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Alternative strategies for the flu pandemic.

Note: This article was composed in mid-August 2009, and it forecast certain outcomes concerning the global epidemic of H1N1 infection. The author's projection of delay in vaccination programs has become clear in recent times, and the evidence of an expanding flu epidemic is quite apparent.

Introduction

Amid mounting public anxiety, several nations are bracing for the further spread of "swine flu" (type A H1N1 virus). (1) On August 24, 2009, the US President's Council of Advisors on Science and Technology opined on the consequences of widespread infection with H1N1 virus in the US. The group's predictable recommendations include intensive case monitoring, flu prevention with vaccination programs, or treatment with antiviral medications (Tamiflu, oseltamivir, etc.). "Common-sense" preventive techniques have been advocated, with hand sanitization, quarantine, mask-wearing, covering coughs, and so on; but the efficacy of these efforts is debatable. (2), (3) Noticeably absent from many proposed preventive tactics is the idea of enhancing the body's defense system against flu, by promoting nutritional and lifestyle supports for immune function.

The notion of "seed and soil" as regulators of growth is a fundamental tenet in the practice of infectious disease. Plant a vital seed (H1N1 virus) in good soil (a debilitated orvulnerable individual), and growth is inevitable. Alter the soil in a manner that does not accommodate the seed (improve immune function), and growth or spread (of the virus) is attenuated or absent. All microbiologists subscribe to these notions.

It is clear that individuals with compromised immunity (infants, children, the elderly, or those with chronic disease) are at special risk of death or serious clinical complications from acute viral infections. (3)

Observations on the Prevalence and Consequence of H1N1

At the time of writing, the prevalence of H1N1 infections was changing rapidly. On August 28, 2009, the World Health Organization (WHO) announced that H1N1 virus had established itself globally as the most common flu strain. The first case of swine flu was detected in Mexico in March 2008, and it has spread to almost every country worldwide. Current estimates by the WHO and others imply that between 15% and 45% of the world's population may become infected, amounting to between 1 and 3 billion people. (2), (3)

Different types (strains) of flu virus may target different age groups. Unlike seasonal flu, swine flu (H1N1) appears to show a predilection for children and young adults. Countries that have already experienced hundreds of deaths from H1N1 include Mexico, the US, the UK, Argentina, and Thailand, but these circumstances are dynamic, on a global basis.

Flu outbreaks tend to emerge in winter and appear to coincide with children's return to school. (2), (3) In the southern hemisphere, between April 1 and August 5, 2009 (winter), deaths from H1N1 infection more than doubled (337 versus 165 deaths). On August 28, 2009, the Public Health Ministry of Thailand reported that 1 million Thai residents had been infected by H1N1 virus in the preceding four months. In England over the summer months (2009), there were several outbreaks of H1N1 with few fatalities, but treatment resources in the British National Health Service were swamped for several weeks with patients in states of panic. Similar episodes of public panic have been documented in India, when initial fatalities from H1N1 were reported. Under these circumstances, many patients request "testing" for the viral disease of H1N1 in a manner that may serve little practical purpose.

Vaccine Promises

Many epidemiologists and physicians are relying on the efficacy of vaccination programs for H1N1, in the absence of the availability of such vaccines, at the time of this writing (August 31, 2009). However, at the time of submission of the article (October 6, 2009) some US states had received initial shipments of nasal vaccine sprays for H1N1. While the US government is attempting to procure a couple of hundred million doses of H1N1 vaccine, it is estimated that only 50 million doses will be available in the mid-October 2009, or thereabouts. These matters are evolving.

In Thailand, one of the countries hit hardest with swine flu, it was reported (August 27, 2009) that the first 1270 doses of a clinical nasal spray vaccine against the type A (H1N1) flu virus were being tested in animals, but production problems and other issues were delaying vaccine research and development. Similar problems are being encountered by the US vaccine makers with a possibility of significant delays in availability.

In Thailand, clinical studies of H1N1 vaccine in human volunteers have been compromised because specific pathogen-free eggs have produced a low yield of the new flu vaccine. Furthermore, vaccine production facilities in Thailand require urgent expansion, if the government can obtain the 20 million doses of vaccine that it has requested.

Several countries may be engaged in "wishful thinking" as they plan widespread vaccination programs for H1N1. Dr. Margaret Chan (head of the World Health Organization) has commented that only 900 million unit doses of vaccine can be made against H1N1. Dr. Chan and others indicate that this volume of vaccines will not meet the needs of the world population (about 6.8 billion) or even come close to dealing with the up to "3 billion individuals" who may become infected. (2), (3)

Even in cases of plentiful supply of flu vaccine, less than one half of the population may go for a flu shot. Perhaps, the imminent panic of the flu pandemic may change this circumstance in several countries. If vaccines against H1N1 were made available by the target date of mid-October 2009, most vaccinations would involve the giving of two flu shots, one month apart. However, some experts predict the efficacy of "one flu shot" of certain vaccines (wishful thinking?). Following the second shot of most H1N1 vaccines, adequate immunity may not be conferred for a further couple of weeks. This means that immunity may not be present in many people who received a timely vaccine until December 2009 or later. If an early spike occurs in the prevalence of H1N1, as anticipated in children's returning to school, the vaccine program could be "too little, too late."

A residual, deep-seated concern is the mutation of the H1N1 virus into a more virulent pathogenic or "antigenic strain" that is not countered by the immunity induced by H1N1 vaccination. Vaccine producers are basing their products on the virus responsible for the original Mexican outbreak, and human clinical vaccination trials have been under way for a couple of months (at the time of writing). One hopes that the virulence of H1N1 undergoes down regulation (an unlikely event) or that the virus, at least, stays the same. It is not long ago that the threat of H5N1 (bird flu) was in the media. If H1N1 and H5N1 "kiss and commingle," could a more lethal circumstance emerge?

At the time of writing, there were hints in the lay press that there was an increase in the reporting of "more severe" forms of H1N1. These appear to cause a direct pneumonitis, respiratory failure, and severe systemic symptoms. Severe attacks of H1N1 require hospital admission, and 15% or more of those who are hospitalized often require acute intensive medical care. While poor standards of living and chronic disease (e.g., diabetes and asthma) may increase severalfold the severity and adverse consequences of H1N1, the WHO has made the puzzling conclusion that established AIDS does not appears to increase risks.

Opinions about ideal vaccine components for the H1N1 pandemic may change following the reports of the dominance of this strain among flu viruses. Old vaccines may become obsolete in this circumstance, and a greater range of viral antigenic components may be required for adequate prevention of flu.

Antiviral Drugs

The old adage that there is "no cure for the common cold" applies generally to swine flu. Antiviral drugs, such as Tamiflu (oseltamivir), do not result in consistent treatment benefits and they are not specific flu preventives. For example, by August 2009, the Thai Ministry of Health had distributed about 6.7 million doses of oseltamivir, but there have been no clear outcome measures of the benefits, as swine flu spreads among farmers and members of the work force. Tamiflu inhibits the neuraminidase enzyme that assists in cellular reproduction and breakout of the virus. The major effects of Tamiflu are to lessen the severity and length of influenza symptoms, if it is given early in the course of the disease. (2)

Tamiflu cannot be administered for long periods or used in children under 14 years of age. And about 20% of all flu viruses are resistant to it. (2) Substantially similar drugs such as Relenza are not to be used in babies (< 1 yr.) or the elderly (> 65 yrs.) Many deaths occurring with the flu are caused by secondary bacterial infections (e.g., bacterial pneumonia), and routine antibiotic administration is advisable in moderate or severe flu symptomatology.

General Precautions

The effectiveness of general precautionary measures for the spread of the flu virus remains in question. Such measures possess disadvantages or limitations. Institutions or aggregates of people in specific locations are "breeding grounds" for the flu. Schools, where outbreaks are inevitable, pose special problems. Spikes in H1N1 occurrence have been associated with school attendance, despite widespread recommendations for sanitization programs, limited quarantine, "defensive" coughing or sneezing, and prompt release of students to the confines of their homes.

In mid-2009, the US Centers for Disease Control (CDC) issued some confusing revised guidelines that discourage school closures, except in the presence of large numbers of high-risk individuals (a circumstance that defies accurate definition). Detecting rises in body temperature is a crude screening technique that has been abused in some "detection" programs. One may travel to China and receive a thermographic image that results in a high false positive detection rate for H1N1 infection. To add to the diagnostic inefficiency of "temperature screening" is the knowledge that H1N1 infection does not always cause a fever.

The Virulence of H1N1

According to the CDC, swine flu in the US has resulted in 522 deaths and approximately 8000 hospital admissions (August 2009). (2) The H1N1 virus has shown clinical and laboratory evidence of greater virulence than seasonal flu. That said, swine flu does not inevitably cause severe disease in otherwise healthy people.

It has been proposed, arguably, that H1N1 infection may not be worse than seasonal flu except in vulnerable (at-risk) groups such as pregnant women, infants, and individuals with chronic diseases (e.g., diabetes mellitus and respiratory disease). (2), (3)

The possibility that H1N1 virus may evolve into a more virulent organism has resulted in a "stepping-up" of surveillance programs. Surveillance programs are perceived to be important in managing the H1N1 pandemic. (4), (5) While these programs (when implemented effectively) may detect changes in patterns of spread and severity of disease, the changing management policies are unlikely to keep pace with putative onerous disease evolution.

The WHO proposes that H1N1 infection is more contagious than seasonal flu, and it occurs often in healthy young individuals. (3) There is a tendency for the clinical outcome of H1N1 infection to be more severe in urban minority-group children (African American and Hispanic), compared with Caucasian children. The reasons for this circumstance are not clear, but they may involve a higher prevalence of coexisting disease, poor nutrition, and lack of social support at home. Per capita death rates from H1N1 infection are likely to be higher in developing countries than industrialized communities. (2), (3)

It appears that obesity may be a risk factor for poor outcome of H1Nl infection. Obesity is often associated with metabolic syndrome X, which in turn is associated with impairments of immune function. Several nutritional deficiencies (e.g., vitamins A, B series, C, and E; or zinc, iron, and selenium) are associated with disorders of immune function, and the nutritional problems are more common in the underprivileged sectors of society. We have learned that economic underprivilege is a strong predictor of obesity. Eulerian logic applies to these circumstances.

Boosting Biodefenses: Nutrition

Malnutrition or several isolated deficiencies of vital nutrients are associated with impairments of immune function (Table 1).

Table 1: Disordered Immune Function Associated with Protein, Calorie, or Nutrient Deficiencies.

An incomplete list of nutrient-related immune deficiencies.

* atrophy or impairment of the thymus gland

* decreased cell-mediated immunity

* impaired antibody production, including decreased antibody responses to vaccination

* reductions in lymphocyte proliferation

* poor phagocyte function

* altered cytokine patterns, e.g., IL-1

* decreased T helper and increase in T suppressor cells

Many studies have linked specific vitamin or mineral deficiencies to the abnormalities listed in Table 1. Examples of the consequences of nutrient deficiencies and the benefits of nutrient administration on immune function are provided in Table 2.
Table 2: Nutrients and Immune Function

Nutrient (Example)                    Comment

Zinc                 Deficiency associated with decreases in
                     cell-mediated immunity, thymic function,
                     lymphocyte proliferation.

Selenium             Improves proliferation of T and B lymphocytes
                     and cell-mediated responses.

Vitamin A            Enhances mucosal integrity (innate immunity),
                     increases cell-mediated immunity and
                     phagocytosis.

Vitamin B            B series deficiency is associated with defect
                     of cell-mediated immunity and poor lymphocyte
                     proliferation.

Vitamin C            Improves cell-mediated and humoral
                     (antibody-dependent) immunity.

Vitamin D3           Modulates and regulates immunity.

Antioxidants         Prevent free radical damage (oxidative
                     stress), which affects white cell functions
                     (proliferation, phagocytosis, etc.).

Omega-3 Fatty Acids  Fish oils (EPA/DHA) increase lymphocyte
                     proliferation in response to mitogens and
                     increase IL-2. They are modulators of immune
                     function (decrease IL-1 and inhibit monocyte
                     function at certain doses).


The wide-ranging benefits of nutritional status on immune function make it prudent to provide basic nutritional insurance to individuals who wish to optimize immune function. This "nutritional boost" is best applied by giving full RDI of vitamins with minerals and phytonutrient co-factors that are found in powders containing berries, fruit, vegetables, and greens (for example, Clinical Daily Prevention from www.naturalclinician.com). The use of adjunctive omega-3 fatty acids, delivered in enteric coated format for better compliance and absorption, is a valuable, versatile nutritional intervention.

Boosting Biodefenses: Lifestyle Factors

Many studies link healthy immune function with positive lifestyle. The maintenance of psychological well-being, interventions to reduce stress (e.g., meditation, yoga, guided imagery, relaxation responses) and restful sleep have a positive impact on immune functions. Measurable reductions in several immune functions are noted in circumstances of sleep deprivation that may affect up to 100 million Americans. Moderate physical activity can boost immunity, especially in the elderly, where documented improvements in lymphocyte function may occur.

The reduction of dietary intake of calories from simple sugar and fat can decrease oxidative stress. These dietary adjustments benefit the individual with insulin resistance, a disorder that is associated with disordered immune function (metabolic syndrome X). A nutrient dense, low calorie diet has been associated with enhanced immune function and the promotion of longevity. (6)

Boosting Biodefenses: Nutraceuticals

Many herbals, botanicals, and nonnutritive dietary supplements may enhance or modulate immune function (Table 3). (7) "Boosting" certain aspects of the complex series of events in some immune-related diseases may sometimes do more harm than good. The additive benefits and versatile nature of many different natural agents in a dietary supplement that can work on different aspects of immune events may help modulate or balance many different immune functions. (Table 3)

Table 3: Nutrients, Herbs, and Botanicals with Good Scientific Agreement of Nutritional Benefits for Immune Function. The basis of a patent-pending formula (Holt MD Labs).

* Andrographis paniculata

* Acanthopanax senticosa

* green tea

* turmeric

* grape seed extract

* zinc

* vitamin C

* Ashwagandha

* Korean ginseng

* active hexose correlate compound (AHCC)

* Oregon grape

* shiitake mushroom

* Echinacea purpurea

* Coriolus versicolor

* beta-glucan

* aloe vera

* garlic

* Astragalus

* golden thread

* goldenseal

Single-agent approaches, with one herb or limited nutrient content, possess disadvantages and limitations. I have proposed that an improved, synergistic dietary supplement can be produced to be used in combination to globally stimulate immune function. (1), (3) This approach highlights the power of synergy in supplement usage.

Any natural agent that exerts an antioxidant function can be potentially valuable in promoting healthy immune function. Oxidative stress (free-radical damage) to components of the immune system is a common reason for disordered immunity. In particular, the following antioxidants are of value for immune well-being: vitamin C, zinc, green tea, turmeric, and grape seed extract (Table 3). (7)

Botanical agents with specific immune-enhancing power include several species of mushrooms such as Coriolus versicolor and shiitake; natural components such as AHCC; plant or yeast sources of beta-glucan; echinacea; and the potent and versatile herb Andrographis paniculata (AP). (7) Recent research implies that AP may be a very powerful stimulator of immune function by its specific actions on chemical signals in certain cells; and it reportedly has antiviral properties. Synergistic formulas of natural substances that promote immune function may outperform "unitary" or single supplements in their ability to modulate immunity.

Silver colloid preparations are antimicrobial in their actions. (7) These are listed among other substances that are known to kill influenza virus, according to the CDC. Other such agents kill influenza virus, including bleach or strong oxidizing agents, certain aldehydes, high concentrations of alcohol (70% and greater), quaternary ammonium compounds, extreme degrees of acidity (pH less than 2), and heat (133 [degrees]C or greater for 60 minutes). Claims that the FDA has approved silver preparations for flu prevention or treatment are materially misleading.

Silver colloid preparations are best used in augmented forms (addition of Tween and certain essential oils). This augmentation assists in bacterial kill. While silver colloids may have synergistic benefits with antibiotics, they are not stand-alone treatments for infection. (8) It is the microbial kill of silver products that is their fundamental and most important property, despite elaborate arguments about physical or chemical differences among colloid preparations, or futile comparisons of parts per million of silver content. The notion that silver is "soluble" in some products is a fairy tale. The intravenous administration of silver colloids is an illegal act. Topical application of silver colloid to the hands and oral application of silver colloid in parts per million may assist in the complementary prevention and management of flu and other infections.

Homeopathic medicine has been used extensively for cases of acute viral infection. (9) The famous British homeopath Richard Savage notes that homeopathy has four effective ways of treatment. (9) One is an ability to generate resistance to infections, and the others include reduction in the duration and severity of the disease, revitalization, and correction of chronic adverse outcome of infections. A particularly effective preparation for influenza management is Oscillococcinum. Its success has led to its being one of the most widely applied prevention and treatment approaches in Western Europe. (9)

Conspiracy Theories

Conspiracy theories pertaining to the current swine flu epidemic are emerging in many media formats. One cannot take seriously many of these "flimsy hypotheses." For example, it is being suggested that covert government agencies are placing immunocontraceptives in vaccines for population control and that swine flu vaccination programs are a hoax. Some individuals have proposed that a virus cannot cross species unless it is manufactured in a specific manner. Another absurd suggestion is the idea that viruses are "created" by the body to cleanse itself. In brief, there is no credible reason to accept many of these preposterous notions, which are accessible on the World Wide Web.

Conclusion

"Curing" and preventing flu and the common cold has become the "holy grail" of infectious disease. The social and economic burden placed on society by flu epidemics, which result in work absenteeism and loss of productivity, is of gargantuan and incalculable proportions. (2), (3) It remains to be seen what the outcome of the H1N1 pandemic will be in the next few months.

While a "Cassandra" approach to the H1N1 epidemic should be avoided, it seems unlikely that vaccination programs or drug treatments will provide a satisfactory or comprehensive solution for this "looming epidemic." A concerted effort to increase "biodefenses of humankind" largely by the natural promotion of immune function seems an appealing and effective preventive option. This putative approach must not be relegated in its importance or overemphasized by individuals who sell supplements for the nutritional support of body defenses against flu.

Notes

(1.) Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;361.

(2.) CDC Update: swine-origin influenza A (H1N1) virus--United States and other countries. MMWR. 2009;58:421.

(3.) World Health Organization. Situation updates--influenza A (H1N1). Geneva: World Health Organization; 2009

(4.) Fitch WM, Leiter JMF, Li X, Palese P. Positive Darwinian evolution in human influenza A viruses. Proc Natl Acad Sci. 1991;88:4270-4272.

(5.) Longini IM, Fine PE, Thacker SB. Predicting the global spread of new infectious agents. Am J Epidemiol. 1986; 123:383-391

(6.) Holt S. Natural Therapeutics: Calorie restriction mimetics. Townsend Lett. November 2009;98-101.

(7.) Holt S. A Primer of Natural Therapeutics. Little Falls, NJ: Holt Institute of Medicine Press; 2008.

(8.) DeSouza A, Mehta D. Bactericidal activity of combinations of silver-water dispersion with 19 antibiotics against seven microbial strains. Curr Sci. October 2006;91(7).

(9.) Ullman D. Discovering Homeopathy. Berkeley, CA: North Atlantic Books; 1991.

[ILLUSTRATION OMITTED]

Stephen Holt, MD PhD, DSc, LLD (Hon.) DNM, ChB, FRCP (C), MRCP (UK), FACP, FACG, FACN, FACAM, KSJ, Distinguished Professor of Medicine (Emerite), scientific advisor, Natural Clinician LLC, is a best-selling author, award-winning medical teacher, researcher, and clinician. He has published several hundred articles in peer-reviewed medical literature and more than 20 books. Dr. Holt has recently been distinguished by his inclusion in the American Academy of Anti-Aging Medicine's "Who's Who in Anti-Aging and Regenerative Medicine."

* Stephen Holt, MD, PhD, DSc, LLD DNM, ChB, FRCP (C), MRCP (UK), FACP, FACG, FACN, FACAM, KSJ, Distinguished Professor of Medicine (Emerite), scientific advisor to www.naturalclinician.com.
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