Optimizing the Intensive Care Treatment of Severe and Complicated Plasmodium falciparum Malaria in Nonimmune Patients.

This study analyses the intensive care treatment of 48 patients admitted to the Intensive Care Unit (ICU) at the Infectious Diseases Clinical Hospital No. 2, Moscow, Russia, between 2007 and 2019, with a severe and complicated form of P. falciparum malaria (B50.8 ICD 10). Objective. The aim of this study was to improve the intensive care treatment for severe and complicated P. falciparum malaria. The treatment strategy implemented was aimed at preventing ischaemia-reperfusion injury to organs, as well as haemorrhagic complications. The ICU Case Management Protocol set up indications for transferring patients to the ICU which provide preventive (prior to the development of renal failure) application of extracorporeal hemocorrection methods (continuous venous-venous hemodiafiltration and plasmapheresis in a plasma exchange mode) and mechanical ventilation under a medically induced coma, given impaired consciousness as the initial symptom of patients. Results. Successful treatment outcome in a majority of the patients (93.8%), shorter ICU length of stay (6.67 ± 1.9 days as compared to 94 ± 1.6 before introduction of the protocol), a median parasite clearance time of 37.50 hours (95% CI 36.21-38.18), and a reduced mortality rate from 29.1% to 6.25% support the efficacy of the ICU protocol in managing severe and complicated P. falciparum malaria.

[Epidemiological and clinical aspects of diagnosis, treatment and prophylaxis of imported malaria cases in Russian Federation].

Actually one of the main tasks of health workers in the field of the tropical diseases prevention (malaria) is early detection of malaria imported cases and efficacious treatment. In order to prevent the re-establishment of local malaria transmission by Anopheles mosquitoes from imported malaria cases, and fatal cases of disease there is develop and implement the Case Management Protocol of malaria diagnosis and treatment (2014, 2019) based on long-term experience of epidemiologists and clinicians, taking into account recommendations of WHO (2013, 2015). In this article the main principles of diagnosis and treatment of different malaria species Plasmodium falciparumand Plasmodium vivax-malaria, prophylaxis measures of autochthonous cases from imported cases of the word endemic region are discussed.

Genetic characterization of Plasmodium vivax in the Kyrgyz Republic.

At the end of 2016, Kyrgyz Republic was certified by the World Health Organization as a malaria-free country, while only a decade ago this disease posed a serious health threat. The progress achieved by Kyrgyz Republic provides a unique example of tertian (Plasmodium vivax) malaria elimination. This success was based on an integrated approach, including measures for the treatment of infected people and disease prevention, vector control and the development of an effective national epidemiological surveillance system. Lower P. vivax msp-1, msp-3α, csp and dbpII genes polymorphism was revealed in Kyrgyz Republic in compare with that in Tajikistan. Molecular characterization of the causative agent found that P. vivax populations in Kyrgyz Republic was comprised by several lineages, highly divergent in the south-western and genetically homogeneous in the northern regions of Kyrgyz Republic, d. Such profile in the northern regions was compatible with several recent introductions rather than a long-term endemic circulation of the parasite. A low level of genetic variability suggested that the parasitic systems of tertian malaria, were not adapted, which, along with other factors, largely determined the possibility of malaria elimination in northern Kyrgyz Republic. Other determinants included environmental, social, and epidemiological factors that limited the spread of malaria. South-western Kyrgyz Republic, a region with a high level of interstate migration, requires considerable attention to prevent the spread of malaria.

Problems of clinical diagnosis and treatment of P. falciparum malaria in Russian Federation.

AIM: To study the causes of falciparum malaria deaths in Russian Federation and to optimize therapy for severe forms of the disease. MATERIALS AND METHODS: The analysis of falciparum malaria cases with deaths recorded in Russian Federation from 2013 to 2017 was conducted. The results of optimization of pathogenetic therapy of severe forms of falciparum malaria for the prevention of adverse outcomes in the intensive care unit of the Infectious Clinical Hospital №2 of Moscow in 44 patients with severe course are presented. Treatment, clinical laboratory and instrumental investigations were carried out in accordance with our intensive care protocol, which took into account the current WHO recommendations. RESULTS: From 2013 to 2017 there were nine deaths from falciparum malaria reported in patients from African countries (6) and India (3). In Russia, due to the lack of effective drugs of artemisinin group, quinine with tetracycline or doxycycline is used for etiotropic therapy of patients with complicated form of falciparum malaria. In the management of such patients, the basis for treatment was the prevention of ischemic, reperfusion injuries of organs and hemorrhagic complications. In the infectious clinical hospital №2 of Moscow, since 2007, the intensive care unit has developed and tested a protocol for intensive therapy in patients with severe and complicated forms of falciparum malaria, including preventive methods of extracorporeal hemocorrection with prolonged veno-venous hemodiafiltration therapy and plasmapheresis, as a result of which the mortality rate decreased from 84 to 6.8. CONCLUSION: The country's lack of anti-malarial drugs, the insufficient awareness of the population about the risk of infection and measures to prevent malaria, late referral of cases for medical care and errors of clinical diagnosis and treatment annually lead to fatal outcomes. In such situation, the experience of optimizing the treatment of severe falciparum malaria is particularly useful, allowing decreasing the mortality.

[(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.

[(THE IMPACT OF MIGRATION PROCESSES ON- BIOSAFETY AND HUMAN HEALTH)].

Infectious diseases are one of the serious threats to biosafety in modern society In recent years, there have been con- siderably increased international migrations: tourism and pilgrimage; labor migration flows; migration of refugees and settlers in times of armed conflicts, household migrations because of family ties and traditions. Since the number of Rus- sian tourists and migrants from endemic countries remains high, these contingents should receive special attention in the malaria epidemiological surveillance system. The paper discusses the risks of possible consequences of population migra- tions and prevention measures.

[(INTRODUCTION OF RESEARCH RESULTS INTO THE TRAINING OF PHYSICIANS IN THE SPECIALTY OF PARASITOLOGY)].

The paper presents the results of theoretical and practical studies into parasitology, which were conducted at the E.I.Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases and then used for the training of specialists with higher medical education at the Department of Tropical Medicine and Parasitic Diseases, I.M.Sechenov First Moscow State Medical University. The need to develop professional skills is related to the increasing learning require- ments due to socioeconomic conditions and the epidemiological situation in the country.

[(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.

[MALARIA IMPORTATION BY RUSSIA'S CITIZENS AND FOREIGNERS, INTO THE CITIES AND TOWNS OF THE RUSSIAN FEDERATION].

A total of 436 malaria cases, including 12 from the CIS countries and 424 from far foreign countries (of Africa and Central and South-East Asia), were imported into the Russian Federation in 2010-2014. Most (96.6%) cases were notified in the urban areas of 52 administrative subjects of Russia. The largest number of the imported cases were seasonal workers (39.2%), tourists (31.3%), students and foreign postgraduate students (19.5%), and ship or aircraft crews (10%). During a short malaria transmission season (June to August), there were 150 cases of different types, out of them there were only 63 cases of tertian malaria (its pathogen is Plasmodium vivax, to which malaria mosquitoes of Russia's fauna are susceptible). The relatively small number of infection sources in the short transmission (June to August) season of malaria, its importation into low-susceptibility large towns, and a small proportion of imported vivax malaria cases substantially reduce the risk of malaria in the highrisk areas of the country.

SCIENTIFIC AND PRACTICAL STUDIES OF MALARIA IN THE CIS COUNTRIES AND GEORGIA.

The paper presents the scientific studies of malaria pathogens and vectors, which have been specially conducted in the endemic areas of the CIS countries and Georgia for use in an epidemiological surveillance system. The main ones investigate the structure of malaria foci and the level of G-6-PD deficiency among residents, determine the malariogenic potential. of the territory and the risk of infection in the population, and specify the taxonomy, systematics, and spread of major malaria vectors in .the countries ofWHO European Region. In addition, the time and magnitude of manifestations of long-term post-incubation tertian malaria were established; th6 susceptibility of P.vivax to antimalarials and the levels of resistance and irritability of malaria vectors to insecticides were studied. The experience in using a geographic information system for the epidemiological surveillance of malaria is given.

[Spread of tropical malaria in the Republic of Tajikistan (1994-2008)].

Tropical malaria occurred in the Republic of Tajikistan in 1994 after 40-year absence and spread in 28 regions of Tajikistan and in 3 cities (Dushanbe, Kulyab, and Kurgan-Tyube), peaking in 2000 (831 cases). A total of 3585 cases of tropical malaria were notified in 602 foci during a 15-year period. Migrants imported the pathogenic agent by the route of Pakistan-Afghanistan-Tajikistan during armed conflicts and in trading activities continually.The emergence of Asian Plasmodium falciparum phenotypes was accompanied by the clinical complications of the disease: the high percentage of moderate and severe forms of the disease was observed in preschool children in the absence of fatal outcomes. The rising incidence of malaria was associated with not only with the intensive import of the infection and the flight of infected malaria mosquitoes, but also with the active examination of the population during homestead rounds and with the timely laboratory diagnosis of malaria pathogens. The long-term goal antimalarial measures in the Republic of Tajikistan in 2009 resulted in the pause in the local transmission of tropical malaria, which meant its elimination in the country.

[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.

[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.

[The current malaria situation in the CIS countries (2011-2012)].

In the last 3 years, the malaria situation has considerably improved in the CIS countries: Three CIS countries, such as Turkmenistan, Armenia, and Kazakhstan, received the malaria-free status (in 2010, 2011, and 2012, respectively) confirmed by the WHO certificate; Azerbaijan, Kyrgyz Republic, Uzbekistan, and Tajikistan are in the elimination period. Despite the continuing intensive migration of CIS citizens to Russia, its malaria situation has been favorable, which is associated with the significant reduction of imported infection cases among migrants.

[The specific features of the epidemiology of tertian (Plasmodium vivax) malaria in the Republic of Tajikistan].

The specific features of the functioning of parasitic systems of tertian malaria were found in the elimination period when the number of foci and patients were drastically reduced. Despite the sporadic cases of tertian malaria, in 2009-2012 each of the 9 areas of the Kurgan Tyubin zone, Khatlon Region notified 12 of the 43 active foci with single manifestations of malaria after a long incubation period in the following spring or March-April a year later. The results of these investigations should be borne in mind when planning and implementing antimalarial measures.