[(INDUCED MALARIA)].

Induced malaria continues to be one of the most pressing public health problems in malaria-endemic countries. Ma- laria parasites remain viable in stored blood at a temperature of 2-6°C for 3 weeks. The paper presents current problems associated with transfusion-induced malaria. In the USSR and then in the Russian Federation, sporadic cases of induced malaria (Plasniodium vivax, P.malariae, rarely P.falciparum) were notified (230 cases in 1958 to 1990 and only 5 in 1991 to 2016). Current (immunological and molecular) methods for the laboratory diagnosis of malaria do not provide a 100% detection rMfteor its pathogens; therefore, it is necessary to search for highly efficient, rapid, and low-cost diagnostic methods to ensure the biological safety of donation.

[(ASSESSMENT OF RISK FOR ARBOVIRUS INFECTIONS IN RUSSIA)].

The sharply increased incidence and geographical expansion of arbovirus diseases in recent years suggest that some Russian areas are vulnerable to vector-borne diseases and that it is important to elaborate control programs to ensure bio- logical safety in our country. Moreover, the main vectors of the pathogens of arbovirus infections (Zika fever, dengue fever, chikungunya fevers), such as Aedes aegypti and Ae.albopictus, have been registered on the Black Sea coast of the Caucasus. The programs must be effective, by taking into account the biological features of each kind of a vector.

[(HUMAN DIROFILARIASIS: CLINICAL DIAGNOSTIC FEATURES ASSOCIATED WITH DIFFERENT DEVELOPMENTAL STAGES OF THE PATHOGEN)].

To seek medical advice is due to the time when a person has become infected during the infection transmission season (July-August) and the duration of development of the pathogen Dirofilaria (N.) repens in his/her body Clinical manifes- tations occurred in 61% of the patients 6-10 months after infection, as confirmed by the maximum body sizes (125-160 mm) of removed females which have reached puberty. PCR-based diagnosis in conjunction with microscopic studies improves the efficiency of identifying the patients and the species of the pathogens D.repens and D.immitis. The use of these methods for the first time in 2016 could confirm D.immitis infestation in a 14-month-old infant living in the Solnechnogorsk District, Moscow Region.

[(EXPERIENCE WITH GEOGRAPHIC INFORRMATION SYSTEMS USED IN EPIDEMIOLOGICAL STUDIES (AS AN EXAMPLE OF MALARIA AND DIROFILARIASIS)].

The effective application of GIS against parasitic diseases requires the patterns of spread of parasitic diseases in certain natural, climatic, and socioeconomic conditions of different regions where there are epidemically effective carriers. The epidemiological parameters defining a high risk of an epidemiological process after P.vivax importation into Russia were calculated using the developed HealthMapper controlled module with a database. Analysis of the average long-term air temperatures in the administrative territories of Russia over 78 years, namely July, the warmest month of the year when there are the largest numbers of all types of mosquito vectors and high levels of microfilaria in the peripheral blood of in- fected dogs (definitive hosts), has shown that the northern border of the maximum possible area of dirofilariasis in Russia is most fully described by the +14C July isotherm.

[CURRENT IDEAS ON OBLIGATE AND FACULTATIVE RELATIONSHIPS BETWEEN MAN AND THE DIROFILARIASIS PATHOGEN DIROFILARIA (N.) REPENS].

The ability of D. repens to complete its ontogenesis in man points to their obligate, rather than facultative rela- tionships. The fact that microfilariae are rarely found in human blood or are absent there may be associated with the removal of developing dirofilariae from humans in earlier than they achieve sexual maturity. Facultative ecological relationships to mosquitoes may be one of the reasons for limitation of human invasion cases. However, in long-standing microfilaremia in man (an obligate host), D.repens may take part in the epidemiological chain of dirofilariasis as a source of invasion.

[THE CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF MALARIA CONCURRENT WITH OTHER INFECTIONS AND INVASIONS].

The present review considers malaria infection concurrent with different species of helminths, bacterial and viral infections, as well as mixed malaria pathogens in the subtropical and tropical countries of the world, causing the clinical picture and epidemiological situation to be different. Malaria co-infections with different pathogenic micro-organisms, such as HIV, tuberculosis, viral hepatitides, and others, affect almost one third of the planet's population. It is known that people who are at risk for malaria may be also at risk for other parasitic and infectious diseases, most commonly helminthisms.

ON THE EPIDEMIOLOGY OF COMPLICATED VIVAX MALRIA.

A larger number of publications on cases of. complicated vivax malaria in the world literature can be. explained by a set of diffeetit faciors'. There has been unification of the definition of complicated tertian malaria allowing ihe clinical nianagement of a patient and the reporting of complicated cases of P.vivax to be improved. The, epidemiological characteristics of complicated vivax malaria are determined by a diversity of geographical, races, variants, gentyies and phenotypes of tertian malaia due to intensive internal and external migration. Chloroquine resistance and primaquine refractoriness contribute to increased local malaria transmission due to a rise in cases of reinfection during-epidemics of vivax malaria. From an epidemiological point of view, the increasing number of complicated vivax malaria cases indicates the untimely detection and treatment of malaria patients, the low level of medical personnel training and a negative attitude of the local population towards the recommendations of national malaria programs for prevention measures. Unsolved problems can substantially retard the time to achieve malaria elimination.

[COMPLEX LABORATORY DIAGNOSIS OF MALARIA PATHOGENS IN THE PRE ELIMINATION PERIOD].

An immunological survey of 8,000 dwellers from 4 districts of Tajikistan failed to detect malaria pathogens by CareStartMalariaHPR2/PLDH (P. falciparum/P. vivax) COMBOGO161 AccessBio tests and showed the possibility of their further use under the Republic's conditions, particularly in the mountain villages and the human settlements bordering on Afghanistan. The results of examining 750 blood samples from the dwellers of sanitized foci in Tajikistan's areas, by applying molecular diagnosis via polymerase chain reaction, indicated no signs of parasites. A set ofthree methods, such as microscopic, immunological, and molecular diagnostic ones, was used to prove the absence of reliable malaria infection and local transmission sources.

[Human dirofilariasis: clinical and diagnostic signs and diagnostic methods].

The clinical and diagnostic signs caused by the tissue location and migration of adult Dirofilaria in the human body determine the use of different methods for the diagnosis of dirofilariasis. During their investigations, the authors modified polymerase chain reaction (PCR): they chose and synthesized primers and selected amplification regimens for them and obtained agarose gel bands that corresponded to PCR fragment length nucleotide sequences that were equal to 245 bp for D. (N.) repens and 656 bp for D. immitis. There was 100% agreement in the results of PCR and microscopic examination of sera from 32 dogs and 1 female patient with low parasitemia and in the blood nucleotide sequence characteristic of D. repens.

[The current status of the resistance of malaria pathogens to antimalarials].

The review presents the results of trials of the clinical efficacy of a test antimalarial drug for each malarial parasite species, which were published in 2000-2013 and supplemented by the data of in vitro studies or investigations using the molecular markers of resistance. There are data on the resistance of each medicament since many of the drugs are used in combination with artermisinin derivatives.

[Results of studies of human dirofilariasis in Russia].

Human dirofilariasis is a pressing health problem in Russia. By 2014, there have been as many as 850 Dirofilaria repens-infested people living in 42 subjects of the Russian Federation. One of the favorable factors for circulation and spread of invasion is a temperature of above +20-24 degrees C; when the latter is maintained during at least 20 days there may be 1.-1.5 circulations of invasion in the carrier and a 2.8-fold increase in transmission intensity. The border ofa dirofilariasis area with a temperate climate is southward to 58 degrees N in European Russia and West Siberia and southward to 50 degrees N in the Far East. The conditions in the human body have been found to be more favorable for the development of Dirofilaria than considered before and allow the helminth to achieve sexual maturity and to propagate. If man has microfilaremia, he may be a source of invasion. It is necessary to examine venous blood by the enrichment method and, if possible, polymerase chain reaction and enzyme immunoassay, which make it possible to establish a diagnosis in occult invasion and to identify a pathogen species.

[The epidemiological features of visceral leishmaniasis, revealed on examination of children by polymerase chain reaction, in the Papsky District, Namangan Region, Uzbekistan].

Patients with visceral leishmaniasis (VL) have been registered in the Papsky District, Namangan Region, Uzbekistan, over the past 23 years. A total of 95 patients were notified in 1987 to 2009. In 2007-2008, a mass survey using the polymerase chain reaction (PCR) within the international INTAS project 05-100006-8043 was conducted in 5 population aggregates of the Papsky District, Namangan Region, Uzbekistan, where VL cases had been regularly registered in the last years. Bone marrow and venous and peripheral blood smears were used as a test material. A total of 234 samples, including 3 bone marrow biopsy specimens, 9 venous blood samples and 222 peripheral blood ones, were tested. All the samples were on the glass slides. Three groups were identified among the examinees. Group 1 consisted of 13 subjects who had been ill at different times. Group 2 comprised 27 children treated at hospital for various diagnoses. Group 3 (the largest one, n=190) included apparently healthy children. All the children of this group felt well and had no symptoms of any illnesses at the examination. In this group, 85 (44.7%) subjects were PCR-positive. Twenty-four (55.8%) of 43 children in the age group of 0-3 years were PCR-positive; the 4-7-year age group comprised 66 subjects and 33 (50%) of them were PCR-positive. Group over 7 years of age included 81 subjects; 45 (55.5%) were PCR-positive. The results of the mass survey with PCR, which covered the 5 population aggregates in the Papsky District, Namangan Region, Uzbekistan, suggest the epidemic activity of a synathropic focus of VL and make us look at many fixed notions of its epidemiology in new contexts.

[Human and canine visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan: seroepidemiological and seroepizootological surveys].

In 2007 - 2008, four (Chodak, Oltinkan, Gulistan, and Chorkesar) of 9 population aggregates in the Papsky District, Namangan Region, Uzbekistan, where visceral leishmaniasis (VL) cases had been registered in the last years were selected to make seroepidemiological and seroepizootological surveys within the international project funded by INTAS grant 05-100006-8043. The surveys of the populations were conducted visiting their homesteads. These additionally included children's and health care facilities where all children aged less than 14 years were examined. On examining the children, their peripheral blood (approximately 0.1 ml) was taken on filter paper for serological assays. Canine blood was sampled from the vein. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect antibodies to VL pathogens. A total of 521 children were examined for two years, by applying ELISA. Five hundred and fourteen blood samples from children younger than 14 years, 162 dogs, 4 foxes, and 1 cat were tested. Testing 514 children's blood samples for VL pathogen antigen ascertained that in the 4 population aggregates there was an average of 10% VL-seropositive children, including those who were ill with VL at the moment of the examination and had been ill. The highest number of VL-seropositive samples (14.9%) was found in the settlement of Chodak. VL pathogen antibodies were detected in 26 (61.9%) of 42 dogs with the clinical signs of VL. VL-positive tests were found in 26 (21.6%) of 120 apparently healthy dogs. The samples from 4 foxes and 1 cat were negative. Immunological findings indicated that 0-3-year-old children were a group that is most susceptible to VL in the study focus of this disease. The high proportion of dogs with VL may account for the rise in infant morbidity and suggests the epizootic strain in the focus of VL in the Papsky District.

[Monitoring delagil (chloroquine) efficacy against imported Plasmodium vivax strains].

The efficiency of P. vivax malaria treatment with delagil (chloroquine) was evaluated in 122 patients, including 82 cases in Moscow and the Moscow region. The origin of the cases was malaria endemic areas in Asia, Africa, the Pacific Region, South America, and Transcaucasia. Forty other cases were imported malaria cases (secondary to imported ones), detected in Moscow and the Moscow region. Standard treatment with delagil (2.5 g) resulted in clinical improvement during 3 days in the majority of cases. Initial signs of degradation of asexual stages of P. vivax--kernels of nucleus, refinement of cytoplasm and its vacuolization, aggregation of pigment in isolated instances, its pushing out from cytoplasm--were observed after 1-2 hours after administration of delagil. Thereafter, parasite degradation was increasing, and it disappeared within 48 hours. Disappearance of fever slowed down in a few cases. However, degradation of parasites occurred during the same period among the rest of cases. It can not be excluded that fever was determined by the pyrogenic effect of remnants of degraded parasites and by the products of destroyed infected erythrocytes. It is probable that the findings of gametocytes, not completely degraded after disappearance of asexual forms in conjunction with prolonged fever, could result in a wrong conclusion of drug resistance. Negative results of microscopy and nested PCR on the last day of treatment, as well as in the following 10 days and absence of complains during 45 days, suggest the absence of resistance to delagil in P. vivax strains imported from different regions of the world. It is also probable that the literature on P. vivax resistance to chloroquine is limited to sporadic cases.

[Human dirofilariasis: diagnosis and the pattern of pathogen-host relations].

Until recently, there has been no consensus of opinion as to that D.repens females can develop in the accidental host (man). The role of man is regarded as a biological dead end for Dirofilaria that are unable to develop the adult stage; human Dirofilaria migration is considered to be larval by the type of larva migrans. Studying these matters on a specific material of 140 cases of invasion by Dirofilaria that had been eliminated in patients in different seasons and the length of their bodies measured showed that the maximum number (51.4%) was mature females, 120 to 190 mm in size; 35.7 and 12.85% had a length of 70-115 and 40-65 mm, respectively, which corresponds to immature young and juvenile specimens. This suggests that Dirofilaria normally develop and achieve the adult stage in the accidental host. A correlation was found in the sizes of the body and the time of D. repens development. Thus, the human organism is not a biological dead end for Dirofllaria. The migration of adult Dirofilaria should be appraised as the imago-migrans phenomenon: As the particular diagnostic sign, it will aid a physician to establish a correct parasitiological diagnosis at the early stages of the disease. In recent years, there has been new evidence in the diagnosis of dirofilariasis that microfilaria have been detected in the skin tumor puncture specimen and blood of the patients. In this connection, it is conceivable that man may be an actual source of mosquito infection even in the presence and paucity of mature males and females.

[Prevalence of human dirofilariasis in Russia].

The nature of regional zoning of the prevalence of dirofilariasis in Russia was first established and a map reflecting the structure of an area with the identification of three zones (low, moderate, and stable transmission risks) was drawn up. In Russia, natural and climatic conditions are favorable for the development of transmitting mosquitoes and larvae of Dirofilaria to the invasion stage in the body of the transmitter to the south of the latitude of 58 degrees north in the European part and Western Siberia and to the south of the latitude of 50 degrees north in the Far East. The region of dirofilariasis covers 53 subjects of the Russian Federation, in 39 subjects (including 29 in the European part and 10 in the Asian part) of which 564 cases of dirofilariasis were notified in 1915-2008. 68.44% of dirofilariasis cases were registered in the endemic area in 11 subjects of the Russian Federation in the stable transmission risk zone while in the moderate and low transmission risk zones these amounted to 31.55% in 28 subjects. Information on the area of dirofilariasis is needed to estimate its incidence in man in different regions of Russia, which will assist in diagnosing this zoogenous transmissible helminthiasis.