Clinical efficacy:
There are innumerable reports of clinical efficacy of Hib vaccines in field trials. Oxford, UK study showed 100% efficacy of PRP vaccines given to infants (given 3 primary doses alone) over 2 years follow up (2). Similar studies from Finland using PRP D vaccine in >0.1 million showed 90% efficacy in infants given 3 primary doses & 1 booster dose (2). Study using HbOC in California showed 100% efficacy & in Finland 97% efficacy using 3 doses and a booster in infants (2). PRP OMP vaccine showed 97% efficacy with first dose itself in Arizona area (2). Other studies done with PRPT have shown 91.7% efficacy in Chile & 100% efficacy in Finland. It is estimated that first dose of vaccine gives 71%, 2^nd dose 89% & 3^rd dose 95%-100% clinical efficacy.

Effect on carrier state:
Study from Oxford, UK showed that there was significantly low level of carriage in vaccinated infants compared to controls. The carrier rate was 1.5% in vaccinated as compared to 6.3% in unvaccinated infants. Amongst children with family history of exposure to Hib the carrier rate was 8.7 % in vaccinated & 38.5& in unvaccinated group. Only 3.7% vaccinated siblings were carrier of an index carrier as compared to 12.0% in unvaccinated group. There was no difference in the period for which a child remained carrier as it was 5.2 weeks in vaccinated Vs 5.6 weeks in unvaccinated group (9). Similar study from Finland has shown that 3.5% of unvaccinated children were carrier as compared to 0% of vaccinated children (2). In Iceland it was shown that carrier rate dropped from 16% to 0.5 % in 2years after mass vaccine.

Decrease in carrier rate can explain herd immunity as seen in countries resorting to mass vaccination.

Impact of mass vaccination:
Various countries took to mass vaccination using conjugate Hib vaccine since 1985-1990. They all have shown more than 95-99% reduction in clinical cases due to Hib just in 2-5 years of such vaccination programme. In some cases the benefits were also seen in unvaccinated minority due to herd immunity effect.

In USA between 1985-87, there was no impact with use of PRP at 18-24 months of age. Between 1987-1990, PRPD was used as 3 primary & 1 booster dose which showed 80% drop in incidence. After 1990, HbOC & PRPT are extensively used. Even with 60% coverage there was 90-95% drop in incidence (2). Similarly Finland resorted to mass vaccination in 1988 using initially PRP OMP or HbOC & later HbOC or PRPT. It showed 87% drop with PRP OMP, 95% drop with HbOC & 95-98% drop with PRPT at coverage of 90-95% (2,19). In UK mass vaccination began in 1992 which showed 99% drop in <1 year old children, 97% drop in 1-2 years old & 94.7% drop in 2-3 years old children at 92% coverage (2,20).

Hence it is possible to eliminate or even eradicate Hib by mass vaccination programme.

Cost effectiveness of mass vaccination:
When considering cost effectiveness of mass vaccination programme by any country one has to take into consideration on one hand the cost of vaccine, cost of administering versus cost of diagnosis, treatment & management of sequelae of Hib disease. These cost will differ from country to country.

The studies from USA have shown that it is cost effective to mass vaccinate with Hib vaccine (2,21). Similar studies from developing countries need to be done depending on local factors & priorities so that decision on govt. sponsored universal immunization can be undertaken. In some countries it is estimated the vaccine will be cost effective only if each dose of vaccine cost less than one US dollar which is still not possible as the vaccines are very costly.

Availability:
All conjugate vaccines are available as 0.5ml volume per dose. It is either ready to use liquid (HbOC) or in lyophilised form (rest of the vaccines) with diluent provided separately. It is either available as single dose or as multi dose (10 doses) vial. HbOC with adjuvant vaccine has adjuvant available separately which has to be mixed with the vaccine just before vaccinating (adjuvant mixed with vaccine is not stable & hence is provided separately). The cost of a unit dose is Rs 350 to 400 per dose.

Route:
Hib vaccines are given intramuscularly. In cases of severe bleeding disorder it can be given subcutaneously if IM injection is contraindicated. If given IM in such cases good pressure should be applied at injection site for 5 minutes & it should be preferably given after factor replacement in cases of factor deficiency (2). It should not be given IV or intradermally.

Schedule:
For all the vaccines the schedule depends on the age. For a child less than 6 months, 3 primary doses are given at 1-2 months interval stating from 6-8 weeks of age. It can be given along with other EPI vaccines on same day using separate sites & separate syringes. For a child between 6-12 months, 2 primary doses are given at 6-8 weeks interval. For 12-15 months old child only one primary dose is given. All these children are given booster dose at 15-18 months of age. Again the booster can be given along with MMR or booster of OPV/DPT. If the child is >15 months old he is given only one dose i.e. directly the booster.

PRP OMP is given as 2 primary doses at 2 months interval followed by a booster at 1 year of age. HbOC vaccine with adjuvant is given as 3 dose schedule below 1 year at 4-8 weeks interval (the 3^rd dose acts as a booster) & as 2 dose schedule at 4-8 weeks interval for>1 year old child (the 2^nd dose acts as booster) (15).