FUNGAL

1. FUNGAL MENINGITIS OUTBREAK 2012

2. The Agent:Exoserohilumrostratum • KINGDOM: Fungi • PHYLUM: Ascomycota • ORDER: Pleosporales • ECOLOGY: • Common mold found in soil and plants, especially grasses • Thrives in warm, humid climates • Some species plant pathogenic, has been used for biological control of certain grassy weeds • Exoserohilum rarely causes infections, but include sinusitis and skin infections, keratitis, subcutaneous phaehyphomycosis, endocarditis, osteomyelitis • Exoserohilum infections most often occur in people with weak immune systems and injuries • Exoserohilum is recognized as a human pathogen, and is the cause of the fungal meningitis outbreak of 2012

4. How Did This Happen? • Beginning May 21, 2012, as many as 14,000 patients were given spinal injections of a contaminated, preservative free steroid, methylpredlisolone acetate– commonly used to treat back and joint pain • The CDC and FDA confirmed the presence of Exoserohilumrostratum in unopened medication vials of MPA • The CDC laboratory confirmation further implicates the New England Compounding Center (a compounding pharmacy in Farmingham, Mass.) in the ongoing outbreak that has sickened over 400 people and killed 29 (as of November 2, 2012) • In early September, the first fungal meningitis patients arrived in emergency rooms around the country, and the fungus was found in the spinal fluid of infected patients • Late September, the fungal outbreak was confirmed and the drug recalled from the three presumed lots

5. Symptoms: • Of the people that received the injection through the spinal cord, 409 cases has been reported (11/5/12) of fungal meningitis, stroke due to presumed fungal meningitis, or other system related infections meeting the outbreak case definition • People receiving the injection to a joint are not presumed to be at risk for fungal meningitis, but 10 peripheral joint infections caused by the fungus have been confirmed • Meningitis affects the memebranous lining of the brain and spinal cord. Early symptoms of final meningitis include : • Headache, fever, dizziness, nausea, sensitivity to light, stiff neck, weakness or numbness, slurred speech and pain, redness or swelling a the injection site • Symptoms can take more than a month to appear; according to the CDC the longest duration from the time of injection to the onset of symptoms in this current outbreak is 42 days • Unlike bacterial meningitis, fungal meningitis Is not contagious. Only people who received injections are though to be at risk

6. CASE DEFINITIONS: • PROBABLE CASE: • A person who received the preservative free MPA injection that definitely or most likely came from the New England Compounding Center and subsequently developed any of the following: • Meningitis of unknown etiology following injection after May 21, 2012 • Posterior circulation stroke without other implicating sources following injection after May 21, 2012 • Osteomyelitis, abscess or other infection near site of infection following injection after 5/21 • Osteomyelitis or worsening inflammatory athritis of peripheral joint following joiunt injection after 5/21 • CONFIRMED CASE: • A probable case with evidence (by culture, histopathology or molecular assay) of a fungal pathogen associated with the clinical syndrome -Center for Disease Control

7. Treatment: • Fungal meningitis is treated with long courses of high dose antifungal medication given intravenously • The length of treatment depends on the status of the immune system • Treatment is often longer for people with immune systems not functioning well due to conditions like AIDS, diabetes and cancer

8. THE DAMAGE:

9. BREAKDOWN BY STATE:

10. These numbers continue to rise, as of Novermber 9th, 19 states have confirmed cases with 438 cause counts and 32 deaths

11. FDA FORM ‘483’: • The FDA issues a 483 at the end of an inspection when the investigators believe they they observed conditions or practices that indicate violations of the FDA • What did the FDA find at the New England Compounding Center? • 321 vials of MPA contained a “greenish-black foreign matter” • 17 other vials from the same bin contained “white filamentous growth” • 50 of the vials were sent and tested at the FDA lab and all were confirmed to have presence of microbial growth • The investigation notes the use of non-sterile active active ingredients • Condensation and discoloration were found on the autoclave used to sterilize the injections • FDA observed different colored residues lining different weigh station hoods • The report details “problems with the NECC’s ability to maintain clean room” • Bacteria and mold were found on multiple surfaces of the clean room • Air conditioning was turned off from 8 pm to 530 am nightly—not a typical practice of a clean room • These observations are merely a glimpse of the full report, which was released and is accessible to the public on the FDA’s website • Form 483 for NECC

12. What Now? • The investigation is not final, and is still underway • Ameridose, another pharmaceutical company linked to the NECC voluntarily recalled all of its products following the outbreak and investigation • Another Massachusetts compounding pharmacy, Resource Infusion, was recently shut down due to sterility concerns following a surprise inspection • Director of the Mass. Pharmacy board along with the Mass. Department of Public Health’s interim commissioner were both terminated after officials uncovered a complaint against the NECC by Colorado pharmacy regulators just months before the outbreak

13. Works Sited “Multistate outbreak of fungal meningitis and other infections”. FDA. 13 Nov 2012.< http://www.fda.gov/ Drugs/DrugSafety/FungalMeningitis/default.htm> “Multistate Fungal Meningitis Outbreak Investigation”. Center for Disease Control and Prevention. 9 Nov 2012. <http://www.cdc.gov/hai/outbreaks/ meningitis.html> Haelewater, Dannny. “Exoserohilumrostratum, the killing fungus”. Scilogs. 24 Oct 2012. <http:// www.scilogs.com/life_off_the_edge/exserohilum- rostratum-the-killing-fungus/>