Assessing the Risk of Creutzfeldt-Jakob Disease
By Lawrence F. Muscarella, Ph.D.
Several recent reports have highlighted confusion, fear, and frustration over the possible transmission of Creutzfeldt-Jakob disease (CJD) during surgery. The ethical, legal, and financial challenges faced by the prospect of a CJD outbreak are unfamiliar, formidable, and limited in precedence.
- In May 2001, the Hotel-Dieu Hospital in Windsor, Ontario temporarily closed its operating rooms fearing a possible CJD outbreak. Neurosurgeons operated in March on a patient who later in May was tested and determined likely to have CJD. The same set of neurosurgical instruments used on this patient was likely used on several other patients.
- In March 2001, St. Joseph Hospital in Denver, Colo. announced that six patients might have been infected with CJD. Brain surgery was performed in November on a patient showing no symptoms, not known to have the disease. The patient died in December and following a postmortem brain biopsy was definitively diagnosed with CJD. The same set of neurosurgical instruments used on this CJD patient was used on six other patients. According to the hospital, this instrument set was washed and steam sterilized after each use.
- In October 2000, Tulane University Hospital in New Orleans, La. reported that eight patients may have been infected with CJD. A patient who underwent brain surgery in March died in May and was determined during autopsy to be infected with CJD. Some of the same potentially contaminated neurosurgical instruments used on this CJD patient were reused on eight other patients. After each use, the instruments were washed and sterilized in accordance with the hospital's decontamination procedures.
Each of these cases is strikingly similar. A hospital performs neurosurgery on a patient not known at the time to have CJD. As many as several months later, this patient dies and during a postmortem brain biopsy is identified to have CJD. Because they are expensive and not disposable, the same set of instruments used on this CJD-infected "index" patient is reprocessed and reused multiple times on several other patients. On news of the autopsy report and fearing a CJD outbreak, the hospital immediately quarantines or destroys its potentially contaminated instrument set(s). Hospital administrators convene and seek counsel from ethicists, risk managers, and legal experts to determine an appropriate course of action. This process takes several weeks if not months, further delaying notification of each potentially CJD-infected patient. Whether the set of neurosurgical instruments was contaminated with prions during surgery on the CJD-infected patient; remained contaminated after standard reprocessing (cleaning and sterilization); and infected several other subsequent patients is unknown and virtually impossible to determine.
Although the risk of CJD infection from a contaminated surgical instrument is extremely remote, the lack of a reliable and effective screening method for patients infected with CJD fuels many of the fears of a outbreak. As a result, the types of cases described above are becoming all too frequent and familiar. Screening tests similar to those used for HIV, hepatitis B, and hepatitis C have not yet been developed for CJD. In general, definitive CJD diagnosis currently requires a postmortem brain biopsy. Adding to the frustration of this disease's prognosis, which is always fatal, is the lack of a well-defined protocol for addressing and resolving a potential CJD outbreak. The extremely low-risk of CJD transmission during surgery ironically further complicates outbreak investigations, as arguments that it is unnecessary to notify patients of a risk that is so remote may have some, albeit very little, credence.
What is CJD?
CJD is a fatal and rare neurological disease that affects approximately one in 1 million people per year worldwide1. Initial symptoms of CJD, whose incubation period can be decades long, include depression and poor memory, followed in its latter stages by dementia and loss of physical functioning. In some cases, patients infected with CJD may not display symptoms for decades. Most cases of CJD occur sporadically1 although as many as 15% of all cases may be inherited.2,3 Less than 5% of all documented CJD cases result from contact with contaminated surgical instruments. Currently there are no treatments for CJD.1
Prions, which are the infectious and rogue proteins believed to cause CJD, are unlike all other known pathogens. They do not contain genetic material and display a remarkable and unique ability to survive routine cleaning and steam sterilization procedures. Prions are produced in cells through the processes known as transcription and translation. Genes on a specific portion of a DNA molecule ordinarily instruct the cell to synthesize "healthy" proteins. Cellular messengers attach to and transport amino acids (the building blocks of proteins) from the cell's cytoplasm to its ribosomes, where protein synthesis occurs. The retrieved amino acids are assembled into a specific order determined by the genes' instructions. Like a chain-link fence, these amino acids bond together to form a protein molecule. For unclear reasons, a mutated or altered gene can cause the sequence of these assembled amino acids to become out of order,4,5 resulting in the production of infectious proteins, or prions.
Assessing the risk of prion infection during surgery
Algorithms designed to assess the risk of prion transmission are helpful, if limited in their usefulness. Without a reliable screening method for CJD, taking precautionary measures to avert CJD infection becomes problematic. Employing a policy that assumes every patient is a CJD-carrier seems unrealistic. To be clear, the risk of being contaminated with prions during surgery is remote. According to the Centers for Disease Control and Prevention (CDC), no reports of CJD transmission during surgery have been reported during the past 20 years. Further, only patients exposed to high-risk tissues, such as pituitary gland hormones, the brain's dura mater, spinal cord, cornea, and other types of neurological tissues, are reported to be at risk for CJD.1 To date, CJD following endoscopy has not been reported.
What decontamination method effectively destroys prions?
Although extremely rare, reports of CJD infection linked to surgical instruments contaminated with prions have been published.1,6,7 Oddly enough, standard sterilization processes, including heat, which are routinely used to destroy all known microorganisms and viruses, may be ineffective against prions1. And while cleaning likely reduces their numbers, it may not always effectively remove all of the prions from a contaminated instrument1. Although some cleaning and sterilization methods are recommended for instruments potentially contaminated with prions, data demonstrating the effectiveness of each are limited.
The minimum requirements for decontaminating surgical instruments potentially contaminated with prions are unclear. Nevertheless, there are a few available options that minimize, if not eliminate, the risk of CJD infection: 1,8,9
- Use only disposable surgical instruments, discarding them after use; reprocess surgical instruments using a pre-vacuum steam sterilization cycle at 135o C (275o F) for 18 minutes; or reprocess surgical instruments using a standard gravity steam sterilization cycle at 132o C (270o F) for 60 minutes.
Each of these two steam sterilization cycles has been reported to be at least somewhat effective against prions. A process that includes cleaning the instruments, exposing them to sodium hydroxide (1N, NaOH, or soda lye) or sodium hypochlorite (NaOCl, or bleach) for 60 minutes, followed by a standard gravity steam cycle, is also a possible option.1 Combining two or more different procedures appears to be most effective.1,9 Incinerating, rather than reprocessing and reusing, reusable instruments should also be considered.
To aid in assessing the potential risk of a surgical instrument transmitting prions during surgery, four scenarios are provided. The first presents the greatest risk of CJD infection, the fourth the least risk. These scenarios, which describe instruments that are either simple or complex in design and construction and tissues that are either low or high risk (e.g., the dura mater, cornea, and spinal cord), can be used as a basis to assess risk and to formulate an appropriate reprocessing procedure. Adapting these four scenarios to a specific surgical setting, as well as creating others that may be more descriptive and apt, may be necessary.
1. Complex instruments that are difficult to clean and sterilize and are in contact with high-risk neurological tissues: These instruments pose the highest risk for transmitting prions. Only disposable instruments should be used. If reusable instruments are used, incinerating them immediately after use should be considered;
2. Simple instruments that are easy to clean and sterilize and are in contact with high-risk neurological tissues: These instruments pose a risk for prion contamination. The use of disposable instruments is recommended. If, however, their use is not feasible, obtaining from the reusable instruments' manufacturers sets of reprocessing instructions and data validating that effective cleaning and sterilization of prions can be achieved without damaging the instruments is recommended. Using an extended sterilization procedure after each use may be necessary (see above);
3. Complex instruments that are difficult to clean and sterilize and are in contact only with low-risk tissues: These instruments pose a negligible risk of prion contamination. Nevertheless, because complex instrument designs can preclude the removal and eradication of all types of microorganisms and viruses during reprocessing, the use of disposable instruments is recommended.10 If, however, their use is not feasible, obtaining from the reusable instruments' manufacturers sets of reprocessing instructions and data validating that effective cleaning and sterilization can be achieved without damaging the instrument is recommended. Using a normal sterilization cycle preceded by thorough cleaning will prevent nosocomial infection; and
4. Simple instruments that are easy to clean and sterilize and are in contact only with low-risk tissues: For these types of instruments, there is virtually no risk of prion transmission. Using a normal a sterilization cycle preceded by thorough cleaning is sufficient and will prevent nosocomial infection. High-level disinfection may also be suitable.
These recommendations may be subject to change, as CJD and methods for the destruction of prions become better understood.
Lawrence F. Muscarella, Ph.D. is the director of research and development chief for Custom Ultrasonics, Inc and infection control editor-in-chief of Q-Net Monthly.