Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea
Abstract 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 phen...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2585-x |
| _version_ | 1819049676393938944 |
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| author | Makoto Sekihara Shin-Ichiro Tachibana Masato Yamauchi Shoki Yatsushiro Steven Tiwara Naoyuki Fukuda Mie Ikeda Toshiyuki Mori Makoto Hirai Francis Hombhanje Toshihiro Mita |
| author_facet | Makoto Sekihara Shin-Ichiro Tachibana Masato Yamauchi Shoki Yatsushiro Steven Tiwara Naoyuki Fukuda Mie Ikeda Toshiyuki Mori Makoto Hirai Francis Hombhanje Toshihiro Mita |
| author_sort | Makoto Sekihara |
| collection | DOAJ |
| description | Abstract 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 IC50 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. |
| first_indexed | 2024-12-21T11:35:56Z |
| format | Article |
| id | doaj.art-0f22cbd8a86445a68061ed4aa03a3ed4 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-21T11:35:56Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-0f22cbd8a86445a68061ed4aa03a3ed42022-12-21T19:05:27ZengBMCMalaria Journal1475-28752018-11-0117111010.1186/s12936-018-2585-xLack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New GuineaMakoto Sekihara0Shin-Ichiro Tachibana1Masato Yamauchi2Shoki Yatsushiro3Steven Tiwara4Naoyuki Fukuda5Mie Ikeda6Toshiyuki Mori7Makoto Hirai8Francis Hombhanje9Toshihiro Mita10Department of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineHealth Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST)Wewak General HospitalDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineCentre for Health Research & Diagnostics, Divine Word UniversityDepartment of Tropical Medicine and Parasitology, Juntendo University, Faculty of MedicineAbstract 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 IC50 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.http://link.springer.com/article/10.1186/s12936-018-2585-xPlasmodium falciparumChloroquineResistanceRecoverypfcrtFitness |
| spellingShingle | Makoto Sekihara Shin-Ichiro Tachibana Masato Yamauchi Shoki Yatsushiro Steven Tiwara Naoyuki Fukuda Mie Ikeda Toshiyuki Mori Makoto Hirai Francis Hombhanje Toshihiro Mita Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea Malaria Journal Plasmodium falciparum Chloroquine Resistance Recovery pfcrt Fitness |
| 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 | Plasmodium falciparum Chloroquine Resistance Recovery pfcrt Fitness |
| url | http://link.springer.com/article/10.1186/s12936-018-2585-x |
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