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OSHA Guidance Update on Protecting Employees from Avian Flu (Avian Influenza) Viruses U.S. Department of Labor Occupational Safety and Health Administration OSHA 3323-10N 2006 Employers are responsible for providing a safe and healthful workplace for their employees. OSHA's role is to assure the safety and health of America's employees by setting and enforcing standards; providing training, outreach and education; establishing partnerships; and encouraging continual improvement in workplace safety and health. This handbook provides a general overview of a particular topic related to OSHA standards. It does not alter or determine compliance responsibilities in OSHA standards or the Occupational Safety and Health Act of 1970. Because interpretations and enforcement policy may change over time, you should consult current OSHA administrative interpretations and decisions by the Occupational Safety and Health Review Commission and the Courts for additional guidance on OSHA compliance requirements. This publication is in the public domain and may be reproduced, fully or partially, without permission. Source credit is requested but not required. This information is available to sensory impaired individuals upon request. Voice phone: (202) 693-1999; teletypewriter (TTY) number: (877) 889-5627.
Contents
[ Purpose ] [ Introduction ] [ Guidance for Poultry Employees ] [ Guidance for Animal Handlers other than Poultry Employees ] [ Guidance for Laboratory Employees ] [ Guidance for Healthcare Workers Who Treat Patients with Known or Suspected AI ] [ Guidance for Food Handlers ] [ Guidance for Airport Personnel Exposed to Passengers Suspected of Being AI-infected ] [ Guidance for Travelers on Temporary Work Assignment Abroad ] [ Guidance for U.S. Employees Stationed Abroad ] [ Guidance for Other Employee Groups that May Be at Risk ] [ Employee Training ]
[ OSHA Assistance ] [ Table of Contents ] Purpose This document is designed to serve two purposes: (1) to provide guidance on health protection to employers whose employees may be exposed to avian influenza (AI) viruses; and (2) to provide technical information (in appendices) about AI viruses and, in particular, about H5N1, an AI virus currently circulating in Asia, Europe and Africa that rarely causes disease in humans but when it does the case fatality rate is high. This document updates guidance on avian flu issued by OSHA in March 2004. [ Table of Contents ] Introduction Numerous stories have aired on radio and television or been published in various news media concerning avian influenza and in particular the H5N1 subtype. Unfortunately there is now much confusion about the different human diseases caused by influenza viruses. Influenza A viruses can cause three distinct diseases in humans: avian, pandemic and seasonal influenza. Avian influenza in humans is rare and the most common route of infection is via direct or indirect contact with secretions (nasal, oral or fecal) from infected poultry. Transmission from human-to-human, if it exists, is extremely rare. However, avian influenza viruses have the potential to mutate or reassort and become pandemic viruses; those that can be readily transmitted between humans and those for which the population has little immunity. If these viruses spread throughout the world, the disease caused by them would be called pandemic influenza and the new viruses would be called pandemic influenza viruses. Previous pandemic influenza episodes have occurred in two or three waves of 6-8 week duration and spanned a 12-18 month period. After this period, the population will have built up immunity to the virus, either naturally or through vaccination. If the virus continues to circulate in the population and causes disease, it would become an influenza virus that causes seasonal influenza (more popularly called human influenza or the flu). Influenza A viruses are subdivided into numerous subtypes. The subtypes are differentiated by variations in two viral surface proteins, hemagglutinin (H) and neuraminidase (N). Sixteen different H proteins and nine N proteins have been identified. Subtypes are designated by numbering particular combinations of these proteins (e.g., H5N1). Therefore, there are a total of 144 possible subtypes (16H x 9N) of influenza A viruses and all or most of these have been found in wild waterfowl. Interestingly only three of the 144 subtypes, H1N1, H2N2 and H3N2, have caused pandemic influenza in the 20th century. Only strains of H1N1 and H3N2 are currently circulating and causing seasonal influenza. Recently a number of different subtypes of influenza A viruses have emerged as agents of avian influenza in humans and these include H5N1, H7N2, H7N3, H7N7 and H9N2. As of October 2006, H5N1 viruses have killed more than 150 people in ten different countries since the beginning of 2003. On the other hand, the H7N7 virus has been associated with a single human death but numerous cases of conjunctivitis (eye infection) in the Netherlands. The H7N2, H7N3 and H9N2 viruses have caused only mild disease in humans. While the number of human deaths caused by the H5N1 virus is small in comparison to the annual deaths attributed to human seasonal influenza viruses (~36,000/ year in the U.S.), it is of particular concern to the public health community because many scientists believe that this virus may continue to mutate or reassort and a strain may ultimately develop the ability to pass readily between humans. If this happens, the virus that emerges may cause the next major influenza pandemic. As of October 2006, the highly pathogenic avian influenza (HPAI) H5N1 virus has not been detected in North or South America and it is important to understand that a pandemic influenza virus has not yet emerged and when, and if, it will emerge is impossible to predict. This document is for current implementation and provides guidance to employees that are likely to become exposed to avian influenza if it reaches the U.S. or if they travel or work abroad. It focuses on the following groups of employees that are at risk of being exposed to avian influenza infections, but the list is not intended to be all-inclusive.
There are many other employees that may become at risk if there is a serious avian flu outbreak. [ Table of Contents ] Guidance for Poultry Employees At the end of 2004, OSHA worked with NIOSH through a joint agency Issues Exchange Group and developed a Safety and Health Information Bulletin (SHIB 12-13-2004) titled, Avian Influenza, Protecting Poultry Workers at Risk. The document details safety measures that should be adopted by poultry employees. (See www.osha.gov/dts/shib/shib121304.html). In addition, the Centers for Disease Control and Prevention (CDC) has issued interim recommendations in a web document titled Interim Guidance for Protection of Persons Involved in U.S. Avian Influenza Outbreak Disease Control and Eradication Activities. 1 The CDC recommendations are based on precautions that are considered best practices for protecting individuals involved in the response to an AI outbreak. The following guidance information synthesizes the recommendations from both the CDC web document and the OSHA SHIB. The guidance provided should be implemented in the event of a suspected or confirmed avian flu outbreak at a poultry facility. Recommendations include the following procedures: basic infection control, personal protective equipment (PPE), antiviral drug use and seasonal flu vaccination, medical monitoring of employees and disinfection of contaminated areas. A safety and medical officer should be identified to ensure compliance with procedures. In addition, the United States Department of Agriculture (USDA) (see: www.aphis.usda.gov/vs/birdbiosecurity/hpai.html) and State biosecurity web sites should be consulted for additional procedures for disease control and eradication. Employees Potentially at Risk
Signs that Poultry May Be Infected with AI Employers should train employees to be alert to poultry that develop one or more of the following signs.
Transmission to Humans Exposure of the conjunctival membranes of the eyes and/or the oral or nasal mucosa to secretions (oral, nasal or fecal) from AI-infected birds is the predominant route of transmission of these viruses to humans. In contrast, seasonal human influenza viruses are primarily transmitted from person-to-person via nasal or oral secretions only. Avoid direct contact with bird secretions and inhalation of dust contaminated with these secretions. Basic Infection Control Measures
Important considerations:
Personal Protective Equipment (PPE) Do not eat, drink, smoke, or use bathroom facilities while engaged in activities where contact with contaminated animals or surfaces are possible. PPE should be properly removed and discarded [see section below titled, “Removal of Personal Protective Equipment (PPE)”] or disinfected. Hands should then be washed thoroughly before eating, drinking, smoking or bathroom use.
Administration of Antiviral Drugs
Medical Monitoring of Employees
Disinfection of Areas Contaminated by AI-infected Birds After an AI outbreak, it is important that the contaminated areas be disinfected. Depending on temperature and moisture conditions (see Appendix D for more specific details and survival and inactivation of influenza viruses), AI viruses can survive in the environment for long periods, even weeks. However, AI viruses are generally susceptible to the following chemical and physical methods of inactivation:
Certain EPA-registered disinfectants labeled for use against avian influenza viruses are effective for use on hard, non-porous surfaces listed on the label (see: www.epa.gov/pesticides/factsheets/avian_flu_products.htm for product listings). The label of an EPA-registered disinfectant describes how to use the product safely and effectively and includes measures that persons applying the products should take to protect themselves. The personal protective equipment (PPE) listed on a disinfectant product label is based on the product's toxicity and potential risks associated with use of the product according to the product label. Wearing less protective PPE than specified on the label is considered misuse of the product and a Federal violation. However, employees may wear more protective PPE than required on the label. [ Table of Contents ] Guidance for Animal Handlers other than Poultry Employees This guidance is for situations in which highly pathogenic avian influenza (HPAI) H5N1 has been diagnosed or is suspected in poultry or wild birds in your area. While AI is mostly a concern in domestic poultry stocks, other farmworkers, pet shop owners and their employees, veterinarians and their employees, and zookeepers should be alert to any sick birds that show any of the AI-associated symptoms (see: www.aphis.usda.gov/vs/birdbiosecurity/hpai.html). If such birds are observed, immediately notify Federal or state animal health officials or call 1-866-536-7593 (toll-free) or your local agricultural control agent. Also note that other animals can be infected with certain AI viruses. In particular, H5N1 has been shown to infect cats, pigs and ferrets. These animals should also be monitored for any unusual flu-like symptoms. If possible, avoid handling potentially infected animals. Allow the Federal or state officials to handle these animals. However, if you must handle the animals to isolate them from others or to remove dead animals, use appropriate personal protective equipment (PPE). Refer to Guidance for Poultry Employees (pages 7-16) for the appropriate types of PPE to wear and also for good personal hygiene practices. A risk assessment by Federal or state officials should assist an employer in deciding the level of PPE that would be most appropriate in a particular situation. The Department of Health and Human Services (HHS) website at www.pandemicflu.gov provides a web document titled, Contact Information for State Departments of Agriculture, Wildlife, and Public Health, which lists contact information for agriculture, wildlife and public health departments for all U.S. states and territories and can be directly accessed at: www.pandemicflu.gov/state/statecontacts.html. [ Table of Contents ] Guidance for Laboratory Employees CDC has made the following recommendations for laboratory testing for H5N1 in a website document titled, Updated Interim Guidance for Laboratory Testing of Persons with Suspected Infection with Avian Influenza A (H5N1) Virus in the United States. 2 Manipulating highly pathogenic avian influenza (HPAI) viruses in biomedical research laboratories requires caution because some strains may pose increased risk to laboratory employees and have significant agricultural and economic implications. Biosafety Level 3 (BSL 3) and Animal Biosafety Level 3 (ABSL 3) practices, procedures and facilities are recommended along with clothing change and personal showering protocols (referred to as enhanced BSL 3 practices). Loose-housed animals infected with HPAI strains must be contained within BSL 3 (Ag) facilities. Negative pressure, HEPA-filtered respirators or positive air-purifying respirators are recommended for highly pathogenic avian influenza (HPAI) viruses with potential to infect humans. The HPAI viruses are agricultural Select Agents requiring registration of personnel and facilities with the lead agency for the institution (CDC or USDA-APHIS). An APHIS permit is also required. Additional containment requirements and personnel practices and/or restrictions may be added as conditions of the permit. Important considerations:
Medical Monitoring
[ Table of Contents ] Guidance for Healthcare Workers Who Treat Patients with Known or Suspected AI The CDC has issued Interim Recommendations for Infection Control in Healthcare Facilities Caring for Patients with Known or Suspected Avian Influenza.3 This document contains the following recommendations:
Standard Precautions
Contact Precautions
Droplet Precautions
Transmission Prevention Strategies in Healthcare Settings
For additional information regarding these and other healthcare isolation precautions, see the Guidelines for Isolation Precautions in Hospitals (www.cdc.gov/ncidod/hip/isolat/isolat.htm). The precautions for healthcare employees listed above should be continued for 14 days after onset of symptoms or until:
Vaccination of Healthcare Workers against Human Influenza Healthcare workers involved in the care of patients with documented or suspected AI should be vaccinated with the most recent seasonal human influenza vaccine. In addition to providing protection against the predominant circulating influenza strains, this measure is intended to reduce the likelihood of a healthcare worker being co-infected with both human and AI viruses, where genetic reassortment could take place, leading to the emergence of potential pandemic strains. Important considerations:
Surveillance and Monitoring of Healthcare Workers
[ Table of Contents ] Guidance for Food Handlers This guidance is for situations in which highly pathogenic avian influenza (HPAI) H5N1 has been diagnosed or is suspected in poultry or wild birds in your area. Although there is no direct evidence that any human cases of AI have been acquired by eating poultry products, raw poultry should always be handled hygienically because it can be associated with many infections, including salmonella. Therefore, all utensils and surfaces (including hands) that come in contact with raw poultry should be cleaned carefully with water and soap immediately afterwards. Infected poultry stocks should be destroyed before having any possibility of entering the food chain. Ducks can be asymptomatic (with no symptoms) H5N1 carriers and duck products could be unknowingly contaminated with the virus. In 2001, frozen duck meat imported to South Korea from China was contaminated with HPAI H5N1. Once isolated from the meat, the virus was still infective to mice (mice are used as an animal model for testing pathogenicity of avian influenza viruses). 5 In a more recent study, an HPAI H5N1 strain was also found in duck meat imported into Japan from China. 6 Eggs from infected poultry could also be contaminated with the virus and, therefore, care should be taken in handling shell eggs or raw egg products. Fortunately, influenza viruses are destroyed by adequate heat. Two groups of employees most at risk in poultry food handling are grocery store employees that process raw chicken (butcher it into parts, package parts, etc.) and cooks at restaurants. Grocery store employees should routinely use good hand hygiene when handling raw poultry or poultry products and observe the additional precautions listed below as important considerations after guidance for cooks. During preparation of poultry, cooks are reminded to follow proper food preparation and handling practices, including the following: 7
[ Table of Contents ] Guidance for Airport Personnel Exposed to Passengers Suspected of Being AI-infected This guidance applies to airport personnel potentially exposed to passengers infected with avian influenza (AI). It is not intended for crewmembers on aircraft in operation. The safety and health of crewmembers on aircraft in operation are the exclusive responsibility of the Federal Aviation Administration (see www.faa.gov). Unless otherwise stated, the recommendations in this guidance section are based on standard infection control practices, available information about avian influenza, and those portions of the CDC guidance titled, Interim Guidance for Airline Flight Crews and Persons Meeting Passengers Arriving from Areas with Avian Influenza 8 that apply to airport personnel. General Infection Control Precautions All employees should always follow basic hygiene practices to prevent becoming ill. Many infectious diseases can be spread by human hands. Soiled hands are an effective means of delivering infectious material (e.g., saliva or other body fluids that may contain viruses) to the nose or eyes, where they can enter the body. Hand washing is an important way to reduce exposure to common infectious diseases. Cleaning one's hands with soap and water removes potentially infectious material from one's skin. Hands should be cleaned before preparing food, eating, or touching one's face, and after handling soiled material (e.g., used tissues, lavatory surfaces), coughing or sneezing, and using the toilet. Waterless alcohol-based hand gels may be used when soap is not available and hands are not visibly soiled. If employees are ill, the following steps should be taken:
For more information about these issues, visit the following CDC websites:
Procedures for Protecting Airport Personnel in Close Proximity to Passengers Suspected of Having an AI-infection
Management of Possibly Infected Airport Personnel
For more information about avian influenza, see www.cdc.gov/flu/avian/facts.htm, and www.cdc.gov/flu/avian/index.htm. [ Table of Contents ] Guidance for Travelers on Temporary Work Assignment Abroad CDC has issued the following notice concerning travel to areas known to have current or past H5N1 outbreaks: Outbreak Notice Update: Human Infection with Avian Influenza A (H5N1) Virus in Asia. 9 From January 2005 through October 2006, the number of countries with outbreaks of H5N1 infection among poultry or wild birds increased more than 3-fold from 15 to the following 54 countries: 10
In November of 2005, human cases had been reported from only 5 countries. As of October 12, 2006, the number of countries with human cases had doubled to the following 10 countries: Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey and Vietnam. Since this information is constantly changing, consult the U.S. Government pandemic influenza website at: www.pandemicflu.gov/, where regularly updated information on cases in both birds and humans worldwide can be accessed. Appendix I contains websites that provide additional information. To reduce the risk of infection, CDC recommends that Americans visiting areas where outbreaks of H5N1 infection among poultry or human cases of H5N1 infection have been reported should observe the following measures to help avoid illness. Before Any International Travel
During Travel
After Your Return
H5N1 infections in humans
Recommendations for enhanced surveillance and infection control precautions for H5N1
Health recommendations for travel to Asia
[ Table of Contents ] Guidance for U.S. Employees Stationed Abroad CDC has issued recommendations for expatriates and U.S. Embassy officials living in areas with past or present H5N1 outbreaks titled, Update: Guidelines and Recommendations, Interim Guidance about Avian Influenza A(H5N1) for U.S. Citizens Living Abroad. 7 CDC continues to recommend surveillance, diagnostic evaluation, and infection control for suspected H5N1 cases in travelers to the U.S. These recommendations are contained in a health update on February 4, 2005 (www.cdc.gov/flu/avian/professional/han020405.htm). CDC remains in communication with WHO and continues to closely monitor the H5N1 situation in Asia. Updated information can be found at the following websites:
Precautions
When Preparing Food During preparation of poultry, cooks are reminded to follow proper food preparation and handling practices, including: 7
For more information on good hand hygiene, consult Hand Hygiene Guidelines Fact Sheet (www.cdc.gov/od/oc/media/pressrel/fs021025.htm). Precautions If You Become Ill If you believe that you might have been exposed to AI, take the following precautions:
For information about safety and security for Americans living abroad, see www.travel.state.gov. [ Table of Contents ] Guidance for Other Employee Groups that May Be at Risk The following employee groups may be at risk under certain circumstances, especially if there is a massive outbreak at a specific area of the U.S. or if there are numerous outbreaks throughout the country:
Employers should train employees to use good hand hygiene and to be aware of the symptoms of avian influenza in birds and other animals. Although the types of personal protective equipment that would be required by each of these groups of employees may be different from those outlined under Guidance for Poultry Employees, these PPE recommendations may serve as a guide for other employees depending on the risk assessment made by their employers of their possible level of exposure. A risk assessment can be made by contacting Federal and State government agencies that will be dealing with these issues. Many of the agencies that will have up-to-date information can be found in Appendix A. Most Federal Agencies have posted avian influenza guidance for their employees. Also most states have guidance for employees that would be most affected if there was an outbreak of avian influenza near them. Consult state health departments for updates on outbreaks and PPE guidance if and when an outbreak occurs. [ Table of Contents ] Employee Training All employees with potential occupational exposure, as described in this document, should be trained on the hazards associated with exposure to influenza A (H5N1) and be familiar with the protocols in place in their facility to isolate and report cases or reduce exposures. [ Table of Contents ] Appendix A Worldwide Occurrence of the H5N1 Virus The first outbreak of highly pathogenic avian influenza (HPAI) H5N1 virus was reported in Hong Kong in 1997. Hong Kong responded appropriately by killing its entire poultry population of 1.5 million birds in 3 days. 11 From 2000 through 2004, there were an additional 15 HPAI outbreaks in Asian countries and 200 million birds were killed. The scale of the problem is enormous, especially when one considers that in the 40-year period before 2000 there were just 18 HPAI bird flu outbreaks (none due to H5N1) and only 23 million birds were destroyed. 12 The H5N1 virus was largely confined to several countries throughout Asia until 2005. Among these were Cambodia, China, Hong Kong, Indonesia, Japan, Lao PDR (Laos), Malaysia, South Korea (Republic of Korea), Thailand, and Vietnam. In 2005, different strains of the virus moved north and westward, first to Russia, Kazakhstan, and Mongolia in July and to Romania, Turkey and Croatia in October. 13 Human cases of H5N1 influenza were first reported in Hong Kong in 1997 with 6 of 18 human infections resulting in death. 14 From December 2003 to November 2005, there have been 126 confirmed human infections resulting in 64 deaths. This is a case fatality rate of approximately 51%. While no new cases were reported from Hong Kong during this time period, cases were reported from Cambodia, Indonesia, Thailand, and Vietnam, increasing the number of countries affected with human H5N1 infections to five. Vietnam had the highest incidence with 92 reported human cases and 42 deaths. 15 The case fatality rate in humans may be somewhat inflated because it appears that many exposed individuals may have had very mild symptoms or may even have been asymptomatic and, therefore, have not been counted in epidemiologic surveys. 16 Although there have been reports that the virus may have been transmitted from human-to-human, this mode of transmission has not been conclusively determined and, if it does occur, it currently seems to be very inefficient. 17 Beyond infecting humans, the H5N1 virus has been found to infect and kill other mammals. It can be transmitted from birds to both wild and domestic felids (cats) that eat infected poultry. However, transmission from birds to pigs does not appear to readily occur, although there is increasing evidence that it is beginning to occur. Pig-to-pig transmission has not been documented experimentally, but felid-tofelid transmission does occur. 18, 19, 20 As of October 2006, highly pathogenic avian influenza HPAI H5N1 viruses have not been reported from North or South America. However, in 2004, an HPAI H5N2 strain was reported in Texas and resulted in the culling of chicken stocks in January and August of that year. 21 During the period from 2004-2005, there have been low pathogenic avian influenza (LPAI) H5N2 outbreaks in Italy, Japan, Mexico, the Republic of Korea, and The Taiwan Province of China and the list of host domestic poultry has been expanded from chickens to include ducks, turkeys, and pheasants. 21 The H5N2 subtype has apparently been causing outbreaks in poultry for quite some time and can readily undergo genetic change from low to high pathogenicity. During a 1983-1984 epidemic in the U.S., an LPAI H5N2 virus mutated into an HPAI H5N2 virus within 6 months and resulted in poultry mortality near 90%. Seventeen million birds had to be destroyed to control the outbreak. 14 Similarly, an epidemic caused by a LPAI H5N2 strain in Mexico in 1992 underwent genetic change and converted from an LPAI H5N2 virus to a HPAI H5N2 virus that was not brought under control until 1995. 14 Although the H5N2 subtype has now been isolated throughout the world, with some strains being highly pathogenic to domestic birds, there have not been any reported cases of human infection. Wild waterfowl are the natural hosts for influenza A viruses and when they migrate they can enhance the spread of a particular viral subtype worldwide. 22 It appears that at least some of the spread of HPAI H5N1 is also occurring via wild bird migrations. From its origin in Hong Kong in 1997, it has moved northward to Lake Qinghai in China, a breeding center for migrant birds that congregate from Southeast Asia, Siberia, Australia, and New Zealand. 23 The H5N1 strains that are migrating westward are genetically almost identical to those that killed wild birds in Lake Qinghai but distinct from those that have caused death in humans in Southeast Asia. It is currently believed that the East Asia/Australian flyway (Pacific Flyway) of migratory birds may carry HPAI H5N1 to the U.S. via Alaska. The University of Alaska and the USDA have been alert to this possibility for some time. From 1998-2004, over 12,000 samples from wild birds in Alaska were evaluated for influenza viruses but H5N1 was not detected. 24 In addition, since 2000 the USDA has tested approximately 4000 migratory birds in the Atlantic flyway and H5N1 was not detected. Since the summer of 2005, the Department of the Interior (DOI) has been working with the State of Alaska to strategically sample migratory birds in the Pacific Flyway. As of March 20, 2006, DOI has carried out more than 1700 tests on samples from more than 1100 migratory birds. Although twenty-two HPAI isolates were identified, the HPAI H5N1 was not found. The USDA, DOI and HHS have developed an Interagency Readiness Plan to monitor wild birds for the early detection of H5N1 and other HPAI viruses in the United States. The plan is part of the President's National Strategy for Pandemic Influenza Preparedness and outlines a prioritized wild bird sampling system with emphasis on Alaska, followed by other areas in the Pacific Flyway and the Pacific islands, and finally the Central, Mississippi and Atlantic Flyways. Emphasis is being placed on Alaska since it is at the crossroads of bird migration flyways and scientists believe that if the strains of H5N1 currently affecting Southeast Asia were to spread to North America via migratory birds they would likely arise first in Alaska. In 2006, USDA and its cooperators plan to collect between 75,000 and 100,000 samples from live and dead wild birds as well as 50,000 samples of water or feces from high-risk waterfowl habitats across the United States. 25 In addition to spreading via migratory birds, the H5N1 virus may also have been spreading through the legal and illegal movement of infected birds and contaminated avian-origin products. The migration of the virus is a matter of great concern, and the sheer numbers of people, pigs, and poultry in Asia also offers a significant opportunity for the H5N1 virus to undergo genetic reassortment (i.e., when two different viruses infect the same bird, the resulting viruses can reassort their genetic material into unique combinations) to a form that can be efficiently transmitted between humans. Since the last pandemic (the Hong Kong flu) in 1968, the populations of human, pigs and poultry in China alone have increased 2-, 100- and 1,000-fold respectively. 26 [ Table of Contents ] Appendix B Background on the Biology of Influenza Viruses The influenza viruses are 80-120 nanometers in diameter but they can be ovoid (egg-shaped) to even filamentous (thread-like). 10 There are three major types of the influenza virus: A, B, and C. Although there are many subtypes of the A virus, there is only one known subtype of the B and C viruses. Within each subtype there are many different strains. The subtypes of the A viruses differ in the combinations of the 16 distinct hemagglutinin (H1-H16) and 9 distinct neuraminidase (N1-N9) viral surface proteins. 10 These are the primary antigens of the influenza viruses against which the human immune system develops antibodies; the H antigen is significantly more immunogenic than the N antigen. There are two major ways in which influenza A viruses can change antigenically: via antigenic drift or shift. During antigenic drift, a variety of mutations including substitutions, deletions, and insertions produce genetic variation in the surface proteins. A second type of variation, antigenic shift, describes a major antigenic change whereby a virus with a new H (with or without a new N) is introduced into the human population. 27 Type A viruses undergo both antigenic shift and drift, while Type B viruses undergo antigenic drift only, and type C viruses are relatively stable. Influenza A viruses cause disease in birds, cats, dogs, ferrets, horses, humans, swine and marine mammals (seals and whales), while type B viruses cause disease in humans and rarely, in seals, and type C occasionally causes a mild disease in humans and swine. 28, 29 All subtypes of influenza type A viruses can be found in waterfowl (e.g., ducks, geese, etc.), where they normally reside in the intestinal tract and cause little, if any, disease. At times, some of these viruses mutate or reassort (i.e., when two different viruses coinfect a bird, their genetic components can recombine to form a new subtype or strain) and cause disease in poultry (e.g., chickens, turkeys, etc.) that is very contagious and sometimes deadly. This poultry disease is called avian influenza (AI) or more commonly “bird” or “avian flu.” When an AI virus causes high mortality in poultry, it is referred to as highly pathogenic avian influenza (HPAI) virus. In the past, the disease caused by HPAI viruses was more commonly called fowl plague. If an AI virus produces mild infection in poultry with little mortality, it is referred to as a low pathogenic avian influenza (LPAI) virus. It should be noted that the mutation from LPAI viruses to HPAI viruses has resulted in bird flu epidemics in poultry 19 times since 1959. 30 The genetic material of influenza A viruses is ribonucleic acid (RNA) and it is arranged in eight separate strands. The two genes coding for the viral surface proteins as well as the other genes coding for internal viral proteins can reassort (recombine with other genes) when a host is infected with more than one viral subtype. This can lead to the generation of novel (new) viral subtypes as well as other genetic changes that affect pathogenicity. The H5N1 virus is an example where reassortment of genes from three different virus subtypes led to its development in Hong Kong in 1997. Apparently, the H5 gene of a H5N1 strain present in geese in 1996 was retained but its remaining genes, including the gene coding for the N1 surface protein, were obtained from a H6N1 strain from a green-winged teal and an H9N2 strain from a quail. 31 Although AI viruses do not typically infect humans, confirmed instances of AI viruses other than H5N1 infecting humans have been documented since 2002 and include: 32 H7 Subtypes
H9 Subtypes
As of October 2006
[ Table of Contents ] Appendix C Genetic Variations in H5N1 Strains and Implications for Human Health Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in 1997 [genotype H5N1/97; different genotypes (clusters of genetically related strains) had not yet been recognized], the parent Gs/Gd genotype of H5N1/97 has undergone additional reassortments with unknown AI viruses. The H5N1/97 genotype did not reappear after the 1997 outbreak. By 2001, six new genotypes (A, B, C, D, E and X0) had emerged. From 2002 onwards, an additional eight genotypes (V, W, X1, X2, X3, Y, Z and Z+) were discovered but the Gs/Gd, A, C, D and E genotypes apparently disappeared. 33 The strain that caused the 2003 outbreak in Hong Kong that resulted in two human cases, one of whom died, belonged to the Z+ genotype. 34 The very similar Z genotype is now dominant in Southeast Asia and was responsible for the poultry and human outbreaks in Indonesia, Thailand and Vietnam in late 2003 and early 2004. 33 The viruses that caused poultry outbreaks in South Korea in 2003 and in Japan in 2003-2004 were members of the V genotype; a genotype that has not been associated with human disease. 35,36 It also appears that the H5N1 viruses from the 2004 Vietnam outbreaks are environmentally more stable than those from the Hong Kong 1997 outbreak; the former survived at 37ºC for 6 days, compared with 2 days for latter at 35ºC. 37 HPAI H5N1 has been moving northward. A new H5N1 genotype emerged at Lake Qinghai in northern China in May of 2005 and eventually killed more than 6,000 migratory waterfowl. 38 While it is unusual for an AI virus to kill waterfowl, this is not unprecedented for the H5 subtype. A H5N3 strain killed 1,300 terns (wild waterfowl) in South Africa in 1961. 39 It is important to note that the H5N1 genotype that affected wild waterfowl in northern China appears to be a new reassortant virus, combining genetic material from at least two other HPAI H5N1 strains. 38 These do not belong to the Z genotype that affected Southeast Asia. Also it is now known that the strains affecting humans in Indonesia are of a different sub lineage of the Z genotype than those that affected humans in Thailand and Vietnam in 2004 and 2005. 40 As of May 29, 2006, there have been no reported human cases of H5N1 in Thailand or Vietnam in 2006 but the number of cases of human infection in Indonesia is greater than for all of 2005 (25 versus 17 total cases in 2005). The Indonesian sub-lineage is particularly virulent since 25 of the 31 persons infected in 2006 have died (a case fatality rate of approximately 80%). 15 While all of these various genetic variants of H5N1 are still classified as HPAI strains, some appear to be non-infectious while others are infectious to humans. The strains of H5N1 migrating north and west from Lake Qinghai in China have attacked poultry and wild waterfowl in many countries but have caused human disease only in Azerbaijan, Djibouti, Iraq, Turkey, and Egypt as of October 12, 2006. Of the 54 countries with H5N1 outbreaks in poultry or wild birds, human disease has been documented in only 10 of them. [ Table of Contents ] Appendix D Survival and Inactivation of Influenza A Viruses, Including H5N1 Environmental Survival Survival of influenza A viruses outside of the host varies with the virus subtype, the strain, the host bird from which it was obtained, pH, salinity, temperature and the type of medium in which the virus is suspended. After excretion by water birds, strains of avian influenza viruses (AIV) of five different subtypes (H3N8, H4N6, H6N2, H10N7, and H12N5) remained infective when suspended in lake water for 30-102 days at 28ºC and for 126-207 days at 17ºC. 41 In the same study it was estimated that the strain of subtype H10N7, the only strain stored at 4ºC, would remain infective for 1333 days. Survival of a strain of the H7N2 subtype was variable in different types of chicken manure and ranged from more than 2 days to 6 days at 15-20ºC, from 24 – 36 hours at 30-37ºC and from 15 to 20 minutes at 56ºC. 42 Another study using a strain from each of three different AIV subtypes (H4N6, H6N2, and H10N7) found that pH, temperature and salinity affected survival of these viruses differently. 43 It can be seen from these studies that many variables affect the environmental survival of AIVs. Therefore, one can only conclude with confidence that AIV viruses survive less well at higher temperatures and lower pH levels. There have been very few studies on the environmental survival of strains of H5N1. Although the studies cited below were not totally comparable, these data suggest that like the genetic data, strains which caused disease in Southeast Asia in 2004-2005 are different from the one that caused disease in 1997. Although it appears that environmental survival of H5N1 appears to be somewhat strain-specific, this must be more fully studied. 1997 Hong Kong H5N1 Strains This strain does not survive complete drying at room temperature. Not surprisingly, the temperature at which it is stored affects its survival when in moist feces.
2004 Vietnam H5N1 Strains Interestingly, H5N1 strains from 2004 Vietnam outbreaks are environmentally more stable than those from the 1997 Hong Kong outbreak; the former survived at 37ºC for 6 days, compared with 2 days for the latter at 35ºC. 37 Inactivation The following provides a list of physical and chemical methods that are considered effective in the inactivation of influenza A viruses in general. 44 Physical Methods
Chemical Methods
Apart from the methods listed above, there are many other methods that can effectively kill these viruses. However, one should use the safest method possible when disinfecting areas known or suspected to be contaminated with the virus. [ Table of Contents ] Appendix E Transmission of the H5N1 Virus The information in this appendix has largely been condensed from reference 45 (see Appendix J at pg. 64). Animals to Animals (Poultry to Poultry) Infected birds shed virus in respiratory secretions via the oral or nasal routes and in feces. Fecal-to-oral transmission is the most common mode of spread between birds.
Contaminated Environment to Humans Several of the many possible modes of transmission are:
While the modes of transmission from animal-to-animal and environment-to-human may be similar for most strains of influenza virus, there are notable differences in the mode of transmission from animal-to-human and human-to-human between the 1997 Hong Kong strains and the 2003-2004 Southeast Asian strains of H5N1. Animals to Humans H5N1 1997 Hong Kong Strains Most infected patients were exposed to:
H5N1 2003-2005 Southeast Asian Strains Most infected patients had engaged in one or more of the following activities:
Humans to Humans H5N1 1997 Hong Kong Strains
H5N1 2003-2005 Southeast Asian Strains
H5N1 versus Human Influenza In contrast to strains of H5N1 which are still largely AI viruses with ineffective transmission between humans, the human flu viruses can be readily passed from human-to-human via one of the following routes.
[ Table of Contents ] Appendix F Symptoms and Outcomes of H5N1 Infection in Hospitalized Patients The data in this appendix have largely been condensed from reference 45 (see Appendix J). The type and severity of symptoms and patient outcomes can vary depending on the properties of a particular viral strain and the patient's age and medical status at the time of infection. The following information is based on a number of studies of H5N1 infected hospitalized individuals and only lists the most common symptoms (those expressed in at least 50% of the patients) and lists these in order of frequency. The number of patients studied that were infected with the 1997 strain was 18 while the number infected with 2004/2005 strains was 41. Symptoms H5N1 - 1997 Hong Kong Strain
H5N1 - 2004/2005 Southeast Asian Strains
The most striking difference in symptoms between those infected with the 1997 strain and the strains circulating in 20042005, was the high prevalence of dyspnea (shortness of breath) and diarrhea in the later patients. Dyspnea was present in only 6% and diarrhea in 17% of patients infected with the 1997 strain. Outcomes H5N1 – 1997 Hong Kong Strain
H5N1 – 2004/2005 Southeast Asian Strains
These data indicate that the 2004/2005 strains were more virulent than the 1997 strain. The time from onset of illness to death was shorter, while respiratory failure and death rate were higher in patients infected with the former strains. Interestingly, the death rate was higher in the victims infected with the 2004/2005 strains even though 68% had received some form of oseltamivir treatment. However, it should be noted that oseltamivir treatment is most effective when given as soon as possible after onset of symptoms. It should also be noted that on rare occasions H5N1-infected patients in Southeast Asia have presented with fever and diarrhea only 46 or severe diarrhea followed by seizure, coma and death. 47 Respiratory symptoms were not evident in these cases. [ Table of Contents ] Appendix G Importation Ban on Birds from Countries Affected by the H5N1 Virus According to the U.S. Fish and Wildlife Service, before 2004 the United States annually imported an estimated 20,000 birds from countries before they were affected with avian H5N1 influenza outbreaks. On February 4, 2004, both the CDC and USDA issued orders banning the importation of all birds whether dead or alive, and all bird products, such as eggs, originating from the Asian countries in which H5N1 AI had been documented. 48 These countries have a single asterisk in the table below. Although the CDC and USDA had bird import restrictions for nine countries in early 2004, in just over 2 years the list has almost quadrupled to 36 as of October 2006. The table below lists the affected countries. This information is constantly changing and is updated as H5N1 outbreaks in poultry occur in different countries. The updated lists can be accessed at: www.cdc.gov/flu/avian/outbreaks/embargo.htm and www.aphis.usda.gov/vs/ncie/country.html#HPAI.
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