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Epidemics Dec 2018From August to November 2017, Madagascar endured an outbreak of plague. A total of 2417 cases of plague were confirmed, causing a death toll of 209. Public health...
From August to November 2017, Madagascar endured an outbreak of plague. A total of 2417 cases of plague were confirmed, causing a death toll of 209. Public health intervention efforts were introduced and successfully stopped the epidemic at the end of November. The plague, however, is endemic in the region and occurs annually, posing the risk of future outbreaks. To understand the plague transmission, we collected real-time data from official reports, described the outbreak's characteristics, and estimated transmission parameters using statistical and mathematical models. The pneumonic plague epidemic curve exhibited multiple peaks, coinciding with sporadic introductions of new bubonic cases. Optimal climate conditions for rat flea to flourish were observed during the epidemic. Estimate of the plague basic reproduction number during the large wave of the epidemic was high, ranging from 5 to 7 depending on model assumptions. The incubation and infection periods for bubonic and pneumonic plague were 4.3 and 3.4 days and 3.8 and 2.9 days, respectively. Parameter estimation suggested that even with a small fraction of the population exposed to infected rat fleas (1/10,000) and a small probability of transition from a bubonic case to a secondary pneumonic case (3%), the high human-to-human transmission rate can still generate a large outbreak. Controlling rodent and fleas can prevent new index cases, but managing human-to-human transmission is key to prevent large-scale outbreaks.
Topics: Animals; Basic Reproduction Number; Epidemics; Humans; Madagascar; Models, Theoretical; Plague; Public Health; Rats; Risk; Siphonaptera; Yersinia pestis
PubMed: 29866421
DOI: 10.1016/j.epidem.2018.05.001 -
MBio Dec 2019Inhalation of causes primary pneumonic plague, the most severe manifestation of plague that is characterized by a dramatic neutrophil influx to the lungs. Neutrophils...
Inhalation of causes primary pneumonic plague, the most severe manifestation of plague that is characterized by a dramatic neutrophil influx to the lungs. Neutrophils are ineffective during primary pneumonic plague, failing to control growth in the airways. However, the mechanisms by which resists neutrophil killing are incompletely understood. Here, we show that inhibits neutrophil degranulation, an important line of host innate immune defense. We observed that neutrophils from the lungs of mice infected intranasally with fail to release primary granules throughout the course of disease. Using a type III secretion system (T3SS) injection reporter strain, we determined that directly inhibits neutrophil granule release by a T3SS-dependent mechanism. Combinatorial mutant analysis revealed that a strain lacking both effectors YopE and YopH did not inhibit primary granule release and is killed by neutrophils both and Similarly, strains injecting only YopE or YopH are able to inhibit the majority of primary granule release from human neutrophils. We determined that YopE and YopH block Rac2 activation and calcium flux, respectively, to inhibit neutrophil primary granule release in isolated human neutrophils. These results demonstrate that coordinates the inhibition of neutrophil primary granule release through the activities of two distinct effectors, and this inhibition promotes survival during primary pneumonic plague. is the causative agent of plague and is one of the deadliest human pathogens. The pneumonic form of infection has played a critical role in the severity of both historical and modern plague outbreaks, yet the host-pathogen interactions that govern the lethality of pulmonary infections are incompletely understood. Here, we report that inhibits neutrophil degranulation during infection, rendering neutrophils ineffective and allowing unrestricted growth of in the lungs. This coordinated inhibition of granule release not only demonstrates the pathogenic benefit of "silencing" lung neutrophils but also reveals specific host processes and pathways that could be manipulated to reduce the severity of primary pneumonic plague.
Topics: Animals; Bacterial Proteins; Disease Models, Animal; Female; Host-Pathogen Interactions; Humans; Lung; Mice; Mice, Inbred C57BL; Neutrophils; Plague; Respiratory Tract Infections; Yersinia pestis
PubMed: 31822588
DOI: 10.1128/mBio.02759-19 -
Virus Research Dec 2022Yersinia pestis is the cause of plague, historically known as the "Black Death". Marmota himalayana in the Qinghai-Tibet Plateau (QTP) natural plague focus is the...
Yersinia pestis is the cause of plague, historically known as the "Black Death". Marmota himalayana in the Qinghai-Tibet Plateau (QTP) natural plague focus is the primary host in China. Although several phages originating from Y. pestis have been characterized. This is the first report of isolation of P2-like phages of Y. pestis from M. himalayana. In this study, the isolation and characterization of three P2-like phages of Y. pestis were reported, which were named as vB_YpM_22, vB_YpM_46 and vB_YpM_50. Comparative genome analysis revealed that vB_YpM_22, vB_YpM_46 and vB_YpM_50 are members of the nonlambdoid P2 family, and are highly similar and collinear with enterobacteriophage P2, plague diagnostic phage L-413C and enterobacteriophage fiAA91-ss. The role of LPS core structure of Y. pestis in the phages' receptor was pinpointed. The findings of this study contribute an advance in our current knowledge of Y. pestis phages and will also play a key role in understanding the evolution of Y. pestis phages.
Topics: Humans; Yersinia pestis; Plague; Bacteriophages; China; Tibet
PubMed: 36169047
DOI: 10.1016/j.virusres.2022.198934 -
Current Biology : CB Aug 2022Ancient DNA methodologies enable research on past prevalence and evolutionary history of pathogens. A new study found plague and typhoid fever-causing bacteria in...
Ancient DNA methodologies enable research on past prevalence and evolutionary history of pathogens. A new study found plague and typhoid fever-causing bacteria in Minoan Crete, showcasing both the potential and the limitations of the growing field of ancient pathogen genomics.
Topics: Biological Evolution; DNA, Ancient; Genomics; History, Ancient; Humans; Plague; Typhoid Fever
PubMed: 35998599
DOI: 10.1016/j.cub.2022.07.032 -
American Journal of Public Health Mar 2021In 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,...
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.
Topics: COVID-19; China; Communicable Disease Control; Epidemics; History, 20th Century; History, 21st Century; Humans; Plague; Politics; SARS-CoV-2; United States
PubMed: 33476233
DOI: 10.2105/AJPH.2020.305960 -
PLoS Neglected Tropical Diseases Aug 2018The Qinghai-Tibet plateau is a natural plague focus and is the largest such focus in China. In this area, while Marmota himalayana is the primary host, a total of 18...
The Qinghai-Tibet plateau is a natural plague focus and is the largest such focus in China. In this area, while Marmota himalayana is the primary host, a total of 18 human plague outbreaks associated with Tibetan sheep (78 cases with 47 deaths) have been reported on the Qinghai-Tibet plateau since 1956. All of the index infectious cases had an exposure history of slaughtering or skinning diseased or dead Tibetan sheep. In this study, we sequenced and compared 38 strains of Yersinia pestis isolated from different hosts, including humans, Tibetan sheep, and M. himalayana. Phylogenetic relationships were reconstructed based on genome-wide single-nucleotide polymorphisms identified from our isolates and reference strains. The phylogenetic relationships illustrated in our study, together with the finding that the Tibetan sheep plague clearly lagged behind the M. himalayana plague, and a previous study that identified the Tibetan sheep as a plague reservoir with high susceptibility and moderate sensitivity, indicated that the human plague was transmitted from Tibetan sheep, while the Tibetan sheep plague originated from marmots. Tibetan sheep may encounter this infection by contact with dead rodents or through being bitten by fleas originating from M. himalayana during local epizootics.
Topics: Animals; DNA, Bacterial; Disease Reservoirs; Genome, Bacterial; Humans; Marmota; Phylogeny; Plague; Polymorphism, Single Nucleotide; Sheep; Sheep Diseases; Yersinia pestis; Zoonoses
PubMed: 30114220
DOI: 10.1371/journal.pntd.0006635 -
Immunogenetics Dec 2023Yersinia pestis is a historically important vector-borne pathogen causing plague in humans and other mammals. Contemporary zoonotic infections with Y. pestis still occur...
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.
Topics: Animals; Humans; Plague; Tanzania; Immunogenetics; Yersinia pestis; Siphonaptera; Murinae; Antibodies
PubMed: 37853246
DOI: 10.1007/s00251-023-01323-7 -
Emerging Infectious Diseases Jan 2015Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in...
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.
Topics: Adolescent; Animals; Base Sequence; Contact Tracing; Disease Outbreaks; Endemic Diseases; Female; Genes, Bacterial; Humans; Madagascar; Male; Molecular Typing; Plague; Polymorphism, Single Nucleotide; Rats; Yersinia pestis
PubMed: 25530466
DOI: 10.3201/eid2101.131828 -
Medical Decision Making : An... Nov 2022For certain communicable disease outbreaks, mass prophylaxis of uninfected individuals can curtail new infections. When an outbreak emerges, decision makers could...
BACKGROUND
For certain communicable disease outbreaks, mass prophylaxis of uninfected individuals can curtail new infections. When an outbreak emerges, decision makers could benefit from methods to quickly determine whether mass prophylaxis is cost-effective. We consider 2 approaches: a simple decision model and machine learning meta-models. The motivating example is plague in Madagascar.
METHODS
We use a susceptible-exposed-infectious-removed (SEIR) epidemic model to derive a decision rule based on the fraction of the population infected, effective reproduction ratio, infection fatality rate, quality-adjusted life-year loss associated with death, prophylaxis effectiveness and cost, time horizon, and willingness-to-pay threshold. We also develop machine learning meta-models of a detailed model of plague in Madagascar using logistic regression, random forest, and neural network models. In numerical experiments, we compare results using the decision rule and the meta-models to results obtained using the simulation model. We vary the initial fraction of the population infected, the effective reproduction ratio, the intervention start date and duration, and the cost of prophylaxis.
LIMITATIONS
We assume homogeneous mixing and no negative side effects due to antibiotic prophylaxis.
RESULTS
The simple decision rule matched the SEIR model outcome in 85.4% of scenarios. Using data for a 2017 plague outbreak in Madagascar, the decision rule correctly indicated that mass prophylaxis was not cost-effective. The meta-models were significantly more accurate, with an accuracy of 92.8% for logistic regression, 95.8% for the neural network model, and 96.9% for the random forest model.
CONCLUSIONS
A simple decision rule using minimal information about an outbreak can accurately evaluate the cost-effectiveness of mass prophylaxis for outbreak mitigation. Meta-models of a complex disease simulation can achieve higher accuracy but with greater computational and data requirements and less interpretability.
HIGHLIGHTS
We use a susceptible-exposed-infectious-removed model and net monetary benefit to derive a simple decision rule to evaluate the cost-effectiveness of mass prophylaxis.We use the example of plague in Madagascar to compare the performance of the analytically derived decision rule to that of machine learning meta-models trained on a stochastic dynamic transmission model.We assess the accuracy of each approach for different combinations of disease dynamics and intervention scenarios.The machine learning meta-models are more accurate predictors of mass prophylaxis cost-effectiveness. However, the simple decision rule is also accurate and may be a preferred substitute in low-resource settings.
Topics: Humans; Cost-Benefit Analysis; Plague; Quality-Adjusted Life Years; Epidemics
PubMed: 35591754
DOI: 10.1177/0272989X221098409 -
Fertility and Sterility May 2019
Topics: Endocrine Disruptors; Female; Fertilization in Vitro; Follicular Fluid; Humans; Phthalic Acids; Plague; Reproductive Health
PubMed: 30975386
DOI: 10.1016/j.fertnstert.2019.01.029