Genetic Variations Associated with Drug Resistance Markers in Asymptomatic Plasmodium falciparum Infections in Myanmar

Abstract

The emergence and spread of drug resistance is a problem hindering malaria elimination in Southeast Asia. In this study, genetic variations in drug resistance markers of Plasmodium falciparum were determined in parasites from asymptomatic populations located in three geographically dispersed townships of Myanmar by PCR and sequencing. Mutations in dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps), chloroquine resistance transporter (pfcrt), multidrug resistance protein 1 (pfmdr1), multidrug resistance-associated protein 1 (pfmrp1), and Kelch protein 13 (k13) were present in 92.3%, 97.6%, 84.0%, 98.8%, and 68.3% of the parasites, respectively. The pfcrt K76T, pfmdr1 N86Y, pfmdr1 I185K, and pfmrp1 I876V mutations were present in 82.7%, 2.5%, 87.5%, and 59.8% isolates, respectively. The most prevalent haplotypes for pfdhfr, pfdhps, pfcrt and pfmdr1 were 51I/59R/108N/164L, 436A/437G/540E/581A, 74I/75E/76T/220S/271E/326N/356T/371I, and 86N/130E/184Y/185K/1225V, respectively. In addition, 57 isolates had three different point mutations (K191T, F446I, and P574L) and three types of N-terminal insertions (N, NN, NNN) in the k13 gene. In total, 43 distinct haplotypes potentially associated with multidrug resistance were identified. These findings demonstrate a high prevalence of multidrug-resistant P. falciparum in asymptomatic infections from diverse townships in Myanmar, emphasizing the importance of targeting asymptomatic infections to prevent the spread of drug-resistant P. falciparum.

Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

“…In Myanmar, CQR in P. vivax was reported as early as in the 1990s [12,13]. Drug resistance in P. falciparum and P. vivax isolates of asymptomatic malaria carriers has also been reported in high-and low-endemic regions of Myanmar [8,9]. Recently, along the China-Myanmar border, the therapeutic responses of P. vivax malaria to CQ treatment were declining [14,15].…”

“…Plasmodium vivax infections from asymptomatic carriers as a potential silent reservoir for transmission are common in both high-and low-endemic areas of Myanmar [6,7]. Previous reports of asymptomatic Plasmodium falciparum infections carrying genes potentially associated with drug resistance suggest a possible spread of drug-resistant parasites in Myanmar [8,9]. However, surveys of P. vivax drug resistance are scant because most drug resistance studies have focused on P. falciparum.…”

A seven-year surveillance of epidemiology of malaria reveals travel and gender are the key drivers of dispersion of drug resistant genotypes in Kenya

“…Single Nucleotide Polymorphisms (SNPs) in the P. falciparum multidrug resistance protein (Pfmdr1) and P. falciparum chloroquine resistance transporter (Pfcrt ) genes confer resistance to a number of anti-malaria drugs. Chloroquine resistance has been associated to Pfcrt K76T SNP (Mohammed et al, 2013;Zhao et al, 2019). Pfmdr1 86Y and Y184 haplotypes have been shown to modulate chloroquine (CQ) resistance in the presence of Pfcrt 76T mutation (Venkatesan et al, 2014).…”

Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar

“…Plasmodium malariae infection rate is generally underestimated and overlooked because it is often asymptomatic and mostly mixed with other Plasmodium species. Drug-resistant P. falciparum and P. vivax have been reported in many regions, including Thailand [9,10] and Myanmar [11,12]. Chloroquine-resistant P. falciparum was first documented in 1957 in Thailand which is now widely spread around the globe [13].…”