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Human Rabies -- New Hampshire, 1996
On August 20, 1996, a 32-year-old resident of New Hampshire died in a Massachusetts hospital from an illness characterized by rapid neurologic deterioration. Rabies had been clinically suspected on the date of her transfer from a New Hampshire hospital (August 14) and was confirmed by CDC on August 17. This report summarizes the investigation of this case by the state health departments of New Hampshire, Massachusetts, Maryland, and Pennsylvania, which implicated a dog in Kathmandu, Nepal, as the probable source of exposure.
The patient initially sought care at a hospital emergency department (ED) in New Hampshire on August 12 for a 2-day history of paresthesias and pain radiating up her left arm from the site of a healed bite. She reported being bitten by a dog on her left hand on June 7 while in Kathmandu, but did not receive rabies postexposure prophylaxis (PEP) for the bite. Physical examination was normal, and left cervical radiculopathy was diagnosed. Anti-inflammatory and analgesic drugs were prescribed, and she was discharged.
On August 14, the patient returned to the ED with complaints of progressive difficulty breathing, throat spasms, nausea, and vomiting and reported severe pharyngeal spasms when she drank fluids or showered. Physical findings included an oral temperature of 97.3 F (36.3 C), pulse rate of 64 beats per minute, respiratory rate of 26 breaths per minute, and blood pressure of 106/60 mmHg. The patient was alert, oriented, and in no acute distress. She had a normal sensory examination; however, painful spasms of the bulbar musculature of the lower face and throat were noted when she brought a cup to her mouth or when air was blown in her face. Routine laboratory evaluation, an electrocardiogram, and radiographs of the chest and lateral neck were normal. On the basis of history and symptoms, clinical rabies was suspected, and the patient was transferred to a hospital in Massachusetts for further evaluation and treatment. On admission, a computerized tomography scan of her head was normal. Cerebrospinal fluid evaluation was normal except for a white blood cell count of 42 cells/L, with a differential of 12% neutrophils, 56% lymphocytes, and 32% monocytes. The patient was initially treated with rabies immunoglobulin (RIG) and human diploid cell vaccine (HDCV) in the standard postexposure regimen (1).
Over the subsequent 12 hours, the patient developed increasing agitation, anisocoria, salivation, and worsening facial and pharyngeal spasms. She suffered a cardiac arrest on August 15, but was successfully resuscitated. She received experimental treatment with high-dose intravenous and intrathecal RIG; however, her condition continued to deteriorate. On August 15, a full-thickness nuchal skin biopsy and saliva sample were obtained and sent to CDC for rabies diagnosis. Both tested positive for rabies virus on August 17 by a nested polymerase chain reaction (PCR) procedure. Patient serum collected on August 16 also was antibody positive, containing a virus neutralizing titer of 1:9 by the rapid fluorescent focus inhibition test. Nucleotide sequence analysis of the PCR product conducted at CDC on August 18 implicated a variant of rabies virus associated with dogs from the Indian subcontinent.
On August 20, neurologic evaluation of the patient revealed no brainstem or cortical function, and life support was discontinued. Because rabies was suspected on admission, appropriate precautions were observed, and no employee at the Massachusetts hospital required PEP.
The patient had been traveling for a 6-month period in New Zealand, Australia, Thailand, and Nepal. She was bitten on the left hand while petting a stray dog on June 7 while in Kathmandu. The wound was immediately washed with peroxide and rubbing alcohol. The dog was observed for about 45 minutes and appeared normal, and no rabies testing was performed on the animal. The patient was reportedly unable to obtain PEP in Kathmandu or Bangkok, Thailand, and was advised to go to Sydney, Australia, for definitive medical care. On June 12, she was examined at a hospital in Sydney and was told that RIG and rabies vaccine were not immediately available and to return the following day for treatment. Because the patient had reportedly received conflicting information from other sources regarding her risk for rabies and the benefit of PEP after the delay between exposure and treatment, she elected not to return to the hospital for treatment.
The patient returned to the United States around June 30 and remained in Maryland during July. While returning to New Hampshire, she visited relatives in Pennsylvania on August 3. During this visit, salivary contact (i.e., kissing and sharing of utensils and drink glasses) was reported with five persons. One other contact, a traveling companion, also reported salivary contact. All six persons were administered PEP. The patient returned to New Hampshire on August 4 and developed her first symptoms on August 10. An investigation was initiated to determine other close contacts to the patient on or after July 31. Other than the six contacts previously noted, a physician in New Hampshire who initially examined the patient in the ED also received PEP.
Reported by: DJ Itkin, MD, J Mastromarino, MD, R Levy, MD, Exeter Hospital, Exeter; R DiPentima, MPH, New Hampshire Dept of Health and Human Svcs. N Basgoz, MD, Massachusetts General Hospital, Boston. M McGuill, DVM, A DeMaria, Jr, MD, State Epidemiologist, Massachusetts Dept of Public Health. S Yeager, JT Rankin, Jr, PhD, State Epidemiologist, Pennsylvania Dept of Health. K Damewood, MA, DM Dwyer, MD, State Epidemiologist, Maryland State Dept of Health and Mental Hygiene. Viral and Rickettsial Zoonoses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.
Editorial Note: This report describes the second case of human rabies reported in the United States in 1996 (2) and the 30th case reported since 1980. Of the 30 cases, 14 (47%) (including this case) have been associated with exposure to dogs; 12 of the 14 were presumed to have been acquired outside the United States.
Although the incubation period for rabies is usually 1-3 months, longer incubation periods have been reported (3). Prevention of disease after exposure is only effective if PEP is administered before the onset of clinical disease. Although treatment should be initiated as soon as possible, the stage of the incubation period during which infection becomes intractable is unknown. Therefore, PEP is recommended for administration anytime before the onset of symptoms, regardless of the time elapsed since exposure. RIG still may be administered for up to 1 week after the rabies vaccine series has been initiated. However, administration of RIG more than 1 week after initiation of the vaccine series is not recommended because antibodies to the virus already will have been induced by the vaccine.
In the United States, the median interval between exposure and administration of PEP is approximately 5 days (4). Regardless of this delay, there have been no reported failures of PEP in the United States in association with the correct implementation of the treatment regimen specified by the Advisory Committee on Immunization Practices (ACIP) (1). In this case, had the patient elected to receive PEP in Sydney, Australia, a delay of about 5 days would have occurred. In countries that have been free of rabies for many years, PEP is infrequently administered, and there may be difficulty in obtaining RIG and rabies vaccine and confusion about the suitability of administering PEP when delays occur between exposure and the presentation for treatment. With the discovery of a new rabies-like lyssavirus from flying foxes and insectivorous bats in Australia and the identification of a human fatality associated with this virus (5), use of PEP in that country is expected to increase.
The risk for rabies for international travelers is greatest in areas where canine rabies is still highly endemic, including many parts of Africa, Asia, and Central and South America. Two countries where the patient in this report had extended stays -- Nepal and Thailand -- are considered to be areas where dog rabies is highly endemic. Preexposure vaccination with HDCV or rabies vaccine adsorbed should be considered for persons living in or visiting (for greater than 30 days) areas where rabies is endemic and appropriate PEP may not be readily obtained.
Preexposure vaccination does not eliminate the need for additional therapy after an exposure but does simplify the postexposure regimen by eliminating the need for RIG and decreasing the number of required vaccine doses (6). Because rabies virus may be present in the saliva of infected animals 3-4 days before onset of clinical symptoms (7), persons who are bitten or scratched by any animal should thoroughly wash all wounds with soap and water and immediately seek medical consultation to evaluate the need for PEP (1,2). In situations associated with a delay between a high-risk exposure and presentation for treatment, PEP should be administered regardless of the delay.
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