Plasmodium vivax malaria in India: microbiological barriers to diagnosis, treatment, and elimination.

SUMMARYPlasmodium vivax remains a major barrier to global malaria elimination due to dormant liver-stage hypnozoites that drive relapse and sustain transmission even in low-endemic settings. India accounts for nearly half of the global P. vivax burden, placing it at the center of elimination efforts. This review synthesizes current evidence on the epidemiology, biology, and control of P. vivax in India. Despite progress, early gametocytogenesis, hypnozoites, low parasitemia, and immune evasion complicate diagnosis and treatment. Recent single-cell and multi-omics studies are elucidating vir gene regulation, epigenetic control of hypnozoite dormancy, and quiescent liver-stage biology. Diagnostic gaps persist because microscopy and rapid diagnostic tests poorly detect asymptomatic infections, and molecular surveillance cannot map relapse without hypnozoite biomarkers. Standard radical cure with chloroquine and 14-day primaquine is limited by poor adherence and restricted glucose-6-phosphate dehydrogenase testing, while single-dose tafenoquine awaits wider implementation. Urban malaria, largely driven by P. vivax and Anopheles stephensi, is increasing as a consequence of rapid urbanization and vector adaptation. National initiatives such as the Integrated Health Information Platform, Tribal Malaria Action Plans, and Urban Malaria Schemes are critical but face constraints in surveillance integration, private sector reporting, and cross-border coordination. We highlight emerging experimental liver models, single-cell technologies, and systems biology frameworks as essential tools for addressing key knowledge gaps in relapse biology. Sustained investment and interdisciplinary collaboration will be required for India to lead P. vivax elimination and translate national progress into global impact.