Today at least 2.6 billion people live in areas of risk for Plasmodium vivax transmission;106 - 313 million cases of vivax malaria annually. While Duffy blood group negativity (Duffy (-)) has been considered to confer resistance to vivax malaria, our recent findings show that P. vivax has gained the capacity to infect erythrocytes and cause disease in Duffy (-) people in Madagascar. Our surveys of school-aged children revealed P. vivax PCR-positivity in 8.8% of asymptomatic Duffy (-) children. We also observed mono-infection P. vivax clinical disease in 4.9% of Duffy (-) people who reported for treatment during in vivo drug efficacy surveys;blood smear diagnosis confirmed P. vivax. Interestingly, preliminary population studies using 6 unlinked microsatellite markers suggested that Duffy (-) infections were caused by multiple P. vivax strains. While our results indicate that P. vivax invasion in Madagascar can occur independent of the erythrocyte's Duffy blood group antigen, we do not know if invasion is dependent or independent of the parasite's 'so-called'Duffy binding protein (PvDBP), the parasite ligand considered essential for invasion of human red blood cells. By DNA sequencing the PvDBP locus we have identified one allele to be over-represented in Duffy (-) infections. Additionally, recent whole genome sequencing has revealed that Malagasy P. vivax strains (and no P. vivax strains outside Madagascar) carry a PvDBP duplication. Overall, our findings suggest that P. vivax in Madagascar is evolving new erythrocyte infection mechanisms. To begin understanding how P. vivax has gained capacity to infect Duffy(-) erythrocytes we propose to study population genetic features of the parasite population while performing in-depth cell and molecular biological analysis of P. vivax strains of Madagascar. Resulting data from these studies will allow us to address the following Specific Aims.
Aim 1 - Determine associations between P. vivax strains and susceptibility of Duffy (-) people to P. vivax blood-stage infection and clinical malaria.
Aim 2 - Assess interactions between P. vivax erythrocyte binding ligands and human erythrocytes that influence merozoite attachment and human red cell invasion.
Aim 3 - Test alternative invasion pathways of Malagasy P. vivax strains in vitro for Duffy (-) and Duffy (+) erythrocytes. Our studies will determine differential susceptibility of Duffy (+) and Duffy (-) people to P. vivax disease. Planne in vitro studies will provide insight regarding new P. vivax erythrocyte invasion mechanisms, with special emphasis on Duffy-independent invasion. Finally, we will determine whether molecular variations involved in P. vivax binding to, and invasion of Duffy (+) and Duffy (-) erythrocytes indicates capacity of Madagascar P. vivax strains to spread into other populations.
Today 2.6 billion people live in areas of risk for Plasmodium vivax (Pv) transmission;106 - 313 million cases of vivax malaria annually. Duffy blood group negativity has been considered to confer resistance to vivax malaria, however, our recent findings indicate that Pv has gained the capacity to infect erythrocytes and cause disease in Duffy-negative people in Madagascar. Epidemiology coupled with cell and molecular biology will investigate Pv strains infecting Duffy-negative vs. Duffy-positive people to identify parasite molecules involved in the Pv Duffy-independent invasion pathway.
|Kang, Su Yun; Battle, Katherine E; Gibson, Harry S et al. (2018) Spatio-temporal mapping of Madagascar's Malaria Indicator Survey results to assess Plasmodium falciparum endemicity trends between 2011 and 2016. BMC Med 16:71|
|Mehlotra, Rajeev K; Blankenship, D'Arbra; Howes, Rosalind E et al. (2017) Long-term in vitro culture of Plasmodium vivax isolates from Madagascar maintained in Saimiri boliviensis blood. Malar J 16:442|
|Howes, Rosalind E; Chan, Ernest R; Rakotomanga, Tovonahary Angelo et al. (2017) Prevalence and genetic variants of G6PD deficiency among two Malagasy populations living in Plasmodium vivax-endemic areas. Malar J 16:139|
|Howes, Rosalind E; Mioramalala, Sedera Aurélien; Ramiranirina, Brune et al. (2016) Contemporary epidemiological overview of malaria in Madagascar: operational utility of reported routine case data for malaria control planning. Malar J 15:502|
|Friedrich, Lindsey R; Popovici, Jean; Kim, Saorin et al. (2016) Complexity of Infection and Genetic Diversity in Cambodian Plasmodium vivax. PLoS Negl Trop Dis 10:e0004526|
|Howes, Rosalind E; Reiner Jr, Robert C; Battle, Katherine E et al. (2015) Plasmodium vivax Transmission in Africa. PLoS Negl Trop Dis 9:e0004222|
|Baniecki, Mary Lynn; Faust, Aubrey L; Schaffner, Stephen F et al. (2015) Development of a single nucleotide polymorphism barcode to genotype Plasmodium vivax infections. PLoS Negl Trop Dis 9:e0003539|
|Zimmerman, Peter A; Howes, Rosalind E (2015) Malaria diagnosis for malaria elimination. Curr Opin Infect Dis 28:446-54|
|Zimmerman, Peter A (2015) Nucleic Acid surveillance and malaria elimination. Clin Chem 61:789-91|
|Chan, Ernest R; Barnwell, John W; Zimmerman, Peter A et al. (2015) Comparative analysis of field-isolate and monkey-adapted Plasmodium vivax genomes. PLoS Negl Trop Dis 9:e0003566|
Showing the most recent 10 out of 12 publications