More than 50 years after its emergence, the Marburg virus remains a part of the mystery

This summer, a resident of the village of Temessadou M'Boket, in Guinea, fell ill. Suffering from fever, headaches and bleeding, he died on August 5. The analyzes revealed that he had been the victim of the Marburg virus, a virus of the Filovirus family, to which the Ebola virus also belongs.

It was the first time that this virus had been detected in this West African country: so far, the rare cases diagnosed had been further east of the continent (in the Democratic Republic of the Congo, in Uganda and in Kenya in particular) or in the South (South Africa).

While the follow-up of more than 155 contact persons has not revealed any other suspected case, vigilance remains essential. Where is the situation, and why is virus surveillance in this family so important?

A virus responsible for severe hemorrhagic fevers

The medical history of the Marburg virus begins surprisingly in Europe, as its name suggests: this virus was first discovered in 1967, simultaneously in Germany, in the city of Marburg as well as in Frankfurt, and in Yugoslavia ( now Serbia), in Belgrade. Laboratory workers have become ill after coming into contact with green monkeys from Uganda, or their tissues (especially when preparing cell cultures). Thirty-one people were infected and developed hemorrhagic fevers. The patients were initially laboratory staff, then the infection spread to members of the medical staff who had treated the first patients, as well as to their families. Seven victims were reported at the time.

After this first outbreak, Marburg did not reappear until 1975, when a traveler, possibly exposed in Zimbabwe, fell ill in Johannesburg, South Africa. The virus was transmitted there to his traveling companion as well as to a nurse. Since then, a few sporadic cases of infection with this virus have been detected. He was also responsible for two major epidemics in the Democratic Republic of the Congo in 1999, where it infected 154 people and claimed 128 victims, as well as in Angola in 2005, where it killed 227 people out of 252 recorded infections.

We now know that the Marburg virus is an RNA virus that belongs to a family of viruses called Filovirus (Filoviridae). So far, three genera of this family of viruses have been identified: Cuevavirus, Marbourgvirus and Ebolavirus (of which six species are known, four of which cause disease in humans). Filoviruses can cause severe hemorrhagic fever in primates, including humans (as well as in pigs in the case of the Ebola Reston strain).

Rare, but severe hemorrhagic fever

Marburg virus disease results in a hemorrhagic fever that affects both humans and non-human primates (the green monkeys that caused the European outbreak may have been in the incubation phase when imported ).

After an incubation period of 2 to 21 days, the onset of symptoms is sudden and marked by fever, chills, headache and myalgia. Around the fifth day after the onset of symptoms, a rash of pimples, more marked on the trunk (chest, back, stomach), may appear. The patient may experience chest pain, sore throat, abdominal pain, and nausea, vomiting, or diarrhea. The symptoms worsen over time. The deterioration of the patient's condition usually involves jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhage and dysfunction of several organs.

Its lethality has varied depending on the epidemics: according to the WHO, it is between 24% and 88%. It depends a lot on the quality of patient care and the available infrastructure, as well as the viral inoculum (the quantity of viral particles) at the time of transmission. One of the difficulties is that the clinical diagnosis of Marburg virus disease can be complicated: many signs and symptoms are similar to those of other infectious diseases such as malaria or typhoid fever, and others. Viral hemorrhagic fevers which may be endemic in the area (such as Lassa fever or Ebola).

There is no specific treatment for Marburg virus disease, neither preventive nor curative. The only solution is to provide patients with supportive hospital treatment, which includes balancing their fluids and electrolytes, maintaining oxygenation and blood pressure, replacing lost blood and clotting factors. , as well as the treatment of any infectious complication. Experimental treatments have been validated in models of non-human primates, but have never yet been tried in humans.

Viruses that are relatively difficult to spread

Fortunately - given their lethality - hemorrhagic fever viruses belonging to the Filovirus family have a relatively low baseline reproduction rate. It is between 1 and 2. In other words, in a non-immune population, without protective measures, a sick person only infects one or two other people on average. As a reminder, the number of reproduction of the influenza virus is between 2 and 3, and that of the Delta variant of the SARS-CoV-2 coronavirus. could reach 6).

This is explained by the mode of transmission of these viruses: for a person to be infected, he must have had close contact with a patient (or with his body fluids, especially blood). In Filovirus outbreaks, people who fed, washed, cared for or worked very closely with infected patients were therefore particularly at risk of becoming infected themselves. Another important factor in the spread of these diseases has probably been transmission in hospitals, through contact with infected bodily fluids - via the reuse of syringes, needles or other unsterilized medical equipment contaminated with these fluids. Conversely, when close contact between uninfected and infected people is minimized, the number of new Filovirus infections is lower.

However, the occurrence of an outbreak of these diseases in a country remains a source of concern. If detected early, contact tracing and isolation of patients and contacts can effectively interrupt chains of transmission. But any delay constitutes a major risk for public health. However, diagnostic and care infrastructures are not available in all regions of the continent. The consequences are therefore not the same depending on where the first infections occur.

In regions where detection devices are lacking, symptomatic or non-symptomatic patients can spread the disease undetected, particularly in city centers. The great Ebola epidemic that occurred in West Africa in 2014-2016 is an example: it started in a small Guinean village, located in the same prefecture as the first case of Marburg in 2021, before spreading in several countries, especially in large cities.

This is probably an isolated case, but the source of contamination remains unidentified. The main hypothesis is that the contamination could have been due to the fauna. Many investigation and research teams, including that of the Guinea Infectious Disease Research and Training Center, as well as the National Institute of Public Health work there.

Another potential source of epidemic risk has recently been put forward to explain the Ebola epidemic that occurred in 2021, not far from the epicenter of that of 2016: the virus at the origin of this second outbreak would have survived, latent, in the body of a survivor of the disease, then would have been transmitted to a person who developed symptoms.

Data on Marburg virus are limited. However, since this virus is from the same family as the virus that causes Ebola virus disease, it can be assumed that the persistence of the virus in body fluids may be similar.

A well hidden virus

This is another of the difficulties in the fight against Filoviruses: if their zoonotic origin is almost certain, the natural reservoir (s) of the Marbourg virus, like that of the Ebola virus, have not yet been fully identified. By “natural reservoir” is meant the animal (or animals) in which the virus survives, but without making it sick.

However, the clues converge on bats: the Marbourg virus has in fact been isolated on several occasions in bats of the genus Rousettus, Uganda. The reservoir host would in particular be the African fruit bat, Rousettus aegyptiacus, because when infected with Marburg virus, she shows no obvious signs of illness. It is she who would infect primates, including humans. The Marburg virus may be able to infect other species, but research is still needed to determine this.

In an epidemic or isolated case in humans, it is not known exactly how the virus is transmitted from the natural reservoir to humans. However, for two cases that occurred among tourists visiting Uganda in 2008, the most likely route of infection appeared to have been unprotected contact with bat feces or aerosols.

One thing is certain: the appearance of diseases of zoonotic origin should no longer surprise us.

Emerging diseases that are becoming endemic

Economic development and globalization lead humans to “attack” more and more forests, which are the melting pot of a large number of germs. The consequence is that some of these emerging diseases have become endemic in many countries. This is for example the case of Lassa fever, endemic in the border area between Guinea, Liberia and Sierra Leone and also in Nigeria.

The latest scientific knowledge on Ebola virus disease shows that sporadic cases can appear at any time. A study using samples taken between 1997 and 2012 in West and Central Africa showed a seroprevalence of around 6% of Marburg fever, thus suggesting circulation of filoviruses outside areas that have already reported cases. It is therefore essential that health systems have diagnostic tools and are adapted to the early management of infected patients, to avoid a wide spread of the disease.

We must also speed up research into treatments and vaccines, and develop the One Health approach, which takes into account the close links between human and animal health and the overall ecological state. This is one of the missions of theANRS Emerging infectious diseases, created in January: this independent agency of Inserm notably supports numerous projects on viral haemorrhagic fevers.

The Covid-19 pandemic has reminded us harshly: if we want to prevent new outbreaks of emerging pathogens from turning into large-scale epidemics, it is essential to remain vigilant, and to be ready for any eventuality. .

Eric D'Ortenzio, Doctor, Epidemiologist, Head of Strategy & Partnerships Department, ANRS I Emerging infectious diseases, Inserm et Abdoulaye Toure, Associate Professor in Public Health, Gamal Abdel Nasser University of Conakry (UGANC)

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

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