Officials in Madagascar are responding to an outbreak of plague, which the Madagascar Health Ministry reports has resulted in 169 cases and 30 deaths as of October 4. According to the WHO, plague has the “potential to trigger severe epidemics if inadequately controlled.” Arguably the most famous epidemic of bubonic plague is the Black Death, which killed more than 50 million people between 1346 and 1351 (with some estimates even higher).

Plague’s re-emergence in sub-Saharan Africa is a stark reminder that this ancient disease, far from an antiquated menace, remains a public health threat in the 21st century. The WHO has determined that the national risk to Madagascans is high, but the outbreak is unlikely to have much of a regional or global impact if outbreak control measures are swiftly implemented alongside deployment of critical resources, supplies, and technical experts. But then again, any occurrence of plague is cause for concern.

High National Risk

Plague has been endemic in Madagascar for years. In fact, between 2010 and 2015, 74% of plague cases worldwide occurred in the island nation, which averages about 400 cases a year, according to WHO epidemiological reports. A total of 584 people died of plague globally during the same period. Yet, there are reasons to believe this outbreak could be larger and deadlier than past occurrences: (1) the majority of cases reported so far are pneumonic plague, and (2) the outbreak has entered urban and non-endemic areas.

Caused by the bacterium Yersinia pestis, human plague exists primarily in two forms: bubonic and pneumonic. Bubonic plague, the more common form, typically results from transmission of Y. pestis to humans via the bite of an infected flea living on nearby rats and small animals. Untreated bubonic plague has an estimated case fatality of approximately 40-70%. Pneumonic plague occurs when the bacteria reach the lungs—by inhalation or by progression of bubonic plague via the bloodstream. Patients with pneumonic plague can transmit Y. pestis directly to others via aerosolized droplets (e.g., by sneezing). Treatment of pneumonic plague is often effective if initiated early in the disease, but with such a small window of opportunity, overall mortality for pneumonic plague hovers around 50%. Untreated, mortality approaches 100%, and it can kill in less than 24 hours.

Both types of plague have been reported during the current outbreak. While the latest Ministry of Health figures do not distinguish between the two types of plague, the WHO report from October 2 specifies there were 58 suspected cases of bubonic plague and 73 suspected cases of pneumonic plague between August 1 and September 30. One outstanding question in the Madagascar outbreak is whether the identified pneumonic plague cases are a result of respiratory exposure (primary) or the bloodborne progression of bubonic plague to the lungs (secondary). The answer to this question will help to identify the source of the infection and inform public health interventions.

In addition to the high percentage of pneumonic cases, the outbreak has another unusual feature: the occurrence of cases in urban areas of Madagascar for the first time. Its presence in densely-populated cities, including the capital of Antananarivo, means more people are at risk of exposure. More than two weeks passed between the first death and the detection of the outbreak, enabling infectious individuals to travel and spread the illness before containment measures could commence.

Low Global Risk

While the outbreak requires a concerted response, the global risk of transmission is low, according to the WHO. No epidemiologically linked cases have been reported outside of the country, and the WHO advises against any travel or trade restrictions at this time.

Unlike Ebola virus disease, another virulent disease to which plague has been compared, treatments for plague are efficacious. Although there is no vaccine, common antimicrobials such as fluoroquinolone or tetracycline classes, will cure most cases if treated early—preferably within 24 hours of symptom onset, according to the CDC. Antibiotic resistant strains of Y. pestis have been documented previously, so authorities will need to carefully monitor for existing or emerging resistance.

Interventions by Madagascan officials include isolating and treating cases, identifying potentially exposed contacts, and spraying rat poison to eliminate vectors. The WHO has also stepped up its response in the region, including the release of $300,000 in emergency funds and the deployment of field teams and medical supplies. As with the Ebola response, interrupting the chain of transmission at critical nodes—such as burial rituals—is key to controlling the outbreak. An epidemiological analysis of the 1997 plague outbreak in Madagascar revealed that “funeral ceremonies and attendance on patients contaminated other villagers” following the initial cases.

Madagascar’s Prime Minister announced on Saturday that public gatherings and demonstrations are banned in Antananarivo, Madagascar’s capital city, to prevent further spread of the disease. Social distancing measures, including bans on public gatherings, have been used for centuries to combat outbreaks, but it remains to be seen if this type of intervention will have any meaningful impact on Madagascar’s plague outbreak. One plague modeling effort found that limiting travel between regions did not appreciably decrease the ultimate size of the outbreak, but it did result in the disease being concentrated in the areas initially affected. This modeled a significantly larger geographical area, but we could potentially see similar effects in Antananarivo.

While the Madagascar outbreak is not thought to pose a high risk of global spread, any significant outbreak of plague is a cause for concern—a fear heightened by plague’s potential as a biological weapon. Plague is considered to be “one of the most serious bioterrorism threats,” and several countries have developed aerosolized plague weapons in the past. Indeed, one of the first instances of biological warfare can arguably be traced to 1346, when plague-infected corpses were loaded onto catapults and launched over the walls of the besieged city of Caffa. Though there is no evidence that the current outbreak in Madagascar is anything other than a naturally occurring one, the abundance of plague cases represents a biosecurity risk and should be monitored closely.

 

Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly in near-real time to allow others to learn from these experiences in order to improve global outbreak response capabilities.

Photo courtesy of National Institute of Allergy and Infectious Diseases (NIAID)