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Mamatova Ranokhon Najmiddinovna, Head of the Emerging and Reemerging Viral Infections Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan E-mail: m.ranokhon@gmail.com
THE URGENCY OF THE PROBLEM OF EMERGING AND RE-EMERGING VIRAL INFECTIONS, STUDY IN UZBEKISTAN
Abstract. Uzbekistan is an area with varied terrain, variety and large number of blood sucking vectors (mosquitoes, ticks, black flies, etc.), and their vertebrate hosts, mammals and birds, which may serve as reservoirs and vectors and viral pathogens of dangerous, new and reemerging viral infections. WNF infection is either asymptomatic (about 80% of infected people) or can lead to the development ofWest Nile fever or severe West Nile disease. Over the past five years of research on the problem of arbovirus infections in our country, scientists - virologists have identified the circulation of the WNF virus in Uzbekistan; found antibodies to the virus in human serum, identified the virus antigen in mosquitoes, ticks and mites, isolated strains of the WNF virus from birds, and patients with meningitis and meningo-encephalitis. The research Institute of Virology plans to conduct molecular genetic studies of isolated strains in order to establish the genotypes of the pathogen circulating in the country.
Keywords: WNF, natural foci, arbovirus infections, carriers, extremely, dangerous infections, morbidity.
Today the world is in the position where the epidemics of 51 million people dying each year in the world. Considered
again spread uncontrollably across the globe, but this time at an unprecedented rate - as a result of the globalization of modern life. Watch and ward is the price of survival in the fight of humans against pathogenic microorganisms [12].
On the threshold of XXI century, the humankind has come to realize the importance of global objectives - security of people's lives. These tasks, in a number of security issues came to the fore among the most important priorities of countries and the international community. The most acute need to address these problems emerged in connection with the threats and challenges that have arisen in the demographic, environmental, political and social spheres of human activity.
Among them - the threat of new and emerging infectious diseases and epidemics, the consequences of which could be catastrophic for humanity. This tragic threat to modern civilization was quite unexpected, since modern medicine, although it assumed the possibility of new infections as a result of the ongoing evolutionary processes and microbial mutations, but not enough reliable assessed the extent ofthe danger. It seemed that everything will be accomplished with "traditional" dangerous infections that are well studied and largely defeated. The emergence of new infections was considered unlikely, not as dangerous, in any case do not threaten with fatal consequences [6].
The only way to prepare for infectious crises that inevitably occur in the XXI century - is to prepare specialists who are able to identify a new disease, assess the epidemiological situation and to develop preventive measures and new drugs.
According to the World Health Organization (WHO), infectious parasitic diseases caused the death of 16 million out
problem lies in the fact that, in spite of the modern sanitation capabilities of medical science, and seemingly streamlined health system over the past decade new and still unrevealed, previously unknown dangerous infections began to emerge.
New infections (Emerging Infections, synonym emerging pathogens.) - the common name of infectious diseases that have been identified and classified taxonomically recently. In the last quarter of the twentieth century, more than 30 such infections been identified, many of which can cause dangerous epidemics. Among them HIV, Ebola virus, hantavirus pulmonary syndrome, hemorrhagic fever with renal syndrome and other viral fevers, Campylobacteriosis, transmissible spongiform encephalopathy, Legionnaires' disease, Lyme disease. Some new infections are presented as "new" diseases of people, for example, HIV infection is probably formed as a human disease in the second half of the twentieth century. Other diseases, such as viral hemorrhagic fever, they are existed for centuries and have been discovered only recently due to changes in environmental conditions, which led to an increase in the risk of infection of humans. Remerged infections - it is some "old" diseases such as tuberculosis and syphilis, which its wave comes again after the change of conditions and the host state, agent and environment factors [17].
For the first time in the early 90's XX cen. J. Lederberg et al. (1992) proposed the term defining them as the disease that became known in the past two decades or significance of which may increase in the near future. It is known that by far described only 15% of microbes and 5% of viruses that exist on Earth [12]. It is not surprising that almost every year
identified a new disease and their pathogens. Since many new infections are extremely dangerous, often fatal completed and fraught with epidemics, the problem of dealing with them, along with other serious global problems is a priority at the international and national levels.
By the middle of the XX century it became apparent increase in the role of viruses in human infectious diseases. Of particular relevance got the problem of so-called new types of recurring infections, as Infectious diseases not only has not lost its socio-economic importance, but also requires more attention by national and international health care systems due to the weakening position ofmedicine in the fight to reduce morbidity and mortality, especially against viral diseases with natural foci.
Among these infections the arbovirus infections - infections transmitted by arthropods occupy a key place. At least 100 of the known natural focal viruses, which include mosquito (mosquito), fever, cause disease in humans. This is an epidemic of dengue fever, O' Nyong-Nyong, equine encephalomyelitis, Japanese, tick-borne and Murray Valley encephalitis, Rift Valley fever, a mosquito, Karelian, West Nile, and others.
Ecological interactions may be complex, a number of factors often interact together or in any sequence one after the other. However, they are the most common of the identified factors that contributes to emerge of one or the other infectious disease [10]. Especially they are often noted when large number of deaths accompanied with the outbreaks of previously unrecognized infections originating from the terrestrial reservoir. Environmental factors commonly accelerate the emergence of infectious diseases by establishing contact humans with the natural reservoir or with the infection host, the infection host could be unknown until the outbreak [21].
This issue is fully relevant for our country and its landscape diversity, the active economic development of uninhabited areas, the influx of population into these areas.
If we consider that through Uzbekistan lies two bird migration route - from East Africa and Indochina to the north of Siberia and back, as well as all the increasing migration of the population, it will be clear to the need for further systematic survey of the territory of the Republic in respect of the natural foci of arboviruses.
It is believed that arboviruses have enormous pathogenic potential. However, the actual medical importance to humans, tend to have only those that were isolated in terms of epidemic outbreaks and are the cause of permanently recorded disease [12].
Uzbekistan is an area with varied terrain, variety and large number of blood sucking vectors (mosquitoes, ticks, black flies, etc.), and their vertebrate hosts, mammals and birds, which may serve as reservoirs and vectors and viral pathogens of dangerous infections. All this contributes to the formation of natural foci of viral diseases. To date, Uzbekistan
detected circulation of more than 20 arboviruses, some of them causes severe disease with high mortality. An example is the Crimean-Congo hemorrhagic fever, the natural foci of which are revealed in almost all landscape zones of regions except for mountainous areas.
If we consider that in the neighboring countries bordering on the territory of the Republic of Uzbekistan on the climatic and geographical conditions, revealed the circulation of many other pathogens of viral infections, there is a possibility registration of these viruses on the territory of Uzbekistan.
Due to the fact that northern - west part of the country (the Republic of Karakalpakstan, Khorezm region) lies on the migration route of birds from East Africa to Kazakhstan and western Siberia; and from Ceylon, India and Afghanistan through the south - east part of the Republic(Surkhandarya and Kashkadarya regions) to the Eastern Siberia, there is a high possibility of occurrence of infections which causes severe diseases in humans with a high mortality rate like Japanese encephalitis virus, Dengue fever, WNF, Rift Valley, Kias-sanur forest disease, yellow fever, hemorrhagic fever with renal syndrome, Omsk hemorrhagic fever, tick-borne encephalitis and others in the territory of the Republic.
Active moving of large number of people across countries and continents during possibilities of air fleet poses a risk in the sense of circulation of such exotic highly contagious hemorrhagic fever for us as Lassa, Marburg, Ebola, Argentinean and Bolivian fevers.
West Nile virus was first isolated from a woman in the West Nile district of Uganda in 1937. In 1953, it was diagnosed in birds (crows and Columbiformes) in the region of the Nile delta. Until 1997, WNV was not considered as pathogenic for birds. At that time in Israel, the death of different species of birds, which had signs of encephalitis and paralysis, resulted in a more virulent strain. Human infections caused by WNV have been registered in many countries of the world for more than 50 years.
In 1999, the WNF virus circulating in Tunisia and Israel was imported to New York, where it resulted in a major and dramatic outbreak, which in the following years spread to the mainland of the United States of America (USA). Outbreak of WNF in the United States (1999-2010 y.) Has shown that the import and fixation of vector-borne pathogens outside their current habitats represent a serious danger to the world.
The largest outbreaks occurred in Israel, Greece, Romania, Russia and the United States. Major migratory pathways of birds are being laid through the outbreak sites. The WNF virus was originally distributed in Africa, in some parts of Europe, the Middle East, Western Asia and in Australia. Since its introduction in 1999, the U.S. virus has spread and is now widely entrenched in the territory from Canada to Venezuela [9].
Human infection is most often caused by bites of infected mosquitoes. Mosquitoes are infected during feeding with the blood of infected birds - in their blood the virus circulates for several days. Eventually the virus gets into the salivary glands of the mosquito. During its subsequent feeding with blood (during mosquito bites) the virus can enter the body of humans and animals, where it can multiply and lead to disease.
The virus can also be transmitted by contact with other infected animals, with their blood or other tissues.
A very small proportion of human infections occur during organ transplant, blood transfusion and breastfeeding. One case of transplacental transmission of the WNF virus (from mother to child) has been registered.
To date, there are no documented cases of transmission of WNV virus from person to person in safe contacts.
WNF infection is either asymptomatic (about 80% of infected people) or can lead to the development of West Nile fever or severe Western Nile disease.
Approximately 20% of infected people develop West Nile fever. Its symptoms include fever, headache, fatigue and body aches, nausea, vomiting and sometimes a skin rash (on the trunk) and swollen lymph nodes.
The symptoms of severe disease (also called neuroinva-sive disease), such as encephalitis or West Nile meningitis or West Nile poliomyelitis, include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness and paralysis. According to estimates, the most severe form of the disease occurs in approximately in one out of 150 people infected with West Nile virus. Serious illness can occur at any age, however people over age 50 and some people with weakened immune systems (for example, transplant patients) are at the highest risk of developing severe disease as a result of infection with WNV virus.
The incubation period is usually 3 to 14 days. The virus contains a single-stranded, unsegmented RNA, its replication occurs in the cytoplasm of infected cells.
Since the discovery of the WNF virus for several decades, there has been a predominantly sporadic incidence of human morbidity within the tropical and subtropical endemic foci of Africa [16; 15] and Asia [24], although in some cases there have been large outbreaks. Thus, in 1974, there was an outbreak of West Nile fever in South Africa, where about 3000 cases were reported [27].
The situation has changed radically since 1996, when in Bucharest and surrounding areas, that is, outside the tropical and subtropical zone there was a large outbreak of West Nile fever. 835 patients with CNS lesions were hospitalized, laboratory confirmed 393 cases, of which 7 (4.3%) Were deadly. The virus was isolated from the cerebrospinal fluid by PCR [18]. Antibodies to the WNV virus among the in-
habitants of Bucharest were found in 4.1% of cases, and in other regions-in 0.9%.
Outbreaks of West Nile infection were also observed in other European countries: in 1997 in the Czech Republic in 1998 in Italy, in 1999-2000 in Israel, in 2000 and in 2004 - in France [22; 15; 28; 30].
In recent years, the WNF virus has become increasingly aggressive and causes disease even in regions where it has not been known before. The epidemic outbreak caused by the WNF virus occurred in New York in 1999, for the first time in the American continent. The disease originated at the end ofJuly - September with a peak in the second half of August in New York and its environs. There were 62 cases reported, 7 ofwhich were fatal [30].
By 2002, WNF virus has spread almost throughout the United States, while described 4156 human cases, including 286 deaths. In 2003, the US has already been registered 9862 cases of the disease, of which 264 - lethal in Canada - 1335 cases, including 10 deaths.
Every year in the Americas, cases of the western Nile infection among humans are identified. In 2006, 4269 cases were identified, of which 177 were fatal, and in 2007, 3576 cases, 115 were fatal [30]. In 2003-2004. The circulation of the WNF virus in Cuba was established [14].
Epidemic outbreaks caused by the WNV virus have also occurred in Russia. In July-September 1999 in the Russian Federation there was a sharp worsening of epidemiological situation on incidence of viral fevers, complicated meningitis and meningoencephalitis.
Outbreaks of disease caused by WNV virus, accompanied by severe clinical course, and even death. Laboratory tests in 190 cases in Volgograd, 89 - in Astrakhan areas and 31 in Krasnodar region identified antibodies to WNV, i.e. it confirmed diagnosis of West Nile infection [23].
It should be noted that the outbreak in Romania, the USA and Russia, caused by WNF virus, characterized by a high proportion of meningitis and meningoencephalitis (over 50%), high mortality (about 10%). Patients with Western Nile infection in endemic areas of Russia are identified every year. In addition, the WNF virus began to be discovered in those areas of Russia, where it had not previously met [2]. For example, in 2004, in Novosibirsk region, three laboratory-confirmed cases of infection caused by the WNV virus in humans were registered for the first time [11].
During an outbreak of WNF in 1996 in Romania, the main carrier of infection in anthropogenic biocenoses was Culex pipiens [26].
In the US in 1999, when WNF virus was first detected in the transmission cycle involved only a few species of mosquitoes, common in North America: Aedes vexans, Culex
pipiens, Culex restuans. However, after 4 years the virus has already been detected in 43 different types of genera Aedes mosquito, Anopheles, Coquillettidia, Culex, Culiseta, Deinoceri-tes, Ochlerotatus, Orthopodomyia, Psorophora, Uranotaenia [13]. Infection with such a large number of different species of mosquitoes most likely was one of the decisive factors in the spread of the WNF virus in the United States. It is assumed that in America infection with WNV in birds takes place with the participation of C. pipiens and C. restuans, among people - C. salinarius, among horses - mosquito genera Aedes and Ochlerotatus [29].
The WNF virus also adapts to the local species of argasi-dae and ixodidae mites involved in the preservation of the viral population in the inter-episodic period [1]. Representatives of a huge number of species ofvertebrates, from amphibians and reptiles to birds and mammals can be infected with the virus WNV, but not all of them achieve the level of viremia, sufficient to infect the feeding on them Mosquitoes. In particular, humans are not a source of mosquito infection, which, like some mammals, does not play a significant role in maintaining the natural foci of the WNF virus [7]. Apparently raising levels of viraemia is insufficient to infect mosquitoes [3]. The main reservoir of the WNF virus is considered to be birds, including migratory birds, which can carry out the introduction of the virus into non-endemic areas, as well as birds of aquatic and near-water ecological complexes [3; 5; 25].
WNF virus was isolated in different geographical areas, from the rock-pigeon, crow, barred warbler, glossy ibis and a rook, blackbird and nuthatch. The commensal foci WNF virus main hosts are Raven - crows, rooks, Jay et al. [7; 30]. In an epidemic outbreak of West Nile infection in Romania, 41% of domestic and 7% of wild birds were found to have specific antibodies to the virus [26]. France had isolated the virus strains ofWNF from the magpies and Sparrow [20]. The outbreak caused by WNF virus in the United States in 1999, has not affected only wild birds, but also some birds of Bronsk and Kvinsk zoos (Chilean flamingos, cormorants, bald eagles, magpies, ducks, pheasants, white owls, and others) [24].
As mentioned above, in recent years there has been an increase in the number of diseases related to the pathogen virus WNF, the weighting of the course and the involvement of new regions, previously "not familiar" with this disease.
Most researchers attribute this to the process of "emerging infections", when in a certain area of the disease reappear, which was not in the last 20 years, or when the incidence of common infections is increasing as a result of long-term changes in the epidemiological process. It is believed that the main cause of these phenomena is complex natural and socio-economic factors leading to an increase in the number of populations of vectors of disease - mosquitoes (irrigation activities, heavy rains followed by flooding, increased average temperature, the formation of the ecological niches that promote a mass feeding mosquitoes, etc.) [18].
Global warming with a predominance of warm and wet weather leads to an increase in the number and distribution of disease vectors [27, 8].
In order to control the incidence of arbovirus infections is necessary to conduct the complex epidemiological, entomological and preventive measures, including monitoring of the number of vector populations, determining the level of infection, serological monitoring of animals - feeders and inhabitants of endemic areas, an adequate level of training and literacy of medical professionals in relation to the WNF infection.
Over the past five years of research on the problem of arbovirus infections in our country, scientists - virologists have identified the circulation of the WNF virus in Uzbekistan; found antibodies to the virus in human serum, identified the virus antigen in mosquitoes, gnats and mites, isolated strains of the WNF virus from birds, and patients with meningitis and meningoencephalitis. The research Institute of Virology plans to conduct molecular genetic studies of isolated strains in order to establish the genotypes of the pathogen circulating in the country.
The recent outbreaks of WNF virus in Romania, Russia, America, Spain and other countries, accompanied by severe course of the disease, a high proportion of meningitis and meningoencephalitis, CNS lesions and high mortality, especially in the group of patients with meningoencephalitis.
In order to prevent human infection with WNV virus necessary to carry out non-specific prevention: treatment of breeding sites of mosquitoes (reservoirs, basements of residential buildings) and personal protection from mosquito attacks while visiting natural arrays, to carry out the health education work among the population.
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