Duffy Binding Protein Ligand (PvDBP) gene duplication in Indian P. Vivax Malaria isolates: implication for malaria research.

Abstract

Plasmodium vivax malaria poses a major global health challenge, fueled by the parasite's ability to establish chronic infections via dormant liver hypnozoites that enable immune evasion and show transmission resilience. A key virulence determinant of P. vivax blood-stage infection is the ligand-receptor interaction of infected erythrocytes mediated by the Duffy Binding Protein (PvDBP) ligand. Gene duplication events leading to increased PvDBP copy numbers have been documented in parasite populations in Cambodia, Brazil, and Sudan, but whether such changes exist in Indian isolates is not known. India shoulders a disproportionately high P. vivax burden in the world. DNA extracted from malaria-positive samples from a multisite survey was subjected to diagnostic PCR to evaluate PvDBP duplication. We identified PvDBP duplication at 18.6% frequency across various regions in India via diagnostic PCR. Both 'Cambodian-type' and 'Malagasy-type' duplication patterns were detected. PvDBP copy number variations associated with specific Duffy antigen receptor genotypes were correlated in the patient cohort. While PvDBP duplication was widespread, its geographic distribution varied, occurring most prevalently in northeastern regions of India. The presence of Duffy binding protein gene duplication in nearly one-fifth of P. vivax isolates in India may have significant epidemiological and clinical implications. This genetic variation could potentially impact, parasite fitness and invasion efficiency, possibly leading to higher parasitemia levels and immune evasion capabilities, which may affect the efficacy of natural immunity and vaccine development efforts and / or transmission dynamics if the duplication confers any advantage in mosquito stages. To fully understand these implications, we propose longitudinal studies tracking patients with and without PvDBP duplications, comparing clinical outcomes, parasitemia levels, and transmission rates. Additionally, spatial and temporal analyses of duplication frequency across India could reveal patterns of spread and potential selective pressures driving this genetic change.