Severe Meningitis: All in the Genes?

Some people may be genetically prone to suffer a worse outcome from acute bacterial blood infections. Researchers trying to figure out why meningococcus infections kill some patients and cause less severe symptoms in others have found that familial differences in blood levels of two immune-system proteins may be the key. The finding, reported in the 18 January issue of The Lancet, could help doctors predict which patients may develop the serious--and often fatal--systemic blood infection, meningococcal sepsis.

Many people harbor meningococcus bacteria without getting sick, but some mysteriously show symptoms. Once a person develops full-blown infection, whether the case is mild or severe has "been like a lottery up to now," says Rudi Westendorp of the department of clinical epidemiology at Leiden University Hospital in the Netherlands. Probing for a biochemical explanation for this difference, Westendorp and his colleagues tested the blood of 190 relatives of meningococcal-disease patients. They found that blood from relatives of 16 patients who had died had significantly lower levels of an immune-boosting cytokine called tumor necrosis factor (TNF) and much higher levels of an immune-suppressing cytokine called interleukin-10 than blood from family members of 45 patients with milder symptoms.

This is the first study that "clearly demonstrates a genetic correlation [between TNF levels and] clinical outcome," says Jan Agosti, director of clinical development at Immunex Corp. in Seattle. She says the work adds to mounting evidence that TNF, which doctors have blamed for organ failure and other fatal complications of infection, "is not an entirely bad player" and could be beneficial in early stages of infection.

The work is "fascinating," adds Steven Opal, an immunologist and infectious-disease expert at Brown University School of Medicine. But he cautions that meningococcal infections are different from many other bacterial infections, and "it may be too big a leap" to apply these findings to other diseases.

Westendorp and his colleagues have not found a genetic marker corresponding to cytokine levels. If such a marker were found, Agosti says, a test for it would be a "very valuable" tool for doctors trying to decide the best therapy for patients.