Year in Review: Meningitis Outbreak Still a Challenge

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It is so far the only case in the outbreak in which A. fumigatus has been found, although a pathogen has not been definitively identified in all cases, largely because fungi are very hard to grow. And it has not been found in any of the unopened vials of the steroid.

Clinical Picture of the Outbreak

For the most part, the earliest cases presented with very severe symptoms, including stroke, Chiller said, and clinicians were initially grappling in the dark.

"When we started, early in the outbreak, we had some very sick people that died of strokes, some of which happened fast before we even knew what was going on," he said.

But almost immediately the clinical picture of the outbreak began to change, largely because of the public health efforts of the CDC and state health authorities.

As events unfolded, details of the NECC customer list allowed health authorities to call thousands of pain patients and get them to hospitals for testing.

One effect of that, Chiller said, is that clinicians saw that unprecedented spectrum of disease – from the deadly symptoms seen commonly in the early days to milder illness that was only picked up because patients were called in for a spinal tap.

Would those patients with mild disease have gone on to become even more ill? No one really knows, but Chiller and his colleagues think they probably saved some lives.

A physician who was involved in combating a similar outbreak in 2002 credits the CDC with an impressive response to what he called a "national disaster."

"I suspect there is nowhere in the world that an agency could respond so efficiently, rapidly, and accurately," commented John Perfect, MD, of Duke University in Durham, N.C.

Indeed, if there is good news about the outbreak, it's the CDC's role, according to Kauffman.

The event "highlights the ability of the CDC to respond quickly in tracking this outbreak and providing timely updates and recommendations for treatment to clinicians," Kauffman said.

A Clinical Conundrum

The outbreak had clinical puzzles from the beginning. Why did some patients show up with serious cerebrospinal illness, but no focal infection where they got the steroid shot?

Equally puzzling, why did some patients, initially treated for meningitis, later develop a focal infection at the injection site?

And why has there been a third wave of disease in which patients only have the focal infection?

For those latter patients, Chiller noted, "the challenge is just identifying them." While they had pain at the injection site, he said, it was hard for patients to tell whether the pain was any worse than the baseline pain that initially led them have the steroid injection.

In the absence of the continuing public health effort, they might not have sought treatment. Whether they would then have developed more serious illness remains uncertain.

There was also the question of treatment, which was developed on the fly in the first few days and weeks of the outbreak – usually a combination of the anti-fungal drugs voriconazole (Vfend) and liposomal amphotericin B.

Both drugs have been used for years, but one lesson of the outbreak was how little was actually known about that combination, according to Kauffman.

The outbreak "reinforces the fact that we do not have ideal antifungal agents," she said. "The experience with giving amphotericin B and voriconazole to these patients has been eye-opening."

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