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.
METHODS: 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.
CONCLUSIONS: 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.

BACKGROUND: Plague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent populations in Africa, Asia, North America, and South America but human plague is rare in most of these locations. However, human plague is still highly prevalent in Madagascar, which typically records a significant part of all annual global cases. This has afforded an opportunity to study contemporary human plague in detail using various typing methods for Y. pestis.
OBJECTIVE: This review aims to summarize the methods that have been used to type Y. pestis in Madagascar along with the major discoveries that have been made using these approaches.
METHODS: Pubmed and Google Scholar were used to search for the keywords: \"typing Yersinia pestis Madagascar,\" \"evolution Yersinia pestis Madagascar,\" and \"diversity Yersinia pestis Madagascar.\" Eleven publications were relevant to our topic and further information was retrieved from references cited in those publications.
RESULTS: The history of Y. pestis typing in Madagascar can be divided in 2 periods: the pre-genomics and genomics eras. During the pre-genomics era, ribotyping, direct observation of plasmid content and plasmid restriction fragment length polymorphisms (RFLP) were employed but only revealed a limited amount of diversity among Malagasy Y. pestis strains. Extensive diversity only started to be revealed in the genomics era with the use of clustered regularly interspaced palindromic repeats (CRISPR), multiple-locus variable number tandem repeats (VNTR) analysis (MLVA), and single-nucleotide polymorphisms (SNPs) discovered from whole genome sequences. These higher-resolution genotyping methods have made it possible to highlight the distribution and persistence of genotypes in the different plague foci of Madagascar (Mahajanga and the Central and Northern Highlands) by genotyping strains from the same locations across years, to detect transfers between foci, to date the emergence of genotypes, and even to document the transmission of antimicrobial resistant (AMR) strains during a pneumonic plague outbreak. Despite these discoveries, there still remain topics that deserve to be explored, such as the contribution of horizontal gene transfer to the evolution of Malagasy Y. pestis strains and the evolutionary history of Y. pestis in Madagascar.
CONCLUSIONS: Genotyping of Y. pestis has yielded important insights on plague in Madagascar, particularly since the advent of whole-genome sequencing (WGS). These include a better understanding of plague persistence in the environment, antimicrobial AMR and multi-drug resistance in Y. pestis, and the person-to-person spread of pneumonic plague. Considering that human plague is still a significant public health threat in Madagascar, these insights can be useful for controlling and preventing human plague in Madagascar and elsewhere, and also are relevant for understanding the historical pandemics and the possible use of Y. pestis as a biological weapon.

Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents.

Plague remains endemic in many parts of the world, and despite efforts, no preventative vaccine is available. We performed a systemic review of available randomised controlled trials (RCTs) of live, attenuated, or killed plague vaccines vs. placebo, no intervention, or other plague vaccine to evaluate their efficacy, safety, and immunogenicity. Data sources included MEDLINE, Embase, and the Cochrane Library; clinical trial registers; and reference lists of included studies. Primary outcomes were efficacy, safety, and immunogenicity. Risk of bias was assessed using the Cochrane Collaborations tool. Only 2 RCTs, both on subunit vaccines, were included out of the 75 screened articles. The 2 trials included 240 participants with a follow-up of 3 months and 60 participants with a follow-up of 13 months, respectively. Safety evidence was limited, but both vaccines were well tolerated, with only mild to moderate adverse events. Both vaccines were immunogenic in a dose-dependent manner. However, given the limited data identified in this systematic review, we are unable to quantify the efficacy of vaccines to prevent plague, as well as their long-term safety and immunogenicity. More trials of plague vaccines are needed to generate additional evidence of their long-term effects.

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.

Plague meningitis is a serious and often fatal manifestation of Yersinia pestis infection. In the aftermath of a bioweapon attack with Y pestis, this typically rare manifestation may develop in a substantial number of patients, particularly if treatment delays occur. Risk factors, clinical evolution, and optimal treatment strategies for plague meningitis are not well understood. We searched PubMed Central and other databases for reports of plague meningitis in any language. Articles containing descriptions of patients with plague meningitis and their treatment and outcomes were included. Among 1,496 articles identified in our search, 56 articles describing 84 cases from 1898 to 2015 met inclusion criteria. The median age of patients was 16 years (range 6 weeks to 64 years); 68% were male. Most patients (n = 50, 60%) developed meningitis following primary bubonic plague. Common signs and symptoms included fever (n = 56, 66%), nuchal rigidity (n = 38, 45%), and headache (n = 33, 36%); 29% (n = 24) of patients had focal neurologic deficits such as cranial nerve abnormalities. Almost all (n = 23, 96%) of the 24 patients who did not receive antimicrobials died, and 42% (n = 25) of the 59 patients treated with antimicrobials died. The case fatality rate of patients grouped by antimicrobial received was 50% (1 out of 2) for fluoroquinolones, 19% (4 out of 21) for aminoglycosides, 14% (2 out of 14) for sulfonamides, 11% (2 out of 18) for chloramphenicol, and 0% (0 out of 13) for tetracyclines. Plague meningitis most often occurs as a complication of bubonic plague and can cause focal neurologic deficits. Survival is more likely in patients who receive antimicrobials; tetracyclines, aminoglycosides, and chloramphenicol had the lowest associated case fatality rates.

Plague is an acute bacterial infection caused by Yersinia pestis. The three major clinical forms of plague are bubonic, pneumonic and septicemic, which have high case-mortality rates. Therefore, rapid and reliable diagnostic tools are crucial. Currently, bacteriological means and traditional serological assays are used for detecting infection with Y. pestis. However, such methods have their limitations. Polymerase chain reaction (PCR) is one of the most useful tools for rapid diagnosis of plague. The present review introduced the main PCR techniques and their applications for detecting and confirmation of Y. pestis. The advantages and disadvantages of the different PCR methods were also summarized.

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.

Plague-a deadly disease caused by the bacterium Yersinia pestis-is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.

Yersinia pestis continues to cause sporadic cases and outbreaks of plague worldwide and is considered a tier 1 bioterrorism select agent due to its potential for intentional use. Knowledge about the clinical manifestations of plague during pregnancy, specifically the maternal, fetal, and neonatal risks, is very limited.
We searched 12 literature databases, performed hand searches, and consulted plague experts to identify publications on plague during pregnancy. Articles were included if they reported a case of plague during pregnancy and at least 1 maternal or fetal outcome.
Our search identified 6425 articles, of which 59 were eligible for inclusion and described 160 cases of plague among pregnant women. Most published cases occurred during the preantibiotic era. Among those treated with antimicrobials, the most commonly used were sulfonamides (75%) and streptomycin (54%). Among cases treated with antimicrobials, maternal mortality and fetal fatality were 29% and 62%, respectively; for untreated cases, maternal mortality and fetal fatality were 67% and 74%, respectively. Five cases demonstrated evidence of Y. pestis in fetal or neonatal tissues.
Untreated Y. pestis infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss. Appropriate antimicrobial treatment can improve maternal survival, although even with antimicrobial treatment, there remains a high risk of pregnancy loss. Limited evidence suggests that maternal-fetal transmission of Y. pestis is possible, particularly in the absence of antimicrobial treatment. These results emphasize the need to treat or prophylax pregnant women with suspected plague with highly effective antimicrobials as quickly as possible.