NOTIFIABLE
Whooping cough is a highly infectious disease that is usually caused by Bordetella pertussis. A similar illness is caused by B. parapertussis, but this is not preventable with presently available vaccines. There is an initial catarrhal stage, followed by an irritating cough that gradually becomes paroxysmal, usually within one to two weeks. The paroxysms are often followed by a characteristic "whoop", often accompanied by vomiting. In young infants, the typical whoop may never develop and coughing spasms may be followed by periods of apnoea. The illness often lasts for two to three months. In older children and adults the disease may be mild and not recognised as whooping cough. Pertussis may be complicated by bronchopneumonia, repeated vomiting leading to weight loss, and by cerebral hypoxia with a resulting risk of brain damage. Severe complications and deaths occur most commonly in infants under six months of age. Minor complications include subconjunctival haemorrhages, epistaxis (nosebleeds), facial oedema, ulceration of the tongue or surrounding area, and suppurative otitis media.
Transmission of the infection is by droplet, and cases are most infectious during the early catarrhal phase. The incubation period is between six and 20 days and cases are infectious from six days after exposure to three weeks after the onset of typical paroxysms.
Before the introduction of pertussis immunisation in the 1950s, the average annual number of notifications exceeded 120,000 in the UK. By 1972, when vaccine coverage was around 80%, there were only 2069 notifications of pertussis. Because of professional and public anxiety about the safety and efficacy of the vaccine, coverage fell to about 30% in 1975 and major epidemics occurred in 1977/79 and 1981/83. In 1978, there were over 68,000 notifications and 14 deaths. The actual number of deaths due to pertussis is higher since not all cases in infants are recognised (Miller and Fletcher, 1976). These two major epidemics illustrate the impact of the fall in coverage of an effective vaccine. The return of professional and public confidence resulted in increased vaccine uptake. Since the mid-1990s coverage has been consistently over 90% by the second birthday with less than 6000 notifications per year. In 2002, only 1,051 cases were reported. The most recent estimate of deaths in England is nine deaths per year (Crowcroft et al., 2002).
Despite the current low levels of disease, pertussis in the very young remains a significant cause of illness and death. The majority of hospitalisations following pertussis have occurred in those under six months of age, some of whom were seriously ill and required admission to paediatric intensive care units (Crowcroft et al., 2003). As the morbidity and mortality are highest in infants, high coverage must be maintained to protect those who are too young to be immunised. Adults and older children may infect younger members of their family too young to be immunised (Crowcroft et al., 2003).
The acellular vaccines are made from highly purified selected components of the Bordetella pertussis organism. These components are treated with formaldehyde or glutaraldehyde and then adsorbed on to adjuvants, either aluminium phosphate or aluminium hydroxide, to improve immunogenicity. Acellular vaccines differ in source, number of components, amount of each component, and method of manufacture, resulting in differences in efficacy and in the frequency of adverse effects (Edwards and Decker, 2004). The vaccine chosen for primary immunisation in the UK programme (Pediacel) contains five purified pertussis components. This vaccine has been shown to offer equal or better protection against clinically typical pertussis disease than the whole-cell pertussis vaccine previously used in the UK (Miller, 1999). The incidence of local and systemic reactions is lower with acellular pertussis vaccines than with whole-cell pertussis vaccines (Miller, 1999). Three- and five-component pertussis-containing vaccines are provided based on their suitability for pre-school boosting. The pre-school vaccines are not provided for the purpose of primary immunisation. The three-component preparation (DTaP/IPV – Infanrix-IPV) does not provide the same level of protection against whooping cough in primary immunisation. The five-component pre-school preparation (dTaP/IPV – Repevax) does not contain the recommended strength of diphtheria for primary immunisation.
The five-component vaccine contains pertussis toxoid (PT), filamentous haemagglutinin (FHA), fimbrial agglutinogens (FIM) 2 and 3, and pertactin (PRN). The three-component contains PT, FHA and PRN. The pertussis vaccines are only given as part of combined products:
The above vaccines are thiomersal free. They are inactivated, do not contain live organisms and cannot cause the diseases against which they protect. Monovalent pertussis vaccine is not available.
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. Pertussis-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 four doses of a pertussis-containing vaccine at appropriate intervals for all individuals up to ten years of age. To fulfil this objective, the appropriate vaccine for each age group is determined also by the need to protect individuals against diphtheria, tetanus, Hib and polio.
The primary course of pertussis vaccination consists of three doses of a pertussis containing product with an interval of one month between each dose. DTaP/IPV/Hib is recommended for all infants from two months up to ten years of age. If the primary course is interrupted it should be resumed but not repeated, allowing an interval of one month between the remaining doses. DTaP/IPV/Hib should be used to complete a primary course, which has been started with wholecell or another acellular pertussis preparations.
Currently immunisation against pertussis is not recommended.
Children under ten years should receive a pertussis booster combined with diphtheria (D or d licensed for boosting), tetanus and polio vaccines. The booster of pertussis-containing vaccine should ideally be given three years after completion of the primary course. Either of the recommended pre-school vaccines should be used to boost a primary course of whole-cell or acellular pertussis preparations. Individuals vaccinated according to a non-UK schedule Unless there is a reliable history of previous immunisation, individuals should be assumed to be unimmunised. The full UK recommendations should be followed. If a child has not had three doses of pertussis vaccine but whose primary immunisations for diphtheria, tetanus and polio are otherwise complete, they may receive an additional dose of pertussis-containing vaccine. Children coming to the UK may have had a fourth dose of a pertussis-containing vaccine as given at around 18 months in some countries. This dose should be discounted as it may not provide satisfactory protection until the time of the teenage booster. The routine pre-school immunisations should be given according to the UK schedule. Achild who has not completed the primary course should have the outstanding doses at monthly intervals. The booster dose may be given as early as one year after the third primary dose to re-establish the child on the routine schedule. If a child attends for a booster dose and has a history of receiving a vaccine following a tetanus-prone wound, attempts should be made to identify which vaccine was given. If the vaccine given was the same as that due at the current visit and at an appropriate interval, then the booster dose is not required. Otherwise, the dose given at the time of injury should be discounted as it may not provide satisfactory protection against all antigens and the scheduled immunisation should be given. Such additional doses are unlikely to produce an unacceptable rate of reactions (Ramsay, 1997).
There are very few individuals who cannot receive pertussis-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 pertussis-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 circumstance 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.
Pertussis-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 pertussis-containing vaccines in accordance with the routine recommended schedule. 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 3.3 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).
Evidence of a neurological abnormality prior to immunisation
If a child experiences encephalopathy or encephalitis within seven days of immunisation, the advice in the flow chart in Figure 3.4 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.
Refer to a paediatrician or paediatric neurologist for investigation
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 pertussis-containing vaccine should continue following a history of:
Previous experience suggested that the above events occurred more often after whole-cell DTP vaccine, than after DT alone or after DTaP. Following the replacement of whole cell pertussis vaccine with an acellular pertussis vaccine (DTaP/IPV/Hib) in Canada, there was a significant reduction in the number of reports of febrile seizures collected through the Immunization Monitoring- Program – Active (IMPACT) (Le Saux et al., 2003). When DTaP vaccines were compared with DT alone, severe general and local reactions occurred at the same rate (Tozzi and Olin, 1997). Therefore, these reactions were not due to the acellular pertussis components. Children who have had severe reactions as above, have continued and completed immunisation with pertussis-containing vaccines without recurrence (Vermeerde Bondt et al., 1998; Gold et al., 2000). 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).
Since local or general reactions are less frequent after acellular than whole-cell pertussis vaccines, the number of children with such events will be few. There is no benefit in withholding acellular pertussis-containing vaccines in order to reduce risks of adverse events, and there is additional protection from completing pertussis immunisation; this should be carried out in accordance with the routine immunisation schedule. Children who have had a local or general reaction after whole-cell pertussis vaccine should complete their immunisation with acellular pertussis preparations.
Pain, swelling, or redness at the injection site are common and may occur more frequently following subsequent doses. A small painless nodule may form at the injection site; this usually disappears and is of no consequence. The incidence of local reactions is lower with vaccines combined with acellular pertussis than with whole-cell pertussis 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.
In the past, there was public and professional anxiety that whole-cell pertussis vaccine contributed to the onset of neurological problems in young children. Between 1976 and 1979, a total of 1182 children with serious neurological illnesses were reported to the National Childhood Encephalopathy Study (NCES). Only 39 of these children had recently received whole-cell pertussis vaccine. The study concluded that whole-cell pertussis vaccine may very rarely be associated with the development of severe acute neurological illness in children who were previously apparently normal; most of these children suffered no apparent harm. The occurrence of a severe encephalopathy after whole cell pertussis immunisation was sometimes associated with long-term residual neurological damage, but the evidence was insufficient to indicate whether or not whole-cell DTP increased the overall risk of chronic neurological dysfunction.
A major review of studies on adverse events after pertussis vaccine was published by the United States Institute of Medicine in 1991 (Institute of Medicine, 1991). This concluded that the evidence did not indicate a causal relationship between pertussis vaccine and infantile spasms, hypsarrhythmia, Reye’s syndrome and Sudden Infant Death Syndrome (SIDS). Cot deaths (SIDS) occur most commonly during the first year of life and may therefore coincide with the giving of pertussis-containing vaccines. Studies have established that this association is not causal (Fleming et al., 2001).
It has been suggested that pertussis vaccine is linked with the development of asthma and allergy (Odent et al., 1994). A recent double-blind study of pertussis vaccines found no significant differences in wheezing, itchy rash or sneezing between DTP immunised children and controls (Nilsson et al., 2003; DeStefano et al., 2002). Asthma or allergy are not contraindications to the completion of pertussis immunisation.
Because three injections are required to protect against pertussis, the vaccine cannot be used to control outbreaks (Dodhia et al., 2002). For outbreaks affecting children under ten years of age, those who have not received four doses of pertussis-containing vaccines should receive an additional dose(s) of dTaP/IPV (DTaP/IPV may be used if there is no dTaP/IPV available). Antibiotic prophylaxis should be offered to unimmunised or partially immunised vulnerable contacts of cases after discussion with the local health protection unit (Dodhia et al., 2002).
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.
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