{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:07:06Z","timestamp":1793203626096,"version":"4.5.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,9,29]]},"abstract":"<jats:p>\n                    Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which\n                    <jats:italic>Onchocerca volvulus<\/jats:italic>\n                    microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12\u201317 times), despite the wide variability in repopulation rates observed in ivermectin-na\u00efve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0906176106","type":"journal-article","created":{"date-parts":[[2009,9,18]],"date-time":"2009-09-18T01:11:21Z","timestamp":1253236281000},"page":"16716-16721","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":74,"title":["Identifying sub-optimal responses to ivermectin in the treatment of River Blindness"],"prefix":"10.1073","volume":"106","author":[{"given":"Thomas S.","family":"Churcher","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien D. S.","family":"Pion","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 145, Institut de Recherche pour le D\u00e9veloppement and University of Montpellier 1, Montpellier, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike Y.","family":"Osei-Atweneboana","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebec H9X 3V9, Canada;"},{"name":"Council for Scientific and Industrial Research, P.O. Box M32, Accra, Ghana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger K.","family":"Prichard","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebec H9X 3V9, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwablah","family":"Awadzi","sequence":"additional","affiliation":[{"name":"Onchocerciasis Chemotherapy Research Centre, Hohoe Hospital, P.O. 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