Medicine

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Isothermal Diagnostic Assays for monitoring single nucleotide polymorphisms in Necator americanus associated with Benzimidazole drug resistance
(Public Library of Science, 2016) Rashwan, N.; Bourguinat, C.; Keller, K.; Gunawardena, N.K.; de Silva, N.; Prichard, R.
BACKGROUND: Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramatically with massive drug donations. Frequent and prolonged use of these drugs could lead to the emergence of anthelmintic resistance as has occurred in nematodes of livestock. Previous molecular assays for putative resistance mutations have been based mainly on PCR amplification and sequencing. However, these techniques are complicated and time consuming and not suitable for resource-constrained situations. A simple, rapid and sensitive genotyping method is required to monitor for possible developing resistance to BZ drugs. METHODS: To address this problem, single nucleotide polymorphism (SNP) detection assays were developed based on the Smart amplification method (SmartAmp2) to target codons 167, 198, and 200 in the β-tubulin isotype 1 gene for the hookworm Necator americanus. FINDINGS: Diagnostic assays were developed and applied to analyze hookworm samples by both SmartAmp2 and conventional sequencing methods and the results showed high concordance. Additionally, fecal samples spiked with N. americanus larvae were assessed and the results showed that the Aac polymerase used has high tolerance to inhibitors in fecal samples. CONCLUSION: The N. americanus SmartAmp2 SNP detection assay is a new genotyping tool that is rapid, sensitive, highly specific and efficient with the potential to be used as a field tool for monitoring SNPs associated with BZ resistance. However, further validation on large numbers of field samples is required.
Making the best of what we have: a plea for wider use of anthelmintics
(Indian Council of Medical Research, 2005) de Silva, N.
No Abstract Available
Clinical use of anthelmintics
(1997) de Silva, N.; Guyatt, H.; Bundy, D.
Anthelmintics: a review of their comparative clinical pharmacology
(Springer International, 1997) de Silva, N.; Guyatt, H.; Bundy, D.
Virtually all the important helminth infections in humans can be treated with one of 5 anthelmintics currently in use: albendazole, mebendazole, diethylcarbamazine, ivermectin and praziquantel. These drugs are vital not only for the treatment of individual infections, but also useful in controlling transmission of the more common infections. This article reviews briefly the pharmacology of these 5 drugs, and then discusses current issues in the use of anthelmintics in the treatment and/or control of soil-transmitted nematode infections, filariasis, onchocerciasis, schistosomiasis (and other trematode infections), neurocysticercosis and hydatidosis. Mebendazole and albendazole are most effective against intestinal nematodes, but are contraindicated during the first trimester of pregnancy. The efficacy of prolonged therapy with these 2 drugs for treatment of larval cestode infections has not yet been established. Diethylcarbamazine is widely used to treat and control lymphatic filariasis, but adverse effects related to death of microfilariae or damage to adult worms may be marked. While ivermectin has been used in the treatment of patients with onchocerciasis, it is also undergoing investigation against lymphatic filariae. Praziquantel, used to treat schistosome infections, is also effective in other trematode infections and adult cestode infections

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