THE OUTBREAK
The virus factories of southern China
by Mark Horstman

It's here that scientists believe it all began: Guangdong province, straddling the Pearl River delta of southern China, a major manufacturing and export region. Hordes of people and goods pass through the teeming hubs of the capital Guangzhou, and nearby Hong Kong.

In the textile town of Foshan, like many in the 80 million-strong province, agricultural and industrial China live side by side. Villagers practise traditional and efficient farming techniques; but these same techniques also make the area a disease factory for the world.

Pigs, ducks, chickens and fish are farmed together, providing ideal opportunities for new and deadly strains of viruses and bacteria to emerge and jump between species. Here, when a pig sneezes � the world catches a cold.

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In November 2002, a mysterious new respiratory illness began to sweep through Guangdong. The first recorded infection, thought to be a Chinese public servant in Foshan, eventually recovered - but not before passing the illness to at least four others.

Six months later, nearly 2,800 people are infected in 19 countries across Europe, Asia and North America. More than 100 have died, mostly in China.

Initially, Chinese officials suppressed news of the outbreak to prevent panic. By February 2003, with more than 300 cases in Guangdong of the atypical pneumonia - now known as SARS, or Severe Acute Respiratory Syndrome - it was not long before the ailment would reach Hong Kong.

When a doctor from Guangzhou - who had treated patients with SARS - visited Hong Kong for a wedding, he checked in to the Metropole Hotel. Shortly after, nine people staying on the same floor ended up in Hong Kong hospitals.

"He actually knew what he got," said Dr Kenneth Tsang, associate professor of medicine at the University of Hong Kong and the clinician who treated the sick man.

"He was working in a hospital in southern China which had a lot of cases similar to what he finally presented with. We had some Guangdong news that there was an outbreak of very severe, highly contagious and rapidly progressive pneumonia over there, so we realised the first case had arrived."

"He was given very aggressive antibiotic therapy, which he did not respond to. We found no pathogens, and he went on a downward spiral course. Unfortunately he did not survive," Tsang told ABC Radio National.

Most of the first people to become ill in Hong Kong had contact with hospital employees or patients. "Hundreds of people [were] affected by one single index case, which was given a nebuliser treatment during his fever," Tsang said. "Every patient on the same ward, including the visitors and the doctors, who looked after him, or walked past, developed the disease."

The other Metropole guests - now unknowingly infected - fanned out to Singapore, Vietnam and Canada, becoming 'index patients' for new outbreaks. Dr Carlo Urbani, an Italian epidemiologist who headed the World Health Organisation's Vietnam office, was called to the French Hospital in Hanoi on 26 February 2003, to see a visiting Chinese-American businessman hospitalised with a strange pneumonia-like illness. Within a week, more than 20 hospital staff were infected.

"[Urbani] recognised the risk of what he was doing, he knew it was something new, and he knew it was an infectious disease," said Professor Aileen Plant, a specialist in communicable diseases from Curtin University of Technology in Perth, Australia. "He was asking and pleading with people to use very good infection control procedures at that time."

Urbani, who identified and named the disease Severe Acute Respiratory Syndrome, alerted the world. But soon after, on 29 March 2003, he died, himself a victim. Since his death, Plant has taken his place, coordinating the World Health Organisation (WHO) Expert Team for SARS in Vietnam, working from Hanoi.

"When I look back and think about what he knew and how he just continued doing it, it's the sort of courage that we'd all hoped to have, but none of us were sure that we would have in those circumstances � Carlo's contribution was enormous," she told ABC Radio National.

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On 12 March 2003, WHO issued a global alert about the outbreak of a new and severe form of atypical pneumonia. By then a mother and her son, recently arrived from Hong Kong, had already died in Canada's biggest city, Toronto. Within three weeks, seven other Canadians were dead, and more than 40 infected.

With more than 150 cases by mid-March, WHO issued emergency guidelines for travellers and airlines. "This syndrome is now a worldwide health threat," said Dr Gro Harlem Brundtland, WHO's director general. "The world needs to work together to find its cause, cure the sick, and stop its spread."

Four months after suppressing information about the first cases in Guangdong, the Chinese government admitted there were actually double the number of cases previously stated - more than 1,200 - and five times the reported deaths (more than 50). Beijing authorities apologised for 'poor coordination', agreeing to cooperate with the WHO and create a disease warning system for better public information.

More than 880 cases have arisen in Hong Kong, largely as the infection was transmitted from patients to nurses and doctors, and then from these health workers to their families, and most recently as the infection has reached schools.

An outbreak among residents in the 33-floor Amoy Gardens apartments - thought to have been brought there by relatives visiting infected patients - caused 268 cases, including people who had never met, seeming to follow a vertical pattern. Scientists are still investigating this branch of the outbreak, trying to establish if the virus - perhaps present in human faeces - was spread by vermin or by leaking sewage along a vertical shaft in the building.

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The rise of SARS has been also been spurred by a handful of 'super-spreaders': people with a very high viral load who infected many others. The woman who carried SARS from Hong to Canada, for example, is believed to have infected as many as 155 people.

Such a disease should be controllable by aggressive quarantine measures, as the outbreak is ignited by a few individuals. As the outbreak radiates further from its source, the pathogen's ability to infect - its virulence - usually weakens, something that also seems to be happening with SARS. This is an evolutionary trade-off between transmissibility and virulence: a virus that is too deadly will burn itself out as it kills its hosts before it can be transmitted.

Mild cases also act like a natural vaccine, infecting people who go on to recover and then have a resistance to future infection. This suggests that the strongest immunities may be found in the people living closest to the source of the outbreak: in this case, the Guangdong province.

Although emerging diseases such as SARS erupt suddenly and without warning, new infections rarely appear without reason. A number of unanswered questions remain about SARS - its origin (likely to be animal, either domesticated or wild, from Guangdong); the identity and nature of the pathogen (a new paramyxovirus, a new coronavirus, or a mixture); its mode of transmission (droplets, contact, airborne, or faecal); as well as effective treatments and mechanisms for immunity.

Dr Stephen Morse, director of the Centre for Public Health Preparedness at Columbia University in New York, believes that infectious diseases emerge in two basic steps: first, the infectious agent is introduced into a new host population. The second is the 'adoption step', where the agent becomes established and is spread within the new host population.

With its high traffic in people - and microbes - from all parts of China, Guangdong province is an important pool from which animal viruses that infects humans can emerge. Many viruses show a high mutation rate, and can rapidly evolve new strains. This 'antigenic drift' creates annual or seasonal epidemics around the world.

Most severe pandemics are caused by 'antigenic shift', when gene segments from two virus strains are recombined to produce a new virus that can infect humans. Pandemic influenza, for example, appears to have an agricultural origin - traditional farming practises that bring ducks, pigs and chickens into close contact. Ducks are reservoirs for the flu virus, and pigs serve as excellent 'mixers' that lead to a new strain.

"Most of [the waterfowl viruses] don't seem able, for one reason or another, to infect human beings, but they may be capable of infecting pigs," Morse told ABC Radio National. "Pigs might be mixing vessels for new influenza strains � perhaps a new combination could occur."

"Then of course the human farmer is right there and could conceivably, when the pig sneezes or coughs, become infected with a new influenza strain - and a new pandemic may be under way. Luckily a combination that hits the jackpot doesn't happen that often," Morse said.

Next >> THE PANIC: Is the panic worse than the disease?

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