Abstract
BackgroundIn Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone®, a combination of atovaquone–proguanil (ATQ–PG), has been used to cease artemisinin pressure in some areas along Thai–Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai–Cambodia border after the artemisinin resistance containment project compared with those collected before.ResultsOne hundred and nine of P. falciparum isolates collected from Thai–Cambodia border from Chanthaburi and Trat provinces during 1988–2016 were used in this study. Of these, 58 isolates were collected after the containment. These parasite isolates were characterized for in vitro antimalarial sensitivities including chloroquine (CQ), quinine (QN), mefloquine (MQ), piperaquine (PPQ), artesunate (AS), dihydroartemisinin (DHA), ATQ and PG and genetic markers for drug resistance including the Kelch13 (k13), Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1) and cytochrome b (cytb) genes. Mean CQ, QN, MQ, PPQ and AS IC50s of the parasite isolates collected from 2009 to 2016 exhibited significantly higher than those of parasites collected before 2009. Approximately 57% exhibited in vitro MQ resistance. Approximately 94% of the isolates collected from 2009 to 2016 contained the pfmdr1 184F allele. Mutations of the k13 gene were detected in approximately 90% of the parasites collected from 2009 to 2016 which were significantly higher than the parasite isolates collected before. No ATQ-resistant genotype and phenotype of P. falciparum were found among the isolates collected after the containment project.ConclusionsAlthough the containment project had been implemented in this area, the expansion of artemisinin-resistant parasites did not decline. In addition, reduced sensitivity of the partner drugs of ACT including MQ and PPQ were identified.
Highlights
In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falci‐ parum malaria since 1995
Increased AS–MQ failure rates observed in Thailand and Cambodia were usually associated with MQ resistance [5, 6]
This study was aimed to determine phenotypes and genotypes of P. falciparum isolated from the Thai–Cambodian border after the artemisinin resistance containment project compared with those collected before
Summary
In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falci‐ parum malaria since 1995. Artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai–Cambodia border after the artemisinin resistance containment project compared with those collected before. Artemisinin-based combination therapy (ACT) has been recommended by the World Health Organization (WHO) to use as the firstline treatment for multidrug-resistant falciparum malaria [1]. A few studies have shown evidence of artemisinin resistance in P. falciparum, defined as delayed parasite clearance, i.e., presence of parasitaemia on day 3 following treatment with AS monotherapy or ACT [7, 8]. The mutations were associated with artemisinin resistance in Cambodia and other countries in the GMS [12, 14,15,16]
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