Case 21-1998: Rabies

N Engl J Med 1999; 340:64-65January 7, 1999

Article

To the Editor:

The death of a 32-year-old American traveler from rabies after a dog bite in Nepal, described in Case 21-1998 (July 9 issue),1 is a sobering reminder that fatal encephalitis can occur when postexposure prophylaxis is not used. Dr. Basgoz, the attending physician and case discussant, commented that the patient had “considerable knowledge about the risk of rabies, as well as relatively ready access to medical care,” yet provided no details regarding her failure to receive prophylaxis. In an earlier description of the case, it was reported that despite three attempts to obtain postexposure prophylaxis before returning home, the patient was either unable to obtain it or unsure of its necessity.2 Sadly, it appears she did not know that the Western-run Canadian International Water and Energy Consultants Clinic Travel Medicine Center in Katmandu has counseled travelers and administered rabies immune globulin and postexposure rabies vaccine 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

3 References

1
Case Records of the Massachusetts General Hospital (Case 21-1998). N Engl J Med 1998;339:105-112
Full Text | Web of Science | Medline

2
Human rabies -- New Hampshire, 1996MMWR Morb Mortal Wkly Rep 1997;46:267-270
Medline

3
Shlim DR, Schwartz E, Houston R. Rabies immunoprophylaxis strategy in travelers. J Wilderness Med 1991;2:15-21
CrossRef

To the Editor:

In discussing the differential diagnosis in Case 21-1998, Dr. Basgoz states that the recommended prophylactic regimen before exposure to rabies consists of “four intramuscular (deltoid) or intradermal injections of vaccine, administered on days 0, 7, 21, and 28.” The correct regimen is actually three vaccinations on days 0, 7, and either 21 or 28. In addition, it is important to emphasize that rabies vaccination does not confer lifetime immunity and that rabies titers should be measured or booster vaccinations given every two years, depending on the risk of exposure.

Emil P. Sfedu, M.D.
Executive Health Services, Philadelphia, PA 19130

To the Editor:

In discussing the case of rabies, Dr. Basgoz stated that “up to half the rabies immune globulin should be administered at the site of the wound (or wounds) and the rest given intramuscularly in the gluteal area.” I take issue with this recommendation.

It is wound injection with rabies immune globulin and not the intramuscular administration of this product that, together with vaccination, prevents death.1 A recent study of the pharmacokinetics of rabies immune globulin further supports the importance of injecting wounds.2 Physicians in countries where canine rabies is endemic may treat patients with multiple severe bite wounds, usually children, in whom the calculated dose of rabies immune globulin is inadequate to infiltrate all wounds.3 I dilute the rabies 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 changed its recommendations regarding the use of rabies immune globulin.4 The committee now recommends that:

Human or equine rabies immune globulin should be infiltrated in and around all wounds using as much volume as possible, all if 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 Europe include these new recommendations.

Henry Wilde, M.D.
Queen Saovabha Memorial Institute, Bangkok 10330, Thailand

4 References

1
Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of rabies infected wounds. Bull World Health Organ 1963;28:477-486
Web of Science | Medline

2
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
CrossRef | Web of Science | Medline

3
Wilde H, Sirikawin S, Sabcharoen A, et al. Failure of postexposure treatment of rabies in children. Clin Infect Dis 1996;22:228-232
CrossRef | Web of Science | Medline

4
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 of rabies immune globulin was changed by the Immunization Practices Advisory Committee of the Public Health Service on February 7, 1997.1 The new guidelines recommend that, “if anatomically feasible, the full dose of human rabies immune globulin should be thoroughly infiltrated in the area around and into the wound(s). Any remaining volume should be administered intramuscularly at a site distant from the vaccine inoculation.”

William F. Stack, D.V.M.
Onondaga County Health Department, Syracuse, NY 13215-0190

1 References

1
Human rabies -- Texas and New Jersey, 1997MMWR 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 rate of about 10 mm per day.” These statements do not reflect current knowledge. In studies of dorsal-root–ganglia neurons, Tsiang et al.1 found that rabies virus travels by retrograde and anterograde fast axonal transport at a rate of 100 to 400 mm per day. It is more likely that the long incubation period in rabies is due to a delay in the movement of virus at the site of exposure (the region of the bite)2 rather than to slow transport within axons of the peripheral and central nervous systems.

Alan C. Jackson, M.D.
Queen's University, Kingston, ON K7L 2V7, Canada

2 References

1
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
CrossRef | Web of Science | Medline

2
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 | Web of Science | Medline

To the Editor:

In his discussion, Dr. Basgoz refers to Antarctica as the only continent in which endemic rabies has not been reported. Australia is also free of this disease, although sporadic cases have been reported in patients who acquired their infection elsewhere.

Nicholas Bett, M.B., B.S.
Prince Charles Hospital, Brisbane 4035, Australia

Author/Editor Response

Dr. Basgoz replies:

To the Editor: Drs. Shlim and Panosian correctly emphasize the importance of reminding travelers that rabies can occur if postexposure prophylaxis is not used.

Dr. Sfedu is correct: the recommended regimen for preexposure prophylaxis is three intramuscular or intradermal injections of vaccine, administered on days 0, 7, and either 21 or 28, not 21 and 28. This is the practice at my institution, and I regret the error. Although the case was discussed at a time when the recommendation for the use of immune globulin was to infiltrate half at the wound site and to administer half intramuscularly, Drs. Wilde and Stack are correct that the new guidelines recommend infiltration of as much of the immune globulin as possible around the wound or wounds, with the rest given intramuscularly.1

The rate of intraaxonal transport of rabies virus of 8 to 20 mm a day is more characteristic of that in rat neurons, and Dr. Jackson correctly points out that the rate in human neurons is thought to be faster.2 Dr. Bett points out that rabies is not endemic in Australia.

Nesli Basgoz, M.D.
Massachusetts General Hospital, Boston, MA 02114-2696

2 References