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Abstract
The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.
Citation: Hotez PJ, Kamath A (2009) Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden. PLoS Negl Trop Dis 3(8): e412. https://doi.org/10.1371/journal.pntd.0000412
Editor: Michael Cappello, Yale Child Health Research Center, United States of America
Published: August 25, 2009
Copyright: © 2009 Hotez, Kamath. 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.
Funding: The authors received no specific funding for this study.
Competing interests: PJH is a co-founder of the Global Network for Neglected Tropical Disease Control and an inventor on two international patents for hookworm vaccines.
Peter J. Hotez is Editor-in-Chief of PLoS Neglected Tropical Diseases. He is Distinguished Research Professor and Walter G. Ross Professor and Chair of the Department of Microbiology, Immunology, and Tropical Medicine at George Washington University, and President of the Sabin Vaccine Institute. Aruna Kamath is a medical student at George Washington University.
Introduction
The neglected tropical diseases (NTDs) are a group of chronic, disabling, and disfiguring conditions that occur most commonly in the setting of extreme poverty, especially among the rural poor and some disadvantaged urban populations [1]. Today, the world's greatest concentration of poverty occurs in sub-Saharan Africa (SSA). According to a recent World Bank analysis, 51% of the population of SSA lives on less than US$1.25 per day, and 73% of the population lives on less than US$2 per day (Table 1) [2]. Previous studies indicate that the NTDs are widespread among the poor in SSA [3]–[6], with the most common NTDs, such as the soil-transmitted helminth (STH) infections, schistosomiasis, lymphatic filariasis (LF), trachoma, and onchocerciasis together affecting more than 500 million people [3], [6]–[8]. Because of their adverse effects on child development, pregnancy outcome, and agricultural worker productivity [1], [3], [6], [7], [9]–[17], the NTDs represent a major reason why the “bottom 500 million” people in SSA cannot escape poverty. Therefore, new and ongoing efforts to control and eliminate the NTDs represent key elements for achieving Africa's Millennium Development Goals (MDGs) for sustainable poverty reduction, including the MDGs to eradicate poverty (MDG 1), promote education (MDG 2), reduce child mortality (MDG 4), improve maternal health (MDG 5), and to combat “other diseases” (MDG 6) [1],[7],[8].
Specific information on the prevalence, distribution, and disease burden resulting from the NTDs in SSA would provide a basis for prioritizing control strategies as a means to address the MDGs. Over the last decade, geographic information systems (GIS) and remote sensing (RS) have facilitated a deeper understanding of the prevalence and distribution of NTDs, particularly for helminth infections in SSA [4], [5], [18]–[21]. Simultaneously, a fresh assessment of the chronic and subtle morbidities caused by NTDs has highlighted a previously underappreciated disease burden [22],[23]. Here, we review current knowledge on the prevalence, distribution, and disease burden resulting from NTDs in SSA, focusing on aspects particular to the region. The review of the literature was conducted using the online database PubMed from 2003 to 2008 with the Medical Subject Headings (MeSH), the specific diseases listed as neglected tropical diseases on the PLoS Neglected Tropical Disease Web site (http://www.plosntds.org/static/scope.action), and the geographic regions and countries of SSA. Reference lists of identified articles and reviews were also hand searched as were databases from the World Health Organization (WHO, http://www.who.int), including the WHO's Weekly Epidemiological Record.
Burden and Geographic Distribution of Disease
Table 2 ranks the major NTDs in SSA by their estimated prevalence, the percentage of the population infected, and the percentage of the world's cases found in the region, while Table 3 ranks the countries with the highest prevalence of each of the NTDs. Helminth infections, especially the STH infections, schistosomiasis, and the filarial infections LF and onchocerciasis, are the most common NTDs in SSA, followed by trachoma and other bacterial infections [3], [21]–[38]. Human African trypanosomiasis (HAT) and leishmaniasis are the most common serious protozoan infections, especially in areas of conflict where these diseases emerge in the setting of inadequate housing and forced migrations [39]–[44]. However, as shown in Table 4, there are more than a dozen important NTDs, including the protozoan infections, amebiasis and toxoplasmosis; bacterial infections such as Salmonella infections (both typhoid fever and non-typhoidal salmonellosis), the tick-borne zoonoses, and yaws; and viral infections such as Rift Valley fever, for which there is insufficient information available in order to estimate their prevalence in SSA. Based on global disease burden estimates in disability-adjusted life years (DALYs) published previously by the WHO and other investigators [3], [35], [45]–[48], a range of estimates for the NTDs in SSA is provided in Table 5. DALY estimates for the STH infections and schistosomiasis were obtained by adjusting a wide range of available global estimates according to the percentage of the total number of cases that occur in SSA, while for the other NTDs the disease burdens were quoted directly from WHO estimates. From this analysis it was determined that the total burden of NTDs in SSA is possibly as high as one-half the disease burden caused by malaria and twice the disease burden caused by tuberculosis in SSA (Table 6), suggesting that the NTDs represent a formidable public health challenge in the region. Up to 85% of the NTD disease burden specifically results from helminth infections (Table 6). However, even this high disease burden resulting from helminth infections and other NTDs may represent an underestimate because they do not incorporate the full spectrum of chronic sequelae [22],[23], and because such estimates do not include NTDs listed in Table 4.
Helminth Infections
STH infections (hookworm infection, ascariasis, trichuriasis).
Since the global prevalence of STH infections was first estimated by Stoll over 60 years ago [31], the overall prevalence of the STH infections is believed to have remained relatively constant in SSA, whereas it has diminished elsewhere in the developing world [24]. Today, between one-quarter and one-third of SSA's population is affected by one or more STH infections [24], with children, especially school-aged children, disproportionately affected. Of the estimated 181 million school-aged children in SSA, almost one-half (89 million) are infected with hookworm, ascariasis, trichuriasis, or some combination of these STH infections [4]. Typically, children exhibit higher STH intensities than any other single population [4] and as a result suffer from profound physical and mental deficits [6], [10], [49]–[51]. Such deficits partially account for their high disease burden in SSA. Moreover, in Kenya (and presumably elsewhere), these effects also translate into increases in school absenteeism and reduced school performance [14].
Hookworm infection (“hookworm”). Hookworm is the most common STH infection and the most common NTD in SSA (Tables 2 and 3). It is also one of the most important in terms of disease burden, accounting for up to one-third of the total burden from NTDs in SSA (Table 5). Based on previous estimates derived in 2002 [24], it is estimated that 198 million people in SSA are infected with hookworm (29% of the region's population), including 40–50 million school-aged children [4],[5]. Approximately one-third of the world's hookworm today occurs in SSA (Table 2) [3], with the greatest number of cases occurring in Nigeria (38 million) and the Democratic Republic of Congo (DRC, 31 million), followed by Angola, Ethiopia, and Cote d'Ivoire (10–11 million) (Table 3). Hookworm is the most widely distributed NTD in SSA and it is pervasive throughout the region (including both rural and urban areas) except in some parts of extreme southern Africa [4],[5]. Two areas are particularly notable for their high hookworm prevalence and intensity compared to other helminth infections, namely coastal regions [52], and areas of extremely high temperatures (where land surface temperatures exceed 37–40°C), including those near the Sahel such as Cameroon [18], Chad [19], and Mali [53],[54]. Through GIS/RS such information can be used to generate predictive maps of areas of high hookworm prevalence as well as their geographic overlap with potential co-infections [4],[5]. For instance, it is estimated that approximately 90% of the 50 million school-aged children with hookworm are at risk for coincident co-infection with falciparum malaria [5],[55]. Both Necator americanus and Ancylostoma duodenale are found in SSA, with the former representing the predominant hookworm species [56]. Because they cause intestinal blood loss, hookworm is a leading cause of iron deficiency anemia in the region [57]. Among school-aged children in Zanzibar, 35% of iron deficiency anemia and 73% of severe anemia was attributable to hookworm [58], while in Kenya and elsewhere in Africa, hookworm also is an important cause of anemia among preschool children [59],[60]. Hookworm has also been recognized as an important cause of anemia and morbidity in women of reproductive age in SSA, especially among pregnant women [57],[61]. At any given time, almost 7 million pregnant women in SSA (up to one-third of pregnant women in the region) are infected with hookworm [17]. Hookworm's high disease burden in SSA reflects its importance as a cause of maternal and child anemia (Table 5).
Ascariasis and trichuriasis. The highest intensity Ascaris and Trichuris infections occur in school-aged children [4]. It is estimated that 173 million and 162 million people are infected in SSA with Ascaris and Trichuris, respectively, with 36 million school-aged children infected with ascariasis and 44 million with trichuriasis [4]. For both infections the largest number of cases occurs in Nigeria, where co-infections with hookworm are common [62]. Tens of millions of cases are also found in Ethiopia, DRC, and South Africa (Table 3). Compared to hookworm, both ascariasis and trichuriasis exhibit a more patchy distribution in SSA, with the highest prevalence occurring in equatorial Central and West Africa, eastern Madagascar, and southeast Africa [4]. In contrast to the high rates of ascariasis and trichuriasis in South Africa [63],[64], hookworm is less common except in KwaZulu-Natal [52]. Moreover, higher prevalence rates of ascariasis and trichuriasis are often present in Africa's urban areas compared to rural areas, unlike hookworm, which is more evenly distributed [4]. These observations may reflect the ability of Ascaris and Trichuris eggs to survive in urban environments, so that increased urbanization in SSA may promote emergence of ascariasis and trichuriasis in the future.
Other STH infections.
Strongyloidiasis causes diarrhea and malnutrition in SSA, although there is little information on its distribution or disease burden (Table 4), in part because of the difficulties in diagnosing this infection. In one study, strongyloidiasis accounted for 5.3% of diarrhea in malnourished Nigerian children [65]. Two other intestinal nematode infections are focally endemic. Oesophagostomum bifurcum is common in northern Ghana and Togo [66], and Ternidens deminutus (the “false hookworm”) occurs in Zimbabwe [67].
Schistosomiasis and other platyhelminthiases.
Of the world's 207 million estimated cases of schistosomiasis, 93% occur in SSA (192 million) (Table 2), with the largest number in Nigeria (29 million) followed by United Republic of Tanzania (19 million), and DRC and Ghana (15 million each) [21] (Table 3). Approximately 76% of the population in SSA lives near rivers, lakes, and other water bodies contaminated with snail intermediate hosts [21], [68]–[70]. Those living near dam reservoirs are at particular risk [21], and SSA has several examples where the infection has emerged or where there has been a dramatic rise in the prevalence of schistosomiasis as a result of irrigation project construction [21],[71]. Climate change and global warming may also be factors [72].
The highest prevalence and intensities of human schistosomiasis occur in school-aged children, adolescents, and young adults who also suffer from the highest morbidity and mortality. There are two major forms of schistosomiasis found in SSA. Approximately two-thirds of the schistosomiasis cases are due to infection caused by Schistosoma haematobium, which represents an important cause of severe urinary tract disease [73]. In 2000, van der Werf et al. estimated that 70 million and 32 million individuals out of 682 million people in SSA had experienced hematuria and dysuria, respectively, within the last two weeks [73]. S. haematobium produces bladder wall pathology in approximately 18 million people in SSA, and 10 million people suffer from hydronephrosis [73]. Renal failure accounts for a large percentage of the estimated 150,000 deaths from urinary tract schistosomiasis in SSA, and there is also a significant association between major bladder wall pathology and squamous cell carcinoma [74]. A significant percentage of women and men with urinary schistosomiasis acquire genital ulcers and other lesions [22]. In the former, urogenital schistosomiasis is a significant cause of poor reproductive health, including sexual dysfunction and infertility [75]. Genital schistosomiasis also promotes the horizontal transmission of HIV/AIDS in SSA [76]. Intestinal schistosomiasis from S. mansoni causes most of the remaining cases in SSA. An estimated 4.4 million people with S. mansoni have bloody diarrhea and bowel ulceration, and 8.5 million develop hepatomegaly and/or associated periportal liver fibrosis, portal hypertension, and hematemesis from S. mansoni infection, with approximately 130,000 deaths [22],[73]. S. intercalatum causes a second form of intestinal schistosomiasis, but with a restricted distribution in West and Central Africa [77].
In addition to the organ-specific pathology described for both S. haematobium and S. mansoni infections, there is increasing evidence for more generalized morbidity resulting from the chronic inflammation of these long-standing infections [22],[23]. Among the most important are anemia of chronic inflammation and iron deficiency anemia, growth stunting and malnutrition, fatigue and diminished physical fitness, and impaired cognitive development [22],[23]. The current disease burden calculations for schistosomiasis range between 1.7 and 4.5 million DALYs lost annually (1.6 and 4.2 million DALYs in SSA) (Table 5), but these current estimates do not fully consider the general morbidities outlined above. It has been suggested that the true disease burden for schistososomiasis may be several fold higher than previous estimates [22], possibly making this infection the most important NTD in SSA. In addition to S. haematobium and HIV co-infections [76], S. mansoni and hookworm co-infections are common in SSA and can lead to severe anemia [78]–[80]. A relationship has also been proposed between schistosomiasis and malaria [81].
Among the other platyhelminth infections in SSA, paragonimiasis has been reported from eastern Nigeria and southwestern Cameroon [82], although there are no estimates of the number of cases. Cysticercosis caused by the pork tapeworm Taenia solium is a major risk factor for epilepsy in SSA except in Muslim areas [83], and it is hyperendemic in Burundi and elsewhere in eastern Africa [84], southern Africa [85],[86], and Cameroon [87]. It has been suggested that cysticercosis may account for the presence of subcutaneous nodules that erroneously have been linked with onchocerciasis and may be responsible for seizures following mass drug administration with anthelminthics [88]. However, the full disease burden of cysticercosis in SSA remains largely unstudied. Both taeniasis caused by the beef tapeworm Taenia saginata and cystic echinococcosis are highly prevalent in East Africa, especially in Ethiopia and Sudan [89],[90].
Filarial infections (LF, onchocerciasis, loiasis, and dracunculiasis).
LF. Approximately 40% of the world's 120 million cases of LF occur in SSA (approximately 46–51 million cases) (Table 2) [3], [7], [25]–[28],[91],[92], with an estimated 382–394 million people at risk of infection, including 176 million children [91],[93]. In the 39 countries where LF occurs in SSA, the greatest numbers of people at risk of infection live in Nigeria, followed by DRC, Tanzania, Ethiopia, and Kenya (Table 3). All of the LF cases in SSA are caused by Wuchereria bancrofti, which are transmitted by a variety of culicine and anopheline mosquitoes [92]. W. bancrofti infection produces a wide range of clinical manifestations, including hydrocele and lymphoedema as the most clinically obvious because of the associated disability, disfigurement, and stigma [94]. Based on global estimates that 12.5% of LF infections are estimated to result in lymphedema and 20.8% in hydrocele [93], there are approximately 5 million cases of lymphedema and 8 million cases of hydrocele in SSA. The estimated 2.0 million DALYs lost annually from LF rank it third or fourth behind hookworm and schistosomiasis (and possibly ascariasis) as the most important NTD in SSA (Table 5). LF is also associated with huge economic losses, impairing economic activity up to 88% [9], and causes almost US$1 billion in annual losses, mostly resulting from the disability linked to hydrocele in men [95],[96]. In addition to LF, endemic non-filarial elephantiasis (podoconiosis) is widespread in SSA, with the areas of highest prevalence in the highlands of East Africa as well as in some West African countries [97].
Onchocerciasis. More than 99% of the estimated 37 million cases of onchocerciasis occur in SSA (Table 2) [15], distributed in a wide belt that extends from Senegal in the west to Ethiopia in the east and from Mali in the north to Angola and Malawi in the south [15],[29]. Based on rapid epidemiological mapping of onchocerciasis (REMO), a non-invasive and practical tool for distribution and disease prevalence, it is estimated that the mean infection rate among the 19 countries targeted by the African Programme for Onchocerciasis Control (APOC) is 38.2% with 87 million persons at risk for contracting the infection [15]. In SSA, the clinical features of the disease vary from the savanna form, more common in West Africa and associated with high rates of blindness, to the rainforest form more common in Central and East Africa in which high rates of onchocera skin disease (OSD) are characterized by severe pruritus and disfigurement (also known as “troublesome itching”) [29]. In hyperendemic communities where the prevalence of onchocerciasis exceeds 60%, blindness can occur in 10% or more of some savanna populations, while OSD can affect more than 50% of some rainforest communities [29]. Both forms are linked with high disability as well as severe socioeconomic consequences. It is estimated that 40% of the DALYs lost from onchocerciasis result from blindness, while 60% are from OSD [29].
Loiasis. The African eyeworm has a high prevalence in rainforest areas of low socioeconomic status and in some savanna regions [32]. The infection is common in Angola, Benin, Cameroon, Central African Republic, Congo, DRC, Equatorial Guinea, Gabon, Nigeria, and Sudan [32]. Loa infection is associated with Calabar swellings that result from filarial migrations in the subcutaneous tissues, but the greatest concern about the infection is the risk associated with ivermectin treatments for onchocerciasis co-infections [98]. Angola, Cameroon, and DRC exhibit the highest rates of co-endemicity and consequently, represent the highest risk areas for serious adverse events during mass drug administration [98]. A rapid assessment method based on a clinical history of eyeworm infection and known as RAPLOA is in use to evaluate local prevalence of loiasis, as well as a spatial model based on environmental factors [98].
Dracunculiasis. All of the world's cases of dracunculiasis occur in SSA. In 2007, only 9,585 cases were reported (Table 2), a 99% reduction in the number of cases since most endemic countries began to report using village-based surveillance systems [36]. During 2007, Sudan (5,815) and Ghana (3,358) accounted for 96% of the total cases, with the remainder in Mali, Niger, and Nigeria (Table 3) [36]. Mali experienced two unexpected outbreaks during this period [99].
Protozoan Infections
HAT and leishmaniasis are the major protozoan infections in SSA, accounting for almost 2 million DALYs lost annually (Table 5). Amebiasis and toxoplasmosis are also highly endemic in SSA, but there are few estimates of their prevalence, incidence, or disease burden (Table 4).
HAT.
Through stepped-up public health control efforts over the last decade, the major endemic countries in SSA have made great strides in reducing the number of cases of HAT from 300,000–500,000 cases to approximately 50,000–70,000 cases, along with 17,000 new cases occurring annually (Table 2) [39]. Approximately 90% of the cases are caused by Trypanosoma brucei gambiense, a cause of chronic Gambian HAT [100], with most of the new cases occurring in DRC (10,369 new cases in 2004), followed by Angola, Sudan, Republic of Congo, and Central African Republic (Table 3). The major reductions in Gambian HAT are a result of interruptions in conflict [39]. Despite these gains, outbreaks of Gambian HAT occurred in Angola, DRC, and Sudan in 2005 [40]. HAT caused by T. b. rhodesiense accounts for the remaining cases of HAT in SSA, with most of the new cases occurring in Malawi, Uganda, and the United Republic of Tanzania [39]. Rhodesian HAT is a zoonosis transmitted from cattle and other mammals, which produces an acute and fulminating sleeping sickness [39],[100]. Populations in the age group between 15 and 45 years and living in remote rural areas are considered especially vulnerable to both forms of HAT [39]. Currently, the only country with both Gambian and Rhodesian HAT is the nation of Uganda, but to date each focus is geographically separated [101].
Leishmaniasis.
Both visceral and cutaneous forms occur in SSA, with the former producing serious disease associated with high mortality. Most of the cases of visceral leishmaniasis (VL) occur in the Horn of Africa, i.e., the East African countries of Sudan, Eritrea, Ethiopia, Kenya, and Somalia [43], with most of them caused by Leishmania donovani (Table 3), although some cases are caused by L. infantum[42]. Because many cases occur in areas of conflict and forced human migrations, the exact number occurring in East Africa is not well established, nor is the disease burden. During the 1980s, an estimated 100,000 people died as a result of VL epidemics [42]. In Sudan alone, as a result of long-standing civil war, hundreds of thousands of cases occurred with death rates exceeding 50% in some areas [43]. Today, the continuing widespread conflict in these countries has destroyed housing and health care infrastructure, and the resultant forced migrations to endemic areas still promote the emergence of VL [42]. Adding to the problem is widespread malnutrition as a result of drought, which increases susceptibility to infection and contributes to the progression of disease [42]. The highest incidence of the disease occurs in Sudan (especially near part of its border with Ethiopia, where 15,000–20,000 new cases occur annually), followed by Ethiopia with approximately 4,000 new cases (Table 2) [41],[43]. The Pokot territory of Kenya and Uganda is also endemic [102]. In these areas VL is considered primarily an anthroponotic infection [103],[104]. VL is also an important opportunistic infection associated with HIV/AIDS in East Africa [41], especially in the Tigray region on the Sudan–Eritrea border where soldiers and seasonal workers sleep outdoors in sandfly-infested areas [43]. Cutaneous leishmaniasis caused by infection with Leishmania major is also endemic in parts of SSA including West Africa, where there has been a major increase in the number of cases near Ougadougou, the Burkina Faso capital [41], and in Sudanese refugee camps in Chad [43].
Amebiasis.
The epidemiology of amebiasis is poorly understood in SSA because few studies differentiate true infection caused by Entamoeba histolytica versus infection resulting from the non-pathogenic variant, E. dispar[105]. Based on seroprevalence studies in Sudan, Cote d'Ivoire, and South Africa, however, the distribution of amebiasis is believed to be widespread [105]. Amebiasis has also been reported from Nigeria [106]. In South Africa it has been observed that invasive E. histolytica infection is associated more commonly with amebic liver abscess than colitis [105].
Toxoplasmosis.
The study of toxoplasmosis has also been neglected in SSA, although investigations conducted in Sudan [107] and Burkina Faso [108] indicate a high seroprevalence among pregnant women, while studies in West Africa [109] indicate a high seroprevalence in children. Toxoplasmosis is considered a common AIDS defining illness in Ethiopia [110], Nigeria [111], and presumably elsewhere in SSA.
Bacterial Infections
The major bacterial NTDs are trachoma, mycobacterial infections, tick-borne zoonoses, typhoid fever and non-typhoidal salmonellosis, and yaws. With the exception of trachoma, data on the regional prevalence and/or incidence of these diseases area severely lacking, as are disease burden estimates in DALYs (Table 4).
Trachoma.
Trachoma is the leading cause of infectious and preventable blindness worldwide [112]–[114], and the most important bacterial infection in SSA. Of the 63 million cases of active trachoma globally (although some estimates indicate 84 million cases worldwide), 48% occur in SSA (30 million) (Table 2) [115]. Nearly half of the global disease burden of active trachoma and a quarter of end-stage trichiasis are concentrated in ten countries alone, with six of these located in SSA [116]. Geographically, trachoma is distributed mainly in the savannah areas of East and Central Africa and the Sahel of West Africa [112]. Ethiopia has the largest number of cases (10.2 million), followed by Sudan (3.6 million) and Tanzania, Kenya, and Niger (2.0–2.1 million each) (Table 3). Approximately one-half of the 2.3 million global trachoma disease burden in DALYs is attributed to SSA (Table 4). Like the other NTDs, trachoma is sustained in a setting of poverty. Additional risk factors for trachoma transmission include crowding and household clustering, insufficient access to water, poor sanitation and facial hygiene, and young children as the reservoir of infection [115]. For instance, in southern Sudan, where more than 90% of the people live on less than US$1 per day, and only 27% have access to water and 16% to improved sanitation conditions, the prevalence of trachoma is ranked among the highest worldwide [117],[118]. Hyper-endemic areas in SSA have been found to have an earlier age of onset of trichiasis [118], while women are two to four times more likely to have trichiasis due to increased exposure to young children [116],[119]. Dry zones with limited water accessibility and hot lowlands (altitude <3,000 m) with dense fly populations also promote transmission [112],[120]. Post-conflict conditions, namely in Sudan and Rwanda, have been assessed, but with differing conclusions on their impact on the prevalence of blindness. In southern Sudan, the prevalence of blindness (4.1%) is four times greater than that of the rest of Africa [121].
Mycobacterial infections.
Buruli ulcer. Of the estimated 7,000 cases of Buruli ulcer reported annually [38], more than 4,000 cases occur in SSA (Table 2), with the largest number reported from the West African countries of Cote d'Ivoire (approximately 2,000 cases) and Benin and Ghana (reporting approximately 1,000 cases each) (Table 3) [37]. The greatest risk factors for acquiring Buruli ulcer include residing in an endemic area, close proximity to specific bodies of water, and age less than 15 years [37],[38].
Leprosy. In Africa, the number of new cases of leprosy has declined every year since 2001 [35]. At the beginning of 2008, approximately 30,055 cases of leprosy were registered in Africa with 31,037 new cases in 2007 (Table 2) [35]. These represent approximately 14% and 12% of the global prevalence and new cases, respectively (Table 2). In SSA, the highest registered prevalence occurs in DRC (6,502 cases), followed by Nigeria (5,381), Ethiopia (4,611), and Mozambique (1,830) (Table 3) [35]. Similarly, in 2007, the largest number of new cases occured in DRC (8,820), Nigeria (46,650), Ethiopia (4,187), and Mozambique (2,610) [35].
Bovine tuberculosis. Tuberculosis is a major opportunistic infection among HIV-infected populations in SSA and it is estimated that 70% (6 million) of the people co-infected with tuberculosis and HIV live in SSA [122]. The proportion of African tuberculosis due to Mycobacterium bovis is unknown [123], although it is estimated that approximately 50% of African cattle live in countries without control measures for the disease [122]. In SSA, bovine tuberculosis frequently passes from livestock to wildlife, while human populations become infected through the consumption of raw milk and raw meat (including bushmeat) [122]. The prevalence and incidence of bovine tuberculosis in SSA has not been established.
Tick-borne zoonoses.
Tick-borne relapsing fever (TBRF). TBRF is an acute febrile illness caused by the spirochaete Borrelia crocidurae and transmitted by an Ornithodoros tick [124]. If left untreated, patients develop severe relapsing remitting fever, and in some parts of Senegal and elsewhere in West Africa this infection is second only to malaria as the most common cause of outpatient visits [124]. However, detailed information on the precise incidence and distribution of TBRF in SSA is lacking because the disease is underdiagnosed and medical personnel have inadequate awareness of this infection and frequently confuse it with malaria [124].
African tick-bite fever. African tick-bite fever is a spotted fever group rickettsiosis caused by Rickettsia africae and transmitted by Amblyomma ticks [125]. It is known to be endemic in Zimbabwe and South Africa, although based on serologic surveys the infection also occurs elsewhere in SSA [125],[126]. Infection with R. africae is common in travelers returning to Europe and North America [125],[126].
Salmonella and other enteric infections.
Although well-publicized outbreaks of typhoid fever (Salmonella typhi infection) have been reported from Kenya [127], the overall incidence of culture-proven typhoid fever may be lower than 1/100,000 person years [128]. In SSA, S. typhi infection has been noted to occur in association with schistosome infections [129]. Of concern is the emergence of drug-resistant typhoid fever [129],[130]. Similarly, nontyphoidal salmonella (NTS) infection and bacteremia (some of which are caused by drug-resistant strains) is emerging as an important opportunistic infection in individuals infected with HIV and in children [131],[132]. In Malawi and elsewhere in SSA, NTS bacteremia typically presents in children less than 3 years of age, especially those with coincident anemia, malaria, malnutrition, and HIV infection [131]–[133]. Among adults, NTS is most commonly associated with advanced HIV disease [131]. In Malawi, approximately 75% of the cases of NTS are associated with Salmonella enterica serovar Typhimrium and 21% with S. enterica serovar Enteritidis [131],[132]. Campylobacter jejuni has emerged as a common cause of enteritis in Nigeria [134].
Yaws.
Yaws is a skin disease caused by Treponema pallidum, subspecies pertennae, and Africa has the highest concentration of the disease [135]. Africa's indigenous pygmies are disproportionately affected, although there are no published estimates of the disease.
Viral Infections
Arboviral infections, including yellow fever, dengue, Chikungunya and Rift Valley fever [136], and rabies stand out as the most important viral NTDs. As with the bacterial infections, there are few estimates of their incidence or disease burden.
Arobviral infections.
Approximately 90% of the world's 200,000 cases of yellow fever (and 30,000 deaths) occur in SSA [33]. Especially in Francophone West Africa, transmission of yellow fever is maintained by high densities of Aedes aegypti mosquitoes in close proximity to unvaccinated human populations [33]. Yellow fever is underreported, although a laboratory network in the endemic countries of West and Central Africa was established in 2002 in order to strengthen capacity for diagnosis [34]. In 2006, cases of yellow fever were reported in Cameroon, Central African Republic, Cote d'Ivoire, Ghana Guinea, Mali, and Togo [34]. Since 2000, four urban outbreaks have occurred in West Africa, including a 2001 outbreak in Abidjan, Cote d'Ivoire, that required the immunization of 2.6 million people in 12 days [137]. All four dengue viral types have been reported from Africa, although to date no epidemic of dengue hemorrhagic fever has been reported [138]. Epidemics of Chikungunya fever have also been reported in Angola, Burundi, Cameroon, CAR, Kenya, Namibia, Nigeria, Senegal, South Africa, Tanzania, Uganda, and Zimbabwe [125]. Rift Valley fever is a bunyavirus infection transmitted by mosquitoes, which is a problem not only for humans but also for sheep, goats, and cattle. Epidemics and epizootics occur after periods of heavy rains [139]. Epizootics are closely linked to excess rainfall resulting from El Niño and sea surface temperature anomalies in the Indian and Pacific Oceans [139].
Concluding Statement: Disease Assessment and Control Priorities
Overall, it should be noted that the estimates of infection prevalence and morbidity provided here are, in many cases, based on limited data. Moreover, there is often spatial heterogeneity of the NTDs within large geographic units, i.e., at the regional or country level. This is particularly true for most of the vector-borne NTDs. From the analysis reported here, two nations stand out has having the largest number of NTD cases and possibly disease burden. Nigeria is estimated to have the highest prevalence of helminth infections such as hookworm, schistosomiasis, ascariasis, trichuriasis, and LF in SSA, as well as the second highest registered prevalence of leprosy (Table 3). In addition, arboviral and other zoonotic infections are common in Nigeria, including yellow fever, rabies, and toxoplasmosis [134], while Buruli ulcer is found in the southern and southeastern areas of the country [142]. Similarly, DRC exhibits the highest prevalence of HAT and leprosy in SSA, as well as the second highest prevalence of hookworm infection and trichuriasis (and possibly LF), and the third highest prevalence of schistosomiasis and ascariasis (Table 3). Together, Nigeria and DRC account for approximately one-third of the helminth infections and leprosy in SSA, as well as up to one-fifth of the cases of HAT. A targeted approach for these two countries could make a substantial impact on Africa's overall NTD disease burden.
The information presented here indicates that helminth infections, especially the three major STH infections, schistosomiasis, LF, and onchocerciasis, account for up to 85% of the disease burden caused by NTDs in SSA (Table 6). Given that NTDs may be responsible for as much as one-half and one-third of the region's malaria and HIV/AIDS disease burden, respectively, helminth control should continue to be prioritized by public health experts, health ministries, and global policy makers. In addition, based on revised estimates for schistosomiasis that fully consider the morbidities of chronic infection including effects on anemia, malnutrition, growth stunting, and diminished child development [22],[23], and the observation that many of these same sequelae occur for STH and other helminth infections [4], [5], [50], [51], [57]–[61], the possibility remains that maternal and child helminthiases may increase even further in their disease control priority rankings. There is an urgent need for better direct or indirect methods of estimating the disease burden for the NTDs and other conditions. Disease burden estimates for the major helminthiases and other NTDs (based on DALYs as the major metric) are currently being re-evaluated in an initiative led by the Institute for Health Metrics and Evaluation at the University of Washington and supported by the Bill & Melinda Gates Foundation [143]–[145]. Another high priority is to begin obtaining prevalence, incidence, and disease burden estimates for many of the non-helminth NTDs. Amebiasis and toxoplasmosis stand out as both common and serious protozoan infections for which we have very little information. Similarly, the data available for human Salmonella and tick-borne zoonotic bacterial infections are minimal even though some reports suggest they be enormously important. Stepped-up surveillance measures for some of Africa's arboviral infections may provide timely and useful data in the coming years. A full analysis of all Africa's NTDs is an essential step towards prioritizing these conditions relative to ongoing HIV/AIDS and malaria control efforts supported by private foundations and the Group of Eight nations.
References
- 1. Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, et al. (2007) Control of neglected tropical diseases. N Engl J Med 357(10): 1018–1027. 10.1056/NEJMra064142.
- 2.
Chen SH, Ravallion M (2008) The developing world is poorer than we thought, but no less successful in the fight against poverty. World Bank Policy Research Working Paper 4703 (WPS 4703). Available: http://www-wds.worldbank.org. Accessed November 2, 2008.
- 3. Molyneux DH, Hotez PJ, Fenwick A (2005) “Rapid-impact interventions”: how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor. PLoS Med 2(11): e336.
- 4. Brooker S, Clements AC, Bundy DA (2006) Global epidemiology, ecology and control of soil-transmitted helminth infections. Adv Parasitol 62: 221–261. 10.1016/S0065-308X(05)62007-6.
- 5. Brooker S, Clements AC, Hotez PJ, Hay SI, Tatem AJ, et al. (2006) The co-distribution of plasmodium falciparum and hookworm among African schoolchildren. Malar J 5: 99. 10.1186/1475-2875-5-99.
- 6. Fenwick A (2006) New initiatives against Africa's worms. Trans R Soc Trop Med Hyg 100: 200–207.
- 7. Fenwick A, Molyneux D, Nantulya V (2005) Achieving the millennium development goals. Lancet 365(9464): 1029–1030. 10.1016/0140-6736(05)71134-X.
- 8. Olsen A (2007) Efficacy and safety of drug combinations in the treatment of schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis and onchocerciasis. Trans R Soc Trop Med Hyg 101(8): 747–758. 10.1016/j.trstmh.2007.03.006.
- 9. Gyapong JO, Gyapong M, Evans DB, Aikins MK, Adjei S (1996) The economic burden of lymphatic filariasis in northern Ghana. Ann Trop Med Parasitol 90(1): 39–48.
- 10. Drake LJ, Jukes MC, Sternberg RJ, Bundy DAP (2000) Geohelminth infections (ascariasis, trichuriasis, and hookworm): cognitive and developmental impacts. Semin Pediatr Infect Dis 11(1): 245–251.
- 11. Drake LJ, Bundy DA (2001) Multiple helminth infections in children: impact and control. Parasitology 122 Suppl S73–S81.
- 12. Jukes MC, Nokes CA, Alcock KJ, Lambo JK, Kihamia C, et al. (2002) Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren. Trop Med Int Health 7(2): 104–117.
- 13. Beasley M, Brooker S, Ndinaromtan M, Madjiouroum EM, Baboguel M, et al. (2002) First nationwide survey of the health of schoolchildren in Chad. Trop Med Int Health 7(7): 625–630.
- 14. Miguel EA, Kremer M (2003) Worms: identifying impacts on education and health in the presence of treatment externalities. Econometrica 72: 159–217.
- 15.
Amazigo U, Noma M, Bump J, Benton B, Liese B, et al. (2006) Onchocerciasis (chapter 15). In: Jamison DT, Feachem RG, Makgoba MW, Bos ER, Bingana FK, Hofman KJ, Rogo KO, editors. Disease and mortality in Sub-Saharan Africa. Second edition. Washington (D.C.): World Bank. pp. 215–222.
- 16. Ajanga A, Lwambo NJ, Blair L, Nyandindi U, Fenwick A, et al. (2006) Schistosoma mansoni in pregnancy and associations with anaemia in northwest Tanzania. Trans R Soc Trop Med Hyg 100: 59–63.
- 17. Brooker S, Hotez PJ, Bundy DA (2008) Hookworm-related anaemia among pregnant women: a systematic review. PLoS Negl Trop Dis 2(9): e291.
- 18. Brooker S, Michael E (2000) The potential of geographical information systems and remote sensing in the epidemiology and control of human helminth infections. Adv Parasitol 47: 245–288.
- 19. Brooker S, Beasley M, Ndinaromtan M, Madjiouroum EM, Baboguel M, et al. (2002) Use of remote sensing and a geographical information system in a national helminth control programme in Chad. Bull World Health Organ 80(10): 783–789.
- 20. Brooker S, Kabatereine NB, Tukahebwa EM, Kazibwe F (2004) Spatial analysis of the distribution of intestinal nematode infections in Uganda. Epidemiol Infect 132(6): 1065–1071.
- 21. Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6(7): 411–425. 10.1016/S1473-3099(06)70521-7.
- 22. King CH, Dangerfield-Cha M (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4(1): 65–79. 10.1177/1742395307084407.
- 23. King CH, Dickman K, Tisch DJ (2005) Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365(9470): 1561–1569. 10.1016/S0140-6736(05)66457-4.
- 24. de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, et al. (2003) Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19(12): 547–551.
- 25. Michael E, Bundy DA (1997) Global mapping of lymphatic filariasis. Parasitol Today 13(12): 472–476.
- 26.
Global Alliance to Eliminate Lymphatic Filariasis (15 November 2008) African programme review group. Accessed 27 July 2009.
- 27. Zagaria N, Savioli L (2002) Elimination of lymphatic filariasis: a public-health challenge. Ann Trop Med Parasitol 96: Suppl 2S3–S13.
- 28.
Global Alliance to Eliminate Lymphatic Filariasis (2005) Global alliance to eliminate lymphatic filariasis—progress as of January 2005. Available: http://www.filariasis.org/pdfs/GAELFnumbers6_13.pdf. Accessed 27 July 2009.
- 29. Boatin BA, Richards FO Jr (2006) Control of onchocerciasis. Adv Parasitol 61: 349–394. 10.1016/S0065-308X(05)61009-3.
- 30.
World Health Organization (2008) Global health atlas. Global Alliance for the Elimination of Blinding Trachoma database. Available: http://www.who.int/globalatlas/. Accessed 27 July 2009.
- 31. Stoll NR (1999) This wormy world. J Parasitol 85(3): 392–396.
- 32. Padgett JJ, Jacobsen KH (2008) Loiasis: African eye worm. Trans R Soc Trop Med Hyg 102(10): 983–989. 10.1016/j.trstmh.2008.03.022.
- 33. Barnett ED (2007) Yellow fever: epidemiology and prevention. Clin Infect Dis 44(6): 850–856. 10.1086/511869.
- 34.
World Health Organization (2008) Yellow fever in Africa and South America, 2006. Wkly Epidemiol Rec. 83(8). : 60–76.
- 35.
World Health Organization (2008) Global leprosy situation, beginning of 2008. Wkly Epidemiol Rec. 83(33). : 293–300.
- 36.
World Health Organization (2008) Dracunculiasis eradication. Wkly Epidemiol Rec. 83(18). : 159–167.
- 37.
World Health Organization (2008) Buruli ulcer: Progress report, 2004–2008. Wkly Epidemiol Rec. 83(17). : 145–154.
- 38. Walsh DS, Portaels F, Meyers WM (2008) Buruli ulcer (mycobacterium ulcerans infection). Trans R Soc Trop Med Hyg 102(10): 969–978. 10.1016/j.trstmh.2008.06.006.
- 39.
World Health Organization (2006) Human African trypanosomiasis (sleeping sickness): epidemiological update. Wkly Epidemiol Rec. 81(8). : 71–80.
- 40.
World Health Organization (August 2006) African trypanosomiasis (sleeping sickness). Accessed 27 July 2009.
- 41. Alvar J, Aparicio P, Aseffa A, Den Boer M, Canavate C, et al. (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21(2): 334–59, table of contents. 10.1128/CMR.00061-07.
- 42. Reithinger R, Brooker S, Kolaczinski JH (2007) Visceral leishmaniasis in eastern Africa—current status. Trans R Soc Trop Med Hyg 101(12): 1169–1170. 10.1016/j.trstmh.2007.06.001.
- 43. Bern C, Maguire JH, Alvar J (2008) Complexities of assessing the disease burden attributable to leishmaniasis. PLoS Negl Trop Dis 2(10): e313.
- 44. Collin S, Davidson R, Ritmeijer K, Keus K, Melaku Y, et al. (2004) Conflict and kala-azar: Determinants of adverse outcomes of kala-azar among patients in southern Sudan. Clin Infect Dis 38(5): 612–619. 10.1086/381203.
- 45.
World Health Organization (2004) World health report 2004 - changing history. 2004. Burden of disease in DALYs by cause, sex and mortality stratum in WHO regions, estimates for 2002. Geneva: WHO. Annex Table. 3. : 126–131. Available: http://www.who.int/whr/2004/en/. Accessed 27 July 2009.
- 46. Chan MS (1997) The global burden of intestinal nematode infections—fifty years on. Parasitol Today 13(11): 438–443.
- 47. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, et al. (2006) Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/ADIS, tuberculosis, and malaria. PLoS Med 3: e102.
- 48. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, et al. (2006) Soil-transmitted helminth infections: Ascariasis, trichuriasis, and hookworm. Lancet 367(9521): 1521–1532. 10.1016/S0140-6736(06)68653-4.
- 49. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, et al. (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118(4): 1311–1321. 10.1172/JCI34261.
- 50. Stephenson LS, Latham MC, Kurz KM, Kinoti SN, Brigham H (1989) Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, trichuris trichiura, and ascaris lumbricoides infections. Am J Trop Med Hyg 41(1): 78–87.
- 51. Stephenson LS, Latham MC, Kinoti SN, Kurz KM, Brigham H (1990) Improvements in physical fitness of Kenyan schoolboys infected with hookworm, trichuris trichiura and ascaris lumbricoides following a single dose of albendazole. Trans R Soc Trop Med Hyg 84(2): 277–282.
- 52. Mabaso ML, Appleton CC, Hughes JC, Gouws E (2004) Hookworm (necator americanus) transmission in inland areas of sandy soils in KwaZulu-natal, South Africa. Trop Med Int Health 9(4): 471–476. 10.1111/j.1365-3156.2004.01216.x.
- 53. Behnke JM, De Clercq D, Sacko M, Gilbert FS, Ouattara DB, et al. (2000) The epidemiology of human hookworm infections in the southern region of mail. Trop Med Int Health 5(5): 343–354.
- 54. De Clercq D, Sacko M, Behnke J, Gilbert F, Dorny P, et al. (1997) Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. Am J Trop Med Hyg 57(1): 25–30.
- 55. Brooker S, Akhwale W, Pullan R, Estambale B, Clarke SE, et al. (2007) Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. Am J Trop Med Hyg 77: (6 Suppl)88–98.
- 56. Albonico M, Stoltzfus RJ, Savioli L, Tielsch JM, Chwaya HM, et al. (1998) Epidemiological evidence for a differential effect of hookworm species, ancylostoma duodenale or necator americanus, on iron status of children. Int J Epidemiol 27(3): 530–537.
- 57. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, et al. (2004) Hookworm infection. N Engl J Med 351(8): 799–807. 10.1056/NEJMra032492.
- 58. Stoltzfus RJ, Chwaya HM, Tielsch JM, Schulze KJ, Albonico M, et al. (1997) Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms. Am J Clin Nutr 65(1): 153–159.
- 59. Brooker S, Peshu N, Warn PA, Mosobo M, Guyatt HL, et al. (1999) The epidemiology of hookworm infection and its contribution to anaemia among pre-school children on the Kenyan coast. Trans R Soc Trop Med Hyg 93(3): 240–246.
- 60. Albonico M, Allen H, Chitsulo L, Engels D, Gabrielli AF, et al. (2008) Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy. PLoS Negl Trop Dis 2(3): e126.
- 61. Crompton DW (2000) The public health importance of hookworm disease. Parasitology 121 Suppl S39–S50.
- 62. Dada-Adegbola HO, Oluwatoba AO, Falade CO (2005) Prevalence of multiple intestinal helminths among children in a rural community. Afr J Med Med Sci 34(3): 263–267.
- 63. Saathoff E, Olsen A, Kvalsvig JD, Appleton CC (2004) Patterns of geohelminth infection, impact of albendazole treatment and re-infection after treatment in schoolchildren from rural KwaZulu-Natal/South-Africa. BMC Infect Dis 4: 27. 10.1186/1471-2334-4-27.
- 64. Saathoff E, Olsen A, Kvalsvig JD, Appleton CC, Sharp B, et al. (2005) Ecological covariates of ascaris lumbricoides infection in schoolchildren from rural KwaZulu-natal, south Africa. Trop Med Int Health 10(5): 412–422. 10.1111/j.1365-3156.2005.01406.x.
- 65. Dada-Adegbola HO, Bakare RA (2004) Strongyloidiasis in children five years and below. West Afr J Med 23(3): 194–197.
- 66. Ziem JB, Magnussen P, Olsen A, Horton J, Asigri VL, et al. (2006) Impact of repeated mass treatment on human oesophagostomum and hookworm infections in northern Ghana. Trop Med Int Health 11(11): 1764–1772. 10.1111/j.1365-3156.2006.01729.x.
- 67. Bradley M (1990) Rate of expulsion of necator americanus and the false hookworm ternidens deminutus railliet and henry 1909 (nematoda) from humans following albendazole treatment. Trans R Soc Trop Med Hyg 84(5): 720.
- 68. Beck-Worner C, Raso G, Vounatsou P, N'Goran EK, Rigo G, et al. (2007) Bayesian spatial risk prediction of schistosoma mansoni infection in western Cote d'Ivoire using a remotely-sensed digital elevation model. Am J Trop Med Hyg 76(5): 956–963.
- 69. Kabatereine NB, Brooker S, Tukahebwa EM, Kazibwe F, Onapa AW (2004) Epidemiology and geography of schistosoma mansoni in Uganda: implications for planning control. Trop Med Int Health 9(3): 372–380.
- 70. Ekpo UF, Mafiana CF, Adeofun CO, Solarin AR, Idowu AB (2008) Geographical information system and predictive risk maps of urinary schistosomiasis in Ogun state, Nigeria. BMC Infect Dis 8: 74. 10.1186/1471-2334-8-74.
- 71. Fenwick A, Rollinson D, Southgate V (2006) Implementation of human schistosomiasis control: Challenges and prospects. Adv Parasitol 61: 567–622. 10.1016/S0065-308X(05)61013-5.
- 72. Mangal TD, Paterson S, Fenton A (2008) Predicting the impact of long-term temperature changes on the epidemiology and control of schistosomiasis: A mechanistic model. PLoS ONE 3(1): e1438.
- 73. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, et al. (2003) Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop 86(2–3): 125–139.
- 74. Maxwell Parkin D (2008) The global burden of urinary bladder cancer. Scand J Urol Nephrol 1–9. 10.1080/03008880802285032.
- 75. Swai B, Poggensee G, Mtweve S, Krantz I (2006) Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: A retrospective histopathological study from Tanzania. BMC Infect Dis 6: 134. 10.1186/1471-2334-6-134.
- 76. Kjetland EF, Ndhlovu PD, Gorno E, Mduluza T, Midzi N, et al. (2006) Association between genital schistosomiasis and HIV in rural Zimbabwean women. AIDS 20: 593–600.
- 77. Tchuem Tchuente LA, Southgate VR, Jourdane J, Webster BL, Vercruysse J (2003) Schistosoma intercalatum: An endangered species in Cameroon? Trends Parasitol 19(9): 389–393.
- 78. Raso G, Vounatsou P, Singer BH, N'Goran EK, Tanner M, et al. (2006) An integrated approach for risk profiling and spatial prediction of schistosoma mansoni-hookworm coinfection. Proc Natl Acad Sci U S A 103(18): 6934–6939. 10.1073/pnas.0601559103.
- 79. Raso G, Vounatsou P, Gosoniu L, Tanner M, N'Goran EK, et al. (2006) Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Cote d'Ivoire. Int J Parasitol 36(2): 201–210. 10.1016/j.ijpara.2005.09.003.
- 80. Hotez PJ, Bethony JM, Oliveira SC, Brindley PJ, Loukas A (2008) Multivalent anthelminthic vaccine to prevent hookworm and schistosomiasis. Expert Rev Vaccines 7(6): 745–752. 10.1586/14760584.7.6.745.
- 81. Sokhna C, Le Hesran JY, Mbaye PA, Akiana J, Camara P, et al. (2004) Increase of malaria attacks among children presenting concomitant infection by schistosoma mansoni in Senegal. Malar J 3: 43. 10.1186/1475-2875-3-43.
- 82. Keiser J, Utzinger J (2005) Emerging foodborne trematodiasis. Emerg Infect Dis 11(10): 1507–1514.
- 83. Preux PM, Druet-Cabanac M (2005) Epidemiology and aetiology of epilepsy in sub-Saharan Africa. Lancet Neurol 4(1): 21–31. 10.1016/S1474-4422(04)00963-9.
- 84. Nsengiyumva G, Druet-Cabanac M, Ramanankandrasana B, Bouteille B, Nsizabira L, et al. (2003) Cysticercosis as a major risk factor for epilepsy in Burundi, east Africa. Epilepsia 44(7): 950–955.
- 85. Boa M, Mukaratirwa S, Willingham AL, Johansen MV (2003) Regional action plan for combating taenia solium cysticercosis/taeniosis in Eastern and Southern Africa. Acta Trop 87(1): 183–186.
- 86. Carabin H, Krecek RC, Cowan LD, Michael L, Foyaca-Sibat H, et al. (2006) Estimation of the cost of taenia solium cysticercosis in eastern cape province, south Africa. Trop Med Int Health 11(6): 906–916. 10.1111/j.1365-3156.2006.01627.x.
- 87. Zoli AP, Nguekam , Shey-Njila O, Nsame Nforninwe D, Speybroeck N, et al. (2003) Neurocysticercosis and epilepsy in Cameroon. Trans R Soc Trop Med Hyg 97(6): 683–686.
- 88. Katabarwa M, Lakwo T, Habumogisha P, Richards F, Eberhard M (2008) Could neurocysticercosis be the cause of “onchocerciasis-associated” epileptic seizures? Am J Trop Med Hyg 78(3): 400–401.
- 89. Abunna F, Tilahun G, Megersa B, Regassa A (2007) Taeniasis and its socio-economic implication in awassa town and its surroundings, southern Ethiopia. East Afr J Public Health 4(2): 73–79.
- 90. Elmahdi IE, Ali QM, Magzoub MM, Ibrahim AM, Saad MB, et al. (2004) Cystic echinococcosis of livestock and humans in central Sudan. Ann Trop Med Parasitol 98(5): 473–479. 10.1179/000349804225003578.
- 91. World Health Organization (2008) Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec 83(37): 333–341.
- 92. Ottesen EA (2006) Lymphatic filariasis: Treatment, control and elimination. Adv Parasitol 61: 395–441. 10.1016/S0065-308X(05)61010-X.
- 93. Ottesen EA, Hooper PJ, Bradley M, Biswas G (2008) The global programme to eliminate lymphatic filariasis: Health impact after 8 years. PLoS Negl Trop Dis 2(10): e317.
- 94. Njenga SM, Wamae CN, Njomo DW, Mwandawiro CS, Molyneux DH (2007) Chronic clinical manifestations related to wuchereria bancrofti infection in a highly endemic area in Kenya. Trans R Soc Trop Med Hyg 101(5): 439–444. 10.1016/j.trstmh.2006.09.006.
- 95. Haddix AC, Kestler A (2000) Lymphatic filariasis: Economic aspects of the disease and programmes for its elimination. Trans R Soc Trop Med Hyg 94(6): 592–593.
- 96. Mathieu E, Amann J, Eigege A, Richards F, Sodahlon Y (2008) Collecting baseline information for national morbidity alleviation programs: different methods to estimate lymphatic filariasis morbidity prevalence. Am J Trop Med Hyg 78(1): 153–158.
- 97. Davey G, Tekola F, Newport MJ (2007) Podoconiosis: non-infectious geochemical elephantiasis. Trans R Soc Trop Med Hyg 101(12): 1175–1180. 10.1016/j.trstmh.2007.08.013.
- 98. Boussinesq M (2006) Loiasis. Ann Trop Med Parasitol 100(8): 715–731. 10.1179/136485906X112194.
- 99. Hopkins DR, Ruiz-Tiben E, Downs P, Withers PC Jr, Roy S (2008) Dracunculiasis eradication: neglected no longer. Am J Trop Med Hyg 79(4): 474–479.
- 100. Fevre EM, Picozzi K, Jannin J, Welburn SC, Maudlin I (2006) Human African trypanosomiasis: epidemiology and control. Adv Parasitol 61: 167–221. 10.1016/S0065-308X(05)61005-6.
- 101. Fevre EM, Picozzi K, Fyfe J, Waiswa C, Odiit M, et al. (2005) A burgeoning epidemic of sleeping sickness in Uganda. Lancet 366(9487): 745–747. 10.1016/S0140-6736(05)67179-6.
- 102. Kolaczinski JH, Reithinger R, Worku DT, Ocheng A, Kasimiro J, et al. (2008) Risk factors of visceral leishmaniasis in East Africa: a case-control study in pokot territory of Kenya and Uganda. Int J Epidemiol 37(2): 344–352. 10.1093/ije/dym275.
- 103. Alvar J, Croft S, Olliaro P (2006) Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol 61: 223–274. 10.1016/S0065-308X(05)61006-8.
- 104. Kolaczinski JH, Hope A, Ruiz JA, Rumunu J, Richer M, et al. (2008) Kala-azar epidemiology and control, southern Sudan. Emerg Infect Dis 14(4): 664–666.
- 105. Stauffer W, Abd-Alla M, Ravdin JI (2006) Prevalence and incidence of entamoeba histolytica infection in South Africa and Egypt. Arch Med Res 37(2): 266–269. 10.1016/j.arcmed.2005.10.006.
- 106. Okeke IN, Ojo O, Lamikanra A, Kaper JB (2003) Etiology of acute diarrhea in adults in southwestern Nigeria. J Clin Microbiol 41(10): 4525–4530.
- 107. Elnahas A, Gerais AS, Elbashir MI, Eldien ES, Adam I (2003) Toxoplasmosis in pregnant Sudanese women. Saudi Med J 24(8): 868–870.
- 108. Simpore J, Savadogo A, Ilboudo D, Nadambega MC, Esposito M, et al. (2006) Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV-positive and -negative pregnant women in Burkina Faso. J Med Virol 78(6): 730–733. 10.1002/jmv.20615.
- 109. Fan CK, Hung CC, Su KE, Chiou HY, Gil V, et al. (2007) Seroprevalence of toxoplasma gondii infection among inhabitants in the democratic republic of Sao Tome and Principe. Trans R Soc Trop Med Hyg 101(11): 1157–1158. 10.1016/j.trstmh.2007.04.010.
- 110. Amogne W, Teshager G, Zenebe G (2006) Central nervous system toxoplasmosis in adult Ethiopians. Ethiop Med J 44(2): 113–120.
- 111. Uneke CJ, Duhlinska DD, Njoku MO, Ngwu BA (2005) Seroprevalence of acquired toxoplasmosis in HIV-infected and apparently healthy individuals in Jos, Nigeria. Parassitologia 47(2): 233–236.
- 112. Polack S, Brooker S, Kuper H, Mariotti S, Mabey D, et al. (2005) Mapping the global distribution of trachoma. Bull World Health Organ 83(12): /S0042-96862005001200013: 913–919.
- 113. Chidambaram JD, Alemayehu W, Melese M, Lakew T, Yi E, et al. (2006) Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma. JAMA 295(10): 1142–1146. 10.1001/jama.295.10.1142.
- 114. Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, et al. (2007) Oral drug therapy for multiple neglected tropical diseases: a systematic review. JAMA 298(16): 1911–1924. 10.1001/jama.298.16.1911.
- 115. Wright HR, Turner A, Taylor HR (2008) Trachoma. Lancet 371(9628): 1945–1954. 10.1016/S0140-6736(08)60836-3.
- 116. Mecaskey JW, Knirsch CA, Kumaresan JA, Cook JA (2003) The possibility of eliminating blinding trachoma. Lancet Infect Dis 3(11): 728–734.
- 117. Ngondi J, Matthews F, Reacher M, Onsarigo A, Matende I, et al. (2007) Prevalence of risk factors and severity of active trachoma in southern Sudan: an ordinal analysis. Am J Trop Med Hyg 77(1): 126–132.
- 118. Ngondi J, Reacher M, Matthews F, Ole-Sempele F, Onsarigo A, et al. (2007) The epidemiology of low vision and blindness associated with trichiasis in southern Sudan. BMC Ophthalmol 7: 12. 10.1186/1471-2415-7-12.
- 119. West S, Nguyen MP, Mkocha H, Holdsworth G, Ngirwamungu E, et al. (2004) Gender equity and trichiasis surgery in the Vietnam and Tanzania national trachoma control programmes. Br J Ophthalmol 88(11): 1368–1371. 10.1136/bjo.2004.041657.
- 120. Alemayehu W, Melese M, Fredlander E, Worku A, Courtright P (2005) Active trachoma in children in central Ethiopia: association with altitude. Trans R Soc Trop Med Hyg 99(11): 840–843. 10.1016/j.trstmh.2005.06.013.
- 121. Mathenge W, Kuper H, Limburg H, Polack S, Onyango O, et al. (2007) Rapid assessment of avoidable blindness in Nakuru district, Kenya. Ophthalmology 114(3): 599–605. 10.1016/j.ophtha.2006.06.057.
- 122. Etter E, Donado P, Jori F, Caron A, Goutard F, et al. (2006) Risk analysis and bovine tuberculosis, a re-emerging zoonosis. Ann N Y Acad Sci 1081: 61–73. 10.1196/annals.1373.006.
- 123. Ayele WY, Neill SD, Zinsstag J, Weiss MG, Pavlik I (2004) Bovine tuberculosis: an old disease but a new threat to Africa. Int J Tuberc Lung Dis 8(8): 924–937.
- 124. Vial L, Diatta G, Tall A, Ba el H, Bouganali H, et al. (2006) Incidence of tick-borne relapsing fever in West Africa: longitudinal study. Lancet 368(9529): 37–43. 10.1016/S0140-6736(06)68968-X.
- 125. Ndip LM, Bouyer DH, Travassos Da Rosa AP, Titanji VP, Tesh RB, et al. (2004) Acute spotted fever rickettsiosis among febrile patients, Cameroon. Emerg Infect Dis 10(3): 432–437.
- 126. Raoult D, Fournier PE, Fenollar F, Jensenius M, Prioe T, et al. (2001) Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa. N Engl J Med 344(20): 1504–1510.
- 127. Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, et al. (2006) Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet 367(9509): 482–488. 10.1016/S0140-6736(06)68180-4.
- 128. Mweu E, English M (2008) Typhoid fever in children in Africa. Trop Med Int Health 13(4): 532–540. 10.1111/j.1365-3156.2008.02031.x.
- 129. Crum NF (2003) Current trends in typhoid fever. Curr Gastroenterol Rep 5(4): 279–286.
- 130. World Health Organization (2008) Typhoid vaccines: WHO position paper. Wkly Epidemiol Rec 83(6): 49–59.
- 131. Graham SM, Molyneux EM, Walsh AL, Cheesbrough JS, Molyneux ME, et al. (2000) Nontyphoidal salmonella infections of children in tropical Africa. Pediatr Infect Dis J 19(12): 1189–1196.
- 132. Gordon MA, Graham SM, Walsh AL, Wilson L, Phiri A, et al. (2008) Epidemics of invasive salmonella enterica serovar enteritidis and S. enterica serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. Clin Infect Dis 46(7): 963–969. 10.1086/529146.
- 133. Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, et al. (2005) Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 352(1): 39–47. 10.1056/NEJMoa040275.
- 134. Coker AO, Isokpehi RD, Thomas BN, Fagbenro-Beyioku AF, Omilabu SA (2000) Zoonotic infections in Nigeria: overview from a medical perspective. Acta Trop 76(1): 59–63.
- 135. Asiedu K (2008) The return of yaws. Bull World Health Organ 86(7): 507–508.
- 136. Kuniholm MH, Wolfe ND, Huang CY, Mpoudi-Ngole E, Tamoufe U, et al. (2006) Seroprevalence and distribution of flaviviridae, togaviridae, and bunyaviridae arboviral infections in rural Cameroonian adults. Am J Trop Med Hyg 74(6): 1078–1083.
- 137. Roberts L (2007) Infectious disease. Resurgence of yellow fever in Africa prompts a counterattack. Science 316(5828): 1109. 10.1126/science.316.5828.1109.
- 138. Malavige GN, Fernando S, Fernando DJ, Seneviratne SL (2004) Dengue viral infections. Postgrad Med J 80(948): 588–601. 10.1136/pgmj.2004.019638.
- 139. LaBeaud AD, Ochiai Y, Peters CJ, Muchiri EM, King CH (2007) Spectrum of rift valley fever virus transmission in Kenya: insights from three distinct regions. Am J Trop Med Hyg 76(5): 795–800.
- 140. Cohen C, Sartorius B, Sabeta C, Zulu G, Paweska J, et al. (2007) Epidemiology and molecular virus characterization of reemerging rabies, South Africa. Emerg Infect Dis 13(12): 1879–1886.
- 141. Pfukenyi DM, Pawandiwa D, Makaya PV, Ushewokunze-Obatolu U (2007) A retrospective study of rabies in humans in Zimbabwe, between 1992 and 2003. Acta Trop 102(3): 190–196. 10.1016/j.actatropica.2007.04.013.
- 142. Chukwuekezie O, Ampadu E, Sopoh G, Dossou A, Tiendrebeogo A, et al. (2007) Buruli ulcer, Nigeria. Emerg Infect Dis 13(5): 782–783.
- 143. Mathers CD, Ezzati M, Lopez AD (2007) Measuring the burden of neglected tropical diseases: the global burden of disease framework. PLoS Negl Trop Dis 1(2): e114.
- 144. Hotez P (2007) Measuring neglect. PLoS Negl Trop Dis 1(2): e118.
- 145. Stein C, Kuchenmuller T, Hendrickx S, Pruss-Ustun A, Wolfson L, et al. (2007) The global burden of disease assessments—WHO is responsible? PLoS Negl Trop Dis 1(3): e161.