Preparing for an influenza pandemic

The most arresting brief I have so far received was that from the Chief Medical Officer, Professor John Horvath, about the potential threat of an influenza pandemic occurring. The brief warned of the far from hypothetical risk of a new disease that could infect up to 25% of the population in the first 3 months of a moderate outbreak in Australia. Since February 2004, the Commonwealth Government has taken this threat just as seriously as it would a threat to national security, and has implemented a series of precautionary measures that mean Australia is better prepared than almost any other country in the world to deal with a new influenza strain if it emerged. This supplement provides a snapshot of the latest research and preparations being undertaken in Australia to adequately respond to an influenza pandemic should it occur. A range of health professionals explore planning to counteract a possible pandemic; the biology and history of the influenza virus; the clinical manifestations of influenza; laboratory diagnosis; the role of antivirals, vaccine development, non-pharmaceutical interventions, and infection control in a pandemic; and the crucial role of general practice. I expect this supplement to generate debate among health professionals and the general community as we all grapple with our roles, responsibilities and possible responses to a potential pandemic influenza outbreak. Tony Abbott Australian Government Minister for Health and Ageing

Tony Abbott

The severe acute respiratory syndrome (SARS) epidemic of 2003 sounded a wakeup call for business and political leaders everywhere. This relatively brief experience with a previously unknown pathogen reminded us that rapidly spreading, lethal respiratory infections are both terrifying and cause substantial economic damage. Although there were only 8000 or so known cases, with about a 10% mortality, the global cost was estimated at between 20 and 40 billion US dollars. We were fortunate that the causative agent was identified quickly and that the epidemic was soon contained. Particularly important was the well established World Health Organization influenza program, which, with its collaborating network of national laboratories, provided the technological and organisational base. SARS illustrated very clearly how the application of contemporary science in the context of open international cooperation serves to protect humanity. We were also reminded of what happened in 1918–1919, when some 40 to 100 million people, including at least 10 000 Australians, died from the “Spanish flu”. Although the accumulation then dispersal of soldiers in the battlefields of Western Europe probably had an effect on transmission, the disease spread everywhere and was by no means confined to countries that had been directly affected by the Great War. At that stage we had no real idea how the pandemic originated, and, in fact, we did not isolate the first human influenza A virus until 1933. Recently, the reconstruction of the 1918 killer has established that this A/H1N1 virus came originally from birds. The same is true for the subsequent 1957 (A/H2N2) and 1968 (A/H3N2) epidemics. For that reason, the influenza research community has been keeping a very close watch on, particularly, aquatic birds — the natural maintaining hosts of these viruses. Over the years, we have seen other occasional instances where A/H7N7 and A/H9N2 infections have transmitted from birds to humans. Much more concerning was the 1997 occurrence in Hong Kong, where an A/H5N1 avian virus infected 18 people and six died. The outbreak was quickly controlled, but the H5N1 infection continued to circulate in apparently healthy ducks in coastal China and spread east and north to Korea and Japan, and south to Vietnam, Cambodia, Thailand, Laos, Malaysia and Indonesia. Then, in May 2005, a massively lethal outbreak in bar-headed geese at China’s Qinghai Lake established the involvement of a much broader range of migratory birds. Monitoring for dead swans and geese showed the virus moving westward to India, Europe and Africa. As at 16 October 2006, there have been 256 human cases with 151 deaths since 2003, including 42 deaths from 93 infections in Vietnam, six from 15 in Egypt and 55 from 72 in Indonesia. Although the virus has been changing rapidly, there is minimal evidence of subclinical “background” infection, and the indications of possible person-to-person spread are very limited. The combination of low infectivity but great severity in humans could reflect that the distribution of the α2-3 sialic acid receptor used by the avian influenza A viruses is limited to the deeper regions of the lung. One fear is that the virus may mutate to bind the “mammalian” α2-6 sialic acid receptor found in the upper respiratory tract. A further possibility is that simultaneous infection of a pig or a person with, say, “human” H3N2 and “avian” H5N1 viruses could give a “reassorted” H5N1 virus that spreads readily between people. The informed research community is divided on whether either scenario is likely. One school has it that, although the H5N1 virus is a terrible pathogen for birds that sometimes crosses into other species (humans, cats) with disastrous consequences for the individuals concerned, it will remain essentially an avian virus. The alternative view is that it is only a mutation or two away from establishing in people. There’s the quandary: the potential threat has horrific proportions, but it is not clear whether anything will actually happen. As you will read in the following pages, the Australian Government, represented by Health Minister Tony Abbott, and the scientists, epidemiologists and medical professionals who plan for epidemic preparedness have taken this very seriously. I’ve been watching mainly from the sidelines as, although our research group works with influenza A viruses (including H5N1) in Melbourne and Memphis, we focus on fundamental aspects of T cell-mediated immunity that have little immediate relevance to the current quandary. The pragmatism and willingness to face what are some very difficult choices has been impressive. In a sense, this has been more like developing a national defence initiative than a medical strategy. Significant dollar sums have been spent preparing for something that we all hope will never happen. A national plan is in place, and both private “think tanks” and elements in the business community have also been addressing the issue. Australians should rest assured that this country is as prepared for a possible H5N1 pandemic as any nation on earth, including the United States, which, with strong leadership from President Bush, has also been very proactive. However, there are no certainties. The virus could mutate to defeat the newly developed “reverse genetics” vaccines or the antiviral drugs (oseltamivir and zanamivir) that are currently being stockpiled. In general, though, the more time goes by, the better off we are likely to be. Also, even if this pandemic does not eventuate, the combination of rapid air travel and greater human population size (threefold increase since 1919) make some such occurrence a certainty for the future. Since 1979, some 30 new viruses (including SARS virus, Ebola virus and HIV) have crossed into humans from animals. Even if we duck the bullet this time, the effort and resources expended here will have ensured that our capacity to deal with an unexpected invader is enhanced. Peter C Doherty Department of Microbiology and Immunology University of Melbourne, Melbourne, VIC

Peter C Doherty

Scenario OneWhile driving to work, Dr Robinson hears on the radio that there has been a marked increase in the past few weeks in the number of human cases of bird flu in Vietnam and Thailand. On arrival at his practice, Dr Robinson notices that the receptionist has put a box of surgical masks on the bench. The practice is busy. His four other partners are already behind schedule. Halfway through the morning, the receptionist knocks on the door. She is wearing a mask. Dr Robinson chides her for scaring patients. She replies that she is not taking the mask off. “Mr Brindol is out there, hasn’t got an appointment. He is coughing and he has just been to Thailand.” She adds, “He is very sick, you should see him straight away.” Dr Robinson follows the receptionist into the waiting room. Matt Brindol is sitting among the patients. Lily Chatwa, due to give birth in 2 weeks, is sitting next to him. Matt Brindol is 26 years old. A triathlete, he is known to the practice for being obsessed with diet and fitness, and concerned about any minor injury. Dr Robinson is struck by Matt’s appearance. He is pale and sweaty, and coughing into a handkerchief. He is holding on to his chair with one hand as if he is afraid he will fall off. Matt tells Dr Robinson he returned from Thailand 2 days earlier. His illness started on the way back: sore throat and muscle pains. The cough started yesterday. His pulse rate is 98 beats/min, blood pressure 100/70 mmHg, and temperature 38°C. Dr Robinson rings the local public health unit, who advise him to collect nasal and throat swabs. The patient, Dr Robinson is told, should be isolated until the results exclude avian influenza. Dr Robinson puts on a surgical mask and gloves, takes swabs for viral studies, and rings the nearest laboratory for the courier service. He puts a surgical mask on Matt and says he must go home, and not see anyone until he is contacted. Dr Robinson tells him it is probably a cold virus, but they had better be careful as there is a slim chance it is bird flu. Three hours later, the laboratory informs him that Matt Brindol, on the first test, is positive for influenza A. They have already sent the sample to a reference laboratory for further testing. It is late afternoon; Dr Robinson hasn’t had a break when the reference laboratory calls. The preliminary tests are positive for influenza A/H5N1. They are running confirmatory tests. The public health physician, Dr Tantu, informs Dr Robinson that Matt should be started on oseltamivir immediately for treatment, as should anyone who has been in close contact. The local pharmacy has no oseltamivir. Dr Robinson gets the receptionist to ring all pharmacies to find some. He asks the other doctors if they could take his remaining patient load so he can work on the contacts. The staff are alarmed at the activity. The public health unit sends a nurse to help with contact tracing and infection control. She arrives wearing a mask, gloves and apron, and carrying a bottle of disinfectant. Dr Robinson rings Matt, but there is no answer, so he drives to Matt’s house. Matt is not at home. One of the neighbours informs Dr Robinson that an ambulance had been a couple of hours ago. Dr Robinson rings the local hospital and informs the emergency department registrar. The registrar replies that Matt has been admitted and was isolated. Dr Tantu is still tracing patients from the practice. She has been called by the hospitals, who are demanding she request a supply of oseltamivir, the influenza antiviral, from either the state or federal stockpile. Dr Tantu asks Dr Robinson to take over contacting the practice’s patients. She needs to get the paperwork done and contact authorities to try to get release of oseltamivir. She hands Dr Robinson a file. “You’ll need to collect these details.” It is almost midnight. On the way back to his practice, Dr Robinson hears that a case of bird flu has been confirmed in his town. He realises with a start that, of course, Matt is the confirmed case. There are three additional suspected cases in Victoria. Overseas, there are confirmed cases in Thailand and Vietnam, and possible cases in Hong Kong and the United States. There is major concern that the avian influenza strain has changed to a form transmissible between humans. The World Health Organization is meeting urgently to review the alert level. At the practice, the receptionist is still there. Dr Robinson asks why she hasn’t gone home. She replies that she is too scared. She listens while he runs his voicemail. There are seven messages: one from one of the other practice doctors stating she is not coming in until the situation is clear in regard to the bird flu. The second is from the Divisions of General Practice wanting to talk to him about the practice being the designated flu practice for the area. The next is a message from Dr Tantu — Lily Chatwa has refused to take antivirals, could he talk to her. Three messages are from media: the local paper, ABC Television and a radio station, all wanting interviews. The seventh is from the hospital saying that Matt Brindol died in intensive care while being intubated. Dr Robinson insists his receptionist take her oseltamivir, and reassures her that if she gets the slightest symptoms all her family will be given antivirals. The receptionist tells him she put all the used masks in the rubbish bin in the staff room, but the cleaning lady won’t touch it. She starts crying and holds up the Australian health management plan for pandemic influenza, and points to the paragraph which says that if someone gets infected the family will be in quarantine for a week. She has tickets to a Barry Manilow concert next week in Sydney and, come hell or high water, she is going to go. Dr Robinson goes home. As he stops the car, he realises he hasn’t taken his oseltamivir, and he has none left. CommentaryInfluenza A/H5N1 (“avian flu” or “bird flu”) has a high fatality rate in humans. Once it gains the ability to transmit from human to human, it is less likely to have as high a fatality rate. Its deadliness to the population will be its ability to spread rapidly.1 Pandemic influenza can potentially be controlled.2 Key to the control is rapid diagnosis and early action. Practices need to have plans in the advent of a contagious respiratory disease.2,3 Knowing who to speak to in the regional laboratory and public health unit is essential.4 Ensuring all health care workers know their roles and have contingency plans for events will reduce the pressure on key individuals. Plans also need to take into consideration the roles and concerns of non-medical staff. Scenario TwoThe federal Chief Medical Officer has announced Pandemic alert level 5 in Australia: Large clusters but human to human transmission still localised, suggesting that the virus is becoming increasingly better adapted to humans, but may not yet be fully adapted (substantial pandemic risk). Dr Mackley is running a “non-flu” practice. She was relieved that the large practice in the next suburb was willing to be a flu practice. “Flu practices” have been designated in her area, as the medical practitioners in discussion with the local council had decided that that was easier then setting up a fever clinic. Radio and television announcements and posters in the street and on the practice door direct people with fever or respiratory symptoms to the flu practice. One of the doctors who had not wanted to work at the flu practice has come over to her practice. Her practice nurse had volunteered to assist the public health unit in monitoring people in quarantine. All in all, a bit chaotic, but the arrangements were working. Dr Mackley is very busy. There are many new patients with chronic illnesses and complex histories. This morning, Mrs Darnley brought in her 3-year-old girl, Phoebe. Phoebe has a 2-day history of diarrhoea and is refusing to eat or drink. The diarrhoea has not been severe, but the child on examination is moderately dehydrated, pale and listless. She is afebrile. Dr Mackley decides to observe the girl for a while in the treatment room, and asks the mother to keep the child sipping on rehydration fluid. Dr Mackley takes a phone call from a regular elderly patient, Mr Stilton, who has a cough, feels unwell and wants to come in. He won’t go to the flu practice. He doesn’t believe he has the flu, but is sure he will catch it if he goes there. Dr Mackley rings the flu practice. They have a home visiting team. The flu practice say they will do a phone assessment, but their home visiting team has at least 10 houses to go, and by the way, did her practice have any extra staff she could send over? As Dr Mackley is speaking on the phone, the daily fax comes through from the public health unit, listing houses in quarantine. She notes how much longer the list is today. She runs her finger down the list and stops at one. The house next door to the Darnleys’ house is in quarantine. Dr Mackley checks on Phoebe. She is feverish and whimpering. Dr Mackley rings the hospital and orders an ambulance. All ambulances are busy. She gets through to the paediatric registrar who informs her that young children with pandemic flu are presenting with atypical symptoms, often with gastrointestinal symptoms and sometimes encephalitis. Dr Mackley quietly informs the rest of the staff that the child is a possible case. Dr Mackley rings the public health unit and requests oseltamivir tablets for the practice and the family, and paediatric suspension for the child. Medication will only be provided for the girl and not for contacts until the case is proven. Dr Mackley puts on a surgical mask, gloves and gown, and enters the treatment room. The mother is distraught. Dr Mackley tries to reassure her. She asks her to wear a mask and gloves and to hold the child while she puts an intravenous line in. Later that day, Phoebe is confirmed as infected. The staff are put on post-exposure prophylaxis, but not required to be in quarantine. Dr Mackley, after discussion with the staff, decides the practice will remain a non-flu practice. In a lengthy meeting, the staff are debriefed. They reconsider the plans as to what to do with a suspect patient. They revise the infection control processes and go through, in detail, the management of personal protective equipment and disinfection of possibly contaminated areas. They all decide to keep a chart monitoring their temperature on a twice daily basis. Only one staff member says she will consider staying at home. As Dr Mackley is winding up the meeting, Mr Stilton walks through the door, coughing. CommentaryAntivirals and personal protective equipment (PPE) from the National Medical Stockpile will be distributed to a nominated point in each jurisdiction. The distribution from there will follow a jurisdictional plan.2 Primary health care practices should maintain a supply of PPE. All staff should be aware of and know how to implement infection control processes.5 The effectiveness of antivirals against a pandemic influenza virus will not be known until cases begin to occur.6 Consider antivirals as one of the tools: infection control practices, social distancing, quarantine practices and clinical control measures will be as important. Atypical presentations of influenza can occur, particularly in the young and elderly.7 The spectrum of disease in an influenza pandemic will only become known as the pandemic evolves. Scenario ThreeIt is 3 months since the first cases of pandemic influenza in Australia. Lime, a town of 23 000 people, has been badly affected by the pandemic influenza. All health care workers in the area have been put on prophylactic antivirals. The government is still maintaining a containment policy. Vaccine is at last being produced, and the town of Lime is one area designated to receive the first consignments. Health care workers will receive the vaccine, then the children. For several weeks, Dr Turner has been working as a member of the home visiting team. He wears PPE all day and at the end of the day disposes of it, showers, and changes into “non-contaminated clothes” in an area set up by the local hospital. His family has been confident, and knows that if any of them get infected they will get antivirals. Dr Turner has also been asked to work with the public health unit and local government to set up the vaccination clinics and education for health care workers. Two weeks ago, Dr Turner had a mild cough. It only lasted a day. He had nasal and throat swabs which came back negative. He decided to stay in the hospital flats to reduce the risk to his family On this day, he is asked to visit a family, the Gowers, who live in the same street as his family. The son, Ben, is sick and on antivirals. The boy’s parents have reported deterioration in his condition. Ben is Dr Turner’s daughter’s boyfriend. Dr Turner examines Ben; he is cyanotic and afebrile, with a very low blood pressure. Dr Turner has seen this look before and knows the boy is likely to die. He notes Mrs Gower is unwell and finds out that she has been giving all her antivirals to Ben. Ben stops breathing. He has no pulse. Dr Turner reaches for the adrenalin in his doctor’s bag. He stops and instead turns to the family and informs them that Ben is dying and that they should say goodbye. “Hold his hand.” He adds, “Then you will need to wash your hands.” Dr Turner writes out a certificate of death. He rings the public health unit and informs them of Ben’s death and that Mrs Gower will need antivirals. He rings the funeral services for the Gowers. At the public health unit, the first batch of vaccines arrives under heavy guard. There had been no time to set up the needed vaccination processes. Of three nurses accredited to give vaccinations, only one has used multidose vials. Dr Turner works with the public health unit around the clock and finally has a flowthrough clinic design organised for the town hall. Six health care workers who can vaccinate have been found. Dr Turner is not sure of the validity of two of the nurses’ accreditation. Immunity will take two doses and 4 weeks for each person. “We can have this town immune in 4 to 5 weeks”, the public health doctor states. Dr Turner is not sure that that is going to be quick enough. Two days later, in his daily phone call to his family, he finds out that his daughter has a temperature and has been assessed at the fever clinic and started on antivirals. The laboratory is no longer doing testing and on the new definition, she has been classified as a positive case. She gave a history to the fever clinic of meeting with Ben while he was supposedly in quarantine. Dr Turner decides to go home and spend the quarantine with his family. He offers to do phone assessments from home. On the first day at home, he gets a call from the laboratory. The second serum test shows he has had infection with A/H5N1 and he now has protective antibodies. They need him in the workforce. CommentaryAs an influenza pandemic progresses, the role of the health care worker may change. This will depend on skills, family pressures and immune status.3,8 Over the years, a move has been made towards specialisation and accreditation in many skills. In a pandemic, ideally, health care workers will need a number of skills. A stocktake in an area of personnel who have the skills and authority to carry out activities such as vaccination should be done before a pandemic.9 In many communities, general practitioners may be dealing with families they have known for many years. GPs may need to make decisions which seem to go against the principles they have been trained in.8 GPs will have a role in ensuring their community understands “social distancing” and the requirement for quarantine within that.3 Compliance with quarantine will rely on many issues, such as provision of food to the quarantined household and ability for people to carry on business and education, perhaps through electronic services.2

Moira McKinnon

Australia’s preparedness for a potential influenza pandemic involves many players, from individual health carers to interdepartmental government committees. It embraces a wide number of strategies from the management of the disease to facilitating business continuity. The key strategy underlying Australia’s planned response is an intensive effort to reduce transmission of the virus. This includes actions to reduce the likelihood of entry of the virus into the country and to contain outbreaks when they occur. Containment will provide time to allow production of a matched vaccine. The health strategies are outlined in the Australian health management plan for pandemic influenza. The plan is accompanied by technical annexes setting out key considerations and guidelines in the areas of clinical management and infection control. National plans present overall strategies and guidance, but the operational details can only be determined by individual states and territories, regions, and the services themselves. Primary health care practices will be on the frontline of an influenza pandemic. Every practice needs a plan that defines the roles of staff, incorporates infection control and staff protection measures, and considers business continuity. Most importantly, a practice needs to know how to implement that plan.

John S Horvath MB BS, FRACP, AO · Moira McKinnon MB BS, MPH, FAFPHM · Leslee Roberts MB BS, MAE, PhD

Human epidemic influenza is caused by influenza type A and B viruses, which continually undergo antigenic change in their surface antigens, haemagglutinin (H) and neuraminidase (N). Influenza epidemics are the consequence of small, ongoing antigenic changes known as “antigenic drift”, which occurs in both influenza types. Pandemic influenza occurs at irregular and unpredictable intervals, and is the result of a major antigenic change known as “antigenic shift”, which occurs only in influenza A. Aquatic birds are the evolutionary hosts of influenza viruses; they harbour many distinct forms or subtypes of influenza A, which are usually present as harmless gut infections. Antigenic shift involves the evolution of a new human influenza A virus through the acquisition of a new haemagglutinin gene encoding a different subtype from an avian influenza, or by the adaptation of an avian virus, causing it to become transmissible between humans. Two subtypes of avian influenza, H5 and H7, can cause severe infections when introduced into domestic poultry. Recently, influenza A/H5N1 viruses have caused widespread outbreaks, starting in Asia and spreading widely to other regions. Avian influenza viruses do not readily infect humans. However, during the past 3 years, more than 250 cases of H5N1 infection of humans have occurred, with associated mortality approaching 60%. It is feared that a new pandemic of human influenza may emerge from this.

Alan W Hampson BSc, MSc · John S Mackenzie PhD

Influenza is an acute febrile illness caused by influenza A or B viruses. It occurs mainly in winter in temperate climates, and throughout the year in tropical Australia. It is highly contagious and of considerable public health concern because of the rapidity with which epidemics evolve and the associated morbidity and mortality. Most influenza illnesses resolve over about 1 week without specific medical intervention. People at particular risk for complicated infection are those > 65 or < 5 years old, those with chronic medical comorbidities, residents of chronic care facilities (including nursing homes), and women in the second or third trimester of pregnancy. Complicated influenza infection most commonly manifests as primary viral pneumonia, combined viral and bacterial pneumonia, and secondary bacterial pneumonia. Rare but serious complications of influenza include central nervous system involvement (eg, encephalitis, transverse myelitis, aseptic meningitis, and Guillain–Barré syndrome). The recent emergence of avian influenza A/H5N1 and confirmation of sporadic cases of human H5N1 infection have heightened concern about an impending human influenza pandemic, either from a human form of H5N1 or a primary new human influenza strain. H5N1 infection in humans has been associated with severe illness and a > 50% mortality rate, with high mortality in people aged 10–39 years.

Mark Boyd MD · Kate Clezy MB BS · Richard Lindley MB BS · Rod Pearce MB BS

Laboratory diagnosis is important to distinguish influenza from other respiratory virus infections. It will be especially important in detecting the first cases of pandemic influenza. Good quality respiratory tract sampling is needed to maximise diagnostic yield in influenza infection. In the appropriate clinical setting, pandemic strain-specific nucleic acid testing is the initial test of choice for suspected pandemic influenza. It is more sensitive than virus isolation, and more sensitive and specific than serology, immunofluorescence and other antigen detection methods. Virus isolation is needed to monitor new influenza strains and for vaccine development. Analysis of influenza isolates is undertaken by the World Health Organization Global Influenza Surveillance Network. Monitoring for antiviral resistance will be needed with widespread use of neuraminidase inhibitors for treatment and prophylaxis during a pandemic.

Dominic E Dwyer MD, FRACP, FRCPA · David W Smith BMedSc, MB BS, FRCPA · Michael G Catton BSc(Hons), MB ChB, FRCPA · Ian G Barr PhD

If an influenza pandemic occurs, the spread of the virus should be reduced for as long as possible while an effective vaccine is produced. Influenza spreads mainly by large respiratory droplets (> 5 μm) depositing onto the mucosal surfaces of the eye, mouth or respiratory tract. Hands are another major means for spread, and are frequently contaminated by droplets. The most effective way to reduce the spread of the virus is with good infection control practices and social distancing. Infection control practices include the use of personal protective equipment (PPE), hand hygiene, and respiratory hygiene and cough etiquette. Infected people should be isolated and spatial separation observed in common areas where infected people may be present. Any practices that create aerosols (eg, nebulisation) should be avoided, unless performed with appropriate precautions, especially with all people in the room wearing appropriate PPE. Now is the time to re-examine all our current practices so that we are better prepared, well practised and have good infection control practices in place for all transmissible respiratory infections.

Peter J Collignon FASM, FRCPA, FRACP · John A Carnie MRCP, FRACMA, FAFPHM

The Australian Government has an extensive stockpile of antivirals (neuraminidase inhibitors) to be used if an influenza pandemic occurs. Neuraminidase inhibitors reduce the duration of the symptoms of seasonal influenza infection by 1 day on average, when used as treatment within 48 hours of disease onset. Neuraminidase inhibitors prevent infection in up to 74% of people when administered as prophylaxis. Resistance of seasonal influenza viruses to neuraminidase inhibitors is low. The safety and efficacy (including resistance) of neuraminidase inhibitors against pandemic influenza or the virus of current concern in pandemic planning, influenza A/H5N1, is not known, and further research is needed.

Mary Ellen Harrod BA, PhD · Sean Emery BSc, PhD · Dominic E Dwyer BScMed, MB BS, MD

Prototype vaccines against influenza A/H5N1 may be poorly immunogenic, and two or more doses may be required to induce levels of neutralising antibody that are deemed to be protective. The actual levels of antibody required to protect against a highly pathogenic virus that potentially can spread beyond the large airways is unknown. The global capacity for vaccine manufacture in eggs or tissue culture is considerable, but the number of doses that can theoretically be produced in a pandemic context will only be sufficient for a small fraction of the world’s population, even less if a high antigen content is required. The safety of new pandemic vaccines should be addressed in an internationally coordinated way. Steps are underway through the Therapeutic Goods Administration to evaluate mock-up vaccines now, so that the time to registration of a new product can be minimised. It will be 3–6 months into the pandemic before an effective vaccine becomes available, so other control measures will be important in the early stages of a pandemic. The primary goal of a pandemic influenza vaccine must be to prevent death, and not necessarily to prevent infection.

Robert Booy MD, FRACP, FRCPCH · Lorena E Brown PhD · Gary S Grohmann PhD, FASM · C Raina MacIntyre FRACP, FAFPHM, MAppEpid

General practice will play a key role in both prevention and management of an influenza pandemic. Australian pandemic plans acknowledge a role for general practice, but there are few published data addressing the issues that general practitioners and their practices will face in dealing with such a crisis. The outcome will revolve around preparation in three key areas: Definition of the role of general practice within a broad primary care pandemic response, and adequate preparation within general practices so they can play that role well. Planning exercises and forums must include GPs, and rehearsals must include practical experience for general practices and their staff. Local Divisions of General Practice and GP practices can advocate for this, can define their role, and can prepare by using pandemic preparedness checklists. Definition and enactment of communication strategies to facilitate transfer of useful clinical and administrative data from practices and rapid dissemination of information into the community via general practice. Resource provision, which should be centrally funded but locally distributed, with personal protective equipment, vaccines and antivirals readily available for distribution. Resources must include support for human resource management to ensure appropriate health care professionals reach areas of workforce demand. Administrative, clinical and financial resources must be available to train GPs and practices in pandemic awareness and response.

Nick Collins FRACGP · John Litt FRACGP, MSc(Epid), DipRACOG, FAFPHM · Michael Moore FRACGP, GradDipPH · Tania Winzenberg FRACGP, PhD · Kelly Shaw FRACGP, MPH, PhD, FAFPHM

Hospitals will be particularly challenged when pandemic influenza spreads. Within the health sector in general, existing pandemic plans focus on health interventions to control outbreaks. The critical relationship between the health sector and other sectors is not well understood and addressed. Hospitals depend on critical infrastructure external to the organisation itself. Existing plans do not adequately consider the complexity and interdependency of systems upon which hospitals rely. The failure of one such system can trigger a failure of another, causing cascading breakdowns. Health is only one of the many systems that struggle at maximum capacity during “normal” times, as current business models operate with no or minimal “excess” staff and have become irreducible operations. This makes interconnected systems highly vulnerable to acute disruptions, such as a pandemic. Companies use continuity plans and highly regulated business continuity management to overcome process interruptions. This methodology can be applied to hospitals to minimise the impact of a pandemic.

Ralf L Itzwerth DipSoz · C Raina MacIntyre FRACP, FAFPHM, MAppEpi · Smita Shah MB ChB, MCH · Aileen J Plant PhD, MPH, FAFPHM

In the event of an influenza pandemic, many ethical issues will arise in terms of health risks, resource allocation, and management decisions. Planning decisions may be controversial, such as rationing of antivirals, resource allocation (including hospital beds and vaccinations), occupational risk, rostering of staff, responsibilities of health care workers, quarantine measures, and governance issues. A clear ethical framework is needed to enable understanding of the decision-making process and optimise acceptance of decisions by health care workers and other members of an affected community. Planning decisions need to start being examined now, and will require input from a broad group of experts: health care providers, infrastructure managers, lawyers, ethicists, public health physicians, and community members. The process will need to be open, honest and dynamic.

Adrienne Torda FRACP, GradDipBioethics, PhD

The Australian management plan for pandemic influenza (2005) highlighted a number of areas where more information may yield better plans for protecting Australia. In 2005, the National Health and Medical Research Council (NHMRC) developed a special “urgent research” funding program to meet those information needs as quickly as possible. The funding program resulted in grants totalling $6.5 million being awarded for 33 research projects, in five broad areas: Detection and identification of the virus; Vaccine development and evaluation; Antiviral medication use and effectiveness; Public health interventions; and Understanding behavioural responses to achieve effective communication and staged implementation of public health strategies. Outcomes of the program will be evaluated formally in 2007.

Tania C Sorrell MD, BS, FRACP · Carey Lonsdale BSc, MSc

It has been enormously gratifying assembling this supplement on pandemic influenza. There are a large number of authoritative articles and supplements worldwide that provide enormously helpful information. Nevertheless, we felt that we lacked a coherent and concise package of information readily available to a broad constituency of health care providers, policymakers and the general public, dealing largely with the Australian health management plan for pandemic influenza. The Australian Government, in collaboration with academic and community expertise, has invested significantly in the development, implementation and monitoring of a national plan to respond to the public health threat of pandemic influenza. This task has been enormous, embracing a “whole of government” approach with the intent of looking after the sick, containing any disease outbreaks and, critically, preserving as much as possible of services and society. State and territory health departments, local area health authorities, public and private medical services and other utilities have each been asked to commence planning and preparation for their respective jurisdictions. Inevitably, there is diversity, reflecting the levels of engagement and the types of responses that are being considered. It is worth asking: How ready is my workplace for a pandemic?; What is my role?; Have I been involved in discussions? Judging by history, all communities will be profoundly affected by an influenza pandemic if it occurs. Furthermore, critical responses were found wanting in many countries during the outbreak of severe acute respiratory syndrome in 2003. Therefore, we felt that there had to be effective communication of the current Australian plan, as well as brief but relevant reviews of some of the issues around influenza that underpin how the plan has evolved. Of course, many of these issues are relevant to seasonal influenza, as well as other emerging infectious diseases. For many issues, there simply are no straightforward solutions, and it is in this context we encourage further discussion and debate to move the field forward. There can be no doubt that the Commonwealth Government response to the threat of pandemic influenza has been remarkable. Australia is acknowledged globally for adopting an incredibly mature and proactive position and, from that political leadership, developing one of the most comprehensive and well equipped responses in the world. Most recently, the pandemic plan has been subjected to an evaluation in the form of Exercise Cumpston (named after the Commonwealth Director of Quarantine during the 1918–1919 pandemic). Over the coming weeks and months, we look forward to hearing the lessons learned from this exercise. We commend all the authors of the articles in this supplement for embracing our vision with rigour. Each responded admirably and willingly to our request, and each complied with brutally short time frames. We acknowledge and thank the Australian Government Department of Health and Ageing for their financial support and guidance in producing this supplement. Sean Emery Head, Therapeutic and Vaccine Research Program National Centre in HIV Epidemiology and Clinical Research University of New South Wales, Sydney, NSW Dominic E Dwyer Medical Virologist Centre for Infectious Diseases and Microbiology Laboratory Services Institute of Clinical Pathology and Medical Research Westmead Hospital, Sydney, NSW Moira McKinnon Senior Medical Officer Department of Health and Ageing Canberra, ACT

Sean Emery · Dominic E Dwyer · Moira McKinnon