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In recent months, widespread concern –sometimes bordering on hysteria — about an H1N1 influenza pandemic has become firmly fixed in the public mind. Statements from health ministers and other officials about the potential for the disease to wreak social havoc have heightened the sense of dread. Long lineups for those wanting the vaccine combined with delays in delivery have further stoked national angst.

Amidst all of this, dissenters have sometimes been branded as medical Luddites, "bad Canadians," or wild-eyed conspiracy theorists. Yet, H1N1 vaccine critics have usually only asked three fundamental questions, none of which necessarily justify ad hominem attacks on their motives or scientific knowledge.

The questions are these: How dangerous is the H1N1 flu strain? Are the vaccines developed against it effective? And, are there any hazards to the vaccine itself, potential health risks that could in some cases have more serious consequences than the disease itself?

The answer to the first question is based on various statistics already in the public domain on various government websites. For example, Australia has already finished its influenza season and the H1N1 virus appears to have run its course. During a "normal" year in Australia, the various flu strains kill between 2,500 and 3,000 people; the H1N1 strain in 2009 accounted for 182 deaths. In Canada and British Columbia, H1N1 fatalities currently stand at 250 and 32, respectively. In contrast, some 2,500 influenza deaths occur annually in Canada, 400 to 800 of these in B.C.

Arguably, H1N1-induced fatalities in Canada could dramatically increase between now and the spring, but the available evidence to date does not appear to support the notion that this virus is either particularly virulent or lethal. Hence, the World Health Organization's initial concerns about the potential of the virus to kill massive numbers of people globally have not yet been realized and may thus have been considerably overestimated.

In regard to vaccine efficacy — the reduction in disease incidence in those vaccinated versus those not — the answer also hinges on several observations. First, recent data show that influenza vaccines against type A influenza viruses have an efficacy rate ranging from under 30 per cent to somewhere above 70 per cent, depending on how the vaccine is prepared. For the H1N1 vaccine in Canada (ArepanrixTM), data provided by the manufacturer (GlaskoSmithKline (GSK)) in an October 21, 2009 "product information leaflet" suggest that 94 to 100 per cent "seropositivity" occurs following administration of the vaccine. For the H1N1 studies, seropositivity reflects antibody production against parts of the virus. These numbers are quite impressive, but it has to be noted that the sample sizes were quite small, consisting of fewer than 70 individuals in each of several treatment groups.

Another problem is that seropositivity alone does not necessarily translate into efficacy, the latter only determined once all of the data on vaccinated and non-vaccinated populations have been compiled.

In addition, a good reason for skepticism arises from a comparison of GSK's seropositivity data for the two versions of the vaccine, specifically with or without the "adjuvant." An adjuvant is a chemical added to vaccines to provide a strong immune system response. In the Arepanrix vaccine, the adjuvant is squalene, a biochemical precursor to cholesterol. In the GSK tests, two different amounts of the virus' antigen-producing component were used with the non-squalene variant containing about 400 per cent more antigen. These data make it difficult to determine the true seropositivity of the antigen alone, an interpretation supported by the animal studies in the same information package which showed no disease protection for ferrets vaccinated with the non-adjuvanted form of the vaccine.

Finally, just how safe is the vaccine for human use? The same information sheets provide some insights: A number of potential treatment groups were not evaluated at all, including most of those under 18 or over 60. Additionally, the adjuvanted form of the vaccine induced a number of immediate post-vaccine complaints, some of them potentially involving the nervous system. For example, 14.3 per cent of those vaccinated with the adjuvanted vaccine reported headaches; half this number occurred with the non-adjuvanted vaccine.

Given the importance of animal studies, usually considered the precursors to human trials, GSK's ferret study did not use an statistically appropriate number of animals to allow proper analysis, had no real control group, and did appear to conduct behavioural or anatomical analyses of the nervous systems of the treated animals. Since a main concern about squalene (as well as the mercury compound, Thimerosal, added to the H1N1 vaccine as a preservative) is the potential impact on the nervous system, the lack of nervous system data is troubling. GSK did try, however, to evaluate the potential impact on pregnancy with two studies on pregnant rats. One of these describes, amongst other problems of the rat pups, "delayed neurobehavioural maturation", whatever that may actually mean. GSK concluded that, ". . . Not all findings were observed in both studies, and hence the toxicological significance is uncertain".

Uncertain, perhaps, but such uncertainty should raise more questions and trigger additional studies.

None of this is particularly surprising to me as a neuroscientist. Two peer-reviewed and published studies from my laboratory have previously documented adverse long-term nervous system outcomes in mice exposed to one of the most common vaccine adjuvants, aluminum hydroxide.

In addition, squalene administration studied in the first of these studies demonstrated significant learning disabilities. It may be noteworthy that squalene has not been widely used previously in North American vaccine manufacture due to past safety concerns.

The questions posed at the beginning of this article now have tentative answers: The H1N1 influenza has not become the horrific pandemic that it was expected to be, the efficacy of the vaccine may be less than hoped for, and the safety data based on animal studies seem highly questionable. These outcomes can only leave the public in a quandary as individuals try to evaluate the potential harm from the disease against any potential benefit/harm from the vaccine.

Public health officials will likely argue that the identified problems do not negate what was perceived as an urgent need for the vaccine in the shortest possible time in the face of the expected pandemic, nor do such problems address the danger that could arise if the H1N1 virus mutates into a far more lethal strain. Both may be valid points. The first, however, presumes that health officials acted with sufficient knowledge in hand, a conclusion that now seems unlikely. The second fails to recognize that if H1N1 changes significantly due to mutation, the existing vaccine might not be of much use at all.

The flip side of the grim prospect for a future pandemic disaster is the potential for an increase in neurological disease rates at some future date.

Without a lot more solid science, deciding whether to get the vaccine or not may, for most people, be less a process of rational decision making than a toss of the coin.

Christopher A. Shaw is a professor in the department of ophthalmology at the University of British Columbia

This entry was posted on Saturday, November 28th, 2009 at 3:40 am and is filed under Health. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.