One of the many troubling aspects of the national meningitis outbreak caused by a tainted steroid drug is that so many people are at risk: 14,000 are thought to have been exposed, mostly through injections near the spine for back or neck problems. The drug was contaminated with a fungus that causes a severe form of meningitis that can result in stroke.
The case count and death toll are still rising — 205 cases and 15 deaths in 14 states — and more are expected. The drug has been recalled, but the incubation period can stretch to 43 days or more. Some patients exposed before the recall may fall ill in the next few weeks or even months.
Even so, it appears that a minority of those at risk have actually become ill. The proportion may be as low as 5 percent, according to health officials in Tennessee, which has been the epicenter of the outbreak, with 53 cases and 6 deaths, more than any other state.
Doctors and epidemiologists have been trying to figure out why some people have been stricken while many others seem to have escaped. There are a number of possible explanations, relating to variations in the extent of contamination, the patients' underlying health and the procedure itself.
The drug was methylprednisolone, made by a pharmacy called the New England Compounding Center in Framingham, Mass. Three lots, containing a total of 17,676 vials, have been implicated in the outbreak.
The fungus in many cases appears to be one called Exserohilum (though one patient was found to have another, Aspergillus). The state health commissioner in Tennessee, Dr. John Dreyzehner, described Exserohilum as "a fungus so rare that most physicians never see it in a lifetime of practicing medicine." He said experts from the Centers for Disease Control and Prevention were making recommendations about how to treat it. Health officials said it was possible that other contaminants would also turn up.
With most infectious diseases, the dose of the germ matters: The more people are exposed to, the more likely they are to get sick, said Dr. William Schaffner, an infectious disease expert at Vanderbilt University. Some patients received a series of three shots of the tainted drug a few weeks apart, and so may have been exposed to more of the fungus.
Apparently not all of the vials were equally contaminated. Dr. Marion Kainer, chief of Tennessee's health-care-associated infections and antimicrobial resistance program, said, "Most of the patients who are affected had injections with one particular lot."
The number of that lot was 06292012@26, and 1,000 vials from it were shipped to one clinic in Nashville, the St. Thomas Outpatient Neurosurgery Center, where many of the state's meningitis patients were infected.
The age of the drug may also have made a difference, Dr. Schaffner said. Contaminated vials that sat on the shelf the longest may have become the most dangerous, because the fungus had time to grow. The vials were a breeding ground, a vessel in which fungus cultures bloomed like mold on a piece of bread.
At least one of the vials confiscated by inspectors from the Food and Drug Administration had so much "foreign matter" floating in it that it could be seen with the naked eye. The agency has found fungus in 50 vials it has tested, but has not revealed details of the level of contamination.
Individual differences in immune systems and the ability to fight off infection also probably played a role. By and large, the people who received these injections were healthy. But they tended to be middle-age or older — when spine problems often occur — and the immune system does become less robust with age.
An insidious factor in these cases is that the injections could well have put the immune system at a disadvantage, by introducing a pathogen into the body along with a steroid. Steroids suppress the immune response and very probably crippled its ability to attack the fungus in many patients — sort of like the scenes in gangster movies where one thug holds the victim's arms while another beats him up.
Another possibility is that differences in the injection technique might have played a role.
An epidural injection is meant to enter an area called the epidural space, near the spinal cord. The needle is not supposed to pierce the dura, one of the membranes that cover the spinal cord and brain.
A needle that went too far in could have nicked the dura and let the fungus into the spinal fluid, from which it could then have easily traveled to the brain. Doctors say that meningitis cannot occur unless the dura is somehow breached.
It is not clear how often nicks or punctures occur. Some doctors use fluoroscopy to help them guide the needle, which may help prevent accidental punctures of the membrane. But other doctors do not.
"I would want it to be performed, if it were my injection, under fluoroscopic guidance," said Dr. Ray M. Baker, president of the International Spine Intervention Society. "But it is not standard of care."
Dr. Baker also said that in some areas, doctors who are not specialists and even people other than physicians — nurse anesthetists, physician assistants, radiation technologists — may be performing epidural injections, something his group opposes as potentially compromising safety.
No information has been released about how or by whom the epidural injections were performed in the patients who contracted meningitis. In any case, doctors may never determine whether a slip of the needle made a difference, because even at autopsy the trajectory of the needle would be extremely difficult, even impossible, to trace.
"This would be a much more elaborate post-mortem dissection than you would normally do," Dr. Schaffner said.
And there is always a still more awful possibility: Even if the needle did not penetrate the dura, the fungus itself might have done the job. It is a fierce pathogen, and in theory, Dr. Schaffner said, it might be capable of eating through the dura on its own to invade the spinal fluid and brain.
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