Iatrogenic CJD: more detail

What are the route-by-route figures?

The reference source is the 2012 international review by Brown, Brandel, Sato and colleagues, which totalled 469 cases.

Dura mater grafts accounted for 228 cases, of which Japan reported 142, about two thirds. Cadaveric pituitary growth hormone accounted for 226, with 119 in France, 65 in the UK and 29 in the United States. The remaining routes were small: gonadotrophin 4, neurosurgical instruments 4, packed red blood cells 3, stereotactic EEG needles 2 and corneal transplants 2.

CDC states separately that 6 CJD cases are known to have been caused by contaminated surgical or medical equipment, with none reported since 1976 after decontamination procedures changed. The difference from the review’s figure of 4 reflects different case definitions for instrument-related transmission rather than new cases, and anyone quoting either number should say which source it comes from.

What incubation periods should be assumed?

They differ by route by an order of magnitude, which is consistent with central versus peripheral inoculation.

Growth hormone cases had a mean incubation of 17 years with a range of 5 to 42, and the country means differed: 13 years in France, 20 in the UK and 22 in the United States. Dura mater cases averaged 12 years, range 1.3 to 30. Gonadotrophin cases averaged 13.5 years, range 12 to 16. The instrument and electrode cases were much shorter: a mean of 1.4 years for neurosurgical instruments, and 1.3 and 1.7 years for the two EEG needle cases. The corneal transplant cases were 1.5 and 27 years, and the three transfusion-associated cases 6.5, 7.8 and 8.3 years.

The practical consequence is that a growth hormone or dura mater history remains relevant for the rest of a patient’s life. CDC notes that growth hormone cases are still being identified roughly 50 years after exposure.

Which exposures ended when?

Pituitary-derived growth hormone was used in the UK between 1958 and 1985 and was replaced by recombinant material; the US stopped distribution in 1977 to 1978. Human dura mater grafting was withdrawn or replaced in the countries that reported cases. Decontamination practice for neurosurgical instruments changed in the 1970s.

When taking a history, the specific questions that are important are treatment with pituitary-derived hormones, including growth hormone and gonadotrophin; grafts of dura mater, cornea or sclera; neurosurgery or spinal surgery, particularly where records are incomplete and dura mater may have been used; and depth EEG recording.

What do the donor rules say?

They are wider than many clinicians expect, and the tissue rules are wider than the blood rules.

For blood and blood components under Directive 2004/33/EC, deferral is permanent for people with a family history that places them at risk of a transmissible spongiform encephalopathy, people who received a corneal or dura mater graft, and people previously treated with medicines made from human pituitary glands. The same three groups are permanently deferred for plasma for fractionation, with a note that further precautionary measures may be recommended for variant CJD.

For tissues and cells under Directive 2006/17/EC the exclusions add: a diagnosis of CJD or variant CJD, or a family history of non-iatrogenic CJD; a history of rapidly progressive dementia or degenerative neurological disease, including cases of unknown origin; and recipients of pituitary-derived hormones, grafts of cornea, sclera or dura mater, and people who had undocumented neurosurgery in which dura mater may have been used. The prion criteria do not appear in the reproductive cell tables.

National rules differ and change. A 2023 Vox Sanguinis review reported that UK plasma had not been fractionated since 1999 as a precaution during the variant CJD outbreak, that more than 40 million UK blood components had been issued since leucodepletion began in 1999 with no reported transfusion-transmitted variant CJD, and that the UK government authorised manufacture of immunoglobulin from UK plasma in February 2021. It also reported that the United States, Australia, Ireland and Hong Kong lifted deferrals for donors with a UK residence history after reviews found no significant difference in risk. The authors concluded that UK plasma is safe for fractionation and called for guidance on UK-residence deferrals to be revised. That is a review with a stated position, so the operative rule for any donor is the one the local blood service applies now.

What governs infection control and instruments?

In the UK, the guidance from the ACDP TSE Risk Management Subgroup, with Part 3 on laboratory containment last updated in November 2021. It is organised as annexes that map onto the practical questions: Annex A1 and A2 on the distribution of infectivity in human and animal tissues and body fluids, Annex C on decontamination and waste disposal, Annex E on quarantining surgical instruments, Annex F on endoscopy, Annex I on brain biopsy procedures, Annex J on presurgical assessment to identify patients with or at risk of CJD or variant CJD, Annex K for pathologists and pathology laboratories, Annex L for ophthalmology and Annex M for general surgery and liver transplantation. There are separate documents on infection control in healthcare and community settings, guidance for ophthalmologists, and an information sheet for funeral directors and relatives.

Two points are worth stating to ward teams directly. Infectivity is concentrated in central nervous system tissue, which is why the surgical precautions are specific to particular procedures. And there is no evidence of transmission by ordinary social or clinical contact, so the general nursing care of a patient does not require those measures.

What residual concerns did the review name?

Four. Long-incubating variant CJD in the UK. Atypical scrapie strains, whose human risk is not well characterised. Chronic wasting disease spreading in North American deer and elk, with potential human exposure through consumption. And instruments that are difficult to decontaminate fully, including endoscopes and electrodes.

The authors’ recommendation was to keep donor deferral and prion reduction measures in place until a validated blood test for preclinical infection exists for human use, which it did not at the time of writing.

Where next?

Iatrogenic CJD is the plain version for families, including the question about a relative’s past surgery, and iatrogenic CJD for researchers carries the transmission literature. How prion disease is diagnosed covers the diagnostic pathway and what to expect the care side.

This page summarises published guidance and literature and is not clinical advice. Decisions about an individual patient, a specific procedure or a donation belong with the treating team, the local infection control service and the national CJD surveillance centre.