1

Theme of the lesson:

MALARIA.

The Activator: plasmodiums of 4 kinds:

Pl.vivax - the activator of a three-day malaria;
Pl.malaria - the activator of a four-day malaria;
Pl.falciparum - the activator of tropical malaria;
Pl.ovale - the activator of oval - malaria.
Plasmodium passes two cycles of development: nonsexual - schizogonia - carries
out in an organism of the person and sexual - sporogonia - proceeds in an organism of a
mosquito of sort Anopheles. At a sting a mosquito of the ill person together with blood
unripe sexual forms of plasmodium - gametes get in a stomach of a mosquito, passes a
sexual cycle of development. In 7-10 days the mosquito becomes infected and at next
hemosuction injects plasmodium with saliva in blood to the person. In a human body in
the beginning tissue schizogonia with development of plasmodiums in Kupferov’s cells
of a liver occurs. Its duration at Pl.falciparum makes 6 day, at Pl.vivax - 8 day,
Pl.malaria - 15 day, Pl.ovale - 9 days. It corresponds to the incubatory period of the
disease. At three-day and an oval - malaria plasmodiums can remain in a liver in a
dozing condition for along time - bradysporozonts. They can cause diseases and its
relapses in some months - 1-2 years.
Plasmodium enters from the hepatic cells in blood and strike root in erythrocytes.
Erythrocytic cycle of schizogonia with growth of plasmodium and division on affiliated
merozoites begins. One cycle of erythrocytic schizogonia at Pl.falciparum and Pl.ovale
lasts 48 hours, at Pl.malaria - 72 hours. Then erythrocyte collapses, young merozoites
from plasma again strike the erythrocytes, and the cycle of their growth and division
repeats, being accompanied by destruction of erythrocytes and anemia.
Alongside with it from a part of merozoites man's and female sexual cells –
gametes - are formed. To the further development in an organism they are not capable,
and, getting in an organism of a mosquito - carrier, pass a sexual cycle of development.
The mosquito becomes infectious.

Epidemiology
The source of malaria is the person - the patient or parasitocarrier. The
mechanism of infection is through a sting of the mosquito having sporozoits in salivary
glands. Infection is possible at hemotransfusions from the donor -parasitocarrier. In this
situation only erythrocytic schizogonia (without tissue and relapses) arises.

Pathogenesis
All manifestations of malaria are connected to duplication of the parasite in
erythrocytes, their destruction and emission in blood of merozoites, toxins, the products
of metabolism having pyrogenic properties. There is an angiospasm (in clinic it is shown
 2
by a fever), and then their dilation with fever and hyperhidrosis. Permeability of a
vascular wall raises, blood flow slows down, and parasitic thrombi are formed.
Stagnation of blood flow in a liver leads to disturbance of synthesis of factors of
coagulation, an opportunity of development of the DIC-syndrome. Expressiveness of
hemolysis is connected also to formation of circulating immune complexes which are
fixed to a surface of healthy erythrocytes. In result of hemolysis there is anemia,
reticulo-endothelial system (RES) is activated, especially RES of spleen that results in
increase of its sizes. Increase of a level of hemoglobin results to hemoglobinuria.

Clinic
Clinical classification:
I. Initial malaria
II. Early relapses
III. Inter-paroxysmal periods:
1. Short (between the nearest relapses)
1. 2.Long (the winter, latent period)
IV. Long malaria
V. Late relapses
VI. Malignant forms and complications:
1. Malarial coma
2. Algid form
3. Hemoglobinuric fever
The classical triad of symptoms, characteristic for malaria, includes malarial
attacks of the fever, an increasing anemia, increase of a liver and a spleen. The attack of
a fever begins a fever with fast rise in temperature of a body up to 39,5-40°C. Then it is
replaced by fever, a headache, the critical temperature is reduced up to normal or
subnormal figures and finished by profuse hyperhidrosis.
Distinguish three forms of malaria: three-day (Pl.malaria), four-day (Pl.vivax)
and tropical (Pl.falciparum). Each of them at presence of the general features differs by
features of clinical current. The tropical malaria especially hardly proceeds. In the
beginning the prodromal phenomena during 2-3 days: a headache, arthralgias, vomiting,
diarrhea are possible. Then suddenly with a fever the body temperature raises, during 3-
7 days keeps at a constant level, in the subsequent gets alternating character. Paroxysm
begins in the morning and proceeds 12-36 hours. Apyrexia is kept less than days. Soon
there are pains in the left sub costal area owing to increase of a spleen.
The tropical malaria proceeds with extensive hemolysis of erythrocytes,
disturbance of microcirculation and complications. The heaviest complication is malarial
coma (cerebral malaria). It proceeds with three stages:
the 1st - somnolentia (excitation, negativism, drowsiness);
the 2nd - precoma (hyperkinesises, tetanic spasms, meningeal syndrome; a high degree of
parasitemia);
 3
the 3rd - coma (absence of consciousness, later - and reflexes, the temperature curve can
have wrong character).
The comatose form of malaria is quite often combined with acute renal insufficiency.
HEMOGLOBINURIC FEVER can develop on a background of treatment by
quinine owing to amplification of hemolysis of erythrocytes. The clinic of hemolytic
jaundice quickly accrues, the body temperature sharply raises, there are pains in
muscles, vomiting of bile, laboratory attributes of anemia. Urine, juicy in a glass or
transparent jar, has a characteristic view: - from above - a layer of a liquid of crimson
color, below – cuboid-form debris of grey - yellow color. In “a thick drop” plasmodium
is not found out is a result of massive hemolysis (the parasite is capable to live outside
of erythrocyte no more than 30 minutes). As a result of one or several waves of
hemolysis there is a blockade of kidneys.
EDEMA OF LUNGS quite often arises after introduction of excessive volumes
of liquids with the purpose of disintoxication. According to recommendations of WHO
the quantity of entered solutions should not exceed 20,0 ml/kg of weight of a body of the
patient; at the phenomena of exsicosis the increase of a dosage, however not from above
2-З litres totally in days is supposed.
At quickly increasing and expressed intoxication complication by
INFECTIOUS-TOXIC SHOCK (synonym: ALGID), characterized by cyanosis, a cold
snap of integuments, decrease of temperature to a subnormal level is possible. The shock
can be aggravated by HYPOGLYCEMIA, caused by increased consumption of sugar at
a fever, recycling of glucose by parasites, emission of insulin under action of quinine.
On a background of treatment by quinine the hemoglobinuric fever can be developed.
All lethal cases of malaria are connected only with Pl.falciparum.
The three-day malaria proceeds is good-quality, lethal cases are not characteristic.
The incubatory period can be short - from 10 up to 21 days and long - about 8-14
months.
In the beginning of the disease the fever from a temperature curve of wrong type
is quite often observed. By the end of the first week typical paroxysms with correct
alternation, there are they mainly in morning and a day time (from 11 o'clock till 16
o'clock are appeared.
Paroxysm begins with a tremendous fever within 2-3 hours. At the patient
weakness, a headache, pains in large joints and a waist sharply accrue, vomiting is
possible. The skin turns pale. After the termination of a fever the patient during 2-6
hours feels arduous, accompanied by thirst, hyperemia of skin, tachycardia, hypotonia,
dyspepsia. Then within 1-2 hours the temperature is reduced, the patient sweats.
Hyperhidrosis is so great, that to the patient repeatedly change under-clothes and bed-
clothes. General duration of paroxysm is from 4 till 8, the inter-paroxysmal period is 40-
44 hours. In two day after the first attack of a fever at the patient at the same hours the
second paroxysm develops. By the second week of the disease a liver and a spleen are
enlarged, hemolytic anemia is gradually developed, but the jaundice appears seldom,
lesion of kidneys is not typically. Without treatment paroxysms repeat about one month,
 4
then stop owing to increase of the immune answer. After one and a half more - two
months the early relapses described from the beginning by correct alternation of attacks
are possible. The remote relapses in 3-6-12 months and even in 2-5 years are possible.
OVAL - MALARIA meets in the Western Africa. The incubatory period - 11-16
days, but for the account of bradyzoits can be long 6-9 months. Current is more good-
quality, than at a three-day malaria, comes spontaneous recovery more often. Relapses
in 6-9 months and later are possible. Paroxysms of fever have the same features, as at a
three-day malaria, but arise in evening and night hours.
FOUR-DAY MALARIA is caused by Pl.malaria. The incubatory period is - 20-
42 days, at intravenous infection through donor blood (“vaccinated malaria”) - is more
often from З about 20 days. The prodromal period is absent; at once regulated attacks -
once at 72 hours arise. Paroxysm is similar to an attack of a three-day malaria, but the
period of ardour lasts longer - till 6 hours. The level of parasitemia accrues slowly,
anemia is insignificant, splenomegalia is revealed on 3-4-й to week of the disease. There
is a danger of development of hephrotic syndrome. At a four-day malaria of the remote
relapses it does not happen, but initial disease can proceed from several months till 2-3
years, sometimes - up to the end of life (in these cases clinical manifestations are
minimal or are absent, however in connection with persisting of plasmodiums
reconvalescentт can not be the donor).

Diagnostics
Statement of the diagnosis malariashould be based on the analysis of a clinical
picture of the disease and obligatory confirmation by its detection of parasites in a thick
drop and smear of blood in which is easier to define a kind of the parasite. The fence of
blood is better for carrying out at height of a fever though at three-day, four-day and an
oval - malaria parasites circulate in blood and the interparoxysmal period. Plasmodiums
differentiate by quantity of parasites in one erythrocyte, to the sizes of damaged
erythrocytes, to presence of toxic granularity, morphology of hepatocytes.
In the general analysis of blood anemia, poicilocytosis, anisocytosis,
reticulocytosis, leukopenia, neutropenia, acceleration of RSE are revealed.

Treatment
Patient with malaria is necessarily hospitalized (under clinical indications), at
tropical malaria - it is urgent. A basis of treatment of malaria is antyparasitic
preparations. As action they share on erythroschizotropic (operate on erythrocytic
schizonts), histoschizotropic (operate on tissue forms of a liver) and gamotropic (operate
on sexual forms for liquidation of malarial paroxysms).
The basic arythroschizotropic mean is Chlorochin (Delagil). It is appointed under
the circuit: in the 1st day at once 4 tablets - 1,0, in 6-8 hours - 2 tablets - 0,5; in the 2nd
and the 3rd day on 0,5 (2 tablets) once a day after meal.
At heavy current of a tropical malaria introduction of Delagil in a vein is
possible: 5 % - 10,0 on glucose of 5 % - within 2 hours. At delagilresistance forms of
 5
malaria quinine sulfate, chloridin, meflochin, the combined preparations can be
appointed. Quinine sulfate is appointed on 0,65 3 times per day within 7-10 days in a
combination with sulfalen on 0,5 and tindurin on 0,025 1 time per day within 3 days.
Besides therapy stopping the paroxysms, patient with heavy and average malaria require
intensive pathogenetic treatment. Desintoxication will be carried out by glucose of 5 %
in volume up to 2-3 liters in days At cerebral malaria (edema of a brain) and renal
insufficiency Lazix (80-120 mg), an ascorbic acid, euphillin intravenously are shown. At
algid (shock) colloid preparations, plasma are introduced. At hemoglobinuric fever 5 %
a solution of bicarbonate of sodium and 10 % a solution of mannit on glucose are
entered.
For treatment of patients with tropical and four-day malaria it is enough stopping
therapy. At three-day and an oval - malaria after a rate of stopping therapy with the
purpose of suppression of tissue and sexual forms of plasmodiums will carry out
treatment by primachin on 0,09 3 times per day within 14 days.

Chemoprophylaxis
Individual prophylaxis of malaria to the persons leaving in the epidemic focuses
of three-day and an oval - malaria, will be carried out by delagil. The preparation is
accepted on 0,5 once a week some days prior to arrival an adverse regimen, during all
term of stay in it and 1 more month after departure.
The basis of public prophylaxis of malaria is made with early revealing and
treatment of patients by malaria and parasitocarriers. With this purpose at fevering
patients, the persons coming from epidemic regions and infection exposed to risk,
investigate blood on malarial plasmodium.
For the persons who have had been ill with malaria it is established dispensary
supervision with periodic research of blood on malarial plasmodium: at a three-day
malaria - during 2,5 years, at tropical malaria - 1,5 years. In case of detection of
plasmodium or relapse of malaria repeated specific treatment will be carried out.

REALIZATION OF THE LESSON

The purpose of the lesson is to learn to diagnose malaria according to clinic, the
epidemiological anamnesis, laboratory inspection and also to make the plan of
treatment. It is paid attention to the natural focuses of malaria.

Control questions to the beginning of the lesson

1. Brief characteristic of activators of malaria. Medicinal stability.
2. Epidemiology of malaria.
3. Bases of pathogenesis.
4. Clinical forms of malaria, the basic clinical symptoms.
5. Complications of malaria, their clinical signs.
6. Methods of laboratory diagnostics.
7. Features of current of tropical malaria.
 6
8. Outcomes of malaria.
9. Principles of treatment of different forms of malaria.
10. Prophylaxis of malaria.

The test
1. Erythrocytic schizogonia lasts 48 hours at:
1. Three-day malaria
2. Oval - malaria
3. Tropical malaria
4. Four-day malaria
5. At all kinds of malaria
2. Pyrogenic reaction at malaria is caused by:
1. Exit of merozonts in plasma of blood
2. Products of metabolism of the parasite
3. Pathologically changed proteins of erythrocytes
4. Biologically active substances of erythrocytes and merozonts
5. Necrobiotic processes
3. Development of anemia at all kinds of malaria is caused by:
1. Destruction of damaged erythrocytes
2. Destruction of not damaged erythrocytes (autoimmune mechanism)
3. Development of splenomegalia
4. Suppression of hemopoiesis
5. Deficiency of iron and a folic acid
4. The periods of development of malaria are:
1. Initial fever
2. Typical malarial paroxysms
3. Secondary latent period
4. Early relapses
5. Late relapses
5. Clinical signs of three-day malaria:
1. Paroxysmal rise in temperature
2. Fever
3. Ardour
4. Hyperhidrosis
5. Tachycardia and arterial hypotension
6. Features of clinical current of tropical malaria:
1. Constantly high temperature
2. Moderate expressiveness of fever and hyperhidrosis
3. Dyspeptic disorders
4. Propensity to malignant current
7. Complications of tropical malaria:
1. Cerebral malaria (malarial coma)
 7
2. Infectious-toxic shock (algid)
3. Hemoglobinuric fever
4. Acute renal insufficiency
5. Acute psychosis
8. For confirmation of the diagnosis and definition of a kind of malaria are
necessary:
1. Microscopy of a thick drop of blood
2. Biochemical analysis of blood
3. Microscopy of smear of blood
4. Seed of blood
5. Microscopy of a spinal liquid
9. In treatment of average tropical malaria now are preferable:
1. Chlorochin
2. Meflochinн
3. Halofontrin
4. Fansidar
5. Artemizin
10. For treatment of heavy forms of tropical malaria intravenously enter:
1. Hematoschizotcydic preparations
2. Solutions of glucose, sodium of bicarbonate
3. Reopolyglucinum
4. Saluretics
5. Solution of an ascorbic acid
Discussion of a theme of the lesson is preceded with work of the student with the
thematic case history. The student prepares for the brief report in the offered case. The
following data are necessary:
1. Surname, name, patronymic, age, a residence and works, date of disease and
hospitalization;
2. Complaints at the moment of hospitalization;
3. The first symptoms of the disease: fever with chills and sweat, general
indisposition, a headache;
4. Development of these symptoms during the disease (increase, stability,
reduction);
5. Epidemic data: seasonal prevalence of disease, presence of mosquitoes, fevering
patients among associates, stay in epidemic region on malaria, malaria in the
anamnesis, hemotransfusion.
The objective data:
1. General condition;
2. Appearance, color of external covers, mucous, yellowness;
3. Condition of the lymphatic device;
4. Condition of respiratory system;
5. Condition of cardiovascular system;
 8
6. Condition of digestive system (increase of a liver and a spleen);
7. Condition of urine-excreting system.
On the end of this work the student writes a substantiation of the provisional
diagnosis. Then the case history of the patient is reported and discussed by malaria in
group. Students jointly make the plan of inspection of the patient, then get acquainted
with results of laboratory researches and discuss them. On the basis of all available data
diagnosis with the indication of the period and severity of the disease is made.
Treatment is discussed: conditions of hospitalization, a regimen, a diet, necessity of the
control for diuresis and defecation. The prognosis of specific complications is marked.
The criteria of recovery and an extract of the patient are discussed.
In the end of the lesson students solve clinical situational problems and answer
the questions to them.

PROBLEM
Patient N., 39 years, was ill sharply in one week after returning from the Central
Africa. In first two days of the disease the strong headache disturbed, pains in muscles
and joints, nausea, two-multiple vomiting, three times - a liquid stool; the temperature
did not raise. On the 3rd day of the disease in the morning - a fever, temperature is
38,5°С; in the subsequent two day a temperature curve - without any laws, with
oscillations from 38,2 ° up to 39,5°С; dyspepsia is not present. For the 5th day of the
disease in a heavy condition he is delivered in a hospital with suspicion to an intestinal
infection.
From the anamnesis: In the past within 8 years he had lived in tropical Africa; has
transferred malaria. Last two years he periodically goes in business trips; last duration is
about 2 weeks. In the preventive purposes accepted delagil - on 0,5 g once a week.
Objectively: a condition is heavy. Т is 39,3°С. Consciousness is confused. He is pale.
On lips there is herpes. Tones of heart are muffled. Frequency of cardiac contractions is
120 in one minute. The arterial pressure is 90/160 m. Hg. An abdomen is moderately
painful around a navel and in both subcostal areas. There is hepatosplenomegalia.

1. Presumable diagnosis.
2. Tactics of the doctor.

PROBLEM
At the patient of 58 years, operated concerning to a bleeding from an ulcer of a
duodenum (with hemotransfusion), in 5 days with a fever the temperature has raised.
1. Tactics of the doctor.