Mass Treatment of Parasitic Disease: Implications for the Development and Spread of Anthelmintic Resistance

Abstract

There has been a dramatic increase in the use of mass drug administration to reduce the morbidity associated with helminth infections of humans, raising the likelihood that anthelmintic resistance may become a public health concern of the future. After highlighting the scope and magnitude of the chemotherapy-based helminth control programs presently in place, this chapter emphasizes the mechanisms of action of the main anthelmintic drugs in use and how resistance may develop. To date, the most established population-based mass drug administration campaigns have been against the filarial parasites which cause human onchocerciasis and lymphatic filariasis. The molecular and parasitological evidence suggesting the presence of drug resistance in human filarial parasites is reviewed and factors influencing the spread of drug resistant parasites are discussed, taking examples from veterinary helminths and the use of mathematical models. In particular, the public health impact of the development of resistance by soil-transmitted helminths, such as hookworm, is a real concern. Implications of the development of anthelmintic resistance are discussed in relation to existing control programs, emphasizing how their monitoring and evaluation is essential to prevent it becoming a major public health concern of the future.Drug resistance is the bane of all chemotherapy-based control programs. Its rapid evolution and spread can quickly render ineffective public health measures which rely on mass drug administration (MDA), wasting valuable health resources whilst failing to control infection and reduce the burden of disease. The dramatic and widespread resistance to many classes of antiparasitic drug provides a warning that,

Modelling Lymphatic Filariasis Transmission and Control: Modelling Frameworks, Lessons Learned and Future Directions

“…High prevalences of resistance are now common in certain farmed ruminants, and include instances of multiple drug resistance (Geerts and Gryseels, 2000). The experience has been that resistance may go unnoticed until the opportunity for resistance management has gone, because its spread often follows a sigmoidal progression: a long latent phase followed by an exponential increase (Churcher et al, 2010;Geerts and Gryseels, 2000). A number of reports suggest that tolerance or resistance of W. bancrofti to ABZ or DEC may exist.…”

A statistical approach for evaluating the effectiveness of heartworm preventive drugs: what does 100% efficacy really mean?

“…However, D. immitis isolates are somewhat different than most other nematode species in that they undergo a fairly severe genetic bottleneck each time they are passaged, because only about 15 to 35 worms will typically establish in a dog following an inoculation of 50 iL3. In addition, helminth parasites have a subdivided population structure as adult worms because they are confined to their definitive host and are only able to mate with worms co-inhabiting the same host [ 8 ]. As a result many microfilariae circulating in the blood of an infected dog are partial or full siblings, and given that relatively few adult worms of each sex are present in a given dog, sibling matings in the F2 generation are probable, and increase in probability with each passage.…”

Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: “The Worminator”

“…However, reports of resistance to several currently available macrocyclic lactone compounds ( Bourguinat et al, 2011; Geary et al, 2011 ) have proven these predictions wrong. Though AR is not yet a problem in human nematodes, sub-optimal responses of ivermectin against Onchocerca volvulus ( Osei-Atweneboana et al, 2007; Churcher et al, 2009 ), and the potential for heavy drug selection pressures on populations of soil transmitted helminths (STH) due to scale up of Mass Drug Administration (MDA) programs are raising serious concerns ( Churcher et al, 2010; Keenan et al, 2013 ).…”