1
Peer reviewer comments on “Recommendations for post exposure interventions to prevent HBV, HCV or HIV infections and tetanus for persons wounded during bombings and similar mass casualty events in the United States—2007.” Summary of Peer Reviewer Comments with CDC Responses embedded: This is a very thorough and well written document. The document appears to be very complete and the information accurate. This document provides very important information to guide providers in Mass Casualty Bombings. In general the peer reviewers agreement with the recommendations, but had several specific comments. A plan for periodic review and updating of the information in this guideline and the links to additional information is essential if this document is to be useful. While the documented is well written and carefully thought out, it applies to an event that is currently rare in the US and thus the document will only be very rarely consulted so. When it is consulted, in several years, it may no longer be current. Thus an ongoing plan for review and revision/updating is essential to ensure that the guidance maintains its value. CDC RESPONSE 1: We agree with the importance of updating guidance. Pending the availability of effective vaccines to prevent infection with Hepatitis C virus or Human Immunodeficiency Virus, or effective pharmacological post-exposure prophylaxis to prevent hepatitis C infection the guidance content of this document is unlikely to outdate in substantial ways. However, the links associated with access to additional information will need review and update. The Division of Injury Response will be responsible for ensuring periodic review and, when appropriate, updating of the information in this document. Other specific peer reviewer comments are delineated below with CDC responses when appropriate. Introduction, and methods: The document is extremely clear and well laid out. In particular the rationale for a seemingly esoteric document is well stated and the background with reference to other countries is clear and reasonable. Bloodborne pathogens of immediate concern: The disease review is concise and appropriate, with the following points of concern: Hepatitis B Virus: The sentence stating: “Newly acquired HBV infection is often asymptomatic, with 30%50% of children aged greater than 5 years and adults having initial clinical signs or symptoms” makes no sense. Did the authors mean to say “having no initial clinical signs…?” Please clarify and/or rewrite this sentence (page 11) CDC RESPONSE 2: We have revised to clarify intent: “Newly acquired HBV infection is often asymptomatic; only 30%-50% of children aged greater than 5 years and adults have initial clinical signs or symptoms.” Hepatitis C Virus: The sentence stating: “However, limited data indicate that antiviral therapy might be beneficial when started early in the course of HCV infection.” To my judgment, the data amount to little more than anecdotes. Since the available drugs do not actually provide prophylaxis against
1
2
HCV infection (as opposed to treating established HCV infection), does this statement really belong in a guideline largely devoted to prophylactic therapies? (page 13) CDC RESPONSE 3: We appreciate your concern. Whether or not to include recommendation of testing for seroconversion to hepatitis C was an aspect of this guidance that provoked intense consideration. It is true that no effective postexposure prophylaxis intervention exists. It is also true that data supporting benefit from early detection and treatment of hepatitis C infection are limited and include a single phase I clinical trial examining early treatment of hepatitis C. Nevertheless, the limited data are mentioned because they provide the basis for the recommendation that testing to identify seroconversion to hepatitis C should be considered for persons who experience penetrating injuries or nonintact skin exposed to exogenous blood during mass casualty events. This advice is consistent with current public health practice. The increased feasibility of testing during a follow up referral and the desirability of seeking assistance from public health authorities in assessing the likelihood that exposure to a hepatitis C positive source occurred is emphasized. HIV Infection: Reviewer concurs with the public response noted in PC4F and is glad that CDC further clarified the language relating to the rare circumstances in which HIV PEP should be considered. Review of categories of individual risk: Reviewer considers this a comprehensive discussion of risk both in and out of the setting of casualty and a reasonable discussion of vaccine supply which is an issue when even a small group prophylaxis is considered. In particular, clarifying that the SNS does not have everything on hand that may be necessary is important as many people unreasonably assume it has everything. Recommendations postexposure management by risk category and specific pathogens: Reviewer suggests that CDC consider adding a recommendation to "Consider using HBIG in addition to hepatitis B vaccine for percutaneous exposure to know or subsequently determined HBsAg-positive blood". This was brought up in the public comments and reviewer agrees with the point made that in the setting of response to a mass casualty event it is very unlikely that we will know anything about HBsAg status of contaminating blood. However, in a scenario where someone involved in a mass casualty (a victim or perpetrator) survives and is known or is found to be HBsAg positive, in the absence of evidence that hep B vaccine is equivalent or superior to HBIG in the setting of post-exposure prophylaxis, the availability and possible role of HBIG should be mentioned. CDC RESPONSE 4: There is no harm and may be marginal gain in augmenting hepatitis B vaccine with HBIG as post exposure prophylaxis for persons who were definitely exposed to HBVinfected blood. However, (1) it is extremely unlikely that anyone would be aware of a definite HBV exposure during a mass casualty event--as the reviewer acknowledges; (2) one dose of hepatitis B vaccine alone has been shown to decrease the risk that exposure to hepatitis B infected blood will progress to infection and it is not clear that the addition of HBIG substantially increases the efficacy of post exposure prophylaxis; (3) HBIG is harder to find
2
3
and store than hepatitis B vaccine; and (4) it complicates the recommendations which are clear as they stand now. In the circumstances of response to a bombing or similar mass casualty event, it is the considered judgment of the injury response expert consultants that simplicity of recommendations will have substantial impact on the feasibility of implementation of response. For these reasons, CDC chooses to retain the simple and adequate recommendation of hepatitis B vaccination alone for postexposure prophylaxis rather than revising to recommend hepatitis B vaccination augmented by HBIG, a combination that may be superior in efficacy but that will also be less feasible to deliver under the circumstances that will activate this guidance. Special situations when HIV PEP is initiated: Why should the initial dose of HIV PEP be taken under direct observation? (page 24). CDC RESPONSE 5: We have deleted this recommendation. A strong determinant of efficacy is the rapidity with which HIV PEP is begun after exposure. In the setting of a mass casualty event response even patients who appear coherent and who suffered minor wounds are likely to be seriously impacted psychologically and may be operating in varying states of shock. Rapid and proper initiation of therapy is best ensured by having the patient take the first dose in the presence of a health care provider. However, staff providing care in a mass casualty response situation may be more concerned about providing trauma care to the most seriously injured victims and the recommendation to directly observe HIV PEP may unnecessarily add to their stress and distract attention from urgent life saving efforts. Directly observed HIV PEP is not recommended in either the occupational or nonoccupational HIV PEP guidelines. The continued recommendation of ZDV/3TC as a first choice regimen for HIV PEP is hard to justify in view of the available human and animal data on TDF and TDF/FTC. Additionally, ZDV is often poorly tolerated in the initial days of therapy. Finally, the recent (2008) USPHS guidelines on treatment of HIV disease no longer recommend ZDV/3TC as a regimen of choice. (page 24) CDC RESPONSE 6: The issue raised by the peer-reviewers highlights the danger of indicating recommended HIV PEP regimens in the document, as these recommendations do change over time. The nPEP guidelines mention several potential choices which reflect the treatment guidelines that were current at the time, but also note that current treatment guidelines should be consulted. The adult and adolescent HIV treatment guidelines were updated during the preparation of this guidance (November 2006 and January 2008) and the drugs of choice for initial therapy changed. The rationale for including mention of a specific regimen in this document was to avoid the need to for emergency
3
4
responders to have to find another document or alternate source of expert consultation. In reality, in the rare situation where HIV PEP is appropriate in response to a mass casualty event, expert consultation should be available from local hospital epidemiology, occupational health or infectious disease consultants; from local, state or federal public health authorities; or through other sources of emergency expert consultation such as the PEPline. A single consultation, properly communicated to responding health care staff, should suffice for almost all patients beginning HIV PEP in response to the same exposure event. Early urgent follow up with infectious disease experts will be essential for all persons who begin HIV PEP under the emergency circumstances of a mass casualty response. Thus we have removed the attempt to suggest specific starting regiments and instead augment the section describing sources of expert consultation as follows: "...Resources for consultation are available from the following sources: Local infectious diseases, hospital epidemiologist or occupational health consultant Local, state or federal public health authorities PEPline at http://www.ucsf.edu/hivcntr/Hotlines/PEPline.html ; telephone 888-448-4911; HIV/AIDS Treatment Information Service at http://aidsinfo.nih.gov . Published guidance (see “INFORMATION SOURCES, Links to information on postexposure prophylaxis (PEP) against HIV”, page 28). Nevirapine should not be included in HIV PEP regimens due to potential severe hepatic and cutaneous toxicity. Efavirenz should not be used if pregnancy is known or suspected because of potential teratogenicity (10,21)." The comment on early discontinuation of PEP “if significant side effects of PEP become manifest” (page 25) also makes little sense in view of the revised language regarding circumstances in which HIV PEP is recommended. If the risk is judged significant enough (e.g. an accident in a lab working with HIV) then PEP should be maintained for a full four weeks CDC RESPONSE 7: We have removed the sentence “Early discontinuation of PEP regimen should be considered if significant side effects of PEP become manifest.” Special Situations:
4
5
Reviewers considered this a good review of necessary prophylaxis, but emphasized the importance of having a plan in place to up date these recommendations as the prophylaxis changes. Pregnancy: Reviewers considered the guidance very helpful given that most people providing prophylaxis in this setting will not be people who routinely care for pregnant women. Responders and other personnel: Reviewers commented that healthcare personnel and first responders should also be routinely vaccinated with tetanus vaccine in addition to hepatitis B vaccine. CDC RESPONSE 8: We have amended the sentence to read “Healthcare personnel and … should have been previously vaccinated against hepatitis B and tetanus.” Links to information on vaccination: Again Reviewers emphasized that while it is essential to provide theses links, it is also essential that a plan be in place to keep the links updated on a regular basis as such links can change frequently (and indeed appeared to change during the public comments period). CDC RESPONSE 9: As noted above, we agree with the importance of updating guidance. The Division of Injury Response will be responsible for ensuring periodic review and, when appropriate, updating of the information in this document. National Vaccine Injury Compensation Program: Reviewers note that whether the National Vaccine Injury Compensation Program applies to adults as well as children should be clarified. CDC RESPONSE 10: The National Vaccine Injury Compensation Program applies only to certain vaccines, but there is no age limit on seeking compensation under the program as long as other legal requirements are satisfied. We have clarified this by specifying that the program is a no-fault system in which persons thought to have suffered an injury or death as a result of administration of a covered vaccine can seek compensation. Claims may be filed on behalf of infants, children and adolescents, or by adults receiving VICPcovered vaccines. Other legal requirements, such as the statute of limitations for filing an injury or death claim, must be satisfied in order to pursue compensation. Response to substantive public comments: Reviewers concurred with the public comment regarding item 4F but otherwise had no comments.
5