Tropical Infection

Diseases
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

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Area kompetensi

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TYPHOID FEVER AND

PARATYPHOID FEVER

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

GSH - Tropmed - 2010

Typhoid and Paratyphoid

Definition
Etiology
Pathogenesis
Epidemiology
Clinical
manifestations
The laboratory and
other examinations

Complications
Diagnosis and
differential
diagnosis
Prognosis
Treatment
Paratyphoid Fever

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Definition of Typhoid fever

Acute enteric & sistemic infectious disease
caused by Salmonella typhi (S.Typhi).
Major symptom : prolonged fever, relative
bradycardia, apathetic facial expressions,
roseola, splenomegaly, hepatomegaly,
leukopenia.

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S. typhi
Serotype : D group of Salmonella, Gramnegative, rod, non-spore, flagella (+),
produced endotoxin
Antigens: located in the cell capsule :

H (flagellar antigen).

O (Somatic or cell wall antigen).

Vi (polysaccharide virulence)
Hidup 2-3 minggu dalam air. 1-2 bulan dalam
tinja. Mati dengan cepat di musim panas,
ketahanan terhadap pengeringan dan
pendinginan
Widal test : identified antigen H & O
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A schematic diagram of a single Salmonella typhi cell

showing the locations of the H (flagellar), O (somatic), and
Vi (K envelope) antigens.
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Salmonella enterica.

Epidemiology

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Transmission
Rute: rute fecal-oral
Risiko: kontak dekat dengan pasien
atau operator
Media: air dan makanan yang
terkontaminasi
Vector: lalat dan kecoak.

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Pathogenesis(1)
Perlu setidaknya 105bacteria untuk
mengembangkan infeksi
Incubation period :
Agent ingested orally stomach barrier
(some Eliminated) masuk kedalam usus
halus penetrate the mucus layer enter
mononuclear phagocytes of ileal peyer's
patches and mesenteric lymph nodes
proliferate in mononuclear phagocytes
menyebar ke darah initial bacteremia
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Pathogenesis(2)
Second bacteriemia
After 1st bacteriemia masuk ke limpa,

hati dan sumsum tulang (sistem

retikulo-endotel) proliferasi lebih lanjut
banyak bakteri memasuki darah

Recovery

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S.Typhi.
2nd bacteremia

liver spleen gall

BM ,ect
early stage&acme stage
(1-3W

stomach

(mononuclea

Bac. In gall

r
phagocytes )

Bac. In
feces

Lower
ileum

peyer's patches &

mesenteric lymph nodes
Enterorrhagi
a, intestinal
perforation

LN Proliferate,
swelling, necrosis
defervescence
stage
3-4w

thoracic
duct

S.Typhi eliminated
convalvescence stage
(4-5w)
1st bacteremia
(Incubation stage)
10-14d

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Pathology (lower ileum)

(1)

Lesi paling khas: ulserasi dari mukosa di

wilayah patch yang Peyer usus kecil
Tahap Hiperplasia (1 minggu):
pembengkakan jaringan limfoid dan
proliferasi makrofag.
Tahap Necrosis (2 minggu): nekrosis
pembengkakan kelenjar getah bening atau
folikel soliter.
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Pathology (lower ileum)

(2)

Tahap ulserasi (minggu ke-3):

penumpahan nekrosis jaringan dan
pembentukan ulkus perdarahan
usus, perforasi.
Tahap penyembuhan (dari
minggu ke-4): penyembuhan
ulkus, tidak ada cicatrices dan tidak
ada kontraksi
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Clinical manifestations(1)
Incubation period: 7 14 hari (3
60 hari )
Periode / tahap awal (minggu
pertama)
- Insidious onset.
- Fever up to 39~400C pada 5~7 hari
- Menggigil Insidious onset, lelah, sakit
tenggorokan, batuk, perut tidak nyaman
dan sembelit dll.
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Clinical manifestations(2)
The fastigium stage (during 2nd & 3rd
weeks)
Demam tinggi yg berlanjutan, partly
remittent fever or irregular fever (10
14 days)
Gastro-intestinal symptoms:
anorexia nyeri abdomen, diarrhea
or constipation
Neuropsychiatric manifestations:
bingung, respon tumpul/lambat,
delirium and coma or meningism
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Clinical manifestations(3)
Circulation system: relative
bradycardia or dicrotic pulse.
Splenomegaly, hepatomegaly toxic
hepatitis.
roseola : 30%, maculopapular rash a
faint pale color, slightly raised round
or lenticular, fade on pressure 2-4 mm
in diameter, kurang dari 10 in number
on the trunk, menghilang dalam 2-3
days.
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 First week: The disease classically presents with

step-ladder fashion rise in temperature (40 - 41C) over
4 to 5 days, accompanied by headache, vague
abdominal pain, and constipation.
Second week: Between the 7 th -10 th day of
illness, mild hepato-splenomegally occurs in majority of
patients. Relative bradycardia may occur and rose-spots
may be seen.
Third week: The patient will appear in the
"typhoid state" which is a state of prolonged apathy,
toxaemia, delirium, disorientation and/or coma.
Diarrhoea will then become apparent. If left untreated
by this time, there is a high risk (5-10%) of intestinal
hemorrhage and perforation.

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Clinical manifestations(4)
Defervescence stage
fever & most symptoms resolve by
the forth week of infection.
Fever come down, gradual
improvement in all symptoms and
signs, but still danger.

Convalescence stage
the fifth week. disappearance of
all symptoms, but can relapse
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Clinical spectrum(1)
Mild infection:
very common, symptom & signs mild, good
general condition, short period of diseases
temperature is 380C
recovery expected in 1~3 weeks
seen in early antibiotics users, young children,
easy to misdiagnose
Persistent infection: diseases continue than 5
weeks
Ambulatory infection: mild symptoms, early
intestinal bleeding or perforation.
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Clinical spectrum(2)
Fulminate infection:
rapid onset, severe toxemia and septicemia.
High fever, chill,circulation failure, shock,
delirium, coma, myocarditis, bleeding and
other complications, DIC
Sepsis & shock
Asymtomatic carrier

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Recrudescence
Clinical manifestations reappear
Less severe than initial episode
Its temperature recrudesce when
temperature start to step down but
abnormal in the period of 2-3 weeks and
persist 5~7 days then back to normal.
Seen in patients with short therapy of
antibiotics.
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Relapse
Serum positive of S.typhi after 1 3
weeks of temperature down to normal.
Symptom and signs reappear
the bacilli have not been completely
removed
Some cases relapse more than once

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Laboratory findings (1)

Routine examinations :
Leukocytopenia
Recovery with improvement of diseases decreased in relapse
Bacteriological examinations:
Blood culture:
The most common use
80~90% positive during the first 2 weeks of illness
50% in 3rd week
Re-positive when relapse and recrudesce
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Laboratory findings (1)

The bone marrow culture
The most sensitive test, specially in patients pretreated with
antibiotics.
Urine and stool cultures (after 1st week)
Increase the diagnostic yield, less frequently positive
Stool culture better in 3~4 weeks
Serological tests (widal test) :
5 types of antigens O, H, and paratyphoid fever flagella A,B,C)
Appear during 1st-2nd week
70% positive in 3~4 weeks and can prolong to several months, in
some cases, antibodies appear slowly, or remain at a low level
10~30%) negative at all.
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Widal test interpretation

"O/H" agglutinin antibody titer 1:160 or "O" 4
times higher supports a diagnosis
"O" rises alone, not "H : early of the disease

Only "H" positive, but "O" negative :

nonspecifically elevated by immunization or
previous infections or anamnestic reaction.

Antibody level maybe lower when have used

antibiotics early.
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Complications
Intestinal hemorrhage
Appear during the 2nd-3rd week
Often caused by unsuitable food, diarrhea et al
Serious bleeding : sudden drop in temperature, rise in pulse,
signs of shock followed by melena/hematochezia
Intestinal perforation:
Appear during 2-3 week, involve lower end of ileum
Abdominal pain, diarrhea, intestinal bleeding, sweating, drop in
temperature, and increase in pulse rate, rebound tenderness,
reduce or disappear bowel sound, liver dumping dissapear ,
leukocytosis (sign of peritonitis)
Free air under x-ray.
Toxic hepatitis : 1st-3rd weeks , hepatomegaly, ALT elevated
Others : Myocarditis, encephalopathy, HUS, cholecystitis,
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meningitis, nephritis, etc

Differential diagnosis
Viral infections
Malaria
Leptospirosis
Louse borne typhus
Riketsiosis
Gram negative bacilli septicemia
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Prognosis
Case fatality 0.5 1%, espesially
in old ages & infant
About 3% of patients become
fecal chronic carriers

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Management(1)
General management
Bed rest, good nursing care and
supportive treatment
Close monitoring VS, abdominal
condition and stool .
Easy digested food or half-liquid food,
good hidration (enteral / par-enteral)
Antipiretic drugs
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Management(2)
Antibiotics
Chloramphenicol : 500 mg, q6h (2 weeks) po/iv
Thiamphenicol : 500 mg, q6h (10-14 days) po
Cotrimoxazole : 2 adult tab, bid (2 weeks) po
Ampicillin / amoxycillin : 50-150 mg/kg BW in 3-4
divided dose (2 weeks) po/iv
3rd generation Cephalosporin :
Ceftriaxone 2-4 g iv single/divided dose (3-5 days)
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Management(3)
Quinolone :
Norfloxacin : 400 mg, bid (2 weeks)
po
Ciprofloxacin : 500 mg, bid (7 days)
po
Ofloxacin : 400 mg, bid (7 days)
Pefloxacin : 400 mg, OD (7 days)
Corticosteroid
Only for toxic/sepsis condition
Dexamethasone 5 mg, tid iv
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Paratyphoid fever A,B,C

Caused by Salmonella paratyphoid A,B,C.
respectively.
In no way different from typhoid fever in
epidemiology, pathogenesis, pathology,
clinical manifestations, diagnosis,
treatment

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Homework
Vaccination for S. Typhi, is it
effective ?
Gall culture, what make it a gold
standard test & how to perform it ?
New serologic test for S. Thypi

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Yersinia infection
Focus on Pes / Plaque
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

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Pes / plaque
A zoonotic infection cause by Yersinia
pestis, humans are accidental host
Yersinia pestis : gram negative bacilli,
facultatif anerob, susceptible to
drying, produce endotoxin (lipid A
Natural reservoir : tikus, tupai, kelinci
& hewan domestik
Menusuk oleh gigitan kutu, kontak
langsung dengan jaringan yang
terinfeksi (darah, unggas) atau
inhalasi aerosol

Epidemiology of Plague
Outbreaks are cyclical corresponding
to rodent reservoir and arthropod
vector populations
Plague recorded more than 2000
years ago
The pandemics :
14th century; Black Death; 25
million dead in Europe alone (>1/4
of entire population)
1990s; From Burma, China, Hong
Kong spread to other continents via

Clinical evaluation
Clinical Forms of Plague
Bubonic plague : with swollen and
painful axillary & inguinal lymph nodes
(buboes)
Transmitted from mammalian
reservoirs by flea (arthropod) bites or
contact with contaminated animal
tissues
Pneumonic plaque
Person-to-person spread
Diagnosis : culture & isolation
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TETANUS
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

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Introduction
Tetanus is an illness characterized by
an acute onset of hypertonia, painful
muscular contractions (usually of the
muscles of the jaw and neck), and
generalized muscle spasms coused by
clostridium tetani infection
Despite widespread immunization of
infants and children in the United
States since the 1940s, tetanus still
occurs in the United States.

Clostridium tetani
Genus Clostridium : gram-positive, sporeforming species, several of which are
able to produce disease in humans.
Most species are obligate anaerobes,
some will grow under microaerophilic
conditions.
Natural habitat: soil and the intestinal
tracts of animals and humans.
Very active metabolisms, ferment a
variety of sugars, very short generation
times.

C. tetani

Large, spore-forming, motile, obligate anaerobic

bacillus, gram positive, drumstick appearence (see
above)
Ferments: proteins or amino acids.
Produces: acetic acid, fatty acids, NH3, CO2, H2, and a

Clostridium
tetani
Gram Stain

NOTE: Round terminal spores give cells a

drumstick or tennis racket appearance.

Tetanus : characteristic
Does not follow typical tranmission from host to host.
Soils or materials in contact with animal wastes are
usually heavily contaminated with C. tetani
Tetanus often resulted from wounds received in battle.
In clean wounds with good blood supply and high
oxygen tension, germination rarely occurs.
In necrotic and infected wounds, anaerobic conditions
will permit germination.
Contaminated puncture wounds can be particularly
dangerous, especially when a foreign body is present.
Spores may occasionally lay dormant in a healed
wound for months or years; trauma to the area may
then cause germination and disease.

Symptoms & signs

Tetanus is an acute, potentially deadly,
systemic infection characterized by
painful involuntary contraction of
skeletal muscles.
Other symptoms include
Febrile (feverish), irritability, heavy
sweating
A stiff neck, a tight jaw
(lockjaw/trismus)
Facial muscle spasms (risus
sardonicus) and difficulty swallowing

Mechanism of Action
of Tetanus Toxin

Risus sardonicus
A soldier dying from tetanus. Painting by Charles Bell

In advanced stages, tetanus

spasms can break bones.
Respiratory complications are
common and death rates high,
especially in children and
elderly persons.

Opisthotonos
(spastic paralysis of the back)

Opisthotonos in Tetanus
Patient

Diagnosis of tetanus
Made on the basis of the clinical
manifestation, and the patients
history may indicate inadequate
immunization.
Since C. tetani is a common
contaminant of wounds and may be
found in patients who do not develop
tetanus isolation of the bacteria
from a patient may not be diagnostic.

Treatment
Antitoxin (tetanus immune globulin) to neutralized
toxin should be administered immediately.
Wounds should be debrided to remove dead
tissue or foreign bodies.
Antibiotics should be given to inhibit growth of C.
tetani.
A tetanus toxoid booster immunization should be
given to patients who have not received one
within the last 5 years.
If spasms occur, antispasmodic drugs should be
used and respiration maintained by a breathing
As soon if
asnecessary.
clinical tetanus is suspected, steps to
apparatus

neutralize existing toxin and prevent the formation of

new toxin must begin.

Prevention
Tetanus carries a 35% mortality rate,
making prevention very important!
Death may occur from tetanus, often
from cardiac (heart) and respiratory
(lung) effects or secondary
complications from the infection
The best course is childhood
immunizations, with consistent booster
doses, and prompt cleaning of wounds with
hydrogen peroxide.