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We present a case of a 22 year old male patient who developed a rabies encephalomyelitis with evolution of six weeks, treated first as a psychiatric disorder and later as an encephalitis. This case had the following important features; 1--A long time with the disease: usually the patients die into the first eight days after diagnosis; 2--The evident reactive gliosis; 3--Almost all the studied fields showed inclusion bodies in both supratentorial and infratentorial portions; 4--The hippocampus and spinal cord neurons had many or unique Negri bodies and some of those were giant; 5--Microglia proliferation and free acidophilus bodies. All those microscopic features mean a long evolution time that is rarely seen in this illness; in medical literature we found only ten long duration cases.

During August 1988 to January 1990, the immunogenicity and safety of purified chick embryo cell rabies vaccine (PCEC) given by the conventional and abbreviated regimens in 82 vaccinees moderately to severely exposed to laboratory proven rabid animals were studied. The 16 vaccinees received PCEC six doses as conventional schedule on days 0, 3, 7, 14, 28 and 90, the 11 vaccinees received six doses of PCEC plus human rabies immune globulin (HRIG) on day 0. The 29 vaccinees received an abbreviated schedule of PCEC as two doses on day 0, one dose each on days 7 and 21 and the 26 cases received PCEC abbreviated schedule plus HRIG on day 0. The kinetics of the neutralizing antibodies on days 0, 7, 14, 28, 56, 180 and 365 were studied for comparative purpose. All vaccinees had high antibody levels from day 14 which last longer than a year and were safe after one year follow up. The adverse reactions of the vaccine were mild and self-limited.

Three of six wild dogs (Lycaon pictus) which died of rabies, and one Alsatian dog which died of adenocarcinoma, were found to harbour sarcocysts in their cardiac and/or skeletal muscles. The bradyzoites and metrocytes of the cysts were smaller than those seen in a lion infected with Microbesnoitia leoni and the common Sarcocystis spp. found in ruminants. It is proposed that Lycaon pictus is the natural intermediate host of the unidentified Sarcocystis-like species.

The epizootic of rabies in raccoons in Maryland has been accompanied by 129 confirmed cases of rabies in cats from Jan 1, 1983 to Sept 30, 1992 and only 12 cases in dogs. An epidemiologic and clinical study of rabies in cats was conducted for the period Jan 1, 1983 to May 31, 1986. Only 3 of 31 rabid cats had a history of being currently vaccinated against rabies, and 13 were of unknown ownership. A history of prior wound or injury within 6 months of onset of signs of rabies was reported in 11 of the cats and most of these had a wound in a hind limb. The median interval between reporting of a wound and a development of rabies was 4 to 6 weeks. Rabies in cats is difficult to diagnose in the early stages and, of the 14 cats examined by a veterinarian, only 3 were believed to have rabies on initial examination. Major signs of rabies in cats reported by veterinarians included behavior change, gait abnormality, strange or unusual look in the eyes, and a wound within the preceding 6 months. Owners reported increased frequency of vocalization as an early sign. Postexposure treatment was given to 194 human beings including 63 veterinarians or their personnel. The estimated cost of postexposure biologics was +68,000.

Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totalling 6,190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible.

Experimental studies in laboratory animals showed reserpine in doses of 0.01-0.05 mg/kg body weight to inhibit the development of rabies infection in white mice and rabbits by 40.0-83.4% depending on the dose and mode of administration. The inhibiting properties of reserpine were demonstrated for both fixed and street rabies virus strains. The protective effect of the drug was manifested after parenteral and oral administration to the infected animals. The experimental data suggest that reserpine may be used as an antiviral drug for protective treatment of rabies in the incubation period.

Today, there are two steps of human rabies impendence: a. exposures to rabid or rabies suspected animals b. human deaths due to rabies. Red foxes, dangerous rabies reservoir are responsible for the main tendency and spread of rabies in Poland (over 2000 cases in 1992). This has a direct bearing on the treatment of exposed persons and on rabies among unvaccinated domestic animals. The number of persons requesting post exposure rabies treatment is also increasing--6500 vaccinees in 1992. During last eight years no case of human death was registered in Poland. Mass parenteral canine vaccination campaign and effective control methods of rabies in dogs in Poland are the mostly successful and significant elements separating wild animal rabies from human society. Any inaccuracy on this field would be the risk of transmission of wild rabies to human surrounding.

The results of intramuscular inoculation of 111 bats (Myotis daubentoni, Myotis brandtii) with three strains of Lyssaviruses--Yuli, Stade, and 1150 are presented. Bats were found to have low susceptibility, especially to strains of serotype 4. After infection with serotype 4 viruses, fewer bats died but within shorter periods than after infection with serotype 1. After inoculation with strain 1150, 60% of bats yielded virus, whereas only 9-24% did after inoculation with type 4 strains. The survival time after inoculation was 32.2 and 19.0 days, respectively. Manifestations of the disease, virus distribution in viscera, and the results of examinations of specimens from bats by express methods are described.

Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation.

Two rabies virus strains collected from naturally infected foxes in France in 1976 and 1986 were inoculated in 2 groups each consisting of 10 foxes (approximately 50 lethal doses50 mouse intracerebral per fox). Another 20 healthy foxes were kept in the same cages as the inoculated animals in order to study the transmission of both strains. All the inoculated foxes became rabid and transmitted rabies to their cage companion. The intervals between death of the inoculated foxes and death of the cage companion were significantly more variable (P less than 0.001) with the earlier strain, from 1 to 33 days compared to the range obtained with the later strain, 10-14 days. However, the mean intervals did not differ. Epidemiological consequences of such a decrease in variability, if confirmed in the field could decrease the epidemiological extent of rabies. Viremia was demonstrated in 2 foxes inoculated with the later strain but we cannot assume this to be a characteristic of this strain compared with the earlier strain. Rabies virus (both strains) was isolated from the saliva of foxes 29 days or less before the onset of clinical symptoms. This last result raises the question of the time limit as regards security before onset of clinical symptoms in animals involved in human contamination.

Twenty-one adult raccoons (Procyon lotor) were radio-marked on each of two areas in Centre County, Pennsylvania from 17 June to 23 August 1987. Raccoons on Area 1 were vaccinated with a commercial inactivated rabies virus vaccine administered intramuscularly, whereas on Area 2 raccoons were not vaccinated. Survival rates were estimated for three periods: pre-season (23 August to 23 October 1987), harvest season (24 October 1987 to 23 January 1988) and post-season (24 January to 26 March 1988). Kaplan-Meier survival rates (+/- SE) were 1.00 +/- 0.00 for both areas during the pre- and post-season periods. Survival rates during the harvest period were 0.67 +/- 0.11 and 0.69 +/- 0.11 for Area 1 and Area 2, respectively. Survival rates between the two areas were not different (P = 0.929). During 23 August 1987 to 26 March 1988, rabies was not an apparent factor in raccoon survival. Conclusions regarding timing an oral rabies vaccination campaign based upon occurrence of rabies-related mortalities could not be presented because of the lack of obvious rabies mortality. However, our findings, combined with information about immunization, vaccine distribution, and peak periods of raccoon rabies, suggest a late winter or early spring vaccination period would be optimum for reducing the number of raccoons susceptible to rabies.

The Thai Red Cross intradermal postexposure rabies treatment schedule was prospectively assessed in 100 Thai patients severely bitten by proven rabid animals. It consists of 0.1 ml of purified Vero cell rabies vaccine containing more than 2.5 IU of rabies antigen per 0.5 ml of reconstituted vaccine given intradermally at two sites on days 0, 3, and 7, followed by one 0.1 ml injection on days 30 and 90. The commercial vaccine used had an antigen content of 3.17 IU per 0.5 ml ampoule. Purified equine or human rabies immuno-globulin was also given on day 0 to patients with severe exposures. As much of the immunoglobulin as possible was infiltrated around the wounds. All patients were followed for 1 year post exposure. There were no deaths; the efficacy of the regimen was 100%. Antibody titre determination in a randomly selected subgroup showed seroconversion in all 10 patients.

Protection against challenge following rabies vaccination occurs early in the mouse. However, before this protection appears, vaccinated mice die earlier than control mice receiving a placebo. Study of this 'early death' shows that this phenomenon occurs when challenge is made with the CVS fixed virus and a field isolate from the salivary glands of the fox; by different routes of inoculation and for various infectious doses, and finally, when this challenge is made before or after vaccination. This phenomenon can be transferred via spleen cells or plasma of vaccinated animals into infected recipients. Lack of thymus in the mouse prevents early death, but reduction of B lymphocytes population by cyclophosphamide have no effect on this death. Kinetic studies of different parameters, taken into account when studying this phenomenon, show fluctuations of the survival time after challenge in inoculated mice, as well as in controls. As a consequence of these fluctuations, a shift between mortalities of vaccinated animals and controls is observed.

Immune response was studied experimentally in mice immunized according to 23 different schedules with rabies vaccine in 1:10 and 1:20 dilutions for the elucidation of principles of developing an optimal vaccination schedule. Each group consisted of 40 to 50 animals. The most objective, reliable, and strict test, challenge of immunity to street rabies virus inoculated peripherally which is closest to natural conditions, was used as the criterion for the evaluation of immune response. The studies showed daily inoculation of the vaccine not to be the optimal schedule for the manifestation of the immune response after vaccinations against rabies. Most intensive immunity was observed after vaccination with intervals between the injections (principle 1). When the vaccine was inoculated at a 5-10-day interval, a booster effect of the type of secondary immune response was observed, and the protection of the animals was significantly higher (p less than 0.001) than after daily inoculation of the same amount of the vaccine, significantly higher than after daily inoculation of the double amount of the vaccine, and as high as after inoculation of the 4-fold amount of the vaccine daily for 8 days. No booster effect of the vaccine was observed when the interval between the injections was no more than 2-3 days. The booster effect of the vaccine injections at intervals is determined by the level of the ground immunity (priming immunization) (principle 2) and the antigenic potency of the vaccine (principle 3).

Serological studies were performed in 1,015 dog brains and 144 cat brains collected in a rabies enzootic area. Significant levels of rabies virus neutralizing activity were observed in two dog brains and in one cat brain which had been negative for rabies by immunofluorescence and mouse inoculation tests. These results were compared with those obtained in the group of surviving animals at different times after onset of experimentally induced abortive rabies. The possibility that naturally infected animals recovered from rabies central nervous system infection is suggested.

Rabies is one of the most severe infectious diseases in Ethiopia, with many cases of the disease diagnosed in various parts of the country. The dog is the species most responsible for human exposure, with over 98% of the human cases and vaccinations due to the bite of rabid or suspected rabid dogs. Most of the treatments are due to stray dogs that bite, escape and are not available for observation. Most of the people who die of rabies are under 40 years of age, and among adults, the majority of these are males, suggesting that the close contact the young men have with dogs causes them to have a higher exposure rate and more deaths from rabies.

The paper presents the results of the experimental study of the action of rifampicin on the process of rabies infection in albino mice contaminated with 1-10 LD50 of the fixed rabies virus. Exposure to rifampicin in doses of 250 and 500 micrograms/mouse (35-70 mg/kg) resulted in survival of 66.7 and 83.4 per cent of the animals respectively while in the controls it did not exceed 16.6 and 25.0 per cent. The average life-span of the albino mice treated with the antibiotic increased 1.6-2.4-fold in comparison with the controls. The chemotherapeutic index of rifampicin representing the ratio of the maximum tolerance dose to the minimum dose providing the protective action was equal to 20. The protective action was observed either after administration of the antibiotic according to the treatment-and-prophylaxis scheme or after administration of its 2- or 3-fold dose once a day immediately after the contamination.

When mice infected 1 or 2 days before by an IM inoculation after high passage of the virus in the species ("challenge virus standard" strain) received an injection of live (Flury) or inactivated virus, their mortality was increased in comparison with unvaccinated controls. In the case of the inactivated virus vaccine, mortality was proportional to the dose of vaccine received. Conversely, when vaccination was carried out in mice recently infected with the same doses of a heterologous strain adapted to foxes, this phenomenon could not be demonstrated. The consequences of these observations on failures of treatment in animals infected with a homologous strain, cases of rabies occurring after vaccination or quality control of vaccines are discussed.

SJL/J mice are resistant, whereas A/WySnJ mice are susceptible to intraperitoneally (i.p.) inoculated street rabies virus (SRV). In this report we determine whether interferon (IFN) induced within the central nervous system (CNS) of these mice during infection is associated with resistance. We show that the high concentration of type 1 interferon (IFN-alpha/beta) within the CNS of A/WySnJ mice is ineffective in inhibiting SRV replication in these tissues, and is unimportant in ameliorating disease. More importantly, the 100% survival of SRV-infected SJL/J mice following neutralization of IFN within the CNS with anti-IFN-alpha/beta suggests that protection of target cells by this minimal amount of IFN is not the mechanism responsible for the innate resistance of SJL/J mice to i.p. inoculated SRV.

A rabid wolf attacked 12 humans and six animals in six villages in the course of a day before it was surrounded and killed. Of the 12 human victims, three had severe wounds to the face and head, five had severe lacerations, two had less severe wounds on the trunk and limbs, and two had minor wounds or scratches. Nine of these victims received antirabies treatment with Semple vaccine (preceded by immune serum in one case). No persons with trunk and limb bites died. All three patients with head wounds died. One of these patients received vaccine and serum, one received vaccine, and the third had no treatment. Neutralizing antibodies were demonstrated in blood samples drawn 58 days after the incident from five survivors who had received a full course of treatment, but such antibodies were absent from the blood of one untreated survivor (who had only minor scratches and had refused treatment) and of the wife of one man who died, who had been in close contact with her husband throughout his illness. All severely bitten animals died of rabies. A dog that the carcass of a pig which had died of rabies itself developed rabies 12 days later. This event raised the possibility of infection by the oral route.

A 40-year-old man who farmed in Mexico and raised dogs as a hobby presented with dysphagia, hydrophobia, insomnia, anorexia, malaise, fever, and decreased strength and sensation in his dominant arm. After a repetitive three-hour history and physical examination, a tentative diagnosis of rabies was made in an atmosphere of patient denial followed by reluctance of hospital personnel to accept such a rare diagnosis. Upon confirmation of the diagnosis by the Center for Disease Control, Atlanta, the patient underwent aggressive therapy, including maximum respiratory support, anticonvulsants, steroids, pressors, hemodialysis and interferon treatment, but died on the 16th day following admission. This case is presented because of its rarity and to review the disease, clinical history, current therapy, and recent literature regarding emergency department differential diagnosis.

Uniform groups of young goats, free from rabies antibody, were inoculated with 600,000 mouse LD50 of a dog origin street virus via the massetter muscle. Two vaccine schedules, one consisting of 24 intramuscular doses of ERA vaccine and the other 4 doses of the same vaccine were given to 2 groups of virus inoculated goats and to 2 groups of uninoculated goats respectively. There were no significant differences in incubation periods of the clinically ill goats when the two pos-exposure vaccinated groups were compared. Both treated groups however, had longer incubation periods that the untreated control groups. Essentially the same experiment was done again, this time with 8.0 ml of high titer anti-rabies goat serum administered simultaneously. The incubation periods were prolonged slightly more than in the first experiment. The antiserum alone had the same effect. While no protection from mortality was observed in any group from these post-exposure treatments, it must be recognized that the virus challenge was severe both in dosage and in route of inoculation, and that the use of antibody also had quantitative aspects which were not taken into account. This work should be repeated giving appropriate consideration to the quantitative aspects of both virus and antibody dosage as well as to a less strenuous route of inoculation.

The social behaviour of red foxes Vulpes vulpes is flexible and is adapted to their environment. Consequently social organization varies from one habitat to another under the influence of factors such as the availability of food and the pattern of mortality. Variations in social behaviour between fox populations are mirrored in different frequencies of encounters between individual foxes and hence in potentially different 'contact rates' for rabies. We present a computer model whose simulations indicate that such variation in contact rate is of overriding importance in the epizootiology of vulpine rabies, and so emphasize the importance to rabies control of understanding the behavioural ecology of foxes.

We have shown previously that a non-fatal outcome of infection with street rabies virus occurs more often when mice are exposed to a high ambient temperature (HAT = 35 degrees C) early in the course of the infection. To determine what influence the virus strain had on this protective effect of HAT, we have extended these observations to studies of a fixed rabies strain, CVS and several substrains of CVS virus derived from temperature-sensitive (ts) mutants. In all cases, mortality was reduced to some extent by exposure of the animals to HAT; however, dramatic strain-specific differences in the extent of the effect were noted. Although each of the virus substrains tested was revertant in the ts character (as tested in vitro using a non-permissive temperature of 40-5 degrees C), several substrains (ts 1, ts 4, RT51) caused disease that was sensitive (greater than 90% reduction in mortality) to HAT. Mortality induced by the parental CVS virus was reduced approx. 50% at HAT. A single CVS virus substrain, VSW89, caused disease that wal less affected by HAT than was disease induced by the parental strain. As in previous studies with street virus, the incubation periods for infection with CVS virus substrains were consistently prolonged at HAT.

Experiments in random-bred and BALB/c white mice inoculated intraperitoneally with street virus, in Syrian hamsters inoculated intramuscularly with fixed viruses as well as experiments reproducing abortive rabies in 99-100% in random-bred white mice inoculated intramuscularly with fixed virus (ERA strain) showed that in the abortive infection the intensity of virus multiplication in the brain is lower than that in fatal infection, the differences being statistically significant. It was found out that from onset of signs of the disease interferon appeared to have no influence on the outcome of infection.

In September 1963 an intensive care unit was established at the Lagos University Teaching Hospital in Nigeria. The incidence of mortality was significantly high (38%). This was attributed to several factors: (1) severity of illnesses, types of illness and antecedent period of neglect; (2) lack of a critical care medicine program; (3) limited numbers of skilled, full-time intensive care unit personnel, including physicians, nurses, inhalation therapists and paramedics, and (4) the high incidence of sepsis in the intensive care unit.

Thailand is an endemic area for rabies, with approximately 300 human deaths reported annually. More than half of the rabies patients are children under 14 years of age. This paper reports clinical data of paediatric rabies cases occurring from 1980 to 1986, and the protective efficacies of human diploid cell rabies vaccine (HDCV) and purified Vero cell rabies vaccine (PVRV) in children exposed to rabid animals. The analysis of 120 medical records revealed that rabies in children had incubation periods which ranged from less than fifteen days to more than three months, but generally between one to three months. The most frequent symptoms observed in the patients were hydrophobia, restlessness, fever, vomiting and aerophobia. Most of the rabid children admitted to hospital died within 24 hours. HDCV was administered to 50 children exposed to rabies with the cumulative dosages of 327 ml. All patients survived without serious adverse effects during a-two year follow-up. Mild reactions were seen in 1.5 percent (5/327 doses). Unfortunately, levels of rabies antibody in these vaccinees were not determined. Among another series of children exposed to rabid animals, comprising 27 individuals who received a total of 168 doses of PVRV, only mild local reactions were seen in 6 subjects. No rabies deaths were reported in 2 years of follow-up. The children who received PVRV either with or without human rabies immune globulin developed similar levels of rabies neutralizing (NT) antibody, which reached the high titers on day 30. At one year after the first dose of vaccination, all vaccinees still had NT antibody at titers higher than 0.5 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

A rabies outbreak in Zorzor District, Liberia, in 1982 resulted in 31 known bitten and 12 known exposed patients. Human diploid cell strain (HDCS) vaccine was used to vaccinate 40 patients. Of these, 34 were vaccinated at Curran Lutheran Hospital, Zorzor, Liberia, mostly by the intradermal (i.d.) route. Five of 28 bitten patients who started their vaccinations did not complete the 4-dose course, including a 16-year-old boy who did not return after the first injection and later died of rabies. There were also 2 deaths in 3 known bitten but unvaccinated patients. None of the 23 bitten who received 4 doses of HDCS vaccine contracted rabies. The i.d. route was also used for pre-exposure prophylaxis. This method of vaccination is less expensive than the intramuscular route and in our clinical setting we would not have been able to vaccinate all the patients without using it. A practical approach to rabies vaccination in a developing country and the technique of intradermal vaccination are discussed.

Three failures of postexposure rabies treatment using imported purified duck embryo cell and Vero cell rabies vaccines are reported from Thailand. Reference is made to eight additional previously reported Thai patients, six of whom had received human diploid cell vaccine. An analysis of these cases reveals that there were serious flaws in management in all of these patients. It is stressed that 45% of human rabies deaths in Thailand occur within 20 days of being bitten and 71% are dead within 28 days. This short incubation period does not allow much time to start immunotherapy. Of Bangkok dogs found to have rabies at autopsy, approximately 8% have a rabies immunization history. Once a dog has bitten a patient immunotherapy should not be delayed in countries with a high incidence of dog rabies. Patients with chronic disease, alcoholics and drug addicts may have an impaired immune response to postexposure rabies vaccines.

Addition of interferon to ineffective rabies virus vaccines by the local injection of either exogenous interferon or a potent interferon inducer (a complex of polyriboinosinic-polyribocytidylic acid containing poly-L-lysine and carboxymethylcellulose) into the footpads of mice previously challenged with rabies virus dramatically reduced the mortality rate. A significant reduction in mortality rate was also noted when the interferon system was administered to rhesus monkeys, but only when treatment was given 6 hr after challenge with rabies virus. Since the monkeys were given an overwhelming challenge of virus, the treatment had to be given quickly to obtain results comparable to those in mice.