Effects of mefloquine use on Plasmodium vivax multidrug resistance

Abstract

Numerous studies have indicated a strong association between amplification of the multidrug resistance-1 gene and in vivo and in vitro mefloquine resistance of Plasmodium falciparum. Although falciparum infection usually is not treated with mefloquine, incorrect diagnosis, high frequency of undetected mixed infections, or relapses of P. vivax infection triggered by P. falciparum infections expose non-P. falciparum parasites to mefloquine. To assess the consequences of such unintentional treatments on P. vivax, we studied variations in number of Pvmdr-1 (PlasmoDB accession no. PVX_080100, NCBI reference sequence NC_009915.1) copies worldwide in 607 samples collected in areas with different histories of mefloquine use from residents and from travelers returning to France. Number of Pvmdr-1 copies correlated with drug use history. Treatment against P. falciparum exerts substantial collateral pressure against sympatric P. vivax, jeopardizing future use of mefloquine against P. vivax. A drug policy is needed that takes into consideration all co-endemic species of malaria parasites.

Figure 1

Geographic distribution of Plasmodium vivax isolates with 1 multidrug resistance-1 (mdr-1) copy (green) and isolates with >1 mdr-1 copies (red) in 607 samples collected in South America, Asia, and Africa during 1997–2010.

Figure 2

Comparative distribution of numbers of Plasmodium falciparum and P. vivax mdr-1 copies in isolates collected from residents of Madagascar and Cambodia. Gray dot, median; dark bars, interquartile range (25%–75%).