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
Shill M, Baynes RD, Miller SD. Fatal rabies encephalitis
despite
appropriate post-exposure prophylaxis. N Engl J Med
1987;316:1257-8.
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.
Dean DJ, Baer GM, Thompson WR. Studies on the local treatment
of
rabies-infected wounds. Bull WHO 1963;28:477-86.
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.
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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