Exploring the Feasibility of a New Low Cost Intra-Dermal Pre & Post Exposure Rabies Prophylaxis Protocol in Domestic Bovine in Jawali Veterinary Hospital, District Kangra, Himachal Pradesh, India

Abstract

Cattle are the backbone of household economy in rural areas of India and many of them die after bites by potentially rabid dogs, despite being given currently recommended five shots of intramuscular (IM) rabies vaccination as Post Exposure Prophylaxis (PEP). In 2016, seven of 21 bovine bitten by rabid dogs given IM rabies vaccination died due to rabies in Shimla Municipality. This scenario prompted the authors to look for a suitable protocol, based on human studies, to save animals. We tested various schedules of IDRV in bovine and found that a schedule of 0.2 ml given in middle 1/3 rd of neck on day 0, 3, 7, 14 and 28 along with local wound infiltration of eRIG is sufficiently immunogenic and life saving in all of them, even if bitten by lab confirmed rabid dogs/mongoose as tested by CRI. Rabivac Vet, a Cell Culture Rabies Vaccine, available as 1 ml per vial was used off level for IDRV. While injecting the vaccine, a raised papule of ≥1 cm will appear slowly causing a peau d'orange appearance. All 60 bovine serum samples tested by RFFIT after IDRV, had titers more than 0.5 IU/ml on day 14. Thereafter, a total of 150 animals were given five doses of IDRV as PEP, with or without RIG, after their exposure to clinically or lab confirmed rabid dogs/mongoose and all sur- vived for more than a year. Serum samples from 15 animals bitten by lab confirmed rabid dogs/mongoose were collected on day 14 and tested for RVNA by RFFIT from NIMHANS Bangalore and all had desired antibody titers above 0.5 IU/ml, without any immunosuppression. The RFFIT titers in 55% bovine in all groups were more than adequate after one year and 100% of them had anamnestic response to a single 0.2 ml booster given at one year. Few of the bovine and even one equine (Horse. Figure 4) brought for PEP at some of nearby vet hospitals were given IM rabies vaccine with local eRIG infiltration also survived. Local eRIG infiltration appeared to have covered the lacuna of longer window period required for indigenous antibodies production through IM route in bovine that are not sufficiently produced by day 14. While five times less vaccine was used in this low cost protocol and the survival was 100% compared to traditional IM protocol where survival was 66%. Pre-exposure prophylaxis was found to be effective as 0.2 ml dose of IDRV on day 0, 3, 7 and all bovine had titers higher than the desired by day seven after single 0.2 ml vaccine booster at one year. Our study points towards a possibility of having short schedules of three shots IDRV vaccination in bovine with or without local RIG (depending on presence or absence of wound/s) as PEP and single shot IDRV as PrEP, but further studies are required on a large number of animals. Our study also points out for allowing intra-dermal use in animals as well and labeling vaccines for the same as this is low cost more immunogenic and less painful compare to IM administration.

Comparative Evaluation of Intradermal vis-à-vis Intramuscular Pre-Exposure Prophylactic Vaccination against Rabies in Cattle

“…This is especially relevant in view of the fact that MSD Intervet (manufacturers of Nobivac ® Rabies vaccine) has been identified as one of the new suppliers for the WOAH rabies vaccine bank [ 27 ]. Hence, this study also aimed to check if there was better immune response as indicated by antibody titers for this vaccine as compared to other vaccines such as Raksharab and Rabivac Vet, used by other workers [ 14 , 15 , 28 ].…”

“…Animals of Group II were immunized with 1 mL of rabies vaccine intramuscularly in the neck region on day 0 without a subsequent booster dose. Animals of Group III were immunized with 0.2 mL of rabies vaccine intradermally at the middle third of the neck region on day 0 and a booster vaccine on day 21 as per the studies of [ 13 , 14 , 15 ]. Animals of Group IV were immunized with 0.2 mL of rabies vaccine intradermally at the middle third of the neck region on day 0 without a subsequent booster dose.…”

Can Rabies Infection have an Abortive Phase? Need for Further Evidence to Understand Rabies Epidemiology

“…In India, no rabies vaccine prophylaxis (Pre-Exposure) is done for domestic bovines. In our study on domestic cows and buffaloes, 5 that are left to graze in open pastures, out of 60 animals recruited, 25 animals (41.7%;17 cows and 8 buffalos), were having natural antibody titers without vaccination above 0.5 IU/ml in the range of 0.9 IU/ml and 15IU/ml by Rapid Fluorescent Focus Inhibition Test (RFFIT). While 12 unvaccinated cows tested at the HP University farm were having neutralizing rabies antibodies below 0.5 IU/ml (0.11-0.46 IU/Ml) because these cows were kept on an isolation farm since birth at Agriculture University, Palampur, Himachal Pradesh, India and did not have any contact with outside stray dogs.…”

“…While 12 unvaccinated cows tested at the HP University farm were having neutralizing rabies antibodies below 0.5 IU/ml (0.11-0.46 IU/Ml) because these cows were kept on an isolation farm since birth at Agriculture University, Palampur, Himachal Pradesh, India and did not have any contact with outside stray dogs. 5 This clearly indicated that domestic cows and buffalos, when left for grazing in the open pastures, interact with the rabies virus carrier stray dogs 11 and get infected and have rabies antibodies in their blood without vaccination.…”

“…1 RABV has evolved diverse strategies for immune evasion as "accessory" functions of the P, N, and M proteins, although many of these studies have used in vitro approaches focusing on the molecular biology of immune evasion. 2 However many in vivo studies have shown rabies antibodies in humans 3,4 cows & buffaloes, 5 dogs, 6 and bats 7 without a rabies vaccination. Abortive vampire bat rabies in Peruvian peri-domestic livestock has been reported.…”