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Aspergillus Moldy Vials of Steroid (Methylprednisolone) Responsible for Meningitis Epidemic 2012
© Donald Reinhardt, October 5, 2012; updated Oct. 6-31; Nov. 1,8,17,27, Dec 18, 28, 2012; Feb 6, 21, 2013; March 7, 25; May 5, Jun23, Sept 8, 2013, Oct 23, 2013 
The mold meningitis epidemic caused by a contaminated, injectable steroid (methylprednisolone) has involved 751 patient infections, 64 deaths from 20 states reporting. However, the number of new cases and deaths has slowed dramatically as the epidemic passes its one year anniversary. The contaminated steroid has been recalled and was used for only a short period of time. The steroid product (methylprednisolone), compounded by the New England Compounding Center (Framingham, Massachusetts), has been linked to this rapidly-expanding epidemic of mold spinal infections (meningitis). There have been 751 patients with 64 deaths spread over these 20 states: Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Maryland, Michigan, Minnesota, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas and Virginia. The top three states with the most cases of fungal meningitis are: Michigan (243), Tennessee (145), and Indiana (79). These 3 states account for almost half of all the known fingal meningitis cases.
 
Two molds have been implicated in the mold meningitis diagnosis: Exserohilum and Aspergillus fumigatus. Exserohilum is the predominant mold involved in these infections.  Both molds are common saprophyes which live in damp or moist environments and feed on simple environmental materials such as cellulose (paper and cardboard), starch or simple sugars. The fungi probably entered the vials during compounding and filling. These fungi were likely living contaminants in the compounding facility and they possibly grew and multiplied at one or more places in this environment. The exact source of these molds has not been determined at this time. These two fungus contaminants obviously survived in the sealed vials and were later injected with the steroid during therapy for spinal inflammation and pain. This is an expanding epidemic with an incubation period for the infection of a few days to over a month to six weeks. Cases should continue to accumulate into October, 2013 and possibly end in November and December, 2013. Thousands of injections were given prior to the recall of the contaminated prednisilone and almost 14,000 vials were shipped to 23 states. Several patients have suffered strokes during their infections.
Patient Fungal (Mycotic) Epidemic Cases by Week – July, 2012 to February, 2013
Graphic data Credit: Centers for Disease Control
 
 
Two molds have been implicated in the mold meningitis diagnosis: Exserohilum and Aspergillus fumigatus. Both molds are common saprophtyes which live in damp or moist environments and feed on simple environmental materials such as cellulose (paper and cardboard), starch or simple sugars. The fungi probably entered the vials during compounding and filling. These fungi were likely living contaminants in the compounding facility and they possibly grew and multiplied at one or more places in this environment. The exact source of these molds has not been determined at this time. These two fungus contaminants obviously survived in the sealed vials and were later injected with the steroid during therapy for spinal inflammation and pain. This is an expanding epidemic with an incubation period for the infection of a few days to over a month to six weeks. Cases should continue to accumulate into October and possibly continue some or eventually end in November and December 2013. Thousands of injections were given prior to the recall of the contaminated prednisilone and almost 14,000 vials were shipped to 23 states. Several patients have suffered strokes during their infections.
Exserohilum mold isolated from 10 different meningitis cases. Photo credit: Centers fo
Aspergillus fumigatus, a common fungus showing typical mold hyphae (filaments) and conidia (spores) stained blue. Credit: NIH, U.S. Centers for Disease Control, U.S
 
Methylprednisolone Acetate Vial Contamination with Aspergillus fumigatus

Dr. John Dreyzehner, Commissioner of the Public Health Department of Tennessee,  held an October 3, 2012 news conference and media briefing in Tennessee  where he discussed  the ongoing epidemic situation in the state. At that time there were at least 18 cases in Tennessee (70 cases as of October 23) and directives were issued to all health providers regarding  the suspect contaminated lots of methylprednisolone acetate. The CDC is providing regular updates during the entire course of this epidemic.

Aspergillus fumigatus Mold – Common Saprophyte and Potential Pathogen

Aspergillus fumigatus is one of the most common airborne and surface molds in the environment and this filamentous fungus is considered a weak pathogen in healthy people, but the mold is a stronger pathogen in patients with various cancers and immune deficiencies. As described by Jean-Paul Latege in a comprehensive review of Aspergillus fumigatus and Aspergillosis,  Aspergillus can be an aggressive and invasive pathogen in those undergoing radiation, chemotherapy, bone marrow transplants and those with various underlying diseases such as leukemia, myeloma, and burns.  

Signs and  Symptoms of Aspergillus Meningitis  

Signs and symptoms of "aspergillosis" include severe and progressive headache with nausea, dizziness and fever. There may also be othersigns of central nervous system involvement such as slurred speech, unsteady gait, urinary retention, weakness and sensory deficits. Tennessee has alerted clinicians to be suspicious and try to recognize patients who may have received epidural steroid injections from any of the three Tennessee clinics involved during the time period of July 1 to Sept. 28.

 Nature and Extent of the Aspergillus fumigatus Epidemic and Its Resolution

This epidemic is associated with three specific lots of preservative-free methylprednisolone acetate of the following lot numbers:
  • Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #05212012@68, BUD 11/17/2012
  • Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #06292012@26, BUD 12/26/2012
  • Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #08102012@51, BUD 2/6/2013
 
In Tennessee,  the first 12 meningitis patients were 49 to 89 years of age – 9 were females and 3 were males.This epidemic is expected to continue despite the recall of the mold-contaminated vials.
 
As of June23, 2013 there have been 745 fungal (mold) meningitis cases with 58 deaths in 20 states, however the actual risk extends to as many as 23 states and hundreds of additional patients. According to Dr. Benjamin Park of the Mycotic Diseases Branch of the CDC the following is the list of these 23 states:
California, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Maryland, Michigan, Minnesota, North Carolina, New Hampshire, New Jersey, Nevada, New York, Iowa, Pennsylvania, Rhode Island, South Carolina, Tennessee, Virginia, Texas, and West Virginia. 
 
The incubation time for this meningeal infectious disease may be up to six sweeks or more and some patients, already injected, may acquire active disease over the next few weeks. Nevertheless, the epidemic should end soon since the contaminated product has been recalled and further use of suspect lots has been banned and stopped. The mold is not spread from person to person and only injected patients are at risk of acquiring the disease. During May and June 2013 the epidemic slowed significantly but a few more patients and victims were added to the eidemic list. I surmised, even with the slowing of cases, that some will still occur over a few more months into the spring and early summer of 2013 and this seems to be the case. Over the next few months and to the end of 2013, the chances of getting meningitis for those who were injected with the steroid, but have not become diseased, are now reduced to probably about 1% or less (i.e., 1 or less out of every 100 remaining patients who were injected with mold-contaminated steroid). 
 
Iatrogenic Disease and Epidemic - Aspergillus, Mycotic Meningitis Epidemic
 
This disease and epidemic is termed an iatrogenic disease – a disease (harmful condition of the patient's body) that was caused or induced unintentionally by a physician or surgeon during a medical treatment or diagnostic procedure. In this case the physician used a product – methylprednisolone – that was thought to be sterile or microbe-free to treat a patient to alleviate inflammation and pain. Because this product is sold and provided typically as safe and microbe-free, physicians injected what was presumed to be such only to cause meningitis in some of those who received the mold spores and/or hyphae. In this writer's and expert's opinion, the liability here rests almost entirely with the compounding facility in Massachusetts. 
 
This epidemic will be updated right here at www.sciencesuperschool.com and at the CDC Multistate Meningitis Outbreak Investigation as new epidemic information is obtained.