Towards Malaria Elimination: A Nationwide Case-Control Study to Assess Risk Factors for Severe Malaria-Related Deaths in Brazil.

Objective: The objective of this study is to describe malaria-related deaths and assess their risk factors.

Methods: This is a case-control study using data from Brazil's Ministry of Health (2011-2020) on malaria-related deaths (ICD-10: B50-B54). A probabilistic record linkage was performed to match epidemiological data (Sivep-Malaria and Sinan) with death records from the Mortality Information System (SIM). Cases were defined as individuals who died of malaria, and controls were malaria cases that did not result in death. Logistic regression models were used to identify the factors associated with malaria mortality.

Results: A total of 632 malaria-related deaths were recorded, with 454 (71.8%) occurring in the Amazon region and 178 (28.1%) outside it. Risk factors in the Amazon included age (< 6 months or > 60 years; p ≤ 0.01), delayed treatment (> 48 h; p < 0.001), illiteracy (p = 0.01), and living in indigenous population villages (p < 0.001), while active case detection was protective (p = 0.01). In the Extra-Amazon, risk factors included delayed treatment (p = 0.049), P. falciparum or mixed infections (p < 0.049), foreign-acquired infections (p = 0.01), and higher education level (p = 0.03)-which is a proxy for increased income and travel frequency, which may increase the likelihood of exposure in endemic areas and delayed diagnosis upon return.

Conclusion: This nationwide record-linkage study shows that malaria deaths remain concentrated in socially vulnerable groups: infants, older adults, and especially indigenous populations living in the Amazon. Delayed treatment is also a determinant for deaths, in both endemic and non-endemic regions, while active case detection markedly reduces the odds of death. To reach Brazil's zero-malaria-death target by 2030, it is needed to improve timely diagnosis and treatment, to enhance epidemiological information systems along with active surveillance amplification in remote communities. Finally, integrating national health-information systems allows real-time monitoring, and with coordinated action, eliminating malaria deaths remains achievable.