Dataset Information

Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections.

ABSTRACT:

Background

Helminthiases are very prevalent worldwide, yet their treatment and control rely on a handful of drugs. Emodepside, a marketed broad-spectrum veterinary anthelminthic with a unique mechanism of action, undergoing development for onchocerciasis is an interesting anthelmintic drug candidate. We tested the in vitro and in vivo activity of emodepside on nematode species that serve as models for human soil-transmitted helminth infection as well as on schistosomes.

Methods

In vitro viability assays were performed over a time course of 72 hours for Trichuris muris, Necator americanus, Ancylostoma ceylanicum, Heligmosomoides polygyrus, Strongyloides ratti, Schistosoma mansoni and Schistosoma haematobium. The drug effect was determined by the survival rate for the larvae and by phenotypical scores for the adult worms. Additionally, mice infected with T. muris and hamsters harboring hookworm infection (N. americanus or A. ceylanicum) were administered orally with emodepside at doses ranging from 1.25 to 75 mg/kg. Expelled worms in the feces were counted until 3 days post-drug intake and worms residing in the intestines were collected and counted after dissection.

Results

After 24 hours, emodepside was very active in vitro against both larval and adult stages of the nematodes T. muris, A. ceylanicum, N. americanus, H. polygyrus and S. ratti (IC₅₀?50?=?1.2 mg/kg). Emodepside was moderately active on schistosomula in vitro (IC₅₀?50: 30-50 µM).

Conclusions

Emodepside is highly active against a broad range of nematode species both in vitro and in vivo. The development of emodepside for treating soil-transmitted helminth infections should be pursued.

SUBMITTER: Karpstein T

PROVIDER: S-EPMC6515646 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections.

Karpstein Tanja T Pasche Valérian V Häberli Cécile C Scandale Ivan I Neodo Anna A Keiser Jennifer J

Parasites & vectors 20190514 1

<h4>Background</h4>Helminthiases are very prevalent worldwide, yet their treatment and control rely on a handful of drugs. Emodepside, a marketed broad-spectrum veterinary anthelminthic with a unique mechanism of action, undergoing development for onchocerciasis is an interesting anthelmintic drug candidate. We tested the in vitro and in vivo activity of emodepside on nematode species that serve as models for human soil-transmitted helminth infection as well as on schistosomes.<h4>Methods</h4>In ...[more]

PMID: 31088525

Similar Datasets

Project description:BACKGROUND: Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases. METHODOLOGY: A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum- or N. americanus-infected hamsters, T. muris- or Ascaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs. PRINCIPAL FINDINGS: Monepantel showed excellent activity on A. ceylanicum adults (IC(50) = 1.7 µg/ml), a moderate effect on T. muris L3 (IC(50) = 78.7 µg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC(50) = 1.6 and 33.1 µg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively. CONCLUSIONS/SIGNIFICANCE: Monepantel reveals low or no activities against N. americanus, T. muris, S. ratti and A. suum in vivo, hence does not qualify as drug development candidate for human soil-transmitted helminthiases.

Project description:BACKGROUND: It is estimated that almost a half of all of people living in developing countries today are infected with roundworms, hookworms, or whipworms or combinations of these types of intestinal nematode worms. They can all be treated using safe, effective, and inexpensive single-dose generic drugs costing as little as USD 0.03 per person treated when bought in bulk. The disease caused by intestinal nematodes is strongly related to the number of worms in the gut, and it is typical to find that worms tend to be aggregated or clumped in their distribution so that <20% of people may harbour >80% of all worms. This clumping of worms is greatest when the prevalence is low. When the prevalence rises above 50%, the mean worm burden increases exponentially, worms are less clumped, and more people are likely to have moderate to heavy infections and may be diseased. Children are most at risk. For these reasons, the World Health Organization (WHO) currently recommends mass treatment of children > or =1 year old without prior diagnosis when the prevalence is > or =20% and treatment twice a year when the prevalence is > or =50%. METHODS AND FINDINGS: The risk of moderate to heavy infections with intestinal nematodes was estimated by applying the negative binomial probability distribution, then the drug cost of treating diseased individuals was calculated based on different threshold numbers of worms. Based on this cost analysis, a new three-tier treatment regime is proposed: if the combined prevalence is >40%, treat all children once a year; >60% treat twice a year; and >80% treat three times a year. Using average data on drug and delivery costs of USD 0.15 to treat a school-age child and USD 0.25 to treat a pre-school child (with provisos) the cost of treating children aged 2-14 years was calculated for 105 low- and low-middle-income countries and for constituent regions of India and China based on estimates of the combined prevalence of intestinal nematode worms therein. The annual cost of the three-tier threshold was estimated to be USD 224 million compared with USD 276 million when the current WHO recommendations for mass treatment were applied. CONCLUSION: The three-tier treatment thresholds were less expensive and more effective as they allocated a greater proportion of expenditures to treating infected individuals when compared with the WHO thresholds (73% compared with 61%) and treated a larger proportion of individuals with moderate to heavy worm burdens, arbitrarily defined as more than 10 worms per person (31% compared with 21%).

Project description:BACKGROUND:An accurate understanding of the geographical distributions of both soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale) and schistosomes (SCH; Schistosoma mansoni and S. haematobium) is pivotal to be able to effectively design and implement mass drug administration (MDA) programmes. The objective of this study was to provide up-to-date data on the distribution of both STH and SCH in Ethiopia to inform the design of the national control program and to be able to efficiently achieve the 75% MDA coverage target set by the WHO. METHODS:Between 2013 and 2015, we assessed the distributions of STH and SCH infections in a nationwide survey covering 153,238 school-aged children (aged 5-15 years), from 625 woredas (districts), representing all nine Regional States and two City Administrations of Ethiopia. Nationwide disease maps were developed at the woreda level to enable recommendations on the design of the national MDA programme. RESULTS:The prevalence of any STH infection across the study population was 21.7%, with A. lumbricoides (12.8%) being the most prevalent STH, followed by hookworms (7.6%) and T. trichiura (5.9%). The prevalence for any SCH was 4.0% in areas where both SCH species were evaluated. Schistosoma mansoni was the most prevalent SCH (3.5 vs 0.3%). STHs were more prevalent in southwest Ethiopia, whereas SCH was found mostly in the west and northeast of the country. The prevalence of moderate-to-heavy intensity infections was 2.0% for STHs and 1.6% for SCH. For STH, a total of 251 woredas were classified as moderately (n = 178) or highly endemic (n = 73), and therefore qualify for an annual and biannual MDA program, respectively. For SCH, 67 woredas were classified as endemic and 8 as highly endemic, and hence they require every two years and annual MDA programme, respectively. CONCLUSIONS:The results confirm that Ethiopia is endemic for both STHs and SCH, posing a significant public health problem. Following the WHO recommendations on mass drug administration, 18 and 14 million school-aged children are in need of MDA for STHs and SCH, respectively, based on the number of SACs that live on the eligible geographical areas.

Dataset Information

Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections.

Background

Methods

Results

Conclusions

Publications

Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure