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Most epidemiological studies of soil-transmitted helminth (STH) infections focus on school-going children. The majority of large-scale cross-sectional and longitudinal community-based studies have been conducted prior to the implementation of wide-scale mass drug administration (MDA). This study investigates age-related patterns in prevalence and intensity of STH infection, and associated risk factors, in a region of south coastal Kenya that had previously received three consecutive years of school-based deworming (2012–14) and four rounds of community-based MDA for lymphatic filariasis between 2003 and 2014. Between March and May 2015, a cross-sectional survey was conducted in 120 community clusters as a baseline for a cluster randomised trial. Individuals aged two years and above were randomly selected during household surveys and requested to provide stool samples, which were assessed for presence and intensity of STH using the duplicate Kato-Katz thick smear method. Species-specific predictors of presence and intensity were investigated through multilevel logistic regression and zero-inflated negative binomial regression models. Of the 19,684 individuals who provided a stool sample, 21.5% were infected with at least one STH. Hookworm was the predominant species, with an overall prevalence of 19.1%; Trichuris trichiura prevalence was 3.6% and Ascaris lumbricoides was negligible (0.4% prevalence). The vast majority were light intensity infections. Prevalence and intensity of hookworm infection were significantly higher in adults and males, and were associated with environmental conditions, low socio-economic status, household flooring, individual and household water, sanitation and hygiene (WASH) characteristics and behaviours, previous treatment, lack of shoe-wearing and not attending school. In contrast, T. trichiura was more commonly found in school-aged boys and those living in communities close to the coast, with reduced infection in the least poor individuals with private latrine access. Overall, results show that despite several years of school-based deworming, hookworm infection remains common among untreated adults in this population, suggesting that this strategy alone is insufficient to reduce community-wide hookworm infection and in the longer term to eliminate transmission. Trial registration ClinicalTrials.gov NCT02397772, Author summary Soil-transmitted helminth (STH) infections, including Trichuris trichiura, Ascaris lumbricoides and the hookworms Ancylostoma duodenale and Necator americanus, remain endemic in many regions of sub-Saharan Africa (SSA), including parts of Kenya. The current WHO-recommended treatment strategy focuses on morbidity control, and comprises periodic deworming of population groups at particular risk, including pre-school and school–age children. Consequently, the majority of epidemiological descriptions of STH have focused on infection in this age group, and are conducted using a school platform. There is therefore a notable lack of age-stratified data (that includes adults) from communities. We present data from a community-wide, cross-sectional survey of STH infection across 19,684 individuals and investigate associated risk factors at the household and individual level. We demonstrate highest prevalence and intensity of hookworm (the predominant species in this setting) in adults and males—a group not routinely included in deworming activities. There was marked geographic variation in infection risk across the study area, and an enduring relationship between infection risk and factors associated with poor access to sanitation and hygiene. Conducted after three years of ongoing, annual school-based deworming, the findings presented here are likely to be representative of many regions of SSA, with similar epidemiological and demographic profiles, implementing the current WHO-recommended STH control strategy.

Background Trichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation. Methods We obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available. Findings Internally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand–1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03–2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283–557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand–1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1–5.2 million). Interpretation The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence., Author summary As an individual with trichiasis blinks, the eyelashes abrade the cornea, which can lead to corneal opacity and blindness. Through high quality surgery, which involves altering the position of the eyelid margin, it is possible to reduce the number of people with trichiasis. Accurate estimates of the number of persons with trichiasis and their geographical distribution are needed in order to effectively align resources for surgery and other necessary services. We obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used the most recently available data and expert assessments to estimate the global burden of trichiasis. We estimated that in 2016 the global burden was 2.8 million cases (95% CI 1.1–5.2 million). The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

Background Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. Methodology/Principal Finding A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. Conclusions We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale., Author Summary About 1.4 billion people are believed to be living in areas where Lymphatic filariasis (LF) is actively transmitted. However, the distribution of this disfiguring mosquito-borne parasitic disease and the true population at risk that can be targeted for treatment have not been defined for all endemic countries. By 2013, Ethiopia had not delineated the majority of the endemic implementation units that can be targeted for MDA. Here, we present the results of a nationwide mapping exercise conducted in 2013 to determine the number of people that should be targeted for treatment in 2016 when nationwide treatment coverage is expected. We adopted a two-stage cluster purposive sampling method for the integrated mapping of LF and podoconiosis in seven regional states and two city administrations. Using a WHO mapping strategy for LF, based on sampling 100 individuals per community ICT positive individuals (ICT+) and two purposely selected communities per district, we examined 130 166 people in 1315 communities in 658 districts. Only 140 people were found to be positive for LF antigen in 89 different communities. According to WHO guidelines, 75 of the 658 districts surveyed in the 9 regions were found to be LF endemic. Including the 37 endemic Woredas identified enprior to this study, 112 woredas across the country are known to be endemic for the disease with 11 580 010 people exposed to infection. However 6 190 482 of those resided in woredas where our survey results were borderline with only one ICT positive individual identified. We have demonstrated that the number of people living in areas of active LF transmission is at least 60% lower than current WHO estimates of 30 million. We also showed that integrated mapping of multiple NTDs is feasible and cost effective. However, the sensitivity of the diagnostic test used for LF is less than 100% and the identification of a single ICT positive adult may not provide evidence of disease transmission. Based on these limitations, and in addition to the restricted geographical representation of just two sites within a woreda, we recommend conducting research in the 45 woredas with borderline results (one ICT+) to shrink the denominator even further.

Background The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya. Materials and Methods Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels. Principal Findings The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores. Conclusions The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes., Author Summary Most countries with endemic soil-transmitted helminth (STH) infections have started implementing deworming programmes in recent years. However, the achievable impact on the prevalence and intensity of infections will depend on the socioeconomic and environmental context in which the programme is implemented. We use a previously developed framework that considers the epidemiology of STH transmission, capacity to deliver treatment, operational and financial feasibility, to investigate reasons for the observed within-country variation of deworming programme impact based on data from the national school based deworming programme in Kenya. The study demonstrates that programme impact varied markedly within the country and that reductions in STH infection were associated with levels of access to water, sanitation and hygiene (at schools or within communities). The described framework can help to identify areas where lower programme impact can be expected, and also to determine which additional interventions should be implemented in support of the deworming efforts.

Morbidity induced by infection with the major soil transmitted infections (STH—Ascaris lumbricoides, Trichuris trichiura, and hookworms) results in an estimated 5.19 million disability-adjusted life years (DALYs) [1]. The World Health Organization’s (WHO) policy for control centres on three groups, preschool aged children (pre-SAC), school-aged children (SAC), and women of child bearing age, on the basis that heavy infection in these groups will have a detrimental impact on anaemia, child growth, and development. The current WHO guidelines focus on school-aged children, both for monitoring infection and as a target for treatment, although treatment of pre-SAC and women of childbearing age is also recommended where sustainable delivery mechanisms exist, especially in areas of intense transmission [2,3]. The guidelines recommend treating SAC annually where any STH prevalence falls between 20% and 50% and twice a year where it exceeds 50% [3].\ud \ud The London Declaration on Neglected Tropical Diseases in 2012 endorsed WHO goals to scale up mass drug administration (MDA) for STH, so that by 2020, 75% of the pre-SAC and SAC in need will be treated regularly [4]. Building on an existing roadmap, WHO announced an intention to meet the target [2,5,6]. Progress has been good in some areas, but less so in others. In 2012, global coverage of those in need was 37% for SAC and 29% for pre-SAC [5]. Data for the more recent years is as yet to be published by WHO [5], but a huge gain in coverage is not expected, despite increased drug donations from the pharmaceutical companies who manufacture the main anthelmintics. This is due in part to the logistical challenges in getting even donated drugs to these populations, who are often beyond “the end of the road.” At present, many countries with endemic STH infections are not availing themselves of the freely donated drugs to treat children.\ud \ud We are still a long way from the 2020 target of 75%. Even if this target is reached, will it be enough to eliminate transmission and the disease arising from heavy infections with STH? If not, how should the guidelines be changed to push towards morbidity control, and ideally, the eventual elimination of transmission?

In Table 3 the entry for Ethiopia contains incorrect sums of the subpopulation data within the larger geographical zones. Please see the corrected Table 3 here

Background Questionnaires of reported blood in urine (BIU) distributed through the existing school system provide a rapid and reliable method to classify schools according to the prevalence of Schistosoma haematobium, thereby helping in the targeting of schistosomiasis control. However, not all schools return questionnaires and it is unclear whether treatment is warranted in such schools. This study investigates the use of bivariate spatial modelling of available and multiple data sources to predict the prevalence of S. haematobium at every school along the Kenyan coast. Methodology Data from a questionnaire survey conducted by the Kenya Ministry of Education in Coast Province in 2009 were combined with available parasitological and environmental data in a Bayesian bivariate spatial model. This modeled the relationship between BIU data and environmental covariates, as well as the relationship between BIU and S. haematobium infection prevalence, to predict S. haematobium infection prevalence at all schools in the study region. Validation procedures were implemented to assess the predictive accuracy of endemicity classification. Principal Findings The prevalence of BIU was negatively correlated with distance to nearest river and there was considerable residual spatial correlation at small (∼15 km) spatial scales. There was a predictable relationship between the prevalence of reported BIU and S. haematobium infection. The final model exhibited excellent sensitivity (0.94) but moderate specificity (0.69) in identifying low (, Author Summary The highly focal nature of schistosomiasis means that treatment is most cost-effective when delivered on a school-by-school basis. Questionnaires of reported blood in urine (BIU) distributed through the existing school system are a rapid, valid method to classify schools according to WHO treatment thresholds. Their usefulness, however, can be hampered by incomplete return rates that impede treatment decisions in schools with missing questionnaire data. Using data from coastal Kenya, this study describes the use of Bayesian spatial modeling that combines questionnaire data with available parasitological data to make predictions of S. haematobium infection prevalence at all schools. Results showed that reported BIU was highly focal and was negatively associated with the distance to the nearest river. The final model was able to discriminate between schools that require treatment or not, but was less reliable at distinguishing between medium and high prevalence schools. Similar Bayesian spatial models may prove useful for modeling and predicting other diseases where multiple diagnostic techniques are employed.

Background Implementation of trachoma control strategies requires reliable district-level estimates of trachomatous inflammation–follicular (TF), generally collected using the recommended gold-standard cluster randomized surveys (CRS). Integrated Threshold Mapping (ITM) has been proposed as an integrated and cost-effective means of rapidly surveying trachoma in order to classify districts according to treatment thresholds. ITM differs from CRS in a number of important ways, including the use of a school-based sampling platform for children aged 1–9 and a different age distribution of participants. This study uses computerised sampling simulations to compare the performance of these survey designs and evaluate the impact of varying key parameters. Methodology/Principal Findings Realistic pseudo gold standard data for 100 districts were generated that maintained the relative risk of disease between important sub-groups and incorporated empirical estimates of disease clustering at the household, village and district level. To simulate the different sampling approaches, 20 clusters were selected from each district, with individuals sampled according to the protocol for ITM and CRS. Results showed that ITM generally under-estimated the true prevalence of TF over a range of epidemiological settings and introduced more district misclassification according to treatment thresholds than did CRS. However, the extent of underestimation and resulting misclassification was found to be dependent on three main factors: (i) the district prevalence of TF; (ii) the relative risk of TF between enrolled and non-enrolled children within clusters; and (iii) the enrollment rate in schools. Conclusions/Significance Although in some contexts the two methodologies may be equivalent, ITM can introduce a bias-dependent shift as prevalence of TF increases, resulting in a greater risk of misclassification around treatment thresholds. In addition to strengthening the evidence base around choice of trachoma survey methodologies, this study illustrates the use of a simulated approach in addressing operational research questions for trachoma but also other NTDs., Author Summary Reliable district-level prevalence estimates of active trachoma are essential to targeting control interventions. While cluster randomised surveys (CRS) remain the recommended strategy for obtaining these estimates, more rapid and cost-effective methods that can be integrated with other diseases are under investigation. One proposed method is Integrated Threshold Mapping (ITM), which incorporates a school-based platform into the sampling protocol. This study uses a computerised sampling approach to evaluate whether ITM and CRS are equivalent, and explore the impact of varying key parameters on the performance of these sampling methodologies. The results from these simulations reflect a known limitation of school-based sampling: that resulting prevalence estimates are unreliable when the enrollment is low and/or the risk of disease in schools differs from communities. However, quantification of the performance of ITM at the district level highlights the variation in performance in different contexts and provides important information for national control programmes. The results from this study strengthen the evidence base around trachoma sampling methodologies and demonstrate the advantages of using a simulated approach to evaluate different sampling scenarios.

JX; Chen, JH; Churcher, TS; Drakeley, CJ; Edwards, T; Fenwick, A; French, M; Gabrielli, AF; Grassly, NC; Harding-Esch, EM; Holland, MJ; Koukounari, A; Lammie, PJ; Leslie, J; Mabey, DC; Rhajaoui, M; Secor, WE; Stothard, JR; Wei, H; Willingham, AL; Zhou, XN; Peeling, RW (2012) A diagnostics platform for the integrated mapping, monitoring, and surveillance of neglected tropical diseases: rationale and target product profiles. PLoS neglected tropical diseases, 6 (7). e1746. ISSN 1935-2727

Background Morbidity due to Schistosoma haematobium and hookworm infections is marked in those with intense co-infections by these parasites. The development of a spatial predictive decision-support tool is crucial for targeting the delivery of integrated mass drug administration (MDA) to those most in need. We investigated the co-distribution of S. haematobium and hookworm infection, plus the spatial overlap of infection intensity of both parasites, in Ghana. The aim was to produce maps to assist the planning and evaluation of national parasitic disease control programs. Methodology/Principal Findings A national cross-sectional school-based parasitological survey was conducted in Ghana in 2008, using standardized sampling and parasitological methods. Bayesian geostatistical models were built, including a multinomial regression model for S. haematobium and hookworm mono- and co-infections and zero-inflated Poisson regression models for S. haematobium and hookworm infection intensity as measured by egg counts in urine and stool respectively. The resulting infection intensity maps were overlaid to determine the extent of geographical overlap of S. haematobium and hookworm infection intensity. In Ghana, prevalence of S. haematobium mono-infection was 14.4%, hookworm mono-infection was 3.2%, and S. haematobium and hookworm co-infection was 0.7%. Distance to water bodies was negatively associated with S. haematobium and hookworm co-infections, hookworm mono-infections and S. haematobium infection intensity. Land surface temperature was positively associated with hookworm mono-infections and S. haematobium infection intensity. While high-risk (prevalence >10–20%) of co-infection was predicted in an area around Lake Volta, co-intensity was predicted to be highest in foci within that area. Conclusions/Significance Our approach, based on the combination of co-infection and co-intensity maps allows the identification of communities at increased risk of severe morbidity and environmental contamination and provides a platform to evaluate progress of control efforts., Author Summary Urinary schistosomiasis and hookworm infections cause considerable morbidity in school age children in West Africa. Severe morbidity is predominantly observed in individuals infected with both parasite types and, in particular, with heavy infections. We investigated for the first time the distribution of S. haematobium and hookworm co-infections and distribution of co-intensity of these parasites in Ghana. Bayesian geostatistical models were developed to generate a national co-infection map and national intensity maps for each parasite, using data on S. haematobium and hookworm prevalence and egg concentration (expressed as eggs per 10 mL of urine for S. haematobium and expressed as eggs per gram of faeces for hookworm), collected during a pre-intervention baseline survey in Ghana, 2008. In contrast with previous findings from the East Africa region, we found that both S. haematobium and hookworm infections are highly focal, resulting in small, localized clusters of co-infection and areas of high co-intensity. Overlaying on a single map the co-infection and the intensity of multiple parasite infections allows identification of areas where parasite environmental contamination and morbidity are at its highest, while providing an evidence base for the assessment of the progress of successive rounds of mass drug administration (MDA) in integrated parasitic disease control programs.

Background Implementation of control of parasitic diseases requires accurate, contemporary maps that provide intervention recommendations at policy-relevant spatial scales. To guide control of soil transmitted helminths (STHs), maps are required of the combined prevalence of infection, indicating where this prevalence exceeds an intervention threshold of 20%. Here we present a new approach for mapping the observed prevalence of STHs, using the example of Kenya in 2009. Methods and Findings Observed prevalence data for hookworm, Ascaris lumbricoides and Trichuris trichiura were assembled for 106,370 individuals from 945 cross-sectional surveys undertaken between 1974 and 2009. Ecological and climatic covariates were extracted from high-resolution satellite data and matched to survey locations. Bayesian space-time geostatistical models were developed for each species, and were used to interpolate the probability that infection prevalence exceeded the 20% threshold across the country for both 1989 and 2009. Maps for each species were integrated to estimate combined STH prevalence using the law of total probability and incorporating a correction factor to adjust for associations between species. Population census data were combined with risk models and projected to estimate the population at risk and requiring treatment in 2009. In most areas for 2009, there was high certainty that endemicity was below the 20% threshold, with areas of endemicity ≥20% located around the shores of Lake Victoria and on the coast. Comparison of the predicted distributions for 1989 and 2009 show how observed STH prevalence has gradually decreased over time. The model estimated that a total of 2.8 million school-age children live in districts which warrant mass treatment. Conclusions Bayesian space-time geostatistical models can be used to reliably estimate the combined observed prevalence of STH and suggest that a quarter of Kenya's school-aged children live in areas of high prevalence and warrant mass treatment. As control is successful in reducing infection levels, updated models can be used to refine decision making in helminth control., Author Summary Effective targeting of mass drug administration for the treatment of soil-transmitted helminths (STH) requires reliable, up-to-date maps that indicate where prevalence exceeds the 20% intervention threshold recommended by the World Health Organization. We present a new approach for mapping the prevalence of STH in Kenya, incorporating observed prevalence data from 945 cross-sectional surveys undertaken between 1974 and 2009. The distribution of each species was modelled using model-based geostatistics; models included information on environmental factors, the spatial distribution of existing surveys and when these surveys were conducted. Resulting risk maps were combined and linked with population data enabling estimation of the population at risk of any STH infection and requiring treatment in 2009. In most areas, there was high certainty that combined STH prevalence was below the 20% intervention threshold, with areas of high prevalence located around the shores of Lake Victoria and on the coast. Results also suggest that observed prevalence decreased over time and emphasise the importance of continued surveillance in areas where observed prevalence was historically high. We show how spatial modelling can be used to develop up-to-date maps of STH risk to help improve the precision of decision making in disease control.

The recent commitment of the Obama administration to establish the Global Health Initiative, which is expected to increase to over US$100 million annually for neglected tropical disease (NTD) control, provides the most significant investment and opportunity for the global control of NTDs to date [1], [2]. These investments, together with commitments by the British Department for International Development, the World Bank, and several key private philanthropies, including the Bill & Melinda Gates Foundation, must be guided by a strong evidence-based approach. First, the problem, and the resources required to tackle it, need to be clearly quantified. Second, mass drug administration (MDA) should be optimally targeted to communities with the highest prevalence of infection and presumed greatest morbidity [3], [4]. Furthermore, for diseases targeted for elimination, including lymphatic filariasis (LF) and onchocerciasis, it will become increasingly important to determine whether MDA can be stopped, and, if so, when and where. In the case of schistosomiasis, as control is scaled up, there is the additional requirement of determining when and where to shift praziquantel treatment from once per year to less frequent intervals.

Background Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan. Methods and Findings Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel. Conclusion The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere., Author Summary Control of neglected tropical diseases (NTDs) is suggested to be more cost-effective when drugs are co-administered through a single integrated delivery system rather than separate systems. An essential prerequisite for such efficiency gains is sufficient geographical overlap of the targeted diseases – lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminth infection and trachoma. Lack of data on geographical NTD distribution currently hampers the implementation of integrated control in many African countries. To generate the required data quickly and efficiently, integrated surveys of several NTDs simultaneously have been recommended. However, experience with integrated surveys is limited and requires additional research on cost and effectiveness to inform improvements in methodology and to guide scale-up. Here we analyse costs of the first integrated NTD survey round in Southern Sudan, generating average costs per implementation unit surveyed. Cost estimates are presented for use of the existing survey method and for modified versions. Key cost drivers were survey consumables and personnel, both of which are recurrent costs. These inputs could be reduced or put to more efficient use by modifying sampling for LF. To generate comparable cost estimates and identify key cost drivers in other settings we provide detailed cost data and guidance on how to replicate this work.

Background Helminth co-infection in humans is common in tropical regions of the world where transmission of soil-transmitted helminths such as Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale as well as other helminths such as Schistosoma mansoni often occur simultaneously. Methodology We investigated whether co-infection with another helminth(s) altered the human immune response to crude antigen extracts from either different stages of N. americanus infection (infective third stage or adult) or different crude antigen extract preparations (adult somatic and adult excretory/secretory). Using these antigens, we compared the cellular and humoral immune responses of individuals mono-infected with hookworm (N. americanus) and individuals co-infected with hookworm and other helminth infections, namely co-infection with either A. lumbricoides, Schistosoma mansoni, or both. Immunological variables were compared between hookworm infection group (mono- versus co-infected) by bootstrap, and principal component analysis (PCA) was used as a data reduction method. Conclusions Contrary to several animal studies of helminth co-infection, we found that co-infected individuals had a further downmodulated Th1 cytokine response (e.g., reduced INF-γ), accompanied by a significant increase in the hookworm-specific humoral immune response (e.g. higher levels of IgE or IgG4 to crude antigen extracts) compared with mono- infected individuals. Neither of these changes was associated with a reduction of hookworm infection intensity in helminth co-infected individuals. From the standpoint of hookworm vaccine development, these results are relevant; i.e., the specific immune response to hookworm vaccine antigens might be altered by infection with another helminth., Author Summary Parasitic infections in humans are common in tropical regions and under bad housing and sanitation conditions multiple parasitic infections are the rule rather than the exception. For helminth infections, which are thought to affect almost a quarter of the world's population, most common combinations include soil-transmitted helminths, such as hookworm, roundworm, and whipworm, as well as extra-intestinal infections by schistosomes. In order to develop and test a hookworm vaccine in endemic areas, the understanding of the impact of multiple helminth infections (co-infection) on the immune response against hookworm in infected individuals is crucial. The authors report in their article, that several parameters of the cellular (T cell markers, cytokines, chemokines) and humoral immune response (e.g. IgG4 and IgE antibodies) against hookworm are significantly affected or modulated in individuals co-infected with hookworm, roundworm and/or schistosomes. These results imply that the immune response against components of a hookworm vaccine might be altered by previous contact with other helminth species in endemic areas.

Background There are few detailed data on the geographic distribution of most neglected tropical diseases (NTDs) in post-conflict Southern Sudan. To guide intervention by the recently established national programme for integrated NTD control, we conducted an integrated prevalence survey for schistosomiasis, soil-transmitted helminth (STH) infection, lymphatic filariasis (LF), and loiasis in Northern Bahr-el-Ghazal State. Our aim was to establish which communities require mass drug administration (MDA) with preventive chemotherapy (PCT), rather than to provide precise estimates of infection prevalence. Methods and Findings The integrated survey design used anecdotal reports of LF and proximity to water bodies (for schistosomiasis) to guide selection of survey sites. In total, 86 communities were surveyed for schistosomiasis and STH; 43 of these were also surveyed for LF and loiasis. From these, 4834 urine samples were tested for blood in urine using Hemastix reagent strips, 4438 stool samples were analyzed using the Kato-Katz technique, and 5254 blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). 4461 individuals were interviewed regarding a history of ‘eye worm’ (a proxy measure for loiasis) and 31 village chiefs were interviewed regarding the presence of clinical manifestations of LF in their community. At the village level, prevalence of Schistosoma haematobium and S. mansoni ranged from 0 to 65.6% and from 0 to 9.3%, respectively. The main STH species was hookworm, ranging from 0 to 70% by village. Infection with LF and loiasis was extremely rare, with only four individuals testing positive or reporting symptoms, respectively. Questionnaire data on clinical signs of LF did not provide a reliable indication of endemicity. MDA intervention thresholds recommended by the World Health Organization were only exceeded for urinary schistosomiasis and hookworm in a few, yet distinct, communities. Conclusion This was the first attempt to use an integrated survey design for this group of infections and to generate detailed results to guide their control over a large area of Southern Sudan. The approach proved practical, but could be further simplified to reduce field work and costs. The results show that only a few areas need to be targeted with MDA of PCT, thus confirming the importance of detailed mapping for cost-effective control., Author Summary Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data.

Background Individuals living in areas endemic for helminths are commonly infected with multiple species. Despite increasing emphasis given to the potential health impacts of polyparasitism, few studies have investigated the relative importance of household and environmental factors on the risk of helminth co-infection. Here, we present an investigation of exposure-related risk factors as sources of heterogeneity in the distribution of co-infection with Necator americanus and Schistosoma mansoni in a region of southeastern Brazil. Methodology Cross-sectional parasitological and socio-economic data from a community-based household survey were combined with remotely sensed environmental data using a geographical information system. Geo-statistical methods were used to explore patterns of mono- and co-infection with N. americanus and S. mansoni in the region. Bayesian hierarchical models were then developed to identify risk factors for mono- and co-infection in relation to community-based survey data to assess their roles in explaining observed heterogeneity in mono and co-infection with these two helminth species. Principal Findings The majority of individuals had N. americanus (71.1%) and/or S. mansoni (50.3%) infection; 41.0% of individuals were co-infected with both helminths. Prevalence of co-infection with these two species varied substantially across the study area, and there was strong evidence of household clustering. Hierarchical multinomial models demonstrated that relative socio-economic status, household crowding, living in the eastern watershed and high Normalized Difference Vegetation Index (NDVI) were significantly associated with N. americanus and S. mansoni co-infection. These risk factors could, however, only account for an estimated 32% of variability between households. Conclusions Our results demonstrate that variability in risk of N. americanus and S. mansoni co-infection between households cannot be entirely explained by exposure-related risk factors, emphasizing the possible role of other household factors in the heterogeneous distribution of helminth co-infection. Untangling the relative contribution of intrinsic host factors from household and environmental determinants therefore remains critical to our understanding of helminth epidemiology., Author Summary Helminth species such as Necator americanus and Schistosoma mansoni are among the most prevalent of chronic human infections in the developing world. Individuals living in endemic areas are commonly infected with both species. Although the implications of being co-infected with helminths are increasingly recognized, factors influencing patterns of co-infection within human communities remain ill-defined. Here, we describe spatial patterns and risk factors for co-infection with N. americanus and S. mansoni in a co-endemic area in south-eastern Brazil. The prevalence of co-infection with these two helminths in this region was high (41%), varied across the study area and was clustered in high-risk households. We reveal that factors associated with lower socio-economic status (relative socio-economic status, household crowding) and residential environment (living in the eastern watershed or in areas with less vegetation) were significantly associated with the risk of co-infection relative to being uninfected with either species. Importantly, much of the variability in risk between households (i.e. household clustering) could not be readily explained by these risk factors. The results suggest that, whilst measures aimed at reducing exposure to infection may have an important impact on co-infection and its associated morbidity, untangling the relative contribution of intrinsic host factors (e.g. immune response) from household and environmental determinants remains critical to our understanding of helminth epidemiology.

Background Originally a binary classifier, Lot Quality Assurance Sampling (LQAS) has proven to be a useful tool for classification of the prevalence of Schistosoma mansoni into multiple categories (≤10%, >10 and, Author Summary The control of schistosomiasis calls for rapid and reliable classification tools. This study evaluates the performance of one such tool, Lot Quality Assurance Sampling (LQAS) for assessing the prevalence of S. mansoni in African schoolchildren. We outline the design considerations and introduce novel sequential sampling plans for Multiple Category-LQAS. We use data from 388 schools in Uganda, Kenya, and Tanzania to assess the performance of LQAS as a tool for classification of S. mansoni infection into one of three classes: ≤10% >10 and

Trachoma is the leading infectious cause of blindness worldwide, and responsible for the loss of an estimated 1.3 million disability-adjusted life years, mainly in sub-Saharan Africa [1]. Geographically, trachoma is a greater public health risk in dry, dusty, and hot settings, where poor, rural communities suffer a disproportionate burden of disease. Trachoma is caused by infection with the bacterium Chlamydia trachomatis, but the condition has a number of clinical manifestations that are the consequences of current or past infection [2]. Prevalence of infection and clinical signs of follicular conjunctivitis are highest in children under 10 y of age. Recurrent episodes of infection and associated inflammation can cause scarring, visual impairment, and potential blindness later in life. In 1998, the World Health Organization (WHO) established an international alliance eliminate trachoma as a public health problem by 2020, called the Alliance for Global Elimination of Trachoma by the year 2020 (GET2020). The goal of GET2020 is to reduce the burden of trachoma in any community to less than one case of trachomatous trichiasis (TT) per 1,000 total population, and to less than 5% prevalence of “trachomatous inflammation–follicular” (TF) in children aged 1–9 y [3]. The strategy employed to reach these targets is based on a combination of interventions known as SAFE: Surgery to correct trichiasis, Antibiotics for C. trachomatis infection, Facial cleanliness, and Environmental improvement to reduce transmission. In order to allow time for programme implementation and impact by 2020, it will be necessary to scale up to full SAFE implementation in all endemic districts by 2015. An essential component of this effort is producing up-to-date and accessible maps of the distribution of trachoma for advocacy, planning, and operational research purposes.

There are remarkably few contemporary, population-based studies of intestinal nematode infection for sub-Saharan Africa. This paper presents a comprehensive epidemiological analysis of hookworm infection intensity in a rural Ugandan community. Demographic, kinship, socioeconomic and environmental data were collected for 1,803 individuals aged six months to 85 years in 341 households in a cross-sectional community survey. Hookworm infection was assessed by faecal egg count. Spatial variation in the intensity of infection was assessed using a Bayesian negative binomial spatial regression model and the proportion of variation explained by host additive genetics (heritability) and common domestic environment was estimated using genetic variance component analysis. Overall, the prevalence of hookworm was 39.3%, with the majority of infections (87.7%) of light intensity (≤1000 eggs per gram faeces). Intensity was higher among older individuals and was associated with treatment history with anthelmintics, walking barefoot outside the home, living in a household with a mud floor and education level of the household head. Infection intensity also exhibited significant household and spatial clustering: the range of spatial correlation was estimated to be 82 m and was reduced by a half over a distance of 19 m. Heritability of hookworm egg count was 11.2%, whilst the percentage of variance explained by unidentified domestic effects was 17.8%. In conclusion, we suggest that host genetic relatedness is not a major determinant of infection intensity in this community, with exposure-related factors playing a greater role., Author Summary Detailed descriptions of the epidemiology of intestinal nematode infections within affected communities remain of considerable importance for the effective design of disease control programmes. We therefore conducted a parasitological survey of 1,803 individuals living in a rural community in eastern Uganda. Two complementary analytical approaches were used to evaluate causes of variation in intensity of hookworm infection in this community, both of which exploit correlation structures between individuals. Infection intensity was higher among older individuals and was also associated with factors influencing environmental exposure to infection, socio-economic indicators and treatment history. After accounting for these risk factors, spatial correlation remained evident between households less than 82m apart. Focusing further on similarities within households, our results suggest that 11% of variation in infection intensity could be explained by genetic differences between individuals and 18% by unmeasured factors associated with the domestic environment. Taken together, these results suggest that exposure-related factors, rather than host genetics, have the greatest influence on variation in infection intensities.

Background We investigated changes in the spatial distribution of schistosomiasis in Mali following a decade of donor-funded control and a further 12 years without control. Methodology/Principal Findings National pre-intervention cross-sectional schistosomiasis surveys were conducted in Mali in 1984–1989 (in communities) and again in 2004–2006 (in schools). Bayesian geostatistical models were built separately for each time period and on the datasets combined across time periods. In the former, data from one period were used to predict prevalence of schistosome infections for the other period, and in the latter, the models were used to determine whether spatial autocorrelation and covariate effects were consistent across periods. Schistosoma haematobium prevalence was 25.7% in 1984–1989 and 38.3% in 2004–2006; S. mansoni prevalence was 7.4% in 1984–1989 and 6.7% in 2004–2006 (note the models showed no significant difference in mean prevalence of either infection between time periods). Prevalence of both infections showed a focal spatial pattern and negative associations with distance from perennial waterbodies, which was consistent across time periods. Spatial models developed using 1984–1989 data were able to predict the distributions of both schistosome species in 2004–2006 (area under the receiver operating characteristic curve was typically >0.7) and vice versa. Conclusions/Significance A decade after the apparently successful conclusion of a donor-funded schistosomiasis control programme from 1982–1992, national prevalence of schistosomiasis had rebounded to pre-intervention levels. Clusters of schistosome infections occurred in generally the same areas accross time periods, although the precise locations varied. To achieve long-term control, it is essential to plan for sustainability of ongoing interventions, including stengthening endemic country health systems., Author Summary Geostatistical maps are increasingly being used to plan neglected tropical disease control programmes. We investigated the spatial distribution of schistosomiasis in Mali prior to implementation of national donor-funded mass chemotherapy programmes using data from 1984–1989 and 2004–2006. The 2004–2006 dataset was collected after 10 years of schistosomiasis control followed by 12 years of no control. We found that national prevalence of Schistosoma haematobium and S. mansoni was not significantly different in 2004–2006 compared to 1984–1989 and that the spatial distribution of both infections was similar in both time periods, to the extent that models built on data from one time period could accurately predict the spatial distribution of prevalence of infection in the other time period. This has two main implications: that historic data can be used, in the first instance, to plan contemporary control programmes due to the stability of the spatial distribution of schistosomiasis; and that a decade of donor-funded mass distribution of praziquantel has had no discernable impact on the burden of schistosomiasis in subsequent generations of Malians, probably due to rapid reinfection.