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Specific treatment is carried out when Giardia is detected and the patient has clinical manifestations. For these
purposes, the following drugs are used.
• Metronidazole.Inside, adults are prescribed 400 mg 3 r / day for 5 days or 250 mg 3 r / day for 7-10 days; children
1-3 years old - 0.5 g / day for 3 days, 3-7 years old - 0.6-0.8 g / day for 3 days, 710 years - 1-1.2 g / day for 5 days.
• Tinidazoleadministered orally once, adults 2 g (if necessary, can be repeated), children - 50-75
mg / kg.
• Ornidazoleapply inside 1.5 g 1 time per day (in the evening) for 5-10 days; for children weighing up to 35 kg,
the drug is prescribed at 40 mg / kg in 1 dose.
• Nimorazoleappoint inside 500 mg 2 r / day for 6 days.
• Nifurateltaken orally: adults 400 mg 2-3 r / day for 7 days, children - 15 mg / kg 2 r / day for 7 days.
• Albendazole.Inside adults 400 mg 2 r / day for 7 days; children - 10 mg / kg per day, but not more than 400 mg
for 7 days. The high giardicidal efficacy of alblidazole was shown, which can be the drug of choice in the
treatment of giardiasis in cases of combination of invasion with intestinal nematodes.
In the practice of treating giardiasis, Nitazoxanide * 8, an antiparasitic drug with a wide spectrum of action,
has recently begun to be used (not available in the Russian Federation).
registered) - inside adults 100 mg 2 times a day for 3 days.
After a course of specific treatment, a control study of feces is carried out.
Forecast
The prognosis is favorable.
dispensary
Dispensary observation is carried out according to clinical and epidemiological indications: with a
long stubborn course of giardiasis, it is recommended to observe
a period of up to 6 months with a double or triple parasitological examination.
BIBLIOGRAPHY
1. Guidelines MUK 4.2.3145-13 "Laboratory diagnosis of helminthiasis and protozoosis".
Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2014.
2. Human parasitic diseases (protozooses and helminthiases): A guide for doctors / Ed. V.P. Sergiev, Yu.V.
Lobzina, S.S. Kozlov. - St. Petersburg: Foliant Publishing LLC, 2011. - 608 p.
3. Sanitary and epidemiological rules and regulations SanPiN 3.2.3215-14 "Prevention of parasitic diseases in
the territory of the Russian Federation". Federal Center for Hygiene and Epidemiology of Rospotrebnadzor,
2014. - 38 p.
4. Sergiev V.P., Yushchuk N.D., Vengerov Yu.Ya. Zavoykin V.D. Tropical Diseases: A Guide for Physicians. - M.:
BINOM, 2015. - 640 p.
5. Tokmalaev A.K., Kozhevnikova G.M. Clinical parasitology: protozooses and helminthoses. - M.: Medical
Information Agency LLC, 2010. - 432 p.
6. Garcia, Lynn Shore. Diagnostic medical parasitology. 5th ed. ASM Press. - Washington:
DC, 2007. - 1202 p.
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7. Tropical Manson Diseases / Edited by G. K. Cook, A. J. Zumba. - 22nd edition. 2009. - 1830 p.
8. WHO Model List of Essential Medicines. eighteenthlist. April 2013. - No. 45.
9. Medical parasitology of Markell and Foge. 9th edition. - USA: Saunders Elsevier, 2006. - 463 p.
22.3. MALARIA
Malaria (English malaria, French paludisme) is an anthroponotic transmissible human protozoal
disease, characterized by a cyclic course, the possibility of relapses, manifested by febrile attacks,
hepatosplenomegaly, anemia.
ICD-10 CODES
B50 Plasmodium falciparum malaria. B50.0 Plasmodium falciparum malaria
with cerebral complications
B50.9 Plasmodium falciparum malaria, unspecified B50.8 Other severe and complicated Plasmodium
falciparum malaria B51 Malaria due to Plasmodium vivax. B51.0 Plasmodium vivax malaria
complicated by ruptured spleen
B51.9 Plasmodium vivax malaria, uncomplicated
B51.8 Plasmodium vivax malaria with other complications B52 Malaria due to Plasmodium malariae.
B52.0 Plasmodium malariae malaria with nephropathy
B52.8 Plasmodium malariae malaria with other complications
B52.9 Plasmodium malariae malaria, uncomplicated
B53 Other parasitologically confirmed malaria. B53.0 Plasmodium ovale malaria
B53.1 Plasmodium monkey malaria
B53.8 Other parasitologically confirmed malaria, not elsewhere classified B54 Malaria, unspecified P37.3
Plasmodium falciparum congenital malaria. P37.4 Other congenital malaria.
ETIOLOGY
The causative agents of malaria belong to the Sporozoa phylum in the Plasmodiidae family. Four types of
pathogen parasitize in humans: Plasmodium vivax - causes three-day malaria, P. malariae - four-day, P.
falciparum - tropical, P. ovale three-day oval-malaria.
Under experimental and sometimes natural conditions, human infection with zoonotic Plasmodium species of
monkeys (P. knowlesi, P. cynomolgi, etc.) is possible [1, 2]. Severe cases of human malaria due to P. knowlesi
have been reported since 2004 among tourists in Southeast Asia.
Malaria parasites in the course of their life go through the following cycles of development with a
change of hosts:
asexual development (schizogony) occurs in the body of an intermediate host - a person;
sexual development (sporogony) takes place in the body of the final host - the female mosquito of the genus
Anopheles.
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Sporozoites enter the human body through the bite of an infected mosquito. After
penetration into the blood, sporozoites in 15-45 minutes are introduced into hepatocytes
from the sinusoidal vessels of the liver and begin the exoerythrocyte cycle (tissue
schizogony). The selectivity and speed of invasion are due to the presence of specific
receptors on the membranes of hepatocytes.
Parasites increase, divide many times and form many small mononuclear merozoites. The
minimum duration of the exoerythrocyte cycle is 5–7 days for P. falciparum, 6–8 days for P.
vivax, 9 days for P. ovale, and 14–16 days for P. malariae. Then the merozoites leave the
hepatocytes into the blood and invade the erythrocytes, where erythrocyte schizogony
occurs. For three-day and oval malaria, a special type of exoerythrocytic development is
characteristic: all parasites or part of them are able to stay in hepatocytes in a “dormant”
state (hypnozoites) for a long time (7-14 months or more), and only after the end of this
period do they begin to turn into merozoites capable of infecting erythrocytes. Thus, this
causes the possibility of long-term incubation and the occurrence of distant relapses (up to 3
years).
Erythrocyte schizogony is accompanied by cyclic development and multiple division of parasites, while malarial plasmodia go through the
following stages: young trophozoite (has the shape of a ring), developing trophozoite, mature trophozoite (has a large nucleus), developing
schizont, mature schizont. After the completion of the schizogony process, the erythrocyte is destroyed. Free merozoites actively penetrate
new erythrocytes, but most of them die from the host's protective immune mechanisms. The duration of erythrocyte schizogony is 48 hours in
P. vivax, P. ovale, P. falciparum, and 72 hours in P. malariae. During the erythrocyte cycle, some merozoites turn into sexual forms - female
(macrogametocytes) or male (microgametocytes). Gametocytes enter the organism of a mosquito-carrier when it feeds on the blood of a
patient with malaria or a parasite carrier, containing mature gametocytes. In the mosquito's stomach, after 9-12 minutes, the male
gametocyte throws out eight thin mobile cords. Loose bundles (microgametes) penetrate the female cell (macrogamete); after the fusion of
the nuclei, a zygote is formed - a round fertilized cell. Further, ookinetes, oocysts with sporozoites develop sequentially, their maturation takes
place in the salivary glands of the mosquito. At the optimum ambient temperature (25 °C), sporogony lasts 10 days for P. vivax, 12 days for P.
falciparum, 16 days for P. malariae and P. ovale; at air temperatures below 15 °C, sporozoites do not develop. after the fusion of the nuclei, a
zygote is formed - a round fertilized cell. Further, ookinetes, oocysts with sporozoites develop sequentially, their maturation takes place in the
salivary glands of the mosquito. At the optimum ambient temperature (25 °C), sporogony lasts 10 days for P. vivax, 12 days for P. falciparum,
16 days for P. malariae and P. ovale; at air temperatures below 15 °C, sporozoites do not develop. after the fusion of the nuclei, a zygote is
formed - a round fertilized cell. Further, ookinetes, oocysts with sporozoites develop sequentially, their maturation takes place in the salivary
glands of the mosquito. At the optimum ambient temperature (25 °C), sporogony lasts 10 days for P. vivax, 12 days for P. falciparum, 16 days
for P. malariae and P. ovale; at air temperatures below 15 °C, sporozoites do not develop.
EPIDEMIOLOGY
Malaria remains the most widespread tropical disease in the world and is a major health
problem for 106 countries in Asia, Africa and South America. According to WHO (2014),
currently 82 countries of the world are highly endemic, the rest are in the pre-elimination
period or have achieved elimination of malaria in their territories. According to WHO (2014),
between 2000 and 2013, there was a decrease in cases of malaria per year from 227 million to
198 million. Mortality in 2013 was estimated at 584 thousand cases (within the uncertainty of
367-755 thousand ). About 90% of deaths are registered in the African region, of which 70% of
deaths from malaria, mainly from tropical, are children of the first 5 years of life. Only
imported cases of malaria are registered in Russia.
The source of the infectious agent is only a person, the carrier is mosquitoes of the Anopheles
genus. Malaria is a natural focal infection. Its distribution in endemic regions is of a zonal-focal
nature, determined by a combination of natural and socio-economic factors. P. vivax causative agent of the three-day
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malaria, widespread in Asia, Oceania, South and Central America; on the African continent, P.
vivax is constantly found in the countries of East Africa among Arabs, Indians, Ethiopians, and
Europeans; in the countries of West Africa, populated mainly by representatives of the Negroid
race, P. vivax is not found, which is explained by the genetically determined innate immunity of
African blacks to this type of Plasmodium. The range of P. ovale is small and consists of 2 parts.
The main - the African part, occupies tropical Africa from the Gambia - in the north to the
Congo - in the south of the continent. The second part of the range is the countries of the
western part of the Pacific Ocean and Southeast Asia. The geographic range of tropical malaria
extends from 40°N. up to 20° S P. falciparum and causes up to 50% of the incidence of malaria
in the world. Four-day malaria is currently found in Africa, parts of Central and South America,
the Caribbean, and Southeast Asia. P. knowlesi, whose reservoir is monkeys, has been recorded
in natural foci of Southeast Asia.
Three ways of transmission of malaria are possible: 1) through a mosquito; 2) from
mother to fetus or newborn (vertical transmission); 3) transfusion through the blood or
during medical manipulations in violation of asepsis during injection (schizontal
malaria). The first way is the main one that ensures the existence of malaria parasites as
biological species.
The source of infection is a person with malaria or a healthy parasitic carrier, in whose blood
there are mature gametocytes. The epidemiological danger of the source of infection is
determined by the number of gametocytes in the blood, the duration of the gametocarrier
period and its availability to mosquitoes. When infected with P. falciparum, a person
becomes a source of infection 10-12 days after the onset of parasitemia and can remain so
for 2 months or more until the asexual parasites disappear naturally or under the influence
of treatment. When infected with other types of malaria, a person is a source of infection
from the moment the asexual forms appear (14-21 days of illness) until they disappear. The
period of development of gametocytes is only a few hours longer than the development of
asexual forms. Gametocytes die a few hours after maturation.
With vertical transmission of malaria, the fetus can become infected through the placenta,
which is rare. More often, infection occurs during childbirth, when a certain amount of
maternal blood enters the fetal bloodstream during placental abruption. Vertical transmission
occurs in mothers who are not immune to malaria. Indigenous inhabitants of endemic foci give
birth to an immune child who remains resistant to malaria for several months.
Susceptibility to malaria is universal. The exception is the indigenous inhabitants of West
Africa, who have an innate immunity to P. vivax, due to the absence of a receptor for
merozoites of this species on the erythrocytes of Africans - Duffy isoantigens (Fya or Fyv). The
hyperendemic foci of tropical Africa, dominated by P. falciparum, are characterized by a
relatively stable immunological structure of the indigenous population: children under the age
of 6 months do not get sick due to passive immunity received from the mother; most children
aged 6-24 months are affected by P. falciparum; passive immunity has faded, active is not yet
developed; this group has the highest mortality from malaria; in children older than 2 years, P.
falciparum is found less frequently, the course of malaria is mitigated as a result of acquired
immunity, with age, the intensity of parasitemia decreases; in adults, P. falciparum is rarely
detected due to the high intensity of immunity; there are no clinical manifestations during
infection.
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Tropical malaria also occurs easily in carriers of abnormal hemoglobin S (sickle cell anemia) and in
individuals with some other genetically determined abnormalities of hemoglobin and erythrocyte
enzymes (deficiency of G-6-FDG). Malaria is a seasonal infection. Its transmission falls on the
season of mosquito activity, i.e. for the warm season. In areas with a temperate and subtropical
climate, the transmission season is limited to the summer-autumn months with a stable average
daily temperature above 16 °C. Its duration ranges from 1.5 to 6-7 months. In the tropical zone,
the duration of the transmission season is year-round, and interruptions in malaria transmission
are associated with rainfall patterns.
Under the influence of a complex of climatic, geographical and socio-economic factors, foci of malaria
have formed in various regions. The center of malaria is considered to be a settlement with
anophelogenous reservoirs adjacent to it. The susceptibility of the population to malaria is judged by a
number of malariometric indices: parasitic (percentage of persons with parasitemia among the surveyed
group); splenic (percentage of persons with an enlarged spleen in the group of examined persons) and
others, as well as the results of serological and epidemiological studies.
According to the WHO classification, there are 4 degrees of endemia:
1) hypoendemia - splenic index in children from 2 to 9 years old within 10%;
2) mesoendemia - splenic index in children aged 2-9 years ranging from 11 to 50%;
3) hyperendemia - the splenic index in children aged 2-9 years is constantly above 50%;
4) holoendemia - the parasitic index in children under the age of 1 year is constantly above 75%, the
splenic index in adults is low (African type) and only in some areas is high (New Guinean type).
Cases of malaria are classified as imported, secondary from imported, local, grafting.
A relapse is a case of malaria with recurrence of the disease several months after the first
illness, if the treatment was incomplete (for example, without taking primaquine for three-day
malaria) or of poor quality (non-compliance with the drug regimen, expired drug, etc.). The
initial manifestations of three-day malaria outside the transmission season (for example, in the
spring of the following year) cannot be considered relapses, these are the primary
manifestations after a long incubation.
PREVENTION MEASURES
WHO is fighting malaria worldwide through the Roll Back Malaria Program adopted in 1998. A new
target has now been set for the WHO European Region: to eliminate P. vivax three-day malaria and
tropical malaria by 2015. In the Russian Federation, the main antimalarial measures are regulated
by SanPiN 3.2.3215-14. The most important link in the complex of measures is the timely detection
and treatment of sources of infection. Vector control plans include entomological observations in
potential outbreaks, hydrotechnical measures, treatment of mosquito breeding sites with
larvicides, and treatment of premises with imagicides. When staying in areas where malaria is
common, you should take precautions to protect yourself from mosquito bites. It is necessary to
conduct consultations of citizens traveling to endemic regions, to inform them about the correct
implementation of individual malaria chemoprophylaxis. The WHO guidelines state that malaria
chemoprophylaxis should be given to people traveling to outbreaks
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medium and high endemicity. Non-immune pregnant women are advised not to visit such areas.
Individual chemoprophylaxis of malaria in endemic foci where tropical malaria is common is
carried out with mefloquine, which is recommended to be taken once a week at 250 mg during
the entire period of stay in the focus, but not more than 6 months. Currently often used
malarone*
- tablets for adults - 250 mg of atovachone* + 100 mg of proguanil hydrochloride, 1 tablet the day before
entering the risk area, 1 tablet daily in the endemic focus and 7 days after departure.Chloroquineused in
the foci of four-day, three-day and oval-malaria in the absence of tropical malaria. In accordance with
existing rules, drugs should be started before leaving the outbreak, the entire period of stay in the
outbreak during the season when there is a risk of infection, and within 4 weeks after leaving the
outbreak. Those arriving from a highly endemic region for the prevention of late relapses of three-day
and oval malaria are additionally prescribed primaquine at a dose of 0.25 mg/kg (base) for 14 days.
Although chemoprophylaxis does not always prevent the development of the disease, it can prevent
severe malaria and death.
PATHOGENESIS AND PATHOMORPHOLOGY
All clinical manifestations of malaria are due to erythrocyte schizogony. Tissue schizogony is not
clinically manifested. The clinical picture of malaria infection is characterized by a triad of
symptoms: an attack of fever, hemolytic anemia, hepatosplenomegaly.
A malarial attack is associated with the completion of erythrocyte schizogony, the massive disintegration
of erythrocytes and the release into the bloodstream of a large number of merozoites, products of
metabolism of parasites and hemolysis, which have pyrogenic and toxic properties, which leads to the
development of a feverish reaction. An attack can occur only when the number of parasites reaches the
so-called pyrogenic threshold. With three-day, oval- and four-day malaria, for an attack to occur, there
should be about 100 parasites in 1 μl of blood, with tropical - up to 600. However, this pyrogenic
threshold is conditional and depends not so much on the number of parasites in the blood, but on the
reactivity of the organism of an infected person. It is known that in relapses, attacks occur with a
significantly higher parasitemia than in primary malaria.
When infected with malaria, a heterogeneous population of parasites enters the human body, and
schizogony in the initial period occurs asynchronously, and therefore the type of fever may be incorrect.
With the formation of immune reactions, the ability to parasitize in erythrocytes is acquired by one leading
generation of plasmodium, which determines the fever rhythm characteristic of this species. Only with
tropical malaria can there be several leading generations of plasmodia, so the fever is often irregular.
Exogenous pyrogens of a parasitic nature are mainly assigned the role of activators of the inflammatory
reaction. Lymphocytes and macrophage cells activated under the influence of parasitic antigens secrete a
large amount of cytokines, in particular IL and TNF, free oxidative radicals, and the complement system is
activated. This leads to damage to the walls of blood vessels, primarily at the level of the microvasculature,
and other pathological changes in the body. The main mechanism for the development of complications in
tropical malaria is the accumulation (sequestration) of invaded erythrocytes in the vessels of internal
organs, mainly the brain, as well as the kidneys, liver, intestines, bone marrow, placenta, etc. This is due to
changes in the properties of erythrocytes, manifested by cyto-
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adhesion and rosetting. Cytoadhesion - adhesion of affected erythrocytes to endothelial cells, leads to
sequestration in capillaries and postcapillary venules. The main role in cytoadhesion is assigned to specific
ligand proteins induced by the parasite on the surface of erythrocytes and receptors located on the outer
surface of endothelial cells. As a result of blockage of blood vessels, ischemia of the affected organs
develops. Prominences (knobs) appear on the membranes of affected erythrocytes, which are in contact
with outgrowths in the form of pseudopodia formed on endothelial cells. Some strains of P. falciparum
have the property of causing healthy red blood cells to adhere to infected ones, resulting in rosettes.
Erythrocytes become rigid, which worsens the rheological properties of the blood and exacerbates
microcirculation disorders.
An important damaging factor is hypoxia caused by insufficient oxygen transport function of
infected erythrocytes. The brain tissue is the least resistant to hypoxia, which plays an important
role in the genesis of cerebral malaria.
Significant disturbances occur in the hemostasis system: in severe tropical malaria, signs of DIC
syndrome (thrombocytopenia and hypofibrinogenemia) are observed. Violation of microcirculation,
metabolism, pulmonary edema, impaired renal function and hemostatic system are the leading
pathogenetic factors in the development of malignant malaria.
The cause of anemia is the destruction of red blood cells by parasites in them. P. vivax and P. ovale
infect mainly young erythrocytes, P. malariae infects mature erythrocytes, P. falciparum infects
erythrocytes of different maturity, therefore parasitemia increases most rapidly in tropical malaria and
reaches a high level with damage to 20% or more of erythrocytes, which leads to to intense hemolysis.
Additional factors of erythrocyte hemolysis can be autoimmune mechanisms or fixation of circulating
immune complexes to uninfected erythrocytes, which also leads to their hemolysis. An important role in
the development of anemia is played by the increased activity of the elements of the reticulohistiocytic
system, which phagocytizes both affected and normal erythrocytes.
Malaria is accompanied by enlargement of the liver and spleen. Initially, this is due to congestion in the
organs, but soon lymphoid and reticuloendothelial hyperplasia occurs in them. Hemolysis of erythrocytes,
as well as damage to hepatocytes, cause jaundice.
Reduced absorption of carbohydrates and inhibition of gluconeogenesis in the liver cause hypoglycemia.
An increase in glucose uptake by host and parasite cells also acts in the same direction. Activation of
anaerobic glycolysis leads to the accumulation of lactate in the blood, CSF and the development of
acidosis, which is one of the causes of death in severe tropical malaria.
The pathomorphological picture in malaria is characterized by the presence of anemia and changes in
organs rich in reticuloendothelial tissue. Due to the deposition of the brown-black pigment
hemomelanin, which is formed during the destruction of erythrocytes, the internal organs acquire a
slate-gray-smoky color. There is a significant increase in the liver and spleen. The spleen is full-blooded,
follicular hyperplasia, proliferation of reticular cells are microscopically determined, heart attacks and
hemorrhages under the spleen capsule are often noted. Hyperemia, proliferation of Kupffer cells,
vascular endothelium are observed in the liver. With a long course of the disease, fibrotic changes
develop. In the bone marrow, a pronounced erythroblastic reaction is detected. In the heart muscle,
degenerative changes are found, hemorrhages under the inner lining of the heart.
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small hemorrhages, the vessels of the lungs are overflowing with infected erythrocytes. In complicated
cases, pneumonia, pulmonary edema are observed. Kidney damage in tropical malaria is characterized by
an increase and plethora of organs, signs of interstitial nephritis and acute tubular necrosis. With a long
course of four-day malaria, a nephrotic syndrome develops, accompanied by the deposition of active
immune complexes (IgM-, IgG-complement) in the glomeruli. In the malignant course of tropical malaria,
degenerative-destructive changes in the adrenal cortex, necrosis and hemorrhage, and poverty of the
organ in lipids are observed. Examination of the gastrointestinal tract reveals necrotic and ulcerative
changes in the mucous membrane, petechial hemorrhages. The most characteristic changes in severe
tropical malaria occur in the brain, where edema and swelling of the brain substance, perivascular and
periganglionic growths of neuroglia (Durck's granulomas) are observed. Capillaries are blocked by
invaded erythrocytes and parasites, there are extensive hemostasis. Perivascular edema develops with
hemorrhages and focal necrosis.
CLINICAL PICTURE
Taking into account the specific features of malaria parasites and the corresponding differences in
clinical manifestations, 4 forms of malaria are distinguished: three-day malaria (vivax - malaria,
malaria tertiana); three-day oval-malaria (ovale
malaria); four-day malaria (malaria quartana); tropical malaria (falciparum-malaria, malaria
tropica). The ICD-10 singles out separately - B53.1 - malaria caused by monkey plasmodia.
In accordance with WHO recommendations, malaria is distinguished: uncomplicated, severe and
complicated. Severe and complicated forms of malaria are characteristic mainly of R. falciparum
infection. The disease caused by R. vivax, R. ovale and R. malariae, as a rule, has a benign course.
In the course of a malarial infection, a distinction is made between primary malaria and relapses - sooner
and later.
Primary malaria covers the initial period of the disease, the period of peak and convalescence.
Without treatment or inadequate etiotropic therapy, the disease goes into a period of recurrent
course. There are exoerythrocyte and erythrocyte relapses, and according to the time of their
development, respectively, early and late.
Erythrocyte relapses are observed when infected with all types of plasmodia. Early ones occur up to 2
months after the initial attacks, developing at a later date are referred to as late relapses. With untreated or
inadequately treated three-day and oval malaria, a "lull" lasting 6-11 months occurs with the disappearance
of parasites from the blood and clinical "recovery". Then late relapses occur (due to the activation of
hypnozoites in the liver), which, without treatment, are again replaced by a latent period, after which the
disease recurs again. The duration of existence in the human body (without treatment) for P. falciparum is
up to 1.5 years, for P. vivax and P. ovale - up to 3 years, for P. malariae - many years, sometimes for life.
Three day malaria
The incubation period ranges from 10-21 days or 6-14 months. Prodromal events before a primary
malarial attack are rare, but often precede relapses. They are manifested by a feeling of general
malaise, weakness, weakness, pain in the lumbar region, limbs, a slight rise in body temperature,
loss of appetite, headache. The duration of the prodromal period averages 1-5 days.
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Initially, the temperature curve is irregular (initial fever), which is explained by the asynchronous release of several
generations of P. vivax into the blood. Subsequently, typical malarial paroxysms with intermittent fever begin. In a
malarial febrile attack, three phases are clinically distinct, immediately following one after another: the stage of chills,
heat and sweating. The attack begins with chills, the intensity of which can be different: from mild chilling to
tremendous chills. The skin becomes dry, rough or "goose-like" to the touch, cold, limbs and visible mucous
membranes become cyanotic. There is a severe headache, sometimes vomiting, pain in the joints and lumbar region.
The chill stage lasts from several minutes to 1-2 hours and is replaced by a heat stage. Body temperature reaches 40-
41 ° C, the skin becomes dry and hot, the face turns red. Headache, pain in the lumbar region and joints intensify. The
heat stage lasts from one to several hours and is replaced by a period of sweating. Body temperature drops critically,
sweating is often profuse. The duration of the attack is 6-10 hours. The onset of attacks of the disease in the morning
and afternoon hours is considered characteristic. After an attack, a period of apyrexia begins, which lasts about 40
hours. The interval between attacks is 48 hours. After 2-3 attacks, the enlarged liver and spleen are clearly detected.
Changes in the blood are characterized by hypochromic anemia, which develops gradually from the 2nd week of
illness. In the peripheral blood, leukopenia, neutropenia with a stab shift, relative lyphocytosis, aneosinophilia, and
elevated ESR are detected. In the natural course of the disease without antiparasitic treatment, after 12-14 attacks, the
intensity of the fever decreases, the attacks gradually fade away, the size of the liver and spleen are reduced. However,
after 2 weeks - 2 months, attacks of fever reappear - early relapses, characterized by a synchronous temperature
curve, an increase in the liver and spleen, and anemia. Subsequently, with an increase in immunity, the parasites
disappear from the blood and a latent period begins. If during this period the treatment with histoschizotropic drugs
is not carried out, then after 6-8 months, and sometimes after 1-3 years, the tissue forms of parasites “dormant” in
hepatocytes will be activated and distant relapses will develop. Distant relapses are characterized by an acute onset,
milder course, early enlargement of the spleen, a short number of attacks up to 7-8,
Oval malaria
Oval malaria is similar in many clinical and pathogenetic features to three-day vivax malaria. The incubation period
lasts 11-16 days. With oval malaria, the pathogen tends to primary latency: the duration of the incubation period
can stretch from 2 months to 2 or more years. In the clinical picture, from the first days of the disease, intermittent
three-day fever prevails, and daily fever is less common. Febrile attacks with great constancy, unlike other types of
malaria, are observed in the evening hours. Oval-malaria is characterized by a predominantly mild course with a
small number of attacks, which is explained by the rapid development of a high level of immunity. Attacks occur
without pronounced chills and with a lower level of body temperature.
Quartan
The incubation period is from 3 to 6 weeks. Prodromal symptoms are rare. The onset of the disease is acute.
From the first attack, intermittent fever is established with a frequency of attacks after 2 days. The onset usually
starts at
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noon, its average duration is about 13 hours. The chill period is long and pronounced. The heat
period lasts up to 6 hours, accompanied by headache, myalgia, arthralgia, sometimes nausea,
vomiting. Patients may be restless and delirious. In the interictal period, the condition of the
patients is satisfactory. Anemia, hepatosplenomegaly develop slowly - not earlier than 2 weeks
after the onset of the disease. Manifestations of four-day malaria stop without treatment after 8-14
attacks, but the process of erythrocyte schizogony at a low level lasts for many years. Most often,
the disease proceeds without activation of erythrocyte schizogony in the form of parasite carriers,
which makes such individuals potentially dangerous donors. The disease is usually benign,
tropical malaria
The most severe form of malarial infection. The incubation period is 8-16 days. At the end of it, in some
non-immune individuals, prodromal phenomena lasting from several hours to 1-2 days are noted: malaise,
weakness, weakness, body aches, myalgia and arthralgia, and headache. In most patients, the disease
begins acutely, without a prodrome, with a rise in body temperature to 38-39 ° C. The absence of cyclical
attacks of fever is characteristic. The attack begins with a chill, the duration of which is from 30 minutes to 1
hour. During this period, the patient is pale, the skin is cold, often with a roughness like "goosebumps".
Chills are accompanied by a rise in body temperature to 38-39 ° C. With the cessation of chills, the second
phase of the attack begins - fever. Patients have a slight feeling of warmth, sometimes they experience a
feeling of true heat. Skin is hot, dry the face is hyperemic. The duration of this phase is about 12 hours, and
it is replaced by mild sweating. Body temperature drops to normal and subnormal figures and after 1-2
hours rises again. In some cases, the onset of tropical malaria is accompanied by nausea, vomiting, and
diarrhea. Observed: cough, runny nose, sore throat. In later periods, herpetic eruptions appear on the lips
and wings of the nose. In the acute stage, patients have hyperemia of the conjunctiva, with a severe course
of the disease, petechial or larger subconjunctival hemorrhages are possible. In the peak period, chills are
less pronounced than in the first days of the disease, its duration is only 15-30 minutes. Fever continues for
days, periods of apyrexia are rarely recorded. With a mild course of the disease, the height of the body
temperature in patients reaches 38.5 ° C, duration of fever - 3-4 days; with moderate severity, respectively 39-39.5 ° C and 6-7 days. The severe course of the disease is characterized by an increase in body
temperature to a high level - 40 ° C and above, the duration of the febrile period is 8 or more days. The
duration of individual attacks (and in fact the layering of several) with tropical malaria reaches 30-40 hours.
The wrong type of temperature curve prevails, remitting is less often observed, occasionally - intermittent
and permanent types. Enlargement of the liver and spleen is usually determined on the 3rd day of illness.
With ultrasound of the abdominal organs, an increase in the size of the liver and spleen is determined
already on the 2-3rd day from the onset of clinical manifestations of tropical malaria. Disorders of pigment
metabolism are observed in patients with severe and, less often, moderate course of tropical malaria. More
than a threefold increase in the activity of aminotransferases in the blood serum is regarded as an indicator
of an unfavorable prognosis. Metabolic disorders include changes in the hemostasis system and
hypoglycemia. Cardiovascular disorders are manifested by tachycardia, muffled heart sounds, and
hypotension. In a severe form of the disease, changes appear on the ECG in the form of deformation of the
final part of the ventricular complex - flattening and negative T wave, decrease in the ST segment, decrease
in R wave voltage in standard muffled heart sounds, hypotension. In a severe form of the disease, changes
appear on the ECG in the form of deformation of the final part of the ventricular complex - flattening and
negative T wave, decrease in the ST segment, decrease in R wave voltage in standard muffled heart sounds,
hypotension. In a severe form of the disease, changes appear on the ECG in the form of deformation of the
final part of the ventricular complex - flattening and negative T wave, decrease in the ST segment, decrease
in R wave voltage in standard
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leads. In tropical malaria, CNS disorders associated with high fever and intoxication are often
observed: headaches, vomiting, meningism, convulsions, drowsiness, sometimes delirium-like states,
but, unlike the cerebral form, the patient's consciousness is preserved. Characteristic are hemolytic
anemia and leukopenia, and in the leukocyte formula - eosin and neutropenia, relative lymphocytosis.
In severe forms of the disease, neutrophilic leukocytosis is often noted; ESR is constantly and
significantly increased. Thrombocytopenia is a symptom typical of all types of malaria. As with other
infectious diseases, febrile proteinuria of a transient nature is observed in patients.
The recurrent course of tropical malaria is due either to inadequate etiotropic treatment, or to the
presence of P. falciparum resistance to the chemotherapy drugs used. The natural course of tropical
malaria with a favorable outcome lasts no more than 2 weeks. In the absence of etiotropic therapy
after 710 days there are relapses. Pregnancy is a recognized risk factor for tropical malaria. This is due to
a higher morbidity in pregnant women, a tendency to severe clinical forms, a risk to the health and
life of the child, and a limited therapeutic arsenal.
Malaria in children
In children, as in adults, three-day and ovale-malaria proceed similarly. The severe periodicity of
attacks characteristic of malaria in adults is rare in children. More common daily attacks of varying
duration, occurring at different times of the day. In older children, at the onset of the disease, a
persistent type of fever is often observed, followed by typical attacks. During an attack, pallor of the
skin, cyanosis,
sometimes vomiting, diarrhea, general restlessness, convulsions. In some cases, there are pains in the
abdomen, appendicular syndrome, requiring urgent consultation with a surgeon. The liver and spleen
enlarge early and almost simultaneously. As the disease progresses, the spleen can become large.
Anemia develops rapidly. With three-day and ovale-malaria, cases with fatal outcomes are rare, they occur
in children with severe anemia and dystrophy. In children and adolescents who received inadequate
therapy or did not receive treatment at all, a malignant fulminant form of three-day malaria has been
described. It was observed in the middle zone of the former USSR, mainly in the spring period of the year.
Children aged 4 to 12 years who had previously had three-day malaria were usually affected. Malignant
manifestations of malaria occurred during relapses or at the onset of the disease, more often during the
second attack. Suddenly, during a paroxysm of fever, severe headaches, vomiting, convulsions,
drowsiness, passing into unconsciousness, appeared. A few hours later, death occurred. Pathological
anatomical examination of the dead revealed acute swelling and increased blood filling of the brain
substance. In contrast to the malarial coma in falciparum malaria, only single plasmodia were detected in
the capillaries of the brain. The fulminant form of three-day malaria was considered as a hyperergic
reaction of the child's organism. However, a retrospective analysis in such cases cannot exclude a mixed
pathology: three-day malaria and neuroviral infection. Four-day malaria in children is very similar to threeday, except for the frequency of attacks. However, it is known that four-day malaria in children can be
complicated by nephrotic syndrome, which is based on the deposition of immune complexes on the
glomerular basement membrane with damage to it and degenerative changes in the tubules. Most often,
nephrotic syndrome develops in children aged 5-8 years. At the same age
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the highest incidence of four-day malaria is also recorded, which also confirms the association
between P. malariae infection and nephrotic syndrome.
In tropical countries with a high level of endemia (holo- and hyperendemic foci), falciparum malaria
remains one of the main causes of morbidity and mortality in children; 5 to 15% of all deaths are due
to this disease. Children from 6 months to 4-5 years of age are most often and seriously ill, so
tropical malaria is reasonably considered a potentially fatal disease in them. Tropical malaria in
older children usually proceeds in the same way as in adults, and presents no special diagnostic
difficulties. In children under 3-4 years old, especially in infants, falciparum malaria is characterized
by a peculiar clinical picture, in which the most striking clinical symptom, a malarial attack, is absent.
At the same time, symptoms such as convulsions, vomiting, diarrhea, abdominal pain are observed,
with a rapidly progressive deterioration in the child's condition. The differences are that during the
period of apyrexia the temperature does not decrease to normal, therefore relapsing fever is
observed, or that the attacks begin earlier each time. In infants, the first attacks of tropical malaria
are very severe, the disease quickly becomes malignant and can result in death. The child becomes
lethargic, capricious, restless, his appetite disappears, vomiting of food eaten is possible. Body
temperature rises to 38-40 ° C, fever can be constant, remittent, intermittent, but often has an
irregular hectic character. Chills are often absent, the attack begins with blanching, then cyanosis of
the skin, cold extremities, pronounced symptoms of neurotoxicosis, convulsions, vomiting,
meningeal syndrome may appear. With the development of a malarial coma, there is a sharp
anxiety, then prostration, a mask-like face, an indifferent look, convulsions, vomiting, loss of
consciousness. In infants, there is a pronounced lability of water-salt metabolism, which predisposes
to the development of edema of organs and tissues, including the brain. Abdominal pain and loose
stools often occur. In the stools there may be an admixture of mucus and blood, sometimes the
stool is watery. Persistent diarrhea can cause severe dehydration. The abdomen is usually enlarged.
There is pain in the hypochondria. The spleen is enlarged, easily palpable, painful. With frequent
repeated infections, the spleen can reach a large size and occupy almost the entire abdominal
cavity. Soreness of the spleen increases with the development of perisplenitis or infarction. There
are cases of spontaneous or as a result of trauma rupture of the spleen. It should be emphasized
that an increase in the spleen in infants with malaria is observed inconsistently and in about 20% of
patients is not detected at all. In children older than 2 years, the spleen is enlarged more often, the
degree of its increase depends on the duration of the disease and concomitant alimentary
dystrophy. Often there is an increase and thickening of the liver, sometimes its soreness, but the
reaction of the liver is less pronounced than that of the spleen. The younger the child, the faster the
anemia develops and grows. The level of hemoglobin in advanced cases drops to 30-50 g/l, the
number of erythrocytes decreases to 2-1x1012/l. characteristic reticulocytosis. Leukopenia,
eosinophilia, relative lymphocytosis and monocytosis are observed, although neutrophilic
leukocytosis and elevated ESR are possible during attacks. Parasitaemia in young children is usually
high: P. falciparum can affect up to 20% of red blood cells. Severe anemia in children is accompanied
by hypoxemia and hypoxia of organs and tissues, so the skin and visible mucous membranes
become pale with an earthy tint, hypotrophy develops. If treatment is not carried out, then the
child's condition quickly worsens and death occurs. The prognosis is aggravated by the addition of
intercurrent diseases: pneumonia, salmonellosis and other intestinal infections. then the child's
condition deteriorates rapidly and death occurs. The prognosis is aggravated by the addition of
intercurrent diseases: pneumonia, salmonellosis and other intestinal infections. then the child's
condition deteriorates rapidly and death occurs. The prognosis is aggravated by the addition of
intercurrent diseases: pneumonia, salmonellosis and other intestinal infections.
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Malaria in humans, caused by P. knowlesi, recorded in Southeast Asia almost exclusively among
tourists, is similar in clinical manifestations and severity to tropical malaria.
Complications
They are observed mainly in tropical malaria and are possible at all stages of the disease. Prognostically
unfavorable clinical signs indicating the possibility of developing malignant malaria are daily fever,
absence of apyrexia between attacks, severe headache, generalized convulsions, recurring more often 2
times in 24 hours, decerebrate rigidity, hemodynamic shock (systolic pressure below 70 mm Hg .st in an
adult and less than 50 mm Hg in a child). This is also evidenced by the results of a microscopic
examination of blood: high parasitemia (more than 100 thousand R. falciparum in 1 μl of blood), detection
of various age stages of the parasite in peripheral blood, the presence of gametocytes, increasing
leukocytosis (more than 12x109 / l). The following laboratory data are also indicators of a poor prognosis:
Cerebral (brain) malaria. Under this name, severe lesions of the central nervous system are
combined in tropical malaria, the main outcome of which is the development of a coma.
Malarial coma can be a complication of primary, recurrent, and recurrent malaria, but is more common in
primary malaria. It occurs mainly in children, pregnant women and in young and middle-aged people. In
the clinical picture of cerebral malaria, three periods are distinguished: somnolence, stupor and true
coma. The stage of somnolence is characterized by mental and physical lethargy of the patient, rapid
exhaustion. The patient is oriented in time and space, but is reluctant to make contact, answers questions
in monosyllables, quickly gets tired. Tendon reflexes are preserved. The stage of stupor that follows it is
manifested by a deep prostration of the patient with rare flashes of consciousness. Ataxia, amnesia,
convulsions, sometimes epileptiform in nature, are possible. Corneal reflexes are preserved, pupils are
normal. Tendon reflexes are increased pathological reflexes appear. With a true coma, the patient does
not respond to external stimuli. There is a violation of convergence, divergent strabismus, floating
movements of the eyeballs with open eyelids (as if the patient is examining the ceiling), horizontal and
vertical nystagmus, paralysis of the VI pair of cranial nerves; tendon and abdominal reflexes are absent,
vegetative functions are sharply disturbed. Meningeal symptoms and pathological reflexes of Babinsky,
Rossolimo, etc. are pronounced. In children older than 4 years and adults, the Glasgow coma scale (1974)
is used to assess the degree of impaired consciousness and coma, as in other CNS lesions. With spinal
puncture, an increase in intracranial pressure is detected without pronounced violations of the protein
and cellular composition of the cerebrospinal fluid. With cerebral malaria, the development of psychosis is
possible. In the acute period, psychoses occur in the form of delirium, amentia, manic states. Epileptic
seizures are possible. Depression, mental weakness, hysteria, schizophrenia-like syndromes are
characteristic of postmalarial psychoses; a temporary delay in mental development is possible in children.
Sometimes there are long-term effects of cerebral malaria:
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hemiplegia, ataxia, focal cranial nerve symptoms, extrapyramidal disorders, mono- and
polyneuritis.
Hypochromic anemia is a common complication of all forms of malaria infection. Severe anemia
is diagnosed when the hematocrit falls below 20% and the hemoglobin level falls below 50 g/l.
Serious manifestations of malaria are violations of hemostasis: bleeding gums, retinal
hemorrhage, spontaneous nasal and gastrointestinal bleeding, DIC.
AKI is diagnosed when urine output decreases to less than 400 ml/day in an adult and less than 12
ml/kg in children (and there is no effect of furosemide), serum creatinine exceeds 265 mmol/l,ureamore than 21.4 mmol / l, hyperkalemia occurs. There are the following stages of acute renal failure:
initial, oligoanuria, polyuria.
Hemoglobinuric fever is a consequence of massive intravascular hemolysis, which may be due to
intensive invasion or the use of certain antimalarial drugs (quinine, primaquine, sulfonamides) in
individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G-6-PD). In its severe
form, intense jaundice, severe hemorrhagic syndrome, anemia and anuria develop, accompanied by
chills, high fever (40 ° C), pain in the lumbar region, repeated vomiting of bile, myalgia, arthralgia.
Urine becomes dark brown in color due to the presence of oxyhemoglobin. The number of
erythrocytes in severe cases decreases to 1x1012 / l, and the hemoglobin level - up to 20-30 g / l.
There are very few or no parasites in the blood with malarial hemoglobinuria. Rapid discontinuation
of an antimalarial drug caused hemolysis of erythrocytes, the patient's condition improves without
serious consequences. In severe cases, due to the development of ARF, the prognosis may be poor.
Malarial algid is characterized by clinical manifestations characteristic of TSS: hemodynamic
disturbances, microcirculation, disturbances in the hemostasis system, multiple organ failure and
hypothermia. Unlike cerebral malaria, consciousness is preserved, although coma may develop in
the future. Algid can develop against the background of pulmonary edema, metabolic acidosis
and severe dehydration. There is usually a high level of parasitemia. The prognosis largely
depends on timely and adequate treatment.
Acute pulmonary edema in patients with tropical malaria is often fatal. The mechanism of this
severe complication is not fully understood. Pulmonary edema can be provoked by excessive
rehydration, hypoproteinemia. It can also develop against the background of normal pressure in
the pulmonary circulation.
Spleen rupture is a rare but severe complication in any clinical form of malaria. Rupture of an organ
can be caused by torsion of its leg with acute blood stasis and the development of a subcapsular
hematoma.
Nephrotic syndrome is a complication of four-day malaria. It is characterized by a slow,
steadily progressive course with an increase in proteinuria, hypoproteinemia, widespread
edema, arterial hypertension and renal failure. The swelling is so pronounced that the children
cannot open their eyes. This is a very characteristic symptom, which makes it possible to make
a diagnosis at a "first sight". Proteinuria reaches 10-20 g/day. Urine contains a significant
amount of globulins, in some cases the excretion of globulins exceeds the excretion of
albumin.
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Eye lesions are possible with tropical malaria: keratitis, less common iritis, iridocyclitis, vitreous
opacity, chorioretinitis and retinal hemorrhages. Optic neuritis is sometimes observed, there are
reports of paresis of III, IV and VI pairs of cranial nerves, accommodation paralysis.
DIAGNOSIS
The diagnosis of malaria is based on an analysis of the clinical picture of the disease, an
epidemiological history with the obligatory confirmation of the diagnosis by the detection of
malaria parasites in the peripheral blood. The probability of a diagnosis of malaria increases if
the epidemiological history establishes stay in an endemic region before the onset of the
disease, blood transfusions and other parenteral manipulations up to 3 months before the
onset of the disease.
Laboratory diagnostics
The main method of laboratory diagnosis of malaria is a microscopic examination of blood preparations
(“thick drop” and “thin smear”) stained according to Romanovsky-Giemsa (MUK 4.2.3222-14 “Laboratory
diagnosis of malaria and babesiosis”). Subject to examination for malaria: febrile patients with an
unidentified diagnosis within 3 days during the epidemic season and 5 days during the rest of the year;
patients with ongoing periodic rises in body temperature despite the ongoing treatment in accordance
with the established diagnosis; recipients with an increase in body temperature in the last 3 months after
blood transfusion; persons living in an active focus, with any fever. With low parasitemia, malaria occurs
in individualsdoxycycline,cotrimoxazole [sulfamethoxazole + trimethoprim] (Biseptol *), sulfonamides],
which have a suppressive effect on malaria plasmodia.
Blood sampling for research is recommended both during fever and during apyrexia. Studies of blood products are carried out
for 2-3 days up to 3-4 times a day. The study of the "thick drop" is designed to detect parasites, since the volume of blood in it
is 30-40 times greater than in the "thin smear". Features of morphology and tinctorial properties (staining) of different age
stages of asexual forms in erythrocytes are clearly distinguishable in a "thin smear". Determination of the parasite species is
mandatory, but it is especially important for P. falciparum, which has a number of inherent features. In primary infection,
other more mature stages of the parasite in the peripheral blood can be found in cases of severe, malignant disease.
Gametocytes mature slowly, but remain viable in the blood for a long time (up to 6 weeks), while gametocytes of other species
die a few hours after their maturation. The detection of gametocytes in tropical malaria is important for judging the period of
the disease: in the early period (with an uncomplicated course) only ring-shaped trophozoites are found, in the peak period rings and gametocytes (with primary infection and no treatment, this indicates the duration of the disease is at least 10-12
days); in the period of convalescence, only gametocytes are found. during the peak period - rings and gametocytes (with
primary infection and no treatment, this indicates the prescription of the disease for at least 10-12 days); in the period of
convalescence, only gametocytes are found. during the peak period - rings and gametocytes (with primary infection and no
treatment, this indicates the prescription of the disease for at least 10-12 days); in the period of convalescence, only
gametocytes are found.
In recent years, rapid tests (immunochromatographic methods) based on the detection of specific
Plasmodium antigens have been used to quickly obtain a preliminary answer. Test systems for rapid
diagnosis of malaria, developed by different manufacturers, are designed to detect P. falciparum, P.
falciparum + P. vivax or Plasmodium species. Using express tests allows you to read the result after 10
minutes. The laboratory staff can master the reaction in 1-2 hours. Express methods allow self-diagnosis
for people living or traveling in endemic regions, and can be carried out in the field. In a clinical setting,
these methods
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are used for the preliminary diagnosis of malaria with a mandatory parallel
parasitological study of blood products.
Currently, PCR is of particular importance. The use of PCR makes it possible to detect carriage in low
parasitemia and mixed infection with different types of plasmodia, as well as to differentiate the
recurrence of drug-resistant falciparum malaria from reinfection with P. falciparum.
Differential Diagnosis
Differential diagnosis of malaria is carried out with a number of infectious and non-infectious diseases,
accompanied by fever, anemia and hepatosplenomegaly. Depending on the severity of the course of the
disease and its duration, malaria must be differentiated from influenza and other acute respiratory viral
infections, typhoid-paratyphoid diseases, dengue fever, pap-patachi, hemorrhagic fevers - Lassa,
Marburg, Ebola, yellow fever, visceral leishmaniasis, viral hepatitis, sepsis, leptospirosis, acute brucellosis,
spirochetosis, PTI, miliary tuberculosis, cholangitis, amoebic liver abscess, acute pyelonephritis,
lymphogranulomatosis, hemolytic anemia, babesiosis blood is very reminiscent of P. falciparum at the
appropriate stage). Malarial coma is differentiated from cerebral, uremic, hepatic, diabetic, hypoglycemic
coma.
Diagnosis example
B50.0 Tropical malaria (P. falciparum 124 thousand parasites in 1 µl). Complications:
cerebral form, coma.
TREATMENT
Indications for hospitalization
Patients with malaria are subject to hospitalization; treatment of patients with
severe and complicated forms is carried out in the ICU.
Medical therapy
Etiotropic treatment of patients with malaria should be prescribed immediately after
establishing a clinical and epidemiological diagnosis and taking blood for a
parasitological study.
The following factors influence the choice of treatment tactics: the type of pathogen, the region where
the infection occurred (to judge the resistance of plasmodia to antimalarial drugs), the period of
illness, the severity of the disease, the presence and nature of complications.
In the classification of antimalarial drugs according to the object of influence, the following main
groups can be distinguished (Table 22.2):
hemoschizontocidal - affect the asexual erythrocyte stages of parasites in the blood, are effective for
the treatment of three-day and ovale-malaria, a radical cure for tropical and four-day malaria;
histoschizontocidal affect the pre-erythrocytic stages of the pathogen in the liver, provide radical
chemoprophylaxis of tropical, partially - three-day malaria;
gametocidal - affect the sexual erythrocyte stages of P.falciparum in the blood, allow you to
neutralize the source of infection; <g hypnozoitocidal act on hypnozoites in the liver, provide a radical cure
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three-day and ovale-malaria, radical chemoprophylaxis of three-day malaria with
long-term incubation.
Table 22.2. Classification of antimalarial drugs by mechanism of action
Mechanism of action
LS
Application results
Gemoshizonto
Mefloquine;
They act on erythrocyte schizonts, stop attacks of three-day malaria
cidal
arte derivatives
and malaria caused by P. ovale, provide a radical cure for tropical and
mysinina*; quinine;
four-day malaria
chloroquine
Histoshizonto
pyrimethamine,
They act on merozoites (in the liver), provide radical
cidal
primaquine, proguanil,
chemoprophylaxis of tropical, partially - three-day malaria
tetracycline
Gametocidal
Primakhin
Influence the sexual erythrocyte stages
P. falciparum, allow to neutralize the source of infection
Hypnozoitocidal Primaquine
Affect hypnozoites (in the liver), provide a radical cure for three-day malaria
and P. ovale malaria, radical chemoprophylaxis for three-day malaria with a
long incubation period
Antimalarial drugs currently used belong to the following groups of chemical compounds (Table
22.3): 4-aminoquinolines (chloroquine),quinolinemethanols (quinine,mefloquine),
phenanthrenemethanols (halo fanthrin8, halfan8), artemisinin derivatives8 (artesunate8,
artemether8, artee-ter8), antimetabolites (proguanil), 8-aminoquinolines (primaquine, tafenoquin8).
In addition, combined antimalarial drugs are used: pyrimethamine + sulfadoxine (Fansidar*),
chloroquine+ proguanil (savarin8), atovachone + proguanil (malarone8), artemether
+ lumefantrine (coartem8 or riamet8).
Table 22.3. Classification of antimalarial drugs by chemical compounds
Drug group (ATC code) Antimalarial drugs
Aminoquinolines (PO1BA) Chloroquine (P01BA01) Hydroxychloroquine (P01BA02) Primaquine (P01BA03)
Quinolinemethanols (PO1BC) Quinine hydrochloride8 (P01BC01) Mefloquine (P01BC02)
Artemisinin derivatives8 (PO1BE) Artemisinin8 , artesunate8 , artemether8 , arteeter8 Biguanides
(P01BB)
Proguanil (P01BB01)
Combined drugs
Savarin8 (chloroquine + proguanil), Malarone8 (atovachone + proguanil), Coartem8 (artemether + lumefantrine)
(POIBX - other antimalarial drugs)
Pyrimethamine +
Pyrimethamine + sulfadoxine (Fansidar)
other antimalarial drugs (P01BD)
Tetracyclines (J01AA)
Tetracycline (J01AA07) Doxycycline (J01AA02)
Antimalarial drugs are not produced in Russia (with the exception of primaquine), and a number of
effective drugs widely used abroad are not registered in the Russian Federation, in particular,
artemisinin derivatives8 and combined antimalarial drugs.
The most important problem in the treatment of malaria is the resistance of the causative agent
of tropical malaria Plasmodium falciparum to chloroquine, which exists almost everywhere. In
some endemic foci, multiresistance of the pathogen to antimalarial drugs is already observed.
In pathogens of three-day malaria (P. vivax), drug resistance is much less pronounced and is
registered only in certain endemic areas.
When P. vivax, P. ovale, or P. malariae is detected in a patient, drugs from the 4-aminoquinoline
group are used, most oftenchloroquine(Delagil *). Treatment regimen: for the first 2 days, the
drug is used at a daily dose of 10 mg/kg base (4 tablets of Delagil* per 1 dose), on the 3rd day 5 mg/kg (2 tablets of Delagil*) once. There are isolated reports of resistance of P. vivax strains to
chloroquine in Burma,
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Indonesia, Papua New Guinea and Vanuatu. In such cases, treatment should be with mefloquine or
quinine in the uncomplicated malaria regimen. Attacks stop after 24-48 hours, and parasites
disappear from the blood after 48-72 hours after the start of chloroquine.
For a radical cure (prevention of distant recurrences) for malaria caused by P. vivax or P. ovale, at the
end of the course of chloroquine, tissue schizontocide, primaquine, is used, which is prescribed for 14
days at a dose of 0.25 mg / kg (base) per day. P. vivax strains resistant to primaquine (so-called
Chesson-type strains) are found in the Pacific Islands and Southeast Asia. In these cases, one
recommended regimen is 0.25 mg/kg primaquine daily for 21 days.
When P. falciparum is detected in the blood of non-immune individuals in cases of mild and
uncomplicated course, treatment regimens with artemisinin-combined antimalarial drugs
(ACT - Artemisinin-based Combination Therapies, WHO, 2010) are used in accordance with
WHO recommendations. Two or more antimalarial drugs are used with different mechanisms
of action:
inside 3 days: atovachone* 1000 mg + proguanil 400 mg 1 r / day;
inside 3 days: artesunate* 4 mg/kg 1 r/day + 1st day sulfadoxine 25 mg/kg +
pyrimethamine1.25 mg/kg 1 r/day;
inside 7 days: artesunate* 2 mg/kg 1 r/day +doxycycline3.5 mg/kg 1 r/day; inside 3 days:
artesunate* 4 mg/kg 1 r/day + 2 days:mefloquine1 r / day (1st day - 15 mg / kg, 2nd day - 10 mg /
kg);
orally 2 days: artemether* 80 mg 1 time, then 80 mg every 8, 24 and 48 hours after the first dose + 2 days:
lumefantrine* 480 mg, then 480 mg every 8, 24 and 48 hours after the first dose . In the above schemes,
the doses of drugs for adults are indicated. For details, including combined antimalarials (coar-tem*,
malarone*), see chapter 9.5 Antiparasitic drugs.
For the treatment of children at the initial stage, candles with artesun-tom * can be used.
In African countries and other regions where multidrug-resistant strains of P. falciparum are
not registered and in cases of importation from these countries, the following combined
preparations are effective: atovachone + proguanil (malarone*), artesunate + amodiaquine,
artesunate + pririmethamine + sulfadoxine (Fansidar*). Artesunate* can also be used in
combination with tetracycline (doxycycline) or clindamycin. In Southeast Asian countries,
where multiresistant strains of P.
Falciparum, apply: artesunate +mefloquine,artemether + lumefantrine (Coartem*). If the patient
has not established the type of pathogen, then treatment is recommended according to the
treatment regimens for tropical malaria. If the patient vomits less than 30 minutes after ingestion
of the prescribed antimalarial drug, the same dose should be taken again, if vomiting was noted
30-60 minutes after taking the tablets, then half the dose of the same drug is additionally
prescribed.
When P. falciparum gametocytocarrier is detected, primaquine (base) 0.25 mg/kg per day is
administered orally for 2-3 days.
In severe and complicated tropical malaria, according to the WHO recommendation (2010), the drug of
choice for treatment is artesunate* IV drip for 7 days: 1st dose - 4 mg/kg, then 2-7 days - 2 mg/kg per
day . Quinine is an alternative drug for the treatment of severe fαlcipαrum malaria and is used in the
absence of artesunate*. Quinine is given by IV drip [in 5% dextrose solution (Glucose*) or isotonic
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solution slowly]: 10 mg / kg for 4 hours, then 20 mg / kg per day in 2-3 injections with an interval
of 8-12 hours (daily dose for an adult should not exceed 2.0 g), followed by transfer to the oral
form of the drug . Monotherapy with quinine does not provide a radical cure (since it is quickly
excreted from the body, and its long-term use often leads to the development of adverse
reactions). Therefore, after the patient's condition improves, a course of treatment with
mefloquine, Fansidar * or tetracycline is carried out.
Patients with severe and complicated forms of malaria undergo intensive pathogenetic therapy in the ICU. During rehydration, one
should be wary of pulmonary and cerebral edema, but the state of hypovolemia is no less dangerous. With insufficient rehydration,
such patients may develop shock and renal failure. Developing anemia usually does not threaten the patient's life, but if the hematocrit
drops to 15-20%, then red blood cells or whole blood should be transfused. Transfusion of fresh whole blood or concentrates of
coagulation factors and platelets is used in the development of DIC. In case of hypoglycemia, intravenous administration of a 40%
dextrose solution (Glucose *) should be resorted to. The basis of therapy for cerebral edema is detoxification, dehydration, oxygen
therapy, the fight against cerebral hypoxia and respiratory disorders. According to the indications, anticonvulsants are administered.
Experience in the treatment of cerebral malaria has proven the inefficiency and even the danger of using some drugs: osmotic diuretics,
low molecular weight dextrans, epinephrine (Adrenaline*), prostacyclin, pentoxifylline (Trental*), cyclosporine, hyperimmune sera.
Hyperbaric oxygen therapy is also not recommended. In cases of development of acute renal or hepatic-renal failure, the daily dose of
quinine is reduced to 10 mg / kg due to the possible accumulation of the drug and the solutions are administered very slowly - 20 drops
per minute. pentoxifylline (Trental*), cyclosporine, hyperimmune sera. Hyperbaric oxygen therapy is also not recommended. In cases of
development of acute renal or hepatic-renal failure, the daily dose of quinine is reduced to 10 mg / kg due to the possible accumulation
of the drug and the solutions are administered very slowly - 20 drops per minute. pentoxifylline (Trental*), cyclosporine, hyperimmune
sera. Hyperbaric oxygen therapy is also not recommended. In cases of development of acute renal or hepatic-renal failure, the daily
dose of quinine is reduced to 10 mg / kg due to the possible accumulation of the drug and the solutions are administered very slowly 20 drops per minute.
In the initial period of acute renal failure, forced diuresis is prescribed, and in the absence of
effect and an increase in azotemia, hemodialysis is performed. However, it should be borne in
mind that hemodialysis is able to correct homeostasis for a short time. At present, it has been
shown that the use of prolonged veno-venous hemodiafiltration for these purposes is much
more effective. With the development of hemoglobinuric fever, the drug that caused hemolysis
is canceled, if necessary, replaced with another antimalarial drug, glucocorticoids are
prescribed simultaneously(prednisoloneone2 mg/kg), detoxification therapy. If the spleen is ruptured, emergency surgery is indicated.
For the treatment of relapses of tropical malaria, a previously unused drug is selected or the former
is used, but in combination with other antimalarial drugs. Treatment of gametocarrier is carried out
with primaquine for 1-3 days in usual therapeutic doses.
For the treatment of patients with P. knowlesi malaria, the falciparum malaria regimens
described above are used.
In the process of treatment, the level of parasitemia is determined in dynamics in the
peripheral blood. A day after the start of etiotropic treatment, the level of parasitemia
should decrease by 25% or more, on the 3rd day - should not exceed 25% of the original.
The presence of parasites in the blood product on the 4th day after the start of
treatment, subject to all the conditions for successful therapy, is a sign of resistance of
the pathogen to the drug used.
Forecast
In the vast majority of cases, lethality is due to tropical malaria, namely its cerebral form,
which occurs in 10% of cases of severe fαlcipαrum malaria. Deaths from other types of
malaria
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Source KingMed.info
very rare. But even tropical malaria, with timely diagnosis and adequate treatment, ends in
complete recovery.
dispensary
For patients who have had tropical malaria, it is recommended to establish dispensary observation for
1-1.5 months and conduct a parasitological blood test at intervals of 1-2 weeks. Clinical examination of
patients who have had malaria caused by P. vivax, P. ovale, P. malariae should be carried out within 2
years. Any increase in body temperature in these individuals requires a laboratory blood test to detect
malarial plasmodia.
BIBLIOGRAPHY
1. Guidelines MUK 4.2.3222-14 "Laboratory diagnosis of malaria and babesiosis". Federal Center for
Hygiene and Epidemiology of Rospotrebnadzor, 2014.
2. Human parasitic diseases (protozooses and helminthiases): A guide for doctors / Ed. V.P. Sergiev, Yu.V.
Lobzina, S.S. Kozlov. - St. Petersburg: Foliant Publishing LLC, 2011.
- 608 p.
3. Sanitary and epidemiological rules and regulations SanPiN 3.2.3215-14 "Prevention of parasitic
diseases in the territory of the Russian Federation". Federal Center for Hygiene and Epidemiology of
Rospotrebnadzor, 2014. - 38 p.
4. Popov A.F., Tokmalaev A.K. Malaria. - Vladivostok: Medicine DV, 2014. - 120 p.
5. Sergiev V.P., Yushchuk N.D., Vengerov Yu.Ya., Zavoykin V.D. Tropical Diseases: A Guide for Physicians.
- M.: BINOM, 2015. - 640 p.
6. Tokmalaev A.K., Kozhevnikova G.M. Clinical parasitology: protozooses and helminthoses. - M.: Medical
Information Agency LLC, 2010. - 432 p.
7. Khodjaeva N.M. Malaria in children: clinical and immunopathogenetic features,
optimization of treatment. // Diss. doc. ... honey. Sciences. - M., 2009. - 280 p.
8. Garcia, Lynn Shore. Diagnostic medical parasitology. 5th ed. ASM Press. - Washington: DC, 2007. - 1202 p.
9. WHO. Guidelines for the treatment of malaria. 2nd edition. - World Health Organization,
Geneva. - 2010. - 141 p.
10. World Malaria Report: 2014. - WHO, Geneva. - 2014. - 227 p.
22.4. TOXOPLASMOSIS
Toxoplasmosis (English toxoplasmosis) is a protozoal disease caused by Toxoplasma gondii, the genus
Toxoplasma, characterized by a variety of course options and polymorphism of clinical manifestations. In the
vast majority of cases, as a result of infection with Toxoplasma
asymptomatic carriage
develops.
ICD-10 CODES
B58 Toxoplasmosis.
Includes: Toxoplasma gondii infection Excludes: congenital toxoplasmosis (P37.1).
B58.0 Toxoplasmic oculopathy
B58.1 Toxoplasmosis hepatitis (K77.0)
B58.2 Toxoplasmic meningoencephalitis (G05.2)
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