Surgery in CJD Patients a Potential Risk Factor for Transmission

About 1 in 6 patients with Creutzfeldt-Jakob disease (CJD) undergo surgery, raising the risk of iatrogenic transmission of this rare but universally fatal prion disease.

In a retrospective analysis, researchers found that 26 of 121 (21%) patients with probable or definite CJD at four US academic medical centers underwent a total of 55 procedures.

These included high-risk procedures for two patients with neuropathologically proven CJD. One underwent ophthalmic artery aneurysm clipping for unruptured aneurysm, and the other underwent diagnostic brain biopsy.

"The findings were definitely surprising to me and my team ― particularly the high frequency with which patients with an irreversible and particularly transmissible neurologic disease underwent invasive medical procedures either just before or shortly after the emergence of symptoms later attributed to CJD," study investigator Gregory Day, MD, with Mayo Clinic College of Medicine, Jacksonville, Florida, told Medscape Medical News.

The study was published online March 9 in JAMA Network Open.

Poor Infection Control

The investigators note that the majority of CJD cases are sporadic or are inherited, but research shows that prion transmission can occur via contaminated tissues or reusable medical equipment.

While the risk of iatrogenic transmission is highest following procedures involving the central nervous system, where prion burden is highest, experimental models suggest CJD transmission can occur after contact with other tissues, including nasal mucosa, lung, lymph nodes, and spleen, the researchers note.

"If these models are accurate, surgical procedures involving these tissues may pose a risk to patients," the investigators write.

To determine the potential scope of this problem, the researchers examined the frequency of invasive procedures performed in patients with CJD at four tertiary care centers.

"In several cases, these procedures were done with clear indications [such as] fixation or joint replacement following a fracture. In several others, however, the procedures were unlikely to help the patient. For instance, a hip replacement for walking difficulties that were actually due to changes in the brain due to CJD," Day said.

"Even more surprising was the low frequency with which appropriate surgical precautions/infection control procedures were used in patients with established diagnoses of CJD," he noted.

Only one procedure was performed with sterilization techniques adequate to prevent CJD.

Day said the findings aren't necessarily cause for immediate alarm, but they do highlight an area for potential improvement, including better screening of patients who have new and unexplained symptoms before proceeding with surgery, especially surgery of the central nervous system, where prion burden is high.

Another potential solution is to develop and support program surveillance and to work with public health organizations such the US Centers for Disease Control and Prevention (CDC) and the US National Prion Disease Pathology Surveillance Center to elicit a surgical history in patients diagnosed with prion disease.

"Active nationwide surveillance is needed to determine the true scope of this potential problem and to develop strategies to mitigate the potential risk of iatrogenic prion transmission to future patients," Day said.

True Prevalence Unknown

The authors of an invited commentary note that while most CJD infections occur sporadically, iatrogenic transmission is possible. Approximately 500 such cases have been reported worldwide to date.

"Yet, reported transmission from surgical procedures remains rare, with fewer than 10 confirmed CJD cases described in the literature, although the true prevalence is difficult to quantify as confirmed diagnosis requires autopsy," write Beatrice Sun, MD, and Joseph Forrester, MD, with the Department of Surgery, Stanford University, in California.

They note that over a 15-year period, 19 suspected iatrogenic CJD exposures were reported to the CDC ― two from ophthalmology procedures, and 17 from neurosurgical procedures.

In all 19 cases, the diagnosis of CJD was unknown before the intervention, and all surgical instruments underwent normal decontamination protocols, which are inadequate to eradicate prion disease.

For patients with suspected or confirmed CJD, the World Health Organization has published infection control guidelines to prevent transmission of spongiform encephalopathies.

The guidelines recommend proper communication with all staff involved in the surgical procedure and the sterilization of supplies to be aware of potential exposure; minimizing the number of staff in the operating room; using single-use equipment whenever possible and disposing of it by incineration; using protective coverings for all nondisposable equipment; and scheduling such procedures at the end of the day to allow adequate time for decontamination.

Funding for the study was provided by the National Institutes of Health. Day owns stock in ANI Pharmaceuticals; serves as a consultant for Parabon Nanolabs, as a topic editor (Dementia) for DynaMed (EBSCO), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Inc, Canada (uncompensated). Forrester reported receiving unrestricted research funding from Varian and has received grant funding from the Surgical Infections Society.

JAMA Netw Open. Published online March 9, 2022. Full text, Commentary

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