Human Rabies --- Virginia, 2009

On October 28, 2009, CDC notified the Virginia Department of Health (VDH) of suspected rabies in a Virginia man aged 42 years. Earlier that day, an infectious disease physician in Virginia had contacted CDC requesting confirmatory diagnostic testing and reported initiating treatment with the Milwaukee protocol (1) after consultation with staff at the Medical College of Wisconsin. This report summarizes the patient's exposure history, clinical course, and treatment, and describes efforts to identify close contacts requiring postexposure prophylaxis (PEP). According to family members, the patient had reported an encounter with a dog while in India approximately 3 months before symptom onset. On October 29, infection with a rabies virus was confirmed by direct fluorescent antibody testing of a nuchal skin biopsy, and reverse transcription--polymerase chain reaction (RT-PCR) typed the virus as a variant associated with dogs in India. The patient died on November 20. Public health authorities conducted rabies exposure assessments of 174 persons associated with the patient, and 32 persons (18%) initiated rabies PEP. This is the seventh case of rabies reported in the United States acquired abroad since 2000. This case highlights the importance of raising public awareness of rabies, particularly the risk for rabies exposures in association with travel to rabies-endemic countries, and the importance of initiating PEP promptly after a potential exposure.

Case Report

On October 23, 2009, a male physician aged 42 years in Virginia experienced the onset of chills and "hot flashes." The next morning, he began experiencing discomfort in his legs, and that evening he developed spontaneous ejaculation occurring up to once per hour, urinary incontinence, and back pain radiating to the left lower extremity. Two days later, on October 26, he visited an ED for assessment. The patient was awake, oriented, and afebrile during this visit. Magnetic resonance imaging of his lumbar spine revealed degenerative disease at L4--L5, and he was discharged with a diagnosis of lumbar back pain, given pain medications, and instructed to follow up with his primary-care physician. That evening he began to gag while drinking and showering. On October 27, the patient contacted his primary-care physician and raised concern about the possibility of rabies. He was referred back to the same ED for evaluation of neurologic disorders, including rabies.

On October 27, the patient returned to the ED and, in addition to the previously noted symptoms, exhibited anxiety and erratic behavior and had involuntary dystonic movements of his upper extremities. The patient reported travel to India approximately 3 months before symptom onset but gave no clear history of animal exposure occurring while in India or in the United States. Physical examination showed tachycardia (134 beats per minute) and elevated blood pressure (153/93 mm Hg) but no fever. The patient was noted to have dystonic movements of the upper extremities and neck and loud involuntary vocalizations. Sensation and motor strength were normal. The patient demonstrated aversion to water when offered. A computed tomography (CT) scan of the head showed only left maxillary sinusitis. The patient was admitted to the hospital (hospital A) with a differential diagnosis that included rabies and other neurologic diagnoses of unknown etiology. Empiric antimicrobial and antiviral therapy for meningioencephalitis was initiated.

Within 24 hours of admission, the patient was noted to be shouting, gagging on copious salivary secretions, and unable to follow commands. His tachycardia and hypertension worsened and, soon after he was transferred to the intensive-care unit, he developed seizures, sustained a cardiac arrest, and required ventilator support. At this time, the patient developed a low-grade fever (99.4°F [37.4°C]). Complete blood count showed mild leukocytosis (15.42 × 109/L [normal: 5--10 × 109/L]), mild hyperglycemia (120 mg/dL [normal: 70--105 mg/dL), and a creatine kinase of >16,000 U/mL (normal: 12--70 U/mL). Urinalysis showed large blood and hyaline casts. Toxicology and heavy metal screenings were unremarkable.

On October 28, the second hospital day, a lumbar puncture showed an elevated cerebrospinal fluid (CSF) glucose of 101 mg/dL (normal: 50--80 mg/dL), normal protein of 31 mg/dL (normal: 15--45 mg/dL), and 6 white blood cells/mm3 (normal: 0--3 cells/mm3). The treating physician initiated the Milwaukee protocol, including ketamine infusion, but in keeping with this protocol, the patient was not given rabies immune globulin, vaccine, or antivirals (1). Serum, CSF, nuchal skin biopsy, and saliva were collected and submitted to CDC for rabies testing. The next day, October 29, CDC detected rabies virus antigen in the skin biopsy by direct fluorescent antibody testing. Rabies viral RNA amplified by RT-PCR was typed as a variant common to dogs in India.

Serial assessments of serum, CSF, and saliva were conducted to monitor for viral clearance. A ventriculostomy drain was placed for continuous monitoring and management of intracranial fluid pressures. With turning and suctioning, the patient experienced asystole. Increasing episodes of asystole resulted in placement of a transvenous pacemaker by hospital day 8. By hospital day 12, the patient developed inappropriate antidiuretic hormone secretion followed by severe central diabetes insipidus treated with desmopressin and continuous vasopressin infusion. By hospital day 15, the patient developed late and marginal antibody response in saliva but never developed neutralizing antibody in CSF, which is necessary for viral clearance and cure. Sedation was tapered over 1 week with clinical evidence of denervation indicated by loss of brain stem reflexes and diminished autonomic dysfunction. The patient died on November 20 (hospital day 25).

Public Health Investigation

VDH and the Fairfax County Health Department (FCHD) were notified of a suspected rabies case on October 28, the patient's second hospital day. FCHD began working with hospital A's epidemiology and occupational health staff to generate a list of potentially exposed hospital employees. In addition, FCHD initiated interviews with family and friends to clarify the patient's exposure history and gather information about persons who had contact with the patient since October 8, the date after which he was considered potentially infectious. According to the patient's father, the patient had an unwitnessed encounter with a dog while he was in India. Family members were unaware of other possible exposures to rabies and did not know if the patient sought medical care or rabies PEP.

The patient was a psychiatrist and worked primarily at a hospital (hospital B), where he supervised psychiatry residents and did not have direct patient contact. He also worked 1 day a week at two additional health-care facilities (facilities A and B). Hospital B is located in the District of Columbia, and the two facilities are located in Maryland. On October 29, VDH contacted the Maryland Department of Health and Mental Hygiene (MDHMH) and the District of Columbia Department of Health (DCDOH) to facilitate assessment of coworkers and patients for PEP according to Advisory Committee on Immunization Practices (ACIP) criteria (2). A survey tool was created to assess health-care contacts, and another questionnaire was developed to assess household contacts and coworkers. A total of 32 (18%) of 174 persons evaluated for potential exposure initiated PEP. No adverse reactions to PEP or additional cases of rabies were reported to public health authorities.

FCHD interviewed all 70 health-care providers who had administered care to the patient in hospital A, and 17 met the criteria for a nonbite exposure to rabies (because of exposure to the patient's saliva). An additional seven assessed persons initiated rabies PEP despite no indication; two had already initiated PEP before the exposure assessment by FCHD. Among the 34 coworkers assessed at hospital B by DCDOH, only one, who identified himself as a close friend of the patient, met the criteria for nonbite exposure and received rabies PEP. MDHMH assessed 37 coworkers and 26 patients associated with facilities A and B. No coworkers or patients at either facility met the criteria for exposure, and none pursued rabies PEP. All six family members and one assessed friend were identified who might have been exposed to saliva from the patient, and all received rabies PEP.

Reported by

P Troell, MD, B Miller-Zuber, MEd, Fairfax County Health Dept; J Ondrush, MD, Inova Fairfax Hospital; J Murphy, DVM, Virginia Dept of Health. N Fatteh, MD, Kaiser Permanente Mid Atlantic, Rockville; K Feldman, DVM, K Mitchell, MPH, Maryland Dept of Health and Mental Hygiene. R Willoughby, MD, Medical College of Wisconsin. C Glymph, MPH, District of Columbia Dept of Health. J Blanton, MPH, C Rupprecht, VMD, PhD, Div of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

Editorial Note

The case described in this report underscores two important aspects of human rabies prevention: 1) the importance of awareness about rabies risks when traveling abroad and 2) the need to seek prompt medical evaluation after an animal exposure (3). Since 2000, seven of the 31 human rabies cases reported in the United States were acquired from exposure abroad; two were acquired in the Philippines (California, 2001 and 2006), and one each were acquired in Ghana (New York, 2000), El Salvador (California, 2004), Haiti (Florida, 2004), Mexico (California, 2008), and India (the 2009 case described in this report) (4). An attempt to treat the patient after the onset of clinical symptoms of rabies using an experimental treatment (the Milwaukee protocol) failed. Prompt administration of rabies PEP after an exposure remains the only documented method for preventing death after an exposure to rabies (2).

Although human-to-human rabies transmission in a health-care setting is theoretically possible, no such occurrence has been documented. Rabies exposure risks for health-care personnel who care for rabies patients include exposure of mucous membranes or open wounds to infectious body fluids or tissue (e.g., saliva, tears, or neurologic tissue). Adherence to standard infection control precautions minimizes the risk for health-care personnel. However, additional precautions, such as wearing face shields when performing higher-risk procedures that can produce droplets or aerosols of saliva (i.e., suction of oral secretions), might be warranted (2). Among the health-care personnel assessed for potential contact in recent human rabies cases in the United States, the proportion that received PEP ranged from 2.5% to 30.0% (5--8). In this report, 34% of health-care personnel received PEP after a potential contact with the patient. However, seven health-care personnel received PEP despite PEP not being recommended after risk assessment. Prompt communication with public health authorities and education of personnel who have contact with a rabies patient is critical to permit appropriate risk assessment and reduce unnecessary PEP (2,9).

Dogs represent the most frequent risk for bite exposures to travelers and should be avoided. Travelers to rabies-endemic countries should be warned about the risk for acquiring rabies and educated about animal bite prevention and appropriate actions to take if an exposure does occur (i.e., wound washing and medical attention to determine if PEP is necessary). Relative rabies risk and recommendations for travelers by region and country can be found in CDC's Health Information for International Travel 2010 (10).

Acknowledgments

The findings in this report are based, in part, on contributions by B Bullock, Fairfax County Health Dept; G Lum, M Hille, District of Columbia Dept of Health; E Jones, Maryland Dept of Health and Mental Hygiene; and F Jackson, MS, L Orciari, MS, S Recuenco, MD, DrPH, P Yager, Div of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

References

1. Medical College of Wisconsin. Rabies registry. Available at: http://www.mcw.edu/rabies. Accessed September 23, 2010.
2. CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57(No. RR-3)
3. Blanton JD, Rupprecht CE. Travel vaccination for rabies. Expert Rev Vaccines 2008;7:613--20.
4. Blanton JD, Palmer D, Rupprecht CE. Rabies surveillance in the United States during 2009. J Am Vet Med Assoc 2010;237:646--57.
5. CDC. Human rabies---Missouri, 2008. MMWR 2009;58:1207--9.
6. CDC. Imported human rabies---California, 2008. MMWR 2009;58:713--6.
7. CDC. Human rabies---Minnesota, 2007. MMWR 2008;57:460--2.
8. CDC. Human rabies---Kentucky/Indiana, 2009. MMWR 2010;59:393--6.
9. CDC. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR 2010;59(No. RR-2):1--9.
10. CDC. Health information for international travel 2010. Atlanta, GA: US Department of Health and Human Services, Public Health Service; 2009. Available at http://wwwnc.cdc.gov/travel/content/yellowbook/home-2010.aspx. Accessed September 23, 2010.

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