Lack of Significant Recovery of Chloroquine Sensitivity in Plasmodium Falciparum Parasites Following Discontinuance of Chloroquine Use in Papua New Guinea

Overview

Journal Malar J

Publisher Biomed Central

Specialty Tropical Medicine

Date 2018 Nov 28

PMID 30477515

Citations 8

Authors

Makoto Sekihara

Shin-Ichiro Tachibana

Masato Yamauchi

Shoki Yatsushiro

Steven Tiwara

Naoyuki Fukuda

Mie Ikeda

Toshiyuki Mori

Makoto Hirai

Francis Hombhanje

Toshihiro Mita

Affiliations

Soon will be listed here.

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 IC 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.

Citing Articles

Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutation and decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea.

Yoshida N, Yamauchi M, Morikawa R, Hombhanje F, Mita T Malar J. 2021; 20(1):410.

PMID: 34666779 PMC: 8524940. DOI: 10.1186/s12936-021-03933-6.

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern uganda by high-resolution melt analysis.

Kassaza K, Long A, McDaniels J, Andre M, Fredrickson W, Nyehangane D Malar J. 2021; 20(1):114.

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Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.

Miotto O, Sekihara M, Tachibana S, Yamauchi M, Pearson R, Amato R PLoS Pathog. 2020; 16(12):e1009133.

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Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region.

Adamu A, Jada M, Haruna H, Yakubu B, Ibrahim M, Balogun E Malar J. 2020; 19(1):439.

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