Simulated post-exposure rabies vaccination with purified chick embryo cell vaccine using a modified Thai Red Cross regimen.

OBJECTIVES: Currently, two intradermal regimens for the administration of cell culture rabies vaccines are approved by the WHO for rabies post-exposure prophylaxis: the two site Thai Red Cross regimen (TRC) and the eight site regimen. For the TRC regimen the volume of vaccine recommended per dose is 0.1 ml of purified Vero cell rabies vaccine (PVRV) and 0.2 ml of purified chick embryo cell vaccine (PCEC). The objective of the present study was to evaluate comparatively the immune response to PCEC and PVRV vaccines administered by the TRC regimen using a uniform dose of 0.1 ml of vaccine. METHODS: Forty-two subjects received TRC regimen (2-2-2-0-1-1) with 0.1 ml of PCEC vaccine and 38 subjects received the same regimen with PVRV. The rabies neutralizing antibody response in these subjects on days 10, 28, 90 and 180 was determined by the standard mouse neutralization test (MNT). RESULTS: There was adequate antibody response with both the vaccines and 100% seroconversion was observed by day 10. Furthermore, the antibody titers obtained with PCEC did not differ significantly from those obtained with PVRV on all days tested (p > 0.05). CONCLUSIONS: It can be concluded from the results that an adequate antibody response can be obtained with PCEC vaccine when administered by the TRC regimen even after reducing the quantity of vaccine from 0.2 ml to 0.1 ml per intradermal dose. The feasibility of using this regimen in true post-exposure cases needs to be further evaluated.     

Clinical trials in healthy volunteers with the new purified chick embryo cell rabies vaccine for man

Behringwerke has developed the new, safe and economical purified chick embryo cell (PCEC) rabies vaccine. Due to the purification by zonal centrifugation the compatibility of this vaccine is excellent. Among 933 vaccinations in 219 healthy volunteers the only side-effect was mild pain at the injection-site in 17 vaccinations (1.7 per cent). The sero-conversion of PCEC rabies vaccine was 100 per cent in the tested healthy volunteers. The kinetics of antibody induction after PCEC rabies vaccine is comparable to antibody induction after HDC rabies vaccine. PCEC rabies vaccine induces cellular immunity as measured in lymphocyte transformation test, but no interferon activity.     

Profile of animal bite cases in Pune

A Cross-sectional study was carried out to determine the profile of animal bite cases reporting to the Anti Rabies clinic of Sassoon Hospital, rune. The data was collected using pretested questionnaire. All 250 cases who reported during the period of study were included in the analysis. The male female ratio was 1.98 : 1. Children in the age group 0-14 years were the victims in 132 (52.8%) cases. Dog was the biting animal in 94.4% cases, followed by cat (2.4%), Jackal (1.2%), mongoose (1.2%), monkey (0.4%) and horse (0.4%). Of the 236 dog bite cases 30% of bites were inflicted by pet dogs of which only 38.02% were immunized. The wound was washed with soap and water in only 3.6% of cases. 64.8% of the bites were on the lower extremity and 63.2% of cases reported within 24 hours of the bite. Of the 247 cases administered Beta Propio Lactone (BPL) inactivated vaccine only 18.8% did not have any local reaction and 58.3% had one or more systemic reaction. A three pronged strategy has been recommended to reduce the burden of morbidity and mortality associated with rabies.     

Economical multi-site intradermal regimen with purified chick embryo cell vaccine (Rabipur) prevents rabies in people bitten by confirmed rabid animals.

OBJECTIVE: To determine the efficacy of a cost-effective multi-site intradermal regimen with purified chick embryo cell vaccine (PCECV, Rabipur) in preventing rabies in people bitten by confirmed rabid dogs. METHODS: Thirty-two people of different age groups who were severely bitten by confirmed rabid dogs were immunized with PCECV using the WHO recommended multi-site intradermal regimen of 0.1 mL of vaccine at eight sites on day 0, at four sites on day 7, and at one site each on days 28 and 90. In addition, passive immunization with human or equine rabies immunoglobulin was administered to 22 of these people before administering vaccine. They were followed for up to 3 years with periodic estimation of neutralizing antibody levels in their serum by mouse neutralization test (MNT). RESULTS: There was an excellent immune response with more than protective titers (>0.5 IU/mL) on all days tested up to the end of the 3-year observation period. More significantly, protective titers were seen in all subjects by day 7. Only minimal side effects were observed. All the patients were doing well at the end of the 3-year observation period, which is generally considered to be the maximum incubation period for rabies in humans. CONCLUSIONS: It can be concluded that this multi-site regimen with or without passive immunization has prevented the development of rabies encephalitis in these people bitten by confirmed rabid dogs. This should encourage more such studies, so that this cost-effective economical regimen with safe and potent cell culture vaccines can replace highly reactogenic neural tissue-derived Semple vaccine in developing countries such as India.     

Skin reaction to yellow fever vaccine after immunization with rabies vaccine of chick embryo cell culture origin

Skin reaction to yellow fever vaccine was examined after immunization with rabies vaccine. The two vaccines contained substrates from chick embryo cells (rabies vaccine) and chick whole embryo (yellow fever attenuated vaccine), as well as gelatin. A prick test with gelatin showed negative results in all vaccinees examined. An intradermal skin test revealed that the yellow fever vaccine had reacted with an anti-egg protein antibody-like substance in a case with a history of egg allergy before rabies vaccination. A case inoculated two times with the rabies vaccine revealed a positive reaction to egg-white protein as well as the yellow fever vaccine. This case had no anamnesis of egg allergy. Thus, an antibody reactive to the egg-white protein and/or the yellow fever vaccine was inducible by the rabies vaccine. The reaction of this antibody was not systemic but local at the skin test by the yellow fever vaccine. The period of the rabies vaccine sensitization reactive to the yellow fever vaccine could be estimated as longer than 14.3 +/- 9.6 days (mean +/- SD), based on a follow-up examination of the positive skin reaction in 41 of 84 cases examined. We therefore conclude that the yellow fever vaccine can be safely administered at an interval of at least four weeks after a second rabies vaccination.     

人用狂犬病纯化疫苗(Vero细胞)临床观察及免疫学效果研究

目的　研究人用狂犬病纯化疫苗的安全性和保护性。方法　采用狂犬病疫苗暴露后免疫程序接种受试人群 ,I期临床接种 2 0人 ,II、III期临床接种 30 4人 ,观察注射后反应 ,采用小鼠脑内中和试验法测定其中 6 2人中和抗体水平。结果　全部受试者有 13.2 7%出现轻度副反应 ,无中强度副反应 ,中和抗体阳转率为 10 0 % ,中和抗体GMT为 11.89IU/ml。结论　该疫苗对人体安全且具有较好的免疫原性     

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.     

Immunogenicity and safety of purified Vero-cell rabies vaccine in severely rabies-exposed patients in China

The immunogenicity and safety of a purified Vero-cell rabies vaccine (PVRV, VERORAB; Aventis Pasteur, France) were evaluated in 171 patients treated for severe exposure to rabies (WHO category III contacts) at the Shandong Provincial Antiepidemic Station in Jinan and an EPI center in Ping Yin, China. Post-exposure treatment consisted of a single dose of equine rabies immunoglobulin (ERIG, 40 IU/kg body weight) on Day (D) 0, and intra-muscular administration of PVRV on D 0, 3, 7, 14 and 28. Antirabies antibody levels were evaluated on D 0, 7, 14, 28, 90 and 180 using the rapid fluorescent focus inhibition test. By D 14 all subjects had seroconverted (> or = 0.5 IU/ml), with a geometric mean titer of 50.3 IU/ml. Antibody titers remained above the seroprotection threshold in all patients for 3 months, and in 98.2% of subjects for 6 months. All patients were still alive 6 months after the start of treatment. PVRV and ERIG were shown to be well tolerated and no serious adverse events were observed. Following PVRV administration, 12 patients (7.0%) had at least one local reaction (mostly pruritus, erythematous rash and pain). Fourteen patients (8.2%) developed local reactions at the site of ERIG administration. Twelve patients (7.0%) developed systemic reactions following post-exposure treatment, the most frequent of which were pruritus, rash and vertigo. This study demonstrates that PVRV is immunogenic and safe in Chinese patients treated according to WHO recommendations for severe rabies exposure.     

High effectiveness of aerosolized chick embryo fibroblast measles vaccine in seven-month-old and older infants

Neither the presence of hypertonic sugar nor the absence of 1% human albumin in the aerosolized chick embryo fibroblast (CEF) measles vaccine was previously found to be responsible for its inadequacy in infants with titers of maternal plaque-neutralizing (PN) antibody at which human diploid cell measles vaccine was immunogenic. Eight weeks after administration of CEF measles vaccine containing 1% human albumin, antibody had developed in all 10 infants 7-10 months old and all 11 children 12-35 months old but in only 26% of 23 infants 3-5 months old and 67% of 9 infants 6 months of age. Failure of antibody development was associated with prevaccination PN antibody titers of greater than or equal to 1:50 (with one exception at a titer of 1:25). The PN antibody response to CEF vaccine (diluted 1:10, approximately 10(5) pfu/ml) in infants under seven months of age (geometric mean titer [GMT], 1:421) was significantly lower (P less than .005) than in older infants (GMT, 1:1,564). At a 1:1,000 dilution of vaccine, only 50% of 10 infants 13-25 months old, 20% of 15 infants 7-10 months old, and none of 8 infants 6 months old developed antibody.     

Pattern and burden of animal bite cases in a tertiary care hospital in Haryana

Rabies is an endemic disease in both developed and developing world and is responsible for a large number of morbidities and mortalities in humans. Limited supply of vaccine hampers the accessibility of life saving treatment. In our study carried out in a tertiary care hospital in Haryana showed that there were 3617 animal bite cases reported in a year with an average of 9.91 new cases per day. The average economic burden related to management of these bite cases is 3.5 lacs per month. This cost along with vaccine demand can be substantially reduced if intradermal schedule is introduced.     

Stimulation of growth and mucopolysaccharide synthesis by insulin treatment of chick embryo chondrocytes in cell culture.

The effect of insulin on growth, mucopolysaccharide synthesis and collagen synthesis by cultured chick cartilage cells was determined. It was found that different fetal calf serum lots had different effects on insulin's action. The selection of one serum lot and elimination of serum from the medium in some instances allowed more precise control of culture conditions. Insulin stimulated the growth of the cells in both serum-supplemented and serum-free medium. Growth was affected initially but during later periods of treatment differences in cell numbers were simply maintained. Mucopolysaccharide (MPS) synthesis was stimulated to a greater extent than general growth under all conditions by insulin, with the greatest stimulation being observed in serum-free cultures. Collagen synthesis was stimulated by insulin to a small degree and only if ascorbic acid was omitted from the medium. It is suggested that insulin principally affects MPS synthesis and not collagen synthesis. It was found that increasing the concentration of certain amino acids enhanced insulin's ability to stimulate MPS synthesis; the results suggest that tyrosine, alanine, glycine, serine and threonine are of specific importance in the insulin effect on cartilage. Although relatively high doses of insulin were used in these studies, it is probable that the minimum amount of insulin necessary to stimulate the cells may be physiological.