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Background  Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and became the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF.    Model  The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola’s YF outbreak. This includes the outbreak’s attack rate, the reproduction number (R  0), the role of the mosquito vector, the influence of climatic factors, and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions).    Findings  While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased cases and deaths. The analysis estimated a meanR  0   ≈  2  .  6  -  3  .  4and an attack rate of 0.09-0.15% (proportion of population infected) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds ofR  0are in line with previous studies. Unusually,R  0oscillated in a manner that was “delayed” with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and lowR  0, and vice-versa. The time-series of Luanda’s YF cases suggest the outbreak occurred in two waves, a feature that would have become far more prominent had there been no mass vaccination. The waves could possibly be due to protective reactive behavioral changes of the population affecting the mosquito population. The second wave could well be an outcome of the March-April rainfall patterns in the 2016 El Niño year by creating ideal conditions for the breeding of the mosquito vectors. The modelling framework is a powerful tool for studying future YF epidemic outbreaks, and provides a basis for future vaccination campaign evaluations.

Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination