Appraisal of surveillance of human rabies and animal bites in seven states of India.

BACKGROUND: The key to understanding the burden of animal bites and rabies lies in accurate and timely data with the help of proper surveillance system across the country. Such a surveillance system needs to be evaluated also for a programmatic purpose. OBJECTIVES: The present study was conducted to appraise the surveillance system of human rabies and animal bites in seven states of India and also to describe the characteristics of human rabies cases in the states. METHODS: The record-based study was conducted from July to December 2017. The survey team collected information about the surveillance status of human rabies from the infectious diseases hospitals and animal bites from integrated disease surveillance programme (IDSP) offices of the respective states for 2012-2016. At the national level, also number of animal exposures and the human rabies cases were collected from the Central Bureau of Health Intelligence and IDSP and compared for concordance. RESULTS: There was a gross underreporting of human rabies from the states to Government of India, and there was no concordance in the reports of animal bites between the IDSP offices of the states and NCDC, New Delhi, India. There was a gradual decline in the reported cases of human rabies from the states during the 5-year period of 2012-2016, attributable to improvement in the overall rabies postexposure prophylaxis services. The documentation of information of the human rabies cases was poor in the infectious disease hospitals. CONCLUSION: The surveillance system on human rabies and animal bites in India has to be improved under the national rabies control program to eliminate rabies by the year 2030.

Market mapping and landscape analysis of human rabies biologicals in India.

BACKGROUND: Rabies vaccines and immunoglobulins are lifesaving in humans following animal exposures. These biologicals should continuously be available throughout the year to prevent and eliminate human rabies by 2030. OBJECTIVES: The present study aimed at assessing availability of different kinds of human rabies biologicals in the country and undertaking market mapping and landscape analysis of human rabies biologicals in India. METHODS: The study comprising both quantitative and qualitative approach was conducted from May to November 2017 as a part of the Indian multicentric rabies survey by Association for Prevention and Control of Rabies in India. All stakeholders (agencies/personnel) associated with rabies biologicals were the study units/participants. Required data were generated through brainstorming sessions with key stakeholders; reviewing of databases/existing literature; conducting in-depth surveys; interviewing; focused group discussions, etc. RESULTS: Two types of cell culture rabies vaccines are available in the country manufactured by different pharmaceutical companies; most of the vaccines are indigenously produced and the market size of the rabies vaccines is about INR 125 crores with highest sales in the northern region followed by South. Likewise, there are 2 types of immunoglobulin available, i.e., equine rabies immunoglobulins (RIGs), which are indigenously produced and human RIGs, which are imported. The market value of RIGs is about INR 83 crores. A novel rabies monoclonal antibody is also been marketed in the country from November 2017. CONCLUSIONS: There are many lacunas in the market availability of rabies biologicals in different parts of the country; therefore, a significant expansion/shift in focus must be considered, through rigorous strategic planning process.

Background paper for developing a policy for the use of rabies biologicals and vaccination of humans in India.

National Rabies Control Programme, India, is in operation since 2012-2013 without much impact due to poor funding and no set policy for the rabies prevention and control. An effort was made to develop a draft policy paper which can help the Government of India to develop a national rabies vaccination policy for humans and for achieving the goal of zero dog-mediated human rabies deaths by the year 2030. A technical stakeholders meeting was held under the chairmanship of the Drug Controller General of India at New Delhi in December 2017 to discuss the problems and solutions for providing essential rabies postexposure prophylaxis (PEP). The following problems and dilemmas were identified: frequent shortages of life-saving rabies vaccines and rabies immunoglobulin for PEP; as rabies vaccines are mostly procured by the state governments that often face resource crunch and hurdles in logistics within the states; production levels of rabies biologicals in the public sector are low; and the export of rabies biologicals from the private sector needs to be critically evaluated in the context of frequent stock-outs in the domestic market and also the national vaccine security.

Safety and immunogenicity study of a new purified chick embryo cell rabies vaccine Vaxirab-N (Pitman-Moore strain) manufactured in India.

Zydus Cadila Health care, India developed a new purified chick embryo cell rabies vaccine (PCECV, Vaxirab-N; 1 mL) by adapting Pitman-Moore strain of virus on to the chick embryo fibroblast cell line in 2006. During 2007-10, a series of safety and immunogenicity studies were conducted as per ICH-GCP guidelines after obtaining permission from Drug Controller General of India. In the first study, Vaxirab-N was administered to 35 healthy adult volunteers by intramuscular (IM) route using pre exposure regimen. The geometric mean concentration (GMC) of rabies virus neutralizing antibody (RvnAb) of 7.5 IU/mL on day 35. In the second study, Vaxirab-N was administered to 35 healthy adult volunteers using simulated post- exposure prophylaxis regimen by IM route. A GMC of 6.3 IU/mL on day 14, 13.2 IU/mL on day 28 and 8.6 IU/mL on day 90 was obtained. In the third study, Vaxirab-N administered by intradermal (ID) route using Updated Thai Red Cross (TRC) regimen in 36 healthy adult volunteers showed GMC of 7.8 IU/mL on day 14, 11.5 IU/mL on day 28 and 6.0 IU/mL on day 90. The 4th study was multi centric and Vaxirab-N was administered to 129 animal bite cases by IM route using post-exposure Essen regimen. The GMC following this schedule was 8.2 IU/mL on day 14, 13.01 IU/mL on day 28, 7.92 IU/mL on day 90 and 3.72 IU/mL on day 180. Mild to moderate adverse events were reported to Vaxirab-N but no serious adverse events were reported in any of these studies. In conclusion, Vaxirab-N developed by Zydus Cadila was found to be safe and immunogenic by both intramuscular and intradermal route and is recommended for rabies prophylaxis (CTRI No. 2010/091/000055 and 2010/091/000509).

Pre-exposure prophylaxis against rabies in children: safety of purified chick embryo cell rabies vaccine (Vaxirab N) when administered by intradermal route.

Animal bites in humans are a public health problem. Children are the most frequently exposed, representing 50% of human exposures in canine rabies infected areas. Pre-exposure vaccination using cell culture vaccines is a safe and effective method of preventing rabies among children in these highly endemic regions. The development of immunological memory after pre exposure vaccination has established long lasting immunity against rabies in humans. The present study assessed the safety of Purified Chick Embryo cell Rabies Vaccine (Vaxirab N) administered as a three-dose intradermal pre-exposure regimen on days 0, 7, and 21 in healthy volunteered children of 5-10 y age group from an urban poor locality in Bangalore, India. One hundred fifty three apparently healthy children of both sexes between 5 and 10 y of age were enrolled in the study and 123 (80.4%) completed all three doses. A total of 405 doses of intradermal vaccine was administered, among which 25 adverse reactions were reported from 17 children. The adverse reactions were pain at the injection site 15 (3.7%), redness 2 (0.5%), itching at the site of injection 1 (0.2%), fatigue 1 (0.2%), fever 3 (0.7%), myalgia 2 (0.5%) and allergy 1 (0.2%). All reactions subsided without any complication. In conclusion, pre exposure vaccination against rabies is a useful tool for protecting children living in highly endemic regions and Vaxirab N has proved to be safe and well tolerated by intradermal route among children.