Tokyo and Munich

A 33-floor apartment block in the bustling Kowloon district of Hong Kong could provide clues to the true risk posed by severe acute respiratory syndrome (SARS), epidemiologists say.

Scientists around the world are racing to gather data that will allow epidemiologists to predict whether SARS is likely to become a full-blown pandemic. Their search has led them to investigate exactly what happened when the disease surged through the Hong Kong residential complex in March.

The study, which is being led by Wilina Lim, head of virology at the Hong Kong Department of Health, is the world's only large-scale investigation of the extent to which people without symptoms are carrying SARS — a critical question for those seeking to predict the epidemic's likely reach.

“The key issue is whether symptomless carriers can infect others, and for how long they can do so,” says Albert Osterhaus, head of the Netherlands National Influenza Centre in Rotterdam. “If carriers are symptomless for extended periods, a pandemic is quite possible. If not, the epidemic is likely to be controlled.”

As of 28 April, 131 cases of SARS had been confirmed among residents of Block E of the heavily hit Amoy Gardens apartment complex in Kowloon. And 241 symptomless residents were quarantined on 1 April for 10 days following the local outbreak.

Just over 100 of the quarantined residents are taking part in Lim's study, the results of which, she says, should be known by mid-May. The researchers are trying to take throat samples from the participants every other day to follow the course of the disease, should it emerge. The samples will be tested for SARS using a version of the polymerase chain reaction (PCR) to amplify and detect genetic material from the coronavirus that is thought to cause the illness. But Lim admits that since the end of the quarantine, sampling has been less consistent as the subjects do not always return to the hospital as requested.

Blood samples were also taken from each of the subjects at the beginning of the quarantine period, and they will be taken again this week. These will be tested for the presence of antibodies against the coronavirus, which will show whether the subjects have been exposed to the virus and have mounted a successful defence. Lim is not prepared to confirm how many of the study's subjects have now developed symptoms of the disease.

Data from these samples, as well as from patients suffering from SARS, will offer clues to some of the key biological questions, says Lim, including when the virus starts to show up in bodily fluids, where in the body it comes from, and whether there are symptomless carriers. “At the moment we don't know enough about the route of transmission of the virus,” Lim says. “There is just not enough material yet for investigation.”

The study has also analysed hundreds of samples taken from surfaces in the Amoy Gardens apartments, such as toilet seats and door handles, some of which have tested positive for SARS in PCR tests.

In the next few weeks, Lim's group will also begin a study on people from outside Amoy Gardens who have had contact with the disease but have yet to display symptoms.

Other researchers involved in the global network established by the World Health Organization (WHO) in response to the SARS outbreak confirm that it will be several weeks, or even months, before they will have enough data to make even the broadest of predictions about the disease's spread.

Samples from patients from countries where SARS infection has been significant, including Hong Kong, Vietnam and Singapore, are also being tested regularly to determine how best to track the virus during the course of the disease. Results of PCR analysis show that stool samples test positive for viral particles for up to 30 days, by which time symptoms have often disappeared. The particles seem to be infective for up to ten days — once isolated they can infect normal cells in culture — but it has not yet been established whether they stay infective after that.

Tracking populations of sick patients and healthy people who have been in contact with them is a powerful method for trying to understand the progress of SARS, but many details can only be investigated in animal models. A monkey model based on macaques, which has just been developed at Erasmus University in Rotterdam, the Netherlands, is now also being used at the US Centers for Disease Control and Prevention in an attempt to understand factors such as how quickly symptoms appear after infection.

But with primates so expensive and awkward to work with, labs in the WHO network are trying to develop models for SARS in more convenient animals such as mice. “We'll need several months to get a suitable small animal model,” says Christian Drosten, of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany.

The WHO, meanwhile, has already issued strict travel guidelines, assuming the worst. “We don't have the luxury of seeing what happens and then acting,” says David Heymann, the WHO's executive director for communicable diseases.

→ http://www.who.int/csr/sars/travel