Wall Street Journal - April 22, 2005
Kevin Voigt, kevin.voigt@awsj.com

Tears filling her goggles, she told the two doctors performing CPR on her husband to stop. His heart rate flat-lined; an alarm pierced through the room. A doctor switched it off. Her husband, Dr. Alexandre Chao -- the father of her two young daughters, a gifted researcher and vascular surgeon at the hospital -- was dead at 37.

Two years ago this weekend, Dr. Chao lost his life to Severe Acute Respiratory Syndrome, contracted while fighting the outbreak in the region. While the threat of SARS has abated, other diseases such as avian flu and Nipah virus have since flared in Asia, urging doctors and researchers to work to find and contain these emerging killers. As viruses jump from animals to humans, and threaten to mutate and outpace the creation of vaccines, medical researchers warn that the next global outbreak of a new disease -- one that humans will have no resistance against -- isn't a question of if but when.

"All experts say the next pandemic is inevitable, and, in fact, overdue," says Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York, who works with Asian researchers studying avian influenza. Pandemic diseases -- ones that reach across the globe -- regularly appear three to four times a century, says Dr. Ho. The last influenza pandemic, the 1968 Hong Kong flu, killed more than one million people world-wide.

The virulent outbreak of SARS in southern China in 2003 left no doubt that Asia is a hotbed for emerging diseases. The chief culprit? A dangerous mix of animals and humans, which produces a sometimes deadly exchange of genetic matter that generates new human-to-human communicable diseases. Rapid economic development also shares blame, as new virulent diseases spring up as a result of loss of natural animal habitat.

Ironically, too, medical research to prevent disease may also cause its unintended spread. Last week it was revealed that a medical company in the U.S. accidentally sent vials containing the H2N2 influenza virus, better known as the Asian flu, to 4,500 labs in 19 countries. This virus caused the 1957 pandemic, which killed as many as four million people. "Anyone born after 1968 will have no natural resistance to the virus," says Klaus Stohr, head of the World Health Organization's global influenza program. SARS also has been loose in labs: last year, breached safety procedures led to contained outbreaks of SARS in medical labs in Singapore and Beijing.

As a result of increased health threats in the region, medical research and monitoring is being stepped up. Since 2003 in Vietnam, the WHO has worked with local officials to create three laboratories capable of researching the strain of avian flu called H5N1, Mr. Stohr says. Vietnamese staff have been sent to the Centers of Disease Control and Prevention, a U.S. government agency, for extensive training. This focus has helped create a network in rural areas to watch for epidemics. And last year in Hong Kong, the Centre for Health Protection was opened to centralize efforts to fight disease, with a $128 million annual budget and staff of 1,500.

While Mr. Stohr and other health investigators have had their eyes trained on the region since the first case of avian flu was found in a boy who died in Hong Kong in 1997, they face a formidable task monitoring all diseases in animals that possibly can jump to humans. "If you look at the animal kingdom -- from goats, sheep, camels, poultry, all fish, just about any animal you can name -- they have probably 30 or 40 major diseases," says Mr. Stohr. "So the possibility for exposure is huge."

Following are some of the key infectious diseases in Asia that concern health officials. While diseases such as SARS already have done damage to the region, and could again, others are still in the early stages of incubation.

Avian Influenza (H5N1)

Since 2003, about 50 people are known to have died in Vietnam, Thailand, Laos and Cambodia from H5N1, a strain of avian flu that is animal borne, and is widespread in poultry. Victims come down with pneumonia-like symptoms, and in 60% of the reported cases have died. So far, the victims appear to have had direct contact with birds in backyards and in large-scale farms, as well as exposure to bird fecal matter and blood.

While the disease has a seemingly high death rate, it still needs a bird to pass itself on; the disease then dies with its new human host. But the more exposure to humans, the greater the chance that it can mutate into a form that can pass from human to human with a simple cough or sneeze.

If the disease mutates, it threatens to become the first global flu pandemic since the 1968 Hong Kong flu. As it spreads, the mortality rates will drop significantly as the virus morphs into a form that keeps its host alive longer to spread, says Mr. Stohr.

Since influenza is highly infectious to humans, of all the diseases facing Asia, this could be the one that at least one-third of the population will catch. Based on estimates from the 1968 pandemic, the WHO predicts between two million and seven million people globally will die from a virulent new human-to-human influenza such as H5N1, and another 1.5 billion will seek medical attention. Once this new strain emerges, a vaccine can be developed, but it may be too little, too late for many victims.

The WHO is urging nations to develop a human vaccine based on the most recent strain of H5N1 to hit humans, but it is an expensive gamble. "We can make stockpiles, but it might be the wrong vaccine" for an ever-changing organism, says Mr. Stohr.

The key to reducing the risk of the disease is to control it in animals, says Mr. Stohr. But with the large number of animals in the region -- there are an estimated two billion domesticated ducks in homes and at farms around Asia, more than 10 times the flocks found in the wild -- the developing world will have a tough time curtailing the risk, Mr. Stohr says.

Nipah Virus

Loss of animal habitat in Asia is pushing together animals and humans in ways they didn't in the past, leading to new viruses. The Nipah virus is a good example of the deadly outcome when pathogens from wild and domesticated animals meet for the first time.

Named after the Malaysian village where the first outbreak occurred, the animal-borne virus killed more than 100 people in Malaysia and Singapore in 1998 and 1999. Last year, an outbreak occurred in Bangladesh where about 100 cases were reported, causing death in nearly half the cases. The Nipah virus triggers encephalitis, which causes inflammation of the brain; symptoms are high fever and muscle pain -- as it worsens, it leads to seizures, dementia and death.

In the Malaysia outbreak, 93% of victims were in the swine industry, in Bangladesh victims lived or worked closely with cows, according to the WHO. In both situations, however, the first carrier of the disease was fruit bats, although humans played a part. The first known cases were closely related to the destruction of natural habitat, with rising consumer demand leading to intensive farming, says Mary Elizabeth Miranda, a Manila-based expert on animal-borne diseases. "In the town of Nipah, the pigs (were raised) in the orchards, right under the bats." Bat feces spread the disease the pigs, which then spread it to human, she says.

Like H5N1 influenza, animal handlers now have the highest risk of contracting Nipah. Researchers in the U.S. and Australia (site of the Hendra virus outbreak, a disease similar to Nipah, which killed 15 horses and two people in 1994) are trying to develop animal vaccines for the virus, but so far the best prevention is better sanitary standards for livestock handlers, such as washing and changing clothes after tending animals. Although the Nipah virus has killed twice as many people as H5N1, it isn't considered as serious a threat because of the isolated nature of the outbreaks. But because it is a new virus, it is uncertain what could happen next.

Mosquito-borne Diseases:

Dengue Fever, Malaria, Japanese Encephalitis

Paradoxically, loss of forest area is giving some aid to fighting the annual malaria epidemics around the region, because the mosquitoes that carry the parasite don't have as much fresh water in which to breed, says Kevin Palmer, the WHO's Manila-based regional adviser for mosquito-borne diseases. Still, malaria kills thousands a year in Southeast Asia, southern China, India and Pacific Islands, and infects as many as 300 million people a year world-wide, hitting the immune system and causing fever, fatigue and anemia.

Victims in Asia are primarily in rural areas, with children under the age of five and pregnant women at greatest risk, according to the WHO. Medical support is under-funded in the poverty-stricken areas hardest hit, and malaria parasites are becoming resistant to inexpensive drugs

Some drugs still are effective "but they are five times more expensive," Mr. Palmer says. Although it's highly treatable, there is no preventative vaccine, he adds.

Mosquito-borne viruses also spread dengue fever, the malady that doctors first thought Dr. Koh's husband had contracted. Known as the "breaking bone" disease for its deep joint pain, as it circulates in the blood victims suffer high fever, stomach pain and rashes. For most victims, the disease means two weeks in bed. Outbreaks in the region are growing fast; in 2002 there were about 135,000 cases reported to the WHO, up from 87,500 in 2001. Death rates vary from 1% to 4%, Mr. Palmer says. Dengue outbreaks can ruin economies that depend on vacationers. When an epidemic struck the Cook Islands in 2002, the country lost about $2.3 million, Mr. Palmer says.

Japanese encephalitis is spread by infected mosquitoes in countries spanning Japan to India. While it affects the central-nervous system, only one in 300 infections result in flu-like symptoms, and in the most severe cases causes encephalitis -- like the Nipah virus -- killing 30% of these victims.

Some people argue that global warming will add to the problem of mosquito-borne diseases. "The warmer it is, the longer mosquitoes live, the greater the chance to infect someone," Mr. Palmer says. For now, the best protection against these diseases is protection against mosquitoes: mosquito netting, clothes that minimize exposed skin and repellent, as well as community efforts that try to eliminate mosquito populations. Taking malaria drugs before traveling into infected areas also reduces risk.

Severe Acute Respiratory Syndrome

The 2003 SARS outbreak showed the world that a virulent killer can come out of nowhere. Believed to have jumped to humans from palm civets, a wild animal and delicacy sold in live-animal markets in Guangzhou in southern China, the viral respiratory disease quickly skipped to Hong Kong, Singapore and Toronto, infecting 8,000 people world-wide, and killing nearly 800.

The virus made a relatively quick transition to human hosts, transmittable to others through feces and respiratory secretions. Many of the victims, like Dr. Koh's husband, were health-care workers -- common victims of emerging diseases. While the SARS death rate was much lower than the more than 180,000 casualties of the Dec. 26 tsunami, such deaths hit the psyche of communities affected, says Cecilia Chan, director of the Centre on Behavioral Health at Hong Kong University. "When doctors and nurses can't take care of themselves, the whole community panics."

To date, there's still no vaccine for SARS and the threat of its return is still real. In late 2003 and early 2004, there were two breakouts in medical labs. Over that time, a public outbreak also infected four people in Guangdong Province, says Dr. K.Y. Yuen, the Hong Kong University epidemiologist whose team discovered that SARS came from palm civets. Although they identified palm civets as passing the disease onto human, it's still unknown what animal passed it to the civets.

Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome

The deadliest new disease of the past two decades, medical researchers fear that, as HIV-AIDS has become epidemic among the rural poor in Africa, India and China, it's a powder keg about to explode.

In a speech this week, Richard Feachem, executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, said India has unofficially leaped ahead of South Africa as the country with the most people living with AIDS -- possible more than eight million people, more than the 5.1 million reported to the WHO. "The epicenter of the HIV/AIDS epidemic is shifting to Asia," he said.

The disease is transmitted primarily by sex and intravenous drug use. Victims can carry and spread the HIV virus for years before they fall ill themselves, from here the virus damages the immune system, which leads to AIDS. Because it attacks the immune system, AIDS patients are open to a host of diseases which ultimately kill them. In China alone, 10 million people will be HIV positive by 2010, estimates Dr. Ho, the famed AIDS researcher who was named Time Magazine's 1996 "Man of the Year" for developing the "AIDS cocktail," a sequence of drugs that has significantly improved the life expectancy of patients.

"In China, health-care funding is inadequate," says Dr. Ho. "It's been neglected despite this single-minded determination to become the economic juggernaut it is. " Part of the reason that the government is more actively fighting the epidemic, he says, was the shattering lessons of SARS. "It was a profound wakeup call for Asia and the world," he says.

The disease has different concerns in different nations, with Cambodia having one the highest infection rates at 2.5% of the population, says Dr. Bernard Fabre-Teste, regional adviser for sexually transmitted disease for the WHO. China, Malaysia and Vietnam have concentrated pockets of epidemics among IV drug users and prostitutes, he says, while infections in Malaysia are primarily among homosexuals.

Besides abstinence, the best protection is avoiding high-risk behavior such as frequenting prostitutes. The WHO estimates 120,000 people will die this year from AIDS in the East-Asian region (which excludes India).

Ebola Virus

So far, Asian has been spared a widespread attack of one of the world's most feared disease, the Ebola virus -- but a strain of it has made its way into the region. A highly infectious haemorrhagic fever, transmission is through direct contact or through dried blood dust left from victims, says Ms. Miranda, the WHO animal disease specialist. Victims suffer fever and pain in the muscle joints, which often escalates to internal and external bleeding.

The Ebola outbreaks have killed nearly 500 people in four African countries since 2000, with a mortality rate of 65%, according to the WHO. Outbreaks are happening with increased rapidity -- in the 1990s, there were seven outbreaks; in the past five years alone, there have been six. Like the Nipah virus, loss of habitat is increasing the likelihood of outbreaks, she says. "It's the price of development," says Ms. Miranda.

The same danger lurks in Asia. In 1996, an Ebola outbreak occurred at monkey-breeding farms in the Philippines, according to Ms. Miranda, who headed the national task force to investigate the episode. The diseased macaques were discovered in the U.S. at medical institutions who purchased the monkeys for use in experiments; the same thing happened in 1989. The Philippines has since stepped up monitoring monkey farms, but the origins of that particular virus are still a mystery. "We found that it was a variety of Ebola that can't infect humans," says Ms. Miranda. But mutation into a form that could infect humans "is always a possibility," she adds.

Legacy of Disease

Whatever disease is next poised to attack the region, there's still the legacy of earlier killers such as SARS. Infectious disease take lives like Dr. Koh's husband every day -- leaving survivors to deal with the anguish and the uphill battle to rebuild their lives.

On the second anniversary of her husband's death this weekend, Dr. Koh recalls the moment the ICU doctors left her alone to say goodbye: She wanted to kiss him but couldn't through her mask. Instead, she held his hand to her chest and quietly promised him she would raise 3-year-old Beatrice and 18-month-old Berenice "to be worthy of their father," she says.

On June 1, 2003, 1,500 people attended Dr. Chao's memorial service, one day after Singapore was declared SARS free. The recovery for Dr. Koh and her family, however, continues. Since his death, the family has moved into a new home to escape painful memories.

There are still long, sleepless nights she spends alone with her thoughts. "With two very young children, I didn't have the luxury to mourn my loss for long because they depend on me for their happiness and well- being now," Dr. Koh recalls. "For our children's sake, [I hope] we may never need to fight another war like the one we fought two years ago."

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