2012 Antigen Review for the New Zealand National Immunisation Schedule: Haemophilus influenza type b

Abstract

Haemophilus influenzae is responsible for a number of diseases including meningitis, pneumonia and epiglottitis. It is a human pathogen and spreads via the transfer of respiratory secretions. Carriage of H. influenzae in the nasopharynx is intermittent and varies with age but peaks in preschool children. The polysaccharide capsule is the most important virulence factor and H. influenzae with the serotype b capsule cause the vast majority of human disease. Vaccines against H. influenzae serogroup b (Hib) have been developed using the polyribosylribitol (PRP) capsule polysaccharide as the immunogen. Conjugation of the polysaccharide to a protein carrier has provided an effective vaccine which can be administered to infants and elicits a protective immune response. The vaccine reduces carriage of Hib interrupting the spread of the organism to non-vaccinated populations, the herd effect. This report summarises new research on Hib vaccines and vaccination published during the past four years. The number of cases of invasive Hib disease in New Zealand (NZ) has fallen dramatically since the introduction of the Hib conjugate vaccine in 1994. In 2011 there were only eight cases of invasive Hib disease only three of whom were in the under-five year old age group and two of whom were in the under-one year old age group. In 2012 provisional data indicated there was only one case of Hib invasive disease in the under-five year old age group who had been fully immunised. There were no cases in the under-one year old age group. The current immunisation schedule has maintained control of invasive Hib disease in NZ. There are a number of vaccines available for the control of invasive Hib disease. The monovalent Hib conjugate vaccines have the PRP polysaccharide conjugated to tetanus toxoid (Hib-T), diphtheria cross-reactive material (Hib-CRM-197), or meningococcal outer membrane protein (Hib-OMP). The monovalent Hib conjugate vaccines have been use as primary or booster doses in different immunisation schedules. In NZ the monovalent Hib-T (Act-HIB) is used as the booster dose. All have an excellent safety record and no safety concerns were identified in the current literature search. To minimise the number of injections in the immunisation schedule and reduce the number of visits to health care facilities, a number of vaccines have been combined. This includes vaccines containing Hib conjugate and there is a range of different Hib conjugate-containing vaccines. Most contain the diphtheria, tetanus and acellular pertussis (DTaP) antigens plus Hib-T and may contain inactivated polio virus and hepatitis B antigen. These vaccines are generally used in the primary vaccination schedule. NZ currently uses a DTaP-HepB-IPV/Hib vaccine (Infanrix-hexa® ) in a three dose primary schedule. All these multivalent combinations have been shown to have an excellent safety record and no safety issues were identified in the literature search. Other multivalent vaccines are available including HibMenC, HibMenCY and HibHBV conjugate vaccines. Carriage of Hib is age related and is most common in preschool children. Vaccination with Hib conjugate vaccine reduces carriage of the organism preventing spread to vulnerable groups. Reducing the spread of the organism protects both vaccinated and unvaccinated populations against invasive Hib disease, the herd effect. This plays a critical role in the control of Hib invasive disease. Monovalent and multivalent vaccines all induce protective levels of antibody. Levels of protective antibody decline but protective levels have been seen following booster doses of the vaccine up to the age of five years. This indicates that the current NZ schedule should provide adequate protective levels of antibody throughout the most vulnerable period for Hib disease. The Hib conjugate vaccines have been shown to have high efficacy and effectiveness in the control of Hib invasive disease. This has been established in both developed and developing countries. Estimates of the effectiveness of 100%, and dose specific estimates of 69% for one dose and 92% for two doses have been reported. There have been no issues regarding implementation of the Hib conjugate vaccines either in the monovalent or multivalent form. No evidence of serotype switching has been reported but the incidence of invasive non-typeable H. influenzae is higher than that of Hib. Serotype e and f are the most common serotypes reported for H. influenzae invasive disease. The case fatality rate is higher for non-typeable H. influenzae than for Hib. The under-five year olds and the under-one year olds remain the most vulnerable population. The current NZ immunisation schedule has successfully controlled the disease in these age groups. Consideration might be given to using a combined Hib-MenC conjugate vaccine as the booster dose and whether two or three doses should be used in the primary schedule. Both would require a cost benefit analysis.