Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies.

The emergence and spread of artemisinin-resistant Plasmodium falciparum is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the Pfkelch13 gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the Pfkelch13 propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin-exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the Pfkelch13 propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of Pfkelch13 polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various Pfkelch13 mutations have been selected under artemisinin pressure.

Use of Rapid Enzyme-Linked Immunosorbent Assays for Serological Screening of Melioidosis in Myanmar.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is an important but under-recognized cause of disease in the tropics. Although first described over a century ago as a septicemic illness associated with morphine addicts in Rangoon, Burma, there is little information regarding the incidence of melioidosis in present-day Myanmar. To address this issue, we used two recently developed and validated serological assays to detect B. pseudomallei-specific antibodies in 124 serum samples obtained from febrile patients in the delta region of Myanmar. Using cutoff values derived from culture-confirmed melioidosis cases in neighboring Thailand, 3.2% of the samples exhibited reactivity profiles consistent with active B. pseudomallei infections. Collectively, these findings indicate that melioidosis likely represents a significant cause of morbidity and mortality in Myanmar and support the need for further studies to assess the true burden of disease in this country.