Closing the Book on Iatrogenic Creutzfeldt-Jakob Disease in Humans


An international team of researchers says the book on iatrogenic Creutzfeldt-Jakob disease (CJD) in humans is almost closed. This form of CJD transmission via medical misadventures was first detected in 1974. Today, only occasional CJD cases with exceptionally long incubation periods still appear. The main sources of the largest outbreaks were tissues from human cadavers with unsuspected CJD that were used for dura mater grafts and growth hormone extracts. A few additional cases resulted from neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infections from blood transfusions. Although the final solution to the problem of iatrogenic CJD is still not available (a laboratory test to identify potential donors who harbor the infectious agent), certain other measures have worked well -- applying special sterilization of penetrating surgical instruments, reducing the infectious potential of donor blood and tissue, and excluding donors known to have higher than normal risk for CJD.

Writing in the current issue of Emerging Infectious Diseases, Brown, et al. (20120) observe, "The first case of what would eventually become a major outbreak of iatrogenic Creutzfeldt-Jakob disease (CJD) was reported in 1974; the patient had received a corneal transplant from an infected cadaver. In the years that followed, other sources of infection were identified: stereotactic electroencephalogram electrodes, neurosurgical instruments, cadaveric dura mater and pituitary glands, and, most recently, secondary variant CJD (vCJD) blood products. The ensemble of iatrogenic cases, including a bibliography of primary references, was last reviewed in 2006. Today, after nearly 40 years of surveillance, the chronology and essential characteristics of iatrogenic CJD have been finalized..."

In their paper, Brown et al. present these data along with a few brief comments about factors that determined the risk for infection and how future risks might be foreseen and avoided.

The researchers say, "The best way to abolish secondary iatrogenic infections is, obviously, to prevent primary infections, but without a test to identify infected but asymptomatic persons, we cannot entirely eliminate the risk inherent in human-to-human tissue transfer. We are therefore obliged to rely on the default strategies of 1) identification and donor deferral of persons at higher than normal risk for CJD development and 2) inclusion of prion-reduction steps in the sterilization of penetrating instruments and the processing of therapeutic tissues and fluids."

They add, "The issue of reducing risk by taking steps to inactivate prions is always a work in progress as new therapeutic products come into production and new methods to inactivate prions are discovered. The tried-and-true laboratory method of prion sterilization (1-hour exposures to either undiluted bleach or 1 N sodium hydroxide followed by steam autoclaving at 3 atmospheres pressure for 20 minutes) is applicable only to nonfragile instruments and not at all to living tissues. The surprising resistance of dura mater to 0.1 N sodium hydroxide and of growth hormone to 6 M urea  led to their incorporation into processing protocols before being replaced by nondural tissue or synthetic patches and recombinant hormone. To reduce infectivity, blood, blood products, and other fluids can be subjected to nanofiltration and prion-affinity ligands, which should also be applicable to other biological products, for example, vaccine and stem cell cultures, should they be susceptible to infection. Fragile instruments such as endoscopes and electrodes remain a challenge, but new and gentler methods alkaline cleaning solutions, phenolics, and gaseous hydrogen peroxidehave proven harmless to instruments and give a high, if not always complete, degree of prion inactivation."

Reference: Brown P., et al. Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment. Emerging Infectious Diseases, Vol. 18, No. 6, June 2012.


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