An immunogenicity, safety and post-marketing surveillance of a novel adsorbed human diploid cell rabies vaccine (Rabivax) in Indian subjects

In 1999, Serum Institute of India indigenously developed an adsorbed human diploid cell rabies vaccine (Rabivax). During 2000-04, this new vaccine was subjected to a series of immunogenecity and safety studies. Initially, an experimental batch of Rabivax (adsorbed) was assessed on ten healthy adult volunteers and its response was comparable with that of Merieux inactivated rabies vaccine (MIRV, lyophilized) which was used as a control. Subsequently, Rabivax (adsorbed) was assessed on forty-five suspect rabid dog bite cases with MIRV as control. The vaccine was found to be equally safe and immunogenic as MIRV and showed better rabies virus neutralizing antibody (RVNA) response on day 90 than MIRV. A post-licensing study conducted on 150 cases of suspect rabid animal bites showed it to be safe and immunogenic. To assess its long-term sero-efficacy some of these subjects tested after one year of follow up showed that 84% of them had adequate RVNA titers. In addition, a routine post-marketing surveillance done on 1608 animal bite cases demonstrated that Rabivax (adsorbed) was safe and efficacious. The adverse events to Rabivax (adsorbed) included pain at injection site (3.4%), swelling with induration (2.8%), fever and headache (1.4%). No serious adverse event was reported from the studies. In conclusion, Rabivax (adsorbed) is an immunogenic, safe and efficacious vaccine for rabies prophylaxis in humans.     

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines. Results of a meta-analysis

A meta-analysis was done to study the relationship between antigenecity and immunogenecity of human rabies vaccines. The data of ten cell culture human rabies vaccine studies conducted at a single centre during 1993-2004 were used in the study. The vaccines studied included Purified Chick Embryo Cell Vaccine (Kaketsuken, Japan and Rabipur, India), Purified Vero cell Rabies Vaccine (Verorab, France), Human Diploid Cell Vaccine (MIRV, France and Rabivax, Adsorbed and Lyophilized, India) and Rhesus Diploid Rabies Vaccine (adsorbed, USA). Interestingly, it was revealed that an higher antigenecity of rabies vaccines viz. potency of > or = 5 IU per single intramuscular dose did not result in significantly higher immunogenecity, as measured by rabies virus neutralizing antibody (RVNA) titers in the vaccinees, both on day 14 (t = 0.42, p > 0.66, GMR = 1.06, 95% CI of GMR = 0.82, 1.37) and day 90 (t = 0.80, p > 0.43, GMR = 1.15, 95% CI of GMR = 0.74, 1.14). However, as there are no reports of meta-analysis of cell culture human rabies vaccine trials, to confirm this observation the authors recommend further studies in this regard.     

A comparative study on the safety and immunogenicity of purified duck embryo cell vaccine (PDEV,Vaxirab) with purified chick embryo cell vaccine (PCEC,Rabipur) and purifed vero cell rabies vaccine (PVRV,Verorab)

Rabies is a fatal but preventable disease. Cell culture vaccines (CCV) and purified duck embryo vaccines (PDEV) are currently recommended by WHO for post-exposure prophylaxis. In India, a PDEV (Vaxirab) is being manufactured and is in use since 2003. In the present study, we have evaluated the safety, immunogenicity and tolerance of this vaccine with two other WHO approved CCVs, viz., purified chick embryo cell vaccine (PCEC, Rabipur) and purified vero cell rabies vaccine (PVRV, Veroroab). This study was an open label, randomized phase IV comparative clinical trial. A total of 152 people bitten by dogs and other animals were recruited from 4 different centres from India. They were randomly assigned to receive one of the vaccines by Essen intramuscular regimen (52 subjects received Vaxirab and 50 each Rabipur and Verorab) and rabies immunoglobulin was also administered in all category III exposures. Their blood samples were collected on day 0 (prior to vaccination), 14, 28, 90 and 180. Side effects if any were monitored. The rabies neutralizing antibody titers in their blood samples were estimated by the rapid fluorescent focus inhibition test (RFFIT). Subjects in all three groups had neutralizing antibody titers by day 14 (>0.5 IU/mL) and geometric mean titers (GMT) observed for different vaccines on all days tested did not vary significantly (p > 0.5). Side effects observed were minimal and did not vary significantly among the groups. The results of the present study indicate that PDEV (Vaxirab) is as safe, tolerable and immunogenic as both PCEC (Rabipur) and PVRV (Verorab). Thus this vaccine can be a good alternative to WHO approved CCVs for rabies post-exposure prophylaxis.     

An epidemiological study of animal bites in India: results of a WHO sponsored national multi-centric rabies survey

This was a WHO sponsored national multi-centric rabies survey and one of its objectives was to find out the incidence of animal bites, anti-rabies treatment practices, Pet dog population and their care. Twenty-one medical colleges chosen with geoscatter representation conducted the survey during February-August, 2003. The survey was conducted in 18 states, covering a population of 52,731 chosen randomly from 8500 households. The annual incidence of animal bites was high, 1.7% and it was more in rural areas (1.8%), children (2.6%) and poor/low income group (75%). The main biting animal was dog (91.5%), mostly stray (63%), followed by cat (4.7%). A high proportion of bite victims did not wash their wounds with soap and water (39.5%), preferred Government hospitals (59.9%) and nerve tissue vaccine (46.9%). The use of rabies immunoglobulin was low (2.1%). A single animal bite episode led to a loss of 2.2 man-days and the cost of medicines including anti-rabies vaccine was Rs.252 (US$6). The recourse to indigenous treatment (45.3%) and local application to wound (36.8%/) was quite prevalent. About 17% of households reported having a pet/domesticated dog and the pet dog: man ratio was 1: 36. Pet dog care/management practices were not satisfactory with a low veterinary consultation (35.5%) and vaccination (32.9%). The situation was slightly better in urban areas. The people also reported the presence (83%) and menace (22.8%) of stray dogs. It is recommended to initiate appropriate community awareness and dog vaccination campaigns and effective stray dog control measures.     

A comparative study on the immunogenicity, safety and tolerance of purified duck embryo vaccine (PDEV) manufactured in India (Vaxirab) and Switzerland (Lyssavac-N): a randomized simulated post-exposure study in healthy volunteers

Purified duck embryo vaccine (PDEV, Vaxirab) for rabies prophylaxis is now indigenously manufactured in India under technology transfer from Berna Biotech who made the original PDEV (Lyssavac). In the present study we have compared the two vaccines in terms of safety, immunogenicity and tolerance. The study was conducted in 220 adult healthy volunteers. It was observed that both vaccines produced neutralizing antibody titers (as determined by rapid fluorescent focus inhibition test, RFFIT) more than 0.5 IU/mL (minimum level for seroconversion) on all days tested but the titers on days 90 and 180 were significantly higher with Lyssavac. The adverse reactions produced were slightly more with Lysssavac but both vaccines were well tolerated. In conclusion, the indigenously produced PDEV (Vaxirab) was found to be equally safe and immunogenic as the original PDEV (Lyssavac) manufactured at Switzerland.     

Prevalence of bronchial asthma and its association with smoking habits among adult population in rural area

A cross-sectional study was conducted in the rural field practice area of Kempegowda Institute of Medical Sciences, Bangalore. A total of 3194 adult individuals (18-70 years) were selected from 30 villages (clusters) using a cluster-sampling technique. Individuals with symptoms suggestive of asthma were subjected for clinical examination for the diagnosis of asthma. Among the 3194 respondents, 1518 (47.5%) were males and 1676 (52.5%) were females. The prevalence of bronchial asthma was 2.88%. The prevalence of asthma was higher among those reporting a history of current smoking. Among current smokers, the number of cigarettes/bidis/hookah smoked daily did not differ (P > 0.05) between individuals without asthma and with asthma, whereas the mean number of years of smoking did differ (P < 0.001). There was significant association between tobacco smoking and bronchial asthma.