Costs of community-wide mass drug administration and school-based deworming for soil-transmitted helminths: evidence from a randomised controlled trial in Benin, India and Malawi.

OBJECTIVES: Current guidelines for the control of soil-transmitted helminths (STH) recommend deworming children and other high-risk groups, primarily using school-based deworming (SBD) programmes. However, targeting individuals of all ages through community-wide mass drug administration (cMDA) may interrupt STH transmission in some settings. We compared the costs of cMDA to SBD to inform decision-making about future updates to STH policy. DESIGN: We conducted activity-based microcosting of cMDA and SBD for 2 years in Benin, India and Malawi within an ongoing cMDA trial. SETTING: Field sites and collaborating research institutions. PRIMARY AND SECONDARY OUTCOMES: We calculated total financial and opportunity costs and costs per treatment administered (unit costs in 2019 USD ($)) from the service provider perspective, including costs related to community drug distributors and other volunteers. RESULTS: On average, cMDA unit costs were more expensive than SBD in India ($1.17 vs $0.72) and Malawi ($2.26 vs $1.69), and comparable in Benin ($2.45 vs $2.47). cMDA was more expensive than SBD in part because most costs (~60%) were 'supportive costs' needed to deliver treatment with high coverage, such as additional supervision and electronic data capture. A smaller fraction of cMDA costs (~30%) was routine expenditures (eg, drug distributor allowances). The remaining cMDA costs (~10%) were opportunity costs of staff and volunteer time. A larger percentage of SBD costs was opportunity costs for teachers and other government staff (between ~25% and 75%). Unit costs varied over time and were sensitive to the number of treatments administered. CONCLUSIONS: cMDA was generally more expensive than SBD. Accounting for local staff time (volunteers, teachers, health workers) in community programmes is important and drives higher cost estimates than commonly recognised in the literature. Costs may be lower outside of a trial setting, given a reduction in supportive costs used to drive higher treatment coverage and economies of scale. TRIAL REGISTRATION NUMBER: NCT03014167.

Effectiveness of community-based burden estimation to achieve elimination of lymphatic filariasis: A comparative cross-sectional investigation in Côte d'Ivoire.

For lymphatic filariasis (LF) elimination, endemic countries must document the burden of LF morbidity (LFM). Community-based screening (CBS) is used to collect morbidity data, but evidence demonstrating its reliability is limited. Recent pilots of CBS for LFM alongside mass drug administration (MDA) in Côte d'Ivoire suggested low LFM prevalence (2.1-2.2 per 10,000). We estimated LFM prevalence in Bongouanou District, Côte d'Ivoire, using a comparative cross-sectional design. We compared CBS implemented independently of MDA, adapted from existing Ministry of Health protocols, to a population-based prevalence survey led by formally trained nurses. We evaluated the reliability of case identification, coverage, equity, and cost of CBS. CBS identified 87.4 cases of LFM per 10,000; the survey identified 47.5 (39.4-56.3; prevalence ratio [PR] 1.84; 95% CI 1.64-2.07). CBS identified 39.7 cases of suspect lymphoedema per 10,000; the survey confirmed 35.1 (29.2-41.5) filarial lymphoedema cases per 10,000 (PR 1.13 [0.98-1.31]). CBS identified 96.5 scrotal swellings per 10,000; the survey found 91.3 (83.2-99.8; PR 1.06 [0.93-1.21]); including 33.9 (27.7-38.8) filarial hydrocoele per 10,000 (PR of suspect to confirmed hydrocele 2.93 [2.46-3.55]). Positive predictive values for case identification through CBS were 65.0% (55.8-73.5%) for filarial lymphoedema; 93.7% (89.3-96.7%) for scrotal swellings; and 34.0% (27.3-41.2%) for filarial hydrocoele. Households of lower socioeconomic status and certain minority languages were at risk of exclusion. Direct financial costs were $0.17 per individual targeted and $69.62 per case confirmed. Our community-based approach to LFM burden estimation appears scalable and provided reliable prevalence estimates for LFM, scrotal swellings and LF-lymphoedema. The results represent a step-change improvement on CBS integrated with MDA, whilst remaining at programmatically feasible costs. Filarial hydrocoele cases were overestimated, attributable to the use of case definitions suitable for mass-screening by informal staff. Our findings are broadly applicable to countries aiming for LF elimination using CBS. The abstract is available in French in the S1 File.

Assessment of the required performance and the development of corresponding program decision rules for neglected tropical diseases diagnostic tests: Monitoring and evaluation of soil-transmitted helminthiasis control programs as a case study.

Recently, the World Health Organization established the Diagnostic Technical Advisory Group to identify and prioritize diagnostic needs for neglected tropical diseases, and to ultimately describe the minimal and ideal characteristics for new diagnostic tests (the so-called target product profiles (TPPs)). We developed two generic frameworks: one to explore and determine the required sensitivity (probability to correctly detect diseased persons) and specificity (probability to correctly detect persons free of disease), and another one to determine the corresponding samples sizes and the decision rules based on a multi-category lot quality assurance sampling (MC-LQAS) approach that accounts for imperfect tests. We applied both frameworks for monitoring and evaluation of soil-transmitted helminthiasis control programs. Our study indicates that specificity rather than sensitivity will become more important when the program approaches the endgame of elimination and that the requirements for both parameters are inversely correlated, resulting in multiple combinations of sensitivity and specificity that allow for reliable decision making. The MC-LQAS framework highlighted that improving diagnostic performance results in a smaller sample size for the same level of program decision making. In other words, the additional costs per diagnostic tests with improved diagnostic performance may be compensated by lower operational costs in the field. Based on our results we proposed the required minimal and ideal diagnostic sensitivity and specificity for diagnostic tests applied in monitoring and evaluating of soil-transmitted helminthiasis control programs.

Prevalence and intensity of soil-transmitted helminth infections of children in sub-Saharan Africa, 2000-18: a geospatial analysis.

BACKGROUND: Driven by global targets to eliminate soil-transmitted helminths as a public health problem, governments have rapidly rolled out control programmes using school and community-based platforms. To justify and target ongoing investment, quantification of impact and identification of remaining high-risk areas are needed. We aimed to assess regional progress towards these targets. METHODS: We did a continental-scale ecological analysis using a Bayesian space-time hierarchical model to estimate the effects of known environmental, socioeconomic, and control-related factors on the prevalence of soil-transmitted helminths, and we mapped the probability that implementation units had achieved moderate-to-heavy intensity infection prevalence of less than 2% among children aged 5-14 years between Jan 1, 2000, and Dec 31, 2018. FINDINGS: We incorporated data from 26 304 georeferenced surveys, spanning 3096 (60%) of the 5183 programmatic implementation units. Our findings suggest a reduction in the prevalence of soil-transmitted helminths in children aged 5-14 years in sub-Saharan Africa, from 44% in 2000 to 13% in 2018, driven by sustained delivery of preventive chemotherapy, improved sanitation, and economic development. Nevertheless, 1301 (25%) of 5183 implementation units still had an estimated prevalence of moderate-to-heavy intensity infection exceeding the 2% target threshold in 2018, largely concentrated in nine countries (in 1026 [79%] of 1301 implementation units): Nigeria, Democratic Republic of the Congo, Ethiopia, Cameroon, Angola, Mozambique, Madagascar, Equatorial Guinea, and Gabon. INTERPRETATION: Our estimates highlight the areas to target and strengthen interventions, and the areas where data gaps remain. If elimination of soil-transmitted helminths as a public health problem is to be achieved in sub-Saharan Africa by 2030, continued investment in treatment and prevention activities are essential to ensure that no areas are left behind. FUNDING: Bill & Melinda Gates Foundation.

Evaluating survey designs for targeting preventive chemotherapy against Schistosoma haematobium and Schistosoma mansoni across sub-Saharan Africa: a geostatistical analysis and modelling study.

BACKGROUND: Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. METHODS: Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. RESULTS: Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness. CONCLUSIONS: This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.

Practical Implications of a Relationship between Health Management Information System and Community Cohort-Based Malaria Incidence Rates.

Global malaria burden is reducing with effective control interventions, and surveillance is vital to maintain progress. Health management information system (HMIS) data provide a powerful surveillance tool; however, its estimates of burden need to be better understood for effectiveness. We aimed to investigate the relationship between HMIS and cohort incidence rates and identify sources of bias in HMIS-based incidence. Malaria incidence was estimated using HMIS data from 15 health facilities in three subcounties in Uganda. This was compared with a gold standard of representative cohort studies conducted in children aged 0.5 to < 11 years, followed concurrently in these sites. Between October 2011 and September 2014, 153,079 children were captured through HMISs and 995 followed up through enhanced community cohorts in Walukuba, Kihihi, and Nagongera subcounties. Although HMISs substantially underestimated malaria incidence in all sites compared with data from the cohort studies, there was a strong linear relationship between these rates in the lower transmission settings (Walukuba and Kihihi), but not the lowest HMIS performance highest transmission site (Nagongera), with calendar year as a significant modifier. Although health facility accessibility, availability, and recording completeness were associated with HMIS incidence, they were not significantly associated with bias in estimates from any site. Health management information systems still require improvements; however, their strong predictive power of unbiased malaria burden when improved highlights the important role they could play as a cost-effective tool for monitoring trends and estimating impact of control interventions. This has important implications for malaria control in low-resource, high-burden countries.

Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda.

BACKGROUND: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. METHODS: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. RESULTS: Overall, 896,550 patient visits were included in the study; 211,632 aged < 5 years, 171,166 aged 5-15 years and 513,752 > 15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in < 5 years decreased from 31 to 16% and 35 to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58 to 30% and 64 to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases > 15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. CONCLUSIONS: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

"For how long are we going to take the tablets?" Kenyan stakeholders' views on priority investments to sustainably tackle soil-transmitted helminths.

Recent global commitments to shift responsibility for Neglected Tropical Disease (NTD) control to affected countries reflect a renewed emphasis on sustainability, away from aid-dependency. This calls for a better understanding of how domestic stakeholders perceive investments in different strategies for NTD control. Soil transmitted helminths (STH) are among the NTDs targeted for elimination as a public health problem by international agencies through mass drug administration, provided periodically to at-risk population groups, often using drugs donated by pharmaceutical companies. This study was conducted in Kenya at a time when responsibilities for long running STH programmes were transitioning from external to national and sub-national agencies. Following an initial assessment in which we identified key domestic stakeholders and reviewed relevant scientific and government documents, the perspectives of stakeholders working in health, education, community engagement and sanitation were investigated through semi-structured interviews with national level policymakers, county level policymakers, and frontline implementers in one high-STH burden county, Kwale. Our conceptual framework on sustainability traced a progression in thinking, from ensuring financial stability through the technical ability to adapt to changing circumstances, and ultimately to a situation where a programme is prioritised by domestic policymakers because empowered communities demand it. It was clear from our interviews that most Kenyan stakeholders sought to be at the final stage in this progression. Interviewees criticised long-term investment in mass drug administration, the approach favoured predominantly by external agencies, for failing to address underlying causes of STH. Instead they identified three synergistic priority areas for investment: changes in institutional structures and culture to reduce working in silos; building community demand and ownership; and increased policymaker engagement on underlying socioeconomic and environmental causes of STH. Although challenging to implement, the shift in responsibility from external agencies to domestic stakeholders may lead to emergence of new strategic directions.

100 Years of Mass Deworming Programmes: A Policy Perspective From the World Bank's Disease Control Priorities Analyses.

For more than 100 years, countries have used mass drug administration as a public health response to soil-transmitted helminth infection. The series of analyses published as Disease Control Priorities is the World Bank's vehicle for exploring the cost-effectiveness and value for money of public health interventions. The first edition was published in 1993 as a technical supplement to the World Bank's World Development Report Investing in Health where deworming was used as an illustrative example of value for money in treating diseases with relatively low morbidity but high prevalence. Over the second (2006) and now third (2017) editions deworming has been an increasingly persuasive example to use for this argument. The latest analyses recognize the negative impact of intestinal worm infection on human capital in poor communities and document a continuing decline in worm infection as a result of the combination of high levels of mass treatment and ongoing economic development trends in poor communities.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol.

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03014167.

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. RESULTS: Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences < 1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. CONCLUSIONS: Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA.

Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya.

INTRODUCTION: In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? METHODS AND ANALYSIS: Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision-termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. ETHICS AND DISSEMINATION: Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. TRIAL REGISTRATION NUMBER: NCT02397772.

Global feasibility assessment of interrupting the transmission of soil-transmitted helminths: a statistical modelling study.

BACKGROUND: Emphasis is being given to the control of neglected tropical diseases, including the possibility of interrupting the transmission of soil-transmitted helminths (STH). We evaluated the feasibility by country of achieving interruption of the transmission of STH. METHODS: Based on a conceptual framework for the identification of the characteristics of a successful STH control programme, we assembled spatial data for a range of epidemiological, institutional, economic, and political factors. Using four different statistical methods, we developed a composite score of the feasibility of interrupting STH transmission and undertook a sensitivity analysis of the data and methods. FINDINGS: The most important determining factors in the analysis were underlying intensity of STH transmission, current implementation of control programmes for neglected tropical diseases, and whether countries receive large-scale external funding and have strong health systems. The composite scores suggested that interrupting STH transmission is most feasible in countries in the Americas and parts of Asia (eg, Argentina [range of composite feasibility scores, depending on scoring method, 9·4-10·0], Brazil [8·7- 9·7], Chile [8·84-10·0], and Thailand [9·1-10·0]; there was perfect agreement between the four methods), and least feasible in countries in sub-Saharan Africa (eg, Congo [0·4-2·7] and Guinea [2·0-5·6]; there was full agreement between methods), but there were important exceptions to these trends (eg, Ghana [7·4-10·0]; there was agreement between three methods). Agreement was highest between the scores derived with the expert opinion and principal component analysis weighting schemes (Pearson correlation coefficient, r=0·98). The largest disagreement was between benefit-of-the-doubt-derived and principal-component-analysis-derived weighting schemes (r=0·74). INTERPRETATION: The interruption of STH transmission is feasible, especially in countries with low intensity of transmission, supportive household environments, strong health systems, and the availability of suitable delivery platforms and in-country funds, but to achieve local elimination of STH an intersectoral approach to STH control will be needed. FUNDING: Bill & Melinda Gates Foundation and Wellcome Trust.

Diagnostic accuracy and cost-effectiveness of alternative methods for detection of soil-transmitted helminths in a post-treatment setting in western Kenya.

OBJECTIVES: This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. METHODS: Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. RESULTS: Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. CONCLUSIONS: The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings.

Geographical inequalities in use of improved drinking water supply and sanitation across Sub-Saharan Africa: mapping and spatial analysis of cross-sectional survey data.

BACKGROUND: Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries. METHODS AND FINDINGS: Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991-2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators. CONCLUSIONS: This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda. Please see later in the article for the Editors' Summary.

Estimating the relative contribution of parasitic infections and nutrition for anaemia among school-aged children in Kenya: a subnational geostatistical analysis.

OBJECTIVES: To quantify geographical variation in the relative contribution of parasitic infections, socioeconomic factors and malnutrition in the aetiology of anaemia among schoolchildren across Kenya, thereby providing a rational basis for the targeting of an integrated school health package. DESIGN: Nationally representative cross-sectional survey data were collected using standard protocols. For all included children, data were recorded on haemoglobin (Hb) concentration and common parasitic infections (Plasmodium falciparum, hookworm and schistosomes) and socioeconomic indicators. Ecological proxies of malnutrition and food security were generated using Demographic and Health Survey and UN Food and Agriculture Organization food security data, respectively. Spatially explicit, multilevel models were used to quantify impact upon child Hb concentration. SETTING: Randomly selected schools in ecologically diverse settings across Kenya. MAIN OUTCOME MEASURES: Mean Hb concentration adjusted for infection, nutritional and socioeconomic risk factors; associated risk ratios and adjusted Population Attributable Fractions (PAFs) for anaemia, by region. RESULTS: Data were available for 16 941 children in 167 schools; mean Hb was 122.1 g/l and 35.3% of children were anaemic. In multivariate analysis, mean Hb was significantly lower in boys and younger children. Severe malnutrition and interactions between P falciparum and hookworm infections were significantly associated with lower Hb, with greater impacts seen for coinfected children. The contribution of risk factors to anaemia risk varied by province: in 14-year-old girls, PAFs ranged between 0% and 27.6% for P falciparum, 0% and 29% for hookworm and 0% and 18.4% for severe malnutrition. CONCLUSIONS: The observed geographical heterogeneity in the burden of anaemia attributable to different aetiological factors has important implications for the rational targeting of antianaemia interventions that can be included in an integrated school health programme.

The global limits and population at risk of soil-transmitted helminth infections in 2010.

BACKGROUND: Understanding the global limits of transmission of soil-transmitted helminth (STH) species is essential for quantifying the population at-risk and the burden of disease. This paper aims to define these limits on the basis of environmental and socioeconomic factors, and additionally seeks to investigate the effects of urbanisation and economic development on STH transmission, and estimate numbers at-risk of infection with Ascaris lumbricoides, Trichuris trichiura and hookworm in 2010. METHODS: A total of 4,840 geo-referenced estimates of infection prevalence were abstracted from the Global Atlas of Helminth Infection and related to a range of environmental factors to delineate the biological limits of transmission. The relationship between STH transmission and urbanisation and economic development was investigated using high resolution population surfaces and country-level socioeconomic indicators, respectively. Based on the identified limits, the global population at risk of STH transmission in 2010 was estimated. RESULTS: High and low land surface temperature and extremely arid environments were found to limit STH transmission, with differential limits identified for each species. There was evidence that the prevalence of A. lumbricoides and of T. trichiura infection was statistically greater in peri-urban areas compared to urban and rural areas, whilst the prevalence of hookworm was highest in rural areas. At national levels, no clear socioeconomic correlates of transmission were identified, with the exception that little or no infection was observed for countries with a per capita gross domestic product greater than US$ 20,000. Globally in 2010, an estimated 5.3 billion people, including 1.0 billion school-aged children, lived in areas stable for transmission of at least one STH species, with 69% of these individuals living in Asia. A further 143 million (31.1 million school-aged children) lived in areas of unstable transmission for at least one STH species. CONCLUSIONS: These limits provide the most contemporary, plausible representation of the extent of STH risk globally, and provide an essential basis for estimating the global disease burden due to STH infection.

Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community.

This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15-0·29) and 70·9 epg (95% CI 47·2-106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03-0·10) and intensity 6·51 epg (95% CI 3·82-11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.