Emerging Plasmodium vivax resistance to chloroquine in South America: an overview

Abstract

The global emergence of Plasmodium vivax strains resistant to chloroquine (CQ) since the late 1980s is complicating the current international efforts for malaria control and elimination. Furthermore, CQ-resistant vivax malaria has already reached an alarming prevalence in Indonesia, East Timor and Papua New Guinea. More recently, in vivo studies have documented CQ-resistant P. vivax infections in Guyana, Peru and Brazil. Here, we summarise the available data on CQ resistance across P. vivax-endemic areas of Latin America by combining published in vivo and in vitro studies. We also review the current knowledge regarding the molecular mechanisms of CQ resistance in P. vivax and the prospects for developing and standardising reliable molecular markers of drug resistance. Finally, we discuss how the Worldwide Antimalarial Resistance Network, an international collaborative effort involving malaria experts from all continents, might contribute to the current regional efforts to map CQ-resistant vivax malaria in South America.

Map showing sites of recent in vivo studies of chloroquine treatment for Plasmodium vivax infections in South America (published between 2000-2013). Triangles indicate study sites where treatment failures have been reported, while squares indicate sites with no treatment failures observed over 28 days of follow-up. Note the close proximity between two sites in Colombia (Uraba and Turbo) and two sites in Bolivia (Riberalta and Guayaramerín). Clinical data are from Villalobos-Salcedo et al. (2000) (Porto Velho, Brazil), Soto et al. (2001) (Uraba and Llanos Orientales, Colombia), Baird et al. (2002) (Georgetown, Guyana), Ruebush et al. (2003) (Iquitos, Caballococha and Sullana, Peru), Alvarez et al. (2006) (Turbo and El Bagre, Colombia), de Santana Filho et el. (2007) (Manaus, Brazil), Osorio et al. (2007) (Tarapacá, Colombia), Carmona-Fonseca and Maestre (2009) (Turbo and El Bagre, Colombia), Añez et al. (2012) (Riberalta, Guayaramerín and Yacuiba, Bolivia) and Marques et al. (2013) (Manaus, Brazil). Shading patterns vary according to P. vivax malaria prevalence (PvPR) data estimated by Gething et al. (2012).