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. 2018 Nov 26;17(1):434.
doi: 10.1186/s12936-018-2585-x.

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

Makoto Sekihara  1 , Shin-Ichiro Tachibana  1 , Masato Yamauchi  1 , Shoki Yatsushiro  2 , Steven Tiwara  3 , Naoyuki Fukuda  1 , Mie Ikeda  1 , Toshiyuki Mori  1 , Makoto Hirai  1 , Francis Hombhanje  4 , Toshihiro Mita  5
Affiliations

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

Makoto Sekihara et al. Malar J. .

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.

Keywords: Chloroquine; Fitness; Papua New Guinea; Plasmodium falciparum; Recovery; Resistance; pfcrt.

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Figures

Fig. 1
Fig. 1
Association between IC50 values for chloroquine and polymorphisms in pfcrt and pfmdr1. Statistical significance was calculated using Welch’s t-test
Fig. 2
Fig. 2
Association between IC50 values for lumefantrine and polymorphisms in pfcrt and pfmdr1. Statistical significance was calculated using Welch’s t-test
See this image and copyright information in PMC

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