Yersinia pestis: the Natural History of Plague

Abstract

The Gram-negative bacterium Yersinia pestis is responsible for deadly plague, a zoonotic disease established in stable foci in the Americas, Africa, and Eurasia. Its persistence in the environment relies on the subtle balance between Y. pestis-contaminated soils, burrowing and nonburrowing mammals exhibiting variable degrees of plague susceptibility, and their associated fleas. Transmission from one host to another relies mainly on infected flea bites, inducing typical painful, enlarged lymph nodes referred to as buboes, followed by septicemic dissemination of the pathogen. In contrast, droplet inhalation after close contact with infected mammals induces primary pneumonic plague. Finally, the rarely reported consumption of contaminated raw meat causes pharyngeal and gastrointestinal plague. Point-of-care diagnosis, early antibiotic treatment, and confinement measures contribute to outbreak control despite residual mortality. Mandatory primary prevention relies on the active surveillance of established plague foci and ectoparasite control. Plague is acknowledged to have infected human populations for at least 5,000 years in Eurasia. Y. pestis genomes recovered from affected archaeological sites have suggested clonal evolution from a common ancestor shared with the closely related enteric pathogen Yersinia pseudotuberculosis and have indicated that ymt gene acquisition during the Bronze Age conferred Y. pestis with ectoparasite transmissibility while maintaining its enteric transmissibility. Three historic pandemics, starting in 541 AD and continuing until today, have been described. At present, the third pandemic has become largely quiescent, with hundreds of human cases being reported mainly in a few impoverished African countries, where zoonotic plague is mostly transmitted to people by rodent-associated flea bites.

Keywords: Yersinia pestis; epidemiology; lice; paleomicrobiology; plague.

FIG 1

World map of plague cases reported to the World Health Organization in the 21st century (39).

FIG 2

All plague cases and plague deaths by year and country reported by the World Health Organization over the last 19 years (39).

FIG 3

Scheme of the natural epidemiology of plague representing all documented natural and animal reservoirs, intermediate reservoirs, sources of infection, and vectors for humans described in the literature. Green represents field isolation and laboratory-confirmed sources. Blue represents potential sources/reservoirs inferred from laboratory experiments.

FIG 4

Different routes of interhuman transmission and human infection from plague sources (as described in Fig. 3). Green represents field observations of confirmed plague sources, such as aerosol transmission, the consumption of raw or poorly cooked meat, transcutaneous contamination by carcass skinning, and nonhuman flea bites. Once humans are infected, effective interhuman transmission can occur through aerosols (in the case of pulmonary plague) and human ectoparasites, such as body and head lice and human fleas (P. irritans).

FIG 5

Example of pediculosis, showing a body louse defecating on skin while feeding. (A) Photograph of a severe pediculosis affecting the back, arms, and neck found on a homeless person in Marseille. (B) Photograph of a Pediculus humanus corporis collected from a homeless person’s skin in Marseille. In this photograph, we see a body louse defecating (body louse feces are indicated by a red arrow) while taking a blood meal (the biting point is indicated by a black arrow). The body louse feces are deposited approximately 3 mm from the biting point. This proximity greatly increases the chance of the penetration of feces inside the broken skin (biting point) during scratching. (Both photos courtesy of Philippe Brouqui, reproduced with permission.)

FIG 6

World map of the first plague pandemic (541 to 750/767). Regions historically affected by plague are represented in green, and regions potentially affected by plague (western part of North Africa) are in dark gray. The biological hypothesis of plague diffusion is represented by green (Eastern European origin) and red (Indian origin) arrows, while the debated historical hypothesis of plague diffusion is represented by a blue arrow (Ethiopian origin). The map was generated in QGIS 3.4. The mapped regions and roads are based on the Digital Atlas of Roman and Medieval Civilizations (DARMC; https://darmc.harvard.edu).

FIG 7

Map of the second pandemic (1346 to 18th century), including the so-called Black Death (1346 to 1353) and pestis secunda (1357 to 1366) episodes. Brown arrows indicate the well-known starting point of the Black Death in 1346 (city of Caffa) and the probable spread of the plague to Europe and Africa via land and maritime routes. Blue arrows indicate the first hypothesis regarding the dynamics of the second pandemic, in which plague was introduced from Eastern Europe to Western Europe before settling in one or several reservoirs and disappearing, followed by reintroduction in Asia giving rise to the third pandemic. The yellow arrow indicates the second hypothesis, indicating that plague was also introduced to Europe from Central Asia by successive waves from the 14th to the 18th centuries. This hypothesis excludes the existence of temporary plague reservoirs in Europe. The plague would have been introduced by successive waves over 4 centuries in Europe, mainly via silk roads and fur roads, by establishing several permanent foci (still existing) along these roads and spreading to Europe along maritime and terrestrial routes. The map was generated in QGIS 3.4. The mapped regions and roads are based on the Digital Atlas of Roman and Medieval Civilizations (DARMC; https://darmc.harvard.edu).

FIG 8

Map of ancient Yersinia pestis (Y. p) genomes.