Cause Of Plague Research Articles

Seroprevalence, Blood Chemistry, and Patterns of Canine Parvovirus, Distemper Virus, Plague, and Tularemia in Free-Ranging Coyotes (Canis latrans) in Northern New Mexico, USA.

Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005-2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.

Identification and characterization of P2-like bacteriophages of Yersinia pestis

Yersinia pestis is the cause of plague, historically known as the “Black Death”. Marmota himalayana in the Qinghai-Tibet Plateau (QTP) natural plague focus is the primary host in China. Although several phages originating from Y. pestis have been characterized. This is the first report of isolation of P2-like phages of Y. pestis from M. himalayana. In this study, the isolation and characterization of three P2-like phages of Y. pestis were reported, which were named as vB_YpM_22, vB_YpM_46 and vB_YpM_50. Comparative genome analysis revealed that vB_YpM_22, vB_YpM_46 and vB_YpM_50 are members of the nonlambdoid P2 family, and are highly similar and collinear with enterobacteriophage P2, plague diagnostic phage L-413C and enterobacteriophage fiAA91-ss. The role of LPS core structure of Y. pestis in the phages’ receptor was pinpointed. The findings of this study contribute an advance in our current knowledge of Y. pestis phages and will also play a key role in understanding the evolution of Y. pestis phages.

Medical knowledge of medieval physician on the cause of plague during 1347/8-1351: traditional understandings to poison theory.

This article sets its investigative goal on determining the medical knowledge of medieval physicians from 1347-8 to 1351 concerning the causes of plague. As the plague killed a third of Europe's population, the contemporary witness at the time perceived God as the sender of this plague to punish the human society. However, physicians separated the religious and cultural explanation for the cause of this plague and instead seek the answer to this question elsewhere. Developing on traditional medical knowledges, physicians classified the possible range of the plague's causes into two areas: universal cause and individual/particular causes. In addition, they also sought to explain the causes by employing the traditional miasma-humoral theory. Unlike the previous ones, however, the plague during 1347-8 to 1351 killed the patients indiscriminately and also incredibly viciously. This phenomenon could not be explained by merely using the traditional medical knowledge and this idiosyncrasy led the physicians employ the poison theory to explain the causes of plague more pragmatically.

PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

Yersinia pestis antibiotic resistance: a systematic review.

Yersinia pestis, the cause of plague and a potential biological weapon, has always been a threatening pathogen. Some strains of Y. pestis have varying degrees of antibiotic resistance. Thus, this systematic review was conducted to alert clinicians to this pathogen’s potential antimicrobial resistance. A review of the literature was conducted for experimental reports and systematic reviews on the topics of plague, Y. pestis, and antibiotic resistance. From 1995 to 2021, 7 Y. pestis isolates with 4 antibiotic resistance mechanisms were reported. In Y. pestis 17/95, 16/95, and 2180H, resistance was mediated by transferable plasmids. Each plasmid contained resistance genes encoded within specific transposons. Strain 17/95 presented multiple drug resistance, since plasmid 1202 contained 10 resistance determinants. Strains 16/95 and 2180H showed single antibiotic resistance because both additional plasmids in these strains carried only 1 antimicrobial determinant. Strains 12/87, S19960127, 56/13, and 59/13 exhibited streptomycin resistance due to an rpsl gene mutation, a novel mechanism that was discovered recently. Y. pestis can acquire antibiotic resistance in nature not only via conjugative transfer of antimicrobial-resistant plasmids from other bacteria, but also by gene point mutations. Global surveillance should be strengthened to identify antibiotic-resistant Y. pestis strains by whole-genome sequencing and drug susceptibility testing.

Платоническая традиция и теория эпидемий в раннее Новое время

Most of the studies on the history of medicine, pay special attention to how the plague epidemics in 14th–16th centuries had changed the medical theory and practice. In the medical discourse, those epidemics helped to shape the “epistemology of particulars (particularia)” which contrast with the scholastic epistemology dealing with the search of universal causes. Marsilio Ficino, one of the most influential natural philosophers of the Renaissance, combines scholastic medicine and philosophy of ancient authors in order to develop his theory of epidemics in the treatises Consilio contra la pestilentia and De vita. He identifies the external and internal causes of plague and describes ways to combat the disease. The external cause is the constellations of planets which cause putrid exhalation in certain territories that is an example of conventional scholastic epistemology dealing with mass diseases. The internal cause is identified with the inability of the body to resist the disease “from within”. The main focus of my paper is the argument that, according to Ficino, philosophers have a special ability to resist disease “from within”. The figure of Socrates and his ability to withstand the Plague of Athens allows Ficino to formulate a new take on epidemics which falls within the scope of “epistemology of particulars”. From the historical point of view, the novelty of my approach comes from the fact that I trace the source of Ficino’s knowledge about Socrates’ disease resistance ability to Noct. Att. 2.1. of Aulus Gellius. Ficino’s natural philosophy suggests that a philosopher from their very birth is “by nature” predisposed to philosophical contemplation, therefore the realization of their vital destination through multiple sympathetic connections affects all levels of the universe. Ficino’s doctrine has a social and political dimension since a philosopher (i.e. a platonist), attracting positive astral influences, levels the effect of negative “heavenly” causes of mass diseases and thus benefits all people around him. Thus, the practice of philosophy (i.e. Platonism in Ficino’s interpretation) during epidemics is not simply a form of leisure time or private activity for a philosopher but a form of concern for public health. The paper also offers a commented Russian translation of chapters 1–2, with the Proem, of Ficino’s treatise Consilio contra la pestilentia.

Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures

Yersinia pestis, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers. Here, we report for the first time in humans that inverse caspase-3 levels, which are measures of protective antibody, significantly increased by 29% and 75% on days 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T-cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4+ T-cell responses. Several genes associated with these responses were identified that could serve as potential correlates of protection.

Regulation of c-di-GMP metabolism and biofilm formation in Yersinia pestis

Yersinia pestis, the cause of plague, is transmitted by flea bite. Y. pestis forms a biofilm in the proventriculus of its flea vector to enhance transmission. Biofilm formation in Y. pestis is positively regulated by the intracellular levels of the second messenger cyclic diguanylate (c-di-GMP). The c-di-GMP in Y. pestis is synthesized by two diguanylate cyclases (DGC), HmsT and HmsD, and degraded by phosphodiesterase (PDE), HmsP. Here we summarized the regulators that modulate c-di-GMP metabolism and biofilm formation in Y. pestis and discussed their regulatory mechanism.

Knowledge and practices related to plague in an endemic area of Uganda

BackgroundPlague is a virulent zoonosis reported most commonly from Sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs the development of educational efforts to reduce plague mortality. MethodsA multi-stage cluster-sampled survey of 420 households was conducted in the plague-endemic West Nile region of Uganda to assess knowledge of symptoms and causes of plague and health care-seeking practices. ResultsMost (84%) respondents were able to correctly describe plague symptoms; approximately 75% linked plague with fleas and dead rats. Most respondents indicated that they would seek health care at a clinic for possible plague; however plague-like symptoms were reportedly common, and in practice, persons sought care for those symptoms at a health clinic infrequently. ConclusionsPersons in the plague-endemic region of Uganda have a high level of understanding of plague, yet topics for targeted educational messages are apparent.

The hmsT 3' untranslated region mediates c-di-GMP metabolism and biofilm formation in Yersinia pestis.

Yersinia pestis, the cause of plague, forms a biofilm in the proventriculus of its flea vector to enhance transmission. Biofilm formation in Y. pestis is regulated by the intracellular levels of cyclic diguanylate (c-di-GMP). In this study, we investigated the role of the 3' untranslated region (3'UTR) in hmsT mRNA, a transcript that encodes a diguanylate cyclase that stimulates biofilm formation in Y. pestis by synthesizing the second messenger c-di-GMP. Deletion of the 3'UTR increased the half-life of hmsT mRNA, thereby upregulating c-di-GMP levels and biofilm formation. Our findings indicate that multiple regulatory sequences might be present in the hmsT 3'UTR that function together to mediate mRNA turnover. We also found that polynucleotide phosphorylase is partially responsible for hmsT 3'UTR-mediated mRNA decay. In addition, the hmsT 3'UTR strongly repressed gene expression at 37°C and 26°C, but affected gene expression only slightly at 21°C. Our findings suggest that the 3'UTR might be involved in precise and rapid regulation of hmsT expression, allowing Y. pestis to fine-tune c-di-GMP synthesis and consequently regulate biofilm production to adapt to the changing host environment.

Investigation of Yersinia pestis Laboratory Adaptation through a Combined Genomics and Proteomics Approach.

The bacterial pathogen Yersinia pestis, the cause of plague in humans and animals, normally has a sylvatic lifestyle, cycling between fleas and mammals. In contrast, laboratory-grown Y. pestis experiences a more constant environment and conditions that it would not normally encounter. The transition from the natural environment to the laboratory results in a vastly different set of selective pressures, and represents what could be considered domestication. Understanding the kinds of adaptations Y. pestis undergoes as it becomes domesticated will contribute to understanding the basic biology of this important pathogen.In this study, we performed a parallel serial passage experiment (PSPE) to explore the mechanisms by which Y. pestis adapts to laboratory conditions, hypothesizing that cells would undergo significant changes in virulence and nutrient acquisition systems. Two wild strains were serially passaged in 12 independent populations each for ~750 generations, after which each population was analyzed using whole-genome sequencing, LC-MS/MS proteomic analysis, and GC/MS metabolomics. We observed considerable parallel evolution in the endpoint populations, detecting multiple independent mutations in ail, pepA, and zwf, suggesting that specific selective pressures are shaping evolutionary responses. Complementary LC-MS/MS proteomic data provide physiological context to the observed mutations, and reveal regulatory changes not necessarily associated with specific mutations, including changes in amino acid metabolism and cell envelope biogenesis. Proteomic data support hypotheses generated by genomic data in addition to suggesting future mechanistic studies, indicating that future whole-genome sequencing studies be designed to leverage proteomics as a critical complement.

HmsC, a periplasmic protein, controls biofilm formation via repression of HmsD, a diguanylate cyclase in Yersinia pestis

Yersinia pestis, the cause of plague, forms a biofilm in the foregut of its flea vector to enhance transmission. Biofilm formation in Y. pestis is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP). HmsT and Y3730, the two diguanylate cyclases (DGC) in Y. pestis, are responsible for the synthesis of c-di-GMP. Y3730, which we name here as HmsD, has little effect on in vitro biofilms, but has a major effect on biofilm formation in the flea. The mechanism by which HmsD plays differential roles in vivo and in vitro is not understood. In this study, we show that hmsD is part of a three-gene operon (y3729-31), which we designate as hmsCDE. Deletion of hmsC resulted in increased, hmsD-dependent biofilm formation, while deletion or overexpression of hmsE did not affect biofilm formation. Localization experiments suggest that HmsC resides in the periplasmic space. In addition, we provide evidence that HmsC might interact directly with the periplasmic domain of HmsD and cause the proteolysis of HmsD. We propose that HmsC senses the environmental signals, which in turn regulates HmsD, and controls the c-di-GMP synthesis and biofilm formation in Y. pestis.

Could the ‘Black Death’ Become a Re-Emerging Infectious Disease?

During the optimal time of the ‘Black Death’, in the fourteenth century, around 75 million people globally perished, mainly through lymphadenitis. This manifestation of the plague continued to be a disease of major importance until the seventeenth century and the main regions affected were Europe (where 30–60% of the European population was wiped out) and Asia [2]. The ‘Black Death’ is conventionally known within the medical field as the Bubonic plague (named after the buboes commonly found in the armpits, upper femoral, groin and neck region). Together with the septicemic plague and the pneumonic plague, these infections are caused by the bacterium Yersinia pestis (formerly described as Pasteurella pestis). The bacterium seemingly evolved several thousand years ago from a far more benign, gut dwelling bug called Y. pseudotuberculosi (one of a group of relatively benign intestinal diseases). Y. pestis is a facultative anaerobic Gramnegative rod-shaped bacterium. It is unknown if Y. pestis caused all causes of plague during this period, although it stands as the main the etiologic agent (many of the skeletons exhumed from ‘plague pits’) have been tested using a rapid diagnostic test for the detection of Y. pestis F1 antigen to confirm the cause of their death. The bacterium is what is known as a zoonotic disease, indicating its ability to be transferred between different species. In terms of animal to human transmission, the role of rats and fleas (like Pulex irritans) and their detailed role in the transmission of plague has been discovered and experimentally verified [3]. The disease affects the lungs and is highly contagious, leading to mass outbreaks across populations. Without treatment, the bubonic plague kills about two thirds of infected humans within four days [4]. Those infected with the bacteria develop symptoms that can include swollen, tender lymph glands, fever, headache, chills, and weakness. Other symptoms may include muscle pain and seizures. The human body is generally unsuccessful in fighting the disease because cells of Y. pestis can resist phagocytosis. Other major plague events have occurred around the world over the past centuries and similar discoveries of the remains of some of the victims have been made. In 2012 an archaeological discovery of the last remnants of a “lazaretto” or “lazaret” was made in the city of Marseille. This was a place equipped with an infirmary and destined to isolate ship passengers quarantined for health reasons. It was a major site of a plague outbreak.

Lipopolysaccharide of Yersinia Pestis, the Cause of Plague: Structure, Genetics, Biological Properties

The present review summarizes data pertaining to the composition and structure of the carbohydrate moiety (core oligosaccharide) and lipid component (lipid A) of the various forms of lipopolysaccharide (LPS), one of the major pathogenicity factors ofYersinia pestis, the cause of plague. The review addresses the functions and the biological significance of genes for the biosynthesis of LPS, as well as the biological properties of LPS in strains from various intraspecies groups ofY. pestis and their mutants, including the contribution of LPS to the resistance of bacteria to factors of the innate immunity of both insect-vectors and mammal-hosts. Special attention is paid to temperature-dependent variations in the LPS structure, their genetic control and roles in the pathogenesis of plague. The evolutionary aspect is considered based on a comparison of the structure and genetics of the LPS ofY. pestis and other enteric bacteria, including otherYersinia species. The prospects of development of live plague vaccines created on the basis ofY. pestis strains with the genetically modified LPS are discussed.

Insights from genomic comparisons of genetically monomorphic bacterial pathogens

Some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. It has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. The genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. Some genetically monomorphic lineages have evolved in the last decades, e.g. antibiotic-resistant Staphylococcus aureus, whereas others have evolved over several millennia, e.g. the cause of plague, Yersinia pestis. Based on recent results, it is now possible to reconstruct the sources and the history of pandemic waves of plague by a combined analysis of phylogeographic signals in Y. pestis plus polymorphisms found in ancient DNA. Different from historical accounts based exclusively on human disease, Y. pestis evolved in China, or the vicinity, and has spread globally on multiple occasions. These routes of transmission can be reconstructed from the genealogy, most precisely for the most recent pandemic that was spread from Hong Kong in multiple independent waves in 1894.

Functional characterization and biological significance of Yersinia pestis lipopolysaccharide biosynthesis genes

In silico analysis of available bacterial genomes revealed the phylogenetic proximity levels of enzymes responsible for biosynthesis of lipopolysaccharide (LPS) of Yersinia pestis, the cause of plague, to homologous proteins of closely related Yersinia spp. and some other bacteria (Serratia proteamaculans, Erwinia carotovora, Burkholderia dolosa, Photorhabdus luminescens and others). Isogenic Y. pestis mutants with single or double mutations in 14 genes of LPS biosynthetic pathways were constructed by site-directed mutagenesis on the base of the virulent strain 231 and its attenuated derivative. Using high-resolution electrospray ionization mass spectrometry, the full LPS structures were elucidated in each mutant, and the sequence of monosaccharide transfers in the assembly of the LPS core was inferred. Truncation of the core decreased significantly the resistance of bacteria to normal human serum and polymyxin B, the latter probably as a result of a less efficient incorporation of 4-amino-4-deoxyarabinose into lipid A. Impairing of LPS biosynthesis resulted also in reduction of LPS-dependent enzymatic activities of plasminogen activator and elevation of LD(50) and average survival time in mice and guinea pigs infected with experimental plague. Unraveling correlations between biological properties of bacteria and particular LPS structures may help a better understanding of pathogenesis of plague and implication of appropriate genes as potential molecular targets for treatment of plague.

The serious plague in Kaifeng in the third year of Chunhua of the Northern Song dynasty and the government's response

In the May of the third year of Chunhua (992) of the Northern Song dynasty, because of a long persistent drought and scorching hot day, the plague occurred and prevailed in Kaifeng, the capital of Northern Song, with a massive death toll, drawing much attention from the government. The cause of plague was related to high temperature, summer-heat warmth in TCM. In response to this, the government issued three imperial edicts: firstly, promulgating the formularies; secondly, sending some doctors to cure patient, as well as giving money and medicines. At the same time, the Imperial Medical Academy to preside over treatment and assigned an inner eunuch to be responsible for intendance; the third was sending the emissary to clear up the prison. This policies of the third year of Chunhua brought important effects to the system of prevention and rescue of epidemic disease in Song dynasty, exerting significant influences on the prevention and treatment of infectious diseases in the Song dynasty.

Gamma‐irradiated pCD1‐ Yersinia pestis vaccine is protective: an anti‐LcrV response is not necessary to protect against the plague

Yersinia pestis is the cause of plague and a potential weapon for bioterrorism. We have reported that immunization with lethally‐irradiated Y. pestis Kim5 is protective against subsequent i.v. challenges with the plague. We report here that pCD1‐Y. pestis, lacking the TTSS, provides protection comparable to wild‐type Y. pestis. Both strains provided protection against >107 CFU challenge of wildtype Y. pestis, compared to sham‐vaccinated mice that displayed an LD50 of 1.4X104 CFUs. This finding suggests that LcrV, located on pCD1 and previously shown to provide significant protection, was not essential for protection. A limited number of antibody specificities were generated by the irradiated wildtype or pCD1‐ Y. pestis, 6–8 unique specificities as determined by immunoblotting. The majority of these immunodominant specificities were shown to reside on the outer surface of the bacteria. Although this work has focused on humoral responses, T cell immunodominant epitopes can be rapidly identified with the irradiated vaccine as well. Lethal gamma‐irradiation provides a novel approach for the rapid production of vaccines that have remained elusive. Using a whole cell vaccine also allows for the rapid assessment of the immunodominant “footprint” to the majority of antigens present, aiding in the identification of putative sub‐unit vaccine candidates.

3 Medieval and Modern Bubonic Plague: Some Clinical Continuities

In his book The Black Death transformed,1 Samuel K Cohn claims that the epidemic disease described in western European historical sources from ad 1347 to the mid-seventeenth century under the names plague, pestis, pestilence, plagen and the like must have been a disease other than the modern plague that reached Hong Kong in May 1894 from other parts of China, and later spread first to India and then to all inhabited continents. Alexandre Yersin showed that the disease in Hong Kong was caused by a bacterium, later named Yersinia pestis. It was also Yersin who claimed that he had found not only the cause of plague in China, but also the cause of the medieval and early modern plague epidemics. Four years after the discovery of the bacillus, Paul-Louis Simond proposed the transmission route from the rat (Rattus rattus) via the flea (Xenopsylla cheopis) to humans, although the scientific community was not fully convinced until ten years later, since this hypothesis did not explain all observations. The problems with the hypothesis were forgotten, which is easy to understand when we remember that the doctors and epidemiologists who were working in India at that time were facing a worsening and very serious epidemic. The simple preventive message to public health workers and the public was: exterminate the rats. The identification of medieval plague as the same disease as modern plague was accepted within thirty years, first by medical scientists and later by historians. Cohn writes, “Without argument, historians and scientists have taken the epidemiology of the modern plague and imposed it on the past, ignoring, denying, even changing contemporary testimony, both narrative and quantitative, when it conflicts with notions of how modern bubonic plague should behave.”2 I agree to some extent with Cohn's criticism of how historians have imposed a modern understanding of plague epidemics in India on historical epidemics, and especially how historians have invented large populations of rats in the medieval towns and countryside of northern Europe without any support from contemporary historical sources or archaeology.3 However, I strongly disagree with his main point, which is that the medieval and modern plague epidemics must have involved different diseases in medical and bacteriological terms. Thus, I argue that Yersinia pestis is the cause of both medieval bubonic plague and modern bubonic plague, and that the symptoms, signs, pathology and pathophysiology are very similar. On the other hand, the two series may have differed in speed of transmission, population mortality and some other epidemiological characteristics because of differences in climate, housing conditions, the availability and population density of flea species and other possible insect vectors, and the availability of susceptible mammals other than rats. Cohn's main arguments are as follows: There is a lack of evidence of involvement of rats and fleas (Xenopsylla cheopis) in late-medieval/early-modern plagues. The speed of transmission is different (medieval being rapid, modern being slow). The mortality and the age and sex distribution of victims are different (e.g. high mortality in Europe in medieval times, low mortality in modern times in India). Acquired immunity is different (long-lasting immunity in medieval times, no lasting immunity in modern times). The signs and symptoms are different (e.g., boils mainly in the neck and armpits in medieval plagues, and in the groin in modern plague). Cohn also claims that when Yersin and his contemporary medical doctors identified plague in Hong Kong with late medieval and early modern plague epidemics, no recent medical knowledge about plague was available to European doctors, and that the medical information available dated back to the last plague epidemic in London in 16654 or to earlier epidemics, even though it was generally known that there had been epidemics of plague in 1722 in Marseilles, in 1743 in Messina and in 1771–2 in Moscow.

Immune Cell Apoptosis Prevention as Potential Therapy for Severe Infections

Some labile cell types whose numbers are normally controlled through programmed cell death are subject to markedly increased destruction during some severe infections. Lymphocytes, in particular, undergo massive and apparently unregulated apoptosis in human patients and laboratory animals with sepsis, potentially playing a major role in the severe immunosuppression that characterizes the terminal phase of fatal illness. Extensive lymphocyte apoptosis has also occurred in humans and animals infected with several exotic agents, including Bacillus anthracis, the cause of anthrax; Yersinia pestis, the cause of plague; and Ebola virus. Prevention of lymphocyte apoptosis, through either genetic modification of the host or treatment with specific inhibitors, markedly improves survival in murine sepsis models. These findings suggest that interventions aimed at reducing the extent of immune cell apoptosis could improve outcomes for a variety of severe human infections, including those caused by emerging pathogens and bioterrorism agents.