Rachel L. Pullan

Background School-based approaches are an efficient mechanism for the delivery of basic health services, but may result in the exclusion of children with disabilities if they are less likely to participate in schooling. Community-based ‘door to door’ approaches may provide a more equitable strategy to ensure that children with disabilities are reached, but disability is rarely assessed rigorously in the evaluation of health interventions. Objectives To describe the prevalence and factors associated with disability among children aged 5–17 years and to assess the relative effectiveness of routine school-based deworming (SBD) compared with a novel intervention of community-based deworming (CBD) in treating children with disabilities for soil-transmitted helminths. Setting DeWorm3 Malawi Site (DMS), Mangochi district, Malawi. Participants All 44 574 children aged 5–17 years residing within the DMS. Primary and secondary outcome measures Disability was defined as a functional limitation in one or more domains of the Washington Group/UNICEF Child Functioning Module administered as part of a community-based census. Treatment of all children during SBD and CBD was independently observed and recorded. For both intervention types, we performed bivariate analyses (z-score) of the absolute proportion of children with and without disabilities treated (absolute differences (ADs) in receipt of treatment), and logistic regression to examine whether disability status was associated with the likelihood of treatment (relative differences in receipt of treatment). Results The overall prevalence of disability was 3.3% (n=1467), and the most common domains of disability were hearing, remembering and communication. Boys were consistently more likely to have a disability compared with girls at all age groups, and disability was strongly associated with lower school attendance and worse levels of education. There was no significant difference in the proportion of children with disabilities treated during SBD when assessed by direct observation (−1% AD, p=0.41) or likelihood of treatment (adjusted risk ratio (aRR)=1.07, 95% CI 0.89 to 1.28). Treatment of all children during CBD was substantially higher than SBD, but again showed no significant difference in the proportions treated (−0.5% AD, p=0.59) or likelihood of treatment (aRR=1.04, 95% CI 0.99 to 1.10). Conclusion SBD does not appear to exclude children with disabilities, but the effect of consistently lower levels of educational participation of children with disabilities should be actively considered in the design and monitoring of school health interventions. Trial registration number NCT03014167.

The World Health Organization’s (WHO’s) 2030 road map for neglected tropical diseases (NTDs) emphasizes the importance of strengthened, institutionalized “post-elimination” surveillance. The required shift from disease-siloed, campaign-based programming to routine, integrated surveillance and response activities presents epidemiological, logistical, and financial challenges, yet practical guidance on implementation is lacking. Nationally representative survey programs, such as demographic and health surveys (DHS), may offer a platform for the integration of NTD surveillance within national health systems and health information systems. Here, we describe characteristics of DHS and other surveys conducted within the WHO Africa region in terms of frequency, target populations, and sample types and discuss applicability for post-validation and post-elimination surveillance. Maximizing utility depends not only on the availability of improved diagnostics but also on better understanding of the spatial and temporal dynamics of transmission at low prevalence. To this end, we outline priorities for obtaining additional data to better characterize optimal post-elimination surveillance platforms.

1. Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this survey aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a household census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional survey was then conducted between March-May 2018 in the enumerated area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. 2. AUTHOR SUMMARY: The major public health strategy to control soil-transmitted helminths (STH) is preventive chemotherapy, whereby those at greatest risk of morbidity – children and women of childbearing age - are presumptively treated with a safe, effective and inexpensive anthelminthic drug. In Malawi, this has been successfully sustained for nearly a decade through annual school-based deworming, in addition to integration within child health campaigns and routine antenatal care. Routine surveillance of schoolchildren demonstrates that STH has been reduced to very low levels in this age group, but few community-based epidemiological surveys have been conducted to investigate STH in the broader population. In this survey, we observed that while infection with STH has been reduced to low levels overall, it is much higher in adults and particularly in males, with the odds of being infected greater in those from less wealthy households or from households with lower levels of adult education. These results underline that while preventive chemotherapy has likely been key to reductions in STH; sub-populations not routinely targeted by preventive chemotherapy, and the most disadvantaged members of society, continue to be disproportionately affected. We propose that evaluation of more comprehensive control strategies – such as entire-community deworming – could overcome these limitations, and present a route to STH elimination.

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, its strong predictive power of unbiased malaria burden when improved highlights the important role it 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.

Background: Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans , an environmental pathogen whose environmental niche and transmission routes are not fully understood. Active BU case searches can limit morbidity by identifying cases and linking them to treatment, but these are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for environmental reservoirs of M. ulcerans and BU disease would advance understanding of the disease’s ecology and burden, and could inform targeted surveillance. Methodology/Principal Findings: We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and diverse environmental datasets. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km × 5km. Climate and atmospheric variables were the strongest predictors of both distributions, while indicators of human disturbance including damming and deforestation, drove local variation in suitability. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 29.1 million. Conclusions/Significance: These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas. Author summary: Like many neglected tropical diseases primarily affecting the rural poor, Buruli ulcer (BU) is under-detected and under-reported within routine health information systems. As such, the burden and distribution are not fully known, impeding appropriate targeting of health resources, control, and care for people affected. Having previously evaluated and mapped the existing evidence for BU and its causative agent M. ulcerans , we concluded that the disease was likely to occur beyond the range of known endemic areas. However, we were left with the question of where exactly these undetected cases might be occurring. Answering this question required a more fine-scale approach: BU is highly focal, presumably due to local variation in the environmental factors which determine suitability for M. ulcerans survival and transmission to humans. We used the compiled evidence and geographical datasets to build statistical models representing the relationship between environmental factors and previously reported cases. This allowed us to define the ecological niche of BU, and subsequently to identify areas across Africa where this niche was met, providing suitable conditions for the disease. We constructed separate models of suitability for M. ulcerans , using locations where its DNA had been detected in environmental sources. Unsurprisingly, suitability for M. ulcerans was predicted to be wider than, but geographically overlapping with that for BU. This implies that beyond the conditions necessary for survival of the bacterium, additional factors are required for transmission to humans. The high-resolution suitability maps we present are intended to guide case search activities which may identify endemic areas beyond the known endemic range. Data on the true prevalence of BU from targeted case searches within predicted-suitable areas will also allow us to validate and refine the models, and potentially predict the actual probability of cases occurring within predicted suitable areas.

We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA) — which we refer to as ‘adherence’ and ‘non-adherence’. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs). Author summary: Mass drug administration (MDA) is an important tool in the prevention of morbidity caused by various NTDs and in the reduction of their transmission. Due to a variety of social and behavioural reasons, many people will either not be offered or refuse such treatment, and if this behaviour is recurring at an individual level, then control measures may face a challenge in achieving their stated goals. Accurately describing the patterns of individual adherence or non-adherence to MDA control measures for NTDs from data, followed by their use in simulated scenarios is a relatively recent development in the study of NTDs. Past analyses assessing individual adherence have informed the approach we take in this work. However, we have sought to provide a framework which encapsulates as many types of adherence behaviour as possible to facilitate the assessment of impact in mathematical models of parasite transmission and control. Our example application to the TUMIKIA data highlights the importance of such a general framework as we find a dependence on past behaviour that may have been missed in standard statistical analyses.

Background: Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa is uncertain. Methods: We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the suitability and human population at risk. Results: In Africa, environmental suitability for podoconiosis was predicted in 29 countries. By 2020, the total population in areas suitable for podoconiosis was estimated at 114.5 million people, (95% confidence interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units defined by WHO in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of IUs with high environmental suitability are located in Angola (80 IUs), Cameroon (170 IUs), the DRC (244 IUs), Ethiopia (495 IUs), Kenya (217 IUs), Uganda (116 IUs) and Tanzania (112 IUs). Of the 1,655 environmental suitable IUs, 960 (58.0%) require more detailed community-level mapping Conclusions: Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes.

Background: As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. Results: Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0–63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R₀ values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. Conclusions: Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches.

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.

The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.