Materiały źródłowe

• #1 Plague: Recognition, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5744195/

  For a presumptive case, the above-described clinical and epidemiological manifestations should be observed. […] For a confirmed case, in addition to meeting the criteria of a suspected case, the patient should meet the following criteria: Y. pestis isolated from bubo aspirate, blood, or sputum; Y. pestis identified by morphological, biochemical, phage lysis, F1 antigen detection, and PCR tests; and 4-fold increase in anti-F1 antibody titer in paired serum samples. […] The gold standard for plague diagnosis in the laboratory is the isolation and identification of the plague pathogen from clinical specimens. […] The keys to the successful treatment of plague are early recognition and timely administration of effective antibiotics. […] Most Y. pestis isolates worldwide are sensitive to streptomycin; however, a multidrug-resistant (MDR) strain was isolated from Madagascar.

• #1 Clinical Testing and Diagnosis for Plague | Plague | CDC

  https://www.cdc.gov/plague/hcp/diagnosis-testing/index.html

  Plague should be considered in any patient with clinical signs of plague and a recent history of residence in or travel to the western United States or other plague endemic areas. […] If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. Local and state health departments should be notified immediately. […] DO NOT WAIT FOR DIAGNOSTIC TEST RESULTS IF YOU SUSPECT PLAGUE. […] The decision to initiate antibiotic therapy for plague should be made based on clinical signs and symptoms and a careful patient history. […] If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. […] Microscopic examination of Gram, Wright, Giemsa, or Wayson’s stained smears of peripheral blood, lymph node specimen, or sputum may yield evidence of Y. pestis infection.

• #1 Diagnosing Plague | Plague | CDC

  https://www.cdc.gov/plague/diagnosis-testing/index.html

  If you live or have recently traveled to the western U.S. or any other plague endemic area and have symptoms suggestive of plague, seek health care immediately. […] Diagnosis is made by taking samples from the patient, especially blood or part of a swollen lymph gland, and submitting them for laboratory testing. […] Plague is a plausible diagnosis for people who are sick and live in, or have recently traveled to, the western United States or any other plague-endemic area. […] A known flea bite or the presence of a bubo may help a doctor to consider plague as a cause of the illness. […] Diagnosis is made by taking samples from the patient, especially blood or part of a swollen lymph gland, and submitting them for laboratory testing. […] If plague is strongly suspected as the cause of illness, antibiotic treatment should begin as soon as samples are collected, without waiting for the final results. […] Plague is a very serious illness but treatable with commonly available antibiotics. […] The earlier a patient seeks medical care and receives treatment that is appropriate for plague, the better their chances are of a full recovery.

• #1 Plague Differential Diagnoses

  https://emedicine.medscape.com/article/235627-differential

  In 2014, an automated system in a Colorado hospital laboratory mistakenly identified a serum isolate as Pseudomonas luteola. Upon further examination, the organism was correctly identified as Y pestis. […] Diagnosis is made by detecting the organism from involved sites, but treatment should not be delayed pending a microbiologic diagnosis when plague is clinically suspected. The organism can be isolated from lymph node aspirates, blood, sputum, and other sites. Gram stain classically demonstrates gram negative organisms with a safety pin morphology. Diagnosis also may be supported by direct fluorescent antibody or PCR testing. Serologic testing may be done, but it requires both acute and convalescent antibody testing. […] An important clinical clue for diagnosing plague is a history of contact with animals from an endemic plague focus, especially dead rodents or other wild animals known to harbor the bacterium.

• #1 Plague: Recognition, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5744195/

  Plague is caused by Yersinia pestis and is not commonly encountered in clinics, although natural plague foci are widely distributed around the world. […] A neglected diagnosis will cause severe consequences. […] This review intends to provide practical information for clinical staff to recognize plague early and provide effective treatment and prevention. […] According to the World Health Organization guideline, plague can be diagnosed as a suspected, presumptive, or confirmed case based on different kinds of evidence. […] For a suspected case, compatible clinical symptoms and signs should always be accompanied by typical epidemiological features, including a trip to an area endemic for the disease within 10 days before the onset of symptoms and signs or residence in such an area, exposure to plague patients or infected animals, and/or obvious history of flea bites.

• #1 Clinical Testing and Diagnosis for Plague | Plague | CDC

  https://www.cdc.gov/plague/hcp/diagnosis-testing/index.html

  Blood cultures are a sensitive means of isolating Y. pestis. […] If cultures yield negative results and plague is still suspected, serologic testing is possible to confirm the diagnosis. […] Plague should be considered in any patient with clinical signs of plague and a recent history of residence in or travel to the western United States or other plague endemic areas. […] Bubonic plague is the most common primary manifestation, with a bubo usually occurring in the groin, axilla, or cervical nodes. […] If plague is suspected, local and state health departments should be notified immediately. […] If the patient has signs of pneumonic plague, they should also be isolated and placed on droplet precautions to reduce the risk of person-to-person transmission of plague. […] If plague is suspected, local and state health departments should be notified immediately.

• #1

  https://www.cbsnews.com/news/plague-what-to-know-symptoms-transmission/

  A human case of the plague has appeared in Pueblo County, Colorado, according to preliminary test results. It is the first case in the state since a child from La Plata County died in 2021. […] Plague is a disease caused by Yersinia pestis, a bacterium found in rodents and their fleas. […] People typically get the plague after being bitten by an inflected flea or handling an infected animal, according to the CDC. […] Health officials say symptoms of plague usually start to appear two to eight days after a person was exposed to an infected animal or flea. […] Symptoms depend on what type of plague someone is infected with. […] Bubonic plague: A key symptom is painful, swollen lymph nodes in the groin or armpits, called buboes. Other common symptoms include fever, weakness, coughing and chills.

• #1 Plague – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/plague/diagnosis-treatment/drc-20351297

  A health care provider will likely make a probable diagnosis of plague based on: […] Treatment will likely start while your provider waits for the results of one or more laboratory tests to identify the Yersinia pestis bacteria. […] Samples for tests may come from:

• #1 The Plague: Types, Causes, and Symptoms

  https://www.healthline.com/health/plague

  The plague is a serious bacterial infection that can be deadly. […] The plague is a rapidly progressing disease that can lead to death if untreated. If you suspect you have it, call a doctor right away or go to an emergency room for immediate medical attention. […] If your doctor suspects you may have the plague, theyll check for the presence of the bacteria in your body: A blood test can indicate whether you have septicemic plague. To check for bubonic plague, your doctor will use a needle to take a sample of the fluid in your swollen lymph nodes. To check for pneumonic plague, doctors will either take a blood sample or sample from the swollen lymph node and send it for laboratory testing. […] If the plague is suspected, your doctor will still begin treatment with antibiotics even before the diagnosis is confirmed. This is because the plague progresses rapidly, and being treated early can make a big difference in your recovery.

• #1 Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics | Genes & Immunity

  https://www.nature.com/articles/s41435-019-0065-0

  Screening of the suspected patients was based on epidemiological and clinical criteria, as described in the case definition provided by the World Health Organization (WHO) and biological samples were collected at the points of care. Biological diagnosis of pneumonic plague highly relies on the quality of the sample: since pneumonic plague is a lower respiratory tract infection, deep respiratory secretions are required for biological tests, not saliva or spit. However, during an outbreak, the aim is to diagnose the disease during the invasion phase before the onset of severe symptoms. Thus, producing good-quality sputum is often difficult for patients with mild symptoms and also for children. Moreover, since sputum specimens can be viscous and thick, liquefaction and homogenization are fully required before execution of some specific biological assays. However, because of lack of reagents, equipment, and trained staff, this first step of the process is seldom performed at local points of care, resulting in wrong interpretations of subsequent biological assays. The rapid diagnostic test (RDT), based on the detection of the F1 antigen of Y. pestis, is a practical method that can be implemented by trained staff at local points of care, can provide results within 15min, and has been validated for diagnosis of bubonic plague. Nevertheless, its performances in sputum still need to be evaluated. Indeed, false-negative and false-positive results may be observed with sticky expectorations, due to absence or incomplete sample migration along the dipstick. False-negative results may also occur with saliva. Therefore, clinically pneumonic plague-suspected patients must be treated without considering the result of the bedside RDT.

• #1 Plague Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/235627-workup

  A fourfold rise in antibody titers to the F-1 antigen of Y pestis also confirms infection. […] A polymerase chain reaction (PCR) using primers derived from Y pestis plasminogen activator gene has been used to detect the pathogen in fleas, but the application of this method in humans still is a matter of speculation. […] Lumbar puncture is strongly recommended when meningeal plague is suspected.

• #1 Plague Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/235627-workup

  The possibility of plague should be strongly considered in febrile patients from endemic areas who have history of exposure to rodents. Rapid recognition of the classic symptoms of this disease and laboratory confirmation are essential to instituting lifesaving therapy. […] Expertise in testing for plague bacilli is limited to reference laboratories in plague-endemic states and the CDC. […] Twenty-seven percent to 96% of blood cultures are positive for Y pestis in patients with bubonic plague and septicemic plague. […] Microbiology staff should be informed of the possibility of Y pestis agents in samples so that they can take adequate precautions when handling specimens. […] Y pestis may be observed on a peripheral blood smear. […] A Wayson stain demonstrates the typical „safety pin” appearance (bipolar staining) of the bacterium.

• #1 Plague | American Veterinary Medical Associationmultiple-users-1

  https://www.avma.org/plague

  Diagnosis: Yersinia pestis may be identified microscopically by examination of Gram, Wright, Giemsa or Wayson’s stained smears of peripheral blood, sputum, and bubo or cerebrospinal fluids. Finding bipolar-staining, Gram-negative bacillus permits a rapid presumptive diagnosis of plague. Bacteria can also be identified through culture of clinical specimens in appropriate media. Phagocytolysis, immunofluorescence, agglutination, phage typing, or PCR tests are also useful for diagnosis. A four-fold rise in antibody titer in patient serum is also diagnostic.

• #1 Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics | Genes & Immunity

  https://www.nature.com/articles/s41435-019-0065-0

  Among the biological diagnostic tests, microbial isolation of Y. pestis remains the gold standard. Although Y. pestis can grow on usual culture media, the use of a selective agar supplemented in cefsulodin-irgasan-novobiocin (CIN) favors the isolation of the bacterium in polymicrobial samples such as sputum. WHO recommendations are to rinse the mouth out with water prior to sample collection in order to reduce the contaminations by the oral flora. After 2- or 3-day incubation at 28C, suspected colonies on CIN agar may be identified by biochemical tests, PCR, and Y. pestis-specific phage lysis. Automated identification systems are more and more often used in the laboratories: they are fast and can efficiently identify a large variety of bacteria; however, misidentifications of Y. pestis have been reported; therefore, a reference laboratory must always confirm the taxonomic assignation.

• #1 Rapid diagnostic tests for plague

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7387759/

  F1RDTIPM pooled sensitivity against culture was 100% (95% confidence interval (CI) 82 to 100; 4 studies, 1692 participants; very low certainty evidence) and pooled specificity was 70.3% (95% CI 65 to 75; 4 studies, 2004 participants; very lowcertainty evidence). […] Against culture, the F1RDT appeared highly sensitive for diagnosing either pneumonic or bubonic plague, and can help detect plague in remote areas to assure management and enable a public health response. False positive results mean culture or PCR confirmation may be needed. F1RDT does not replace culture, which provides additional information on resistance to antibiotics and bacterial strains. […] F1RDT appears to be highly sensitive for pneumonic or bubonic plague. As a simple test that can be performed at a patient’s bedside in remote and lowresource areas, F1RDT can assist with plague diagnosis for early management, and appropriate preventive measures to avoid spread of the disease.

• #1 Applications of polymerase chain reaction‑based methods for the diagnosis of plague (Review)

  https://www.spandidos-publications.com/10.3892/etm.2022.11438?text=fulltext

  PCR is well suited molecular biology tool for diagnosis of pathogens. At present, confirmation of plague is performed using reverse transcription PCR targeting a plasminogen activator gene (pla) and 60-Md plasmid-located gene (caf1) and in the case of discordant or uncertain results, a PCR targeting pla, caf1 and an invasin protein gene (inv) is performed. […] The rapid identification of the Y. pestis is crucial, so that more specific therapy can be initiated. PCR is a key technique for accurate detection of Y. pestis due to its higher sensitivity and specificity within several hours and without any cultivation. […] Standard PCR is a cost-effective approach for the rapid detection of Y. pestis. […] Reverse transcription PCR is proposed as a timely, cost-effective and accurate diagnostic assay.

• #1 Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics | Genes & Immunity

  https://www.nature.com/articles/s41435-019-0065-0

  Molecular biology tests have been developed in order to reduce the delay and increase the sensitivity of diagnostics. Conventional polymerase chain reactions (PCR) targeting the pla, caf1, inv, and yopM genes reduce the delay of diagnostics to 3-4h, while real-time PCR can be performed in only 2h. The pla gene is located on the pPla/pPCP1 plasmid, which is present in 150-200 copies per bacterium, resulting in a high sensitivity. A real-time PCR targeting pla in the sputum displays a sensitivity of 100 cfu/ml in spiked sputum. However, pla may also be found in other Enterobacteriaceae such as Citrobacter koseri and Escherichia coli and these bacteria may be present in the sputum. Therefore, the sputum must be tested by multiplex real-time PCR, targeting additional genes. The caf1 gene is located on the pFra/pMT1 plasmid, which is considered specific to Y. pestis, but it is present in only about two copies per bacterium. A multiplex real-time PCR on pla and caf1 has been described but it was tested only in patients with suspected bubonic plague (not on sputum). The yopM gene, located on the Yersinia virulence plasmid pYV/pCD1, is present in about four copies per bacterium, but pYV may also be found in Y. pseudotuberculosis and pathogenic Y. enterocolitica strains. The inv gene is a chromosomal gene present in Y. pestis and Y. pseudotuberculosis; an insertion in Y. pestis made it larger and a conventional PCR may distinguish it by the amplicon sizes produced in Y. pseudotuberculosis (400bp) compared with Y. pestis (1100bp). During the 2017 pneumonic plague outbreak in Madagascar, the strategy chosen to detect Y. pestis DNA was first to test the samples by a multiplex real-time PCR targeting pla and caf1, and to confirm the uncertain cases by a conventional PCR targeting pla, caf1, inv 1100bp, and yopM. It is worth mentioning that the chromosomal gene ypo2088 is specific to Y. pestis and spiked expectorations have been successfully tested by real-time PCR targeting this gene. Molecular biology tests are usually performed in hospitals and research institutions; however, portable real-time PCR instruments are being developed and could be helpful in remote plague endemic areas. Assays relying on the loop-mediated isothermal amplification (LAMP) technology have also been developed, but they still remain to be evaluated on sputum.

• #1 SciELO Brazil – Diagnosis of plague and identification of virulence markers in Yersinia pestis by multiplex-PCR Diagnosis of plague and identification of virulence markers in Yersinia pestis by multiplex-PCR

  https://www.scielo.br/j/rimtsp/a/LhB4zLNQyx3TfK7NLy6nJXp/

  Although it does not replace bacteriological isolation, the multiplex-PCR technique described here may be useful for the quick detection and characterization of Y. pestis. The amplification of four virulence genes of Y. pestis strains directly from the blood culture, provides a diagnosis faster than the traditional techniques. At the same time, it characterizes the virulence properties of the strain. […] It is likely that the multiplex-PCR technique directed at Y. pestis virulence markers will certainly be a practical tool for the plague surveillance programs among rodents and fleas. Therefore, studies are in progress in our laboratory in order to evaluate the usefulness of the multiplex-PCR in animal samples.

• #1 Plague and its laboratory diagnosis – Clinical Laboratory int.

  https://clinlabint.com/plague-and-its-laboratory-diagnosis/

  This includes microscopy, isolation by cultivation, identification and confirmation by NAT tests and animal pathogenicity tests for Y. pestis. […] Serological tests are useful especially when cultures yield negative results and/or only serum samples are available as clinical specimens. […] Such tests are often used retrospectively to confirm the diagnosis of plague; paired serum samples are collected during either the acute and convalescent phases or the convalescent and post-convalescent phases. […] When live organisms are not available, e.g., in specimens taken postmortem from lymphoid tissues, lung and bone marrow, DNA of Y. pestis can still be detected. […] Even though a number of presumptive and confirmative techniques are available, none are sufficiently simple, economical and non-instrumental to be used routinely by clinical laboratories and in field studies, surveillance or point-of-care testing. […] The RDT for plague based on F1 antigen has been tested in laboratories and has provided promising results.

• #1 Plague and its laboratory diagnosis – Clinical Laboratory int.

  https://clinlabint.com/plague-and-its-laboratory-diagnosis/

  Plague is an acute bacterial infection in man caused by Yersinia pestis. […] A precise and quick diagnosis of plague allows prompt intervention, especially necessary during plague outbreaks. […] The diagnosis of plague still relies on clinical symptoms and exposure history in most endemic areas. […] Laboratory diagnosis of plague is mainly based on bacteriological and/or serological evidence. […] The presumptive diagnosis of plague can be made if: an immunofluorescence stain of a relevant sample is positive for the presence of Y. pestis Fraction 1 capsular (F1) antigen; and a single serum specimen is tested and the anti-F1 antigen titre by agglutination is 1:10. […] Confirmed plague is diagnosed if: an isolated culture is lysed by specific bacteriophage; two serum specimens demonstrate a four fold anti-F1 antigen titre rise by agglutination testing; and a single serum specimen tested by agglutination has a titre of 1:128 and the patient has no known previous plague exposure or vaccination history.

• #1 Evaluation of a multi-species Protein A-ELISA assay for plague serologic diagnosis in humans and other mammal hosts | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009805

  Altogether, the Protein A-ELISA showed high performance when compared both to HA and Anti-IgG ELISA, with a polyvalent single protocol that requires reduced amounts of antigen and can be employed to any plague hosts. […] Here, we developed and evaluated an ELISA diagnostic test based on the Protein A-peroxidase conjugate that allows the test to be used for plague laboratorial diagnosis not only in humans, but also in a wide range of mammalian species. This particularity is specifically important for plague epidemiological surveillance, given that Yersinia pestis, the causative agent of plague, have a long list of animal reservoirs across distinct ecosystems. Briefly, we first evaluated the best reaction parameters, such as antigen concentration, serum and protein A-conjugate dilutions. Next, we used serum samples from humans, dogs, rodents and rabbits (n = 288) with known results for plague serology by a conventional method, to evaluate the performance of the new Protein A-ELISA test. We observed a good performance of the novel Protein A-ELISA test, with high sensitivity and specificity rates. Evaluation of the coefficient of variation revealed that the test measurements suffer little variation, and therefore, has high repeatability and reproducibility. Next, by evaluating 487 samples, we observed a high degree of concordance between the Protein A-ELISA with a conventional IgG-based ELISA. Furthermore, this test showed no significant cross-reaction with other common infectious diseases. Altogether, the Protein A-ELISA showed high performance when compared both to HA and Anti-IgG ELISA, with a single protocol that requires reduced amounts of antigen and can be employed to several plague hosts.

• #1 Pneumonic plague: Symptoms, causes, treatment, and more

  https://www.medicalnewstoday.com/articles/pneumonic-plague

  Pneumonic plague occurs when plague bacteria enter the lungs. It is the only form of plague that can spread between people. […] The disease requires prompt treatment with antibiotics. Pneumonic plague is the most severe form of the condition and can be fatal without treatment. […] According to the WHO, symptoms of pneumonic plague may include: weakness, headache, fever, chills, body aches, nausea and vomiting. […] Additionally, pneumonic plague may cause rapidly developing pneumonia with: shortness of breath, cough, which may produce bloody or watery mucus, chest pain. […] A doctor may begin the diagnostic process by looking for physical signs of plague, such as fleabites or swollen lymph nodes. […] Therefore, healthcare professionals may take blood, pus, or sputum samples to test in a laboratory following evaluation of a person’s symptoms, according to the WHO.

• #1 Septicemic plague: Symptoms, causes, treatment, and more

  https://www.medicalnewstoday.com/articles/septicemic-plague

  Septicemic plague is a complication of pneumonic or bubonic plague and can also occur independently. It develops when bacteria that cause plague multiply in the blood. […] This article explores septicemic plague in more detail, including its symptoms, causes, and diagnosis. […] Septicemic plague can develop independently or as a complication of other types of plague. […] If a person does not have buboes, the bacteria may have directly passed into their blood, causing septicemic plague. […] Septicemic plague is often a complication of bubonic or pneumonic plague, but it can develop independently if Yersinia pestis passes directly into the blood. […] However, the only way to confirm plague is with a blood test, which screens for Yersinia pestis markers. […] If septicemic plague develops independently, a person would not have buboes, which may delay diagnosis. […] Prompt treatment with antibiotics is necessary after infection, as symptoms can progress very quickly. […] A person needs to call 911 if they experience any symptoms of plague or think they may have received exposure to Yersinia pestis, the bacterium that causes plague.

• #1 Plague and Other Yersinia Infections – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/plague-and-other-yersinia-infections

  Plague is caused by the gram-negative bacterium Yersinia pestis. […] Diagnosis is epidemiologic and clinical, confirmed by culture and serologic testing. […] Rapid diagnosis of plague is important because mortality increases significantly the longer treatment is delayed. […] Diagnosis is made by stain and culture of the organism, typically by needle aspiration of a bubo (surgical drainage may disseminate the organism); blood and sputum cultures should also be obtained. […] Other tests include immunofluorescent staining and serology; a titer of 1:16 or a 4-fold rise between acute and convalescent titers is positive. PCR testing, if available, is diagnostic. […] The laboratory should be informed if plague is suspected to ensure proper handling of specimens and avoid potential transmission. […] Patients with pulmonary symptoms or signs should have a chest radiograph, which shows a rapidly progressing pneumonia in pneumonic plague. […] Prior vaccination does not exclude plague; clinical illness may occur in vaccinated people.

• #1 The plague dipstick—Bringing the laboratory to the bedside

  https://www.ghtcoalition.org/blog/the-plague-dipstick-bringing-the-laboratory-to-the-bedside

  In my laboratory, a team of CDC researchers has developed, manufactured, and field-tested a rapid, affordable diagnostic toolthe plague dipstick. The point-of-care plague dipstick, which works like a pregnancy test, brings the laboratory to the bedside. […] Before the dipstick was introduced, early clinical diagnosis of plague was difficult and could delay life-saving treatment. […] The plague dipstick is now being submitted to the US Food and Drug Administration for 510(k) clearance, which is the next step in showing the dipstick to be a clinically validated, sensitive, and specific test.

• #1 Rapid diagnostic tests for plague

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7387759/

  Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the disease. A rapid diagnostic test (RDT) could help in establishing a prompt diagnosis of plague. This would improve patient care and help appropriate public health response. […] To determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease. […] We included crosssectional studies that assessed the accuracy of the F1RDT for diagnosing plague, where participants were tested with both the F1RDT and at least one reference standard. The reference standards were bacterial isolation by culture, polymerase chain reaction (PCR), and paired serology (this is a fourfold difference in F1 antibody titres between two samples from acute and convalescent phases).

• #1 Plague: Recognition, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5744195/

  In a large-scale plague outbreak or bioterrorism attack setting, oral doxycycline and ciprofloxacin are recommended to treat the plague for both adult and child patients. […] Bubonic plague patients without secondary pneumonic and septicemic plague have a very low risk of spreading plague to close contacts. […] However, a patient with secondary or primary pneumonic plague can transmit Y. pestis to close contacts through coughing respiratory droplets. […] There is still no effective vaccine for plague prevention, although a live attenuated vaccine is used in some countries, such as China and Russia. […] Because Y. pestis is also an important bioterrorism agent and the perpetrators may intentionally use this pathogen to threaten societal stability, clinicians need to pay attention to this rare but harmful disease to prevent its further spread.

• #2 Plague: Overview, Symptoms, and Types (Bubonic, Septicemic and Pneumonic)

  https://www.webmd.com/a-to-z-guides/plague-faq

  Your doctor might suspect you’ve been infected with plague if you have certain symptoms and live in an area where animals are known to carry it or have visited such a place recently. […] To find out if you have plague, your doctor will take samples from your body. Those could include blood or tissue from a swollen lymph gland. The samples are sent to a lab, which tests them for the bacteria that causes plague. […] In the past few years, researchers have come up with a rapid test that can spot signs of the plague bacteria within 15 minutes. It tests fluid from infected lymph nodes or that you cough up. It’s not widely used, but it could be an important first test in parts of the world where it isn’t as easy to get samples tested in a lab.

• #2 Clinical Testing and Diagnosis for Plague | Plague | CDC

  https://www.cdc.gov/plague/hcp/diagnosis-testing/index.html

  Plague should be considered in any patient with clinical signs of plague and a recent history of residence in or travel to the western United States or other plague endemic areas. […] If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. Local and state health departments should be notified immediately. […] DO NOT WAIT FOR DIAGNOSTIC TEST RESULTS IF YOU SUSPECT PLAGUE. […] The decision to initiate antibiotic therapy for plague should be made based on clinical signs and symptoms and a careful patient history. […] If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. […] Microscopic examination of Gram, Wright, Giemsa, or Wayson’s stained smears of peripheral blood, lymph node specimen, or sputum may yield evidence of Y. pestis infection.

• #2

  https://www.cbsnews.com/news/plague-what-to-know-symptoms-transmission/

  Septicemic plague occurs when the bacteria gets into the bloodstream. Patients may develop fever, chills, extreme weakness, abdominal pain, shock and possibly internal bleeding. […] Pneumonic plague: Untreated bubonic or septicemic plague can develop in the pneumonic plague, which spreads to the lungs. These patients may develop fever, headache, weakness, pneumonia, shortness of breath, chest pain, cough and sometimes bloody or watery mucous. […] Plague can be successfully treated with antibiotics, the CDC says, but the earlier the better to improve chances of a full recovery. […] The key for clinicians is suspecting plague in the first place, obtaining the right specimens to make a diagnosis, and initiating treatment even before the diagnosis is made as soon as you suspect it, you should start treating while the evaluation is ongoing.

• #2 Plague Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/235627-workup

  Gram stain shows small gram-negative coccobacilli. […] Lymph node aspirates often demonstrate Y pestis. […] Cerebrospinal fluid (CSF) analysis in meningeal plague may show pleocytosis with a predominance of polymorphonuclear leukocytes. […] Gram stain of CSF may show plague bacilli. […] Updated (2014) guidelines on the diagnosis and treatment of bubonic plague have been published by the Infectious Diseases Society of America (IDSA). […] Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis. […] A novel rapid diagnostic test capable of detecting miniscule amounts of Y pestis F1 antigen within 15 minutes has been developed and field tested in Madagascar. […] This test yields 100% sensitivity and specificity for Y pestis and other Yersinia species. […] A passive hemagglutination test (performed on serum from a patient in acute or convalescent stages) with a 16-fold or greater increase in titer (single titer) suggests plague infection.

• #2 Rapid diagnostic tests for plague | Cochrane

  https://www.cochrane.org/CD013459/INFECTN_rapid-diagnostic-tests-plague

  Plague is a severe disease associated with high death rates. […] A rapid diagnostic test (RDT) could help prompt diagnosis of plague, especially in low-resource settings. This would improve patient care and help appropriate response to avoid the disease spread. […] To assess the accuracy of the F1RDT for detecting plague in people with suspected plague. […] F1RDT is a test that detects the F1 antigen, which is part of the outer surface of Yersinia pestis, the bacteria causing plague. […] Seven studies (reported in eight manuscripts) provided findings of F1RDT used in people with suspected plague in three African countries. […] For any form of plague and when compared to culture, F1RDT registered positive in 100% of people who had plague and registered negative in 70% of people who actually did not have plague.

• #2 Rapid diagnostic tests for plague | Cochrane

  https://www.cochrane.org/CD013459/INFECTN_rapid-diagnostic-tests-plague

  To determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease. […] We included cross-sectional studies that assessed the accuracy of the F1RDT for diagnosing plague. […] F1RDT-IPM pooled sensitivity against culture was 100% and pooled specificity was 70.3%. […] Performed in sputum, F1RDT-IPM pooled sensitivity against culture was 100% and pooled specificity was 71%. […] Performed in bubo aspirate, F1RDT-IPM pooled sensitivity against culture was 100% and pooled specificity was 67%. […] F1RDT-IPM pooled sensitivity against PCR for the caf1 gene was 95% and pooled specificity was 93%.

• #2 Plague | PPT

  https://www.slideshare.net/slideshow/plague-238747432/238747432

  1) Laboratory diagnosis of plague involves collecting specimens from buboes, sputum, or blood for microscopy, culture, and molecular detection of Yersinia pestis. […] 2) Direct microscopy can reveal gram-negative coccobacilli while culture grows brown pigmented colonies. […] 3) F1 Antigen Detection may be detected from bubo aspirate or sputum by direct immunofluorescence test, ELISA or Immunochromatographic test (ICT) by using monoclonal antibodies. […] 4) Antibodies may be detected by passive hemagglutination or complement fixation test or ELISA. Antibodies have a limited diagnostic value as they appear late but antibodies are useful epidemiological markers as they remain positive for several years. […] 5) PCR can be used to detect gene coding F1 antigen, pesticin gene, and the plasminogen activator gene.

• #2 A new multi-species Protein A-ELISA assay for plague diagnosis in humans and other mammal hosts | medRxiv

  https://www.medrxiv.org/content/10.1101/2021.09.21.21263536v1.full-text

  Here, we describe a Protein A-based approach designed to overcome some limitations faced by routine laboratories when using other serological methods, such as HA (subjective interpretation, high consumption of antigen, perishable reagents) and conventional ELISA (requires specific IgG-peroxidase conjugate, cut-off calculation and positive controls for each species). […] Throughout a broad range of host species hereby tested, the Protein A-ELISA method showed high sensitivity, specificity and reproducibility rates even with a single cut-off value for all species. […] Altogether, we validated a new indirect ELISA test that is sensitive, specific and reproducible, with a single protocol that can be used for both diagnosis of plague in humans and epidemiological surveillance in animal reservoirs from active foci.

• #2 Plague and its laboratory diagnosis – Clinical Laboratory int.

  https://clinlabint.com/plague-and-its-laboratory-diagnosis/

  Plague is an acute bacterial infection in man caused by Yersinia pestis. […] A precise and quick diagnosis of plague allows prompt intervention, especially necessary during plague outbreaks. […] The diagnosis of plague still relies on clinical symptoms and exposure history in most endemic areas. […] Laboratory diagnosis of plague is mainly based on bacteriological and/or serological evidence. […] The presumptive diagnosis of plague can be made if: an immunofluorescence stain of a relevant sample is positive for the presence of Y. pestis Fraction 1 capsular (F1) antigen; and a single serum specimen is tested and the anti-F1 antigen titre by agglutination is 1:10. […] Confirmed plague is diagnosed if: an isolated culture is lysed by specific bacteriophage; two serum specimens demonstrate a four fold anti-F1 antigen titre rise by agglutination testing; and a single serum specimen tested by agglutination has a titre of 1:128 and the patient has no known previous plague exposure or vaccination history.

• #2

  https://www.gov.uk/guidance/plague-epidemiology-outbreaks-and-guidance

  If health professionals suspect a case of plague, they should discuss this with their local microbiology, virology or infectious disease consultant. […] Antibiotic treatment is effective against plague, but early diagnosis and treatment are vital to reduce mortality. […] Plague: interim guidance for clinical laboratories (PDF, 259 KB, 11 pages)

• #2 Plague: Types, History, Causes & Prevention

  https://my.clevelandclinic.org/health/diseases/17782-plague

  Plague needs to be treated with antibiotics right away. Your healthcare provider will give medication to you either through your veins (IV) or in a pill to take. […] You take antibiotics by mouth or through your veins to treat plague. […] You can reduce your risk of plague by avoiding flea bites and being careful around animals that could be infected. […] Immediate treatment with antibiotics will help you survive the plague. With quick treatment, about 90% of people with all forms of plague survive. […] Without treatment, plague is nearly always fatal. With treatment, there’s a 5 to 15% mortality (death) rate for bubonic plague and around a 50% mortality rate for pneumonic and septicemic plague.

• #2 Plague and Other Yersinia Infections – Infections – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/infections/bacterial-infections-gram-negative-bacteria/plague-and-other-yersinia-infections

  Plague is a severe infection caused by the gram-negative bacteria Yersinia pestis. It often affects the lymph nodes or lungs. […] Identifying the bacteria in samples of blood, sputum, or pus from lymph nodes confirms the diagnosis. […] Rapid diagnosis of plague is important because the longer treatment is delayed, the higher the risk of dying. […] To diagnose plague, doctors take samples of blood, sputum, or pus from lymph nodes. Samples are examined under a microscope and sent to a laboratory to grow (culture) bacteria. […] If doctors suspect pneumonic plague, a chest x-ray is taken.

• #2 Diagnosis during plague epidemics: the contribution of statistics | Pasteur Network

  https://pasteur-network.org/news/diagnosis-during-plague-epidemics-the-contribution-of-statistics/

  During an epidemic, it can happen that no diagnostic test is perfectly adapted to the pathogen. […] Using the plague outbreak that affected Madagascar in 2017 as a case study, researchers from the Institut Pasteur and the Institut Pasteur de Madagascar propose an analytical framework to characterize the performance of different tests and estimate the true prevalence of the outbreak. […] The samples were analyzed using three types of diagnostic tests: bacterial culture, rapid plague test, and molecular biology or qPCR. […] The analytical framework used in this study estimated that 7-15% of suspected cases were carriers of Yersinia pestis for this outbreak. […] Two parameters, specificity and sensitivity, determine the performance of a test. […] In the absence of a reference test, as was the case for this plague epidemic, the authors had to estimate the performance of each test and then the prevalence of the epidemic.

• #2 Plague and its laboratory diagnosis – Clinical Laboratory int.

  https://clinlabint.com/plague-and-its-laboratory-diagnosis/

  This includes microscopy, isolation by cultivation, identification and confirmation by NAT tests and animal pathogenicity tests for Y. pestis. […] Serological tests are useful especially when cultures yield negative results and/or only serum samples are available as clinical specimens. […] Such tests are often used retrospectively to confirm the diagnosis of plague; paired serum samples are collected during either the acute and convalescent phases or the convalescent and post-convalescent phases. […] When live organisms are not available, e.g., in specimens taken postmortem from lymphoid tissues, lung and bone marrow, DNA of Y. pestis can still be detected. […] Even though a number of presumptive and confirmative techniques are available, none are sufficiently simple, economical and non-instrumental to be used routinely by clinical laboratories and in field studies, surveillance or point-of-care testing. […] The RDT for plague based on F1 antigen has been tested in laboratories and has provided promising results.

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