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Control trial of soil-transmitted helminthic infections with pyrantel pamoate.

Pyrantel pamoate at dosage of 10 mg per kilogramme body weight was given to each villager at 4-6 weeks intervals for three times. The infection rates of hookworms among those who received and did not received the drug decreased from 60.5% pre-treatment to 19.6% after the third treatment and then increased to 32.4% one year after the third treatment. Infection rates of A. lumbricoides and Strongyloides spp. among the villagers who received and did not received the drug decreased from 27.5% pre-treatment to 2.2% after the third treatment and then increased to 20.1% one year later for the former, while the latter decreased from 6.5% pre-treatment to 2.3% after the third treatment and 0.4% one year later. The infection rate of T. trichiura was found to increase as pyrantel pamoate had no effect on this nematode. The authors suggested that to obtain more satisfactory results the anthelmintic drug used must likewise be effective against T. trichiura particularly in areas where this nematode is a public health problem. It was also suggested that the duration of treatment should be prolonged.

Adolescent

Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.

Soil-transmitted helminth (STH) infections affect one-fourth of the global population and pose a significant threat to human and animal health, with limited treatment options and emerging drug resistance. Trichuris trichiura (whipworm) stands out as a neglected disease, necessitating new drugs to address this unmet medical need. We discovered that several different chemical series of related human Provirus Integration sites for Moloney murine leukemia virus (PIM) family kinase inhibitors possess potent anthelmintic activity by using whole-worm motility assays. Systematic structure-activity relationship (SAR) studies based on the pan-PIM kinase inhibitor CX-6258 were conducted to identify compounds displaying improved in vitro motility inhibition of both adult hookworm (Ancylostoma ceylanicum) and adult whipworm (Trichuris muris) nematodes. A broad kinase selectivity screen of >450 human kinases confirms PIM1 kinase and others as potential targets for CX-6258 and analogues thereof. In addition, we demonstrated that CX-6258 significantly reduced worm burden and egg counts in the T. muris infection model of mice, establishing it as a new oral small molecule anthelmintic therapeutic.

Animals

Ambient temperature storage of individual parasitic nematode larvae for whole genome sequencing.

Soil-transmitted helminth (STH) infections are a major public health burden, and there are programmes of mass drug administration that attempt to ameliorate the harm that they cause. There has been increasing use of genomics to study STH infections and other parasitic nematodes, with particular interest in whole genome sequencing (WGS). For such studies, samples are commonly stored frozen, but in settings where these infections are endemic this can be difficult, and so there would be advantages to having ambient temperature storage methods. We investigated two ambient temperature storage methods - FTA cards and DESS buffer - for infective larvae of the rat parasites Nippostrongylus brasiliensis and Strongyloides ratti, prior to DNA extraction and then WGS. Our results showed that for individual larvae stored on FTA cards or in DESS buffer, this resulted in a lower proportion of sequence reads that mapped to the reference genomes, compared to the frozen control samples. Generally, for individual larvae, DESS-storage resulted in better sequencing results than FTA-storage. However, for pools of 10 or 50 larvae, then these ambient temperature storage methods generally resulted in comparable sequence read mapping to the frozen control samples.

Animals

Scalable assembly of Ascaris mitogenomes from whole-genome data reveals a novel clade.

The genus Ascaris is an important group of giant parasitic roundworms, infecting over 700 million people globally and causing substantial economic losses in domestic pigs. Whilst species of Ascaris are morphologically indistinguishable, analysis of mitochondrial loci has revealed three clades (A, B, C) broadly associated with host species and geographic distribution. The diversity within these lineages may expand with the addition of further genomic data. Here, we present a bioinformatic framework for de novo assembly of complete mitochondrial genomes (mitogenomes) from low-coverage whole-genome data through host-read depletion or mtDNA read enrichment, followed by mtDNA-specific assembly. Our approach yielded 149 high-quality Ascaris mitogenome assemblies, enabling the study of population-level diversity, including the identification of a novel clade (Clade D, designated here) associated with human samples from Ethiopia. Our analysis further revealed Clade C to comprise of pig-derived samples from Europe based on characterisation of worms isolated in Germany. The methods described here provide a scalable framework for mitogenome reconstruction with insights into roundworm population-genomic and phylogenetic studies.

Animals

STRONGYLID COINFECTIONS IN SYMPATRIC CHIMPANZEES AND GORILLAS FROM THE REPUBLIC OF THE CONGO REVEALED BY FECAL METAGENOMICS.

Soil-transmitted strongylid nematodes are common intestinal parasites of African great apes, yet most surveys have relied on microscopy or targeted PCR assays that are limited in taxonomic breadth and comparability across hosts. I reanalyzed 46 publicly available shotgun fecal metagenomes from sympatric central chimpanzees (Pan troglodytes troglodytes; n = 18) and western lowland gorillas (Gorilla gorilla gorilla; n = 28) in the Goualougo Triangle, Nouabalé-Ndoki National Park, Republic of the Congo, to test whether host species structures genus-level strongylid community composition and relative read signal. Non-host reads were classified against a custom strongylid-focused database targeting 4 genera repeatedly reported from African apes: Ancylostoma, Necator, Oesophagostomum, and Trichostrongylus. All 4 focal genera were detected in every library under baseline filtering, and multi-genus detection remained robust under increasingly stringent read-count thresholds. However, host species differed strongly in community composition. Chimpanzee libraries had relatively even genus-level profiles, whereas gorilla libraries were consistently Necator-dominated. Gorillas also had substantially higher relative strongylid read abundance. The results show that shotgun metagenomic reanalysis can recover host-structured strongylid community signals from wildlife samples and can complement targeted parasitological surveys in conservation and One Health surveillance.

Animals