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4. AVIAN INFLUENZA

Control Guideline

Last updated: 01 July 2012

1. Summary

Public health priority
Urgent. Respond to a suspected case immediately on notification. Report details of the case to state/territory communicable diseases branch (CDB) within 1 hour of notification. State/territory CDB should report confirmed cases to the National Incident Room on day of notification.

Case management
Suspected cases must be cared for in a single room, and if available, a negative pressure room. If identified within 48 hours of illness onset, cases should be treated with anti-influenza medications (neuraminidase inhibitors - oseltamivir or zanamivir).

Contact management
Contacts of confirmed cases and infected birds must be rapidly identified, counselled about their risk, provided with anti-influenza medications (if indicated), and placed under surveillance. The Communicable Diseases Network of Australia (CDNA) will convene an expert panel to advise on actions.

Note. This guideline is concerned with the public health response to people with avian influenza infection, and people who have been exposed to another person or to birds with avian influenza infection. It is not concerned with human pandemic influenza. In the unusual event that an AI strain transforms into one that is easily transmitted between humans, it is no longer avian influenza, but becomes human (and possibly pandemic) influenza. The response to human pandemic influenza is described in the national and state influenza pandemic management plans. The pandemic phases are outlined in the Australian Heath Management Plan for Pandemic Influenza (www.flupandemic.gov.au). The case definitions have been developed in relation to H5N1 avian influenza, and it is recognised these may need to change should a different strain of avian influenza emerge as a public health threat.

2. The disease

Infectious agents
Avian influenza virus. All AI viruses are influenza A viruses and multiple subtypes of influenza are known to infect birds. AI viruses can have low or high pathogenicity in poultry - LPAI or HPAI. To date, only H5 and H7 varieties have been known to cause outbreaks of HPAI in birds although both LPAI and HPAI can rarely cause illness in humans following very close contact. It is believed that human pandemic influenza strains may mutate from AI viruses.

Mode of transmission
Infected birds shed virus in their saliva, nasal secretions, and faeces. Susceptible birds become infected when they have contact with contaminated excretions from infected birds or from contaminated environments. Transmission of infection from birds to humans is uncommon. When it has occurred, it is believed to have resulted from close contact with infected poultry or breathing in dust contaminated with their excretions. A small number of human cases are thought to have occurred as a result of close and prolonged person-to-person transmission, the precise mode of which is unknown. The virus can survive on poultry products (including eggs and blood) but the risk of infection from these can be minimised by cooking the products, and regular hand-washing.

The likely scenarios in which a human infection with avian influenza could occur in Australia are:

1. a person is infected overseas after close and sustained contact with infectious material from birds or a human case and enters Australia
2. a laboratory worker is infected while working with human or animal specimens that contain avian influenza
3. a person is infected in Australia after close and sustained contact with infectious material from birds, should avian influenza affect local bird populations.

Timeline
Although the incubation period for avian influenza may vary with the subtype, the incubation period for influenza is less than 7 days and typically 2 to 5 days.

Infectious period

• Adults >12 years old are thought to be infectious from the day before symptoms begin until 7 days after resolution of fever
• Children up to 12 years old are thought to be infectious from the day before symptom onset until up to 21 days after symptom onset, although young children can shed virus for several days before their illness onset.
• Severely immunocompromised persons can shed virus for weeks or months.
• For more information, see: http://www.who.int/csr/disease/avian_influenza/guidelines/EPR_AM_final1.pdf

Clinical presentation
The clinical presentation of AI in humans may vary with the virus subtype. As with seasonal human influenza, a person infected with AI may have no symptoms, mild upper respiratory symptoms, or symptoms typical of influenza (fever, cough, fatigue, myalgia, sore throat, shortness of breath, runny nose, headache). The most common presentation of humans infected with H7 strains is conjunctivitis. The H5N1 subtype has caused viral pneumonia with a high mortality rate, and in a small number of cases, an encephalitic or diarrhoeal presentation has been reported.

3. Risk assessment

Routine prevention activities
The prevention of AI in Australians principally relies on advice to travellers to avoid close contacts with birds when travelling in AI-affected countries. In the absence of local transmission of AI in Australian birds or people, the highest risk of infection will be among people who have recently travelled in AI-affected countries or laboratory workers handling AI specimens. As AI in humans is a quarantinable disease, people entering Australia with fever and a respiratory symptom who have a history of exposure to AI should be reported by Australian Quarantine and Inspection Service officers to the state/territory Chief Quarantine Medical Officer to allow a public health investigation. Cases identified in Australia are notifiable to the local PHU to allow investigation. Departments of Primary Industry are responsible for the surveillance and control of AI in birds, and should involve health authorities in human risk assessment and control.

Threat and vulnerability
Various strains of AI are endemic in bird populations around the world. Over the last century there have been a small number of outbreaks of AI in Australian chicken flocks which were contained by isolation and culling of the affected flocks. These outbreaks presumably stemmed from exposure to AI excreted by wild birds in the vicinity of the chicken flocks, although AI-contaminated materials carried by humans or material bought into Australia from AI-infected countries could also pose a risk. It is possible that similar incursions could occur in the future.

Risk mitigation
Bio-security measures have been put in place in many commercial bird facilities to minimise the risk of future AI infections in birds. Strict quarantine and inspection measures at Australian airports and seaports are designed to prevent the importation of bird products into Australia.

4. Surveillance objectives

• To rapidly identify, isolate, and treat cases.
• To rapidly identify and manage contacts of cases and of infected birds
• To describe the epidemiology of avian influenza (AI) in humans in Australia, and to detect changes in the epidemiology that may indicate mutations with the potential to cause a pandemic of human influenza.

5. Data management

Within 1 working day of confirmation, enter confirmed case on state/territory notifiable diseases database.

6. Communications

Immediately report suspected and confirmed cases to the state/territory CDB by telephone with the patient's age, sex, date of onset, laboratory status, possible sources of infection, other people thought to be at risk and follow up action taken.

State/territory CDB should immediately notify confirmed cases to the National Incident Room.

In the event of AI being identified in birds, the state/territory Department of Primary Industries (DPI) should notify the state/territory CDB, which should notify the relevant Public Health Unit.

7. Case definition

Suspected case¹

1. A person presenting with unexplained acute lower respiratory illness with fever (>38 ºC ) and cough, shortness of breath or difficulty breathing, AND
2. One or more of the following exposures in the 7 days prior to symptom onset:
   1. Close contact (within 1 metre) with a person (e.g. caring for, speaking with, or touching) who is a suspected, probable, or confirmed H5N1 case;
   2. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation for consumption) to poultry or wild birds or their remains or to environments contaminated by their faeces in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month;
   3. Consumption of raw or undercooked poultry products in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month;
   4. Close contact with a confirmed H5N1 infected animal other than poultry or wild birds (e.g. cat or pig);
   5. Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting.

Probable case
Probable definition 1:

1. A person meeting the criteria for a suspected case, AND
2. One of the following additional criteria:
   1. infiltrates or evidence of an acute pneumonia on chest radiograph plus evidence of respiratory failure (hypoxemia, severe tachypnea), OR
   2. positive laboratory confirmation of an influenza A infection but insufficient laboratory evidence for H5N1 infection.

Probable definition 2:

1. A person dying of an unexplained acute respiratory illness who is considered to be epidemiologically linked by time, place, and exposure to a probable or confirmed H5N1 case.

Confirmed case

1. A person meeting the criteria for a suspected or probable case, AND
2. One of the following positive results conducted in a national, regional or international influenza laboratory whose H5N1 test results are accepted by WHO as confirmatory:
   1. Isolation of an H5N1 virus;
   2. Positive H5 PCR results from tests using two different PCR targets, e.g. primers specific for influenza A and H5 HA;
   3. A fourfold or greater rise in neutralization antibody titer for H5N1 based on testing of an acute serum specimen (collected 7 days or less after symptom onset) and a convalescent serum specimen. The convalescent neutralizing antibody titer must also be 1:80 or higher;
   4. A microneutralization antibody titer for H5N1 of 1:80 or greater in a single serum specimen collected at day 14 or later after symptom onset and a positive result using a different serological assay, for example, a horse red blood cell haemagglutination inhibition titer of 1:160 or greater or an H5-specific western blot positive result.

An AI-affected area is defined as a region within a country with confirmed outbreaks of AI strains in birds or detected in humans in the last month (seek advice from the National Incident Room when in doubt). With respect to the H5N1 AI outbreak that commenced in Asia in 2003, information regarding A(H5)-affected countries is available at: http://gamapserver.who.int/mapLibrary/.

8. Laboratory testing

Testing guidelines
Laboratory confirmation should be urgently sought to confirm all suspected cases. Consult with the virologist, but combined nose and throat swabs (usually for adults) or nasopharyngeal aspirates (NPA) (usually for children) are recommended.
Specimens should be sent in viral transport media (VTM).

Samples should be tested at a reference laboratory for:

• PCR and/or IF for AI
• Viral culture and immunofluorescence (IF)/ PCR for influenza.

Other tests should be done at the discretion of the treating doctor.

Nasopharyngeal and throat swabs may induce coughing and should preferably be collected in a negative pressure room, if available, by HCWs wearing full PPE. Write on specimen forms and containers before entering the patient's room to collect the specimens.

Specimens should be clearly marked SUSPECTED AVIAN INFLUENZA to ensure prioritisation by the laboratory. Specimens must be enclosed in a leak proof container with a secure closure. The container must be placed in an appropriate biohazard bag with the biohazard symbol displayed. Specimens should not be transported in a pneumatic tube system.

9. Case investigation

Response times
Investigation
Immediately on notification of a suspected case, begin follow up investigation and notify the state/territory CDB. For confirmed case, the form "Avian Influenza (AI) in humans - Investigation Form" (see appendices) should be completed and transferred to state/territory CDB the same day.

Response procedure
Case investigation
The response to a notification will normally be carried out in collaboration with the case's health carers. Regardless of who does the follow-up, for confirmed cases, PHU staff should ensure that action has been taken to:

• confirm the onset date and symptoms of the illness
• confirm results of relevant pathology tests, or recommend that tests be done (the laboratory should be advised before sending the specimens)
• find out if the case or relevant care-giver has been told what the diagnosis is before beginning the interview
• seek the doctor's permission to contact the case or relevant care-giver
• review case and contact management
• ensure appropriate infection control professionals are notified and infection control policies are available to those caring for the case
• identify the likely source of infection.

Obtain a travel history, and follow up clinical results and case details.

Note. If interviews with suspected cases are conducted face-to-face, the person conducting the interview must have a thorough understanding of infection control practices, be competent in using appropriate personal protective equipment (PPE), and ideally have been vaccinated with the current (human) influenza vaccine.

Case treatment
Treatment of a case is the responsibility of the clinician in consultation with an expert virologist. Antiviral medications have been shown to attenuate disease in cases of human influenza if given early in the course of the illness (ideally within 48 hours). They may also be effective for treating AI. The preferred agents are neuraminidase inhibitors (oseltamivir and zanamivir).

Education
Provide Avian Influenza Fact Sheet to cases. Ensure that they are aware of the signs and symptoms of AI, the requirements of isolation, contact details of the PHU and the infection control practices and precautions that can prevent the transmission of AI.

Isolation and restriction
Infectious cases must be isolated until no longer infectious (see Timeline). Advice from the facility's infection control professional should be sought. Health care workers and others who come into contact with the case must use airborne, droplet, contact and standard infection control precautions (including eye protection if within 1m). The mode of transmission is unclear, but postulated to be mainly droplet and direct contact. However, the possibility of airborne transmission remains, and airborne precautions must be used. (See: http://www.who.int/csr/disease/avian_influenza/guidelines/EPR_AM_final1.pdf.)
Patients should be managed in a single room with airborne, droplet, contact and standard precautions and if available, a negative pressure room. Similarly, in a primary care setting such as a GP surgery, patient isolation and airborne, droplet, contact and standard infection control precautions should be employed. Acute cases should be managed in hospital. When discharged home, a comprehensive discharge plan must be made by the treating hospital medical team in liaison with the PHU ensuring that the case and contacts are counselled about risk, and that appropriate infection control measures are in place.

Active case finding
None routinely.

10. Control of environment

Where local transmission of AI is thought possible, a thorough review of contributing environmental factors should be performed. If transmission is thought to be poultry-related, the environmental assessment should include a review of opportunities for exposure to infected birds, in collaboration with state/territory DPI and the state/territory work safety authority. If health care-associated infection is suspected, the adequacy of infection control procedures must be reviewed.

Staff conducting the environmental evaluation must have a thorough understanding of infection control practices, be competent in using personal protective equipment (PPE), and have been vaccinated with the current (human) influenza vaccine. They must follow airborne, droplet, contact and standard infection control precautions, including appropriate PPE (gown, gloves, protective eyewear and P2 mask).

11. Contact management

Identification of contacts
AI is not easily transmitted between humans, and probably requires close and prolonged contact. Public health interventions need careful consideration on a case-by-case basis. Following a report of a confirmed case, a CDNA Panel should be convened by the state/territory CDB to help plan the public health response. The Panel may include the patient's clinician and the local PHU.

Contact definition
The evidence base for defining what constitutes "contact" with a human case is limited. For the purposes of the contact definition, it is taken to mean being within one metre (e.g. caring for, speaking with, or touching) of an infectious case within the previous 7 days, in the absence of appropriate infection control. The CDNA panel will advise on a more specific contact definition as required. Where a case has travelled on an aeroplane, contacts are defined as persons sitting in the seats immediately beside the case.

Prophylaxis
Antiviral medications may be effective in preventing disease in contacts. Unless the available evidence clearly shows lack of efficacy, close contacts of confirmed cases will generally receive anti-influenza medication (neuraminidase inhibitors - oseltamivir and zanamivir) to prevent infection. The CDNA panel will provide more specific advice as needed.

Education
Contacts should be counselled about their risk and the symptoms of AI and placed under surveillance (see "Avian influenza ("bird flu") advice for people under surveillance" in appendices).

Isolation and restriction
Contacts are not required to isolate themselves from the community but must adhere to advice regarding self-monitoring until the incubation period expires (see Timeline, above).

The PHU should ensure that contacts are reviewed daily for 7 days to determine if symptoms of AI have developed. If symptoms develop, the contact must be rapidly isolated until AI is excluded. The PHU should arrange assessment by an appropriately skilled medical practitioner. This must take place in a setting where risk is managed through the use of appropriate infection control precautions.

12. Special situations

AI in birds in Australia
Where state/territory DPI reports an outbreak of AI in birds in Australia, the PHU is responsible for ensuring that the risk of human infection is minimised. The public health actions should be guided by the CDNA Panel, which will be convened by state/territory CDB and include the local PHU director. Issues to be addressed include:

• Working with state/territory DPI and work safety authority to ensure that people entering the area deemed by state/territory DPI to harbour infection have been trained in the use of PPE, and use it where the potential for exposure to infected birds or the dust from infected birds is present.
• Providing oral and written information to people who were exposed to the infected birds about the risk of infection, the methods of minimising the risk, symptoms to be alert for, and to report to the PHU immediately, should symptoms occur.
• Assessing whether people who were exposed to infected birds require anti-influenza medicine, and if so arranging supply (via the state/territory health department) and administration of the medicine. Ordinarily anti-influenza medicines will be limited to persons with direct exposure to infected birds in the absence of appropriate PPE.
• Placing exposed people under surveillance for seven days. Should symptoms develop, the PHU should arrange for a medical assessment and diagnosis of the person.
• People co-infected with avian influenza and human influenza infections are thought to provide the potential for re-assortment of genes from the two strains of influenza, that could result in a new human pandemic influenza strain. Poultry workers and other people directly involved in culling poultry infected with avian influenza should receive annual influenza immunisation. While immunisation will not prevent AI, it will help prevent infection with seasonal human influenza strains and therefore reduce the risk of co-infection, re-assortment and a pandemic.

13. Additional sources of information

• http://gamapserver.who.int/mapLibrary/
• http://www.oie.int/eng/en_index.htm
• http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1195733850800
• http://www.who.int/csr/disease/avian_influenza/country/en/.
• Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on Avian Influenza A (H5N1) Virus Infection in Humans. N Engl J Med 2008: 358: 261-273. http://content.nejm.org/cgi/content/full/358/3/261

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14. Jurisdiction specific issues (NSW)

Legislation

• Avian influenza in humans is notifiable by doctors, hospital CEOs and laboratories under the NSW Public Health Act 1991
• Avian influenza is a quarantinable disease under the Australian Quarantine Act 1908

Area Health Service coordination
The local Health Service Functional Area Co-ordinator (HSFAC) can assist with logistics issues.

Appendices

• Avian influenza factsheet
• PHU Avian influenza Check list
• Avian Influenza in Humans Investigation form
• Avian Influenza ("Bird Flu") Advice for People Under Surveillance.
• Avian influenza (AI) in humans: Interim guidance for health care workers