{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:10:01Z","timestamp":1790208601624,"version":"4.1.0"},"reference-count":44,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,6]]},"abstract":"<jats:p>Hookworm infection causes anemia, malnutrition, and growth delay, especially in children living in sub-Saharan Africa. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics to school-age children (SAC) as a means of reducing morbidity. Recently, questions have been raised about the effectiveness of MDA as a global control strategy for hookworms and other soil-transmitted helminths (STHs). Genomic DNA was extracted from <jats:italic>Necator americanus<\/jats:italic> hookworm eggs isolated from SAC enrolled in a cross-sectional study of STH epidemiology and deworming response in Kintampo North Municipality, Ghana. A polymerase chain reaction (PCR) assay was then used to identify single-nucleotide polymorphisms (SNPs) associated with benzimidazole resistance within the <jats:italic>N. americanus<\/jats:italic> \u03b2-tubulin gene. Both F167Y and F200Y resistance\u2013associated SNPs were detected in hookworm samples from infected study subjects. Furthermore, the ratios of resistant to wild-type SNP at these two loci were increased in posttreatment samples from subjects who were not cured by albendazole, suggesting that deworming drug exposure may enrich resistance-associated mutations. A previously unreported association between F200Y and a third resistance-associated SNP, E198A, was identified by sequencing of F200Y amplicons. These data confirm that markers of benzimidazole resistance are circulating among hookworms in central Ghana, with unknown potential to impact the effectiveness and sustainability of chemotherapeutic approaches to disease transmission and control.<\/jats:p>","DOI":"10.4269\/ajtmh.18-0727","type":"journal-article","created":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T07:00:58Z","timestamp":1544511658000},"page":"351-356","source":"Crossref","is-referenced-by-count":56,"title":["Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana"],"prefix":"10.4269","volume":"100","author":[{"given":"Ambrose R.","family":"Orr","sequence":"first","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine E.","family":"Quagraine","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"},{"name":"Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Suwondo","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"George","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Pio","family":"Dornas","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalgisa","family":"Caccone","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Humphries","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cappello","sequence":"additional","affiliation":[{"name":"Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Parasit Vectors","first-page":"37","article-title":"Global numbers of infection and disease burden of soil transmitted helminth infections in 2010","volume":"7","author":"Pullan","year":"2014"},{"key":"b2","series-title":"Int J Parasitol","first-page":"1137","article-title":"Estimating the global distribution and disease burden of intestinal nematode infections: adding up the numbers\u2014a review","volume":"40","author":"Brooker","year":"2010"},{"key":"b3","series-title":"PLoS Negl Trop Dis","first-page":"e0003877","article-title":"Soil-transmitted helminths in southwestern China: a cross-sectional study of links to cognitive ability, nutrition, and school performance among children","volume":"9","author":"Liu","year":"2015"},{"key":"b4","series-title":"PLoS Negl Trop Dis","first-page":"e0004566","article-title":"Complexities and perplexities: a critical appraisal of the evidence for soil-transmitted helminth infection-related morbidity","volume":"10","author":"Campbell","year":"2016"},{"key":"b5","series-title":"Soil-Transmitted Helminthiases: Eliminating Soil-Transmitted Helminthiases as a Public Health Problem in Children: Progress Report 2001\u20132010 and Strategic Plan 2011\u20132020","author":"World Health Organization","year":"2012"},{"key":"b6","series-title":"Cochrane Database Syst Rev","first-page":"CD000371","article-title":"Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance","volume":"7","author":"Taylor-Robinson","year":"2015"},{"key":"b7","series-title":"Trends Parasitol","first-page":"97","article-title":"A critical appraisal of control strategies for soil-transmitted helminths","volume":"32","author":"Campbell","year":"2016"},{"key":"b8","series-title":"J Glob Antimicrob Resist","first-page":"229","article-title":"Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy","volume":"3","author":"Albonico","year":"2015"},{"key":"b9","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"14","article-title":"Is anthelmintic resistance a concern for the control of human soil-transmitted helminths?","volume":"1","author":"Vercruysse","year":"2011"},{"key":"b10","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"218","article-title":"Anthelmintics\u2014from discovery to resistance","volume":"4","author":"Wolstenholme","year":"2014"},{"key":"b11","series-title":"Vet Parasitol","first-page":"29","article-title":"Managing anthelmintic resistance\u2014variability in the dose of drug reaching the target worms influences selection for resistance?","volume":"243","author":"Leathwick","year":"2017"},{"key":"b12","series-title":"Vet Rec","first-page":"546","article-title":"Widespread anthelmintic resistance in European farmed ruminants: a systematic review","volume":"176","author":"Rose","year":"2015"},{"key":"b13","series-title":"Vet Parasitol","first-page":"84","article-title":"Rapid selection for \u03b2-tubulin alleles in codon 200 conferring benzimidazole resistance in an Ostertagia ostertagi isolate on pasture","volume":"209","author":"Knapp-Lawitzke","year":"2015"},{"key":"b14","series-title":"Vet Parasitol","first-page":"344","article-title":"Relationship between increased albendazole systemic exposure and changes in single nucleotide polymorphisms on the \u03b2-tubulin isotype 1 encoding gene in Haemonchus contortus","volume":"186","author":"Barrere","year":"2012"},{"key":"b15","series-title":"J Mol Graph Model","first-page":"275","article-title":"A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement","volume":"23","author":"Robinson","year":"2004"},{"key":"b16","series-title":"Mol Biochem Parasitol","first-page":"221","article-title":"Specific interaction of benz-imidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in H. contortus","volume":"38","author":"Lubega","year":"1990"},{"key":"b17","series-title":"Am J Trop Med Hyg","first-page":"234","article-title":"Detection of benzimidazole resistance-associated mutations in the filarial nematode Wuchereria bancrofti and evidence for selection by albendazole and ivermectin combination treatment","volume":"73","author":"Schwab","year":"2005"},{"key":"b18","series-title":"Mol Biochem Parasitol","first-page":"10","article-title":"Single nucleotide polymorphisms in \u03b2-tubulin selected in Onchocerca volvulus following repeated ivermectin treatment: possible indication of resistance selection","volume":"185","author":"Nana-Djeunga","year":"2012"},{"key":"b19","series-title":"Mol Biochem Parasitol","first-page":"281","article-title":"Molecular analysis of the beta-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island","volume":"134","author":"Albonico","year":"2004"},{"key":"b20","series-title":"PLoS Negl Trop Dis","first-page":"e2247","article-title":"Association between response to albendazole treatment and \u03b2-tubulin genotype frequencies in soil-transmitted helminths","volume":"7","author":"Diawara","year":"2013"},{"key":"b21","series-title":"Am J Trop Med Hyg","first-page":"1052","article-title":"Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths","volume":"88","author":"Diawara","year":"2013"},{"key":"b22","series-title":"Mol Biochem Parasitol","first-page":"167","article-title":"Characterization of beta-tubulin genes in hookworms and investigation of resistance-associated mutations using real-time PCR","volume":"156","author":"Schwenkenbecher","year":"2007"},{"key":"b23","series-title":"Am J Trop Med Hyg","first-page":"540","article-title":"Hookworm infection among school age children in Kintampo north municipality, Ghana: nutritional risk factors and response to albendazole treatment","volume":"89","author":"Humphries","year":"2013"},{"key":"b24","series-title":"Am J Trop Med Hyg","first-page":"792","article-title":"Epidemiology of hookworm infection in Kintampo north municipality, Ghana: patterns of malaria coinfection, anemia, and albendazole treatment failure","volume":"84","author":"Humphries","year":"2011"},{"key":"b25","series-title":"Am J Trop Med Hyg","first-page":"347","article-title":"Effectiveness of albendazole against hookworm varies widely by community and correlates with nutritional factors: a cross-sectional study of school-age children in Ghana","volume":"96","author":"Humphries","year":"2017"},{"key":"b26","series-title":"Assessing the Efficacy of Anthelminthic Drugs against Schistosomiasis and Soil-Transmitted Helminthiases","author":"World Health Organization","year":"2013"},{"key":"b27","series-title":"Infect Immun","first-page":"2214","article-title":"Molecular characterization of Ancylostoma ceylanicum Kunitz-type serine protease inhibitor: evidence for a role in hookworm-associated growth delay","volume":"72","author":"Chu","year":"2004"},{"key":"b28","series-title":"Genome Res","first-page":"258","article-title":"High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR","volume":"10","author":"Germer","year":"2000"},{"key":"b29","series-title":"Vet Parasitol","first-page":"291","article-title":"Real time PCR for the diagnosis of benzimidazole resistance in trichostrongylids of sheep","volume":"129","author":"Alvarez-Sanchez","year":"2005"},{"key":"b30","series-title":"J Biomol Tech","first-page":"S13","article-title":"Detecting and quantifying low level gene variants in sanger sequencing traces using the ab1 peak reporter tool","volume":"25","author":"Roy","year":"2014"},{"key":"b31","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"164","article-title":"Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug\/receptor interactions","volume":"4","author":"Kotze","year":"2014"},{"key":"b32","series-title":"Ann Trop Med Parasitol","first-page":"231","article-title":"An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana","volume":"98","author":"Awadzi","year":"2004"},{"key":"b33","series-title":"PLoS Negl Trop Dis","first-page":"e0005113","article-title":"Isothermal diagnostic assays for monitoring single nucleotide polymorphisms in Necator americanus associated with benzimidazole drug resistance","volume":"10","author":"Rashwan","year":"2016"},{"key":"b34","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"92","article-title":"Relative level of thiabendazole resistance associated with the E198A and F200Y SNPs in larvae of a multi-drug resistant isolate of Haemonchus contortus","volume":"2","author":"Kotze","year":"2012"},{"key":"b35","series-title":"Lancet Glob Health","first-page":"e583","article-title":"MDA helminth control: more questions than answers","volume":"3","author":"Medley","year":"2015"},{"key":"b36","series-title":"J Biosoc Sci","first-page":"S116","article-title":"Deworming delusions? Mass drug administration in east African schools","volume":"48","author":"Allen","year":"2016"},{"key":"b37","series-title":"Int J Parasitol","first-page":"1205","article-title":"Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control","volume":"34","author":"Albonico","year":"2004"},{"key":"b38","series-title":"JAMA","first-page":"1937","article-title":"Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis","volume":"299","author":"Keiser","year":"2008"},{"key":"b39","series-title":"Parasit Vectors","first-page":"1","article-title":"Monitoring the impact of a national school based deworming programme on soil-transmitted helminths in Kenya: the first three years, 2012\u20132014","volume":"9","author":"Okoyo","year":"2016"},{"key":"b40","series-title":"Parasit Vectors","first-page":"266","article-title":"Can chemotherapy alone eliminate the transmission of soil transmitted helminths?","volume":"7","author":"Truscott","year":"2014"},{"key":"b41","series-title":"Parasitology","first-page":"379","article-title":"Reinfection with hookworm after chemotherapy in Papua New Guinea","volume":"106","author":"Quinnell","year":"1993"},{"key":"b42","series-title":"PLoS Negl Trop Dis","first-page":"e1621","article-title":"Soil-transmitted helminth reinfection after drug treatment: a systematic review and meta-analysis","volume":"6","author":"Jia","year":"2012"},{"key":"b43","series-title":"Vet Parasitol","first-page":"201","article-title":"Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population","volume":"123","author":"Drogemuller","year":"2004"},{"key":"b44","series-title":"Pharmacogenet Genomics","first-page":"129","article-title":"Genetic analysis of a relationship between macrocyclic lactone and benzimidazole anthelmintic selection on Haemonchus contortus","volume":"18","author":"de Lourdes Mottier","year":"2008"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/100\/2\/article-p351.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/100\/2\/article-p351.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/100\/2\/article-p351.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T13:17:00Z","timestamp":1722431820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/100\/2\/article-p351.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,6]]},"references-count":44,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.18-0727","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,6]]}}}