Amplification of pfmdr1 , pfcrt , pvmdr1 , and K13 Propeller Polymorphisms Associated with Plasmodium falciparum and Plasmodium vivax Isolates from the China-Myanmar Border

Abstract

bMalaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, the pfmdr1, pfcrt, pvmdr1, and K13-propeller genotypes were determined in 26 Plasmodium falciparum and 64 Plasmodium vivax isolates from Yingjiang county of Yunnan province. The pfmdr1 (11.5%), pfcrt (34.6%), and pvmdr1 (3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% for pfmdr1 N86Y, pfcrt K76T, and pfcrt M74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes of pfmdr1 and pfcrt were Y 86 Y 184 and M 74 N 75 T 76 , respectively. No pvmdr1 mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region. Malaria is a serious public health problem in the Greater Mekong Subregion (GMS), which includes Cambodia, Laos, Thailand, Vietnam, Myanmar, and Yunnan province of China (1). Within this region, malaria transmission is particularly intense in international border areas. The malaria prevalence along the China-Myanmar border is particularly high, and malaria outbreaks have occurred frequently (2). In 2010, China initiated the National Malaria Elimination Action Plan, which aims to eliminate local malaria transmission nationwide by 2015 with the exception of the border region in Yunnan province and to completely eliminate malaria from China by 2020 (3). Despite a great reduction in the number of local malaria cases recently, both Plasmodium falciparum and Plasmodium vivax infections persist in the counties at the China-Myanmar border.Effective chemotherapy is essential for malaria control, but the emergence and spread of multidrug-resistant (MDR) P. falciparum strains have led to the adoption of artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated falciparum malaria in the GMS. However, the confirmed emergence of artemisinin resistance in western Cambodia is a major threat for malaria control and elimination (4). Artemisinin resistance has since spread or emerged independently or both in other areas of mainland Southeast Asia (5). Because this area has been the origin of both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance (6, 7), the consequences of a similar spread of artemisinin resistance will be catastrophic. Therefore, the World Health Organization (WHO) is coordinating a largescale elimination campa...

Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India

“…However, this mutation has been detected at a lower frequency and no correlation with treatment outcome has been observed. In Bangladesh, A578S mutation in the k13 propeller region has been reported, however, no data on clinical outcome are available [21]. A recent study has revealed that A578S mutation is commonly observed in Africa and is not associated with artemisinin resistance [22].…”

Understanding artemisinin-resistant malaria

“…Molecular surveillance studies have greatly expanded the map of K13-propeller polymorphism to include additional areas of Cambodia [29], Thailand [30], Myanmar [31, 32], China [32, 33], and Bangladesh [34]; some of these mutations have been previously associated with slow parasite clearance at other sites, but most have not and require validation. Currently, C580Y predominates in Cambodia [22, 28, 29, 35, 36] and along the Thailand-Myanmar border [22, 28, 31], while F446I predominates along the Myanmar-China border [16, 31, 33].…”

Domestic trends in malaria research and development in China and its global influence

“…Luckily, there is a pipeline of more than 10 new antimalarial drugs in various stages, such as the new antimalarial compound OZ439 [32, 33]. Routine monitoring and surveillance, as recommended by the WHO Global Plan for Artemisinin Resistance Containment, should be strengthened [34]. Unfortunately, this study shows that artemisinin-based drugs are still the main focus for researchers in China [35].…”