Biosocial Determinants of Persistent Schistosomiasis among Schoolchildren in Tanzania despite Repeated Treatment.

Schistosomiasis is a parasitic disease endemic to Tanzania and other countries of the global south, which is currently being addressed through preventive chemotherapy campaigns. However, there is growing recognition that chemotherapy strategies will need to be supplemented to sustainably control and eventually eliminate the disease. There remains a need to understand the factors contributing to continued transmission in order to ensure the effective configuration and implementation of supplemented programs. We conducted a cross-sectional questionnaire, to evaluate the biosocial determinants facilitating the persistence of schistosomiasis, among 1704 Tanzanian schoolchildren residing in two districts undergoing a preventive chemotherapeutic program: Rufiji and Mkuranga. A meta-analysis was carried out to select the diagnostic questions that provided a likelihood for predicting infection status. We found that self-reported schistosomiasis continues to persist among the schoolchildren, despite multiple rounds of drug administration.Using mixed effects logistic regression modeling, we found biosocial factors, including gender, socio-economic status, and water, sanitation, and hygiene (WASH)-related variables, were associated with this continued schistosomiasis presence. These findings highlight the significant role that social factors may play in the persistence of disease transmission despite multiple treatments, and support the need not only for including integrated technical measures, such as WASH, but also addressing issues of poverty and gender when designing effective and sustainable schistosomiasis control programs.

Urban schistosomiasis and soil transmitted helminthiases in young school children in Dar es Salaam and Tanga, Tanzania, after a decade of anthelminthic intervention.

Rapid urbanization in resource poor countries often results in expansion of unplanned settlements with overcrowding and inadequate sanitation. These conditions potentially support transmission of schistosomiasis and soil transmitted helminths (STH), but knowledge on the occurrence, transmission and control of these infections in urban settings is limited. The present study assessed the status of urinary schistosomiasis and STH across two different-sized cities in Tanzania - Dar es Salaam and Tanga - after a decade of anthelminthic intervention. Primary school children were examined for parasite eggs in urine and stool. Questionnaires were administered to the children, and observations were made on the urban environments. The burden of urinary schistosomiasis and STH was found to be low in both cities (overall 1.2% in Dar es Salaam and 0.3% in Tanga for urinary schistosomiasis; overall <1% in Dar es Salaam and 1-2% in Tanga for each STH infection), and the identified cases showed no clear pattern of spatial distribution. The findings indicated that a marked decrease in prevalence of these infections had occurred in the two cities during recent years. The observed promising developments appeared to have been accomplished by implementation of drug based intervention programs, in combination with environmental change (fewer snail habitats) and generally improved levels of hygiene. Continued efforts, including anthelminthic treatment and health education, are important to maintain these positive achievements.

Urban lymphatic filariasis in the city of Tanga, Tanzania, after seven rounds of mass drug administration.

Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas - where most LF occurs - do not easily comply with human organization and behaviour in urban areas, and partly because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites with varying distance from the city centre were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Although there was evidence of considerable reduction in infection and transmission, there was still LF in the city, with mf and CFA prevalences well above the cut-off levels for stopping MDA. In this respect, the LF situation resembled that seen in nearby rural areas outside the city. The study emphasizes the importance of motivating the urban individuals to engage and comply with the full range of LF intervention measures (MDAs, use of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources for morbidity management, to ensure true elimination of LF as a public health problem.

Lymphatic filariasis control in Tanzania: effect of six rounds of mass drug administration with ivermectin and albendazole on infection and transmission.

BACKGROUND: Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania. METHODS: The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. RESULTS: Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. CONCLUSIONS: Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination.

Neglected tropical diseases and the millennium development goals: why the "other diseases" matter: reality versus rhetoric.

Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs) as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO) has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date.The paper acknowledges that in undertaking any health programme in environments such as post-conflict countries, there are always challenges. It is also recognised that NTD control must always be undertaken within the health system context. However, it is important to emphasise that the availability of donated drugs, the multiple impact of those drugs, the willingness of countries to undertake their distribution, thereby committing their own resources to the programmes, and the proven beneficial results outweigh the problems which are faced in environments where communities are often beyond the reach of health services. Given the availability of these interventions, their cost effectiveness and the broader development impact we believe it would be unethical not to continue programmes of such long term benefit to the "bottom billion".

Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes.

The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

Immunoepidemiology of Wuchereria bancrofti infection in two East African communities: antibodies to the microfilarial sheath and their role in regulating host microfilaraemia.

The response pattern of specific antibodies to the microfilarial sheath (sheath-Ab) of the mosquito-borne filarial parasite Wuchereria bancrofti was investigated in individuals from two East African communities with different levels of endemicity. Individuals from both communities presented a strong inverse relationship between positivity for sheath-Ab and being positive for microfilariae (mf) and circulating filarial antigens (CFA). The prevalence of sheath-Ab positivity was highest in young individuals, but peaked at a younger age in the high (1-14 years) than the low (15-19 years) endemicity community. IgG1, IgG2, IgG3 and IgE intensities to a crude adult filarial worm antigen were higher, and IgG4 intensities were lower, in sheath-Ab positive than in sheath-Ab negative individuals, probably reflecting the infection status of individuals. From the study it appears that individuals become sheath-Ab positive before mf and/or CFA can be detected in the peripheral blood, and only after later disappearance of sheath-Ab from the circulation can CFA and mf be diagnosed. In light of the findings, possible roles of the distinct sheath-Ab in the host-parasite relationship are discussed, and a hypothesis is proposed which suggests that sheath-Ab play an important role in the regulation of host microfilaraemia.

Immunoepidemiology of Wuchereria bancrofti infection: parasite transmission intensity, filaria-specific antibodies, and host immunity in two East African communities.

We compared the age profiles of infection and specific antibody intensities in two communities with different transmission levels in East Africa to examine the contribution of humoral responses to human immunity to the vector-borne helminth Wuchereria bancrofti. The worm intensities were higher and exhibited a nonlinear age pattern in a high-transmission community, Masaika, in contrast to the low but linearly increasing age infection profile observed for a low-transmission community, Kingwede. The mean levels of specific immunoglobulin G1 (IgG1), IgG2, IgG4, and IgE were also higher in Masaika, but intriguingly, the IgG3 response was higher in Kingwede. The age-antibody patterns differed in the two communities but in a manner apparently contrary to a role in acquired immunity when the data were assessed using simple correlation methods. By contrast, multivariate analyses showed that the antibody response to infection may be classified into three types and that two of these types, a IgG3-type response and a response measuring a trade-off in host production of IgG4 and IgG3 versus production of IgG1, IgG2, and IgE, had a negative effect on Wuchereria circulating antigen levels in a manner that supported a role for these responses in the generation of acquired immunity to infection. Mathematical modeling supported the conclusions drawn from empirical data analyses that variations in both transmission and worm intensity can explain community differences in the age profiles and impacts of these antibody response types. This study showed that parasite-specific antibody responses may be associated with the generation of acquired immunity to human filarial infection but in a form which is dependent on worm transmission intensity and interactions between immune components.

Bancroftian filariasis infection, disease, and specific antibody response patterns in a high and a low endemicity community in East Africa.

Bancroftian filariasis infection, disease and specific antibody response patterns in a high and a low endemicity community in East Africa were analyzed and compared to assess the relationship between these parameters and community transmission intensity. Overall prevalences of microfilaremia and circulating filarial antigenemia were 24.9% and 52.2% in the high and 2.7% and 16.5% in the low endemicity community, respectively. A positive history of acute attacks of adenolymphangitis was given by 12.2% and 7.1% of the populations, 4.0% and 0.9% of the adult (> or = 20 years old) individuals presented with limb lymphedema, and 25.3% and 5.3% of the adult males had hydrocele, in the high and the low endemicity community, respectively. Both infection and disease appeared earlier and reached much higher levels in the high than in the low endemicity community. The observed overall and age-specific infection and disease patterns in the two communities were in agreement with the view that these are primarily shaped by transmission intensity. No statistically significant relationships between infection status of fathers and mothers and that of their children were observed in any of the communities for either microfilaremia or for circulating filarial antigenemia. The overall levels (prevalence and geometric mean intensity) of filarial-specific IgG1, IgG2, IgG4, and IgE were significantly higher in the high endemicity community than in the low endemicity dommunity. Surprisingly, the opposite pattern was found for IgG3. Community transmission intensity thus appears to be an important determinant of observed inter-community variation in infection, disease, and host response patterns in Bancroftian filariasis.