Article:Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden (2727001)

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Journal Information

Title: PLoS Neglected Tropical Diseases

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

  • Peter J. Hotez
  • Aruna Kamath

[1]Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, D.C., United States of America

[2]Sabin Vaccine Institute, Washington, D.C., United States of America

  • Michael Cappello (Editor)

Yale Child Health Research Center, United States of America

Publication date (collection): 8/2009

Publication date (epub): 8/2009

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.

Paper

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].

10.1371/journal.pntd.0000412.t001Table 1

Poverty in Sub-Saharan Africa.

Percentage of SSA population living on less than US$1.25 per day 51%
Total SSA population living on less than $1.25 per day 390.6 million
Percentage of world's population living on less than US$1.25 per day in SSA 28%
Percentage of SSA population living on less than US$2 per day 73%
Total SSA population living on less than $2 per day 556.7 million
Percentage of world's population living on less than US$2 per day in SSA 22%

From reference [2].

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.

10.1371/journal.pntd.0000412.t002Table 2

Ranking of Neglected Tropical Diseases (NTDs) in SSA by Prevalence and Distribution.

Disease Estimated Population Infected in SSA Estimated % of SSA Population Infected Estimated % Global Disease Burden in SSA Reference
Hookworm 198 million 29%a 34%b [3],[24]
Schistosomiasis 192 million 25% 93% [21]
Ascariasis 173 million 25%a 21%2b [3],[24]
Trichuriasis 162 million 24%a 27%b [3],[24]
Lymphatic filariasis 46–51 million 6%–9% 37%–44%c [25][28]
Onchocerciasis 37 million 5% >99% [15],[29]
Active trachoma 30 million 3% 48% [30]
Loiasis ≤13 million 1%–2% 100% [31],[32]
Yellow fever 180,000 0.02% 90% [33],[34]
Human African trypanosomiasis 50,000–70,000 (17,000 new cases annually) <0.01% 100% [39],[40]
Leprosy 30,055 (registered prevalence); 21,037 new cases in 2007 <0.01% 14% [35]
Leishmaniasis (visceral) 19,000–24,000 new cases annually in Sudan and Ethiopia <0.01 ND [41][44]
Dracunculiasis 9,585 <0.01% 100% [36]
Buruli ulcer >4,000 <0.01% 57% [37],[38]
a

Based on reported 2003 population of 683,330,334 [24]. For all other estimated population prevalence, we use the 2005 value of 764,328,000 published by the United Nations, http://esa.un.org/unpp/, and querying sub-Saharan Africa and 2005, accessed July 29, 2009.

b

Calculated from global burden data from [48].

c

The lower value is from [3],[26],[27]; the higher value from [25].

10.1371/journal.pntd.0000412.t003Table 3

Geographic Distribution and Estimated Burden of the Major Helminth NTDs in SSA.

Disease (Number of Cases in SSA) Country with Highest Prevalence Country with Second Highest Prevalence Country with Third Highest Prevalence Country with Fourth Highest Prevalence Reference
Hookworm infection (198 million) Nigeria 38 million DR Congo 31 million Angola and Ethiopia 11 million cases each Cote d'Ivoire 10 million [24]
Schistosomiasis (192 million) Nigeria 29 million Tanzania 19 million DR Congo and Ghana 15 million cases each Mozambique 13 million [21]
Ascariasis (173 million) Nigeria 55 million Ethiopia 26 million DR Congo 23 million South Africa 12 million [24]
Trichuriasis (162 million) Nigeria 34 million DR Congo 26 million South Africa 22 million Ethiopia 21 million [24]
Lymphatic filariasis (382–394 million at risk) Nigeria 106 million at risk DR Congo 49 million at risk Tanzania 31 million at risk Ethiopia 30 million at risk, Kenya 29 million at risk [28]
Trachoma (30 million) Ethiopia 10.3 million Sudan 3.6 million Tanzania 2.1 million Kenya and Niger 2.0 million cases each [30]
Yellow fever (180,000) Cote d'Ivoire 16 reported cases in 2006 Mali 5 reported cases in 2006 Cameroon, CAR, Ghana, and Guinea 1 case each in 2006 [33],[34]
Human African trypanosomiasis (50,000–70,000) DR Congo 10,369 Angola 2,280 Sudan 1,766 Congo 839 [39]
Leprosy (30,055) DR Congo 6,502 Nigeria 5,381 Ethiopia 4,611 Mozambique 1,830 [35]
Leishmaniasis (visceral) (19,000–24,000 new cases) Sudan 15,000–20,000 new cases Ethiopia 4,000 new cases Kenya and Uganda not determined [41][44]
Dracunculiasis (9,585) Sudan 5,815 Ghana 3,358 Mali 313 Nigeria and Niger<100 cases each [36]
Buruli ulcer (>4,000) Cote d'Ivoire 2,000 Benin and Ghana 1,000 each [37]
10.1371/journal.pntd.0000412.t004Table 4

Major NTDs with No Regional Prevalence or Incidence Estimates in SSA.

Helminth Infections Protozoan Infections Bacterial Infections Viral Infections Other Conditions
Strongyloidiasis Amebiasis Bovine tuberculosis Dengue fever Podoconiosis
Taeniaisis Toxoplasmosis Tick-borne relapsing fever Rift Valley fever
Paragonimiasis African tick-bite fever Chikungunya
Oesophagostomiasis Typhoid fever Rabies
Non-typhoidal salmonellosis
Yaws
10.1371/journal.pntd.0000412.t005Table 5

Disease Burden (DALYs) in SSA Resulting from the NTDs.

Disease Estimated Global Disease Burden in DALYs Estimated % Disease Burden in SSA Estimated SSA Disease Burden in DALYs Reference
Hookworm 1.5–22.1 million 34% 0.5–7.5 million [46][48]
Schistosomiasis 1.7–4.5 million 93% 1.6–4.2 million [21],[45],[47]
Ascariasis 1.8–10.5 million 21% 0.4–2.2 million [46][48]
Lymphatic filariasis 5.8 million 35% 2.0 million [45]
Trichuriasis 1.8–6.4 million 27% 0.5–1.7 million [46][48]
Human African trypanosomiasis 1.5 million 100% 1.5 million [45]
Trachoma 2.3 million 52% 1.2 million [45]
Onchocerciasis 0.5 million 99% 0.5 million [45]
Leishmaniasis 2.1 million 18% 0.4 million [45]
Leprosy 0.2 million 14% 0.02 million [35],[45]
Dengue 0.6 million <1% 0.005 million [45]
Total NTDs ≤56.6 million 15%–37% 8.6 million–21.2 million [47]

DALY estimates for 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.

10.1371/journal.pntd.0000412.t006Table 6

Ranking by Disease Burden (DALYs) and Comparison of Total NTDs with HIV/AIDS, Tuberculosis, and Malaria.

Disease Disease Burden in SSA (DALYs) Reference
HIV/AIDS 64.0 million [45]
Malaria 40.9 million [45]
NTDs 8.6–21.2 million
Helminth infections 5.4–18.3 million
Tuberculosis 9.3 million [45]

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].

Rabies

Following India, the greatest number of cases of human rabies transmitted from dogs occurs in SSA [140]. In Limpopo Province (South Africa) alone, 100 cases occurred in 2006 [140]. There are two distinct biotypes in southern Africa, a canid virus and a mongoose virus [141].

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. PJ HotezDH MolyneuxA FenwickJ KumaresanSE Sachs2007Control of neglected tropical diseases.N Engl J Med357(10)1018102710.1056/NEJMra06414217804846
  2. SH ChenM Ravallion2008The 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. DH MolyneuxPJ HotezA Fenwick2005“Rapid-impact interventions”: how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor.PLoS Med2(11)e336doi:10.1371/journal.pmed.002033616212468
  4. S BrookerAC ClementsDA Bundy2006Global epidemiology, ecology and control of soil-transmitted helminth infections.Adv Parasitol6222126110.1016/S0065-308X(05)62007-616647972
  5. S BrookerAC ClementsPJ HotezSI HayAJ Tatem2006The co-distribution of plasmodium falciparum and hookworm among African schoolchildren.Malar J59910.1186/1475-2875-5-9917083720
  6. A Fenwick2006New initiatives against Africa's worms.Trans R Soc Trop Med Hyg10020020716343572
  7. A FenwickD MolyneuxV Nantulya2005Achieving the millennium development goals.Lancet365(9464)1029103010.1016/0140-6736(05)71134-X15781095
  8. A Olsen2007Efficacy and safety of drug combinations in the treatment of schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis and onchocerciasis.Trans R Soc Trop Med Hyg101(8)74775810.1016/j.trstmh.2007.03.00617481681
  9. JO GyapongM GyapongDB EvansMK AikinsS Adjei1996The economic burden of lymphatic filariasis in northern Ghana.Ann Trop Med Parasitol90(1)39488729626
  10. LJ DrakeMC JukesRJ SternbergDAP Bundy2000Geohelminth infections (ascariasis, trichuriasis, and hookworm): cognitive and developmental impacts.Semin Pediatr Infect Dis11(1)245251
  11. LJ DrakeDA Bundy2001Multiple helminth infections in children: impact and control.Parasitology 122 SupplS73S81
  12. MC JukesCA NokesKJ AlcockJK LamboC Kihamia2002Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren.Trop Med Int Health7(2)10411711841700
  13. M BeasleyS BrookerM NdinaromtanEM MadjiouroumM Baboguel2002First nationwide survey of the health of schoolchildren in Chad.Trop Med Int Health7(7)62563012100447
  14. EA MiguelM Kremer2003Worms: identifying impacts on education and health in the presence of treatment externalities.Econometrica72159217
  15. U AmazigoM NomaJ BumpB BentonB Liese2006Onchocerciasis (chapter 15).DT JamisonRG FeachemMW MakgobaER BosFK BinganaKJ HofmanKO RogoDisease and mortality in Sub-Saharan Africa. Second editionWashington (D.C.)World Bank215222
  16. A AjangaNJ LwamboL BlairU NyandindiA Fenwick2006Schistosoma mansoni in pregnancy and associations with anaemia in northwest Tanzania.Trans R Soc Trop Med Hyg100596316219330
  17. S BrookerPJ HotezDA Bundy2008Hookworm-related anaemia among pregnant women: a systematic review.PLoS Negl Trop Dis2(9)e291doi:10.1371/journal.pntd.000029118820740
  18. S BrookerE Michael2000The potential of geographical information systems and remote sensing in the epidemiology and control of human helminth infections.Adv Parasitol4724528810997209
  19. S BrookerM BeasleyM NdinaromtanEM MadjiouroumM Baboguel2002Use of remote sensing and a geographical information system in a national helminth control programme in Chad.Bull World Health Organ80(10)78378912471398
  20. S BrookerNB KabatereineEM TukahebwaF Kazibwe2004Spatial analysis of the distribution of intestinal nematode infections in Uganda.Epidemiol Infect132(6)1065107115635963
  21. P SteinmannJ KeiserR BosM TannerJ Utzinger2006Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.Lancet Infect Dis6(7)41142510.1016/S1473-3099(06)70521-716790382
  22. CH KingM Dangerfield-Cha2008The unacknowledged impact of chronic schistosomiasis.Chronic Illn4(1)657910.1177/174239530708440718322031
  23. CH KingK DickmanDJ Tisch2005Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis.Lancet365(9470)1561156910.1016/S0140-6736(05)66457-415866310
  24. NR de SilvaS BrookerPJ HotezA MontresorD Engels2003Soil-transmitted helminth infections: updating the global picture.Trends Parasitol19(12)54755114642761
  25. E MichaelDA Bundy1997Global mapping of lymphatic filariasis.Parasitol Today13(12)47247615275135
  26. Global Alliance to Eliminate Lymphatic Filariasis15 November 2008African programme review group.Available: http://filariasis.org/resources/africanprg.htmAccessed 27 July 2009
  27. N ZagariaL Savioli2002Elimination of lymphatic filariasis: a public-health challenge.Ann Trop Med Parasitol96Suppl 2S3S13
  28. Global Alliance to Eliminate Lymphatic Filariasis2005Global alliance to eliminate lymphatic filariasis—progress as of January 2005.Available: http://www.filariasis.org/pdfs/GAELFnumbers6_13.pdf. Accessed 27 July 2009
  29. BA BoatinFO Richards Jr2006Control of onchocerciasis.Adv Parasitol6134939410.1016/S0065-308X(05)61009-316735169
  30. World Health Organization2008Global health atlas. Global Alliance for the Elimination of Blinding Trachoma database.Available: http://www.who.int/globalatlas/. Accessed 27 July 2009
  31. NR Stoll1999This wormy world.J Parasitol85(3)39239610386427
  32. JJ PadgettKH Jacobsen2008Loiasis: African eye worm.Trans R Soc Trop Med Hyg102(10)98398910.1016/j.trstmh.2008.03.02218466939
  33. ED Barnett2007Yellow fever: epidemiology and prevention.Clin Infect Dis44(6)85085610.1086/51186917304460
  34. World Health Organization2008Yellow fever in Africa and South America, 2006.Wkly Epidemiol Rec83(8)607618293534
  35. World Health Organization2008Global leprosy situation, beginning of 2008.Wkly Epidemiol Rec83(33)29330018705152
  36. World Health Organization2008Dracunculiasis eradication.Wkly Epidemiol Rec83(18)15916718453066
  37. World Health Organization2008Buruli ulcer: Progress report, 2004–2008.Wkly Epidemiol Rec83(17)14515418437758
  38. DS WalshF PortaelsWM Meyers2008Buruli ulcer (mycobacterium ulcerans infection).Trans R Soc Trop Med Hyg102(10)96997810.1016/j.trstmh.2008.06.00618657836
  39. World Health Organization2006Human African trypanosomiasis (sleeping sickness): epidemiological update.Wkly Epidemiol Rec81(8)7180
  40. World Health OrganizationAugust 2006African trypanosomiasis (sleeping sickness).Fact sheet no. 259. Available: http://www.who.int/mediacentre/factsheets/fs259/en/print.htmlAccessed 27 July 2009
  41. J AlvarP AparicioA AseffaM Den BoerC Canavate2008The relationship between leishmaniasis and AIDS: the second 10 years.Clin Microbiol Rev21(2)33459, table of contents10.1128/CMR.00061-0718400800
  42. R ReithingerS BrookerJH Kolaczinski2007Visceral leishmaniasis in eastern Africa—current status.Trans R Soc Trop Med Hyg101(12)1169117010.1016/j.trstmh.2007.06.00117632193
  43. C BernJH MaguireJ Alvar2008Complexities of assessing the disease burden attributable to leishmaniasis.PLoS Negl Trop Dis2(10)e313doi:10.1371/journal.pntd.000031318958165
  44. S CollinR DavidsonK RitmeijerK KeusY Melaku2004Conflict and kala-azar: Determinants of adverse outcomes of kala-azar among patients in southern Sudan.Clin Infect Dis38(5)61261910.1086/38120314986243
  45. World Health Organization2004World 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 Table3126131Available: http://www.who.int/whr/2004/en/. Accessed 27 July 2009
  46. MS Chan1997The global burden of intestinal nematode infections—fifty years on.Parasitol Today13(11)43844315275146
  47. PJ HotezDH MolyneuxA FenwickE OttesenS Ehrlich Sachs2006Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/ADIS, tuberculosis, and malaria.PLoS Med3e102doi:10.1371/journal.pmed.003010216435908
  48. J BethonyS BrookerM AlbonicoSM GeigerA Loukas2006Soil-transmitted helminth infections: Ascariasis, trichuriasis, and hookworm.Lancet367(9521)1521153210.1016/S0140-6736(06)68653-416679166
  49. PJ HotezPJ BrindleyJM BethonyCH KingEJ Pearce2008Helminth infections: the great neglected tropical diseases.J Clin Invest118(4)1311132110.1172/JCI3426118382743
  50. LS StephensonMC LathamKM KurzSN KinotiH Brigham1989Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, trichuris trichiura, and ascaris lumbricoides infections.Am J Trop Med Hyg41(1)78872764230
  51. LS StephensonMC LathamSN KinotiKM KurzH Brigham1990Improvements 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 Hyg84(2)2772822389321
  52. ML MabasoCC AppletonJC HughesE Gouws2004Hookworm (necator americanus) transmission in inland areas of sandy soils in KwaZulu-natal, South Africa.Trop Med Int Health9(4)47147610.1111/j.1365-3156.2004.01216.x15078265
  53. JM BehnkeD De ClercqM SackoFS GilbertDB Ouattara2000The epidemiology of human hookworm infections in the southern region of mail.Trop Med Int Health5(5)34335410886798
  54. D De ClercqM SackoJ BehnkeF GilbertP Dorny1997Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali.Am J Trop Med Hyg57(1)25309242313
  55. S BrookerW AkhwaleR PullanB EstambaleSE Clarke2007Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control.Am J Trop Med Hyg776 Suppl889818165479
  56. M AlbonicoRJ StoltzfusL SavioliJM TielschHM Chwaya1998Epidemiological evidence for a differential effect of hookworm species, ancylostoma duodenale or necator americanus, on iron status of children.Int J Epidemiol27(3)5305379698148
  57. PJ HotezS BrookerJM BethonyME BottazziA Loukas2004Hookworm infection.N Engl J Med351(8)79980710.1056/NEJMra03249215317893
  58. RJ StoltzfusHM ChwayaJM TielschKJ SchulzeM Albonico1997Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms.Am J Clin Nutr65(1)1531598988928
  59. S BrookerN PeshuPA WarnM MosoboHL Guyatt1999The epidemiology of hookworm infection and its contribution to anaemia among pre-school children on the Kenyan coast.Trans R Soc Trop Med Hyg93(3)24024610492749
  60. M AlbonicoH AllenL ChitsuloD EngelsAF Gabrielli2008Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy.PLoS Negl Trop Dis2(3)e126doi:10.1371/journal.pntd.000012618365031
  61. DW Crompton2000The public health importance of hookworm disease.Parasitology 121 SupplS39S50
  62. HO Dada-AdegbolaAO OluwatobaCO Falade2005Prevalence of multiple intestinal helminths among children in a rural community.Afr J Med Med Sci34(3)26326716749359
  63. E SaathoffA OlsenJD KvalsvigCC Appleton2004Patterns of geohelminth infection, impact of albendazole treatment and re-infection after treatment in schoolchildren from rural KwaZulu-Natal/South-Africa.BMC Infect Dis42710.1186/1471-2334-4-2715310401
  64. E SaathoffA OlsenJD KvalsvigCC AppletonB Sharp2005Ecological covariates of ascaris lumbricoides infection in schoolchildren from rural KwaZulu-natal, south Africa.Trop Med Int Health10(5)41242210.1111/j.1365-3156.2005.01406.x15860087
  65. HO Dada-AdegbolaRA Bakare2004Strongyloidiasis in children five years and below.West Afr J Med23(3)19419715587827
  66. JB ZiemP MagnussenA OlsenJ HortonVL Asigri2006Impact of repeated mass treatment on human oesophagostomum and hookworm infections in northern Ghana.Trop Med Int Health11(11)1764177210.1111/j.1365-3156.2006.01729.x17054758
  67. M Bradley1990Rate 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 Hyg84(5)7202278080
  68. C Beck-WornerG RasoP VounatsouEK N'GoranG Rigo2007Bayesian spatial risk prediction of schistosoma mansoni infection in western Cote d'Ivoire using a remotely-sensed digital elevation model.Am J Trop Med Hyg76(5)95696317488922
  69. NB KabatereineS BrookerEM TukahebwaF KazibweAW Onapa2004Epidemiology and geography of schistosoma mansoni in Uganda: implications for planning control.Trop Med Int Health9(3)37238014996367
  70. UF EkpoCF MafianaCO AdeofunAR SolarinAB Idowu2008Geographical information system and predictive risk maps of urinary schistosomiasis in Ogun state, Nigeria.BMC Infect Dis87410.1186/1471-2334-8-7418513442
  71. A FenwickD RollinsonV Southgate2006Implementation of human schistosomiasis control: Challenges and prospects.Adv Parasitol6156762210.1016/S0065-308X(05)61013-516735173
  72. TD MangalS PatersonA Fenton2008Predicting the impact of long-term temperature changes on the epidemiology and control of schistosomiasis: A mechanistic model.PLoS ONE3(1)e1438doi:10.1371/journal.pone.000143818197249
  73. MJ van der WerfSJ de VlasS BrookerCW LoomanNJ Nagelkerke2003Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa.Acta Trop86(2–3)12513912745133
  74. D Maxwell Parkin2008The global burden of urinary bladder cancer.Scand J Urol Nephrol1910.1080/03008880802285032
  75. B SwaiG PoggenseeS MtweveI Krantz2006Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: A retrospective histopathological study from Tanzania.BMC Infect Dis613410.1186/1471-2334-6-13416928276
  76. EF KjetlandPD NdhlovuE GornoT MduluzaN Midzi2006Association between genital schistosomiasis and HIV in rural Zimbabwean women.AIDS2059360016470124
  77. LA Tchuem TchuenteVR SouthgateJ JourdaneBL WebsterJ Vercruysse2003Schistosoma intercalatum: An endangered species in Cameroon?Trends Parasitol19(9)38939312957514
  78. G RasoP VounatsouBH SingerEK N'GoranM Tanner2006An integrated approach for risk profiling and spatial prediction of schistosoma mansoni-hookworm coinfection.Proc Natl Acad Sci U S A103(18)6934693910.1073/pnas.060155910316632601
  79. G RasoP VounatsouL GosoniuM TannerEK N'Goran2006Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Cote d'Ivoire.Int J Parasitol36(2)20121010.1016/j.ijpara.2005.09.00316259987
  80. PJ HotezJM BethonySC OliveiraPJ BrindleyA Loukas2008Multivalent anthelminthic vaccine to prevent hookworm and schistosomiasis.Expert Rev Vaccines7(6)74575210.1586/14760584.7.6.74518665774
  81. C SokhnaJY Le HesranPA MbayeJ AkianaP Camara2004Increase of malaria attacks among children presenting concomitant infection by schistosoma mansoni in Senegal.Malar J34310.1186/1475-2875-3-4315544703
  82. J KeiserJ Utzinger2005Emerging foodborne trematodiasis.Emerg Infect Dis11(10)1507151416318688
  83. PM PreuxM Druet-Cabanac2005Epidemiology and aetiology of epilepsy in sub-Saharan Africa.Lancet Neurol4(1)213110.1016/S1474-4422(04)00963-915620854
  84. G NsengiyumvaM Druet-CabanacB RamanankandrasanaB BouteilleL Nsizabira2003Cysticercosis as a major risk factor for epilepsy in Burundi, east Africa.Epilepsia44(7)95095512823579
  85. M BoaS MukaratirwaAL WillinghamMV Johansen2003Regional action plan for combating taenia solium cysticercosis/taeniosis in Eastern and Southern Africa.Acta Trop87(1)18318612781395
  86. H CarabinRC KrecekLD CowanL MichaelH Foyaca-Sibat2006Estimation of the cost of taenia solium cysticercosis in eastern cape province, south Africa.Trop Med Int Health11(6)90691610.1111/j.1365-3156.2006.01627.x16772013
  87. AP ZoliNguekamO Shey-NjilaD Nsame NforninweN Speybroeck2003Neurocysticercosis and epilepsy in Cameroon.Trans R Soc Trop Med Hyg97(6)68368616117963
  88. M KatabarwaT LakwoP HabumogishaF RichardsM Eberhard2008Could neurocysticercosis be the cause of “onchocerciasis-associated” epileptic seizures?Am J Trop Med Hyg78(3)40040118337333
  89. F AbunnaG TilahunB MegersaA Regassa2007Taeniasis and its socio-economic implication in awassa town and its surroundings, southern Ethiopia.East Afr J Public Health4(2)737918085135
  90. IE ElmahdiQM AliMM MagzoubAM IbrahimMB Saad2004Cystic echinococcosis of livestock and humans in central Sudan.Ann Trop Med Parasitol98(5)47347910.1179/00034980422500357815257797
  91. World Health Organization2008Global programme to eliminate lymphatic filariasis.Wkly Epidemiol Rec83(37)33334118788146
  92. EA Ottesen2006Lymphatic filariasis: Treatment, control and elimination.Adv Parasitol6139544110.1016/S0065-308X(05)61010-X16735170
  93. EA OttesenPJ HooperM BradleyG Biswas2008The global programme to eliminate lymphatic filariasis: Health impact after 8 years.PLoS Negl Trop Dis2(10)e317doi:10.1371/journal.pntd.000031718841205
  94. SM NjengaCN WamaeDW NjomoCS MwandawiroDH Molyneux2007Chronic clinical manifestations related to wuchereria bancrofti infection in a highly endemic area in Kenya.Trans R Soc Trop Med Hyg101(5)43944410.1016/j.trstmh.2006.09.00617145069
  95. AC HaddixA Kestler2000Lymphatic filariasis: Economic aspects of the disease and programmes for its elimination.Trans R Soc Trop Med Hyg94(6)59259311198636
  96. E MathieuJ AmannA EigegeF RichardsY Sodahlon2008Collecting baseline information for national morbidity alleviation programs: different methods to estimate lymphatic filariasis morbidity prevalence.Am J Trop Med Hyg78(1)15315818187799
  97. G DaveyF TekolaMJ Newport2007Podoconiosis: non-infectious geochemical elephantiasis.Trans R Soc Trop Med Hyg101(12)1175118010.1016/j.trstmh.2007.08.01317976670
  98. M Boussinesq2006Loiasis.Ann Trop Med Parasitol100(8)71573110.1179/136485906X11219417227650
  99. DR HopkinsE Ruiz-TibenP DownsPC Withers JrS Roy2008Dracunculiasis eradication: neglected no longer.Am J Trop Med Hyg79(4)47447918840732
  100. EM FevreK PicozziJ JanninSC WelburnI Maudlin2006Human African trypanosomiasis: epidemiology and control.Adv Parasitol6116722110.1016/S0065-308X(05)61005-616735165
  101. EM FevreK PicozziJ FyfeC WaiswaM Odiit2005A burgeoning epidemic of sleeping sickness in Uganda.Lancet366(9487)74574710.1016/S0140-6736(05)67179-616125592
  102. JH KolaczinskiR ReithingerDT WorkuA OchengJ Kasimiro2008Risk factors of visceral leishmaniasis in East Africa: a case-control study in pokot territory of Kenya and Uganda.Int J Epidemiol37(2)34435210.1093/ije/dym27518184669
  103. J AlvarS CroftP Olliaro2006Chemotherapy in the treatment and control of leishmaniasis.Adv Parasitol6122327410.1016/S0065-308X(05)61006-816735166
  104. JH KolaczinskiA HopeJA RuizJ RumunuM Richer2008Kala-azar epidemiology and control, southern Sudan.Emerg Infect Dis14(4)66466618394290
  105. W StaufferM Abd-AllaJI Ravdin2006Prevalence and incidence of entamoeba histolytica infection in South Africa and Egypt.Arch Med Res37(2)26626910.1016/j.arcmed.2005.10.00616380329
  106. IN OkekeO OjoA LamikanraJB Kaper2003Etiology of acute diarrhea in adults in southwestern Nigeria.J Clin Microbiol41(10)4525453014532177
  107. A ElnahasAS GeraisMI ElbashirES EldienI Adam2003Toxoplasmosis in pregnant Sudanese women.Saudi Med J24(8)86887012939674
  108. J SimporeA SavadogoD IlboudoMC NadambegaM Esposito2006Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV-positive and -negative pregnant women in Burkina Faso.J Med Virol78(6)73073310.1002/jmv.2061516628587
  109. CK FanCC HungKE SuHY ChiouV Gil2007Seroprevalence of toxoplasma gondii infection among inhabitants in the democratic republic of Sao Tome and Principe.Trans R Soc Trop Med Hyg101(11)1157115810.1016/j.trstmh.2007.04.01017606284
  110. W AmogneG TeshagerG Zenebe2006Central nervous system toxoplasmosis in adult Ethiopians.Ethiop Med J44(2)11312017447372
  111. CJ UnekeDD DuhlinskaMO NjokuBA Ngwu2005Seroprevalence of acquired toxoplasmosis in HIV-infected and apparently healthy individuals in Jos, Nigeria.Parassitologia47(2)23323616252478
  112. S PolackS BrookerH KuperS MariottiD Mabey2005Mapping the global distribution of trachoma.Bull World Health Organ83(12)/S0042-9686200500120001391391916462983
  113. JD ChidambaramW AlemayehuM MeleseT LakewE Yi2006Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma.JAMA295(10)1142114610.1001/jama.295.10.114216522834
  114. M ReddySS GillSR KalkarW WuPJ Anderson2007Oral drug therapy for multiple neglected tropical diseases: a systematic review.JAMA298(16)1911192410.1001/jama.298.16.191117954542
  115. HR WrightA TurnerHR Taylor2008Trachoma.Lancet371(9628)1945195410.1016/S0140-6736(08)60836-318539226
  116. JW MecaskeyCA KnirschJA KumaresanJA Cook2003The possibility of eliminating blinding trachoma.Lancet Infect Dis3(11)72873414592604
  117. J NgondiF MatthewsM ReacherA OnsarigoI Matende2007Prevalence of risk factors and severity of active trachoma in southern Sudan: an ordinal analysis.Am J Trop Med Hyg77(1)12613217620643
  118. J NgondiM ReacherF MatthewsF Ole-SempeleA Onsarigo2007The epidemiology of low vision and blindness associated with trichiasis in southern Sudan.BMC Ophthalmol71210.1186/1471-2415-7-1217725828
  119. S WestMP NguyenH MkochaG HoldsworthE Ngirwamungu2004Gender equity and trichiasis surgery in the Vietnam and Tanzania national trachoma control programmes.Br J Ophthalmol88(11)1368137110.1136/bjo.2004.04165715489474
  120. W AlemayehuM MeleseE FredlanderA WorkuP Courtright2005Active trachoma in children in central Ethiopia: association with altitude.Trans R Soc Trop Med Hyg99(11)84084310.1016/j.trstmh.2005.06.01316107273
  121. W MathengeH KuperH LimburgS PolackO Onyango2007Rapid assessment of avoidable blindness in Nakuru district, Kenya.Ophthalmology114(3)59960510.1016/j.ophtha.2006.06.05717141319
  122. E EtterP DonadoF JoriA CaronF Goutard2006Risk analysis and bovine tuberculosis, a re-emerging zoonosis.Ann N Y Acad Sci1081617310.1196/annals.1373.00617135495
  123. WY AyeleSD NeillJ ZinsstagMG WeissI Pavlik2004Bovine tuberculosis: an old disease but a new threat to Africa.Int J Tuberc Lung Dis8(8)92493715305473
  124. L VialG DiattaA TallH Ba elH Bouganali2006Incidence of tick-borne relapsing fever in West Africa: longitudinal study.Lancet368(9529)374310.1016/S0140-6736(06)68968-X16815378
  125. LM NdipDH BouyerAP Travassos Da RosaVP TitanjiRB Tesh2004Acute spotted fever rickettsiosis among febrile patients, Cameroon.Emerg Infect Dis10(3)43243715109409
  126. D RaoultPE FournierF FenollarM JenseniusT Prioe2001Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa.N Engl J Med344(20)1504151011357153
  127. AJ BrentI AhmedM NdirituP LewaC Ngetsa2006Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study.Lancet367(9509)48248810.1016/S0140-6736(06)68180-416473125
  128. E MweuM English2008Typhoid fever in children in Africa.Trop Med Int Health13(4)53254010.1111/j.1365-3156.2008.02031.x18312473
  129. NF Crum2003Current trends in typhoid fever.Curr Gastroenterol Rep5(4)27928612864957
  130. World Health Organization2008Typhoid vaccines: WHO position paper.Wkly Epidemiol Rec83(6)495918260212
  131. SM GrahamEM MolyneuxAL WalshJS CheesbroughME Molyneux2000Nontyphoidal salmonella infections of children in tropical Africa.Pediatr Infect Dis J19(12)1189119611144383
  132. MA GordonSM GrahamAL WalshL WilsonA Phiri2008Epidemics of invasive salmonella enterica serovar enteritidis and S. enterica serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi.Clin Infect Dis46(7)96396910.1086/52914618444810
  133. JA BerkleyBS LoweI MwangiT WilliamsE Bauni2005Bacteremia among children admitted to a rural hospital in Kenya.N Engl J Med352(1)394710.1056/NEJMoa04027515635111
  134. AO CokerRD IsokpehiBN ThomasAF Fagbenro-BeyiokuSA Omilabu2000Zoonotic infections in Nigeria: overview from a medical perspective.Acta Trop76(1)596310913768
  135. K Asiedu2008The return of yaws.Bull World Health Organ86(7)50750818670660
  136. MH KuniholmND WolfeCY HuangE Mpoudi-NgoleU Tamoufe2006Seroprevalence and distribution of flaviviridae, togaviridae, and bunyaviridae arboviral infections in rural Cameroonian adults.Am J Trop Med Hyg74(6)1078108316760524
  137. L Roberts2007Infectious disease. Resurgence of yellow fever in Africa prompts a counterattack.Science316(5828)110910.1126/science.316.5828.110917525307
  138. GN MalavigeS FernandoDJ FernandoSL Seneviratne2004Dengue viral infections.Postgrad Med J80(948)58860110.1136/pgmj.2004.01963815466994
  139. AD LaBeaudY OchiaiCJ PetersEM MuchiriCH King2007Spectrum of rift valley fever virus transmission in Kenya: insights from three distinct regions.Am J Trop Med Hyg76(5)79580017488893
  140. C CohenB SartoriusC SabetaG ZuluJ Paweska2007Epidemiology and molecular virus characterization of reemerging rabies, South Africa.Emerg Infect Dis13(12)1879188618258039
  141. DM PfukenyiD PawandiwaPV MakayaU Ushewokunze-Obatolu2007A retrospective study of rabies in humans in Zimbabwe, between 1992 and 2003.Acta Trop102(3)19019610.1016/j.actatropica.2007.04.01317543871
  142. O ChukwuekezieE AmpaduG SopohA DossouA Tiendrebeogo2007Buruli ulcer, Nigeria.Emerg Infect Dis13(5)78278318044041
  143. CD MathersM EzzatiAD Lopez2007Measuring the burden of neglected tropical diseases: the global burden of disease framework.PLoS Negl Trop Dis1(2)e114doi:10.1371/journal.pntd.000011418060077
  144. P Hotez2007Measuring neglect.PLoS Negl Trop Dis1(2)e118doi:10.1371/journal.pntd.000011818060078
  145. C SteinT KuchenmullerS HendrickxA Pruss-UstunL Wolfson2007The global burden of disease assessments—WHO is responsible?PLoS Negl Trop Dis1(3)e161doi:10.1371/journal.pntd.000016118160984
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