July 25, 1997 - Tuberculosis Guidelines

Vickie Rather
Office of Health and Safety
Centers for Disease Control and Prevention
1600 Clifton Road, NE
MS-F05
Atlanta, Georgia 30333

Comments on: Federal Register, Part V, Department of Health and Human Services, Centers for Disease Control and Prevention. Vol. 62 (81), April 28, 1997, GOALS FOR WORKING SAFELY WITH MYCOBACTERIUM TUBERCULOSIS IN CLINICAL, PUBLIC HEALTH AND RESEARCH LABORATORIES; NOTICE

The American Society for Microbiology (ASM) appreciates the opportunity to submit comments to the Centers for Disease Control and Prevention (CDC) on the Federal Register Notice published by the Department of Health and Human Services, Goals for Working Safely with Mycobacterium Tuberculosis in Clinical, Public Health and Research Laboratories; Notice. The ASM is the largest, single life science society in the world with an active membership of over 42,000. The ASM represents microbiologists who work in clinical, public health, industrial and research laboratories including those laboratories which detect and diagnose Mycobacterium tuberculosis.

ASM commends the CDC for addressing the critical issue of laboratory acquired tuberculosis prevention. In particular, the Spill Response Plan can serve as an excellent model of laboratory safety procedures and bio-hazard control. Recent events have underscored the vulnerability of health care workers to acquisition of Mycobacterium tuberculosis. With the advent of increasing numbers of multiple drug resistant strains of tuberculosis, the concern for laboratory worker safety is certainly warranted. The goal to protect laboratory workers from acquiring tuberculosis is a laudable one. However, there are specific requirements contained in this document which have no proven benefit to the laboratory professional, yet will add substantial cost to the detection, diagnosis and treatment of patients. The data used to demonstrate the need for significant changes to the engineering controls, administrative procedures, and workplace practices of mycobacteriology laboratories is not current and in some cases flawed. CDC does not cite any reliable current data on the actual scope of the problem of tuberculosis transmission in the clinical laboratory. The ASM has received information from its members indicating a very low level of skin test conversions is occurring in clinical laboratories operating within a Biosafety level (BSL) 2 facility using BSL 3 practices (for example using a bio-safety cabinet (BSC)).

The ASM suggests the CDC conduct or sponsor research which will assist in the development of guidelines based on actual data and laboratory performance. The ASM offers its assistance in this effort and would also recommend CDC consult with other scientific and professional associations. ASM has received information from its membership to suggest that in most incidences of skin test conversion, it is the individual's safety practices or lack thereof, and not the facility design, that is responsible for the majority of conversions. The safety of the clinical microbiologist is of the utmost concern to the ASM. However, there is no evidence that mandating expensive Biosafety level 3 facilities will guarantee worker safety.

I. MORE DATA ARE NEEDED THAT ACCURATELY REFLECT CURRENT RISK

ASM recommends that an active surveillance and research program (similar to the National Nosocomial Infection Survey) be implemented by CDC to determine the risks associated with tuberculosis, and other laboratory acquired infections, as they reflect current safety practices and laboratory technologies. Regulatory guidelines should be based on current practices and current, non-anecdotal, verifiable data. The citation of data from the 1950's and from other countries, where practices in safety differ significantly from those currently in place in most laboratories in the United States, may substantially overstate the current hazard to the laboratorian in the United States. An ongoing surveillance program would be a source of valuable information for the CDC to base additional regulatory requirements.

The ASM strongly advocates laboratory safety education for all laboratory workers be conducted on an ongoing basis. Laboratory safety training is essential for laboratory professionals to be aware of the potential risks of their work, understand and utilize safety precautions, and know how to respond in case of an accident. Many of the requirements stated in the CDC document seemed to be based on anecdotes and may well reflect on laboratories that have never fully implemented the safety practices that are currently recommended. There is not enough emphasis on the training of laboratory personnel in the biohazard potentials and precautions needed to prevent accidental infection in the workplace.

II. THE REQUIREMENT FOR BSL-3 CONTAINMENT FOR ROUTINE PROCESSING OF SUSPECTED AND CONFIRMED MYCOBACTERIAL SPECIMENS HAS NOT BEEN JUSTIFIED

According to some preliminary data submitted to the ASM, the BSL-3 facility requirement will force over two-thirds of the microbiology laboratories in this country to either undergo very expensive remodeling and re-engineering or in many cases cease to provide mycobacteriology testing. This could have a serious impact on patient care. The ASM is concerned that the CDC has published these regulatory guidelines without adequate justification.

ASM conducted a preliminary survey of laboratories to determine the current safety risks. Twelve laboratories reported no skin test conversions. Of these, six operated with no respirators in BSL-2 style facilities and processed over 100,000 (1300 positive cultures) specimens for tuberculosis culture. One laboratory operated in a BSL-2 facility but used respirators and processed 4500 (135 positive) specimens for TB. Two laboratories used masks rather than respirators but had BSL-3 facilities and processed 36,000 (440 positive) cultures for TB. Two laboratories operated with BSL-3 style facilities and employed respirators, processing 20,000 specimens (145 positive). Of the 3 reporting skin test conversions, cited causes were cases in which a biosafety level 3 facility would have had little or no impact in preventing the skin test conversion. The ASM would be pleased to have the opportunity to work with the CDC on designing a more comprehensive survey of laboratories working with Mycobacterium tuberculosis which will generate considerably more current and accurate data than which currently exists. The ASM strongly recommends that before requiring all clinical laboratories convert to a BSL-3 facility, more data be generated to demonstrate the need for this requirement.

III. THE "ONE SIZE FITS ALL" RECOMMENDATION MAY INCREASE HAZARDS

The span of safety hazards covered in this document is wide, ranging from the clinical specimens (of which few are positive and many contain few organisms), to clinical cultures (which contain amplified numbers of organisms), and finally to research applications (involving large volumes of organisms amplified many-fold and manipulated with aggressive means of aerosolization). Whereas the requirement of BSL-3 practices and facilities may be excessive for manipulation of clinical specimens, it may be insufficient for the research arena. For the management of clinical cultures, BSL-3 practices and facilities may be necessary only in cases where there is extensive work with procedures that involve aerosolizing, to include sonication and/or vortexing of culture amplified organisms.

The requirement of BSL-3 for the management of clinical specimens may not only be unnecessary, it may increase the hazard to the laboratorian. The requirement would cause the laboratorian working with specimens to work in the BSL-3 laboratory where culture-amplified organisms are manipulated. Thus, an individual would spend many hours working with low risk specimens in a room where higher risk is expected to be present.

When operating under BSL-3 practices and facilities there may be conditions in which a respirator is indicated. However, the universal requirement for N95 respirator use under all BSL-3 conditions is not consistent with good risk assessment practices and implementation. ASM believes that safety practices would be more effective if stratified to accommodate the relative risk of each procedure and task.

IV. HAZARDS ASSOCIATED WITH NON-RESPIRATORY SPECIMENS AND NON-TB LABORATORIES DEMAND ATTENTION

The focus of the new CDC guidelines is on the management of specimens in the TB diagnostic laboratory, with virtually no attention to the clinical bacteriology, pathology, chemistry or hematology sections. A single specimen for TB culture is often split and manipulated in the routine bacteriology, cytopathology, chemistry and hematology laboratory.

In addition, the most well-documented hazards are in anatomic pathology, where the frozen section procedures and the autopsy suite procedures have been shown to induce skin test conversions that approach 100% of those present in the room. ASM recommends that CDC develop safety protocols for the operation of the microtome cryostat, centrifugation of body fluids, preparation of frozen sections and the performance of autopsies.

The clinical laboratory is at greater risk now that Mycobacterium tuberculosis is frequently found in blood specimens. Although blood is mentioned as a new specimen of concern, there are no practices suggested for its management other than "minimizing aerosolization". While this suggestion may be sufficient, the CDC requirements for sputum samples appear draconian in comparison.

The cytopathology practices also deserve thorough review. The cytospin operations can be contained in aerosol proof enclosures but there is no discussion of which containment devices are effective. ASM recommends that a stratification of safety practices appropriate to the hazard should be developed, so that all laboratorians will be provided a safe working environment. Placing all risk in the TB laboratory in the same category, and requiring a similar level of safety for both specimens and culture amplified materials, does not readily accommodate the development of intermediate safety containment procedures appropriate to routine clinical and anatomic laboratory functions. This disparate management of different laboratory sections will lead to confusion in the clinical laboratory.

V. SPECIFIC PRACTICES ARE ADVOCATED THAT ARE HAZARDOUS, CONTRADICTORY OR UNCLEAR

Whereas the requirements for the facility and many practices represent far more stringency than seems to be necessary, certain elements in the document provide insufficient safety and represent potential hazards to the laboratorian. For example:

A. Page 23071 Autoclaves

A serious flaw in the document is the procedures specified for disposal of waste. Tubes and bottles contain residual aerosols that continue to leak out for hours after they have been "vortexed" or sonicated. Pipettes tend to release bubbles of air that burst droplets of residual fluid. Yet, the guidelines only call for shallow levels of disinfectant, insufficient for submerging most tubes, and only specifies a closed container, not a sealed one. Such a practice represents a grave hazard when the discard container is removed from the biological safety cabinet before it is autoclaved. This practice will allow residual aerosols to diffuse into the room and place at risk people who work in the vicinity of the area involved in disposal and autoclaving. The ASM recommends the guidelines be revised to recommend waste items be submerged completely in disinfectant and that containers for larger items be tightly sealed and aerosol-proofed before removal from the BSC.

The ASM also recommends the CDC provide guidance on the proper selection and installation of autoclaves. Many unanswered questions remain, such as: Can a "pre-vac" autoclave that exhausts air from the chamber before it injects steam be employed? If so, are there guidelines for insuring that the duct work is sealed and the exhaust site isolated from air intakes, etc.?

B. Page 23070 Centrifugation.... and Page 23070 Preparation of Concentrated AFB....

The CDC guidelines contain appropriate recommendations regarding centrifugation safety in the latter section of the document. In the former section, it specifies only that tubes be equipped with O-rings. However, no data are presented to suggest that plastic tubes equipped with O-rings would not release aerosols upon compression.

C. Page 23069 Biological Safety Cabinets (BSC) A third area in which there is insufficient safety specification is in the proper selection and management of the biological safety cabinet. The guidelines provide conflicting or misleading information on the proper application of the biological safety cabinet. Table I calls for Class I or Class II BSC's for use with ATS level I and for Class II and III BSC's for use with ATS levels II and III. There is very little attention devoted to the exact type of BSC, its installation and operation. Proper selection, use and maintenance of the BSC is one of the primary components to insuring safety when working with Mycobacterium tuberculosis. The ASM recommends this section be strengthened and emphasized.

VI. THERE SHOULD BE ATTENTION TO SAFETY USING NEWER TECHNOLOGIES

The document provides insufficient details regarding safety practices with newer procedures and devices. Yet, these newer procedures and devices present an equal, if not greater hazard, to the laboratorian. Manipulation of fluid cultures is the greatest source of hazard and the newer culture methods require extensive manipulation, some with hazardous means of withdrawing or injecting fluids from or into the container. Molecular technologies call for increased involvement with methods that are efficient at aerosolization. Many questions remain unanswered by these guidelines, such as: Can sonication be safely performed on the bench top in devices that are sealed when an accident would yield an extremely infectious aerosol? What types of heating and lysis procedures render the organisms completely safe for manipulation in the molecular diagnostics laboratory? Newer means of susceptibility testing may also present hazards to the laboratorian; these need to be evaluated and advice and counsel provided on their safe performance. The ASM recommends CDC address these questions regarding the safety requirements using these new technologies.

CONCLUSION:

The ASM commends the CDC for its initiative in preparing these draft guidelines. However, the final document should reflect more current, reliable data. The ASM and the CDC share the same goal - to reduce the risks associated with handling specimens which may potentially harbor the hazardous microorganism Mycobacterium tuberculosis. The ASM looks forward to working with the CDC and other scientific and professional societies to achieve this goal. Clinical microbiology laboratories play a pivotal role in the diagnosis and control of tuberculosis, including multi-drug resistant TB. CDC has published established goals for turn around time for acid-fast smear results, detection of positive cultures, identification of M. tuberculosis and susceptibility results. The cost and impact of these regulatory guidelines will cause laboratories in many communities to close, leading to decreased availability, and increased turn around time for these critical laboratory services. The ASM is confident that it was not the CDC's intent to cause such disruption in the way mycobacteriology service are delivered in this country.

In summary, the ASM recommends active surveillance for laboratory-acquired tuberculosis be conducted to determine the actual hazards confronted by laboratory personnel and to illustrate the causes of such inadvertent transmission. With this knowledge, CDC can then revise these regulatory guidelines and requirements to match the actual risk involved. Without these data and knowledge, the ASM believes it is inappropriate to recommend all laboratories working with Mycobacterium tuberculosis convert their facilities to BSL3. ASM recommends revisions to the sections on autoclaving, centrifugation, and biological safety cabinets. Some of the recommendations contained in these sections pose substantial hazards to the laboratory worker.

In addition, the ASM believes the CDC guidelines provide inadequate protection for personnel working in the bacteriology, pathology, chemistry and hematology sections of the laboratory, as well as for individuals preparing frozen sections and working in the autopsy suite. All of the above individuals may also be potentially exposed to Mycobacterium tuberculosis. The final CDC guidelines should also incorporate the ASM recommendations pertaining to newer technologies and laboratory personnel safety education.

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