Background
Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues.

Methodology/principal findings
We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty.

Conclusions/significance
The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance.

Author summary
Metrics such as the per susceptible rate of infection acquisition (Force-of-Infection) are crucial to understand the current epidemiological situation and the impact of control interventions for long-lasting diseases in which the infection event might have occurred many years previously, such as Chagas disease. FoI values are estimated from serological age profiles, often obtained in a few locations. However, when using predictive models to estimate the FoI over time and space (including areas where serosurveys had not been conducted), methods able to handle and propagate uncertainty must be implemented; otherwise, overconfident predictions may be obtained. Although Machine Learning (ML) methods are powerful tools, they may not be able to entirely handle this challenge. Therefore, the use of ML must be considered in relation to the aims of the analyses. ML will be more relevant to characterise the central trends of the estimates while Linear Models will help identify areas where further serosurveys should be conducted to improve the reliability of the predictions. Our approaches can be used to generate FoI predictions in other Chagas disease-endemic countries as well as in other diseases for which serological surveillance data are collected.