Rabies is an acute, progressive, incurable viral encephalitis, caused
by the bite of an infected animal. In March 2003, a previously healthy man
aged 25 years from northern Virginia died from a diagnosed illness of meningoencephalitis
of unknown etiology after a 3-week illness. Histopathologic review of central
nervous system tissues at CDC revealed viral inclusions suggestive of Negri
bodies, and subsequent tests confirmed a diagnosis of rabies. Genetic sequencing
identified a rabies virus variant associated with raccoons, but how the patient
became infected remains unknown. This report summarizes the investigation
of the first documented case of human rabies associated with a raccoon rabies
virus variant in the United States and highlights the importance of continued
education in the prevention and diagnosis of rabies.
In February 2003, the patient visited his physician with head and body
aches, nausea, abdominal pain, chills, fever of 99°–100° F (37.2°
C–37.7° C), dry cough, and listlessness. Upon retrospective questioning,
his wife reported that he had showed mild personality changes during the previous
days. Six days later, the patient awoke disoriented with unsteady gait and
slurred speech. He was evaluated in a local emergency department and admitted
to the hospital. Physical examination revealed mild ataxia and confusion.
Laboratory values were substantial for decreased sodium. A lumbar puncture
revealed a white blood cell count of 24/µL (normal: 0-5 cells/µL),
a red blood cell count of 10/µL (normal: 0-5 cells/µL), a glucose
concentration of 58 mg/dL (normal: 40-70 mg/dL), and a protein concentration
of 81 mg/dL (normal: 15-45 mg/dL). An electroencephalogram demonstrated generalized
slowing. Magnetic resonance imaging of the brain was interpreted with a high
T2 signal in the hypothalamus and bilateral mesial temporal lobes.
The patient remained febrile and hyponatremic (range: 119-125 mmol/L)
with declining mental status. On the fifth day of hospitalization, the patient
was intubated, and twitching on his right side was noted. On day six, he was
unresponsive and had near-constant myoclonic activity. On the 11th day, a
computerized tomography scan of the head showed sulcal effacement and diffuse
cerebral edema. The patient remained comatose and intermittently febrile.
Despite aggressive critical care management, the patient died on the 14th
At autopsy, histopathologic evaluation showed severe meningoencephalitis
involving the cortex and white matter of the cerebral hemispheres, deep gray
nuclei, cerebellum, and spinal cord. Brain tissue submitted to a research
laboratory was positive by polymerase chain reaction (PCR) for Naegleria.
The possibility of rabies was discussed briefly during hospitalization
but was discarded from further consideration on the basis of a review of the
history and clinical signs and symptoms. A brain biopsy was planned but was
canceled because of hemodynamic instability. Initial microscopic examination
of brain tissue did not detect any inclusions suggestive of viral infection.
Tissues were forwarded to CDC for pathologic evaluation for Naegleria. Immunohistochemical (IHC) assays for various amoebae, including Naegleria fowleri, were negative. However, abundant intracytoplasmic
inclusions of neurons in several areas of the brain suggested a diagnosis
of rabies. The diagnosis was confirmed by IHC stains for rabies virus. Further
testing, including both indirect and direct fluorescent antibody tests and
reverse transcriptase-PCR of fixed brain tissue, supported the diagnosis of
rabies. Nucleotide sequence analysis and antigenic typing with monoclonal
antibodies on frozen brain tissue indicated that the specific etiologic agent
was a southeastern raccoon rabies virus variant. Genetic sequence analysis
indicated 100% homology with a raccoon rabies virus variant from Virginia.
Approximately 125 family members and friends and 173 health-care workers
were questioned retrospectively about direct unprotected exposures to the
patient's secretions and tissues. After detailed investigation, five family
members and three hospital employees received postexposure prophylaxis for
potential exposure to patient secretions.
The patient was an office worker who for the previous 6 years had lived,
worked, and recreated in areas in which raccoon rabies was endemic. However,
extensive interviews with family, friends, and co-workers revealed that he
had no specific exposure to terrestrial animals likely to be infected with
the raccoon rabies virus variant. The patient did not spend much time outdoors,
but the potential existed for encountering a rabid mammal while camping or
in a trash can, wood pile, or other outdoor environment.
MA Silverstein, MD, Herndon Family Medicine, Herndon; CD Salgado, MD,
S Bassin, MD, TP Bleck, MD, MB Lopes, MD, BM Farr, MD, Univ of Virginia Health
System, Charlottesville; SR Jenkins, VMD, DC Sockwell, MSPH, JS Marr, MD,
GB Miller, MD, Office of Epidemiology, Virginia Dept of Health. Div of Viral
and Rickettsial Diseases, National Center for Infectious Diseases, CDC.
Approximately 7,000-9,000 cases of animal rabies are diagnosed annually
in the United States.1 This report describes the first documented
case of human rabies associated with a raccoon rabies virus variant. Of the
37 human rabies cases reported in the United States since 1990, no history
of suspicious animal bite exposure was documented for 28 of the 30 cases presumed
to be acquired in the United States. With the isolation of raccoon rabies
virus from this patient, human cases have been associated with all of the
major reservoirs and vectors of the disease in the United States, including
dogs, cats, bats, foxes, skunks, coyotes, and bobcats. Human rabies cases
without a definitive history of animal exposure are associated commonly with
bat rabies viruses.2 Challenges to implicating an animal source
readily can include failure to seek medical care for perceived minor lesions,
nonrecognition of the actual exposure event, communication (i.e., language)
barriers, and recall bias from memory loss or impaired speech in encephalitic
patients. Incubation periods range typically from 1 to 3 months after exposure
but in rare cases can exceed 1 year in duration, further complicating collection
of an adequate history.
During the late 1970s, rabid raccoons were identified in Virginia and
West Virginia after probable translocation of infected animals from the southeastern
United States. Raccoon rabies spread throughout the region, with approximately
50,000 rabid raccoons diagnosed to date. During 2003, Tennessee became the
twentieth affected state, and the enzootic area now stretches from eastern
Canada to Florida.3
Rabies should be considered in the differential diagnosis of any acute,
rapidly progressive encephalitis, regardless of documented history of animal
bite. Prompt ante- or postmortem diagnosis is necessary for accurate reporting
of human rabies to public health officials and implementation of appropriate
infection-control measures, including prompt administration of prophylaxis
to exposed persons.
The Advisory Committee on Immunization Practices publishes guidelines
for human rabies prevention,4 and recommendations have been published
for the management of suspected cases.5 Human rabies postexposure
prophylaxis is effective when administered promptly and properly. Human-to-human
transmission is a concern, but no cases among health-care workers exposed
to a rabies patient have been reported.6,7 In the case described
in this report, careful risk assessment based on identifiable contact with
the patient's secretions limited the number of persons receiving prophylaxis.
Emergency medicine physicians, infectious-disease consultants, and state and
national public health officials can provide advice on rabies prophylaxis
for complicated or unusual exposure scenarios to prevent this fatal disease
and aid in its diagnosis.
This report is based, in part, on contributions by M Prosniak, PhD,
B Dietzschold, DVM, Thomas Jefferson Univ, Philadelphia, Pennsylvania.
References: 7 available
First Human Death Associated With Raccoon Rabies—Virginia, 2003. JAMA. 2003;290(22):2930-2931. doi:10.1001/jama.290.22.2930