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Zoonoses – Pandemics

VIRUSES:
THE INVISIBLE DANGER FROM THE WILDS

Monkeypox, COVID-19, Ebola: viruses that jump from animals to humans can cause pandemics. LMU scientists are studying the tricks of the pathogens and developing suitable vaccines.

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How the coronavirus pandemic began

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Flashback: the first coronavirus patient in Germany

On the morning of 27 January 2020, the phone rings in the Division of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich. The caller says he has mild cold symptoms. In ordinary circumstances, a blocked nose in winter would scarcely be worth mentioning, never mind making a call to an institution specialized in tropical diseases. However, a few weeks previously a new viral disease had emerged in the Chinese city of Wuhan. Resembling a traditional cold at the onset, the disease could end in severe inflammation of the lungs and death. Could the caller be the first case in Germany? The staff think this is unlikely but invite him in anyway. Not taking any risks is the policy.

The events of that day read like something out of a movie script. Because the episode was so important for the initial assessment and course of the coronavirus pandemic, LMU researcher Dr. Camilla Rothe, who heads the outpatient department at the Division of Infectious Diseases and Tropical Medicine, has told the story many times. Experts know that similar scenes will play out in the future – it is just a matter of time before another virus causes the next pandemic.

“At the time, people thought the outbreak was restricted to China,” recalls Rothe, who examined and interviewed the first patient herself. “The man had not even been to China,” she recounts. Rather, he had had contact with a Chinese colleague who did not have any symptoms. “From SARS-CoV-1 in 2002, we knew that infected people are only infectious if they also have symptoms,” says Rothe. And it was assumed that it would be the same for this new coronavirus. So Rothe and her colleagues were stunned when the test result came back positive.

Alarm bells started to ring in my head immediately,

remembers Rothe – and not because the first German coronavirus patient had been found, but because he had caught the virus from somebody who had no symptoms. “How do you quarantine a person who does not feel ill?” explains Rothe. “It was clear that we would be having a hard time containing a virus that behaves like that.”

Dr. Camilla Rothe sitzt neben einem Mikroskop im Tropeninstitut des LMU Klinikums.

Dr. med. Camilla Rothe

Head of outpatient department at the Division of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich

Camilla Rothe is considered as discoverer of the first coronavirus case in Germany. Together with her team, she swiftly communicated her assumption that an asymptomatic COVID-19 infection was possible. Initially, she was heavily criticized by parts of the scientific community but in the end her hypothesis was proven right. In all likelihood, her decision to quickly go public saved a lot of lives. For her research achievements, Time Magazine included Rothe in its list of the 100 most influential people of 2020. And in September 2022, she received the Order of Merit of the Federal Republic of Germany.

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Why zoonoses are becoming more frequent

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Exotic pathogens are threatening people in the Global North

The pandemic probably began in December 2019 at a market in the Chinese city of Wuhan. According to experts, this is where a human most likely contracted the virus from a wild animal for the first time. In medical language, an infectious disease that originally comes from animals is called a zoonosis. From Wuhan, the virus spread around the world within months, as studies have demonstrated. The rest is history, as they say.

A concerning trend in recent times is the increasing frequency with which exotic pathogens from remote regions of the Global South have been threatening people in the Western world.

Since 1999, scarcely a year has gone by where we do not identify a major new outbreak event,

says Gerd Sutter, Professor of Virology at LMU’s Faculty of Veterinary Medicine. Sutter is an expert in emerging zoonotic pathogens and observes their global spread, partly in collaboration with the World Health Organization.

Prof. Gerd Sutter lehnt am Schreibtisch in seinem Büro am Institut für Infektionsmedizin und Zoonosen der LMU.

Prof. Dr. med. vet. Gerd Sutter​

Gerd Sutter is Chair of Virology at the Institute for Infection Medicine and Zoonoses at LMU. He studied veterinary medicine at LMU, where he also obtained his doctorate. He went to the National Institutes of Health (NIH) at Bethesda, Maryland as a postdoc, before returning to LMU to complete his habilitation in virology. Having headed a research group in the Institute for Molecular Virology at Helmholtz Munich and the department of virology at the Paul Ehrlich Institute in Langen, Sutter accepted an invitation to join the staff at LMU in 2009.

Editor’s note: Professor Gerd Sutter passed away in October 2023

Gerd Sutter is in demand at various international institutions as an expert in poxviruses and vaccines, including the European Commission, the NIH, and the WHO. As a senior scientist at the German Center for Infection Research (DZIF), his work focuses particularly on the development of vaccines against infectious diseases that are transmitted from animals to humans. For his actions during the COVID-19 pandemic, Gerd Sutter was awarded an honorary doctorate by the University of Veterinary Medicine Hannover, together with Professor Christian Drosten and Professor Lothar Wieler.

Pathogens are constantly trying to cross species boundaries

“Pathogens crossing from animals to humans is in itself nothing unusual,” says Gerd Sutter. “There have always been zoonoses. Our ancestors knew that getting too close to animals could bring ill fortune – even if they knew nothing about pathogens.”
Professor Oliver T. Keppler, Chair of Virology at LMU’s Max von Pettenkofer Institute, agrees: ​

Pathogens are constantly trying to cross from one species to another.

Keppler studies the interactions of viruses with their hosts, with a special interest in HIV. “This zoonotic transmission usually fails, however, because there are specific hurdles for the spread of viruses in every species.” Put simply, the pathogen is not sufficiently adapted to the new host. And even if transmission to a human is successful, the infection generally dies out, because the pathogen is not transmitted any further. So it is a dead end for the virus in most cases.

But: “In rare cases, the pathogen does actually manage to adapt to the new host and to become a serious infectious disease for humans,” explains Keppler. This is the moment at which an epidemic or even pandemic can arise. Mostly, these are viral diseases and frequently – like coronaviruses – they can be transmitted through the air. A high mutation rate also helps viruses adapt quickly to the new host. In this way, they sometimes manage to get round the host’s antiviral immune defenses. Experts refer to this strategy as immune evasion. “The ability to quickly mutate can also help viruses become resistant to drugs,” adds Keppler.

Prof. Oliver Keppler steht in seinem Büro am Gene Center Munich der LMU.

Prof. Dr. med. Oliver Keppler​

Oliver T. Keppler is Chair of Virology and Director of the Max von Pettenkofer Institute. He is also principal investigator at the Gene Center Munich. Keppler studied human medicine, initially in Freiburg im Breisgau and then at Heidelberg University, where he also completed his doctoral studies. After clinical posts in the domain of internal medicine in Switzerland, he obtained his medical license.

After that, Keppler had research stints at the German Cancer Research Center (DKFZ) in Heidelberg and the Gladstone Institute of Virology and Immunology at University of California San Francisco. From 2002 to 2012, Keppler worked at the Department of Infectiology at Heidelberg University Hospital, where he completed his habilitation in 2005. In 2009, he was appointed adjunct professor at Heidelberg University. In the same year, he was appointed consultant physician for microbiology, virology, and infection epidemiology. From 2012 to 2015, Keppler was director of the Institute of Medical Virology at Frankfurt University Hospital and full professor at Goethe University Frankfurt, before he took up the invitation to join the LMU staff in 2015. He is director of the German National Reference Center for Retroviruses and a researcher at the German Center for Infection Research (DZIF). In his research, he studies retroviruses and SARS-CoV-2 in relation to topics such as pathogenesis, test development, and possible therapies. For his role in helping to manage the coronavirus pandemic, Oliver Keppler was awarded the Bavarian Order of Merit.

Briefly explained

How viral zoonoses arise

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Humans are encroaching on natural habitats

Regions in Asia, Africa, and Latin America, in particular, are main starting points for infection events. “In these places, contact between people and wild animals is becoming increasingly frequent – particularly in regions with strong population growth,” says Professor Michael Hoelscher, Director of the Division of Infectious Diseases and Tropical Medicine. The specialist in tropical medicine researches various infectious and tropical diseases, develops diagnostic techniques, and collaborates with researchers in partner countries in the Global South.

In such regions – Wuhan is a prominent example – people use every source of protein they can access, meaning that meat from exotic animals often ends up on their plates. Moreover, global population growth is causing people to settle new areas and create new agricultural land by means such as jungle clearances. “Of course, this removes natural barriers to wild animals,” says Hoelscher.

The same happens when big corporations – often with the participation or under the leadership of Western actors – mine natural resources or create huge plantations or cattle farms in these locations, for which massive tracts of woodland are cleared. This unhappy state of affairs is driven by the excessive consumption behavior of the Global North.

Naturally, zoonotic transmissions happen in Europe as well,

notes Hoelscher. The Borna disease virus, for instance, circulates in shrews in this part of the world and can cause encephalitis in humans. In both 2019 and 2022, a child died in Bavaria from an infection with this virus. However, our contacts with pets and livestock tend to be less problematic: “We’ve been living with domesticated animals for tens of thousands of years, and the transmissions took place at an earlier time.” This means that the human immune system has already learned to deal with these pathogens. If viruses from exotic wild animals arrive here, however, they can spread among domestic livestock. This caused the coronavirus outbreak in European mink farms, for instance.

In addition to the increased number of contact points between humans and wild animals, global warming is also facilitating the emergence of zoonoses. Changing climatic conditions can prompt so-called vectors – that is, transmitters of infectious diseases – to seek out new habitats. This includes the tick that spreads the Crimean-Congo hemorrhagic fever, which has increasingly been found over here in recent years. For virologist Gerd Sutter, one reason stands out in particular: the mobility of people. Once pathogens manage the leap to humans, they can sometimes spread rapidly around the world thanks to global connectivity and high levels of trade and foreign travel.

Prof. Dr. med. Michael Hoelscher

Michael Hoelscher is Director of the Division of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich. He studied medicine at LMU and obtained his doctorate in 1996 at the division he leads today. His time at LMU was interrupted by several study and research stints to learn about infectious and tropical diseases at other institutions (such as the Walter Reed Army Institute of Research). Mbeya Referral Hospital in Tanzania became his second home. This was where he not only completed part of his infectiology training, but was also instrumental in establishing one of the largest research institutions in Africa, the Mbeya Medical Research Center.

Since 2010, Hoelscher has been DZIF Professor of Global Health & Infectious Diseases at University of Munich Hospital. In addition, he is a researcher and location spokesperson at the German Center for Infection Research (DZIF, coordinator for tuberculosis) and scientific lead of the consortium UNITE4TB, which is dedicated to the fight against tuberculosis. Michael Hoelscher conducts research into various infectious and tropical diseases, carries out clinical studies, develops diagnostic techniques, and collaborates with researchers in partner countries in the Global South, where he also works to improve health care. For his contributions to managing the coronavirus pandemic, Michael Hoelscher was awarded the Bavarian Order of Merit. Since 2022, he also heads the newly founded Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology) office for immunology, infection, and pandemic research (IIP) in Munich/Penzberg.

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The dynamics of epidemics