Pathogens on the move

The array of creatures on sale at the Seafood Market in Wuhan is bewildering: a huge variety of fish as well as lobsters, crabs, shrimps, and mussels – pretty much everything the ocean holds. And despite the name, stalls are also crammed with all kinds of land animals: dogs, rats, snakes, lizards, birds, and much more besides. “Due to explosive population growth in China, the people have to use any source of protein they can get their hands on,” says Gerd Sutter, specialist in veterinary microbiology and Professor of Virology at LMU. And in other parts of the world, people are equally dependent on wild animals as a source of food. “In some African countries, for example, bushmeat is a staple part of people’s diet.”

Enlarge

Hardly a year goes by without a new outbreak

There is nothing wrong in principle with people eating meat other than beef, pork, and poultry. According to Sutter, the problem is that the zones of contact between wild animals and humans are becoming more numerous. This increases the likelihood that zoonoses will occur – that is to say, infectious diseases that are often caused by viruses but also by bacteria, parasites, and other pathogens, and which are transmitted reciprocally between animals and humans.

People have been all too aware of the devastating consequences that zoonoses can have since the Covid-19 pandemic. Much evidence points to the pandemic having originated at the wet market in Wuhan in November and December 2019 – probably in an area where traders sell live wild animals. It is still unclear, however, from which animal SARS-CoV-2 jumped to humans. Studies to date have indicated that bats were the virus reservoir. But researchers are still working to establish whether another animal acted as an intermediate host.

Leaving aside the open questions surrounding the origin of Covid-19, there have been multiple other examples of zoonoses over the past two decades: SARS, a coronavirus also known as SARS-CoV-1, was transmitted to humans by civets in 2002 – mammals, incidentally, that were also on sale at the wet market in Wuhan. Then came swine flu and bird flu, Ebola from small insect-eating bats, MERS from dromedary camels, and the Zika virus, which circulates among monkeys. And barely was the Covid crisis somewhat under control when monkeypox started doing the rounds. So must we resign ourselves to the zoonosis carousel turning ever faster in the future?

“Zoonoses are natural occurrences that have always happened,” clarifies Sutter. Although the pathogens themselves are not increasing, the same cannot be said for cross-species transmission to humans, says the virologist: “For the past two decades or so, scarcely a year goes by in which we do not register a new outbreak event.” In addition to the consumption of wild animal meat, there are several other reasons for this development – such as “the growth of the host population,” in Sutter’s words. He uses an analogy comparing people on Earth to bacteria on a culture plate. “When the bacteria increase beyond a certain point, bacteriophages – viruses that exclusively infect bacteria – eventually come along and wipe out 99 percent of the population.” In other words: As a result of population growth, the likelihood increases that people become infected with pathogens already at large in the animal kingdom. And in the worst case, one of these viruses will almost wipe out humanity someday.

More and more natural barriers against pathogens are coming down

Moreover, people are encroaching ever further on the natural habitats of wild animals in order to extract raw materials and carve out new farmland. We could think, for example, of the clearing of virgin forest in many parts of the world. “There we meet pathogens we’ve never encountered before,” explains Sutter. During the Ebola fever epidemic in Western Africa from 2014 to 2016, for instance, researchers were able to almost minutely trace where the epidemic began: In the Guinean hinterland, lumberjacks had cut down areas of dense jungle and thus removed a natural barrier to the growing settlements in the region. In December 2013, the virus jumped from a small species of bat to a two-year-old boy, who died of the infection shortly afterward. By March 2014, the authorities had recorded dozens more cases in forested areas of southeastern Guinea. The disease then spread to several Western African countries and even outside of Africa for the first time.

In addition to the increased points of contact between people and wild animals, global warming also facilitates the occurrence of zoonoses. After all, changed climatic conditions can lead to so-called vectors – that is, transmitters of infectious diseases – colonizing new habitats. Due to milder temperatures, for example, the tick species Hyalomma marginatum has already appeared in some European countries. The parasitic arachnids transmit Crimean-Congo hemorrhagic fever, a dangerous viral disease that causes high fever, head, joint, and muscle ache, nausea, and severe bleeding.

Mosquitoes, too, which are actually native to exotic regions, are increasingly making a home for themselves in Europe – such as the Asian tiger mosquito, which transmits various topical diseases, like the chikungunya virus and dengue fever. In addition, the close contact that sometimes exists between people and host animals facilitates outbreaks of disease. For example, the MERS virus, which circulates among herds of dromedary camels in desert areas on the Arabian Peninsula, crossed over to their owners in isolated instances and spread further from there. Like SARS-CoV-2, the pathogen causes severe respiratory infection in humans.

Hitchhiking around the world

One reason for the greater prevalence of zoonoses stands out for Sutter, however: “The mobility of people has sharply increased over the past two decades – and without doubt this is a key factor,” he says. In this way, pathogens are able to travel the globe in a way they could not do naturally, says the virologist. As an example, he cites monkeypox, which is actually not very infectious at all. The fact that the virus nevertheless cropped up in different corners of the globe is merely a function of global connectivity, says Sutter. “The rapid spread even surprised us experts.”

How the West Nile virus caught a plane to New York

The growth in global travel and trade also allows disease vectors to spread. As an example, Sutter cites the international trade in used car tires. Small amounts of water sometimes gather in the tires, offering mosquitoes a place to lay their eggs. The tires are then carried across the ocean on ships while the larvae develop. In the 1980s and 1990s, for instance, the yellow fever mosquito, whose bite can also transmit dengue fever, spread in just this way. By contrast, the West Nile virus traveled in style, catching a plane to New York with a mosquito in 1999. Before long, there were the first infected birds in the metropolitan area, and within a few years the virus had spread throughout the American continent.

According to infectious disease specialist Sutter, however, the increase in zoonoses is no reason to panic. Instead, he calls for alertness and sensible precautions. “We must always be on our guard against infection events. As virologists know, there are much more unpleasant viral diseases out there than monkeypox or Covid-19.”

Notwithstanding the above, there have also been positive developments: “Over the past two decades, our technical capabilities in virological research have rapidly expanded.” Sutter points to our ability, for example, to swiftly identify the complete genome sequence of a pathogen. At the beginning of the Covid-19 pandemic, LMU researchers analyzed weekly waste water samples from the Munich municipal area for viruses. This helped trace the spread of SARS-CoV-2, while also providing information about new variants of the virus by sequencing the genome. Such monitoring mechanisms are extremely valuable in pandemic times so as to be able to rapidly respond to events with suitable measures.

Genetic and molecular information also form the basis for the development of drugs and vaccines, as they reveal characteristic structures of the pathogen and thus potential points of attack. An effective vaccine must contain antigens from the pathogen, for example, upon which the immune system can be trained. “In my view, vaccination is hands-down the best means of protecting us from infectious diseases,” says Sutter.

The coronavirus pandemic showed that the vaccines were a game changer and the years of research into mRNA technology paid off. RNA acts as a messenger, carrying the genetic information for the production of a protein into the cell. That being said, the coronavirus lends itself to the new technology, because a single feature of the pathogen – the spike protein – is enough to induce a sufficiently strong antibody response in the body. With many other pathogens, such as poxviruses, this is not the case. “Their biology, structure, and life cycles are complex, and effective vaccines require more viral proteins than coronavirus vaccines,” explains Sutter.

Based on a vaccinia virus that is no longer replication-competent, the vaccine platform developed by Sutter and colleagues is capable of integrating up to ten different antigens of a pathogen. The team is already using the platform to work on vaccines against viruses that could become dangerous in future, such as MERS or flu viruses. Furthermore, the researchers want to set up the vaccine platform such that it can be swiftly adapted to unknown pathogens. An advantage of vector vaccines compared to mRNA-based versions is that they are more stable and have longer shelf lives. It is thought that stocks of emergency vaccines could be held for decades. Moreover, they are easier to manufacture from a technological standpoint, which means they can also be produced in poorer countries.

Global measures are crucial

But of course vaccines are not everything. Back at the turn of the millennium, Sutter was one of the experts involved in devising a national pandemic plan. The authors of this plan recommended measures such as maintaining a stock of personal protective equipment and preparing the health system for a severe outbreak. Clearly, such recommendations have not always been implemented. Sutter argues that we should invest in this kind of preventive healthcare in future and not just think of the initial costs. After all, investments in prevention can have economic benefits as well.

And even more important perhaps than national measures are global ones. The World Health Organization is advocating for the One Health principle, which is based on the premise that because the health of people, animals, and nature is mutually dependent, we should protect the environment as well as promoting veterinary medicine and public health.

Better healthcare in poorer countries, for example, would help stem infectious diseases at source. And according to Sutter, we could do even more: “We should help these societies reach a place where people are not reliant on wild animal meat. This would prevent some epidemics, for sure.” But despite our best efforts, outbreaks will occur from time to time, says the expert. The good news is that we can prepare for them.

Enlarge

Prof. Dr. Gerd Sutter ist Inhaber des Lehrstuhls für Virologie am Institut für Infektionsmedizin und Zoonosen der LMU. Sutter, Jahrgang 1962, studierte Tiermedizin an der LMU, promovierte ebendort und ging als Postdoktorand an die National Institutes of Health, Bethesda, USA, bevor er sich an der LMU im Fach Virologie habilitierte. Sutter leitete eine Forschungsgruppe am Institut für Molekulare Virologie des Helmholtz Zentrums München und die Abteilung für Virologie am Paul-Ehrlich-Institut in Langen, ehe er 2009 den Ruf an die LMU annahm.

Read more articles of the current issue and other selected stories in the online section of INSIGHTS/EINSICHTEN. Magazine.