Challenging fears of vaccine side-effects
Dr David Baxter dispels the confusion highlighted by his recent research over what advice to give about adverse reactions to vaccines
MR vaccine: you're discussing MMR vaccination and the parents ask about the usual side-effects. What do you say?
MMR is the combined measles, mumps, and rubella vaccines: each is a live attenuated vaccine strain that generates both antibody and cell-mediated immune responses. MMR is given as a two-dose schedule at 12-15 months and again at pre-school age. The second MMR is not a booster, rather it is given to provide protection to the 10 per cent of children who are primary vaccine failures following the first dose.
The first thing to say to the parents is the majority of children (about 80 per cent) experience no signs or symptoms of illness after the MMR. The following side-effects occur but with varying frequency.
Pallor or erythema confined to the area of the injection site can occur within a minute or two of immunisation and persists for a similar time. This is presumably due to local cytokine or heat shock protein release from damaged cells. There are no systemic features and no treatment is required.
Type I hypersensitivity reactions (anaphylaxis) occur with an estimated frequency of about one in 150,000 immunisations: these come on within five to 10 minutes and present with difficulty breathing (stridor or wheezing depending on whether the obstruction is in the upper or lower airways) and tissue hypoperfusion (presenting as shock and a declining conscious level). Immediate management involves maintaining a patent airway, ensuring adequate respiration and circulation and administering intramuscular adrenaline.
No further adverse events would then be expected until around the 10th day post-immunisation (but ranges from five to 14 days) when about one child in five will develop a mild 'measles vaccine strain' illness with rash, fever or irritability that lasting less than 24 hours, although on occasion it can persist for two or three days.
One in 100 children will develop mild 'vaccine strain mumps or rubella' between 14 and 26 days post-immunisation. Both illnesses, which usually last only a day or two, can present with a rash, fever and irritability. Additionally, mumps vaccine strain can give rise to a parotitis, whereas rubella vaccine strain can cause posterior cervical adenopathy.
Rubella vaccine can also cause an acute arthropathy involving mainly the metacarpophalangeal and proximal interphalangeal joints bilaterally: as many as 20 per cent of adult vaccinated women will develop this, with much lower rates seen in children and adolescents. Rubella arthropathy resolves spontaneously and usually lasts less than two weeks.
Approximately one in 5,000 children will experience a febrile convulsion post-MMR:
most seizures occur about the 10th day and are related to the measles component of the vaccine
(by comparison, wild measles infection causes febrile convulsions about once every 100 clinical illness episodes). The frequency is probably higher in children who have experienced a previous febrile convulsion. While febrile convulsions don't cause epilepsy or brain damage, 2 per cent of children with epilepsy experience a febrile convulsion as their first seizure. Thrombocytopenia, which may be clinically significant, occurs in about one in 35,000-40,000 vaccinees.
There is insufficient evidence to support or reject an association between MMR and encephalitis, aseptic meningitis, sub-acute sclerosing pan-encephalitis, residual seizure disorder, transverse myelitis, Guillain-Barre syndrome, type 1 diabetes, chronic arthritis or sterility due to bilateral orchitis.
The association between MMR and pervasive development disorder (including autism) has been extensively reviewed elsewhere. The current data do not support the view that MMR administration increases the risk of a child developing pervasive development disorder.
Polio vaccine: a baby is brought for its first set of immunisations and the parents ask whether they and the grandparents should also have the polio vaccine.
Oral polio vaccine (OPV) is a trivalent preparation comprising attenuated type I, II and III vaccine strains. OPV is given at two, three and four months of age, with booster doses given to pre-school and school leavers.
Side-effects due to OPV are rare but poliomyelitis in vaccine recipients has been described and is due to reversion to virulence of the vaccine strain as it replicates in gut enterocytes.
Poliomyelitis can occur after vaccination it is estimated that about one in 520,000 vaccinees will acquire disease after the first dose of OPV, with a risk of one in 12,300,000 for all subsequent doses. In contrast IPV, which is the inactivated form of polio vaccine (available only on a named individual basis), cannot cause paralytic disease. By definition, polio due to vaccine occurs between seven and 30 days after OPV. All vaccine strains can cause polio but most cases are associated with type III.
Vaccine strains can be identified in the vaccinee's faeces within 48 hours of OPV administration with excretion lasting between six and 12 weeks. Faeco-oral spread to close contacts has been reported where standards of hygiene are low.
If reversion to virulence of a vaccine strain also occurs then such close contacts are at risk of developing disease: contact-associated poliomyelitis comes on between seven and 60 days post-exposure. The risk is estimated to be about one in 3,000,000 exposed close contacts.
Some people who develop poliomyelitis (vaccine recipients or close contacts) have an underlying immunodeficiency disorder, but in the majority of cases no such abnormality is reported.
In order to prevent poliomyelitis being acquired from recently vaccinated infants, OPV is sometimes given to susceptible close contacts at the same time as the infant. Such an approach is only useful in the longer-term because polio has an incubation period as short as three days and immunity to OPV takes a minimum of about four weeks to appear.
So there is a window when vaccination does not provide immediate protection, and because virus starts to appear in faeces within 48 hours of OPV administration, close contacts must be advised to maintain scrupulous standards of hygiene to prevent faeco-oral transmission.
OPV vaccination of contacts is valuable only in the long-term if the contact is susceptible. For most young parents who have been through the current UK schedule their five doses of OPV should provide lifelong protection. For older grandparents who have probably had more than five doses of OPV (or IPV) during the outbreaks in the 1950s, 1960s and 1970s, vaccination may be of value if they have an age-related decline in immune responsiveness. As a rule, where there is an incomplete vaccination history an additional dose of OPV seems a sensible precaution (albeit for a very low risk) but must be combined with advice about appropriate hygiene.
BCG vaccine: a 14-year-old is brought to your surgery with an abscess at the site of a BCG vaccination that was given at school six weeks earlier. What should you do?
BCG is a live attenuated vaccine with an estimated efficacy of about 70 per cent. The duration of protection is unknown but the original MRC studies suggest it is at least 14 years. In the UK control of TB is based on both neonatal and an adolescent programmes.
At-risk newborns are defined as those with a family history of TB, migration (or regular travel) to or from high-endemicity areas, an occupational risk or parent request. BCG is offered within four to six weeks of birth: usually this service can be accessed through the local TB specialist.
Adolescents who are purified protein derivative grade 0 or 1 and who have not been previously immunised are offered BCG as part of the universal adolescent school programme. Vaccine is administered intradermally usually in the left arm at the insertion of the deltoid muscle. Where there is concern about hypo- or hyperpigmentation (particularly in black people) then alternative sites (for example the thigh or ankle) should be considered.
BCG vaccine was originally given orally but within a few years this method was discontinued because of uncertain efficacy. It was then given subcutaneously, but such an approach gave rise to many 'cold abscesses'. The intradermal approach was first introduced in Sweden in 1927 and is now used throughout the world.
Three weeks after vaccination most children will develop a small erythematous popular swelling at the BCG site. This normally disappears over the next few weeks. In less than 5 per cent of children this lesion will become fluctuant and discharge. The usual explanation for abscess formation after BCG is faulty technique with the vaccine being given subcutaneously rather than by the intradermal route.
In such circumstances, one might argue that the abscess reflects an impaired immune response due to fewer tissue-based macrophages and reduced vascularity, making it more difficult to eliminate the mycobacteria, so local infection persists. In contrast, there are a small number of people who develop an abscess formation where BCG was definitely given correctly. The most likely explanation for this is an enhanced immune response associated with their genetic make-up.
The natural history of one of these post-BCG lesions is one of repeat scabbing followed by discharge; healing takes three to six months. Management depends on the size of the lesion and the time when the individual presents.
Small lesions seen early after the vaccine was administered simply require wound care with the use of non-stick dressings and review if they aren't healing. Larger, discharging lesions seen later after BCG administration are variously managed with some chest physicians using antituberculous therapy (for example Rifinah for four weeks) or antibiotics (for example clarithromycin for four weeks).
In my own district, it is recommended that lesions greater than 2cm in diameter are usually referred to the local TB specialist for management. Very rarely, where scarring is extensive or cosmetically poor, the advice of a plastic surgeon may be necessary.
Challenging fears of vaccine side-effects
About one in 5,000 children will experience a febrile convulsion after MMR vaccination with
most seizures happening about the 10th day~
The usual explanation for abscess formation after BCG is faulty technique, with the vaccine being given subcutaneously rather than by the intradermal route~