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Type A Influenza H5N1

Introduction:  A zoonotic disease at the center of the world's attention is Type A Influenza H5N1.  It has been labeled "Asian flu" or "Bird flu".  Popular press has been quite alarmist!   

There is significant concern for this disease not only because of its potential impact on the worldwide poultry industry and its markets but, more importantly, its significance to public health.

  Influenza, both Type A and Type B, commonly referred to as the "flu", manifests itself in susceptible humans with cold-like symptoms aggravated by fever, malaise, muscle and joint aches, nausea and vomiting.  Immuno-compromised, the young, and the elderly are particularly susceptible if unprotected.

  Type A influenzas have been subtyped into 16 H and 9 N surface proteins.  Type B influenzas, are thought to be more stable, and are more amenable to becoming vaccine candidates.  Type A influenza reservoirs are considered to be migratory waterfowl.  Among poultry veterinarians, migratory waterfowl are considered to be in "4-F" status - "fowl feathered flu factories".  Influenza breaks in domestic poultry have largely been traced to migratory waterfowl or live bird markets to the extent that some state plans for emergency disease planning in poultry discourage poultrymen and service personnel from hunting and processing migratory waterfowl due to the asymptomatic shedding of type A viruses and the ease of fecal-oral transmission to poultry.  In poultry, signs of influenza may vary from negligible, with no effect on growth or laying, to extreme mortality, leaving a decimated, cyanotic flock with digestive and respiratory tract hemorrhages.

  In 1997, six human deaths in Hong Kong were attributed to a pathogenic strain of type A influenza H5N1.  Because of intermingling of migratory and domestic waterfowl and live bird markets, concerns for genetic mutations allowing bird to human transmission were raised.  Since 2003, there have been 225 confirmed cases of H5N1 influenza in humans with 128 fatalities.  As of this writing, human to human transmission has not been demonstrated.

  As of June 1, 2006, H5N1 has been reported from wild and domestic birds in 49 countries in Asia, the middle East, Africa  and some parts of Europe.  

Etiology:  Influenza viruses are of the Orthomyxoviridae family and have three types: type A (found in both humans and animals), type B (found only in humans), and type C (uncommon strain found only in humans).  Type A may be subtyped according to two surface glycoproteins.  There are  16 H or hemagglutinins and 9 N or nueraminadases, allowing 144 different subtype combinations.  For the human, type A provides a more ominous threat due to the assortment of virus components.  Recurrent epidemics of type A flu are a constant challenge to the CDC in predicting future subtype candidate viruses.     

Epidemiology:  Type A influenza viruses in domestic poultry are categorized into Low Pathogenic AI (LPAI), which is the most common, and Highly Pathogenic AI (HPAI), or the lethal form, uncommon in US poultry.

  LPAI viruses cause mild infections (no weight loss or respiratory signs) in domestic birds and are not considered a threat to public health.  Generally, world marketing agreements do not turn away finished products from an LPAI geographic area.

  HPAI virus strains H5 and H7 can cause alarming losses with 90-100% mortality in commercial poultry.  HPAI has been a problem in live bird markets of some east coast US cities where the USDA has continually monitored the eradication efforts.  H5N1 subtype is an HPAI.  It has cost the poultry industry of Asia millions of dollars in bird losses and marketing barriers have been established.  H5N1 influenza has been isolated from domestic cats, captive tigers, and leopards in Asia.  In 2005, there was an unusually high death loss of migratory birds due to H5N1 in central China.  In the past 30 years, there have been 24 outbreaks of HPAI worldwide; most of these were confined to a single flock or farm. 

   International vigilance in monitoring avian influenza outbreaks is occurring because LPAI H5 and H7 viruses are capable of evolving into HPAI.  Likewise, there is fear that HPAI viruses could transmit to humans through genetic mutation.   At present, extensive monitoring for H5N1 virus among  waterfowl migrating to US flyways is being carried out across the United States.

Diagnosis:  Detection of type A influenza is dependent upon diagnostic tests.  Antigen capture screening tests are available.  Nasopharyngeal, tracheal or cloacal swabs are used, and results can be determined in a short period of time.  Positives are subtyped.  ADDL has continuous settings of SPF chicken eggs for virus isolation attempts from tracheas, bronchi, cloacal, or nasopharyngeal swabs. Embryo harvest is followed by electron microscopy, antigen capture immunoassay, and subtyping.

  Real time Reverse Transscription Polymerase Chain Reaction (RT-PCR) test is available at ADDL.  This test allows greater sensitivity and is useful for large scale screening during epidemics.  Results are available quickly.  Advantages to this method are small sample size requirement, timeliness, and the ability to subtype.  Suitable samples to submit for this test are tracheal and nasopharyngeal swabs of Dacron on plastic sticks (1 swab per tube with 1 ml viral transport media), with no blood contamination, shipped on cold paks.

  Serological type A screening, using the Agar Gel Precipitin (AGP) or Agar gel Immunodeficiency (AGID) method, requires a minimal amount of serum and can be read within 1-2 days.    In some instances where only eggs were available, yolk antibodies have been tested.

Surveillance and Control (Biosecurity):  Surveillance of type A influenza viruses in the Indiana poultry industry is based on monitoring sera for the presence of type A antibodies.  The USDA provides antigen and antibody to perform the AGP test to private and public laboratories upon request.  The National Poultry Improvement Plan (NPIP) provides protocol and uniform procedures that are acceptable according to world standards.  Seropositive samples are submitted to the National Veterinary Services Laboratory (NVSL) for subtyping.  Commercial poultry farms exercise biosecurity precautions in housing that limits access by wild birds, unwanted visitors, vermin, and rodent entry.  Visitors are required to put on disposable suits, head, hand and shoe covers before entry and removal at exit. Delivery traffic and utility personnel respect biosecurity protocols.      Commercial killed vaccines have been advocated and stockpiled by the USDA for commercial poultry use.  In a 2004 outbreak of type A influenza (LPAI-H7N2) among commercial poultry in the eastern United States, eradication was the response of choice.

  On a regional basis, biosecurity concerns are implemented according to the location of disease.  A Level 1 would be the minimum amount of acceptable biosecurity for poultry, while Level IV would indicate that poultry are in imminent threat and biosecurity is at its highest level.  A communication network between the Indiana State Poultry Association and poultry producers is being updated in order for sound and current information to be made available.  Outdoor poultry that can be exposed to migratory waterfowl, directly or indirectly, as well as farm ponds, remain a threat to disease prevention programs.

  Strict surveillance of poultry populations is enforced in most countries in an attempt to contain the H5N1 outbreaks.  Continuous research on methods of identifying the constantly changing AI virus is key to finding a solution to this impending global problem.

-by Maria Solacito, ECFVG Student

-edited by Dr. Tom Bryan, Avian Diagnostician,  Heeke ADDL

References:

  1. Avian Influenza.  Field Manual of Wildlife Diseases: General Field Procedures and Diseases of Birds.  National Wildlife Health Center/US Geological Survey: 1999.  Friend M and Franson C (eds.).  22:181-184.

  2. Centers for Disease Control: 2005.  Spread of Avian Influenza Viruses Among Birds. www.cdc.gov/flu/avian/gen-info/spread.htm

  3. Centers for Disease Control: 2006.  New Laboratory Assay for Diagnostic Testing of Avian Influenza A/H5 (Asian lineage).  MMWR  February 3.  pp 55.

  4. Lee CW, Senne DA, Linares JA, Woolcock PR, et al: 2005.  Characterization of recent H5 subtype avian influenza viruses from US poultry.  Avian Path 33(3): 288-297.

  5. Newton DW, Mellen CF, Baxter BD et al: 2002.  Practical and Sensitive Screening Strategy for Detection of Influenza Virus.  J Clin Microbiol 40(11): 4353-4356.

  6. Ng EK, Cheng :K, NgAy et al: 2005.  Influenza A H5N1 detection.  Emerg Infect Dis 11(8)

  7. Payungporn S, Chutinimitkul S, Chaisingh A et al: 2005.  Single step multiplex real time RT-PCR for H5N1 Influenza A virus detection.  J Virol Meth 131: 143-147.

  8. Tiensin T, Chaitaweesub P, Songserm T et al: 2005.  Highly Pathogenic Avian Influenza H5N1, Thailand, 2004.  Emerg Infec Dis 11(11): 1664-72.

  9. USDA/APHIS: 2006.  Screening for Highly Pathogenic H5N1 Avian Influenza in Migratory Birds.  USDA Fact Sheet. March www.aphis.usda.gov.

  10. World Health Organization (Writing Committee of WHO Consultation on Human Influenza A/H5).  Avian Influenza A (H5N1) Infection in Humans.  New England J Med 353 (13): 1374-85.

  11. Xu X, Jim M, Yu Z et al: 2005.  Latex Agglutination Test for Monitoring Antibodies to Avian Influenza Virus Subtype H5N1.  J Clin Microbiol 43(4): 1953-1955.

 

 

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