Is anthelmintic resistance a concern for the control of human soil-transmitted helminths?

Abstract

The major human soil-transmitted helminths (STH), Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura have a marked impact on human health in many parts of the world. Current efforts to control these parasites rely predominantly on periodic mass administration of anthelmintic drugs to school age children and other at-risk groups. After many years of use of these same drugs for controlling roundworms in livestock, high levels of resistance have developed, threatening the sustainability of these livestock industries in some locations. Hence, the question arises as to whether this is likely to also occur in the human STH, thereby threatening our ability to control these parasites. This is particularly important because of the recent increase in mass control programmes, relying almost exclusively on benzimidazole anthelmintics. It will be important to ensure that resistance is detected as it emerges in order to allow the implementation of mitigation strategies, such as use of drug combinations, to ensure that the effectiveness of the few existing anthelmintic drugs is preserved. In this review we address these issues by firstly examining the efficacy of anthelmintics against the human STH, and assessing whether there are any indications to date that resistance has emerged. We then consider the factors that influence the effect of current drug-use patterns in selecting for resistant parasite populations. We describe the tools currently available for resistance monitoring (field-based coprological methods), and those under development (in vitro bioassays and molecular tests), and highlight confounding factors that need to be taken into account when interpreting such resistance-monitoring data. We then highlight means to ensure that the currently available tools are used correctly, particularly with regard to study design, and we set appropriate drug-efficacy thresholds. Finally, we make recommendations for monitoring drug efficacy in the field, as components of control programmes, in order to maximise the ability to detect drug resistance, and if it arises to change control strategy and prevent the spread of resistance.

Keywords: Anthelmintic resistance; Anthelmintics; Guidelines; Soil-transmitted helminths.

Fig. 1

Flow chart on how to monitor and to interpret drug efficacy during mass drug administration programmes. ^∗N is based on the formula below $N=\frac{200}{(100\%\text{-expected proportion of subjects not meeting the inclusion criteria in}\%)\times (100\%\text{-expected dropout in \%})}$$N=\frac{200}{(0.95)\times (0.95)}=222$. For example, for 5% of the subjects not meeting the inclusion criteria and an expected dropout of 5% recruitment of 222 subjects is recommended. ^∗∗At present, there is no inference available to calculate 95% confidence interval for the ERR formula. Bootstrap analysis, therefore is recommended. ^∗∗∗Baseline FEC of all subjects examined are lowly aggregated when k > 0.01. $k=\frac{{(\text{arithmetic mean of baseline FEC})}^2}{\text{Variance baseline FEC}-\text{arithmetic mean of FEC}}$. ^∗∗∗∗Based on baseline FEC of infected subjects only.