Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered.