Nearly six months after the start of a deadly fungal meningitis outbreak blamed on tainted pain shots, patients who originally tested clear are showing up sick, raising worries that the incubation period for illness may be longer than anyone thought.
Though the flood of patients has slowed dramatically, two or three people each week are still reporting infections caused by contaminated steroids in the outbreak that has killed 48 and sickened more than 700, officials with the Centers for Disease Control and Prevention said.
Among those new patients are people who received mold-tainted doses of the drug methylprednisolone, but who previously got MRIs or lumbar punctures that showed they were free of infection. These slow-growing infections aren't as severe as meningitis, but worrying nonetheless.
“If you had an MRI in October, I don’t know that you’re out of the woods,” said Dr. Anurag Malani, an infectious disease expert at St. Joseph Mercy Hospital in Ann Arbor, Mich., the state that has seen the most cases -- 253 -- in the outbreak.
CDC officials issued a health alert this week urging clinicians to remain vigilant for new infections, even in people who show subtle symptoms -- or none at all.
“We are seeing some patients with very long incubation periods,” said Dr. Tom Chiller, associate director for epidemiological science in the CDC’s division of foodborne, waterborne and environmental diseases. “We expect to see people getting infections months after their injections.”
Nearly 14,000 people in 23 states were exposed to the contaminated drugs produced by the now-shuttered New England Compounding Center of Framingham, Mass. An estimated 11,000 actually received shots for back or neck pain, the CDC says. So far, 720 people in 20 states have fallen ill.
Most of the seriously ill people – those with fungal meningitis infections that caused strokes, for instance – showed up within several weeks or one to two months starting in late September.
Back then, CDC officials told worried patients that the greatest risk for meningitis was likely in the first 42 days -- six weeks -- after the shots, suggesting that they could breathe easy after the first week in November.
But patients have continued to become ill, most often not with meningitis, but with infections at the injection site, with epidural abscesses or with a condition called arachnoiditis, an inflammation of the nerves near the spine.
Though doctors have little experience with such fungal infections, the incubation period appears to be stretching longer than a previous outbreak in 2002, when a patient became ill 152 days – five months – after getting a steroid shot.
“I don’t think at this time we know how long the incubation period is,” Malani said.
That’s worrisome for people like John Horrell, 54, of Nashville, Tenn., who received a steroid shot for back pain from one of three tainted lots in September. He says he’s feeling “remarkably well” these days, with no signs of infection. Health officials told him the biggest worry was after 90 days or so, but now he’s not so sure.
“There’s people still having problems,” said Horrell, who owns a sound system firm. “We just keep our fingers crossed. I try not to worry about it.”
CDC officials want health workers to continue to monitor patients who got shots, particularly those whose have pain that is worse or different from the initial symptoms. But even patients who previously tested negative for infections and those with no apparent symptoms are at risk.
“These infections may be unrecognized because some patients have not continued to receive close clinical follow-up or because they have not recognized symptoms suggestive of a localized infection,” the new alert says.
CDC recommends that health workers have a low threshold for considering MRIs, or magnetic resonance imaging, to detect unseen infections.
Even patients who initially resisted MRIs because they didn’t want them or didn’t think they needed them have turned up with infections, said Malani.
The danger of not detecting the infections is that they only will get worse, Chiller said.
“Any untreated infection can sit there and smolder and spread,” he said, noting it can move beyond soft tissue to bone and the central nervous system, with devastating, even deadly, effects.
That, however, raises the next question in the ongoing meningitis puzzle: How long should infected patients be treated? Some patients say they’ve been told three months, then nine months -- then a year.
The primary drugs used to treat the fungus -- voriconazole and amphotericin B -- are both expensive and toxic, with a host of side effects ranging from hair loss and hallucinations to liver problems.
Margaret Snopkowski, 51, of Fowlerville, Mich., has been on the drugs since early October, when she developed meningitis -- and later, arachnoiditis -- after getting a contaminated shot.
She's back home, but life is hardly back to normal, especially with the high doses of antifungal drugs necessary to keep her infection in check.
“She walks around like a zombie,” said her husband, Tom Snopkowski. “It just knocks her on her butt.”
Family members had hoped she’d be better by now, or at least looking to wean herself from the drugs. But that’s not happening, her husband said. Another MRI is scheduled for next week to see whether the infection has gotten worse.
“Now, they don’t even have an end date for that treatment," he added.