It is estimated that HIV-1 entered the human population in Africa in the early 1900s; however symptomatic infections were not reported until the 1980s. The HIV-1 epidemic is therefore far too young to be the source of positive selection that drove the frequency of CCR5 Δ32 from zero to 10% in 2000 years. Stephens, et al. (1998), suggest that bubonic plague ("Yersinia pestis") had exerted positive selective pressure on CCR5 Δ32. This hypothesis was based on the timing and severity of the Black Death pandemic, which killed 30% of the European population of all ages between 1346 and 1352. After the Black Death, there were less severe, intermittent epidemics. Individual cities experienced high mortality, but overall mortality in Europe was only a few percent. In 1655-1656 a second pandemic called the "Great Plague" killed 15-20% of Europe's population. Importantly, the plague epidemics were intermittent. Bubonic plague is a zoonotic disease, primarily infecting rodents, spread by fleas, and only occasionally infecting humans. Human-to-human infection of bubonic plague does not occur, though it can occur in pneumonic plague, which infects the lungs. Only when the density of rodents is low are infected fleas forced to feed on alternative hosts such as humans, and under these circumstances a human epidemic may occur. Based on population genetic models, Galvani and Slatkin (2003) argue that the intermittent nature of plague epidemics did not generate a sufficiently strong selective force to drive the allele frequency of CCR5 Δ32 to 10% in Europe.