• Alex Cloherty

A previous plague, another outbreak

It was the year 1967. The year of Sgt. Pepper's Lonely Hearts Club Band, The Six Day War, the first successful heart transplant, Canada's Expo '67, the release of the first issue of Rolling Stone Magazine, and the appointment of Thurgood Marshall to the US supreme court. And, it was the year that a new virus made its way into Europe.

1967 was a year in which polio was still heavy on the minds of virologists. That is why researchers at the Behringwerke, a vaccine producer in Marburg, Germany (or, in 1967 terms, West Germany) were hard at work making polio vaccines. In order to do this, these researchers were using grivets, a type of monkey that lives in savannah woodlands. Monkeys, or monkey cells, can be very useful experimental models for developing vaccines and other treatments against human diseases because we are quite close to each other evolutionarily - which means the cells that make up human bodies, including human immune systems, are relatively similar to the cells that make up monkey bodies. And that's why, simultaneously, laboratories at the Paul Ehrlich Institute in Frankfurt and the Institute of Virology, Vaccines and Sera “Torlak” in Belgrade were also importing grivets via the same Ugandan supplier.

But, unbeknownst to the importers or the researchers, polio wasn't the only virus around. In fact, there was a problem with these monkeys they were planning to use to study polio. These monkeys were carrying a previously undescribed virus: the Marburg Virus.

Marburg virus is a nasty one. At first, it will cause a sudden high fever, complete with headaches, muscle pain, and malaise. At its worst, though, like the related Ebola virus, Marburg virus can cause deadly viral haemorrhagic fever, meaning that patients start to bleed out of all of their orifices as their organs shut down. In short, it's awful.

And those symptoms were exactly what doctors in Marburg, Frankfurt, and Belgrade started to see in employees that had handled contaminated grivets, or their organs, blood, or other cells.The eponymous Marburg was hit the hardest, with 24 patients infected with the virus. There were also 6 patients in Frankfurt, and 2 in Belgrade.

Notably, there was a key protocol difference that may help explain why Belgrade was less hard-hit by the virus than the two locations in Germany. Pre-emptive quarantine! While the monkeys were sacrificed for laboratory experiments soon after arriving in Marburg and Frankfurt, they entered a quarantine period upon arrival in Belgrade. And there, during the quarantine, it became clear that these monkeys were very sick indeed. A full third of the grivets died. This was quite suspect, so an experienced veterinarian employed by the Institute of Virology performed autopsies on some of the dead animals. This was a great idea - to investigate what was wrong with the monkeys - but it was also the source of the two cases of Marburg virus disease in Belgrade.

Now this veterinarian was, in general, very careful. He double-masked (yes, it's been a thing since the '60s), and wore goggles, rubber gloves, a rubber apron over his lab coat, and rubber boots covered in extra plastic sheets for protection. After performing the autopsies and placing specimens into petri dishes for later analysis, he left the surgical room with the dishes, washed his hands, and showered. But, he made one nearly fatal mistake: while placing a piece of grivet liver into a petri dish, the vet didn't notice that he'd accidentally contaminated the outside of the petri dish with grivet blood. It was only once outside of the surgical room, after handling this petri dish without gloves, that he noticed some blood on his palm.

It's not entirely clear how the grivet blood got from the outside of the vet's body to the inside of it - perhaps through a small and undetected cut on his skin, or by touching his face - but what is certain is that the unlucky veterinarian was infected with Marburg virus. Both him and his wife, who was his caregiver during the milder first week of his illness prior to his transfer to the University Clinic of Infectious Diseases, contracted the virus, but luckily both survived. Notably, both of these patients in Belgrade received a transfusion of plasma (a component of blood that contains antibodies) from a recovering patient from the West German Marburg virus outbreak. Getting transfusions containing antibodies from previously recovered patients can help the immune person of the sick person to control the virus, and can make the difference between life and death - especially with brand-new viruses that we aren't sure how to treat.

In the end, it was very lucky for us humans that, although Marburg Virus is very deadly once you get infected, it is not nearly as infectious as, say, SARS-CoV-2. It doesn't transmit by air. Rather, very close contact, for example contact with bodily fluids from an infected person, is necessary for the virus to jump from one human (or one monkey) to another.

We were also incredibly lucky that the virus didn't escape out into more cities along the travel route of the grivets. After patients started getting sick, and after contact tracing revealed that they had all had direct or indirect contact with grivets that were shipped together, the route of the monkeys was traced. It was anything but direct. Because of the Six Day War, the grivets were diverted to London airport before going on to Frankfurt. To delay matters further, there was an employee strike on at the airport in London, which meant that the animals were temporarily housed there for a few days. In one of the review manuscripts I read to prepare for this article, I came across the dispassionate, scientific sentence, "Fortunately, the monkeys did not distribute the virus in the London population." Fortunate indeed.

If I look back at this outbreak from 2021, I can see that we've come a long way since the Marburg virus outbreaks in 1967. I work in a Biosafety Level 3 lab (a high-security lab where we work with particularly dangerous microbes), and you would have to make a very long series of very serious protocol errors to be contaminated in the way that the veterinarian in Belgrade was. We know so much more about viruses, and about how to protect ourselves from them, thanks to research such as that which was done in the aftermath of the European Marburg Virus outbreaks. But what I think was particularly laudable about this example of a viral outbreak was the relatively quick and open cooperation of the Yugoslavians and West Germans to make sure that the outbreak was contained. Information was shared, an emergency panel of experts was called, and the plasma from a West German patient that likely saved the lives of the Belgrade patient was transported. The collaboration saved lives. You can take from that message what you will.

Until next time… Respect quarantines, they are there for a reason!

~ Alex

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