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 1/3rd 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 survived 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.

Highlights

  • The exposure of domestic farm animals like cattle, buffaloes, horses, goats and sheep to bites of rabid dogs is of great socio-economic concern especially in rural areas where the cattle are the backbone of family economy and a dependable livelihood

  • 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)

  • Considering the enormous burden of rabies, we were able to demonstrate clinical effectiveness of a novel low cost protocol based on our previous experience with human rabies vaccination and local infiltration of Equine rabies immunoglobulin (eRIG) and we called this protocol to memorise our guru as “Madhusudana-Bharti-Uppinder” protocol

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Summary

Introduction

The exposure of domestic farm animals like cattle, buffaloes, horses, goats and sheep to bites of rabid dogs is of great socio-economic concern especially in rural areas where the cattle are the backbone of family economy and a dependable livelihood. In Shimla Municipality in 2016, seven of 21 jersey cows died due to clinical rabies despite having been given post-exposure prophylaxis (PEP) with recommended IM injections of rabies vaccine on day 0, 3, 7, 14 and 28. One of the adult cows died after 20th day of exposure and another after 35th day of exposure. This may have occurred due to a short incubation period consequent to bite wounds mostly near brain (on head and neck region) or non-administration of rabies immunoglobulin (RIG) into wounds or failure of IM vaccination to induce early protective response. Even vaccine antigen titers when raised to 4.0 IU or even higher resulted in failure [3] underlining the inappropriateness of rabies vaccine alone in animal post exposure prophylaxis

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