MALARIA (ital. mala aria bad air) — the acute protozoan disease caused by malarial plasmodiums and which is characterized by periodic attacks of fever, increase in a spleen and liver, anemia, a recurrence. Carriers of activators — mosquitoes of different types of the sort Anopheles.
- 1 History
- 2 Distribution and statistics
- 3 An etiology
- 4 Epidemiology
- 5 The pathogeny
- 6 Pathological anatomy
- 7 Immunity
- 8 The clinical picture
- 9 The diagnosis
- 10 Treatment
- 11 The forecast
- 12 Prevention
- 13 Features of malaria at children
- 14 Malaria
the Term mal’ aria arose in Italy. It is mentioned in Francesco Sansovino's book (Francesco Sansovino, 1560), used in the medical text of Zhakye (F. Jacquier, 1743).
To m of the person it is known since the most ancient times. Klien, a picture of feverish attacks at M. is described by Hippocrates in 400 years BC. A. Tsels (30 AD) described two types of fever at three-day M., and in 150 years after that K. Galen pointed to communication of such fevers with a summer season. In 1880 A. Laveran opened the activator M. of the person, and in 1884 Ya. Danilevsky — malarial parasites of birds. In 1891 D. L. Romanovsky offered original coloring of plasmodiums that allowed to study their fine structure. R. Ross (1897) observed early stages of development of Plasmodium falciparum in the mosquitoes of the sort Anopheles fed on patients whose blood contained a large number of gametocytes. In 1898 he described a sporogony of the activator M. of birds in mosquitoes of the sort Culex and experimentally proved ability of mosquitoes to transfer activators M. of birds. D. Grassi, Binyami and Bastianelli (A. Bignami, G. Bastianelli) in 1898 — 1899 observed all stages of a sporogony of activators of three-day, four-day and tropical M. of the person at mosquitoes of the sort Anopheles, having established thus their exclusive role as carriers of activators M. of the person. At the end of 19 — the beginning of 20 EL of Grassi and N. Jancso established that R. of vivax does not develop in a body of a mosquito at air temperature lower than 15,5 or 16 °. Opening of ekzoeritrotsitarny stages of development of the activator M was an important stage. In 1900 D. Grassi assumed a possibility of erythrocyte stages of development of a parasite from sporozoit in the indirect way, but only in 1948 Mr. Shortt and Garnem (H. E.Shortt, R. S. S. of Garnham) showed a preeritrotsitarny stage of development of activators M. of the person. Ladda (R. L. Ladda, 1969) with sotr. for the first time in details described process of an invasion of an erythrocyte merozoites.
Transfusion M.'s history begins since 1884 when Gerhardt showed that M. can be caused by the activators entered into a human body at hemotransfusion from the donor — the carrier of activators M. Valuable information on various aspects of M. was given by the method of treatment of a general paralysis M.'s inoculations offered in 1922 by Yu. Wagner-Yauregg.
The first mentioning in the European literature on treatment of the alternating fevers extract from bark of a cinchonic tree belongs to 1643. In 1820 fr. chemists Pelletye and Kavantu (P. J. Pelletier, J. Century of Caventou) emitted in pure form alkaloid quinine. Shuliemang, Shonkhofer and Vingler (Schuleman, Schonhofer, Wingler) in 1926 received the first synthetic antimalarial drug — plasmochin. In 1931 O. Yu. Magidson, I. T. Strukov, G. V. Chelintsev and I. L. Knunyants synthesized Plasmocidum, in 1933 I. L. Knunyants, G. V. Chelintsev, And. M. Grigorovsky and S. V. Benevolenskaya — quinacrine.
In 1939 Swiss Müller (R. N. of Muller) opened insecticidal action of DDT synthesized in 1874 that gave the chance to develop works on fight against M. V carrier of 1944 in England Paludrinum, in 1945 in the USA — the first of 4-aminoquinolinic derivatives — chloroquine was synthesized.
Distribution and statistics
consider Ancient primary center of M. tropical Africa from where the disease extended to India, China and Indochina, and through the valley of Nile — to Mesopotamia and the countries of the Mediterranean. According to V. V. Favr, to Russia M. was brought from Iran.
Sowing. the border of an area of M. reached 49 °C. highway in North America and 64 °C. highway — in Europe and Asia; yuzh. the border reached to 33 ° SL in South America, 31 ° SL — in Africa and 20 ° SL — in Australia. In these borders M. was absent in mountain and desert districts, on a number of islands of the Quiet and Atlantic oceans which are not occupied by mosquitoes of Anopheles. The most highly located M.'s centers were registered at the height of 3500 m above sea-level. To the north of 49 — 64 °C. highway and to the south 33 — 20 ° SL M.'s transfer does not happen because of a lack of heat for development of a plasmodium in an organism of a mosquito.
The global area of M. represents set of areas of four of its forms: tropical, three-day, four-day and M. oval. More widely than other types R. extended vivax occupying almost all group nozoareat, except for some districts of the Western Africa. Three-day M. was the only form in a number of the countries of a temperate climate (England, Germany, Finland, the North of the USA) or sharply prevailed over other its forms (France, the Netherlands). It was caused by hl. obr. R.'s ability of vivax to develop in a body of a carrier at lower temperatures in comparison with other activators M. High adaptability of R. of vivax to different climatic conditions is provided with also genetically caused ability of a parasite to stay in an organism of the owner in not active state (hibernation) within many months, is more rare than years. In the north of R.'s area of vivax in a gene pool of population the genes causing 6 — a 13-month incubation interval prevail that was shown in M.'s disease in the spring at infection with summer of last year (M. with a long incubation). In process of advance to the equator and reductions of a seasonal break of transfer of activators a variety of a gene pool of population increases: the genes providing early activity of the activator M. that is shown in a disease after an incubation lasting from 7 up to 21 days prevail (M. with a short incubation). In tropics R.'s gene pool of vivax is most various, and the caught person can receive sporozoita of different potentialities which posterity becomes more active immediately or later different terms. In this case M.'s signs arise after a short incubation, and then, according to each new wave of an ekzoeritrotsitarny schizogony, there are frequent repeated manifestations — a recurrence.
At P. falciparum adaptive properties for existence out of a zone of hot climate are not revealed. At considerable delivery of its flash by tropical M. arose in separate hot years at such latitudes as 61 °C. highway (Solvychegodsk, the USSR), and at such heights as 2590 m above sea-level (Kenya). Steady border of an area of P. falciparum in sowing. a hemisphere passed 45 — 50 °C. highway, in southern — on 20 ° SL.
The area of P. ovale is small: its centers are dated almost only for tropical Africa; this parasite sporadic is found in Papua New Guinea, on Philippines and in the countries of the Indochina peninsula. The wide spread occurance of P. ovale is interfered by low and non-constant products of gamonts, weak intensity of infection of a carrier, big duration of a sporogony (15 — 16 days at t ° 25 °).
The area of P. malariae is limited to 53 °C. highway (Netherlands) and 29 ° SL (Argentina). The expressed gnezdnost of the centers of four-day M. is characteristic; in many areas, endemic according to three-day and tropical M., four-day M.'s diseases are absent.
Exerted m huge impact on life of many people. So, by the beginning of the 30th of 20 century in the world M. apprx. 700 million people from which it died apprx. 7 million annually got sick.
The purposeful fight against M. which is carried out in 20 century in many countries of the world and especially in the USSR, significantly changed a situation.
In 1921 obligatory registration of sick M. V was entered the next years into RSFSR the task to considerably reduce M.'s incidence, to suppress the outbreaks of a disease, to reduce losses of disability as a result of M. Eto's disease was set it was reached by the complex of antimalarial actions developed by the Soviet scientists (E. I. Martsinovsky, etc.) and the carried-out Soviet bodies of health care.
In 1949 in the USSR the task of elimination of M. as mass disease was set (decrease in an intensive indicator of incidence of M. is lower 10 on 10 Ltd companies of the population). High performance of methods of controlling M. (fig. 1), in particular effective treatment of patients, use of resistant contact insecticides for fight with inspired with Anopheles, allowed to achieve by 1952 M.'s elimination as a mass disease in general across the USSR (an intensive indicator of incidence of M. 9,8 on 10 Ltd companies of the population).
In 1951 P. G. Sergiyev scientifically proved a possibility of complete elimination of M. in the USSR. At the same time major importance was attached to exhaustive identification of patients to M. obligatory for a blood analysis on M. at in the fever patients, especially among arrived from foreign countries, isolation of patients and their effective treatment, dispensary observation for had, parazitonositel and to their treatment. Practical elimination of M. was reached by 1960 (fig. 2) when in all territory of the USSR the number of cases of M. and parazitonositel made 425, i.e. less than 2 patients on each one million population, number of the centers — 238. Since 1960 planned work on elimination of the residual centers of M. and the prevention of emergence of M. in other territory was developed. M.'s transfer completely stopped almost in all territory of the USSR. In the country more than 15 years were not found in the population P. falciparum, only isolated cases of four-day M. arising later hemotransfusions come to light (the evidence of existence at the population of P. malariae), and three-day M.'s cases in the boundary districts of Azerbaijan and some republics of Central Asia are registered. Epid, a situation according to M. is reliably controlled, despite intensive delivery of all four forms M. from foreign countries.
Big changes in M.'s incidence happened around the world during implementation of the global program of its elimination which began in 1955 under the auspices of WHO. In the first 10 years (1956 — 1965) considerable success on all continents, except Africa was achieved. There were extensive zones, free from M., in Europe, India, the USA, on islands of the Caribbean Sea, in Mexico, Venezuela.
Further process of elimination of M. was slowed down and, at last, practically stopped. In the 70th M.'s diseases in earlier revitalized districts of Iran, Iraq, Turkey and Syria are noted again. Became m the most important problem of health care in India, Sri Lanka and Burma; incidence of it sharply increased in Thailand, on Philippines, in a number of the countries of Central and South America. In the territories of Europe, North America and Japan revitalized from M. the number of brought in cases of M. Eto increased was followed by development of outbreaks of a disease, increase in a lethality and privivny M.
Chislo's growth sick M. in the world in 1976 made 150 million persons. 50% of all cases of diseases, three-day — 43% and four-day — 7% fall to tropical M.'s share. In Africa (world «epicenter» of M.) annually, according to incomplete data, from 2 to 17 thousand diseases on 100 000 inhabitants are registered. In a number of the countries of tropical Africa M.'s diseases average St. 12% of the general incidence.
The lethality which is directly connected with M. is equal to about 1%. More than 1 million persons „in a year, hl perish from M. obr. in tropical Africa» during catastrophic epid, rises the lethality at M. reached 3 — 5%, in certain areas and settlements — 20 — 40%. P. falciparum is the reason of 98% of all lethal outcomes at M. V 60 — the 70th the greatest lethality at tropical M. is noted in Europe and the USA; during 1967 — 1972 it made in Europe 2,7% (in Great Britain in 1970 — 1973 — 5,2%), in the USA — 8,4%. It is caused by lack of immunity at most of the diseased and the wrong or overdue diagnosis of a disease.
Failures of the program of elimination of M. in the world are connected with a number of factors: the inflation which captured the capitalist world, reduction of financial support from the developed capitalist countries, shortage and rise in price of insecticides, emergence of resistance in carriers to insecticides and at activators M. — to medicines, insufficient number of the prepared personnel and an unsatisfactory condition of health services in some countries.
The Soviet citizens, the country, leaving in endemic on M., are exposed to risk of infection: in tropical Africa — R. is preferential falciparum, P. ovale and P. malariae is more rare and R. is very rare vivax; in North Africa — R. vivax; in Asia — R. is preferential vivax, R. is more rare than falciparum (in Nepal and on Philippines — P. malariae); in Central and South America — in the main R. vivax, is more rare than P. falciparum.
Activators M. — the one-celled microorganisms relating to the Protozoa type, the class Sporozoa, Haemosporidia group, the Plasmodiidae family, the sort Plasmodium. 4 types of activators M. of the person are known: Plasmodium vivax (Grassi et Feletti, 1890) Labbe. 1899 — three-day M.'s activator; Plasmodium malariae (Laverau, 1881) Grassi et Feletti, 1890 — four-day M.'s activator; Plasmodium falciparum Welch, 1897 — tropical M.'s activator; Plasmodium ovale Stephens, 1922 — the activator an oval of M.
Activators M. differ on a number of signs: virulence, resistance to influence of chemotherapeutic drugs, duration of an incubation interval, immunol, to characteristics, ability to infect mosquitoes, etc.
Date of opening of the activator M. would be considered November, 1880 when the doctor of fr. army A. Laveran observed an eksflagellyation of gamonts of a semi-lunar form (P. falciparum) in sick M.'s blood, it in 1881 described the erythrocyte schizonts characteristic of P. malariae. Considering that activators M. belong to one look, A. Laveran gave them one name — Oscillaria malariae. In 1885 Markiafava and Chelli (E. Marchiafava, A. Celli) offered for the activator M. a generic name — Plasmodium. C. Golgi the same year divided on morfol, to signs of the intracellular parasites causing three-day and - four-day M. (but did not give the name to them), and established connection between process of parasites and feverish displays of a disease. In 1887. I. I. Mechnikov for the first time proved belonging of activators M. to the Protozoa type and defined their systematic situation, having pulled together with koktsidiya.
N. A. Sakharov in 1889 gave the first detailed description of the activator of tropical M., and in 1893 described flagellar little bodies as stages of development of malarial plasmodiums. In 1890 D. Grassi and R. Feletti gave the first separate description of the activator of three-day M. — R. of vivax and four-day M.'s activator — R. to malariae. Welsh (W. The N of Welch) in 1897 offered a specific name of «falciparum» for tropical M.'s activator. In 1922 J. W. W. Stephens offered the name and described morphology and development of P. ovale.
Activators M. are characterized by a difficult development cycle with change of the owner (tsvetn. fig. 1). Sexless development (schizogony) happens in a human body, sexual development (sporogony) — in an organism of females of mosquitoes of the sort Anopheles (see. Anofeles ).
In a human body distinguish two phases of development of activators M.: in cells of a liver — ekzoeritrotsitar-ny (ectoglobular, fabric) a schizogony and in erythrocytes — an erythrocyte schizogony.
Infection of the person M. occurs at a sting of the infected mosquito, with saliva to-rogo sporozoita get into an organism. With blood and a lymph of a sporozoita are brought in a liver and are implemented into hepatocytes, are rounded and turn into trofozoita (the beginning of an ekzoeritrotsitarny schizogony). Here they then turn into ekzoeritrotsitarny schizonts. The schizont ripens depending on a species of a parasite within 5 — 15 days. The kernel and cytoplasm of a schizont repeatedly share, forming up to 10 000 — 50 000 ekzoeritrotsitarny merozoites of the oval or extended form, length apprx. 2,5 microns and 1,5 microns wide which leave in a blood plasma. At activators M. of the person the ekzoeritrotsitarny phase of development is limited to one generation. Its duration P. falciparum apprx. 6 days, at R. has vivax — 8, R. have ovale — 9, R. have malariae — 15 days.
The erythrocyte schizogony begins after penetration of ekzoeritrotsitarny merozoites into erythrocytes. This process comes to the end for 30 sec. The merozoite is attached to an erythrocyte, the membrane of an erythrocyte in a point of an attachment is invaginated and absorbs a merozoite, forming a parazitoforny vacuole.
The erythrocyte membrane is invaginated in the place of an attachment of a merozoite of R. of vivax only in cases when on a surface of an erythrocyte there are isoantigens of group of Daffi (Fya or Fyb). The membrane of the erythrocytes which do not have isoantigens of group of Daffi at an attachment of a merozoite R. vivax is not invaginated and the erythrocyte schizogony does not occur. Such erythrocytes occur very often at natives of the Western Africa owing to what they are steady against three-day M. though they easily catch other types of plasmodiums of the person.
In erythrocytes merozoites increase and turn into sexless stages — trofozoita (i.e. the growing parasites), and then into schizonts (the sharing parasites) or into sexual forms — gametocytes (gamonts).
Process of sexless development in erythrocytes consists in increase in mass of a parasite, growth of a kernel, increase of quantity of a pigment, emergence in cytoplasm of an erythrocyte of azurophilic elements (at R.'s invasion of vivax, P. ovale less often than P. falciparum) and increase in an erythrocyte (at R.'s invasion of vivax and P. ovale). Then there comes division of a plasmodium (a stage of a schizont), in the course the cut occurs crowding of a pigment. Conditionally allocate the following stages of development of a plasmodium in an erythrocyte (tsvetn. fig. 2): ring-shaped trofo-zoit — size 1 — 2 microns, cytoplasm surrounds a vacuole in the form of a rim, the pigment is absent, the parasite borrows 1/3 — to 1/6 dia, an erythrocyte; young trofozoit — the volume of cytoplasm more, than at a stage of a ring, in it there are fine grains of a pigment, the parasite occupies less than a half of an erythrocyte, quite often has pseudopodiums; the semi-adult trofozoit — the size 4 — 5 microns, the volume of cytoplasm and quantity of a pigment is more, than at a young trofozoit, the parasite occupies more than a half of an erythrocyte, pseudopodiums are sharply expressed at R. to vivax, at other types are absent; the adult trofozoit — the volume of cytoplasm and a kernel more, than the semi-adult has a trofozoita, a small vacuole, often is absent, a lot of pigment contains, occupies almost all erythrocyte, pseudopodiums are absent. The schizont fills an erythrocyte almost entirely, has a pigment, the vacuole is absent. At an unripe schizont several kernels are in yet not divided cytoplasm, the form their wrong that indicates the continuing division, a pigment lies in the form of several glybok. At a mature schizont cytoplasm was divided, kernels roundish, a pigment in a compact small group (from 8 to 24 erythrocyte merozoites depending on a type of the activator were formed).
After formation of erythrocyte merozoites the erythrocyte is broken off therefore merozoites — mobile parasites of the oval or extended form 1,5 microns long and 1 micron wide are released. Merozoites are in a blood channel about 10 — 15 min., then are attached to new erythrocytes, forming a parazitoforny vacuole. The erythrocyte schizogony cyclically repeats. At an intensive parasitemia erythrocytes can be infested by two or more merozoites that is more often observed at infection of P. falciparum (at the same time 10% of erythrocytes and more can be struck), at R. of vivax the number of the struck erythrocytes seldom exceeds 2%, at R. of malariae — 1%.
Duration of a schizogony at R. of vivax, P. ovale and P. falciparum — 2 days, at P. malariae — 3 days.
Gametocytes also develop in erythrocytes. Mature gametocytes — one-nuclear parasites roundish or semi-lunar forms without pseudopodiums — occupy almost all erythrocyte (P. falciparum). The vacuole is absent, the pigment is evenly distributed in cytoplasm in the form of large glybok. Cytoplasm of mature female gametocytes (macrogametocytes) is painted across Romanovsky — to Gimza in intensive-blue color. A kernel — 1/8 — to 1/10 dia. a parasite, compact, it is usually located excentricly, it is painted in intensive-red color. Cytoplasm of men's gametocytes (microgametocytes) is painted in pale blue color. The kernel borrows 1/2 — 1/3 parasites, friable, is located usually in the center of a gametocyte, is painted in pink color.
Duration of maturing of gametocytes (gametotsitogoniya) at R. of vivax, P. ovale and P. malariae several watch bigger, than duration of an erythrocyte schizogony. Gametocytes P, falciparum ripen only in 10 — 12 days. Mature gametocytes of further changes in a human body do not undergo and if do not get to an organism of a mosquito, die off: R.'s gametocytes of vivax, P. ovale and P. malariae — in several hours after achievement of a maturity, P. falciparum — several weeks later.
The cover of erythrocytes in which there are activators M. at different stages of a schizogony and a gametotsitogoniya at R. of vivax of P. ovale and R. of malariae, and also does not undergo ring-shaped trofozoita and gametocytes of P. falciparum, changes. On a cover of erythrocytes of the subsequent (behind ring-shaped trofozoita) stages of development of P. falciparum there is a ledge having affinity with an endothelium of capillaries of internals where they also are late. Therefore in peripheral blood it is usually possible to find all stages of a schizogony and R.'s gametotsitogoniya of vivax, P. ovale and R. of malariae and only ring-shaped trofozoita and gametocytes of P. falciparum.
Sexual development happens in a stomach of a mosquito, nasosavshegosya from the sick person of blood to parasites. Schizonts are digested, further development is undergone only by gametocytes. One macrogamete is formed of a female gametocyte. The men's gametocyte throws out 4 — 8 plaits microgametes. This process carries the name «eksflagellyation». In 10 — 15 min. plaits gametes come off and freely move in contents of a stomach of a mosquito. As a result of merge macro - and microgametes the zygote is formed rounded shape, edges it is extended, becomes mobile and turns into an ookinete. The last gets through a wall of a stomach of a mosquito under its outside cover, is rounded, around it the capsule is formed, and it turns into an oocyst. Oocysts depending on air temperature and a type of the activator appear on 2 — the 7th day after a krovososaniye. The number of oocysts can vary from units to 200 — 500. In an oocyst the kernel and cytoplasm share therefore there are sporoblasts, and then and sporozoita (to 10 000) — spindle-shaped educations 11 — 15 microns long, 1,5 microns wide. Sporozoita get into a hemolymph and extend on all organism of a mosquito. The mosquito becomes infectious for the person after emergence of sporozoit in its sialadens. Reaches sialadens apprx. 2% of sporozoit. The mosquito is capable to transfer to the person of a sporozoita until the end of the life: at the wintering females of a sporozoita die off. Duration of a sporogony is various at different types of activators M. — from 7 to 45 days depending on air temperature.
the Source of an invasion at M. — the person, in peripheral blood to-rogo the sexual forms of malarial plasmodiums are had (gamonts). Efficiency of a source of an invasion is defined by the number of gamonts in its blood and availability to mosquitoes. Sick M. with primary or repeated manifestations and a parazitonositel can be a source of an invasion. In the centers with a high level of an endemia the main source of M. children are.
Under natural conditions activators M. of the person transfer only females of mosquitoes of the sort Anopheles. There are more than 450 species of these mosquitoes, but M.'s carriers are apprx. 80 types, i.e. less than 20%. Epidemiol, value of mosquitoes Anopheles is defined by many factors of their biology from which are most important a susceptibility to infection, the number of population, activity and life expectancy, extent of communication with the person and his dwelling. Various susceptibility of mosquitoes to infection with those of a pla with other types of activators M is noted. So, mosquitoes catch R. of vivax and R. of falciparum much easier, than P. malariae. There are examples of an unequal susceptibility of mosquitoes to infection with various races of the same species of a parasite. So, mosquitoes of Southern Europe, including A. atroparvus, do not catch P. falciparum from Africa.
As a rule, in each country, a zone, in a certain territory meet 1 — 2 type of a carrier, and in general on the globe — 25 — 30 types of the carriers defining the main incidence of M. Chast of carriers of M. (A. gambiae, A. punctulatus, A. leucosphyrus, A. barbirostris, A. umbrosus) make so-called specific complexes. E.g., the A. gambiae complex consists of 6 types which do not have absolute distinctive morfol, (external) features and identified only on chromosomal complement. At the same time the types entering a complex differ on behavior and ability to transfer activators M.
Are considered as the most effective carriers of M. from the A. gambiae complex as A. funestus in tropical Africa and A. punctulatus in Papua New Guinea. These mosquitoes are highly sensitive to infection with plasmodiums of M. of the person, the big percent lives them up to epidemic dangerous age (i.e. before emergence in sialadens of sporozoit), they differ in high degree of an antropofilnost (i.e. preferably eat blood of the person) and endofilnost (attack the person preferential in premises). Territories with the most high level of a prevalence of the population of M. — a goloendemiya belong to an area of these carriers. The hyper endemic centers create And. darlingi and A. albimanus in South and Central America; A. fluviatilis, A. culicifacies, A. sundaicus, A. maculatus and A. minimus in Southeast Asia; A. labranchiae, A. sacharovi, A. sergenti, A. stephensi and A. superpictus in the countries of the Mediterranean, the Middle East. The USSR treats effective carriers of M. A. maculipennis (with subspecies), A. sacharovi, A. superpictus and A. pulcherrimus.
Defined epidemiol, the Transfusion M. arising after hemotransfusion from the donor-parazitonositelya or at manipulations with the tools contaminated by the infected blood can matter. P. falciparum and P. malariae keep the viability in stored blood within 10 days and more, especially in that case when anticoagulant contains a dextrose.
Depending on social and the environment promoting or interfering M.'s distribution in each its center a certain level of intensity of transfer is established. In many countries with hot climate this level remains invariable within decades. There are M.'s centers with a certain level of a prevalence (local level) and characteristic immunol, structure of the population.
The prevalence of the population of M. can be characterized parasitic and splenic by indexes. A parasite rate — a share of persons (as a percentage) from among inspected in which plasmodiums in blood are found; a splenic index — a share of the inspected persons (as a percentage) at whom increase in a spleen is revealed. As an indicator of existence and intensity of transfer of M. in given epid, the season is of special value a parasite rate of babies and as an indicator of level of an endemia in this type of the center — a selezonochny index at children from 2 to 9 years.
According to the WHO classification distinguish 4 types of local M.: hypoendemic M. — a splenic index at children of 2 — 9 years in limits to 10%; mesoendemic M. — a splenic index at children of 2 — 9 years ranging from 11 to 50%; hyper endemic M. — the splenic index at children of 2 — 9 years constant higher than 50% is also high at adult population; goloendemichny M. — a parasite rate at babies constant is higher than 75%, a splenic index at adult population high (new Guinean type of an endemia) or low (the African type of an endemia). In naked and hyper endemic M.'s centers of the person, not died from tropical M., as a result of frequent defeats gain noticeable resistance to reinfection, the damaging action of a parasite, and M. are ill only children. By less intensive and non-constant transfer where the seasonal break in incidence is observed, stable immunity is not developed, M. are surprised both children, and adults.
The risk of infection of M. in the centers is established depending on type of an endemia. The size of risk of infection characterizes probability for the inhabitant of this center to be attacked by the infected mosquito. The naked and giperedemichny centers of M. differ in high risk of infection, meso - and hypoendemic — according to average and low risk of infection. The risk of infection initially inherent in the center of this type can be significantly reduced planned antimalarial actions. The structure of an area of M. on the risk of infection which developed by 1972 is presented in the figure 3.
From natural factors the climate, a land relief and vegetation exert impact on M.'s distribution. Heating environments have the greatest value in development of water stages of mosquitoes of Anopheles. Development of larvae of the most frigostable species of mosquitoes is impossible at water temperature lower than 10 °. The thermal factor limits distribution of activators M. as closing of the circuit of a sporogony in a body of a carrier happens at a certain air temperature (tab).
Table. Duration of a sporogony at &razlichnykhnbsp; &vidovnbsp; malarial parasites depending on air temperature
Air temperature influences also duration of the gonotrofichesky cycle of mosquitoes which is beginning with a krovososaniye and coming to an end with an otkladka of eggs. At high temperature (from 25 to 30 °) duration of a gonotrofichesky cycle — 2 days; at less high — to 7 days and more. During a sporogony the female of a mosquito makes several gonotrofichesky cycles. Physiologically old females of mosquitoes who did several gonotrofichesky cycles present the greatest to Epi-demiol. danger as the probability of existence of sporozoit at them becomes especially high. Heating environments of a sporogony define also intensity of infection of females of mosquitoes with malarial plasmodiums. At high temperature the bigger quantity of oocysts and consequently, and sporozoit is formed.
Thus, in the conditions of tropical countries M.'s carrier eats on the person more often, rather most part of his population lives up to an infectious state and it is more intensively infected with the activator M. All this affects epidemic process, intensity to-rogo in the countries of hot climate in tens and hundreds of times is higher, than in the countries of a temperate climate. In the countries of hot climate of draft exert impact on the place of breeding and number of carriers, defining geographical and seasonal distribution of M. V the season of heavy rains usually decreases or practically breeding of mosquitoes stops and their number sharply falls. By means of wind some mosquitoes (e.g., A. pharoensis) can dissipate on tens and hundreds of kilometers from places of breeding and even to cause there flashes of M.
M.'s transfer decreases with increase in height above sea level and at big heights usually stops; in the most part of mountain territories endemic M. is absent. The greatest number of types of a carrier at any latitudes is dated for low and moderate heights about 1000 m above sea-level. With increase in height the fauna of mosquitoes of Anopheles is impoverished, and at very big heights their breeding is possible only in tropical and subtropical belts, but also here it does not occur at the heights more than 3500 m. The land relief determines system of a drain of waters and by that existence, the area and type of the reservoirs suitable for settling by their larvae by Anopheles, and also familiarity of the territory by the person.
Vegetation can gain value of a natural barrier to M.'s carriers, but can under certain conditions and promote breeding of mosquitoes.
From social factors the greatest impact on formation of an area of M. is exerted by economic activity and migration of people. Deforestation, irrigation of new lands, construction iron and highways etc. led to creation of a huge number of small reservoirs — places of breeding of mosquitoes of Anopheles, and the migrating population brought M. in zones, earlier free from this disease. The conditions of the prof. of activity of the person promoting increase in contact with a carrier can cause rather bigger distribution of M. to certain prof. groups of people, generally in the persons working near anophelogenous reservoirs, in the open air and at night.
The m — a seasonal invasion, transfer of the activator falls on a season of activity of mosquitoes, i.e. on warm season. In districts with temperate and subtropical climate the season is limited aestivo-autumnal months with steady average daily air temperature over 16 °. Duration of a season of transfer of M. fluctuates in this case from 1kh/2 up to 6 — 7 months. In winter and spring months parasites remain only in a human body. Each new season M.'s transfer begins with infection vyplodivshikhsya in this year of mosquitoes and comes to an end after leaving of females in a condition of a diapause on a wintering. In a zone of tropical climate, especially in highlands, there are also M.'s centers with the seasonal transfer determined by a lack of heat or surplus of rainfall. Duration of a season of transfer of M. in these conditions would make — 9 months in a year. Seasonality of incidence of M. V tropical countries is considerably connected with seasonality of transfer other factors exert impact on the course of incidence of M. also: a combination in one center of several forms M., features immunol, structures of the population in different types of the centers, etc.
M.'s epidemics can arise after the long periods of low transfer when at the population decreases or in general there is no immunity to M. and most of people becomes highly sensitive to infection. At the same time the parasite rate is approximately identical at persons of all age groups. M.'s epidemic on the lake Ceylon in 1934 — 1935 caused by P. falciparum and which led to death of more than 80 thousand persons can be an example.
In the presence of sources of an invasion (patients and parazitonositel) emergence of epidemics of M. is possible everywhere where after the termination of actions for fight against mosquitoes their number and high potential of transfer were recovered. In the late sixties are 20 century old in the territory of a number of the countries (Venezuela, Tobago, Jordan, Syria, India, Sri Lanka, etc.) there were M.'s epidemics, excellent on a nek-eye to characteristics from epidemics of previous years. These post-liquidating epidemics are caused mainly by one type of the activator M., as a rule R. vivax (that is extremely unusual to the tropical countries), differ in high quality, a low lethality, explosive character of a current. So, in Sri Lanka in July, 1967 the number of patients of three-day M. was apprx. 100, in November — exceeded 1000, in January, 1968 made 10 thousand, and for 1968 — 1969 the St. 2,5 million persons ached. Premature phase-out of DDT was the main reason for this epidemic that under a favorable environment led to bystry recovery of number of a carrier.
M.'s epidemics can arise at delivery of an effective carrier in the area where it was absent earlier. Delivery by the ships on the lake of Mauritius of A. gambiae and A. funestus caused M.'s epidemic in 1867 — 1868, in time a cut 43 thousand cases of death are registered; delivery in the 30th 20 century to Brazil led A. gambiae from Africa to M.'s epidemic, and from 100 thousand sick 14 thousand died.
the Paroxysm of malarial fever (attack) at the patient arises at a mass exit of merozoites from erythrocytes. At not immune persons which caught M. in the first days of a disease irregular alternation of attacks in connection with non-simultaneous end of a schizogony of several generation of a parasite is observed. Afterwards under the influence of immunity development of parasites in blood accepts synchronous character and there occurs the correct alternation of attacks. At R.'s infection with vivax, P. ovale and P. falciparum attacks arise with an interval of 1 days, at infection of P. malariae — 2 days.
Destruction of erythrocytes as a result of a schizogony, the hemolysis of not struck erythrocytes caused by formation of autoantibodies can be led to development anemias (see) and thrombocytopenia (see). Increase in a liver and spleen is caused by a hyperplasia of lymphoid and reticuloendothelial elements that is defined by influence of parasites, products of their disintegration and hemozoin. An important role in a pathogeny is played by the allergic factor which is shown a small tortoiseshell, intestinal frustration, acute wet brain at a fulminant current of three-day M., representing reaction of giperergichesky type (see. Allergy ). At tropical M. when the high parasitemia takes place, there is a disturbance of microcirculation of internals where the schizogony of P. falciparum comes to the end. Capillaries are filled with the infested erythrocytes, the blood stream is slowed down, the endothelium is damaged, permeability of walls of vessels increases that is promoted by action of the kinin, a histamine and other substances which are released from gemolizirovanny erythrocytes. Oxidizing phosphorylation is at the same time broken. Aggregation of thrombocytes in capillaries and weakening of a fibrinolysis is led to intravascular coagulation. Clinically specified processes are shown by disturbance of activity of c. N of page, development of acute renal or pulmonary failure. Hemoglobinuric fever at tropical M. arises at persons with inborn deficit glyukozo-6-fosfatdegidrogenazy at reception of quinine or drugs of group 8 of aminoquinoline. There is an acute intravascular hemolysis, a consequence to-rogo is haemoglobinuria (see) with the subsequent development of acute renal failure (see).
As for a recurrence, on former representations, all species of malarial parasites make the preeritrotsitarny schizogony corresponding on time to an incubation interval of an invasion in a liver. It was assumed that R. have vivax, P. ovale and P. malariae (unlike P. falciparum) the fabric merozoites formed during a preeritrotsitarny schizogony not completely leave in blood, a part them gets into cells of a liver again, giving rise to a paraerythrocyte cycle. Was considered that an exit in blood of the merozoites formed during this fabric cycle leads to development of the late (remote) recurrence. The fact that at three-day M. primary manifestations can occur after long (till 1 year) incubations, gave the grounds to allocate two groups of so-called strains of R. vivax. Believed that the «southern» strains cause a disease with a short incubation and a late recurrence, «northern» strains — a disease with a long incubation. V. P. Nikolaev (1949) designated these groups of strains of R. vivax as subspecies (according to R. of vivax vivax and R. of vivax hibernans).
A. Ya. Lysenko, A. E. Belyaev, B. M. Fishing (1977) offered other explanation of a pathogeny of a long incubation and a late recurrence of M., considering that at three-day M. and M.'s oval the mosquito usually enters heterogeneous set of sporozoit in the genetic relation. At a part of their (takhisporozoit) development begins immediately, other part (bradisporozoita) stays in a liver in not active (dozing) state, duration to-rogo is predetermined genetically and several months, on average 8 — 9 can last (as much as possible up to 4,5 years). After escaping of the dozing condition of sporozoit development of ekzoeritrotsitarny stages happens a usual order. The current of an invasion is defined by way of introduction takhi-or bradisporozoit — separately or in a combination. If only bradisporozoita are entered, then the invasion with a long incubation if only takhisporozoita — an invasion with a short incubation if that and others — an invasion with a short incubation and late a wedge, manifestations (a late recurrence) develops. The immunity developing on the course of acute process can interrupt or suppress a schizogony that in the first case will lead to the spontaneous termination of attacks, and in the second — to emergence of a parasitosis. On this background under the influence of various factors weakening immunity there can be a reproduction of parasites and arise repeated attacks of M., a so-called early (neighbors) recurrence. At four-day M. the parasitosis can proceed is long; a recurrence when they came, are erythrocyte by the nature, i.e. are caused by easing of immunity against erythrocyte stages of a parasite.
the Form M. caused by plasmodiums of different types, having much in common, differ in nek-ry essential features.
At three day M. the erythrocyte schizogony occurs in the circulating blood. Parasitizing in an erythrocyte, plasmodiums not completely acquire hemoglobin, and its remains, turning into kernels of a dark-brown pigment, gradually collect in cytoplasm of the growing schizonts. At division of parasites the pigment is released, gets to a blood plasma, and then is taken macrophages of a spleen, liver and marrow. In the same bodies there is also a phagocytosis of schizonts limiting a possibility of their reproduction. After digestion of the absorbed parasites the pigment which is contained in six to cytoplasm remains in reticuloendothelial cells. Bodies in which the pigment collects get characteristic brownish-gray, sometimes almost black coloring. At a prolonged disease a part of a pigment moves to interstitial fabric, forming massive accumulations there. Processing and release of hemozoin come from an organism slowly therefore brown-gray color of a spleen, a liver and marrow remains for quite long term, not always demonstrating existence of activity of process.
The investigation raised funkts, loadings, and also irritant action of decomposition products and alien substances is the hyperplasia of fabric elements of a spleen and liver with increase in the sizes of these bodies. At a frequent recurrence and lack of treatment the sclerosis of a pulp with expansion of sine is observed. In acute stages of an invasion tissue of a spleen very friable, plethoric, and the capsule thin and intense. Ruptures of body at an insignificant injury are possible and even without the clear reasons. Later the capsule is thickened, and the pulp grows coarse, getting the dense fleshy consistence remaining and at total disappearance of a pigment. The weight of a spleen can exceed 1 kg, occasionally reaches 5 — 6 pg and more.
Clear increase in a liver is caused by hl. obr hyperplasia of reticuloendothelial cells and plethora. Further fibrosis — diffusion growth of fibrous connecting fabric between segments is possible and between hepatocytes, however the phenomena characteristic of typical cirrhosis, at the same time are not observed.
In marrow at M. along with phagocytosis of parasites, adjournment of a pigment and a hyperplasia of a reticuloendothelium the strengthened formation of blood cells, hl is observed. obr. erythrocytes. The disturbance of the hemopoietic function which is shown an aplasia of marrow is in some cases noted.
Morfol, changes of other bodies and fabrics at three-day M. are less constant and caused generally by the anemia which is quite often reaching very considerable degree. One of the conditions which are adversely influencing regeneration of blood is vivax property P. to settle preferential in young red blood cells — reticulocytes.
Patol, four-day M.'s anatomy is generally similar to three-day.
At tropical M. there are also specified changes of a spleen, a liver and marrow, but, besides, also others are inherent in this form M. patol, processes. The erythrocytes containing schizonts accumulate in sine of a spleen and marrow (where also gametocytes also develop), in small blood vessels of a fatty tissue, a mucous membrane of a stomach and intestines, in a pancreas. At the pregnant women sick with tropical M., there are a lot of parasites in mezhvorsinochny spaces of a placenta and in capillaries of a mammary gland. Less often the infected erythrocytes collect in capillaries of a myocardium, kidneys and some other bodies. Parasitic staza in vessels of a brain and cerebellum cause defeat of c. N of page.
At big accumulation of the plasmodiums containing a pigment, any fabrics gain smoky or grayish-brown color. However along with permanent pigmentation of a spleen, liver and marrow the changed coloring of other bodies and fabrics disappears after elimination of parasitic staz after the next division of schizonts.
In places of accumulation of the ripening plasmodiums also many free cells capable to phagocytosis are concentrated. The structure of these cells is various depending on a stage of development of parasites. During the periods of division of schizonts polymorphonuclear leukocytes which number in the circulating blood usually decreases collect preferential. Polinukleara very actively destroy parasites, but plasmodiums are available to them only at a stage of the merozoites leaving the collapsing erythrocytes (tsvetn. fig. 7). The macrophages taking hl are more constant. obr. decomposition products and the pigment remaining after division of plasmodiums (tsvetn. fig. 8). But they can absorb also entirely red blood cells with the schizonts which are in them, i.e. show the same properties, as a reticuloendothelium of a spleen, liver and marrow (tsvetn. fig. 9).
Accumulation of the infected erythrocytes in these or those bodies (except for a brain), as a rule, does not cause essential damages. As the reason of deaths at tropical M. most often serves defeat of c. N of page. Many researchers observed that at the patients who died from a malarial coma, the capillary network of a brain is almost entirely filled with the erythrocytes infected with schizonts of P. falciparum. Outward of a brain and cerebellum of the patients who died from a malarial coma is most characteristic when the deep loss of consciousness proceeded apprx. the 24th hour. In such cases bark, and partly and white matter of a brain have brown-gray color. Unusual coloring of nervous tissue is clearly visible also at early death of patients, but has a bit different, as if a cyanotic shade. Along with discoloration the smoothness of furrows and flattening of crinkles are noted that demonstrates increase in volume of a brain. Very often in substance of a brain dot hemorrhages, sometimes numerous are found. They arise hl. obr. on border between bark and white matter of hemispheres, in internal capsules and in a corpus collosum, and also in bark and area of gear kernels of a cerebellum.
Increase in volume and discoloration of a brain are caused by filling of almost all capillary network with the erythrocytes infected with schizonts of P. falciparum. At short-term coma these schizonts are rather small. But when the coma lasts about days, in vessels of a brain mature schizonts prevail. The analysis morfol, and a wedge, data shows that approach of a coma matches those periods of a disease when parasites gain ability to collect in vessels of internals.
At the loss of consciousness proceeding more than 1 — 1,5 days, vessels of a brain can be exempted from the parasites divided into merozoites and who left erythrocytes substantially. But by this time in nervous tissue changes — diffusion dystrophic processes like «ischemic disease of ganglionic cells» and focal defeats, the shown hl develop heavy patol. obr. in the form of small, usually ring-shaped, hemorrhages. The center of such hemorrhages forms the small vessel filled with the bound together struck erythrocytes or homogeneous hyaline blood clot and surrounded with a zone of a necrosis. Further on border of a necrosis and the hemorrhage bordering it there is reactive accumulation and proliferation of cells of a glia thanks to what so-called granulomas of Dyurk form (tsvetn. fig. 10) found at the coma which dragged on on 1,5 — 2 days and more.
Serves much more rare a cause of death at tropical M. intensive reproduction of parasites in all blood channel without their selective accumulation in vessels of a brain.
in the course of evolution at the person the inborn and acquired mechanisms of resistance to M. which are defined by the genetic constitution of the owner were created. Inborn stability is defined by properties of an erythrocyte. E.g., relative stability of some persons to P. falciparum decides by type of hemoglobin, a quantitative change of synthesis of its chains (a thalassemia — inborn family hemolitic anemia on the increased osmotic resistance of erythrocytes), deficit glyukozo-6-fosfatdegidrogenazy, the ATP level. Newborns in goloendemichny and hyper endemic districts are not ill M., possessing passive immunity (see). By the end of the first year of life of the child immune globulins disappear, and children catch the prevailing type of a plasmodium. As a result of the postponed disease or repeated infection at children on 2 — the 4th year of life active immunity develops. Decrease in frequency of a disease and weight its wedge, manifestations is a consequence of it. At more advanced age the high level of artificial immunity provides absence a wedge, symptoms and extremely low level of a parasitemia. Immunity at adults is maintained by repeated infections. Moving of the inhabitant from the intensive center of M. to the district, free from it, within 1 — 2 years leads to decrease and disappearance of immunity. Loss of artificial immunity is observed also during pregnancy. Artificial immunity is invasive, unsterile, species-specific, it is unstable and short, is caused by cellular and humoral factors. The spontaneous termination of attacks and even radical treatment is explained by development of immunity. At an early stage of an invasion protection of an organism is carried out with the help phagocytosis (see), especially intensive in a spleen. At M. intensive products are observed antibodies (see). Protective antibodys belong generally to IgG. They interfere with an attachment of merozoites to erythrocytes, blocking an erythrocyte development cycle of parasites. The inhibiting antibodies have preferential species-specific character, however at the same time also cross reacting antibodies in the quantity sufficient for suppression of proliferation of the majority of other antigenic options of a look are developed. Release of cross reacting antigens can form a basis for creation of an effective vaccine against erythrocyte forms of parasites.
The clinical picture
M.'s Current includes an incubation interval, primary attack with typical attacks and a recurrence. On the offered E. M. Tareev (1946) a wedge, M.'s classifications taking into account specific features of the activator and according to various a wedge, a picture allocate four a wedge, forms: three-day M. (malaria tertiana), four-day M. (malaria quartana), tropical M. (malaria tropica) and M. oval (malaria ovale). At the same time consider the period of a disease and weight of process, as criterion to-rogo serve the nature of fever, intoxication (a headache, nausea, vomiting), degree of anemia, level of a parasitemia. Depending on expressiveness of the specified symptoms allocate an easy, medium-weight and heavy current
of M. Prodolzhitelnost of the invasive process caused by P. falciparum in a human body seldom exceeds 1 year, vivax caused by R. and P. ovale — are reached by 2 years, 4 — 5 years, P. malariae — 2 — 3 years, sometimes decades are rare.
The incubation interval depends on a type of the activator. At tropical M. duration makes it 6 — 31 day, at the three-day, caused by R. vivax with a short incubation — 7 — 21 day, vivax caused by R. with a long incubation — 6 — 13 months, at M.'s oval — 7 — 20 days, at four-day — 14 — 42 days. At defective chemoprophylaxis the incubation interval can increase considerably.
The prodromal phenomena observed sometimes at primary infection are shown by an indisposition, drowsiness, a headache, subfebrile condition which fever of the wrong type quite often follows. 3 — 4 days later there is a characteristic attack, during to-rogo the wedge, phases are allocated three: fever, heat, sweat. During the first phase of the patient muscular pains, especially in extremities and in a waist disturb, headache (see), sometimes vomiting. Skin becomes cold, cyanotic. Pulse becomes frequent, shallow breathing. Duration of a fever is from 30 — 60 min. to 2 — 3 hours and more. In the phase of heat proceeding of several hours to 1 days and more the general state worsens. Temperature reaches high figures (40 — 41 °), the person reddens, short wind, excitement, often vomiting develop. The headache amplifies. Sometimes there is a nonsense, a kollaptoidny state. The amount of urine decreases (see. Oliguria ). The termination of an attack is defined by decrease in temperature to normal and subnormal figures and is followed by strengthened sweating (see), proceeding 2 — 5 hour. Then there comes the deep sleep. In general the attack lasts 6 — 10 hours, sometimes longer. Further during 1 — 2 days depending on a type of the activator standard temperature remains, but the patient tests the weakness increasing after each next attack. Attacks usually come at the same time, but sometimes before previous or later. Quite often during a disease there are herpetic rashes (see. Herpes ), small tortoiseshell (see) or (at tropical M.) a hemorrhage, a thicket in a look petechias (see). After a number of attacks skin of the patient gets a characteristic pale yellow shade. At heavy disease emergence of hypostases is possible. After 3 — 4 attacks the liver and a spleen increase. Splenomegaly (see) is an important diagnostic symptom, however at heavy disease the sizes of a spleen remain normal. At persons at the age of 40 — 50 years at any forms M. the splenomegaly is expressed more weakly. At defective treatment and repeated infections the spleen can reach the big sizes (hypersplenism), anemia, a leukopenia develop. Defeat liver (see), observed at most of patients, it is shown by its increase, morbidity, quite often jaundice (see), increase in amount of direct bilirubin (see. Hyperbilirubinemia ) and activities of transaminases, decrease in cholesterol (see. Hypochilesterinemia ). Changes of cardiovascular system (tachycardia, muting of cardiac sounds, hypotonia, systolic noise on a top and at the basis of heart) are noted preferential during an attack. At severe forms at the weakened and incorrectly treated patients develops myocardial dystrophy (see). Damage of kidneys is most often shown by a feverish proteinuria, edges has passing character. At heavy tropical M., as a rule, there is acute tranzitorny nephrite with preferential defeat of tubules, is more rare — hron. the renal syndrome etiologically connected with an invasion of P. malaria. About disturbance of activity went. - kish. a path during an attack the loss of appetite, frustration of a chair disappearing on elimination of the acute attacks of a disease testify. Defeat of c. the N of page is shown by a headache, especially intensive at tropical M., nausea, vomiting. In the heat of attacks there can be a feverish nonsense, vegetative neuroses, psychoses. At height, and sometimes only at the end of the feverish period in blood a leukopenia the relative lymphocytosis and a monocytosis decide on a neutropenia. After several attacks anemia of hemolitic character develops (see. Hemolitic anemia ), Polikhromatofiliya, reticulocytosis. Without treatment attacks can repeat 10 — 12 times both more and to stop spontaneously (but not at tropical M.!), however the absolute recovery does not come. Upon termination of the stage of latency lasting from several weeks to 2 — 3 months there comes the period of a recurrence which on a wedge, to manifestations in many respects repeats clinic of primary attacks.
The m at pregnant women accepts a heavy current, especially tropical. Quite often the malignant forms which are followed by severe defeat of c develop. N of page, liver, kidneys, acute hemolysis, disturbance of a course of pregnancy (abortions, premature births, pre-natal death of a fruit).
The residual phenomena in the form of hyporegenerative anemia, the splenomegaly reaching the considerable degree and which is followed by a pancytopenia, vegetative neuroses can be defectively treated M.'s consequence.
The tetrian fever in most cases happens moderately severe. At a typical current attacks arise every other day (fig. 4, a), but there can be also a daily type of fever (fig. 4,6). During the first 3 — 6 days temperature of the wrong or constant type is possible. Further the attack proceeds 6 — 10 hours with the subsequent apireksiya. There are attacks usually in the morning. The termination of a paroxysm is followed by profuse sweating. Three-day M. on islands of the West Pacific area differs in heavier current, is characterized by a frequent recurrence and smaller sensitivity of activators to 8-aminoquinolinic drugs.
The quartan malaria proceeds is good-quality. Attacks arise in 2 days of an apireksiya (fig. 4, c). Dual attacks — two days running with the subsequent period of an apireksiya (one day), seldom daily are sometimes noted. Attacks are more long, than at three-day M., their number in the absence of treatment is especially big. A frequent recurrence is characteristic, the amyloid and lipoid nephrosis is possible.
Tropical malaria differs in the heaviest current, bigger variability a wedge, manifestations, but smaller duration. It is characterized by the wrong type of a temperature curve (fig. 4, d). Oznoba are expressed more weakly and can be absent at all. Sweating insignificant. In certain cases fever accepts character three-day, however attacks are much more long (24 — 36 hours), the periods of an apireksiya short. There are a severe headache, often vomiting, ponosa, jaundice, anemia, sometimes vestibular and cochlear defeats quickly develops. Without timely treatment tropical M. can accept a malignant current.
An oval malaria proceeds as three-day, but it is easier. Attacks arise in evening and night time. Spontaneous recovery is often observed.
Complications most often happen at tropical M., usually at not immune persons (to a high parasitemia). The heaviest complications which are often found in the endemic centers are wet brain, a malarial coma and an acute renal failure, mental disorders are more rare malarial algid. Hemoglobinuric fever is inherent to the persons living in M.'s centers (see. Enzimopenichesky anemia ).
The malarial coma develops at tropical M. preferential at not immune persons in the absence of specific treatment. The coma can suddenly arise or against the background of the accruing cerebral frustration. In a wedge, a current it is distinguished by three periods: a somnolention (the prekoma which is characterized by an oglushennost), a sopor (deep hibernation with glimmers of consciousness), a deep coma with switching off of consciousness, an areflexia. The first two periods can be short-term or one of them drops out. In the subsequent period temperature can be very high, but also the hypothermia is observed (fig. 4,(d). The most frequent symptoms of a malarial coma: frustration consciousnesses (see), the Meningeal phenomena (see. Meningism ), spasms (see). Initial increase is characteristic tendon jerks (see), emergence clonuses (see), and then total disappearance of reflexes. From cutaneous reflexes the first disappear and the last recover belly. Cerebrospinal liquid is not changed or changed slightly. Quite often arise hemiplegia (see), aphasia (see). The malarial coma often is followed by acute hemolysis, disturbance of cardiovascular activity, functions of a liver, kidneys, lungs.
In blood at height of a coma the leukocytosis, and in far come cases a hyperleukocytosis, a neutrocytosis, acceleration of ROE, decrease in a hematocrit, disturbance of an acid-base state, a hypopotassemia is observed. In blood a large number of parasites in different phases of development is found, however emergence of a coma and against the background of a scanty parasitemia is possible.
The acute renal failure arises quite often in cases of severe forms of tropical M. as a result of intensive hemolysis with the subsequent haemoglobinuria and is connected with disturbance of renal microcirculation and a cellular anoxia.
Malarial algid happens only at tropical M. It is characterized by a kollaptoidny condition, decrease in temperature to subnormal figures (35 — 35,5 °), considerable dehydration is possible. Consciousness is kept, but the patient is indifferent. Features are pointed, skin of a tsianotichn, is covered with clammy cold sweat, reflexes are lowered or are absent. Ponosa are sometimes observed. Pulse threadlike. ABP low.
Wet brain at a fulminant form of three-day M. was registered at children of 4 — 12 years in time epid, flashes usually in spring months. During the next attack the severe headache, spasms, foam from a mouth suddenly developed. In several hours there came death.
Mental disorders meet more often at tropical M. (apprx. 1,6% of cases). Among psychoses exogenous forms of reactions of Bongeffer prevail (see. Bongeffera exogenous types of reactions ) — an amentia (see. Amental syndrome ), twilight stupefaction (see) and devocalization (see). Feature of an amentia consists in sharply expressed chaotic motive excitement which is combined with affect of fear. Twilight stupefaction proceeds usually with epileptiform excitement. Devocalization can be limited only to somnolence, and during the weighting of a state to be replaced by a sopor and a coma. When such transformation a wedge, pictures happens in short terms (within a day and less), speak about an apoplectic malarial coma. A delirium (see. Delirious syndrome ) meets seldom and in the reduced form. It can precede emergence of an amentia. Much less often at M. there are endoformny pictures with a protragirovanny current. Most often meet maniacal syndromes (see) when motive excitement without purposeful activity with irascibility prevails. Sometimes there are depressive and paranoid states (see. Paranoid syndrome ) and gallyutsinoza (see. Hallucinations ). Malarial psychoses are always replaced by an adynamy (see. Asthenic syndrome ).
Malarial psychoses arise in the apyretic period, at a repeated, including and persistent recurrence of malaria more often.
Hemoglobinuric fever (chernovodny fever, a hinno-malarial Haemoglobinuria) observed at tropical M. is described as a complication of M. Meanwhile this disease of a medicamentous, but not parasitic origin. There is at persons, a long time of M. which were in an endemic zone, repeatedly transferred, in several hours after reception of quinine or, more rare, other drugs (e.g., groups 8 of aminoquinoline). Most often occurs at indigenous people of Africa, the basin of the Mediterranean Sea, Transcaucasia that is connected with deficit of protective enzyme of erythrocytes — glyukozo-6-fos-fatdegidrogenazy. It is clinically shown by a sudden fever, temperature increase to high figures, a headache, joint pains, a waist, vomiting, a hiccups. There are painful a liver and a spleen. After the fever proceeding 2 — 4 hours there comes the condition of prostration, pulse becomes weak, small. The integument gets an icteric and at the same time cyanotic shade. Extremities cold. Sometimes urticaria, skin itch. The main symptom — emergence of urine of color of black coffee or red wine that is caused by availability of oxyhemoglobin in it. Urine contains erythrocytes, hyaline and granular cylinders, a large amount of protein. In blood — the neutrophylic leukocytosis, sharply decreases hemoglobin. Parasitemia insignificant. Release of urine continues 1 — 3 days, then there comes the anury and death of the patient from an acute renal failure. At a favorable current in 3 — 5 days temperature decreases, urine brightens, the general state improves.
At establishment of the diagnosis is considered epidemiological, clinical and a lab. data. At typical disease with existence of the characteristic attacks coming with accurate frequency, which are followed by increase in a liver and spleen, herpetic rashes, yellowness of scleras, the diagnosis does not raise doubts. The instruction on stay in the area, endemic on malaria, facilitates a task. Crucial importance in the diagnosis has detection of plasmodiums in blood (in a smear and a thick drop). Researches need to be conducted in all cases of fever of the obscure etiology, especially in the presence of corresponding epidemiol, the anamnesis.
Lab. diagnostic methods of M. include microscopy of stained preparations of blood for the purpose of detection of erythrocyte forms of parasites and serol, reactions for detection of specific antibodies.
Microscopy of blood the most reliable diagnostic method of M. Parazita can be found in peripheral blood in the first days of a disease: River of vivax — in 10 — 12 days after infection (the earliest term — 8 days), P. falciparum — in 8 — 12 days (it is minimum in 51/2 days), P. malariae — in 21 days (it is minimum in 15 days) and P. ovale — in 14 — 15 days (it is minimum in 9 days). In blood parasites come to light not only during feverish attacks and intervals between them, but also at a parasitosis.
At a blood analysis on M. prepare smears and thick drops of blood. In practical work investigate preferential thick drop (see), painted across Romanovsky — to Gimza. In a thick drop for the same interval of time it is possible to see by 30 — 50 times bigger amount of blood, than in a smear. Address a smear when specific accessory of the found parasites on a thick drop does not manage to be established. The thick drop of blood is painted in an unstable look in this connection erythrocytes are leached, and malarial parasites are considerably deformed (tsvetn. fig. 3B, 4B, 5B, 6B). The erythrocytes containing P. malariae and P. falciparum are leached completely, and the erythrocytes containing R. of vivax and P. ovale — partially. The remains of the erythrocytes struck with R. vivax are painted in pink color, R. by ovale — in red color. Trofozoita R. vivax of irregular shape are also broken often off on several fragments. Trofozoita of other types are compact and always falciparum and P. malariae and large — at P. ovale remain whole, with small kernels at R. Crowding of a pigment (1 — 2 small groups) at a stage of a semi-adult trofozoit, at other types of plasmodiums — at a stage of mature schizonts is characteristic of P. falciparum.
At microscopy of a smear find the plasmodiums lying in erythrocytes about one pl several kernels of red color and blue cytoplasm (tsvetn. fig. 3A, 4A, 5.A, 6.A). Diameter of the erythrocytes struck with P. malariae or R. falciparum, usual, diameter of the erythrocytes struck with R. vivax and P. ovale is increased; in the first case small plentiful granularity, in the second — large, rare is noted. At tropical M. parasites are numerous, only rings and gametocytes are usually observed, several parasites in one erythrocyte are frequent. At three-day, four-day and M.'s oval of parasites it is not enough, usually of no more than one in an erythrocyte. Trofozoita R. vivax have a bizzare shape, small kernels and the expressed pseudopodiums. At other types of a trofozoita are compact, with large kernels at P. ovale and the flocking pigment at P. falciparum. At an invasion of P. falciparum schizonts in peripheral blood meet seldom, existence them usually testifies to very intensive invasion. Mature schizonts of P. ovale and P. malariae contain 8 — 10 merozoites, R. of vivax — 16 — 24 and P. falciparum — 12 — 24 (sometimes 16 — 32). Merozoites are located randomly or the correct socket on the periphery of the pigment gathered in a heap (P. malariae, is more rare than P. ovale). Gametocytes of P. falciparum of a semi-lunar form, P. malariae, R. of vivax and P. ovale — rounded shape.
From serol, reactions which were applied to detection of malarial antibodies reaction was the most sensitive and specific immunofluorescence (see) in indirect option. The caption 1 is considered diagnostic: 20 — 1: 40 and above. High credits (1: 160 N are higher) testify about active or recently transferred M. Detection of antibodies specifies in low credits on postponed in last M. Antibodies at M. appear on 8 — the 27th day after emergence of a parasitemia: in the beginning — antibodies of the class IgM, then specific antibodies of IgG. An anti-subject also even 13 — 20 years after radical treatment can be found in blood within 0,5 — 2 years, however over time the caption gradually decreases. Blood of the donor, in a cut antibodies even in low credits are found (1: 20 — 1: 80) it can be used only for preparation of plasma or its derivatives.
Serol, reactions are used for an exception of the diagnosis of M. at patients with fever of not clear origin, gepatosplenomegaliy. and at a blood analysis of the donor, from to-rogo presumably the recipient caught anemia. They find application also as a method epidemiol, observations on unsuccessful according to M. in the past of the territory. Existence of antibodies in a high caption in blood serum of residents of the ecdemic or freed from M. districts is the proof of infection of M.; in this regard survey of the patient about his stay in the endemic area or the postponed hemotransfusion shall be conducted.
The reaction enzyme-marked antibodies (REMA) having a number of important advantages before reaction of an immunofluorescence (REEF) is implemented into practice. At statement the REEF as antigen is used by mature erythrocyte schizonts of plasmodiums of the person or monkeys, and REMA — soluble antigens from erythrocyte parasites.
The differential diagnosis
Some general the wedge, M.'s signs (especially tropical M.) with a dengue, flebotomny fever, flu, yellow fever, a hay fever cause the necessity to carry out the differential diagnosis. It is necessary to consider that for dengue (see) the two-phase temperature curve, rash, joint and muscular pains, change of gait are characteristic. to Flebotomny fever (see) megalgias in a backbone, muscular lower extremity pains, sharp morbidity in eyeglobes are inherent at the movement and in upper eyelids in attempt to lift them, injections of vessels of a sclera in the form of a triangle in the field of an outside corner of an eye. During the carrying out the differential diagnosis with flu (see) it is necessary to consider existence of the catarral phenomena at the last, a hyperemia of the person, a conjunctiva. For yellow fever (see) in an initial phase the bright hyperemia of an integument and mucous membranes, the expressed bradycardia in an icteric phase, two-staging of disease is characteristic. to the Hay fever (see), unlike M., severe pains in gastrocnemius, occipital, cervical muscles, puffiness and a hyperemia of the person, a conjunctiva are inherent. The malarial coma is taken sometimes for overheating to the sun, a drunkenness, an encephalomeningitis. The correct diagnosis can be helped in this case by in details collected anamnesis (temperature increase, feeling sick to a sudden aggravation of symptoms), these researches of cerebrospinal liquid, edge at a malarial coma does not change. Cholera or salmonellosis can be suspected of cases of a malarial algid. Lack of the dispeptic phenomena in an onset of the illness and data epidemiol. the anamnesis exclude the last.
Sometimes it is necessary to differentiate M. with such diseases as cholecystitis, the cholangitis, abscess of a liver, pyelonephritis, a lymphogranulomatosis which can be mistakenly taken for M.
by Fundamentals of M.'s chemotherapy is the specific impact of drug on malarial parasites causing their death or disturbance of life activity. As action distinguish drugs gemoshizotropny (influencing sexless blood forms of plasmodiums), gamontotropny (influencing sexual forms) and gistioshizotropny (influencing on the plasmodiums which are in hepatocytes). Specific treatment should be begun immediately after establishment of the diagnosis. Timeliness of purpose of antiparasitic means is especially important at tropical M. since overdue treatment can cost to the patient life. For elimination of attacks of M. use drugs of gemoshizotropny action. The most expressed action among them derivative 4 aminoquinolines, in particular Chingaminum possess (a synonym: delagil, Resochinum, chloroquine). Similarly quinacrine, Bigumalum, Chloridinum and quinine work. The most effective gemoshizotropny drug is Chingaminum. In uncomplicated cases drug is appointed inside after food: in the 1st day — 600 mg of Chingaminum basis (1 g of mass of drug), in 6 — 8 hours of 300 more mg of Chingaminum basis (0,5 g of mass of drug); during the 2nd and 3rd day — on 300 mg of Chingaminum basis. At treatment three-day and four day M. in the 1st day it is possible to be limited to a daily dose of 600 mg of Chingaminum basis. At tropical M. treatment according to indications can be continued up to 5 days. Use of gemoshizotropny drugs at tropical M. provides radical treatment if it was caused by the strain of a parasite sensitive to the specified drug. At three-day and M.'s oval radical treatment is reached by purpose of the gistioshizotropny drugs influencing the stages of a parasite which are in hepatocytes for the prevention of a so-called late recurrence. 8 aminoquinolines use derivatives: domestic drug Chinocidum and foreign drug Primachinum. Chinocidum is appointed inside after food in one or two receptions in a daily dose of 30 mg within 10 days, Primachinum basis — on 15 mg (0,027 g of mass of drug) within 14 days. It is necessary to consider that reception of these drugs lindens with inborn deficit glyukozo-6-fosfatdegid-rogenazy can cause an acute intravascular hemolysis.
At resistance of parasites to derivatives 4 aminoquinolines carry out treatment by Chloridinum (a daily dose of 30 mg, in the 1st days it is possible to appoint 60 mg, a course of treatment of 3 — 6 days) in combination with streptocides (a daily dose of 2 g, a course of treatment of 7 days), and also quinine (1 — 1,2 g a day inside) either quinine in combination with tetracycline or sulfanamide drugs.
At coma M. carry out intensive complex care. Intravenously enter 10 ml of 5% of Chingaminum kapelno into 5% solution of glucose (500 ml) or isotonic solution of sodium chloride, repeating a single dose of 10 ml each 6 — 8 hours (without exceeding a daily dose of 30 ml) before improvement of a condition of the patient then pass to administration of drug inside. At the same time make parenteral (intravenous and intramuscular) administration of corticosteroid drugs (dexamethasone, a hydrocortisone, Prednisolonum) contributing to normalization of a vascular wall, elimination of fabric hypostasis diuretic (furosemide) and antihistaminic drugs. Besides, appoint assisted ventilation of lungs the mix rich with oxygen. Considering a possibility of resistance of a parasite to chloroquine, it is recommended to begin in these cases treatment with intravenous administration of the quinine-dihydrochloride possessing bystry action and intensive visceral and especially cerebral diffusion. It is important also that quinine has effect practically on all strains of parasites. In order to avoid a collapse quinine is entered very slowly into 500 ml of isotonic solution of sodium chloride on 0,5 g on a bottle. The daily dose of 1 — 2 g is entered with an interval 6 — 8 hour. At an abnormal liver function and kidneys the daily dose is reduced in 11/2 — 2 times. Intravenous administration of quinine-dihydrochloride is stopped after return of consciousness and further drugs appoint per os.
At treatment by antimalarial drugs by-effects — nausea and a skin itch are possible. Administration of quinine can cause also convulsive state and even to whom. At emergence of these and other signs of intolerance of drugs treatment by them is stopped.
At an acute renal failure the regidratation by isotonic solutions, a diathermy of area of kidneys, perinephric novocainic blockade is recommended; in an early stage appoint high doses of furosemide (80 — 120 mg) and a mannitol. At emergence of a resistant anury carry out peritoneal dialysis (see) or hemodialysis (see).
At severe forms of anemia when the hematocrit is lower than 20%, it is recommended exchange hemotransfusion (see). At less expressed hemolysis use usual transfusions of blood. At mental disorders purpose of sedatives is shown (Seduxenum, aminazine, etc.).
Timely treatment by favorably proceeding M. provides an absolute recovery. At a heavy current the forecast often adverse, especially at children and pregnant women.
M.'s prevention is carried out To the USSR in three directions: the prevention of possible infection of the Soviet citizens at their departure in the area, endemic according to M.; prevention wedge, and epidemiol. effects at M.'s delivery in the USSR; actions for fight against M. in the residual centers.
At departure in the area, endemic according to M., personal chemoprophylaxis is carried out. It consists in regular reception by healthy faces of antimalarial drugs. Right choice of drug and its dose, and, above all, a regularity of its reception — important premises of success of chemoprophylaxis of M. Chemoprophylaxis should be begun in 2 — 3 days prior to arrival in the area, endemic on M., and to continue during the whole season of transfer of M. It is for this purpose recommended to accept Chingaminum (delagil) on 2 tablets (0,25 g) once a week. In districts of distribution of hingaminustoychivy M. chemoprophylaxis is carried out by means of a fansidar (a combination of sulphadoxine and Pyrimethaminum) on one tablet a week. In tropical countries where M.'s transfer happens all the year round, personal prevention is carried out during the whole year. Chemoprophylaxis shall continue within 1 month after departure from the malarial area, and after stay in the center three-day or M.'s oval, besides, it is possible to treat with Chinocidum or Primachinum for impact on the dozing R.'s stages of vivax and P. ovale and the prevention of a disease after long stage of latency. Also protection against stings of mosquitoes is important: mechanical protection — a zasetchivaniye of windows and doors in rooms, use of bed curtains (see. Protecting screens ) and drawing repellents (see) on skin of open parts of a body, clothes and curtains at windows and doors.
Actions for the prevention of clinical and epidemiological effects of delivery of M. include early identification of sick M., parazitonositel and their radical treatment in the country. At all in a fever patients, areas, arriving from endemic on M., it is necessary to carry out parazitol, a blood analysis. The revealed patients are hospitalized, by it immediately appoint the corresponding treatment. During the summer period tropical M.'s patient surely appoint gamontotropny drugs (Bigumalum, Chinocidum, Primachinum). Radical treatment provides epidemiol. effect: the patient gets rid of repeated manifestations of M. and, therefore, stops being a source of an invasion. Also actions for maintenance of number of a carrier on low, epidemiol, harmless level are important.
In the residual centers of M. overseeing by the population for the purpose of early detection of possible diseases of M. is conducted constant epidemiol; the revealed patients are hospitalized in the chambers protected from it is filled in mosquitoes. All in a fever patients are inspected on M. (microscopy of smears and a thick drop of blood). Carry out radical treatment of sick M., write out them from a hospital only after control blood analyses on M. with a negative take. The listed measures are rather effective for sanitation of patients and parazitonositel as sources of an invasion, interfere with infection of mosquitoes.
The second group of actions is directed to fight against a carrier: reduction and elimination of places of breeding of a mosquito, destruction of larvae of a mosquito in reservoirs, destruction of the inspired mosquitoes in rooms and in the nature (see. Bonification , Disinsection ).
And, at last, an important measure is protection of the person against mosquitoes. It warns as possible infection of M. of the person, and a mosquito from the sick person or a parazitonositel.
Features of malaria at children
At children distinguish the inborn and acquired M. Vrozhdennaya M. arises at hit of parasites from blood of mother in blood of a fruit through the changed placenta at its rejection and at the time of delivery — through the cut umbilical cord or at a birth trauma. At transplacental infection often children are born premature or with displays of a pre-natal hypotrophy, further increase of body weight at them is slowed down. The expressed pallor of an integument with earthy, wax-like, and sometimes an icteric shade is characteristic, long time, despite treatment sticks to edge. M.'s attacks are, as a rule, atypical, the disease is not always followed by temperature reaction, can be shown cyanosis (see), kloniko-tonic spasms, phenomena of a meningism, vomiting, emergence of a dispeptic chair and other equivalents of an attack. At inborn M. significant increase in a spleen and to a lesser extent — a liver, and also anemia, a leukopenia, a lymphocytosis, a monocytosis, an eosinopenia is always observed.
At infection at the time of delivery the body weight and the general condition of the child at the birth are usually not broken.
Then after an incubation interval the first symptoms of a disease characteristic of the child of early age begin to come to light.
The current of the acquired M. at children of chest and early age also has the features. Typical attacks of a disease meet very seldom. The period of a fever can be absent, it is replaced by a cold snap, cyanosis, sometimes clonic and tonic spasms. There is a concern, a sleep disorder, appetite. Temperature can increase to 39 — 40 °, but during the period between attacks often does not decrease to normal figures, remaining subfebrile. The expressed period of sweating usually does not happen, only the light perspiration on a nape and behind ears is noted. The spleen considerably increases in early terms, dystrophy develops, dispeptic frustration are often observed. Repeated attacks can come either slightly earlier previous, or a bit later.
At children of advanced age of M. proceeds usually as the alternating feverish attacks (a tremendous fever, high temperature, pouring sweat), as well as at adults. But at children yellowness of an integument, rash meets more often (urtikarny, hemorrhagic, scarlatinous and korepodobny). Gepatosplenomegaliya, tachycardia at children's age are expressed more clearly. At children more often than at adults, in the period of attacks vomiting, ponosa, spasms, damage of kidneys (a proteinuria, a cylindruria) are observed, anemia develops in shorter terms. The anisocytosis, a poikilocytosis, Polikhromatofiliya, normoblasts, erythroblasts are noted. ROE is usually raised, the leukopenia, a relative lymphocytosis, a monocytosis, an eosinopenia are observed. The quantity of thrombocytes during an attack decreases, but with its termination is recovered to norm. During the period between M.'s attacks overall health of children can remain quite satisfactory or good, special deviations from various bodies and systems are not noted. Three-day fulminant M. occurs at children of preschool and school age very seldom, as a rule, at uncured or badly treated. The malarial coma accompanying tropical M. at children of younger age is observed exclusively seldom.
The diagnosis is based on identification of the activators at a research of a thick drop and blood smear painted across Romanovsky — to Gimza. It is also necessary to consider a wedge, manifestations and epidemiol, data. At differential diagnosis it must be kept in mind the following diseases: hemolitic disease of newborns (see), sepsis (see), septic endocarditis (see), miliary tuberculosis (see), pyelonephritis (see), hemolitic anemia (see), a sapropyra (see. Sapropyra epidemic ), typhoid (see), typhinia (see), brucellosis (see), food poisonings (see), in the conditions of hot climate — a leushmaniosis of internals (see. Leyshmanioza ).
As causal treatment apply to stopping of attacks more often Chingaminum. Drug is given inside after food to children up to one year in the 1st day 0,05 g, for the 2nd and 3rd day on 0,025 g on one reception; to children from 1 to 6 years — respectively 0,125 and 0,05 g; 6 — 10 years — 0,25 and 0,125 g; 10 — 15 years — 0,5 and 0,25 g. Intravenous and intramuscular administration of Chingaminum is appointed in especially hard cases; the daily dose shall not exceed 8,3 mg (5 mg of the basis of drug) on 1 kg of body weight of the child; enter into 2 receptions with an interval of 6 — 8 hour. After improvement of a state stop injections and pass to administration of drug inside. At damage of kidneys, a liver the daily dose of Chingaminum is reduced by 1,5 — 2 times and administer the drug kapelno in a vein very slowly once a day.
At drug resistant forms M. appoint quinine sulfate in a daily dose to children up to one year on 0,01 g to every month of life, but no more than 0,1 g; to children from 1 year to 10 years — on 0,1 g for a year of life of the child, from 11 to 15 years — 1 g. Quinine is appointed to 14 days. In the first 3 days its reception is combined with Chloridinum in a daily dose to children up to one year 0,0025 g, from 1 year to 2 years — 0,005 g, from 2 to 4 years — 0,0075 g, from 4 to 6 years — 0,01 g, from 6 to 8 years — 0,015 g, from 8 to 11 years — 0,02 g, completely 16 years — 0,025 g. Drug is given in 2 — 3 receptions. Its use is contraindicated at a disease of the hemopoietic bodies and kidneys.
Quinine can also be combined with sulfanamide drugs (Sulfazinum, Sulfapyridazinum, sulfalene, etc.) and sulphones in doses according to age.
Use of Primachinum within 14 days can be other method of treatment of three day and M.'s oval: to children at the age of 1 — 2 years — 1/2 of a tablet (0,0045 g), 3 — 4 years — 3/4 tablets, 5 — 7 years — 1 tablet, 8 — 12 years — 1,5 tablets, 13 — 15 years — 2 tablets, are more senior than 15 years — 3 tablets.
In addition to specific, also fortifying treatment is necessary. Upon termination of specific treatment at indications use iron preparations, vitamins of group B, in particular B12, physiotherapeutic procedures.
M. are ill animals vertebrate animals (mammals, birds, reptiles). The disease of parasitic protozoa of the sort Plasmodium is caused. Carriers of activators — different types of mosquitoes and, perhaps, other dipterous (Diptera), napr, mosquitoes.
M.'s studying at animals began after opening by V. Ya. Danilevsky in 1884 of parasites of blood of birds. R. Ross in 1898 established that a carrier of a parasite of birds of R. of relictum are mosquitoes of the sort Culex. In 1934 — 1936 G. Raffaele proved that plasmodiums of birds have an ectoglobular phase of development. At the beginning of 20 century different types of plasmodiums of monkeys were found, some of them were pathogenic for the person. In 1948 Mr. Shortt and Garnem (H. E. Shortt, R. S. S. of Garnham) proved existence of an ectoglobular phase of development in P. cynomolgi — a parasite of macaques. Systematic studying of M. of monkeys began since 1960 after accidental infection of the person R. of cynomolgi in laboratory through a sting of a mosquito. In 1948 Mr. of Vinke and the Linden (L. Vincke, M. of Lips) allocated in Zaire of the first activator M. of rodents — P. berghei.
At animals the St. 100 species of malarial parasites of the sort Plasmodium are described. A life cycle of plasmodiums at animals occurs alternately in organisms of two owners: vertebral (sexless development — a schizogony) and in an invertebrate (sexual development — a sporogony). The schizogony proceeds in cells of a parenchyma of a liver (a plasmodium of monkeys and rodents), reticuloendothelial system or in cells of the hemopoietic system (a plasmodium of birds and reptiles). An exit of a parasite in blood where in erythrocytes the schizogony proceeds is obligatory and there is a gametogonium. Blood forms of malarial zooparasites are most often used in the experimental purposes (tsvetn. fig. 11). Carriers of plasmodiums of monkeys and rodents are mosquitoes of the sort Anopheles, plasmodiums of birds — mosquitoes of the sorts Culex, Aedes, Anopheles is more rare. Plasmodiums of reptiles succeeded to infect in an experiment of mosquitoes of the sort Lutzomyia and to observe at them all process of a sporogony.
The m at animals proceeds more often as chronic, sometimes as an acute deadly invasion, napr, the caused P. knowlesi at macaques. The person does not catch plasmodiums of reptiles, birds and rodents, and these vertebrata are not sensitive to M. of the person. Some plasmodiums of monkeys which got into a human body with the infected blood (P. knowlesi) or through a sting of a mosquito (R. of shortti, R. of brasilianum, P. schwetzi, etc.), can develop in its blood. Cases of infection of people of M. of monkeys in the nature (P. knowlesi), however serious epidemiol are described, M. of monkeys does not matter. In an experiment it was succeeded to infect M. of the person of both highest (chimpanzees), and the lowest (sort Aotus) monkeys. The m of rodents, monkeys, and in certain cases and birds represents valuable model for M.'s studying of the person, on a cut it is possible to find out many questions of biology of a parasite (his relationship with the owner, emergence of immunity), and also to make primary selection of antimalarial drugs, to develop immunol, diagnostic methods, to study a possibility of creation of a malarial vaccine.
Bibliography: Ambroise-Thomas P. Reaction of an immunofluorescence at seroimmunologichesky studying of malaria, Bulletin WHO, t. 50, No. 3-4, page 270, 1975, bibliogr.; Bystrov P. V. To pathological anatomy of acute tetrian «hypertoxical» fever (malaria tertiana), Arkh. stalemate. annate., t. 6, century 1-2, page 111, 1940, bibliogr.; Boyno-Yasenetsky M. V. Pathological anatomy and some questions of a pathogeny of malaria, M., 1950, bibliogr.; Dvorkina N. Ya. Infectious psychoses, page 133, M., 1975, bibliogr.; Kassirsky I. A., etc. Guide to tropical diseases *, page 38, M., 1974; Clinical psychiatry, under the editorship of G. Grule, etc., the lane with it., page 288, M., 1967; K. M. Mullet and E. S. O Slider clinical features of brought in malaria and efficiency of modern methods of its treatment, Rubbed arkh t. 45, No. 7, page 84, 1973; L about f of p e of N To.’ Modern aspects of development of hmetod of fight against mosquitoes, Bulletin WHO, t. 50 No 3-4, page 324, 1975, bibliogr.; Lysenko A. Ya. and d river. The major tropical diseases and their prevention, M., 1973; M yo-in and with with e of N And. Reaction of indirect hemagglutination at malaria and its use for epidemiological surveillance Bulletin WHO, t. 50, No. 3-4, page 280, 1975,’ bibliogr.; The multivolume guide to microbiology, clinic and epidemiology of infectious diseases, under the editorship of H. N. Zhukova-Verezhnikov, t. 9, page 37, M., 1968; M about l about x about in A. N. Malarial psychological frustration, Chisinau, 1953, bibliogr.; Nikolaev. D. Malyariya at children, Kuibyshev, 1948; Osino in with to and y N. I. Malyariya at children, M., 1949; Tareev E. M and About z e p e of c to about in - Skye H. H. Clinical problems of malaria in the USSR in 50 years, in book: Vopr. medical parazitol., under the editorship of V. P. Podjyapolskaya and L. I. Prokopenko, page 42, M., 1970; Aikawa M. a. Sterling Ch. R. Intracellular parasitic protozoa, N. Y., 1974, bibliogr.; Coatney G. R. a. o. The primate malarias, Bethesda, 1971; Eckstein A. Malaria in Kindesalter, Basel — N. Y., 1946, Bibliogr.; Garnham P. Page of S. of Malaria parasites and other Haemosporidia, Oxford, 1966; K i 1 1 i with k-Kendrick R. Parasitic protozoa of the blood of rodents, Acta trop. (Basel), v. 31, p. 28, 1974; Lysenko A. J., Bei-j an e v A. E. a. R y b a 1 k a V. M. Population studies of plasmodium vivax, Bull. Wld Hlth Org., v. 55, p. 541, 1977, bibliogr.; Manson’s tropical diseases, ed. by Ch. Wilcocks a. P. Manson-Bahr, Baltimore, 1972; Parasitology of malaria, Techn. rep. ser. No. 433, Geneva, WHO, 1969; Schmid A. H. Cerebral malaria, Europ. Neurol., v. 12, p. 197, 1974; S ey f arthC. Die Malaria, Handb, spez. path. Anat. u. Histol., hrsg. v. F. Henke u. O. Lubarsch, Bd 1, T. 1, S. 178, B., 1926, Bibliogr.; Shute G. T. a. Sodeman T. M. Identification of malaria parasites by fluorescence microscopy and acridine orange staining, Bull. Wld Hlth Org., v. 48, p. 591, 1973, bibliogr.; Shute P. G. a. M a-r at o n M. E. Laboratory technique for the study of malaria, L., 1966; Spencer H. Tropical pathology, B. — • N. Y., 1973, bibliogr.; Wintrob R. M. Malaria and the acute psychotic episode, J. nerv. ment. Dis., v. 156, p. 306, 1973; Z u with k e r-m and n A. Recent studies of factors involved in malaria anemia, Milit. Med., v. 131, p. 1201, 1966, bibliogr.
A. Ya. Lysenko, H. V. Astafyeva; B. P. Bisyarina (ped.), M. V. Voyno-Yasenetsky (stalemate. An.), Yu. E. Rakhalsky (psikhiat.).