Автор(ы): Алуа О. Омарова 1*, http://orcid.org/0000-0002-2087-3824 Камшат М. Тусупова 2, http://orcid.org/0000-0001-8005-0371 Ронни Берндтссон 2, http://orcid.org/0000-0003-1473-0138 Марат Г. Калишев 1, http://orcid.org/0000-0002-6693-8646 1 Карагандинский государственный медицинский университет, Кафедра гигиены питания, общей гигиены и экологии, г. Караганда, Республика Казахстан; 2 Лундский университет, Кафедра инженерии водных ресурсов и Центр Ближневосточных исследований, г. Лунд, Швеция.
UDC 613.31/.34 + 616.9
БРЕМЯ БОЛЕЗНЕЙ, СВЯЗАННЫХ С ВОДОЙ,
В РАЗВИВАЮЩИХСЯ СТРАНАХ. ОБЗОР ЛИТЕРАТУРЫ
1 Карагандинский государственный медицинский университет, Кафедра гигиены питания, общей гигиены и экологии, г. Караганда, Республика Казахстан;
2 Лундский университет, Кафедра инженерии водных ресурсов и Центр Ближневосточных исследований, г. Лунд, Швеция.
Введение. Качество питьевой воды является серьезной проблемой развивающихся стран, где половина населения подвергаются одному или нескольким заболеваниям, связанным с водоснабжением и санитарией.
Целью был обзор литературных источников, посвященных изучению разрушительного бремени болезней, связанных с водой, в развивающихся странах.
Методы. Были проанализированы публикации результатов исследований зарубежных и отечественных исследователей. Поиск литературных источников проводился в базах данных PubMed, Scopus, GoogleScholar и eLibrary. Было найдено 166 источников, из которых 77 источников были отобраны в качестве аналитического материала статьи. Глубина исследования c 1972 по 2016 годы.
Критерии включения публикаций в обзор: публикации на русском и английском языках, находящиеся в открытом полнотекстовом доступе и несущие статистически выверенные выводы.
Критерии исключения: резюме докладов, газетные публикации, личные сообщения.
Результаты. Анализ источников показал, что желудочно-кишечные инфекции, кишечные гельминтозы, протозойные инфекции и риск воздействия на организм канцерогенных и мутагенных соединений во многом связаны с потреблением недоброкачественной питьевой воды.
Заключение. Качественное водоснабжение существенно влияет на сокращение бремени болезней, связанных с водой, повышение уровня и качества жизни населения. Значительное число случаев заболевания можно предотвратить, особенно в развивающихся странах, с помощью лучшего доступа к безопасному водоснабжению, адекватным санитарно-техническим средствам и лучшей гигиенической практике.
Ключевые слова: питьевая вода, диарея, протозойные инфекции, кишечные гельминтозы, химические вещества.
BURDEN OF WATER-RELATED DISEASES IN DEVELOPING COUNTRIES. REVIEW
1 Karaganda State Medical University,Department of Food Hygiene, General Hygiene, and Ecology, Karaganda, Kazakhstan;
2Lund University, Department of Water Resources Engineering & Center for Middle Eastern Studies, Lund, Sweden.
Introduction. The quality of drinking water is a serious problem in developing countries, where half the population is exposed to one or more diseases associated with water and sanitation.
The objective was a review of literature that deals with study of devastating burden of water-related diseases in developing countries.
Methods. The publications of findings of both foreign and domestic researchers were analyzed. Literature sources were searched in the PubMed, Scopus, GoogleScholar и eLibrary databases. Out of 166 literature sources, 77 were selected as the analytical material of the article. The depth of the search was from 1972 to 2016.
Criteria for the inclusion of publications in this review are the following: publications in Russian and English languages that are in open full-text access and bear statistically verified conclusions.
Exclusion criteria are as follows: summary reports, newspaper articles and personal messages.
Results. Review sources revealed that gastrointestinal diseases, intestinal helminth infestations and protozoan infections as well as the risk of carcinogenic and mutagenic effects on the human body are to a great extent attributed to poor-quality water consumption.
Conclusion. Based on the above, high-quality water supply exerts a considerable impact on reduction of water-related diseases and rise in the living standards of population. A significant number of cases can be prevented with a better access to safe water supply, adequate sanitation facilities and better hygienic practices.
Key words: drinking water, diarrhea, protozoan infections, intestinal helminth infections, chemicals.
СУМЕН БАЙЛАНЫСТЫ СЫРҚАТТАРДЫҢДАМУШЫЕЛДЕРДЕГІАУЫРТПАЛЫҒЫ. ӘДЕБИЕТКЕШОЛУ
1 Қарағанды мемлекеттік медицина университеті, Тамақтану гигиенасы, жалпы гигиена және экология кафедрасы, Қарағанды қ., Қазақстан Республикасы;
2 Лунд университеті, Су ресурстар инженериясы кафедрасы және Таяу Шығыс зерттеулері отралығы, Лунд қ., Швеция.
Кіріспе. Ауыз су сапасы дамушы елдердің аса маңызды мәселесі болып табылады, өйткені тұрғындардың жартысы сумен қамтамасыздандырумен және санитариямен байланысты сырқаттардың біреуіне немесе бірнешеуіне шалдыққан.
Мақсатысумен байланысты сырқаттардың дамушы елдердегі талқандаушы ауыртпалығын меңгеруге арналған әдебиет көздерін шолу.
Әдістері. Шетелдік және отандық зерттеушілер жұмыстары нәтижелерінің жарияланымдары талданды. Әдебиет көздерін іздеу PubMed, Scopus, GoogleScholar және eLibrary мәліметтер базасында жүргізілді. Мақаланың талдау материалы ретінде 166 әдебиеттен 77 іріктелді. Зерттеу тереңдігі 1972 жылдан 2016 жылға дейін.
Шолуға жарияланымды енгізу критерийлері: ашық жағдайда толық мәтіні қол жетімді және статистикалық нақтыланған нәтижелері бар орыс және ағылшын тілдеріндегі жарияланымдар.
Алып тастау критерийлері: баяндамалардың тұжырымдары, газеттегі жарияланымдар, жеке хабарлар.
Нәтижелері. Әдебиет талдау көрсеткендей, асқазан-ішек инфекциялары, ішек гельминтоздары, протозойлы инфекциялар және ағзаға канцерогенді және мутагенді қосылыстардың әсер ету қаупі, көбінесе, сапасы нашар ауыз суды қолданумен байланысты.
Қорытынды. Сапалы ауыз сумен қамтамасыздандыру сумен байланысты сыртқаттар ауырпалығын қысқартуға, тұрғындардың өмір деңгейі мен сапасын көтеруге елеулі әсер етеді. Сырқат жағдайларының бірталайын, әсіресе дамушы елдерде, қауіпсіз сумен қамтамасыздандыруға жақсы қолжетімділік, адекватты санитарлық-техникалық құралдар және жақсы гигиеналық тәжірибе арқылы алдын алуға болады.
Негізгі сөздер: ауыз су, диарея, протозойлы инфекциялар, ішек гельминтоздары, химиялық заттар
ОмароваА.О., ТусуповаК.М., БерндтссонР., Калишев М.Г.Бремя болезней, связанных с водой, в развивающихся странах. Обзор литературы / / Наука и Здравоохранение. 2017. №3. С. 95-109.
Omarova A.O., Tussupova K.M., Berndtsson R., Kalishev M.G. Burden of water-related diseases in developing countries. Review. Nauka i Zdravookhranenie [Science & Healthcare]. 2017, 3, pp. 95-109.
ОмароваА.О., ТусуповаК.М., БерндтссонР., Калишев М.Г.Сумен байланысты сырқаттардың дамушы елдердегі ауыртпалығы. Әдебиетке шолу / / Ғылым және Денсаулық сақтау. 2017. № 3. Б. 95-109.
The quality of drinking water is a serious problem in developing countries, where half the population is exposed to one or more diseases associated with water and sanitation [1,7,36,60]. In developing countries about 400 children per hour die from diseases that are transmitted by water . The sources of drinking water pollution are agricultural chemicals, inappropriate operation of sewerage system, improper storage and disposal of domestic waste, spillage of industrial materials and natural substances [4,36].
The objective was a review of literature that deals with study of devastating burden of water-related diseases in developing countries.
The publications of findings of both foreign and domestic researchers were analyzed. Literature sources were searched in the PubMed, Scopus, GoogleScholar и eLibrary databases. Out of 166 literature sources, 77 were selected as the analytical material of the article. The depth of the search was from 1972 to 2016.
Criteria for the inclusion of publications in this review are the following: publications in Russian and English languages that are in open full-text access and bear statistically verified conclusions.
Exclusion criteria are as follows: summary reports, newspaper articles and personal messages.
- 1. Classification of Water-Related Diseases. Water-RelatedInfectiousDiseases.
All over the world about 2.4 million deaths (4.2% of all deaths)  could have been prevented with a good and reliable sanitation and drinking water. Diarrhea is the cause of 3.3 million deaths per year, basically among children under five (and nearly a billion cases of diarrhea each year); about one-third of people in developing countries are infected with intestinal worms; 6-9 million people suffer from blindness after trachoma; 200 million people are infected with schistosoma .
Frequent bouts of diarrhea and intestinal parasitosis are important causes of malnutrition, which makes children more susceptible to other diseases. For example, when malnourished children recover from a diarrhea episode, they are susceptible to pneumonia. 26% of all cases of childhood pneumonia can be associated with susceptibility induced by diarrhea . Similarly, 7% of the HSW-associated disease burden is directly related to malnutrition, and 29% accounts for diseases that are malnutrition consequences [20,57].
Lack of access to safe drinking water is also associated with several non-diarrheal diseases . Chronic or acute influence of many organic and inorganic chemicals adversely affects the consumers health. The consequences vary from acute nausea, vomiting or skin rash to cancer and fetal abnormalities [8,11,42].
The first attempt to simplify the connection between water and public health in developing countries was made by David Bradley [27,72], who developed a classification of water-related diseases:
- Waterborne diseases occur when people ingest water contaminated with faecal matter. Cholera and typhoid fever are classic examples of the waterborne diseases. It takes only a few microorganisms with high infectivity to cause severe diarrhea. Shigellosis, hepatitis A, amoebic dysentery and other gastrointestinal diseases can also be transmitted by water.
- Water-washed diseases are due to the lack of quality water for washing, bathing and cleaning. Pathogenic organisms are transmitted from human to human or upon contact with contaminated surfaces. Under such conditions, there can be skin and eye infections, as well as diarrheal diseases. Bacteria, viruses, protozoa and helminths are transmitted through water.
- Water-based diseases are caused by parasites, particularly helminths of various kinds, which spend a part of their life cycle in the different hosts. They spend one cycle of development in water shellfish, the other, as adult parasites, in the body of the host – an animal or a human. Since a favorite inhabitation for parasites is stagnant surface water, e.g. reservoirs, human activities significantly affect the occurrence of the diseases, such as dracunculiasis and schistosomiasis.
- Water-related insect vector routes diseases are caused by stings of insects that breed in water. Transmitting insects, such as mosquitoes, carry malaria, chikungunya and other diseases.
However, as noted by a number of authors [33,41,47,62], there are some shortcomings in the classification, as follows:
- The classification has no chemically-mediated diseases, such as poisoning with arsenic and fluoride, which have a serious impact in some parts of the world [33,47].
- The classification does not consider that the need to collect and transport water affects the health of many people in the world. For example, a lot of children and women in developing countries have to carry heavy water containers for long distances every day. There have been no systematic studies on how this affects the locomotor apparatus .
- Long walks to collect water may also increase the spread of some other communicable diseases .
- Unpleasant tastes or odors of delivered water (e.g., arising from chlorination or iron content in the ground water), which is microbiologically safe, can serve as a deterrent to the use of safe sources, and therefore expose the users to the health risks associated with unprotected water sources .
According to the World Health Organization [6,28], water contains 13 thousand potentially toxic elements. Over the past few decades, the problem of contamination of water sources, such as lakes, rivers and ground water, has become very acute . Harmful substances can accumulate in the body causing a variety of diseases up to malignant neoplasms [6,28,44,74,75,76].
Osman A. Dar and Mishal S. Khan  propose to amend the Bradleys classification by adding neoplasms caused by high concentrations of arsenic in drinking water and fluorosis caused by intake of water with a toxic dose of fluoride into the category "waterborne diseases".
Access to clean water is essential for the individual and public health, especially in reducing the burden of infectious gastrointestinal diseases [2,52].
According to the WHO , infectious diseases caused by pathogenic bacteria, viruses and protozoa or parasites are the most widespread, and they make a principal risk factor for the public health associated with drinking water. Ten major diseases transmitted through water are responsible for more than 28 billion cases of disease in developing countries each year. Gastrointestinal diseases among them have the highest mortality rates .
In addition, the main reason of growth retardation for millions of children in developing countries is poor nutrition as a result of frequent bouts of diarrhea. Repeated bouts of diarrhea inhibit the bodys ability to assimilate food for a longer period than the actual duration of diarrhea. Thus, children who had diarrheal diseases are at risk of stunting from malnutrition .
One of the studies of diarrheal diseases in rural areas of Bolivia reports that only 30% of respondents associate diarrhea with dirty water, and that many people view diarrhea as a normal phenomenon at an early age . This lack of knowledge about the possible cause-and-effect relationships and casual views of diarrhea in children are common in developing countries .
On the average, the minimum infectious dose (the smallest amount of ingested pathogens required to cause a disease) for healthy adult varies widely depending on different kinds of microorganisms. This dose ranges from several organisms for Salmonella Typhi, several hundred organisms for Shigella Flexneri, several million cells for Salmonella Enterica and up to one hundred million cells for Vibrio Cholerae. The minimum infectious dose also varies depending on the age, state of health, nutrition and immunological status of the person .
Over a year diarrhea kills more small children than the so-called big three (HIV/AIDS, tuberculosis and malaria taken together) . The key to its control is hygiene, sanitation and water . 90% of all deaths from diarrhea diseases accrue to children under five, and 15 developing countries account for 73% of them .
Contamination of tap water remains a serious problem of health system in Turkey throughout the history of the countrys existence. After contamination of drinking water by sewage in the Turkish cities for 2005 – 2008, 17,000 people were hospitalized due to acute intestinal infections .
- 2. Water-Related Parasite Invasion.
Good sanitation can prevent not only endemic diarrhea but parasitic diseases transmitted through water by protozoa, intestinal helminth infestations, as well as many other globally important diseases .
In the period of infancy parasitic diseases may result in immune system imbalance . Helminthiases have an adverse effect on the nutritional status of infected individuals with subsequent impact on the growth process in young children and cause anemia, especially in pregnant women [49,68]. Helminthiases also reduce the effectiveness of some vaccines, e.g. against tuberculosis, HIV and malaria [6,50].
WHO expert judgment shows that helminth infections have the third highest number of patients in the world, and malaria is the fourth among the most important infectious and parasitic diseases: 1.4 billion and 600 million patients respectively. For comparison, the annual number of patients with influenza and other acute respiratory infections in the world is 395 million (the sixth place) . Based on the damage for human health, intestinal helminth infections are included in the four leading causes of all diseases and injuries [5,12].
Adult helminths live in the gastrointestinal tract where they reproduce sexually. Their eggs are ejected from the infected host with faeces, and in such a way they are passed to other people, mainly, when defecating in the open air. Replacement of the open defecation for a good sanitation can reduce this transmission path completely, but the majority of modern helminth control programmes is based on drug treatment, the intake of which must be periodically repeated in the absence of sanitation [17,39].
Up to 10% of population in developing countries is infected with helminths, a large percentage of which is caused by ascarid. Severe forms of ascariasis are responsible for 60,000 deaths per year, mostly in children . To a large extent, this is a disease of people exposed to raw wastewater or food products grown on it. Eighty-five thousand hectares in the Meskital valley in central Mexico is a classic example of using raw wastewater for irrigation of crops, which leads to a considerable increase in the incidence of diarrhea and ascariasis [18,29].
Worldwide, about 190 million people are infected with schistosomes, which can lead to chronic exhaustion, hematuria, dysplasia, urocyst diseases and colorectal cancer, as well as a significant malfunction in organs . Adult schistosomes live in the portal vein, where they pass their eggs into the environment through the urine (Schistosoma haematobium) or faeces (other human schistosomiasis). After completing a part of their life cycle in aquatic snails, where they reproduce asexually, cercariae are discharged into the water, where they come into contact and infect humans through the skin. Thus, measures to improve sanitation and water are essential to any long-term control and elimination of Schistosomiaisis .
Trachoma is an endemic disease in many poor countries of the world. It is due to a clamidiosis bacterium and is a leading cause of blindness in the world . Trachoma control is conducted mainly on the basis of antibiotics, despite the existence of a management strategy SAFE (surgery, antibiotics, face washing and environmental protection measures, namely the strengthening of sanitation) [30,54]. However, in recent times a cluster randomized trial in Ghana  found that the provision of toilets reduced a significant number of flies Musca Sorbens (a vector for trachoma) and decreased the incidence of trachoma by 30%, thus confirming the role of improved sanitation in the control of trachoma.
For nearly a hundred years, between the past century and 2004, around the world it has been reported 325 protozoal parasitic outbreaks transmitted by water, whereas during a much shorter period of time, between 2004 and 2010, there were 199 reports of such outbreaks. . Such essential difference in the number of reported outbreaks is caused by significant improvement in data reporting and establishment of surveillance systems in the developed countries. The highest prevalence of parasitic protozoa infections are known to occur in developing countries because of low sanitation and hygiene standards .
The etiologic agent in the reported outbreaks was Cryptosporidium spp. in 60.3% (120) of cases, Giardia lamblia in 35.1% (70) and other protozoa in 4.5% (9). Four outbreaks (2%) were caused by T. gondii, and three ones (1.5%) by C. cayetanensis. During two outbreaks (1%), Acanthamoeba was identified as the causative agent .
An overview of food-borne diseases and deaths made in the United States of America shows that 2.5 million diseases (7%) were caused by parasites (300,000 by Cryptosporidium parvum; 2,000,000 by Giardia lamblia; 225,000 by Toxoplasma and 52 by Trichinella spiralis) [53,70].
For 12 years, 39 documented outbreaks of waterborne cryptosporidiosis have occurred in the USA, Canada, UK, and Japan . Activities related to livestock-breeding, in particular, the spread of faecal, as well as deposition and wash-out from contaminated pastures, have been proposed as the cause of many of these outbreaks [43,66-67].
Developments in the molecular genetic analyze of water-borne protozoan parasites including the determination of the identity of species and subtypes will help to understand their contribution to the environmental pollution. Significant research in this area is ongoing, and several methods of genotyping have been designed for Cryptosporidium, Giardia, Microsporidia spp. and Toxoplasma [16,40,51,55,69].
Spores of Microsporidia are persistent in the environment and remain infectious from a few days to a few weeks outside the host [64-65,71]. Their small size (5±1 mm) makes them difficult to remove using conventional filtration methods. It is also feared that they may have improved resistance to chlorine disinfection [70,73].
Two toxoplasmosis outbreaks associated with the consumption of water contaminated by oocysts were well documented [21,26]. The first outbreak occurred in the British army in Panama. Epidemiological data showed that the most likely means of transmission had been contaminated brook water. The second outbreak occurred in British Columbia, Canada, in 1995: 110 acute infections, 55 cases of which were related to infection of non-pregnant women, were determined. Forty-two cases included pregnant women and eleven ones were associated with children [26,70].
The latest advances in immunology and molecular biology allowed more sensitive and specific rapid tests that could replace the existing methods .
Among 1377 refugees and asylum seekers arrived in Sweden, intestinal parasites were more often identified in refugees from Southeast Asia, Africa and Latin America (infection rates of 48%, 43% and 42% respectively) than in those who had come from the Eastern Europe (22%) and Middle East (32%) [22,31].
The need to provide pure water and basic sanitation to everyone is a priority for the environmental health in Latin America because of the high rates of diarrheal and other water-borne diseases .
In the estimation of specialists, the annual number of people falling ill with parasitic diseases in Russia exceeds 20 million and tends to increase [9,13]. Thus, according to the number of patients, parasitic diseases in Russia are second only to acute respiratory infections .
Investigations carried out in Medical Parasitology and Tropical Medicine named after E.I. Martsinovski  showed that water in open reservoirs near water intakes often contained lamblia cysts. This pathogen is also found in the tap water. Outbreaks of giardiasis associated with poor quality of tap water are regularly registered in the USA and other developed countries where the necessary investigations are conducted. In Russia, the only interpreted giardiasis outbreak has been registered in the city of Perm .
- 3. General concept of Non-Communicable Diseases Associated with Water.
Inorganic contaminants in drinking water, which are the causes of diseases, include arsenic, copper, fluorine, lead and nitrates. Organic compounds sparking concern include pesticides, chlordane, phenol and trihalomethanes [3,69].
Evaluation of possible links between drinking water and malignant neoplasms means identifying chemicals that are found in the water in concentrations sufficient to represent a significant risk of cancer .
Some chemicals matters such as arsenic, asbestos, radon, agricultural chemicals and hazardous waste are of the greatest interest to researchers of environmental risk of tumors [14-15,44]. Epidemiological studies in Taiwan [75-76] assumed that arsenic in drinking water posed a significant risk of canceration in liver, lungs, bladder, kidneys, pancreas , gullet , rectum  and breast . Although the toxicological studies do not provide an unequivocal evidence of carcinogenicity of the given element, other epidemiological studies [44-45] also confirm the results of the Taiwan ones. Estimates of the risk of malignancy  show that the average arsenic level of 2.5 mg/l in drinking water in the United States is responsible for about 3,000 cases of cancer per year.
Lead: concerns about the potential impact of dissolved lead on the health led to significant efforts to reduce its concentrations in drinking water. Elevated lead levels are found in nature only in a few areas, such as the Debet River basin in Armenia. The usual sources of lead contamination are pipes used in plumbing, and their replacement is the only long-term strategy. Reduced water capacity of dissolving lead can be achieved by dosing orthophosphate or adjusting the pH from acid to alkaline, or both .
Arsenic is a known human carcinogen that causes various types of cancer diseases. In the estimation of specialists, in the south-eastern part of Hungary and along the border with Romania, 400,000 people were affected by this element in concentrations exceeding WHO standards in 1981 . At the present time, in the areas with no alternative source for the removal of arsenic from drinking water, a chemical precipitation technology is used. In 1995, it was estimated that the number of people exposed to arsenic in Romania and south-eastern Hungary was reduced to 20,000 people . High concentration of arsenic in the drinking water is an acute problem for Turkey .
Fluoride: excess concentration of fluoride in drinking water is the cause of fluorosis. Although the exact prevalence of the disease is unknown, according to WHO estimates, fluorosis affects millions of people worldwide. According to WHO guidelines, in most countries the concentration of fluoride is less than 1.5 mg/l. However, in Estonia 25%-35% of drinking water samples that have been analyzed since 1988 exceeded the standard, and 0.7% of population were subjected to high concentrations of this element . In Sweden, where fluoride occurs naturally, according to experts, 2.4% of population is exposed to concentrations above the standard . 35% of population in Moldova is also exposed to high concentrations of fluoride . In India, 62 million people in 17 of the 32 states suffer from dental, skeletal and/or non-skeletal fluorosis .
Nitrates (and nitrite): a lot of European countries report the high concentrations of nitrates in drinking water. Nitrate can be reduced to nitrites in the body and may cause juvenile methemoglobinemia. Only a few countries keep records of the disease, and the majority of reported cases are associated with well water, which often comes from shallow wells affected by agricultural activities. Indicators of the reported cases of methemoglobinemia per 100,000 people is 0.26 in Hungary, 0.56 in Slovakia, 0.74 in Romania and 1.26 in Albania . It is estimated that one third of the European population is exposed to nitrates in concentrations above the WHO standard.
Review sources revealed that gastrointestinal diseases, intestinal helminth infestations and protozoan infections as well as the risk of carcinogenic and mutagenic effects on the human body are to a great extent attributed to poor-quality water consumption.
In the literature the pathogenic water pollutants have been given more attention than the chemical ones. The classification of water-related diseases traditionally focuses on diseases caused by infectious microorganisms. However ingestion of toxic chemicals from contaminated water sources is becoming more and more recognized as a source of morbidity and mortality of population in recent decades. These diseases can also be classified as water-related ones.
Based on the above, high-quality water supply exerts a considerable impact on reduction of water-related diseases and rise in the living standards of population. A significant number of cases can be prevented with a better access to safe water supply, adequate sanitation facilities and better hygienic practices, especially in the developing countries.
Conflicts of Interest: The authors declare no conflict of interest.
Author Contributions: Alua O. Omarova planned the study, performed the review, and wrote the first version of the paper; Kamshat M. Tussupova, Ronny Berndtsson and Marat G. Kalishev contributed in an equal manner to the paper by adding comments and writing parts of the final paper.
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*Омарова Алуа Ораловна - докторант PhD 1 года обучения по специальности "Общественное здравоохранение" Карагандинского Государственного медицинский университета, г. Караганда, Республика Казахстан.
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