Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum

Malaria Journal

Research

Anand P Patil¹  Simon I Hay¹  Meera Venkatesan²  Cally Roper³  Inbarani Naidoo⁴  Carol Hopkins Sibley⁵  Philippe J Guerin⁶  Jennifer A Flegg⁶ 

[1] Department of Zoology, Spatial Ecology and Epidemiology Group, University of Oxford, Oxford, UK;Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, MD, USA;WorldWide Antimalarial Resistance Network Molecular Module, University of Maryland School of Medicine, Baltimore, MD, USA;London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Malaria Research Unit, Medical Research Council, Durban, South Africa;WorldWide Antimalarial Resistance Network (WWARN) and Department of Genome Sciences, University of Washington, Seattle, USA;WorldWide Antimalarial Resistance Network (WWARN), University of Oxford, Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;

关键词: Malaria;    Artemisinin Combination Therapy;    Spatiotemporal Model;    Malaria Atlas Project;    Mutant Haplotype;   

DOI  :  10.1186/1475-2875-12-249

 received in 2013-04-18, accepted in 2013-07-02,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPlasmodium falciparum has repeatedly evolved resistance to first-line anti-malarial drugs, thwarting efforts to control and eliminate the disease and in some period of time this contributed largely to an increase in mortality. Here a mathematical model was developed to map the spatiotemporal trends in the distribution of mutations in the P. falciparum dihydropteroate synthetase (dhps) gene that confer resistance to the anti-malarial sulphadoxine, and are a useful marker for the combination of alleles in dhfr and dhps that is highly correlated with resistance to sulphadoxine-pyrimethamine (SP). The aim of this study was to present a proof of concept for spatiotemporal modelling of trends in anti-malarial drug resistance that can be applied to monitor trends in resistance to components of artemisinin combination therapy (ACT) or other anti-malarials, as they emerge or spread.MethodsPrevalence measurements of single nucleotide polymorphisms in three codon positions of the dihydropteroate synthetase (dhps) gene from published studies of dhps mutations across Africa were used. A model-based geostatistics approach was adopted to create predictive surfaces of the dhps 540E mutation over the spatial domain of sub-Saharan Africa from 1990-2010. The statistical model was implemented within a Bayesian framework and hence quantified the associated uncertainty of the prediction of the prevalence of the dhps 540E mutation in sub-Saharan Africa.ConclusionsThe maps presented visualize the changing prevalence of the dhps 540E mutation in sub-Saharan Africa. These allow prediction of space-time trends in the parasite resistance to SP, and provide probability distributions of resistance prevalence in places where no data are available as well as insight on the spread of resistance in a way that the data alone do not allow. The results of this work will be extended to design optimal sampling strategies for the future molecular surveillance of resistance, providing a proof of concept for similar techniques to design optimal strategies to monitor resistance to ACT.

【 授权许可】

CC BY   
© Flegg et al.; licensee BioMed Central Ltd. 2013