Integrating causal inference and machine learning to quantify climate-malaria relationships: Evidence of temperature and rainfall thresholds from Colombian municipalities

Rainfall and temperature are key climate determinants of malaria incidence; yet their causal exposure-response curves on malaria incidence across the entire Colombian territory remain unquantified. We estimated the effects of rainfall and temperature on malaria incidence at the municipal scale from 2007 to 2023. We conducted an ecological observational study in 969 Colombian municipalities located below 1,600 meters. The monthly Standardized Incidence Ratio (SIR) of malaria was calculated for each municipality. Directed acyclic graphs guided the identification of the appropriate adjustments needed to emulate the corresponding experimental design and avoid inducing bias, and the effect was estimated using a modified approach of the Targeted Maximum Likelihood Estimation (TMLE). Exposure-response curves were estimated for two outcomes: the current month and the moving average for the current and previous month. A total of 1,075,112 cases of malaria were reported. The results suggest a non-linear relationship between rainfall and temperature concerning the SIR of malaria, indicating an optimal temperature of 25 °C and approximately 37 mm of rainfall for the highest incidence. The negative control test revealed the presence of residual confounding bias (p < 0.05) in all estimates. Meanwhile, the estimations of the E-value indicated low to moderate tolerance (E-value = 1.14 - 1.48) to an unmeasured confounder. These findings support the integration of rainfall and temperature thresholds into early-warning systems for targeted malaria control.