SARS May Be Just the Start

In the few months since its emergence, the SARS virus has killed hundreds, sickened thousands and scared millions. But many infectious disease experts believe it is only a dress rehearsal for some other, more dangerous outbreak that could strike at any time.

Perhaps this future scourge will be an old, familiar foe, such as the influenza virus, ramped up to new lethality after borrowing genetic information from a related bird virus. Or maybe that foe is still faceless because it has only recently evolved, or has been skulking in an isolated part of the world, unable until now to obtain a wider foothold.

The whens, wheres and whats are uncertain, but disease specialists believe that the emergence or spread of noxious bacteria and viruses has never been more likely.

“What we have today is the perfect storm -- an entire puzzle that favors the microbes,” said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota’s School of Public Health.

Today, there are more people than ever before packed onto the planet -- 6 billion compared with about 1.5 billion at the start of the 20th century. The human race has become a vast petri dish for the growth, evolution and spread of microbes.

More than ever, we are a species on the move, abandoning countryside for closely packed cities, and boarding planes, trains and buses that can swiftly transport a SARS virus, flu virus or mosquito infected with West Nile or dengue virus far afield.

The need to feed a booming world population has altered how and where food is grown. It has pushed farmers into marginal lands -- sometimes into closer contact with microbes they may have only rarely encountered before.

It has turned food production into a giant, industrial undertaking that crowds animals together in huge congregations where they can pick up bacterial or viral contaminants that in the past would have stayed localized. The resulting ground beef, cutlets and chops are shipped far and wide.

The Human Element

Many human actions -- such as vaccine production and water treatment -- tip the balance in favor of human beings. But countless other actions favor the bugs. Promiscuous unprotected sex, intravenous drug use and even blood transfusions have helped HIV spread.

Countering emerging diseases requires an effort as multi-pronged as the factors that make microbes a threat. It involves increased surveillance, diagnostics and public health responsiveness so that outbreaks can be quickly attacked. It requires the rapid development of vaccines against lethal new strains of flu, and the stockpiling of antiviral drugs that can be used until the vaccine is prepared.

Utterly annihilating a microbe from the world is usually impossible.

“There may well have been infectious diseases we accidentally eradicated in the process of killing off the dodo or the passenger pigeon, but the sad reality is smallpox is the only infectious disease we have intentionally eradicated,” said Stephen Morse, director of the Center for Public Health Preparedness at Columbia University’s Mailman School of Public Health.

Even in that remarkable case, Morse said, we neither finished the job, nor, as it turned out, removed the threat. Small samples of the virus are still maintained by the U.S. and Russian governments, and possibly others.

Plagues are by no means new to our species; they have long ravaged the world. In the 1300’s, the bubonic plague, or so-called black death, that spread from China to Europe, killing 25 million Europeans, or about one third of the population there. Smallpox, the “speckled monster,” crossed the Atlantic to the Americas in the 1500s, ravaging the Aztecs and Incas.

Records of deadly flu epidemics and pandemics date back as far as ancient Greece and Rome -- and one of these, in 1918, claimed at least 20 million lives.

It is also true that infectious disease experts are spotting more pathogens because they are looking more closely, aided by the tools of modern biomedicine.

Before 1993 nobody knew that a virus, now known as Sin Nombre, was endemic to this country, living its life for the most part in populations of deer mice, only occasionally hopping into people who were exposed to the rodents’ urine, feces and saliva.

Then a spate of abnormally warm and wet winters caused a bumper crop of vegetation, leading to an explosion in the deer mice population. That was followed by a cluster of human deaths from a mystery respiratory disease in the Four Corners region of the southwestern U.S. -- and the discovery of a new virus that had been there all along. Since then, 25 viruses related to Sin Nombre have been discovered in the Americas.

Problems of Proximity

But other bacteria and viruses are truly emerging anew, or are spreading far beyond their traditional range, often because of the actions of human beings. Frequently, the diseases come from animals that we cultivate for food.

In Malaysia, the close proximity of pig herds and fruit bats allowed a previously unknown agent now known as the Nipah virus to jump from bat to pig -- and eventually to people, where it caused more than 100 deaths from encephalitis in 1998 and 1999.

In the United Kingdom, the practice of feeding ground animal carcasses to cattle may have allowed an agent causing a deadly, degenerative disease (known colloquially as “mad cow disease”) to jump from sheep to cows in the 1980s. When the beef was turned to burgers, the agent managed to cross the species barrier to people, killing at least 117 people since 1996.

The common practice of feeding antibiotics to animals may contribute to a sharp increase in antibiotic-resistant pathogens found in food. In studies of microbes that cause food poisoning, 26% of Salmonella specimens and 54% of Campylobacter specimens now seem to be resistant to at least one antibiotic. A particularly noxious food-borne threat -- Salmonella typhimurium DT104 -- is resistant to multiple antibiotics and has spread across the globe since its emergence in cattle in the 1980s.

Perhaps the biggest threat linked to our close association with animals is influenza, which strikes every year, killing 36,000 Americans in a typical flu season.

But as past pandemics show, it has the potential to do much more damage than that.

Flu viruses infect people, pigs, seals, horses, chickens and in particular, in the guts of many species of waterfowl, where they cause little by way of disease.

Several factors make the virus such a problem for human beings. First among these is the biological nature of the virus. Its genome is comprised not of DNA like our own, but of RNA, which accrues high numbers of errors when it’s copied. As a result, the virus is constantly accumulating small genetic changes, and constantly evading our immune systems. That’s why flu shots are annual events.

The virus’ genome is also divided into eight separate strands, so if two different flu strains infect the same cell, they can easily mix and match individual pieces and come up with brand new variants. When pieces of bird flu meld with pieces of human flu -- often in the body of a pig, where both can happily live -- huge shifts in the virus can occur. The new strains, unfamiliar to humans, can overwhelm the body’s defenses, causing deadly, global pandemics.

Nowhere is the flu virus more likely to mutate in this way than in countries such as China, where crowded conditions and traditional farming practices pack pigs, birds and people close together. Shoppers throng the live bird markets for fresh meat, and the need to feed a growing population has significantly increased the number of animals raised.

Such a concentration of live animals near people could be the reason why SARS emerged in southern China, although the origin of the virus is still a mystery. It isn’t known yet if the virus was transferred from some creature or already existed in our species, perhaps in a less lethal form.

In recent years there have been several close calls with bird-related influenza viruses. For instance, in 1997, 18 people in Hong Kong were infected by a new bird virus, six of whom died. All Hong Kong poultry were slaughtered to prevent an opportunity for the virus to evolve into a form that could spread among humans.

Wide-scale slaughter of millions of chickens, ducks and geese is underway in the Netherlands in an effort to eradicate yet another particularly worrisome bird flu that has caused dozens of conjunctivitis infections in people and killed a 57-year-old veterinary surgeon.

“We’re seeing a lot more influenza activity, particularly in chicken populations, in recent years,” said Richard Webby, an influenza researcher at St. Jude Children’s Research Hospital in Memphis, Tenn. “We don’t really know why it’s happening. It may be that a lot of producers are moving toward raising a lot of chickens in very small areas.... It is really only a matter of time before one of these leaps into humans.”

Weapons other than surveillance exist for fighting flu. There are antiviral drugs that target the influenza virus. The virus, for all its mutability, appears unable to develop resistance easily to at least one class of these drugs.

In another development, Webby and colleagues have devised a way to grow a dangerous version of bird flu in fertile chicken eggs, which is the customary way that vaccines are prepared. Normally, this strain is so lethal that it kills the embryos outright, so that vaccine cannot be grown. By slightly altering the genetic structure of the virus, the scientists have removed this chick embryo lethality while retaining features that would make it an effective vaccine.

Vaccine in Short Supply

Yet, in spite of such developments, we are hardly prepared for an influenza pandemic, experts say. Even in the normal flu years of 2001 and 2002 there were insufficient stocks of vaccine to supply demand. The demand in those years was a fraction of what it would be if an especially lethal flu were to strike.

Moreover, there are no stockpiles of antiviral drugs -- even though it takes at least six months to create a vaccine once a new strain of flu is identified.

It has been more than 30 years since a flu pandemic swept the globe -- and if the past is anything to go by, we are overdue for another one.

As they survey the invisible threat, infectious disease specialists say they walk a fine line between being unnecessarily alarming and leaving the country unprepared.

“There are a lot of lessons from SARS that go beyond the worry at the moment,” Morse said. “Long after that worry has dissipated I hope we will have learned from it -- about preparedness, about improving capacity, about asking questions such as how can we better understand the sources of these infections, and what can we do about them -- particularly what we can do about them.”

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Other viruses

Virus; Symptoms; Mode of transmission.

E. coli, type 0157: H7; Severe bloody diarrhea, kidney failure; Ingestion of contaminated food or water.

Lyme disease; Muscle pains, arthritis, fatigue; Bite of infectious tick.

Ebola; Hemorrhagic fever; Spread from infected person with blood, secretions or other material.

Hantavirus pulmonary syndrome; Flulike respiratory illness; Presumed aerosol transmission of excreta from infected rodents.

HIV; Loss of immunity, leading to many opportunistic infections; Person to person via blood and body fluids.

Nipah virus; Fever, drowsiness, coma; Human cases resulted from contact with infected pigs.

vCJD; Degenerative brain disease; Presumed via consumption of flesh from cattle with bovine spongiform encephalopathy (mad cow disease).

West Nile virus; Fever, brain inflammation; Bite of infectious mosquito.