Case Report

On May 3, 2017, a woman aged 65 years with no preexisting health conditions began experiencing pain and paresthesia in her right arm while gardening. On May 6, the patient sought care at an urgent care facility for the arm pain. She received a diagnosis of carpal tunnel syndrome and was prescribed a nonsteroidal anti-inflammatory drug and hydrocodone. On May 7, she was evaluated at hospital A with shortness of breath, anxiety, insomnia, and difficulty swallowing water. The patient expressed concern about exposure to a toxic substance. Diagnostic test results including complete blood count, serum chemistry, D-dimer (to rule out thromboembolism), troponin, magnesium, electrocardiogram, and chest radiographs were unremarkable. She was given 0.75 mg of lorazepam for a presumed panic attack and discharged. Upon entering the car, she experienced claustrophobia and shortness of breath and immediately returned to hospital A’s emergency department (ED), where she received an additional 0.25 mg of lorazepam and was again discharged.

On May 8, she was transported from her residence by ambulance to the ED of hospital B with chest discomfort, shortness of breath, progressive paresthesia involving the right shoulder and arm, and increased anxiety. On examination, she was agitated, tachycardic, and intermittently tachypneic. Her neurologic exam was notable for dysmetria (a type of ataxia). Laboratory results were notable for elevated cardiac enzymes, a serum troponin I level of 1.05 ng/mL (normal <0.02 ng/mL), and a serum lactate level of 8.8 mmol/L (normal, 0.7–2.1 mmol/L). Electrocardiogram results* suggested acute cardiac ischemia with atypical chest pain. The patient underwent emergency cardiac catheterization, which indicated normal coronary arteries.

On the evening of May 8, the patient became progressively agitated and combative and was noted to be gasping for air when attempting to drink water. Hospital staff members questioned family about animal exposures, and the patient’s husband reported that she had been bitten on the right hand by a puppy approximately 6 weeks before symptom onset while touring in India. According to the husband, the patient cleaned the wound with the help of the tour operator but did not seek further medical treatment. The patient had no record of a pretravel health screening, did not receive rabies preexposure vaccination before the trip, nor had she ever been vaccinated against rabies.

On the morning of May 9, the patient required endotracheal intubation and mechanical ventilation for increasing somnolence, oral secretions, and oxygen desaturation; peak axillary temperature was 100.6°F (38.1°C). Electroencephalography demonstrated low-amplitude unreactive delta activity suggestive of severe encephalopathy. In light of the concern for human rabies, the patient was sedated with ketamine and midazolam, and the Virginia Department of Health was notified; because rabies PEP is ineffective for treatment of rabies and not indicated after the onset of symptoms, PEP was not administered. A lumbar puncture was performed. Cerebrospinal fluid (CSF) lactate was elevated (2.6 mmol/L; normal = 0.5–2.2 mmol/L), and CSF white blood cell count was 1 cell/μL (normal = 0–5 cells/μL) with 19% polymorphonuclear leukocytes and 81% mononuclear leukocytes, consistent with encephalitis. CSF, serum, saliva, and nuchal skin biopsy specimens were collected on May 9 and submitted to CDC for rabies testing on May 10.

On May 11, rabies was confirmed by the detection of rabies virus RNA by real-time reverse transcription polymerase–chain reaction (real-time RT-PCR) in saliva and skin biopsy specimens, and rabies virus antigen by direct fluorescent antibody testing of the skin biopsy (Table 1). No antirabies virus antibodies were detected in serum or CSF. Sequencing of the virus identified a canine rabies virus variant associated with dogs in India.

On May 13, the full Milwaukee protocol (an experimental protocol for persons with rabies that has demonstrated inconsistent, rare success) (1) was implemented with the addition of favipiravir (2). On May 15, the patient developed profuse oral secretions. On May 17, aggressive titering of ketamine and midazolam was initiated to address increased agitation, and dexmedetomidine was started to limit sympathetic responses during weaning. On May 18, repeat CSF studies continued to demonstrate no white blood cells, normal protein level of 36.0 mg/dL, and a normalized lactate level of 2.2 mmol/L. Interferon beta was started May 18 in the hope of stimulating an immune response; however, repeat CSF analysis demonstrated no evidence of antirabies virus antibodies (Table 1). Rabies virus nucleic acid was again detected in saliva by real-time RT-PCR on May 19. On May 21, the family decided to withdraw advanced medical support, and the patient died shortly thereafter. Rabies virus was isolated from brain tissue postmortem.