Haemophilus influenzae type b (Hib)

What

Haemophilus influenzae is a bacterium that is a normal part of the upper respiratory tract flora. H. influenzae type b (Hib) can cause invasive diseases in children and in people who are immunocompromised. These diseases include bacterial meningitis, pneumonia, epiglottitis, septic arthritis and cellulitis.

Who

Hib-containing vaccine is recommended for:

• routine vaccination in infants and children
• infants and children <5 years of age who have missed a dose of Hib-containing vaccine
• people who are immunocompromised, including people with asplenia and people who have received a haematopoietic stem cell transplant

How

Infants and children are recommended to receive Hib-containing vaccine at 2, 4, 6 and 18 months of age.

People who have functional or anatomical asplenia are recommended to receive 1 dose of Hib vaccine.

People who have received a haematopoietic stem cell transplant are recommended to receive 3 doses of Hib vaccine commencing from 6 months after the transplant.

Why

Hib can cause invasive diseases in young children and people who are immunocompromised. The case-fatality rate for Hib meningitis is between 3% and 6%. Up to 30% of individuals who survive Hib disease have permanent neurological sequelae.

Hib vaccines available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Dose and route

The dose of all Hib-containing vaccines is 0.5 mL given by intramuscular injection.

Co-administration with other vaccines

People can receive Hib-containing vaccines at any time before or after, or with, most other vaccines or immunisation products (such as RSV-specific monoclonal antibody).

Vaxelis can be given at the same time as other scheduled vaccines, including MenB vaccines.

Interchangeability of Hib vaccines

If possible, use the same brand of Hib-containing vaccine for all primary doses.

Overseas born children who have received different Hib-containing vaccines (such as PRP-OMP [polyribosylribitol phosphate-outer membrane protein conjugate] and PRP-T [PRP conjugated to tetanus toxoid] vaccines) should complete their course according to the recommended routine or catch-up schedule, to receive a total of 4 doses of Hib-containing vaccine at appropriate intervals. However, if a child has received 2 primary PRP-OMP doses, a 3rd primary dose is not required. A booster dose should still be given.

If possible, complete the vaccination schedule for Infanrix Hexa and Vaxelis with the same vaccine brand. If this is not possible, use an alternative brand following the dose recommendations. See Recommendations - Infants and children are recommended to receive 4 doses of Hib-containing vaccine.

Contraindications

The only absolute contraindications to Hib-containing vaccines are:

• anaphylaxis after a previous dose of any Hib-containing vaccine
• anaphylaxis after any component of a Hib-containing vaccine

Precautions

Women who are pregnant or breastfeeding are not routinely recommended to receive Hib vaccine. The exception is for women with functional or anatomical asplenia who were not fully vaccinated against Hib in childhood.

See Table. Vaccines that are not routinely recommended in pregnancy: inactivated bacterial vaccines in Vaccination for women who are planning pregnancy, pregnant or breastfeeding for more details.

People with latex allergy

The product information for Act-HIB states that the tip cap of the syringe contains latex. Consider using an alternative product in people with an allergy or sensitivity to latex.

Swelling and redness at the injection site after the 1st dose are common and have been reported in 5–30% of vaccinated children. Fever in up to 31% has also been reported. These adverse events usually appear within 3–4 hours of vaccination and resolve completely within 24 hours.²

The incidence of these adverse events declines with subsequent doses.

Local and systemic adverse reactions are more common after hexavalent vaccines than after monovalent vaccines. There is little to no difference in the rates of adverse events after hexavalent vaccines compared with other combination vaccines including other hexavalent vaccines.^2-4

Haemophilus influenzae is a gram-negative coccobacillus that is part of the normal flora of the upper respiratory tract.

Hib has a capsular form and a non-capsular form. Strains isolated from respiratory tract specimens, such as sputum, or middle ear or sinus fluid usually do not have a capsule. These are known as non-typeable H. influenzae (NTHi).

There are 6 capsular types (a to f). Before Hib vaccination started, almost all H. influenzae isolates from sterile sites (blood, cerebrospinal fluid, joint or pleural fluid) were type b. ²

Pathogenesis

The incubation period of Hib disease is not definitively known, but is estimated to be 2–4 days.

Transmission

Hib can be transmitted from symptomatic or asymptomatic carriers by direct contact with respiratory droplets or nasal discharge.⁵ An infected person can transmit Hib disease for as long as the bacteria are present, which may be several months.

Laboratory diagnosis

Identification of gram-negative coccobacilli in body fluid suggests Hib disease. Culturing Hib from body fluids can be difficult because the organism needs specific growth media and culturing conditions.

Newer non-culture diagnostic methods, such as PCR, are more sensitive and rapid.

It is important that all isolates of Hib are serotyped because only type b is vaccine-preventable.

Clinical categories of invasive disease caused by Hib include:⁶

• meningitis
• epiglottitis
• septic arthritis
• cellulitis
• pneumonia

Non-typeable Haemophilus influenzae strains are a common cause of otitis media in children and bronchitis in adults. They occasionally cause invasive disease.² Hib vaccines do not prevent non-typeable H. influenzae infections.

Meningitis

Hib is rarely isolated from the blood without a focal infection being evident or developing subsequently. Focal infections due to Hib do not have any specific clinical features that can differentiate them from those due to other organisms.

Infants often do not present with classical clinical signs of meningitis (neck stiffness and photophobia). Instead, they may present with drowsiness, poor feeding, high fever or irritability.⁵

Epiglottitis

Epiglottitis presents with respiratory obstruction, associated with soft stridor and often drooling. Children with epiglottitis are pale, febrile and anxious. They should remain upright to open up their airway as much as possible.

Before Hib vaccines were introduced, Hib caused >95% of epiglottitis cases.⁷

Complications

Meningitis and epiglottitis are almost always fatal without appropriate treatment. The case-fatality rate for Hib meningitis in developed countries is at least 3%, even with treatment. 15–30% of survivors have permanent neurological sequelae.⁵

Hib disease in Australia

Australia has one of the lowest incidence rates of invasive Hib disease worldwide. Invasive Hib disease is rare in Australia following vaccine inclusion in the NIP schedule from 1993.

In 1992 alone, before introduction of the vaccine, there were 549 Hib notifications in Australia. In contrast, between 2000 and 2017, there were 345 notifications of Hib. The all-age national incidence halved from 0.13 per 100,000 population in 2000 to 0.06 per 100,000 in 2017.⁸ The median age at notification was 8 years, with infants accounting for the highest age-specific notification rate (45% aged <5 years). Adults aged ≥70 years represented 11% of age-specific notification rates and the lowest age-specific notification rate was in adults aged 20–49 years.⁸ 

The reduction in Hib incidence after routine vaccination was introduced has been particularly marked in Aboriginal and Torres Strait Islander children. However, absolute rates in these children remain substantially higher than in the non-Indigenous population.^9,10  Between 2000 and 2017, there were 153 notifications in people born after 2000, of which 51 (one-third of notifications) were in Aboriginal and Torres Strait Islander children. Aboriginal and Torres Strait Islander children had a significantly younger median age than non-Indigenous cases (9 months compared to 17 months).⁸

Septicaemia and meningitis are the most commonly reported clinical presentations of Hib disease in Australia, followed by pneumonia and epiglottis. Between 2000 and 2017, there was a higher proportion of meningitis presentations in Aboriginal and Torres Strait Islander cases (49%) than in non-Indigenous cases (28%).⁸

Types of conjugate Hib vaccines

All Hib-containing vaccines in Australia contain the Hib capsular polysaccharide polyribosylribitol phosphate conjugated to tetanus toxoid (PRP-T), except Vaxelis for which it is conjugated to meningococcal protein.

Vaccine efficacy and effectiveness

Vaccine efficacy against invasive Hib disease is estimated to be 95% for 3 doses of Hib-containing vaccine.¹¹ Vaccine effectiveness against invasive Hib disease in cohort studies has been estimated at 94% for 3 doses of Hib-containing vaccine.^12,13 Several case–control studies have estimated the vaccine effectiveness against Hib meningitis to be:

• 55% for 1 dose
• 96% for 2 doses
• 96% for 3 doses¹²

Transport according to National Vaccine Storage Guidelines: Strive for 5.¹⁴ Store at +2°C to +8°C. Do not freeze. Protect from light.

Act-HIB

Act-HIB vaccine must be reconstituted. Add the entire contents of the diluent syringe to the vial and shake until the powder completely dissolves. Use the reconstituted vaccine immediately.

Hiberix

Hiberix vaccine must be reconstituted. Add the entire contents of the diluent container to the vial and shake until the pellet completely dissolves. Use the reconstituted vaccine as soon as practicable. If storage is needed, store at +2°C to +8°C for no more than 24 hours.

Infanrix hexa

Infanrix hexa vaccine must be reconstituted. Add the entire contents of the syringe to the vial and shake until the pellet completely dissolves. Use the reconstituted vaccine as soon as practicable. If storage is needed, store at room temperature for no more than 8 hours.

Hib is a notifiable disease in all states and territories in Australia. The Communicable Diseases Network Australia national guidelines for Hib invasive infection¹⁵ have details about the management of Hib cases and contacts.

State and territory public health authorities can provide further advice about the public health management of Hib.

Routine vaccination in children and adults

Infanrix hexa

The product information for Infanrix hexa states that this vaccine is for:

• primary immunisation of infants from the age of 6 weeks
• booster dose in children 18 months of age if they need boosting for all antigens

The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that Infanrix hexa may also be used for catch-up of the primary schedule or as a booster dose in children <10 years of age.

The product information for Infanrix hexa states that this vaccine is contraindicated in children with either:

• encephalopathy of unknown aetiology, or
• neurologic complications occurring within 7 days after a vaccine dose

ATAGI recommends that the only contraindications are:

• anaphylaxis after a previous dose of any Hib-containing vaccine
• anaphylaxis after any component of a Hib-containing vaccine

Vaxelis

The product information for Vaxelis states that this vaccine is for:

• primary immunisation of infants from the age of 6 weeks
• a booster dose at least 6 months after the last priming dose

ATAGI recommends that Vaxelis may also be used for catch-up of the primary schedule or as a booster in children <10 years of age.

Act-HIB

The product information for Act-HIB states that the antibody response appears to be greater following subcutaneous administration than that after intramuscular administration.

ATAGI does not have preference for either of the two routes of administration for Act-HIB.

Act-HIB and Hiberix

The product information for Act-HIB and Hiberix states that these vaccines are for use in children aged 2 months to 5 years.

ATAGI recommends that the following people can also receive Act-HIB or Hiberix:

• older people with asplenia
• people who have received an allogeneic or autologous haematopoietic stem cell transplant

Contraindications

The product information for Infanrix hexa and Vaxelis states that this vaccine is contraindicated in children with either:

• encephalopathy of unknown aetiology, or
• neurologic complications occurring within 7 days after a vaccine dose 

ATAGI recommends that the only contraindications are: 

• anaphylaxis after a previous dose of any Hib-containing vaccine
• anaphylaxis after any component of a Hib-containing vaccine 
  
   

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9. Wang H, Deeks S, Glasswell A, McIntyre P. Trends in invasive Haemophilus influenzae type b disease in Australia, 1995–2005. Communicable Diseases Intelligence 2008;32:316-25.
10. Menzies RI, Bremner KM, Wang H, Beard FH, McIntyre PB. Long-term trends in invasive Haemophilus influenzae type b disease among Indigenous Australian children following use of PRP-OMP and PRP-T vaccines. Pediatric Infectious Disease Journal 2015;34:621-6.
11. Mulholland K, Hilton S, Adegbola R, et al. Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants. The Lancet 1997;349:1191-7.
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13. Monge S, Hahne SJ, de Melker HE, et al. Effectiveness of the DTPa-HBV-IPV/Hib vaccine against invasive Haemophilus influenzae type b disease in the Netherlands (2003–16): a case-control study. The Lancet Infectious Diseases 2018;18:749-57.
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