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      Ten Global “Hotspots” for the Neglected Tropical Diseases

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      PLoS Neglected Tropical Diseases
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          Abstract

          Since the founding of PLOS Neglected Tropical Diseases more than six years ago, I have written about the interface between disease and geopolitics. The neglected tropical diseases (NTDs) are the world's most common infections of people living in poverty [1]. Where they are widespread in affected communities and nations, NTDs can be highly destabilizing and ultimately may promote conflict and affect international and foreign policy [2]. Many of the published papers in this area were recently re-organized in a PLOS “Geopolitics of Neglected Tropical Diseases” collection that was posted on our website in the fall of 2012, coinciding with the start of our sixth anniversary [3]. From this information, a number of new and interesting findings emerged about the populations who are most vulnerable to the NTDs, including the extreme poor who live in the large, middle-income countries and even some wealthy countries (such as the United States) that comprise the Group of Twenty (G20) countries [4], as well as selected Aboriginal populations [5]. Together, the PLOS “Geopolitics of Neglected Tropical Diseases” collection and the G20 analyses identified more than a dozen areas of the world that repeatedly show up as ones where NTDs disproportionately affect the poorest people living at the margins. Here, I summarize what I view as ten of the worst global “hotspots” where NTDs predominate (Figure 1). They represent regions of the world that will require special emphasis for NTD control and elimination if we still aspire to meet Millennium Development Goals (MDGs) and targets by 2015; they are regions that may need to be highlighted again as we consider post-MDG aspirations and new Sustainable Development Goals (SDGs). 10.1371/journal.pntd.0002496.g001 Figure 1 Ten neglected tropical disease “hotspots” around the globe. The Americas In the Americas, there are at least three major zones where NTDs concentrate. Brazil and the Amazon Region In 2008, I found that Brazil has the largest number of NTDs in the Western hemisphere; they are particularly common among the millions of Brazilians who live on less than US$2 per day [6]. Brazil has almost all of the cases of blinding trachoma, leprosy, and schistosomiasis in the Americas, as well as most of the visceral leishmaniasis, hookworm, and dengue, and one-half of the ascariasis cases [6]. Lymphatic filariasis (LF) and onchocerciasis also occur, and Brazil has the largest number of Chagas disease cases in the world—1.9 million cases—although transmission of Chagas disease in the country has been greatly diminished or even eliminated [7]. Poverty reduction measures constituted an important component of former President Luiz Inácio Lula da Silva's administration and are subsequently being continued by President Dilma Roussef [8]. These measures include efforts at NTD control; however, it remains unclear the extent to which the total NTD burden has diminished over the last five to six years. Also in Brazil and immediately beyond its border is the Amazon region shared among the nations of Brazil, Colombia, Peru, Venezuela, Ecuador, Bolivia, Guyana, Suriname, and French Guiana, with a substantial but as-still-yet-unmeasured number of NTD cases and disease burden from Chagas disease, vivax malaria, arbovirus infections, leishmaniasis, and intestinal helminthiases. Gran Chaco Almost 10 million people inhabit the Gran Chaco, an area that spans eastern Bolivia, Paraguay, northern Argentina, and portions of two Brazilian states—Mato Grosso and Mato Grosso do Sul [9]. The area is an agriculturally intensive lowland region with a warm climate [9]. Among the major NTDs endemic to the region are intestinal helminth infections, including strongyloidiasis [10] and widespread Chagas disease [11] with triatomine insecticide resistance [12], although no disease burden information specifically for this region is available. Mesoamerica and Texas Mesoamerica includes Mexico's poorest states in the southern region, such as Chiapas, Guerrero, and Oaxaca [13], and impoverished Central American countries, such as El Salvador, Guatemala, Honduras, and Nicaragua. In Mexico, approximately 11 million people live in extreme poverty, with intestinal helminth infections, cysticercosis, cutaneous leishmaniasis (CL), and dengue representing the most common NTDs [13], [14], in addition to at least 1 million cases of Chagas disease [7], [14]. These same diseases are also widespread among the 30% of the population who live in extreme poverty in Central America [15], including approximately 800,000 cases of Chagas disease [7]. Although Texas is not generally considered a part of the Mesoamerican region, there is evidence that cysticercosis, CL, dengue, and even Chagas disease are widespread in South Texas and even in parts of Houston, which is emerging as the first major city in the United States with serious NTDs [16]. According to one estimate, Chagas disease results in almost US$1 billion in economic losses annually in the US [17]. Sub-Saharan Africa (SSA) SSA has a high concentration of NTDs globally, accounting for approximately one-quarter to one-third of the world's cases of the three major intestinal helminth infections (namely, ascariasis, trichuriasis, and hookworm infection), more than one-third of the LF, one-half of the trachoma, and all or most of the schistosomiasis, onchocerciasis, loiasis, and human African trypanosomaisis (HAT) [18]. Nigeria I have referred to Nigeria as “ground zero” for the NTDs because it ranks first in SSA in terms of the number of cases of all three intestinal helminth infections, schistosomiasis, LF, and onchocerciasis [18], [19]. Following publication of this information, the government of Nigeria redoubled efforts to expand NTD control and elimination efforts [20]. Democratic Republic of Congo (DRC) and Adjoining Nations: South Sudan, Central African Republic, Northern Uganda, and Angola DRC ranks closely behind Nigeria in terms of the total number of NTD cases, ranking second or third in most of the NTD disease categories and first in HAT and leprosy [18], [21]. DRC is still recovering from the last quarter of the 20th century when it was known as Zaire, during the reign of Mobutu Sese Seku, which was accompanied by the re-emergence of HAT and other diseases [21]. However, DRC is not alone, as long-standing conflicts and public health infrastructure declines in neighboring South Sudan, Central African Republic, northern Uganda, and Angola, may make this part of SSA one of the most NTD-affected regions in the world [18], [22]. South Sudan, which became an independent state in 2011, will likely soon become the last country to eradicate guinea worm infection [18]. Chad, Niger, and Mali and Adjoining Sahelian Areas These three adjoining nations have also suffered from widespread conflict and NTDs in recent years, and with it high rates of trachoma, schistosomiasis, and intestinal helminth infections [18], [23]. The nations of Niger and Mali are representative of the problem of high rates of NTDs occurring among selected nations of the Organisation of the Islamic Conference—the world's Islamic countries [23]. Still another region for strong consideration is among the southern and eastern African countries of Mozambique, Malawi, Tanzania, and Zimbabwe, where female urogenital schistosomiasis and other NTDs are widespread. Asia and Oceania The largest number of NTDs currently occurs in Asia, led by the large emerging market economies of India, Indonesia, and China [24]–[27]. Indonesia and Papua New Guinea Indonesia alone has approximately 10% of the world's cases of intestinal helminth infections, LF, and leprosy, in addition to more than one-half of the dengue deaths in Southeast Asia and a significant problem with other arbovirus infections and yaws [24]. Neighboring Papua New Guinea also accounts for most of the cases of hookworm infections and LF in Oceania, in addition to large numbers of cases of yaws and scabies, trachoma, leprosy, balantidiasis, and cholera outbreaks [25]. India and South Asia Nearly one-half or more of the cases of visceral leishmaniasis, LF, and leprosy occur in India and South Asia, in addition to one-third of the rabies deaths, one-quarter of the cases of intestinal helminth infections, and a massive but still ill-defined burden of disease from dengue and Japanese encephalitis [26]. China Rapid economic growth in eastern China has left behind high levels of disease and poverty in China's southwestern provinces of Sichuan, Guizhou, and Yunnan, where some of the highest rates of intestinal helminth infections are found [27]. China has the largest number of cases of the food-borne trematode infections, clonorchiasis, and paragonomiasis occurring in Guangdong Province in the South and some northern provinces, while more than 500,000 cases of schistosomiasis occur along the Yangtze River and its tributaries [27]. Trachoma and leprosy still occur [27]. A recent Global Burden of Disease analysis for China found that the NTDs are responsible for 3.7 million disability-adjusted life years (DALYs) lost annually, more than the DALYs lost from HIV/AIDS and tuberculosis [28]. The Middle East Approximately 65 million people live on less than US$2 per day in the Middle East and North Africa. These impoverished individuals suffer from high rates of intestinal helminthiases, LF, schistosomiasis, fascioloiasis, leishmaniasis, leprosy, and trachoma [29]. Overall, the highest rates of NTDs are found in Egypt and Yemen, but there are also a significant number of NTDs in Iran, Algeria, and elsewhere [28]. Concluding Comments These ten areas exhibit some of the world's highest concentrations of NTDs, although they vary with respect to having a modest prevalence among a large population versus hyperendemicity among a smaller population. Of interest is the finding that, with the important exception of SSA, they mostly include middle-income countries and nations belonging to the G20 [4]. The hotspot areas represent regions that require intensified efforts for NTD control and elimination, which would include access to essential NTD medicines through mass drug administration (also known as preventive chemotherapy), but also vector management and control. In a previous paper I pointed out the opportunities for the G20 countries to engage in scientific research and development to produce new drugs and vaccines affecting their regions, and possibly diplomacy to promote international scientific cooperation [4]. These regions would comprise key areas to target as a means to achieve the MDGs and to help set goals and targets past 2015 and for the new SDGs [30], [31]. This list represents a personal view of what I consider some of the most important NTD-affected areas in the world. I welcome comments and opinions from the NTD community on other regions and parts of the world I might have missed or where the readers believe there should be renewed emphasis for control and elimination.

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          Control of neglected tropical diseases.

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            Neglected Tropical Diseases of Oceania: Review of Their Prevalence, Distribution, and Opportunities for Control

            Among Oceania's population of 35 million people, the greatest number living in poverty currently live in Papua New Guinea (PNG), Fiji, Vanuatu, and the Solomon Islands. These impoverished populations are at high risk for selected NTDs, including Necator americanus hookworm infection, strongyloidiasis, lymphatic filariasis (LF), balantidiasis, yaws, trachoma, leprosy, and scabies, in addition to outbreaks of dengue and other arboviral infections including Japanese encephalitis virus infection. PNG stands out for having the largest number of cases and highest prevalence for most of these NTDs. However, Australia's Aboriginal population also suffers from a range of significant NTDs. Through the Pacific Programme to Eliminate Lymphatic Filariasis, enormous strides have been made in eliminating LF in Oceania through programs of mass drug administration (MDA), although LF remains widespread in PNG. There are opportunities to scale up MDA for PNG's major NTDs, which could be accomplished through an integrated package that combines albendazole, ivermectin, diethylcarbamazine, and azithromycin, in a program of national control. Australia's Aboriginal population may benefit from appropriately integrated MDA into primary health care systems. Several emerging viral NTDs remain important threats to the region.
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              Nigeria: “Ground Zero" for the High Prevalence Neglected Tropical Diseases

              Among all of the African nations, Nigeria has the greatest number of people infected with neglected tropical diseases (NTDs). With the right political will, the country has sufficient resources to expand its current investments for the important work of Nigeria's NTD program. In a 2009 analysis of the NTDs in sub-Saharan Africa, one of us identified Nigeria as the country with the greatest number of cases of the so-called high prevalence NTDs, such as the intestinal helminth infections, schistosomiasis, and lymphatic filariasis (LF) [1]. Shown in Table 1 is a list of the major NTDs that can be targeted for integrated NTD control and/or elimination, which also includes onchocerciasis. The information confirms that Nigeria has the greatest number of intestinal helminth infections, i.e., ascariasis, hookworm, and trichuriasis, among all African nations, ranking fourth or fifth globally behind only the much higher populated middle-income Asian nations, such as China, India, and Indonesia [1]–[4]. Nigeria also has the greatest number of cases of schistosomiasis worldwide, with both intestinal schistosomiasis caused by Schistosoma mansoni and the urogenital schistosomiasis caused by Schistosoma haematobium endemic to that country [1], [5]. In terms of the high prevalence vector-borne NTDs, Nigeria has the greatest number of cases of LF and onchocerciasis in Africa, ranking globally third and first, respectively, and accounting for one-fourth or more of the global disease burden from these two NTDs [6]–[9]. Nigeria also has an estimated 18 million people at risk for trachoma, with nearly 1.3 million people living with trichiasis [10], and the third or fourth largest number of new cases of leprosy in Africa (behind Ethiopia and the Democratic Republic of Congo) [11], in addition to some of the greatest number of cases of the lower prevalence NTDs, including yellow fever, rabies, and Buruli ulcer in Africa [1]. The World Health Organization (WHO) reports that there may be 21 “alleged" or “suspected" remaining cases of dracunculiasis in Nigeria [12], although it is widely accepted that transmission of guinea worm has been interrupted there. 10.1371/journal.pntd.0001600.t001 Table 1 Ranking of Nigeria by neglected tropical diseases cases and prevalence. Disease Estimated Number of cases in Nigeria Ranking in Africa Percentage of Global Disease Burden Ranking Globally Reference Ascariasis 55 million 1 7% 5th behind India, Indonesia, China, and Bangladesh [1]–[4] Hookworm 38 million 1 7% Tied for 4th with China behind India, Indonesia, and Bangladesh [1]–[4] Trichuriasis 34 million 1 6% 4th behind India, Indonesia, and Bangladesh [1]–[4] Schistosomiasis 29 million 1 14% 1 [2], [5] Lymphatic filariasis • 25 million• 80–121 million estimated at risk, requiring mass drug administration 1 21% 3rd [6]–[8], [27] Onchocerciasis 30 million at risk, requiring mass drug administration 1 36% 1 [6], [9] Trachoma 18 million at risk Not determined Not determined Not determined [10] Leprosy 4,531 registered prevalence 4 2% 7th [11] The high prevalence NTDs are responsible for an enormous disease burden in Africa, equivalent to almost one-half the disease burden from malaria when measured in disability-adjusted life years [1]. There is an equally important adverse economic impact because of the effects of these NTDs on maternal-child health and worker productivity in Africa [1]. However, the seven most common NTDs can often be controlled or in some cases even eliminated through low cost “rapid-impact" packages of drugs, which are either donated by multinational pharmaceutical companies or through the purchase of low-cost generic drugs. At a cost of less than US$1 per person annually, the prevalence of the intestinal helminth infections and schistosomiasis could be reduced in some areas, while LF, onchocerciasis, and trachoma might even be eliminated over a period of several years. Therefore, based on Nigeria's current population estimate of approximately 150 million people [13], we estimate that such goals could be achieved in Nigeria for significantly less than US$100 million annually. Because the seven high prevalence NTDs have been shown to actually cause poverty, the economic rate of return for integrated NTD control and elimination would be substantial. The enormous disease and economic burden resulting from the seven high prevalence NTDs persist in Nigeria despite the country's economic capacity to absorb some or all of the costs required for disease control and elimination. Nigeria is the most populated nation in Africa, accounting for approximately 20% of Africa's population (Figure 1, Table 2) [6], [13], [14]. It is also the 8th most populated nation worldwide, roughly equivalent to the population of Bangladesh and Brazil [13], [14], but with a gross domestic product (GDP) and purchasing power parity that ranks it with several western European countries such as Belgium or Sweden [15]. Indeed, Nigeria has the third largest economy in Africa, behind South Africa and Egypt, ranking 32nd globally with a GDP of over US$300 billion [15], [16]. Additional estimates indicate that Nigeria is ranked among the top 20 countries globally for foreign direct investments [17]. Moreover, Nigeria is currently experiencing enormous economic growth, which exceeded 8% in 2010 [18], [19], and was almost 7% in 2011 [19]. 10.1371/journal.pntd.0001600.g001 Figure 1 Location of Nigeria. From CIA – The World Factbook (https://www.cia.gov/library/publications/the-world-factbook/geos/ni.html), accessed 1 February, 2012. 10.1371/journal.pntd.0001600.t002 Table 2 Facts and figures about Nigeria. Category Number Ranking Countries with Comparable Ranking Reference Population • 152 million (2010)• 165 million (projected in 2015) 8 Bangladesh And Brazil [13], [14] GDP (purchasing power parity) 378 billion (2010) 32 Belgium andSweden [15] Ranking of economy in Africa 3 Behind South Africa and Egypt [15], [16] HDI (Human Development Index) 0.470 (2005) 158 Eritrea andTanzania [22] Increasingly, much of Nigeria's economic growth depends on oil and other fossil fuels. Today, Nigeria ranks 15th globally in world oil production and 5th in oil exports, in addition to 11th in natural gas exports [20]. The excessive dependence on fossil fuels has created a structural imbalance and lack of diversification leading to high youth unemployment and widespread insecurity [18]. The term “resource curse" has been applied to countries such as Nigeria that have enormous natural resources but underperform with respect to their human development index (HDI) and other metrics linked to a robust economy [21]. Indeed, despite its wealth, Nigeria ranks only 158th in terms of its HDI [22], and so far the country has been unable to meet its Millennium Development Goals (MDGs), including MDG 6 for combating HIV/AIDS, malaria, and other diseases [13]. Additionally, between the years 1990 and 2006, Nigeria regressed in several developmental indices, notably the percentage of its population that had access to safe water coverage and basic sanitation. As of 2006, a majority of Nigerians lack access to safe water coverage (53%) and sanitation (70%) [23]. This situation is not unique to Nigeria, but unfortunately is common among many African nations. The good news is that Nigeria has made some important strides in NTD control and elimination [6], [24]. Some of these successes were accomplished in collaboration with the WHO, UNICEF-Nigeria, and the Atlanta-based Carter Center and its Nigerian offices in Jos, as well as other non-governmental developmental organizations (NGDOs) [6], [8], [24], [25], [26]. The clearest public health victory has been with respect to guinea worm (dracunculiasis) eradication. In 1986, Nigeria accounted for approximately 75% of the world's 3.3 million cases of dracunculiasis. Through investments by the Nigerian government that exceeded US$2 million, in addition to other public and private support, transmission of guinea worm has been halted since 2009 [6]. In addition, with support from the International Trachoma Initiative (ITI), the Nigeria national program has received more than 4.7 million Zithromax treatments since 2010 [10]. In 2011, Nigeria was scheduled to treat 3.1 million people [10], or possibly as many as 5 million [27]. Moreover, in collaboration with the African Programme for Onchocerciasis Control (APOC), the Nigerian Federal Ministry of Health has ensured that more than 96% of 35,000 Nigerian communities at risk for river blindness have received or still receive annual community-directed treatments with ivermectin (CDTI) [24] (Figure 2). These activities have occurred through support of the APOC Trust Fund, NGDOs, and the Nigerian government [24]. Outcomes of recent epidemiological assessments conducted with support from APOC indicate that onchocerciasis transmission has been halted in foci in Ebonyi, Kaduna, and Zamfara states [27]. For onchocerciasis and the other high prevalence NTDs, including LF, schistosomiasis, and trachoma, some of the most notable gains have occurred in the states of Plateau and Nasarawa, where the Carter Center maintains active programs of mass drug administration [6], [25], [26]. As a result, there has been a 95% reduction in onchocercal nodules in these two states, and an 83% reduction in the prevalence of LF [6], [25], [26]. Moreover, praziquantel mass drug administration for schistosomiasis is being integrated with LF and onchocerciasis control and elimination efforts, with targeted praziquantel treatment for schistosomiasis now ongoing in six states [6], [8], [27] (Supporting Document S1). 10.1371/journal.pntd.0001600.g002 Figure 2 Map of Nigeria. From CIA – The World Factbook (https://www.cia.gov/library/publications/the-world-factbook/geos/ni.html), accessed 1 February, 2012. Despite these victories and accomplishments, much of the Nigerian population still lacks access to essential medicines for the high prevalence NTDs. Beginning in 2009, a national program for NTD control and elimination was initiated to promote integrated control nationally. The NTD program of the Nigerian Federal Ministry of Health currently addresses the following diseases: LF, onchocerciasis, schistosomiasis, soil-transmitted helminth infections, trachoma, leprosy, Buruli ulcer, human African trypanosomiasis, and guinea worm disease. The strategy of the NTD program is to progressively reduce morbidity, disability, and mortality due to NTDs using integrated and cost-effective approaches with the goal to eliminate NTDs in Nigeria by the year 2020 [27]. Nigeria has sufficient wealth and resources in order to build on its past successes and embark on an expanded and aggressive program of national disease control and elimination for its highest prevalence NTDs. Costing less than 0.1% of its GDP annually, the program would be comprised of integrated mass drug administration efforts to target the intestinal helminth infections, schistosomiasis, LF, and onchocerciasis, possibly together with administration of long-lasting insecticide-treated nets to also target malaria and LF, as well as the SAFE (surgery, azithromycin antibiotics, facial cleanliness, and environmental control) strategy for trachoma elimination. Through its long-standing collaborations with international agencies such as APOC, WHO, and UNICEF, as well as CBM, ITI, the Carter Center, Helen Keller International, Sightsavers International, Mission to Save the Helpless (MITOSATH), and other NGDOs, the Nigerian Federal Ministry of Health has acquired deep and lasting technical expertise in order to ensure such expanded activities are conducted at maximal efficiencies, minimal costs, and with adequate monitoring and evaluation. A key component would include accelerated mapping of NTDs in Nigeria [28], including an ongoing partnership with the Swiss Tropical and Public Health Institute [29]. A national program of NTD control and elimination, coupled with increased access to clean water and sanitation, would simultaneously serve to strengthen health systems in many of the more fragile Nigerian states, and would represent a highly effective pro-poor strategy for Nigerian President Goodluck Jonathan in his first elected term. Doing so would be an appropriate activity for a nation currently undergoing its longest period of civilian rule since independence and one recently awarded a seat on the United Nations Security Council [30]. There is also an urgent need for new and improved control tools for Nigeria's NTDs, including the development of a new macrofilaricide for onchocerciasis and other medicines, simpler and less expensive diagnostic reagents, and NTD vaccines [6]. In parallel with expanded disease control and elimination efforts, Nigeria's best universities and research institutes must expand their research and training capacity for NTDs. Several Nigerian capacity-building and partnering programs with institutions in the United States and United Kingdom are already in place, including one between the Nigeria's National Academy of Science together with the US National Academies through the African Science Academy Development Initiative (ASADI) [31], and between the University of Ibadan (in partnership with several other Nigerian universities) and two US universities (Northwestern University and Harvard School of Public Health) through the Medical Education Partnership Initiative in Nigeria (MEPIN) supported by the US National Institutes of Health [32], but these too could be expanded. A Nigeria free from its high prevalence NTDs can be expected to accelerate that nation's economic development through improvements in child growth, intellect and cognition, pregnancy outcome, and worker productivity. Through expansions in integrated NTD control and disease elimination, Nigeria would become an important role model for all of Africa. Supporting Information Supporting Document S1 “Brief on NTD," unpublished document by Nigerian Ministry of Health, received January 24, 2012. (DOC) Click here for additional data file.
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                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                May 2014
                29 May 2014
                : 8
                : 5
                : e2496
                Affiliations
                [1 ]National School of Tropical Medicine at Baylor College of Medicine, Houston, Texas, United States of America
                [2 ]Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Houston, Texas, United States of America
                [3 ]James A. Baker III Institute at Rice University, Houston, Texas, United States of America
                Author notes

                The author has declared that no competing interests exist.

                Article
                PNTD-D-13-00877
                10.1371/journal.pntd.0002496
                4038631
                24873825
                a8072bb3-aaee-47eb-a6ab-7e4dce25139e
                Copyright @ 2014

                Hotez. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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                Categories
                Editorial
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Treponematoses
                Yaws
                Cholera
                Parasitic Diseases
                Helminth Infections
                Soil-Transmitted Helminthiases
                Ascariasis
                Hookworm Diseases
                Strongyloidiasis
                Onchocerciasis
                Schistosomiasis
                Tropical Diseases
                Neglected Tropical Diseases

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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