Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

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Upon completion of this activity, participants will be able to:
• Distinguish the principal sources of iatrogenic CJD
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AUTHORS

Disclosures: Paul Brown; Jean-Philippe Brandel; Takeshi Sato, MD; Yosikazu Nakamura, MD, MPH, FFPH; Jan MacKenzie; Anna Ladogana; Ellen W. Leschek, MD; and Lawrence B. Schonberger, MD, MPH, have disclosed no relevant financial relationships. Robert G. Will, FRCP, has disclosed the following relevant financial relationships: served as an advisor or consultant for LFB, Farring. Maurizio Pocchiari, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for LFB, Farring.

Prions and related diseases article
Volume 18, Number 6–June 2012

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

Paul Brown

, Jean-Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Jan MacKenzie, Robert G. Will, Anna Ladogana, Maurizio Pocchiari, Ellen W. Leschek, and Lawrence B. Schonberger

Author affiliations: Centre à l’Energie Atomique, Fontenay-aux-Roses, France (P. Brown); Institut National de la Santé et de la Recherche Médicale, Paris, France (J.-P. Brandel); Nanohana Clinic, Tokyo, Japan (T. Sato); Jichi Medical University, Yakushiji, Japan (Y. Nakamura); Western General Hospital, Edinburgh, Scotland, UK (J. MacKenzie, R.G. Will); Istituto Superiore de Sanità, Rome, Italy (A. Ladogana, M. Pocchiari); National Institutes of Health, Bethesda, Maryland, USA (E.W. Leschek); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (L.B. Schonberger)

Abstract

The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic disease until a blood screening test for the detection of preclinical infection is validated for human use.

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 (1). 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 (2). Today, after nearly 40 years of surveillance, the chronology and essential characteristics of iatrogenic CJD have been finalized, and the purpose of this article is to 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.

Figure

Thumbnail of Annual incidence of variant Creutzfeldt-Jakob disease (vCJD) caused by ingestion of meat products contaminated with bovine spongiform encephalopathy agent (A) and iatrogenic CJD caused by contaminated dura mater (B) and cadaveric human growth hormone (C), 1982–2011. White bars in panel A represent cases from outside the United Kingdom, which were delayed in parallel with the later appearance of bovine spongiform encephalopathy outside the United Kingdom (not a second wave resulting

Figure. . . . . Annual incidence of variant Creutzfeldt-Jakob disease (vCJD) caused by ingestion of meat products contaminated with bovine spongiform encephalopathy agent (A) and iatrogenic CJD caused by contaminated dura...

By far the most common sources of iatrogenic disease were human cadavers from which pituitary hormones and dura mater grafts were obtained (Table 1; Figure); the other major variety of environmentally acquired disease is vCJD. The incidence curves of human growth hormone–associated and dura mater–associated CJD are almost superimposable; a broad peak occurred in the mid-to-late 1990s, just ahead of the sharper peak incidence of vCJD in the United Kingdom at the turn of the century. The incidence in other countries peaked a few years later, in 2004, as a result of the delayed appearance of bovine spongiform encephalopathy in those countries.

The long incubation periods—years to decades—of these low-dose infections pose a particularly difficult problem for public health officials, whose recommendations may diminish the number of new cases but are impotent when it comes to preventing cases in already-infected persons in the preclinical phase of disease. It is worth remembering that the early recognition of iatrogenic sources of CJD was entirely because of a few remarkably astute neurologists, neurosurgeons, and, astonishingly, a pediatric endocrinologist who pursued the unlikely (and unpopular) diagnosis of CJD in a growth hormone recipient (3). It is true that some of these connections had the benefit of comparatively short intervals between the infecting events and the onset of CJD. It is especially fortunate from the standpoint of early recognition of the dura mater association that the interval of 19 months between the operation and onset of symptoms in the first case-patient was among the shortest on record for this form of iatrogenic CJD (Table 2).

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Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment - Vol. 18 No. 6 - June 2012 - Emerging Infectious Disease journal - CDC