Human Rabies -- Alabama, Tennessee, and Texas, 1994

In October and November 1994, three persons (one each in Alabama, Tennessee, and Texas) died from rabies. This report summarizes the investigations of these cases by state and local health departments and CDC. Alabama

On September 29 and 30, a 24-year-old woman residing in Barbour County, Alabama, who was 5-6 weeks pregnant sought care on two occasions at a local hospital emergency department (ED) for subscapular back pain, nausea, vomiting, and paresthesia of the left arm. She was treated for musculoskeletal pain and released. She returned to the ED on October 1 and was referred to a regional hospital for complaints of left-sided chest pain. While in the ED at the regional hospital, she had onset of seizures followed by multiple episodes of projectile vomiting and was admitted to the hospital. Initially, she was alert, but shortly after admission she required intubation and ventilation for respiratory distress and had a spontaneous abortion. On October 2, clinical conditions included acute respiratory distress syndrome, frequent seizures, severe rhabdomyolysis and compartmental syndrome requiring a fasciotomy, and acute renal failure.

On October 6, nasal and vaginal cultures were positive for Candida albicans and C. tropicalis. Coxsackie B6 virus titer was 16:1, and B1 was 8:1; all other coxsackie viral titers were negative. All other cultures and serologic tests for viral and bacterial cultures were negative.

She developed disseminated intravascular coagulation and multiorgan failure; she died on October 11. Autopsy results indicated evidence of disseminated candidiasis and mucormycosis, which were attributed to antibiotic and steroid therapy.

On December 2, intracytoplasmic structures (Negri bodies) were identified in tissue samples sent to the Armed Forces Institute of Pathology. On December 12, the fixed tissues analyzed at CDC were positive by immunofluorescence for rabies. Nucleotide sequence analysis identified a variant of rabies virus associated with the Mexican free-tailed bat (Tadarida braziliensis).

From 1987 through the onset of her illness, the woman frequently removed and discarded dead or dying bats from a chimney in the facility where she worked. On December 14, Alabama health department investigators retrieved five live bats (all Mexican free-tailed bats) from the facility's fireplace; three tested positive for rabies, and the rabies virus variants were identical by sequence analysis at CDC to the rabies variant isolated from the decedent.

Rabies postexposure prophylaxis was administered to 99 persons (four staff of the local hospital, 78 staff of the regional hospital, seven co-workers, three staff at a dental clinic where the patient had received treatment on September 18, two staff of the state forensic laboratory, one mortician, and four family members and friends). Tennessee

On November 8, a 42-year-old woman from Cumberland County, Tennessee, visited a local physician because of an illness characterized by influenza-like symptoms. Possible herpes zoster was diagnosed, and antibiotics and symptomatic treatment were prescribed. On November 10, she sought care at a local ED for recurring upper back pain, left-sided chest pain, and left arm paresthesia. Bronchitis with pleurisy was diagnosed, and she received outpatient treatment with antibiotics and analgesics. On November 12, she visited a different ED with complaints of chest and breast numbness and was released without further treatment. On November 13, she returned to the first ED complaining of shaking and numbness. Anxiety and lower back strain were diagnosed; she was given hydroxyzine pamoate and prescriptions for cyclobenzaprine and naproxen and released.

On November 14, she was transported by ambulance from her home to a local hospital because of shaking, abdominal cramps, headache, and lower back pain. She was febrile (101.5 F {38.6 C}) and, except for coarse shivering and general myoclonic activity, had a normal neurologic examination. Because of continued myoclonic activity and elevated temperature, on November 15 she was transferred to a regional hospital with a diagnosis of aseptic meningitis. On arrival, she was alert and oriented, with a normal mental status examination; later that day, she had generalized tonic-clonic seizures with respiratory arrest, and she was intubated and mechanically ventilated under pharmacologically induced paralysis and sedation.

Evaluation during November 14-19 included a normal computerized cranial tomography. On November 19, neurologic examination revealed loss of pain and corneal reflex responses, although her pupils still responded to light. On November 21, rabies was suspected, and corneal impressions were sent to the state laboratory for rabies testing. She died on November 23.

On November 22, the corneal impressions were positive for rabies virus by immunofluorescence, and on November 30 brain tissue obtained at autopsy revealed the presence of rabies virus. Nucleotide sequence analysis at CDC identified a rabies virus variant associated with silver-haired bats (Lasionycteris noctivagans).

In an interview on November 15, the patient denied any animal bites or history of international travel. She had kept many pets (including 18 dogs, five cats, and three horses); rabies vaccinations had not been administered to seven dogs, two cats, and all three horses. Family members denied any deaths among these animals during the 2 years preceding her illness.

Rabies postexposure prophylaxis was administered to 47 persons (35 health-care providers, eight family members and friends, and four co-workers). Texas

On November 13, a 14-year-old boy residing in Hidalgo County, Texas, was evaluated in a local ED for sore throat and dyspnea. Upper respiratory infection was suspected, and he was released with a prescription for amoxicillin. On November 14, his family noted changes in behavior (alternating hyperactivity and withdrawal). Following an episode of apparent seizure but no loss of consciousness, he was transported to his physician's office and then to the ED where he was admitted for acute central nervous system deterioration.

On admission, he was hyperventilating, incoherent, and hallucinating, and he required suctioning for oral secretions; physical examination findings included fever (104 F {40 C}), tachycardia, and hypotension (blood pressure: 96/46 mm Hg). He was transferred to an intensive-care unit where he was intubated and pharmacologically paralyzed.

The primary diagnosis was meningitis, but encephalitis and brain abscess also were considered; treatment included cefotaxime sodium, metronidazole, and acyclovir. Because of his rapidly deteriorating clinical status, on November 14 he was transferred to a tertiary-care facility where fluctuating fever and cardiovascular instability necessitated treatment with both vasopressors and dilators. On November 16, massive rhabdomyolysis occurred (serum creatinine phosphokinase: 69,000 international units {IU}/L {normal: 12-70 IU/L}), and he developed renal failure requiring dialysis. On November 23, rabies was suspected, and serum and cerebrospinal fluid (CSF) were obtained for antibody testing; saliva and a skin biopsy specimen from the nape of the neck also were obtained. The patient died on November 27.

Although the serum and CSF specimens were negative for evidence of rabies, a postmortem skin biopsy specimen (obtained November 28) and saliva samples (obtained November 30) were both positive for rabies virus at state laboratories and CDC. Nucleotide sequence analysis at CDC identified a rabies virus variant associated with Texas coyote/border dogs.

The patient had no known history of exposure to rabies. However, family members reported that he had been given a 3-week-old puppy in late September 1994. The puppy had onset of a diarrheal illness 2 weeks later and died after 1 week. The puppy's mother had been properly vaccinated in July 1994 and remained healthy, as did four littermates.

Rabies postexposure prophylaxis was administered to 54 persons (28 health-care providers at the tertiary-care facility, 10 at the local hospital, 13 family and friends, and three persons who had had contact with the puppy before its death). Reported by: CL Coe, MD, NC Carroll, MD, PN Zenker, MD, Flowers Hospital, Dothan; WB Johnston, DVM, SG Thompson, JP Lofgren, MD, State Epidemiologist, Alabama Dept of Public Health. JS Adams, MD, J King, MD, St. Mary's Medical Center, S Hall, MD, Knox County Health Dept, Knoxville; M Carver, MD, J BeVille, MD, GL Swinger, DVM, KW Gateley, MD, State Epidemiologist, Tennessee Dept of Health and Environment. R Thorner, MD, S Milliken, J Norberg, MD, Southwest Texas Methodist Hospital, San Antonio; M Kelley, MD, L Robinson, DVM, R Chapman, PhD, D Simpson, MD, State Epidemiologist, Texas Dept of Health. Viral and Rickettsial Zoonoses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: In 1994, six rabies-associated deaths (including the three cases described in this report) occurred in humans -- the highest annual number of rabies deaths in the United States since 1979. In each of the three cases described in this report, epidemiologic investigation failed to identify a clear history of animal bite exposure. Clear evidence of an animal bite (as reported by the patient or a family member) was documented for nine (27%) of the 33 human rabies deaths during 1977-1994, compared with 24 (89%) of 27 deaths during 1960-1976. Of the nine bite exposures in cases that occurred during 1977-1994, eight were associated with dogs outside the United States or near the Mexico-U.S. border, compared with five of 24 bite exposures during 1960-1976.

Nucleotide sequence analysis enables the identification of rabies virus variants responsible for human infection and assists in elucidating the circumstances that may have led to virus exposure (1). This analysis has been conducted on specimens from all 18 cases since 1980 for which no animal bite was identified. Of these, 10 (56%) cases were associated with variants present in insectivorous bats; seven (39%) were associated with variants present in domesticated dogs outside the United States or at the U.S.-Mexico border; and one was associated with a variant present in skunks in the south-central United States.

The investigation of the first case described in this report underscores the importance of avoiding contact with downed bats and other wildlife. Bat rabies is enzootic in the United States (2) and has been documented in all 48 contiguous states. Because some bat bites may be less severe -- and therefore more difficult to recognize -- than bites inflicted by larger animals, rabies postexposure prophylaxis should be considered for any physical contact with bats when bite or mucous membrane contact cannot be excluded (3).

Despite the increase in human rabies in 1994, the overall occurrence of human rabies in the United States has declined since the mid-1950s. This trend reflects several factors, including improvements in human postexposure prophylaxis (3) and dog rabies control. Most cases of human rabies in the United States now result from a lack of identification or recognition of risks (e.g., contact with bats) and the failure to administer treatment.

In 1993, the number of reported cases of animal rabies in the United States reached a record level (9495 cases), primarily reflecting the ongoing epizootic of raccoon rabies in the eastern United States and the emergence of coyote rabies in south Texas (2). The estimated cost of human postexposure prophylaxis as a result of potential exposure to these animals is $45 million annually. The cases described in this report and the substantial medical costs associated with prophylaxis emphasize the need for strengthening control and prevention measures, including appropriate vaccination of all dogs and cats (4), consideration of rabies in the differential diagnosis early in the course of neurologic disease of unknown origin, avoidance of stray and wild animals by humans and pets, and consideration of postexposure prophylaxis for persons potentially exposed to bats even where a history of physical contact cannot be elicited.

References

1. Smith JS, Orciari LA, Yager PA, Seidel HD, Warner CK. Epidemiologic and historical relationships among 87 rabies virus isolates as determined by limited sequence analysis. J Infect Dis 1992;166:296-307.

2. Krebs JW, Strine TW, Smith JS, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1993. J Am Vet Med Assoc 1994;205:1695-1709.

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

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

   
   

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