Hidden burden of malaria in pregnancy in hard-to-reach areas of Odisha, India: challenges to elimination and the case for integrating molecular surveillance.

BACKGROUND: Malaria in pregnancy (MiP) remains a major public health concern due to its detrimental effects on maternal and foetal health, posing a substantial challenge to malaria control and elimination efforts. Asymptomatic/Sub-patent malaria infections, which escape detection under routine surveillance warrant focused investigation in high-burden, hard-to-reach areas of Odisha, India. METHODS: Pregnant women were enrolled as part of repeated cross-sectional community-based DAMaN Assessment surveys conducted in 2019, 2021, and 2024 in malaria-endemic districts of Odisha. Malaria infection was detected using rapid diagnostic tests (RDTs), microscopy, and polymerase chain reaction (PCR), and hemoglobin levels were measured using a HemoCue Hb 201 + analyser. Prevalence estimates were calculated with 95% confidence intervals (CIs). Multivariable logistic regression was used to identify factors associated with malaria infection and sub-patent malaria, and to examine the association between malaria infection and anemia. RESULTS: A total of 861 pregnant women were included. Overall malaria prevalence was 33.0% (95% CI: 29.9-36.3), varying from 51.1% (95% CI: 45.8-56.5) in 2019 to 9.8% (95% CI: 7.0-13.6) in 2021 and 41.1% (95% CI: 33.8-48.8) in 2024. Among malaria-positive women, 79.6% were asymptomatic and 74.3% (95% CI: 68.7-79.2) had sub-patent infections. Residence in a high-transmission season was independently associated with malaria infection (adjusted odds ratio [aOR] 8.23, 95% CI: 4.30-15.78), whereas Indoor residual spraying (IRS) (aOR 0.02, 95% CI: 0.01-0.04) and bed-net use (aOR 0.25, 95% CI: 0.10-0.62) were protective. Among malaria-positive women, increasing maternal age (aOR 1.05, 95% CI: 1.01-1.15) and higher gravida (aOR 1.70, 95% CI: 1.07-1.25) were associated with sub-patent malaria. Overall anemia prevalence was 62.3% (95% CI: 58.9-65.5), but malaria infection was not significantly associated with anemia after adjustment for confounders (aOR 0.98, 95% CI: 0.55-1.74). CONCLUSION: The high burden of asymptomatic/sub-patent malaria, coupled with mixed Plasmodium infections and anemia among pregnant women, represents a significant impediment to malaria elimination in endemic, underserved regions. These findings underscore the need for strengthening pregnancy-focused active surveillance in high burden settings using sensitive molecular tools in sentinel surveillance sites to guide targeted intervention strategies within programmatic frameworks to support India's goal of malaria elimination by 2030.