23 June 2003 10:50 GMT

by Alex Venter

Experts predict that molecular detection methods will reveal polymicrobial etiologies for some singular diseases - maybe even severe acute respiratory syndrome (SARS).

Multi-agent diseases are probably more common than is traditionally believed, suggests Kim Brogden, polymicrobial disease expert and specialist in respiratory diseases of livestock with the US Department of Agriculture. When researchers isolate different microorganisms in association with the same disease, it could be a sign that more than one agent is involved. Such results might suggest that "something interesting is happening," said Brogden.

Researchers have identified at least three potential pathogenic agents in SARS patients.

While Hong Kong researchers report consistently finding an atypical coronavirus in SARS patients, Health Canada confirms finding the coronavirus as well as human metapneumovirus (hMPV), which belongs to the measles virus family. Investigators from China have found evidence linking Chlamydia species to SARS. In a recent commentary in The Lancet, US researchers underlined the need for further studies to determine the role of both hMPV and Chlamydia "in causality or as cofactors for severe disease."

There are different categories of polymicrobial disease, Brogden explains. In some cases, an initial infection damages the body, allowing a severe secondary, or super-infection to take hold. The flu followed by bacterial pneumonia is one example. In other instances, each disease agent by itself causes only mild symptoms or lesions, but the cumulative effect of the different infections is severe. The synergistic effects of two viruses, for example, can cause a massive immune response, which does more harm than good.

Researchers have also reported that the combination of a porcine coronavirus and the lipopolysaccharide portion of Escherichia coli cell walls causes an extreme immune response and severe respiratory disease in pigs.

Periodontal disease is a well-documented example of polymicrobial infection. Janet Guthmiller, who studies periodontal disease at the University of Iowa, says that dental plaque contains over 500 bacterial species. Cytomegalovirus and Epstein-Barr virus type 1 are also associated with periodontal disease.

Sorting out the roles of the different organisms in polymicrobial infections is difficult. "Koch's postulates don't work quite so well when you have a chronic, multi-agent disease," said Dennis Mangan, of the US National Institute of Dental and Craniofacial Research. Microbiology and virology are built on the premise of "[a] single bug, a single disease," he said.

With the availability of molecular tools, Brogden expects research into polymicrobial disease, now in "its infancy," to take off. To date, many polymicrobial associations might have been overlooked. Diseases classified as syndromes, such as multiple sclerosis, might turn out to have a polymicrobial atiology, he says.

Mangan agrees. "What it means for diagnosis and treatment and prevention [is that] we will have to look beyond the single magic bullet," he concluded.

An American Society for Microbiology (ASM) conference on polymicrobial diseases will be held later this year at Lake Tahoe, 19-23 October.