Infectious diseases

To the Editor: A seminal 1997 article by Fine et al described the pneumonia severity score from the Pneumonia Patient Outcomes Research Team study and raised the role for Hospital in the Home (HIH): For the remaining patients in [risk] classes II and III for whom treatment at home with oral antimicrobial therapy is judged to be unsuitable, there are alternatives to traditional inpatient care. These include parenteral antimicrobial therapy at home or a short stay . . . in a hospital observation unit.1 A recent article in the Journal by Charles et al2 omitted a role for HIH in managing community-acquired pneumonia (CAP). Where their protocol mentions outpatient care, readers are led to interpret this as oral therapy only, managed by a general practitioner. Similarly, it is implied that inpatient therapy relates to traditional treatment in a hospital ward. No further clarification is given. This is a surprising omission, given that one of the authors has written extensively in support of HIH in the past.3 HIH administers hospital-level therapy (intravenous antibiotics, oximetry, rehydration, medical and nursing attendance, with 24-hour cover) to a clinical subgroup of CAP patients who can be defined and included within any protocol. Evidence suggests that HIH can offer effective and safe treatment of patients with acute CAP referred directly from hospital emergency departments after diagnosis.4-6 Many patients with pneumonia appreciate the option of well organised, acute, home-based care. An important and growing subgroup of patients living in residential nursing care facilities can also receive acute CAP treatment in facilities with HIH involvement.7 A significant proportion of patients receiving HIH care have failed oral therapy.4-7 Why the omission of HIH? Protocols are tools of influence to be tussled over. This sometimes conflicts with their general aim of organising science into process and progress. Fine and colleagues’ intent in investigating the use of pneumonia severity scores was to help address the question of where and how to treat acute pneumonia. One of the aims of developing scores was to broaden the treatment options, not to narrow them.

Michael Montalto

To the Editor: The recent editorial on community-acquired pneumonia (CAP) stated that “even in an era in which penicillin resistance appears to be increasing among some Streptococcus pneumoniae isolates, there have been no documented failures of high-dose penicillin in treating pneumococcal pneumonia or bacteraemia”.1 The medical literature suggests otherwise. Firstly, North American guidelines do not mention penicillin at all, and, in one analysis of 25 996 hospitalised patients who received monotherapy, mortality was about 50% higher with penicillin monotherapy than with monotherapy with ceftriaxone, another cephalosporin, a macrolide or a quinolone.2 More importantly, however, the same study found that the mortality rate in patients (even low-risk patients) treated with two antibiotics, one of which was a macrolide, was half the mortality rate of patients treated with one antibiotic. Dual therapies used were a macrolide agent in combination with ceftriaxone, another cephalosporin, a penicillin or a quinolone. Best outcomes were achieved with a ceftriaxone–macrolide combination. In a review of seven studies, Waterer3 found that patients with severe pneumococcal pneumonia or bacteraemic pneumococcal disease who were treated with two antibiotics had a significantly lower mortality rate than patients treated with a single antibiotic. This was despite the fact that the patients treated with a single antibiotic were not as ill initially as those treated with two antibiotics. Research by Waterer and colleagues4 showed that the benefit of taking two antibiotics was most apparent in the highest risk hospitalised patients, in whom mortality was five times higher in those receiving one antibiotic than in those receiving two. Thus, it is imperative that all patients with severe pneumococcal CAP be treated with two antibiotics, one of which should be a macrolide.

Patrick J Bradley

In reply: Whether Hospital in the Home (HIH) care is suitable for managing patients with community-acquired pneumonia (CAP) depends on what is considered an appropriate use of resources. Overall, we see relatively few indications for treating CAP patients with parenteral antibiotics via HIH, as, in our experience, most patients who do not need supplemental oxygen and are well enough to be treated at home are usually also well enough to be treated with oral antibiotics. If they are not well enough to take oral antibiotics, then admission to hospital as an inpatient is generally appropriate. The occasional exceptions to this are selected patients in nursing homes (where around-the-clock supervision is available if required) and some patients with CAP caused by pathogens like Pseudomonas or Acinetobacter who benefit from longer treatment courses and may not have the option of oral antibiotics. Furthermore, a report submitted to the Victorian Department of Human Services regarding HIH care of CAP patients at a number of Melbourne HIH units identified significantly worse outcomes at some centres, mainly related to inappropriate patient selection. Notable, but fortunately rare, cases included some patients with pulmonary embolism incorrectly diagnosed as CAP. Given that between 20% and 50% of patients given a diagnosis of CAP in the emergency department do not have pneumonia confirmed by a radiologist,1-3 the ability of busy emergency department doctors to select patients appropriately is definitely a concern. Thus, HIH treatment of CAP patients may be appropriate occasionally, but very careful patient selection is vital. In response to Bradley, the statement that there have not been any failures in treating pneumococcal CAP with penicillins refers to microbiological failures due to antibiotic resistance. Although several studies have suggested that combination therapy may reduce mortality from bacteraemic pneumoccocal infections, all of these have been retrospective observational studies. Thus, they lack the ability to control accurately for potential confounding variables such as disease severity, patient or family wishes, pre-morbid quality of life, or “not for resuscitation” status. Data are also lacking on co-infection with “atypical” pathogens such as Legionella. The immunomodulatory effects of macrolides, quinolones and tetracyclines on treatment response are also still being elucidated.4 We agree with the CAP treatment recommendations in the Australian antibiotic guidelines,5 which recommend dual therapy with a β-lactam antiobiotic plus either a macrolide or doxycycline for all patients who are not allergic to these drugs.

Patrick G P Charles · Paul D R Johnson · M Lindsay Grayson

A national strategy for meeting the particular health needs of refugees would provide a more comprehensive approach The profile of refugees being resettled in Australia depends on global geopolitical conflicts, representations from the United Nations High Commissioner for Refugees to the Australian Government, and Australia’s response. Recent years have seen an enormous shift within Australia’s annual refugee intake, with 70% originating from countries in sub-Saharan Africa.1 The Australian Government requires those migrating under its Humanitarian Program to undertake certain health checks before being issued with a visa.2 Additionally, since mid 2005, the Department of Immigration and Multicultural Affairs (DIMA) has been rolling out an additional medical check known as a predeparture medical screen (PDMS) in the few days before departure (Kathy King, Director, Special Health Projects, DIMA, personal communication). This medical check was introduced in response to significant numbers of cases of communicable diseases being identified among new arrivals. Conducted mainly by medical staff of the International Organization for Migration (IOM), it is largely a fitness-to-fly check, although it does include screening for malaria, measles–mumps–rubella vaccination, and empirical treatment for intestinal parasites. Although DIMA is expanding the geographical coverage for the PDMS, not all current humanitarian entrants are subject to this screening. In this issue of the Journal, a collection of articles and a letter on refugee health indicate a high prevalence of various conditions among recent refugee arrivals (Chih et al, Outpatient treatment of malaria in recently arrived African migrants; Tiong et al, Health issues in newly arrived African refugees attending general practice clinics in Melbourne; Martin and Mak, Changing faces: a review of infectious disease screening of refugees by the Migrant Health Unit, Western Australia in 2003 and 2004; Cherian et al, Severe Plasmodium falciparum malaria in refugee children despite reported predeparture antimalarial treatment). Some of the data were collected before the introduction of the PDMS, which may have lowered the rate of malaria and intestinal parasite burdens. However, recent experience in New South Wales has been that cases of malaria continue to be detected despite antigen testing overseas. The detection rate for HIV among this previously screened population reported here by Martin and Mak (page 607) is low (0.12%), but is not zero. Further consideration of whether to repeat routine HIV screening after arrival is warranted. Hepatitis B tests are only conducted in a minority of entrants,2 yet this disease has important personal and public health implications. It is apparent that the screening conducted overseas, no doubt under difficult circumstances, remains suboptimal. Additionally, conditions such as anaemia, schistosomiasis and vitamin D deficiency flagged in the articles are, appropriately, not screened for overseas, yet warrant early detection and treatment. At the same time, the risk to the public from various conditions must not be exaggerated, as this is potentially detrimental to attitudes about already marginalised people, as shown by Leask et al (page 591). The fact that refugees have considerable health care needs is well documented, and these needs vary with region of origin and other factors.3,4 Health care professionals in Australia may be unfamiliar with some conditions, and diagnosis might be delayed if these conditions are not detected in their asymptomatic stages through adequate screening. The principles of prevention and early intervention, our existing knowledge about refugee health care needs, and the additional evidence from the articles in this issue of the Journal justify a call for nationally coordinated, comprehensive health assessments to be offered to all newly arrived refugees. This need for comprehensive health assessments was highlighted in a recent report on refugee children.5 However, entire families in this setting have the same requirements, and a family-centred approach is needed. Health assessments must not only focus on infectious diseases, but should take into account the refugee trauma experiences of families and individuals, and assess physical, psychological and psychosocial needs. Sufficient attention needs to be given to oral health, nutrition, undermanaged chronic conditions, and the impacts of violence. Currently, each state and territory has a different model and varying coverage for postarrival checks, as shown by some of the reports in this issue. Some jurisdictions have centralised clinics in public hospital venues, focusing mainly on infectious disease screening (eg, Tasmania, Western Australia). NSW, with an annual intake of 4000 refugees who are dispersed widely across the state, has a state-funded Refugee Health Service with some clinical role but which also supports mainstream health services to assist refugees. Victoria has a different model again, with a focus on general practitioners in community health centres and private practice, supported by refugee health nurses. Sheikh-Mohammed et al (page 594) and Tiong et al (page 602) highlight the important role that GPs play in providing health care services to refugees. However, there are limitations to GPs being able to perform comprehensive assessments, including time constraints, the challenges of using an interpreter over the phone, and the need for specialised knowledge. The release in May this year of a new Medicare item number for refugee health assessments goes some way towards supporting GPs who take on this role.6 Unfortunately, the opportunity to link the release of this item number to targeted GP education was missed at the national level. Indeed, a system of “accredited practices” could even be envisaged, with key GPs linked into, and supported by, clinicians and public health staff experienced in refugee health. As with health care provision to other special-needs groups, there are debates about the need for mainstream versus specialised services.7 In locations with significant ongoing refugee settlement, a mix of models is likely to be needed. Publicly funded clinics offer a number of advantages, including centralised knowledge and strong links with key refugee agencies. Specialised health care services targeting refugees also provide important education and support to GPs and other health care staff. Whatever the model for providing health assessments, newly arrived refugees need help to overcome the barriers they face in accessing health care.8 Increased availability of DIMA-funded case workers and of volunteers will help refugees negotiate our complex health care systems.9 Community education about available health care services is also important. Mainstream health care services must be capable of providing sensitive, culturally appropriate care to these vulnerable groups. At the national level, there are a number of initiatives underway in refugee health in addition to the new Medicare item number. In response to issues similar to those raised in the articles in this issue, the Department of Health and Ageing has, over the past year, convened a working group on refugee health, with representatives from all states and territories. This group has made recommendations to the Australian Health Ministers’ Advisory Council, some of which aim to address issues raised by Tiong et al (page 602). These include the cost of certain medications, such as praziquantel for schistosomiasis, and the limited availability of some vaccines for catch-up schedules. Refugee health is a varied field crossing multiple disciplines and presenting complex issues. The development of a national refugee health strategy would promote greater direction, coordination and standardisation nationally. One aspect should be data collation and monitoring of disease detection prevalence across jurisdictions. National guidelines relevant to refugee health, some of which are already being developed, are required. Finally, although clinicians and others working with refugees do network informally, more formalised networks between these health professionals will aid communication and collaboration across borders.

Mitchell M Smith MB BS, MPH, FAFPHM

Objective: To report on perceptions about the risk of infectious diseases from new arrivals to Australia arising from a wider study of mothers’ attitudes to childhood vaccination.Design, participants and setting: Six focus groups on perceptions about the benefits and risks of vaccination with 37 mothers of children aged 5 weeks to 18 years, mostly conducted in middle-class areas of Sydney between 6 October and 15 December 1999.Main outcome measures: Mothers’ views about infectious disease risk posed by immigration as a major reason to favour immunising children.Results: The idea of immigration being the primary source of infectious diseases was striking, and arose among a number of participants in every group conversation. Mothers expressed their dread of new diseases “from overseas”, and a sense that there are “more germs nowadays”, mostly from increased immigration to Australia and international travel. Some perceived people coming from other countries as having more disease because of an innate susceptibility or through cultural practices.Conclusion: Recent media coverage about infectious diseases importation by African refugees not only feeds, but reflects, community concerns about new arrivals as a source of allegedly rampant infection threatening Australians. These concerns have little evidence base. Public health advocates need to be proactive with the media to provide sophisticated counter-messages that expose the underlying subtexts and educate the community about the true risks of infectious diseases.

Julie Leask PhD, MPH, DipAppSci · Mohamud Sheikh-Mohammed MIPH, MHSc, DipMedLabSci · C Raina MacIntyre FRACP, FAFPHM, PhD · Alexander Leask MPH, DipAppEpi, BAgSci · Nicholas J Wood MB BS, FRACP

To the Editor: Predeparture screening and treatment for Plasmodium falciparum malaria is increasingly administered to humanitarian refugees from malaria-endemic areas immediately before resettlement in Australia. It is undertaken by the International Organization for Migration (IOM), under contract from the Department of Immigration and Multicultural Affairs (DIMA).1 Combination therapy (usually an artemisinin derivative in combination with another drug, or chloroquine) is used for both adults and children. The first dose (of what is usually a 3–5-dose treatment course) is supervised, and written documentation of the treatment should accompany the refugee to Australia.1 Giving predeparture antimalarial treatment has the potential benefit of reducing the incidence of malaria after arrival, as well as reducing the risk of local transmission in malaria-receptive areas of Australia. Onshore health assessments are performed in about 80% of humanitarian refugees resettled in Western Australia (A Thambiran, Medical Director, Migrant Health Unit, Perth, WA, personal communication). Between August 2005 and March 2006 — a period of increased offshore predeparture management of malaria (in line with DIMA/IOM policy in response, presumably, to the increasing burden of imported malaria in refugees coming to Australia) — 336 African refugee children were screened on arrival in WA. Thirty-two children (9.5%) with P. falciparum malaria were identified, of whom 20 (10 Burundian, eight Congolese and two Sudanese) had received predeparture antimalarial medications. Eleven children who presented in a 3-week period had all been treated at a single centre in Kenya with pyrimethamine–sulphadoxine and artesunate, according to sighted IOM documentation. Of the remaining nine children, some had transited through countries other than Kenya, but not all had complete documentation. Three children presented with malaria parasite loads ranging from 6% to 14% within 7–10 days of arrival in WA. One child had severe malaria (14% parasite load), was obtunded at presentation and required intravenous quinine therapy and resuscitation. Overall, 15 of the 20 children treated before departure required hospital admission, despite our selective non-admission policy for uncomplicated P. falciparum malaria. No child had long-term sequelae and all had parasitological cure at Day-28 follow-up. Possible explanations for these apparent failures of predeparture treatment include: (i) incorrect documentation of treatment; (ii) poor compliance; (iii) lack of supervision; and (iv) inactive or expired medication. Delays in departure must also be considered at assessment, as these allow potential re-infection — in this cohort, the time between treatment and migration was poorly documented. Subsequent clinical presentation in WA ranged from 24 to 31 days after treatment in Africa (in cases where documentation was available). As all children were not treated at a single centre offshore, these cases are likely to reflect more widespread and multifactorial issues about the effectiveness of predeparture antimalarial management. Another concern is the rise of multidrug-resistant strains of P. falciparum, particularly throughout sub-Saharan Africa and South-East Asia. Combination therapy with artemisinin derivatives is now recommended by the World Health Organization as first-line treatment.2 However, many of the patients in this cohort received treatment with pyrimethamine–sulphadoxine and artesunate, despite reported high levels of parasite resistance.3 IOM protocols are evolving in an attempt to reflect the rapidly changing multidrug-resistance patterns in these malaria-endemic regions.1 A recent Ugandan study reported high Day-28 cure rates with artemether–lumefantrine (despite a relatively complex dosing schedule) because of lower drug resistance.4 These cases highlight the continuing need for comprehensive and timely onshore assessment (including malaria screening), irrespective of predeparture treatment. P. falciparum malaria remains a major global cause of morbidity and mortality — there were an estimated 515 million clinical infections in 2002, with 70% occurring in Africa.5 P. falciparum has a significant case-fatality rate (up to 20% in cerebral malaria6), even when managed appropriately. It results in 1–2 million deaths each year,3 mainly of children, and about 18% of all child deaths in sub-Saharan Africa are directly attributable to malaria.7 Australia resettles more humanitarian refugees per capita than any other nation8 and many are from malaria-endemic regions. Predeparture antimalarial treatment should reduce the number of clinical episodes of malaria presenting within Australia, but the efficacy of this unproven intervention warrants prospective study. Importantly, documented predeparture antimalarial treatment should not distract health care providers from considering this potentially life-threatening infection in a febrile child recently migrated from a malaria-endemic area.

Sarah Cherian · Joanna M Fagan · Aesen Thambiran · Janet Geddes · David Burgner

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

A veterinarian became infected with Hendra virus (HeV) after managing a terminally ill horse and performing a limited autopsy with inadequate precautions. Although she was initially only mildly ill, serological tests suggested latent HeV infection. Nevertheless, she remains well 2 years after her initial illness. Recently emerged zoonotic viruses, such as HeV, necessitate appropriate working procedures and personal protective equipment in veterinary practice. Hendra virus (HeV) and Nipah virus together comprise the genus Henipavirus within the family Paramyxoviridae (Box 1).1 HeV, formerly called equine morbillivirus, was first described after an outbreak of severe respiratory disease in horses, leading to the deaths of 14 horses and a horse trainer in Brisbane in September 1994.2,3 The trainer had had very close manual contact with frothy nasal and oral secretions, some of which were blood-tinged, from several of the very ill horses, as did a stable-hand; he developed an influenza-like illness but made a full recovery. The horses and both people were infected with HeV.2,3 An earlier outbreak of HeV disease was not recognised until the death, in 1995, of a farmer in Mackay. He had assisted his veterinarian wife with the autopsies of two horses that died suddenly from unknown cause in August 1994. He was hospitalised about 2 weeks later with an aseptic meningitis, from which he apparently made a full recovery.3,4 However, about a year later he became acutely unwell again, and died from a severe encephalitis caused by HeV.3,4 The two horses were (retrospectively) shown to have also been infected with HeV.5 After these two outbreaks, extensive investigations identified fruit bats (Pteropus spp.), commonly known as flying foxes, as the likely natural reservoir of HeV; the infection is probably subclinical in most infected flying foxes.6,7 Although it is not certain how HeV could be transmitted from flying foxes to horses, the isolation of the virus from uterine fluid and aborted fetal tissue of flying foxes suggests that horses could ingest the virus on feed or pasture recently contaminated by birth products (Box 2).6,7 The available evidence indicates that transmission of the virus from horses to people, albeit rare, occurs through physical contact with nasal and oral secretions emanating from very ill, dying or dead horses.8 The third recognised outbreak of HeV disease occurred in January 1999, when a horse in a northern suburb of Cairns died from pneumonia.9 No human infection associated with this equine HeV case was detected. We report here the fourth known outbreak of HeV infection and discuss the implications of this recently emerged virus for veterinary practice. Clinical recordIn early November 2004, a veterinarian notified the Tropical Population Health Unit (TPHU) in Cairns that one of his colleagues had become unwell a week after performing an autopsy on a horse. Two other people who had assisted with the autopsy, both members of the family who owned the horse, had apparently also become unwell, and the notifying veterinarian asked about the possibility of HeV infection in the three individuals. The horse: The horse was a 10-year-old gelding located on a property about 25 km south of Cairns. It had been acutely unwell for 1 day, with restlessness, increased respiratory effort and profuse sweating. On examination, the horse was febrile (41°C per rectum), tachycardic (120 beats/min), markedly dyspnoeic and very weak; it lay in a lateral recumbent position and could not raise its head. It was very dehydrated, and had injected mucous membranes and large amounts of blood-stained frothy secretions issuing from its nose. A decision was made to euthanase the horse, but it had a convulsion and expired before this could be performed. Blood-stained froth emanated from its nose and mouth as it died. Autopsy on the horse: Because the diagnosis was uncertain, the treating veterinarian performed a limited autopsy on the horse in the paddock where it died. She initially wore gloves, but quickly abandoned these as they were not of an appropriate design and soon became contaminated inside. No other personal protective equipment was used. For the procedure she had to reach deep into the carcass to examine some internal organs. The autopsy resulted in the veterinarian becoming heavily contaminated with the horse’s body fluids, especially those from the abdominal cavity. Contamination from the thoracic cavity was less, as this was opened only through a relatively small “window” over the heart. The veterinarian had a thorough shower immediately on returning home after completing the autopsy. The main gross findings at autopsy were massive fluid congestion of the lungs, cardiomegaly with marked thickening of the ventricular walls, and a grossly enlarged liver. The veterinarian concluded that the horse had died from acute heart failure and pulmonary oedema of unknown aetiology; no tissue samples were collected for further laboratory studies. At the completion of the autopsy, the horse was deep-buried using a back hoe. The veterinarian: Seven days after performing the autopsy, the veterinarian developed a dry cough and sore throat, associated with cervical lymphadenopathy and a fever lasting 4 days. She had generalised body aches and was very tired. The illness continued for about 8 days, during which time she was unable to work. She was seen 2 days after the onset of symptoms by a medical practitioner who had been informed (by the TPHU) of the possibility of HeV infection. However, the practitioner considered that her illness was consistent with a tonsillar infection and prescribed an antibiotic; blood was collected for HeV laboratory studies only. Follow-up serum samples were collected for further HeV studies at 14, 30, 50, 363, 470 and 559 days after the onset of symptoms. Laboratory studies: HeV RNA was not detected by a reverse transcriptase polymerase chain reaction (RT-PCR) (TaqMan) assay10 on the initial serum sample. Similarly, HeV IgM and IgG antibodies were not detected by either immunofluorescence assay (IFA) or enzyme-linked immunoassay (EIA).11 However, the subsequent samples demonstrated clear HeV IgM and IgG seroconversions by both IFA and EIA. A serum sample taken nearly a year later was initially reported as having a very high antibody titre on IgG IFA (>1024), but on repeat testing this was revised to a level of 512 (Box 3). Subsequent antibody levels have fallen by one dilution. A plaque reduction neutralisation test11 showed that the serum collected 14 days after the onset of illness neutralised HeV at a dilution of 1 : 5. Autopsy assistants: An adult member of the family who owned the horse held the dying animal’s head; two others assisted with the autopsy. All three were exposed to the frothy nasal secretions to varying degrees. Although the two who assisted were reported as having become unwell after the procedure, further investigation revealed that neither had a febrile illness. Rather, both seemed to have had symptoms of pre-existing conditions. HeV serological studies on samples collected from all three adults 3–4 weeks after the autopsy did not show any evidence of HeV infection. Site visit: A site visit took place on the day of the notification to TPHU, which was about 2 weeks before laboratory confirmation of HeV infection was obtained. The paddock was in a semi-rural area and held seven other horses, all of which appeared in good health. It was surrounded by other paddocks, some of which held horses. There was no obvious flying fox colony nearby; the owner of the property voluntarily quarantined the property (not allowing any horse movement in or out). Once the HeV infection in the veterinarian was confirmed, the other seven horses in the paddock were tested for serological evidence of HeV infection (38 days after the horse died); all were negative. The quarantine was subsequently lifted. DiscussionAll four reported outbreaks of HeV infection have occurred in Queensland, and three have occurred in the northern part of the state. Although no samples were collected from the horse, with hindsight it clearly had an illness consistent with previous clinical reports of HeV disease in horses. The disease is usually fulminant in nature, with fever, tachycardia, respiratory distress and a frothy nasal discharge being the typical reported features in horses.8,12 Facial oedema, physical distress and unease (suggestive of colic), and the close proximity of flying foxes add further support to the clinical suggestion of HeV disease in horses.12 The most obvious gross pathology is marked fluid congestion in the lungs, with a thick, foamy haemorrhagic exudate in the airways.8 Although there was no obvious flying fox colony nearby, large numbers of flying foxes are usually obvious in the evening sky in the latter part of the year in and around Cairns. The timing of the horse’s illness is not only the flying foxes’ birthing season,13 but also the season for many domestic and rainforest fruits in Far North Queensland; flying foxes travel considerable distances on nocturnal forays from their colonies in search of these foods. The owner of the horse reported frequently seeing flying foxes in the vicinity of the property. We assume that the veterinarian’s symptoms were caused by HeV, occurring after an apparent incubation of 7 days. Unfortunately, haematological and biochemical investigations were not requested after her initial medical consultation. The illness was mild, despite her being heavily contaminated with blood and body fluids during the autopsy. This veterinarian is the fourth person known to have been infected with HeV. All four had direct exposure to secretions and tissues from very ill, dying or dead horses; two were directly involved in autopsies of these horses. Two of the four died, whereas the other two had relatively mild illnesses.2-4 The veterinarian has remained clinically well for 2 years since her initial illness. A rise in the antibody titre 1 year after the initial illness was of concern in view of the observed late neurological relapse (13 months after acute illness), associated with increasing antibody levels, in one of the other cases of HeV infection.4 The closely related Nipah virus has also been associated with late neurological relapse in 7.5% of cases, occurring up to 22 months after initial infection.14 In one case, late-onset Nipah virus encephalitis coincided with rising antibody titres.15 The veterinarian undertook a high-risk procedure, taking less than optimal precautions. She was a relatively recent graduate, and her training may not have adequately impressed upon her the need to undertake such procedures with due care. Just as human health workers have had to accept that several recently emerged viruses (eg, blood-borne viruses and the SARS coronavirus) have changed working procedures, those working in animal health also must accept that recently emerged zoonotic viruses (eg, HeV and Australian bat lyssavirus) necessitate appropriate working procedures and personal protective equipment in veterinary practice. After this HeV incident, the Queensland Department of Primary Industries and Fisheries published revised guidelines for veterinarians handling horses suspected of being infected with HeV.12 These guidelines provide clinical case definitions and the recommended response measures, including the personal protective equipment that should be used when managing a suspected case, and the necessary reporting procedures.12 We suggest that these guidelines should be widely disseminated throughout the Australian veterinary community. AddendumIn early December 2004, a horse on a property just south of Townsville died of laboratory-confirmed HeV disease; there were no human infections associated with this fifth recognised outbreak of HeV disease. In mid June 2006, a horse on a property near Peachester on the Sunshine Coast hinterland died of laboratory-confirmed HeV disease; to date there have been no apparent human infections associated with the sixth outbreak of HeV disease. 1 Electron micrograph of the Hendra virus Courtesy, Mr Howard Prior, Senior Technician, Queensland Department of Primary Industries and Fisheries. 2 Possible mode of transmission of Hendra virus (HeV) infection 3 Hendra virus (HeV) laboratory studies in serum collected from the veterinarian at various intervals after the onset of symptoms. The onset occurred 7 days after the autopsy of the horse Laboratory studies Days after symptom onset 2 14 30 50 363 470 559 HeV RNA Not detected HeV IgM (IFA) < 8 8 32 16 < 8 < 8 < 8 HeV IgG (EIA) Non-reactive Reactive Reactive Reactive Reactive Reactive Not performed HeV IgG (IFA) < 8 256 256 128 512 256 256 IFA = immunofluorescence assay. EIA = enzyme-linked immunoassay.

Jeffrey N Hanna DTCH, MPH, FAFPHM · William J McBride FRACP, FRCPA, PhD · Dianne L Brookes MPH · Jack Shield BVSc · Carmel T Taylor BSc · Ina L Smith PhD · Scott B Craig BSc(Hons) · Greg A Smith PhD

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

Clinical record A 10-week-old baby presented to a local general practitioner with a 2-day history of discharge from her left eye. This was accompanied by an upper respiratory tract infection. The baby was otherwise healthy, born at term, and had no history of trauma to the eye. Her brother had had conjunctivitis a week earlier, which resolved with chloramphenicol drops within a few days. The treating doctor made the diagnosis of bacterial conjunctivitis and prescribed chloramphenicol ointment to be used four times daily. The discharge became more profuse and purulent, prompting a return to the GP 2 days later. At that consultation, the GP observed lid swelling, and treated a presumed lid infection by adding framycetin eye drops and oral amoxycillin. A further 2 days later, the baby returned with worsening of the lid swelling and green discharge covering the cornea. This prompted the GP to refer the baby to the local hospital, where a corneal abscess was diagnosed. A swab was taken for culture. The child was urgently referred to a paediatric tertiary referral hospital. At the tertiary hospital, the child was found to have copious purulent discharge from the left eye, mild lid swelling, severe conjunctival injection, and a dense opacity in the superior half of the left cornea. There was severe thinning and descemetocele formation over most of the inferior half of the cornea. A corneal scrape was sent for microbiology. A diagnosis of severe bacterial keratitis with impending perforation was made. Topical gentamicin 1.5% eye drops and vancomycin 5% eye drops were given every 30 minutes; and topical ceftazidime 5% was given every hour. Intravenous ceftazidime 50 mg/kg (235 mg) was commenced 6-hourly. Six hours later, the globe had perforated, with widespread iris prolapse through the now necrotic cornea. Pseudomonas aeruginosa was cultured from the conjunctival specimen taken at the referring hospital. The eye was considered unsalvageable (Box 1), so after discussion with the parents, a decision was made to eviscerate the left eye. After evisceration of the ocular contents, the sclera was closed without an implant, and a conformer was placed in the conjunctival fornix. The eye tissue specimen also grew P. aeruginosa, which was sensitive to gentamicin, tobramycin, timentin, ceftazidime and ciprofloxacin. The child was discharged on the third post-operative day with oral ciprofloxacin 10 mg/kg twice a day and topical tobramycin drops 0.3% four times daily. Three months later, an acrylic ball was inserted into the eye cup to restore orbital volume. Infectious conjunctivitis is the most common inflammatory eye condition, comprising 0.7% of all presentations to general practitioners in Australia.1 In contrast, infectious keratitis is rare, but is one of the most visually threatening ocular conditions. Infections initially manifesting as conjunctivitis can spread to involve the cornea. Pseudomonas is one pathogen known for this, as appears to have occurred in this patient. The symptoms of conjunctivitis include irritation, stinging and discharge, whereas severe foreign body sensation, pain, photophobia and blurred vision should raise suspicion of keratitis. Signs differentiating conjunctivitis from keratitis are listed in Box 2. Lessons from practice Examination is of utmost importance in the paediatric population as less information can be gleaned from the history. Keratitis can be mistaken for conjunctivitis in its early stages, especially when an adequate view of the globe is not obtained. Where there is no or limited response to treatment in young infants, the working diagnosis must be reconsidered: a good rule of thumb is if the conjunctivitis does not respond within 72 hours on second-hourly antibiotic drops, either you have the wrong drug or the wrong diagnosis. Make early referral to an ophthalmologist where there is periorbital cellulitis, or when in doubt. Examination findings are most important in young children, because they cannot describe the symptoms. However, examining the eyes of distressed babies and children can be extremely difficult. A few drops of local anaesthetic can make examination easier. Restraining a child or wrapping a baby in a sheet may be necessary. With a baby, a small lid speculum may be necessary to gain an adequate view, and magnification and a bright light source are essential. Progressive ulceration can lead to corneal perforation and endophthalmitis, as in the baby described in this report. Swabs should be considered when there is profuse discharge. Risk factors for keratitis in children include trauma, pre-existing corneal disease, prior corneal surgery, contact lens wear and systemic illness.2,3 Endophthalmitis caused by P. aeruginosa has a particularly poor visual prognosis; a case series of 28 patients reported an evisceration or enucleation rate of 64% and a final visual acuity of 5/200 or better achieved in only 7% of patients.4 In a case series of neonates, septicaemia complicated more than half of all cases of Pseudomonas keratitis, and led to death in 40%.5 The differential diagnosis in our 10-week-old patient is similar to the differential diagnosis of ophthalmia neonatorum, which is defined as severe conjunctivitis arising within 1 month after birth.6 These infections, which include Chlamydia trachomatis and Neisseria gonorrhoea, can be acquired at time of delivery, or from the nasopharyngeal passage and from carers.6 Dacryocystitis can also cause marked lid swelling. This case highlights the importance of considering alternative diagnoses to conjunctivitis, especially where a presumed conjunctivitis does not respond to initial treatment. 1 Keratitis, corneal necrosis and perforation of the globe 2 Clinical signs differentiating conjunctivitis from keratitis Conjunctivitis Keratitis Conjunctiva Inflamed Reactive inflammation is usually present Cornea Clear Opacification (ie, infiltrate ± stromal oedema) An epithelial defect will stain with fluorescein Lid swelling None to mild Adenoviral conjunctivitis can cause moderate lid swelling None to severe Discharge Purulent: generally bacterial Watery: generally viral Little to profuse Usually purulent Anterior chamber Quiet Usually some anterior chamber reaction Can progress to hypopyon

Frances M Kearney BSc(Hons), MB BS · Luke J Maccheron MB BS · Glen A Gole MD, FRANZCO

To the Editor: I wholeheartedly agree with Giles at al1 regarding the need for universal HIV antenatal screening in Australia. However, it is worth noting that, at least in private practice, there is already a significant amount of antenatal HIV screening taking place. In November 2005, several Medicare Benefits Schedule (MBS) item numbers were introduced for antenatal screening for infectious diseases including HIV testing. I am unaware of any specific HIV-testing restrictions relating to national policy (other than the obligations of informed consent and such like) attached to these item numbers. Four MBS item numbers for “microbiological serology during a pregnancy” may include HIV testing (69405, 69408, 69411 and 69413), and one MBS item number (69415) must include HIV testing. From November 2005 to June 2006, there were 137 732 claims for antenatal serological tests, of which at least 46 085 (33%) included HIV testing (see Box).2 There is some variation from state to state (New South Wales, 25%; Victoria, 34%; and Queensland, 38.5%). Significant state-to-state variation of claims for different Medicare items is not unusual but, in this case, it does not appear to follow any pattern (of the epidemiology of HIV infection in Australia). I suspect that the proportion of pregnant women having HIV tests is closer to 50%, assuming that at least some of the other item numbers claimed included testing for HIV. It would be worthwhile taking these figures into account when formulating national policy. Medicare items for antenatal serological testing, which may include HIV testing — number of items processed in Australia from November 2005 to June 2006 by state Item NSW VIC QLD SA WA TAS ACT NT All states 69405 2 664 1 905 1 291 149 919 177 142 269 7 516 69408 2 375 1 191 1 080 115 769 205 170 114 6 019 69411 16 169 5 493 6 758 549 1 890 913 912 284 32 968 69413 15 874 10 267 9 488 2 792 4 171 1 229 588 735 45 144 69415 12 283 10 138 11 695 3 095 6 710 784 424 956 46 085 Total 49 365 28 994 30 312 6 700 14 459 3 308 2 236 2 358 137 732 Item 69415 must include HIV testing.

Len D Moaven

To the Editor: We report three cases of locally acquired Entamoeba histolytica infection in men who have sex with men (MSM) in Sydney, New South Wales. E. histolytica is an invasive pathogenic amoeba that can cause invasive intestinal and extraintestinal amoebiasis. Entamoeba dispar is morphologically identical but is considered non-pathogenic and non-invasive.1 The three patients presented with a 1–3-week history of diarrhoea and abdominal pain. Routine bacterial cultures were negative for pathogens. Ova, cyst and parasite investigations showed cysts and trophozoites of E. histolytica/dispar complex in permanently stained, fixed faecal smears. Stool samples were tested for E. histolytica and E. dispar by polymerase chain reaction (PCR), using a previously described method.2 All three patients were positive for E. histolytica by PCR; sequencing of the amplicons verified the presence of E. histolytica DNA. The three patients presented within a 12-month period in 2005–2006. All were homosexually active men (ages, 31–53 years) who lived in inner Sydney. None had a history of overseas travel within the previous 5 years, suggesting that the infections were locally acquired. High rates of intestinal parasitism are found in MSM throughout the world. Oral–anal and oral–genital sexual practices are reported to predispose to infection with enteric pathogens, particularly protozoa. A 1991 study reported a higher prevalence (37%) of E. histolytica/dispar complex in a homosexual population in Sydney when compared to non-MSM.3 However, that study did not differentiate between the two species E. histolytica and E. dispar. Amoebiasis has become endemic in MSM in Japan and causes significant morbidity and mortality; complications such as colitis and liver abscesses occur more frequently in homosexual and bisexual men than in heterosexual men.4 Similar findings on amoebiasis are reported from Taiwan, with MSM at increased risk for invasive amoebiasis and intestinal colonisation with E. histolytica.5 The discovery of E. histolytica infection in MSM in Australia is of public health concern and highlights the importance of continued surveillance, as the organism has the potential to become endemic in the gay population and to cause significant morbidity. Clinicians should also be aware that E. histolytica is present in urban settings in Australia and should be included in differential diagnoses.

Damien J Stark · Rashmi Fotedar · John T Ellis · John L Harkness

Rotavirus vaccines are finally available, and introducing them into the routine vaccination schedule will have a significant impact on the health of children After a dramatic false start, oral rotavirus vaccines are now available to prevent severe, dehydrating diarrhoea in small children. Rotavirus infection in children can be as severe as cholera in adults, but affects a group who cannot complain. Since its discovery in Australia in 1973, rotavirus has become accepted as the single most common cause of severe diarrhoea in children worldwide. It still kills over 500 000 young children each year. In Australia, it is estimated that 10 000 children require hospitalisation annually1,2 (more than 4000 actually coded for proven rotavirus3), and as Schultz reports in this issue of the Journal, the impact on Indigenous children is especially severe.4 Oral rehydration has greatly reduced mortality, but the World Health Organization recognises the potential of rotavirus vaccines to further reduce under-5-year mortality rates, Goal 4 of the Millenium Development Goals.5 It is exciting to have two efficacious oral rotavirus vaccines, RotaRix (GlaxoSmithKline [GSK], Boronia, VIC) and RotaTeq (Merck/CSL, Parkville, VIC) licensed this year in Australia. Each has been extensively tested in placebo-controlled trials of more than 60 000 participants. Both vaccines prevented severe disease, and reduced the need for hospitalisation by 85%–94%. There was a reassuring lack of intussusception, a rare (one in 10 000–32 000) event associated with RotaShield, the first licensed rotavirus vaccine, which led to its withdrawal from the United States market in 1999, just 12 months after its introduction.6 Re-analysis of the data suggested that the intussusception risk emerged in infants receiving the first vaccine dose after 3 months of age.7 Thus both GSK and Merck/CSL state that the first dose should be administered before that time. Several issues remain to be resolved with these two new vaccines. Efficacy has not been established in developing countries. Availability will depend on distribution (including the need for a cold chain), the ability to piggyback rotavirus vaccines with other routine vaccinations, and manufacturing capacity. The greatest uncertainty is the cost of the vaccine. Current prices exceed $200 per course in the private market. While tier pricing and subsidisation by international agencies for poorer countries is being considered, it is not clear whether these mechanisms will sustain programs in most parts of the world. Hence, other candidate vaccines linked to developing country manufacture are under early development in China, India, Indonesia and elsewhere. Who should get rotavirus vaccine in Australia? Ideally all children under 3 months of age, as all will eventually be exposed to rotavirus, and one in 25 will be admitted to hospital for rotavirus gastroenteritis during the first 5 years of life. Morbidity across our country is high. Apart from the 10 000 annual hospital admissions, there are 22 000 visits to emergency departments and 115 000 visits to general practitioners.2 Nosocomial infection rates are as high as 14% in children’s hospital wards and may be higher in childcare centres.8,9 Schultz’s report indicates that Indigenous children have 2–4 times the disease burden of non-Indigenous children.4 Gastroenteritis in Indigenous children comes with comorbidities and a significantly increased average length of hospital stay. Add to that the large costs of air transport of patients for hospital admission in northern and western Australia and the disruption to remote families, and the case for rotavirus vaccination of Indigenous infants becomes compelling. The Northern Territory Health Department recognised the importance of rotavirus infection by making it a notifiable disease, and Queensland recently followed suit. Breaking news is that from October 2006, the NT Government will include rotavirus vaccine in the routine vaccination schedule for NT children.10 The only real issue is cost. A 1999 cost–benefit analysis suggested that break-even vaccine cost was $78 per course,11 somewhat less than current prices. However, the community should be prepared to pay something to prevent this wretched disease. For maximum benefit, the first dose should be given before 3 months of age. Infants under 6 months of age accounted for 24% and 9% of rotavirus gastroenteritis cases in studies in the NT and Melbourne, respectively.4,12 In Africa, many infants are infected in the first 2 weeks of life.13 There is enthusiasm for giving the first dose of vaccine within the first month of life, but neither licensed vaccine has been tested at this age. Roll-out of a universal program in Australia has a few caveats. The inevitable concern about intussusception, in spite of the reassuring clinical trial results, probably means that catch-up campaigns, where the first dose is given after 3 months of age, will not happen. Evidence of the spectrum of protection afforded by both vaccines against the full range of human rotavirus serotypes is still lacking. There is a need to continue national strain surveillance to ensure that the current vaccines are appropriately protective against the range of serotypes in Australia, and to monitor the effect of vaccine pressure on the evolution of strains. After three decades, there is real excitement at suddenly having such an effective tool to prevent a common, miserable disease affecting infants and children. Rotavirus vaccination is not only justified on the basis of disease burden, but will be welcomed by all who care for sick children. It will not be hard to measure real improvement for Indigenous children in the NT, given the baseline data presented elsewhere in this issue of the Journal.4 While other candidate vaccines are in development, there is no excuse for waiting any longer for a national program. The improvement in child health will be obvious.

Graeme L Barnes MD, FRACP · Ruth F Bishop AO, DSc, PhD