NOTIFIABLE (EXCEPT IN SCOTLAND)
The disease Haemophilus influenzae can cause serious invasive disease especially in young children. Invasive disease is usually caused by encapsulated strains of the organism. Six typeable capsular serotypes (a– f) are known to cause disease; nontypeable encapsulated strains can occasionally cause invasive disease. Before the introduction of vaccination, type b (Hib) was the prevalent strain. The proportion of typeable to non-typeable strains depends largely on the prevalence of the type b strain. Non-encapsulated strains are mainly associated with respiratory infections such as exacerbation of chronic bronchitis and otitis media. The most common presentation of invasive Hib disease is meningitis, frequently accompanied by bacteraemia. This presentation accounts for approximately 60% of all cases (Anderson et al., 1995). Fifteen per cent of cases present with epiglottitis, a potentially dangerous condition that presents with airways obstruction. Bacteraemia, without any other concomitant infection, occurs in 10% of cases. The remainder is made up of cases of septic arthritis, osteomyelitis, cellulitis, pneumonia and pericarditis. The sequelae following Hib meningitis may include deafness, convulsions and intellectual impairment. In studies conducted in Wales and Oxford, 8 to 11% had permanent neurological sequelae (Howard et al., 1991, Tudor-Williams et al., 1989). The case fatality ratio from Hib meningitis is 4 to 5%. Individuals can carry Hib bacteria in their nose and throat without showing signs of the disease. Before Hib vaccine was introduced, about four in every 100 preschool children carried the Hib organism; after the vaccine was introduced, carriage rates fell below the level of detection (McVernon et al., 2004). Hib is spread through coughing, sneezing or close contact with an infected person.
Before the introduction of Hib immunisation, the estimated annual incidence of invasive Hib disease was 34 per 100,000 children under the age of five years. One in every 600 children developed some form of invasive Hib disease before their fifth birthday (Booy et al., 1994). Disease was rare in children under three months of age, but incidence rose progressively during the first year, reaching a peak between 10 and 11 months of age. Thereafter, the incidence declined steadily to four years of age after which infection becomes uncommon. Vaccines against Hib were first produced in the early 1970s and they contained purified capsular polysaccharide. These vaccines were effective in children over 18 months of age, but failed to protect younger children, in whom the risk of disease was highest. The development of conjugate Hib vaccines overcame this problem. In these vaccines, the capsular polysaccharides were linked to proteins, improving the vaccine’s immunogenicity, particularly in children less than one year of age. In 1992, Hib conjugate vaccine was introduced into the routine UK immunisation schedule. Hib conjugate vaccine was originally administered as a single vaccine. In 1996, combination vaccines (DTwP/Hib) were introduced, and more recently Hib vaccines combined with DTaP and IPV have become available. The efficacy and safety of the conjugate Hib vaccines have been demonstrated in large field trials in Finland, the United States and in the UK, where efficacy ranged from 83 to 100% (Black et al., 1991a; Black et al., 1991b; Eskola et al., 1991). Studies comparing different vaccines, using the present UK primary schedule, have shown that 90– 99% of children developed protective levels of antibody, following three doses of vaccine (Booy et al., 1994). Cases of invasive disease in fully vaccinated children (vaccine failures) have been reported from countries, including the UK (Heath and McVernon, 2002). Asmall proportion of such cases have underlying conditions, such as immunoglobulin deficiency, predisposing the child to vaccine failure. Since the introduction of Hib immunisation in the UK, disease incidence has fallen. In 1998, only 21 cases of invasive Hib were reported in England and Wales in children under five (0.65 per 100,000) compared to 803 in 1991 (20.5 per 100,000). In infants under one, the highest risk age group for disease, reported cases fell by over 95% (from 300 to 7). Notifications of H. influenzae meningitis for the same period declined from 485 to 29. In 1998, coverage by the second birthday was 95%.
From 1999, there was a small but gradual increase in the number of cases of Hib disease reported, mostly in children less than four years of age. However, this increase was most notable amongst children born in 2000 and 2001 (McVernon et al., 2003). Reasons for this increase in vaccine failures are thought to include an effect of the DTaP/Hib combination vaccine that was in use at that time, and a wearing off of the impact of the catch-up programme when the vaccine was introduced. In this latter group who were immunised at an older age, the efficacy was higher than in children vaccinated routinely as infants.
In 2003, a booster campaign was implemented with call-back of children aged six months to four years (Chief Medical Officer, 2004). The aim of this campaign was to boost immunity in young children and return to the low levels of disease achieved previously.
Hib vaccines are made from capsular polysaccharide that has been extracted from cultures of Hib bacteria. The polysaccharide is linked (conjugated) to protein, according to the manufacturer’s methodology. In the UK, Hib vaccines have been used that have been conjugated with either CRM197 (a non-toxic variant of diphtheria toxin) or tetanus toxoid. The conjugation increases the immunogenicity especially in young children in whom the plain polysaccharide vaccines are not immunogenic.
Some DTaP/Hib combination vaccines have been shown to attenuate the Hib response in comparison to DTwP/Hib combinations (Trotter et al., 2003). The Hib-containing vaccine chosen for primary immunisation in the UK programme (Pediacel) has been shown not to have this problem (Miller et al., 2003). The Hib vaccine is given as part of a combined product or as a single product:
The above vaccines are thiomersal free. They are inactivated, do not contain live organisms and cannot cause the diseases against which they protect.
These vaccines should be stored at +2 to +8oC and protected from light. If the vaccine has been frozen, it must not be used as this can reduce its potency and increase local reactions. Vaccines should be disposed of by incineration at a suitably authorised facility.
Vaccines are routinely given intramuscularly into the upper arm or anterolateral thigh. This is to reduce the risk of localised reactions, which are more common when vaccines are given subcutaneously (Mark et al, 1999; Diggle and Deeks, 2000; Zuckerman, 2000). For individuals with a bleeding disorder, however, vaccines should be given by deep subcutaneous injection to reduce the risk of bleeding.
The vaccines should be shaken before administration and must not be given intravenously.
Hib-containing vaccines can be given at the same time as other vaccines such as MMR, MenC and hepatitis B. The vaccines should be given at a separate site, preferably in a different limb. If given in the same limb, they should be given at least 2.5 cm apart (American Academy of Pediatrics, 2003). The site at which each vaccine was given should be noted in the child’s records.
The objective of the immunisation programme is to provide a minimum of three doses of a Hib-containing vaccine at appropriate intervals for all infants less than one year of age. Satisfactory long-term protection is achieved from a single dose of Hib vaccine in children commencing immunisation above the age of one year and under ten years, irrespective of incomplete Hib immunisation before one year of age.
To fulfil the objective of protection against Hib disease, the appropriate combination vaccine for each age group is determined especially by the need to protect individuals against tetanus, pertussis, diphtheria and polio. Although only one dose of Hib vaccine is required from one year of age, three doses of DTaP/IPV/Hib should be given in order to fully protect individuals against diphtheria, tetanus, pertussis and polio.
The primary course of Hib vaccination in infants consists of three doses of a Hib containing product with an interval of one month between each dose. DTaP/IPV/Hib is recommended for all children from two months up to ten years of age. Although one dose of Hib vaccine is effective from one year of age, three doses of DTaP/IPV/Hib should be given in order to be fully protected against diphtheria, tetanus, pertussis and polio. If the primary course is interrupted it should be resumed but not repeated, allowing an interval of one month between the remaining doses.
No reinforcing (booster) doses are currently recommended for children who have received a complete course of three injections. However, the need for boosting against Hib disease is under review by the Joint Committee on Vaccination and Immunisation.
Unless there is a reliable history of previous immunisation, individuals should be assumed to be unimmunised. The full UK recommendations should be followed. Achild who has not completed the primary course should have the outstanding doses at monthly intervals. Children who have only completed their primary immunisations for diphtheria, tetanus, pertussis and polio will need to be protected against Hib. Children aged under one year need three doses at monthly intervals, and those aged from one to ten years need one dose, of single Hib vaccine.
Children and adults with splenic dysfunction may be at increased risk of invasive Hib infection. It is important that such children under ten years of age should complete the primary immunisation schedule. Unimmunised individuals aged ten years and over should receive a dose of single Hib vaccine. One dose of Hib vaccine is immunogenic in splenectomised older children and adults. At present, there are no data to indicate a need for Hib booster doses in younger children. Individuals immunised in infancy who then acquire splenic dysfunction should receive a single Hib booster after the age of one. This is advised as a precautionary measure because protection from vaccination above the age of one year is more long lasting than vaccination in infancy. When splenectomy is performed electively, the vaccine should be given ideally at least two weeks before surgery, or as soon as possible afterwards.
There are very few individuals who cannot receive Hib-containing vaccines. Where there is doubt, appropriate advice should be sought from a consultant paediatrician, immunisation co-ordinator or consultant in communicable disease control rather than withhold vaccine.
The vaccines should not be given to those who have had:
Confirmed anaphylaxis after Hib-containing vaccines is extremely rare (0.65 to 3 anaphylaxis events per million doses, Bohlke et al., 2003; Canadian Medical Association, 2002). Other allergic conditions, such as rashes, may occur more commonly and are not contraindications to further immunisation. A careful history of the event will often distinguish between anaphylaxis and other events that are either not due to the vaccine or are not life-threatening. In the latter circumstance, it may be possible to continue the immunisation course. Specialist advice must be sought on the vaccines and circumstances in which they could be given. The risk to the individual of not being immunised must be taken into account.
Minor illnesses without fever or systemic upset are not valid reasons to postpone immunisation. If an individual is acutely unwell, immunisation may be postponed until they have fully recovered. This is to avoid wrongly attributing any new symptom or the progression of symptoms to the vaccine.
Hib-containing vaccines may be given to pregnant women when clinically indicated. There is no evidence of risk from vaccinating pregnant women or those who are breast-feeding with inactivated virus or bacterial vaccines or toxoids (Plotkin and Orenstein, 2004).
It is important that premature infants have their immunisations at the appropriate chronological age, according to the schedule. There is no evidence that premature babies are at an increased risk of adverse reactions from vaccines (Slack et al., 2001).
Individuals with immunosuppression and HIV infection (regardless of CD4 count) should be given Hib-containing vaccines in accordance with the recommendations above. These individuals may not make a full antibody response. Re-immunisation should be considered after treatment is finished and recovery has occurred. Specialist advice may be required.
The presence of a neurological condition is not a contraindication to immunisation. Where there is evidence of a neurological condition in a child the advice given in the flow chart in Figure 2.2 should be followed. If a child has a stable pre-existing neurological abnormality such as spina bifida, congenital abnormality of the brain, or perinatal hypoxic ischaemic encephalopathy, they should be immunised according to the recommended schedule. When there has been a documented history of cerebral damage in the neonatal period, immunisation should be carried out unless there is evidence of an evolving neurological abnormality. If there is evidence of current neurological deterioration, including poorly controlled epilepsy, immunisation should be deferred and the child should be referred to a child specialist for investigation to see if an underlying cause can be identified. If a cause is not identified, immunisation should be deferred until the condition has stabilised. If a cause is identified, immunisation should proceed as normal.
A family history of seizures is not a contraindication to immunisation. When there is a personal or family history of febrile seizures, there is an increased risk of these occurring after any fever, including that caused by immunisation. Seizures associated with fever are rare in the first six months of life and most common in the second year of life. After this age the frequency falls and they are rare after five years of age. When a child has had a seizure associated with fever in the past, with no evidence of neurological deterioration, immunisation should proceed as recommended. Advice on the prevention and management of fever should be given before immunisation.
When a child has had a seizure that is not associated with fever, and there is no evidence of neurological deterioration, immunisation should proceed as recommended. Children with a family or personal history of seizures when immunised with DTP vaccine had no significant adverse events and these children’s developmental progress was normal (Ramsay et al., 1994).
If a child experiences encephalopathy or encephalitis within seven days of immunisation, the advice in the flow chart in Figure 2.3 should be followed. It is unlikely that these conditions will have been caused by the vaccine and should be investigated by a specialist. Immunisation should be deferred in children where no underlying cause was found, and the child did not recover completely within seven days, until the condition has stabilised. If a cause is identified or the child recovers within seven days, immunisation should proceed as recommended.
If a seizure associated with a fever occurs within 72 hours of an immunisation, further immunisation should be deferred if no underlying cause has been found, and the child did not recover completely within 24 hours, until the condition is stable. If a cause is identified or the child recovers within 24 hours, immunisation should continue as recommended.
There will be very few occasions when deferral of immunisation is required (see above). Deferral leaves the child unprotected; the period of deferral should be minimised so that immunisation can commence as soon as possible. If a specialist recommends deferral this should be clearly communicated to the general practitioner and he or she must be informed as soon as the child is fit for immunisation.
This section gives advice on the immunisation of children with a history of a severe or mild systemic or local reaction within 72 hours of a preceding vaccine. Immunisation with Hib-containing vaccine should continue following a history of:
In Canada, a severe general or local reaction to DTaP/IPV/Hib is not a contraindication to further doses of the vaccine (Canadian Medical Association, 1998). Adverse events after childhood immunisation are carefully monitored in Canada (Le Saux et al., 2003) and their experience suggests that further doses were not associated with recurrence or worsening of the preceding events (S Halperin and R Pless, personal communication, 2003).
Pain, swelling or redness at the injection site are common and may occur more frequently following subsequent doses. Asmall painless nodule may form at the injection site; this usually disappears and is of no consequence. The incidence of local reactions is lower with tetanus vaccines combined with acellular pertussis vaccines than with whole-cell pertussis vaccines and similar to that after DT vaccine (Miller,1999; Tozzi and Olin,1997). Fever, convulsions, high-pitched screaming, and episodes of pallor, cyanosis and limpness (HHE) occur with equal frequency after both DTaP and DT vaccines (Tozzi and Olin,1997). Confirmed anaphylaxis occurs extremely rarely. Data from the UK, Canada and the US point to rates of 0.65 to 3 anaphylaxis events per million doses (Bohlke et al., 2003; Canadian Medical Association, 2002). Other allergic conditions may occur more commonly and are not contraindications to further immunisation.
All suspected adverse reactions to vaccines occurring in children, or in individuals of any age after vaccines labelled with a black triangle, should be reported to the Committee on Safety of Medicines using the Yellow Card Scheme. Serious suspected adverse reactions to vaccines in adults should be reported through the Yellow Card Scheme.
Unimmunised cases up to the age of ten years should also be immunised since recurrence of Hib infection can occur. Individuals who have been vaccinated against Hib, but who later acquire Hib infection, should have their convalescent antibody levels measured and booster vaccination may be advised. Where antibody testing is not possible, an additional dose of Hib vaccine should be given. Household contacts of a case of invasive Hib disease have an increased risk of contracting disease. Unimmunised children under four years of age are at substantial risk, older unimmunised children and even fully immunised children may be vulnerable.
When a case occurs in a playgroup, nursery, crèche or school, the opportunity should be taken to identify and vaccinate any unimmunised children under ten years of age. When two or more cases of Hib disease have occurred in a playgroup, nursery, crèche or school within 120 days, chemoprophylaxis should be offered to all room contacts – teachers and children. This is a precautionary measure as there is little evidence that children in such settings are at significantly higher risk of Hib disease than the general population of the same age.
These vaccines are supplied by Farillon (Tel: 01708 330200) as part of the national childhood immunisation programme.
In Scotland, supplies should be obtained from local childhood vaccine holding centres. Details of these are available from Scottish Healthcare Supplies, telephone 0131 275 6154.
American Academy of Pediatrics (2003). Active immunization. In Pickering LK (Ed) Red Book: 2003 Report of the Committee on Infectious Diseases. Twenty-sixth edition. Elk Grove Village, IL: American Academy of Pediatrics, p. 33. Anderson EC, Begg NT, Crawshaw SC et al. (1995). Epidemiology of invasive Haemophilus influenzae infections in England and Wales in the pre-vaccination era (1990–2). Epidemiol Infect 115: 89 –100. Black S B, Shinefield H R, Fireman B et al. (1991a). Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61 080 children. Pediatr Infect Dis J: 10: 97–104. Black S B, Shinefield H, Lampert D et al. (1991b). Safety and immunogenicity of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in infancy. Pediatr Infect Dis J 10: 2. Bohlke K, Davis RL, Marcy SH et al (2003). Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 112: 815–20. Booy R, Hodgson S, Carpenter Let al. (1994). Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T. Lancet Aug 6; 344(8919): 362– 6. Canadian Medical Association (1998). Pertussis vaccine. In Canadian Immunisation Guide. Fifth edition. Canadian Medical Association, p.133. Canadian Medical Association (2002). General considerations. In Canadian Immunisation Guide. Sixth edition. Canadian Medical Association, p.14. Chief Medical Officer, Chief Nursing Officer and Chief Pharmaceutical Officer (2004). Planned Hib vaccination catch-up campaign – further information. http://www.doh.gov.uk/cmo/letters/cmo0302.htm (accessed 10 February, 2004) Diggle L and Deeks J. (2000). Effect of needle length on incidence of local reactions to routine immunisation in infants aged 4 months: randomised controlled trial. BMJ 321: 931–3. Eskola J, Kayhty H, Takala AK et al. (1990). Arandomised, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. New England Journal of Medicine 323(20): 1381–7. Heath PT and McVernon J (2002). The UK Hib vaccine experience. Arch Dis Child 86: 396–9. Howard AJ et al. (1991). Epidemiology of Haemophilus influenzae type b invasive disease in Wales. BMJ 303: 442–5. McVernon J, Andrews N, Slack, MPE and Ramsay ME (2003). Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 361: 1521–3. Mark A, Carlsson RM and Granstrom M (1999) Subcutaneous versus intramuscular injection for booster DT vaccination in adolescents. Vaccine 17:2067-72 Miller E. (1999). Overview of recent clinical trials of acellular pertussis vaccines. Biologicals 27: 79–86. Miller E, Southern J, Kitchin N et al. (2003). Interaction between different meningococcal C conjugate vaccines and the Hib component of concomitantly administered diphtheria/ tetanus/pertussis/Hib vaccines with either whole cell or acellular pertussis antigens. 21st Annual Meeting of the European Society for Paediatric Infectious Diseases, Sicily 2003. Plotkin SAand Orenstein WA(Eds) (2004) Vaccines (Fourth edition) Philadelphia: WB Saunders Company, chapter 8. Ramsay M, Begg, N, Holland B and Dalphinis J (1994). Pertussis immunisation in children with a family or personal history of convulsions: a review of children referred for specialist advice. Health Trends 26: 23–4. Le Saux N, Barrowman NJ, Moore D et al. (2003). Canadian Paediatric Society/Health Canada Immunization Monitoring Program – Active (IMPACT). Decrease in hospital admissions for febrile seizures and reports of hypotonic-hyporesponsive episodes presenting to hospital emergency departments since switching to acellular pertussis vaccine in Canada: a report from IMPACT. Pediatrics 112(5): e348. Slack MH, Shapira D, Thwaites RJ et al. (2001) Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis- Haemophilus influenzae type b conjugate vaccines. J Infect Dis 184 (12): 1617-20. Tozzi AE and Olin P. (1997) Common side effects in the Italian and Stockholm 1 Trials. In Brown F, Greco D, Mastranonio P, Salmaso S and Wassilak S. Pertussis vaccine trials. Dev Biol Stand 89: 105–8. Trotter CL, Ramsay ME and Slack MPE (2003). Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign. Commun Dis Public Health 6: 55–8. Tudor-Williams G, Frankland J et al. (1989). Haemophilus influenzae type b disease. Arch Dis Child 64: 517–19. UK Health Departments (2001) Health information for overseas travel, Second edition. Edited by Lea G and Leese J. The Stationery Office. Zuckerman J (2000) The importance of injecting vaccines into muscle. BMJ 321:1237-8.