The e-mail Dr. Marion A. Kainer received on Sept. 18 suggested an investigation of a case of fungal meningitis and stroke in a man whose immune system was normal and whose only risk for the infection was a spinal injection of a steroid.
“Alarm bells went off” because of its rarity, Dr. Kainer, an epidemiologist at the Tennessee health department, said in an interview.
She immediately began what became a national investigation that has now identified 409 cases, including 30 deaths, from a fungus so unusual that it is not in medical textbooks. The fungus was transmitted through injections of a contaminated steroid drug prepared by the New England Compounding Center in Framingham, Mass.
Dr. Kainer’s investigation led Tennessee to take extraordinary measures to track down 1,009 people at risk of the fungal infection. The state is credited as the driving force in discovering one of the most shocking outbreaks in the annals of American medicine.
The discovery came in large part because of Dr. Kainer’s diligence and expertise in infectious diseases, neurology and public health. It came, too, from the clinical acumen of Dr. April C. Pettit, an infectious disease specialist at Vanderbilt University who sent the e-mail to the health department.
The still-evolving findings also illustrate the strengths of the government’s response to a public health crisis.
Dr. Kainer, like other physicians in hospitals and clinics, often detect the initial cases. But usually only health departments and other government agencies have the ability and authority to track down additional cases to document disease outbreaks and warn those at risk. It is work that private groups seldom can do, in part for lack of funds and the authority to examine patient records.
The national surveillance system for outbreaks of infectious and other communicable diseases relies on reports that physicians are required to send to local and state health departments and that are then relayed to the Centers for Disease Control and Prevention. At the federal agency in Atlanta, epidemiologists identify outbreaks by studying trends.
At the same time, the fungal meningitis cases have exposed weaknesses in government. A dispute surrounds the Food and Drug Administration’s failure to act earlier to prevent the outbreak. The federal agency has been attacked for failing to use its authority to protect the public from the dangerous practice of large-scale drug compounding that led to the outbreak. But the agency, whose top officials have remained relatively silent, says Congress has not given it the clear authority needed to have taken action.
Dr. Kainer’s investigation progressed in steps similar to peeling the layers of an onion.
Within two days of receiving Dr. Pettit’s e-mail, Dr. Kainer learned that the steroid had come from the New England Compounding Center.
“That got me very concerned,” Dr. Kainer said, because she had taken part in epidemiologic investigations involving different infections linked to compounding centers. Inquiries determined that the New England center had received no reports of infections linked to its steroid, and the C.D.C. knew of no additional recent cases of fungal meningitis and stroke.
An inspection by Dr. Kainer’s staff and from the clinic that administered the injection showed no obvious source of local fungal contamination, like recent construction or water leaks.
Then Dr. Kainer learned of three additional suspect cases of meningitis and stroke linked to the clinic. But fungi had not yet been identified in those patients’ spinal fluid. Also, her team could find no correlations in factors like time of day or week when the patients received the injections. One patient had a particular kind of stroke known as posterior circulation, which attracted Dr. Kainer’s attention because she had learned in neurology that fungal infections can cause such strokes.
“What didn’t make sense was that two patients appeared to be improving without antifungal treatment, and that didn’t fit the clinical picture,” Dr. Kainer said.
So she and her team took additional steps. One was to issue a statewide alert to identify similar cases; none were reported.
“We tell doctors and health workers we would rather have 15 false alarms than miss one case,” Dr. Kainer said.
Then she learned that the two patients who had been improving had taken a turn for the worse.
Fungi in spinal fluid grow slowly in the laboratory, and there had not been enough time for any to appear in cultures from the suspect cases. Though the small case count was rising, Dr. Kainer was convinced that fungal meningitis was the one diagnosis that explained their illness. She reminded laboratories of the most appropriate way to look for fungi in spinal fluid and not to discard any from the lumbar punctures on suspect cases.
On Sept. 26, the Tennessee cases led the New England Compounding Center to stop producing and shipping the steroid and to recall vials already distributed. Dr. Kainer’s team received a list of clinics that had received the steroid in Tennessee. From it, health workers identified 1,009 people who were possibly exposed to contaminated steroid. Under the order of the Tennessee health commissioner, they sought out each one.
There was a sense that the first crop of patients appeared in emergency rooms for symptoms linked to conditions like urinary tract infections. That did not suggest meningitis, and there were not the stiff necks and fever typical of bacterial and viral meningitis.
The purpose of the search was to warn patients to pay attention to mild symptoms and to alert physicians to consider fungal meningitis in such cases. A hope was that starting antibiotic treatment in the earliest stages of the infection would be more effective. The effort involved nurses and extended to national park tour guides, military personnel and law enforcement officials to find patients who were scattered in remote places like Yellowstone Park and even abroad. Additional cases were detected.
Dr. William Schaffner, the head of preventive medicine at Vanderbilt, and other experts said they could not recall searches for potential victims that were so persistent and extensive.
“It was a gutsy move,” Dr. Schaffner said admiringly, adding that he was uncertain he would have taken the same bold action if he were the health commissioner.
Dr. Kainer said her suspicions were confirmed on Oct. 4 when the F.D.A. announced that it had found fungal contamination in an unopened vial of steroid from the New England Compounding Center.
Dr. Schaffner credits the close relationship that Vanderbilt and the Tennessee health department have cultivated over the last 30 years, much of it linked to the training that he and other Tennessee epidemiologists received at the Centers for Disease Control and Prevention. (I was part of the same program.) Similar relationships have developed in other parts of the country, like California, Connecticut, Georgia, Minnesota and Washington State.
As a result of their actions, they determined that the first case in the outbreak apparently had occurred in July in Florida. But a perplexing aspect of the outbreak is why the fungus Aspergillus was identified in Dr. Pettit’s case but a different one, Exserohilum, in an overwhelming majority of the remaining cases. “I just don’t understand it,” Dr. Kainer said.
The near-miss discovery of the fungal meningitis outbreak raises questions about other outbreaks that possibly were not detected. “Surely things have gone by, but I don’t know how often, and as good as our surveillance system is, it is not as good as it could be,” Dr. Kainer said.