Independent Evolution of Pyrimethamine Resistance in
            <i>Plasmodium falciparum</i>
            Isolates in Melanesia

Mita, Toshihiro; Tanabe, Kazuyuki; Takahashi, Nobuyuki; Tsukahara, Takahiro; Eto, Hideaki; Lek, Dysoley; Ohmae, Hiroshi; Kita, Kiyoshi; Krudsood, Srivicha; Looareesuwan, Sornchai; Kaneko, Akira; Björkman, Anders; Kobayakawa, Takatoshi

doi:10.1128/aac.01186-06

Cited by 42 publications

(52 citation statements)

References 32 publications

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“…5). The haplotype H1, displaying a microsatellite combination of 193-175-201-110 bp on 4 loci, was described previously as the Southeast Asia (SEA) haplotype (19,28). The H19 haplotype, 199-155-201-104, however, had not been reported yet.…”

Section: Identification Of Infection Complexity In Field Isolatesmentioning

confidence: 99%

“…This mutant allele evolved and was introduced into other regions in Southeast Asia and Africa through a similar spread pathway of chloroquine resistance (12)(13)(14)(15). Nevertheless, multiple indigenous origins of some single, double, or triple pfdhfr alleles were also reported in Southeast Asia, Africa, South America, and Papua New Guinea (16)(17)(18)(19). To date, the evolution and spread of resistant lineages are traced by the pfdhfr rather than the pfdhps gene, but there are still several surveys that showed that unlike the pfdhfr gene, various sulfadoxine-resistant pfdhps alleles originated independently in each of those areas, including Thailand, Cambodia, Kenya, Cameroon, and Venezuela (17,18,(20)(21)(22).…”

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confidence: 99%

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Distinctive Origin and Spread Route of Pyrimethamine-Resistant Plasmodium falciparum in Southern China

Zhang

Wei

et al. 2014

Antimicrob Agents Chemother

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bSoutheast Asia (the Thailand-Cambodia border) has been considered the primal epicenter for most antimalarial drug resistance; however, numerous molecular epidemiological studies have successively reported multiple independent origins of sulfadoxinepyrimethamine (SP) resistance-associated Plasmodium falciparum dhfr (pfdhfr) and pfdhps alleles in other areas. To better understand the origin and evolutionary pathway of the SP resistance in Southeast Asia, a total of 374 P. falciparum field isolates from the Yunnan-Burma border and Hainan Island in southern China have been collected for comprehensive investigations on the mutation patterns of the pfdhfr/pfdhps genes as well as their microsatellite haplotypes. By comparative analysis of singlenucleotide polymorphism (SNP) genotyping and flanking microsatellite haplotypes, we reveal a unique origin of pyrimethamine-resistant mutations in Pfdhfr gene in Hainan Island and an oriented spread route of the pyrimethamine resistance from the Thailand-Cambodia border into the Hainan area, which reflects the geographical traits and SP administration histories in the two geographically independent areas. Moreover, genetic linkages between the high-level SP resistance-conferring pfdhfr/ pfdhps alleles have been established in the isolates from the Yunnan-Burma border, raising the concern of a genetic basis in adopting combination chemotherapies against falciparum malaria.

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Section: Identification Of Infection Complexity In Field Isolatesmentioning

confidence: 99%

mentioning

confidence: 99%

Distinctive Origin and Spread Route of Pyrimethamine-Resistant Plasmodium falciparum in Southern China

Zhang

Wei

et al. 2014

Antimicrob Agents Chemother

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“…5A) (6,21,58,59) 4-2. Pyrimethamine It has recently been shown that highly pyrimethamine-resistant forms of dhfr (carrying three or more mutations in dhfr) expanded from very limited foci to almost all endemic areas where pyrimethamine/sulfadoxine-resistant parasites are prevalent (7,8,10,60,61) (Fig. 5B).…”

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confidence: 99%

“…Recent population geneticsbased analyses using microsatellite markers that flank drug-resistance genes have revealed that parasite lineages that are resistant to either chloroquine or pyrimethamine/sulfadoxine are of considerably limited geographic origin, suggesting that these resistant lineages subsequently were dispersed to many endemic areas (6)(7)(8)(9)(10)(11)(12)(13). Here, we review our recent understanding of the evolution of P. falciparum resistance to chloroquine and pyrimethamine/sulfadoxine, with special emphasis on the geographic epicenter of drug resistance, and consider the implications for the development and containment of artemisinin resistance.…”

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confidence: 99%

Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance

Mita¹,

Tanabe²

2012

Jpn J Infect Dis

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100

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“…The Southeast Asian triple mutant dhfr allele AIRNI later spread to Africa, where this is in abundance (7,14,24,28,29). However, there is evidence of indigenous origins of triple mutant dhfr allele AIRNI in several African countries like Kenya, Ghana, and Cameroon (18,19). Two distinct lineages of triple mutant dhfr alleles (RICNI and CICNL) have been reported from South America (8,17,27).…”

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confidence: 99%

Multiple Origins of Plasmodium falciparum Dihydropteroate Synthetase Mutant Alleles Associated with Sulfadoxine Resistance in India

Lumb

Das

Singh

et al. 2011

Antimicrob Agents Chemother

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With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the Plasmodium falciparum parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian P. falciparum isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (H e ) around mutant dhps alleles (H e ‫؍‬ 0.55; n ‫؍‬ 81) associated with sulfadoxine resistance was lower (P < 0.05) than the mean H e around the wild-type dhps allele (H e ‫؍‬ 0.80; n ‫؍‬ 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine-and pyrimethamine-resistant parasites in the past.

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Independent Evolution of Pyrimethamine Resistance in Plasmodium falciparum Isolates in Melanesia

Abstract: Pyrimethamine resistance in

Cited by 42 publications

References 32 publications

Distinctive Origin and Spread Route of Pyrimethamine-Resistant Plasmodium falciparum in Southern China

Distinctive Origin and Spread Route of Pyrimethamine-Resistant Plasmodium falciparum in Southern China

Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance

Multiple Origins of Plasmodium falciparum Dihydropteroate Synthetase Mutant Alleles Associated with Sulfadoxine Resistance in India

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