Malaria

The source of the infectious agent is a sick person or a parasite carrier in whose blood the gametocytes are contained. Malaria is a transmissible infection transmitted through a mosquito bite. The gametocytes P. Vivax, P. Ovale and P. Malariae are found in the blood in the early days of the disease; their number increases after several cycles of erythrocytic schizogony. When P. Falciparum is infected a person becomes a source of infection 10-12 days after the beginning of parasitemia and can stay for 2 months or more.

With malaria, different mechanisms for transmission of infection are possible:

Transmissive transfer mechanism (with mosquito bite)

This mechanism is the main one, which ensures the existence of plasmodia as a biological species. The source of the infection is a person (a malaria patient or a parasite carrier), in the blood of which there are mature gametocytes (male and female germ cells of the parasite). The carriers of malaria are only females of the genus Anopheles.

In the stomach of a mosquito, where both male and female gametocytes, which are inside the erythrocytes, get together with the blood, their further maturation (after lysis of red blood cells), fusion and multiple division with the formation of sporozoites, which accumulate in the salivary glands of the mosquito. Sexless forms of the parasite (trophozoites, schizonts), having got into the stomach of a mosquito, perish.

Thus, in the human body there is an asexual path of development of parasites (schizogony) with the formation and accumulation of gametocytes, and in the body of a mosquito - sexual (sporogony), the fusion of male and female gametocytes with their further development and the formation of sporozoites.

Vertical Transmission Transmission Mechanism

The vertical mechanism of transmission (from the mother to the fetus) or from the mother to the newborn (in the process of delivery, the parenteral mechanism). In vertical transmission, the fetus rarely becomes infected through the placenta. More often, infection occurs in childbirth when a newborn enters the bloodstream of a certain amount of maternal blood, in the red blood cells of which are the asexual forms of the parasite.

The parenteral delivery mechanism

The parenteral mechanism of infection leads to the development of so-called schizon malaria. It is realized with blood transfusions or less with violations of aseptic injections (for example, among drug users using a single syringe). In case of infection with blood transfusion, the source of infection is a parasitic donor, often with sublatent parasitemia (the number of parasites is less than five in one μl of blood). Therefore, in the malaria endemic regions of the world, in addition to parasitological methods (parasite detection in thick drops and blood smears) and serological (immunological) methods for the laboratory diagnosis of malaria (RNIF, ELISA, etc.), it is necessary to use blood parity to control blood donors. Given that parenteral infection usually involves a few parasites (especially with injections), the incubation period can be extended to 3 months (with a massive infection, the incubation period, on the contrary, can be very short - several days), which is important to know when diagnosis of malaria in patients who underwent surgical treatment, drug addicts.

Conditions for the spread of malaria

The following conditions are necessary for the spread of malaria in a certain region (country, province, region):

1. Source of infection (malaria or parasite carrier).
2. The presence of an effective carrier (mosquitoes of the genus Anopheles). Susceptibility to malarial parasites is the main quality of a specific type of mosquito from the genus Anopheles. The number of mosquitoes of the genus Anopheles among the populations of other species is not as high as that of non-malarial mosquitoes, and they rarely seriously bother with their bites. However, small species under other favorable circumstances (proximity of mosquito breeding sites to people's homes) can play quite a serious role. More than 70 species of Anopheles mosquitoes (among more than 200 known species) can be effective carriers of malaria.
3. Favorable climatic conditions: average daily air temperature above 16 ° С and availability of mosquito breeding sites: water reservoirs, water reservoirs, irrigation facilities, etc. The minimum daily mean air temperature required for the development of the mosquito in the body Pl. Vivax, - 16 ° C, for Pl. Falciparum - 18 ° C, at a lower temperature sporogony does not occur. The duration of sporogony is less, the higher the temperature (up to a certain level, since the average daily temperature of 30 ° C and above is unfavorable for sporogony). At the optimal average daily temperature (25-26 ° C), sporogony in Pl. Vivax takes 8-9 days, from Pl. Falciparum - 10-11 days.

The whole area of malaria spreading on the globe (between 45 ° N and 40 ° S to 64 ° N and 45 ° S in different years) is occupied by malaria-vivax. The areas of malaria-falciparum and malaria-malaria are somewhat smaller due to the necessary higher temperature for effective sporogony; The area of malaria-ovale is located in two regions that are not geographically interconnected: tropical Africa and the states of the western Pacific (Indonesia, Vietnam, the Philippines, New Guinea, etc.). In mountainous countries, foci of malaria can form up to heights of 1000 m in the zone of temperate climate and up to 1500-2500 m in the zone of subtropics and tropics, and only foci of malaria-vivax occur at high altitudes (1000-1500 m and above).

Malaria is characterized by pronounced seasonality. In temperate and subtropical climates, the malaria season is divided into periods: effective mosquito infestation, transmission of infection and mass manifestations of the disease. The beginning of the period of effective mosquito infestation (in the presence of a source of infection - patients, parasites) coincides with the moment of a steady increase in the average daily temperature to 16 ° C. The beginning of the transmission period is associated with the completion of sporogony in the mosquito, which depends on the specific daily average temperatures of the given year. In the Moscow region, the transmission of malaria-vivax can reach 1.5-2 months or more, before the first autumn frosts. The boundaries of the period of mass manifestations are less defined. In foci, where only three-day malaria is transmitted, the mass morbidity may begin long before the transmission period begins. The observed cases are primary manifestations of malaria-vivax with prolonged incubation (3-10 months) due to infection in the previous season and the preservation of hypnosis in the liver (without primary manifestations with a short incubation), as well as distant exoerythrocyte relapses (after a series of malaria attacks with a short incubation last season, without adequate anti-relapse therapy).

The susceptibility to malaria is universal. The outcome of infection after the causative agent enters the bloodstream and the clinical course of the disease is determined by individual immunological status, the activity of factors of nonspecific congenital resistance, the intensity of post-infection immunity, and for newborns - by the level of specific antibodies of class G, received from the mother. Exceptions are indigenous people of West Africa and New Guinea, most of them immune to infection Pl. Vivax, which is due to the genetically determined absence of erythrocyte isoantigens of the Daffy group performing the function of receptors for merozoites PI. Vivax. Accordingly, in this region is much less likely than in other regions of tropical Africa, there are cases of infection with malaria-vivax.

Relatively resistant to infection by all types of plasmodia are people who are carriers of abnormal hemoglobin (thalassemia, sickle cell anemia, carriage of hemoglobin E, C, etc.), with disturbances in the structure of the cytoskeleton of erythrocytes (hereditary spherocytosis, southeastern ovalocytosis, hereditary elliptic cytosis) or having a deficiency of the enzyme glucose-6-phosphate dehydrogenase of erythrocytes. In the case of malaria infection, they are easily affected, the number of parasites in the blood is kept at a relatively low level, cases of malignant course (cerebral form of malaria-falciparum) are practically absent. On the other hand, people with glucose-6-phosphate dehydrogenase deficiency risk developing acute hemolysis with a number of antimalarial drugs (primaquine, quinine, etc.). Mechanisms of natural resistance to various types of malaria are largely not yet clear and continue to be studied.

Newborns also have a certain resistance to infection with all forms of malaria. This is due to:

1. the presence of passive immunity due to antibodies of class G, obtained by the newborn from the hyperimmune mother (in foci with a high incidence of malaria);
2. maintenance of specific immunity after birth due to antibodies of class A, obtained by newborns with breast milk;
3. the presence of a fetal hemoglobin in a newborn, a malarial parasite that is not suitable for nutrition.

After the first three to six months of life in newborns, the risk of developing severe, malignant forms of malaria-falciparum (changing red blood cells containing fetal hemoglobin into erythrocytes containing normal hemoglobin, the transfer to mixed nutrition - the ingestion of parahaminobenzoic acid necessary for the development of the parasite , which is absent in human milk).

Immunity with malaria

Immunity in malaria is non-sterile, species-specific and strain-specific, unstable and short-lived. To maintain a protective level of antibodies, constant antigenic stimulation is required in the form of repeated infections with malaria. Immunity to Pl. Malariae and Pl. Vivax is installed earlier and is maintained longer than to Pl. Falciparum. Antimalarial immunity includes cellular and humoral responses. The beginning of immune processes that stimulate the synthesis of antibodies is the phagocytosis of malarial parasites by macrophages. This is manifested by hyperplasia of the histiophagocytic system of the spleen, liver, bone marrow.

Prevalence of malaria

Of the four types of pathogens of human malaria, the most common in the world is P. Vivax. In the subtropics and tropics in the gene pool of the P. Vivax population, sporozoites predominate. The cause of the disease after a short incubation (10-21 days). On the African continent P. Vivax is constantly found in the countries of East Africa among Arabs, Indians, Ethiopians, Europeans. In West African countries inhabited mainly by representatives of the Negroid race, P. Vivax is not met, which is explained by the genetically conditioned congenital immunity of African negroes to P. Vivax [on the erythrocytes there is no receptor for merozoites P. Vivax - isoantigens Daffy (Fy ^d or Fy ^b )] . The area 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 South-East Asia. The geographical area of tropical malaria reaches 40 ° N latitude and 20 ° S latitude P. Falciparum accounts for up to 50% of the incidence of malaria in the world. Four-day malaria is currently found in Africa, parts of Central and South America, the Caribbean. South-East Asia.

Most people are susceptible to malaria. The exception is indigenous to West Africa. For hyperendemic foci of tropical Africa, where P. Falciparum predominates, the relatively stable immune structure of the indigenous population is characteristic:

• children under the age of 6 months do not fall ill due to passive immunity received from the mother:
• most children aged 6-24 months are affected by P. Falciparum; passive immunity is extinct, active is not yet developed; in this group the highest mortality from malaria is observed:
• in children older than 2 years P. Falciparum is less common, the course of malaria is mitigated as a result of acquired immunity, the intensity of parasitemia decreases with age:
• in adults P. Falciparum is rarely found due to high immunity, there are no clinical manifestations when infected.

Tropic malaria is also easily tolerated by carriers of abnormal hemoglobin S (sickle-cell anemia) and faces with some other genetically determined hemoglobin anomalies and erythrocyte enzymes (deficiency of G-6-FDH).

History of the study of malaria

The study of malaria (one of the most ancient 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 intensive development of agriculture, trade, development of new lands. In ancient Egyptian papyri, Chinese ancient literature and canons ("Charaka" and "Sushrutha") of classical ancient Indian medicine ("Ayurveda"), the descriptions of the clinic and epidemics of malaria have survived to this day; already then there were suggestions of a possible connection between the development of the disease and mosquito bites. Later (5th-6th centuries BC), the ancient physicians of Greece: Hippocrates, Geradot, Empedocles described in detail the malaria clinic. Hippocrates deserves credit for the allocation of malaria from the group of febrile illnesses: he proposed to isolate 3 forms of the disease: "quotidian" (daily bouts), "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 Juan del Vego (Nyap del Vego) used the cinchona bark extract, previously used by the Indians of Peru and Ecuador as an antiplatelet agent, for the treatment of malaria. Merit in the name of the disease "malaria" (ital "mal aria" - bad air) belongs to the Italian Lancisi (1717), which linked the infection of people with malaria through "poisonous" fumes from the marshes. In 1880 the French doctor A. Laveran, working in Algiers, described in detail the morphology of the pathogen of malaria. In 1897 the English military doctor Ronald Ross (Ronald Ross) in India had 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 with the risk of contracting malaria. Almost all countries in Europe and North America annually register hundreds of imported cases of malaria among people who come from the regions where it is spread, the number of cases of so-called airport malaria is increasing. According to the WHO, 200-250 million people worldwide get malaria every year, at least 80% of all malaria cases are registered in sub-Saharan Africa. Every year from 1 to 2 million people die from malaria, mostly children under 5 years old. Social and economic losses in Africa alone are estimated at 2 billion US dollars per year. Since 1998, under the auspices of WHO, the World Bank, UNICEF, the Roll Back Malaria Initiative has been implemented to monitor malaria (mainly in the developing world). The program is valid until 2010-2015. Efforts are actively being made to create an effective antimalarial vaccine, but this will require at least another 10-15 years. The search, development and improvement of drugs for the treatment of malaria are one of WHO's priority programs, various pharmaceutical companies, research institutes around the world. In recent years, as a result of the growth of migration processes, intensive development of international tourism, an increase in imported cases of malaria has been noted in Russia.