Plague: Past, Present, and Future

Neglected Diseases R ecent experience with SARS (severe acute respiratory syndrome) [1] and avian flu shows that the public and political response to threats from new anthropozoonoses can be near-hysteria. This can readily make us forget more classical animal-borne diseases, such as plague (Box 1). Three recent international meetings on plague (Box 2) concluded that: (1) it should be re-emphasised that the plague bacillus (Yersinia pestis) still causes several thousand human cases per year [2,3] (Figure 1); (2) locally perceived risks far outstrip the objective risk based purely on the number of cases [2]; (3) climate change might increase the risk of plague outbreaks where plague is currently endemic and new plague areas might arise [2,4]; (4) remarkably little is known about the dynamics of plague in its natural reservoirs and hence about changing risks for humans [5]; and, therefore, (5) plague should be taken much more seriously by the international community than appears to be the case. The plague bacillus causes a rapidly progressing, serious illness that in its bubonic form is likely to be fatal (40%–70% mortality). Without prompt antibiotic treatment, pneumonic and septicaemic plague are virtually always fatal. For these reasons Y. pestis is considered one of the most pathogenic bacteria for humans. Yersinia pestis is transmitted by fleas, while the other two species of Yersinia known to be pathogenic for humans (Y. enterocolitica and Y. pseudotuberculosis) are transmitted by the faecal–oral route and cause intestinal symptoms of moderate intensity. Yersinia pestis is believed to be a clone of Y. pseudotuberculosis that emerged within the last 1,500 to 20,000 years [6,7]. This divergence was characterised by the acquisition of a few genetic elements; more particularly, two plasmids that play a key role in flea-borne transmission [8,9]. The exceptional pathogenicity of Y. pestis compared to the enteropathogenic species may be explained by its new mode of transmission. Indeed, the only means for this bacterium to be transferred to new hosts is through septicaemia, which allows the bacteria present in the bloodstream to be efficiently taken up by the flea during its blood meal [10]. Soon after Yersin's identification of the plague bacillus [11], it became clear that urban outbreaks were linked to transmission among commensal rats and their fleas. In this classic urban-plague scenario, infected rats (transported, for example, by ships) arrive in a new city and transmit the infection to local house rats and their fleas, which …