Optimising control programs for soil-transmitted helminths

Abstract

Soil-transmitted helminths (STH) are parasitic intestinal worms that are widely prevalent in impoverished populations, causing a significant burden of morbidity worldwide. Recent years have seen a remarkable global commitment to controlling STH infections. Current World Health Organization (WHO) guidelines for STH control focus on large-scale deworming programs, in which anthelminthic medications (albendazole or mebendazole) are delivered regularly to at-risk population groups in endemic countries. The WHO target for 2020 is regular deworming of 75% of at-risk children; as such, existing control programs have a strong emphasis on treating children. The overarching aim of this thesis is to provide empirical evidence to guide the optimisation of STH control programs. To achieve this aim, I address four key evidence gaps in the understanding of STH control, by evaluating the potential impact of additional or alternative control strategies, compared to existing strategies and guidelines. First, I examine the efficacy of alternative anthelminthic drugs. I present the most comprehensive comparison of anthelminthic medications, conducted using network meta-analysis. Findings of this analysis show that several anthelminthic drug combinations, including albendazole-ivermectin and albendazole-oxantel pamoate, are more efficacious than the current standard treatment against Trichuris trichiura, the most challenging STH to control. Second, I investigate the potential impact of expanding STH control programs community-wide. I report the first experimental evidence - obtained using both meta-analysis and a field-based pilot study - comparing community-wide and child-targeted approaches to STH control. Results of both analyses suggest a greater impact of community-wide STH control programs on STH prevalence in children, compared to child-targeted approaches. Third, I explore the role of water, sanitation, and hygiene (WASH) in STH control. I present results of the first randomised controlled trial comparing a community-wide WASH and deworming program to deworming alone. These results demonstrate no additional impact of the community WASH intervention on STH infections above that achieved by deworming over a two-year period. I also report the findings of an observational risk factor analysis. These findings demonstrate few associations between WASH and STH, with regular deworming and sociodemographic variables representing the main predictors of infection. Finally, I examine the potential utility of quantitative PCR (qPCR) for monitoring STH control programs. I present the first quantitative comparison of qPCR and sodium nitrate flotation, a microscopy-based diagnostic technique. Findings confirm the higher diagnostic sensitivity of qPCR, particularly for light-intensity infections, and demonstrate correlations between infection intensity measurements obtained using the two techniques.

The findings presented in this thesis provide robust evidence that will be instrumental to policymakers at a time when the future of STH control efforts is being vigorously discussed. Specific priorities and recommendations for STH control guidelines arising from this research are: including drug combinations as recommended anthelminthics, expanding deworming programs community-wide, and adding qPCR as a diagnostic option in low-transmission settings. Complementing deworming with WASH interventions should also be encouraged, although additional impact on STH may not be apparent for some time. This thesis argues that we must build on the global momentum towards controlling neglected tropical diseases, and re-evaluate global STH control guidelines to ensure that they reflect the available scientific evidence and maximise benefits to afflicted populations.