Haemophilus influenzae type b (Hib) is an important cause of childhood meningitis and pneumonia. It is estimated to cause at least 3 million cases of invasive disease and up to 386,000 deaths worldwide annually.¹ Expression of the polysaccharide capsule increases bacterial virulence and is associated with severe disease. Vaccination confers protection by induction of anticapsular antibodies and immunological memory. Conjugate Hib vaccines were introduced during the 1990s and are considered safe and highly efficacious.¹

Efficacy and coverage

The clinical efficacy of the conjugate Hib vaccines is estimated as 94-100%.² However, there was a reduction in efficacy of Hib-tetanus toxoid (Hib-TT) vaccines in the UK between 1999 and 2003, which remains unexplained and was unrelated to the quality of the vaccine.³ The vaccine used in the current UK primary schedule induces protective antibody levels in 90-99% of children.⁴ The vaccination also reduces nasopharyngeal carriage in asymptomatic carriers and therefore confers herd immunity to unvaccinated children.⁵ The uptake of Hib vaccine peaked in the UK during the late 1990s. From 2002 to 2004, the Hib vaccine 2-year coverage rates in England remained stable at 93%.⁶

UK programmes

Conjugate Hib vaccination was introduced into the UK routine childhood immunisation schedule in 1992. In 1996, the single Hib vaccine was replaced by a diphtheria, tetanus, pertussis and Haemophilus influenzae type b (DTP/Hib) combination⁴ but, due to a shortage of product, a preparation containing acellular pertussis (DTaP/Hib) was used during 2000 and 2001. The original DTP/Hib combination was subsequently reintroduced⁷ but was replaced by the current diphtheria, tetanus, acellular pertussis/inactivated polio/Haemophilus influenzae type b (DTaP/IPV/Hib) vaccine in 2004.⁴

Epidemiology

The introduction of immunisation in the UK caused an immediate decline in the incidence of Hib. Only 37 Hib isolates were identified in England and Wales in 1998, compared with 892 cases in 1991. However, the incidence of disease then increased to a maximum of 269 Hib cases in 2002.⁸ It has since been confirmed that the temporary DTaP/Hib vaccine was less immunogenic and is believed to have contributed to recent vaccination failures. A Hib booster campaign was therefore launched in 2003 to reinforce immunity in young children⁷ and the incidence of infection has again decreased.⁸

Preparation⁴

Hib vaccines are composed of capsular polysaccharide from cultured Haemophilus influenzae type b bacteria, conjugated to protein to strengthen immunogenicity.
The Hib vaccine is available as:

• Diphtheria, tetanus, acellular pertussis/inactivated polio/Haemophilus influenzae type b (DTaP/IPV/Hib) vaccine.
• Hib/meningitis C (Hib/MenC) combined vaccine.

Although the current DTaP/IPV/Hib vaccine contains an acellular pertussis component, the preparation does induce an effective immunological response to Hib antigens.

Administration⁴

Hib vaccines are injected intramuscularly. Upper arm or anterolateral thigh sites are recommended to minimise the risk of local reactions. Other vaccinations such as measles, mumps, rubella (MMR), meningitis C (MenC) or hepatitis B can be given at the same time but should be injected at an alternative site and preferably in a different limb.

Schedule⁴

All infants should receive the primary Hib immunisation course. The DTaP/IPV/Hib vaccine is given at 2, 3 and 4 months of age, whilst levels of maternal antibodies wane.⁹ Children also receive a booster of Hib (as Hib/MenC) vaccine at 12 months (given at the same time as MMR and pneumococcal conjugate). If primary immunisation has been delayed, children up to 10 years of age can be given three doses of combination vaccine at monthly intervals. Although only one dose of Hib vaccine is necessary to achieve immunity in children aged over 1 year, the extra doses are required to provide immunity to diphtheria, tetanus, polio (and pertussis if given).

Adults and children aged over 1 year who have completed a primary course of diphtheria, tetanus, pertussis and polio but have not received Hib-containing vaccines, should be given a single dose of Hib/MenC vaccine.⁴

Recommendations⁴

Immigrants

The cost of the Hib vaccine has prevented its use in routine childhood immunisation schedules in many poorer countries.^5,10 Children from developing countries may therefore have not received the vaccination. If the history is unclear, children are considered unimmunised and should complete the full UK schedule.

Splenic dysfunction or complement deficiency

These Individuals are at increased risk of invasive Hib infection:

• Children under 2 years of age should complete the primary immunisation course including Hib/MenC at 12 months, and then a MenACWY conjugate vaccine at least a month after the MenC.⁴
  They also need a second Hib/Men C after their second birthday, with a pneumococcal booster - pneumococcal polysaccharide vaccine (PPV). (NB: if their previous pneumococcal conjugate vaccine (PCV) booster dose was PCV7 rather than PCV13 (before April 2010), they need two pneumococcal vaccines - give PCV13 first, with a PPV two months later.)
• Children aged 2-5, having completed the normal primary course and one booster, aged around 1 year, need a Hib/MenC booster with a PCV13 booster (as they will have had PCV7), followed by a MenACWY conjugate vaccination a month later, and a PPV booster a further month afterwards.
• Children aged over 5 and adults need a Hib/MenC booster with a PPV booster, followed by a MenACWY conjugate vaccine a month later.

Patients undergoing splenectomy should ideally be offered the vaccines two weeks before surgery, or as soon as possible postoperatively.

Index cases

Unimmunised patients with diagnosed Hib infections should be immunised, as recurrence of disease can occur. Patients who have been immunised but later acquire Hib infection may benefit from a booster dose of vaccine, depending on convalescent antibody levels.

Contacts

Children who are household contacts of an index case should be fully immunised as per previous recommendations.

Contra-indications⁴

The vaccination should not be administered to individuals with:

• Confirmed anaphylactic reaction to Hib-containing vaccine.
• Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B, as they may be present in small amounts.
• Acute illness with systemic upset and fever.
• Evolving or undiagnosed, deteriorating neurological abnormalities.

The following situations do not prohibit vaccination:

• History of a stable neurological condition, seizures or febrile convulsions (without neurological deterioration).
• There is no evidence of increased risks of adverse reactions from vaccinations in preterm babies: premature infants should receive vaccinations at appropriate chronological age, according to the schedule.
• Fever, persistent screaming, severe local reactions or hypotonic-hyporesponsive episodes following previous Hib-containing vaccinations.
• Immunosuppression including HIV infection (but individuals may not achieve an adequate immunological response and may benefit from re-immunisation).
• Pregnancy or breast-feeding.

Document references

1. Haemophilus influenzae type B vaccine, World Health Organization, 2003
2. Bedford H and Elliman D; Concerns over immunisation. BMJ 2000;320:240-243
3. Bolgiano B, Mawas F, Burkin K, et al; A Retrospective Study on the Quality of Haemophilus influenzae type b Vaccines Used in the UK Between 1996 and 2004. Hum Vaccin. 2007 Apr 27;3(5). [abstract]
4. Immunisation against infectious disease - 'The Green Book', Dept of Health (various dates)
5. Swingler G, Fransman D, Hussey G; Conjugate vaccines for preventing Haemophilus influenzae type b infections. Cochrane Database Syst Rev. 2003;(4):CD001729. [abstract]
6. Vaccine coverage and COVER (Cover of Vaccination Evaluated Rapidly), Health Protection Agency, Spring 2009; The COVER programme monitors immunisation coverage data for children in the United Kingdom who reach their first, second or fifth birthday during each evaluation quarter
7. Heath P and Ramsay M. Haemophilus influenzae type b vaccine-booster campaign. BMJ 2003;326:1158-9
8. Laboratory reports of Haemophilus influenzae type b infection by age group and quarter: England and Wales: 1990 - 2009*, Health Protection Agency (last reviewed 2010); *Provisional data
9. Mimms C, Playfair J, Roitt I, Wakelin D and Williams R; Obstetric and Perinatal infections. In: Medical Microbiology, Second edition (1998), pp 287-294. London: Mosby
10. Swingler GH, Michaels D, Hussey GG; WITHDRAWN: Conjugate vaccines for preventing Haemophilus influenzae type B Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001729. [abstract]