Artemisinin resistance containment project in Thailand. II: responses to mefloquine-artesunate combination therapy among falciparum malaria patients in provinces bordering Cambodia

Abstract

BackgroundThe area along the Thai-Cambodian border is considered an epicenter of anti-malarial drug resistance. Recently, parasite resistance to artemisinin-based therapies has been reported in the area. The artemisinin resistance containment project was initiated in November 2008, with the aim to limit resistant parasites and eliminate malaria in this region. This study describes the response to artemisinin-based therapy among falciparum malaria patients in the area, using data from the malaria surveillance programmed under the containment project.MethodsThe study was conducted in seven provinces of Thailand along the Thai-Cambodian border. Data of Plasmodium falciparum-positive patients during January 2009 to December 2011 were obtained from the electronic malaria information system (eMIS) Web-based reporting system. All P. falciparum cases were followed for 42 days, as the routine case follow-up protocol. The demographic characteristics of the patients were described. Statistical analysis was performed to determine the cure rate of the current standard anti-malarial drug regimen--mefloquine-artesunate combination therapy (MAS). The proportion of patients who remained parasite-positive at each follow-up day was calculated. In addition, factors related to the delayed parasite clearance on day-3 post-treatment, were explored.ResultsA total of 1,709 P. falciparum-positive cases were reported during the study period. Almost 70% of falciparum cases received MAS therapy (n = 1,174). The majority of cases were males, aged between 31 and 50 years. The overall MAS cure rate was >90% over the three-year period. Almost all patients were able to clear the parasite within 7 to 14 days post-treatment. Approximately 14% of patients undergoing MAS remained parasite-positive on day-3. Delayed parasite clearance was not significantly associated with patient gender, age, or citizenship. However, delayed parasite clearance varied across the study area.ConclusionAnti-malarial drug-resistant parasites should be closely monitored in the area along the Thai-Cambodian border. Although the MAS cure rate in this study area was above 90%, an increasing trend of treatment failure has been reported in neighboring parts. Effective malaria surveillance is an important component to monitor drug-resistance in the malaria containment project.

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

“…In recent years, evidence of confirmed emerging resistance to artemisinins has been gathered from clinical studies in western Cambodia as well as the bordering areas between Thailand and Myanmar [27][28][29][30] . Furthermore, the observation of pfmdr1 wild type and increasing of gene copy number may suggest declining of artesunate-mefloquine treatment efficacy in P. falciparum isolates in this border area.…”

Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Malaria in Children in Zaire and Uíge Provinces, Angola

“…Widespread resistance to conventional antimalarials, such as chloroquine, sulfadoxine-pyrimethamine, and mefloquine, motivated the World Health Organization (WHO) to recommend the use of artemisinin-based combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria (1). Although ACTs were introduced only in the 1990s, studies have documented the emergence of resistance to artemisinins in limited areas of the Greater Mekong Subregion (2)(3)(4)(5)(6)(7)(8)(9)(10), and a recent dispatch reported a case of frank artemisinin treatment failure in a traveler from Angola (11).…”

Clarithromycin enhances the antimalarial efficacy of mefloquine via its increased bioavailability and disrupting P. falciparum apicoplast

“…(ter Kuile et al, 1992;Schlagenhauf, 1999). However, due to the emergence of MQ resistance and reduced cure rates of its combinations with SP, artesunate and artemether are the major problems of concern (Price et al, 1995;Thimasarn et al, 1997;Ekanem et al, 2000;Wongsrichanalai and Meshnick, 2008;Na-Bangchang et al, 2010;Satimai et al, 2012). In spite of MQ resistance in some areas, its antimalarial profile makes this particular drug more valuable and it is, therefore, recommended to save the protective life of MQ by employing it only in combination therapy with suitable partner drug (Schlagenhauf et al, 2010;WHO, 2012).…”

“…Due to rising failure rates for mefloquine monotherapy, WHO had recommended to introduce new mefloquine combinations (WHO, 2004) but MQ in widely used combinations could not give 100% cure (Price et al, 1995;Thimasarn et al, 1997;Ekanem et al, 2000;Wongsrichanalai and Meshnick, 2008;Na-Bangchang et al, 2010;Satimai et al, 2012) which is worrisome.…”