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

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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 malariaII. Early relapsesIII. Inter-paroxysmal periods:

1. Short (between the nearest relapses)1. 2.Long (the winter, latent period)

IV. Long malariaV. Late relapsesVI. Malignant forms and complications:

1. Malarial coma2. Algid form3. 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 39,5-40C. 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);

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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,

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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

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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 lesson1. 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.

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8. Outcomes of malaria.9. Principles of treatment of different forms of malaria.10.Prophylaxis of malaria.

The test1. Erythrocytic schizogonia lasts 48 hours at:

1. Three-day malaria2. Oval - malaria3. Tropical malaria4. Four-day malaria5. At all kinds of malaria

2. Pyrogenic reaction at malaria is caused by:1. Exit of merozonts in plasma of blood2. Products of metabolism of the parasite3. Pathologically changed proteins of erythrocytes4. Biologically active substances of erythrocytes and merozonts5. Necrobiotic processes

3. Development of anemia at all kinds of malaria is caused by:1. Destruction of damaged erythrocytes2. Destruction of not damaged erythrocytes (autoimmune mechanism)3. Development of splenomegalia4. Suppression of hemopoiesis5. Deficiency of iron and a folic acid

4. The periods of development of malaria are:1. Initial fever2. Typical malarial paroxysms3. Secondary latent period4. Early relapses5. Late relapses

5. Clinical signs of three-day malaria:1. Paroxysmal rise in temperature2. Fever3. Ardour4. Hyperhidrosis5. Tachycardia and arterial hypotension

6. Features of clinical current of tropical malaria:1. Constantly high temperature2. Moderate expressiveness of fever and hyperhidrosis3. Dyspeptic disorders4. Propensity to malignant current

7. Complications of tropical malaria:1. Cerebral malaria (malarial coma)

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2. Infectious-toxic shock (algid)3. Hemoglobinuric fever4. Acute renal insufficiency

5. Acute psychosis8. For confirmation of the diagnosis and definition of a kind of malaria are necessary:

1. Microscopy of a thick drop of blood2. Biochemical analysis of blood3. Microscopy of smear of blood4. Seed of blood5. Microscopy of a spinal liquid

9. In treatment of average tropical malaria now are preferable:1. Chlorochin2. Meflochinн3. Halofontrin4. Fansidar5. Artemizin

10. For treatment of heavy forms of tropical malaria intravenously enter:1. Hematoschizotcydic preparations

2. Solutions of glucose, sodium of bicarbonate3. Reopolyglucinum4. Saluretics5. 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;

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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.

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