written by Lynne McTaggart
What Doctors Don’t Tell You (WDDTY)
“The Government has reacted swiftly to the public’s worries about meningitis with a mass immunisation programme. But has it all been too hurried, and are our children been made guinea pigs” asks Lynne McTaggart.
The UK is the first country in the world to launch a mass immunisation programme against meningitis C, the disease that is probably one of the most feared by parents.
All of the nation’s 14 million schoolchildren will have been inoculated within the year, with the at-risk groups of I5- to I 7-year-olds and babies under a year being first in the queue.
This ambitious programme, which is costing an already cash-strapped NHS around 10 million, is a swift response to a sometimes deadly disease that is able to kill healthy children within hours, as every newspaper reader must know.
Liam Donaldson, the nation’s Chief Medical Officer for Health, announced the programme with the confident message that, by the end of 2000, we hope to have confined this particular strain of meningitis largely to the history books’.
The Department of Health (D0H) has pushed forward the launch date for the campaign by a year, so treating at face value a few initial studies into the new vaccine, which has been developed and manufactured in the UK by the pharmaceutical company Wyeth.
Although the new vaccine wasn’t to be ready until last November, the Government paved the way for publicity about it In August last year by launching a vaccine drive for university students, who would receive the old A and C combined polysaccharide vaccine. Although the old vaccine is considered less effective and shorter-lasting than the new one, the idea, said a DoH spokesperson, was that at least the vaccine would see the nation’s 480,000 freshmen students through their three-year university tenure.
But behind the smiles at the DoH and all the self-congratulatory back-patting lies a rash decision and all the makings of a scandal not dissimilar to that of the measles campaign of 1994. At that time, all of the nation’s school children were pressed into receiving a booster measles jab supposedly to ward off a predicted measles epidemic. The epidemic never arrived, but at least several hundred families are currently suing vaccine manufacturers over apparent brain damage, paralysis and even death suffered by their children allegedly due to the measles booster.
With the new meningitis vaccine, the press has whipped up a fury over the limited supplies of the old vaccine, which were inadequate to meet the demands of the university students. In focusing on the shortage, journalists have missed the real scandal here, which has to do with expediency and, inevitably, politics. In the wholly laudable desire to staunch the increasing number of meningitis cases on the part of all involved, an alliance with no checks and balances has been forged between a government wishing to be regarded as heroic and a private company with its need to turn a profit. In the process, our entire population of children is being exploited as a giant, convenient pool of guinea pigs.
Not an epidemic
Much has been made of meningitis as a random killer of children, and there is no doubt that the disease is horrendous and frightening in its rapid, potentially fatal onset. But how much actual risk does your child face.
Although the plan is to give all children the vaccine, rather than simply individual groups at high risk, children between five and 15 are at virtually no risk of contracting meningitis C. In the five-year period between 1994 and 1999, group C meningococcal disease killed approximately 20 babies under one year of age, 21 one-yearolds, 18 two year olds. Approximately 15 three year olds. a handful of four, five and six year olds, and almost no other children under adolescence.
After babies are a year old, they develop active immunity by being exposed to a non-pathogenic form of meningococcus.
Casualties did not pick up again until I5 to 20 years of age, the so-called highest cluster. In this age category, meningitis killed around 82 young people. So, in total, the disease killed less than 200 young children, or an average of 40 children a year (70 a year in 1999).
While no one wishes to denigrate the tragic loss of these lives, in strictly epidemiological terms, the death rate of this form of meningitis is low.
It rates well behind conditions or accidents which account for appreciable numbers of childhood deaths. For instance, your baby is five times more likely to drown in a bath tub and 86 times more likely to die of cot death than die from meningitis C. Six times as many children and young adults get knocked over and killed by cars than die of meningitis C. British traffic deaths of all varieties among children — representing the highest fatalities among this age group in all of Europe — claim the lives of 1,309 children and young adults every year —more than 32 times the rate of meningitis deaths.
If there were 70 childhood deaths due to meningitis C in 1999 and there are 14 million British children, generally speaking, your child’s chances of catching this disease at the moment are one in 200,000, with slightly higher risks in babyhood and late teens. However, it is the tragic swiftness of the disease’s deadly progress and the existence of so-called local clusters that put the disease on the front pages. Media coverage, more than the actual prevalence of the disease, accounts for its high profile and also for the irrational fear instilled in the public mind about it.
No one would wish to put a price tag on the heads of these dead children. But one must question the wisdom of throwing such heavy economic resources at a disease which causes relatively few fatalities rather than simply concentrating on groups at high risk: those without spleens, those with chronic underlying illness and those living in crowded or impoverished conditions.
Heikki Peltola. professor of infectious diseases and pediatrician at the University of Helsinki and the Hospital for Children and Adolescents, confirmed that, although the UK has a higher per capita incidence of this disease than other countries do, including his native Finland,”the question was whether the incidence of this disease was high enough to merit mass immunisation. In no country is there an epidemic of this disease”. As he wrote recently in an article about meningitis vaccination (Drugs, 1998; 55: 347—66), “Generally speaking, the incidence of meningococcal disease is too low to indicate vaccinations for the whole population, or even children, but some risk groups and epidemics are important exceptions”.
A deadlier form of meningitis
The British Government has touted Neisseria meningitidis group C as the most deadly bacterium causing meningococcal disease, which affected 1530 people in Britain last year and claims the lives of one-tenth of those who contract it.
But not according to the DoH’s own ‘fact sheet’. Group C meningococcal disease, which began appearing only a decade ago, accounts for only 40 per cent of cases of meningitis contracted in Britain and elsewhere. Between 1994-1999, meningitis B killed nearly 70 infants under one year of age. This incidence represents more than three times the number of deaths due to meningitis C among this age group during the same period. Strain B also killed twice as many one-year-olds as did strain C. In all, meningitis B killed approximately 170 children under six — which represents the same number of deaths from meningitis C among all age groups combined. Although meningitis C is the major cause of meningococcal death among teenagers, accounting for 80 per cent of deaths (meningitis B only claimed the lives of around 24 teenagers and young adults), the B version is far more deadly to babies and small children, representing at least two-thirds of all meningococcal deaths in this age group.
David Hall, corporate affairs manager for Wyeth, says that so far, producing a vaccine for the B strain has proved elusive. “B has structural differences having to do with one of the antigens on the polysaccharide protein code,’ he says. “For some reason, that makes it difficult to come up with a workable vaccine.”
Dr Richard Nicholson, editor of the Bulletin of Medical Ethics, is concerned that even if this vaccine prove 100 per cent effective, it will protect against only minority of meningococcal cases. Nevertheless, its existence could cause the public to become complacent about watching for warning signs of the disease caused by the ocher strains.
Immunity for life?
This vaccine will offer teenagers “almost 100 per cent immunity for life”, wrote The Times, and the DoH confirms that besides babies, who will get three doses, a single dose is sufficient in all other children. In 1989, the then Health Minister Edwina Currie claimed that the new triple measles—mumps—rubella (MMR) vaccine would offer “life-long protection with a single jab”. Five years later, the British Government launched the countrywide booster campaign after massive epidemics of measles among previously vaccinated youngsters in America proved that the MMR does not, after all, give you protection for life.
If the meningitis vaccine works similarly — and most vaccines appear to wane over a decade — then teenagers and young adults vaccinated as babies and toddlers will experience waning immunity gust at a point where they are most vulnerable to the disease.
Besides not knowing how long this vaccine will last, no one is sure how many shots and of which variety will confer long-term protection.
In one study of 114 infants from West Gloucestershire, babies were randomly divided into groups to receive either 2 or 10 micrograms of meningococcal C vaccine. Half of the infants then received the old A and C polysaccharide vaccine at 5—20 months. (The others were to receive this booster at age four.)
Among those getting the lower initial dose, bactericidal antibody titres rose at five months, but fell by 14 months to not much higher than they were originally (I:4 to I: l057 to I: 19). In those receiving the 10-microgram dose, antibody responses were significantly higher at five months than in the 2-microgram group, but were lower after boosting with the plain polysaccharide vaccine than with the lower-dose vaccine group.
This appears to mean that 1) the Government believes that boosters will be necessary at some point and is probably already planning for them, and 2) nobody really knows which combination of vaccines — higher or lower doses for initial shot and follow-up boosters — is really going to work, or whether using the old polysaccharide vaccine actually lowers your immunity, as it appears to do in one study (J Infect Dis, 1999; 179: 1569—72).
The researchers say in the conclusion of their report that ”total antibody levels required for protection against serogroup C disease are not known”.
In another study (J Infect Dis, 1996; 174; I360—3) of a conjugate meningococcal combination A and C product, antibodies also fell rapidly 12—14 months later, even after three doses.
Because the antibody levels fell so rapidly, the researchers addressed themselves to what they say is the good news — the presence of immunologic ‘memory’. The Hib vaccination, they claim, offers long-term protection despite the fact that antibody levels fall rapidly with that vaccine as well. As the Hib vaccine has only been around for a handful of years, time will tell whether that theory is correct.
According to David Hall at Wyeth, the old polysaccharide vaccine works at best 75 per cent of the time on older children and wears off after a few years. It does not work in babies and toddlers. The new conjugated variety, called Meningitec, has produced immunological ‘memory’ cells in babies and toddlers by being piggybacked onto the diphtheria toxoid, which produces a sort of red-alert immune system response. The presence of these memory cells means that it’s likely the vaccine will last longer, but nobody knows for sure. “We know that this is a sign of long-lasting immunity:’ says Hall,”but until you embark on a mass vaccination programme, you’re never going to prove it.”
Lucky for Wyeth, then, to be located in Britain. Several years ago, the DoH and its Government sidekick The Public Health Laboratory Service (PHLS), which studies, monitors and formulates immunisation policy, approached Wyeth and other vaccine companies, asking them to step up research into a meningitis C vaccine and even offered to help research it.
When Wyeth got to the finish line first with a product, the PHLS basically took over its testing. Many of the larger trials were conducted by the PHLS. “One way we were able to bring forward our launch date was because we worked together in collaboration with the DoH:’ says Hall. “Rather than our company having to set up trials, the PHLS did much of the studies for us.’
In other words, Wyeth was able to fast-track this drug through the usual drug-approval procedure, which ordinarily requires a drug company to set up its own trials. The Government is then supposed to act as an independent judge, approving them on the basis of safety and effectiveness. In this instance, defendant, prosecution, judge and jury were all effectively on the same team.
A further wrinkle that might be labeled a conflict of interest has to do with the monitoring system of the PHLS. In 1994, the PHLS devised a surveillance system for monitoring side-effects of vaccines. This was first tested out with the all-country measles booster scheme, leading the cynical to wonder whether the mass measles campaign was manufactured to test the effectiveness of the new system.
By working with the PHLS, the third party in the collaboration, Wyeth ensured not only that its studies had the most positive spin possible, but also that the product would be given a blessing to be test-marketed on a mass basis through this new surveillance system. As Hall maintains, no one would know the effectiveness of the vaccine until it is mass-marketed. In effect, the Government is carrying out the best post-marketing testing that Wyeth could ever have dreamt of.
Illness from the jab
The vaccine is highly safe, says the DoH, or “harmless”, as Heikki Peltola put it. That is an assertion that no one can make about any vaccine, let along a brand new one that is neither tried nor tested. Although the meningitis C vaccine was tested on 6000 British children, and more than 21,000 people outside the UK, these were short-term tests lasting at most a few weeks, and many of the trials remain unpublished — that is, unavailable to anyone outside of Wyeth and the Government.
In the largest of three published trials, all conducted partly or entirely by the PHLS with 114 infants vaccinated at two, three or four months, side effects were only recorded for seven days by parents and a health nurse (J Infect Dis. 1999: 179: 1569—72). Any symptoms outside this window of time probably would not have been associated with the vaccine. Nevertheless, within the small cohort of babies, 26 of those receiving the lower dose and 53 of those receiving the higher dose had systemic symptoms within the first 24 hours from one of three shots.
Although ‘systemic symptoms’ were not defined, they presumably mean that the children were generally ill after the jab. According to this report, more than one-fifth of the jabs — 79 out of a total of 344 jabs — made the babies in the vaccine group ill. Seven of the low-dose group and eight of the high-dose group — more than 13 per cent — developed a fever higher than 38 degrees centigrade. Five of the babies had persistent crying for more than one hour in the first day after the vaccine. Nine babies had erythema (reddening of the skin) of more than 2.5 centimetres and eight had swelling of more than 2.5 centimetres.
These latter side effects — which consisted of mainly swelling at the injection site — were noted to be less than those caused by the Hib vaccine, leading to the often quoted remark that this vaccine produces fewer reactions than other ones.
In its data sheet, Wyeth reports that systemic reactions usually include crying, irritability, drowsiness, impaired sleeping, anorexia, diarrhoea and vomiting, all conditions that are ‘common’ after vaccination. Nevertheless, the company points out that “there was no evidence that these were related to Meningitec rather than concomitant vaccines, particularly DTP vaccines” as most of these have been given at the same time.
Those reactions that the company admits “may possibly be related to the vaccine” include headache and myalgia in adults, and irritability and drowsiness in younger children. One baby was hospitalised for a viral illness following the second vaccination, although the PHLS maintains that this illness was not attributable to the vaccine. Another baby given the old A and C polysaccharide jab developed a generalized rash, ‘mild’ facial swelling, cough and coryzal (acute rhinitis) symptoms within five hours after vaccination, although these symptoms resolved within two days after oral antihistamines were given. This baby had no evidence of antibodies to A or C meningococcus — in other words, the vaccine didn’t work on him. The researchers again concluded that these adverse events, despite happening within hours of the jab, were “not vaccine-related”.
In one independent case study, a 25-year-old woman developed acute disseminated post-vaccinal encephalomyelicis (ADEM) after vaccination with the old combination group A and C polysaccharide vaccine (Arq Neuropsiquiatr, 1997; 55: 632—5). The symptoms only disappeared, and the lesions on the myelin sheath of her nervous system finally resolved, after treatment with high doses of intravenous steroids. As the researchers noted, although most cases of ADEM have been related to other vaccinations or conditions, this case report indicates that it may also be related to exposure to A and C polysacchande-protein vaccines and meningococcal vaccine. Whether ADEM will become a new condition in children once the meningitis C vaccine is widely disseminated is anyone’s guess.
In an adult study of another meningitis C vaccine conjugated with the tetanus toxoid, half the 30 subjects reported tenderness at the injection site and half showed erythema, 13 or nearly half reported pain, two reported headaches and one reported myalgia.
One patient had a fever higher than 38 degrees centigrade five to seven days after vaccination, but this again was discounted because the researchers said it was associated with a “viral illness” (Vaccine, 1999; 18:641—6).
As David Hall says, we won’t really know the long term effects until the product is out in the mass market. Indeed, we won’t be sure of anything until virtually every child in Britain has been given the jab. “There is no evidence that multiple vaccines overload a child’s immune system,” says the DoH fact sheet. But we don’t know the effect of this vaccine on other vaccines given at the same time as this wasn’t really tested for because multiple vaccines are always presumed to be safe before proven dangerous.
Including the meningitis C vaccine on the standard schedule of infant vaccinations now increases to six the number of vaccines given simultaneously to infants at two months of age. In the British infant study, the researchers admitted that “increased amounts of carrier protein may interfere with immunologic priming with other conjugate vaccines. This should not affect protection induced by this vaccine, but may be important in combination conjugate vaccines using the same carrier proteins”. This means that the new vaccine may interfere with other conjugate vaccines like the Hib vaccine —although again, we won’t know until we suck it and see.
No doubt the Government was motivated by nothing but good intentions in rushing through this new vaccine. But the history of vaccination shows that it is always wise to err on the side of caution. In the US, a vaccine for pneumococcal meningitis under development, also produced by Wyeth, was carefully tested for four years on a sample population of 38,000 children in Northern California before being released to the public at large.
In the UK, however, as with the measles epidemic, the DoH is rashly attempting wholesale herd immunity with an untested product rather than carefully weighing up the risks and benefits of a new, potentially dangerous jab on individual children. One day, the Government may learn to lead with its head as well as its heart.
Reprinted with permission from Lynne McTaggart of WDDTY – (What Doctors Don’t Tell You)