The Filoviruses

Dr Jean-Jacques Muyembe was a newly-qualified microbiologist working as a field epidemiologist when he got a call in 1976 to help investigate an outbreak. A pernicious disease had taken hold in the village of Yambuku in central Zaire, now the Democratic Republic of Congo. People were dying in large numbers of the infection – one that appeared at first to be like malaria or typhoid or yellow fever, but was clearly something even worse.  

Muyembe knew that some of the Belgian nuns working in the village had been vaccinated against yellow fever and typhoid, yet this infection was easily flooring those defences. It was a swift and gruesome new killer.  

Reflecting on his experience with these first few patients, Muyembe said the most striking thing was when he drew blood from them. Removing the syringe and needle, he found that the tiny puncture hole would continue to gush blood. It was the first time he’d seen such a thing, he recalled, and he knew it was an ominous sign. 

After asking one of the infected nuns to fly back with him to Kinshasa, Muyembe took blood samples from her and sent them to Belgium for testing. The analysis that followed produced a shocking result. The blood of the nun, who by now had been killed by the disease, was infected with a virus that caused an acute haemorrhagic fever – one that scientists now describe as “one of the most lethal infections you can think of”.  

The pathogen swiftly became known as Ebolavirus after the river that runs near Yambuku where it infected the villagers and the nuns. It was also swiftly recognised as a member of the Filovirus family - one of The Viral Most Wanted.  

One unique aspect of Filoviruses is their distinctive shape. They are enveloped viruses with a single-stranded RNA genome. Filovirus virions, or virus particles, are long and ribbon- or thread-like and appear to snake into distinctive shapes under a microscope. Some investigators say the shape resembles a shepherd’s crook.

Filovirus particles use a protein known as a glycoprotein to bind to receptors on the surface of host cells. The binding of these receptors triggers what Filovirus specialists refer to as a cell “eating” process called macropinocytosis. This process, in turn, results in the Filovirus being engulfed by a wave-like motion of a host cell’s membrane and taken into the cell, where it replicates and begins to spread. 

Filovirus infections can have gruesome and often deadly effects on people. 

In victims of Marburg virus infection, the illness begins very suddenly with high fever, acute headache and severe malaise. Case notes detailing human outbreaks show that muscle aches, extreme watery diarrhoea, abdominal cramping, nausea and vomiting can begin by the third day. Patients are sometimes described as this stage as being “ghost-like”, with deep-set eyes, expressionless faces and extreme lethargy. Some Marburg victims have a rash during this mid-phase of illness, before going on to develop severe haemorrhagic systems within about a week of first falling sick. Internal and external bleeding is common and can be profuse, including from the nose, mouth and vagina. Those who are not able to overcome the viral attack are usually killed by it within nine days.  

People infected with Zaire Ebolavirus or Sudan Ebolavirus suffer a largely similar series of symptoms. Because initial symptoms of fever, headache and muscle pain are similar to the early symptoms of other diseases like malaria and Yellow Fever, which are endemic to countries where Ebolavirus outbreaks often occur, the diagnosis of Ebolavirus infection is sometimes confused and delayed. Subsequent symptoms become increasingly severe, with vomiting, diarrhoea and, in many ultimately fatal cases, external and internal bleeding. 

Although their work came tragically too late to make an impact on the biggest outbreak of Ebola in recorded history - the devastating West Africa epidemic in 2014 to 2016 - vaccinologists have now successfully developed two approved vaccines against Zaire Ebolavirus vaccines. Both the single-dose Ervebo vaccine and the two-shot Zabdeno plus Mvabea vaccines are licensed by drugs regulators and approved by the World Health Organization. These scientific successes mean that now, when new outbreaks of Zaire Ebolavirus crop up, disease detectives are able to swiftly deploy defensive immunisation strategies to contain their spread and minimise the number of victims. 

During an outbreak of Zaire Ebolavirus in The Democratic Republic of the Congo in 2019 – the second largest outbreak of this disease in history - CEPI joined a consortium to support the DRC government in conducting a large-scale clinical trial of the two-shot vaccine. CEPI is also supporting ongoing research to help expand access to Zaire Ebolavirus vaccines to vulnerable groups and at-risk populations, including pregnant women.  

Scientific investigations into how to protect people against other deadly Filoviruses are active and also showing some promise. Several potential vaccines against Sudan Ebolavirus are in development.  Towards the end of an outbreak of Sudan Ebola in Uganda in 2022 doses of the first candidate vaccine arrived in the country in record time – just 79 days after the Uganda outbreak began – but the planned trial was no longer needed because the outbreak was already petering out, with fewer and fewer cases.   

As another line of enquiry on Ebolaviruses, CEPI is supporting the development of an international antibody standard against Sudan Ebolavirus. When it is successfully established, the antibody standard will become an important scientific tool for assessing and comparing the performance of experimental vaccines against the deadly disease.