Malaria remains a major health problem in nearly 100 countries in Asia, Africa and South America.
Malaria endemic countries. Table 1.
|
Continent, region WHO |
The country |
|
Asia and Oceania |
Afghanistan, Bangladesh, Bhutan, Vanuatu, Vietnam, India, Indonesia, Iran, Iraq, Yemen, Cambodia, PRC, Laos, Malaysia, Myanmar, Nepal, UAE , Oman, Pakistan, Papua - New Guinea, Saudi Arabia, Solomon Islands, Syria, Tajikistan, Thailand, Philippines, Sri Lanka, Azerbaijan, Armenia, Turkmenistan, Turkey. |
|
Africa |
Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Djibouti, Egypt , Zaire, Zambia, Zimbabwe, Cameroon, Capo Verde, Kenya, Congo, Ivory Coast, Comoros islands, Liberia, Mauritius, Mauritania, Madagascar, Malawi, Mali, Morocco, Mozambique, Namibia, Niger, Nigeria, Rwanda , Sao Tome and Principe , Swaziland, Senegal, Somalia, Sudan, Sierra Leone, Tanzania, Togo, Uganda, CAR, Chad, Eq. Guinea, Ethiopia , Eritrea, South Africa. |
|
Central and South America |
Argentina, Belize, Bolivia, Brazil, Venezuela, Haiti, Guyana, Guatemala, Guiana FR., Honduras, Dominican Republic, Colombia, Costa Rica, Mexico, Nicaragua, Panama, Paraguay, Peru, El Salvador, Suriname, Ecuador. |
Between 300 and 500 million clinical cases of malaria occur worldwide every year, and 1.5 to 2.7 million people, mostly children under 5 years of age, die from it every year. Despite significant advances in the study of biology, epidemiology and clinical problems of the disease, more people now die from malaria than 30 years ago. Sub-Saharan Africa has the highest morbidity and mortality rates. Countries with malaria epidemics are listed in Table 1. Countries in bold type are where strains are prevalent.P. falciparum,resistant to chloroquine. In many countries, mainly in the regions of Asia, Oceania, South and Central America, resistant strains are not found throughout the country, but only in certain areas.
In recent years, in many parts of the world with political and economic instability, increased migration and irrigation activities, there has been an increase in the incidence of malaria and its return to those regions where it was almost eradicated. Every year, thousands of malaria patients travel to non-endemic countries, putting the infection at risk of taking hold. Many imported cases are responsible for local transmission and spread of malaria. Malaria epidemics have emerged in Azerbaijan, Armenia, Tajikistan, Turkmenistan and Turkey. A high risk of malaria recurrence is noted in Georgia, Kazakhstan, Kyrgyzstan, Russia and Uzbekistan. An analysis of the malaria situation in Russia shows that it is deteriorating - both the number of cases of local transmission and the number of imported cases are growing.
In the countries of Europe and North America, where malaria has been eliminated, about 10 thousand imported cases are recorded annually among tourists returning from endemic regions, while about 1% of those with tropical malaria die. Identification and timely treatment malaria among tourists is complicated by the fact that a significant proportion are patients with mild clinical manifestations of the disease, obviously due to insufficiently effective treatment of acute attacks.
Deaths from tropical malaria are also recorded in the Russian Federation, which is mainly due to incorrect recommendations on chemoprophylaxis for those leaving for the tropics, late diagnosis and prescription of ineffective antimalarial drugs, and a number of other factors.
In recent years, due to the significant expansion of flights to malaria endemic countries in Europe and the United States, cases of "airport" malaria have begun to be noted among people working at airports or living in the immediate vicinity of them, associated with the importation of malarial mosquitoes from endemic regions on aircraft. Due to the development of resistance to insecticides in mosquitoes, current measures for the disinsection of air vehicles do not completely eliminate the risk of importation of infection vectors.
BIOLOGY OF PATHOGENS
P. vivax-causative agent of three-day malaria; widespread in the countries of South and Central America, Asia and Oceania;
P. ovale(oval-malaria) - the causative agent of three-day malaria; distributed mainly in Equatorial Africa; separate cases are registered on some islands of Oceania and in Thailand;
P. malariae- the causative agent of four-day malaria; occurs within the world range in all regions;
P. falciparum - the causative agent of tropical malaria, the main type of pathogen in Equatorial Africa, is widespread in some countries of Asia, Oceania, South and Central America.
PATHOGENESIS
Fever in malaria is due to the release of merozoites into the plasma and hemolysis of red blood cells. In this case, as a rule, anemia always develops.
P. vivax and P.ovale predominantly infect young erythrocytes, andP.malariae- mature while P. falciparum infects erythrocytes of varying degrees of maturity. This leads to infection P. falciparum 30% or more of the red blood cells may be affected, which contributes to significant hemolysis. In addition to intravascular hemolysis, phagocytosis by spleen cells of both infected and uninfected erythrocytes, sequestration of erythrocytes in the bone marrow, and immune mechanisms are important in the development of anemia in malaria.
Illness due to infection P. vivax, P. ovale and P. malariae,proceeds normally benignly. infection P. falciparum in cases of late or incorrect treatment, it can take a "malignant" course. In pagogenesis, "mechanical" and "immunological" factors are important, leading to the release of cytokines and pro-oxidants that damage the vascular endothelium, promote sequestration and adhesion of erythrocytes, hemolysis, and disruption of microcirculation and metabolism.
Clinic
During the first days of illness, there may not be a typical malarial attack, but only a slight fever or an initial fever of the wrong type.
A typical attack proceeds with an alternation of phases: chills, fever, sweat. The attack usually begins in the first half of the day with chills lasting from 15 minutes to 2-3 hours. The temperature rises to ³ 39 0 and the chills are replaced by fever, which usually lasts up to 6 hours. Then the temperature begins to decrease within 1-2 hours, which is accompanied by profuse sweating. The next paroxysm begins in a day.
If left untreated, attacks recur for 3 weeks to 2 months or more, then they become irregular and stop on their own.
Insofar as P. vivax and P. ovale predominantly infect young erythrocytes, usually no more than 2-5% are affected total number erythrocytes. During the first two weeks of the disease, if untreated, anemia develops, the liver and spleen increase. At the onset of the disease, the soft edge of the spleen is palpated, and with treatment in the initial stages of the disease, it returns to normal sizes. In cases of chronic infection, if malaria is not treated, the spleen becomes hard, enlarges significantly, and does not return to normal after treatment. Leukopenia is usually noted, but leukocytosis may occur during fever.
A rare but serious complication of three-day malaria is rupture of the spleen, requiring surgical repair.
Oval malaria tends to be more mild than 3-day malaria, relapses are less common, and spontaneous recovery occurs in 6-10 paroxysms.
The onset of the disease is acute, and from the first attack their periodicity is established - after 2 days on the 3rd. Compared to three-day malaria and oval-malaria, the period of chills and fever is longer. After 2 weeks from the onset of the disease, if untreated, anemia develops and spleno- and hepatomegaly is detected.
Four-day malaria is usually benign. However, in endemic areas of Africa, an association has been found between infectionP. malariae and development of nephrotic syndrome in children.
tropical malaria . This is the most severe form of malaria.P. falciparuminfects both young and mature erythrocytes, and the level of erythrocyte involvement can reach 50% or more.
The incubation period ranges from 8 to 16 days. Headache, fatigue, nausea, loss of appetite may occur 3-4 days before the development of clinical symptoms. Initial manifestations diseases are characterized by severe chills, a feeling of heat, severe headache. In some cases, attacks of malaria (paroxysms) occur without chills. Fever at the onset of the disease can be constant without pronounced paroxysms, which greatly complicates the diagnosis. As a rule, there is a polymorphism of temperature curves in tropical malaria from typical paroxysms every other day to daily and even attacks that occur twice a day. Possible persistent fever, and instead of periods of apyrexia, subfebrile temperature is noted.
A week after the onset of the disease, hepato- and splenomegaly, anemia are detected. There may be jaundice and diarrhea. Young children often experience agitation, refusal to eat, and vomiting.
With late diagnosis and delay in treatment, tropical malaria can take a "malignant" course. . Especially increases the risk of developing "malignant" malaria with a delay in treatment for more than 6 days from the onset of the disease. Mortality in tropical malaria ranges from 10 to 40%, depending on the time of initiation of treatment, the correct selection of antimalarial drugs and the equipment of the clinic. Children, pregnant women and non-immune adults are more likely to develop severe tropical malaria.
The main indicators of the unfavorable course of tropical malaria.
1.Clinical indicators:
age up to 3 years;
convulsions;
absence of corneal reflexes;
decerebrate rigidity or opisthotonus;
acute renal failure;
acute pulmonary edema;
collapse, shock, septicemia ("malarial algid");
respiratory failure (acidosis);
papilledema and/or retinal edema;
bleeding;
jaundice;
hemoglobinuria;
high fever.
2. Laboratory indicators:
leukocytosis (> 12.109);
leukocytes in peripheral blood with malarial pigment (> 5%);
hematocrit (< 15 %);
hemoglobin (< 50 г / л);
blood glucose less than 2.2 mmol/l;
urea in the blood more than 10 mmol / l;
creatinine over 265 µmol/l;
low glucose in cerebrospinal fluid;
high level lactic acid in CSF (> 6 mmol/l);
high level of lactic acid in venous blood (> 5 mmol/l);
an increase in the plasma level of 5-nucleotidase;
low level of antithrombin 3;
high plasma levels of tumor necrosis factor (TNF);
more than threefold increase in serum aminotransferase levels.
In case of primary infection with tropical malaria, the detection of gametocytes in the peripheral blood is an unfavorable prognostic sign, indicating the duration of the disease for at least 10-12 days.
hypoglycemia is an essential manifestation of severe tropical malaria. Most often, hypoglycemia develops in young children and pregnant women, as well as in the treatment of quinine or quinidine due to quinine-induced hyperinsulinemia. Typical Symptoms hypoglycemia - anxiety, sweating, dilated pupils, increased respiration, oliguria, tachycardia. In the absence of treatment - a violation of consciousness, shock and coma. Hypoglycemia is difficult to recognize because the above symptoms are characteristic of severe tropical malaria. Therefore, if possible, it is necessary to study the level of glucose in the blood, especially in high-risk groups.
Violations of water and electrolyte balance. Patients with severe tropical malaria often present with symptoms of hypovolemia (low venous pressure, orthostatic hypotension, oliguria with high urine specific gravity) and dehydration (dry mucous membranes and reduced skin turgor). Severe patients with hypoglycemia or renal insufficiency may experience deep breathing with hyperventilation, which leads to acidosis and accumulation of lactic acid in the blood and CSF.
Shock/collapse (“malarial algid”). Some patients develop collapse with blood pressure less than 80 mm Hg. In some cases, the development of collapse is associated with septicemia caused by gram-negative flora.
Bleeding and disseminated intravascular coagulation (DIC). There may be bleeding gums, petechiae and hemorrhages under the conjunctiva of the eye. 10% of patients may develop DIC with intestinal bleeding.
Hyperthermia. High temperature (39-40 0 C) is more common in children and may contribute to the development of seizures and impairment of consciousness.
Hemoglobinuria occurs as a result of massive intravascular hemolysis, which in some cases can be provoked by the administration of primaquine to persons with G6PD deficiency. Hemoglobinuria is a rare complication, more common in adults, leading to anemia and renal failure. The main symptom of hemoglobinuria is red or black urine.
For kids younger age and pregnant severe tropical malaria is a particularly dangerous problem. The most common are cerebral malaria, severe anemia, metabolic acidosis, and hypoglycemia. In pregnant women, serious consequences are possible for both the mother and the fetus - miscarriages, growth retardation and fetal death.
LABORATORY DIAGNOSIS
Malaria is characterized by non-specific clinical symptoms, mainly manifested by an increase in temperature. Therefore, on the basis of clinical data, one can only assume infection with malaria. Any increase in temperature within 3 days in persons who have been in endemic foci during the past 3 years requires testing for malaria. Additional information about the possibility of infection is provided by a geographical history indicating the patient's stay in malaria-endemic areas. Due to the fact that fever in persons who were in endemic foci of malaria may be due to many other bacterial and viral infections, only a laboratory study can finally establish the diagnosis.
In connection with the above problems that arise in the laboratory diagnosis of malaria by microscopy, in recent years, immunodiagnostic methods using monoclonal antibodies have received significant development. The advantage of express methods is the possibility of urgent diagnosis of malaria in situations where there are no conditions for microscopy, in particular among military personnel and tourists.
TREATMENT
For the treatment of acute manifestations prescribe drugs from the group of 4-aminoquinolines (chloroquine, etc.).
Treatment of malaria patients infected P. vivax, P. ovale and P. malariae
Chloroquine is prescribed at a dose of 25 mg base/kg per course of treatment for 3 days:
1st and 2nd day - 10 mg base / kg once, 3rd day - 5 mg base / kg once
or
1st day - 15 mg base / kg (10 mg / kg and 5 mg / kg with an interval of 6 hours), 2nd and 3rd day - 5 mg base / kg.
In order to prevent distant relapses inP. vivax and P. ovale, caused by hypnozoites, apply tissue schizontocide - primaquine. It is prescribed at a dose of 0.25 mg base/kg per day for 14 days.
For treatment of resistant strains, other primaquine regimens are recommended: 0.25 mg base/kg per day in a single dose for 21 days or 0.5 mg base/kg per day in 2 doses for 14 days, or no primaquine, and all subsequent relapses (usually 3-6) are treated with chloroquine alone.
Treatment of malaria patients infected P. Falciparum. Currently, the problem of treating tropical malaria is significantly complicated by the wide spread of strains resistant to antimalarial drugs. Along with the ubiquity of chloroquine-resistant strains and the wide distribution of strains resistant to sulfadoxine-pyrimethamine and dapsone-pyrimethamine, the number of observations of the identification of strainsP. falciparum,resistant to other antimalarial drugs.
Treatment of uncomplicated tropical malaria. Due to the fact that the increase in the intensity of invasionP. falciparum occurs very quickly and mainly in the vessels of the internal organs, the risk of developing serious complications within a short time after infection is very high.
Considering the possibility of lethal outcomes in tropical malaria and the rapid transition from a benign to a “malignant” course, treatment should be prescribed urgently. Therefore, if malaria is suspected and the first symptoms of the disease appear (acute fever, headache, muscle pain, etc.), if it is impossible to immediately laboratory research it is necessary to urgently prepare thin smears and thick drops of blood and, without waiting for a laboratory test, carry out preventive treatment.
Currently, for the treatment of uncomplicated malaria due toP. falciparum,it is recommended to use mefloquine, sulfadoxine-pyrimethamine, quinine, drugs from the artemisinin group.
Mefloquine. 2 treatment regimens are used: 15 mg base/kg or 25 mg base/kg per course of treatment
15 mg base/kg in 2 divided doses 6-8 hours apart
or
15 mg base / kg in 2 doses with an interval of 6-8 hours. After 6 - 24 hours - 10 mg base / kg in 1 dose.
The second regimen is recommended for patients who may be suspected of being infected with strainsP. falciparumresistant to mefloquine, in particular in persons who became infected at the border of Thailand and Cambodia.
Sulfadoxine pyrimethamine(tablets contain 500 mg sulfadoxine + 25 mg pyrimethamine). Doses are shown in Table 2.
Table 2.
Doses of sulfadoxine-pyrimethamine for the treatment of tropical malaria
|
Weight, kg) |
Age (years) |
Number of tablets |
|
5 - 6 |
2 - 3 months |
0,25 |
|
7 - 10 |
4 - 11 months |
|
|
11-14 |
1 - 2 |
0,75 |
|
15 - 18 |
3 - 4 |
|
|
19 - 29 |
5 - 9 |
|
|
30 - 39 |
10 - 11 |
|
|
40 - 49 |
12 - 13 |
|
Quinine.
Quinine is prescribed at 8 mg base / kg per dose - 3 times a day for 7 days.
If the patient is suspected to have been infected with strainsP. falciparum,resistant to quinine, in particular in regions of Southeast Asia, it is recommended to treat with quinine in combination with doxycycline, tetracycline or clindamycin:
Quinine: 8 mg base/kg per dose - 3 times a day for 7 days
Doxycycline: 100 mg daily for 7 days (contraindicated in children under 8 and pregnant women)
Or
Tetracycline: 250 mg - 4 times a day for 7 days (contraindicated in children under 8 years of age and pregnant women)
Or
Clindamycin: 10 mg/kg per day, 2 doses for 7 days.
Artemisinins. For the treatment of uncomplicated tropical malaria, tablet forms are used, and for the treatment of severe tropical malaria, dosage forms for intramuscular, intravenous and rectal administration are used. To prevent recurrence of tropical malaria, treatment with artemisinin drugs is recommended in combination with mefloquine or other antimalarial drugs.
Artemisinins have no effect on hypnozoites. Therefore, in the treatment of artemisinins in persons infected withP. vivax or P. ovale,primaquine should also be given.
Artesunate(in tablets):
1st day - 4 mg / kg per day in 2 divided doses
2-5th day - 2 mg / kg per day in 2 divided doses
Or
4 mg/kg per day in 2 divided doses for 3 days.
After treatment with artesunate, treat with mefloquine ( c m. above).
Contraindication: pregnancy, especially the first 3 months.
In recent years, combinations of new antimalarial drugs have been developed, which are beginning to be produced in fixed combinations.
Artemether-lumefantrine (tablets contain 20 mg artemether + 120 mg lumefantrine). The average per course of treatment is 9.6 mg/kg of artemether and 57.9 mg/kg of lumefantrine.
For adults (weighing over 35 kg): 4 tablets 2 times a day - 3 days (6 doses).
Children (weighing up to 15 kg): 1 tablet 2 times a day - 3 days (6 doses).
Other combinations of antimalarial drugs are being studied for the treatment and prevention of tropical malaria caused by resistant strains, in particular: pyrimethamine / c sulfadoxine + artesunate, artemether + lumefantrine, amodiaquine + artesunate, chlorproguanil/dapsone + artesunate. The most promising in terms of efficacy, tolerability and pharmacokinetic parameters is the combination of chlorproguanil / dapsone + artesunate.
(Ending follows.)
Therapy for complicated tropical malaria (severe, “malignant” course)
For the treatment of severe tropical malaria, dosage forms of drugs intended for parenteral administration are used. Quinine has been the drug of choice for many years, and in the absence of quinine, quinidine. There are also dosage forms of kinimax containing several quinine alkaloids for intramuscular administration.
In addition to quinine, other dosage forms have been obtained in recent years, including artemisinin for parenteral administration (intravenously and intramuscularly).
Along with injectable dosage forms of artemisinins, clinical trials of rectal suppositories - artemisinin and artesunate - have been completed. It is advisable to prescribe rectal suppositories in cases where the administration of drugs orally and in the form of injections is not possible, for example, in young children, in remote rural areas, in the absence of qualified medical personnel and the necessary medical equipment. The introduction of rectal suppositories prevents the development and progression of severe complications and creates a reserve of time that allows, if necessary, to transport the patient to the clinic.
Treatment of severe tropical malaria.
Quinine (adults): 20 mg of quinine dihydrochloride salt per 1 mg of body weight (20 mg/kg) diluted in 10 ml of isotonic solution per 1 kg of body weight (10 ml/kg) and administered intravenously over 4 hours; after 8 hours from the start of the 1st dose, switch to a maintenance regimen of quinine administration - 10 mg / kg for 4 hours. Subsequent doses of quinine - 10 mg / kg should be administered intravenously every 8 hours from the start of quinine administration. Intravenous administration of quinine should be continued until the patient can swallow the tablets. Continue taking quinine tablets - 10 mg / kg of quinine dihydrochloride salt every 8 hours. The total duration of treatment with quinine is 7 days.
QININE (children): dilute 20 mg of quinine dihydrochloride salt per 1 kg of body weight (20 mg/kg) in 10 ml of isotonic solution per 1 kg of body weight (10 mg/kg) and inject intravenously over 4 hours: after 12 hours from the beginning of the introduction of the 1st dose, switch to a maintenance regimen of quinine administration - 10 mg / kg for 2 hours. Subsequent doses of quinine - 10 mg / kg administered intravenously every 12 hours. Continue intravenous administration of quinine until the patient can swallow pills. Continue taking quinine tablets - 10 mg/kg quinine dihydrochloride salt every 8 hours. The total duration of treatment with quinine is 7 days.
If intravenous administration of quinine is not possible, quinine can be injected intramuscularly into the outer thigh (not into the buttocks). The total dose of quinine should be divided into 2 parts
and each is inserted into a different thigh. If possible, for intramuscular administration, quinine should be diluted with saline to a concentration of 60-100 mg/ml.
The first dose of quinine may be administered in 2 divided doses: initially 7 mg/kg IV over 30 minutes, then 10 mg/kg over 4 hours.
If the patient has become infected in areas where a 7-day course of quinine is not effective enough (for example, in Thailand), additional antibiotics should be prescribed as soon as the patient can swallow tablets:
tetracycline - 4 mg / kg per day in 4 doses (except for children under 8 years old);
doxycycline - 3 mg / kg per day in 1 dose (except for children under 8 years old);
clindamycin - 10 mg / kg per day in 2 divided doses.
Antibiotics are prescribed for 3-7 days.
If clinical improvement does not occur within 48 hours after parenteral administration of quinine, the dose of the drug should be reduced first by 1/3, then by 2 times, that is, to 5-7 mg/kg of quinine dihydrochloride.
The total daily dose of quinine administered intravenously in patients who have not improved after 48 hours, parenteral administration is:
adults: 1st day of treatment: 30-40 mg/kg body weight;
2nd day of treatment: 30 mg/kg;
Day 3 and subsequent days of treatment: 15 - 21 mg/kg body weight.
Children: 1st day of treatment: 30-40 mg/kg body weight;
2nd day of treatment: 20 mg/kg;
3rd day and subsequent days of treatment: 10-14 mg/kg body weight.
Usually, treatment with quinine by intravenous infusion is carried out for no more than 4-5 days. If it is nevertheless necessary to continue intravenous infusions of quinine, then in this case, constant intravenous administration at a rate of 5 mg/kg of body weight per hour is better.
The first administration of quinine at a dose of 20 mg/kg should not be administered if the patient has already received quinine or mefloquine for a period up to 12 hours before this administration.
Patients with severe tropical malaria should be admitted to intensive care units with hemodialysis equipment
In all cases, regardless of the ongoing pathogenetic therapy, antimalarial drugs are immediately prescribed.
It is also advisable to examine blood products for the presence of malaria pathogens within 1-1.5 months after completion of the course of chemotherapy with an interval of 1-2 weeks.
INDIVIDUAL PREVENTION
Prevention of malaria and complications is based on 4 principles:
identification of the risk of possible infection;
protection against mosquito bites;
prophylactic use of antimalarial drugs;
urgent diagnostics and treatment for suspected disease.
Identification of the risk of infection. Before leaving, you should find out the risk of malaria infection in the country and specific region where you plan to travel, as well as which season has the highest risk of infection.
Mosquito bite protection:
from dusk to dawn (during the period of the greatest activity of mosquitoes), when outdoors, dress in such a way as not to leave arms and legs open and apply repellents to exposed skin;
sleep in rooms where windows and doors are covered with mesh, or under a mesh canopy, preferably impregnated with insecticide;
in the evening and at night, use insecticides in rooms intended for sleeping.
Prophylactic administration of antimalarial drugs. Due to the fact that a malaria vaccine is under development, prophylactic administration of antimalarial drugs is one of the ways to prevent the disease. Prophylactic administration of antimalarial drugs is recommended for persons traveling to foci of medium and high endemicity. It is not recommended to visit areas where malaria is endemic for non-immune women during pregnancy due to the more severe course of malaria in pregnant women, the threat to normal fetal development, and the problems associated with taking antimalarial drugs for prevention and treatment.
Currently the drug of choice for malaria prevention in areas with resistanceP. falciparumto chloroquine is mefloquine. It is recommended to take it once a week at 250 mg (children at the rate of 5 mg / kg once, 1 time per week) during the entire stay in the outbreak, but not more than 6 months. Start taking mefloquine 2 weeks before leaving for the outbreak and continue taking it for 4 weeks after leaving. Mefloquine is not recommended for children weighing less than 5 kg under 3 months of age. Adverse reactions when taking mefloquine, as a rule, are mild, mainly drowsiness, dizziness. A rare but serious complication when taking mefloquine (in 1 in 10-20 thousand taking the drug) is an acute cerebral syndrome, which usually develops 2 weeks after the start of treatment and stops within a few days.
Prompt diagnosis and treatment of suspected malaria. Currently, there are no preventive measures that reliably protect against infection with malaria. Therefore, even if all preventive measures are followed, including regular prophylactic use of antimalarial drugs, there is always a risk of contracting malaria. Prophylactic use of antimalarial drugs or the use of antibiotics, anti-inflammatory and antipyretic drugs for self-treatment can change the clinical picture of the disease and make timely diagnosis more difficult.
In the event of symptoms suggesting the possibility of malaria, laboratory diagnostics should be urgently carried out and treatment should be started immediately. For the treatment of malaria in patients taking prophylactic antimalarial drugs, antimalarial drugs of a different chemical group should be used, for example, if prophylaxis with mefloquine is ineffective, treatment with artemisinins, quinine with doxycycline, or atovaquone-proguanil.
If malaria is suspected in cases of impossibility or delay in laboratory testing, urgently, without waiting for the results of laboratory testing, empirical therapy with antimalarial drugs intended for the treatment of tropical malaria should be carried out
In many cases, patients seek medical help relatively late, because they do not realize the threat to their health and life. Individuals at risk of contracting malaria should be made aware of the need for prompt diagnosis and treatment.
Vladislav LUCSHEV,
Head of the Department of Infectious Diseases, Tropical Medicine and Epidemiology.
Alexander BRONSHTEIN, professor of the department.
Russian State Medical University.
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Malaria (English malaria; French paludisme) is an acute anthroponotic transmissible protozoal disease with a transmissible mechanism of infection, characterized by severe symptoms of intoxication, a cyclic course with alternating attacks of fever and periods of apyrexia, enlargement of the spleen and liver, the development of hemolytic anemia with a progradient course, relapses illness.
, , , , ,
ICD-10 code
B50 Plasmodium falciparum malaria
B51 Plasmodium vivax malaria
B52 Plasmodium malariae malaria
B53.0 Plasmodium ovale malaria
In malaria, various mechanisms of transmission of infection are possible:
Transmissive transmission mechanism (when bitten by a mosquito)
, , , , , , , ,
Vertical Gear Transfer Gear
parenteral transmission mechanism
Conditions for the spread of malaria
For the spread of malaria in a certain region (country, territory, region), the following conditions are necessary:
The entire distribution area of malaria on the globe (between 45°N and 40°S to 64°N and 45°S in different years) is occupied by vivax malaria. The areas of malaria-falciparum and malaria-malariae are somewhat smaller due to the necessary more high temperature for effective sporogony; The range of malaria-ovale is located in two regions that are not geographically connected with each other: tropical Africa and the states of the western part of the Pacific Ocean (Indonesia, Vietnam, the Philippines, New Guinea, etc.). In mountainous countries, malaria foci can form up to an altitude of 1000 m in the temperate climate zone and up to 1500-2500 m in the subtropics and tropics, and at high altitudes (1000-1500 m and above) only vivax malaria foci are found.
Susceptibility to malaria is universal. The outcome of infection after the pathogen enters the bloodstream and clinical course diseases are determined by the individual immunological status, the activity of factors of nonspecific innate resistance, the intensity of post-infection immunity, and for newborns, by the level of specific class G antibodies obtained from the mother. The exception is indigenous people. West Africa and New Guinea, which are mostly immune to Pl. vivax, which is associated with a genetically determined lack of erythrocyte isoantigens of the Duffy group, which act as receptors for PI merozoites. vivax. Accordingly, in this region, compared to other regions of sub-Saharan Africa, cases of infection with malaria-vivax are observed much less frequently.
Also, newborns have a certain resistance to infection with all forms of malaria. This is due to:
, , , ,
Immunity against malaria
Prevalence of malaria
Of the four types of human malaria pathogens, P. vivax is the most common in the world. In the subtropics and tropics, the gene pool of the P. vivax population is dominated by sporozoites. causing disease after a short incubation (10-21 days). On the African continent, P. vivax is constantly found in the countries of East Africa in Arabs, Indians, Ethiopians, and Europeans. In the countries of West Africa, populated mainly by representatives of the Negroid race, P. vivax is not found, which is explained by the genetically determined congenital immunity of African blacks to P. vivax [there is no receptor for P. vivax merozoites on erythrocytes - Duffy isoantigens (Fy d or Fy b)] . The range of P. ovale is small and consists of two parts. The main, African part occupies tropical Africa from the Gambia in the north to the Congo in the south of the continent. The second part of the range is the countries of the Western Pacific and Southeast Asia. The geographical range of tropical malaria reaches 40° north latitude and 20° south latitude P. falciparum causes up to 50% of the incidence of malaria in the world. Four-day malaria is currently found in Africa, some parts of Central and South America, and the Caribbean. South-East Asia.
Tropical malaria is also easily tolerated by carriers of abnormal hemoglobin S (sickle cell anemia) and individuals with some other genetically determined abnormalities of hemoglobin and erythrocyte enzymes (deficiency of G-6-PD).
History of the study of malaria
The study of malaria (one of the oldest human diseases) is inextricably linked with the very history of the development of human civilization. It is assumed that malaria began to spread on Earth (from the African region of the Mediterranean) about 10,000 years ago due to the intensive development of agriculture, trade, and the development of new lands. In ancient Egyptian papyri, ancient Chinese literature and canons ("Charaka" and "Sushrutha") classical ayurveda ("Ayurveda") descriptions of the clinic and epidemics of malaria have survived to our time; even then there were suggestions about a possible connection between the development of the disease and mosquito bites. Later (5th-6th centuries BC), the ancient doctors of Greece: Hippocrates, Geradotus, Empedocles described in detail the clinic of malaria. Hippocrates is credited with distinguishing malaria from the group of febrile diseases: he proposed to distinguish 3 forms of the disease: "quotidian"(daily attacks), "tertian" (attacks every other day) and "quartan"(attacks after 2 days).
The beginning of the era of scientific discoveries in the study of malaria is associated with 1640, when for the first time the Spanish conquistador doctor Juan del Vego (Niap del Vego) used an infusion of cinchona bark, previously used by the Indians of Peru and Ecuador as an anti-febrile agent, to treat malaria patients. The merit in the name of the disease "malaria" (ital. "malaria"- bad air) belongs to the Italian Lancisi (1717), who linked the infection of people with malaria through "poisonous" fumes from swamps. In 1880, the French physician A. Laveran, working in Algeria, described in detail the morphology of the causative agent of malaria. In 1897, the English military doctor Ronald Ross in India established a transmissible mechanism for the transmission of malaria.
Currently, malaria is one of the most serious health problems for more than 100 countries in Africa, Asia and South America, about half of the world's population lives at risk of contracting malaria. In almost all countries of Europe and North America, hundreds of imported cases of malaria are recorded annually among people arriving from regions where it is common, and the number of cases of so-called airport malaria is growing. According to WHO, 200-250 million people fall ill with malaria every year in the world, at least 80% of all cases of malaria are registered in sub-Saharan Africa. Every year, 1 to 2 million people die of malaria, mostly children under the age of 5. Social and economic losses in Africa alone are estimated at US$2 billion per year. Since 1998, under the auspices of WHO, the World Bank, UNICEF, a scientific and practical program (Roll Back Malaria Initiative) has been implemented to control malaria (mainly in the developing countries of the world). The duration of the program is calculated until 2010-2015. Work is underway to develop an effective malaria vaccine, but this will take at least another 10-15 years. The search, development and improvement of drugs for the treatment of malaria is one of the priority programs of WHO, various pharmaceutical companies, and research institutes around the world. In recent years, as a result of the growth of migration processes and the intensive development of international tourism, an increase in imported cases of malaria has been noted in Russia.
Causes of malaria
The name of the disease "malaria" actually generalizes four separate protozoal diseases, caused respectively by four types of pathogens.
causative agents of malaria
Most domestic publications (textbooks, manuals, reference books) retain the former names of malaria forms: tropical malaria (malaria-falciparum), three-day malaria (malaria-vivax), oval-malaria (malaria-ovale) and four-day malaria (malaria-malariae).
Each of the four forms of malaria has its own clinical, pathogenetic and epidemiological features. The most important place is occupied by malaria-falciparum, accounting for 80-90% of all cases of malaria in the world, the causative agent of which belongs to a special subgenus (Laverania). Only malaria-falciparum can proceed malignantly, leading to death.
The causative agents of malaria in the process of life go through the following cycle of development with a change of hosts:
- asexual development (schizogony) occurs in the body of an intermediate host - a person;
- sexual development (sporogony) takes place in the body of the final host - the female mosquito of the genus Anopheles.
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Enlargement of the liver and spleen is initially due to congestion in the organs, but soon lymphoid and reticuloendothelial hyperplasia occurs in them. As a result of hemolysis of erythrocytes, as well as damage to hepatocytes, jaundice develops. Reduced absorption of carbohydrates and inhibition of gluconeogenesis in the liver causes hypoglycemia. Activation of anaerobic glycolysis leads to the accumulation of lactate in the blood, cerebrospinal fluid and the occurrence of lactic acidosis, which is one of the causes of the severe course of tropical malaria.
Malaria infection can disrupt the host's immune response, which triggers a cascade of immunopathological reactions. Fixation of immunoglobulins and complement on the basement membranes of the glomeruli causes acute nephropathy. nephrotic syndrome, which develops in patients with four-day malaria, is referred to as immunocomplex glomerulopathies.
Life cycle of all malaria pathogens
Life cycle of all malaria pathogens includes two hosts: humans (schizogony - asexual development cycle) and mosquitoes of the genus Anopheles (sporogony - sexual development cycle).
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exoerythrocytic schizogony
Sporozoites introduced with mosquito saliva into the human body very quickly (within 15-30 minutes) enter the liver with the bloodstream, where they actively penetrate into hepatocytes without damaging them. Sporozoites Pl. falciparum, Pl. malariae and tachysporozoites Pl. vivax and Pl. ovale immediately begin EES with the formation of a large number of exoerythrocytic merozoites (up to 40,000 from one sporozoite in malaria-falciparum). Hepatocytes are destroyed, and merozoites again enter the bloodstream, followed by rapid (within 15-30 minutes) penetration into erythrocytes. The duration of EES with malaria-falciparum is usually 6 days, with vivax malaria - 8 days, with ovafe malaria - 9 days, with malariae - 15 days.
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hibernation stage
In malaria-vivax and malaria-ovale, bradysporozoites that have invaded hepatocytes turn into inactive forms - hypnozoites, which can remain without division for several months or even years until subsequent reactivation (division and formation of merozoites). Thus, long-term incubation (up to 3-10 months or more) and the development of distant exoerythrocyte relapses, characteristic only for these forms of malaria, are associated with hypnozoites.
Erythrocyte schizogony
Features of the cycle of erythrocyte schizogony and the main pathogenetic mechanisms for the development of severe and complicated forms of malaria-falciparum:
- accumulation (sequestration) of invaded erythrocytes containing adult trophozoites (from the stage of amoeboid trophozoite), schizonts in the vessels of internal organs, mainly the brain, as well as kidneys, liver, intestines, bone marrow, placenta, etc .;
- the formation of so-called rosettes, consisting of invaded and unaffected erythrocytes;
- development of microcirculation disorders, tissue hypoxia, metabolic acidosis(significant accumulation of lactic acid);
- activation of MFS (mainly Th-1 immune response) with increased synthesis of a-tumor necrosis factor, y-interferon, interleukin-1 and other cytokines that damage the vascular endothelium and cause erythrocyte adhesion to the endothelium of blood vessels.
In recent years, the special role of increased synthesis of nitric oxide (NO) by the endothelial cells of cerebral vessels in the development of the cerebral form of malaria-falciparum has been considered.
The occurrence of febrile paroxysms in malaria is due to hemolysis of erythrocytes, the release of merozoites into the plasma, the destruction of some of them (the other part of the merozoites is again introduced into erythrocytes), MFS activation and increased synthesis of interleukin-1, -6, a-tumor necrosis factor and other endogenous pyrogens ( pro-inflammatory cytokines) that affect the thermoregulatory center of the hypothalamus.
If there is one generation of plasmodia in the blood from the first days of the disease, regularly alternating paroxysms occur. Often, with malaria-falciparum and malaria-vivax (in hyperendemic regions with intense malaria transmission), non-immune individuals experience an initial (initial) fever associated with the development of several generations of pathogens in the erythrocytes of patients at once with a different end of the development cycle in time, which leads to layering seizures, smoothing the period of apyrexia, distortion of a typical paroxysm.
An increase in the liver and spleen in all forms of malaria is associated with their significant blood supply, edema, hyperplasia of the MFS.
The stage of gametocytogonia is, as it were, an offshoot of the ES stage. Part of the merozoites (a genetically determined process), instead of repeating the asexual development cycle after being introduced into the erythrocyte, turns into sexual forms - gametocytes (male and female).
Features of the stage of gametocytogonia in malaria-falciparum:
- gametocytes appear in the peripheral blood not earlier than 10-12 days of illness;
- gametocytes, accumulating during the course of the disease, can circulate in the bloodstream for a long time (up to 4-6 weeks or more).
In other forms of malaria (vivax, ovale, malariae), gametocytes can be detected in the peripheral blood from the first days of the disease and quickly (within a few hours - days) die.
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P. falciparum live in the human body (without treatment) up to 1.5 years, P. vivax and P. ovale - up to 3 years, P. malariae - for many years, sometimes for life.
Forms
According to WHO recommendations, malaria is divided into uncomplicated, severe and complicated. Malignant forms of malaria and complications are characteristic mainly of P. falciparum infection. Disease caused by P. vivax, P. ovale, and P. malariae is usually benign.
Three day malaria
The incubation period of three-day malaria ranges from 10-21 days to 6-14 months. Prodromal symptoms of malaria before a primary malarial attack are rarely observed, but they often precede relapses and are expressed by a feeling of general malaise, weakness, fatigue, pain in the lumbar region, limbs, a slight rise in body temperature, loss of appetite, headache. The duration of the prodromal period averages 1-5 days.
oval malaria
In many clinical and pathogenetic features, oval malaria is similar to three-day vivax malaria. The incubation period of oval-malaria is 11-16 days. With oval malaria, the pathogen tends to primary latency. In this case, the duration of the incubation period can stretch for 2 months-2 years or more. Symptoms of malaria are intermittent three-day fever, less often it is daily. Fever attacks often occur in the evening hours, and not in the morning, as is typical for other forms of malaria. Oval-malaria is characterized by a predominantly mild course with a small number of paroxysms that occur without severe chills and with a lower temperature at the peak of attacks. It is characteristic that paroxysms during the primary attack very often stop spontaneously. This is due to the rapid formation of stable immunity. If treatment with histoschizotropic drugs is not carried out, 1-3 relapses are possible with an interrecurrent interval of 17 days to 7 months.
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tropical malaria
The most severe form of malarial infection. The incubation period is 8-16 days. At the end of it, some non-immune individuals have prodromal symptoms of malaria lasting from several hours to 1-2 days: malaise, weakness, weakness, body aches, myalgia and arthralgia, headache. In most patients, tropical malaria begins acutely, without a prodromal period, with a rise in body temperature to 38-39 ° C. If the cycles of erythrocyte schizogony do not end simultaneously in an infected organism in several generations of P. falciparum, this is often clinically expressed by the absence of a cyclic periodicity of febrile attacks. Attacks that occur with an alternating phase change begin with chills lasting from 30 minutes to 1 hour. During this period, the skin is pale, cold to the touch, often with a roughness like "goosebumps". Chills are accompanied by a rise in body temperature to 38-39 ° C. With the cessation of chills, the second phase of paroxysm begins - fever. Patients have a slight sensation of warmth, sometimes they experience a feeling of true heat. The skin becomes hot to the touch, the face is hyperemic. The duration of this phase is about 12 hours, it is replaced by mild sweating. Body temperature drops to normal and subnormal figures and after 1-2 hours rises again. In some cases, the onset of tropical malaria is accompanied by nausea, vomiting, and diarrhea. Sometimes register catarrhal symptoms of malaria from the upper respiratory tract: cough, runny nose, sore throat. In later periods, herpetic eruptions on the lips and wings of the nose are observed. AT acute stage in patients, hyperemia of the conjunctiva is noted; in severe cases of the disease, it may be accompanied by petechial or larger subconjunctival hemorrhages.
During the height of tropical malaria, chills are less pronounced than in the first days of the disease, its duration is 15-30 minutes. Fever continues for days, periods of apyrexia are rarely recorded. With a mild course of the disease, the body temperature at the peak reaches 38.5 ° C, the duration of the fever is 3-4 days; with moderate severity - respectively 39.5 ° C and 6-7 days. The severe course of the disease is characterized by an increase in body temperature to 40 ° C and above, and its duration is eight or more days. The duration of individual paroxysms (and in fact the layering of several) with tropical malaria reaches 30-40 hours. The wrong type of temperature curve prevails, remitting is less often observed, occasionally - intermittent and constant types.
An increase in the liver is usually determined on the 3rd day of illness, an increase in the spleen - also from the 3rd day, but it is recorded more often only by percussion; clear palpation becomes possible only for 5-6 days. With ultrasound of the abdominal organs, an increase in the size of the liver and spleen is determined already 2-3 days after the clinical manifestations of tropical malaria have arisen. Violations of pigment metabolism are observed only in patients with severe and less often moderate course of tropical malaria. More than a three-fold increase in serum aminotransferase activity is regarded as an indicator of a poor prognosis. To metabolic disorders in tropical malaria include changes in the hemostasis system and hypoglycemia. Violations by of cardio-vascular system have a functional character, are expressed by tachycardia, muffled heart tones, hypotension. Occasionally, a transient systolic murmur is heard at the apex of the heart. In a severe form of the disease, changes in the ECG are noted in the form of deformation of the final part of the ventricular complex: flattening and reverse configuration of the T wave, a decrease in the ST segment. At the same time, the voltage of the R waves in standard leads decreases. In patients with a cerebral form, P-wave changes are of the P-pulmonale type.
In tropical malaria, CNS disorders associated with high fever and intoxication are often observed: headache, vomiting, meningism, convulsions, drowsiness, sometimes a delirium-like syndrome, but the patient's consciousness is preserved.
Characteristic signs of moderate and severe malaria infection are hemolytic anemia and leukopenia, eosin and neutropenia, relative lymphocytosis are noted in the leukocyte formula. In severe forms of the disease, neutrophilic leukocytosis is possible; ESR is constantly and significantly increased. Thrombocytopenia is a symptom typical of all types of malaria. As with other infectious diseases, transient proteinuria is observed in patients.
The recurrent course of tropical malaria is due either to inadequate etiotropic treatment, or to the presence of P. falciparum resistance to the chemotherapy drugs used. The natural course of tropical malaria with a favorable outcome lasts no more than 2 weeks. In the absence of etiotropic therapy, relapses occur after 7-10 days.
Severe lesions of the central nervous system in tropical malaria are united under the name "cerebral malaria", its main symptom is the development coma. Malarial coma is a complication of primary, recurrent and recurrent malaria, but more often it is observed in primary malaria, mainly in children, pregnant women and in young and middle-aged people.
The cerebral form is the most common complication severe course of malaria-falciparum. AT modern conditions the cerebral form develops in 10% of all cases of malaria-falciparum in the world, and 60-80% of all deaths of the disease are associated with this complication. The cerebral form can develop from the first days, but is more often recorded on the 2nd week of the disease in the absence of specific or inadequate therapy. Death can occur within 1-2 days. In the clinical picture of cerebral malaria, three periods are distinguished: stunning, stupor and true coma.
The stage of stunning is characterized by mental and physical lethargy of the patient, rapid exhaustion. He is oriented in time and space, but he is reluctant to make contact, answers questions in monosyllables, and quickly gets tired. Tendon reflexes are preserved.
The stupor stage is expressed by a deep prostration of the patient with rare flashes of consciousness. Ataxia, amnesia, convulsions, sometimes epileptiform in nature, are possible. Corneal reflexes are preserved, pupils are normal. Tendon reflexes are increased, pathological reflexes occur.
With cerebral malaria, psychosis may develop as a result of degenerative changes in the brain parenchyma. In the acute period, psychoses occur in the form of delirium, amentia, epileptic seizures, and manic states. Postmalarial psychoses are characterized by depression, mental weakness, hysteria, schizophrenia-like syndromes; in children, a temporary delay in mental development. Sometimes there are long-term consequences of cerebral malaria: hemiplegia, ataxia, focal symptoms from cranial nerves, extrapyramidal disorders, mono- and polyneuritis.
The development of acute renal failure is usually observed in malignant, complicated course of malaria-falciparum. The development of oliguria and anuria with an increase in creatinine and urea in the blood is characteristic; in the analysis of urine, pronounced proteinuria, cylindruria, pyuria, and microhematuria are determined.
Nephrotic syndrome - a characteristic complication of malaria-malariae, characterized by a slow, steadily progressive course, accompanied by edema, arterial hypertension, proteinuria, the development of renal failure.
Acute pulmonary edema in patients with tropical malaria often leads to death. The mechanism of this severe complication is not fully understood. Pulmonary edema is provoked by excessive rehydration, but it can also develop against the background of normal pressure in the pulmonary circulation. Currently, most researchers consider acute respiratory failure in tropical malaria as a manifestation of adult respiratory distress syndrome.
A rare but formidable complication in any clinical form of malaria with or without hyperreactive splenomegaly is splenic rupture. The rupture can be caused by torsion of the splenic pedicle with acute blood stasis and the development of a subcapsular hematoma.
With tropical malaria, lesions of the cornea of the eye, iritis, iridocyclitis, clouding of the vitreous body, optic neuritis, chorioretinitis and retinal hemorrhages are possible, there are reports of paralysis of the eye muscles caused by damage to the III, IV and VI pairs of cranial nerves, accommodation paralysis.
Relapses of malaria
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Diagnosis of malaria
Diagnosis of malaria is based on epidemiological data (stay in the focus of malaria, lack or insufficiency of chemoprophylaxis). on the clinical picture of the disease (characteristic seizures) and is confirmed by laboratory tests.
Diagnosis of malaria should take into account:
- acute onset of the disease, severe symptoms of intoxication, cyclical course with alternating attacks of fever and periods of apyrexia, enlargement of the liver and spleen, development of progressive hemolytic anemia;
- epidemiological anamnesis data (stay in an area unfavorable for malaria, blood transfusion, drug addiction);
The duration of the course of malaria, taking into account the development of relapses with a single infection and without adequate etiotropic therapy
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form of malaria |
Duration of infection |
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Maximum |
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Malaria-falciparum |
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Malaria-malariae |
possible for life |
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Malaria-vivax and ovale |
up to 1.5-2 years |
It's necessary:
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1-20 in 100 fields |
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10-100 in 100 fields |
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1-10 in 1 field |
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More than 10 in 1 field |
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Laboratory diagnosis of malaria consists in microscopic examination of blood products (thick drop and thin smear methods) stained according to Romanovsky-Giemsa.
In recent years, rapid tests (immunochromatographic methods) based on the detection of the specific HRP-2a protein and the pLDH enzyme have been used in endemic foci to quickly obtain a preliminary response. P. falciparum. Tests of one of the famous rapid tests KAT-P.F. ("KAT MEDICAL", South Africa) showed high efficiency and specificity in relation to P. falciparum. Comparison of the results of the rapid test, microscopy and PCR showed that its diagnostic efficiency reaches 95-98%. The use of rapid tests allows you to find out the result after 10 minutes. The reaction can be mastered by laboratory staff in 1-2 hours. Express methods make it possible to carry out self-diagnosis for people living or traveling in endemic regions, they can be carried out in the field. In Russia, express diagnostics of malaria is still limited to individual clinical trials.
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Differential Diagnosis
Differential diagnostic search for malaria is carried out depending on the severity clinical manifestations illness and its duration. First of all, malaria is differentiated from diseases that occur with prolonged fever, enlargement of the liver, spleen, and the possible development of anemia: typhoid fever and paratyphoid, brucellosis, leptospirosis, sepsis, lymphogranulomatosis. In the first 5 days from the moment of illness, influenza (or other acute respiratory viral infections) is a common misdiagnosis for malaria in non-endemic regions.
In the tropical countries of South America, Africa, Southeast Asia, India, a differential diagnosis of malaria with hemorrhagic viral fevers (yellow fever, dengue fever, etc.) is carried out.
In the cerebral form of malaria-falciparum, differential diagnosis of malaria is carried out with encephalopathies (coma) that develop with decompensated diabetes mellitus, liver and kidney failure, as well as edema and swelling of the brain with meningitis or meningoencephalitis of bacterial or viral etiology.
Malaria treatment
The treatment of malaria includes the relief of acute attacks of the disease, the prevention of relapses and gametocarriers, as well as the restoration of impaired body functions.
Currently used drugs are classified into six groups chemical compounds: 4-aminoquinolines (chloroquine - delagil, chloroquine phosphate, nivaquine), quinolinemethanolam (quinine - quinine dihydrochloride, quinine sulfate, quinimax, mefloquine), phenanthrenemethanolam (halfan, halofantrine), artemisinin derivatives (artesunate, artemether, arteeter), antimetabolites (proguanil ), 8-aminoquinolines (primaquine, tafenoquine). In addition, combined antimalarial drugs are used: savarin (chloroquine + proguanil), malarone (atovachone + proguanil), coartem or riamet (artemether + lumefantrine).
For a radical cure (prevention of distant relapses) in malaria caused by P. vivax or P.ovale, at the end of the course of chloroquine, a tissue schizontocide, primaquine, is used. It is taken for 14 days at a dose of 0.25 mg/kg (base) per day. Strains P. vivax, primaquine-resistant strains (so-called Chesson-type strains) are found in the Pacific Islands and Southeast Asia. In these cases, one recommended regimen is 0.25 mg/kg primaquine daily for 21 days.
Upon detection P. falciparum in the blood of non-immune persons in cases of mild course, the drugs of choice, in accordance with WHO recommendations, are mefloquine and artemisinin derivatives (artemether, artesunate, arteeter); halofantrine may also be used. In the absence of mefloquine and halofantrine and / or the presence of contraindications to the use of these drugs, quinine is prescribed in combination with antibiotics (tetracycline, doxycycline). Tetracycline is taken 0.5 g twice a day for 7-10 days; it can be replaced with doxycycline in a daily dose of 0.1 g, the duration of administration is 7-10 days. In regions where P. falciparum resistant to mefloquine and quinine, for the treatment of uncomplicated tropical malaria, it is recommended to use a combination of mefloquine with artemisinin (artes)nat, artemether). Effective treatment of uncomplicated tropical malaria with a combination of fansidar and artesunate. Artemisinin preparations are widely used for the treatment of multidrug-resistant tropical malaria in Southeast Asia, a number of countries in South America and Africa. They act very quickly both on the blood stages and on the gametocytes. However, these drugs are quickly excreted from the body, so relapses of malaria occur. It is more advisable to prescribe them in combination with mefloquine in the following doses:
- artesunate: 4 mg/kg twice a day for 3 days; mefloquine: 15 mg/kg once on day 2 or at a dose of 25 mg/kg in two divided doses on days 2 and 3;
- artemether: 3.2 mg/kg once daily for 3 days; mefloquine: 15 mg/kg once on day 2 or at a dose of 25 mg/kg in two doses on days 2 and 3.
Treatment regimens for uncomplicated malaria
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Application schemes |
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A drug |
first dose, mg/kg |
subsequent doses, mg/kg (interval, h) |
course duration, days |
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Chloroquine |
10 (bases) |
10 - 1-2 days 5 - 3 days |
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Fansidar (sulfadoxine + pyrimethamine) |
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Quinine, kinimax, kinoform |
10 (bases) |
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Mefloquine |
15 (bases) |
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Halofantrine |
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Artesunate |
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Artemether |
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Quinine-tetracycline |
10,0 (8)+5,0 (6) |
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Coartem (artemether + lumefantrine) |
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When the type of pathogen is not established, treatment is recommended according to the treatment regimens for tropical malaria. If the patient vomits earlier than 30 minutes after ingestion of the prescribed antimalarial drug, the same dose should be taken again. If vomiting occurs 30-60 minutes after taking the tablets, then an additional half dose of this drug is prescribed.
Patients with severe form Tropical malaria must be hospitalized in the intensive care unit or intensive care unit. Quinine remains the treatment of choice for severe tropical malaria. In the treatment of complicated forms (cerebral malaria, algid), the first dose (7 mg/kg) of quinine base is administered intravenously over 30 minutes. Then another 10 mg/kg is administered intravenously by drip over 4 hours. Thus, the patient receives 17 mg/kg of quinine base during the first 4.5 hours after the start of treatment. According to another scheme, the initial dose of 20 mg/kg of quinine base is administered over 4 hours. Patients tolerate both schemes satisfactorily - without cardiovascular or other disorders. A maintenance dose of 10 mg/kg of quinine base is administered at intervals of 8 hours, the duration of administration is 1.5-2 hours. It is advisable to combine quinine with tetracycline (250 mg four times a day for 7 days) or with doxycycline (0.1 g in day for 7-10 days). For the treatment of children, it is recommended to administer a loading dose (15 mg / kg) of quinine base intravenously in 5% glucose solution for 4 hours. A maintenance dose (10 mg / kg) is administered for 2 hours with an interval of 12 hours. The same dose is used and at intramuscular injection, but quinine is recommended to be diluted five times in distilled water and divided into two injections in different buttocks.
As an alternative drug for the treatment of complicated tropical malaria, artemether is used at a daily dose of 3.2 mg/kg on the first day of treatment. In the next six days, it is administered at a dose of 1.6 mg/kg intramuscularly in combination with a single dose of mefloquine.
Patients with severe and complicated forms of malaria are prescribed intensive pathogenetic therapy. During rehydration, one should be wary of pulmonary and cerebral edema, but the state of hypovolemia is no less dangerous. Failure to rehydrate these patients may result in tissue perfusion failure, acidosis, hypotension, shock, and renal failure. Developing anemia is usually not life threatening, but if the hematocrit is reduced to 15-20%, then red blood cells or whole blood should be transfused. Transfusion of fresh whole blood or concentrates of clotting factors and platelets is used for DIC. In case of hypoglycemia, intravenous administration of a 40% glucose solution should be resorted to.
The basis of treatment for cerebral edema is detoxification, dehydration, the fight against cerebral hypoxia and respiratory disorders (oxygen therapy, mechanical ventilation). According to the indications, anticonvulsants are administered. Experience in the treatment of cerebral malaria has proven the ineffectiveness and even the danger of using osmotic diuretics: low molecular weight dextrans; adrenaline; prostacyclin; pentoxifylline; cyclosporine; hyperimmune sera. Hyperbaric oxygen therapy is also not recommended.
With the development of acute renal failure or acute renal-hepatic insufficiency, the daily dose of quinine should be reduced to 10 mg kg due to the possible accumulation of the drug and solutions should be administered at a rate of 20 drops per minute. In the initial period of acute renal failure, forced diuresis is carried out, and in the absence of effect and an increase in azotemia, hemodialysis or peritoneal dialysis, usually giving good result. With the development of hemoglobinuric fever, the drug that caused hemolysis is canceled. If necessary, it is replaced with other antimalarial drugs, at the same time glucocorticoids (prednisolone 1-2 mg / kg), detoxification therapy are prescribed.
With a rupture of the spleen, which usually develops in cases of rapid and significant enlargement of the organ, emergency surgical intervention is indicated.
For the treatment of relapses of tropical malaria, a previously unused drug is selected or the former is used, but in combination with other antimalarial drugs. Gametocarriage is eliminated with primaquine within 1-3 days at usual therapeutic doses.
Evaluating the effectiveness of malaria treatment (WHO, 1996)
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Radical treatment of malaria
Radical treatment of malaria is carried out simultaneously with stopping or immediately after it.
- Primaquine is prescribed to prevent exoerythrocytic relapses of malaria-vivax and malaria-ovale with the aim of influencing the hypotozoites. (Primaquine) 45 mg (27 mg of base) per day (3 tablets) - a course of 14 days or 6 tablets. - 1 time per week - 6-8 weeks (with deficiency of glucose-6-phosphate dehydrogenase). Tafenoquine undergoing clinical trial (Tafenoquine) - analogue of primaquine, but with higher clinical efficacy and a lower incidence of adverse reactions.
- Primaquine is used to rule out malaria-falciparum transmission (by targeting gametocytes). (Primaquine) 45 mg (27 mg base) per day (table 3) - 3 days. Treatment is carried out in regions endemic for tropical malaria. When used in the treatment of fansidar in patients who have had falcirarum malaria, primaquine is not prescribed due to the effective effect of pyrimethamine (Pyrimethamine), which is part of fansidar, on the gametocytes of Pl. falciparum.
Treatment of severe and (or) complicated malaria-falciparum is carried out in intensive care units, intensive care units. If it is impossible to take drugs orally, parenteral therapy is carried out with one of the following drugs:
- quinine dihydrochloride (quinine dihydrochloride)- 10-20 mg / kg (up to 2.0 g per day) intravenously in 500 ml of a 5% glucose solution, slowly, 2-3 times a day until the patient recovers from a serious condition, then one of the oral preparations for treatment regimen for uncomplicated malaria-falciparum;
- in modern conditions, for the treatment of severe forms of malaria-falciparum in some countries, new herbal preparations are used (in Russia these preparations are not certified): Artemether (Artenam) - IM 160 mg on the first day, then 80 mg - 6 days; Artesunate - in / m (in / in) 50 mg 2 times a day - 7 days; Artemisinine- IM 1200 mg - 7 days.
The ongoing pathogenetic treatment of malaria depends on the severity of the course of malaria and the development of complications. Carry out detoxification therapy, correction of metabolic acidosis, hypoglycemia, prescribe diuretics, antihistamines, glucocorticosteroids (according to indications), vitamins, cardiovascular and other drugs. With anuria, peritoneal dialysis is possible. In the treatment of hemoglobinuric fever, the drugs that caused hemolysis are first of all canceled, and red blood cell transfusion is performed.
Prevention
WHO is fighting malaria worldwide through the Roll Back Malaria Program adopted in 1998. WHO has now set a new target for the European Region to eliminate three-day malaria (P. vivax) by 2010 and tropical malaria by 2015 d. The most important link in the complex of measures is the timely detection and treatment of sources of infection.
Individual prophylaxis of malaria while staying in an endemic focus is aimed at preventing infection and preventing a malarial attack. Prevention of infection consists in taking measures to protect against mosquito bites (using repellents, nets on windows and doors, bed curtains, clothing that covers arms and legs when outdoors in the evening and at night). In accordance with WHO recommendations, prevention of a malaria attack consists of taking antimalarial drugs, it is recommended only for non-immune persons traveling to foci with a high risk of contracting malaria and lack of available medical care(remoteness of medical institutions, the impossibility of a quick blood test for malaria).
The need for use, duration and frequency of taking drugs is determined only after consultation with an infectious disease specialist. It is important to identify contraindications for taking chemotherapy drugs, the presence of severe concomitant diseases. Pregnant non-immune women and young children should not travel to areas where malaria is endemic.
Given the high resistance of Pl. falciparum to chloroquine, the standard for the prevention of malaria-falciparum, as recommended by WHO, is currently mefloquine (250 mg once a week, 2 weeks before departure to an endemic region and within 4 weeks after return). The use of other drugs (doxycycline, chloroquine in combination with proguanil, atovakin in combination with proguanil, primaquine, and others) is determined by the infectious disease specialist, taking into account the epidemic situation in the region of stay and other above-mentioned factors.
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The content of the article
Malaria(synonyms of the disease: fever, swamp fever) - an acute infectious protozoal disease that is caused by several species of plasmodia, transmitted by mosquitoes of the genus Anopheles and characterized by a primary lesion of the system of mononuclear phagocytes and erythrocytes, manifested by attacks of fever, hepatolienal syndrome, hemolytic anemia, a tendency to relapse.Historical malaria data
As an independent disease, malaria was isolated from the mass of febrile diseases by Hippocrates in the 5th century BC. BC e., however, the systematic study of malaria began only in the 17th century. So, in 1640, the doctor Juan del Vego proposed an infusion of cinchona bark for the treatment of malaria.For the first time detailed description the clinical picture of malaria was made in 1696 by the Genevan physician Morton. The Italian researcher G. Lancisi in 1717 connected cases of malaria with the negative impact of fumes from marshy areas (translated from Italian Mala aria - spoiled air).
The causative agent of malaria discovered and described in 1880 p. A. Laveran. The role of mosquitoes from the genus Anopheles as carriers of malaria was established in 1887 by p. R. Ross. Discovery in malariology, which were made in the XX century. (Synthesis of effective antimalarial drugs, insecticides, etc.), studies of the epidemiological characteristics of the disease made it possible to develop a global program for the eradication of malaria, adopted at the VIII session of the WHO in 1955. The work carried out made it possible to drastically reduce the incidence in the world, however, as a result of the emergence of resistance of individual strains of plasmodia to specific treatment and carriers to insecticides, the activity of the main foci of invasion has remained, as evidenced by an increase in the incidence of malaria in recent years, as well as an increase in the importation of malaria into non-endemic regions.
Etiology of malaria
The causative agents of malaria belong to the Protozoa phylum, class Sporosoa, family Plasmodiidae, genus Plasmodium. Known four types of malarial plasmodium that can cause malaria in humans:- P. vivax - three-day malaria,
- P. ovale - three-day ovalemalaria,
- P. malariae - four-day malaria,
- P. falciparum - tropical malaria.
Sporogony
Mosquitoes of the genus Anopheles become infected by sucking the blood of a malaria patient or carrier of Plasmodium. At the same time, male and female sexual forms of plasmodium (micro- and macrogametocytes) enter the stomach of the mosquito, which turn into mature micro- and macrogametes. After the fusion of mature gametes (fertilization), a zygote is formed, which later turns into an ookinet.The latter penetrates the outer shell of the mosquito's stomach and turns into an oocyst. In the future, the oocyst grows, its content divides many times, resulting in the formation of a large number of invasive forms - sporozoites. Sporozoites are concentrated in salivary glands ah mosquito where can be stored for 2 months. The speed of sporogony depends on the type of plasmodia and the ambient temperature. So, in P. vivax at the optimum temperature (25 ° C), sporogony lasts 10 days. If the ambient temperature does not exceed 15 ° C, sporogony stops.
schizogony
Shizogony occurs in the human body and has two phases: tissue (pre-, or extra-erythrocyte) and erythrocyte.tissue schizogony occurs in hepatocytes, where tissue trophozoites, schizonts and an abundance of tissue merozoites are sequentially formed from sporozoites (in P. vivax - up to 10 thousand per sporozoite, in P. falciparum - up to 50 thousand). Shortest duration tissue schizogony is 6 days in P. falciparum, 8 in P. vivax, 9 in P. ovale, and 15 days in P. malariae.
It has been proven that with four-day and tropical malaria, after the end of tissue schizogony, merozoites completely exit the liver into the blood, and with three-day and oval malaria, due to genetic heterogeneity of sporozoites, tissue schizogony can occur both immediately after inoculation (tachysporozoites), and after 1, 5-2 years after it (brady or hypnozoites), which is the cause of prolonged incubation and distant (real) relapses of the disease.
High susceptibility to infection especially in young children. Carriers of abnormal hemoglobin-S (HbS) are relatively resistant to malaria. Seasonality in regions of temperate and subtropical climate is summer-autumn; in countries with a tropical climate, cases of malaria are recorded throughout the year.
Today, malaria is rarely observed in temperate zones, but is widespread in Africa, South America, and Southeast Asia, where stable foci of the disease have formed. In endemic regions, about 1 million children die every year from malaria, which is the main cause of their deaths, especially in early age. The degree of spread of malaria in certain endemic regions is characterized by the splenic index (SI) - the ratio of the number of persons with an enlarged spleen to the total number of those examined (%)
Pathologically, significant dystrophic changes are found in the internal organs. The liver and, especially the spleen, are significantly enlarged, slate-gray in color due to the deposition of pigment, foci of necrosis are found. Necrobiotic changes and hemorrhages are found in the kidneys, myocardium, adrenal glands and other organs.
After the first attacks, patients develop subicteric sclera and skin, enlarge the spleen and liver (splenohepatomegaly), which acquire a dense texture. A blood test reveals a decrease in the number of erythrocytes, hemoglobin, leukopenia with relative lymphocytosis, thrombocytopenia, an increase in ESR.
In primary malaria, the number of paroxysms can reach 10-14. If the course is favorable, from the 6-8th attack, the body temperature during paroxysms gradually decreases, the liver and spleen contract, the blood picture returns to normal and the patient gradually recovers.
malarial coma develops in malignant forms of the disease, more often in primary tropical malaria. First, against the background of high body temperature, an unbearable headache, repeated vomiting appear.
A disturbance of consciousness develops rapidly, which goes through three successive phases:
- doubt - adynamia, drowsiness, sleep inversion, the patient is reluctant to make contact,
- stupor - consciousness is sharply inhibited, the patient reacts only to strong stimuli, reflexes are reduced, convulsions, meningeal symptoms are possible,
- coma - fainting, reflexes are sharply reduced or not called.
Lethality is high. The patient dies with manifestations of azotemic coma. More often, hemoglobinuric fever develops in individuals with a genetically determined deficiency of glucose-6-phosphate dehydrogenase, which leads to a decrease in erythrocyte resistance.
The rupture of the spleen occurs suddenly and is characterized by dagger pain in the upper abdomen with spread to the left shoulder and shoulder blade. There is a sharp pallor, cold sweat, tachycardia, thready pulse, blood pressure decreases. Free fluid appears in the abdominal cavity. If an emergency surgical intervention is not carried out, patients die from acute blood loss against the background of hypovolemic shock.
To others possible complications include malarial algid, pulmonary edema, DIC, hemorrhagic syndrome, acute renal failure, etc.
Microscopic examination of blood for malaria should be performed not only in patients with suspected malaria, but also in all patients with fever of unknown origin.
If with tropical and four-day malaria with the help of hemoschizotropic drugs it is possible to completely free the body from schizonts, then for radical treatment three-day and ovalemalaria requires the appointment of drugs with a histoschizotropic effect (against extra-erythrocyte schizonts) at a time. Apply primaquine at 0.027 g per day (15 mg of base) in 1 - C intake for 14 days or quinocide at 30 mg per day for 10 days. Such treatment is effective in 97-99% of cases.
Chloridin, primaquine have a gamototropic effect. With three-day, oval- and four-day malaria, gamontotropic treatment is not carried out, since in these forms of malaria, gamonts quickly disappear from the blood after the cessation of erythrocyte schizogony.
Persons traveling to endemic areas undergo individual chemoprophylaxis. For this purpose, hemoschizotropic drugs are used, more often hingamin 0.5 g once a week, and in hyperendemic areas - 2 times a week. The drug is prescribed 5 days before entering the endemic zone, during the stay in the zone and within 8 weeks after departure. Among the population of endemic areas, chemoprophylaxis begins 1-2 weeks before the appearance of mosquitoes. Chemoprophylaxis of malaria can also be carried out with bigumal (0.1 g per day), amodiaquine (0.3 g 1 time per week), chloridine (0.025-0.05 g 1 time per week), etc. The effectiveness of chemoprophylaxis increases in the case of alternating two or three drugs every one to two months. In endemic foci caused by chingamino-resistant strains of malarial plasmodium, for the purpose of individual prevention, fanzidar, metakelfin (chloridin-Lsulfalen) are used. Persons arriving from three-day malaria cells are given seasonal prophylaxis of relapses with primaquine (0.027 g per day for 14 days) for two years. To protect against mosquito bites, repellents, curtains and the like are used.
The proposed merozoite, schizont and sporozoite vaccines are at the testing stage.
belong to the same genus Plasmodium, class Sporozoa(from spora - seed), order Coccidiida (true coccidia), suborder Haemosporina.
There are four types of Plasmodium that cause malaria in humans.The first of them - Plasmodium malariae - was discovered in 1880 by the founder of protistology, laureate Nobel Prize A. Laveran; P. vivax - V. Grassi and R. Feletti (1890); P. falciparum - W. Welch (1897); P. ovale - J. Stevens (1922). P. Malariae causes 4-day malaria, P. vivax 3-day malaria, P. falciparum tropical malaria, and P. ovale malaria ovale. Plasmodium differ not only in that they cause different forms malaria, but also virulence, sensitivity to chemotherapy drugs and other biological features, which, in particular, is reflected in the names of two varieties of P. vivax: northern (P. v. hibernans) - with an incubation period of 6–13 months. and southern (P. v. vivax), with an incubation period of 7–21 days.
Plasmodium malaria is characterized by a complex development cycle. One of them - schizogony (asexual cycle)- occurs in the human body, the other - sporogony (sexual development)- in the body of females mosquitoes of the genus Anopheles.
Schizogony.
The asexual cycle of development of plasmodia occurs after penetration into humans sporozoites from the salivary glands of mosquito bites. At the same time, exoerythrocyte and erythrocyte schizogony are distinguished.
exoerythrocytic schizogony takes place in the human liver where sporozoites are carried with blood. Here they are introduced into hepatocytes, rounded and turned into trophozoites, and then into exoerythrocyte schizonts. The maturation of schizonts in hepatocytes lasts from 6 (P. falciparum) to 15 days. (P. malariae) and ends with the entry into the blood plasma of 10,000 - 50,000 oval exoerythrocyte merozoites 2.5 × 1.5 μm in size.
More mature trophozoites, up to 4–6 µm in diameter, have a distinct cytoplasm, nucleus, and pigment; a semi-adult trophozoite occupies more than half, and an adult - almost the entire erythrocyte. The schizont, which fills the entire erythrocyte, has no vacuole, the nucleus is rounded, the cytoplasm is divided, and the pigment is in the form of a compact pile.
Depending on the type of plasmodium, the schizonts in an erythrocyte form from 8 to 24 mobile, elongated merozoites 1.5 × 1.0 μm in size.
After rupture of erythrocytes, they enter the bloodstream and, after 10-15 minutes, are introduced into new red blood cells. blood cells. The duration of schizogony in P. vivax, P. Ovale, and P. falciparum is 2 days; in P. malariae, it is 3 days.
Sporogony.
The sexual cycle of development of malarial plasmodium occurs in the body of the female Anopheles mosquito, which, unlike the male, feeds on human blood. Once in her stomach, macro- and microgametes merge into a zygote, which, lengthening and gaining mobility, turns into an ookinete.
Having penetrated through the wall of the mosquito's stomach under its outer shell, the ookinete rounds off, a capsule forms around it, and it turns into an oocyst, inside which, as a result of the division of the nucleus and cytoplasm, about 10,000 sickle-shaped sporozoites 10–15 µm long and 1.5 µm wide appear. Sporogony proceeds at a temperature of 10–30 °C. Its duration in different types of malaria pathogens ranges from 7 to 45 days. A mosquito becomes infectious when sporozoites from its hemolymph enter the salivary glands.
Clinic and epidemiology.
Malaria (from mal and aria - bad air)- natural endemic invasion. The incubation period of malaria depends on the type of pathogen and ranges on average from 6 to 42 days (with the exception of the northern variety of P. vivax).
malarial attack begins with a chill that lasts from 30 minutes to 2–3 hours and passes into a heat phase lasting from several hours to 1 day. The temperature in the heat phase reaches 40–41 ° C, the patient's face turns red, shortness of breath, agitation, often vomiting, and a sharp increase in headache appear. The attack ends with a decrease in temperature to normal, which is accompanied by intense sweating for 2-5 hours. Then comes a deep sleep. With 3-day malaria and oval-malaria, attacks of fever recur after 48 hours, with 4-day - after 72 hours. Usually they occur at the same time.
After several attacks, the spleen enlarges and (jaundice often occurs), anemia develops. Without any treatment, attacks of malaria after repeated repetition may spontaneously stop, with the exception of tropical malaria. Full recovery, however, does not occur.
Laboratory diagnostics.
P. vivax trophozoites have a bizarre shape, small nuclei and pseudopodia, in other types of plasmodia they are, as a rule, compact. The schizonts of P. ovale and P. malariae are divided into 8–10 merozoites, P. vivax, into 16–24, and P. falciparum, into 12–24. However, P. falciparum schizonts are extremely rare in peripheral blood; usually only rings and gametes are found in it. The diameter of erythrocytes affected by P. vivax is increased, and erythrocytes containing P. ovale become elongated. At the same time, according to Romanovsky - Giemsa, erythrocytes are stained in a slightly pink color; the body of plasmodium - in blue, its nucleus - in red, clumps of pigment - in brown; cytoplasm of macrogametocytes - in bright blue, and their nuclei - in intense red; the cytoplasm of microgametocytes is in pale blue, and their nuclei are in pink.
Recently, indirect RIF and ELISA have been used to confirm the diagnosis of malaria, which make it possible to detect antibodies specific to plasmodia at the 2nd week of the disease. Great hopes are placed on DNA probes, which can be used to detect even a small amount of specific plasmodium DNA nucleotides.
Immunity.
In the process of evolution, a person has developed innate genotypic and acquired resistance to malaria. In particular, innate resistance to P. falciparum determined by the type of hemoglobin in erythrocytes, a violation of the synthesis of its constituent globin (thalasemia), deficiency of glucose-6-phosphate dehydrogenase.
In adults, immunity to malaria is maintained by repeated infections.
Antimalarial immunity in people is lost after 1–2 years if they move to malaria-free regions. After suffering from malaria, non-sterile, species-specific, unstable and short-lived immunity occurs, which is provided by cellular and humoral factors. At an early stage of invasion, the body is protected by phagocytes..
Prevention and treatment.
Prevention of malaria is carried out in several directions. When people leave for malaria-endemic areas, they are prescribed regular appointments hingamina (delagila), and in areas with Chingamine resistant strains of Plasmodium - fansidar(combination sulfadoxine and perimethamine).
Chemoprophylaxis begins 2-3 days before arrival at the infection foci and ends after 1 month. after leaving them.
Another group of activities is aimed at the extermination of larvae in water bodies and winged mosquito vectors using landscaping and insecticides. Means of mechanical protection of people from mosquitoes and the use of repellents are also important.
Numerous antimalarial drugs are used in the treatment of malaria, which, according to the mechanism of action, are divided into hemoschisontotropic, causing the death of asexual blood forms of plasmodia; histoschisontotropic, affecting plasmodium developing in hepatocytes; gamonotropic, having a protistocidal effect on the sexual forms of plasmodium. In particular, hemoshisontotropic drugs are chloroquine, pyrimethamine, chloridine, quinine, artemisinin, etc. The best among histoschisontotropic and gamonotropic drugs are pyrimetanim, chloridine, primahvin, quinocide, as well as a true gamonotropic thiazine metabolite - proguanil.
Content
What is malarial plasmodium
- malariae- the disease has a duration of 4 days;
- plasmodium vivax (plasmodium vivax)– three-day type of malaria;
- falciparum (falciparum)– Tropical species of Plasmodium malaria;
- plasmodium ovale- another form of a three-day disease;
- plasmodium knowlesi- the sporozoan replication cycle is 24 hours, so any infection (even a weak one) quickly develops into a serious illness.
The structure of the malarial plasmodium
Life cycle of malarial plasmodium
Before being formed into a full-fledged microorganism dangerous to humans, plasmodium goes through several stages of formation. Infection occurs when a mosquito bites, which are injected along with saliva by sporozoites of Plasmodium. Next, the process of maturation takes place inside the human body and either asexual division can occur in the internal organs, or the cells will again get to the mosquito and sexual division will occur there. The life cycle of the malarial Plasmodium involves a change of hosts at different stages.
Primary host of malarial plasmodium
The mechanism of how malaria is transmitted involves several stages of maturation of the sporozoan. For the formation of sporogony, you need to get into the body of the main host of the malarial plasmodium - the Anopheles mosquito. At this stage, gametocytes are already at the stage when they are ready for division into macrogametocytes and microgametocytes. When bitten by a mosquito carrying malaria, gametocytes migrate to the main host.
Inside the body of an insect, one half of the cells becomes male, the second - female. Each of them has one chromosome set, during the process of fusion of gametes of different sexes, diploid cells with a full set of chromosomes are formed. So appear, having an elongated shape, the zygotes of Plasmodium malaria. They have high mobility, immediately penetrate the walls of the mosquito's stomach, form sporocysts - these are incubator cells that are covered with a membrane.
Intermediate host of malarial plasmodium
- Through the bite, sporozoites are transferred into the bloodstream, which quickly enter the liver tissue. Schizogony (asexual reproduction) begins, after which merozoites are formed.
- The latter penetrate into erythrocytes (red blood cells), begin to feed on hemoglobin from them and continue to multiply intensively. At this stage, the cell looks like a circle or an oval with protoplasm up to 2 microns in size.
- At the next stage, the merozoites leave the erythrocytes, take the form of rings, cavities are formed inside the protoplasm, which are called digestive vacuoles. They accumulate nutrients and excrete waste products - these are toxins that enter the bloodstream.
- Every 48 hours there is a stage of development of plasmodium, which coincides with an attack of chills, fever in humans, simple temperature.
- The erythrocyte schizogony is repeated cyclically, continues until the desired level of merozoites is reached. After this, the next stage begins - gametocytes are formed, which were described above.
Diagnosis of malaria
Microscopic examination of the sample is used to confirm the diagnosis. Laboratory diagnosis of malaria consists in taking blood from a finger in the usual way. The smear is applied to a sterile glass slide, which is examined by a specialist under magnification. Diagnosis of malaria helps to identify different types Plasmodium, each of them has certain diagnostic features. Infected erythrocytes in the analysis can be identified by a change in size, shape or color.
Malaria treatment
The main objective of the treatment of this disease is to prevent the occurrence / recurrence of attacks, the complete destruction of the pathogen. The disease malaria or swamp fever is more common in endemic areas, so travelers should take preventive measures in advance. Treatment of malaria is carried out with the help of drug therapy, as a rule, Primaquine, Chloroquine, Atabrine (quinacrine hydrochloride), Akrikhin are used.
Medicines for malaria
Drug therapy for this disease is considered an effective method. There are proven drugs for malaria that have been used for a long time. An example of such a drug is Quinine, which was replaced by Chloroquine for a while, but then began to be actively used again. The reason for this was the emergence and then spread in Asia and Africa of Plasmodium falciparum, which had resistance to Chloroquine.
Depending on the region where the infection occurred, certain drugs against Plasmodium malaria may be used. Most of them are suitable for both treatment and prevention. Artemisia annual extract, containing artemisinin and analogs of synthetic origin, have high efficiency but also high cost. The disease poses a great danger to residents who live in endemic areas where there is no access to drugs. In developed countries, there are no problems with the purchase of medicines.
Complications of malaria
Timely provision of the correct therapy ensures complete recovery in the vast majority of cases. Mortality under such conditions does not exceed 1% of the total. The lethal outcome is provoked not by the pathology itself, but by the complications of malaria. Possible consequences diseases:
- mental disorders;
- acute renal failure;
- swelling of the brain;
- malarial coma (cerebral pathology).
To help avoid death, the development of complications will help urgent timely therapy. Kidney failure leads to the growth of nitrogenous waste products in the blood, which will lead to infectious-toxic shock. The clinic of cerebral edema, as a rule, is observed in children with a fulminant form of malaria. Unlike adults, with a tropical form of pathology, a child may develop mental disorders. In the event of a fatal outcome, the disease will develop in the following sequence:
- an attack of fever;
- severe headache and convulsions;
- there is a violation of the work of the vascular and respiratory center;
- cessation of breathing and cardiac activity;
- fatal outcome.
Prevention of malarial plasmodium
On the this moment There is no vaccine for this disease. For this reason, the prevention of malarial plasmodium comes to the fore. In areas where the Anopheles mosquito can live, it is necessary to carry out measures to destroy them with the help of insecticides. Without these insects, Plasmodium malaria would not be able to go through the entire life cycle. To protect against bites and use suitable repellents, it is recommended to wear long clothing, which should also be sprayed with an aerosol.
Plasmodium malaria will not be able to spread throughout the body if preventive drugs are taken. If you travel to places where you are likely to contract malaria, you must protect yourself by taking medication. It is strictly forbidden to travel to such countries during pregnancy (during this period, a woman's body is especially susceptible to various diseases).
Rezokhin, Chloroquine, Delagil tablets are used as medicines against Plasmodium malaria. The action of the drug is based on the substance of the 4-aminoquinlone derivative, which stops the synthesis of nucleic acids, which leads to the destruction of Plasmodium malaria. Do not use these medicines in liver, kidney or heart failure disorders. Prohibited drugs and children, pregnant women. To protect against Plasmodium malaria, it is recommended to take pills for another month after leaving the danger zone.
Video: malarial plasmodia
Attention! The information provided in the article is for informational purposes only. The materials of the article do not call for self-treatment. Only qualified doctor can make a diagnosis and give recommendations for treatment, based on the individual characteristics of a particular patient.
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