avian flu h5n1 pandemic type public health & integrative medical care

Avian Flu H5N1 Pandemic Type Public Health & Integrative Medical Care

Dr. Wm. R. Deagle MD,DABFP,FCFP,CCFP,AAEM,ACOEM,AAPM,AASM,CIME

Pandemic Factors H5N1 Past Two Years Viral Pathogenicity: Newer strains of H5N1 Avian flu are now very pathogenic

in cell culture. Pathogenicity is measured by cytokine release by white

cells in culture on exposure to influenza virus SB2 Avian genes are similar to H1N1 1918 Spanish Flu

that resulted in 25 to 40 million worldwide deaths NS1 gene is unique in the current human victums with

total bypass of mammalian immune defenses Spread to wild birds in the past year has killed many

hundreds of thousands and resulted in dealths and culling of 100 million poultry and wild waterfowl.

Public Health Measures: Worldwide viral subtype and pathogenicity labs in

Asia, Europe, North America with sharing and tracking database

Vaccine research to develop CD8(+) and CD4(+) immune recall

Nutraceutical host support of immune defenses and antiviral nutraceuticals during peak risk periods and pandemics

NIOSH N-95 Masks, Anviral soaps and sprays for killing Influenza on keyboards, bathrooms, doorknobs, and all public surfaces by regulation for all cleaners with testing of kill rates for all cleaners.

Pandemic Prevention and Control Reduction Measures: Stockpiling of Vaccine for H5N1 Influenza Stockpiling of zanamivir and oseltamivir, which

reduce viral replication and organ burden in lung, liver, and brain. (Tamiflu, etc and newer anti-influenza meds.)

Home quaranteen procedures with manuals for home food, etc. delivery and regulatory procedures such as SARS in Toronto, Ontario, Canada.

Hospital reverse protection and quaranteen to prevent spread to other patients and personelle, IV antivirals, ICU with ventilator, and intensive care.

Pandemic Prevention and Control Reduction Measures: Antiviral Nutraceuticals

Virus Blocking Nutraceuticals: MD Qualtiy Pharmaceutical Grade Immune Support and Antiviral Herbals and Nutritional Supplements:

NutriMedical provides the most up to date health news and information. Click on the links below to learn more.

Lactoferrin Plus 60 medium capsules Fight viral, bacterial, and parasit 60 Capsules per bottle $29.95

$26.96 ADP Oil of Oregano #1101 60 tablets Standardized extract of oregano (50 60 tablets $19.00

$14.25 ADP Oil of Oregano #1104 180 tablets Standardized extract of oregano (50 180 tablets $36.00

$27.00


Garlic Plus #1102 100 tablets Garlic concentrate,Vit C, Chlorophy 100 tablets $18.00

$13.50 Immuno-gG #5291 100 capsules Immunoglobulin G, Lysine, Arginine 100 capsules $25.00

$18.75 Ultra Vir-X #6360 Antiviral & Immune Support (90capsules) Antiviral & Immune Support Nutraceu 90 capsules $24.00

$18.00


POA-Phytolens #6305 (Cat’s Claw) US Patent# 5,762,936 Cat's Claw and Phytolens 30 capsules $49.00

$36.75 Eurocel A complex of Korean and Chinese her 180 capsules $149.00

$104.30 BioPotent C Capsules 90 veggiecaps Powerful Vitamin C Plus Bioflavonoi 90 veggiecaps $24.00

$17.52


LarreaRx Lotion Antibacterial, Anti-HIV,Anti-Herpes,Antifungal Virastatin 1 oz Antibacterial,Antifungal,,Antiviral 1 oz. lotion $38.00

$27.74 Viricidin Antiviral Capsid Blocker 90 caps Preventatitve for Viral Capsid 90 caps $11.95

$8.96 Monolaurin Herpes Natural Suppression Viral Capsid Blocker Lauric Acid Lauricidin 300 mg - Blocks Viral Ca 90 capsules $16.95

$12.71 Laurisine Antiviral Anti Herpes Virus Formula 90 caps Lauricidin 200 mg and Lysine 200 mg 90 capsules $15.95

$11.96


Nutricillin Lactoferrin Binds Free Iron Reducing Viral and Bacterial Infect

Lactoferrin 60 mg with colostrum, o 50 capsules $15.00

$11.25 Colostrum Immune Stimulation 300 mg 60 caps 26 % Immunoglobulins from Colostrum 60 capsules $9.95

$7.46 Allicidin™ 180mg 60 capsules Natural Antiviral Antibacterial All 60 capsules $39.00


LarreaRx Caps Antibacterial, Anti-HIV,Anti-Herpes,Antifungal Virastatin 60 Cap

Antibacterial,Antifungal,,Antiviral 60 capsules $58.00

$42.34 LarreaRx Spray Antibacterial, Anti-HIV,Anti-Herpes,Antifungal

Virastatin 2 oz Antibacterial,Antifungal,,Antiviral 2 oz. spray bottle $44.00

$32.12 Ultra Vir-X #6360 Antiviral & Immune Support (90capsules) Antiviral & Immune Support Nutraceu 90 capsules $24.00

$18.00

Pandemic Prevention and Control Reduction Measures: Immune Stimulation

SHIITAKE MUSHROOM #7503 90 capsulesShiitake Mushroom Immune Support90 capsules$17.00$12.75

Neutrophil Plus #6350 90 capsulesImmune Bacterial Fighting Support90 capsules$24.00$18.00

Taurox SB™ 6X Enhancedhomeopathic preparations for immune1/2 ounce, 15 mls per bottle$99.50$69.65

Imm-Kineupport for the immune system60 capsules$60.00$42.00

Immune Prime 10 ml, liquidSupports and enhances the phagocyti10 ml$79.95$55.96

IMUPlus 60 individual 10-gram packets Undenatured Whey Glutathione Detox SuPure undenatured whey protein powde60 packs$110.00$77.00

Pandemic Prevention and Control Reduction Measures: Immune Stimulation

ImmunoPro Rx™ (also known as ImmunePro Rx)Effective immune support & detoxifi300 grams per container, 5 grams per scoop serving$59.95$53.96

Beta Glucan 500mgULTIMATE IMMUNE DEFENSE MECHANISM60 Capsules per bottle$29.99$26.99

Transfer Factor Basics NK White Immune Cell Support 60 capsulesNK Killer Cell Immune Stimulation t60 capsules per bottle$59.95

Oregacyn -- P73 Wild OreganoSupports Powerful Immune Health*60 vegi-caps, 30 day supply$39.95$27.96

Andrographus Pro Immune Moduating Formula 60 capsulesImmune Modulating Andrographus Form60 Capsules, 30 day supply$25.99$19.49

RIC-TF 60 medium capsulesTRANSFER FACTOR FOR RESPIRATORY HEA60 medium capsules$39.95$35.96

Precepts and Principals: An H5N1 Pathogenic Strain now exists and has demonstrated a wild animal

reservoir that is killing many diverse mammals daily in Asia including fowl, etc. and new animals such as cats.

A Pandemic Is Inevitable with Gene Recombinations as the last two years have demonstrated major increase pathogenicity

Public Health Virology and Pathogenic Monitoring Globally is Essential Antiviral Drugs Do Prevent Viral Burden in Lung, Liver and Brain Vaccine Stores are Inadequate and Time is Late to Stockpile Personal NIOSH N-95 Masks, Antiviral Cleaners and Simple Measures

Greatly Reduce Risks Nutraceuticals Kill Viruses, Reduce Chances of Inoculum to Cause infection,

and can stimulate a strong immune response Home quaranteen, hospital procedures for pandemic management and drills to

cover all possibilities without losing civil liberties and privacy must be priority one, now.

The New Public Health Threat is Coming, Lets Prepare NOW!

Microbial adaptation and change: avian influenza. Pandemic Conditions 1: Rev Sci Tech. 2004 Aug;23(2):453-65.

Related Articles, Links

Microbial adaptation and change: avian influenza.

Webster RG, Hulse DJ.

Saint Jude Children's Research Hospital, Department of Infectious Diseases, Division of Virology, 332 North Lauderdale, Memphis, TN 38105, USA.

The evolution of influenza is a continuing process involving viral and host factors. The increasing frequency of emergence of the highly pathogenic H5N1, H7N3 and H7N7 influenza viruses and the panzootic spread of H9N2 influenza virus, all of which can be potentially transmitted to humans, are of great concern to both veterinary and human public health officials. The question is how soon the next pandemic will emerge. A convergence of factors, including the population densities of poultry, pigs and humans, are likely factors affecting the evolution of the virus. Highly concentrated poultry and pig farming, in conjunction with traditional live animal or 'wet' markets, provide optimal conditions for increased mutation, reassortment and recombination of influenza viruses. Strategies to reduce the evolution of influenza and the emergence of pandemics include the separation of species, increased biosecurity, the development of new vaccine strategies and better basic knowledge of the virus. More effective co-operation between scientists and veterinary and public health officials is required to achieve these goals.

PMID: 15702713 [PubMed - in process]

Characterization of Highly Pathogenic H5N1 Avian Influenza A Viruses Isolated from South Korea.Genetic Pandemic Profile Characteristics 1: J Virol. 2005 Mar;79(6):3692-702.


Characterization of Highly Pathogenic H5N1 Avian Influenza A Viruses Isolated from South Korea.

Lee CW, Suarez DL, Tumpey TM, Sung HW, Kwon YK, Lee YJ, Choi JG, Joh SJ, Kim MC, Lee EK, Park JM, Lu X, Katz JM, Spackman E, Swayne DE, Kim JH.

Southeast Poultry Research Laboratory, USDA-ARS, 934 College Station Rd., Athens, GA 30605. [email protected].

An unprecedented outbreak of H5N1 highly pathogenic avian influenza (HPAI) has been reported for poultry in eight different Asian countries, including South Korea, since December 2003. A phylogenetic analysis of the eight viral genes showed that the H5N1 poultry isolates from South Korea were of avian origin and contained the hemagglutinin and neuraminidase genes of the A/goose/Guangdong/1/96 (Gs/Gd) lineage. The current H5N1 strains in Asia, including the Korean isolates, share a gene constellation similar to that of the Penfold Park, Hong Kong, isolates from late 2002 and contain some molecular markers that seem to have been fixed in the Gs/Gd lineage virus since 2001. However, despite genetic similarities among recent H5N1 isolates, the topology of the phylogenetic tree clearly differentiates the Korean isolates from the Vietnamese and Thai isolates which have been reported to infect humans. A representative Korean isolate was inoculated into mice, with no mortality and no virus being isolated from the brain, although high titers of virus were observed in the lungs. The same isolate, however, caused systemic infections in chickens and quail and killed all of the birds within 2 and 4 days of intranasal inoculation, respectively. This isolate also replicated in multiple organs and tissues of ducks and caused some mortality. However, lower virus titers were observed in all corresponding tissues of ducks than in chicken and quail tissues, and the histological lesions were restricted to the respiratory tract. This study characterizes the molecular and biological properties of the H5N1 HPAI viruses from South Korea and emphasizes the need for comparative analyses of the H5N1 isolates from different countries to help elucidate the risk of a human pandemic from the strains of H5N1 HPAI currently circulating in Asia.


Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Host Receptor Viral Pathogenetics

1: Biol Pharm Bull. 2005 Mar;28(3):399-408. Related Articles, Links

Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses.

Suzuki Y.

Department of Biochemistry, University of Shizuoka School of Pharmaceutical Sciences.

The gene pool of influenza A viruses in aquatic birds provides all of the genetic diversity required for human and lower animals. Host range selection of the receptor binding specificity of the influenza virus hemagglutinin occurs during maintenance of the virus in different host cells that express different receptor sialo-sugar chains. In this paper, functional roles of the hemagglutinin and neuraminidase spikes of influenza viruses are described in the relation to 1) host range of influenza viruses, 2) receptor binding specificity of human and other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host range variation of influenza viruses, 5) role of the neuraminidase spike for the host range of influenza viruses, and 6) Development of anti-influenza drugs.


[Avian influenza virus]Co-infection Avian and Human Influenza Gene Reassortment Pandemic Spread

1: Uirusu. 2004 Jun;54(1):93-6. Related Articles, Links

[Avian influenza virus]

[Article in Japanese]

Kida H.

Department of Disease Control Hokkaido University Graduate School of Veterinary Medicine, Kita18, Nishi 9, Kita-ku, Sapporo 060-0818. [email protected]

Recent outbreaks of highly pathogenic avian influenza in chickens and ducks that occurred in 9 Asian countries including Japan alarmed to realize that there is no border for infections and gave a rise to great concern for human health as well as for agriculture. This H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in Viet Nam and Thailand; 15 deaths of 22 cases and 8 of 12, respectively. A second concern was the possibility that the situation could give rise to another influenza pandemic in humans since genetic reassortment may occur between avian and human influenza viruses when a person is concurrently infected with viruses from both species. This process of gene swapping inside the human body can give rise to a new subtype of the influenza virus to which humans would not have immunity. The outbreaks also emphasized the need to continue active surveillance on avian influenza throughout the year to undertake aggressive emergency control measures as soon as an infection is detected.

Publication Types: Review Review, Multicase Review, Tutorial

PMID: 15449909 [PubMed - indexed for MEDLINE]

Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Avian Pathogenic Reservoir of H5N1 Difficult to Eradicate 1: Nature. 2004 Jul 8;430(6996):209-13.


Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia.

Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS.

Joint Influenza Research Centre (SUMC & HKU), Shantou University Medical College, Shantou, Guangdong 515031, China.

A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.


H5N1 influenza: a protean pandemic threat. overproduction of proinflammatory cytokines by primary human macrophages in vitroPandemic Risk of Human Virulence Strains! 1: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8156-61. Epub 2004 May 17.


H5N1 influenza: a protean pandemic threat.

Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, Chan KH, Sturm-Ramirez KM, Cheung CL, Leung YH, Yuen KY, Webster RG, Peiris JS.

Department of Microbiology, University of Hong Kong, Hong Kong SAR, People's Republic of China. [email protected]

Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03 and A/HK/213/03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.


Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what's in the pipeline?The neuraminidase inhibitors zanamivir and oseltamivir, and the M2 inhibitors amantadine and rimantadine, remain the only options for controlling respiratory disease caused by influenza viruses, although the latter two could not be used against very recent H5N1 strains.

1: Curr Opin Pulm Med. 2004 May;10(3):197-203. Related Articles, Links

Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what's in the pipeline?

Brooks MJ, Sasadeusz JJ, Tannock GA.

Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Victoria, Australia.

PURPOSE OF REVIEW: The emergence of severe acute respiratory syndrome in late 2002 and the recent outbreaks of avian influenza in Asia are timely reminders of the ever present risks from respiratory viral diseases. Apart from influenza, there are no vaccines and very few antiviral chemotherapeutic agents available for the prevention and treatment of respiratory viral infections-the most common cause of human illness. If the current H5N1 avian influenza outbreak ever assumes the role of a pandemic, formidable technical difficulties relating to the properties of the agent, itself, will ensure that vaccines will only become available after a significant lead time and then only to a relatively small percentage of the population. The use of existing antivirals could be critical in limiting the initial spread of a pandemic, although their use in the control of epidemics caused by nonpandemic viruses has not been evaluated. It is against this background that a review of recent developments in respiratory antivirals has been undertaken. RECENT FINDINGS: The late 1990s were a period of unprecedented activity in the development of new and much superior antivirals for the treatment of influenza infections. However, during the past 2 to 3 years and largely for commercial reasons, there has been a decline in interest in their further development by major drug companies. This situation may soon change with the possible advent of new pandemic viruses, and moves are afoot in several countries to consider the stockpiling of antivirals. The neuraminidase inhibitors zanamivir and oseltamivir, and the M2 inhibitors amantadine and rimantadine, remain the only options for controlling respiratory disease caused by influenza viruses, although the latter two could not be used against very recent H5N1 strains. There are several other neuraminidase inhibitors in development. Compounds with activity against other respiratory viruses, notably rhinoviruses, are also in development, many based on a newer knowledge of viral protein structure and function (rational drug design). SUMMARY: The following is an overview of recent papers on the further development of neuraminidase inhibitors against influenza viruses and on recent development of newer antivirals against RSV and rhinoviruses. Where possible, comparisons are made with existing antivirals. For considerations of space, this review has been structured around stages in the replication cycle of significant respiratory viruses that have been traditionally used as targets for inhibition.

Publication Types: Review Review, Tutorial


Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines. Rapid Reverse Genetics Attenuated Virus Production for Research 1: Lancet. 2004 Apr 3;363(9415):1099-103.


Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines.

Webby RJ, Perez DR, Coleman JS, Guan Y, Knight JH, Govorkova EA, McClain-Moss LR, Peiris JS, Rehg JE, Tuomanen EI, Webster RG.

Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA. [email protected]

BACKGROUND: In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. METHODS: We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. FINDINGS: A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.


[From fowl plague to influenza pandemic; a reason for taking precaution] Rapid Vaccine and Antiviral Stockpiling for Possible Pandemic

1: Ned Tijdschr Geneeskd. 2004 Mar 6;148(10):458-63. Related Articles, Links

[From fowl plague to influenza pandemic; a reason for taking precaution]

[Article in Dutch]

Kroes AC, Spaan WJ, Claas EC.

Leids Universitair Medisch Centrum, Centrum voor Infectieziekten, afd. Medische Microbiologie, Postbus 9600, 2300 RC Leiden. [email protected]

Throughout Eastern Asia, there is currently an epidemic of fowl plague or highly pathogenic avian influenza, on an unprecedented scale. The prospects for rapid containment are poor. The causative virus, influenza A of the H5N1 subtype, is of limited infectivity for humans. If infection occurs, however, then the consequences are serious and even fatal in a majority of cases. In view of the receptor specificity of avian influenza viruses, this may be related to individually increased susceptibility, which does not lead to further spread. However, it is known that influenza A viruses can readily adapt to replication in the human host by the acquisition of specific gene segments or even by mutations of the avian virus. The extreme scale of human contact with influenza virus of the H5N1 subtype at present engenders fear that there is a high risk of such adaptation and a subsequent pandemic spread. Adequate precautions are necessary, not only in terms of an acceleration of vaccine production but primarily in arranging for sufficient availability of the new antiviral drugs.


The impact of avian influenza viruses on public health. Viral reassortment increases Pandemic Potential!

1: Avian Dis. 2003;47(3 Suppl):914-20. Related Articles, Links

The impact of avian influenza viruses on public health.

Katz JM.

Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, G-16, Atlanta, GA 30333, USA.

In the late 1990s, H5N1 and H9N2 avian influenza viruses caused respiratory infections in humans in Hong Kong. Exposure to domestic poultry in live-bird markets was significantly associated with human H5N1 disease. Seroepidemiologic studies conducted among contacts of H5N1-infected persons determined that human-to-human transmission of the avian H5N1 viruses occurred but was rare. The relatively high rates of H5 and H9 antibody seroprevalence among Hong Kong poultry workers in 1997 highlight the potential for avian viruses to transmit to humans, particularly those with occupational exposure. Such transmission increases the likelihood of reassortment between a currently circulating human virus and an avian virus and thus the creation of a strain with pandemic potential.

Publication Types: Addresses


The epidemiology and clinical impact of pandemic influenza. Breakdown of Public Health With High Attack Rate Infections

1: Vaccine. 2003 May 1;21(16):1762-8. Related Articles, Links

The epidemiology and clinical impact of pandemic influenza.

Nguyen-Van-Tam JS, Hampson AW.

Aventis Pasteur MSD, Mallards Reach, Bridge Avenue, SL6 1QP, Maidenhead, UK. [email protected]

It is impossible to predict when the next pandemic of influenza will occur; however, it is almost 35 years since the last pandemic, and the longest inter-pandemic interval recorded with certainty is 39 years. The next pandemic virus is likely to emerge in southeast Asia, as have two of the last three pandemic viruses. Complete global spread is likely to occur in 6 months or less, due to increased travel and urbanisation. It is likely that the usual inter-pandemic pattern of age-specific mortality will deviate temporarily towards higher mortality in younger adults. The extent to which this will happen is unclear, as the shift was extreme in 1918-1919 but less so in subsequent pandemics. Nevertheless, this may have important implications for the protection of essential workers such as health care, emergency service and military personnel. The extent to which elderly persons will be affected will depend upon previous exposure to similar influenza viruses. It is impossible to predict the likely increase in excess mortality that will occur when a new pandemic virus emerges. However, whilst mortality on the scale experienced in 1918-1919 is probably unlikely, there was a high level of mortality among those infected with the A/H5N1 virus in 1997, so it cannot be assumed that a future pandemic will be as mild as those in 1957-1958 or 1968-1969. There is likely to be more than one wave of infection and health services in most countries will be hard pressed to provide vaccines or to manage populations with clinical attack rates of approximately 25-30% and concomitant increases in demand for both primary and secondary health care services.


Cross-species infections. Increased virulence when viral infections go back and forth between animal vectors and man.

1: Curr Top Microbiol Immunol. 2003;278:47-71. Related Articles, Links

Cross-species infections.

Weiss RA.

Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London, W1T 4JF, UK. [email protected]

Animals have always been a major source of human infectious disease. Some infections like rabies are recognized as primary zoonoses caused in each case by direct animal-to-human transmission, whereas others like measles become independently sustained within the human population so that the causative virus has diverged from its morbillivirus progenitor in ruminants. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Recent epidemic diseases of animal origin are the 1918-1919 influenza pandemic, and the acquired immune deficiency syndrome pandemic caused by human immunodeficiency virus. Some retroviruses move into and out of the chromosomal DNA of the host germline, so that they may oscillate between being an avirulent inherited Mendelian trait in one species and an infectious pathogen in another. Cross-species viral and other infections are reviewed historically with respect to the evolution of virulence and the concern about iatrogenic enhancement of cross-species transfer by medical procedures akin to xenotransplantation.

Publication Types: Review Review, Tutorial


The next influenza pandemic: lessons from Hong Kong. Principals to co-ordinate world wide poultry and viral gene shift monitoring to prevent future pandemics.

1: J Appl Microbiol. 2003;94 Suppl:70S-79S. Related Articles, Links

The next influenza pandemic: lessons from Hong Kong.

Shortridge KF, Peiris JS, Guan Y.

Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. [email protected]

Pandemic influenza is a zoonosis. Studies on influenza ecology conducted in Hong Kong since the 1970s in which Hong Kong essentially functioned as an influenza sentinel post indicated that it might be possible, for the first time, to have influenza preparedness at the baseline avian level. This appreciation of influenza ecology facilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and, if so, was the first instance where a pandemic may have been averted. The 2001 and 2002 H5N1 incidents demonstrated that it was possible to have an even higher order of baseline preparedness with the recognition in chicken of a range of genotypes of H5N1-like viruses before they had the opportunity to infect humans. Investigations of these incidents revealed a complex ecology involving variously precursor avian H5N1 virus in geese and ducks, and H9N2 and H6N1 viruses in quail, the quail possibly functioning as an avian 'mixing vessel' for key genetic reassortment events for onward transmission of H5N1 viruses highly pathogenic for chicken and humans. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic. For example, there is now an increasing prevalence of avian influenza viruses in terrestrial (in contrast to aquatic) poultry. Prior to 1997, no particular virus subtype other than H4N6 would have been considered a candidate for pandemicity and this was based, in the absence of any other data, on its high frequency of occurrence in ducks in southern China. Now,with the isolation of H5N1 and H9N2 viruses from humans supported by genetic, molecular and biological studies on these and other avian isolates, there is credible evidence for the candidacy, in order, of H5N1, H9N2 and H6N1 viruses.These viruses have been made available for the production of diagnostic reagents and exploratory vaccines. The 1997 incident upheld the hypothesis that southern China is an epicentre for the emergence of pandemic influenza viruses. However, the intensification of the poultry (chicken) industry worldwide coupled with the spread of viruses such as the Eurasian lineage of H9N2 suggest that the genesis of a pandemic could take place elsewhere in the world. This re-emphasizes the importance of systematic virus surveillance of poultry globally for international public health and for economic and food concerns. Faced with an incipient pandemic in 1997, Hong Kong brought in international experts to join the investigative effort. Good teamwork at all levels is essential in dealing with the many facets. The threat of a pandemic should not be minimized, nor should governments be lulled into a sense of false security. The media is a powerful channel and has the responsibility and the avenues to convey and influence public perception of events. Close liaison between the media and those on the operational side ensures effective, accurate and timely dissemination of information. This will enhance public confidence in the investigative process and in steps taken for its safety and health.


H5N1 influenza in Hong Kong: virus characterizations. New poultry to human H5N1 never found before.

1: Vaccine. 2002 May 15;20 Suppl 2:S82-3. Related Articles, Links

H5N1 influenza in Hong Kong: virus characterizations.

Osterhaus AD, de Jong JC, Rimmelzwaan GF, Claas EC.

National Influenza Centre of the Netherlands, Erasmus University Rotterdam, Rotterdam, The Netherlands. [email protected]

In 1997, 18 people were infected in Hong Kong with an avian influenza A(H5N1) virus from chicken. This type of interspecies transmission was never detected before and could have resulted in the development of a pandemic strain. The occurrence suggests that the pig is not needed for the emergence of pandemic influenza virus strains. Characteristics of the strains involved are discussed in relation to the question why, on the one hand, these strains were able to infect humans but on the other hand were not able to start an epidemic.


Protection against a lethal avian influenza A virus in a mammalian system. Related non-human viruses can produce CD8(+) and CD4(+) vaccine induced host response offering protection from H5N1 Influenza. 1: J Virol. 1999 Feb;73(2):1453-9.


Protection against a lethal avian influenza A virus in a mammalian system.

Riberdy JM, Flynn KJ, Stech J, Webster RG, Altman JD, Doherty PC.

Department of Immunology, St. Jude Children's Hospital, Memphis, Tennessee 38101, USA.

The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from birds. Little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza A viruses using contemporary immunology techniques. Such experiments with the H5N1 viruses are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-expressing (Ig+/+) and Ig-/- mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8(+) T-cell memory in the Ig-/- mice provided some small measure of resistance to a low-dose H3N8 challenge. The H3N8 virus also replicated in the respiratory tracts of the H3N2-primed Ig+/+ mice, generating secondary CD8(+) and CD4(+) T-cell responses that may contribute to recovery. The results indicate that the various components of immune memory operate together to provide optimal protection, and they support the idea that related viruses of nonhuman origin can be used as vaccines.


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