Maneerat Benjavongkulchai

What is an acceptable delay in rabies immune globulin administration when vaccine alone had been given previously

Rabies immune globulins (RIG) are not always available. Rabies-exposed patients often present to medical centers, particularly in canine rabies infested regions, after a vaccine series has been started without immune globulin administration. It is known that rabies immune globulin can result in suppression of the neutralizing antibody response which usually yields detectable antibodies by day 7. We have shown that it can be administered with a delay of up to 5 days after the start of vaccine treatment without significant antibody suppression within the first month. This study utilized the WHO approved multisite Thai Red Cross intradermal postexposure regimen. Effective use of rabies immune globulin in severe and multiple wounds, particularly in small children, may require dilution of the RIG in normal saline to provide a volume adequate for infiltration of all wounds.

Antibody Response After a Four-Site Intradermal Booster Vaccination with Cell-Culture Rabies Vaccine

The current World Health Organization recommendation for booster vaccination of previously immunized individuals with potential exposure to rabies is two doses of vaccine intramuscularly or intradermally on days 0 and 3. We report responses to two types of postexposure treatment of healthy individuals who had received preexposure rabies vaccination 1 year previously. Group A individuals received four intradermal doses (one-fifth of the diluent volume of vaccine per dose) on day 0, and group B individuals received two intramuscular doses on days 0 and 3. Immunogenicity of the two booster regimens was assessed by titrating the amount of neutralizing antibody (Nab). We found that the booster doses of vaccine produced remarkable responses in all subjects. Nab titers of > or = 0.5 IU/mL (acceptable antibody level for protection against rabies) were detected in all subjects on day 14, and they were shown to be consistently high 1 year after the booster vaccination. We also found that the Nab titers for group A were significantly higher (two- to eightfold) than those for group B on days 5, 14, 150, and 360 after the initial booster vaccination (P < .05). Our study shows that the four-site intradermal booster regimen with use of one-fifth of the diluent volume of cell-culture rabies vaccine on day 0 is associated with a significantly higher antibody response than is the conventional booster regimen for subsequent postexposure rabies treatment of individuals who have received preexposure rabies vaccination with cell-culture rabies vaccine 1 year previously.

Immune response to tissue culture rabies vaccine in subjects who had previous postexposure treatment with Semple or suckling mouse brain vaccine.

Nerve tissue derived Semple and suckling mouse brain rabies vaccines are still widely used. Patients who experience a new rabies exposure and who were given such vaccines decades earlier are not uncommon in rabies endemic countries. The World Health Organization recommends that persons who have had a previous course of a potent tissue or avian culture rabies vaccine and are reexposed, be given booster infections on days 0 and 3 without rabies immune globulin. Persons who have had previous pre- or postexposure vaccination with a vaccine of unproven potency, should receive a full course of tissue or avian cell vaccine and immune globulin in the event of a new exposure. This study evaluated the immune response in 98 Thai patients who gave a history of rabies postexposure treatment with Semple or suckling mouse brain vaccines 10-50 years previously. The majority (81) had an anamnestic response and developed neutralizing antibodies that were above the recommended minimal acceptable level (0.5 IU ml-1) on day 7. This suggests that they still had immunological memory. A minority of 18% had antibody titers below this level on day 7. However, they all developed titers above 0.5 IU ml-1 on days 14 and 30. Failure to have an accelerated response to revaccination by day 7 did not appear to be related to age or time elapsed since previous nerve tissue derived vaccine administration. It was not possible to predict which subject will or will not have an acceptable level of antibody before day 14. Rabies exposed patients who give a prior history of vaccination with an unknown or nerve tissue derived vaccine should therefore be treated as if they had never been vaccinated.

Efficacy study of a new albumin-free Human Diploid Cell Rabies Vaccine (Lyssavac-HDC, Berna) in 100 severely rabies-exposed Thai patients

A newly developed human diploid cell rabies vaccine (Lyssavac-HDC), produced without added serum albumin and with an effort to remove the virus-inactivating beta-propriolactone prior to addition of the gelatin, L-cysteine and potassium phosphate stabilizer, was tested for safety immunogenicity, adverse reactions and efficacy in 100 severely rabies-exposed Thais. All patients also received human rabies immune globulin and vaccine was administered using the conventional 5-dose intramuscular schedule of one dose on days 0, 3, 7, 14 and 28. One hundred percent of a subgroup of 40 subjects, where blood had been collected, had neutralizing antibodies greater than 0.5 IU ml-1 on days 28 and 90 and all had detectable titers on days 7, 14, 28, 90, 180 and 360. All patients could be followed for at least 1 year and remained well. No significant side-effects from this vaccine were noted.

POSTEXPOSURE RABIES VACCINATION DU RING PREGNANCY : EFFECT ON 202 WOMEN AND THEIR INFANTS

This prospective study of 202 pregnant Thai women who received postexposure treatment for rabies with a tissue culture-derived rabies vaccine and human or equine rabies immune globulin revealed an adverse reaction rate similar to that seen among nonpregnant Thai patients who received the same treatment. Tissue culture-derived rabies vaccines as well as immune globulins are safe to use for postexposure prophylaxis during pregnancy. Such treatment should never be withheld or delayed if the patient possibly was exposed to rabies.