Evaluation of immune dependence of anthelmintic treatment of Heligmosomoides polygyrus in CBACa mice

Soil-transmitted helminths are parasitic nematodes that inhabit the human intestine. These parasites, which include two hookworm species, Ancylostoma duodenale and Necator americanus, the whipworm Trichuris trichiura , and the large roundworm Ascaris lumbricoides , infect upwards of two billion people and are a major cause of disease burden in children and pregnant women. The challenge with treating these diseases is that poverty, safety, and inefficient public health policy have marginalized drug development and distribution to control infection in humans. Anthelmintics (anti-worm drugs) have historically been developed and tested for treatment of non-human parasitic nematodes that infect livestock and companion animals. Here we systematically compare the in vitro efficacy of all major anthelmintic classes currently used in human therapy (benzimidazoles, nicotinic acetylcholine receptor agonists, macrocyclic lactones, nitazoxanide) against species closely related to human parasitic nematodes-Ancylostoma ceylanicum, Trichuris muris , and Ascaris suum --- as well as a rodent parasitic nematode used in veterinary drug discovery, Heligmosomoides bakeri , and the free-living nematode Caenorhabditis elegans. Extensive in vitro data is complemented with single-dose in vivo data in three rodent models of parasitic diseases. We find that the effects of the drugs in vitro and in vivo can vary greatly among these nematode species, e.g., the efficacy of albendazole is strong on A. ceylanicum but weak on H . bakeri . Nonetheless, certain commonalities of the in vitro effects of the drugs can be seen, e.g., nitazoxanide consistently shows an all-or-nothing response. Our in vitro data suggest that further optimization of the clinical efficacy of some of these anthelmintics could be achieved by altering the treatment routine and/or dosing. Most importantly, our in vitro and in vivo data indicate that the hookworm A. ceylanicum is a particularly sensitive and useful model for anthelmintic studies and should be incorporated early on in drug screens for broad-spectrum human soil-transmitted helminth therapies.

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“…The generalized anthelmintic dose used with each parasite was based on comparisons with previously reported findings [23,26,33–36]. …”

Section: Methodsmentioning

confidence: 99%

An Extensive Comparison of the Effect of Anthelmintic Classes on Diverse Nematodes

et al. 2013

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“…Mice were challenged s. c. with 600 infective larvae and were killed on days 5, 10 and 15 after infection. Worm recovery was determined by dissection of the intestines [32]. Blood and serum were recovered to determine eosinophilia and antibody responses, respectively.…”

Section: N Brasiliensis Infectionsmentioning

confidence: 99%

Defective in vivo induction of functional type 2 cytokine responses in aged mice

2001

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“…The challenge of insufficient supply of praziquantel due to scarcity of funds and the resistance of schistosome parasites to the drug of choice [ 79 ] led to the increasing call for the use of molluscicide to curtail snail distribution, but molluscicide application is yet to be substantially utilized in many countries endemic for schistosomiasis in Africa. This is partly due to reliance on prioritized chemotherapy treatment of school-aged children with praziquantel, which is not very effective due to the high re-infection rate few weeks after treatment or due to insensitivity or poor knowledge about snail hosts’ role in schistosomiasis transmission.…”

Section: Introductionmentioning

confidence: 99%

Differentiating snail intermediate hosts of Schistosoma spp. using molecular approaches: fundamental to successful integrated control mechanism in Africa

et al. 2018

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BackgroundSnail intermediate hosts play active roles in the transmission of snail-borne trematode infections in Africa. A good knowledge of snail-borne diseases epidemiology particularly snail intermediate host populations would provide the necessary impetus to complementing existing control strategy.Main bodyThis review highlights the importance of molecular approaches in differentiating snail hosts population structure and the need to provide adequate information on snail host populations by updating snail hosts genome database for Africa, in order to equip different stakeholders with adequate information on the ecology of snail intermediate hosts and their roles in the transmission of different diseases. Also, we identify the gaps and areas where there is need for urgent intervention to facilitate effective integrated control of schistosomiasis and other snail-borne trematode infections.ConclusionsPrioritizing snail studies, especially snail differentiation using molecular tools will boost disease surveillance and also enhance efficient schistosomaisis control programme in Africa.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0401-z) contains supplementary material, which is available to authorized users.

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Evaluation of immune dependence of anthelmintic treatment of Heligmosomoides polygyrus in CBACa mice

Cited by 3 publications

References 11 publications

An Extensive Comparison of the Effect of Anthelmintic Classes on Diverse Nematodes

An Extensive Comparison of the Effect of Anthelmintic Classes on Diverse Nematodes

Defective in vivo induction of functional type 2 cytokine responses in aged mice

Differentiating snail intermediate hosts of Schistosoma spp. using molecular approaches: fundamental to successful integrated control mechanism in Africa

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