Positive Health Online

Where Are We in the Winter of 2006?

Many of us have heard about the risk of a flu pandemic, initiated from the H5N1 virus in birds, over a year ago. Reports in the media made headline news for a few months following October 2005. The reports then went quiet through much of the summer, but with the advent of the northern winter, news reports are again hotting up.

There is now increasing evidence that the H5N1 possesses remarkably dynamic powers of evolution, and is continuing to evolve new genetic clades (groups) and sub-clades, meaning that much of the vaccine development research undertaken since 2004 is next to worthless.[1] The recent changes in the genetics of the virus have caused the World Health Organization (WHO) to change its candidate virus strains in August 2006 for the first time since 2004.[2] Adding insult to injury, significant parts of the existing vaccine stockpiles that have been accumulated since 2005 are beginning to lose their potency.[3]

Even the United States, which tends to be a little ahead of the curve in terms of developing plans to protect its population, the vaccine and anti-viral drug stockpile is looking somewhat inadequate. A report just released by the US Department of Health and Human Services indicates that only five million doses of vaccine will be available by the end of 2006 – this equates to just a single dose for 1.7% of the US population. In the same timeframe, there will only be enough anti-viral drugs (Tamiflu and Relenza) for 25% of its population.[3]

Adding insult to injury, the Royal Society, represented by the likes of Sir John Skehel, one of the most eminent virologists in the world, said last November that the UK is simply not ready for a pandemic, and much more is needed by way of preparedness.[4-5] The UK, rather typically, is even further behind the US. In a recent collaborative study by John Hopkins Bloomberg School of Public Health and Ben Gurion University Israel, involving analysis of pandemic plans from 19 developed and 26 developing countries which contain around two-thirds of the world’s population, researchers found that 62% of the plans prioritized flu vaccination, while almost half favoured anti-viral medications, such as Tamiflu.[6]

It is becoming increasingly evident that reliance on pharmaceuticals as the central plank of preparedness plans is going to lead to catastrophe. Anti-viral drugs have unknown efficacy in a pandemic; resistance is likely the potential for neuropsychiatric effects associated with Tamiflu use which has already been reported.[7] In relation to vaccines, they will always be delayed in their arrival, they may need to be developed for multiple strains, they will always be scarce given manufacturing limitations, and they also may be ineffective.

With all this focus on potentially worthless pre-pandemic vaccines and anti-viral drugs of unknown efficacy, and potentially serious side-effects, the pharmaceutical industry may be the clear winner, even before a pandemic has occurred. Tamiflu is made by Roche, and Relenza by GlaxoSmithKline. A small cluster of companies make the vaccines.

How Much of a Threat is H5N1 to Humans?

Given the relatively trivial number of confirmed human cases and deaths (258 cases confirmed by WHO, resulting in 153 deaths [59% fatality rate]),[8] many have chosen to think of avian flu as hype perpetuated by over zealous media and greedy pharmaceutical companies, keen to peddle vaccines and anti-viral drugs.

It is easy to lay the blame for all this money-making on nature – and wild birds in particular. However, one of the world’s leading virologists, Dr Robert Webster from St Jude’s Children’s Research Hospital in Memphis, Tennessee, US, who has been focusing his recent research on H5N1, points his finger in more than one direction, saying, “The global poultry industry is the main spreader of H5N1, but migratory birds have certainly played a role”.[9]

Prof Neil Ferguson, a leading epidemiologist from Imperial College London, has modelled the epidemiology of avian influenza that could arise from a single infected human. The model (Figure 1)[10] shows that in the first 30 days of the pandemic, virtually no cases of infection would be evident, despite extremely high transmission rates, yet peak infection and cases would occur around 60 days after the initial single infection. This emphasizes just how brutal a pandemic could be; of course, as we have seen already, it is more or less impossible to predict the actual pathogenicity of the final pandemic strain(s).

The significance of each human case is widely misunderstood by those sceptical of the pandemic risk, who have generally made judgements based on the comparative rarity of human cases. As pointed out by the WHO Secretariat at last year’s World Health Assembly in Geneva, “Each human case gives the virus an opportunity to develop into a form that spreads efficiently and sustainably among humans, at which point a pandemic is expected to start”.[11]

As we enter another winter in northern Europe, the risks increase rather than decrease. This is due to such factors as the continuing evolution of the virus, migratory patterns of asymptomatic wild birds, and the wide scale, and often illegal use of vaccines in poultry populations, as well as the movement of the virus into non-avian hosts. Vaccines used not only kill the virus, they may also contribute to untoward genetic changes and increase the number of poultry that are asymptomatic, so increasing the risk of undiagnosed transmissions.

International experts are keeping a particularly close watch on China, Indonesia and Thailand as the countries where a flu pandemic seems most likely to be initiated.

Apart from the health consequences, the economic consequences of a pandemic could be disastrous. Professor Warwick McKibbin and Dr Alexandra Sidorenko, from the Lowy Institute and Australian National University in Australia, have estimated that the pandemic might kill 142 million people and wipe about US$4.4 trillion from economic output, according to a worst-case scenario. Even the mild scenario projected loss of 1.4 million lives and close to 0.8% of GDP (approximately US$330 billion) in lost economic output.[12]

Why is the H5N1 Virus Potentially so Lethal?

In short, people who are infected with the H5N1 virus undergo an extraordinarily severe immune response, which appears, at the present time, to have a more than 50% chance of leading to death within a matter of days. This immune response is initiated by pro-inflammatory cytokines from the cell-mediated (adaptive) side of the immune system. This hyper-induction of cytokines causes massive respiratory distress, and death is primarily the result of severe viral pneumonia. However, the recent isolation of the virus in extra-pulmonary sites, as well as a wide diversity of symptoms evident in lethal cases,[13] suggests other mechanisms may also be active.[14]

Of critical importance, however, is the fact that lethal H5N1 influenza viruses, unlike other human, avian and swine influenza viruses, are resistant to the anti-viral effects of interferons and tumour necrosis factor (TNF)-alpha (Th-1 pro-inflammatory cytokines).[15]

It appears that those with the healthiest immune systems, notably the young, are most likely to die as a result of this immune system over-response. Let us not forget that during the 1918 H1N1 pandemic, most of the 50 million or so deaths around the world were among 18 to 40 year-old men, generally viewed as the fittest and strongest members of any population.[10]

Could Natural Products Save the Day?

Regulators and the orthodox medical community around the world have generally scorned the use of natural health products for prevention or treatment of serious diseases, this being regarded widely as the sole preserve of licensed medicines. This view is epitomized by two recent scathing attacks on complementary medicine by Professor Michael Baum (May 2006)[16] and Professor Jonathan Waxman (November 2006)[17] in which both oncologists claim, in profound error I should add, that there is no scientific evidence of any benefits for complementary medicine or food supplement products.

In contrast, it should be recognized, as stressed in a 2005 report by the House of Common Health Committee, The Influence of the Pharmaceutical Industry,[18] that the drugs companies have for decades ‘cosied-up’ with regulators, creating, in the process, licensing regimes that allow ring-fencing of drug interests to the exclusion of others. The British Medical Journal’s own website Clinical Evidence reports that, of the 2,404 orthodox medicine treatments they have surveyed, only 15% are rated as beneficial, while 47% are of unknown effectiveness![19] In my view, human ingenuity is such that in the case of an emergency, real needs come to the fore, and it is much more likely that Big Pharma’s treasured rule book might get pushed to one side. The US government has already taken a very keen interest in one UK-developed and patented zinc product, for which it is funding further research, and it seems likely that use of such natural products will be advocated by more enlightened governments during times of emergency.

Conspicuously absent from present strategies being considered by health authorities around the world, is the potential use of prophylactic, natural product-based approaches designed to modulate immune system function in the event of infection. This is, in part, because there is relatively very little data available on the efficacy of natural products specifically on H5N1, and none, as far as I am aware, on H5N1 infected humans. That which is available, such as on the patented zinc product indicated above, is bound by confidentiality agreements and as yet unpublished. The work has been conducted both in-vitro and in-vivo, in a mouse model, using the very same US National Institutes of Health laboratory in which the anti-viral drug Tamiflu was tested. There has also been some other work, which I believe has been mainly carried out within in-vitro systems, using a black elderberry formulation.

Aside from this, any other assertions made about natural products, and their potential role in the mitigation of H5N1 is speculative, and made on the basis of knowledge of the mechanism of infection by H5N1 and the progression of the resulting disease in humans, as well as the biochemical, immunological and pharmacological nature of particular natural products. Justification for the potential use of a diverse range of vitamins, minerals, herbal and fungal products have been collated within the report: The Pivotal Role for Natural Products in Countering an Avian Influenza Pandemic, released last April by the Alliance for Natural Health (ANH) Avian Influenza Expert Committee, of which I am a member. The report is available free of charge online.20 The report was precipitated by a direct request by the WHO last February to provide an opinion from the British Society of Ecological Medicine and the ANH, on those natural products and dosages that may be candidates for immune system modulation in the event of a high pathogenicity H5N1 pandemic.

In my view, should a pandemic be sparked in the near future, it is going to be down to practitioners, consumers and other advocates of natural health approaches, to publicize what individuals can do to increase their chances of defending themselves and their families in the event of a pandemic. If one government, such as the United States, takes a lead on the basis of their own research and knowledge of a given product, this will be very helpful and may trigger some other governments to follow suit.

Summary of the Potential Role of Natural Products

The following information is derived from some of the recommendations given in the thoroughly referenced ANH report, The Pivotal Role for Natural Products in Countering an Avian Influenza Pandemic.[20] The report proposes protocols for three types of situations:
1.    Prophylaxis;
2.    Self-treatment;
3.    Medical treatment (including intravenous use of nutrients) which have been developed in collaboration with the British Society of Ecological Medicine.

This information is not presented as medical advice, but rather as a representation of the current state of scientific knowledge on the potential role of natural products in the event of highly pathogenic H5N1 pandemic.

•    Zinc deficiency is a very well-established cause of immune system imbalance, and the vast majority of people in the world are zinc deficient. The amount of zinc from the diet, or from multivitamin and mineral tablets alone, tends not to provide the body with sufficient zinc, owing to the way in which zinc complexes with other compounds, especially phytates in cereals. Liquid (ionic) zinc supplements taken between meals appear to be a better option. One such supplement, shortly to be commercially available in the US, has undergone extensive testing, including in mouse models with the H5N1 virus, and may be one of the best options available at present;

•    The short half-life of vitamin C means that vitamin C should be taken at around three-hourly intervals throughout the day. This presents problems at night time, so it can be useful to take a high strength (e.g. 1500 mg) slow release formulation before going to bed, which can be taken again during the course of the night if a person wakes. Dosage should be increased to bowel tolerance, and then should be backed off slightly. The bowel tolerance level is likely to alter considerably between prophylaxis and treatment situations, owing to the considerably greater demand by the body during infection;

•    High doses of vitamin A, or better still, pro-vitamin A mixed carotenoids (containing 60mg beta-carotene for prophylaxis or double this dosage for self-treatment) will help to modulate the immune system;

•    Extremely high doses of vitamin B12 (20-100mg), delivered intravenously by medical doctors, may be able to play an important role in medical treatment of those infected by H5N1. Such dosages have been used for treatment of haemorrhagic shock and cyanide poisoning and, based on scientific understanding of B12’s action, are likely to be able to quell cytokine storms in infected individuals;

•    Certain botanical and fungal products may be very helpful in the modulation of the immune system, while others may hyper-induce pro-inflammatory cytokines, particularly if excessive dosages are consumed. This includes products such as black elderberry and Echinacea. Nutrients such as resveratrol (from grapes) and beta-glucans (from maitake mushrooms, oats, etc.) are of particular interest. Responsible manufacturers will likely make very clear statements over recommended dosages in the event of a pandemic to help consumers to avoid over-dosing;

•    All interventions should be undertaken in conjunction with dietary and lifestyle approaches designed to optimize immune system function. They include proper hydration, consumption of a varied, high fruit and vegetable content, high protein and complex carbohydrate, low saturated fat diet, as well as the inclusion of moderate (but not excessive) exercise. These sorts of recommendations, although well-understood by complementary medicine practitioners, are still not practised by the majority, and of course will be even more challenging during a pandemic. Ideally they should be initiated at least two months prior to being exposed to the virus.

In Conclusion

The dosages of micronutrients likely to be required either in prophylaxis, but especially for treatment, generally far exceed the relevant Recommended Daily Allowance (RDA), and are, in the main part, orders of magnitude greater than those contemplated by the European Commission and various international bodies working to set EU-wide maximum permitted levels for food supplements (under Article 5 of the EU Food Supplements Directive). This will come as no surprise to many, as the levels being considered by the authorities are not designed to either prevent or treat disease. The regulators appear to be doing everything in their capacity to make therapeutic dosages the exclusive domain of licensed medicines.

Why the need for such apparently high doses? Firstly, the science being used to establish so-called safe upper levels and maximum permitted levels is deeply flawed and suggests dosages that are unnecessarily low for many nutrients.[21] Secondly, the levels required to help the body once under attack by infectious agents, tend to be much greater than those required for normal physiological maintenance. This might prompt you to ask: why are concentrated forms of food products that happen to be delivered in capsules, tablets or powders, as food supplements, treated so differently from healthy foods which are well-acknowledged to reduce the risk of a wide range of important diseases, including cancer and cardiovascular disease?

It is possible that the imminent threat of a human form of bird flu may just help to sharpen the minds of orthodox doctors, governments and regulators. Failing this, consumers will do what they need to do, to protect themselves and their families. As with so many paradigm shifts, this one is most likely to be driven by need and consumer demand.

The first line of defense should always be trying to avoid infection in the first place. Approaches such as social isolation, school and workplace closures and travel restrictions have accordingly already been proposed.[22-23] Prophylactic approaches accessible to all should be the second most important consideration – and natural products, freely available to consumers as food/dietary supplements or as homoeopathic remedies, are in our reckoning the best options we have.

Once a pandemic is triggered, it seems that the anti-natural product lobby might have to learn to accept that it is not so easy to separate humans from their natural heritage. As a species, we have always had a tendency to look to nature for solutions. Even the pharmaceutical industry has built most of its immense profits by tweaking molecules originally sourced from nature. Millions of people will inevitably seek out natural approaches to give themselves the best opportunity of protecting both themselves and their loved ones. Practitioners owe it to their clients and patients to keep themselves as well-informed as they can.

References

1.    WHO working group. Influenza research at the human and animal interface. Report from 21-22 September workshop. World Health Organization. Geneva. 2006. www.who.int/csr/resources/publications/
influenza/WHO_CDS_EPR_GIP_2006_3C.pdf [last accessed 25 November 2006].
2.    WHO advisory notice of H5N1 candidate viruses. 18 August 2006. www.who.int/csr/disease/
avian_influenza/guidelines/h5n1virus2006_08_18/en/index.html [last accessed 25 November 2006].
3.    Department of Health and Human Services. Pandemic Planning Update III. Report from Secretary Michael O Leavitt. DHHS. Washington. 13 November 2006. www.pandemicflu.gov/plan/pdf/panflureport3.pdf [last accessed 25 November 2006].
4.    BBC News. Report: Experts call for better flu plans. 20 November 2006. http://news.bbc.co.uk/1/hi/ health/6158310.stm [last accessed 21 November 2006].
5.    The Royal Society/The Academy of Medical Sciences. Pandemic Influenza: science to policy. Policy document 36/06. The Royal Society. London. ISBN-13: 978 0 85403 635 6.
6.    Uscher-Pines L, Omer SB, Barnett DJ, Burke TA and Balicer RD. Priority setting for pandemic influenza: An analysis of national preparedness plans. PLoS Med 3 (10): e436. 2006.
7.    US Food and Drug Administration. Drug Alerts 2006; Tamiflu. www.fda.gov/medwatch/safety/2006/safety06. htm#tamiflu [last accessed 25 November 2006].
8.    World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. 13 November 2006. (www.who.int/csr/disease/avian_ influenza/country/cases_table_2006_08_14/en/index.html) [last accessed 21 November 2006].
9.    BBC News. Report: Wild Bird Role in Flu ‘Unclear’. 31 May 2006. http://news.bbc.co.uk/1/hi/sci/tech/ 5032904.stm [last accessed 21 November 2006].
10.    House of Lords. Science and Technology Committee. Pandemic Influenza. Fourth Report of Session. 2005-2006. The Stationary Office Ltd. London. 2006.
11.    WHO Secretariat. Strengthening pandemic-influenza preparedness and response. 1 December 2005. www.who.int/gb/ebwha/pdf_files/EB117/ B117_5-en.pdf [last accessed 25 November 2006].
12.    McKibbin WJ and Sidorenko AA. Global Macroeconomic Consequences of Pandemic Influenza. Lowy Institute for International Policy Report. Lowy Institute. Sydney. 79pp. (www.lowyinstitute.org/Publication.asp?pid=345) [last accessed 20 March 2006].
13.    Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, Lochindarat S, Srisan P, Suwan P, Osotthanakorn Y, Anantasetagoon T, Kanjanawasri S, Tanupattarachai S, Weerakul J, Chaiwirattana R, Maneerattanaporn M, Poolsavathitikool R, Chokephaibulkit K, Apisarnthanarak A and Dowell SF. Human Disease from Influenza A (H5N1). Thailand. 2004. Emerging Infectious Diseases 11: 201-9. 2005.
14.    Wong SSY and Yuen K. Avian influenza virus infections in humans. Chest. 129: 156-168. 2006.
15.    Seo SH, Hoffmann E and Webster RG. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nature Medicine. 8: 950-4. Epub. 26 Aug 2002.
16.    Times Online. Full letter: doctor’s campaign against alternative therapies (by Michael Baum and others). www.timesonline.co.uk/article/ 0,,8122-2191985,00.html [last accessed 25 November 2006].
17.    Waxman J. Shark cartilage in the water (BMJ/Personal Views). BMJ 333: 1129. 2006.
18.    House of Commons Health Committee. The Influence of the Pharmaceutical Industry. The Stationary Office. London. www.publications.parliament.uk/pa/cm200405/ cmselect/cmhealth/42/42.pdf [last accessed 24 November 2006].
19.    BMJ Clinical Evidence website: How much do we know. www.clinicalevidence.com/ceweb/about/ knowledge.jsp [last accessed 25 November 2006].
20.    Alliance for Natural Health Avian Influenza Expert Committee. The Pivotal Role for Natural Products in Countering an Avian Influenza Pandemic. April 2006. Alliance for Natural Health. Dorking. UK. www.alliance-natural-health.org/_docs/ ANHwebsiteDoc_232.pdf [last accessed 25 November 2006].
21.    Alliance for Natural Health (ANH) submission to FAO/WHO Nutrient Risk Assessment Project. December 2003. www.alliance-natural-health.org/_docs/ANHwebsiteDoc_121.pdf and ANH Submission to the European Commission’s Consultation on the Setting of Maximum Permitted Levels. September 2006. www.alliance-natural-health.org/_docs/ANHwebsiteDoc_251 .pdf [last accessed 25 November 2006].
22.    Ferguson NM and Cummings DA. Strategies for Mitigating an Influenza Pandemic. Nature. 442: 448-52. Epub. 2006.
23.    Wu JT, Riley S, Fraser C and Leung GM. Reducing the Impact of the Next Influenza Pandemic using Household-based Public Health Interventions. PLoS Med. 3: e361. 2006.