Assessing the impact of mass deworming: changes in soil-transmitted helminth burden and characteristics, co-infections and the gut microbiome

Abstract

Approximately two billion people worldwide are infected with a soil-transmitted helminth (STH) and could benefit from anthelmintic treatment. Evaluating the impact of mass drug administration (MDA) for STH infection, however, is highly challenging, due in part to the absence of a gold-standard diagnostic. This thesis examines the impact of MDA using both standard parasitological and novel molecular methods. Kato Katz (KK) provides false negative results in approximately 68% of Necator americanus infections detectable by quantitative PCR (qPCR). KK also fails to detect many low-intensity infections caused by Ascaris lumbricoides and other gastrointestinal parasites. Both qPCR and KK are equally good predictors of A. lumbricoides worm burden (as measured by chemo-expulsion), and approximately equally precise in their quantitation of infection intensity. For both qPCR and KK, methodological sources of error were identified by regression, but were sufficiently small as to be irrelevant relative to the person-to-person differences in infection intensity measured. Chemo-expulsion provided useful information about the life cycle and population ecology of A. lumbricoides. Sequencing of these worms showed that the populations of worms found in different villages and at different time-points were significantly different, suggesting that villages may be an appropriate unit to target for MDA. Finally, it is important to understand the impact of MDA on the total sum of measurable changes to the body’s ecosystem, of which the gut microbiome is a key part. The host microbiome appears to be influenced both by STH infection and anthelmintic treatment. Although there is much we can learn from molecular tools, one of the greatest lessons of this thesis is just how much we still do not know. Overconfidence in our ability to understand, model and predict the response of STH infection in a community to MDA could lead to well-intentioned interventions that ultimately result in unsustainable outcomes.