Why malaria persists despite decline: disentangling environmental, socioeconomic, and demographic drivers in the Brazilian Amazon

Despite significant reductions in malaria cases across Brazil, residual transmission persists in the Legal Amazon, threatening the national goal of elimination by 2035. The Amazonian socio-ecological landscape creates a complex environment where environmental degradation and socioeconomic vulnerabilities intersect. However, the independent and combined effects of these drivers remain poorly quantified at a regional scale. We conducted a retrospective, longitudinal ecological study analyzing a comprehensive panel dataset from 2021 to 2025 across all 773 municipalities in the Brazilian Legal Amazon. We evaluated the independent effects of prior-year deforestation, extreme poverty, population density, fire activity, macroclimatic variables, and primate reservoir abundance on malaria incidence. Deforestation emerged as the dominant predictor of malaria intensity. A one-standard-deviation increase in lagged deforestation area was associated with a 48.3% increase in expected malaria cases. Socioeconomic deprivation also significantly sustained transmission, with extreme poverty increasing cases by 18.8%. Conversely, population density exhibited a strong protective effect, reducing incidence by 72.2%, reflecting the phenomenon of urban protection. While an overall temporal decline of 17.4% annually was observed, profound spatial heterogeneity persisted, with the state of Amazonas maintaining consistently high transmission without a discernible downward trend. Macroclimatic factors and primate abundance did not show statistically significant independent effects at the annual municipal scale. The persistence of malaria in the Brazilian Amazon is not merely a biomedical issue but a profound sustainable development challenge driven by the synergistic effects of land-use change and socioeconomic inequality. Deforestation and extreme poverty create a resilient reservoir of transmission risk that undermines conventional control efforts. Achieving the 2035 elimination goal demands a paradigm shift toward a One Health approach, integrating rigorous environmental protection, targeted social development, and spatially stratified public health interventions. Ultimately, the health of the Amazonian population is inextricably linked to the health of the forest itself.