Multiple Introductions of Yersinia pestis during Urban Pneumonic Plague Epidemic, Madagascar, 2017.

Pneumonic plague (PP) is characterized by high infection rate, person-to-person transmission, and rapid progression to severe disease. In 2017, a PP epidemic occurred in 2 Madagascar urban areas, Antananarivo and Toamasina. We used epidemiologic data and Yersinia pestis genomic characterization to determine the sources of this epidemic. Human plague emerged independently from environmental reservoirs in rural endemic foci >20 times during August-November 2017. Confirmed cases from 5 emergences, including 4 PP cases, were documented in urban areas. Epidemiologic and genetic analyses of cases associated with the first emergence event to reach urban areas confirmed that transmission started in August; spread to Antananarivo, Toamasina, and other locations; and persisted in Antananarivo until at least mid-November. Two other Y. pestis lineages may have caused persistent PP transmission chains in Antananarivo. Multiple Y. pestis lineages were independently introduced to urban areas from several rural foci via travel of infected persons during the epidemic.

Surveillance of Fleas and Their Small Mammal Hosts for Plague Risks in Some Main Seaports of the Islands of the Southwestern Indian Ocean.

Since ancient times, seaports have been the hot spots for plague introduction into free countries. Infected ship rats reached new areas, and epizootics occurred prior to human infection via flea bites. Beginning in the 1920s/1930s, rodent and flea surveillance was carried out as part of plague hazard management in seaports of the world. Nowadays, such activity is not done regularly. In the southwestern Indian Ocean (SWIO) region, plague surveillance is of great importance given plague endemicity in Madagascar and thus the incurred risk for neighboring islands. This study reports animal-based surveillance aimed at identifying fleas and their small mammal hosts in SWIO seaports as well as Yersinia pestis detection. Small mammal trappings were performed in five main seaports of Madagascar (Toamasina and Mahajanga), Mauritius (Port Louis), and the Union of Comoros (Moroni and Mutsamudu). Mammals were euthanized and their fleas collected and morphologically identified before Y. pestis detection. In total, 145 mammals were trapped: the brown rat Rattus norvegicus (76.5%), the black rat Rattus rattus (8.3%), and the Asian house shrew Suncus murinus (15.2%). Fur brushing allowed collection of 1,596 fleas exclusively identified as Xenopsylla cheopis. All tested fleas were negative for Y. pestis DNA. This study shows that both well-known plague mammal hosts and flea vectors occur in SWIO seaports. It also highlights the necessity of carrying out regular animal-based surveillance for plague hazard management in this region.

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.

The surveillance of plague among rodents and dogs in Western Iran.

BACKGROUND: The causative agent of plague, Yersinia pestis, is maintained in nature via a flea-rodent cycle. Western Iran is an old focus for plague, and recent data indicate that rodents and dogs in this region have serological evidence of Y. pestis infection. The purpose of this study was to conduct a large-scale investigation of Y. pestis infection in shepherd dogs, rodents, and their fleas in old foci for plague in Western Iran. MATERIALS AND METHODS: This study was conducted in Hamadan province from 2014 to 2020. Rodents and fleas were collected from various locations throughout this region. Y. pestis was investigated in rodent spleen samples and fleas using culture, serology, and real-time PCR methods. Additionally, sera samples were collected from carnivores and hares in this region, and the IgG antibody against the Y. pestis F1 antigen was assessed using an ELISA. RESULTS: In this study, 927 rodents were captured, with Meriones spp. (91.8%) and Microtus qazvinensis (2.6%) being the most prevalent. A total of 6051 fleas were collected from rodents and carnivores, most of which were isolated from Meriones persicus. None of the rodents or fleas examined tested positive for Y. pestis using real-time PCR and culture methods. Meanwhile, IgG antibodies were detected in 0.32% of rodents. All serologically positive rodents belonged to M. persicus. Furthermore, none of the sera from the 138 carnivores (129 sheepdogs, five Vulpes vulpes, four Canis aureus), and nine hares tested positive in the ELISA test. CONCLUSION: This primary survey of rodent reservoirs shows serological evidence of Y. pestis infection. Western Iran is an endemic plague focus, and as such, it requires ongoing surveillance.

Learning from history in the midst of the COVID-19: epidemics/pandemics of antiquity up to the fall of the Western Roman Empire.

When humans discovered agriculture and livestock, they ceased to be nomads and began to settle in towns until they created large cities. From the first human settlements in Egypt, Mesopotamia, and the Anatolian Peninsula, populations were exposed and susceptible to new infectious agents, leading to epidemics and pandemics. Great civilizations emerged, such as Egypt, the land of Hatti, Israel, Greece, Carthage, and Rome, among others. Contact between different populations through wars or maritime trade is well documented and has been described as a source of epidemics throughout history. Epidemics described as plagues or pestilences, such as those of Egypt, the Hebrews, or the Hittites, are based on biblical texts or evidence such as tablets or hieroglyphic writings. We also reviewed classical books by authors such as Homer, Aeschylus, Herodotus of Halicarnassus, Thucydides, Diodorus Siculus, Dionysius of Halicarnassus, Titus Livius, Suetonius, and others; and described all epidemics/pandemics chronologically. This article describes the epidemics/pandemics for which there is written evidence from ancient Egypt to the fall of the Roman Empire. We should not be surprised when new epidemics/pandemics appear as causes of political and economic collapse, as this has been common throughout history, decimating, blocking, or even destroying cultures and civilizations repeatedly.

Cuando el hombre descubrió la agricultura y la ganadería, dejó de ser nómada y empezó a asentarse en pueblos hasta crear grandes ciudades. Desde los primeros asentamientos humanos en Egipto, Mesopotamia y la península de Anatolia, las poblaciones estuvieron expuestas y susceptibles a nuevos agentes infecciosos, dando lugar a epidemias y pandemias. Aparecieron grandes civilizaciones como Egipto, la Tierra de Hatti, Israel, Grecia, Cartago y Roma, entre otras. El contacto entre las distintas poblaciones a través de las guerras o el comercio marítimo está muy bien establecido y descrito como focos de epidemias a lo largo de la historia. Las epidemias descritas como plagas o pestilencias, como las que ocurrieron a los egipcios, los judíos, o los hititas, se describen con base en textos bíblicos o mediante evidencias como tablillas o escritos jeroglíficos. También revisamos libros clásicos de autores como Homero, Esquilo, Herodoto de Halicarnaso, Tucídides, Diodoro Sículo, Dionisio de Halicarnaso, Tito Livio, Suetonio, entre otros. Este artículo describe cronológicamente todas las epidemias/pandemias de las que existe evidencia a través de la escritura desde el antiguo Egipto hasta la caída del Imperio Romano. No debemos sorprendernos cuando aparecen nuevas epidemias/pandemias como causantes del colapso político y económico, ya que ha sido algo común a lo largo de la historia, diezmando, bloqueando o incluso destruyendo culturas y civilizaciones reiteradamente.

Tuberculosis before and after the Black Death (1346-1353 CE) in the Hospital of St John the Evangelist in Cambridge, England.

This research explores how the prevalence of tuberculosis (TB) in a medieval hospital was affected by the demographic and social changes that following the Black Death (1346-1353 CE), the initial years of the Second Plague Pandemic. To do this, skeletal remains of individuals buried at the Hospital of St John the Evangelist in Cambridge, England, that could be dated to living before (n = 77) or after (n = 55) the Black Death were assessed for evidence of TB (indicated by destructive lesions of the spine, ribs, large joints, and other recognised criteria). Overall, the odds of females having skeletal lesions caused by TB were over four times higher than males. No significant difference was detected in the prevalence rates in those who lived before and after the Black Death (7.8%, 6/77 before and 11.0%, 6/55 after). However, the odds of females having skeletal evidence of TB were over five times greater after the Black Death than they were before. These findings indicate that women may have been 1) more susceptible to TB, 2) surviving longer post-infection than men, and/or 3) that women with TB were more likely to be admitted to the Hospital especially following the Black Death. It is also possible that impairment due to TB infection may have been a contributing factor for entry into the Hospital for women but not men.

Immunogenetics, sylvatic plague and its vectors: insights from the pathogen reservoir Mastomys natalensis in Tanzania.

Yersinia pestis is a historically important vector-borne pathogen causing plague in humans and other mammals. Contemporary zoonotic infections with Y. pestis still occur in sub-Saharan Africa, including Tanzania and Madagascar, but receive relatively little attention. Thus, the role of wildlife reservoirs in maintaining sylvatic plague and spillover risks to humans is largely unknown. The multimammate rodent Mastomys natalensis is the most abundant and widespread rodent in peri-domestic areas in Tanzania, where it plays a major role as a Y. pestis reservoir in endemic foci. Yet, how M. natalensis' immunogenetics contributes to the maintenance of plague has not been investigated to date. Here, we surveyed wild M. natalensis for Y. pestis vectors, i.e., fleas, and tested for the presence of antibodies against Y. pestis using enzyme-linked immunosorbent assays (ELISA) in areas known to be endemic or without previous records of Y. pestis in Tanzania. We characterized the allelic and functional (i.e., supertype) diversity of the major histocompatibility complex (MHC class II) of M. natalensis and investigated links to Y. pestis vectors and infections. We detected antibodies against Y. pestis in rodents inhabiting both endemic areas and areas considered non-endemic. Of the 111 nucleotide MHC alleles, only DRB*016 was associated with an increased infestation with the flea Xenopsylla. Surprisingly, we found no link between MHC alleles or supertypes and antibodies of Y. pestis. Our findings hint, however, at local adaptations towards Y. pestis vectors, an observation that more exhaustive sampling could unwind in the future.

Engagement with Traditional Healers for Early Detection of Plague in Uganda.

In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.

Comparative sequence analysis elucidates the evolutionary patterns of Yersinia pestis in New Mexico over thirty-two years.

Background: Yersinia pestis, a Gram-negative bacterium, is the causative agent of plague. Y. pestis is a zoonotic pathogen that occasionally infects humans and became endemic in the western United States after spreading from California in 1899. Methods: To better understand evolutionary patterns in Y. pestis from the southwestern United States, we sequenced and analyzed 22 novel genomes from New Mexico. Analytical methods included, assembly, multiple sequences alignment, phylogenetic tree reconstruction, genotype-phenotype correlation, and selection pressure. Results: We identified four genes, including Yscp and locus tag YPO3944, which contained codons undergoing negative selection. We also observed 42 nucleotide sites displaying a statistically significant skew in the observed residue distribution based on the year of isolation. Overall, the three genes with the most statistically significant variations that associated with metadata for these isolates were sapA, fliC, and argD. Phylogenetic analyses point to a single introduction of Y. pestis into the United States with two subsequent, independent movements into New Mexico. Taken together, these analyses shed light on the evolutionary history of this pathogen in the southwestern US over a focused time range and confirm a single origin and introduction into North America.

Socioenvironmental determinants as indicators of plague risk in the central highlands of Madagascar: Experience of Ambositra and Tsiroanomandidy districts.

BACKGROUND: Human plague cases are reported annually in the central highland regions of Madagascar, where the disease is endemic. The socioenvironmental characteristics and lifestyles of the populations of the central highland localities could be linked to this endemicity. The aim of this study was to determine socioenvironmental determinants that may be associated with plague risk and explain this variation in epidemiological contexts. METHODS: The current study was based on the distribution of plague cases between 2006 and 2015 that occurred in localities of districts positioned in the central highlands. Household surveys were performed from June to August 2017 using a questionnaire and direct observations on the socioenvironmental aspects of households in selected localities. Bivariate and multivariate analyses were performed to highlight the socioenvironmental parameters associated with plague risk in both districts. RESULTS: A total of 503 households were surveyed, of which 54.9% (276/503) were in Ambositra and 45.1% (227/503) were in Tsiroanomandidy. Multivariate analyses showed that thatched roofs [adjusted odds ratio (AOR): 2.63; 95% confidence interval (95% CI): 1.78-3.88] and ground floor houses [AOR: 2.11; 95% CI: 1.3-3.45-] were significantly associated with the vulnerability of a household to plague risk (p value<0.05). CONCLUSIONS: Plague risk in two districts of the Malagasy central highlands is associated with human socioenvironmental characteristics. Socioenvironmental characteristics are parameters expressing spatial heterogeneity through the difference in epidemiological expression of the plague in Ambositra and Tsiroanomandidy. These characteristics could be used as indicators of vulnerability to plague risk in plague-endemic areas.

Plague Gives Surprises in the Second Decade of the Twenty-First Century.

From 2010 through 2019, the six leading countries by numbers of human plague cases reported to the WHO were, in order from highest to lowest, Madagascar, Congo, Uganda, Peru, Tanzania, and the United States. From these countries, there was a total of 4,547 cases, of whom 786 (17%) died. Top plague events were four outbreaks of primary pneumonic plague in Madagascar that affected 1,936 persons, including index cases, of whom 137 died. One of the outbreaks was caused by a streptomycin-resistant strain of Yersinia pestis. Person-to-person transmission occurred in a taxi, in households with family caregivers, at burial ceremonies and wakes for victims, and at a hospital where cases were treated. Unique clinical presentations in the United States included a dog owner who acquired pneumonic plague from his sick dog, a boy with septicemic plague who developed complications of osteomyelitis and arthritis that required surgery for bone removal and bone grafting, and a prairie dog handler who acquired bubonic plague from a bite by a sick prairie dog. Efficacy of antibiotics in a model of pneumonic plague in African green monkeys for use in bioterrorism revealed the most effective drugs to be gentamicin, ciprofloxacin, and levofloxacin. A recombinant vaccine containing Fraction 1 antigen and V antigen of Y. pestis designed for first responders during a bioterrorism attack and military personnel was tested for safety and immunogenicity but was not licensed for use by the end of the decade.

Genomic diversity of Yersinia pestis from Yunnan Province, China, implies a potential common ancestor as the source of two plague epidemics.

Plague, caused by Yersinia pestis, is a zoonotic disease that can reemerge and cause outbreaks following decades of latency in natural plague foci. However, the genetic diversity and spread pattern of Y. pestis during these epidemic-silent cycles remain unclear. In this study, we analyze 356 Y. pestis genomes isolated between 1952 and 2016 in the Yunnan Rattus tanezumi plague focus, China, covering two epidemic-silent cycles. Through high-resolution genomic epidemiological analysis, we find that 96% of Y. pestis genomes belong to phylogroup 1.ORI2 and are subdivided into two sister clades (Sublineage1 and Sublineage2) characterized by different temporal-spatial distributions and genetic diversity. Most of the Sublineage1 strains are isolated from the first epidemic-silent cycle, while Sublineage2 strains are predominantly from the second cycle and revealing a west to east spread. The two sister clades evolved in parallel from a common ancestor and independently lead to two separate epidemics, confirming that the pathogen responsible for the second epidemic following the silent interval is not a descendant of the causative strain of the first epidemic. Our results provide a mechanism for defining epidemic-silent cycles in natural plague foci, which is valuable in the prevention and control of future plague outbreaks.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y. pestis strains in this region remain unknown. Here, we performed high-resolution genomic epidemiological analysis of 175 Y. pestis strains isolated from five counties and 19 towns in DH between 1953 and 2007. Phylogenetic analysis revealed that most DH strains were located in lineage 1.ORI2, which could be further subdivided into seven sub-phylogroups (SPG1-SPG7). The dominant sub-phylogroups of Y. pestis in DH varied during different periods and presented a population shift. Genomic evidence showed that plague might have emerged from the southwest of DH (e.g., Longchuan or Ruili counties) or its bordering countries, and subsequently spread to the northeast in multiple waves between 1982 and 2007. Our study infers a fine-scale phylogeny and spread pattern of the DH Y. pestis population, which extends our knowledge regarding its genetic diversity and provides clues for the future prevention and control of plague in this region.

14th century Yersinia pestis genomes support emergence of pestis secunda within Europe.

Pestis secunda (1356-1366 CE) is the first of a series of plague outbreaks in Europe that followed the Black Death (1346-1353 CE). Collectively this period is called the Second Pandemic. From a genomic perspective, the majority of post-Black Death strains of Yersinia pestis thus far identified in Europe display diversity accumulated over a period of centuries that form a terminal sub-branch of the Y. pestis phylogeny. It has been debated if these strains arose from local evolution of Y. pestis or if the disease was repeatedly reintroduced from an external source. Plague lineages descended from the pestis secunda, however, are thought to have persisted in non-human reservoirs outside Europe, where they eventually gave rise to the Third Pandemic (19th and 20th centuries). Resolution of competing hypotheses on the origins of the many post-Black Death outbreaks has been hindered in part by the low representation of Y. pestis genomes in archaeological specimens, especially for the pestis secunda. Here we report on five individuals from Germany that were infected with lineages of plague associated with the pestis secunda. For the two genomes of high coverage, one groups within the known diversity of genotypes associated with the pestis secunda, while the second carries an ancestral genotype that places it earlier. Through consideration of historical sources that explore first documentation of the pandemic in today's Central Germany, we argue that these data provide robust evidence to support a post-Black Death evolution of the pathogen within Europe rather than a re-introduction from outside. Additionally, we demonstrate retrievability of Y. pestis DNA in post-cranial remains and highlight the importance of hypothesis-free pathogen screening approaches in evaluations of archaeological samples.

Ancient Yersinia pestis genomes lack the virulence-associated YpfΦ prophage present in modern pandemic strains.

Yersinia pestis is the causative agent of at least three major plague pandemics (Justinianic, Medieval and Modern). Previous studies on ancient Y. pestis genomes revealed that several genomic alterations had occurred approximately 5000-3000 years ago and contributed to the remarkable virulence of this pathogen. How a subset of strains evolved to cause the Modern pandemic is less well-understood. Here, we examined the virulence-associated prophage (YpfΦ), which had been postulated to be exclusively present in the genomes of strains associated with the Modern pandemic. The analysis of two new Y. pestis genomes from medieval/early modern Denmark confirmed that the phage is absent from the genome of strains dating to this time period. An extended comparative genome analysis of over 300 strains spanning more than 5000 years showed that the prophage is found in the genomes of modern strains only and suggests an integration into the genome during recent Y. pestis evolution. The phage-encoded Zot protein showed structural homology to a virulence factor of Vibrio cholerae. Similar to modern Y. pestis, we observed phages with a common origin to YpfΦ in individual strains of other bacterial species. Our findings present an updated view on the prevalence of YpfΦ, which might contribute to our understanding of the host spectrum, geographical spread and virulence of Y. pestis responsible for the Modern pandemic.

Natural foci of plague in Kazakhstan in the space-time continuum.

The relevance of the problem of the stated topic lies in the fact that the causative agent of the plague infection demonstrates high survival while maintaining high virulence in the territories, which are enzootic in terms of the plague. The study aimed to investigate the geographic distribution and genetic diversity of the plague pathogen in endemic regions through molecular genetic research. The work included the results of laboratory studies of 3058 samples, including soil - 1154, burrow substrates - 549, the contents of the feeding chamber - 349, bone remains - 18, biological objects - 988 samples of sera and suspensions from carriers and vectors of plague infection collected from 14 autonomous plague foci of Kazakhstan for the period 2021-2022. The leading method in the study was a laboratory experiment, thanks to which, using a new advanced technology on a microbiological analyser VITEK 2 COMPACT 30, it was possible to study pathogenic and non-pathogenic strains of the genus Yersinia isolated during field experiment. As a result of experimental work, it was shown that during a long inter-epizootic period, the plague pathogen can persist in the soil in symbiosis with soil microorganisms, and in this area, it chooses soil with a low-quality index of 10 points, where soils with a low total microbial number and species landscape prevail.

Climate-driven marmot-plague dynamics in Mongolia and China.

The incidence of plague has rebounded in the Americas, Asia, and Africa alongside rapid globalization and climate change. Previous studies have shown local climate to have significant nonlinear effects on plague dynamics among rodent communities. We analyzed an 18-year database of plague, spanning 1998 to 2015, in the foci of Mongolia and China to trace the associations between marmot plague and climate factors. Our results suggested a density-dependent effect of precipitation and a geographic location-dependent effect of temperature on marmot plague. That is, a significantly positive relationship was evident between risk of plague and precipitation only when the marmot density exceeded a certain threshold. The geographical heterogeneity of the temperature effect and the contrasting slopes of influence for the Qinghai-Tibet Plateau (QTP) and other regions in the study (nQTP) were primarily related to diversity of climate and landscape types.

A Perilous Combination: Streptococcus Coinfection with Human Plague-Report of Two Cases and Review of the Literature, 1937-2022.

Background: Plague in humans and animals is caused by Yersinia pestis, a zoonotic gram-negative bacterium endemic in certain regions of Asia, Africa, and the United States. Coinfection with both Y. pestis and Streptococci species has been anecdotally reported in humans and associated with severe and rapidly fatal disease. Methods: This report presents two cases of patients who died following Y. pestis and Streptococcus coinfection. Additional cases of previously published Y. pestis-Streptococcus coinfection were identified and reviewed using a search of electronic databases. Results: The first case patient developed cough and dyspnea following 4 days of fever, malaise, and back pain and died before receiving medical care. Postmortem blood cultures were positive for Y. pestis, Streptococcus pyogenes, and Streptococcus dysgalactiae. The second case patient was hospitalized with fever, vomiting, diarrhea, and dyspnea and died of sepsis and respiratory failure on the day of admission. Y. pestis and Streptococcus pneumoniae were isolated from blood cultures drawn on admission. Seven additional cases of Y. pestis and Streptococcus coinfection were identified, dating between 1948 and 2009. These patients were healthy overall before their illness, with ages ranging from 9 to 60 years. The majority of patients had primary bubonic plague with associated pneumonia or septicemia. None of the patients who died received timely antimicrobial therapy directed against gram-negative pathogens. In every case but one, an occupational or environmental risk factor for plague was later identified. Conclusion: Y. pestis infection begins with a pre-inflammatory phase, during which Y. pestis and other pathogens can rapidly proliferate. Streptococci, which are frequently asymptomatic colonizers, may become invasive in this environment, leading to coinfection. The challenges of diagnosing Y. pestis in the context of coinfection may delay effective treatment. This case series and literature review illustrate the importance of clinicians remaining alert to environmental and occupational exposures in patients presenting with an infectious syndrome, especially in those who have an unexpectedly severe clinical presentation.