatic impairment;

avoid in moderate or severe hepatic impairment

Acetylsalicylic acid Avoid-increased risk of gastrointestinal bleeding

Alcuronium Possibly slower onset, higher dose requirement and

prolonged recovery time

Allopurinol Reduce dose

Aluminium hydroxide In patients with fluid retention, avoid antacids containing

large amounts of sodium; also avoid those causing
constipation (can precipitate coma)

Aminophylline Reduce dose

Amitriptyline Sedative effects increased (avoid in severe liver disease)

Amoxicillin + Clavulanic acid

Monitor liver function in liver disease. Cholestatic jaundice
reported either during or shortly after treatment; more
common in patients over the age of 65 years and in males;
duration of treatment should not usually exceed 14 days

Azathioprine May need dose reduction

Bupivacaine Avoid (or reduce dose) in severe liver disease

Indian J for Practising Doctor; Vol I; No. 4

Carbamazepine Metabolism impaired in advanced liver disease

Ceftriaxone Reduce dose and monitor plasma concentration if both

hepatic and severe renal impairment

Chloral hydrate Can precipitate coma (avoid in severe impairment)

Chloramphenicol Avoid if possible-increased risk of bone-marrow depression;

reduce dose and monitor plasma-chloramphenicol

Chlorphenamine Sedation inappropriate in severe liver disease-avoid

Chlorpromazine Can precipitate coma; hepatotoxic

Ciclosporin May need dose adjustment

Cimetidine Increased risk of confusion; reduce dose

Ciprofloxacin Hepatitis with necrosis reported

Clindamycin Reduce dose

Clomifene Avoid in severe liver disease

Clomipramine Sedative effects increased (avoid in severe liver disease)

Clonazepam Can precipitate coma

Cloxacillin Cholestatic jaundice may occur up to several weeks after

treatment has been stopped; administration for more than 2
weeks and increasing age are risk factors
Codeine Avoid or reduce dose-may precipitate coma

Contraceptives, oral Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Cyclophosphamide Reduce dose

Cytarabine Reduce dose

Dacarbazine Dose reduction may be required in mild to moderate liver

disease; avoid if severe

Daunorubicin Reduce dose

Indian J for Practising Doctor; Vol I; No. 4

Dextromethorphan Avoid or reduce dose-may precipitate coma

Diazepam Can precipitate coma

Didanosine Insufficient information but consider dose reduction

Doxorubicin Reduce dose according to bilirubin concentration

Doxycycline Avoid (or use with caution)

Efavirenz In mild to moderate liver disease, monitor liver function;

avoid in severe hepatic impairment

Ergometrine Avoid in severe liver disease

Ergotamine Avoid in severe liver disease-risk of toxicity increased

Erythromycin May cause idiosyncratic hepatotoxicity

Ether, anaesthetic Avoid

Etoposide Avoid in severe hepatic impairment

Fluconazole Toxicity with related drugs

Fluphenazine Can precipitate coma; hepatotoxic

Furosemide Hypokalaemia may precipitate coma (use potassium-sparing

diuretic to prevent this); increased risk of hypomagnesaemia
in alcoholic cirrhosis

Glibenclamide Increased risk of hypoglycaemia in severe liver disease;

avoid or use small dose; can produce jaundice

Griseofulvin Avoid in severe liver disease

Haloperidol Can precipitate coma

Halothane Avoid if history of unexplained pyrexia or jaundice

following previous exposure to halothane

Heparin Reduce dose in severe liver disease

Hydralazine Reduce dose

Indian J for Practising Doctor; Vol I; No. 4

Hydrochlorothiazide Avoid in severe liver disease; hypokalaemia may

precipitate coma (potassium-sparing diuretic can prevent
this); increased risk of hypomagnesaemia in alcoholic

Ibuprofen Increased risk of gastrointestinal bleeding and can cause

fluid retention; avoid in severe liver disease

Indinavir Reduce dose to 600 mg every 8 hours in mild to moderate

hepatic impairment; not studied in severe impairment

Iopanoic acid Avoid in severe hepatic disease

Isoniazid Avoid if possible-idiosyncratic hepatotoxicity more


Levonorgestrel Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Lidocaine Avoid (or reduce dose) in severe liver disease

Lopinavir with Ritonavir Avoid oral solution because of propylene glycol content; use
capsules with caution in mild to moderate hepatic
impairment and avoid in severe impairment

Magnesium hydroxide Avoid in hepatic coma if risk of renal failure

Magnesium sulfate Avoid in hepatic coma if risk of renal failure

Medroxyprogesterone Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Mefloquine Avoid for prophylaxis in severe liver disease

Metformin Avoid-increased risk of lactic acidosis

Methotrexate Dose-related toxicity-avoid in non-malignant conditions (for

example, rheumatic disorders)

Methyldopa Manufacturer advises caution in history of liver disease;

avoid in active liver disease

Metoclopramide Reduce dose

Metronidazole In severe liver disease, reduce total daily dose to one-third

and give once daily

Indian J for Practising Doctor; Vol I; No. 4

Minocycline Avoid (or use with caution)

Morphine Avoid or reduce dose-may precipitate coma

Nalidixic acid Partially conjugated in liver

Nelfinavir No information available-manufacturer advises caution

Nevirapine No information available-manufacturer advises avoid

Nifedipine Reduce dose

Nitrofurantoin Cholestatic jaundice and chronic active hepatitis reported

Norethisterone Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Ofloxacin Reduce dose in severe liver disease

Paracetamol Dose-related toxicity-avoid large doses

Pentavalent antimony compounds

Increased risk of liver damage and hepatic failure in pre-
existing liver disease

Pethidine Avoid or reduce dose-may precipitate coma

Phenobarbital May precipitate coma

Phenytoin Reduce dose to avoid toxicity

Prazosin Initially 500 micrograms daily; increased with caution

Prednisolone Adverse effects more common

Procainamide Avoid or reduce dose

Procarbazine Avoid in severe hepatic impairment

Promethazine Avoid-may precipitate coma in severe liver disease;


Propranolol Reduce oral dose

Propylthiouracil Reduce dose;

Indian J for Practising Doctor; Vol I; No. 4

Pyrazinamide Avoid-idiosyncratic hepatotoxicity more common

Rifampicin Impaired elimination; may be increased risk of

hepatotoxicity; avoid or do not exceed 8 mg/kg daily

Saquinavir Plasma concentration possibly increased; manufacturer of

gel-filled capsules advises caution in moderate hepatic
impairment and avoid in severe impairment; manufacturer
of capsules containing saquinavir mesilate advises caution
in severe impairment

Sodium nitroprusside Avoid in severe liver disease

Sulfamethoxazole + Trimethoprim
Manufacturer advises avoid in severe liver disease

Suxamethonium Prolonged apnoea may occur in severe liver disease due to

reduced hepatic synthesis of pseudocholinesterase

Testosterone Preferably avoid-possibility of dose-related toxicity and fluid


Theophylline Reduce dose

Thiopental Reduce dose for induction in severe liver disease

Valproic acid Avoid if possible-hepatotoxicity and hepatic failure may

occasionally occur (usually in first 6 months)

Verapamil Reduce oral dose

Vinblastine Dose reduction may be necessary

Vincristine Dose reduction may be necessary

Warfarin Avoid in severe liver disease, especially if prothrombin time

already prolonged

Zidovudine Accumulation may occur