Antemortem diagnosis of human rabies

Journal of Family Practice, July, 1996 by Elena Sang, Wesley Farr, Melanie A. Fisher, Stephan D. Hanna

Human rabies is a rare but fatal disease. In the United States, the majority of people infected with rabies contract the disease by being bitten by a wild animal, most commonly bats. Because rabies is so rarely seen, it is often not diagnosed until after death, at which time exposed health care workers will require rabies prophylaxis. We describe a case for which the diagnosis was made before death. The prompt consideration of this diagnosis allowed early isolation of the patient and prevented unnecessary risk to health care workers.

Key words. Rabies; infectious diseases; diagnosis; patient isolation; health care workers; fatal outcome. (J Fam Pract 1996; 43:83-87)

Rabies, recognized since ancient times, continues to be a fatal disease. The incidence in the United States declined dramatically with the implementation of dog vaccination and stray animal control programs in the 1940s.' The incidence decreased from 50 to 60 cases per year prior to 1940 to two or fewer cases per year since 1960.[2,3] Because of the success of these programs, wild animals such as foxes, skunks, bats, and raccoons, rather than dogs, are now the primary means of rabies transmission to humans.[4]

Because of the low incidence of rabies and the absence of an animal bite history, physicians often do not consider a diagnosis of rabies in patients presenting with encephalopathy. The result has been failure to institute strict isolation early in the hospitalization, a delayed diagnosis, unnecessary exposure of health care workers to potentially infectious secretions, and excessive need for postexposure prophylaxis.[5-13]

We present a case for which the diagnosis was considered within 24 hours of admission to a regional hospital, which permitted early patient isolation and therefore minimized postexposure prophylaxis to health care personnel. Early suspicion of rabies contributed to the antemortem diagnosis and an informed decision to withdraw intensive life support.

Case Report

A 41-year-old man from West Virginia presented to a rural hospital with a 2-day history of nausea, headache, malaise, and tremors and a 1-day history of severe anxiety, hallucinations, vomiting, and an inability to bring liquids to his mouth. He denied fever and chills. His examination revealed good recall, a short attention span, severe agitation, and, in retrospect, early hydrophobia. He had a known history of substance abuse, and the preliminary diagnosis was acute psychotic reaction secondary to ethanol and marijuana toxicity. He became more agitated and left the emergency department. Over the next 24 hours, his condition worsened, and he was admitted to a regional hospital on day 3 of his illness.

The patient lived in a cabin in a rural forested area. He was a musician and an animal trapper. His history, obtained antemortem, revealed two episodes of animal exposure that were either too short or too long for the usual incubation period of rabies, but indicated that his activities may have placed him at risk for rabies exposure. Five days before the onset of symptoms, he had killed and skinned a muskrat. He kept two dogs outside his cabin but denied any animal bites. Questioning of his family and friends revealed that he had "brain-tanned" a fox pelt 15 months prior to onset. The brain tanning process involved holding the fox brain in his bare hands and rubbing it over the fox pelt.

A physical examination at admission revealed a temperature of 100.1[degrees]F. He was alert, coherent, diaphoretic, and agitated. He displayed tremors, spastic extremity movements, and hydrophobia. There were no mucocutaneous lesions. Frequent spitting of frothy saliva and withdrawal from objects placed near his mouth were noted. Laboratory studies revealed white blood cell (WBC) count, 18,100/[mm.sup.3]; creatinine phosphokinase, 1912 IU (normal, 5 to 50); serum ethanol, <10 mg/dL; and urine drug screen positive for cannabis. On day 4 of the illness, a lumbar puncture revealed the following cerebrospinal fluid findings: an opening pressure of 330 mm Hg; protein, 148 mg/dL; glucose, 128 mg/dL; WBC, 18/[mm.sup.3] (10% polymorphonuclear [PMN] cells; and 90% monocytes); red blood cell count, 725/[mm.sup.3]; and the cerebrospinal fluid culture showed no growth. On day 5 of the illness, he developed respiratory distress requiring mechanical ventilation and was transferred to the university hospital.

The patient's condition continued to deteriorate. He demonstrated severe spastic muscle activity, and his temperature rose to 102.7[degrees]F. Laboratory values revealed WBC, 18,999/[mm.sup.3] (87% PMN, 4% bands); erythrocyte sedimentation rate, 58 mm/h; blood and urine cultures, no growth; and creatinine phosphokinase, 6000 IU. Computed tomography of the head revealed diffuse cerebral edema and low attenuation in the left temporal lobe (Figures 1 and 2). An electroencephalogram showed a possible left temporal abnormality. He was treated empirically with intravenous acyclovir, ceftriaxone sodium, penicillin G, and doxycycline hyclate. There was no improvement.

A skin biopsy of the posterior neck on day 6 was positive for rabies antigen by indirect fluorescent antibody test. These results were available after a temporal brain biopsy was performed on day 9, which revealed Negri bodies (Figure 3). The patient developed flaccid paralysis after being taken offparalytic agents and died on day 14 of the illness.

The Centers for Disease Control and Prevention (CDC) identified the specific viral ribonucleic acid (RNA) as a variant associated with the silver-haired bat, Lasionycteris noctivagans. Postmortem interviews of additional friends of the patient revealed that 5 months before his terminal illness, he had killed a bat and examined its oral cavity. The description of the bat was consistent with Lasiurus borealis, the red bat. Inoculation of sites rich in innervation, such as the head and digits, is more likely to result in rabies infection.[14,15]