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Exploring the Darker Side of Everything

Marburg Virus: The Untreatable Virus

Mortality rate, the percentage of people likely to die out of everyone who contracts a disease. It varies wildly from one illness to another. To give you a rough idea Covid-19 has a mortality rate of 1.4%, Typhoid 15% and Tuberculosis kills 43%. Marburg virus disease is so deadly that during the worst outbreak it killed 90% of those infected. That’s a massive rate of fatality.

It’s an untreatable virus so once you’ve got it there’s no cure. One slip up when treating a patient, disposing of their possessions or conducting an autopsy and your odds of survival are 1 in 10. It’s not a nice way to go either…

Symptoms

The first signs that you’ve been infected with Marburg are pretty common to most illnesses. They include fever, headache, sore joints and rashes. Next comes diarrhoea which can last a week. And on the third day, you can expect to start vomiting with the accompanying abdominal pain and cramps.

Marburg virion structure and genome organization. Above, schematic of Marburg virion. Below, structure of the MARV genome with transcription signals. The colors of the open reading frames correspond to the colors of the viral proteins.
Marburg virion structure and genome organization. Above, schematic of Marburg virion. Below, structure of the MARV genome with transcription signals. The colors of the open reading frames correspond to the colors of the viral proteins. By Kristina Brauburger, is licensed under CC-BY

The diarrhoea and vomiting are especially unfortunate as Marburg spreads through bodily fluids. Anyone caring for you in this stage of the illness has a high likelihood of contracting it too. Unless they wrap themselves in multiple layers of PPE and dowse everything in chlorine.

Finally, after worsening for a few days the internal haemorrhaging begins. You start bleeding from every orifice and at this point are beyond saving. Previous patients have bled from their eyes, nose, gums and needle puncture wounds. Haemorrhaging can even be seen beneath the skin. Most people die of excessive blood loss and shock 8-9 days after the first symptoms begin.

Treatment

It’s known as the untreatable disease for a reason. Once you’re infected there’s nothing that can be done. Doctors will provide pain relief to ease suffering but there’s no cure. The only hope is rehydration to try and maintain oxygen status and blood pressure.

Transmission

Marburg spreads through contact with the bodily fluids of an infected patient. Blood, saliva, vomit and even urine can be carriers. For this reason, outbreaks are particularly common in rural areas lacking running water and sanitation. Places with poor health facilities are particularly at risk as the sick will arrive and not be immediately diagnosed. Medical staff then won’t use adequate PPE and many will contract the disease themselves.

One of the features that make Marburg particularly dangerous is its ability to remain dormant in recovered patients. The virus can survive in the eyes, testes, placenta and amniotic fluid. This means that the 10% lucky enough to survive the disease can still pass it on many months later. Men through unprotected sex and pregnant women to the foetus and through breast milk. It makes it difficult to control the spread as recovered patients can travel to other areas and start new outbreaks months later. Medical staff have to provide extensive education on the importance of using condoms before releasing survivors. However, in many areas they’re not easily available or in common use which makes the task much harder.

Another key risk factor with Marburg is the long incubation period. It can take 3 weeks from exposure to symptoms developing. This means a carrier can be actively spreading in a community or could even travel to another country before they know they’re infected.

Where did it come from?

The Marburg virus first appeared in humans in 1967 in Marburg and Frankfurt in Germany, Belgrade and Serbia. 31 people became ill and 7 died. Of these, 25 were lab workers, 5 medical personnel and 1 was a family member who cared for their sick relative. The virus had been imported from Uganda in a shipment of African Green Monkeys. The labs were working on polio vaccines and were using the monkeys to culture kidney cells for research. Unfortunately, some needle stick accidents led workers to be exposed to the blood and tissues of the animals. In one case a lab worker cut himself while conducting an autopsy.

View of Marburg, dominated by the castle and St. Elizabeth's Church.
View of Marburg, dominated by the castle and St. Elizabeth’s Church. By Philippe , is licensed under CC-BY-SA

Monkeys are not reservoir hosts of the disease as although they can be infected they often die quickly. This means it should be incredibly unlikely for a Marburg carrier to make it all the way from Uganda to Germany. Sick monkeys are not of much use to labs and are usually not sold to them. However, the Ugandan monkey trappers had come up with a way to protect themselves against the financial loss of catching unhealthy animals. They’d started taking all of the sick monkeys they caught to an island in Lake Victoria. Leaving them to either die or recover and survive. If ever the trappers didn’t have enough monkeys to fulfil a shipment they’d return to the island and take the healthiest. As Marburg can remain in recovered patients for many months these, now seemingly healthy, monkeys were taken but still infectious. When lab workers were then exposed to the bodily fluids they contracted the disease and the first human outbreak was underway.

The actual reservoir hosts of Marburg are now known to be Rousettus bats. Also known as dog-faced fruit bats or flying foxes. They live in most parts of Africa and some regions of Southeast Asia. Humans are very unlikely to have contact with them in their normal day to day lives, which is why we don’t hear of Marburg often. However, miners, forestry workers and tourists sometimes enter caves where they roost. Exposing themselves to faeces and saliva that can transmit the virus. As seen in the first outbreak, bats can also transmit to non-human primates, particularly gorillas and chimpanzees. Humans that hunt and butcher these animals will come into contact with their blood and have a chance to contract the virus themselves.

Michelle Barnes, from Colorado, is a recent Marburg survivor who contracted the disease from bats. She was on holiday in Uganda in 2007 and visited a python cave in the Maramagambo Forest in Queen Elizabeth Park. Unfortunately, the cave is a roosting spot for thousands of fruit bats and both Michelle and a woman from the Netherlands contracted the disease. Michelle spent 12 days in hospital, 8 in intensive care and had to have her gall bladder removed but she survived. The other patient, unfortunately, died after experiencing renal failure. Neither passed the disease on and so the outbreak was contained.

Why Bats?

SARS, MERS, Ebola and Marburg, all awful viral epidemics. All started in Bats. Bats have even been named as a potential culprit for Covid-19. Work is still being done to identify the exact source of the pandemic. But we do know that Covid is zoonotic, meaning a human disease of animal origin. While it probably didn’t come directly from bats they may have transmitted it to an intermediary species that in turn transmitted it to us.

Now I’ve never had a particular problem with bats. Some of them are actually pretty cute. But I’m starting to think they might have it out for us. Seriously, how many times do they have to try and take down humanity with horrific, bleeding from the eyes, diseases before we start treating them with a bit more suspicion?

The Cute Bat
The Cute Bat

But, before I accidentally start some kind of world domination bat conspiracy theory, we should probably take a look at what’s actually responsible for them being super virus breeders.

Bats have an incredible immune response to viruses. Their cells are constantly primed and ready to fend off viral attacks. When a virus enters their systems the response is immediate and walls the virus out of their cells. While this is great for the bats, it’s not so good for us. Viruses that are faced with this line of defence can survive in the bats for a long time without killing them. They use this time to figure out what to do about these defences and evolve. They speed up their rates of reproduction to try and overcome the bat’s lightning-fast immune response. When the same viruses then make the jump into humans their incredible reproduction rate overwhelms our immune systems. Viral loads skyrocket and fatality rates soar.

So maybe bats aren’t trying to kill all humans on purpose. But if they could just try to avoid exposing themselves to so many viruses it would be appreciated. Perhaps keep their caves a bit cleaner and practice some personal hygiene.

Outbreaks

There have so far been 14 outbreaks of Marburg. In most cases, these have been limited to a handful of patients and one or two deaths. Almost all have been in Africa with some in labs and a few in the victims who carried the virus home from Uganda.

The Outbreak of 2004-2005

One outbreak though was far worse than all others. Marburg was transmitted between humans and killed hundreds before being contained. It began in 2004 in Uige, rural Angola.

Once it was identified the everybody took it incredibly seriously. The World Health Organisation mobilised its Global Outbreak and Alert Response Network team. They sent anthropologists, virologists, pathologists and medical specialists. A safety ward was set up at the main hospital to diagnose potential Marburg patients and suspected cases were sent to isolation wards.

Staff arrived highly trained for dealing with infectious diseases and brought PPE. They’d wear 3 layers of gloves, goggles and ensure that no skin was exposed. Measures we’re used to now but were incredibly scary for the residents of rural Uige at the time.

The World Health Organisation’s community outreach teams also visited the villages to try and get the virus under control. However, due to cultural issues and suspicions, they were often met with fear or anger. Some medical staff were even stoned. The use of body bags and high tech medical equipment was rare and scary and the fear of the disease added to tensions. To further complicate infection control, the cultural tradition in Uige for funerals was to display the body. Friends and family would dance and sing and kiss their departed loved one. With Marburg, this would effectively guarantee transmissions and had to be banned. Not being able to provide proper funerals for their dead was incredibly painful for the local communities.

The distrust also meant that many would not call for help if they suspected Marburg. Instead, they’d wait until the patient was close to death or already dead. By this time it was likely another person would’ve been infected. A huge push had to be made for community engagement and education as one of the first steps to stop the epidemic.

Recent Cases

The most recent Marburg outbreak was in Guinea in July 2021. A man presented at a local health centre with fever, headache, fatigue, abdominal pain and bleeding from the gums. As the disease is difficult to diagnose he was given a test for malaria. When the test came back negative he was sent home. Unfortunately, his condition deteriorated and he died the next day. Samples taken post mortem were positive for Marburg and work began immediately to trace his contacts. Fortunately, all remained negative and the outbreak was declared over on the 16th of September.

Guinea, having never had a case of Marburg before has brought in several measures to ensure they never experience an outbreak as severe as Angola. Bats are being captured and sampled, health care and hygiene training has been increased, PPE supplies distributed and water, sanitation and hygiene measures are being implemented in health facilities and communities. Their success in preventing the spread provides hope for other countries in the region. It seems likely that, as long as a new variant doesn’t jump from bats, the threat of another massive outbreak is low.

Potential as a Biological Weapon

But could another outbreak be caused by something other than bats? Unfortunately, yes. The Soviet Union’s biological weapons program saw the potential in the Marburg virus and undoubtedly others have seen it too. During the Cold War, at least 3 Soviet research institutes had programs focussed on weaponising the disease. Ken Alibek, a biological warfare expert for the Soviet Army defected to the United States in 1992 and became a contributor to the US biodefense strategy. He provided intelligence that the Soviet Union had successfully weaponised Marburg. His claims were that warheads had been created containing the disease and were even tested at Stepnogorsk Scientific Experimental and Production Base. His story hasn’t been corroborated but there are records of 2 Marburg deaths in Koltsovo in the Soviet Union that fit the timeline. Firstly, Russian bioweapon scientist, Nikolai Ustinov, who accidentally infected himself while injecting guinea pigs with Marburg. His symptoms were horrifying. He suffered severe haemorrhages that left him bleeding from his nose, mouth and even sweat glands. The pages of his notebook were left covered in un-clotted blood from the star-shaped haemorrhages under his skin. In a freak coincidence, during his autopsy, the pathologist accidentally stuck himself with a needle too. He also contracted the disease and suffered the same fate as Ustinov.

Soviet scientists went on to isolate a new strain of Marburg from Ustinov’s body. It was found to be especially deadly when airborne, ideal for distribution from a biological weapon. They named it Variant U in his honour. Dr Alibek claims that the manufacture of large amounts of Variant U was ready to begin in 1991 with plans to load it into 10 separate warheads. As he defected, we don’t know the outcome of these plans beyond the fact that they’ve never been successfully deployed.

Due to its potential as a biological weapon the US has declared Marburg a ‘select agent’. This is an agent or toxin with the potential to pose a severe threat to public health and safety. Select agents are strictly regulated and unauthorised possession, use or transfer incurs a severe fine.

How can Marburg be contained?

There’s currently no licenced vaccine for the Marburg virus. Vaccine efforts have been made more difficult by its classification as a select agent. This means it can only be handled by a few maximum containment labs. On one hand, this is great as it reduces the number of people who could be secretly plotting to use it as a weapon. Marburg has also killed many researchers through needle sticks, so strict measures are clearly needed. On the other hand, it massively reduces the number of companies that can work on a vaccine.

Another reason for the slow development of a vaccine is, of course, money. Due to the relatively small number of people affected in previous outbreaks, there’s been no financial incentive to create one. It costs around $1 billion to develop a vaccine and, since its discovery in 1967, Marburg has only killed 383 people. Why would anyone buy the vaccines?

Ebola, a close relative of Marburg, is a great example of this stunted vaccine development. A team in Winnipeg, Canada had been working on an Ebola vaccine for years but hadn’t been able to get any pharmaceutical company to develop it. Then the 2013-16 Ebola outbreak in West Africa hit. Development suddenly became much more urgent. Unfortunately, the World Health Organisation wouldn’t give them the go-ahead to trial it in the affected countries. This was largely due to ethical concerns of testing it in African countries following deaths from an experimental meningitis vaccine. However, when the death toll started to soar, rapid clinical trials were initiated. The results looked great but it wasn’t enough to get the vaccine licenced. In 2018 a further outbreak in the Democratic Republic of Congo led the country to agree to use it under a ‘compassionate use protocol’ and 260,000 people were vaccinated. By 2019 it was finally licenced and approved by the FDA after over 11,000 deaths.

Ebola highlighted the potential damage filoviruses can do and funding started rolling in for Marburg. Several different types of vaccine are now under investigation and have progressed into animal and human studies. However, without an outbreak that kills more than 10,000 or a biological weapon attack that kills more, progress will be slow. Even when a vaccine is developed how many would actually bother to get a dose?

Therefore extreme hygiene and sanitation measures remain the only way to contain Marburg. Chlorine kills the virus so spraying contaminated areas and washing shoes in chlorine baths can work well. Safe burial practices are also vital to prevent the spread.

Ideally though, we want to stop Marburg jumping to humans in the first place. Then we don’t have to contain it or vaccinate against it. The only solution may be contentious but people just really need to stop eating bats. Oh, and keep out of caves full of bat faeces.

Sources

https://en.wikipedia.org/wiki/List_of_human_disease_case_fatality_rates

https://en.wikipedia.org/wiki/Marburg_virus

https://pubmed.ncbi.nlm.nih.gov/31589088/

https://pubmed.ncbi.nlm.nih.gov/28447193/

https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease

https://www.gavi.org/vaccineswork/next-pandemic/marburg

https://www.irishexaminer.com/news/arid-40356392.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497034/

https://academic.oup.com/jid/article/196/Supplement_2/S131/858753

https://en.wikipedia.org/wiki/Rousettus

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/flying-fox

https://www.bats.org.uk/about-bats/bats-and-disease/covid-19-and-bats

https://www.cc.nih.gov/about/news/newsletter/2009/july09/newsletter.html

https://www.who.int/emergencies/disease-outbreak-news/item/marburg-virus-disease—guinea

https://www.globalsecurity.org/wmd/intro/bio-marburg.htm

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