Assessing the origins of the European Plagues following the Black Death: A synthesis of genomic, historical, and ecological information.

The second plague pandemic started in Europe with the Black Death in 1346 and lasted until the 19th century. Based on ancient DNA studies, there is a scientific disagreement over whether the bacterium, Yersinia pestis, came into Europe once (Hypothesis 1) or repeatedly over the following four centuries (Hypothesis 2). Here, we synthesize the most updated phylogeny together with historical, archeological, evolutionary, and ecological information. On the basis of this holistic view, we conclude that Hypothesis 2 is the most plausible. We also suggest that Y. pestis lineages might have developed attenuated virulence during transmission, which can explain the convergent evolutionary signals, including pla decay, that appeared at the end of the pandemics.

Genetic source tracking of human plague cases in Inner Mongolia-Beijing, 2019.

On 12 November 2019, one couple from the Sonid Left Qi (County) in the Inner Mongolia Autonomous Region was diagnosed with pneumonic plague in Beijing. The wife acquired the infection from her husband. Thereafter, two bubonic plague cases were identified in Inner Mongolia on November 16th and 24th. In this study, genome-wide single nucleotide polymorphism (SNP) analysis was used to identify the phylogenetic relationship of Yersinia pestis strains isolated in Inner Mongolia. Strains isolated from reservoirs in 2018 and 2019 in Inner Mongolia, together with the strain isolated from Patient C, were further clustered into 2.MED3m, and two novel lineages (2.MED3q, 2.MED3r) in the 2.MED3 population. According to the analysis of PCR-based molecular subtyping methods, such as the MLVA 14 scheme and seven SNP allele sequencing, Patients A/B and D were classified as 2.MED3m. In addition, strains from rodents living near the patients' residences were clustered into the same lineage as patients. Such observations indicated that human plague cases originated from local reservoirs. Corresponding phylogenetic analysis also indicated that rodent plague strains in different areas in Inner Mongolia belong to different epizootics rather than being caused by spreading from the same epizootic in Meriones unguiculatus in 2019.

Antibody Opsonization Enhances Early Interactions between Yersinia pestis and Neutrophils in the Skin and Draining Lymph Node in a Mouse Model of Bubonic Plague.

Bubonic plague results when Yersinia pestis is deposited in the skin via the bite of an infected flea. Bacteria then traffic to the draining lymph node (dLN) where they replicate to large numbers. Without treatment, this infection can result in highly fatal septicemia. Several plague vaccine candidates are currently at various stages of development, but no licensed vaccine is available in the United States. Though polyclonal and monoclonal antibodies (Ab) can provide complete protection against bubonic plague in animal models, the mechanisms responsible for this antibody-mediated immunity (AMI) to Y. pestis remain poorly understood. Here, we examine the effects of Ab opsonization on Y. pestis interactions with phagocytes in vitro and in vivo Opsonization of Y. pestis with polyclonal antiserum modestly increased phagocytosis/killing by an oxidative burst of murine neutrophils in vitro Intravital microscopy (IVM) showed increased association of Ab-opsonized Y. pestis with neutrophils in the dermis in a mouse model of bubonic plague. IVM of popliteal LNs after intradermal (i.d.) injection of bacteria in the footpad revealed increased Y. pestis-neutrophil interactions and increased neutrophil crawling and extravasation in response to Ab-opsonized bacteria. Thus, despite only having a modest effect in in vitro assays, opsonizing Ab had a dramatic effect in vivo on Y. pestis-neutrophil interactions in the dermis and dLN very early after infection. These data shed new light on the importance of neutrophils in AMI to Y. pestis and may provide a new correlate of protection for evaluation of plague vaccine candidates.

Two cases of imported pneumonic plague in Beijing, China.

INTRODUCTION: Plague is an acute, often fulminating infectious disease caused by Yersinia Pestis transmitted by rodents. It is rarely encountered in clinics, although natural plague foci are widely distributed around the world. PATIENT CONCERNS: A couple who are cattle and sheep herdsmen from the Inner Mongolia Autonomous Region presented with cough, expectoration and fever. The husband developed sudden onset of fever and bloody sputum after working the soil on his farm. The wife also developed fever after nursing his husband. Both patients were preliminarily diagnosed with severe pneumonia, but antimicrobial treatments in the local hospital were unsuccessful. Their conditions deteriorated and they were transferred to our center. DIAGNOSIS: Preliminary etiological examinations were unremarkable, while blood and sputum specimens were found to be positive by RT-PCR and colloidal gold-immunochromatography assay targeting the F1 antigen and by reverse indirect hemagglutination assay. Pneumonic plague was confirmed. INTERVENTIONS: Both patients were transferred to special infectious disease hospital for further treatment. OUTCOMES: The condition of the female patient deteriorated. The male recovered after treatment, while the female patient finally died. CONCLUSION: There are 3 main forms of plague: bubonic, pneumonic and septicemic. Humans can be infected by the bites of bacterium-bearing fleas or direct contact of wild animals that died from plague. Human plague can be transmitted by close contact through coughing droplet. Neglected diagnosis of plague could cause severe consequences. Strict surveillance and protection measures should be taken and the public should be alerted about potential risks when epizootic plague is detected.

A Dual Role for the Plasminogen Activator Protease During the Preinflammatory Phase of Primary Pneumonic Plague.

Early after inhalation, Yersinia pestis replicates to high numbers in the airways in the absence of disease symptoms or notable inflammatory responses to cause primary pneumonic plague. The plasminogen activator protease (Pla) is a critical Y. pestis virulence factor that is important for early bacterial growth in the lung via an unknown mechanism. In this article, we define a dual role for Pla in the initial stages of pulmonary infection. We show that Pla functions as an adhesin independent of its proteolytic function to suppress early neutrophil influx into the lungs, and that Pla enzymatic activity contributes to bacterial resistance to neutrophil-mediated bacterial killing. Our results suggest that the fate of Y. pestis infection of the lung is decided extremely early during infection and that Pla plays a dual role to tilt the balance in favor of the pathogen.

Modeling Pneumonic Plague in Human Precision-Cut Lung Slices Highlights a Role for the Plasminogen Activator Protease in Facilitating Type 3 Secretion.

Pneumonic plague is the deadliest form of disease caused by Yersinia pestis Key to the progression of infection is the activity of the plasminogen activator protease Pla. Deletion of Pla results in a decreased Y. pestis bacterial burden in the lung and failure to progress into the lethal proinflammatory phase of disease. While a number of putative functions have been attributed to Pla, its precise role in the pathogenesis of pneumonic plague is yet to be defined. Here, we show that Pla facilitates type 3 secretion into primary alveolar macrophages but not into the commonly used THP-1 cell line. We also establish human precision-cut lung slices as a platform for modeling early host/pathogen interactions during pneumonic plague and solidify the role of Pla in promoting optimal type 3 secretion using primary human tissue with relevant host cell heterogeneity. These results position Pla as a key player in the early host/pathogen interactions that define pneumonic plague and showcase the utility of human precision-cut lung slices as a platform to evaluate pulmonary infection by bacterial pathogens.

Modeling of spatio-temporal variation in plague incidence in Madagascar from 1980 to 2007.

Plague is an infectious disease caused by the bacterium Yersinia pestis, which, during the fourteenth century, caused the deaths of an estimated 75-200 million people in Europe. Plague epidemics still occur in Africa, Asia and South America. Madagascar is today one of the most endemic countries, reporting nearly one third of the human cases worldwide from 2004 to 2009. The persistence of plague in Madagascar is associated with environmental and climatic conditions. In this paper we present a case study of the spatio-temporal analysis of plague incidence in Madagascar from 1980 to 2007. We study the relationship of plague with temperature and precipitation anomalies, and with elevation. A joint spatio-temporal analysis of the data proves to be computationally intractable. We therefore develop a spatio-temporal log-Gaussian Cox process model, but then carry out marginal temporal and spatial analyses. We also introduce a spatially discrete approximation for Gaussian processes, whose parameters retain a spatially continuous interpretation. We find evidence of a cumulative effect, over time, of temperature anomalies on plague incidence, and of a very high relative risk of plague occurrence for locations above 800 m in elevation. Our approach provides a useful modeling framework to assess the relationship between exposures and plague risk, irrespective of the spatial resolution at which the latter has been recorded.

Travel history key to picking up on signs of bubonic plague.

Health officials note an uptick in cases of bubonic plague in the United States this year, with at least 12 reported human cases reported since April 1. The CDC notes that healthcare providers should consider plague in patients who have traveled to plague-endemic areas and exhibit fever, headache, chills, weakness, and one or more swollen or tender and painful lymph nodes, referred to as buboes. Officials note that the disease rarely passes from person to person, but that this is a concern with patients who have developed the pneumonic form of the disease. Health officials note that in recent years there has been an average of seven cases of human plague each year in the United States, and that most of these cases are the bubonic form of the illness. Four patients confirmed to have plague this year have died, including the most recent case, a Utah man in his 70s. Most cases of plague in the United States occur in two regions. The first includes northern New Mexico, northern Arizona, and southern Colorado, and the second includes California, southern Oregon, and far western Nevada. When plague is suspected, treatment with antibiotics should begin immediately.

[The spread of the plague: A sciento-historiographic review]. / Diseminación de la peste: revisión científico-historiográfica.

There is still uncertainty about the diagnosis and nature of the plague; some scholars have been forced to abandon certainties and be filled with doubts: from believing that the mediaeval Black Plague was, in reality, the bubonic plague (although with unusual characteristics) to stating that there is very little evidence to support a retro-diagnosis. This article looks at this in depth, not only reviewing the historiography but also giving new interpretations which question previous hypotheses through research on images of the time, comparing them to the most recent investigative data. Two primary sources are analysed: Renaissance treaties written by four Italian doctors: Michele Savonarola, Marsilio Ficino, Leonardo Fioravanti and Gioseffo Daciano; and iconography: an illustrated manuscript of the Decameron by Giovanni Boccaccio and a Hebrew Haggadah from the XIVth century. The results are compared to the most recent research on DNA and in micropaleontology.

Mapping risk of plague in Qinghai-Tibetan Plateau, China.

BACKGROUND: Qinghai-Tibetan Plateau of China is known to be the plague endemic region where marmot (Marmota himalayana) is the primary host. Human plague cases are relatively low incidence but high mortality, which presents unique surveillance and public health challenges, because early detection through surveillance may not always be feasible and infrequent clinical cases may be misdiagnosed. METHODS: Based on plague surveillance data and environmental variables, Maxent was applied to model the presence probability of plague host. 75% occurrence points were randomly selected for training model, and the rest 25% points were used for model test and validation. Maxent model performance was measured as test gain and test AUC. The optimal probability cut-off value was chosen by maximizing training sensitivity and specificity simultaneously. RESULTS: We used field surveillance data in an ecological niche modeling (ENM) framework to depict spatial distribution of natural foci of plague in Qinghai-Tibetan Plateau. Most human-inhabited areas at risk of exposure to enzootic plague are distributed in the east and south of the Plateau. Elevation, temperature of land surface and normalized difference vegetation index play a large part in determining the distribution of the enzootic plague. CONCLUSIONS: This study provided a more detailed view of spatial pattern of enzootic plague and human-inhabited areas at risk of plague. The maps could help public health authorities decide where to perform plague surveillance and take preventive measures in Qinghai-Tibetan Plateau.

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.

Entre o Carlo R. e o Orleannais: a saude publica e a profilaxia maritima no relato de dois casos de navios de imigrantes no porto do Rio de Janeiro, 1893-1907 / Between the Carlo R. and the Orleannais: public health and maritime prophylaxis in the description of two cases of ships transporting immigrants arriving in the port of Rio de Janeiro, 1893-1907

Aborda as mudanças ocorridas nas práticas da profilaxia marítima brasileira. Por meio de dois casos de navios de imigrantes, que chegaram ao porto do Rio de Janeiro com epidemias a bordo, são analisados a compreensão sobre a etiologia, a forma de prevenção e o combate às três doenças com regulamentação portuária internacional: febre amarela, peste bubônica e cólera. Até o final do século XIX, uma das principais práticas de profilaxia era a quarentena. No início do XX, identificamos a emergência do ideário da microbiologia e dos vetores no serviço sanitário dos portos. A quarentena, que já vinha sendo criticada como antiquada e ineficaz, é limitada a alguns casos, e novos métodos e tecnologias da higiene passam a ser aplicados na defesa sanitária dos portos.

We address the changes in Brazilian maritime prophylaxis by studying two cases of immigrant ships arriving at the port of Rio de Janeiro with epidemics onboard. The objective is to understand the etiology, means of prevention and methods used to combat the three diseases subject to international port regulations: yellow fever, bubonic plague and cholera. Until the late nineteenth century, quarantines were one of the main disease prevention practices. In the early twentieth century, microbiology and the concept of vectors in ports sanitation services emerged. Quarantines, which were already being criticized as antiquated and ineffective, were limited to a few cases, and new hygiene methods and technologies began to be applied in port sanitary defense.

Yersinia pestis DNA from skeletal remains from the 6(th) century AD reveals insights into Justinianic Plague.

Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics.

Small oversights that led to the Great Plague of Marseille (1720-1723): lessons from the past.

In recent decades, the issue of emerging and re-emerging infectious diseases has become an increasingly important area of concern in public health. Today, like centuries ago, infectious diseases confront us with the fear of death and have heavily influenced social behaviors and policy decisions at local, national and international levels. Remarkably, an infectious disease such as plague, which is disseminated from one country to another mainly by commercial transportation, remains today, as it was in the distant past, a threat for human societies. Throughout history, plague outbreaks prevailed on numerous occasions in Mediterranean harbors, including Marseille in the south of France. A few months ago, the municipal authorities of the city of Marseille, announced the archaeological discovery of the last remnants of a "lazaretto" or "lazaret" (http://20.minutes.fr, March 3th, 2012), a place equipped with an infirmary and destined to isolate ship passengers quarantined for health reasons. More recently, on September 16th, 2012, the anchor of the ship "Grand Saint Antoine" responsible for bringing the plague to Marseille in 1720, was recovered and it will be restored before being presented to the public in 2013 (http://www.libemarseille.fr/henry/2012/09/lancre-du-bateau-qui-amena-la-grande-peste-%C3%A0-marseille.html). In the light of these recent archaeological discoveries, it is quite instructive to revisit the sequence of events and decisions that led to the outbreak of the Great Plague of Marseille between 1720 and 1723. It comes to the evidence that although the threat was known and health surveillance existed with quite effective preventive measures such as quarantine, the accumulation of small negligence led to one of the worst epidemics in the city (about 30% of casualties among the inhabitants). This is an excellent model to illustrate the issues we are facing with emerging and re-emerging infectious diseases today and to define how to improve biosurveillance and response tomorrow. Importantly, the risk of plague dissemination by transport trade is negligible between developed countries, however, this risk still persists in developing countries. In addition, the emergence of antibiotic resistant strains of Yersinia pestis, the infectious agent of plague, is raising serious concerns for public health.