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ABSTRACT: G6PD deficiency is common in malaria endemic regions and is estimated to affect more than 400 million people worldwide. Treatment of malaria patients with the anti-malarial drug primaquine or other 8-aminoquinolines may be associated with potential haemolytic anaemia. The aim of the present study was to investigate the prevalence of G6PD variants in Thai population who resided in malaria endemic areas (western, northern, north-eastern, southern, eastern and central regions) of Thailand, as well as the Burmese population who resided in areas along the Thai-Myanmar border.
The ten common G6PD variants were investigated in dried blood spot samples collected from 317 Thai (84 males, 233 females) and 183 Burmese (11 males, 172 females) populations residing in malaria endemic areas of Thailand using PCR-RFLP method.
Four and seven G6PD variants were observed in samples collected from Burmese and Thai population, with prevalence of 6.6% (21/317) and 14.2% (26/183), respectively. Almost all (96.2%) of G6PD mutation samples collected from Burmese population carried G6PD Mahidol variant; only one sample (3.8%) carried G6PD Kaiping variant. For the Thai population, G6PD Mahidol (8/21: 38.1%) was the most common variant detected, followed by G6PD Viangchan (4/21: 19.0%), G6PD Chinese 4 (3/21: 14.3%), G6PD Canton (2/21: 9.5%), G6PD Union (2/21: 9.5%), G6PD Kaiping (1/21: 4.8%), and G6PD Gaohe (1/21: 4.8%). No G6PD Chinese 3, Chinese 5 and Coimbra variants were found. With this limited sample size, there appeared to be variation in G6PD mutation variants in samples obtained from Thai population in different regions particularly in the western region.
Results indicate difference in the prevalence and distribution of G6PD gene variants among the Thai and Burmese populations in different malaria endemic areas. Dosage regimen of primaquine for treatment of both Plasmodium falciparum and Plasmodium vivax malaria may need to be optimized, based on endemic areas with supporting data on G6PD variants. Larger sample size from different malaria endemic is required to obtain accurate genetic mapping of G6PD variants in Burmese and Thai population residing in malaria endemic areas of Thailand.
Malaria Journal 12/2011; 10:368. · 3.19 Impact Factor
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ABSTRACT: The aim of this study was to investigate the association between genetic polymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum ATPase (pfatp6) and clinical outcome after a three-day mefloquine-artesunate combination therapy in 134 patients with uncomplicated Plasmodium falciparum malaria in an area with multidrug resistance along the Thailand-Myanmar border. Analysis of gene mutation and amplification were performed by nested real-time polymerase chain reaction and SYBR Green I real-time polymerase chain reaction, respectively. The mutation for pfcrt (codons 76, 220, 271, 326, 356, and 371) was found in all isolates (100%), whereas no mutation of pfmdr1 (codon 86) and pfatp6 (codons 37, 693, 769, 898) was found. The Pfmdr1 copy number was significantly higher in isolates with recrudescence (median number = 2.44) compared with a sensitive response (median number = 1.44). The gene copy number was also found to be significantly higher in paired isolates collected before treatment and at the time of recrudescence. All isolates carried one pfatp6 gene copy.
The American journal of tropical medicine and hygiene 09/2011; 85(3):568-72. · 2.59 Impact Factor
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ABSTRACT: The association between pfatp6, pfmdr1 polymorphisms (gene mutation and amplification) and in vitro susceptibility to mefloquine (MQ), artesunate (AS), quinine (QN), and chloroquine (CQ) was investigated in a total of sixty-three Plasmodium falciparum isolates collected from the Thai-Myanmar border. The mutations of pfatp6 at codons R37K, G639D, S769N, and I898I and of pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Pfatp6 and pfmdr1 gene copy numbers were analyzed by quantitative real time-polymerase chain reaction (qRT-PCR). In vitro susceptibility test was successful in 58 culture-adapted isolates. Median (range) IC(50) values for MQ, AS, QN, and CQ were 28.96 (3.4-100.5), 1.74 (0.8-5.57), 223.9 (14.99-845.47), and 69.93 (9.6-183.18) nM, respectively. There was a significant positive correlation (R(2) = 0.58) of parasite susceptibility to MQ, AS, and QN. Twelve isolates showed marked decline in susceptibility to AS [median (range) IC(50) = 3.78 (3.07-5.57) nM]. Almost all isolates carried wild-type pfatp6 and pfmdr1 alleles at the investigated codons, while only three isolates (5%) carried pfmdr1 mutation alleles at codon 86. Mutation at codon 86 was associated with a significant increase in the susceptibility of parasite isolates to MQ and QN. All of the sixty-three isolates carried only one pfatp6 copy number. Thirty-three out of the 58 isolates showed increase in pfmdr1 gene copies, which was associated with reduced in vitro susceptibility to MQ, AS, and QN. No association between mutation or amplification of pfatp6 gene and in vitro susceptibility of P. falciparum isolates was found.
Acta tropica 07/2011; 120(1-2):130-5. · 2.22 Impact Factor
