Human Rabies --- Missouri, 2008

On November 24, 2008, the Missouri State Public Health Laboratory notified CDC of suspected rabies in a man aged 55 years from Missouri. The man had been bitten by a bat 4--6 weeks before symptom onset and had not sought medical care at the time of the bite. After visiting two emergency departments (EDs) with symptoms consistent with rabies, he was hospitalized on November 23 and treated using the Milwaukee protocol (1). On November 26, infection with a rabies virus variant associated with silver-haired bats was confirmed. The patient died on November 30. This report summarizes the patient's treatment and clinical course. The report highlights the importance of raising public awareness of rabies, particularly the risk for rabies after bat and other wildlife exposures. Health-care providers should maintain a high clinical suspicion for rabies in patients with a recent animal bite history and unexplained encephalitis.

Case Report

On November 19, a man in Missouri aged 55 years experienced pruritus on his left ear that spread to his left face and arm. On November 21, he began experiencing mild chest pain and went to a local ED. He was evaluated by electrocardiogram and cardiac enzymes; findings were negative for acute myocardial infarction. He was discharged with instructions to return if symptoms worsened. On November 22, the patient returned to the ED with panic attacks and anxiety associated with swallowing water. He reported that he had been bitten by a bat on the left earlobe 4--6 weeks earlier. He was treated with rabies post-exposure prophylaxis (PEP) consisting of 15.4 mL of rabies immune globulin and 1 mL of rabies human diploid cell vaccine, administered a tetanus-diphtheria vaccine booster, and released.

The next day, on November 23, the man visited a second ED because of continuing chest pain and new numbness of the left ear and face. He also reported difficulty in swallowing water. He told the ED physician that he had been bitten on the left ear by a bat and that he had received rabies PEP the previous day. He also reported a history of chronic neck and back pain that occasionally featured numbness. The physician told the patient that the PEP he had received was appropriate, but that it might not be helpful if it was administered late in the course of rabies disease. Before releasing him from the ED, the physician advised the patient that he should seek medical attention if his symptoms progressed.

Later the same day, the patient returned to the ED complaining of dehydration. ED staff members observed that he became anxious when he tried to drink fluids offered to him. The next day, on November 24, he was transferred to a tertiary-care facility. The differential diagnoses on admission included rabies and other causes of infectious meningitis and encephalitis. A lumbar puncture yielded cerebrospinal fluid (CSF) with glucose of 78 mg/dL (normal = 50--80 ng/dL), protein 39 mg/dL (normal = 15--45 mg/dL), six red blood cells/mm3 (normal = 0), and one white blood cell /mm3 (normal = 0--3 cells/mm3); differential showed lymphocytic predominance of 68%, 26% monocytes, and 6% neutrophils. Complete blood cell count, metabolic panel, drug screen, and computerized tomography scan of the head were unremarkable. Serum, CSF, nuchal skin biopsy, and saliva were collected and submitted on November 24 to CDC, where a rabies diagnosis was confirmed on November 26. Viral antigen and RNA were detected by CDC in the skin biopsy by direct fluorescent antibody testing and reverse transcription--polymerase chain reaction (RT-PCR), respectively. Viral RNA also was detected in the patient's saliva by RT-PCR. Serum was positive for neutralizing antibodies against rabies by rapid fluorescent focus inhibition test (RFFIT), and CSF was negative by RFFIT and indirect fluorescent antibody. Rabies viral RNA amplified by RT-PCR was typed as a variant common to silver-haired bats (Lasionycteris noctivagans).

On November 25, the patient began rabies treatment using the Milwaukee protocol (1), which included coma induction and administration of amantadine. On the following day, he became bradycardic and hypotensive and was administered atropine and dopamine. On November 28, the dopamine was replaced with norepinephrine for persistent hypotension and bradycardia. The patient received diuretics because of signs of increased intracranial pressure. On November 29, his hypotension worsened, he developed oliguric acute renal failure with lactic acidosis and was placed on dialysis. When signs of increased intracranial pressure herniation were detected on November 30, the family elected to withdraw life support, and the patient died shortly thereafter. Autopsy confirmed the suspected cerebellar tonsillar herniation and moderate bilateral uncal herniation. On histological examination, multiple neurons had eosinophilic cytoplasmic inclusion bodies, particularly in specimens from the hippocampi, nucleus basalis, and Purkinje cells.

Public Health Investigation

On November 23, the Texas County Health Department (TCHD) was notified of a suspected rabies patient and informed the Missouri Department of Health and Senior Services on November 24. After CDC confirmed on November 26 that the patient had rabies, TCHD initiated interviews with family, friends, and hospital personnel to clarify the patient's exposure history and determine whether any contacts of the patient required rabies PEP according to Advisory Committee on Immunization Practices (ACIP) criteria. The family described an encounter with a bat that had occurred at their home approximately 4--6 weeks before onset of symptoms. Family members reported that they saw the bat in the rafters of the front porch for several days before it flew into the house. The patient caught the bat and allowed it to crawl up his arm and neck, and it bit him on the left ear. At the time of the bite, he mentioned to his family the possibility of rabies transmission from bats, but did not report the incident to public health authorities or seek medical evaluation. Instead, the patient, an avid outdoorsman who had kept many wild animals as pets, left the bat unrestrained in the house for 2 days. When the bat appeared to be well after that period, he released it outside.

Four family members and friends were identified who might have been exposed to saliva from the patient or the bat. All four received rabies PEP beginning on November 26. Among approximately 40 health-care workers who had administered care to the patient in the EDs and at the tertiary-care facility, only one was deemed to meet the ACIP guidelines for PEP, because that person had not worn gloves when examining the patient's mouth. The patient owned a dog and cat, which might have been bitten by the bat. The dog, which had been vaccinated against rabies, received a rabies vaccine booster and was placed under a 45-day home quarantine. The cat, which had never been vaccinated against rabies, was immunized and placed under 6-month quarantine at a local veterinary facility. Neither the animals nor the humans who received PEP in connection with this case have developed any signs or symptoms of rabies infection.

Reported by: HL Pue, DVM, G Turabelidze, MD, S Patrick, PhD, A Grim, MPH, Missouri Dept of Health and Senior Svcs; C Bell, V Reese, Texas County Health Dept; R Basilan, MD, Univ Hospital, Columbia, Missouri. C Rupprecht, VMD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; K Robertson, DVM, EIS Officer, CDC.

Editorial Note:

The death described in this report illustrates the importance of promptly seeking medical evaluation after any potential bat exposure (i.e., any direct contact between a human and a bat) regardless of the health of the bat. Rabies is preventable if rabies immune globulin and vaccine are administered soon after an exposure (4). Bat exposures are of special concern because of the higher risk associated with bat exposures and because the wounds they inflict often are minor and easily overlooked. For bat contacts, even finding a bat in the same room might qualify as a potential exposure if the person might be unaware that a bite or direct contact had occurred (e.g., a deeply sleeping person awakens to find a bat in the room, an adult sees a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person), although such situations should not be considered exposures if rabies can be ruled out by diagnostic testing of the bat, or circumstances suggest it is unlikely that an exposure took place (4).

Once symptoms begin, rabies has no standard treatment and is nearly always fatal. The Milwaukee protocol is an experimental treatment for rabies that was first used in 2004 as therapy in a Wisconsin patient who recovered from the disease (1). Subsequent attempts to treat rabies patients have been unsuccessful in North America (5,6); however, initial recovery was noted in one patient in Equatorial Guinea, whose subsequent death was attributed to malnutrition rather than rabies (7).

The case described in this report is the first case of human rabies in Missouri since 1959. During 2000--2008, a total of 27 human rabies cases were reported in the United States and Puerto Rico, including six cases acquired overseas. Among the 21 domestically acquired cases, 19 (90%) were associated with bat variants of the rabies virus. In Missouri, principal reservoirs of rabies are bats and skunks (8). The bat that exposed the patient in this report should have been submitted for testing. All bats or wild terrestrial carnivores implicated in a possible rabies exposure should be euthanized and tested for rabies. Testing ensures that rabies PEP can be administered in time to prevent disease, if needed, or that unnecessary PEP can be avoided. The public should be educated that wild animals often mask outward signs of rabies illness, and that observation, as used in this case, is not a recommended method to rule out rabies. Health-care providers should include rabies in the differential diagnosis of any patient with a recent animal bite history and unexplained encephalitis, and laboratory diagnosis should be pursued promptly.

Five contacts of the patient in this report received PEP. Of these five persons, only one was a health-care worker. A review of human rabies cases during 1980--1996 found that a median of 54 contacts (range: 4--179) received PEP per case (3). According to indications for rabies PEP described by ACIP (4), few if any health-care workers in facilities that consistently use standard infection-control measures would be expected to require PEP.

Public education remains an important part of rabies prevention. Persons who are unvaccinated against rabies or lack appropriate training should be warned against handling bats (4). Campaigns aimed at elevating rabies awareness also should address misconceptions and attitudes that can lead to a lack of timely responsiveness to rabies virus exposures.

Acknowledgments

This report is based, in part, on contributions by staff members of the Texas County Health Dept, Houston, Missouri; and J Blanton, MPH, and A Vellasco, PhD, Rabies Laboratory, CDC.

References

1. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508--14.
2. Wilde H. Failures of post-exposure rabies prophylaxis. Vaccine 2007;25:7605--9.
3. Noah DL, Drenzek CL, Smith JS, et al. Epidemiology of human rabies in the United States, 1980 to 1996. Ann Intern Med 1998;128:922--30.
4. CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57(No. RR-3).
5. CDC. Human rabies---Alberta, Canada, 2007. MMWR 2008;57;197--200.
6. CDC. Human rabies---Indiana and California, 2006. MMWR 2007;56:361--5.
7. Rubin J, David D, Willoughby RE, et al. Applying the Milwaukee protocol to treat canine rabies in Equatorial Guinea. Scand J Infect Dis 2009;41:372--5.
8. Blanton JD, Robertson K, Palmer D, Rupprecht CE. Rabies surveillance in the United States during 2008. J Am Vet Med Assoc 2009;235:676--89.

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Date last reviewed: 11/5/2009