Abstract
Soil-transmitted helminth infections represent a large burden with over a quarter of the world’s population at risk. Low cure rates are observed with standard of care (albendazole); therefore, a more effective combination therapy (albendazole and ivermectin) is being investigated but showed variable treatment efficacies without evidence of intrinsic parasite resistance. Here, we analyzed the microbiome of Trichuris trichiura and hookworm-infected patients and found an association of different enterotypes with treatment efficacy. 80 T. trichiura-infected patients with hookworm co-infections from Pak-Khan, Laos, received either albendazole (n = 41) or albendazole and ivermectin combination therapy (n = 39). Pre-/post-treatment stool samples were collected to monitor treatment efficacy and microbial communities were profiled using 16S rRNA gene sequencing, qPCR, and shotgun sequencing. We identified three bacterial enterotypes and show that pre-treatment enterotype is associated with efficacy of the combination treatment for both T. trichiura (CRET1 = 5.8%; CRET2 = 16.6%; CRET3 = 68.8%) and hookworm (CRET1 = 31.3%; CRET2 = 16.6%; CRET3 = 78.6%). This study shows that pre-treatment enterotype enables predicting treatment outcome of combination therapy for T. trichiura and hookworm infections.Trial registration: ClinicalTrials.gov, NCT03527732. Registered 17 May 2018, https://clinicaltrials.gov/ct2/show/NCT03527732.
Highlights
(Ancylostoma duodenale and Necator americanus) account for most soil-transmitted helminths (STH) infections and the current recommended treatment is mainly based on two benzimidazole drugs, albendazole, and mebendazole, which display varying species-specific treatment efficacies[2]
Between January and May 2019, people from ten villages in Nambak, Luang Prabang district in Laos were tested for T. trichiura. 549 people were included and randomly assigned to either monotherapy or combination therapy[21]
The key findings are (i) that taxonomically distinct communities were found in this setting in terms of both, relative and absolute abundance of specific taxa, and (ii) that pre-treatment community composition, or enterotype, is associated with treatment outcome of the combination therapy, albendazole, and ivermectin, for T. trichiura as well as for hookworm infections
Summary
(Ancylostoma duodenale and Necator americanus) account for most STH infections and the current recommended treatment is mainly based on two benzimidazole drugs, albendazole, and mebendazole, which display varying species-specific treatment efficacies[2]. Ivermectin is a derivate of avermectin, which was initially isolated in Streptomyces avermectinius and is commonly used in human and veterinary medicine[10] It possesses a 16-membered macrocyclic lactone group and belongs to the macrolide drug class, which encompasses antibiotic drugs such as azithromycin and erythromycin, used to treat mostly gram-positive bacterial infections. We aimed to identify potential inter-kingdom mechanisms of resilience (i.e., bacteria modulating anti-parasitic drug efficacy) in the treatment of T. trichiura and hookworm infections. Understanding possible interactions between gut microbes and anthelmintic drugs could help to improve and optimize current treatment efficacy while avoiding selection towards resistant microbial communities. In the framework of this randomized trial, we assessed the efficacy of two anthelminthic treatments, albendazole alone (400 mg), and in combination with ivermectin (200 μg/kg), in the context of gut microbial communities. We conducted taxonomic profiling of gut microbial communities on pre-treatment stool samples to predict treatment efficacy assessed by post-treatment egg reduction rates
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
