Haemophilus Influenzae type b

1. Causative Organism
2. Clinical Signs, Symptoms and Complications
3. Method of Transmission
4. Public Health Significance
5. Prevention - Non Immunisation Methods
6. Prevention - Immunisation
7. Vaccine/s and Vaccination
8. Efficacy and Effectiveness
9. Availability
10. Dosage and Administration
11. Indications and Recommendations
12. Adverse Events
13. Contraindications
14. Risks vs Benefits

Causative Organism

Haemophilus influenzae type b is a gram-negative coccobacillus, which occurs in encapsulated (typeable) and non-encapsulated(untypeable) forms. There are six antigenically distinct capsular types (a-f), type b being the most important.

Signs, Symptoms and Complications

• Mainly affects infants and children up to 5 years old.
• Meningitis symptoms - generally unwell, fever, headache, vomiting, irritability, neck stiffness, refusing feeds, drowsiness, confusion, seizures and coma. Sensorineural hearing loss and neurodevelopmental disorders may result as sequelae of meningeal infection.
• Epiglottitis - rapid onset of fever and dyspnoea (breathing difficulty) progressing to dysphagia (difficulty swallowing), pooling of oral secretions and drooling of saliva. Affected individuals characteristically sit upright with their neck extended and tongue protruding to mitigate the effects of airway obstruction.
• Can also cause septic arthritis, cellulitis, pneumonia, septicaemia, osteomyelitis, bacteraemia and empyema in infants and young children. Individuals with septicaemia may develop gangrene requiring limb amputation. 
• Disseminated intravascular coagulation may result from septicaemic shock. 
  

Child has swollen face due to Hib infection. Courtesy of Children’s Immunization Project, St. Paul, Minnesota

Method of Transmission

Hib bacteria are found in the nose and throat, usually without causing symptoms, and are spread mainly by breathing, coughing and sneezing.
Asymptomatic nasopharyngeal Hib carriage rates, in children in countries with developed economies, before vaccination was introduced, were 2-5%. Vaccination is thought to reduce carriage rates of Hib.

Public Health Significance

• Hib is a major cause of morbidity and mortality in children under the age of 2 years worldwide.
• Hib is responsible for 60-70% of all cases of meningitis in children under 2 years in countries with developed economies.
• The case fatality rate for invasive Hib disease is 5-10% in countries with developed economies.
• Survivors of Hib meningitis have a 30-40% risk of long-term neurodevelopmental impairment.

New Zealand Epidemiology

In 1993, 101 isolates of Hib from children under 5 years of age with invasive disease were referred to the Institute of Environmental Science and Research (ESR). This equates to an age specific rate of 36.4 per 100,000, which can be compared with five isolates referred in 1999 for a rate of 1.7 per 100,000. Since the introduction of Hib vaccine in January 1994 there has been a greater than 90 percent reduction in the incidence of Hib disease in children less than 5 years of age. However, the reduction of Hib incidence in New Zealand has not been as great as in those countries where immunisation coverage is higher.

Before immunisation was available in New Zealand, Hib was the commonest cause of life threatening bacterial infection, usually meningitis, in children under 5 years of age. Approximately one in every 350 New Zealand children developed an invasive Hib infection by that age. The peak occurrence of invasive disease in New Zealand was between 6 and 11 months of age. Despite the availability of antibiotics and medical care, the case fatality rate remains up to 5 percent, and survivors of Hib meningitis have a 30–40 percent risk of long term neurological developmental impairment.

In the pre-vaccine era, Maori and Pacific children had higher rates of Hib infection, especially meningitis, and presented at a younger age. More than 25 percent of Hib meningitis in Maori and Pacific children occurred before the age of 6 months, and 80 percent by 18 months. Overcrowding and early exposure to the disease were seen as contributing factors. European children were more likely to be affected at an older age and to suffer from epiglottitis. 

Analysis of the cases of invasive Hib disease from 1995 to 1999 showed that 43 cases were in children less than 5 years of age, and that of these, 12 cases were babies under 5 1/2 half months of age; 14 children were not fully vaccinated for their age, and nine cases occurred in children who were fully immunised. The New Zealand epidemiology suggested that early protection was important and supported the change to a Hib-OMP (outer membrane protein) vaccine, which provides protection after one dose. In 2000 there were seven laboratory confirmed cases of Hib reported in children under the age of 5 years, followed by six cases in 2001 and zero cases in 2002.

Of the cases in 2000 and 2001, 11 out of 13 children had either received no Hib immunisation or were incompletely immunised for their age. The other two children, aged 4 months and 4 years, had both received Hib immunisation appropriate for their age. In 2003 there were seven laboratory confirmed cases of Hib in children under the age of 5 years. The children’s ages ranged from 2 to 14 months. Four infants were of European ethnicity, one was Maori, one Pacific and the ethnicity of one child was not reported. Three of the four infants with Hib infection under the age of 1 year were not up to date with their immunisations, one baby of 2 months had not received Hib vaccine, and two infants aged 5 to 11 months had both received only one dose of Hib vaccine. The immunisation history on the fourth infant under one year of age was not known. There were two infants aged 12 months who had both received the scheduled two doses of vaccine, and one child aged 14 months whose immunisation history was uncertain. In 2004 there were two laboratory confirmed cases of Hib in children, both over the age of 1 year. One child had received no Hib vaccine and the other the first two doses. Of the small numbers of children who have developed Hib infection in New Zealand since the change in schedule in 2000, most were incompletely vaccinated for their age. It is important to continue to monitor the epidemiology of Hib to provide the optimum schedule for protecting children. However, at the present time improving coverage and providing immunisation on time are the most important factors.

Prevention - Non Immunisation Methods

• General hygiene measures and avoidance of overcrowded living conditions.
• Rifampin prophylaxis of household or daycare contacts of persons who contract Hib disease.
  

Prevention - Vaccination

An effective vaccine is available for infants, young children and those with impaired immune systems.

Vaccine/s and vaccination

• Inactivated protein conjugate polysaccharide bacterial vaccine.
• Vaccines from different manufacturers provide protection at different ages.
• The vaccine consists of 7.5-10 ug Hib polyribosylribitol phosphate (PRP) polysaccharide from Hib capsule conjugated to a protein carrier – either outer membrane protein of Neisseria meningitidis (PRP-OMP), a mutant diphtheria toxin (PRP-OC) or tetanus toxoid (PRP-T). This preparation is dissolved in 0.5mL buffer. Some preparations also contain aluminium salts as adjuvants.
• These protein conjugate vaccines do not give protection against diphtheria, tetanus or N. meningitidis.
• These vaccines are available as monodose preparations or in combination with hepatitis B, polio, diphtheria, tetanus and pertussis.
  

Efficacy & Effectiveness

• 95-100% of children are protected by the vaccines. 
• This level of protection is reached after two doses for PRP-OMP based vaccines and after three doses for other Hib conjugate vaccines when administered in the first six months of life. However, for all vaccines as immunogenicity and protection wane booster doses in the second year of life are recommended.
• The vaccines only protect against invasive Hib disease (septicaemia, meningitis, epiglottitis, etc caused by Haemophilus influenzae b). 
• The vaccines do not protect against sinusitis, otitis media, upper respiratory tract infections and bronchitis caused by non-encapsulated strains or against disease caused by other serotypes of Haemophilus influenzae.

Availability

 Vaccines currently available in New Zealand are:

• PRP-T – The vaccine is the monovalent Hib vaccine (Hib-PRP-T, Hiberix™, GSK).
• The Hib is given as the combination vaccine diphtheria, tetanus, whooping cough, polio and Hepatitis B (Infanrix^®-hexa). 
• The other protein conjugate Hib vaccine licensed for distribution, but not marketed, in New Zealand is Hb-OC (HibTITER, Wyeth). The vaccine was mostly given as the combination vaccine DTwPH (TETRAMUNE^®or Hib-Hepatitis B, COMVAX^®, MSD), which are no longer available.
• The cost of Hib conjugate vaccines (including combination vaccines) tends to limit their availability to countries with developed economies. The WHO is currently investigating strategies to widen the implementation of Hib immunisation to children under the age of 5 years in countries with developing economies.

Dosage and Administration

• In the current New Zealand schedule, the vaccines are given in combination with Hib-hepatitis B at six weeks, three months and five months, (Infanrix™-hexa) followed by a single dose at 15 months (Hiberix™.)
• The dose for all Hib vaccines is 0.5mls and is given by intramuscular injection. 
• It can be given with the normal scheduled childhood vaccinations. 
• Hib vaccines usually require 3 doses at 4-8 weekly intervals in the first year of life, followed by a booster dose at 15 months-2 years. 
• Hib-OMP only requires 2 doses at 4-8 weekly intervals in the first year of life, followed by one dose at 12-18 months. With this vaccine a protective immune response is seen after the first dose in many children.
• Children aged between 15 months and 7 years of age, who are on catch-up immunisation schedules, only need one dose of Hib vaccine. Most countries including New Zealand do not recommend Hib immunisation after 5-7 years of age as older children and adults are at very low risk of invasive Hib disease.
  

Indications

• Hib vaccine is recommended for all children from 6 weeks of age.
• Some countries specifically recommend use of Hib-OMP for their indigenous populations, where there is a high incidence of Hib invasive disease under six months of age, because it protects a substantial percentage of children after a single dose.
• Premature or low birth weight babies: Babies whose birth weight is under 1000gms or whose gestation is less than 29 weeks should have 3 doses of Hib vaccine in the first 6 months, regardless of type of Hib vaccine. A booster dose is recommended at 12-18 months.
• Immunosuppression - Hib vaccine is also recommended for adults and older children with anatomic or functional asplenia (if possible, immunise before splenectomy), children with partial immunoglobulin deficiency, haematologic malignancies, nephritic syndrome and HIV.
• Children under 2 years who have had an episode of invasive Hib disease should still undergo the appropriate course of immunisation, as the immune response to the vaccine is more reliable than the immune response to the disease. Some experts believe this similarly applies to individuals over 2 years and therefore also recommend immunisation for this group.

Contraindications

• Previous anaphylactic reaction to the vaccine or any of the vaccine components.
• Encephalopathy within 7 days following a pertussis containing vaccine is a contraindication to similar Hib combination vaccines which have a pertussis component (e.g. DTaP/Hib(PRP-T), DTaP-IPV-Hib, DTaP-IPV-HepB-Hib, DTPH). Use of a monodose or HepB-Hib combination vaccine instead is recommended.
• Individuals with an evolving neurological condition should either be vaccinated with monodose Hib or HepB-Hib instead of combination vaccines with a pertussis component (e.g. DTaP/Hib(PRP-T), DTaP-IPV-Hib, DTaP-IPV-HepB-Hib, DTPH) or if these combinations are used, immunisation should be delayed until the condition is stabilised or diagnosed. The former option is preferable where feasible to confer timely protection against invasive Hib disease.
  

Adverse Events

• Swelling and redness at the injection site following the first dose has been reported in up to 5% of cases.
• No serious adverse reactions were observed during clinical trials.
  

Risks vs Benefits

DISEASE	EFFECTS OF DISEASE	SIDE EFFECTS OF VACCINE
Hib - contagious bacteria spread by droplets, causes meningitis, epiglottitis, septicaemia, osteomyelitis.	About 5% of meningitis patients die and 1 in 4 survivors have permanent brain or nerve damage. About 1% of epiglottitis patients die.	About 1 in 20 have discomfort or local inflammation. About 1 in 50 have fever. These side effects disappear usually within 24 hours.

• Link to Immunisation Handbook (2006) Chapter 7  -  Haemophilus Influenzae type b (Hib)