INTERNATIONAL: SARS - shape of epidemics to come?

Analysis

The World Health Organisation (WHO) on March 12 took the unprecedented step of issuing a Global Alert for Severe Acute Respiratory Syndrome (SARS). SARS is a new and highly infectious human disease of the respiratory pathway, with symptoms resembling influenza or, in more acute cases, pneumonia. Symptoms include the onset of a sore throat, headaches, fever, coughing, and respiratory difficulties. If the patient is otherwise healthy, recovery usually occurs within a week of hospitalisation. However, the disease is fatal in approximately 4% of cases, especially among the elderly and those already compromised by other infections, diabetes, heart disease or a suppressed immune system.

Spread pattern.The first identifiable case of the disease occurred on November 16 near the town of Foshan in the southern Chinese province of Guangdong. From there it spread within the province, with almost 1,200 reported cases and 46 deaths, and thence to nearby Hong Kong, which has seen 761 cases and 46 deaths. Assisted by air travel, SARS spread subsequently to other countries in Asia and Australasia (with over 180 reported cases in Australia, Japan, Singapore, Taiwan, Thailand, and Vietnam); to Europe (with a small number of cases recorded in Belgium, France, Germany, Italy, Ireland, Romania and the United Kingdom); and to North America (with over 100 cases reported in the United States and 69 in Canada).

Coronavirus causation?The causative agent for SARS has yet to be determined and will not be known definitively until results from genome-sequencing experiments are available later this week. However, it is likely that a coronavirus is responsible. Viruses of this type cause about one-third of common colds, but the SARS virus appears much more virulent and dangerous. Researchers believe that it may be a virus that normally infects pigs or chickens, which has recently crossed the species barrier to become infectious to man. Alternatively, it may have originated from a relatively harmless human virus that has acquired new virulence through genetic exchange with another virus genus.

Coronaviruses are known to be easily transformed in this way; genetic exchange between a mouse coronavirus and the feline infectious peritonitis virus has already been observed in laboratory experiments. Conditions in southern China, where people live in close proximity to farm livestock, especially favour cross-species transmission. In 1997, Hong Kong suffered an outbreak of an influenza-like disease that originated in chickens, which led the authorities to order the slaughter of the entire chicken population as a control measure.

Transmission.SARS can be spread during face-to-face contact by droplet infection, as with influenza and the common cold. This makes the wearing of face masks a sensible precaution to prevent inhalation of exhaled droplets. However, there is a suspicion from epidemiological analysis of the spread of the disease within Hong Kong that there may be other forms of transmission, either via fine aerosol droplets that can remain suspended in the air for prolonged periods, or from physical contact (for example, of the hand with a wet contaminated surface and then with the mouth or eyes). There is also considerable concern that asymptomatic carriers may inadvertently spread the disease. Certain puzzling peculiarities have emerged, as seen in the apparent susceptibility of healthcare workers and an apparently low rate of infection among children and staff resident in the Hong Kong Metropole Hotel, a centre of the outbreak. At present, there remains insufficient data about the transmission parameters, incubation times and infectivity to permit accurate mathematical modelling of the potential epidemiological spread of the disease.

Treatment.At present, there is no known treatment for the SARS disease beyond good nursing care, together with strict quarantine measures. While the Hong Kong authorities claim to have developed "an efficient and rapid diagnostic test", an unambiguous test may still be several days away. Moreover, production of a vaccine will take several weeks. Both measures are dependent upon biomedical research establishing the exact nature of the causative agent.

Containment.Since the original WHO warning, all suspected cases and their contacts have been strictly quarantined wherever possible, in an attempt to control transmission of the disease. However, its international spread demonstrates that these measures have not been fully effective. At international airports, incoming passengers showing flu-like symptoms are currently being intercepted and isolated by medical staff to prevent the virus from entering the wider community. International air travel to and from Hong Kong has already seen an 18% decline, which in conjunction with the WHO's travel alerts to the territory and Guangdong, can only help to limit the disease's further spread.

In an unusually frank admission, the Chinese Health Minister has apologised for having done too little too late to contain the initial outbreak. However, WHO head Gro Harlem Brundtland has since criticised China's authorities for not reporting the outbreak more quickly.

WHO role.The WHO has taken an exemplary lead in facilitating the investigation and control of this new disease. On April 3, a WHO investigative team of four doctors arrived in Foshan to try to unravel the precise origins of the outbreak. WHO headquarters is organising daily video conferences between leading investigators in order to promote cooperation in the investigation, and to reduce the usual delays in transmission of information between potentially rival research groups.

Publication risks.Combating SARS will require the rapid world-wide sharing of the results of expert biomedical research into its causes, including details of any virulent genes that the virus may have acquired. This follows moves aimed at countering the publication of information likely to aid potential bioterrorists: the editors of 32 leading scientific journals recently agreed to withdraw papers submitted for publication, if it is decided that the potential dangers of publishing outweigh scientific benefits as a result of security vetting (see INTERNATIONAL: Bioterrorism puts drug patents at risk - October 26, 2001).

Commercial implications.Since the WHO Global Alert, various governments have advised their citizens against travel to Hong Kong and China and some have started to withdraw non-essential embassy staff. The US Navy's Seventh Fleet has cancelled all port calls and travel to Hong Kong and southern China. Airlines and hotels are reporting severe drops in bookings and financial markets have suffered as a consequence. Such repercussions are not restricted to Asia -- in Toronto, a major cancer conference for 16,000 delegates has been cancelled because of the SARS outbreak.

Global epidemic?Fears that the SARS virus might cause a repeat of the global influenza epidemic of 1918, which claimed 40 million lives, appear unfounded on present trends. However, it is significant that SARS has arisen in Asia, the feared source of the next major influenza epidemic. Prompt actions taken by the international medical community in combating SARS should enhance the chances that the next lethal flu outbreak will be efficiently controlled.