Monkey pox: "This circulation of the disease is completely new"

Since the beginning of May, more than a hundred suspected cases of monkeypox, a disease originating in Africa, have been detected in several European countries as well as in North America, Australia and Israel. What is this virus? Who is concerned ? Should we be worried about this outbreak? Committed to the project for 3 years Afripox, which aims to better understand monkeypox in its region of emergence, Camille Besombes, infectious disease specialist and doctoral student in the unit of Arnaud Fontanet, project coordinator, takes stock.

The Conversation: What is monkeypox virus, or monkeypox ?

Camille Besombes: The monkeypox virus (monkeypox) belongs to the genus Orthopoxvirus, to which the smallpox virus belongs. It is a large DNA virus that has a particular appetite for skin tissue. However, unlike the smallpox virus, which only infected humans and was thus able to be eradicated following mass vaccination of the world's population, the monkeypox has an animal reservoir. And contrary to what one might think, this reservoir is not the monkey.

Indeed, if the monkeypox owes its name to the fact of having been isolated for the first time in captive primates (in 1958 in Denmark), its reservoir would actually be a rodent or a squirrel. The first human case of infection with monkeypox, a 9-month-old child, was detected in 1970, in the Democratic Republic of Congo, as part of the reinforcement of the smallpox eradication campaign.

Two strains of the virus are currently known monkeypox. The so-called “West Africa” strain, whose lethality is around 1%, is rampant in Nigeria, Liberia, Sierra Leone and Côte d'Ivoire. It is this strain which is implicated in the cases currently detected in Europe. The second strain, known as "from the Congo Basin", circulates in the Democratic Republic of Congo (DRC), in the Republic of Congo, in the Central African Republic (CAR), in Gabon and also in Cameroon (this country is located at the limit of the distribution of the two strains, and cases from Nigeria have recently been described there). Associated with more severe clinical forms, the “Congo Basin” strain has a lethality of 10%.

It should be remembered, however, that these figures relate to countries where, unfortunately, the medical care of patients is difficult in the most remote regions. Currently, about ten patients are hospitalized, for some in order to better isolate them, but no severe form has been identified in Europe.

TC: What are the symptoms of the disease?

CC: After a relatively long incubation period (from 6 to 13 days, even up to 21 days), the disease begins with two days of "prodromes", early symptoms of the disease: a fever which may be high, headaches, an increase in the volume of the lymph nodes (which is a differential sign with smallpox), muscle pain, fatigue… Patients are considered contagious from this phase.

Skin rashes then occur, often on the face at first. They gradually spread to the rest of the body. This cutaneous involvement is painful because of the inflammation caused around the lesions, in addition there is significant itching. In the case of the West African strain, these lesions may initially be rare and inconspicuous, and therefore potentially go unnoticed. The disease typically lasts 2 to 4 weeks, and resolves spontaneously in the majority of cases.

The main complications are the occurrence of dehydration, due to the loss of water that occurs when the lesions are numerous and extensive, bacterial superinfection of the said lesions and septicemia, as well as ocular / corneal lesions which can lead to a loss of vision. In addition, encephalitis (inflammation of the brain, editor's note) have been described.

Children are more often victims of complications and therefore have a higher mortality rate than adults. It is assumed that immunocompromised people (especially HIV-positive individuals) also have a greater risk of developing severe forms, but data are still lacking to be able to say this with certainty. During the outbreak in Nigeria, 4 of the 7 people who died were HIV positive.

Management of the disease is essentially symptomatic: disinfection of lesions, administration of antibiotic therapy in the event of superinfection, rehydration, etc. Certain antiviral molecules are currently being evaluated for their efficacy on monkeypox (the tecovimat notably), but the results are not yet available.

TC: Is this the first time that this virus has spread beyond the African continent? How many cases have been identified so far, and where?

CC: No, it's not the first time. While the Congo Basin strain has never left Africa, the West African strain has already made inroads into the United States in 2003, following the importation of infected animals. More recently, several imported human cases have also been reported in various countries.

In 2003, American patients had been contaminated following contact with infected prairie dogs, purchased in pet stores where they had rubbed shoulders with Gambian rats (Cricetomys gambianus) imported from Ghana and carrying the monkeypox. There were 47 suspected human cases, resulting from animal-to-human transmission (so-called “zoonotic” transmission). No human-to-human transmission had taken place. At the time, US authorities were concerned about the risk of the virus taking hold in an indigenous animal reservoir, but this did not occur.

In 2017, a larger outbreak occurred in Nigeria, a country that had not recorded a monkeypox outbreak for 40 years. This epidemic continues today, fueled by sporadic and regular zoonotic and human-to-human transmissions. Just over 500 suspected cases have been reported to date (including 215 confirmed). Reassuring point: in 5 years, only 8 deaths have been deplored.

This Nigerian epidemic, however, has changed the situation. Indeed, whereas previously the virus was more prevalent in forest regions with little connection to the rest of the country and the world, in 2017 it reached the urban areas of Nigeria, from where it could more easily spread outside the continent. Consequence: in 2018 several cases occurred in Singapore, Israel, and England, among travelers returning from Nigeria.

In the latter country, an indigenous transmission occurred: a British nurse became contaminated while cleaning a patient's bed. The outbreak had not spread, but further cases subsequently emerged in the UK in 2021, again linked to returning travelers from Nigeria, as well as in the US (two cases reported).

TC: How is the current context different?

CC: The situation is very different. Admittedly, the first case of the current outbreak, which occurred on May 7 in the UK, was a traveler returning from Nigeria. But since then, several other cases have been confirmed in the United Kingdom without it being possible to establish a link either with the case of May 7 or between them. No travel abroad compatible with contamination could be demonstrated, and direct chains of transmission could not be established. This situation suggests that there are several chains of transmission and autochthonous circulation of the virus.

Since May 18, cases have also been detected in Spain (7 confirmed cases, 16 suspected cases), Portugal (5 confirmed cases and 15 suspected cases), Sweden (1 confirmed), Italy (1 confirmed, 2 suspected cases ), Belgium (1 confirmed, 2 suspected), Canada (12 suspected cases in Montreal), Australia (1 confirmed case, 1 suspected case), Germany and Belgium. A case was also confirmed in the United States (this person had recently traveled to Canada). In France, a suspected case was reported by the Directorate General of Health on May 19.

So far all of these infections have been mild. Of the 80 confirmed cases and the fifty suspected cases, around ten patients are currently hospitalized in Europe, but more from a perspective of isolation than due to clinical severity.

This autochthonous circulation of the disease is completely new. Another novelty: these cases concern almost exclusively young men, declaring themselves, for the majority of them, as having sexual relations with other men. A case in a woman was announced in Spain on May 20, 2022.

TC: How is this new? What are the usual modes of contamination?

CC: Monkeypox epidemics usually begin with animal-to-human transmission, although the details are unknown, and the same virus strain has never been isolated from an animal and a human. It could be direct contact with a live animal, during hunting, or during the consumption of bushmeat.

More specifically, in the context of the research we are conducting in the CAR, we have observed a seasonal upsurge in epidemics suggesting a link with certain seasonal activities, such as the collection of edible caterpillars in the forest, suggesting exposure to local fauna during these collections.

Although scientists have been tracking the reservoir of this virus since the 1970s, it has only been isolated from wild animals 5 times so far: in 1985 in the Democratic Republic of Congo in a squirrel, the Stripe-backed Funisciure (Funisciurus anerythrus, which is suspected to be the reservoir of monkeypox), then in 1992 in a monkey mangabey (Cercocebus atys) in Côte d'Ivoire, and finally, two decades later, in the Gambian rat and another rodent (Stochomys longicaudatus), as well as in another Funisciure (Funisciurus bayonii). At present, therefore, the main suspects are rodents, including squirrels.

Interestingly, the monkeypox has been isolated on chimpanzee faeces, in the Taï National Park in Côte d'Ivoire, during an epidemic in primates, suggesting the possibility of environmental contamination.

Beyond zoonotic transmission, human-to-human transmission occurs, following direct and prolonged contact with patients, with their bodily fluids or by touching contaminated surfaces (clothing, bedding, surfaces, etc.), most of the time within fireplace.

Transmission by respiratory droplets is also mentioned, but this point is difficult to establish clearly. Indeed, contaminations generally occur within families, where the proximity is close and the modes of contact numerous and varied. In Africa, nosocomial transmissions have also been documented.

When describing in detail the cases of the 2017 Nigeria epidemic, the high proportion of genital involvement (68%) raised for the first time a suspicion of a potential transmission by close contact during sexual intercourse. This proportion is also very high for the cases in CAR for which we have this data.

Intimate and close contacts during sexual intercourse would explain the facilitation of human-to-human transmission of a virus usually known as not very transmissible. This hypothesis seems supported by the fact that – for the moment – ​​the “outside Africa” cases of recent weeks mainly concern young men who have sex with other men, or defining themselves as homosexual. Note that this transmission could also occur during heterosexual intercourse.

TC: Should we fear a strong spread of this disease? How to limit it?

CC: For the moment, we cannot be certain about what will happen. The problem is these new cases which do not yet correspond to any defined chain of transmission. As the daily evolution shows and due to a relatively long incubation, there is a real risk that new infections will break out in the countries already affected or in other countries in the coming days or weeks. Several cases that occurred in Spain and Italy appear in connection with a festive event on the Canary Islands between May 5 and May 15, having gathered 80 people, and having been able to play the role of propagating event. Similarly, in Spain, the country with the highest number of cases to date, a sauna in the capital seems to have been a hotbed of contamination.

In order to limit the spread of the virus, it is necessary to raise awareness and inform the communities and people concerned as well as the doctors, in order to quickly identify all cases and trace their contacts. A difficulty for doctors is that the lesions resemble those of chickenpox, and that genital lesions can be confused with the symptoms of certain STDs (syphilis, herpes, etc.). A PCR test and the isolation of the virus can confirm the diagnosis, but only certain specialized laboratories are equipped to carry out this type of analysis.

A rather reassuring point is that epidemics of monkeypox die out quite quickly spontaneously. The longest chain of transmission identified spanned 7 generations, in other words 7 humans pass the disease consecutively before the transmission stops.

The reasons for this spontaneous extinction of the spread are poorly understood. One hypothesis is that these epidemics have hitherto occurred in small villages, within communities of limited size with certain individuals potentially already immunized: the virus only infects people who have never been in contact with it. The 2003 epidemic in the United States had also stopped quickly, without secondary human-to-human contamination.

To be continued this time…

TC: Could the smallpox vaccine be used against this virus?

CC: Natural infection with variola virus is known to cross-protect against monkeypox. In the 1980s, it was shown that the smallpox vaccine also conferred cross-protection, estimated at 85%. However, these estimates were made only a few years after mass vaccination campaigns aimed at eradicating smallpox. Currently, it is considered that the effectiveness rather revolves around 65%.

In addition, smallpox vaccination was suspended in the 1980s, after the eradication of the disease. Today only certain health personnel are still vaccinated (to be able to respond to a bioterrorist risk – the virus remaining stored under close surveillance in certain laboratories). The first generation smallpox vaccine is no longer used, due to significant adverse effects.

For now, the vaccine most likely to be deployed if needed is a so-called "3^e generation”, Imvamune (or Imvanex). This is'an attenuated vaccine, however, unlike older vaccines, it can be given to immunocompromised people. It has already been used in Israel, Singapore, and the United Kingdom among healthcare workers and contacts of imported cases. Its effectiveness is currently in evaluation course in the DRC, among health personnel.

4 vaccines^e generation are also under development. These are “subunit” vaccines, which no longer contain attenuated virus, but only fragments. Their effectiveness is also being evaluated.

The vaccine can be used not only in pre-exposure (administration before encountering the virus), but also in post-exposure. In the United States, the recommendation is to administer it preferably within 4 days post-exposure, and up to 14 days.

TC: Is there a risk of seeing other monkeypox variants emerge? Is the genome of the virus currently circulating in Europe strictly the same as that of the West African strain?

CC: Since monkeypox is a DNA virus, it is less likely to mutate than RNA viruses like SARS-CoV-2.

It is quite easy to determine whether we are dealing with the West African strain or that of the Congo Basin: all that is needed is to sequence short specific sequences of its DNA. On the other hand, given the large size of the genome of this virus, it is longer and more tedious to obtain a complete sequence, which is necessary to detect sequence differences more finely, and thus establish chains of transmission and links. between cases. But the experience of SARS-CoV-2 has shown us that general mobilization could greatly speed things up...

The first sequences carried out in a Portuguese patient and a Belgian patient highlight on the one hand the genetic proximity of this virus with those isolated in Nigeria and in previous 2018 exports, And the similarity of the two genomes, suggesting community transmission in Europe. Other sequencing is necessary to answer all the persistent questions, and in particular to see if an adaptation of the genome is in progress and this towards a greater transmissibility of the virus. For the moment, there are no elements that go in this direction.

TC: To better understand monkeypox and its circulation dynamics. the Institut Pasteur and its partners in France and the CAR set up in 2019 the Afripox project. What does it consist on ?

CC: This transdisciplinary project was set up after Emmanuel Yandoko Nakoune, who heads the laboratory for arboviruses, haemorrhagic fevers, emerging viruses and zoonoses at the Institut Pasteur de Bangui in CAR, reported an increase in the number of smallpox epidemics in monkey in the country.

More broadly, in recent decades there has been an increase in the number and frequency of monkeypox epidemics in Africa, as well as an expansion into areas where the disease was not endemic. Improved surveillance and waning immunity (smallpox vaccination was stopped in 1980) probably contribute to this increase, however it also seems to reflect increased viral circulation, in a region of the world experiencing disruptions major environmental issues.

Faced with the large number of unknowns around the epidemiology of monkeypox, the idea of ​​this project was to rely on the national surveillance already in place in the CAR to develop an approach OneHealth of monkeypox by focusing on its epidemiological, ecological, zoological, anthropological and virological aspects.

In partnership with researchers from the National Museum of Natural History, we are trying, for example, to identify its animal reservoir. With the team of SESSIM in Marseille, we are exploring the ecology of the disease in order to understand, for example, what explains its rather forest-based distribution, to identify the impact of deforestation on epidemics, to determine whether there is a seasonality, etc.

The development of diagnostic PCR tests that can be used in the field, by the team of the Emergency Biological Intervention Unit (Cibu) at the Institut Pasteur in Paris, is also one of the goals of Afripox (currently, the suspect samples are analyzed in Bangui). This would reduce the confirmation time and facilitate the rapid implementation of appropriate measures.

Finally, the epidemiological and anthropological aspects are explored by teams from the Institut Pasteur Paris (Emerging Disease Epidemiology Unit and Anthropology and Ecology of Disease Emergence Unit), in collaboration with local researchers, in order to determine more precisely what are the risk factors for zoonotic or human-to-human transmission, and why monkeypox has been on the rise since the 1980s. Indeed, while understanding the dynamics of this new human-to-human epidemic and its relatively unprecedented, understanding the emergence and circulation of monkeypox on its continent of origin is just as fundamental.

When Afripox was set up 3 years ago, few people imagined that this disease might one day leave the African continent to spread across the planet. The current epidemic once again underlines the importance of investing in scientific research over the long term, in order to prepare for all eventualities...

Camille Besombes, Doctor of infectious diseases in epidemiology thesis - Epidemiology of emerging diseases unit, Pasteur Institute et Arnaud Fontanet, Doctor, director of the Emerging Diseases Epidemiology Unit at the Institut Pasteur in Paris, professor of public health, National Conservatory of Arts and Crafts (CNAM)

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.