To the Editor: The death of a 32-year-old American travelerfrom rabies after a dog bite in Nepal, described in Case 21-1998(July 9 issue),1 is a sobering reminder that fatal encephalitiscan occur when postexposure prophylaxis is not used. Dr. Basgoz,the attending physician and case discussant, commented thatthe patient had "considerable knowledge about the risk of rabies,as well as relatively ready access to medical care," yet providedno details regarding her failure to receive prophylaxis. Inan earlier description of the case, it was reported that despitethree attempts to obtain postexposure prophylaxis before returninghome, the patient was either unable to obtain it or unsure ofits necessity.2 Sadly, it appears she did not know that theWestern-run Canadian International Water and Energy ConsultantsClinic Travel Medicine Center in Katmandu has counseled travelersand administered rabies immune globulin and postexposure rabiesvaccine for the past 15 years.3
David R. Shlim, M.D. Shoreland Kelly, WY 83011
Claire Panosian, M.D. UCLA Medical Center Los Angeles, CA 90095-1688
References
Case Records of the Massachusetts General Hospital (Case 21-1998). N Engl J Med 1998;339:105-112. [Free Full Text]
Human rabies -- New Hampshire, 1996. MMWR Morb Mortal Wkly Rep 1997;46:267-270. [Medline]
Shlim DR, Schwartz E, Houston R. Rabies immunoprophylaxis strategy in travelers. J Wilderness Med 1991;2:15-21.
To the Editor: In discussing the differential diagnosis in Case21-1998, Dr. Basgoz states that the recommended prophylacticregimen before exposure to rabies consists of "four intramuscular(deltoid) or intradermal injections of vaccine, administeredon days 0, 7, 21, and 28." The correct regimen is actually threevaccinations on days 0, 7, and either 21 or 28. In addition,it is important to emphasize that rabies vaccination does notconfer lifetime immunity and that rabies titers should be measuredor booster vaccinations given every two years, depending onthe risk of exposure.
Emil P. Sfedu, M.D. Executive Health Services Philadelphia, PA19130
To the Editor: In discussing the case of rabies, Dr. Basgozstated that "up to half the rabies immune globulin should beadministered at the site of the wound (or wounds) and the restgiven intramuscularly in the gluteal area." I take issue withthis recommendation.
It is wound injection with rabies immune globulin and not theintramuscular administration of this product that, togetherwith vaccination, prevents death.1 A recent study of the pharmacokineticsof rabies immune globulin further supports the importance ofinjecting wounds.2 Physicians in countries where canine rabiesis endemic may treat patients with multiple severe bite wounds,usually children, in whom the calculated dose of rabies immuneglobulin is inadequate to infiltrate all wounds.3 I dilute therabies immune globulin with normal saline for such patients,so that all wounds can be infiltrated.3
The rabies committee of the World Health Organization has changedits recommendations regarding the use of rabies immune globulin.4The committee now recommends that:
Human or equine rabies immune globulin should be infiltratedin and around all wounds using as much volume as possible, allif necessary. The rest, if any, is administered intramuscularly.If the calculated volume is inadequate to infiltrate all wounds,the rabies immune globulin can be diluted with normal saline.
Package inserts supplied with rabies immune globulin in Europeinclude these new recommendations.
Henry Wilde, M.D. Queen Saovabha Memorial Institute Bangkok 10330,Thailand
References
Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of rabies infected wounds. Bull World Health Organ 1963;28:477-486. [Medline]
Lang J, Gravenstein S, Briggs D, et al. Evaluation of the safety and immunogenicity of a new, heat-treated human rabies immune globulin using a sham, post-exposure prophylaxis of rabies. Biologicals 1998;26:7-15. [Medline]
Wilde H, Sirikawin S, Sabcharoen A, et al. Failure of postexposure treatment of rabies in children. Clin Infect Dis 1996;22:228-232. [Medline]
World Health Organization. Report of a WHO consultation on intradermal application of human rabies vaccine. Geneva: World Health Organization, 1995.
To the Editor: The recommendation for the administration ofrabies immune globulin was changed by the Immunization PracticesAdvisory Committee of the Public Health Service on February7, 1997.1 The new guidelines recommend that, "if anatomicallyfeasible, the full dose of human rabies immune globulin shouldbe thoroughly infiltrated in the area around and into the wound(s).Any remaining volume should be administered intramuscularlyat a site distant from the vaccine inoculation."
William F. Stack, D.V.M. Onondaga County Health Department Syracuse,NY 13215-0190
References
Human rabies -- Texas and New Jersey, 1997. MMWR Morb Mortal Wkly Rep 1998;47:1-5. [Medline]
To the Editor: In reviewing the differential diagnosis of rabies,Dr. Basgoz states that the intraaxonal transport of rabies virus"occurs at a rate of 8 to 20 mm per day. In the case under discussion,the incubation period of approximately 65 days suggest a rateof about 10 mm per day." These statements do not reflect currentknowledge. In studies of dorsal-root–ganglia neurons,Tsiang et al.1 found that rabies virus travels by retrogradeand anterograde fast axonal transport at a rate of 100 to 400mm per day. It is more likely that the long incubation periodin rabies is due to a delay in the movement of virus at thesite of exposure (the region of the bite)2 rather than to slowtransport within axons of the peripheral and central nervoussystems.
Alan C. Jackson, M.D. Queen's University Kingston, ON K7L 2V7,Canada
References
Tsiang H, Lycke E, Ceccaldi P-E, Ermine A, Hirardot X. The anterograde transport of rabies virus in rat sensory dorsal root ganglia neurons. J Gen Virol 1989;70:2075-2085. [Free Full Text]
Charlton KM, Nadin-Davis S, Casey GA, Wandeler AI. The long incubation period in rabies: delayed progression of infection in muscle at the site of exposure. Acta Neuropathol (Berl) 1997;94:73-77. [CrossRef][Medline]
To the Editor: In his discussion, Dr. Basgoz refers to Antarcticaas the only continent in which endemic rabies has not been reported.Australia is also free of this disease, although sporadic caseshave been reported in patients who acquired their infectionelsewhere.
Nicholas Bett, M.B., B.S. Prince Charles Hospital Brisbane 4035,Australia
Dr. Basgoz replies:
To the Editor: Drs. Shlim and Panosian correctly emphasize theimportance of reminding travelers that rabies can occur if postexposureprophylaxis is not used.
Dr. Sfedu is correct: the recommended regimen for preexposureprophylaxis is three intramuscular or intradermal injectionsof vaccine, administered on days 0, 7, and either 21 or 28,not 21 and 28. This is the practice at my institution, and Iregret the error. Although the case was discussed at a timewhen the recommendation for the use of immune globulin was toinfiltrate half at the wound site and to administer half intramuscularly,Drs. Wilde and Stack are correct that the new guidelines recommendinfiltration of as much of the immune globulin as possible aroundthe wound or wounds, with the rest given intramuscularly.1
The rate of intraaxonal transport of rabies virus of 8 to 20mm a day is more characteristic of that in rat neurons, andDr. Jackson correctly points out that the rate in human neuronsis thought to be faster.2 Dr. Bett points out that rabies isnot endemic in Australia.
Nesli Basgoz, M.D. Massachusetts General Hospital Boston, MA02114-2696
References
Human rabies -- Texas and New Jersey, 1997. MMWR Morb Mortal Wkly Rep 1998;47:1-5.
Lycke E, Tsiang H. Rabies virus infection of cultured rat sensory neurons. J Virol 1987;61:2733-2741. [Free Full Text]
Correction
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Basgoz and Frosch, 
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