Human Rabies --- Iowa, 2002

On September 28, 2002, a man aged 20 years residing in Linn County, Iowa, died from rabies encephalitis caused by infection with a variant of rabies virus associated with silver-haired (Lasionycteris noctivagans) (Figure) and eastern pipistrelle (Pipistrellus subflavus) bats. This is the first case of human rabies in Iowa since 1951. This report summarizes the investigation of the case by the Linn County and Iowa public health departments. Bats found in living quarters should be submitted to local public health laboratories for rabies testing.

On September 16, the man sought care at the emergency department of a Cedar Rapids hospital complaining of nausea and vomiting, generalized abdominal pain, shortness of breath, headache, and back stiffness. He reported drinking numerous beers and expressed a concern about alcohol poisoning. The patient was treated with an antiemetic and discharged with prescriptions for antianxiety and antinausea medications. He returned later the same day for reevaluation but left without being seen. He returned again the next day complaining of the same symptoms, at which time he was noted to be hostile, paranoid, and hallucinating. He was admitted to the hospital with a diagnosis of suspected drug reaction or withdrawal syndrome. Brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) performed during the first 24 hours of hospitalization were normal, and the patient received multiple doses of sedative-hypnotic drugs for treatment of agitation. His condition deteriorated with development of fever of 101.5^º F (38.6^º C) and increasing tremors, followed by intractable seizure requiring intensive care. On September 19, he was placed on ventilator support. He received empiric therapy for encephalitis, including acyclovir and ceftriaxone, and multiple anticonvulsants. On September 23, the patient had evidence of profound neurologic impairment with fixed and unreactive pupils, and repeat neuroimaging showed early herniation. A surgical procedure to decrease intracranial pressure was performed, and a brain biopsy (occipital lobe) was taken. Contact and droplet precautions were initiated after the procedure. On September 28, ventilator support was withdrawn, and the patient died.

On September 25, clinical specimens, including occipital lobe biopsy tissue impression slides, cerebrospinal fluid, and saliva, were submitted for rabies virus evaluation to the University of Iowa Hygienic Laboratory (UHL). Direct fluorescent antibody (DFA) staining of the occipital lobe biopsy slides was inconclusive but suggestive of rabies infection. A subsequent nuchal biopsy, taken on September 27 and sent to CDC laboratories, was strongly positive by DFA for rabies virus antigen and was positive by reverse transcription polymerase chain reaction (RT-PCR) for rabies virus RNA. The virus variant involved in this infection was determined by DNA sequence analysis to be most similar to variants found in silver-haired and eastern pipistrelle bats. The diagnosis was confirmed postmortem at UHL by DFA examination of specimens from the brain stem and cerebellum.

The source of the patient's infection remains unclear. No specific history of exposure to bats was reported. The patient had been bitten by a dog approximately 12 days before admission; the animal was determined to be free of rabies. No evidence of bat infestation in the patient's house was found, and family and friends did not recount any episodes of potential contact between the patient and bats.

The patient apparently was healthy before this incident. A substantial portion of the patient's social activity occurred during evenings, and preliminary investigation suggested that multiple persons could have been exposed to live virus from the patient through shared use of glasses, bottles, cigarettes, and other vehicles for saliva contamination of mucus membranes. The patient was a musician and had traveled to recording studios in several cities in Iowa and Illinois during the prodrome of his illness. Because family members were not able to provide public health authorities with contact information for many of the patient's associates, a decision was made, with consent of family members, to release the patient's name to the media to facilitate contact tracing and screening for rabies post-exposure prophylaxis (PEP). County public health staff also attended funeral services to counsel associates of the patient who had not yet come forward. A total of 53 family members or associates of the patient received PEP. No persons with potential exposure outside of the Cedar Rapids area were identified.

Several hospital staff also reported potential exposure to the patient's bodily fluids before isolation precautions were initiated. Public health officials presented information to potentially exposed employees on September 30. Hospital staff were requested by hospital administrators to make their own risk assessment and decision about starting PEP based on the information provided. A total of 71 hospital staff, including five physicians, received PEP.

Reported by: F Franks, DO, St. Luke's Hospital, Cedar Rapids; M Gilchrist, PhD, R Groepper, M Pentella, PhD, Univ of Iowa Hygienic Laboratory, Iowa City; R Currier, DVM, P Quinlisk, MD, C Lohff, MD, Iowa Dept of Health. C Rupprecht, VMD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; MG Reynolds, PhD, T Boo, MD, EIS officers, CDC.

Editorial Note:

Incidence of human rabies in the United States has declined sharply during the last several decades, from an average of 11 persons per year in the 1950s to fewer than three persons per year during the 1990s (1,2). This decline is associated largely with successful control of rabies in domestic dogs. Nonbite-associated (i.e., cryptic) cases of rabies --- those cases for which no evidence or history of animal bite is established (3) --- now constitute the largest category of human rabies cases in the United States (78% of all cases occurring during the 1990s compared with 23% during the 1950s). A history of animal bite was reported in only seven of the last 35 documented human rabies cases (five dog bites acquired overseas and two bat bites acquired domestically). The high proportion of cases that are reported as cryptic probably is attributable to several factors, including the difficulties associated with obtaining detailed exposure histories from neurologically impaired patients and the possibility that bites from very small mammals, such as bats, might go unnoticed.

Molecular typing of viral RNA obtained from clinical specimens permits rapid identification of the virus variant involved in the infection, but virus typing in the absence of specific exposure history cannot identify the source of human rabies infections definitively. Variants specific to one vertebrate host can be found in animal species other than that of their natural reservoir; for example, bat-variant rabies viruses have been found in domestic cats (4). However, virus typing provides a valuable epidemiologic clue to the source of an infection and is important for targeting prevention efforts. In the case described in this report, the rabies virus type was determined to be most similar to that found naturally in silver-haired and eastern pipestrelle bats, which range widely throughout North America, including Linn County. Both are solitary, forest-dwelling animals not found commonly in human dwellings.

This is the third report of human rabies published during 2002 (5,6). All were attributed to viruses identified as bat variants (two silver-haired/eastern pipistrelle variant and one Mexican free-tail variant); none of the three cases had a specific history of bat bite recorded. Of 35 human rabies deaths recorded since 1990 in the United States, 26 (74%) have been associated with bat-variant rabies viruses, but in only two cases was a bite history documented (2). Human rabies is preventable with properly performed and timely administration of rabies PEP (7). However, prevention efforts are complicated if the patient does not recognize that an exposure has occurred.

Although bats have an important role in local ecosystems, they can be a source of rabies infection in humans. Messages to the public should emphasize that bats can transmit rabies virus to humans. Bats should be excluded from human living quarters and should never be handled with bare hands. When a bat is found in living quarters and the possibility exists that an unrecognized exposure has occurred, the animal should be submitted to a local public health laboratory for diagnostic testing. Testing of suspect animals ensures rapid PEP where indicated and minimizes unnecessary prophylaxis in persons not exposed to rabies virus.

Acknowledgments

This report is based on data reported by K Erickson, Linn County Public Health Dept, Iowa. C Hanlon, VMD, L Orciari, MS, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

References

1. Anderson LJ, Nicholson KG, Tauxe RV, Winkler WG. Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis, and prevention. Ann Intern Med 1984;100:728--35.
2. Krebs JW, Noll HR, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 2001. J Am Vet Med Assoc 2002;221:1690--701.
3. Messenger SL, Smith JS, Rupprecht CE. Emerging epidemiology of bat-associated cryptic cases of rabies in the United States. Clin Infect Dis 2002;35:738--47.
4. Mcquiston JH, Yager PA, Smith JS, Rupprecht CE. Epidemiologic characteristics of rabies virus variants in dogs and cats in the United States, 1999. J Am Vet Med Assoc 2001;218:1939--42.
5. CDC. Human rabies---California, 2002. MMWR 2002;51:686--8.
6. CDC. Human rabies---Tennessee, 2002. MMWR 2002;51:828--9.
7. CDC. Human rabies prevention---United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(No. RR-1).

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