Plague

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Nearly 50,000 human cases of plague were reported to the World Health Organization (WHO) by 26 countries between 1990 and 2015

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Epidemiology

Nearly 50,000 human cases of plague were reported to the World Health Organization (WHO) by 26 countries in Africa, Asia and America between 1990 and 2015. Sub-Saharan Africa is currently the most affected region, with the Democratic Republic of Congo, Uganda and above all Madagascar, which reports the highest number of human cases of plague in the world (between 250 and 500 cases a year). In Asia, the largest plague foci are in China. On the American continent, the main focus is Peru, but the USA is not exempt: indigenous cases of plague are reported on its west coast every year. No cases of plague have been reported in recent years in Oceania or Europe. The last cases in France occurred in Corsica in 1945.

One of the characteristics of plague outbreaks is their capacity to "disappear" for a number of years and then suddenly resurface and cause a further outbreak. In India, an outbreak of pneumonic plague erupted in 1994, although it was thought until then that the disease had been eradicated nearly 30 years earlier. Almost at the same time, 128 cases of bubonic plague were reported in Mozambique following more than 15 years' absence; these cases spread to neighboring Zimbabwe and Malawi. An outbreak occurred almost simultaneously in Peru, with 1,031 cases, in 1993-1994. Although closely spaced in time, there was probably no epidemiological link between the Asian, American and African outbreaks. In 1997, cases of plague in humans occurred in Jordan, following nearly 80 years' absence. Plague also reappeared in the Oran region of Algeria in 2003, following 50 years without an outbreak. An outbreak of pneumonic plague also occurred in a diamond mine in the Democratic Republic of Congo in December 2004, and a larger scale outbreak occurred in the same country in 2006.

Human cases of plague occurred in Afghanistan in 2007 whereas no cases had ever been reported there previously. More recently, plague re-emerged in Libya in 2009 after a gap of 25 years, and in Kyrgyzstan and Russia in 2013 after a gap of 30 and 34 years, respectively. Similarly, in 2016 a plague outbreak hit South-East Madagascar, in a region where no cases had been reported since 1950 and outside the known plague-endemic areas.

The natural plague foci in the world in March 2016 (WHO)

Clinical aspects

In humans, the disease takes two main forms – bubonic, contracted via flea bite, and pneumonic, contracted via airborne transmission.

Bubonic plague, which is the most common clinical form, has an incubation period of a few days and is characterized by a very severe infectious syndrome, with high fever and deterioration of general health, accompanied by a swelling of the lymph node (bubo) draining the flea bite site. In 20 to 40% of cases, the bubo suppurates and the person recovers, with convalescence being relatively slow.

Alternatively, the disease develops into septicemia and is quickly fatal. In some cases, the bacillus reaches the lungs and human-to-human transmission then takes place through inhalation of saliva droplets expelled by the patient when coughing. People thus infected go on to develop pneumonic plague. If appropriate early treatment is not administered, pneumonic plague is always fatal within three days.

Diagnosis

Clinical diagnosis of plague is based on patient symptoms and relevant history, such as travel to an endemic region or contact with a plague patient. This is followed by a laboratory analysis of fluid samples (blood, sputum, bubo samples) to identify the presence of Yersinia pestis bacteria.

Treatment

Streptomycin, tetracyclines and fluoroquinolones are the antibiotics of choice for treating plague. These antibiotics are completely effective if administered early.

Prophylactic measures

Early chemoprophylaxis with tetracyclines, sulfonamides or fluoroquinolones is generally a highly effective strategy for preventive treatment in close contacts of plague sufferers.

Recommendations for travelers to endemic foci are to avoid contact with rodents and to protect themselves from flea bites with skin repellents effective in these endemic areas. In the event of contact with a plague patient with a cough, advice should be immediately sought from a doctor who can prescribe prophylactic antibiotic treatment.

Prevention by vaccination was discontinued as the first vaccines caused side effects that were sometimes severe. Subsequently, other vaccines were developed but they are not effective on pneumonic forms. There are several vaccines currently under investigation but validation in humans is still required.

At the Institut Pasteur

The work of the Yersinia research unit primarily focuses on the analysis of:

  • Mechanisms used by Yersinia to acquire virulence factors;
  • Comparative genomics and transcriptomics between Y. pestis and Y. pseudotuberculosis;
  • Molecular bases for the exceptional pathogenicity of Y. pestis;
  • Mechanisms of innate and adaptive immunity in the host;
  • Antibiotic resistance in pathogenic Yersinia;
  • Evolution of pathogenic Yersinia.

The unit is also developing:

  • A bubonic and pneumonic plague vaccine. A vaccine candidate was patented in 2014. The next step involves preclinical trials;
  • Real-time in vivo imaging technology to study the kinetics of Y. pestis development in its host;
  • Tools for gene complementation and gene expression in vitro and in vivo;
  • Techniques for molecular characterization of the various Yersinia species.

The unit plays an active role in the surveillance and control of enteropathogenic Yersinia through its activities at national level (National Reference Center and National Surveillance Network), and in the fight against plague at the international level (World Health Organization Collaborating Center, or WHOCC).

 

Research units:

Yersinia research unit, led by Javier Pizarro-Cerdá

Public health and surveillance:


October, 2017

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