IOWA CITY — "Everybody knows that pestilences have a way of recurring in the world; yet somehow we find it hard to believe in ones that crash down on our heads from a blue sky." — Albert Camus, "The Plague"

In May, 1997, a 3-year-old boy was admitted to an ICU in Hong Kong after suffering from influenza for a week. Two days later, the boy died of pneumonia. His case would have been merely a curiosity if it weren't for 17 more patients who came down with the illness months later. In all, six people died from a strain of influenza that had never been seen in humans before, dubbed H5N1.

However, H5N1 wasn't really "new." It had caused outbreaks in Scottish chickens in 1959 and British turkeys in 1991. It had killed geese in Guangdong, China, in 1996. But these bird outbreaks weren't considered important by physicians or researchers on human disease — this was an avian strain of influenza, and it was thought that humans had little to be concerned about.

That changed abruptly in 1997, when the human cases led to the destruction of 1.3 million chickens in Hong Kong to stop the outbreak. That strategy seemed to work in the short term, but H5N1 has since surfaced in more than two dozen countries and caused more than 600 human infections since 1997 — almost half of them fatal.

While scientists were closely following the movements of H5N1, another influenza virus — H1N1 — snuck up on us in 2009 and spread around the world in a matter of weeks. This was the first influenza pandemic of the 21st century, and like H5N1, it moved to humans from animals — in this case, from pigs.

When new infectious diseases are discovered, one of the first questions is "where did this come from?" More often than not, the answer is one of our animal friends — a kind of disease called a zoonosis. Studies have shown that about 75 percent of emerging infectious diseases (diseases that are newly discovered, are increasing in frequency or have moved into a new geographic area) are of animal origin, as are 60 percent of all known pathogens. Even diseases that have spread freely in the human population, such as tuberculosis, HIV, measles and smallpox, have their roots in infections carried by animals.

Which animals are the most likely to harbor zoonotic pathogens?

Bats

For reasons that are not currently understood, bats are able to be infected with a huge variety of viruses. They pass these viruses to other animal species via bites or guano. The classic bat-origin virus is rabies, but bats have also been implicated as possible reservoir species for the Ebola and Marburg viruses, Nipah, Hendra and others. Even influenza has recently been found in bats. Bats also appear to be the reservoir for the SARS coronavirus, which surfaced in 2002 in Asia. SARS eventually infected more than 8,000 individuals around the world and killed almost 800 of them between November 2002 and July 2003, spreading to at least 37 countries. A new SARS-related virus has recently surfaced in Saudi Arabia, and speculation is that it's also from bats.

Other Wild Animals

While bats appear to be responsible for a disproportionate amount of novel pathogens, every animal species carries its own unique microbiota — the collection of microbes that live on and in an animal's body. Some of those can also spread to humans. As mentioned above, birds can spread many different types of influenza viruses. In fact, wild waterfowl serve as the ultimate reservoir for all known types of influenza viruses. Birds also can transmit a number of encephalitis viruses, such as West Nile. Because many migrate long distances, birds may be particularly efficient at introducing pathogens into new areas.

Primates also harbor a number of pathogens that have crossed over into human populations, often an easy jump since we are so closely related. HIV is the result of multiple species jumps from nonhuman primates into human populations, likely due to butchering of infected animals. Research carried out by Nathan Wolfe and others has shown that bushmeat hunters in Africa are still being infected with viruses from our primate relatives.

Rats and mice, of course, have long been associated with disease. Plague-infected fleas on rats spread Yersinia pestis, the bacterium responsible for the Black Death. We know today that other species can also transmit this pathogen — including much cuter prairie dogs in the southwestern United States. Mice have recently been implicated in an outbreak of hantavirus pulmonary syndrome in Yosemite National Park that has killed three and sickened at least 10 campers. Mice carry this virus without showing symptoms and spread it to humans via urine and feces.

Livestock and Pets

The domestication of livestock and the taming of animals for pets certainly marked a turning point in human history. Having these animals on hand to provide food and milk, as well as companionship and assistance with hunting, gave humans a more ready food supply and meant less time had to be spent gathering food. However, it also put us in regular contact with germs that these animals carried. Human measles virus infections may have evolved from a similar cattle virus, rinderpest. Cattle can also be a source of tuberculosis in humans, even today. Industrial livestock production means that it's not just a farm family that may be sickened by pathogens from a pig or cow, but potentially hundreds or thousands who consume meat or other products from those animals. Foodborne illnesses are estimated to sicken 76 million people yearly in the United States and kill approximately 5,000. Economic costs from these food-borne illnesses alone are estimated at approximately $77 billion per year

Finally, our smaller domesticated friends can expose us to their own pathogens, including the parasite Toxoplasma gondii in cats (which is particularly dangerous to pregnant women), and they can also bring along unintended visitors and their pathogens into the home in the form of fleas and ticks. Even "pocket pets" such as hamsters and guinea pigs can bring along potentially deadly viruses and infect their owners.

So, Why Aren't We All Dead?

With so many potentially deadly organisms lurking in the animal species we share the Earth with, the question becomes not if we'll have another novel pandemic, but when. However, these events — the new influenzas, the SARS coronaviruses, the HIV outbreaks — are actually relatively rare. "Spillover" events — an individual becoming infected with a zoonotic pathogen — are common, but typically the infected host is a dead end. He or she doesn't spread the germ to a second person, which is necessary for an epidemic (which is a localized outbreak) or a pandemic (a worldwide infection) to occur. Going back to H5N1 influenza versus H1N1, that's why the former has caused only sporadic outbreaks and the latter has become pandemic. H1N1 is readily transmissible between people, and H5N1 (so far) is not. This is also why there was so much concern earlier this year when a genetically modified H5N1 was created in a laboratory setting. This modified virus was able to spread readily between ferrets, a common animal model for human influenza research. The work caused worry that such a virus may escape from a lab and spread in the wild — "The Stand" come to life.

This controversy also highlights the difficulty in studying potential zoonotic pathogens. Many of these organisms have adapted to their hosts and do not always cause symptoms in their "natural" species. As such, it's difficult to anticipate which microbes will 1) make the species jump successfully; 2) cause illness in the new host species (for example, in humans); and 3) transmit efficiently among members of the new host species. Prediction right now is very foggy, though we're beginning to better understand the diversity of organisms out there, and with that, hopefully gain understanding into why some spill over and others do not.

One final note — while we often consider humans the victims of such pandemic events, that's not always the case. Zoonoses are a two-way street, and humans can also spread our own native microbes to other species. Recent studies have shown that humans have spread antibiotic-resistant strains of Staphylococcus aureus to many different species, including domestic chickens, pigs and even chimpanzees and dolphins. We, too, are a walking biohazard.

Tara C. Smith is an associate professor of epidemiology at the University of Iowa, where she serves as co-director of the Center for Emerging Infectious Diseases. She studies zoonotic diseases, focusing on Staphylococcus aureus, and maintains a blog on infectious diseases at scienceblogs.com/aetiology. You can also follow her on Twitter at @aetiology.