Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago.

The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.

Diseases Transmitted by Man's Worst Friend: the Rat.

Historically, the rat has been considered a scourge to mankind, for example, rats infected with the plague bacillus that caused the Black Death, which accounted for millions of deaths in Europe during the Middle Ages. At least three pandemics (in the 5th and 6th, 8th through 14th, and 19th through 21st centuries) of plague ravaged civilizations, and the disease undoubtedly plagued humankind prior to recorded history. Also, numerous other diseases are spread to humans by rats; thus, a quote from Hans Zinsser's text Rats, Lice, and History, "Man and rat will always be pitted against each other as implacable enemies," conveys the general revulsion that society holds for the wild rat.

Socio-epidemiological determinants of 2002 plague outbreak in Himachal Pradesh, India: a qualitative study.

BACKGROUND: This qualitative investigation was conducted to determine the socio-epidemiological factors related to the plague outbreak (2002) in Himachal Pradesh (HP), India. METHODS: The data for socio-epidemiological factors related to the plague outbreak (2002) in HP was obtained from residents through 150 in-depth Interviews (IDI) and 30 Focus Group Discussions (FGD) during six visits (from May 2011 to April 2012) by the research team. Natives, health officials and the nomadic population were interviewed. According to their opinion and viewpoints data was collected and their lifestyle and hunting practices were studied in detail. Tape recorders were used during various FGDs and IDIs. The interviews and FGDs were later transcribed and coded. In-depth analysis of the recorded data was done using an inductive thematic analysis approach. RESULTS: The study reports that the outbreak in 2002 in a few villages of Himachal Pradesh was that of plague and it occurred by the contact of an index case with wild animals after hunting and de-skinning. The first wave of plague transmission which took 16 lives of residents was followed by a second wave of transmission in a ward of a tertiary care hospital where one visitor acquired it from relatives of the index case and succumbed. The life-style practices of residents (hunting behavior, long stay in caves and jungles, overcrowding in houses, poor hygiene and sanitation, belief in 'God' and faith healers for cure of diseases) was optimal for the occurrence and rapid spread of such a communicable disease. The man-rodent contact is intensified due to the practice of hunting in such a rodent-ridden environment. The residents harbor a strong belief that plague occurs due to the wrath of gods. Various un-reported outbreaks of plague were also observed by officials, residents and old folk. The persistence of plague in HP is favoured by its hilly terrain, inaccessible areas, inclement weather (snow) in winters, unhygienic lifestyle, hunting practices of residents, and treatment practices through faith healers. CONCLUSIONS: This study suggests that the lifestyle of the natives of HP and other socio-epidemiological factors played a role in the outbreak of plague in that area.

[The Justinian plague (part one)]. / La peste di Giustiniano (prima parte).

In their medical-historical review, the authors assess the evolution of bubonic plague epidemics: after breaking out in the Egyptian port of Pelusium in October 541 AD, the epidemics hit several regions in the Mediterranean basin in a succession of waves. The so-called Justinian plague took its name from the Byzantine emperor of the period, and seriously conditioned the expansionary aims of the Eastern Roman empire towards Italy (which was occupied by Goths), and Northern Africa (where the Vandals had settled), during the first decades of its spread. In the Eastern Empire the plague played a considerable role in reducing the tensions between Persians and Byzantines, especially on the Syrian and Anatolian fronts. It had a major demographic impact, reducing the possibility of recruitment to the Roman legions and leading to a significant drop in tax revenues, which were essential to sustain the state and its military machine. Finally, the plague also took its toll on economic resources (especially agriculture), indirectly leading to a vicious inflationary circle. In the space of over two centuries, plague epidemics paralyzed most trade and commercial exchanges. Furthermore, the Justinian plague, halting the consolidation of the influence of the Eastern Roman empire over some Western regions (including Italy and Northern Africa, which were ruled by Barbarians), supported the development and rise of a number of Roman-Barbarian kingdoms. It may therefore be suggested that the Justinian plague occurred at a very critical historical moment, which represents the real watershed between the Ancient World and the upcoming Middle Ages.

Model-guided fieldwork: practical guidelines for multidisciplinary research on wildlife ecological and epidemiological dynamics.

Infectious disease ecology has recently raised its public profile beyond the scientific community due to the major threats that wildlife infections pose to biological conservation, animal welfare, human health and food security. As we start unravelling the full extent of emerging infectious diseases, there is an urgent need to facilitate multidisciplinary research in this area. Even though research in ecology has always had a strong theoretical component, cultural and technical hurdles often hamper direct collaboration between theoreticians and empiricists. Building upon our collective experience of multidisciplinary research and teaching in this area, we propose practical guidelines to help with effective integration among mathematical modelling, fieldwork and laboratory work. Modelling tools can be used at all steps of a field-based research programme, from the formulation of working hypotheses to field study design and data analysis. We illustrate our model-guided fieldwork framework with two case studies we have been conducting on wildlife infectious diseases: plague transmission in prairie dogs and lyssavirus dynamics in American and African bats. These demonstrate that mechanistic models, if properly integrated in research programmes, can provide a framework for holistic approaches to complex biological systems.

Lack of antimicrobial resistance in Yersinia pestis isolates from 17 countries in the Americas, Africa, and Asia.

Yersinia pestis is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance in Y. pestis was reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392 Y. pestis isolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.

The Eyam plague revisited: did the village isolation change transmission from fleas to pulmonary?

Back in the 17th century the Derbyshire village of Eyam fell victim to the Black Death, which is thought to have arrived from London in some old clothes brought by a travelling tailor. The village population was 350 at the commencement of plague, of which only 83 survived. Led by the church leaders, the village community realized that the whole surrounding region was at risk from the epidemic, and therefore decided to seal themselves off from the other surrounding villages. In the first 275 days of the outbreak, transmission was predominantly from infected fleas to susceptible humans. From then onward, mortality sharply increased, which indicates a changing in transmission pattern. We hypothesize that the confinement facilitated the spread of the infection by increasing the contact rate through direct transmission among humans. This would be more consistent with pulmonary plague, a deadlier form of the disease. In order to test the above hypothesis we designed a mathematical model for plague dynamics, incorporating both the indirect (fleas-rats-humans) and direct (human-to-human) transmissions of the infection. Our results show remarkable agreement between data and the model, lending support to our hypotheses. The Eyam plague episode is celebrated as a remarkable act of collective self-sacrifice. However, to the best of our knowledge, there were no evidence before that the confinement actually increased the burden payed by the commoners. In the light of our results, it can be said that the hypothesis that confinement facilitated the spread of the infection by increasing the contact rate through direct transmission is plausible.

[The history of the flea in art and literature]. / La storia della pulce nell'arte e nella letteratura.

The flea has been, indirectly, one of the protagonists in the history of man. As one of the two vectors of Yersinia pestis, the etiological agents of the Black Death, the flea (Xenopsylla cheopis) has contributed, over the centuries, to the death of millions of people in many countries. Galileo Galilei was the first to observe the flea with a microscope (1624), but the credit of depicting it with a stunning drawing goes to the Britisher Robert Hooke in 1665. A number of zoologists, including Antonie Van Leeuwenhoek and Diacinto Cestoni, well described and illustrated the life cycle of the flea in the XVII century. Some of these reports inspired scholars such as J. Swift and J. Donne for the composition of classic poems. Also, the flea, alone and with its hosts, has inspired a number of artists to create fine paintings; among them: G. M. Crespi, G. B. Piazzetta, G. de la Tour and others. Colorful sonnets on the flea in the Roman dialect were written by G. Belli and Trilussa. The flea also, as a theme, inspired musicians such as G. F. Ghedini and M. Mussorgsky, play writers such as Feydeau and moviemakers such as Charlie Chaplin. The flea is, indissolubly, connected with the history of Black Death. This disease in man is, in fact, caused--as demonstrated by Yersin and Simond--by the triad: bacterium (Yersinia pestis)/rat/flea (Xenopsylla cheopis). Over the centuries, Black Death has had a deep impact on both the visual arts and literature and, as a result, a very large number of paintings and other works of art have been produced to remember these tragic episodes. In the field of literature, Black Death has been skillfully described by writers such as Boccaccio, Manzoni and Camus. Finally, in recent years, following the discovery of the existence of a large market for the control of fleas in small animals, the interest in this minute insect has been resurrected and, parallel to that, the rebirth of the flea iconography, through electromicroscopy, has also taken place.

The history of the plague and the research on the causative agent Yersinia pestis.

The plague is an infectious bacterial disease having a high fatality rate without treatment. It has occurred in three huge pandemics since the 6th century with millions of deaths and numerous smaller epidemics and sporadic cases. Referring to specific clinical symptoms of pulmonary plague the disease became known as the Black Death. This pandemic probably originated in central Asia and began spreading westward along major trade routes. Upon the arrival in the eastern Mediterranean the disease quickly spread especially by sea traffic to Italy, Greece and France and later throughout Europe by land. Until the 18th century many European cities were frequently affected by other great plague epidemics. The worldwide spread of the third pandemic began when the plague reached Hong Kong and Canton in the year 1894. The gram-negative coccobacillus now designated as Yersinia pestis has been discovered as the causative agent of plague in this Hong Kong outbreak. In the following years the role of rats and fleas and their detailed role in the transmission of plague has been discovered and experimentally verified. Today the plague is still endemic in many countries of the world.

[The black rat (Rattus rattus) and the plague in ancient and medieval western Europe]. / Le rat noir (Rattus rattus) et la peste dans l'occident antique et médieval.

The first time plague affected Western Europe was in the early Middle Ages: rom 541 to 767, there were no fewer than 15 outbreaks in southern parts of the continent. Plague then disappeared from Europe for some seven centuries but came back with a vengeance in 1347, this time by way of the Mediterranean, and ravaged the entire continent for five years, resulting in a serious demographic depression. From then on until 1722 (and 1771 in Moscow), the disease remained endemic to Europe, periodically undermining its economy. These epidemics were major determinants of medieval history, but their study has not been completed to this day. It was not until the 1970s that archeo-zoologists finally discovered that the black rat had indeed been present in Europe since Roman times. Further extensive research revealed that the rat population had gradually grown from a fairly restricted one in the early Middle Ages to a significant one in the 11th and 13th centuries. The rodents spread along the major highways explaining the very different geographical impact of the various plague epidemics of the early and late medieval periods. However, the mystery of the exact mechanisms by which plague spread has still not been entirely elucidated, since the Asian rat flea, Xenopsylla cheopis, whose role as vector was demonstrated by P. L. Simond, could not have survived in the temperate European climate. Thus, the question of the European vector is still left hanging: was it a human or a rat flea? Was the rat a propagator or simply an initiator? This article considers these unresolved questions by re-examining P. L. Simond's very precise observations.