Information about AVIAN Influenza Harvey Kayman, MD, MPH, PHMO III California Department of Public Health Division of Communicable Disease Control Immunization Branch

Objectives Learn about Global Avian Influenza Learn what challenges we face Learn how to prevent, protect, and mitigate

Why is there such concern now? Health professionals are concerned that the continued and expanded spread of a highly pathogenic AVIAN H5N1 virus across eastern Asia and other countries represents a significant threat .

Challenge The current outbreaks of highly pathogenic avian influenza, which began in South-East Asia in mid-2003, are the largest and most severe on record. Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds.

Influenza A viruses have 16 H subtypes and 9 N subtypes. In poultry, the viruses can mutate, usually within a few months, from then low pathogenic avian influenza (LPAI) form into the highly pathogenic form (HPAI). Only viruses of the H5 and H7 subtypes are known to cause the highly pathogenic (HPAI) form of the disease.

Influenza A HA and NA Subtypes H15, H16

Highly Pathogenic Avian Influenza HPAI In 2004, over 120 million birds died or were destroyed as a result of a current avian influenza type, the H5N1 strain. This number is higher than the combined total bird deaths of all prior highly pathogenic outbreaks recorded throughout the world over the last four decades.

Changing viral behavior in natural reservoir, wild waterfowl, The spring 2005 die-off of upwards of 6,000 migratory birds at a nature reserve in central China, caused by highly pathogenic H5N1, was highly unusual and probably unprecedented. In the past, only two large die-offs in migratory birds, caused by highly pathogenic viruses, are known to have occurred: in South Africa in 1961 (H5N3) and in Hong Kong in the winter of 2002–2003 (H5N1).

Acceleration of HPAI Furthermore, the 2004 deaths occurred in just three months. In the subsequent months, H5N1 has expanded to include other wild birds as well as domesticated ducks, and its host range now also includes mammals.

More lethal in more animals When compared with H5N1 viruses from 1997 and early 2004, H5N1 viruses now circulating are more lethal to experimentally infected mice and to ferrets (a mammalian model) and survive longer in the environment.

The AVIAN H5N1 virus has raised concerns about a potential human pandemic because: It is especially virulent. It is being spread by transported domestic poultry. It can be transmitted from birds to mammals and in some limited circumstances to humans.

A growing number of human H5N1 cases have been reported in Azerbaijan, Cambodia, China, Egypt, Indonesia, Iraq, Thailand, Turkey and Vietnam. More than half of the people infected with the H5N1 virus have died. Most of these cases are believed to have been caused by exposure to infected poultry. The concern is that H5N1 will evolve into a virus capable of human-to-human transmission.

H7N# Disease Risks An H7N2 virus strain isolated in 2003. This North American avian influenza A--H7 virus is partially adapted to recognize human upper respiratory tract sugar receptors. Alpha 2-6 receptors are found in humans Alpha 2-3 receptors are found in the guts of wild birds (their natural host) and domestic poultry. Those receptors are scarce in the human upper respiratory tract. CDC's Division of Media Relations (6/10/08)-http://www.cdc.gov/flu/avian/

H7N# Disease Risks H7N7 outbreak in the Netherlands in 2003 H7N3 viruses responsible for British Columbia's massive poultry outbreak in 2004 > 17 million chickens destroyed to stop 2004 outbreak. Need to develop vaccines for H7, as well as H5N1 Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands. (5/08)

Human-Poultry interaction Poultry being carried on the Siliguri-Darjeeling highway, that harbored the H5N1 virus, helped it to spread to a region where 4,000,000 poultry had previously been culled in West Bengal to decrease risk of Avian influenza. Sources said that the Panchayat elections in West Bengal had severely affected the state's bird flu control and containment operations. State officials in 4 districts did not want to intimidate villagers by taking away their birds. This, they said, could cost their vote during upcoming elections. May 11, 2008 The Times of India Group

Time to prepare While no one can state with complete certainty that a pandemic will occur, the signs point to it being a prudent time to begin careful and thorough preparation.

Low Pathogenic Avian Influenza LPAI H5 and H7 viruses are introduced to poultry flocks in their low pathogenic form (LPAI). The so-called “low pathogenic” form commonly causes only mild symptoms (ruffled feathers, a drop in egg production) and may easily go undetected.

HPAI First identified in Italy in 1878 HPAI causes severe disease, rapid contagion and lethal for > 6 of 8 chickens inoculated with the virus. It spreads very rapidly through poultry flocks, causes disease affecting multiple internal organs, and Has a mortality that can approach 100%, often within 48 hours.

HPAI Environmental Survival Highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low. For example, the highly pathogenic H5N1 virus can survive in bird feces for at least 35 days at low temperature (4°C). At a much higher temperature (37°C), H5N1 viruses have been shown to survive, in fecal samples, for six days.

The role of migratory birds in the spread of HPAI The role of migratory birds is not fully understood. Wild waterfowl are considered the natural reservoir of all influenza A viruses. They have probably carried H5 and H7 subtypes of LPAI, with no apparent harm, for centuries.

In the past, HPAI was rare in Migratory Birds In the past, only a few migratory birds were found dead within the flight range of a poultry outbreak. Current concept is that wild waterfowl are not agents for the onward transmission of HPAI.

The role of Ducks in the spread of HPAI Domestic ducks excrete large quantities of highly pathogenic virus without showing signs of illness. Mallards act as a “silent” reservoir of the virus, perpetuating transmission to other birds. Adding another layer of complexity to control efforts and removes the warning signal for humans to avoid risky behaviors.

HPAI Transmission Migratory birds can introduce LPAI H5 and H7 viruses to poultry flocks, which then mutate to HPAI. Avian influenza viruses are readily transmitted from farm to farm by the movement of live birds, People (especially when shoes and other clothing are contaminated), and Contaminated vehicles, equipment, feed, and cages.

Human controlled intensive rice-domestic duck agriculture Virus persistence after extensive culling is increasingly confined to areas in eastern and southeastern Asia where humans cultivate rice and duck meat. ~90% of the world’s 1.044 billion domestic ducks are in Asia. China and Viet Nam=775 million or 75%. Thailand=11 million ducks. http://www.fao.org/newsroom/en/news/2008/1000817/index.html

Dead birds don't fly Governments should stop blaming wild birds for outbreaks of the disease. Migratory birds do not move during the summer, (Ornithologist Martin Williams) Waterfowl carry a lot of bird flu viruses, but they don't carry the Highly Pathogenic Avian H5N1 flu, because it kills them. June 2008 South China Morning Post Publishers Limited, Hong Kong.

Backyard flocks=a heightened risk of human exposure and infection. Backyard flocks usually roam freely. Backyard flocks scavenge for food Backyard flocks mingle with wild birds or share water sources with them. Abundant opportunities for human exposure to the virus with birds in households, especially during adverse weather, or when they share areas where children play or sleep.

Endemic Zoonotic H5N1 virus -- especially tenacious. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in many parts of Indonesia and Viet Nam and in some parts of Cambodia, China, Thailand, and possibly also the Lao People’s Democratic Republic. Control of the disease in poultry is expected to take several years.

Disease outbreak maps June 2008

Ducks, rice and people A strong link between duck grazing patterns and rice cropping intensity in H5N1 highly pathogenic avian influenza in Thailand and Viet Nam. Ducks feed mainly on leftover rice grains in harvested paddy fields, so free-ranging ducks in both countries are moved to many different sites in line with rice harvest patterns. Virus persistence is now increasingly confined to areas with intensive rice-duck agriculture in eastern and southeastern Asia. "Mapping H5N1 highly pathogenic avian influenza risk in Southeast Asia: ducks, rice and people", Proceedings of the National Academy of Sciences of the United States (PNAS), http://www.fao.org/newsroom/en/news/2008/1000817/index.html

90 % of the world’s 1.044 billion domestic ducks are in Asia China and Viet Nam account for the bulk of this – 775 million or 75 percent. Thailand has about 11 million ducks.

Control of HPAI in Thailand The local movements of ducks decreased when the Thai government started to support in-door keeping of ducks, offering feed subsidies and construction of enclosures. Together, these measures stopped the H5N1 transmission cycle and since late 2005 Thailand has suffered only sporadic outbreaks.

Control of HPAI in Vietnam Viet Nam started nationwide vaccination of all poultry at the end of 2005, including the Mekong delta which is home to 50 million ducks. This large-scale vaccination was repeated in 2006/07. Initially, human infections disappeared and levels of disease in poultry fell noticeably. Only gradually did H5N1 viruses re-appear, mostly in unvaccinated ducks and particularly in the Mekong delta.

How avian influenza A/H5N1 might enter the U.S. bird population Poultry imported into South America (where poultry trade is less restricted) from countries where H5N1 has affected domestic or wild birds poses the greatest risk of introducing H5N1 into the U.S. H5N1 could be transmitted from poultry in South America to birds that migrate to North America* *Kilpatrick et al. Proc Natl Acad Sci. 2006 Dec 19;103(51):19368-73

By 2004, expanded to other mammalians. Now found in: Tigers, Leopards, Pigs, Domestic cats, Palm civets, Humans

World wide Human Mortality Rate=63% June 2008

Protective and Mitigating responses Governmental preparedness Cross Sector planning and collaboration Cross Boundary planning and collaboration Expansion of Surveillance, Case tracking and Epidemiology Laboratory Diagnostic Enhancement Improved information systems

WHO guidance on public health measures in countries experiencing their first outbreaks of H5N1 avian influenza-October 2005 Coordination of services. Multi-sectoral procedures should be put in place to coordinate the work of agricultural, veterinary and public health services (and any other sectors deemed appropriate in a country context) and facilitate the exchange of laboratory and epidemiological data. http://www.who.int/csr/disease/avian_influenza/guidelines/firstoutbreak/en/index.html

Control Measures Rapid culling of all infected or exposed birds, proper disposal of carcasses, the quarantining and rigorous disinfection of farms, and the implementation of strict sanitary, or “bio-security”, measures

Control Measures Restrictions on the movement of live poultry, both within and between countries, The logistics of recommended control measures are most straightforward when applied to large commercial farms, where birds are housed indoors, usually under strictly controlled sanitary conditions, in large numbers. http://www.who.int/mediacentre/factsheets/avian_influenza/en/index.html

Control Measures Control is far more difficult under poultry production systems in which most birds are raised in small backyard flocks scattered throughout rural or peri-urban areas. http://www.who.int/mediacentre/factsheets/avian_influenza/en/index.html

Vaccination for public health purposes. At least some pandemic viruses are known to have emerged following a re-assortment event. Vaccination against seasonal influenza will not protect people against infection with the H5N1 virus; no vaccine against H5N1 is presently available.

Potential sources of exposure Swimming in water bodies with discarded infected carcasses or contaminated by infected ducks feces. No known plausible exposure source, suggesting an unknown environmental factor, involving contamination with the virus. A possible role of peri-domestic birds, such as pigeons The use of untreated bird feces as fertilizer.

Poverty exacerbates the problem In situations where a prime source of food and income cannot be wasted, households frequently consume poultry when deaths or signs of illness appear in flocks. This practice carries a high risk of exposure to the virus during slaughtering, de-feathering, butchering, and preparation of poultry meat for cooking, but has proved difficult to change.

Smoldering Rural Outbreaks Owners may not interpret deaths or signs of illness in a flock as a signal of avian influenza and a reason to alert the authorities. The absence of compensation to farmers for destroyed birds works against the spontaneous reporting of outbreaks Encourages owners to hide their birds during culling operations.

Protection of persons at risk of occupational exposure Personal protective equipment. Those at risk of occupational exposure on affected or at-risk farms should wear personal protective equipment: 1. Protective clothing, preferably coveralls plus an impermeable apron or surgical gowns with long cuffed sleeves plus an impermeable apron; 2. Heavy-duty rubber work gloves that may be disinfected;

Personal protective equipment 3. Standard well-fitted surgical masks should be used if high-efficiency N95 respiratory masks (NIOSH-certified N-95 or equivalent) are not available. Masks should be fit-tested and training in their use should be provided; 4. Goggles; 5. Rubber or polyurethane boots that can be disinfected or protective foot covers that can be discarded.

Pharmaceutical prophylaxis and treatment. Those at risk of occupational exposure on affected or at-risk farms can be protected via antiviral prophylaxis (oseltamivir) or post-exposure prophylaxis. Antivirals should be readily available for the treatment of suspected and confirmed cases. http://www.who.int/csr/disease/avian_influenza/en/

WHO Recommendations WHO continues to recommend that travelers to affected areas should avoid contact with live animal markets and poultry farms, and any free-ranging or caged poultry. Large amounts of the virus are known to be excreted in the droppings from infected birds. Populations in affected countries are advised to avoid contact with dead migratory birds or wild birds showing signs of disease. http://www.who.int/csr/disease/avian_influenza/en

Exposure Risk Direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is considered the main route of human infection. Exposure risk is considered highest during slaughter, de-feathering, butchering, and preparation of poultry for cooking. There is no evidence that properly cooked poultry or poultry products can be a source of infection.

Poultry Consumption or Traveling to an Affected Country Not a risk factor, provided poultry is thoroughly cooked and the person is not involved in food preparation. Traveling to a country with outbreaks in poultry or sporadic human cases does not place a traveler at enhanced risk of infection. Currently, no efficient human-to-human transmission of the virus. Avoid visiting live or “wet” poultry markets, farms, or other environments where exposure to diseased birds may occur.

Health monitoring. Those at risk of occupational exposure should: 1. Be aware of the early clinical signs of H5N1 infection, but also understand that many other common diseases – of far less health concern – will show similar early symptoms. 2. Check for these signs (especially fever) each day during potential exposure and for 14 days after last exposure. 3. Communicate any symptoms to a designated local physician and provide background information on exposure history.

Symptoms Most patients infected with the H5N1 virus show initial symptoms of fever (38 C or higher) followed by influenza-like respiratory symptoms, including cough, rhinorrhea, sore throat, and (less frequently) shortness of breath. Watery diarrhea is often present in the early stages of illness, and may precede respiratory symptoms by up to one week. Gastrointestinal symptoms (abdominal pain, vomiting) may occur and headache has also been reported.

Challenges Disposal Occupational health Developing new wild bird surveillance program Hunting? Public perception – panic?

General Resources Links to Additional Information http://www.pandemicflu.gov/ (managed by the Department of Health and Human Services) http://www.cdc.gov/flu/avian/ (managed by the Centers for Disease Control and Prevention)

WHO Resources http://www.who.int/csr/disease/avian_influenza/avian_faqs/en/index.html#howdoes http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_05_8-EN.pdf

The STATE BIRD HOTLINE: 866–922–BIRD (2473) http://www.cdfa.ca.gov/ahfss/Emergency_Projects_Support/Bird_Hotline.html People can call this number to quickly report sick or dead poultry, wild birds, or pet birds. The public can obtain information on how to know when their birds are sick, and how to protect their birds from disease.