ADVERTISEMENT

How Serious Is the Fungal Meningitis Outbreak?

Contaminated medication has put thousands at risk for a rare form of meningitis—and the outbreak may last longer than first thought. An infectious disease expert explains what fungal meningitis is and the possible course the unfolding illness may take



CDC/Dr. Libero Ajello

The case count continues to climb as people contract a rare form of meningitis that produces strokelike symptoms. As of this posting, 14 patients have died and 156 others have fallen ill across 11 states. The U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) have traced the unusual outbreak to three lots of steroid medication injected into the spine to treat pain.

Meningitis is an infection of the membranes surrounding the spinal cord and brain. It can be caused by a number of infectious agents. Viral meningitis is relatively benign, and those infected may recover without specific therapy. Bacterial meningitis—particularly meningococcal meningitis—can be acute and severe but is treatable if diagnosed early. The current outbreak is fungal meningitis, a rare form because fungi do not usually infect individuals with a healthy immune system. Unlike viral and bacterial meningitis, fungal meningitis is not contagious—and it is treatable if detected early.

The tainted drug is preservative-free methylprednisolone acetate contaminated with different fungus species. The CDC has identified two kinds of fungi in the meningitis patients: Aspergillus, commonly found in moldy leaves, and Exserohilum, which is involved in wood rot. Epidural steroid injections—a procedure to relieve back pain—likely delivered the fungus adjacent to membranes surrounding the spinal cord, according to the ongoing investigation. The meningitis symptoms can take weeks or even months to develop.

The contaminated lots came from the New England Compounding Center beginning May 21. The center, which voluntarily recalled all its products last week, is a so-called compounding pharmacy: it creates tailored formulations of medications by packaging different doses or changing a medicine from solid to liquid, for example. Compounding facilities do not fall under the same regulatory categories as larger pharmaceutical companies.

To learn more about the outbreak, Scientific American spoke with William Schaffner, an infectious diseases specialist and chair of the Department of Preventive Medicine at Vanderbilt University School of Medicine. He describes what we know about fungal meningitis, how it is being treated and how the unfolding investigation may subject compounding facilities to closer scrutiny.

[An edited transcript of the interview follows.]

How many people are at risk in this outbreak?
The investigation indicates that there were over 17,000 vials of this potentially contaminated medication produced. There may be some variability from vial to vial within each batch. It has been estimated that something like 13,000 people were exposed to this medication; some of it hadn't been used yet by the time the alert went out, and some people received more than one dose. That's very large. If there is a silver lining in this dark cloud, it's that the proportion of people who received this medication who are actually getting sick is rather low. It looks to be less than 5 percent.

What are the symptoms?
The symptoms are insidious. They begin slowly and not very dramatically: fever and chills, headache and a stiff neck from the inflammation. People lose their appetite, feel ill, can be nauseated and can vomit. But there's something else that's subtle: It seems these fungi have the capacity to invade little blood vessels in and around the brain, cause bleeding and produce symptoms that mimic a stroke—difficulty speaking, loss of balance and trouble walking. Those symptoms can occur even without fever, so physicians have to learn that patients who present with stroke symptoms may actually be part of this.

Membranes protect the brain and spinal column from harmful particles that might be circulating in the blood. How does the fungus get past the blood–brain barrier?
The fungi were inoculated adjacent to this barrier but it is still a bit of a mystery how they were able to translocate from outside the membranes into and beyond the membranes.

There are a couple of theories. One is that the fungi begin to multiply in a secluded space, then they kind of eat their way through the membranes. Another hypothesis is: Could the inoculation have nicked the membrane and provided a microscopic mode of access? Practitioners who perform these procedures say this happens very rarely, but it remains to be seen.

People who die of the infection will receive postmortem examinations—autopsies. Careful study will help us understand what happened in this circumstance and how to prevent this from happening in the future.

What treatment options are available?
There are two major drugs, called amphotericin B and voriconazole. Both of those drugs are effective if we get in early. They are given intravenously initially, and then we hope we can transition to oral variations. They have substantial side effects, and we have to walk a kind of tightrope to treat the patient without damaging the kidneys or the liver.

This is all new territory for all of us, so we will learn as we go how completely we can treat these patients and how quickly or slowly it takes them to get better. We know that it is much slower than the treatment of bacterial meningitis.

Could you get fungal meningitis from an injection in locations other than adjacent to the spinal cord—the knee or shoulder, for example?
We know that some of these steroid vials were injected into the knees and shoulders and other joints for people who had painful inflammation in those joints. We anticipate that in the course of this outbreak we will discover people who developed infections in those joints. But those infections would not then cause meningitis.

How could the fungus have contaminated the medication?
All pharmaceutical manufacturers should adhere to good manufacturing practices and guidelines. We don't know what went wrong, but certainly some of those practices were likely not adhered to and that opened the door for contamination. We'll have to wait and see what the investigation tells us.

Are epidural steroid injections safe from other facilities?
Yes. Steroid preparations from other manufacturers are safe, and they can continue to be used. If you received an injection from one of those, you need not worry.

Do you think this outbreak should prompt a change in how compounding facilities are overseen?
I think these compounding pharmacies have fallen into a gap within our regulatory framework. I daresay we will see congressional hearings that address that. My own thought is that the Food and Drug Administration needs to be given explicit authority, and it needs to be given the appropriate resources so it can do the job. I think the whole role of these compounding facilities in our society and our medical care system will come under close examination.

How much longer will this outbreak last? When do we know it has run its course?
Sadly, we will see more cases. The incubation interval—the interval between the exposure, the inoculation and the onset of symptoms—can be quite prolonged. We initially thought it might extend as long as a month. But just recently it has been suggested that it can go beyond that—two months, maybe even three months. As the outbreak evolves and we gather new information, we'll get a better idea, but for the next several weeks we will continue to see, unfortunately, new patients identified and needing therapy.

Rights & Permissions
Share this Article:

Comments

You must sign in or register as a ScientificAmerican.com member to submit a comment.
Scientific American Holiday Sale

Give a Gift &
Get a Gift - Free!

Give a 1 year subscription as low as $14.99

Subscribe Now! >

X

Email this Article

X