Pneumonic Plague Outbreak Research Articles

Plague and local response in North China, 1900-28.

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

An epidemiological modeling investigation of the long-term changing dynamics of the plague epidemics in Hong Kong

<p>Identifying epidemic-driving factors through epidemiological modeling is a crucial public health strategy that has substantial policy implications for control and prevention initiatives. In this study, we employ dynamic modeling to investigate the transmission dynamics of pneumonic plague epidemics in Hong Kong from 1902 to 1904. Through the integration of human, flea, and rodent populations, we analyze the long-term changing trends and identify the epidemic-driving factors that influence pneumonic plague outbreaks. We examine the dynamics of the model and derive epidemic metrics, such as reproduction numbers, that are used to assess the effectiveness of intervention. By fitting our model to historical pneumonic plague data, we accurately capture the incidence curves observed during the epidemic periods, which reveals some crucial insights into the dynamics of pneumonic plague transmission by identifying the epidemic driving factors and quantities such as the lifespan of flea vectors, the rate of rodent spread, as well as demographic parameters. We emphasize that effective control measures must be prioritized for the elimination of fleas and rodent vectors to mitigate future plague outbreaks. These findings underscore the significance of proactive intervention strategies in managing infectious diseases and informing public health policies.</p>

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.

Analytical framework to evaluate and optimize the use of imperfect diagnostics to inform outbreak response: Application to the 2017 plague epidemic in Madagascar.

During outbreaks, the lack of diagnostic "gold standard" can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with 3 diagnostic tests (based on up to 7 diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Y. pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Y. pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

Pneumonic Plague: Incidence, Transmissibility and Future Risks

Pneumonic plague outbreaks are relatively infrequent in modern times, but in the early part of the 20th century, they were commonplace including several well-documented epidemics responsible for the deaths of thousands. The transmissibility of this disease seems to be discontinuous since in some outbreaks few transmissions occur, while in others, the progression of the epidemic is explosive. Modern epidemiological studies explain that transmissibility within populations is heterogenous with relatively few subjects likely to be responsible for most transmissions and that ‘super spreading events’, particularly at the start of an outbreak, can lead to a rapid expansion of cases. These findings concur with outbreaks observed in real-world situations. It is often reported that pneumonic plague is rare and not easily transmitted but this view could lead to unnecessary complacency since future risks such as the spontaneous incidence of anti-microbial strains, climate change leading to a disruption of natural cycles within plague foci and use of plague as a bioweapon cannot be discounted. Carers and first responders are vulnerable, particularly in poorer countries where access to medicines and protection equipment may be limited, outbreaks occur in inaccessible areas or where there is a lack of surveillance due to a paucity of funds.

Clinical picture of pulmonary plague observed in the paediatric wards of antananarivo

Introduction: In Madagascar, plague is a highly contagious acute endemic infectious disease. The diagnosis of the most severe form of pneumonic plague remains difficult in children, hence the objectives of the present study; which is to identify the clinical signs of this clinical form in children and to describe its epidemiological and evolutionary profile. Methods: A retrospective case-control study was conducted in four pediatric wards in Antananarivo during the urban pneumonic plague outbreak from September 2017 to January 2018. Those cases were defined as children aged 0-15 years old suspected of having plague with positive RDT and PCR, and they were defined as children aged 0-15 years old with negative RDT and PCR. Results: Fifty-two cases of pneumonic plague were identified, half of which (50%) were under 24 months of age. A male predominance was noted with a sex ratio of 1.23 and 86.54% of the patients were from urban areas. Several clinical signs were found but none was specific for pneumonic plague: cough (59.62% p: 0.5), dyspnea (3.85% p: 0.16), chest pain (3.85% p: 0.26%), hemoptysis (7.69% p: 0.17), vomiting (9.62% p: 0.14), diarrhea (11.54% p: 0.45), altered general condition (38.46% p: 0.24%). Two deaths were noted (3.8%). Conclusion: No specific clinical warning signs have been identified in childhood pneumonic plague. In the event of an epidemic of urban pneumonic plague, any bacterial pneumonia should at least initially include active treatment against Yersinia pestis.

A novel mechanism of streptomycin resistance in Yersinia pestis: Mutation in the rpsL gene.

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai-Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance.

The Manchurian Plague and COVID-19: China, the United States, and the "Sick Man," Then and Now.

In this article, I explore the historical resonances between China's 1911 pneumonic plague and our current situation with COVID-19. At the turn of the 20th century, China was labeled "the Sick Man of the Far East": a once-powerful country that had become burdened by opium addiction, infectious disease, and an ineffective government. In 1911, this weakened China faced an outbreak of pneumonic plague in Manchuria that killed more than 60 000 people. After the 1911 plague, a revolutionized China radically restructured its approach to public health to eliminate the stigma of being "the Sick Man." Ironically, given the US mishandling of the COVID pandemic, observers in today's China are now calling the United States "the Sick Man of the West": a country burdened by opioid addiction, infectious disease, and an ineffective government. The historical significance of the phrase "Sick Man"-and its potential to now be associated with the United States-highlights the continued links between epidemic control and international status in a changing world. This historical comparison also reveals that plagues bring not only tragedy but also the opportunity for change.

Human plague: An old scourge that needs new answers.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach.

Phylogeny of Yersinia pestis Strains Belonging to 0.ANT Branch, Isolated in Tien-Shan and Pamir-Alay in XX–XXI Centuries

Objective of the study was to conduct phylogenetic analysis of Yersinia pestis strains of the main subspecies, belonging to antique biovar, phylogenetic branch 0.ANT, isolated in XX – early XXI centuries in the foci of Tien-Shan and Pamir-Alay to identify the regularities of spatial-temporal circulation of plague agent in the territory of the foci. Materials and methods. We have carried out whole genome SNP-analysis of Y. pestis strains of antique biovar, isolated in natural foci of Kyrgyz Republic in 1928–2016. Phylogenetic investigation is based on 1646 identified core SNPs in 51 included in the analysis strains of different phylogenetic lines. Phylogenetic tree was constructed using Maximum Likelihood algorithm, PHYML software package, and HKY85 model. Results and discussion. All 29 studied Y. pestis strains isolated between 1928 and 2016 in the foci of Tien-Shan and Pamir-Alay fall under the phylogenetic branches 0.ANT3 and 0.ANT5 of antique biovar of the main subspecies. Strains of 0.ANT3 branch were collected predominantly in Aksay and Alay foci, while strains of 0. ANT5 – in Upper-Naryn and Sarydzhas foci of Tien-Shan. Strains of phylogenetic lines 0.ANT1 and 0.ANT2 were not found in the foci of Kyrgyz Republic. According to the results of whole genome SNP-analysis, Y. pestis strains isolated in the XXI century belong to phylogenetic branch 0.ANT5. This branch also comprises a strain obtained from a patient (lethal case) in Sarydzhas plague focus in 2013. Genetic homogeneity of the modern strains of 0.ANT5 branch and their wide dissemination testify to the extension of the areal of this population and activation of Tien-Shan foci, caused by climate warming. For the first time ever, genomes of Y. pestis 0.ANT5 branch, isolated in XXI century, including clinical strain dated 2013, have been sequenced. We have obtained the whole-genome sequence of Y. pestis strain, 0.ANT3 branch, which caused pneumonic plague outbreak in Tien-Shan in 1928.

Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study.

.In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.

The rise of pneumonic plague in Madagascar: current plague outbreak breaks usual seasonal mould.

Madagascar has just emerged from the grip of an acute urban pneumonic plague outbreak, which began in August 2017, before the usual plague season of October-April and outside the traditional plague foci in the northern and central highlands. The World Health Organization reported a total of 2417 confirmed, probable and suspected cases, including 209 deaths between 1 August and 26 November 2017. The severity and scope of this outbreak, which has affected those in higher socioeconomic groups as well as those living in poverty, along with factors including the potential for use of multi-drug-resistant strains of plague in bioterrorism, highlights the ongoing threat posed by this ancient disease. Factors likely to have contributed to transmission include human behaviour, including burial practices and movement of people, poor urban planning leading to overcrowding and ready transmission by airborne droplets, climatic factors and genomic subtypes. The outbreak demonstrates the importance of identifying targeted pneumonic plague therapies and of developing vaccines that can be administered in planned programmes in developing countries such as Madagascar where plague is endemic. The dominance of pneumonic plague in this outbreak suggests that we need to focus more urgently on the danger of person-to-person transmission, as well as the problem of transmission of plague from zoonotic sources.

Medical Legacy of Gandhi: Demystifying Human Diseases.

Medical Legacy of Gandhi: Demystifying Human Diseases.

Plague and listeriosis: current outbreaks, and an historical South African connection

No abdtract available.

Outbreak of Pneumonic Plague in 2017 on Madagascar

The causes of emergence and development of pneumonic plague outbreak in 2017 on Madagascar were analyzed. Summarized were the literature data, characterizing the spatial and biocoenotic structure of natural plague focus on Madagascar, assessed were the risk factors of plague infection among rural and urban population of the island, as well as the properties of Yersinia pestis strains isolated there in the XX century. It is substantiated that the distinctive type of plague outbreaks on Madagascar is a rural one. It is demonstrated that one of the main causes of wide spread of plague in 2017 is importation of the infection from central regions of the Republic of Madagascar into big cities with further formation of multiple epidemic foci. Confirmed was the circulation of Y. pestis strains that belong to the third branch of irradiation of oriental biovar (1.ORI3). Discussed are the issues of diagnostics and treatment of plague in epidemic foci in the territory of the Republic of Madagascar. The evidence is provided to the fact that the plague outbreak in 2017 on Madagascar is the consequence of a lower surveillance level, first and foremost undervaluation of specific and non-specific prophylaxis capacities regarding this infection.

Pneumonic Plague Transmission, Moramanga, Madagascar, 2015.

During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.

Moving to the right place at the right time: Economic effects on migrants of the Manchuria Plague of 1910–11

How do initial arrival conditions in a host locality affect migrants’ subsequent economic welfare? Manchuria (Northeast China), which attracted millions of migrants from North China during the first half of the twentieth century, experienced a devastating pneumonic plague outbreak in 1910–11. Using data from a rural household survey in the mid-1930s, we explore how the post-plague conditions in various villages affected migrant cohorts’ long-term wealth accumulation. We find that the migrant households that moved to plague-hit villages soon after the plague ended prospered the most: they owned at least 112% more land than migrant households that either moved elsewhere or migrated to the same village before or long after the plague outbreak. Our results are robust after controlling for factors that influence the long-term wealth accumulation of migrants and are not caused by selection.

Mortality risk factors show similar trends in modern and historic populations exposed to plague

Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered. The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted. The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults). Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

Active surveillance for human plague in Northwestern Uganda, 2008-2014

Background: Plague is a life-threatening flea-borne zoonosis caused by Yersinia pestis. Over 95% of cases worldwide are reported from rural Africa. In Uganda, the active plague foci remains in West Nile region bordering Democratic Republic of Congo. To better define the epidemiology, clinical features, and outcome of human plague in Uganda, several surveillance strategies and networks used have significantly reduced morbidity and mortality. Methods & Materials: Active surveillance, coupled with central laboratory support, was established in 10 clinics and 2 hospitals in the endemic West Nile region. Community awareness was enhanced though training of Village Health Team workers and a small number of traditional healers. For surveillance purposes, a suspect plague case was defined as rapid onset of fever and painful lymphadenopathy or hemoptysis. A confirmed case was defined as a suspect case with isolation of Y. pestis from a clinical specimen (blood, bubo aspirate, or sputum) confirmed by phage lysis, or a 4-fold increase in anti-F1 antibody titers. A probable case was defined as a suspect case epidemiological linked to a laboratory-confirmed case. Results: A total of 256 cases were identified during January 2008 – March 2014, including 75 laboratory confirmed and 25 probable cases. The number of cases per full year ranged from a high of 153 in 2008 to a low of 6 in 2014. Median patient age was 11 years (range <1-70 yrs); 53% were female. Overall, 217 patients had bubonic, 20 septicemic, and 18 pneumonic forms of plague. Among 254 patients with a documented outcome, 26% (26/100) with confirmed or probable plague died, as compared with 8% (12/154) of those with suspect plague. Mortality among patients with pneumonic plague was 44% (8/18) overall, and 55% (5/9) for those with confirmed pneumonic plague. Antimicrobials used for treatment included doxycycline, gentamycin, chloramphenicol, co-trimoxazole, and ciprofloxacin. Forty-nine (19.6%) cases were outbreak-related. Conclusion: Plague remains a public health concern in the West Nile region of Uganda. Although most cases are bubonic and sporadic, small outbreak of pneumonic plague with person-to-person transmission do occur, with the potential for larger outbreaks. Mechanisms to enhance prompt referral, rapid diagnosis, and effective antimicrobial treatment are needed to reduce mortality.

Pneumonic plague outbreak, Northern Madagascar, 2011.

Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies.