HAEMOPHILUS INFLUENZAE-B VACCINATION PROGRAMS HIGHLY EFFECTIVE, BUT HOW SAFE?
By Bob Greenfield, grandfather of an autistic child.

When invited to write an article on Haemophilus influenzae-b (Hib) vaccines, I thought this would be straight forward considering the huge amount of material available on this topic. However, I am not competent to discuss most of this material, so I have described my efforts to establish the increased risk of contracting Hib disease soon after Hib vaccination. First a personal experience.

Mid October 1992 we became aware that our two and a quarter year old grand-daughter Laura had become unresponsive to her family. From being a very easy child to manage, she became increasingly difficult, losing all understanding and speech, and a year later was given a diagnosis of Childhood Disintegrative Disorder (CDD). CDD is at the severe end of the autistic spectrum, the "mild" end being Attention Deficit Hyperactive Disorder (ADHD). About mid 1993 we realised that our grand-daughter's regression began just after her Hib vaccination of October 1, 1992. Then, reviewing our home video record, we found no autistic behaviours in clips taken before this date.

Because CDD is a rare disorder and vaccination at Laura's age is uncommon, it seemed unlikely that such a coincidence could be due to chance alone.

We learned of another Australian child, David, who also developed CDD after a Hib vaccination in May 1992. His grandmother went overseas in April of that year but, when she returned in July, she was immediately aware that her grandson had changed. David was three years old, even more removed from the common age of 18 months for acquired autism. Parents of Laura and David tell their stories in "When Autism Strikes", by Robert Catalano, MD (Plenum Publishing Corporation, New York ISBN 0-36-45789-X90000).

In 1992, Australia and the UK introduced programs to vaccinate against Hib disease. In Australia there was a strong media push for the program, emphasising a high risk of Hib meningitis in children under five. My wife and I remember being surprised that we had never heard of this disease that was apparently the most common brain damaging illness in young children.

The package insert for the vaccine used on our grand-daughter carried the warning:

"Physicians should be aware that recipients of Haemophilus-b vaccines may develop Hib disease in the week after vaccination, prior to the onset of the protective effects of the vaccine."

Did this mean that the vaccine could cause Hib disease or just that the vaccine was ineffective until after a week? We had no obvious way of knowing, we found that the monitoring needed to answer this question was either not done or the data was unavailable. Australia has a Freedom of Information Act, but a Confidentiality of Epidemiological Information Act just predates it. The equivalent UK arrangement would be the Committee for the Safety of Medicines whose Proceedings are confidential.

Sir Graham Wilson, in the introduction to his book "The Hazards of Immunisation" (1967), commentson the secrecy surrounding accidents of vaccination:

"The late Dr J R Hutchinson of the Ministry of the Ministry of Health collected records of fatal immunological accidents during the war years, and was kind enough to show them to me. I was frankly surprised, when I saw them, to learn of the large number of persons in the civil and military population that had died apparently as the result of attempted immunisation against some disease or other. Yet very few of these were referred to in the medical journals."

Thus direct evidence relating to vaccine damage is unlikely to be reported or published and would be hard to access. However, in 1985, when the US introduced a Hib vaccination program, efficacy studies indicated that, in the week following vaccination, children had an increased risk of contracting Hib disease. The program used an unconjugated (PRP) vaccine, which was suitable for children over two years old only. "Early-onset" Hib disease occurring within a week of PRP Hib vaccination became eligible for compensation under the US Vaccine Damage Payments Scheme.

Hib vaccines should be very safe because no live biological material was involved. What could be going on? In chapter 25 of "The Hazards of Immunisation", on "Provocation Disease", Sir Graham writes:

"It seems clear that any latent infection, particularly when accompanied by transient bacteraemia or viraemia, may be wakened into activity by the disturbing effect on the tissue resistance of various factors, among which vaccines and certain medicaments are prominent. Ideally, vaccination against any disease should be preceded by a survey of the patient's medical history and a simple physical examination to detect signs of any obvious infection. Mass vaccination, in which this is impossible, is bound to be a hazardous procedure and is bound to be followed by undesirable consequences of one sort or another."

Reviewing Sir Graham's book in the British Medical Journal, (18 November 1967, p 407), A Melvin Ramsay comments:

"He (Sir Graham) strongly condemns mass immunisation with its inevitable masking of much latent infection ... This is a work of outstanding merit."

It seems that, although Hib vaccines may not directly cause Hib disease, individuals exposed to Hib disease could more easily develop serious Hib illness soon after Hib vaccination.

In 1987 the US introduced a more effective Hib vaccine, diphtheria conjugated vaccine (PRP-D), which was suitable for 18 month and older children. It was this vaccine that Australia licensed in 1992, also for 18 month and older children. Did this vaccine also carry an increased risk of early-onset Hib disease?

The possible increased risk of Hib disease soon after Hib vaccination prompted immunological studies into several Hib vaccines. Animals more easily developed meningitis soon after Hib vaccination. 18 month old children with natural Hib antibody experienced a fall in antibody two days after vaccination before protection developed. The studies indicated that PRP-D was the most potent vaccine, but this vaccine produced most early-onset meningitis and most bacteraemia and the biggest fall in natural antibody at day two. The most effective vaccine appeared to involve the greatest risk.

The concentration of serum Hib antibody needed for protection is believed to be at least 0.15 but possibly 1.0 micro-grams per millilitre. In 18 month old children PRP-D vaccination caused natural Hib antibody to fall typically from 0.18 to 0.04 micrograms per millilitre at day two before rising to 7.20 micrograms permillilitre at day seven.

In 1994 the prestigious US Institute of Medicine (IOM) published a major report "Adverse Events Associated with Childhood Vaccines, Evidence Bearing on Causality". This report acknowledged the increased risk of early-onset hib disease with unconjugated vaccine but not with conjugate vaccines. The immunological evidence would seem to require careful monitoring of the use of hib vaccines but the IOM report can produce only a few very small epidemiological studies. In concluding that there is no increased risk of early-onset Hib disease with Rib conjugate vaccines is the IOM report wrong?

The report's conclusions are based on four cases of early-onset Rib disease in a meta analysis of 19 small studies. (A meta analysis attempts to combine results from small studies to give greater certainty). Addressing the general question of whether an increased risk of early-onset Hib disease occurs with conjugate Rib vaccines, the report can answer "no".

But we are specifically concerned about a possible increased risk of early onset hib disease with PRP-D conjugate vaccine in 18 month and older children. Just three studies qualify to answer this question, the answer being "yes", with a Relative Risk of 2.88. A vaccinated child was 2.88 times more likely than an unvaccinated child to contract Rib disease in the following week, or the odds of the vaccine being responsible for a particular case is 1.88 to 1. Three of the four cases of the IOM report's early-onset disease occur for PRP-D in 18 month and older children.

Two reports in the American Journal of Diseases in Children (AJDC, March 1990 and December 1991) analyse the incidence of hib disease in vaccinated children to demonstrate the greater efficacy of PRP-D conjugate vaccine in 18 month and older children over that of unconjugated hib vaccine. Both reports compare failure rates of PRP and PRP-D vaccines but also assume that early-onset hib disease is the same for both PRP and PRP-D. The data came from the Centres for Disease Control (CDC) and Food and Drugs Administration (FDA) data, but the AJDC reports.were not considered in the IOM report.

Both data show a large fall in the incidence of hib disease starting a week after vaccination, as would be expected for a vaccine that takes a week for protective antibodies to develop. However, the falls are much greater than could be due to vaccine efficacy. The only possible explanation for these data is that there is more than the "background" rate of early-onset hib disease after PRP-D vaccination in children older than 18 months.

If there were no increased risk, early-onset hib disease would be the same as the background rate in unvaccinated children, which can be calculated from the known vaccine failure rate and vaccine efficacy. Comparison of actual and calculated background rates of early-onset hib disease indicate the relative risk to be in the range of 2 to10.

Do the calculations give the right answer? We can check the method using the data for unconjugated hib vaccine which are also provided in the AJDC reports. For unconjugated hib vaccine, the method gives a relative risk of early-onset hib disease of 2.7, a good agreement with the 2.62 quoted in the IOM report.

Are UK families affected? The UK used a tetanus conjugate vaccine for babies and HbOC conjugate vaccine for children older than one year. The fourth case of early-onset hib disease in the IOM meta analysis occurs in the study for 15 to 18 month old children vaccinated with HbOC, the relative risk being 1.5. On its own, a single case would be insufficient to draw conclusions, but the IOM report also compares nine cases of early-onset Hib disease after HbOC, with one after PRP-D, occurring between November 1990 and July 1992, this being assumed to reflect the greater use of HbOC during this period.

In Vol 5, No 10 of the UK monthly "What Doctors Don't Tell You", an acupuncturist reported that a child she was treating had been hospitalised for asthma, become hyperactive and running around like a madman. She discovered that the child had just had a "meningitis" vaccination, observing that such incidents go unreported because "no connection is made between such episodes". The first symptom Laura's grandmother noticed was that she "ran aimlessly to and fro across the room".

Although until recently the most common brain damaging illness in children, hib meningitis has been associated with just two cases of autism, one child becoming autistic after having been diagnosed with hib epiglottis (inflammation of the windpipe).

The Medical Journal of Australia of March 6, 1995 published data on the effect of Rib vaccination in the Sydney region, demonstrating the potency of the hib vaccination program, but also revealing other features. For almost the first year of the program, when vaccination was offered to 18 month and older children only, hib disease fell fastest in younger unvaccinated children. Excess early-onset hib disease in vaccinated children could explain this effect but the case-by-case investigation needed to confirm this was not done.

The Sydney experience is not unique. On first use of conjugate hib vaccines in the US and UK, comparable falls in hib disease occurred in unvaccinated and vaccinated children, which was noted but not explained. Published information contains insufficient detail for analysis.

Hib disease in young children has greatly decreased following the introduction of hib vaccination programs, also reducing the actual, (but not relative), risk of vaccine provoked hib disease. But questions about the safety of hib vaccination programs need to be answered.

· Is meningitis always recognised?

· Do hib vaccines "mask" the symptoms of serious infections?

· Do parents mistake a serious brain damaging illness for a normal vaccine reaction?

· Australian and UK vaccine adverse reaction surveillance systems ought to have detected noticeable post vaccination "early-onset" and vaccine failure hib disease. Whey wasn't this detected?

· Did Australian and UK Governments fail to exercise a proper "duty of care" for hib vaccinees in failing to educate parents about symptoms requiring urgent medical attention?

A paradox. Hib disease was the most common brain damaging illness in young children, but little detail on outcomes are described. Autistic disorders are among the most common outcomes of childhood brain damage, yet a cause is rarely identified. Why?

Bob Greenfield, Oct.1998

Recommended reading: "Hidden Truths" by Robert Matthews, in the 23 May 1998 "New Scientist" describing methods used by "Data Sleuths" to identify consistencies in published data and to extract meaning from limited or incomplete data.

Source: Informed Parent