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Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent Burkholderia pseudomallei (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS ΔcapB, previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS ΔcapB/Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS ΔcapB/Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS ΔcapB/Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS ΔcapB vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS ΔcapB/Bp vaccines are exceptionally promising safe and potent melioidosis vaccines.ImportanceMelioidosis, a major neglected disease caused by the intracellular bacterial pathogen Burkholderia pseudomallei, is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, B. pseudomallei is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with B. pseudomallei in a highly sensitive small animal model-even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of B. pseudomallei; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.

Yersinia pestis, the causative agent of plague and a biological threat agent, presents an urgent need for novel medical countermeasures due to documented cases of naturally acquired antibiotic resistance and potential person-to-person spread during a pneumonic infection. Immunotherapy has been proposed as a way to circumvent current and future antibiotic resistance. Here, we describe the development and characterization of two affinity matured human antibodies (αF1Ig AM2 and αF1Ig AM8) that promote survival of mice after exposure to aerosolized Y. pestis. We share details of the error prone PCR and yeast display technology-based affinity maturation process that we used. The resultant matured antibodies have nanomolar affinity for Y. pestis F1 antigen, are produced in high yield, and are resilient to 37°C stress for up to 6 months. Importantly, in vitro assays using a murine macrophage cell line demonstrated that αF1Ig AM2 and αF1Ig AM8 are opsonic. Even more importantly, in vivo studies using pneumonic plague mouse models showed that 100% of the mice receiving 500 μg of IgGs αF1Ig AM2 and αF1Ig AM8 survived lethal challenge with aerosolized Y. pestis CO92. Combined, these results provide evidence of the quality and robustness of αF1Ig AM2 and αF1Ig AM8 and support their development as potential medical countermeasures against plague.

The last major plague epidemic in France hit Marseille in 1720 and ultimately took the lives of over 120,000 people across the city and Provence. Yet to what degree did the act of naming the plague impact on its deadly dissemination in the city and beyond? This article seeks to answer that question. In the process, it contends that equivocations in designating the disease as 'la peste' revived fraught relations between the cosmopolitan sea port and central government in Versailles and Paris; and, more locally, they exposed how power was unevenly exercised economically, socially, and medically in the city. Such discursive choices cost thousands of lives. Naming the plague had a performative power beyond simple diagnosis; and medical and religious responses in particular to the Marseille epidemic suggest how the name of the plague was deployed (or withheld) to gain control over the narrative of the catastrophe. [ABSTRACT FROM AUTHOR]

This paper has several aims: to determine if Yersinia pestis was the causative agent in the last Scottish plague outbreak in the mid-17th century; map the geographic spread of the epidemic and isolate potential contributing factors to its spread and severity; and examine funerary behaviours in the context of a serious plague epidemic in early modern Scotland. Results confirm the presence of Y. pestis in individuals associated with a mid-17th century plague pit in Aberdeen. This is the first time this pathogen has been identified in an archaeological sample from Scotland. The geographic spread of the plague from 1644 through to 1649 is generally, with some key exceptions, restricted to the central lowlands of Scotland. The role of administrative responses to the epidemic in managing its spread and distribution is unclear. Finally, normative funerary practices tended to co-exist with mass burial scenarios. In conclusion, the distribution of the epidemic is arguably a function of population density/distribution, transportation networks, and the chaos associated with the concurrent civil war. Administrative responses to the epidemic likely had a variable, albeit limited, effect in the central lowlands. More peripheral cities, such as Aberdeen, while also employing sophisticated plague prevention measures, were perhaps initially spared simply due to their distance from the central plague belt. It is unclear if a general fear of the dead and contracting the Pest from plague victims can be used to characterise mid-17th century Scottish public opinion. Mass burial appears to have been a practical approach to the logistical problems mass mortality presented, while many instances of normative burial treatment can also be seen. [ABSTRACT FROM AUTHOR]

Plague is a zoonotic disease caused by Yersinia pestis, and it is endemic in Madagascar. The plague cycle involves wild and commensal rodents and their fleas; humans are an accidental host. Madagascar is the country where plague burden is the highest. Plague re-emerged in Mahajanga, the western coast of Madagascar, in the 1990s and infected populations in the popular and insalubrious zones. Sanitation is considered a primary barrier to infection by excluding pathogens from the environment and reservoirs. Poor housing and hygiene and proximity to rodents and fleas in everyday life are major and unchanged risk factors of plague. The aim of this study was to measure the impact of sanitation on Yersinia pestis bacteria in human and small mammal reservoirs and flea vectors. This study was conducted on 282 households within 14 neighborhoods. Two sessions of sampling were conducted in 2013 and 2016. Small mammals were trapped inside and around houses using live traps. Fleas, blood and spleen were sampled to detect Y. pestis infection and antibodies and determine the level of plague circulation before and after the installation of sanitation in order to assess the impact of sanitation improvement on inhabitant health. Two major types of housing can be described, i.e., formal and informal (traditional), scattered in all the suburbs. Among the small mammals captured, 48.5% were Suncus murinus, and 70% of houses were infested. After sanitation, only 30% of houses remained infested, and most of them were located around the market. Fleas were mostly Xenopsylla cheopis. Before and after intervention, the overall prevalence of fleas was the same (index 4.5) across the 14 suburbs. However, the number of houses with fleas drastically decreased, and the flea index increased significantly in rodent-infested houses. Rodent abundance also decreased from 17.4% to 6.1% before and after intervention, respectively. A serology study highlights that plague is still circulating in Mahajanga, suggesting that small mammals maintain enzootic plague transmission in the city. [ABSTRACT FROM AUTHOR]

Yersinia pestis, the causative agent of plague, is a highly virulent bacterium that poses a significant threat to human health. Preserving this bacterium in a viable state is crucial for research and diagnostic purposes. This paper presents and evaluates a simple lyophilization protocol for the long-term storage of Y. pestis strains from Fiocruz-CYP, aiming to explore its impact on viability and long-term stability, while replacing the currently used methodologies. The lyophilization tests were conducted using the non-virulent Y. pestis strain EV76, subjected to the lyophilization process under vacuum conditions. Viability assessment was performed to evaluate the effects of lyophilization and storage conditions on Y. pestis under multiple temperature conditions (− 80 °C, − 20 °C, 4–8 °C and room temperature). The lyophilization protocol employed in this study consistently demonstrated its efficacy in maintaining high viability rates for Y. pestis samples in a up to one year follow-up. The storage temperature that consistently exhibited the highest recovery rates was − 80 °C, followed by − 20 °C and 4–8 °C. Microscopic analysis of the post-lyophilized cultures revealed preserved morphological features, consistent with viable bacteria. The high viability rates observed in the preserved samples indicate the successful preservation of Y. pestis using this protocol. Overall, the presented lyophilization protocol provides a valuable tool for the long-term storage of Y. pestis, offering stability, viability, and functionality. By refining the currently used methods of lyophilization, this protocol can improve long-term preservation for Y. pestis strains collections, facilitating research efforts, diagnostic procedures, and the development of preventive and therapeutic strategies against plague. [ABSTRACT FROM AUTHOR]

Using the examples of plague, smallpox, and HIV/AIDS, the present essay argues for the benefits of incorporating the evolutionary histories of pathogens, beyond visible epidemic spikes within human populations, into our understanding of what pandemics actually are as epidemiological phenomena. The pandemic arc — which takes the pathogen as the defining "actor" in a pandemic, from emergence to local proliferation to globalization — offers a framework capable of bringing together disparate aspects not only of the manifestations of disease but also of human involvement in the pandemic process. Pathogens may differ, but there are common patterns in disease emergence and proliferation that distinguish those diseases that become pandemic, dispersed through human communities regionally or globally. The same methods of genomic analysis that allow tracking the evolutionary development of a modern pathogen such as SARS-CoV-2 also allow us to trace pandemics into the past. Reconstruction of these pandemic arcs brings new elements of these stories into view, recovering the experiences of regions and populations hitherto overlooked by Eurocentric narratives. This expanded global history of infectious diseases, in turn, lays a groundwork for reconceiving what ambitions a truly global health might aim for. [ABSTRACT FROM AUTHOR]

The image of dazed, plague-infected rats coming out of their nests and performing a pirouette in front of the surprised eyes of humans before dying is one well-known to us through Albert Camus's The Plague (1947). This article examines the historical roots of this image and its emergence in French missionary narratives about plague outbreaks in the Chinese province of Yunnan in the 1870s on the eve of the Third Plague Pandemic. Showing that accounts of the "staggering rat" were not meant as naturalist observations of a zoonotic disease, as is generally assumed by historians, but as a cosmological, end-of-the-world narrative with a colonial agenda, the article argues for an approach to historical accounts of epidemics that does not succumb to the current trend of "virus hunting" in the archive, but rather takes colonial outbreak narratives ethnographically seriously. [ABSTRACT FROM AUTHOR]

Understanding Kazakhstan’s plague history is crucial for early warning and effective health disaster management. We used descriptive-analytical methods to analyze spatial data for human cases in natural plague foci in Kazakhstan during 1926–2003. The findings revealed 565 human cases across 82 outbreaks in Almaty (32.22%), Aktobe (1.59%), Atyrau (4.42%), Mangystau (21.24%), and Kyzylorda (40.53%) oblasts. Before antibiotic drugs were introduced in 1947–1948, major plague outbreaks occurred in 1926, 1929, 1945, 1947, and 1948, constituting 80.7% of human transmission. Plague spread through flea bites, camel handling, wild animal contact, aerosol transmissions, and rodent bites. Patients were up to 86 years of age; 49.9% were male and 50.1% female. Pulmonary cases were reported most frequently (72.4%), and person-to-person infection occurred at an incidence rate of 0.29 cases/10,000 population. Risk increased with human expansion into natural plague foci areas. Swift diagnosis and treatment are essential for curbing plague outbreaks in Kazakhstan.

The aim of the work was to study the effect of the azoximer bromide immunoadjuvant (polyoxidonium, PO) on certain molecular-genetic and proteomic properties of Yersinia pestis EV NIIEG strain, when added to the culture medium. Materials and methods. Y. pestis EV NIIEG was grown at 28 °C for 48 hours on LB agar pH 7.2 (Miller), with and without PO (EV+PO). Whole-genome sequencing of EV and EV+PO strains was performed on the Ion S5 XG generation II platform. Whole-genome SNP analysis and search for marker SNPs were conducted in the Wombac 2.0 program. Mass-spectra of Y. pestis EV extracts and EV+PO cells were recorded using a Microflex LT mass spectrometer. Protective properties of the test cultures were evaluated by the integral ImD50 index in BALB/c mice when infected with Y. pestis 231(708). Results and discussion. Comparative analysis has not revealed deletions, insertions and single nucleotide polymorphisms in the structure of Y. pestis EV+PO strain genome leading to a violation of the production of pathogenicity, immunogenicity and ensuring the vital activity factors of the plague pathogen. The MALDI-TOF mass spectrometry has shown that Y. pestis EV+PO strains changed the intensity of 22 % of the total number of peaks in the range of 2000–20000 Da. Most of the altered peaks in the UniProtKB protein bank belong to uncharacterized proteins and metabolic proteins. At the same time, the ImD50 was 2–3.3 times lower in cultures grown with the addition of PO than in Y. pestis EV. Thus, the addition of PO to Y. pestis EV NIIEG culture medium does not cause changes in the genes of pathogenicity and vital activity support factors of plague pathogen, but modulates its protein profile, which is accompanied by an increase in the protective potential of the EV vaccine strain.

Plague is a deadly zoonosis that still poses a threat in many regions of the world. We combined epidemiologic, host, and vector surveillance data collected during 1961–1980 from the Araripe Plateau focus in northeastern Brazil with ecologic, geoclimatic, and Yersinia pestis genomic information to elucidate how these factors interplay in plague activity. We identified well-delimited plague hotspots showing elevated plague risk in low-altitude areas near the foothills of the plateau’s concave sectors. Those locations exhibited distinct precipitation and vegetation coverage patterns compared with the surrounding areas. We noted a seasonal effect on plague activity, and human cases linearly correlated with precipitation and rodent and flea Y. pestis positivity rates. Genomic characterization of Y. pestis strains revealed a foundational strain capable of evolving into distinct genetic variants, each linked to temporally and spatially constrained plague outbreaks. These data could identify risk areas and improve surveillance in other plague foci within the Caatinga biome.

At the end of the nineteenth century, Hong Kong was in the midst of a malaria and plague epidemic which caused a fierce dispute within the medical community over disease theories and quarantine practices. However, the Hong Kong colonial authorities and medical community did not immediately accept the theory of etiology based on germ theory. Although germ theory was becoming scientifically established through research on plague and malaria in the 1890s, the Hong Kong colonial authorities and medical community did not immediately accept it.Patrick Manson (1844-1922) began studying tropical medicine based on germ theory by studying elephantiasis and malaria in Amoi and Hong Kong during the 1880s. However, he was unable to strongly advocate for a quarantine policy based on germ theory because the exact transmission routes of these diseases were not yet fully understood. Although the scientific community began to shift towards germ theory after the discovery of causative bacteria for diseases like malaria and plague in the 1880s and 1890s, many medical and colonial health officials in Hong Kong still held on to the quarantine policy based on miasma theory. However, a series of infectious diseases and destructive miasma theory-based quarantine measures were pushing Hong Kong society into chaos, and the existing quarantine measures was no longer sustainable.In the twentieth century, colonial authorities and medical community in Hong Kong adopted tropical medicine and quarantine measures based on germ theory as their prominent position. Despite the establishment of tropical disease theory based on germ theory, racial perceptions of disease did not change significantly. Instead, the theory of tropical medicine reinforced orientalist views of disease.

The persistent presence of the plague, following the first wave of the Black Death in the 14th century AD, continued to affect human societies. In the 15th century, this disease had destructive effects on the social situation of the cities of Herat during the Timurid period and Cairo during the Mamluk era, as they were administrative centers of government and centers of various social classes. The present research, employing a descriptive-analytical approach, aims to compare the social consequences of the disease in these two cities. The findings of this study show that, despite the absence of a well-equipped hospital like the one in Cairo, Herat suffered less devastation from the disease due to the construction of a hospital after estimating the plague casualties and its geographical extent. The mortality rate in Herat was significantly lower, and its population structure underwent fewer changes. This is because Herat had recently been chosen as the capital under Shahrukh’s rule, which led to a transition from a nomadic to a settled lifestyle, resulting in a lower population density than Cairo. Herat’s mountainous climate and limited trade accessibility through land routes made it less susceptible to recurrent disease outbreaks and their enduring adverse effects. Conversely, Cairo’s hot, humid climate, flourishing maritime trade, and dependence on land and agriculture contributed to its economic recession during the plague. The economy of Herat, still a young city in the 15th century, was less vulnerable to economic recession due to the plague.

Climatic factors are closely associated with the occurrence of vector-borne diseases, and they also influence the distribution of vectors. The occurrence of plague is closely related to the population dynamics of fleas and their host animals, as well as climatic conditions. This study focused on Xilingol League, utilizing climatic and flea index data from 2012 to 2021. Spearman correlation and ''Boruta'' importance analysis were conducted to screen for climatic variables. A generalized additive model (GAM) was employed to investigate the influence of climatic factors and rodent density on the flea index. GAM analysis revealed distinct trends in flea index among different rodent hosts. For Meriones unguiculatus, the flea index declined with increased density and with higher humidity, yet rose with greater lagged sunshine duration. For Spermophilus dauricus, an initial increase in flea index with density was observed, followed by a decrease, and a rise in the index was noted when ground temperatures were low. This study reveals the nonlinear interactions and lag effects among climatic factors, density, and flea index. Climatic factors and density variably influence the flea index of two Yersinia pestis hosts. This research advances the prediction and early warning efforts for plague control, providing a theoretical basis for rodent and flea eradication strategies.

Abstract Background Plague is an acute infectious disease caused by the Yersinia pestis. Historically, it has been a major pandemic with high mortality rates, known as the “Black Death” in the 14th century, which resulted in millions of deaths in Europe. With increasing economic prosperity, more and more people are traveling to Xizang. However, this trend also hides significant safety hazards. Currently, there are few recent reports on plague, especially those with imaging manifestations available. In this study, we report the detailed clinical and radiological data of the patient with pneumonic plague in Xizang, China, in 2023. Case presentation We report a case of pneumonic plague in Xizang, which occurred in a herdsman living in an area where dead marmots were found. The patient presented with symptoms such as fever, hemoptysis, dyspnea and coma. Chest computed tomography (CT) scans showed multiple nodules distributed in the central regions of lung lobes, consolidation distributed in secondary pulmonary lobules, and had a gravity-dependent distribution pattern. These imaging findings were consistent with pulmonary hemorrhage and diffuse alveolar damage. Despite emergency treatment, the patient died within 48 h of admission. Through retrospective medical history investigation, laboratory examination and autopsy, the final diagnosis was confirmed as pneumonic plague. Conclusion Pneumonic plague is the most deadly infectious disease, and its pathological features mainly include damage to the alveoli, pulmonary hemorrhage, and pulmonary edema. Corresponding to CT, it manifests as acute and rapidly progressing pneumonia, alveolar damage, and pulmonary hemorrhage. The value of this article lies in the completeness and typicality of the imaging data, vivid hand-drawn illustrations of transmission pathways, and comprehensive literature review, all of which serve to enhance public understanding of plague and play an important warning role.

ObjectiveTo establish an evaluation index system for the effectiveness of plague prevention and control in demonstration areas to strengthen the plague prevention and control system. MethodsAfter constructing a primary index system to evaluate the effectiveness of plague prevention and control through literature study and expert interview, we conducted three rounds of online Delphi consultation among 20 authoritative experts and scholars engaged in plague prevention, control, and research from 5 provincial-level administrative divisions from June to August 2023. The response rate of the questionnaire was used to represent the expert activity coefficient. The analytical hierarchy method was used to calculate the weights of indicators at three levels. The coefficient of expert authority (Cr) was used to reflect the expert authority, and the coefficient of variation (CV) and Kendall's coefficient of concordance (Kendall′s W) were used to reflect the coordination of expert consultation. SPSS 25.0 and yaahp 10.1 software were used for statistical analysis. ResultsThe activity coefficients of the three rounds of expert consultation were all 100%, indicating a high degree of expert activity. The Cr values of the three rounds were all greater than 0.7, indicating a high degree of expert authority. In the third round, the coefficient of variation (CV) was < 0.25, and the Kendall's W of the indicators increased compared to those of the first and second rounds, approaching 0.4 (P < 0.01). The final index system consisted of 3 first-level indicators (pre-event preparedness, in-event handling ability, and post-event recovery ability, with weights of 33.33%, 33.34%, and 33.33%, respectively), 10 second-level indicators (among which, summary analysis ability and damage repair ability had the highest weights of 16.67%, followed by monitoring and early warning ability with 15.68%), and 58 third-level indicators (among which, network direct reporting rate and professional responsible for plague data had the highest weights of 4.76%, followed by plague monitoring database and early warning platform with 3.62%, 3.10% , respectively). ConclusionThe established index system has certain scientific validity and reliability to comprehensively and accurately evaluate the effectiveness of plague prevention and control in demonstration areas, and is conducive to building a more complete prevention and control system, and provides a reference for other regions to carry out plague prevention and control work.

Objectives: This study seeks to identify signals of the male–female health‐survival paradox in medieval London. Materials and Methods: This study uses skeletal data on age, sex, dental caries (n = 592) and antemortem tooth loss (n = 819) from adult individuals from medieval London cemeteries (c. 1200–1540 CE). The association between age and dental caries was assessed using binary logistic regression. The associations among age, time period (pre‐ vs. post‐Black Death), oral biomarker (dental caries or antemortem tooth loss), and sex were tested using hierarchical log‐linear analysis. Results: The analyses reveal significantly higher odds of dental caries with increasing adult ages, more older adults after the Black Death, different age distributions of dental caries between the sexes, and a greater decrease in the prevalence of dental caries for females after the Black Death. These results appear not to be an artifact of trends in AMTL. However, this study does not yield evidence suggesting that females experienced both a survival advantage and a decline in oral health at late adult ages after the Black Death relative to males. Conclusions: These results do not provide evidence of the existence of a male–female health‐survival paradox, but they do corroborate existing evidence of improvements in health in general in the aftermath of the Black Death. The decreased prevalence of dental caries after the Black Death may reflect dietary improvements or the effects of selective mortality during the epidemic. [ABSTRACT FROM AUTHOR]

The lack of a universally accepted definition of a pandemic hinders a comprehensive understanding of and effective response to these global health crises. Current definitions often lack quantitative criteria, rendering them vague and limiting their utility. Here, we propose a refined definition that considers the likelihood of susceptible individuals contracting an infectious disease that culminates in widespread global transmission, increased morbidity and mortality, and profound societal, economic, and political consequences. Applying this definition retrospectively, we identify 22 pandemics that occurred between 165 and 2024 AD and were caused by a variety of diseases, including smallpox (Antonine and American), plague (Justinian, Black Death, and Third Plague), cholera (seven pandemics), influenza (two Russian, Spanish, Asian, Hong Kong, and swine), AIDS, and coronaviruses (SARS, MERS, and COVID-19). This work presents a comprehensive analysis of past pandemics caused by both emerging and re-emerging pathogens, along with their epidemiological characteristics, societal impact, and evolution of public health responses. We also highlight the need for proactive measures to reduce the risk of future pandemics. These strategies include prioritizing surveillance of emerging zoonotic pathogens, conserving biodiversity to counter wildlife trafficking, and minimizing the potential for zoonotic spillover events. In addition, interventions such as promoting alternative protein sources, enforcing the closure of live animal markets in biodiversity-rich regions, and fostering global collaboration among diverse stakeholders are critical to preventing future pandemics. Crucially, improving wildlife surveillance systems will require the concerted efforts of local, national and international entities, including laboratories, field researchers, wildlife conservationists, government agencies and other stakeholders. By fostering collaborative networks and establishing robust biorepositories, we can strengthen our collective capacity to detect, monitor, and mitigate the emergence and transmission of zoonotic pathogens. [ABSTRACT FROM AUTHOR]

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Plague is an important and serious zoonotic disease caused by the bacterium Yersinia pestis. This study is a narrative review. The required data for the research were gathered through a search in search engines such as Google Scholar and international scientific databases, including PubMed, Web of Science, ScienceDirect, Scopus, Elsevier, and Lilacs, as well as Persian databases like the Barakat Knowledge Network System (Barakatkns), the Scientific Information Database (SID), the Iranian Medical Library (Medlib), and Civilica. The search was conducted using both Persian and English keywords, including "Plague," "Yersinia pestis," "Plague outbreak," "Flea," and "Control," through individual and combined searches over a period from 1974 to June 2024. In the present article, the agents and types of plague, its transmission methods, diagnostic approaches, the status of plague in the world and Iran, fleas in Iran, and methods for prevention and control of the disease will be discussed. This disease has caused three major historical pandemics, including the Black Death in the 14th century, which claimed millions of lives in Europe, Asia, and Africa and profoundly affected the populations of the impacted countries. Recently, the highest number of human plague cases has been reported from Madagascar. The main vector of the disease in humans is known as Xenopsylla cheopis worldwide. In Iran, records of human plague date back to the past. Climate change and ecological shifts may influence the distribution of plague vectors and hosts, increasing the risk of its resurgence even in areas where the disease is currently dormant. In Iran, increasing interactions between human communities and wildlife, along with changes in agricultural practices influenced by climatic factors, could facilitate the spread of the plague. Reports of the pathogen in rodents and dogs in western Iran (Kurdistan and Hamadan) underscore the significance of the potential re-emergence of plague in the region. There are three clinical forms of this disease bubonic, septicemic, and pulmonary. The most common type of plague is bubonic plague, which occurs following the bite of a flea that has previously fed on an infected animal. It presents with symptoms including fever, headache, chills, weakness, fatigue, and swollen, inflamed lymph nodes. Delayed treatment increases the risk of mortality associated with the disease. Plague, with a history of horror and devastation, remains a global health challenge. Understanding the current situation of this disease and reviewing its prevention and control is very important to prevent its re-emergence. Considering the current plague situation in Iran, there is a need for continuous monitoring and more detailed studies on the ecology of vectors, as well as the development of effective strategies for disease control and prevention. International cooperation in scientific research and exchanging information about plague outbreaks and control strategies are among the other effective approaches in this field. Finally, strengthening the health infrastructure and developing educational programs for the community is one of the most important requirements to prevent the spread of plague and other infectious diseases in Iran. [ABSTRACT FROM AUTHOR]

This essay seeks to understand the writing strategies and structures that David Peace uses in Occupied City, the second novel of his Tokyo Trilogy set in the American occupation period (1945–52). Focusing on the (still unsolved) historical crime of the Teikoku Bank mass murders of 1948 and its linkages to the Japanese army's Unit 731 wartime experiments with plague and germ warfare in China—war crimes that were covered up by the Americans—Peace sustains Artaud's notions of plague and theater as he uses spirit mediumship within implicit textual figurations of the Rashōmon complex (as medieval tale, as modernist literary icon Akutagawa Ryūnosuke's retelling, and Akira Kurosawa's occupation‐era filmic allegory) to stage multiple haunted and contesting testimonies about these unjustly repressed and unresolved crimes of war and postwar. [ABSTRACT FROM AUTHOR]

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis, Yersinia pestis, and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis, Y. pestis, and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y. pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata, Paraceras melis, Ctenophthalmus rettigi smiti, Rhadinopsylla bivirgis, Paradoxopsyllus grenieri, and Nosopsyllus iranus. Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis. The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis. Conclusions:F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas. [ABSTRACT FROM AUTHOR]

Antwerp's response to the outbreak of plague in the 1570s offers new insights into the effects of epidemics on urban communities in relation to their religious, economic, and spatial fabric. Antwerp's transition from a Catholic to Calvinist government in 1577, and back to Catholicism in 1585, allows us to study its reaction to and the effects of plague across religious boundaries within a short time span. Using GIS, we have compared various rich datasets concerning plague: the register of houses locked in quarantine; the health certificates issued by authorities; plague fatalities recorded in St. Jacob's parish; a wide range of urban regulations; and information about the size of households, their composition, rents and real estate values in Antwerp. Combined analysis shows that Catholics and Protestants, whose houses were concentrated in different city districts and who had distinct professional and economic profiles, experienced plague quite differently, both physically and spiritually. [ABSTRACT FROM AUTHOR]

The persistent presence of the plague, following the first wave of the Black Death in the 14th century AD, continued to affect human societies. In the 15th century, this disease had destructive effects on the social situation of the cities of Herat during the Timurid period and Cairo during the Mamluk era, as they were administrative centers of government and centers of various social classes. The present research, employing a descriptive-analytical approach, aims to compare the social consequences of the disease in these two cities. The findings of this study show that, despite the absence of a well-equipped hospital like the one in Cairo, Herat suffered less devastation from the disease due to the construction of a hospital after estimating the plague casualties and its geographical extent. The mortality rate in Herat was significantly lower, and its population structure underwent fewer changes. This is because Herat had recently been chosen as the capital under Shahrukh’s rule, which led to a transition from a nomadic to a settled lifestyle, resulting in a lower population density than Cairo. Herat’s mountainous climate and limited trade accessibility through land routes made it less susceptible to recurrent disease outbreaks and their enduring adverse effects. Conversely, Cairo’s hot, humid climate, flourishing maritime trade, and dependence on land and agriculture contributed to its economic recession during the plague. The economy of Herat, still a young city in the 15th century, was less vulnerable to economic recession due to the plague. [ABSTRACT FROM AUTHOR]

This article evaluates the place of The Plague in the emergent cultural memory of the COVID-19 pandemic, a time when the novel was said to have "gone viral" in popular culture. I ask what it means to reread The Plague in the current moment, a time characterized not just by a pandemic but by widespread unrest and social movements on both ends of the political spectrum. While rereadings of Camus in light of COVID-19 seem predicated on a turn away from the novel's allegorical dimension, The Plague has taken on new metaphorical meanings in its Covid-era reception. Examining the proliferation of "readings" of the pandemic, in which the virus has been understood as a figure for collective social ills, this article highlights the place of Camus's novel in the cultural memory of the crisis and proposes that it can illuminate some of the complex entanglements of our present. [ABSTRACT FROM AUTHOR]

Objective To analyze the factors influencing the abundance of floor fleas from households of the commensal rodent plague foci in Yunnan Province. Methods A total of 320 households in 16 natural villages in the commensal plague natural foci were selected from Mangshi City, Lianghe County, and Mile City in Yunnan Province. Floor fleas were collected using the water-containing plate method, with 10 pans placed per household for two consecutive nights. The potential factors influencing the abundance of floor fleas in households were collected through a self-made questionnaire. A hurdle Poisson regression model under R4.3.0 was performed to analyze the factors influencing the abundance of floor fleas in households. Results A total of 6 400 plates were placed per night in 320 households, with 44 households capturing floor fleas, resulting in an infestation rate of 13.75% (44/320). A total of 136 floor fleas were collected in water pans, with a floor fleas index of 0.021 (136/6 400). Ctenocephalides felis felis was the dominant flea species, accounting for 61.76% (84/136), followed by Xenopsylla cheopis and Pulex irritans, each accounting for 19.12% (26/136). The multivariate hurdle Poisson regression model of the abundance of floor fleas showed that the probabilities of capturing floor fleas in households with other houses ground structure, garbage dumping outdoors, raising cat, rodent's activities, and fleas activities were 4.39, 3.16, 3.09, 3.08, and 2.29 times higher than the corresponding reference groups. The probability of capturing floor fleas in households with the Dai ethnic group was 0.30 of that in the Han ethnic group. The number of captured floor fleas in households in Mile City, of the Dai ethnicity, with chickens, and surrounded by other houses were 3.84, 2.95, 7.58, and 5.37 times higher than the corresponding reference group, while the number of captured floor fleas in households with migrant workers, other ground structure, and rodent eradication behavior were 0.32, 0.45, and 0.28 of the corresponding reference group. Conclusions The abundance of floor fleas from households of the commensal rodent plague foci in Yunnan Province is influenced by the basic family situation, indoor and outdoor environmental factors, and human interference factors. To avoid the spread of flea-borne diseases to humans, it is necessary to take comprehensive measures to control the abundance of floor fleas in households. [ABSTRACT FROM AUTHOR]

Background: Plague is an acute infectious disease caused by the Yersinia pestis. Historically, it has been a major pandemic with high mortality rates, known as the "Black Death" in the 14th century, which resulted in millions of deaths in Europe. With increasing economic prosperity, more and more people are traveling to Xizang. However, this trend also hides significant safety hazards. Currently, there are few recent reports on plague, especially those with imaging manifestations available. In this study, we report the detailed clinical and radiological data of the patient with pneumonic plague in Xizang, China, in 2023. Case presentation: We report a case of pneumonic plague in Xizang, which occurred in a herdsman living in an area where dead marmots were found. The patient presented with symptoms such as fever, hemoptysis, dyspnea and coma. Chest computed tomography (CT) scans showed multiple nodules distributed in the central regions of lung lobes, consolidation distributed in secondary pulmonary lobules, and had a gravity-dependent distribution pattern. These imaging findings were consistent with pulmonary hemorrhage and diffuse alveolar damage. Despite emergency treatment, the patient died within 48 h of admission. Through retrospective medical history investigation, laboratory examination and autopsy, the final diagnosis was confirmed as pneumonic plague. Conclusion: Pneumonic plague is the most deadly infectious disease, and its pathological features mainly include damage to the alveoli, pulmonary hemorrhage, and pulmonary edema. Corresponding to CT, it manifests as acute and rapidly progressing pneumonia, alveolar damage, and pulmonary hemorrhage. The value of this article lies in the completeness and typicality of the imaging data, vivid hand-drawn illustrations of transmission pathways, and comprehensive literature review, all of which serve to enhance public understanding of plague and play an important warning role. [ABSTRACT FROM AUTHOR]

COVID-19 brought back to the attention of the scientific community that males are more susceptible to infectious diseases. What is clear for other infections—that sex and gender differences influence both risk of infection and mortality—is not yet fully elucidated for plague, particularly bubonic plague, although this knowledge can help find specific defences against a disease for which a vaccine is not yet available. To address this question, we analysed data on plague from hospitals in different parts of the world since the early eighteenth century, which provide demographic information on individual patients, diagnosis and course of the disease in the pre-antibiotic era. Assuming that the two sexes were equally represented, we observe a worldwide prevalence of male cases hospitalized at any age, a result which seems better explained by gender-biased (thus cultural) behaviours than biological sex-related factors. Conversely, case fatality rates differ among countries and geographic macro-areas, while globally, lethality appears slightly prevalent in young females and older adults (regardless of sex). Logistic regression models confirm that the main risk factor for bubonic plague death was the geographical location of the cases and being older than 50 years, whereas sex only showcased a slight trend. [ABSTRACT FROM AUTHOR]

Criticism in early modern English drama continues to expose the socio‐spatial anxieties generated by plague that shaped both plays and the playhouse space. What has not yet been considered in any detail, however, are the numerous public health measures born out of these anxieties that altered the lived experience of space during outbreaks. This article begins to address this lacuna by reading Thomas Heywood's domestic tragedy A Woman Killed with Kindness through the lens of contemporary plague prevention. Plague policy repurposed the home into a space that might not only contain the infected but, with competent governance, might also provide the first line of defence against infection. Woman Killed, a play that likely premiered in the wake of an outbreak, is vigorously alert to the dynamics of plague‐time domestic space and the onus placed on householders to cleanse and manage the home and its peripheries. This article examines how Heywood draws on plague prevention practices to introduce and remove ‘infectious’ sources to and from the Frankford home. Heywood utilizes the cultural immediacy of plague measures to expose and explore the dangers of female adultery that, like plague, threatened the integrity and autonomy of domestic space. [ABSTRACT FROM AUTHOR]

Breakthroughs in international biomedical science circa 1900 meant that plague could be contained through strict quarantine regulations. These measures were successfully deployed with help from local governments during outbreaks of pneumonic plague in Manchuria (1910–11), Shanxi (1918), and elsewhere in North China. This containment shows the effectiveness of uniting international knowledge and local cooperation in disaster response. Yet, in later outbreaks in similar locations, control measures identical to those instituted a decade earlier were rejected, and plague spread largely unchecked. Historical case studies of the control and spread of infectious disease in North China reveal the complexities of the relationship between global knowledge and its broader, local integration, variation in what constitutes effective 'local' cooperation in adopting international knowledge, and the paramount importance of the locality to the landscape of disaster response. History can reveal critical issues in localisation of disaster response still salient today. [ABSTRACT FROM AUTHOR]

We examine how the "Justinian Plague" (or "First Pandemic") could have influenced the post-Roman mind in the medium term. We start from an analysis of the written sources of the Latin West. In these, the terms and themes linked to the plague show that it probably did leave a strong impression on the society as a whole. After the first experiences, the successive outbreaks of plague could have created a particular way of approaching it in the social imaginary, which lasted after the conclusion of the epidemic outbreaks. [ABSTRACT FROM AUTHOR]

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In his small work entitled De mortalitate, written in the form of a letter, St.Cyprian of Carthage includes a beautiful teaching on suffering, dying and death. The bishop comforts those who have been affected by the present plague and are facing their departure from this world. He teaches them to view death from the perspective of a believer and to see it as a positive, although painful, phenomenon. Since death must be experienced in an eschatological spirit, as an encounter with the Risen Christ and with all those who preceded us on the pilgrimage to immortality. According to the Bishop of Carthage, death teaches man right attitudes, such as patience, courage, and acceptance of the will of God. Moreover, Cyprian shows specific benefits that death brings to Christians. He calls it a journey to a better, eternal life. Thus those who relate their earthly lives to Christ should not fear death. The purpose of this study is therefore to study the statements of St. Cyprian contained in De mortalitate on the subject of death. It is not only about assessing it, but primarily about reading the practical instructions addressed to Christians on how they should behave in the face of this inevitable reality, especially during the current plague. [ABSTRACT FROM AUTHOR]

ABSTRACTThe genus Yersinia includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are Yersinia enterocolitica and the Yersinia pseudotuberculosis complex, with four human pathogenic species that are highly related at the genomic level including the causative agent of plague, Yersinia pestis. Extensive laboratory, field work, and clinical research have been conducted to understand the underlying pathogenesis and zoonotic transmission of these pathogens. There are presently more than 500 whole genome sequences from which an evolutionary footprint can be developed that details shared and unique virulence properties. Whereas the virulence of Y. pestis now seems in apparent homoeostasis within its flea transmission cycle, substantial evolutionary changes that affect transmission and disease severity continue to ndergo apparent selective pressure within the other Yersiniae that cause intestinal diseases. In this review, we will summarize the present understanding of the virulence and pathogenesis of Yersinia, highlighting shared mechanisms of virulence and the differences that determine the infection niche and disease severity.

The study aimed to investigate the prevalence of antibiotic resistance genes (ARGs) within the ecosystem of natural plague foci, assessing their potential impact on the efficacy of plague treatments. Employing 16S rRNA gene sequencing and high-throughput quantitative PCR, microbial communities and ARGs were detected, with subsequent analysis of interactions among ARGs, mobile genetic elements (MGEs), environmental factors, and microbial species. Tetracycline resistance genes were found to be dominant, with multidrug and tetracycline resistance ARGs primarily associated with marmots and ecological soil, while pikas predominantly harbored β-lactam resistance ARGs. High detection rates were observed for resistance genes rpsl and sul1, which are relevant to streptomycin and sulfonamides, antibiotics commonly used in plague treatment. The total dissolved solids (TDS) in soil significantly promoted the presence of tetR-02, and Ni was found to inhibit vanHB. The tnpA-03 MGE was identified as a significant contributor to the dissemination of the aadE gene. The high prevalence of ARGs, particularly rpsl and sul1, poses a potential risk to the efficacy of main antibiotic treatments for plague. The study suggests that environmental microbiomes may be the greatest risk factor for the emergence of drug-resistant Yersinia pestis, given the low misuse of antibiotics in animals within natural plague foci. Monitoring the risk of drug-resistant strain emergence and preparing alternative antibiotic or combination therapy strategies based on ARG pollution levels in plague-affected areas is deemed necessary.

Introduction. Immunomodulatory drugs (IMD) have great potential to increase the nonspecific reactivity of the organism in a set of measures for emergency prevention of plague. The purpose of the work is to evaluate the protective effectiveness of the use of IMD of different groups in experiments on modeling infection with a highly virulent strain of the plague microbe. Materials and methods. IMD (rIFN-γ — recombinant interferon-gamma, PO — azoximer bromide, synthetic immunomodulatory oligopeptides O1, O2, O3) was administered to white mice and guinea pigs subcutaneously thrice by the schedule 3 days, 1 day, and 1 hour prior the infection with a virulent test strain of plague Yersinia pestis 231 (708) at dose from 1 to 625 CFU. In addition, the effect of IMD on the production of IFN-γ and interleukin-10 was investigated in white mice before infection. Results. The study of the effect of IMD on the survival of unvaccinated biomodels made it possible to establish that only rIFN-γ and PO increase the survival of two types of laboratory animals by 20–50% and significantly increase the LD50. All tested IMD contribute to an increase in the average life expectancy of biomodels by at least one day. An increase in spontaneous and mitogen-induced cytokine production was found only in white mice receiving rIFN-γ and PO, which correlates with animal survival rates. Conclusion. The obtained data indicate the effectiveness of the use of IMD, especially rIFN-γ and PO in protecting the macroorganisms from infection with Y. pestis, which determines the prospects for research on the further improvement of emergency prevention of plague.