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Thursday, 15 November 2012

Rare events – a Public health case history of US fungal meningitis outbreak

When rare organisms cause disease, finding the problem should not be a challenge.

How many of those working in communicable disease have ever seen a case of Exserophilum rostratum meningitis (and meningitis of all causes is notifiable in most jurisdictions)?  In fact the Mayo Clinic reported only one case over 40 years of a skin infection in an immunocompromised person. So when a cluster happens, alarms will sound and the system jumps into overdrive. 

The public health question is why have there been 32 deaths and over 400 illnesses from such an oddity? 

The first case was reported September 21 out of Tennessee where the bulk of initial cases were noticed.  By October 1, eleven cases from a single pain management clinic had been identified.  It only took just over a week to focus attention on the implicated methylprednisolone product, and that most of the deaths occurred in persons who received epidural injections.  The product was recalled by October 3rd.  By October 5th, active trace back was encouraged for persons receiving the product and many of the cases are related to the active trace back despite cessation of infections.

So far, Michigan has had 50% more cases than Tennessee and therefore should have been able to identify a problem sooner.  Based on the state's reaction, a delay in obtaining notices and initiating trace back occurred. Perhaps a reflection of the lack of depth of the state public health service.  

Not that any more rigorous process would have prevented infections or saved lives.   No doubt, there will be the occasional case that could argue they were injected after the lots were recalled, but most cases did not develop symptoms until 1-4 weeks after injection. The retrospectoscope will likely find flaws in the notification system, in the surveillance system, in the recall and trace back processes and likely in microbiological laboratories.  The ultimate critical question being how did contaminated injectable drug product enter into consumer circulation? and what drug preparation processes were lacking before lot release?

We are fortunate the product was not distributed in Canada – or maybe just lucky on this one.  Pharmaceutical quality control requirements are similar between countries and product can readily cross the international border. 

It will make for a fascinating series of monographs and publications.  For those interested in following the outbreak, check out the CDC outbreak website .   A notable omission in the public information are the epi-curves relating date of injection and onset of symptoms.  With such an extensive trace back, one has to wonder when did the first cases occur? And who missed the first rare bird that might have protected others?    

Rare birds incite curiosity, provide an opportunity to test the system, are unlikely to recur in an identical fashion, and may or may not contribute to improving the system required for the common, mundane and potentially larger outbreak scenarios.

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