The disease is distinguished by the presence of cytoplasmic eosinophilic inclusions, the Negri bodies. They are most prominent in pyramidal cells of the hippocampus and Purkinje cells but have been seen in nerve cells throughout the brain and spinal cord. In addition there is widespread perivascular cuffing and meningeal infiltration with lymphocytes and mononuclear cells and small foci of inflammatory necrosis, such as those seen in other viral infections. The inflammatory reaction is most intense in the brainstem. The focal collections of microglia in this disease are referred to as Babes nodules (named for Victor Babes, a Romanian microbiologist).
Bites and scratches from a potentially rabid animal should be thoroughly washed with soap and water and, after all soap has been removed, cleansed with benzyl ammonium chloride (Zephiran), which has been shown to inactivate the virus. Wounds that have broken the skin also require tetanus prophylaxis.
After a bite by a seemingly healthy animal, surveillance of the animal for a 10-day period is necessary. Should signs of illness appear in the animal, it should be killed and the brain sent, under refrigeration, to a government-designated laboratory for appropriate diagnostic tests. Wild animals, if captured, should be killed and the brain examined in the same way.
If the animal is found by fluorescent antibody or other tests to be rabid, or if the patient was bitten by a wild animal that escaped, postexposure prophylaxis should be given. Human rabies immune globulin (HRIG) is injected in a dose of 20 U/kg of body weight (one-half infiltrated around the wound and one-half intramuscularly). This provides passive immunization for 10 to 20 days, allowing time for active immunization. Duck embryo vaccine (DEV) was previously used for this purpose and greatly reduced the danger of serious allergic encephalomyelitis from about 1 in 1,000 cases (with the formerly used equine vaccine) to 1 in 25,000 cases; it is still used in many parts of the world. The more recently developed rabies vaccine grown on a human diploid cell line (human diploid cell vaccine [HDCV]) has reduced the doses needed to just 5 (from the 23 needed with DEV); these are given as 1-mL injections on the day of exposure and then on days 3, 7, 14, and 28 after the first dose. The HDCV vaccine has increased the rate of antibody response and reduced even further the allergic reactions by practically eliminating foreign protein. A thorough trial of the new antiviral agents in patients already symptomatic has not been undertaken. Persons at risk for rabies, such as animal handlers and laboratory workers, should receive preexposure vaccination with HDCV. A preventative DNA rabies vaccine has been genetically engineered and is being tested for use in animal handlers and others at high risk.
With modern intensive-care techniques, there have been a number of survivors of the encephalitic illness, all of whom had received postexposure immunization. In addition to mechanical respiratory support, several secondary abnormalities must be addressed, including raised intracranial pressure, excessive release of antidiuretic hormone, diabetes insipidus, and extremes of autonomic dysfunction, especially hyperand hypotension. Willoughby and colleagues were successful in treating a 15-year-old girl who had not received vaccine by using an empirical approach of induced coma with ketamine and midazolam supplemented by ribavirin and amantadine. The goal was to support the patient while her antibody response matured. At least two other cases treated in a similar manner, reported anecdotally, did not survive.
Acute Cerebellitis (Acute Ataxia of Childhood)