Human Rabies -- California, 1995

In September and November 1995, two men in California died from infection with bat-associated variants of rabies virus. This report summarizes the investigations of these cases. Case 1

On September 9, 1995, a 27-year-old farm worker in San Benito County was examined in the emergency department (ED) of a local hospital because of a 1-day history of vomiting and severe headache. Computerized axial tomography of the brain and cerebrospinal fluid (CSF) analysis were within normal limits, and he was discharged with a diagnosis of cephalgia. He returned to the ED two additional times that day with complaints of headache and sore throat, for which amoxicillin was prescribed. On September 10, he was admitted to the hospital because of severe supraorbital headache and intermittent vomiting.

Findings on admission included an oral temperature of 103.1 F (39.5 C) and mild nonexudative pharyngitis; in addition, the patient rejected oral medications because of an intermittent inability to swallow. A peripheral white blood cell (WBC) count was 14,000/mm3 (normal: 5000-10,000/mm3) with 82% neutrophils, 9% lymphocytes, 5% monocytes, and 4% bands. The CSF contained 0 WBC/mm3 (normal: 0-5 WBC/mm3), total protein of 68 mg/dL (normal: less than 40 mg/dL), and glucose of 65 mg/dL (normal: 70-110 mg/dL). A chest roentgenogram revealed right lower lobe pulmonary infiltration, and treatment for pneumonia was initiated with intravenous cefuroxime and erythromycin. On September 11, his oral temperature was 104.9 F (40.5 C), and he coughed blood-tinged mucus. He became acutely agitated and confused and required physical restraints. Because of alteration of mental status, later that day he was transferred to a tertiary-care facility.

Findings on admission included an oral temperature of 104.5 F (40.3 C), peripheral WBC count of 17,000/mm3, and CSF containing total protein of 124 mg/dL, glucose of 92 mg/dL, and 6 WBC/mm3. Nonspecific encephalitis was tentatively diagnosed, and treatment was initiated with acyclovir, ceftizoxime, vancomycin, and doxycycline. Magnetic resonance imaging and electroencephalogram results were consistent with encephalitis. However, analysis of CSF specimens were negative for herpes simplex virus (by polymerase chain reaction {PCR} assay) and bacteria (by standard culture methods). Rabies was included in the differential diagnosis on September 12; the patient became comatose on September 15 and died September 21. A limited autopsy was performed.

A CSF specimen collected September 12 and serum and nuchal skin biopsy specimens collected September 13 were sent to the Viral and Rickettsial Disease Laboratory (VRDL) of the California Department of Health Services and to CDC for rabies testing, and corneal impression specimens were sent to the VRDL. Both laboratories reported the CSF and serum specimens to be negative for rabies antibody (by rapid fluorescent focus inhibition test {RFFIT} assay at CDC and indirect immunofluorescence {IIF} assay at the VRDL). The nuchal skin biopsy was negative for rabies virus antigen by direct fluorescent antibody (DFA) testing at both laboratories (although only two hair follicles were present in the biopsy). The corneal impression specimen was inconclusive for rabies antigen (by DFA) at the VRDL. However, rabies was diagnosed by the VRDL on September 20 based on rising rabies antibody titers of less than 1:8 to 1:256 by IIF in serum samples collected on September 13 and September 19, respectively. An IIF titer of greater than 1:2048 was detected in a follow-up serum specimen collected September 21, and brain tissue specimens collected at autopsy were positive for rabies virus (by both DFA and PCR assays) at the VRDL on September 25. At CDC, nucleotide sequence analysis of rabies viral nucleic acid from brain tissue implicated a variant of rabies virus associated with Mexican free-tailed bats (Tadarida brasiliensis).

The patient had immigrated from Mexico and had last been in Mexico during November 1994-April 1995. In California, he resided on a ranch that produced vegetables, and he worked primarily in a packing shed; a bat colony inhabited the roof area of the shed. A family member believed that a bat had landed on and was brushed off the patient's chest, but was unable to provide any specific details of the incident. The complete colony of 76 bats, including a mixture of Mexican free-tailed and pallid bat species, was collected for evaluation; all tested negative for rabies.

Rabies postexposure prophylaxis (PEP) was administered to 12 persons (11 co-workers and one health-care professional) because of possible percutaneous or mucous membrane exposure to the patient's vomitus or saliva. Case 2

On October 26, a 74-year-old resident of Butte County was evaluated in a local ED because of paresthesia and weakness in the right arm and chronic cough. He was discharged but returned to the hospital on October 30 and was admitted because of shortness of breath, confusion, vomiting, and right arm weakness. On admission, he was afebrile; other findings included right arm weakness, bilateral ptosis, severe dysarthria, ataxia, moderate confusion, and a productive cough. He declined to drink fluids and gagged and vomited when offered food. Laboratory findings on admission included a WBC count of 13,000/mm3 with 88% neutrophils, 4% lymphocytes, 4% monocytes, and 4% bands; CSF containing 3000 red blood cells/mm3, 1000 WBC/mm3, and total protein of 174 mg/dL; chest radiograph with bilateral pulmonary infiltrates; and nerve conduction abnormalities of the right upper extremity consistent with axonal and demyelinating neuropathy. Admitting diagnoses included pneumonia and cerebrovascular accident.

During the first 24 hours after admission, the patient became progressively agitated, confused, and ultimately unresponsive; he was intubated and placed on mechanical ventilatory support. During November 1-9, he did not regain consciousness and was intermittently febrile (high of 102.7 F {39.3 C}). On November 9, when the patient died, the differential diagnoses included respiratory failure and Guillain-Barre syndrome.

Although rabies was not considered before death, examination of brain material at autopsy revealed intracytoplasmic inclusions consistent with rabies virus infection. On December 30, paraffin-embedded brain specimens were sent to CDC, where rabies antigen was detected by DFA staining. Nucleotide sequence analysis of the specific viral RNA found in the brain tissue identified the rabies virus variant associated with the silver-haired bat (Lasionycteris noctivagans). The diagnosis was confirmed at the California VRDL on January 4 by the detection of rabies virus-specific antibody (by IIF assay; titer of 1:8) in an antemortem sample of CSF.

The patient had lived alone on a ranch in Butte County and herded his cattle to a grazing area in adjacent Lassen County during the summer. Multiple potential sources of exposure to both domestic and wild animals were present in both the grazing area and the ranch. The patient's son reported that the patient would sometimes catch bats, but he knew of no incidents of animal bite.

A total of 76 persons received rabies PEP because of possible contact with the patient's oral and respiratory secretions during his illness. The group of exposed persons included 71 health-care workers, three family members, one housekeeper, and the pathologist who performed the autopsy.

Reported by: E Falade, MD, M Andazola-Boyd, R Shingai, San Benito County Health Dept, Hollister; B Littfin, Hazel Hawkins Memorial Hospital, Hollister; M Lundberg, MD, D Murrill, Butte County Health Dept, Oroville; R Murray, DrPH, L Dales, MD, C Glaser, MD, K Reilly, DVM, D Schnurr, PhD, M Ascher, MD, S Waterman, MD, State Epidemiologist, California Dept of Health Svcs. Viral and Rickettsial Zoonoses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: During 1995, a total of four cases of human rabies were documented in the United States, including the two cases described in this report. In all four cases, the rabies virus variant was associated with insectivorous bats; however, a definite history of bite exposure could not be identified for any of these cases. Characteristics of these cases are consistent with an emerging pattern in the epidemiology of human rabies in the United States: bat-related variants have been identified from 15 of the 28 cases of human rabies diagnosed in the United States since 1980, while contact of any sort with bats could be documented in only seven of the 15 cases (of which 10 were associated with virus from the silver-haired bat variant). These findings indicate that limited physical contact with rabid bats may be associated with rabies virus transmission. In addition, bat bites are small and less likely to be recognized than bites inflicted by many terrestrial animals.

Because bat rabies is enzootic in the contiguous United States (1) and reduction of bat populations is not appropriate as a strategy for controlling rabies in bats, human and domestic animal contact with bats should be minimized by the physical exclusion of bats from human dwellings (2). Bats should not be captured, handled, or kept as pets. In addition, rabies vaccination should be current for all dogs and cats.

The difference in the number of persons receiving rabies PEP as a result of exposure to the two human rabies cases described in this report (76 versus 12) illustrates variations in the interpretation and systematic application of the Advisory Committee on Immunization Practices (ACIP) guidelines concerning PEP administration (3). The number of persons requiring PEP can be minimized by 1) early consideration of rabies as a differential diagnosis in any progressive neurologic disease of unknown etiology, 2) prompt initiation of standard barrier techniques against infectious diseases in the hospital, and 3) strict adherence to ACIP guidelines.

References

1. Krebs JW, Strine TW, Smith JS, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1994. J Am Vet Med Assoc 1995;207:1562-75.

2. CDC. Compendium of animal rabies control, 1995: National Association of State Public Health Veterinarians, Inc. MMWR 1995;44(no. RR-2).

3. ACIP. Rabies prevention -- United States, 1991: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-3).

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