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Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea

BACKGROUND: Chloroquine treatment for Plasmodium falciparum has been discontinued in almost all endemic regions due to the spread of resistant isolates. Reversal of chloroquine susceptibility after chloroquine discontinuation has been reported in dozens of endemic regions. However, this phenomenon h...

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Autores principales: Sekihara, Makoto, Tachibana, Shin-Ichiro, Yamauchi, Masato, Yatsushiro, Shoki, Tiwara, Steven, Fukuda, Naoyuki, Ikeda, Mie, Mori, Toshiyuki, Hirai, Makoto, Hombhanje, Francis, Mita, Toshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260888/
https://www.ncbi.nlm.nih.gov/pubmed/30477515
http://dx.doi.org/10.1186/s12936-018-2585-x
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author Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Yatsushiro, Shoki
Tiwara, Steven
Fukuda, Naoyuki
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Hombhanje, Francis
Mita, Toshihiro
author_facet Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Yatsushiro, Shoki
Tiwara, Steven
Fukuda, Naoyuki
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Hombhanje, Francis
Mita, Toshihiro
author_sort Sekihara, Makoto
collection PubMed
description BACKGROUND: Chloroquine treatment for Plasmodium falciparum has been discontinued in almost all endemic regions due to the spread of resistant isolates. Reversal of chloroquine susceptibility after chloroquine discontinuation has been reported in dozens of endemic regions. However, this phenomenon has been mostly observed in Africa and is not well documented in other malaria endemic regions. To investigate this, an ex vivo study on susceptibility to chloroquine and lumefantrine was conducted during 2016–2018 in Wewak, Papua New Guinea where chloroquine had been removed from the official malaria treatment regimen in 2010. Genotyping of pfcrt and pfmdr1 was also performed. RESULTS: In total, 368 patients were enrolled in this study. Average IC(50) values for chloroquine were 106.6, 80.5, and 87.6 nM in 2016, 2017, and 2018, respectively. These values were not significantly changed from those obtained in 2002/2003 (108 nM). The majority of parasites harboured a pfcrt K76T the mutation responsible for chloroquine resistance. However, a significant upward trend was observed in the frequency of the K76 (wild) allele from 2.3% in 2016 to 11.7% in 2018 (P = 0.008; Cochran–Armitage trend test). CONCLUSIONS: Eight years of chloroquine withdrawal has not induced a significant recovery of susceptibility in Papua New Guinea. However, an increasing tendency of parasites harbouring chloroquine-susceptible K76 suggests a possibility of resurgence of chloroquine susceptibility in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2585-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-62608882018-12-10 Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea Sekihara, Makoto Tachibana, Shin-Ichiro Yamauchi, Masato Yatsushiro, Shoki Tiwara, Steven Fukuda, Naoyuki Ikeda, Mie Mori, Toshiyuki Hirai, Makoto Hombhanje, Francis Mita, Toshihiro Malar J Research BACKGROUND: Chloroquine treatment for Plasmodium falciparum has been discontinued in almost all endemic regions due to the spread of resistant isolates. Reversal of chloroquine susceptibility after chloroquine discontinuation has been reported in dozens of endemic regions. However, this phenomenon has been mostly observed in Africa and is not well documented in other malaria endemic regions. To investigate this, an ex vivo study on susceptibility to chloroquine and lumefantrine was conducted during 2016–2018 in Wewak, Papua New Guinea where chloroquine had been removed from the official malaria treatment regimen in 2010. Genotyping of pfcrt and pfmdr1 was also performed. RESULTS: In total, 368 patients were enrolled in this study. Average IC(50) values for chloroquine were 106.6, 80.5, and 87.6 nM in 2016, 2017, and 2018, respectively. These values were not significantly changed from those obtained in 2002/2003 (108 nM). The majority of parasites harboured a pfcrt K76T the mutation responsible for chloroquine resistance. However, a significant upward trend was observed in the frequency of the K76 (wild) allele from 2.3% in 2016 to 11.7% in 2018 (P = 0.008; Cochran–Armitage trend test). CONCLUSIONS: Eight years of chloroquine withdrawal has not induced a significant recovery of susceptibility in Papua New Guinea. However, an increasing tendency of parasites harbouring chloroquine-susceptible K76 suggests a possibility of resurgence of chloroquine susceptibility in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2585-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-26 /pmc/articles/PMC6260888/ /pubmed/30477515 http://dx.doi.org/10.1186/s12936-018-2585-x Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Yatsushiro, Shoki
Tiwara, Steven
Fukuda, Naoyuki
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Hombhanje, Francis
Mita, Toshihiro
Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title_full Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title_fullStr Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title_full_unstemmed Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title_short Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
title_sort lack of significant recovery of chloroquine sensitivity in plasmodium falciparum parasites following discontinuance of chloroquine use in papua new guinea
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260888/
https://www.ncbi.nlm.nih.gov/pubmed/30477515
http://dx.doi.org/10.1186/s12936-018-2585-x
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