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.

Intestinal Parasitic Infections among Long-Term-Residents and Settled Immigrants in Qatar in the Period 2005 to 2011

“…With the recent introduction of the PEC, and treatment of helminth carrying subjects with albendazole before arrival in Qatar, another possible explanation is that hookworms locally in Nepal have developed resistance to these benzimidazoles through the frequent de-worming programs that have been implemented in the country, especially among children. 8 The possibility of benzimidazole resistance having arisen in human hookworms has been recently reviewed, 12 but there is still no indisputable evidence, although the efficacy of mebendazole in particular has been shown to have declined in some parts of the tropics, notably in Zanzibar, Vietnam, and Mali and instances of failure with albendazole have also been reported in Ghana. [13][14][15][16] Another trend in the current analysis worth commenting on was the age-related increase in the prevalence of B. hominis ( Figure 4B), which was much like that we reported earlier 2 and hence largely unaffected after the addition of data from the three most recent years.…”

The Impact of Two Semiannual Treatments with Albendazole Alone on Lymphatic Filariasis and Soil-Transmitted Helminth Infections: A Community-Based Study in the Republic of Congo

“…The resistance risk may be higher for STH. To date, ALB resistance has not been reported in human STH, but recommendations for monitoring drug efficacy for early detection of suboptimal responses have been proposed, [34][35][36][37] and we think that this should be a high priority in areas that use semiannual MDA with ALB alone. The potential risk of ALB resistance in STH would favor restricting the use of ALB alone for MDA to areas where IVM cannot be safely used.…”

An automated high-throughput system for phenotypic screening of chemical libraries onC. elegansand parasitic nematodes

“…Despite encouraging progress with MDA programs, 480 current strategies and therapies will not achieve eradication of, for example, T. trichiura (Keiser J and 481 Utzinger J, 2008;Turner et al, 2016). Furthermore, MDA, particularly with drugs that do not fully 482 clear infection, may lead to drug resistance (Vercruysse et al, 2011). The experience from veterinary 483 parasitology is that resistance to new anthelmintics can develop relatively rapidly after registration, 484 causing major economic impacts and risks to global food security (Scott et al, 2013).…”