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Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      , suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6\u00a0years,\u00a0proof of\u00a0persistent re-emergence\/stable recovery\u00a0of susceptible parasite populations\u00a0using both molecular and phenotypic methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ex vivo drug-susceptibility assays to chloroquine (n\u2009=\u2009319) and lumefantrine (n\u2009=\u2009335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of\n                      <jats:italic>pfcrt<\/jats:italic>\n                      and\n                      <jats:italic>pfmdr1<\/jats:italic>\n                      was also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Chloroquine resistance (\u2265\u2009100\u00a0nM) was observed in only 3 (1.3%) samples. Average IC\n                      <jats:sub>50<\/jats:sub>\n                      values for chloroquine were persistently low throughout the study period (17.4\u201324.9\u00a0nM). Parasites harbouring\n                      <jats:italic>pfcrt<\/jats:italic>\n                      K76 alleles showed significantly lower IC\n                      <jats:sub>50<\/jats:sub>\n                      s to chloroquine than the parasites harbouring K76T alleles (21.4\u00a0nM vs. 43.1\u00a0nM, p-value\u2009=\u20093.9\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study found evidence of stable persistence of chloroquine susceptibility with the fixation of\n                      <jats:italic>pfcrt<\/jats:italic>\n                      K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-020-03157-0","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T07:02:49Z","timestamp":1582009369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda"],"prefix":"10.1186","volume":"19","author":[{"given":"Betty","family":"Balikagala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Sakurai-Yatsushiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ichiro","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osbert T.","family":"Katuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Ntege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sekihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouki","family":"Yatsushiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Opio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Obwoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis A.","family":"Anywar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Auma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirianne M. 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