Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard.

Reliable, sensitive and practical diagnostic tests are an essential tool in disease control programmes for mapping, impact evaluation and surveillance. To provide a robust global assessment of the relative performance of available diagnostic tools for the detection of soil-transmitted helminths, we conducted a meta-analysis comparing the sensitivities and the quantitative performance of the most commonly used copro-microscopic diagnostic methods for soil-transmitted helminths, namely Kato-Katz, direct microscopy, formol-ether concentration, McMaster, FLOTAC and Mini-FLOTAC. In the absence of a perfect reference standard, we employed a Bayesian latent class analysis to estimate the true, unobserved sensitivity of compared diagnostic tests for each of the soil-transmitted helminth species Ascaris lumbricoides, Trichuris trichiura and the hookworms. To investigate the influence of varying transmission settings we subsequently stratified the analysis by intensity of infection. Overall, sensitivity estimates varied between the different methods, ranging from 42.8% for direct microscopy to 92.7% for FLOTAC. The widely used double slide Kato-Katz method had a sensitivity of 74-95% for the three soil-transmitted helminth species at high infection intensity, however sensitivity dropped to 53-80% in low intensity settings, being lowest for hookworm and A. lumbricoides. The highest sensitivity, overall and in both intensity groups, was observed for the FLOTAC method, whereas the sensitivity of the Mini-FLOTAC method was comparable with the Kato-Katz method. FLOTAC average egg count estimates were significantly lower compared with Kato-Katz, while the compared McMaster counts varied. In conclusion, we demonstrate that the Kato-Katz and Mini-FLOTAC methods had comparable sensitivities. We further show that test sensitivity of the Kato-Katz method is reduced in low transmission settings

How effective is school-based deworming for the community-wide control of soil-transmitted helminths?

Background: The London Declaration on neglected tropical diseases was based in part on a new World Health Organization roadmap to “sustain, expand and extend drug access programmes to ensure the necessary supply of drugs and other interventions to help control by 2020”. Large drug donations from the pharmaceutical industry form the backbone to this aim, especially for soil-transmitted helminths (STHs) raising the question of how best to use these resources. Deworming for STHs is often targeted at school children because they are at greatest risk of morbidity and because it is remarkably cost-effective. However, the impact of school-based deworming on transmission in the wider community remains unclear. Methods: We first estimate the proportion of parasites targeted by school-based deworming using demography, school enrolment, and data from a small number of example settings where age-specific intensity of infection (either worms or eggs) has been measured for all ages. We also use transmission models to investigate the potential impact of this coverage on transmission for different mixing scenarios. Principal Findings: In the example settings <30% of the population are 5 to <15 years old. Combining this demography with the infection age-intensity profile we estimate that in one setting school children output as little as 15% of hookworm eggs, whereas in another setting they harbour up to 50% of Ascaris lumbricoides worms (the highest proportion of parasites for our examples). In addition, it is estimated that from 40–70% of these children are enrolled at school. Conclusions: These estimates suggest that, whilst school-based programmes have many important benefits, the proportion of infective stages targeted by school-based deworming may be limited, particularly where hookworm predominates. We discuss the consequences for transmission for a range of scenarios, including when infective stages deposited by children are more likely to contribute to transmission than those from adults

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

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

Improved household flooring is associated with lower odds of enteric and parasitic infections in low- and middle-income countries: A systematic review and meta-analysis

Enteric and parasitic infections such as soil-transmitted helminths cause considerable mortality and morbidity in low- and middle-income settings. Earthen household floors are common in many of these settings and could serve as a reservoir for enteric and parasitic pathogens, which can easily be transmitted to new hosts through direct or indirect contact. We conducted a systematic review and meta-analysis to establish whether and to what extent improved household floors decrease the odds of enteric and parasitic infections among occupants compared with occupants living in households with unimproved floors. Following the PRISMA guidelines, we comprehensively searched four electronic databases for studies in low- and middle-income settings measuring household flooring as an exposure and self-reported diarrhoea or any type of enteric or intestinal-parasitic infection as an outcome. Metadata from eligible studies were extracted and transposed on to a study database before being imported into the R software platform for analysis. Study quality was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale. In total 110 studies were eligible for inclusion in the systematic review, of which 65 were eligible for inclusion in the meta-analysis after applying study quality cut-offs. Random-effects meta-analysis suggested that households with improved floors had 0.75 times (95CI: 0.67-0.83) the odds of infection with any type of enteric or parasitic infection compared with household with unimproved floors. Improved floors gave a pooled protective OR of 0.68 (95CI: 0.58-0.8) for helminthic infections and 0.82 OR (95CI: 0.75-0.9) for bacterial or protozoan infections. Overall study quality was poor and there is an urgent need for high-quality experimental studies investigating this relationship. Nevertheless, this study indicates that household flooring may meaningfully contribute towards a substantial portion of the burden of disease for enteric and parasitic infections in low- and middle-income settings

"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

Plasmodium infection and its risk factors in eastern Uganda

BACKGROUND: Malaria is a leading cause of disease burden in Uganda, although surprisingly few contemporary, age-stratified data exist on malaria epidemiology in the country. This report presents results from a total population survey of malaria infection and intervention coverage in a rural area of eastern Uganda, with a specific focus on how risk factors differ between demographic groups in this population. METHODS: In 2008, a cross-sectional survey was conducted in four contiguous villages in Mulanda, sub-county in Tororo district, eastern Uganda, to investigate the epidemiology and risk factors of Plasmodium species infection. All permanent residents were invited to participate, with blood smears collected from 1,844 individuals aged between six months and 88 years (representing 78% of the population). Demographic, household and socio-economic characteristics were combined with environmental data using a Geographical Information System. Hierarchical models were used to explore patterns of malaria infection and identify individual, household and environmental risk factors. RESULTS: Overall, 709 individuals were infected with Plasmodium, with prevalence highest among 5-9 year olds (63.5%). Thin films from a random sample of 20% of parasite positive participants showed that 94.0% of infections were Plasmodium falciparum and 6.0% were P. malariae; no other species or mixed infections were seen. In total, 68% of households owned at least one mosquito although only 27% of school-aged children reported sleeping under a net the previous night. In multivariate analysis, infection risk was highest amongst children aged 5-9 years and remained high in older children. Risk of infection was lower for those that reported sleeping under a bed net the previous night and living more than 750 m from a rice-growing area. After accounting for clustering within compounds, there was no evidence for an association between infection prevalence and socio-economic status, and no evidence for spatial clustering. CONCLUSION: These findings demonstrate that mosquito net usage remains inadequate and is strongly associated with risk of malaria among school-aged children. Infection risk amongst adults is influenced by proximity to potential mosquito breeding grounds. Taken together, these findings emphasize the importance of increasing net coverage, especially among school-aged children

Implementer and recipient perspectives of community-wide mass drug administration for soil-transmitted helminths in Kwale County, Kenya.

Soil-transmitted helminthiases (STH) are one of 17 neglected tropical diseases (NTDs) earmarked for control or elimination by 2020 in the WHO's Roadmap on NTDs. Deworming programs for STH have thus far been focused on treating pre-school and school-aged children; however, there is a growing consensus that to achieve elimination of STH transmission, programs must also target adults, potentially through community-wide mass drug administration (MDA). There is currently a gap in the literature on what components are required to deliver community-wide MDA for STH in order to achieve high intervention reach and uptake. Nested within the TUMIKIA Project, a cluster randomized trial in Kenya evaluating the effectiveness of school-based deworming versus community-wide MDA, we collected qualitative data from program implementers and recipients in eight clusters where community-wide MDA was delivered. Data collection included semi-structured in-depth interviews (n = 72) and focus group discussions (n = 32). A conceptual framework for drug distribution was constructed to help build an analysis codebook. Case memos were developed for each top-level theme. Community-wide MDA for STH was perceived as a complex intervention with key administrative and social mobilization domains. Key actionable themes included: (1) developing an efficient strategy to allocate reasonable workload for implementers to cover all targeted households; (2) maximizing community drug distributors' motivation through promoting belief in the effectiveness of the intervention and providing sufficient financial incentives; (3) developing effective capacity building strategies for implementers; and (4) implementing a context-adapted community engagement strategy that leverages existing community structures and takes into consideration past community experiences of MDAs. Transitioning from STH control to elimination goals requires significant planning and action to ensure community-wide MDA is delivered with sufficient reach and uptake. We present findings that can inform national deworming programs to increase intervention delivery capacity

Human helminth co-infection: no evidence of common genetic control of hookworm and Schistosoma mansoni infection intensity in a Brazilian community.

Strong statistical associations between soil-transmitted helminths and schistosomes are frequently observed in co-endemic human populations, although the underlying explanations remain poorly understood. This study investigates the contribution of host genetics and domestic environment to hookworm and Schistosoma mansoni infection intensity and evaluates the role of genetic and non-genetic factors in co-variation of infection intensity. Detailed genealogical information allowed assignment of 1303 individuals living in the Brazilian community of Americaninhas, Minas Gerais state, to 25 pedigrees (containing between two and 1159 members) residing in 303 households. The prevalence of co-infection with both hookworms and schistosomes was high (38.5%), with significant correlation between Necator americanus and S. mansoni faecal egg counts. Bivariate variance component analysis demonstrated a modest but significant species-specific heritability for intensity of N. americanus (h(2)=0.196) and S. mansoni infection (h(2)=0.230). However, after accounting for demographic, socio-economic and household risk factors, no evidence for common genetic control of intensity of hookworm and schistosome infection was observed. There was some evidence for residual clustering within households but the majority (63%) of the covariance between N. americanus and S. mansoni infection intensity remained specific to the individual and could not be explained by shared genes, shared environment or other shared demographic, socio-economic or environmental risk factors. Our results emphasize the importance of exposure to hookworm and schistosome infection in driving the association between levels of infection with these species in hosts resident in areas of high transmission and suggest that much of this common exposure occurs outside the home

Malaria Burden through Routine Reporting: Relationship between Incidence and Test Positivity Rates.

Test positivity rate (TPR)-confirmed cases per 100 suspected cases tested, and test-confirmed malaria case rate (IR)-cases per 1,000 population, are common indicators used routinely for malaria surveillance. However, few studies have explored relationships between these indicators over time and space. We studied the relationship between these indicators in children aged < 11 years presenting with suspected malaria to the outpatient departments of level IV health centers in Nagongera, Kihihi, and Walukuba in Uganda from October 2011 to June 2016. We evaluated trends in indicators over time and space, and explored associations using multivariable regression models. Overall, 65,710 participants visited the three clinics. Pairwise comparisons of TPR and IR by month showed similar trends, particularly for TPRs < 50% and during low-transmission seasons, but by village, the relationship was complex. Village mean annual TPRs remained constant, whereas IRs drastically declined with increasing distance from the health center. Villages that were furthest away from the health centers (fourth quartile for distance) had significantly lower IRs than nearby villages (first quartile), with an incidence rate ratio of 0.40 in Nagongera (95% CI: 0.23-0.63; P = 0.001), 0.55 in Kihihi (0.40-0.75; P < 0.001), and 0.25 in Walukuba (0.12-0.51; P < 0.001). Regression analysis results emphasized a nonlinear (cubic) relationship between TPR and IR, after accounting for month, village, season, and demographic factors. Results show that the two indicators are highly relevant for monitoring malaria burden. However, interpretation differs with TPR primarily indicating demand for malaria treatment resources and IR indicating malaria risk among health facility catchment populations