Mefloquine-resistant falciparum malaria on the Thai-Burmese border

Nosten, François; Kuile, Feiko O. ter; Chongsuphajaisiddhi, T; Luxemburger, Christine; Webster, H. K.; Edstein, Michael D.; Phaipun, L; Thew, Kyaw Lay; White, Nicholas J.

doi:10.1016/0140-6736(91)92798-7

Cited by 220 publications

(118 citation statements)

References 8 publications

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“…[1][2][3] In Myanmar (Burma), chloroquine has been the fi rst-line treatment for falciparum malaria until recently. Studies in 1995 and 1998 by Médecins Sans Frontières (Holland), with the support of the Department of Health and the Vector Borne Disease Control Department, in the western and northern parts of the country showed very high rates of resistance to chloroquine and sulfadoxinepyrimethamine, the recommended treatments at the time.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison

Smithuis¹,

Kyaw²,

Phe³

et al. 2006

The Lancet

137

104

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CitationEfficacy SummaryBackground Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefl oquine is widely recommended in southeast Asia, but its high cost and tolerability profi le remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefl oquine, we compared the safety, tolerability, effi cacy, and eff ectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma).

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Section: Introductionmentioning

confidence: 99%

Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison

Smithuis¹,

Kyaw²,

Phe³

et al. 2006

The Lancet

137

104

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“…The parasites were incubated at 37ЊC in a candle jar for 18 hr. To assess parasite growth, 3 Hhypoxanthine (1 Ci/well; Amersham, Buckinghamshire, United Kingdom) was added. The plates were frozen to terminate the incorporation after 24 hr of additional incubation.…”

Section: Methodsmentioning

confidence: 99%

“…Increasing levels and prevalence of Plasmodium falciparum resistance to choloroquine 1 and mefloquine [2][3][4] have been reported. This has made the treatment and prophylaxis of malaria increasingly complicated.…”

mentioning

confidence: 99%

Analysis of mefloquine resistance and amplification of pfmdr1 in multidrug-resistant Plasmodium falciparum isolates from Thailand.

Chaiyaroj

Buranakiti²,

Angkasekwinai³

et al. 1999

Am J Trop Med Hyg

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Abstract. Resistance to quinoline-containing compound has been associated with the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene. We analyzed wild P. falciparum isolates with high levels of chloroquine and mefloquine resistance for their macrorestriction maps of chromosome 5 and sequence of pfmdr1. Two types of chromosome 5 amplification were found. Eleven of 62 resistant isolates displayed Bgl I fragments larger than 100 kb. Twenty-nine isolates possessed multiple copies of the fragments. We failed to detect any amplification of this region on chromosome 5 in 22 mefloquine-resistant isolates, suggesting that other mechanisms can mediate the mefloquine-resistant phenotype. There was no direct association between pfmdr1 mutations and chloroquine sensitivity. Resistant lines could have Asn-86 and Tyr-184 or Phe-184, the predicted sequence of those chloroquine-sensitive isolates. No mutation at Asn-1042 and Asp-1246 was detected among these chloroquine-resistant isolates. Therefore, a few base substitutions in the pfmdr1 gene may not be sufficient to account for all chloroquine-resistant phenotypes.In Thailand, malaria continues to be a major public health problem due to the emergence of multidrug-resistant organisms. Increasing levels and prevalence of Plasmodium falciparum resistance to choloroquine 1 and mefloquine 2-4 have been reported. This has made the treatment and prophylaxis of malaria increasingly complicated. Although new drugs and several drug combinations are being introduced, it is important to elucidate the molecular mechanism of aminoquinoline drug resistance to develop the appropriate strategies for malaria therapy.A P-glycoprotein homolog (Pgh 1) has been implicated in chloroquine-and mefloquine-resistant phenotypes of P. falciparum. [5][6][7][8] It is encoded by the P. falciparum multidrug resistance 1 (pfmdr1) gene and is localized on the membrane of the digestive vacuole of this parasite. 8,9 High levels of Pgh 1 expression have been shown in drug-resistant cell lines to confer a chloroquine-sensitive phenotype and in yeast to complement the ste 6 functions, 10 suggesting a role as a drug transporter. Controversy exists regarding the pfmdr 1 gene and chloroquine resistance from the work of Wellems and others 11 in that there is no linkage between pfmdr 1 and such resistance. In addition, in vitro selection of parasites for increased chloroquine resistance resulted in parasites with higher sensitivity to mefloquine. 12 Surprisingly, chromosome 5 of these parasite clones demonstrated deamplification and the expression of Pgh 1 was also decreased. 12 In subsequent drug selection studies, the higher levels of mefloquine resistance have been associated with amplification of pfmdr1. 8,13 Data from several field isolates with mefloquine resistance suggested that the amplification of pfmdr1 and an increase in mRNA expression is associated with natural resistance. Furthermore, cross-resistance to other related drugs such as halofantrine and quinine was also observed. [13][14][15] In this s...

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“…In 1986 the established combination of mefloquine with sulfadoxine and pyrimethamine, which had been introduced to delay the evolution of resistance to mefloquine, was effective in 98 % of all P. jalciparum infections. However, in a prospective study conducted in the same area in 1990, the efficacy had al ready dropped to 71 % [14]. This increase in resistance to mefloquine mayaiso increase the resistance to quinine because of structural similarities [24].…”

Section: Malaria Situationmentioning

confidence: 99%