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PubMed2002

[Anti-rabies antibody titers among subjects who received rabies post-exposure prophylaxis with foreign-made rabies vaccines at the beginning and followed with Japanese rabies vaccine].

Recently travelers who were bitten by possibly rabid animals in rabies endemic regions and returned to Japan have increased in number. About half of them received rabies post-exposure prophylaxis (RPEP) with one or more doses of foreign-made rabies vaccines (FRV) in the local medical institutions. FRV, however, are not available in Japan so we have to continue the RPEP with Japanese rabies vaccine (JRV). It has not been demonstrated that an anti-rabies antibody induced with JRV following Vero cell rabies vaccine (PVRV) or chick embryo cell rabies vaccine (PCEC) could be high enough to prevent clinical rabies. We examined anti-rabies antibody (ARA) titers among the subjects visited our vaccine clinic to receive RPEP and obtained results as follows: the ARA titers after a total of 5 doses of PCEC or PVRV and JRV were high enough to prevent clinical rabies as after 5 doses of JRV. However, ARA titers obtained after receiving one dose of PVRV and 2 doses of JRV seemed lower than those produced after one dose of PCEC and 2 doses of JRV or 3 doses of JRV. To accelerate antibody production, consequently, the simultaneous intradermal and subcutaneous injection method of rabies vaccine may be applied to those who were bitten in their hands or head by possibly rabid animals and received only one dose of PVRV in rabies endemic regions.

Adolescent↗
PubMed1988

Efficacy of rabies vaccines against Duvenhage virus isolated from European house bats (Eptesicus serotinus), classic rabies and rabies-related viruses.

Isolates of rabies from separate enzootics can be distinguished by their reactions with panels of monoclonal antibodies (mAbs) directed to different sites on the nucleocapsid and glycoproteins of the virus. Estimates of antigenic relatedness can be made by comparing similarities among groups. In this manner it can be shown that while classic strains of rabies react with most of the mAbs, the rabies related Lyssaviruses (Mokola, Lagos and Duvenhage) react with only a few of the mAbs and isolates of rabies from Eptesicus serotinus bats in Europe are intermediate between the two groups. Mice immunized intraperitoneally with human diploid vaccine (HDCV) or animal vaccines (Rabisin and Rabiffa) were protected against a challenge with DBV, DUV-1 and most classic rabies strains. HDCV gave only partial protection against human virus isolates from Finland and Saudi Arabia. The HDCV did not protect mice against challenges with Lagos bat or Mokola virus (rabies-like viruses). The animal vaccines, however, did protect mice against Lagos bat virus, but not against Mokola. Dogs immunized with Rabisin were protected against an intracerebral challenge with DBV. Dogs developed rabies-neutralizing antibody titres after intramuscular or intravenous inoculation with live DBV or DUV-1 virus; these dogs were protected against an intramuscular canine street rabies virus challenge. We conclude that the rabies vaccines tested protect against DBV/DUV-1 and classic street rabies strains, but not Mokola.

Animals↗
PubMed1998

Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCECV) both confer protective immunity against infection with the silver-haired bat rabies virus strain (SHBRV).

The demonstration of extensive differences in the antigenic makeups of the silver-haired bat rabies virus (SHBRV) and canine rabies virus (COSRV) strains raised concerns as to whether current licensed rabies vaccines are sufficiently protective against SHBRV. NIH mouse protection test results show that both the human diploid cell culture rabies vaccine (HDCV) and the purified chicken embryo cell rabies vaccine (PCECV) protected against lethal infection with SHBRV as well as the canine rabies strain COSRV. However, in this investigation, the potencies of both vaccines in mice were found to be significantly higher for COSRV than for SHBRV. The in vivo protection data are confirmed by in vitro virus neutralizing antibody (VNA) test results which demonstrate that mice immunized with HDCV or PCECV develop significantly higher VNA titres against COSRV than against SHBRV. In contrast, VNA tests of sera from individuals immunized with HDCV or PCECV showed that humans, as opposed to mice, develop significantly higher VNA titres against SHBRV than against COSRV. These data suggest that HDCV and PCECV will protect humans against infection with the silver-haired but rabies virus strain in addition to canine rabies virus strains.

Animals↗
PubMed1991

One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine.

The 2-1-1 rabies postexposure treatment schedule is an abbreviated regimen in which a tissue culture rabies vaccine is administered intramuscularly at two sites on day 0, and at one site on days 7 and 21. Compared to the standard five-dose intramuscular regimen, the 2-1-1 schedule reduces the number of clinic visits from five to three and the amount of vaccine used by 20%. One hundred Thai patients, who were severely exposed to rabies, were treated with rabies immune globulin and the 2-1-1 regimen using purified Vero cell rabies vaccine. They were followed for 1 year. Rabies antibody titres were measured in 10% of this group. All patients survived and adverse reactions were mild. A satisfactory antibody response (a titre greater than 0.5 IU ml-1) occurred in all ten patients studied at day 14, but persisted for 90 days in 80% and for 360 days in only 50%. The authors therefore do not recommend use of the 2-1-1 schedule in severely exposed patients who also need to receive rabies immune globulin.

Adolescent↗
PubMedDate not supplied

Antigenic diversity of the glycoprotein and nucleocapsid proteins of rabies and rabies-related viruses: implications for epidemiology and control of rabies.

Rabies virus-specific monoclonal antibodies (MAbs) have served to describe operationally the topography of the antigenic structure of the glycoprotein and nucleocapsid proteins of rabies virus. With the use of nucleocapsid protein-specific MAbs and cleavage fragments of the nucleoprotein and phosphoprotein, it has been possible to identify the chemical structure of two antigenic sites of the nucleoprotein and one antigenic site of the phosphoprotein. Antisera produced to synthetic peptides that make up the structure of these antigenic sites exhibited reactivities similar to those of MAbs. Analysis of a large number of isolates of rabies virus from different animal species and from different geographic locations revealed that rabies viruses differ considerably in their antigenic structure and can be identified according to their characteristic reactivity patterns with MAbs. Analysis of field virus isolates has also revealed that strains of rabies virus generally are associated with only one or a few major mammalian hosts within any given geographic area. Protection experiments in mice have not demonstrated correlations between protective activity and degree of antigenic difference between the vaccine strain and the challenge virus. Therefore, changes in antigenic structure, as determined by analysis with rabies virus-specific MAbs, cannot predict whether a given rabies vaccine will protect against a particular field virus.

Animals↗
PubMed1983

Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. II. Results of clinical studies simulating prophylactic therapy for rabies exposure.

Rhesus diploid-cell-strain rabies vaccine (RDRV) (adsorbed) is a new rabies vaccine intended for use in man. Sixty volunteers were given five doses of RDRV at 0, 3, 7, 14, and 28 days to simulate prophylactic treatment of persons exposed to a rabid animal. Thirty-five volunteers were given commercial high-titer rabies immune globulin, 20 IU/kg, before the first dose of RDRV, and 25 were given RDRV without prior rabies immune globulin. Antibody responses at 14, 28, and 42 days were comparable with those reported with human diploid rabies vaccine. Simulated postexposure prophylactic treatment with RDRV was associated with acceptable levels of local and constitutional symptoms.

Adsorption↗
PubMed1993

Rabies virus antinucleoprotein antibody protects against rabies virus challenge in vivo and inhibits rabies virus replication in vitro.

We previously reported that A/WySnJ mice vaccinated via a tail scratch with a recombinant raccoon poxvirus (RCN) expressing the rabies virus internal structural nucleoprotein (N) (RCN-N) were protected against a street rabies virus (D. L. Lodmell, J. W. Sumner, J.J. Esposito, W.J. Bellini, and L. C. Ewalt, J. Virol. 65:3400-3405, 1991). To improve our understanding of the mechanism(s) of this protection, we investigated whether sera of A/WySnJ mice that had been vaccinated with RCN-N but not challenged with street rabies virus had anti-rabies virus activity. In vivo studies illustrated that mice inoculated in the footpad with preincubated mixtures of anti-N sera and virus were protected. In addition, anti-N sera inoculated into the site of virus challenge protected mice. The antiviral activity of anti-N sera was also demonstrated in vitro. Infectious virus was not detected in cultures 24 h following infection with virus that had been preincubated with anti-N sera. At later time points, infectious virus was detected, but inhibition of viral production was consistently > or = 99% compared with control cultures. The protective and antiviral inhibitory activity of the anti-N sera was identified as anti-N antibody by several methods. First, absorption of anti-N sera with goat anti-mouse immunoglobulin serum, but not normal goat serum, removed the activity. Second, radioimmuno-precipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of sucrose density gradient-fractionated anti-N sera showed that antiviral activity was present only in the fraction containing anti-N antibody. Finally, absorption of anti-N sera with insect cells infected with a baculovirus expressing the N protein removed the protective activity. These data indicate that anti-N antibody is a component of the resistance to rabies virus infections.

Animals↗
PubMed1998

A review of the economics of the prevention and control of rabies. Part 2: Rabies in dogs, livestock and wildlife.

Although rabies in domestic and wild animals represents a significant threat to public health and can cause economic losses among livestock, there are very few studies that examine the economics of rabies in animals. The literature that does exist can be characterised as poorly documented estimates of costs, with insufficient information to allow replication of the analyses. Most papers have numerous 'violations' of the standard recommended procedures for assessing burden of disease and the cost and benefits of interventions. For example, most studies do not distinguish between financial charges and true economic costs. Further, despite the fact that controlling rabies in animal populations is often a multi-year task, only a few papers contain a multi-year framework, complete with discounting of future costs and benefits. Globally, dog-transmitted rabies represents the largest threat to human health. In order to prevent the transmission of rabies in a dog population, it is theoretically necessary to vaccinate a minimum of 60 to 70% of the dogs. Even countries with potentially sufficient resources, however, do not often meet and sustain these rates. One reason for such failure might be that individual dog owners might feel that it is too expensive to vaccinate their pets. Recent estimates in the US of the cost of vaccinating dogs range from $US16 to $US24 per dog. In developing countries, estimates range from $US0.52 in Thailand, to $US1.19 in the Philippines, to $US2.70 in Malawi. None of these estimates include indirect costs accured by the pet owners. Lethal methods of dog population control are even more expensive, and attempting to control rabies by reducing dog populations has not worked for any extended period. Rabies in livestock is often reported, but the impact in the US and most developed countries appears relatively small. Vampire bat-transmitted rabies in Latin America appears to be the most serious rabies problem in livestock. The largest cost due to wildlife rabies is the cost of vaccinating domestic animals, both large and small. In the US, domestic animals face multiple sources of wildlife rabies. Attributing the entire cost of vaccinating domestic animals to 1 species can result in the over estimation of the benefits of immunising a given wildlife population via vaccine-laden baits. For example, despite a definite decline in the number of rabid foxes, it has been difficult to obtain the promised benefits of using oral vaccines in Europe to control fox rabies. Other authors maintain that the use of oral vaccines to control fox rabies is cost beneficial, but there are no convincing data supporting that claim. Additionally, vaccinating raccoons with an oral vaccine requires approximately 4 times more vaccine-laden baits vaccinating foxes, which makes it highly questionable if it would be cost beneficial to use oral vaccine to attempt raccoon rabies elimination in areas where it is already enzootic. The economics of using oral vaccines to prevent raccoon rabies invading uninfected areas has yet to be examined.

Animal Diseases↗
PubMed2001

Immunogenicity and efficacy of Fermi-type nerve tissue rabies vaccine in mice and in humans undergoing post-exposure prophylaxis for rabies in Ethiopia.

Rabies is an acute viral encephalitis that is invariably fatal following the manifestations of clinical signs. To subvert the course of the disease, rabies post-exposure prophylaxis (PEP) is widely utilized. The immunogenicity and efficacy of Fermi-type rabies vaccine produced in Ethiopia was determined in mice subjected to intracranial challenge with rabies virus, and in humans undergoing rabies PEP in Ethiopia. Mice were randomly assigned into 5 groups. Group 1 received 0.25 ml each of phenolized saline intraperitoneally for 14 consecutive days. Mice in groups 2-5 received 0.25 ml of rabies vaccine for human PEP for the same period of time. Blood samples were drawn from the retro-orbital vein of all mice on designated days for the determination of rabies virus neutralizing antibody (VNA) using the mouse serum neutralization test. Mice were subsequently challenged intracranially with rabies virus at a concentration of 64 MICLD50 90 days post initial vaccination. Rabies neutralizing antibody titers in the sera of immunized mice ranged from 4.6 to 25 IU/ml. Booster vaccine doses did not seem to induce significant increases in the immune response of vaccinated mice, all of whom withstood intracranial challenge with rabies virus. Rabies VNA was further determined in 12 patients vaccinated in accordance with the prescribed dosage of Fermi-type vaccine for human rabies PEP. Most had > 0.5 IU/ml of rabies VNA by day 14, and none detectable at day 1. In contrast to mice, booster doses of vaccine may contribute to slightly higher rabies VNA titers in humans but our small sample size, on top of significant defaulter rates in the study participants, limits our interpretation of the effects of booster vaccine doses. The results of this study are the first documentation of the efficacy and immunogenicity of the Ethiopian Fermi type nerve tissue vaccine in both humans and mice.

Adolescent↗
PubMed1999

The epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis familiaris).

The epidemiology of rabies in dogs in Zimbabwe is described using data from 1950, when rabies was re-introduced after a 37-year absence, to 1996. Dogs constituted 45.7% of all laboratory-confirmed rabies cases and were the species most frequently diagnosed with the disease. Slightly more cases were diagnosed from June to November than in other months. From 1950 to the early 1980s, most dog cases were recorded from commercial farming areas, but since the early 1980s most have been recorded from communal (subsistence farming) areas. This change appears to be due to improved surveillance in communal areas and not to any change in the prevalence of rabies. Dog rabies therefore appears to be maintained mainly in communal area dog populations, particularly the large communal area blocks. Urban rabies was not important except in the city of Mutare. Where dog rabies prevalence was high, the disease was cyclic with periods between peak prevalence ranging from 4-7 years. Dog rabies cases were, on the whole, independent of jackal rabies and rabies in other carnivores. There was a significant negative relationship between the annual number of rabies vaccine doses administered nationally to dogs and the annual number of dog rabies cases lagged by one year, indicating that the past levels of immunisation coverage have had a significant effect on the number of rabies cases. However, dog vaccination coverage has clearly not been adequate to prevent the regular occurrence of rabies in dogs.

Animals↗
PubMed2000

Immunogenicity and effectiveness of post-exposure rabies prophylaxis with a new chromatographically purified Vero-cell rabies vaccine (CPRV): a two-stage randomised clinical trial in the Philippines.

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab; Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure rabies prophylaxis with this new vaccine were evaluated in a two-stage clinical trial conducted in the Philippines. In both study stages. post-exposure treatment consisted of five injections of vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of rabies immunoglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects with low-risk rabies exposure (WHO category I or II), and who had a negative ERIG skin test, were treated with either CPRV (n = 114) or PVRV (n = 117). By D14, all subjects in each group had achieved rabies antibody titres over ten times that recommended by the WHO as indicating seroconversion (> or = 0.5 IU/ml). The kinetics of the immune response to vaccination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Following these positive results, 132 subjects with severe rabies exposure were included in the second stage of this trial. All were scheduled to receive four vaccine doses with CPRV. After D14, only those 57 patients with confirmed rabies exposure (animal with positive FA test) and seven patients for whom rabies exposure could not be excluded (animal lost or not tested) completed the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe rabies exposure had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No severe local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage clinical trial attests to the safety and satisfactory immunogenicity of CPRV in post-exposure rabies treatment, and confirms the effectiveness of a new rabies vaccine in patients with severe confirmed exposure.

Adolescent↗
PubMed1986

Genetic control of serum neutralizing-antibody response to rabies vaccination and survival after a rabies challenge infection in mice.

Quantitative differences in serum neutralizing-antibody (SNAb) responses to rabies vaccination and survival after a rabies challenge infection between two inbred mice strains, C3H/J and C57BL/6J, were shown to be under genetic control. A 99% confidence limit calculated from the SNAb response titers of 14 C57BL/6J mice resulted in an upper limit for the SNAb response titer of C57BL/6J mice at 50.63. A SNAb titer less than or equal to 50.63 in response to rabies vaccination was assigned the phenotype of hyporesponder, and a SNAb titer greater than 50.63 in response to rabies vaccination was assigned the phenotype of hyperresponder in this study. The hyper-SNAb response to rabies vaccination and the higher frequency of survival after rabies challenge infection behave as Mendelian dominant alleles in F1 hybrids (C3H/J X C57BL/6J) and backcross (BC) (F1 [C3H/J X C57BL/6J] X C57BL/6J) progeny. Both a relatively hyper-SNAb response and a higher frequency of vaccine-inducible survival phenotypes occur in C3H/J mice. On the other hand, both the relatively hypo-SNAb response and a lower frequency of vaccine-inducible survival phenotypes behave as Mendelian recessive alleles and occur in C57BL/6J mice. C3H/J mice are H-2 Kk, and C57BL/6J mice are H-2 Kb. All three phenotypic traits (H-2 type, SNAb response, and survival after rabies challenge infection) segregate as independent (unlinked) monogenic traits in BC progeny (F1 [C3H/J X C57BL/6J] X C57BL/6J). The genetically controlled survival trait is inducible by rabies vaccination, but SNAb response is not a parameter that measures successful vaccine induction of preexposure protection from a rabies challenge infection in the BC progeny. The essential role of vaccination in developing preexposure protection in genetically responsive mice is confirmed, but indicates that in vitro measurements other than SNAb titers need to be developed to identify mice that have failed to achieve preexposure protection by rabies vaccination. This study confirms Lodmell's findings (D. L. Lodmell and B. Chesebro, J. Virol. 50:359-362, 1984; D. L. Lodmell, J. Exp. Med. 157:451-460, 1983) that susceptibility to rabies infection is genetically controlled in some mice strains. Additionally, this study indicates that conventional rabies vaccination even with more potent vaccines may not induce protection from infection in some genetically susceptible individuals.

Animals↗