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Modeling malaria genomics reveals transmission decline and rebound in Senegal.

ABSTRACT: To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006-2010 with a significant rebound in 2012-2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.

SUBMITTER: Daniels RF

PROVIDER: S-EPMC4460456 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Modeling malaria genomics reveals transmission decline and rebound in Senegal.

Daniels Rachel F RF Schaffner Stephen F SF Wenger Edward A EA Proctor Joshua L JL Chang Hsiao-Han HH Wong Wesley W Baro Nicholas N Ndiaye Daouda D Fall Fatou Ba FB Ndiop Medoune M Ba Mady M Milner Danny A DA Taylor Terrie E TE Neafsey Daniel E DE Volkman Sarah K SK Eckhoff Philip A PA Hartl Daniel L DL Wirth Dyann F DF

Proceedings of the National Academy of Sciences of the United States of America 20150504 22

To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 comp ...[more]

PMID: 25941365

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Project description:BackgroundThanks to the scale up of malaria control interventions, the malaria burden in Senegal has decreased substantially to the point that the National Malaria Control Programme plans to achieve malaria elimination by 2030. To guide such efforts, measuring and monitoring parasite population evolution and anti-malarial drugs resistance is extremely important. Information on the prevalence of parasite mutations related to drug resistance can provide a first signal of emergence, introduction and selection that can help with refining drug interventions. The aim of this study was to analyse the prevalence of anti-malarial drug resistance-associated markers before and after the implementation of artemisinin-based combination therapy (ACT) from 2005 to 2014 in Dielmo, a model site for malaria intervention studies in Senegal.MethodsSamples from both malaria patients and Plasmodium falciparum asymptomatic carriers were analysed with high resolution melting (HRM) technique to genotype P. falciparum chloroquine resistance transporter (Pfcrt) gene haplotypes and multidrug-resistant protein 1 (Pfmdr1) gene at codons N86 and Y184.ResultsAmong the 539 samples analysed, 474, 486, and 511 were successfully genotyped for Pfmdr1 N86, Y184, and Pfcrt, respectively. The prevalence of drug resistance markers was high, particularly during the malaria upsurges. Following the scale-up in bed net distribution, only the mutant (86F-like) variant of Pfmdr1 86 was present while during the malaria upsurges the predominance of two types 86Y-86N (43%) and 86F-like (56%) were observed. Most infections (87%) carried the wild type Y-allele at Pfmdr1 184 during the period of nets scale-up while during the malaria upsurges only 16% of infections had wild type and 79% of infections had mixed (mutant/wild) type. The frequency of the mixed genotypes SVMNT-like_CVMNK and SVMNT-like_CVIET within Pfcrt gene was particularly low during bednet scale up. Their frequency increased significantly (P < 0.001) during the malaria upsurges.ConclusionThis data demonstrated the effect of multiple interventions on the dynamics of drug resistance-associated mutations in the main malaria parasite P. falciparum in an endemic village in Senegal. Monitoring drug resistance markers should be conducted periodically to detect threats of emergence or resurgence that could compromise the efficacy of anti-malarial drugs.

Project description:BackgroundThe United Nations forecasts that by 2050, more than 60% of the African population will live in cities. Thus, urban malaria is considered an important emerging health problem in that continent. Remote sensing (RS) and geographic information systems (GIS) are useful tools for addressing the challenge of assessing, understanding and spatially focusing malaria control activities. The objectives of the present study were to use high spatial resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to identify some urban environmental factors in Dakar associated with Anopheles arabiensis densities, to assess the persistence of these associations and to describe spatial changes in at-risk environments using a decadal time scale.MethodsTwo SPOT images from the 1996 and 2007 rainy seasons in Dakar were processed to extract environmental factors, using supervised classification of land use and land cover, and a calculation of NDVI (Normalized Difference Vegetation Index) and distance to vegetation. Linear regressions were fitted to identify the ecological factors associated with An. arabiensis aggressiveness measured in 1994-97 in the South and centre districts of Dakar. Risk maps for populated areas were computed and compared for 1996 and 2007 using the results of the statistical models.ResultsAlmost 60% of the variability in anopheline aggressiveness measured in 1994-97 was explained with only one variable: the built-up area in a 300-m radius buffer around the catching points. This association remained stable between 1996 and 2007. Risk maps were drawn by inverting the statistical association. The total increase of the built-up areas in Dakar was about 30% between 1996 and 2007. In proportion to the total population of the city, the population at high risk for malaria fell from 32% to 20%, whereas the low-risk population rose from 29 to 41%.ConclusionsEnvironmental data retrieved from high spatial resolution SPOT satellite images were associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed.

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Modeling malaria genomics reveals transmission decline and rebound in Senegal.

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Modeling malaria genomics reveals transmission decline and rebound in Senegal.

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