Volunteers for America: Tennessee cracks meningitis outbreak with existing network built on 'trust'

"By the time we learned this was a problem around the country, the information from Tennessee had already narrowed it down to what the problem was. [It was] a textbook case of how to do it right." Paul Jarris, MD, executive director of the Association of State and Territorial Health Officials.1

By Gary Evans, Executive Editor

Recent U.S. Senate hearings on the national meningitis outbreak predictably found plenty of blame to go around, but also underscored the wisdom of investing in public health and clinical partnerships.

Marion Kainer, MD"These pre-existing relationships allowed us to respond quickly because we trusted each other," said Marion Kainer, MD, director of the Healthcare Associated Infections & Antimicrobial Resistance Program at the Tennessee Department of Health (TDH) in Nashville.

Kainer was recognized at a Nov 15, 2012 hearing of the U.S. Senate Health, Education, Labor and Pensions Committee for leading an epidemiological investigation that resulted in the nationwide recall of contaminated steroid products distributed by the New England Compounding Center (NECC) in Framingham, MA. The TDH had access to Centers for Disease Control and Prevention resources and expertise due to an existing partnership between the department and the agency. Moreover, Kainer had cultivated relationships with infection preventionists and key clinicians as part of the departments HAI prevention efforts.

Alerted by an astute clinician, Kainer rapidly assembled a team of IPs, epidemiologists and other clinical and public health contacts. They essentially solved the mysterious outbreak over 18 long days in September and October, prompting a national recall of NECC products. (See timeline, below.)

"Fungal meningitis is extremely rare. One of our great challenges was knowing just what we were dealing with as more and more patients fell ill," she said. "Even though we were looking for a fungus — because the initial patient reported to us had been diagnosed with a fungal meningitis — none of the diagnostic tests yielded confirmed results until October 3 — fifteen days after we initiated our investigation of the first case."

The NECC announced a voluntary recall of all its products on Oct 6, 2012, the same day the Food and Drug Administration issued a MedWatch Alert asking providers to stop using any NECC products. At that point, the outbreak numbered 29 cases that included three deaths. As of Nov. 19, 2012 there were 490 infections that included 34 deaths in 19 states. Cases have continued to occur due in part to the prolonged incubation period of the implicated fungal pathogens, but the actions of the Tennessee team clearly saved many lives.

"We did an analysis to assess the potential impact if there had been a delay in the recall from NECC by nine days," Kainer said. "In Tennessee alone, we estimate that by now we would have seen an additional 59 cases and at least five additional deaths."

Still, Kainer emphasized that compounding pharmacies play an important role in health care if the service can be provided with an assurance of sterility and patient safety. (See related story, below.)

"Compounding of medications must be performed safely," Kainer emphasized. "Compounding pharmacies do provide a needed service. If compounded products are unavailable to meet the unique needs of some patients, providers may perform compounding or repackaging themselves at the bedside and may also put patients at risk."

The index case

April Pettit, MDThe first case was detected by April Pettit, MD, an infectious diseases specialist at Vanderbilt University School of Medicine, who began looking for other risk factors after finding that a patient was not responding to empiric antibiotic treatment for meningitis. Lab tests and word from family members that the patient had previously received a steroid shot for back pain at an outpatient clinic prompted Pettit to contact Kainer on Sept. 18, 2012. Though she ultimately lost the patient she was trying to save, Pettit's persistence was key to uncovering the outbreak.

The index case was a man in his 50s who presented four weeks after lumbar epidural injections with an eight-day history of headache and neck pain. Writing with some understatement in the New England Journal of Medicine, Pettit concluded, "If an atypical pathogen such as A. fumigatus is identified, a careful search for potential sources of exposure should be performed. In this case, the identification of potential exposure through epidural injection and the reporting of the case to the state health department led to an epidemiologic investigation that identified a multistate outbreak of fungal meningitis associated with epidural glucocorticoid injections."2

Pettit's public health contact was Kainer, who in turn called Candace Smith, RN, an infection preventionist at St Thomas Hospital, which is affiliated with the outpatient neurosurgical center where the index patient received the injection.

"To prevent healthcare associated infections, our team has built very close relationships with infection preventionists," Kainer told the Senate Committee. "These relationships are built on mutual trust and are invaluable in promoting open communication."

The CDC subsequently convened an expert fungal panel to develop diagnostic and management guidance that has been updated through the outbreak.

"This has been very helpful to clinicians, many of whom have never treated fungal meningitis before, and this guidance without a doubt saved a lot of lives," Kainer said. "Of the 33 Tennessee patients who sought medical care before October 3, nine (27.3%) died. Of the 48 patients who sought medical care on or after October 3 — when the first CDC treatment guidance was issued — four (8.3%) died."

Federal, state funds well spent

The department's HAI team includes CDC Epidemic Intelligence Service officers on site to assist in clinical data abstraction, she said. Six members of the team are funded through various federal grants tied to programs in public health epidemiology, laboratory capacity, and emerging infections. Again, the investment in public health infrastructure paid off in spades, as Tennessee was the one state poised to rapidly respond and deconstruct the outbreak.

"Our HAI team had the expertise to conduct on-site visits, to ask the right questions, create a data base, enter and analyze the data swiftly to determine the cause of the outbreak and those at highest risk of getting sick," Kainer testified. "Staff reviewed clinical information and helped track down more than 1,000 exposed patients. Contact by phone or in person was made by local public health staff funded by the state of Tennessee. Outreach included frequent telephone calls and knocking on doors."

Some exposed patients were living in or traveling in other states or were overseas when they developed symptoms, she noted. "Our nurses contacted one patient by contacting a tour operator in Yellowstone Park," Kainer said.

The focus on emergency preparedness and on reducing HAIs enabled rapid communication between public health departments and hospitals. However, some program challenges remain, especially with providers who do not work in hospitals (e.g., ambulatory surgery centers) and with medical specialists who are not traditional emergency response partners, she said.

Another encouraging finding was that the use of electronic health records allowed investigators to monitor the clinical progress of patients, resulting in a tremendous savings of time and resources, she added.

"This has been a devastating outbreak for patients, their families and friends, healthcare providers and clinics," Kainer said. "In Tennessee we still have many patients hospitalized and suffering from complications and others who are exposed and frightened that they may become infected. Sustained commitment to funding from CDC for emergency preparedness and reduction of health care associated infections has supported our productive relationships with partners and healthcare providers across the state."


  1. Wilemon, T. "Disease detectives curbed spread of meningitis" Nashville Tennessean Nov. 5, 2012: http://ow.ly/fpL9n
  2. Pettit AC, Kropski JA, Castilho JL, et al. The index case for the fungal meningitis outbreak in the United States. N Engl J Med October 19, 2012 DOI: 10.1056/NEJMoa1212292

Eighteen long days in the menigitis outbreak

The following timeline of the response to a meningitis outbreak by the Tennessee Department of Health (DTH) is summarized from submitted written testimony by Marion Kainer, MD, director of the Healthcare Associated Infections & Antimicrobial Resistance Program at TDH in Nashville. Kainer testified at a Nov 15, 2012 hearing of the U.S. Senate Health, Education, Labor and Pensions Committee.

Day 1 Sept 18: Kainer receives an email from April Pettit, MD, Infectious Diseases Physician at Vanderbilt University Medical Center (VUMC) about a patient with meningitis caused by Aspergillus fumigatus. The patient had a recent epidural injection at a pain clinic. After Kainer and Pettit discuss the case, Kainer speaks with Candace Smith, RN, an infection preventionist (IP) at St Thomas Hospital (STH), which is organizationally affiliated with the St Thomas Outpatient Neurosurgical Center (STONC) where the patient received the injection. Kainer requests details of the procedure and states that the infection is a sentinel event of concern, which deserves a careful investigation. She requests that Smith commence an inspection of the pain clinic (e.g. evidence of any construction, water damage) and inquire about any potential additional cases.

Day 3 Sept 20: Smith, the IP from STH, contacts Kainer and confirms that the index case had an epidural steroid injection (ESI) at STONC. She provides details of the procedure. Because the Facility Manager of STONC is on vacation, the IP at STH continues to help in the investigation. Kainer contacts Joseph Perz, PhD, an epidemiologist in the division of healthcare quality promotion at the Centers for Disease Control and Prevention. She asks Perz whether any cases of Aspergillus meningitis had been reported to CDC from any other ambulatory surgery centers or pain clinics. Fungal meningitis is rare, but is not required to be reported to the CDC. Even without any requirement, clinicians or states often contact CDC about unusual infections. However, no one had recently contacted the mycotics branch at the CDC to report any cases of Aspergillus meningitis. STH reports two additional patients with meningitis with high levels of white blood cells but no known cause. Both had undergone ESIs at STONC. Diagnoses were complicated because the patients appeared to be getting better and the cause of their meningitis was unknown. Kainer works with clinicians to request exhaustive diagnostic tests. The patients also had their ESI performed by the same anesthesiologist at STONC. The preservative-free methylprednisolone acetate used in their ESIs was obtained from New England Compounding Center (NECC). It is arranged for one of Kainer's staff to visit STONC the next morning, along with the IP the ID physician from STH. On this day, STONC closes voluntarily, sequesters supplies and orders new supplies from other distributors.

Day 4 Sept 21: Visit to STONC by TDH staff for a careful review of all procedures and the physical environment. They find no evidence of environmental conditions that would have led to fungal contamination of procedures. TDH contacts the CDC and describes findings of site visit. TDH asks the CDC to help with laboratory testing of patients with meningitis of unknown cause (because fungus is very hard to diagnose) and also for testing of environmental samples from the clinic, if needed. Another patient with meningitis and stroke with a history of ESI at STONC is identified. VUMC also reports yet another patient who had a stroke and had an epidural injection, but at the time it was not clear where the ESI was done (it was confirmed as STONC on Day 7). TDH sends out a Health Alert using its TN Health Alert Network (THAN), asking clinicians to look for and report any cases of meningitis following epidural injection to the TDH. At this time, the leading suspected causes of meningitis are the contrast media and methylprednisolone acetate (MPA) from NECC, as both were used in each patient and are commonly given together for an ESI. Other less likely possibilities include local anesthetic, local skin preparation and needles used for the injection.

Day 8 Sept 25: Two new cases of meningitis are reported to TDH. Both had ESI using MPA from NECC at STONC. However, one of the patients did not receive the suspected contrast, and the procedure was done by a different anesthesiologist. A Conference call is held with TDH, CDC, NECC and the Massachusetts Department of Health and Board of Registration in Pharmacy (MABRP). NECC states no adverse events reported, no new suppliers of ingredients or changes in procedures. TDH describes severity of cases and that preservative free MPA was the leading hypothesis. TDH requests distribution list and verifies that voluntary recall procedures were in place. TDH staff begin collecting all the medical information needed to conduct their epidemiologic studies. STONC starts contacting potentially exposed patients. A new patient who had an ESI at STONC was admitted to STH with numbness and bowel/bladder control problems, but no headache or fever. Her spinal tap shows signs of meningitis of unknown cause, but with a much lower white blood cell count than the other cases of meningitis.

Day 9 Sept 26: NECC issues a voluntary recall for three lots of preservative-free MPA and provides distribution list of consignees to MABORP and FDA. TDH and CDC draft an Epi-X Alert (national emergency alert system for public health professionals) to report cases of meningitis related to epidural injections. TDH continues to follow up on patients who received ESI at STONC to look for any other unusual illnesses or complications. CDC helps TDH by making available a medical doctor with expertise in treating fungus to assist TN clinicians in caring for patients.

Day 10 Sept 27: TDH staff complete first round of epidemiologic studies. TDH asks STONC to contact all patients who had procedures since July 30. Analysis of the NECC distribution list shows two other clinics in TN received MPA. These clinics are contacted and all MPA is sequestered. Both clinics cease performing ESIs. The first clear evidence that the meningitis cause is not related to the STONC clinic comes from North Carolina (NC), where a patient with meningitis received MPA from NECC.

Day 11 Sept 28: It is still not absolutely clear that the MPA from NECC is the only possible source of contamination. The NC case patient had also received lidocaine and povidone iodine from the same manufacturers used by STONC. The lidocaine was the same lot number. CDC notifies all State Health Departments of situation and urges them to contact clinics who do ESIs and ask them to contact and check on the health of recipients of MPA. The departments use a script prepared by the CDC, which asks that this be done immediately without waiting until after the weekend. CDC issues another national Epi-X alert indicating that this now is a multi-state outbreak and requests reports of meningitis, other neurological infections, and stroke. TDH sends its own alert through THAN to clinicians and hospitals in TN to look for and report meningitis, stroke and focal infections in patients who have had epidural injections. Still, all diagnostic tests on these cases remain negative. The only patient with a confirmed diagnosis remains the first case patient reported. This highlights the difficulty of diagnosing a fungal infection, even when one is looking very hard to find it. TDH continues to work on epidemiologic studies to learn more about these patients, despite not yet having a confirmed diagnosis. TDH requests assistance from CDC to abstract clinical data from patient records (help arrives on Day 14).

Day 16 Oct 4: A final identification of the fungus-causing illness is still not made, but a specimen from another patient who died shows a fungus that is not Aspergillus. FDA announces that fungus was seen on microscopic examination of an unopened vial of MPA from Lot 08102012. This now is very strong evidence that MPA is the cause of the outbreak. TDH alerts TN healthcare facilities using THAN to cease use of all medications and products from NECC.

Day 17 Oct 5: TDH opens state health operations center to assist in case tracking, active surveillance, and reaching out to all patients who received MPA from NECC at any of the 3 Tennessee clinics - a total of 1009 people. Regional health operations centers are mobilized, using public health nurses to contact hard-to-reach patients and going door-to-door when necessary. Public health nurses maintained regular phone and in-person contact with affected patients for weeks, changing messaging as needed to adjust to the changes in the science and related patient needs. The CDC has another meeting of its expert fungal panel.

Day 18 Saturday Oct 6: The New England Compounding Center (NECC) announces a voluntary recall of all NECC products. The Food and Drug Administration issues MedWatch alert asking providers to stop using any NECC products.