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Influenza A H5N1: Suggested Recommendations for Metametrix Clinical Laboratory Influenza A virus subtype H5N1 is known commonly as bird flu. The majority of the cases of H5N1 have occurred in Asia, and thus far remain largely contained to the avian population. All reported cases have been the avian form of H5N1(1,2,3). Human to human transmission of H5N1 is not efficient at this time; there have been an estimated 6 cases reported to date (1,2,3). The H5N1 subtype has been around since 1959; however, in 1999 the Z genotype became the dominant form (1,8). The virulence of the Z genotype is high, with a greater than 50% death rate in humans who have acquired H5N1. The current death rate stands at 88 persons. The highest death rates are associated with immunocompromised persons (4). The human incubation period of H5N1 is 2 to 17 days. Once infected, the virus can spread by cell-to-cell contact, bypassing receptors. So even if a strain is very hard to catch initially, once infected, it spreads rapidly within a body (3). The pathogenic mechanism of H5N1 appears to be related to a Th1/innate immune-driven cytokine storm, lead by TNFalpha, INFgamma Il-6 and macrophages in bronchial and alveolar epithelial tissues of the lung (5,6). It appears that the hyperinduction of the immune system is at the heart of the virulence of H5N1. While the lungs appear to be the main area of viral replication, passage to other organs leads to widespread symptomology including respiratory distress/failure, dyspnea, fever, diarrhea, and lethargy (6, 7). The usual antiviral protocols such as INFgamma are useless against the virus (6,7). The neuraminidase inhibitor class of antivirals including oseltamivir (Tamiflu) has shown some effectiveness against the virus in vitro and in mice studies, although it is dose-dependent (3,7). Currently, the standard oseltamivir dosing for seasonal influenza is inadequate for H5N1. Furthermore, with inadequate dosing, concern exists for the development of viral resistance due to incomplete viral eradication (3,7). A H5N1 mutation could produce a strain non-responsive to oseltamivir (3). Finally, there is concern with whether or not Roche will be able to meet demand for oseltamivir (3).

Image 1: H5N1 subtype CDC/ Courtesy of Cynthia Goldsmith, Jacqueline Katz, and Sharif R. Zaki Creation Date: 1997

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Image 2: red: countries with avian cases of H5N1. Dark red: human cases of H5N1
accessed 06/06: http://en.wikipedia.org/wiki/Image:Global_spread_of_H5N1_map.PNG

The Point: Metametrix needs to be adequately prepared in the event H5N1 reaches us here in Atlanta. Given the draw backs of Tamiflu, this is a particularly good time to consider alternative interventions and general immune boosting strategy, as mortality is most associated with the immunocompromised population. Starting with good basic health habits, there are a number of options we can employ to be prepared for the 2007 influenza season (see table). Perhaps the easiest and most important action we can take at Metametrix is improving immunocompetancy by testing for nutritional deficiencies using the ION or Organix assays, and resolving any abnormal markers using appropriate supplementation. This basic intervention will ensure we are adequately replete with nutrients, and thus able to mount appropriate immune responses when confronted with challenges. The 05/06 Townsend Letter outlined a well-designed antiviral intervention specifically created with H5N1 in mind. In addition to offering general immune-boosting and antioxidant support, anti-inflammatories to reduce the cytokine storm as well as nourish lung tissue are included. The product is made by Douglas Laboratories. While the product contains NAC, a powerful antioxidant and mucolytic sulfur-containing amino acid, given its high presence in lung tissue, a nebulized form of NAC or glutathione itself may be a superior delivery method, and is known to be effective in various lung/ respiratory illnesses (9). The inclusion of herbs in the nebulized formula specific for respiratory illnesses with elevated Th1 cytokines may also be appropriate. In addition, consideration should be given to the on-going use of support products which modulate the Th1cytokines involved in the pathophysiology of H5N1. These include the omega 3 fatty acids EPA/DHA and the probiotic bifidobacterium. Consideration should also be given to zinc (8), as well as high-dose vitamin A, given their known immunomodulating properties. Finally, history is replete with stories relating to the efficacy of homeopathic interventions for pandemics prior to the arrival of antibacterial and antiviral pharmaceuticals. Usual, a remedy is prescribed based on the genus epidemicus that is, the most common pattern of symptoms seen in the population are most closely associated with a single remedy. Given the low transmission to humans of H5N1, the genus epidemicus has not yet been established. However, knowing what we do about the presentation of H5N1 as well as other homeopathic influenza remedies, we should be able to compile a good arsenal of remedies.

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Metametrix Testin gimmun ocomp etancy is the best defens e against H5N1

Basic

Immune H e boosting a su lt pp h le h m a en b tsit to s be us ed on go in g at on set of flu se as on

DHA/ n ut ri ti o n al d ef ic ie n ci es , u se o ng oi EPA

Influenz Homeopathic Remedies specific for a influenza-like symptoms. Use A the remedy most specific to the , presenting symptoms H 5 N 1 s p e c if i c s u p p l e m e n t s
HiV i d o m i n N u tr it i o n a l I m m u n Genus epidemicus. The first priority in homeopathy is to discover the genus epidemicus that is, the remedy most suited to the symptoms specific to H5N1. This will only be possible once the virus mutates to a human transmittable form. Read about it here: http://www.wholehealthnow.com/homeopath y_pro/wt10.html

Best: ION

Treat

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n g n ut ri e nt s u p p or t as di re ct e d b y h e al th c ar e pr o vi d er / te st in g Good: Organix Compre hensive Profile Good h y gi e n e! w as h h a n d s! Probiotics

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e M u lt i D o u g l a s L a b o r a t o ri e s

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Nebulized g l u t a t h i o n e o r N A C

Gelsemium- keynotes: marked debility, weakness, sleepiness Oscillococcinum: a long-used influenza remedy; a nosode from duck liver and heart Aconite: sudden onset after exposure or shock Eupatorium Perfoliatum: high fever, severe, unbearable aching

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Minimum: Oxidative stress markers , Organix basic or Organix dysbiosi s markers

De-stress a ct iv iti es / h a v e fu n / A d e q u at e sl e e p

Antioxidant su pp ort A, C, E, sel eni um , zin c

Very h i g h d o s e s h o rt t e r m v it a m i n A a n

Arsenicum: influenza with gastroenteritis, vomiting and diarrhea Carbo Vegetalis: copious expectoration, severe apathy, difficulty breathing, cold but averse to being covered. paroxysm of cough.

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d z i n c

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Amino Acid 20

Exercise

Immune pol ys ac ch ari de scor dy ce ps lar ix,

Sleep, si m p l e, n u tr i e n td e n s e b r o t h , s u n li g h t, g o o d c ir c u l a ti o n

Fatty Acid profile or blood spot (note that

Dietary c o n si d

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er at io n s: d e cr e as e si m pl e c ar b o h y dr at es (p re p ar e d fo o d s, s w e et s) m in i m iz e c af fe in e a n d al c o

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minimu m testing will not provide a compre hensive evaluati on of immuno competa ncy, only function ality of that particul ar system)

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h ol in ta k e, Lots of fr es h fr ui ts & v e g gi es , g o o d pr ot ei n

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Sites & Journals accessed:

1. http://content.nejm.org/cgi/content/full/353/13/1374 NEJM: Avian Influenza A (H5N1) Infection

in Humans^ 2. International Institute for Sustainable Development (IISD) SCIENTIFIC SEMINAR ON AVIAN INFLUENZA, THE ENVIRONMENT AND MIGRATORY BIRDS ON 10-11 APRIL 2006 published 14 April 2006. 3. "Avian influenza situation in Indonesia update 17", WHO, June 6, 2006.Bird Flu: Public Health Implications for India (spread) 4. Bird Flu Fatality Rate in Humans Climbs to 64% as Virus Spreads 5. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells by M. C. Chan et al in Respiratory Research (symptoms, include t ownsend) 2005 6. Annu Rev Med. 2006;57:139-54.Avian flu to human influenza. Townsend Letter 5/06 http://www.nature.com/nm/journal/v8/n9/full/nm757.html;jsessionid=213D18BAB5D4AEB1AE277826 DF46277E Virology. 2006 May 17; [Epub ahead of print] Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam.

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J Infect Dis. 2005 Aug 15;192(4):665-72. Epub 2005 Jul 15. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. Paediatr Respir Rev. 2005 Jun;6(2):88-93.The burden of pneumonia in children: an Asian perspective. Chest. 2005 Jan;127(1):12-4.A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis.