Bacterial banes
Anthrax and the Black Death are two bacterial zoonoses that have linked people and animals through the centuries (see Modern Drug Discovery, June 2001, and November/December 2000, respectively). Salmonella is another well-known zoonosis in the annals of public health. More recently, E. coli O157:H7 is one of the most publicized bacterial infections of animals in the West that impacts human health. Although people once ate raw or undercooked beef and dairy products without fear, recent and large outbreaks of food poisoning from E. coli have put an end to that. In fact, this variant of one of the most common of the intestinal flora is also one of the deadliest pathogens. The Centers for Disease Control and Prevention (CDC) estimates that 76 million Americans contract foodborne disease each year, including E. coli infection.

Outbreaks of E. coli were first reported in American cattle in the 1970s. Recent surveys have shown that it is found in more than a quarter of the animals entering slaughterhouses. O157:H7 is not only a risk to human health; it also makes animals—the same animals humans eat—sick. When infected animals are slaughtered and processed, feces containing the virulent strain of E. coli contaminate the carcass and meat. Poor meat-handling practices, followed by consumption of the undercooked animal product, leads to poisoning. People with impaired immune function then run the highest risk of food poisoning and even death.

Although tighter meat-handling standards can prevent contamination, and pasteurization or irradiation can remove the risk of infection after contamination, new techniques are being developed that address both animal health and human food safety. New possibilities currently under investigation include

• food additives that contain benign or beneficial bacteria, which would “outcompete” O157:H7, and
• inoculations to induce immunity to the pathogen, thereby preventing cattle from carrying the lethal bacteria in the first place.

(For more information, see “Better farming, new animal vaccines could mean safer food”, http://europe.cnn.com/2000/FOOD/news/09/07/safer.food.ap/).

On the flip side, the massive use of antibiotics in animal feed to control communicable bacterial diseases, especially in pigs and chickens raised on “factory” farms, has led to controversy about the possibility of animals developing antibiotic-resistant bacteria that could infect humans.

Viral zoonoses
The relationship between animal and human health is not limited to bacteria. Viruses that affect animals also pose a threat to humans. One of the most familiar—and surprisingly, one of the most deadly—has been the common flu (see box, “Birds and swine and flu”). In some cases, however, investigations into animal viral infections have led to new ways of looking at similar aspects of human diseases and even to new methods of treatment.

Birds and swine and flu

According to the CDC, during the past two and a half centuries, 10–20 human influenza pandemics occurred, with the “Spanish flu” of 1918 and 1919 being the most devastating—more than 20 million died and over 200 million people were infected. Many of these pandemics probably originated from viruses mutating from aquatic bird reservoirs. Phylogenetic evidence shows “that a totally new virus of avian origin could have appeared in humans or swine before the 1918 influenza and replaced the previous human virus strains. Whether the virus was first introduced into humans and then transmitted to pigs, or vice versa, remains unknown.” (For more information, see “Influenza: An emerging disease”, www.cdc.gov/ncidod/EID/vol4no3/webster.htm.)

Rabies is one the most striking and feared viral diseases at the human–animal health interface. It is an ancient disease; the origin of the word is Sanskrit dating to 3000 BC, and it means “to do violence”. References to the disease predate Pasteur’s development of a postexposure vaccine for “la rage” by millennia. In animals, there are two primary forms—the paralytic, usually seen in rodents, and the furious, which is seen in carnivores. Both have been seen in humans.

Rabies is characterized by encephalitis and, in the absence of postexposure treatment within a critical interval, death. There are several vectors, but the most common for human exposure are bats, cats, and dogs. Thus, prevention of rabies in animals, particularly house pets, and avoidance of potentially infected wildlife, is the best prevention. (For more information, see “Rabies”, www.pasteur.fr/recherche/rage/rage-eng.html.)

Rabies is an ancient disease, or at least a disease long familiar to human populations, but there are also emergent viral diseases to contend with. Variants of the Ebola virus, which causes a hemorrhagic fever, are particularly alarming. In North America, however, two novel viral infections of animals have emerged, the West Nile virus in birds and hantavirus in rodents. Both affect animals, and both are lethal to humans.

The West Nile virus is a newcomer (1999) to North America. It is currently found primarily along the East Coast, and there is nothing preventing its spread. While it is harmless to some bird species, it kills others, especially crows, and there have been cases of transmission via mosquitoes to horses and humans. Symptoms range from none, to coldlike, to a deadly encephalitis (particularly threatening to older people and the immunocompromised). In 2000, the virus was found in birds in 12 states and Washington, DC. Two people died in New York City, and 11 mosquito species were found to be carrying the virus.

Hantavirus is found in the Southwest. In the summer of 1993, apparently healthy adults sickened and died suddenly of an unknown disease. Autopsies revealed that victims essentially drowned in their own blood serum, which leaked from vessels into the pleural cavity.

Navajo leaders were able to supply public health physicians with clues. That year had seen a particularly bountiful harvest of piñon nuts, and with it a large population of deer mice. The years 1918 and 1936 had also seen large harvests and large deer mouse populations, as well as unexplained epidemics.

That information proved to be what researchers from the CDC needed. The blood of the victims reacted to antibodies from the viral family hantaan (hanta). As CDC scientists isolated and amplified viral DNA from victims’ blood, trappers caught deer mice, which proved to carry hantavirus. (For more information, see “Plague Patrol”, www.discovery.com/stories/science/infectious/death.html.)

The other side of the story

Just as animal health can carry over to human concerns, trends in human health care can have an impact on the health and treatment of animals (See also "Veterinary Vexations", this issue.). And the story is far more complex than simply the use of antibiotics in animal feed. In this case, the tremendous growth in the use of antidepressants and antianxiety medications has hit the animal world. The FDA recently approved Novartis AG’s application to market meat-flavored antianxiety medications as a treatment for separation anxiety in dogs. The FDA has also approved Pfizer’s drug Anipryl, which is used to treat canine cognitive dysfunction syndrome, referred to as “Alzheimer’s for dogs”. Then, too, Prozac has been used to treat obsessive–compulsive disorder in certain overbred varieties of dog. (For more information, see “Dog owners hail ‘Prozac’ for pets”, www.bergen.com/news/dogmedlw19990106.htm.)

The list goes on. Animal reservoirs are known or suspected to play roles in AIDS, Ebola, sleeping sickness, and some herpes virus infections, as well as in measles, viral hepatitis, and other diseases. In the last decade, Japanese (viral) encephalitis of pigs caused human fatalities nearly every year, especially in Malaysia, where it was carried by mosquitoes from swine to farmers.

But not all viral infections of animals are dangers to human health; in fact, they can provide valuable models for human diseases, or at least important clues to understanding them. At first glance, feline leukemia virus (FeLV) seems to have nothing to do with humans. Yet FeLV increased awareness of retroviruses, and research into FeLV led to an increased understanding of the natural history of such pathogens. This has had a direct impact on human health in the initial understanding of HIV, the retrovirus that causes AIDS.

Mad cows and putative prions
Perhaps the most current of the troubling intersections of animal health and human disease is bovine spongiform encephalopathy (BSE), or mad cow disease. BSE affects the central nervous system of cattle. Worldwide, almost 200,000 cases have been reported since the disease was first diagnosed in 1986. Although it has shown up in several countries, more than 95% of all BSE cases have occurred in Britain. BSE is not known to exist yet in the United States.

BSE belongs to a group of diseases known as transmissible spongiform encephalopathies. An as-yet unknown agent causes these diseases. They have the following characteristics in common:

• their incubation period is long (months or years),
• both diseases show a progressive, fatal neuropathy,
• brain tissue from animals and humans affected by these diseases shows similarities to the brains of sheep infected with scrapie,
• pathological changes appear to be confined to the central nervous system, and
• the causative agent sparks no detectable immune response.

(For more information, see “Bovine Spongiform Encephalopathy (BSE)”, www.aphis.usda.gov/oa/bse.)

While theories of causative agents abound, BSE is thought to result from a prion. A prion is an abnormal protein that is partially resistant to proteinase K. Prions lack nucleic acids, yet they can reproduce in cells. The characteristics of BSE bear a striking resemblance to Creutzfeld–Jakob disease (CJD)—a slow degenerative disorder of the human nervous system that causes progressive dementia and brain degeneration. CJD occurs sporadically worldwide at a rate of one case per million people per year.

Are the diseases the same? On March 20, 1996, the British government announced the identification of 10 cases of a new variant form of CJD (vCJD). Research published in 1996 and 1997 found evidence to support a causal association between vCJD and BSE. Two significant studies published in the October 2, 1997, issue of Nature led a British government panel to conclude that the BSE agent is highly likely to be the cause of vCJD. If this is true, and if a prion is indeed the cause of the animal and human diseases, a new form of zoonoses has entered the picture, further tangling the link between human health and animal well-being.

The lion and the lamb
Ultimately, our link to animals is as medically profound as our strikingly overlapping genomes would suggest, whether it be dog or cat, mouse or rat, pig or primate. Through their baneful effect as vectors or reservoirs of serious maladies, or through the benefits they provide from their use in the testing of human drugs and treatments (see Rules and Regulations), the health of our pets, our livestock, and our neighbors in the wild is linked forever with our welfare. Understanding diseases unique to animals, and those we share with them, provides endless opportunities to understand and enhance human health. The zoological kingdom, whether peaceable or pestilential, proves profoundly to be our own. And with deforestation and global climate change shifting the landscapes and transforming the human–animal interface across the world, veterinary medicine may prove to be the salvation of more than just a barnyard full of cows.

Christopher S. W. Koehler holds a Ph.D. in the history of science. He writes and teaches in northern California. Send your comments or questions regarding this article to mdd@acs.org or the Editorial Office by fax at 202-776-8166 or by post at 1155 16th Street, NW; Washington, DC 20036.