Person:

Bei, Amy

Background: Malaria treatment efforts are hindered by the rapid emergence and spread of drug resistant parasites. Simple assays to monitor parasite drug response in direct patient samples (ex vivo) can detect drug resistance before it becomes clinically apparent, and can inform changes in treatment policy to prevent the spread of resistance. Methods: Parasite drug responses to amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately 400 Plasmodium falciparum malaria infections in Thiès, Senegal between 2008 and 2011 using a DAPI-based ex vivo drug resistance assay. Drug resistance-associated mutations were also genotyped in pfcrt and pfmdr1. Results: Parasite drug responses changed between 2008 and 2011, as parasites became less sensitive to amodiaquine, artemisinin and chloroquine over time. The prevalence of known resistance-associated mutations also changed over time. Decreased amodiaquine sensitivity was associated with sustained, highly prevalent mutations in pfcrt, and one mutation in pfmdr1 – Y184F – was associated with decreased parasite sensitivity to artemisinin. Conclusions: Directly measuring ex vivo parasite drug response and resistance mutation genotyping over time are useful tools for monitoring parasite drug responses in field samples. Furthermore, these data suggest that the use of amodiaquine and artemisinin derivatives in combination therapies is selecting for increased drug tolerance within this population.

A challenge to conducting high-impact and reproducible studies of the mechanisms of P. falciparum drug resistance, invasion, virulence, and immunity is the lack of robust and sustainable in vitro culture in the field. While the technology exists and is routinely utilized in developed countries, various factors–from cost, to supply, to quality–make it hard to implement in malaria endemic countries. Here, we design and rigorously evaluate an adjustable gas-mixing device for the in vitro culture of P. falciparum parasites in the field to circumvent this challenge. The device accurately replicates the gas concentrations needed to culture laboratory isolates, short-term adapted field isolates, cryopreserved previously non-adapted isolates, as well as to adapt ex vivo isolates to in vitro culture in the field. We also show an advantage over existing alternatives both in cost and in supply. Furthermore, the adjustable nature of the device makes it an ideal tool for many applications in which varied gas concentrations could be critical to culture success. This adjustable gas-mixing device will dramatically improve the feasibility of in vitro culture of Plasmodium falciparum parasites in malaria endemic countries given its numerous advantages.

Background: As public health interventions drive parasite populations to elimination, genetic epidemiology models that incorporate population genomics can be powerful tools for evaluating the effectiveness of continued intervention. However, current genetic epidemiology models may not accurately simulate the population genetic profile of parasite populations, particularly with regard to polygenomic (multi-strain) infections. Current epidemiology models simulate polygenomic infections via superinfection (multiple mosquito bites), despite growing evidence that cotransmission (a single mosquito bite) may contribute to polygenomic infections. Methods: Here, we quantified the relatedness of strains within 31 polygenomic infections collected from patients in Thiès, Senegal using a hidden Markov model to measure the proportion of the genome that is inferred to be identical by descent. Results: We found that polygenomic infections can be composed of highly related parasites and that superinfection models drastically underestimate the relatedness of strains within polygenomic infections. Conclusions: Our findings suggest that cotransmission is a major contributor to polygenomic infections in Thiès, Senegal. The incorporation of cotransmission into existing genetic epidemiology models may enhance our ability to characterize and predict changes in population structure associated with reduced transmission intensities and the emergence of important phenotypes like drug resistance that threaten to undermine malaria elimination activities. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0398-0) contains supplementary material, which is available to authorized users.

Background: The World Health Organization (WHO) recommends the use of insecticide-treated nets (ITNs) and intermittent preventive treatment in pregnancy (IPTp) as a cost-effective intervention for the prevention of malaria during pregnancy in endemic areas. This study was conducted to investigate: (1) the extent of use of both IPTp and ITNs, and (2) conduct multinomial regression to identify factors affecting the optimal usage of IPTp and ITNs among women with a recent pregnancy in Senegal. Methods: Data was drawn from the 2013–2014 Demographic and Health Survey. A total of 4616 women aged 15–49 years old, who had a recent pregnancy were analyzed. Multinomial logistic regression model was used to assess factors associated with optimal uptake of malaria preventive strategies (both IPTp and ITN use). Results: Amongst women who had a recent pregnancy, less than half of them used ITNs (46.84%) however, 80.35% reported taking IPTp during their last pregnancy. Overall, 37.51% reported using the optimal malaria preventive strategies. Women aged 35–49 years and living in the richer or middle wealth quintile were more likely to use optimal prevention methods. Pregnant women living in Diourbel, Saint-Louis, Thies, Louga, Fatick and Matam were more likely to use both IPTp-SP and ITNs compared to those living in Dakar. Additionally, women who initiated antenatal care in at least at 6 weeks of pregnancy or who attended four antenatal visits or more were more likely to use optimal malaria preventive methods during pregnancy. Conclusions: This study has shown important factors that influence the uptake of malaria prevention methods during pregnancy in Senegal. These findings highlight the need for targeted preventive strategies when designing and implementing policies aimed at improving the uptake of these measures during pregnancy in Senegal.