Analysis of the population-level impact of co-administering ivermectin with albendazole or mebendazole for the control and elimination of Trichuris trichiura

Abstract

IntroductionSoil-transmitted helminth (STH) infections are predominately controlled by providing children with preventive chemotherapy with either albendazole or mebendazole. However, neither has a high efficacy against Trichuris trichiura. This low efficacy limits the overall effectiveness of the current STH control programmes against T. trichiura. It has been demonstrated that co-administering ivermectin with albendazole or mebendazole significantly increases the efficacy of current treatments, which may increase the overall effectiveness of control programmes.MethodsUsing a STH transmission mathematical model, we evaluated the potential impact of co-administering ivermectin with albendazole or mebendazole to treat T. trichiura within a preventive chemotherapy programme targeting children (2–15 year olds). We evaluated the impact in terms of reduction in prevalent infections, mean worm burden, and prevalence of heavy infections.ResultsAlthough the current treatment strategy reduced T. trichiura worm burden and prevalence of heavy infections, due to their poor efficacy the long term impact of preventive chemotherapy for children was smaller compared to the other STH. Co-administering ivermectin increased the projected impact of the preventive chemotherapy programme in terms of all three of the explored metrics, practically in high transmission settings. Furthermore, ivermectin co-administration greatly increased the feasibility of and timeframe for breaking transmission.ConclusionsCo-administering ivermectin notably increased the projected impact of preventive chemotherapy in high transmission settings and increased the feasibility for breaking transmission. This has important implications for control programmes, some of which may be shifting focus from morbidity control to interruption of transmission, and some of which may be logistically unable to provide preventive chemotherapy twice a year as recommended. However, the benefit of co-administering ivermectin is limited by the fact that 2–5 year olds are often ineligible to receive treatment.

An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes

“…There is an urgent need for new anthelmintics. Despite encouraging progress with MDA programs, current strategies and therapies will not achieve eradication of, for example, T. trichiura ( Keiser and Utzinger, 2008 , Turner et al, 2016 ). Furthermore, MDA, particularly with drugs that do not fully clear infection, may lead to drug resistance ( Vercruysse et al, 2011 ).…”

“…There are concerns that mass drug administration (MDA) programs aimed at controlling or eradicating human parasitic nematodes will be made unsustainable by anthelmintic resistance, jeopardising attempts to eradicate these important tropical diseases ( Prichard et al, 2012 ). In the case of Trichuris, modelling indicates that existing benzimidazole drugs are insufficiently effective for single dose MDA programs designed to break transmission; therefore eradication cannot be achieved ( Keiser and Utzinger, 2008 , Levecke et al, 2014 , Turner et al, 2016 ). The current arsenal of veterinary anthelmintics is threatened by the emergence and spread of resistance in parasitic nematodes of domesticated animals, a recent example of which is the report of resistance to monepantel in sheep nematode species only four years after introduction of the compound ( Sales and Love, 2016 , Scott et al, 2013 ).…”

Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study

“…trichiura and S . stercoralis in clinical trials and mathematical models [ 20 , 50 – 52 ]. In summary, albendazole/ivermectin applied as community based PC in communities with high prevalence of hookworm and S .…”

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).…”

“…of Trichuris, modelling indicates that existing benzimidazole drugs are insufficiently effective for 45 single dose MDA programs designed to break transmission; therefore eradication cannot be achieved 46 (Keiser J and Utzinger J, 2008;Levecke et al, 2014;Turner et al, 2016). The current arsenal of 47 veterinary anthelmintics is threatened by the emergence and spread of resistance in parasitic 48 nematodes of domesticated animals, a recent example of which is the report of resistance to 49 monepantel in sheep nematode species only four years after introduction of the compound (Scott et 50 al., 2013).…”