Shift from primary #pneumonic to secondary #septicemic #plague by decreasing the volume of intranasal challenge with #Yersinia pestis in the murine model (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model

Rachel M. Olson , Deborah M. Anderson

Published: May 23, 2019 / DOI: https://doi.org/10.1371/journal.pone.0217440

 

Abstract

Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10μL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30μL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.

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Citation: Olson RM, Anderson DM (2019) Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestisin the murine model. PLoS ONE 14(5): e0217440. https://doi.org/10.1371/journal.pone.0217440

Editor: Matthew B. Lawrenz, University of Louisville School of Medicine, UNITED STATES

Received: February 24, 2019; Accepted: May 10, 2019; Published: May 23, 2019

Copyright: © 2019 Olson, Anderson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: Financial support for this work came from the National Institutes of Health/ National Institute of Allergy and Infectious Disease, public health service award #R01A129996 (DA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yersinia pestis; Pneumonic plague; Septicemic plague; Sepsis; Animal models.

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#Epidemiological characteristics of an #urban #plague #epidemic in #Madagascar, August–November, 2017: an outbreak #report (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Epidemiological characteristics of an urban plague epidemic in Madagascar, August–November, 2017: an outbreak report

Rindra Randremanana, PhD, Voahangy Andrianaivoarimanana, PhD, Birgit Nikolay, PhD, Beza Ramasindrazana, PhD, Juliette Paireau, PhD, Quirine Astrid ten Bosch, PhD, Jean Marius Rakotondramanga, MSc, Soloandry Rahajandraibe, MSc, Soanandrasana Rahelinirina, PhD, Fanjasoa Rakotomanana, PhD, Feno M Rakotoarimanana, MD, Léa Bricette Randriamampionona, MD, Vaoary Razafimbia, MD, Prof Mamy Jean De Dieu Randria, MD, Mihaja Raberahona, MD, Guillain Mikaty, PhD, Anne-Sophie Le Guern, PharmD, Lamina Arthur Rakotonjanabelo, MSc, Prof Charlotte Faty Ndiaye, MD, Voahangy Rasolofo, PhD, Eric Bertherat, MD, Maherisoa Ratsitorahina, MD, Simon Cauchemez, PhD, Laurence Baril, MD, André Spiegel, MD, Minoarisoa Rajerison, PhD

Open Access / Published: March 28, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30730-8

 

Summary

Background

Madagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200–700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings.

Methods

Clinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations.

Findings

2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (<1%) septicaemic case, and 140 (6%) cases with unspecified clinical form. 386 (21%) of 1878 notified pneumonic plague cases were probable and 32 (2%) were confirmed. 73 (18%) of 395 notified bubonic plague cases were probable and 66 (17%) were confirmed. The case fatality ratio was higher among confirmed cases (eight [25%] of 32 cases) than probable (27 [8%] of 360 cases) or suspected pneumonic plague cases (74 [5%] of 1358 cases) and a similar trend was seen for bubonic plague cases (16 [24%] of 66 confirmed cases, four [6%] of 68 probable cases, and six [2%] of 243 suspected cases). 351 (84%) of 418 confirmed or probable pneumonic plague cases were concentrated in Antananarivo, the capital city, and Toamasina, the main seaport. All 50 isolated Yersinia pestis strains were susceptible to the tested antibiotics.

Interpretation

This predominantly urban plague epidemic was characterised by a large number of notifications in two major urban areas and an unusually high proportion of pneumonic forms, with only 23% having one or more positive laboratory tests. Lessons about clinical and biological diagnosis, case definition, surveillance, and the logistical management of the response identified in this epidemic are crucial to improve the response to future plague outbreaks.

Funding

US Agency for International Development, WHO, Institut Pasteur, US Department of Health and Human Services, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, AXA Research Fund, and the INCEPTION programme.

Keywords: Yersinia pestis; Plague; Bubonic plague; Pneumonic plague; Madagascar.

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#Pneumonic #Plague in a #Dog and Widespread Potential #Human #Exposure in a #Veterinary Hospital, #USA (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 4—April 2019 / Dispatch

Pneumonic Plague in a Dog and Widespread Potential Human Exposure in a Veterinary Hospital, United States

Paula A. Schaffer1, Stephanie A. Brault1, Connor Hershkowitz1, Lauren Harris, Kristy Dowers, Jennifer House, Tawfik A. Aboellail, Paul S. Morley, and Joshua B. Daniels

Author affiliations: Colorado State University, Fort Collins, Colorado, USA (P.A. Schaffer, S.A. Brault, C. Hershkowitz, L. Harris, K. Dowers, T.A. Aboellail, P.S. Morley, J.B. Daniels); Colorado Department of Public Health and Environment, Denver, Colorado, USA (J. House)

 

Abstract

In December 2017, a dog that had pneumonic plague was brought to a veterinary teaching hospital in northern Colorado, USA. Several factors, including signalment, season, imaging, and laboratory findings, contributed to delayed diagnosis and resulted in potential exposure of >116 persons and 46 concurrently hospitalized animals to Yersinia pestis.

Keywords: Yersinia pestis; Plague; Pneumonic plague; Dogs; USA; Colorado.

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Estimation of #Pneumonic #Plague #Transmission in #Madagascar, August–November 2017 (PLoS Curr., abstract)

[Source: PLoS Currents Outbreaks, full page: (LINK). Abstract, edited.]

Estimation of Pneumonic Plague Transmission in Madagascar, August–November 2017

NOVEMBER 1, 2018 · DISCUSSION

AUTHORS: Maimuna S. Majumder, Emily L. Cohn, Mauricio Santillana, John S. Brownstein

 

ABSTRACT

Introduction:

Between August and November 2017, Madagascar reported nearly 2500 cases of plague; the vast majority of these cases were pneumonic, resulting in early exponential growth due to person-to-person transmission. Though plague is endemic in Madagascar, cases are usually bubonic and thus result in considerably smaller annual caseloads than those observed from August–November 2017.

Methods:

In this study, we consider the transmission dynamics of pneumonic plague in Madagascar during this time period, as well as the role of control strategies that were deployed to curb the outbreak and their effectiveness.

Results:

When using data from the beginning of the outbreak through late November 2017, our estimates for the basic reproduction number range from 1.6 to 3.6, with a mean of 2.4. We also find two distinctive periods of “control”, which coincide with critical on-the-ground interventions, including contact tracing and delivery of antibiotics, among others.

Discussion:

Given these results, we conclude that existing interventions remain effective against plague in Madagascar, despite the atypical size and spread of this particular outbreak.

FUNDING STATEMENT

This work was supported by the National Library of Medicine of the National Institutes of Health (R01LM010812). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords: Plague; Madagascar.

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The 2017 #plague #outbreak in #Madagascar: Data descriptions and #epidemic modelling (Epidemics, abstract)

[Source: Science Direct, full page: (LINK). Abstract, edited.]

Epidemics / Available online 2 June 2018 / In Press, Corrected Proof / Open Access

The 2017 plague outbreak in Madagascar: Data descriptions and epidemic modelling

Van Kinh Nguyen, César Parra-Rojas, Esteban A. Hernandez-Vargas, Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, 60438, Frankfurt am Main, Germany

Received 22 January 2018, Revised 27 April 2018, Accepted 2 May 2018, Available online 2 June 2018 / DOI: https://doi.org/10.1016/j.epidem.2018.05.001

 

Abstract

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.

Keywords: Plague;  Outbreak;  Modelling;  Stochastic;  Climate;  Seasonal;  Madagascar

Keywords: Plague; Bubonic plague; Pneumonic plague; Madagascar.

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#Investigation of Pneumonic #Plague, #Madagascar (Emerg Infect Dis., edited)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Edited.]

Volume 24, Number 1—January 2018 / Letter

Investigation of Pneumonic Plague, Madagascar

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To the Editor: In an investigation of a pneumonic plague outbreak in Madagascar, Ramasindrazana et al. reported isolation of Yersinia pestis from 2 patients and seroconversion in 2 additional patients; these data indicated 4 (28.7%) of 14 diagnosed cases among described cases (1). The risk for overestimation of pneumonic plague contagion was illustrated by an outbreak in the Democratic Republic of the Congo that included cases of leptospirosis (2). In fact, thorough investigations in Uganda indicated that 2 index patients transmitted Y. pestis to only 1 caregiver each and none to 23 additional untreated close contacts (3). Another investigation in China showed that 3 index patients exposed 214 contacts during 3–13 days; all contacts were quarantined, and no secondary cases were reported (4). Transmission of Y. pestis by respiratory droplets requires face-to-face exposure with a coughing patient, as can occur during funerals by close contact with coughing persons who may have been exposed to the pathogen while visiting or attending the patient before he or she died. Therefore, the threat for plague epidemics fueled by pneumonic plague can be reduced by measures such as isolating patients and wearing a mask when exposure is likely (5).

We propose the hypothesis that only the transmission of Y. pestis by ectoparasites, such as lice and fleas, by close contact with infected humans can sustain outbreaks and epidemics. In plague-endemic regions, to support the appropriate management of patients and provide a rapid and accurate microbiological diagnosis, we recommend point-of-care laboratories, some of which are now operating in a few remote regions of Africa. In addition to direct diagnosis of disease in humans, direct detection of Y. pestis at the point-of-care in potential sources and vectors would facilitate understanding of how plague epidemics sustain.

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Dr. Drancourt is Professor of Medical Microbiology at the IHU Mediterranee Infection and Aix-Marseille University in Marseille, France.

Dr. Raoult is Professor of Microbiology at Aix-Marseille University; he created ex nihilo, a research laboratory in the field of infectious diseases in Marseille currently located in the IHU Mediterranee Infection.

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Michel Drancourt   and Didier Raoult

Author affiliations: Aix-Marseille Université, Marseille, France

 

References

  1. Ramasindrazana B, Andrianaivoarimanana V, Rakotondramanga JM, Birdsell DN, Ratsitorahina M, Rajerison M. Pneumonic plague transmission, Moramanga, Madagascar, 2015. Emerg Infect Dis. 2017;23:521–4.
  2. Bertherat E, Mueller MJ, Shako JC, Picardeau M. Discovery of a leptospirosis cluster amidst a pneumonic plague outbreak in a miners’ camp in the Democratic Republic of the Congo. Int J Environ Res Public Health. 2014;11:1824–33.
  3. Begier EM, Asiki G, Anywaine Z, Yockey B, Schriefer ME, Aleti P, et al. Pneumonic plague cluster, Uganda, 2004. Emerg Infect Dis. 2006;12:460–7.
  4. Li YF, Li DB, Shao HS, Li HJ, Han YD. Plague in China 2014-All sporadic case report of pneumonic plague. BMC Infect Dis. 2016;16:85.
  5. Ratsitorahina M, Chanteau S, Rahalison L, Ratsifasoamanana L, Boisier P. Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in Madagascar. Lancet. 2000;355:111–3.

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Suggested citation for this article: Drancourt M, Raoult D. Investigation of pneumonic plague, Madagascar. Emerg Infect Dis. 2018 Jan [date cited]. https://doi.org/10.3201/eid2401.170760

DOI: 10.3201/eid2401.170760

Keywords: Plague; Madagascar.

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