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.

Awareness of rabies and response to dog bites in a Bangladesh community.

Community awareness regarding rabies and treatment seeking behaviours are critical both for the prevention and control of the disease in human and animals. We conducted a study to explore people's awareness about rabies, their attitudes towards dogs and practices associated with treating dog bites in Satkhira Sadar, a south-western sub-district of Bangladesh. Of the total 3200 households (HHs) surveyed, the majority of the respondents have heard about rabies (73%) and there was a high level of awareness that dog bite is the main cause of rabies (86%), and that rabies can be prevented by vaccination (85%). However, 59% of the dog bite victims first seek treatment from traditional healers instead of visiting the hospitals, 29% received the rabies vaccine, 2% practiced proper wound washing with soap and water, while 4.8% have not taken any measures. None of the victims have received rabies immunoglobulin (RIG). Of the respondents, 5.2% reported a history of dog bite in at least one family member, and 11.8% reported a history of dog bite in domestic animals during the previous year. The HHs having a higher number of family members (OR: 1.13, 95% CI: 1.07-1.2), having a pet dog (OR: 2.1, 95% CI: 1.4-3.2) and caring or feeding a community dog (OR: 2.1, 95% CI: 1.4-2.9) showed an increased risk of getting a dog bite. Among the bite victims, 3.6% (n = 6) humans and 15.8% (n = 60) animals died. As a measure for dog population management (DPM), 56% preferred sterilization while the rest preferred killing of dogs. The current treatment seeking behaviours of the respondents should be improved through additional education and awareness programme and better availability for the provision of post-exposure prophylaxis in Bangladesh. We recommend scaling up national mass dog vaccination and DPM to reduce the burden of rabies cases and dog bites in Bangladesh.