Malaria in the Greater Mekong Subregion: Heterogeneity and complexity

Abstract

The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by ‘border malaria’ and ‘forest malaria’ with high transmission occurring along international borders and in forests or forest fringes, respectively. ‘Border malaria’ is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and P. vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is severely undermined due to high prevalence of glucose-6-phosphate dehydrogenase deficiency in target human populations. In the GMS, the dramatically different ecologies, diverse vector systems, and insecticide resistance render traditional mosquito control less efficient. Here we attempt to review the changing malaria epidemiology in the GMS, analyze the vector systems and patterns of malaria transmission, and identify the major challenges the malaria control community faces on its way to malaria elimination.

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

“…Thailand-Cambodia border: epicenter of drug resistance It has recently been recognized that an initial emergence of drug-resistant P. falciparum has been restricted to limited geographic regions, the so-called``epicenters of resistance.'' The Greater Mekong subregion is the most threatening focus of malaria in terms of antimalarial drug-based control (94). This area comprises six countries: Cambodia, Thailand, China's Yunnan province, Lao PDR, Myanmar, and Vietnam.…”

Clinical Efficacy of Dihydroartemisinin–Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria at the China–Myanmar Border

“…1,2 In recent years, substantial progress has been made in reducing the regional malaria burden; several countries have entered the malaria preelimination and elimination phases. 3 This success is attributed, in part, to the deployment of artemisinin-based combination therapies (ACTs) in malaria-endemic countries.…”

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

“…Such interventions, including increased vector control, increased surveillance, and improved access to quality artemisinin-combination therapy (ACT), would be expected to curtail coendemic Plasmodium vivax as well. However, even as P. falciparum infections in Cambodia decreased by 81% between 2009 and 2013, P. vivax cases have increased, making it the predominant species in the Mekong region (3)(4)(5)(6). This scenario, repeated in Brazil and other areas of coendemicity, has led to growing awareness that P. vivax, although infecting the same populations and transmitted by the same mosquito vectors, will likely be the more challenging species to eradicate (6)(7)(8)(9).…”