In October 2001, the government added a new 'safer' vaccine to its booster schedule, with no real safety testing. But new evidence shows that whooping cough is mutating and may not respond.
Last October, with a minimum of fanfare, the British government made a small adjustment to its vaccination schedule. As of 5 November 2001, the Department of Health (DoH) modified its booster schedule to include another dose of the whooping cough vaccine.
Children who have already had the standard three doses of the whooping cough vaccine at two, three and four months of age are now to receive a preschool booster when they are three and five, at the same time as the diphtheria and tetanus booster. The government has even been considering this as a 'one-stop' shot with the measles-mumps-rubella triple booster, so that preschoolers could receive at least six vaccines all on the same day.
Concealed behind this seemingly innocuous addition to the preschool vaccine schedule lies some enormous concerns on the part of officialdom, not least of which is that the whooping cough jab may have spawned a new disease immune to vaccination.
The DoH readily admits that the new booster drive has been initiated because the ordinary vaccine is failing to prevent cases of whooping cough among the very young. According to a DoH press release on 15 October, despite a 95 per cent vaccination take-up rate, pertussis is still a source of considerable illness and death among babies. The DoH maintains that babies are catching whooping cough from either their older siblings or parents.
The evidence suggests that the DoH figures have been highly inflated to justify the new vaccine. According to the Public Health Laboratory Service (PHLS) - the UK's chief body for monitoring and formulating policy on infectious disease - in 1999, the last year that full figures are available, there were 1139 notifications of whooping cough in England and Wales, and two deaths. In 1980, there were 21,131 cases of disease and six deaths.
In 2000, there were only 712 reported cases of the disease. These two years represent the lowest notification on record for two years running, according to the PHLS.
Nevertheless, the fatality ratio (number of deaths per 100 notifications of the disease) is going up. In 1980, the fatality ratio was 0.03. In 1998, this swelled to 0.25 (or eight times) and, in 1999, it was 0.18, or six times what it was in 1980.
Despite nearly universal vaccination coverage in very young infants, the proportion of disease is increasing among very young babies. The PHLS analysed the numbers for the years 1990-97 and found that, although the total number of cases fell during this period, the number of pertussis cases in children under three months didn't. Children in this age group accounted for 48 per cent of cases in 1999-2000. In the first quarter of 2001, of 47 confirmed cases, 62 per cent were under three months old (CDR Weekly, 21 June 2001).
Although the PHLS maintains that most babies getting whooping cough are too young to be vaccinated, the fact is that babies get their first shots at two months. A proportion of the under-one-year-olds who get whooping cough would have had at least one of their three doses of DPT. What is more likely is that the vaccine isn't working, even among children who have just received their shots.
With the preschool booster, the government may be attempting to make a preemptive strike on a disease that is reemerging in many places around the globe.
Because of the increase in cases among infants, not children, five-year-olds are being given a booster in an attempt to reestablish countrywide herd immunity rather than protect them per se. In effect, the immune system of your child is being exploited to prevent this ubiquitous disease from spreading among infants.
Whooping cough returns
In the Netherlands, despite universal vaccine coverage since the 1940s, whooping cough cases are increasing (CDC, Emerging Infectious Diseases [Suppl] June 2001). Indeed, the rate of infection may be as high as 1-4 per cent among the population (Infect Control Hosp Epidemiol, 1999; 20: 120-3).
Many other countries with vaccination coverage of over 90 per cent, such as Canada and Australia, have recently had epidemics of whooping cough (Can Commun Dis Rep, 1995; 15: 45-8; Commun Dis Intell, 1997; 21: 145-8).
In the US, the Centers for Disease Control and Prevention (CDC) recently announced that, in the last three years, the number of cases of whooping cough has more than trebled to 7000 cases per year since the 1980s, when only 2000 cases were reported a year.
As with England, this increase - 29 per cent - has mainly occurred among children under a year old. This is despite the fact that at least two-thirds of all children receive some form of the whooping cough jab, and the vaccine is touted as being 88 per cent effective among children 7-18 months old (MMWR, 2002; 51: 73-6).
The reemergence of whooping cough in the US is hardly a new trend. After the vaccine was launched in the 1940s, cases of pertussis declined to an historic low in 1976. But, since the early 1980s, the incidence of whooping cough has increased cyclically, peaking every three to four years independently of vaccination (MMWR, 2002; 51: 73-6).
During a nationwide epidemic of whooping cough in 1993, a group of researchers at Cincinnati Children's Hospital, examining 352 children who had come down with the disease, discovered that 82 per cent had completed their full complement of DPT vaccines (N Engl J Med, 1994; 331: 16-21).
One immediate cause is that the vaccine simply wears off after a few years. In one Italian study of 38 children, aged five to six years, who'd routinely received three doses of pertussis vaccine, very few children had significant antibodies to all three pertussis antigens five years after vaccination (Infect Immun, 2001; 69: 4516-20).
The mutated gene
If Bordetella pertussis has made a worldwide comeback, for the most part it has done so in a slightly different guise. Epidemiologists believe that, among highly vaccinated populations, B. pertussis has mutated, changing its DNA 'fingerprint' and the genetic coding of its outer coat of surface proteins (Infect Immun, 1998; 66: 670-5; Microbiology, 1996; 142: 3479-85).
In the Netherlands, scientists have observed significant changes in the structure of the wild circulating bacteria when comparing blood samples of victims of whooping cough with those who were vaccinated. The main differences involved not only the outer membrane protein pertactin, but also the pertussis toxin itself. A similar genetic 'drift' has been observed in Poland, Finland and the US (Vaccine, 2001; 20: 299-303; Emerg Infect Dis, June 2001).
'It seems like the bacterium is changing part of its coat, thereby disguising itself' from the immune system, said Dr Audrey King of the National Institute of Public Health and the Environment in Bilthoven, the Netherlands, at the annual meeting of the American Society for Microbiology in June 2001.
Since vaccines attempt to prime the immune system to recognise and attack these types of outer proteins, any alterations would render the mutated bacteria immune to vaccination.
King's team tried out their theory in mice vaccinated with the whooping cough jab, infecting them with either an older or a more recent strain of B. pertussis. Animals given the current strain of bacteria were more ill than those given the older strain.
Although animal tests don't necessarily apply to humans, the researchers concluded that the whooping cough vaccines of today may not protect children from newer forms of the illness.
Clinical evidence also shows that the disease is changing in character. Many cases of this new-style whooping cough differ from the illness of old, and may even lack the characteristic 'whoop'. Some studies have shown that up to 30 per cent of individuals with a persistent cough are infected with B. pertussis (Clin Infect Dis, 1999; 28: S112-7). Unless a patient has a sputum sample analysed by a laboratory, the doctor may not recognise a persistent cough as whooping cough. It may well be that the PHLS has grossly underestimated the true incidence of whooping cough. Many more thousands of cases of mutated whooping cough may occur that are given names like 'atypical asthma', as they don't resemble any known disease.
The acellular vaccine
The vaccine used for boosters is not the same one given to babies. Infants receive whole-cell or 'crude' vaccine, made up of the whole pertussis bacterium cell. The formula is essentially unchanged from the first formulation by French bacteriologists nearly a century ago, in 1912. Pertussis bacteria are grown in large pots, killed by heat and preserved with formaldehyde, the main ingredient of embalming fluid. That is the original brew jabbed into the arms of babies all those years ago. The only modern additions are a metal salt to heighten the effect of the drug (usually aluminium), plus thimerosal, a mercury derivative used as a preservative.
According to the DoH, the whole-cell variety is unsuitable for older children because of 'an increased rate of reactions' (DoH letter, 15 October 2001).
However, an 'acellular' vaccine (in which the whooping cough toxin is inactivated by glutaraldehyde or hydrogen peroxide, or genetically modified supposedly to make it safer) is now available, and it is this acellular variety (usually noted as 'aP' and 'DaPT' in the triple jab) that is being offered with the triple booster.
In introducing what is, for all intents and purposes, a new vaccine, the DoH has entirely relied upon the say-so of the US and those countries in Europe using the acellular vaccine where, it says, 'there has not been cause for concern over either efficacy or safety'. Thus, the acellular jab is simply assumed to be safe with no British testing, based upon the clinical experience of other countries.
The PHLS did conduct a single study, which didn't examine the safety of the triple jab on its own, but with simultaneous administration of the MMR jab (Vaccine, 2001; 19: 3904-11). The main purpose of the UK study was to find any extra reactions if you gave the DaPT booster at the same time as the MMR.
According to the DoH, 'no new safety concerns were identified and good antibody responses were achieved'. The report found no increase in reactions or fevers in the 10 days after vaccination or in the proportion requiring a visit to the doctor four to six weeks after vaccination.
This, of course, means that any child not reacting during the tiny 10-day window (and both DPT and MMR typically cause reactions after a latent stage) or not taken to the doctor would not have been recorded as having a reaction.
The US and a number of European countries are beginning to substitute the acellular pertussis vaccine for the old whole-cell variety as they regard it as safer, producing fewer of the more serious reactions linked with the old vaccine: very high fever, hypotonia/hyporesponsive events, persistent high-pitched crying, and convulsions or seizures (N Engl J Med, 1995; 333: 1045-50).
The entire rationale for the acellular vaccine is that it is safer than the whole-cell variety. However, the US Nationwide Multicenter Acellular Pertussis trial, which compared over 2000 babies given either acellular or whole-cell vaccine, found that the number of serious adverse reactions linked to the jab, but not proven to be caused by it - sudden infant death, nearly death, seizures, developmental delay, hospitalisation, encephalitis and vomiting - was similar in both groups.
However, those side-effects acknowledged as due to the vaccine, such as high fever, occurred less often and with less severity among the acellular groups. Other studies from Italy and Sweden concur (JAMA, 1995; 274: 446-7).
One question concerns how many components of the whole pertussis cell make for a safe, effective vaccine. The Swedish Ad Hoc Group for the Study of Pertussis Vaccines found that some of the most serious side-effects, like hypotonia/hyporesponsiveness, high fever and seizures, were most common among those given vaccines with the least number of components and those given the whole-cell vaccine. The safest vaccines were those containing three and five components.
Although deaths were comparable between various component vaccines and the whole-cell variety, basically, the more components present in the vaccine, the more reactions there were, with 39 adverse events in the three-component group vs 60 in
the whole-cell group.
Five times as many babies had a high fever and three times as many had convulsions with the whole-cell jab as with the five-component acellular vaccine.
Many more cases of hypotonia/hyporesponsiveness occurred among the children receiving all varieties of acellular vaccine than the researchers expected (nearly one in every thousand babies).
As for effectiveness, most studies show that the acellular vaccine is about 85 per cent effective, but this may not last for very long (Presc Int, 2000; 9: 220-3; J Pediatr, 1998; 132: 983-8).
The bottom line is, though the acellular vaccine is far from 'safe' or highly effective, it is probably safer than the whole-cell vaccine and just as effective (see box, p 1).
Babies and the whole-cell vaccine
The use of the acellular vaccine in older children begs the obvious question: why are we still using the whole-cell vaccine in babies?
In 1996, acellular pertussis vaccines were licensed in the US for routine use in 15-month-olds (MMWR CDC Surveill Summ, 2002: 61). By 1997, the US Advisory Committee on Immunization Practices (ACIP) recommended switching to the acellular pertussis vaccine for infants.
According to the DoH, the reason for sticking with the whole-cell vaccine has to do with efficacy. A review, written by the PHLS's Elizabeth Miller, says, 'With the exception of the five-component vaccine, acellular vaccines are less efficacious than a good whole-cell vaccine' (Biologicals, 1999; 27: 79-86).
At present, the five-component vaccine isn't available in the UK. This means that the UK government has opted to stay with a vaccine known to cause the greatest number of reactions in babies rather than change to the purified newer version with an arguably comparable efficacy.
The biggest controversy with the old whole-cell vaccine has to do with thimerosal. This mercury-based preservative is used in vaccines to prevent contamination or to inactivate live bacteria. Although not present in most other vaccines, it is still used in DTP vaccines produced by Evans-Medeva and Aventis Pasteur, and DT vaccines produced by Aventis Pasteur and Chiron Behring.
Thimerosal has recently been the subject of congressional hearings in the US (see box, p 2) as a neurotoxin possibly contributing to the huge increase in autism.
Significantly, the new acellular vaccine does not contain thimerosal.
The British government defends its position on the grounds that UK babies are not exposed to 'high doses' of thimerosal because amounts in the UK schedule are roughly half those of the US.
But that's only because the US uses more vaccines containing thimerosal than we do in the UK. Nevertheless, this fails to address the real issue, which is that one of the most toxic substances known to man has no business being present in any quantity in a substance injected into the bodies of newborns.
European and American authorities have given the vaccine manufacturers the gentlest of slaps on the wrist, recommending that vaccine manufacturers 'phase out' the use of thimerosal 'whenever possible'.
But they have not recommended that any vaccines be withdrawn from use. This allows manufacturers to take their time in investigating ways to substitute thimerosal in vaccines, without liability, and to use up their existing stocks.
The Committee on Safety of Medicines reviewed data relating to possible neurodevelopmental effects from thimerosal. Not surprisingly, it concluded that there is no evidence of harm caused by current doses of thimerosal in vaccines, other than 'hypersensitivity reactions'. Once again, the ostrich has spoken.