Beginning of the plague season in Madagascar: what did we learn from previous events?

Plague investigation, Manandriana, Madagascar, 2019

Throughout human history, plague has proven its capacity to disrupt human society and its socioeconomic and cultural impacts. For the past 30 years, WHO has reported a continuously increasing number of human cases of plague and the disease is considered as “re-emergent” in different countries. Areas that have reported human cases in the last 6 years are limited to sub-Saharan Africa, Asia, and North and South America. Together with the Democratic Republic of the Congo (DRC), Madagascar continues to report the most cases of plague in the world[1].  Recently, Mongolia reported human cases of bubonic plague. The DRC has seen an upsurge of plague cases since June 2020 from its endemic Ituri province[2].

Plague is endemic in Madagascar, with a number of reported human cases ranging from 280 to 600 per year. In Madagascar, plague shows a recrudescence mainly between September and March, which coincides with the hot and rainy season in the agricultural highlands, one of the main plague foci of the island.

In 2017, Madagascar faced an unprecedented epidemic of urban pulmonary plague. We argue that, viewed alongside the recent large-scale Ebola outbreaks in densely populated and extremely poor areas in Africa, this should be taken as a serious warning. Prior to the West Africa Ebola tragedy, there were few indicators that a massive Ebola epidemic was possible. We cannot say as much about plague; the distant and recent history is in plain sight. This is a tipping point in human plague epidemiology and a call to elevate research priorities on plague as a matter of some emergency. Indeed, we have an opportunity to act preventively and enable evidence-based measures to avoid major health crises due to plague outbreaks in the near future.

Almost 125 years after the discovery of Yersinia pestis, the agent of plague, its enduring threat to human health is a testament to the neglect of this disease. For instance, we do not have reliable means for the rapid diagnosis of pneumonic plague nor a safe and effective vaccine for its prevention. The overall short-term focus should therefore be on specific research priorities that would facilitate better control of human plague: mapping plague risk (through an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment), improving diagnostic tools and case management, developing a vaccine and strengthening community-based interventions. A cross-disciplinary approach is therefore needed, that spans preclinical research, clinical research, behavioral and social sciences and ecological sciences. A two days’ workshop was organized in July 2018 in Institut Pasteur (Paris), bringing together some of the plague specialists around the world and potential funding institutions (54 participants from 12 countries) to identify the activities of priority, to move forward key translational and operational research activities. Human (public health and medical sciences), animal (wild & peri-domestic) and environmental components were addressed through a “One health” approach.

Two papers summarize this workshop’s conclusions (“Can we make human plague history? A call to action”, by Baril L et al. in BMJ Global Health in 2019) and describe research priorities (“Human plague: An old scourge that needs new answers”, by Vallès X et al., in PLoS Neglected Tropical Disease on August 27, 2020).

Resolutions from this workshop coupled with public health priorities identified during the outbreak allowed us to develop from now 2 projects. The first, An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial, should help to improve plague case management. The second, a research project selected for the creation of the Pasteur joint International research Unit (PIU) 2020, which, thanks to the synergistic approaches of the PIU members (the ‘Plague Unit’ and the ‘Medical Entomology Unit’ of the Institut Pasteur in Madagascar, the ‘Plague and Yersinia pestis Unit’ of the Institut Pasteur in Lille, and the ‘Yersinia Research Unit’ of the Institut Pasteur in Paris), their common goals and on-going collaborations, is investigating the “Emergence, maintenance and spread of plague in Madagascar”. In addition to the subvention from each IP members, the PIU received support from IP-International Direction through an ACIP for investigating the role of fleas and a PhD fellowship for studying the immune response against plague infection in human, both in order to achieve partially the objectives of the PIU project.

All these studies will help in better understanding plague in Madagascar and improving its control.

[1] WHO, WER 2019