The history of mpox: from the very first cases to new findings

In the Central African Republic, local populations depend on hunting for animal protein. But over the decades, access to this source of animal protein has become increasingly difficult. Large game has become less abundant, and there has been a new trend towards hunting smaller animals, including rodents, some of which are thought to be an animal reservoir for mpox (see below).

In 2010, the CAR took the decisive step of making mpox a notifiable disease, thereby stepping up its surveillance of this emerging health threat. This resulted in better documentation and a more structured response to any new cases.

In 2012, the CAR began to experience a period of socio-political instability which led people to flee villages and take refuge in forests, and it is likely that this created favorable conditions for direct contact with animals that were potential carriers of MPXV, especially the small animals already suspected. "Despite the sporadic presence of medical groups like Médecins Sans Frontières (MSF), it was hard to maintain continuity of care. MSF regularly sent me samples to confirm the diagnosis," says Emmanuel Nakouné. This enabled them to observe a link between the localization of forest populations and their proximity with animal reservoirs.

Between 2013 and 2016, a slowdown was observed, with an average of 5 to 10 cases a year in the CAR. In 2013, Emmanuel Nakoune decided to submit a research proposal (an "Inter-Pasteurian Concerted Action" or ACIP) to investigate the epidemiology of mpox. The research found that more than 50% of the population studied had antibodies against orthopoxviruses. Older people had developed these antibodies after being vaccinated for smallpox. As smallpox vaccination continued until 1980, this likely explains why mpox outbreaks were contained in villages.

The largest outbreak in the CAR over this period was in 2016, following the late detection of a case in a child. After an initial visit to a dispensary, the family had to travel to a regional hospital using various means of transport, which facilitated the spread of the virus to multiple contacts, including family members and medical staff without sufficient protection. A total of 13 people were infected from this one initial case. This outbreak revealed the shortcomings in the local health system.

The Afripox project was launched in 2019 but soon had to be put on hold because of the COVID-19 pandemic. However, the multi-country mpox outbreak in 2022 sparked renewed concern among health authorities and the scientific community, leading to the resumption of Afripox and its conclusion in 2024, with significant new discoveries.

The teams at the Institut Pasteur in Paris (Antoine Gessain, Arnaud Fontanet, Jean-Claude Manuguerra and Tamara Giles-Vernick) and the Institut Pasteur de Bangui (Emmanuel Nakouné) worked together on the Afripox project, which was funded by the French National Research Agency (ANR). They had several objectives:

• To gain a more detailed understanding of the conditions for the emergence of MPXV;
• To provide a more precise description of the clinical forms of mpox in an African context;
• To identify the animal reservoirs and secondary hosts of the virus;
• To improve diagnostic tests for use in remote areas;
• To understand the practices of local populations and their perception of the disease.

Knowledge about the clinical profile of mpox has developed. Since 2021, physicians have followed a strict protocol when administering tecovirimat, a treatment used for mpox. Every day after administering the drug, they count the number of skin lesions. This led them to notice that in the vast majority of cases, patients had skin lesions near their genital organs. "This indicates possible transmission during sexual intercourse," explains Arnaud Fontanet. "It can even be considered as a high-risk behavior. These lesions could explain transmission between parents within the household," he adds.

The team led by Alexandre Hassanin at the French Museum of Natural History in Paris and the Oncogenic Virus Epidemiology and Pathophysiology (EPVO) team led by Antoine Gessain have contributed to research on viral reservoirs for mpox. They compared the ecological niche of MPXV with the ecological niches of the African mammals most likely to be infected. With the help of this information, they were able to analyze overlaps in ecological niches using modeling and create maps to identify which animal species is most likely to be the MPXV reservoir. The results showed that the Thomas’s rope squirrel (Funisciurus anerythrus) is probably the reservoir for MPXV. The species is found in the tropical rainforest areas of Central and West Africa.

The animal reservoir, the Funisciurus anerythrus squirrel © Mathias D'haen-GabonBiota.org portal

Tamara Giles-Vernick, an anthropologist at the Institut Pasteur, carried out a study to find out about the hunting practices of local populations. Having completed her PhD in the CAR 30 years ago, she was able to demonstrate that hunting practices have changed. "Forty-five years ago, people hunted large game more easily, so rodents were not consumed or even sought after. But with the difficulties in animal breeding and the reduction in populations of large animals, people have become dependent on small animals for animal proteins. We are observing a change in hunting practices," explains Tamara Giles-Vernick. "In areas where large game is declining, rodents seem to be reproducing quickly, leading to a change in the profile of forest animals." Observations show that the capture and consumption of squirrels has been on the rise over the past 30 years.

Tamara's study also shows how local populations have interpreted the arrival of mpox. "It is important to be aware of the way in which people experience illnesses and explain them among themselves. Local populations do not know where mpox comes from but the arrival of such novel diseases is seen as a reflection of a political and economic decline since the 1980s. If an adult contracts mpox, it can also be perceived as being linked to witchcraft, often blamed for bad fortune. So it is crucial to adapt communication at a local level to remove any stigma, make sure that people understand what is happening and encourage them to comply with public health advice," adds Tamara. Even the name of the disease is different from one region to another, highlighting the need for communication tailored to each area.

Novel sequencing methods are being developed using techniques suitable for less well equipped laboratories. This technology can be used to monitor the spread of the virus, quickly detect mutations and adapt response strategies. It plays an important role in the general surveillance of the disease, facilitating anticipation and ensuring a more effective response to outbreaks.

Viral sequencing has shown that the strains circulating in the CAR are closely related to the DRC strain, and that the first cases of these strains are likely to have emerged in 1945. They are thought to have separated in the 1960s-70s following population movements at the time, which would explain the difference between the strains in south-west and south-east CAR.