IDCM CME 1-3: Old Disease in Modern Times: Plague and the 2017 Madagascar Outbreak

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Natasha Chida, MD, MSPH

Old Disease in Modern Times: Plague and the 2017 Madagascar Outbreak

In August 2017, one of worst plague epidemics in 50 years began in Madagascar, after an infected man traveled from the central highlands to several urban cities.1 He died in transit. Dozens of people who were in contact with him became ill, and the disease spread to nearly half of the districts in the country. It took until November to contain the epidemic, and by then a total of 2,348 confirmed, probable, and suspected cases of plague were identified. Of these, 202 people died (for a case fatality rate of 8.6%).2 Before response to this outbreak is discussed, we provide some context about the severity of plague.

It is estimated that plague infection has killed more than 200 million humans throughout history, and has been linked to three major pandemics:3

  1. 6th century Eastern Roman Empire, known as the Justinian Plague, is the first recorded pandemic
  2. 14th century European outbreak known as the “Black Death” killed a third of the European population
  3. Late 19th century outbreak began in China and spread to multiple continents through the shipping trade.4 This third pandemic led to the establishment of enzootic foci in multiple areas throughout the world, including the central highlands of Madagascar.

The primary natural hosts of Y. pestis are rodents, but other mammals can be infected.5 Plague may be transmitted to humans though bites from rodent fleas, scratches, or bites from infected cats, inhalation of respiratory secretions of infected animals or humans, and exposure to infected tissue. Human-to-human transmission occurs primarily via infected respiratory droplets when the organism has infected the lungs. 

Plague is the disease caused by the gram-negative coccobacillus Yersinia pestis. There are 3 main syndromes6:

  1. Bubonic Plague: Most often occurs when Y. pestis enters the body through a flea bite. The organism travels to the closest lymph node and replicates, resulting in tender, swollen lymph nodes (buboes), fevers, chills, head and body aches, vomiting and nausea. Bubonic plague can lead to bacteremia, meningitis, and secondary pneumonic plague.
  2. Primary Pneumonic Plague: Most often occurs when a person inhales Y. pestis via infected droplets from another person. It is characterized by rapid onset of dyspnea, high fever, pleurisy, and cough (sometimes with bloody sputum).
  3. Primary Septicemia: Occurs when plague bacteremia is present in the absence of buboes, primary pneumonia, etc. It presents similarly to bubonic plague, but lacks the buboes.

Aminoglycosides are the mainstay of treatment, followed by tetracyclines and fluroquinolones.7 The mortality rate of treated bubonic plague ranges from 10-20%, while untreated bubonic plague has a mortality rate of 50-90%. Pneumonic plague has 50% mortality with treatment, and 100% with no treatment. 48-hour postexposure prophylaxis (options include tetracyclines, fluroquinolones, chloramphenicol, and others) is recommended for persons who have had close contact with someone with pneumonic plague.

Plague in Modern Times
Although plague is often thought of as an “old world” disease, infections continue to occur. Between 2010 and 2015, 3248 cases and 584 deaths were reported worldwide.6 The organism is found on all continents of the globe except Australia, and the most endemic countries are the Democratic Republic of Congo, Madagascar, and Peru. While endemic in the United States (particularly the western states), the rate of plague in the US is low due to affected areas being generally uninhabited. A total of 91 cases of human plague were reported in the US from 2000 to 2015; 80% were bubonic.8

Madagascar reports nearly one third of all cases of plague globally.9 Cases are reported every year, are usually bubonic, and are often confined to rural regions. Plague “season” in Madagascar is September–April, and it occurs due to environmental changes that decrease the rat population, leading fleas to feed off humans at a greater rate.1

Madagascar faces several challenges that may increase its risk for outbreaks: 

  • Underfunded health system. Madagascar has been ineligible for foreign aid since a 2009 coup.1 The country spends $14 per capita on healthcare annually—the lowest in the world.
  • Reliance on traditional medicine. In rural regions, people who are ill prefer to see traditional healers, which can delay treatment of plague. This may be due in part to the fact that 40% of the population lives far from a health center.10
  • Funeral practices. Ritual exhumation of corpses, a practice in Madagascar, has been associated with clusters of infection.9
  • Opportunities for rodent infestation. The practice of storage of crops in houses (which prevents theft) can increase the presence of rodents (and fleas), while bushfires, farming, and deforestation can contribute to the spread of rats.
  • Poverty. Overcrowded living conditions associated with poverty contribute to increased transmission of disease. 

2017 Outbreak Response
The 2017 outbreak was unusual because urban areas were affected, and cases were detected in nearly half the country (55 out of 114 districts).2 The majority of cases (1791) were pneumonic, and 22% were confirmed. Outbreak response was hampered by weak supply chains, poor healthcare infrastructure, shortages of necessary equipment and materials, and lack of available rapid diagnostic tests.1 When diagnosis is delayed, person-to-person transmission increases; more than 70 healthcare workers were infected during the outbreak.

After the initial delay, the Madagascar Ministry of Public Health (with support from multiple multinational agencies and partners including the WHO), launched an effective multipronged public health response. This included measures such as  strengthened epidemiologic surveillance, enhanced case finding and the use of rapid diagnostic tests, isolation of cases, active case finding, contact tracing, disinfection, and public awareness measures including distribution of information on burial practices and avoiding animal carcasses, etc.1,4 As a result, containment was announced at the end of November.2

Bottom line: Plague is a bacterial infection that can be associated with high mortality. The 2017 Madagascar outbreak highlights how under-resourced health systems can put a country at risk for a serious infectious disease outbreak, and how public health strategies can control the spread of disease.

Bottom line: Plague is a bacterial infection that can be associated with high mortality. The 2017 Madagascar outbreak highlights how under-resourced health systems can put a country at risk for a serious infectious disease outbreak, and how public health strategies can control the spread of disease.


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  2. WHO. Plague-Madagascar. Accessed 1/31/18.
  3. Rollins SE, Rollins SM, Ryan ET. Yersinia pestis and the plague. Am J Clin Pathol. 2003 Jun;119 Suppl:S78-85.
  4. Mead PS. Plague in Madagascar - A Tragic Opportunity for Improving Public Health. N Engl J Med. 2018 Jan 11;378(2):106-108.
  5. Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. 1997 Jan;10(1):35-66.
  6. WHO. Plague. Accessed 1/31/18.
  7. Prentice MB, Rahalison L. Plague. Lancet. 2007 Apr 7;369(9568):1196-207.
  9. Andrianaivoarimanana V, et al. Understanding the persistence of plague foci in Madagascar. PLoS Negl Trop Dis. 2013 Nov 7;7(11):e2382.
  10. Barmania S. Madagascar's health challenges. Lancet. 2015 Aug 22;386(9995):729-30.