Community-Based Cohort Study of Hidden Malaria Infections, Diagnostic Gaps, & Mosquito Vector Dynamics in Odisha, India (CSCMi3)

Malaria transmission has declined in many parts of India as a result of expanded control efforts. However, persistent transmission continues in several regions despite high intervention coverage. Increasing evidence suggests that asymptomatic and subpatent Plasmodium infections may form an important hidden reservoir that sustains transmission and complicates malaria elimination. These infections are often missed by routine diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), particularly in low-transmission or pre-elimination settings.

Local mosquito vector dynamics, including species composition, density and behaviour, are also likely to play a critical role in sustaining residual transmission, but remain insufficiently characterised in these settings.

This study is part of the Center for the Study of Complex Malaria in India 3 (CSCMi-3) and aims to characterise the epidemiology and biological determinants of hidden malaria infections in Odisha, India. It will also examine how vector, human and parasite factors interact to sustain transmission. The study is a prospective, community-based cohort conducted in selected rural villages across three endemic districts, representing different malaria transmission settings. Participants will be enrolled through household-based community surveys and followed longitudinally to monitor malaria infection dynamics over time.

The parent cohort study will enrol approximately 3,000 individuals, who will be followed through repeated visits to estimate the prevalence and incidence of asymptomatic malaria infections. The study will also assess the frequency of false-negative results and species misclassification by comparing routine diagnostic methods with molecular detection. In addition, it will evaluate Pfhrp2/Pfhrp3 gene deletions and explore potential shifts in Plasmodium species composition over time. Blood samples collected during study visits will be used for parasitological testing and laboratory analyses to better understand the persistence of malaria transmission.

Concurrent entomological surveys will be conducted in and around participant households to characterise mosquito vector species, density and seasonal patterns, and to examine their relationship with household-level infection patterns and ongoing transmission.

A nested biomarker sub-cohort will include a subset of participants who will undergo more frequent sampling to investigate circulating host- and parasite-derived biomarkers associated with malaria infection and transmission. These data will support the identification of biological indicators that may improve the detection of hidden infections and inform malaria surveillance strategies in elimination settings.

In parallel with the active community-based cohort, routinely collected malaria surveillance data from the Government of Odisha will be obtained for the study villages throughout the study period. These data will be used to characterise temporal trends in routine malaria surveillance, compare passive and active malaria case detection, and generate evidence to inform malaria surveillance and elimination strategies.

Together, the study will generate longitudinal epidemiological, diagnostic, biomarker and entomological data to improve understanding of residual malaria transmission and support evidence-based malaria surveillance, control and elimination strategies in India.