Prevalence and temporal changes of mutations linked to antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Palawan, Philippines.

OBJECTIVE: This study provides 2016 data on the prevalence of key single nucleotide polymorphisms (SNPs) associated with antimalarial drug resistance in Palawan, Philippines. Findings were combined with historical data to model temporal changes in the prevalence of these SNPs in Plasmodium isolates. METHODS: Plasmodium isolates were genotyped using drug resistance markers pfmdr1, pfcrt, pfdhfr, pfdhps, kelch-13, pvmdr1, pvdhfr, and pvdhps. Temporal trends in the probability of mutations were estimated as a function of time using a binomial generalised linear model. RESULTS: All samples sequenced for Plasmodium falciparum chloroquine markers pfmdr1 and pfcrt had wild-type alleles. Varying mutation patterns were observed for the sulphadoxine/pyrimethamine markers pfdhps and pfdhfr; complete quintuplet mutations were not found. No SNPs were observed for the artemisinin marker kelch-13. For Plasmodium vivax, differing patterns were detected for pvmdr1, pvdhfr, and pvdhps. CONCLUSIONS: The study findings suggest that the current drugs remain effective and that there is limited importation and establishment of resistant parasites in the area. Clear temporal trends were recognised, with prominent decreases in the proportions of pfcrt and pfmdr mutations detected within the past 15 years, consistent with a change in antimalarial drug policy. Continuous surveillance of antimalarial drug resistance is important to support malaria elimination efforts.

Investigating the Contribution of Peri-domestic Transmission to Risk of Zoonotic Malaria Infection in Humans.

BACKGROUND: In recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated. METHODOLOGY/PRINCIPAL FINDINGS: We integrated entomological surveillance within a comprehensive case-control study occurring within a large hotspot of transmission in Sabah, Malaysia. Mosquitoes were collected at 28 pairs households composed of one where an occupant had a confirmed P. knowlesi infection within the preceding 3 weeks ("case") and an associated "control" where no infection was reported. Human landing catches were conducted to measure the number and diversity of mosquitoes host seeking inside houses and in the surrounding peri-domestic (outdoors but around the household) areas. The predominant malaria vector species was Anopheles balabacensis, most of which were caught outdoors in the early evening (6pm - 9pm). It was significantly more abundant in the peri-domestic area than inside houses (5.5-fold), and also higher at case than control households (0.28±0.194 vs 0.17±0.127, p<0.001). Ten out of 641 An. balabacensis tested were positive for simian malaria parasites, but none for P. knowlesi. CONCLUSIONS/SIGNIFICANCE: This study shows there is a possibility that humans can be exposed to P. knowlesi infection around their homes. The vector is highly exophagic and few were caught indoors indicating interventions using bednets inside households may have relatively little impact.