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International Notes Human Rabies Despite Treatment With Rabies Immune Globulin and Human Diploid Cell Rabies Vaccine -- Thailand

On March 6, 1987, a rabid dog severely bit a ten-year-old Thai boy on the left calf and forehead and on the right eyelid through to the bulbar conjunctiva. The wounds were immediately flushed with saline alone and sutured at a local hospital. Tetanus toxoid and suckling mouse rabies vaccine were given intramuscularly (IM). The following day, 21 hours after exposure, the patient received 1 mL human diploid cell rabies vaccine (HDCV) IM in the gluteal area and 20 IU/kg of human rabies immune globulin (HRIG) IM in the opposite gluteal area. Subsequent 1 mL injections of HDCV were given IM in the gluteal area on days 2, 6, and 13. Twenty-one days after exposure, the patient developed fever, headache, lethargy, vomiting, and progressive paralysis of all extremities. The patient died 15 days later, 36 days after exposure. His brain tissue was positive for rabies virus by direct fluorescent antibody. Reported by: P Lumbiganon, MD, V Bunyahotra, MD, C Pairojkul, MD, Khon Kaen University, Khon Kaen; Thailand Ministry of Public Health, Bangkok, Thailand. Viral and Rickettsial Zoonoses Br, Div of Viral Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: This is the second laboratory-confirmed case of rabies reported to have occurred despite administration of HDCV and HRIG within 24 hours of exposure. The previous case involved a 20-year-old South African male who received HRIG 13 hours after a rabid mongoose bit his finger. One milliliter of HRIG was infiltrated around the wound, and the remainder of the dosage was given IM in the deltoid (1). All injections of HDCV (days 0, 3, 7, and 14) were given IM in the gluteal area. On day 21, the patient developed paresthesia of the bitten arm. He died of rabies 16 days later.

There are several possible explanations for the observed failure of HDCV and HRIG to protect against rabies in these cases. Although the timing of vaccine administration was similar to the recommended schedule in both cases (2), vaccine was given in the gluteal area. A reduced antibody response has been shown when hepatitis B vaccine is administered in the gluteal area instead of the deltoid (3). Presumably, subcutaneous fat in the gluteal area may interfere with the immunogenicity of HDCV. Moreover, only saline solution was used to flush the Thai patient's wounds. Cleaning bite wounds with saline alone has been shown to be less effective in decreasing the risk of rabies than cleaning with anti-viral solutions, such as soap and water (4). Finally, persons with severe bites to the head and digits, sites of rich innervation, are more likely to develop rabies than persons bitten elsewhere (5). Inoculation of rabies virus near or into the peripheral nerves might bypass the protection conferred by rabies immune globulin and vaccine, both of which are ineffective after the virus invades the nervous system. Evidence did not indicate immune deficiency in these patients or decreased immunogenicity of the vaccine lots. Also, HDCV has been shown to be stable even when exposed to high ambient temperatures for up to 11 weeks (6).

Approximately 18,000 persons receive rabies postexposure prophylaxis in the United States per year (CDC, unpublished data). Severe attacks by rabid wild animals and dogs like that suffered by the Thai patient are rare in developed countries. No treatment failures have been reported when the recommended postexposure prophylaxis regimen of wound cleaning, HRIG, and 5 doses of HDCV have been strictly observed (2). Although the reasons these two patients developed rabies are unknown, proper wound management and proper administration of HRIG and HDCV might have prevented disease. Wounds inflicted by animals suspected or confirmed to be rabid should be immediately and thoroughly cleaned with soap and water. If anatomically possible, up to half of the HRIG dose should be infiltrated around the wound and the rest given IM in the gluteal area or lateral thigh. For postexposure prophylaxis, adults and children should always receive HDCV IM in the deltoid. Infants can be given the vaccine in the anterolateral upper thigh.

References

  1. Shill M, Baynes RD, Miller SD. Fatal rabies encephalitis despite appropriate post-exposure prophylaxis. N Engl J Med 1987;316:1257-8.

  2. Immunization Practices Advisory Committee. Rabies prevention--United States, 1984. MMWR 1984;33:393-402,407-8.

  3. Shaw FE Jr, Guess HA, Coleman PJ, et al. The effect of anatomic injection site and other host factors on the immunogenicity of hepatitis B vaccine. In: Program and abstracts of the 26th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1986:155.

  4. Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of rabies-infected wounds. Bull WHO 1963;28:477-86.

  5. McKendrick AG. Ninth analytical review of reports from Pasteur Institutes on results of anti-rabies treatment. Bull Hlth Organ, League of Nations 1940;9:31-78.

  6. Nicholson KG, Burney MI, Ali S, Perkins FT. Stability of human diploid-cell-strain rabies vaccine at high ambient temperatures. Lancet 1983;1:916-8.

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