Viral Trade and Global Public Health

In June 2003, some 80 people in three Midwestern states were stricken with monkeypox. Until then, the disease–a sometimes fatal viral infection related to smallpox–had never been seen outside Central and West Africa. In the United States, the virus is believed to have spread to humans from pet prairie dogs, which in turn were likely infected by a giant Gambian rat held by a Chicago exotic pet dealer. So far, no one has died. But if the outbreak is confirmed to be an inadvertent byproduct of trade, then it is yet another warning sign of the growing international exchange of viruses.

The increase in viral traffic is the result of two converging trends: Deadly new viruses are appearing at an accelerating rate, and viruses are traveling around the world faster than ever before. During the past several decades, a number of new or changing viruses have emerged, wreaking havoc wherever they strike. The deadly avian influenza virus that hit Hong Kong in 1997-1998 and the Netherlands in 2003, for example, required the mass slaughter of poultry to control the outbreaks. And HIV has decimated much of the working population in sub-Saharan Africa and threatens other parts of the world.

Today, a virus that emerges in one place can quickly find its way to any other place on earth. Witness the discovery of the West Nile virus in New York City in 1999 or the recent global spread of severe acute respiratory syndrome (SARS). SARS illustrates one of the new realities of the global economy: Except for war, terrorism, and natural disasters, nothing stops global trade and travel as effectively as a deadly disease outbreak.

Such outbreaks will become more common unless stringent steps are taken to prevent them. The biggest obstacle to effective control is the unevenness of public health capabilities around the world. Although an individual country might attempt to stem viral outbreaks within its borders, one nation’s public health laws and disease control efforts are only as good as those of its neighbors. This is a global problem, and it requires a global solution. The only way to ensure that all countries pull their weight is to allow the World Health Organization (WHO) to establish stringent global public health laws and standards. Although enforcement would be difficult, another global body, the World Trade Organization (WTO), could provide strong incentives by allowing only countries that adhere to these laws and standards to participate fully in global trade. By working together, these two organizations could create effective strategies for preventing and controlling the inadvertent trade of viral infections.

In the battle between humans and viruses, viruses have all the advantages. One reason is the sheer number of viral particles. The oceans alone contain more than 1030 bacterial viruses. That number is larger than the number of stars in the observable universe, and it describes just a small subset of viruses: those that infect only bacteria. And most viruses are completely unknown. According to Lynn Enquist, a virologist at Princeton University, scientists have identified only 1 percent of the viruses on the planet.

An infected person or animal can shed enormous numbers of new viral particles. For example, one 35-ton gray whale, infected with a virus that causes diarrhea, has been estimated to excrete over 1013 new viruses into the ocean each day. This class of virus, the noroviruses, can infect terrestrial hosts, including humans. They have been implicated in outbreaks of illness aboard cruise ships. On a lesser scale, one human with end-stage AIDS can produce a billion new viral particles per day. Given that upward of 40 million people worldwide are estimated have HIV infection or AIDS, one gets an idea of what humans are up against.

Viruses are the most successful life form on the planet, yet they are not even technically alive. Their complex chemical structures consist of a strand or two of DNA or RNA and a protein coat. They are parasites; they replicate by entering the cells of bacteria, plants, or animals. Once inside their host, they hijack the cell’s machinery to produce new viral progeny.

Viruses also have an evolutionary advantage. Their replication is sloppy. Mutations, recombinations, and reassortments of viral genetic information occur at high rates, helping viral offspring to adapt and survive. It is these inherent viral properties of parasitism and mutation that make it difficult to develop effective drugs and vaccines. Viruses are rarely conquered and eliminated. Smallpox is the exception, and even it could be lying in wait as a potential bioweapon.

Many factors contribute to the increasing emergence of previously unknown viruses into human populations. Global deforestation, destruction of natural habitats, and human population pressures are well-described worldwide problems. But viruses can also be introduced into human populations by certain cultural and trade practices. Because many of the newly discovered viruses spread between animals, either through direct transmission or through insects, anything that alters the fragile animal-viral ecologic cycles is dangerous. Some of the worst offenders include the slaughter and consumption of wild animals, the trade of exotic animals as pets and laboratory specimens, and the trade and dumping of mosquito-infested scrap tires.

Bush meat and cannibalism

The practice of slaughtering and eating wild animals has been blamed for both the AIDS and the SARS epidemics. Researchers found that a substantial fraction of wild monkeys in Cameroon are infected with SIV, the simian cousin of HIV, and that the humans who hunt them are exposed to a wide range of viruses. HIV itself has been isolated from common chimpanzees, which are believed to be the original source of the AIDS pandemic after hunters killed and ate them. Ironically, a recent article in Science suggests that chimpanzees acquired their SIV from monkeys they had killed and eaten.

Despite the AIDS epidemic, many African leaders have done little to halt the spread of the disease or to decrease the risk of new viruses affecting humans. In Africa, bush meat is still widely eaten, often in preference to domestic meat from cows, pigs, and chickens. Although great apes such as chimpanzees and gorillas make up only about 1 percent of the game caught in the forests in remote areas of western and equatorial Africa, their meat poses the greatest risk to human health.

Great apes are humankind’s closest living relatives, sharing more than 98 percent of our DNA. Viruses that infect and sicken these animals are therefore more than likely to afflict humans, and vice versa. For example, the Ebola virus, one of the deadliest viruses to humans, is now killing many great apes. Because Ebola is transmitted through contact with blood and bodily fluids, the virus would certainly spread to humans who slaughtered and consumed infected apes.

Previous experience suggests that unhealthy cultural practices can be stopped through education and well-enforced legal bans. One example is the epidemic of kuru in Papua New Guinea. Kuru, a debilitating brain disease similar to mad cow disease, was spread by the custom of eating dead relatives. It produces holes in the brain like those in Swiss cheese. Most of the victims were women, who traditionally ate the brain and internal organs, the most heavily infected parts. Because kuru has a long incubation period, it was not obvious to its victims that the illness had come about from eating unsafe meat. The practice of cannibalism was banned once this was known, and kuru epidemics disappeared.

AIDS, too, has a long incubation period that can obscure the process of cause and effect. So just as educational efforts and cultural reforms were vital in stopping kuru in Papua New Guinea, similar measures could help fight the transmission of AIDS from apes to humans in Africa, where trade in ape meat is illegal but still practiced.

The Chinese commonly eat exotic wild animals, oblivious to the dangers of infection. The virus that causes SARS has been identified in the masked palm civet, a cat-sized animal that the Chinese consider a delicacy. Several of the first SARS victims were chefs, and all six of the initial patients linked to SARS outbreaks in the Guangdong province had handled or eaten wild animals before becoming ill.

In response to the SARS epidemic, the Chinese government recently banned the capture, transport, sale, and purchase of virtually all wild animals, according to the Wall Street Journal. But open-air markets in China are reportedly still filled with animals of all species–some covered with the feces of adjacent caged animals, a perfect setup for viral transmission from one species to another. Clearly, China’s new law will be a challenge to enforce, particularly if inspections are conspicuous and vendors have time to hide their illegal wares.

Live imports

As the case of monkeypox shows, humans do not have to kill or eat wild animals to acquire their viruses. The trade in exotic animals as laboratory research specimens or as pets is just as dangerous. Monkeys make valuable laboratory specimens because of their physiological similarity to humans. But that same attribute puts human handlers at risk of contracting monkeys’ diseases.

In the 1960s, monkeys from Uganda were imported to Marburg, Germany, for use in vaccine development. The monkeys turned out to be infected with deadly viral hemorrhagic fever, which spread to animal handlers and technicians. Many people died as a result of the outbreak, and the causative agent, a relative of the Ebola virus, became known as the Marburg virus. Another outbreak of an Ebola-related virus occurred in laboratory monkeys imported from the Philippines to Reston, Virginia, in 1989. Luckily, the virus was not deadly to humans, but a warehouseful of monkeys had to be slaughtered.

In 1997, a young female worker at a primate research center died from a herpes B virus infection 42 days after a macaque splashed her right eye with what was presumed to be fecal matter. Macaques are frequently used in biomedical research, and more than 80 percent of them carry the herpes B virus. In some 40 reported cases, macaques have infected humans with the virus, which can cause a potentially fatal brain infection, meningoencephalitis. Before antiviral agents became available, the death rate was over 70 percent. Survivors often suffer permanent neurologic damage. Even though keeping these animals as pets has been illegal in the United States since 1975, the Centers for Disease Control and Prevention has received numerous reports of macaque bites in private households during the past decade.

Stricter regulation and legislation could help. The federal government has allowed the unregulated import of exotic animals to “spiral out of control,” as Wayne Pacelle, senior vice president of the Humane Society of the United States, has put it. In response to the monkeypox outbreak in the Midwest, the U.S. government has banned the sale of prairie dogs and the importation of rodents (including the offending Gambian giant pouched rat species) from Africa. Two senators have called for a special committee to look into the regulations governing the importation of exotic pets. However, although these responses make sense in the short term, they do not address the problem in the long run. The real dangers of viral outbreaks suggest that a ban on imported pets should extend to all wild animals. As usual, enforcement will be another matter entirely. According to the U.S. Fish and Wildlife Service, the illegal wildlife trade in the United States amounts to $3 billion annually. Primates are believed to constitute a significant part of that trade.

Travel by tire

Some viruses are transmitted from animals to humans by insects such as mosquitoes. Whether or not they carry viruses, mosquitoes often manage to hitch a ride in scrap tires during shipping. Because their interiors are dark and often contain standing water, scrap tires make excellent incubators for mosquito eggs. In Taiwan, such tires have been found to serve as breeding sites for mosquitoes that transmit dengue fever.

A 1992 National Academy of Sciences report on emerging infections found that the United States generates a quarter of a billion discarded tires each year and imports several million more. Because the market for shredded tires is small, fewer than 5 percent of the world’s scrap tires are recycled. But even a modest level of international trade in scrap tires poses dangers. Traveling in tires, exotic mosquitoes from Asia have managed to spread to distant points. Some have taken up permanent residence.

In 1985, the Asian tiger mosquito, Aedes albopictus–a known vector for dengue fever, yellow fever, and viral encephalitis–was found to have ridden in a shipment of scrap tires from Japan to the United States. This mosquito has now been found in 16 states. In New Zealand, a 1992-1993 survey published in the Journal of the American Mosquito Control Association found mosquito-infected scrap tires aboard five ships from Japan and one from Australia. A similar hunt in South Africa turned up the immature stages of various mosquitoes in a shipment of tires from Japan. Scrap tire shipments have also enabled the yellow fever vector mosquito, Aedes aegypti, to establish itself in previously unaffected areas of Pakistan. Although those mosquitoes do not cause disease by themselves, they are essentially tinder waiting for a viral match.

A few governments are trying to do something about the scrap tire problem. Taiwan, for example, requires tire manufacturers to prepay deposits or charges according to the size of the tires they produce. The funds are then used to recover and recycle the tires. In Kaohsiung City, more than 80,000 scrap tires have been collected to make an ocean jetty.

In the United States, there are no federal laws dealing with the disposal of scrap tires, and state requirements vary considerably. According to the Rubber Manufacturers Association, New York state recently enacted legislation to clean up 40 to 50 million stockpiled scrap tires, the largest inventory outside Texas. The new law creates a dedicated fund to collect scrap tires and to promote their use in recycled products such as playground coverings. In Illinois, legislators responded to the Asian tiger mosquito problem by passing the Illinois Waste Tire Act. The law calls for scrap tires to be collected from dumps for recycling and encourages the building of waste tire processing facilities and the development of new recycling technologies.

Those efforts are a good start, but much more needs to be done. Not only should national governments address this problem, but organizations such as the World Bank should help promote recycling projects and new uses for scrap tires worldwide.

Uneven defenses

With so many possible avenues of transmission, the inadvertent trade of viruses will continue to plague nations as they struggle to keep their populations healthy. One government’s success or failure will be highly dependent on the public health capabilities of its trading partners and neighbors. Unfortunately, the capabilities of different governments are grossly uneven. The frailty of a country’s public health policies becomes glaringly obvious when they are tested by novel diseases such as SARS. But inadequacies are also reflected in the way many nations deal with common, easily preventable diseases.

In the instance of SARS, China provided the classic example of how not to respond to an epidemic. It suppressed information for four months and then hindered investigations of the outbreak. And in contrast to Vietnam, Canada, Singapore, and Taiwan, which quarantined thousands of people in their homes, Hong Kong officials strongly resisted such measures. Those mistakes dealt a blow to China’s credibility and economic growth, and they took a heavy toll in human lives: By June 2003, according to WHO, the disease had struck 29 countries, afflicting 8,000 people and killing 800.

In response to the SARS epidemic, WHO’s 192 member nations have granted the agency broad new powers for responding to the next crisis. Although WHO is required to collaborate with the affected country, it can now apply pressure to send in its own investigators to conduct epidemiologic studies. The agency can also collect data from nonofficial sources, and now has the power to issue global health alerts, something it did for SARS in March 2003 without explicit authority. Although this is an important development in the arena of international health, it still does not address the vast differences of capabilities and competencies in individual nations’ responses to health threats.

A good yardstick of such capabilities is the way in which a country manages routine vaccine-preventable diseases: If it cannot handle the easy diseases, it stands little chance of handling the difficult, unexpected, exotic diseases, including those that might arise from bioterrorism. A particularly useful viral disease to study in that regard is measles, because it is highly contagious yet easily controlled. Measles can cause complications such as pneumonia, encephalitis (brain infection), seizures, and subacute sclerosing panencephalitis, a rare degenerative condition of the brain. Although in the United States measles is fatal in only 1 or 2 out of 1,000 reported cases, it can have a death rate as high as 25 percent in malnourished children.

The measles vaccine is cheap (about 26 cents), readily available, and highly effective in controlling outbreaks. Nevertheless, measles kills roughly a million people per year worldwide. Not all of those deaths are in developing countries, either. Between 1989 and 1991, the United States witnessed more than 55,000 cases of measles, some 120 of them fatal. Aggressive U.S. vaccination programs since 1993–including the requirement in 49 states that children receive two measles vaccinations before entering kindergarten–have drastically reduced the number of cases. Indeed, epidemiologic studies indicate that none of the outbreaks of measles after 1993 were from strains endemic to the United States–all were imported. In other words, U.S. domestic strains have been stamped out. By dividing the virus into eight distinct genetic groups based on geographic distribution, researchers found that countries as different as Japan and Germany have served as the source of at least five separate U.S. measles outbreaks from 1994 to 1997.

In Japan, an estimated 100,000 to 200,000 cases of measles occur each year, killing 50 to 100 people. Only about 80 percent of the population have been vaccinated: less than WHO’s international goal of 90 percent. That is because Japan revised its vaccination law in 1994 in response to some alleged cases of meningitis in children who were vaccinated for measles, mumps, and rubella between 1989 and 1993. Under the revised law, childhood vaccinations against measles are recommended but not mandatory. Not only does Japan now have a high incidence of measles, but unvaccinated Japanese travelers have been suspected of causing outbreaks elsewhere. In New York City, for example, a measles outbreak in July 2001 was traced to a group of Japanese students who were visiting a university. Similarly, a large outbreak that struck Anchorage, Alaska, in 1998 was caused by viruses closely related to known Japanese strains. It began four weeks after a boy visiting from Japan came down with the disease.

Germany provides a unique perspective on the impact of public health measures on measles because of its history of reunification. Before reunification, East Germany was close to eliminating the disease, thanks to mandatory vaccination, excellent surveillance, and successful vaccination strategies. In contrast, West Germany, with none of those defenses in place, had a significant measles burden.

Under reunification, the lax standards of the former West Germany have prevailed nationwide. Despite the passage of the Communicable Diseases Law Reform Act of 2001, which mandated national surveillance and required children to be vaccinated before entering school, Germany’s vaccination coverage remains low. Coverage is only 22 percent at 15 months, 77 percent at 24 months, and 87 percent at 36 months. Even upon school entry, fewer than 90 percent had received the first dose of the vaccine. Not surprisingly, Germany has experienced many measles outbreaks since reunification.

Germany’s poor performance illustrates how difficult it will be for WHO to achieve the goal of eliminating measles from Europe by 2007. Although WHO recommends that children receive the measles vaccine at 9 months of age and a second dose between the ages of 4 to 6 before the child enters school, the agency does not have the authority to mandate public health requirements.

In the absence of such authority, the world’s defenses against communicable diseases remain a patchwork of unequal and often ineffective national policies. Countries with weaker laws and public health practices have a greater burden of disease and are more likely to export those diseases to other nations. Not even the more developed regions have adequately dealt with this problem. The European Union has managed to institute a single market and currency, yet it has not established laws to ensure a uniform public health system. The relatively strong health policies of Finland and Sweden coexist alongside the weaker policies of Germany and Italy. As long as such disparities in public health laws, surveillance, and disease control strategies continue, so will the inadvertent trade of viral diseases.

Global public health standards

What is needed is the establishment of stringent public health laws and standards that all nations must meet. As the means of transporting viruses around the planet continue to multiply, all countries will have to be prepared to stem the spread of new and exotic diseases such as HIV, dengue fever, and SARS. But they can do that only if they are capable of containing common diseases such as measles, influenza, and hepatitis. Countries should have to demonstrate some minimum level of competency in dealing with those ordinary diseases as a prerequisite to full participation in global trade and travel.

Accomplishing that goal would not be easy. Some countries, such as those of the former Soviet Union, are struggling to develop functional bureaucracies and legal systems. Others are plagued by political or economic instability. Even the United States might prove to be a hard sell. An indication of that is the resistance that has greeted efforts to implement model public health laws across all 50 states: laws designed to improve readiness to respond to bioterrorism.

Virtually every United Nations member nation, regardless of the condition of its public health apparatus, is a member of WHO. Although membership requires nations to uphold the agency’s constitution, which is part of international law, many of its laws are vague; they do not specify how countries should ensure public health. In the age of emerging viruses, international public health laws need to be more explicit on issues such as vaccination requirements and the consumption of wild and exotic animals.

Strong economic incentives might be required to convince political and economic leaders that public health is important and that their nations’ trading partners and neighbors are serious about the issue. WTO membership could be contingent on the requirement that countries meet global public health laws and standards. Countries would have to ensure that their exported goods are not contaminated. They would have to certify, for example, that used tires do not contain mosquito eggs or larvae. Countries would also have to eliminate those enormous stockpiles of used tires.

The stakes are high. The social, political, and financial consequences of future emerging viral outbreaks could be even worse than those of the most recent viral scourges. WHO and the WTO have worked together since 1995 to promote international food safety standards. This type of collaboration could help ensure the competency of public health systems across nations and curtail the economic and cultural activities most likely to promote the emergence and spread of disease.