Human Rabies --- Minnesota, 2007

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On October 20, 2007, a Minnesota resident died from rabies, approximately 1 month after initial symptoms of limb paresthesia, which progressed to flaccid weakness and ataxia. This was the only human rabies case reported in the United States in 2007. A presumptive diagnosis of idiopathic transverse myelitis was considered initially, because of abnormalities detected via spinal cord imaging studies and a lack of laboratory confirmation of a specific infectious etiology. The presumptive diagnosis subsequently was changed to include rabies, based on the patient's rapidly deteriorating neurologic status and elicitation of a history involving bat exposure during the month before illness onset. This report summarizes the medical and epidemiologic investigation by the Minnesota Department of Public Health and CDC and the ensuing public health response. The findings underscore the need for early inclusion of rabies in the differential diagnosis of rapidly progressive encephalitis, improved public awareness of the risks associated with animal bites, and appropriate rabies prophylaxis after exposure.

Case Report

On September 19, 2007, a man aged 46 years visited an outpatient facility with paresthesia in his right hand. During the next 3 days, the paresthesia spread proximally, and the patient developed flaccid weakness in the right upper extremity. Electromyography (EMG) performed at a local outpatient facility on September 24 revealed evidence of axonal nerve damage. Within 3 days, the patient developed paresthesia and weakness in his left upper extremity and gait unsteadiness. Magnetic resonance imaging (MRI) of the brain on September 28 was unremarkable, but MRI of the cervical spine showed central spinal cord T2-signal abnormalities with associated edema spanning the C3 to C6 levels, suggestive of an inflammatory process.

On September 29, the patient had a fever of 101.1°F (38.4°C) and was hospitalized. He developed double vision, tremulousness, and rapidly progressive respiratory failure, which required intubation and ventilator support the next morning. He had no laryngospasm or dysphagia. Analysis of cerebrospinal fluid (CSF) by lumbar puncture revealed a pleocytosis of 12 cells/mm³ (normal: 0--5 cells/mm³), 85% lymphocytes, elevated protein of 107 mg/dL (normal: 15--45 mg/dL), normal glucose, and negative bacterial culture and acid-fast bacilli screening. West Nile virus and herpes simplex virus testing of the CSF were negative by polymerase chain reaction (PCR). Additional CSF studies were negative for cryptococcal antigen, antibody for syphilis, and Lyme disease antibody. The patient's serum was negative for evidence of antinuclear antibodies, extractable nuclear antibodies, or antibody to West Nile virus, Borrelia sp., Treponema pallidum, Mycoplasma pneumoniae, human T-lymphotropic virus I and II, human immunodeficiency virus, and hepatitis A, B, and C viruses. Because his clinical and laboratory profiles were suggestive of idiopathic transverse myelitis, he was treated with intravenous methylprednisolone.

The patient's symptoms did not improve, and his fever reached 102.7°F (39.3°C). In three procedures, MRI of the brain did not demonstrate significant abnormalities, but MRI of the spinal cord revealed progressive extension of the previously detected cervical segment abnormalities. He became comatose on October 5 and had no clinical evidence of cranial nerve function except infrequent spontaneous respiration. A repeat lumbar puncture showed a normal white blood cell count of 1 cell/mm³, elevated protein of 75 mg/dL, normal glucose, and eight unique oligoclonal bands by electrophoresis (normal: none), indicative of immunoglobulin production by plasma cells and central nervous system disease. The CSF immunoglobulin G synthesis rate by spectrophotometry was borderline elevated at 12.04 (normal: <12), consistent with an ongoing inflammatory process. Bacterial cultures of CSF remained negative, and additional CSF evaluation showed negative viral PCR tests for cytomegalovirus, Epstein-Barr virus, enterovirus, and herpes simplex virus. Analysis of CSF also was negative for neuromyelitis optica antibody, associated with Devic's disease. Repeat neuroimaging on October 7 revealed further caudal to rostral progression of the brainstem and spinal cord abnormalities observed on October 5. Because of progressive neurologic decline, the patient was transferred to a tertiary-care center.

On arrival at the tertiary-care center, the patient was comatose with a Glasgow coma score of 3 without demonstrable cranial nerve function. A neurologic examination revealed flaccid quadriparesis and hyporeflexia. EMG revealed severe, acute polyradiculoneuropathy. Auditory evoked potential testing indicated absent responses. With the presumptive diagnosis of idiopathic transverse myelitis, the patient was treated with methylprednisolone and plasmapheresis. On October 15, CSF analysis revealed a pleocytosis of 22 cells/mm³ (94% lymphocytes), red blood cell count of 2,519 cells/mm³ (normal: 0 cells/mm³), elevated protein of 235 mg/dL, normal glucose, and further elevated immunoglobulin G synthesis rate of 43 mg/24 hours (normal: -9.9 to 3.3 mg/24 hours). MRI of the brain revealed new symmetric T2-signal abnormalities within the basal ganglia and medial temporal lobes, with subtle leptomeningeal gadolinium enhancement. The ascending paralysis and coma appeared atypical of idiopathic transverse myelitis, and the patient's clinical progression and brain imaging abnormalities were noted to resemble those observed in rabies encephalitis (1).

Once rabies was suspected, the patient's family was interviewed on October 16 for a history of potential exposure. According to his family, the patient had handled a bat with his bare hands in a semi-open cabin porch in north-central Minnesota on August 19, 2007. He had reported feeling a needle prick sensation before releasing the bat. Because no blood or wound was visible, the patient concluded he had not been bitten and did not seek medical attention. Neither the patient nor his family was aware that this exposure constituted a rabies risk.

On October 17, specimens of the patient's serum, CSF, saliva, and a nuchal biopsy were sent to CDC. Rabies virus antibodies were detected in stored CSF and serum samples collected before plasma exchange, confirming the suspected diagnosis. However, no rabies virus antigens were detected in the skin biopsy using fluorescent microscopy, and no rabies virus amplicons were detected in saliva or skin biopsy samples by reverse transcription--PCR; therefore, antigenic characterization and genetic sequencing of the rabies virus variant were not possible. Because of the poor prognosis, medical care was withdrawn after extended family discussions, and the patient died on October 20, the twenty-second day of hospitalization.

Public Health Investigation

After diagnosis of rabies, the Minnesota Department of Health assessed the need for rabies postexposure prophylaxis (PEP) among close contacts of the patient and health-care workers and searched the likely site of rabies exposure. Family members, other close contacts, and health-care workers were interviewed using a standard questionnaire to identify possible exposures to the patient's saliva. Three of 14 family contacts and 51 of 524 health-care workers who participated in the man's care received rabies PEP, administered chiefly at the respective hospital emergency departments. The Minnesota Department of Health received no information from health-care providers suggesting incomplete PEP administration or adverse events resulting from rabies vaccination. Although a search of the cabin site on October 26 revealed no evidence of bat infestation, given the reported bat exposure on August 19, initial symptoms on September 19, and an incubation period of approximately 1 month, investigators concluded that a bite from a bat was the most likely source of rabies virus infection.

Reported by: AH Yee, DO, RT Merrell, MD, AY Zubkov, MD, PhD, AJ Aksamit, MD, WT Hu, MD, PhD, EM Manno, MD, Mayo Clinic, Rochester; J Scheftel, DVM, A DeVries, MD, D Neitzel, MS, R Danila, PhD, KE Smith, DVM, PhD, Minnesota Dept of Health. CE Rupprecht, VMD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; S Holzbauer, DVM, EIS Officer, CDC.

Editorial Note:

This report describes the only reported case of human rabies in the United States in 2007 and the first case in Minnesota since 2000. Investigators determined that the likely source of rabies in this case was a bat. In Minnesota, bats and skunks are the only known reservoirs of rabies. In 2006, 42 rabid animals were reported in the state, including 17 bats and 20 skunks (2).

During 2000--2007, a total of 25 cases of human rabies were reported in the United States (2). Eighteen (28%) cases were associated with suspected exposure to rabid bats or infection with bat rabies virus variants. Most of these human cases occurred in late summer or early autumn, coincident with a seasonal increase in the prevalence of rabid bats detected in the United States (2). Despite repeated documentation of human rabies attributable to bat exposures and identification of 1,212--1,692 rabid bats in the United States during 2000--2006, the significance of bat exposures often is ignored (3,4).

The animal contact, incubation period, clinical presentation, and laboratory findings for the patient described in this report were typical of human rabies cases reported in the United States. However, a diagnosis of rabies was not considered until the clinical course appeared atypical of the presumptive diagnosis of idiopathic transverse myelitis and brain imaging abnormalities resembled those observed in rabies. One unusual facet of this case was the inability to detect viral antigens or nucleic acids in patient samples, although rabies virus antibodies were identified in the serum and CSF. The only other human rabies case in the United States in which viral antigens or nucleic acids could not be detected, since such laboratory methods became more widely available in the early 1990s, was a 2004 Wisconsin patient, who survived rabies after a bat bite (1,5). However, the Wisconsin patient was an adolescent girl treated successfully with a drug-induced coma and antiviral drugs, and the significance of any similarities between that case and the Minnesota case is unclear.

This report underscores the need for increased public awareness of the risks of direct contact with bats and other wild animals. After exposure, human rabies is preventable with timely and appropriate PEP, consisting of proper wound care and prompt administration of rabies biologicals (4). Rabies PEP is recommended for all persons with direct transdermal or mucous membrane exposure to a bat, unless the animal is found not to have rabies. However, bite lesions from certain animals, including bats, can be difficult to detect. Consequently, proper tailoring of health communications to medical practitioners and the public remains a challenge to ensure that appropriate PEP is administered when indicated but not unnecessarily.

Rabies should be considered in the differential diagnosis of human cases involving acute, rapidly progressive encephalitis, especially when the clinical course and neuroimaging findings are compatible, regardless of history of animal exposure (1,4). If a patient is unresponsive, interview of family members and close contacts might reveal potential exposures. Prompt diagnosis of rabies can enable rapid case investigation, implementation of appropriate infection-control measures, and consideration of experimental therapy (5).

The findings in this report are based, in part, on contributions by M Junna, MD, A Frye, MD, Mayo Clinic, Rochester, Minnesota; and R Franka, DVM, PhD, M Niezgoda, MS, L Orciari, MS, and P Yager, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC.

References

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