1. How can long term protection be achieved after a complete post-exposure treatment especially with Vero Cell vaccine like Verorab (Ranbaxy)?

          Dr.A.K.Gupta, Delhi

By using the phrase “Long term protection”, I could get that you are asking about either the Pre-exposure vaccination status or how long are the neutralizing antibodies against the rabies virus present in the circulation after a post-exposure, or pre-exposure course of vaccination.

As per the current WHO guidelines a pre-exposure course by the IM route, consists of a dose of TCV or modern Avian Embryo derived vaccine having a potency of 2.5 IU, or more per IM dose, taken on the deltoid or the anterolateral aspect of the thigh in small children on Days 0,7, and 21 or 28 only. Boosters are recommended, in the case of persons working with the virus in laboratories, etc, where the RIFFIT shows an antibody titre of < 0.5 IU/m.l. of serum. The RIFFIT has to be done once in every six months. For other categories, two boosters are recommended, one on Day 0 and one on Day 3, in case of a fresh exposure after the primary course of vaccination. No cut out time has been mentioned for this to be effective after the primary course.

I maintain that this piece of advice is very risky. I have passed this comment based on a very long and vast field experience, and on review of scientific literature.

C. Strady, et al.  in their paper “Predictive factors for the neutralizing antibody response following pre-exposure rabies immunization: validation of a new booster dose strategy”, published in Vaccine 18 (2000) 266H:2667 mentions that the predictive factors for the durability of the neutralizing antibody response to pre-exposure immunization are surely, not, all identified. The influence of age has been mentioned. In a univariate analysis carried out in a prospective study over a 10-year period, we have shown the influence of the type of vaccine and the immunization route used as well as the predictive value of the results of a titer measurement at 14 days following the1-year booster dose on the subsequent evolution of antibody titers in immunized subjects. Furthermore, discriminating factors between a``good'' and a ``poor'' responder have never been analyzed in a systematic way, although observation has long suggested that such a dichotomy does indeed exists. Based on all these factors, institutional recommendations advise that antibody titers be monitored every 6 months in subjects with a continuous risk of exposure and once every one (WHO) to two(ACIP) years in subjects with a frequent risk of exposure.

Alain Strady, et all, in their paper “Antibody Persistence Following Pre-exposure Regimens of Cell-Culture Rabies Vaccines: 10- Year Follow-Up and Proposal for a New Booster Policy” published in the The Journal of Infectious Diseases 1998;177:1290-5, says that HDCV and PVRV in three doses were equally immunogenic. A booster injection at 1 year provides long-term seroconversion (titer >0.5 IU/mL). Antibody titers 2 weeks after the 1-year booster allowed prediction of long-term immunity. Good responders, with titers >30 IU/mL, were protected for at least 10 years. An algorithm for differentiation between good responders and poor responders with respect to vaccine booster strategies is proposed.

Persons getting pre-exposure vaccinated against rabies should receive three doses of HDCV or PVRV, one each on Days 0,7, and 28, in the first year. After one year, they should receive a Booster. 14 days after the booster, the serum should be tested for rabies virus neutralizing antibodies by RIFFIT. In situations where this is not available, Booster doses should be taken once in every five years. In situations where the RIFFIT is available, and the test could be carried out, if the titre is > 30 IU/m.l. of serum, then boosters are to be taken once in every 10years, and no further testing are required. If the RIFFIT done 14 days after the booster dose taken one year after the primary course of vaccination, shows the titre to be < 30 IU/m.l. of serum, then boosters are to be taken once in every three years

AK Dutta, et all, in their paper, “Worldwide experience with a purified vero-cell-culture rabies vaccine”, published in the “APCRI Journal” , Vol VIII, issue 1, mentions that the “Management of vaccinated people who are exposed again at a later date involves local treatment of the wound and repeat booster vaccination with 2 doses given on days 0 and 3. If there was a complete post-exposure or pre-exposure treatment previously within 3 years, 2 injections of a cell culture vaccine can be given without need for RIG. Any exposure 3 years or more after vaccination should be treated with complete post-exposure vaccination and administration of RIG. Previously vaccinated patients who have neutralizing antibody titres of less than 0.5 IU/mL, immunocompromised  patients, including those on steroid therapy, should receive the complete immunization schedule including RIG.”

A recent evaluation of response to a PVRV booster in people vaccinated from between 5 and 20 years earlier has confirmed the very long lasting immune memory conferred by PVRV and that RIG need not be given in cases of re-exposure in previously vaccinated individuals.[i]

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