Declining Artesunate-Mefloquine Efficacy against Falciparum Malaria on the Cambodia–Thailand Border

Abstract

Resistance to many antimalaria drugs developed on the Cambodia-Thailand border long before developing elsewhere. Because antimalaria resistance is now a global problem, artemisinin-based combination therapies (ACTs) are the fi rst-line therapies in most malaria-endemic countries. However, recent clinical and molecular studies suggest the emergence of ACT-resistant Plasmodium falciparum infections in the Cambodia-Thailand border area, where standard ACT is artesunate and mefl oquine. These ACT failures might be caused by high-level mefl oquine resistance because mefl oquine was used for monotherapy long before the introduction of ACT. This observation raises 2 questions. First, how can existing P. falciparum-resistant strains be controlled? Second, how can the evolution of new ACT-resistant strains be avoided elsewhere, e.g., in Africa? Enforcement of rational drug use and improved diagnostic capacity are among the measures needed to avoid and contain ACT resistance.

Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border

“…Mefloquine was introduced for clinical use in Thailand since 1983, and since then, it has effectively select resistance genotype particularly the pfmdr1 codon 86 wild type (N86) [21,22] . Extensive use of mefloquine in area along ThaiMyanmar border provided significant impact on the intensity and patterns of P. falciparum drug resistance genotypes, the pfmdr1 mutation at codon 86 is gradually replaced by wild type (N86) genotype [21] .…”

Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

“…32,34,[37][38][39][40][41] However, in certain areas, for example, along Cambodia-Thailand and northwestern border of Thailand, the efficacy of AMQ is declining primarily because of resistance to MQ. 42,43 Recently, artemisinin resistance has been reported in Cambodia. 44 Thus, close monitoring will be needed with the use of AMQ in those areas of West Africa where reduced in vitro susceptibility has been reported to MQ and artemisinin 13 and where patients are more likely to take the artesunate and leave the MQ component or the possibility of providers selling one drug to reduce costs in co-packaging now available in many endemic areas of West Africa.…”

“…Follow-up with clinical and parasitologic evaluation was done daily on Days 1-7 and then on Days 14,21,28,35,and 42. This consisted of enquiry about the patient's well being, presence or absence of initial presenting symptoms, presence of additional symptoms, measurement of body temperature, heart and respiratory rates, and taking a blood smear for the quantification of parasitemia.…”

Global Infectious Disease Surveillance at DoD Overseas Laboratories, 1999–2007

“…21 DoD-GEIS scientists in Asia, East Africa, and South America have documented the continued spread of markers suggesting the potential for malaria drug resistance emergencenotably recent artesunate-class drug resistance-while working to standardize laboratory methodology and microscopy. [22][23][24][25][26][27][28][29][30] A collaboration between the National Aeronautics and Space Administration, USAMRU-K, and DoD-GEIS headquarters has developed an effective, satellite-based early warning tool for rift valley fever in East Africa and is now working to expand its applicability to other climate-dependent epidemic diseases. [31][32][33][34][35][36] The network has also overseen the development and refinement of a series of systems designed to bring real-time disease surveillance to remote or low-resource settings, including Cambodia, Laos, Thailand, the Philippines, and Andean Ridge countries of South America.…”