Infectious diseases

MMR, Wakefield and The Lancet: what can we learn? Julie Leask, Robert Booy and Peter B McIntyre MJA 2010; 193 (3): 192 Missing text: In “MMR, Wakefield and The Lancet: what can we learn?” in the 5 July 2010 issue of the Journal (Med J Aust 2010; 193: 5-7), a line of text was omitted in the third-last paragraph (page 6). The text, from the beginning of the paragraph, should be “Second, public communication about vaccine risk, particularly regarding responses to adverse events following vaccination in new vaccine programs, needs to be planned, and should involve multiple stakeholders, as new issues can arise with little warning. This occurred as recently as 23 April 2010, when Australia’s Chief Medical Officer advised a temporary suspension of the 2010 trivalent seasonal influenza vaccine to children 5 years of age and under.15”

Julie Leask · Robert Booy · Peter B McIntyre

Vaccine scares are inevitable and we need to plan accordingly Twelve years after The Lancet published the study by Wakefield and colleagues1 that suggested a link between measles–mumps–rubella (MMR) vaccination, inflammatory bowel disease and autism, the journal has fully retracted the article. The retraction followed the findings of the Fitness to Practise Panel of the UK General Medical Council, released 28 January 2010, that certain statements in the article were false — namely, that children were “consecutively referred” and that investigations were “approved” by the local ethics committee.2 Wakefield’s theory had a significant impact on MMR vaccination rates in the United Kingdom. Looking at why Australia was relatively unaffected provides insights into how to better manage vaccine scares in the future. After publication of the article, many readers had written without delay to The Lancet regarding methodological deficiencies of the original research.3 Subsequent studies overwhelmingly supported the safety of MMR vaccination, but the accumulation of this evidence took years to achieve, with considerable opportunity costs, including time and resources spent on investigations which could have been better directed elsewhere.4 In the UK, the MMR vaccination rate fell from 91% in 1997–98 to 80% in 2003–04.5 Notably, there has been no decline in coverage for other vaccines for children in the UK. Despite a recovery in the MMR vaccination rate to 85% by 2008–09,5 there was a large upsurge in measles occurrences in the UK, beginning in 2002.6 In 2009, 1144 laboratory-confirmed measles cases were reported in England and Wales.6 The impact was also felt in the United States, where Wakefield’s theory augmented unsubstantiated fears about thiomersal (a mercury-based preservative) in some vaccines leading to autism. A recent survey found that one in four US parents believed that some vaccines cause autism in healthy children.7 Vaccine scares are typically depicted as conflicts between science and dogma; between the informed and the misinformed.8 The publication of Wakefield et al’s article in The Lancet breached the boundary between the two: here was a well credentialled specialist at a highly regarded teaching hospital whose findings were published in a renowned journal. These signifiers of prestige may have overshadowed the relatively poor quality of the science in the original article. Fortunately, in the years since the article was published, Australia’s MMR vaccine uptake has been relatively stable, as measured by the Australian Childhood Immunisation Register9 (Box). However, there were other consequences of Wakefield et al’s article, including the time and resources needed to address parents’ concerns.11 Some health professionals appeared to accept Wakefield’s theory. A 2006 survey of doctor and nurse vaccination providers in regional New South Wales found that 12% believed there was an association between MMR and autism, with a further 29% being unsure.11 Despite this, Australian MMR coverage remained essentially unaffected. The fact that Australian MMR vaccination rates remained stable may be related to some key differences between Australia and the UK: (i) in Wakefield, the UK had a “home-grown champion” for the MMR–autism theory; (ii) the extensive and sustained coverage of this issue in the UK media continually exposed new cohorts of parents of MMR-eligible children to the theory, while Australian television only sporadically reported the story; (iii) there is bipartisan political support for immunisation in Australia, whereas there was grandstanding by a member of the UK Conservative opposition and a refusal by the nation’s Labour Prime Minister to reveal whether his own son was immunised;12 and (iv) a foundation of mistrust in UK government assurances was perpetuated by public perceptions of the management of the Creutzfeldt–Jakob disease issue.13 The child vaccination program is held in high regard by most Australians, and, for this reason, the media have traditionally sidelined our small but vocal antivaccination lobby. This high level of public confidence has been helped by the structural support originating from the first National Immunisation Strategy in 1993, followed in 1997 by the federal Immunise Australia: Seven Point Plan, including financial incentives for parents and providers to adhere to the national vaccination schedule.14 What can the world learn from the Wakefield experience? First, we should accept vaccine scares as inevitable and plan accordingly. There remains the potential for vaccine safety scares to lead to large-scale opting out of vaccination, exacerbated by dwindling familiarity with the severe effects of vaccine-preventable diseases, and a groundswell of dissent from the antivaccination movement. Second, public communication about vaccine risk, particularly regarding responses to adverse events following vaccination in new vaccine programs, needs to be planned, and should involve multiple stakeholders, as new issues can arise with little warning. This occurred as recently as 23 April 2010, when Australia’s Chief Medical Officer advised a temporary suspension of the 2010 trivalent seasonal influenza vaccine to children 5 years of age and under.15 This suspension followed an increase in febrile convulsions among young child vaccine recipients reported in Western Australia. Third, the current level of trust in vaccine programs that we enjoy in Australia is a precious resource and must be continually fostered with good communication. Such communication is more than a didactic one-way process — it requires an interactive engagement between professionals, the public and the media. Clearly, this will be important and challenging after the recent suspension of the trivalent influenza vaccine, because professional and public concern generated by this suspension could spread to concern about influenza vaccination for other age groups.16 Australian federal, state and territory governments are now developing a new national vaccination strategy. Essential considerations in this strategy will be how the postmarketing surveillance of adverse events following vaccination is to be conducted, and authoritative and timely communication about vaccine safety with professionals and the public. MMR, DTP, OPV, Hib and hepatitis B vaccine coverage for Australian children at 24 months of age, 2000 to 2009*10 MMR = measles–mumps–rubella. DTP = diphtheria–tetanus–pertussis. OPV = oral polio vaccine. Hib = Haemophilus influenzae type b. Hep B = hepatitis B. * Figure updated with 2008–2009 data (Brynley Hull, Epidemiologist, National Centre for Immunisation Research and Surveillance, personal communication).

Julie Leask PhD, MPH, DipAppSci · Robert Booy MD, FRACP, FRCPCH · Peter B McIntyre PhD, FRACP, FAFPHM

Laboratory-confirmed influenza is a nationally notifiable disease in Australia. According to notification data, Queensland has experienced more severe influenza seasons than other states and territories. However, this method ignores available denominator data: the number of laboratory tests performed. We propose that negative results of laboratory tests for influenza should be made notifiable, alongside laboratory-confirmed disease, and used to calculate the proportion of positive test results in real-time. Using data from the public health pathology services of three Australian states — Queensland Health laboratories, the Victorian Infectious Diseases Reference Laboratory and Western Australia’s PathWest — for 2004 to 2008, we show that incorporating laboratory-negative test data into national surveillance data would add to and improve our understanding of influenza epidemiology.

Stephen B Lambert MB BS, MAppEpid, PhD · Cassandra E Faux MSc(ClinMicro) · Kristina A Grant BSc · Simon H Williams BSc(Hons) · Cheryl Bletchly BSc(Hons), GradCertHlthMgt, PhD · Michael G Catton MB BS, FRCPA · David W Smith MB BS, FRCPA, FACTM · Heath A Kelly MB BS, MPH

Clinical record A previously well 4-month-old girl presented to an Australian Capital Territory hospital emergency department in August 2009 with a 2-day history of fever, vomiting and bloody diarrhoea with rectal prolapse. On arrival, she was alert, active and afebrile but had profuse diarrhoea and tachycardia. She was admitted, and stool cultures were requested. Intussusception was considered unlikely, and oral rehydration via a nasogastric tube was commenced. Over the following 48 hours, diarrhoea persisted, with some vomiting and low-grade fevers. Stool culture showed Salmonella species. After 4 days, the child was afebrile, had good oral intake and was discharged from hospital, although diarrhoea continued. No other family members were ill. Salmonellosis is a notifiable infection in all Australian states and territories, and interviews are sought with all affected patients in the ACT to locate sources of infection. Following receipt of the laboratory notification, an environmental health officer interviewed the mother of the infant. Exclusive breastfeeding meant that food-related illness was unlikely. The infant’s siblings were reported to handle kangaroo excreta and to examine the infant for new teeth. This was nominated as a possible source and mode of transmission. The household pet cat and dog were healthy. No other environmental exposures, including recent travel, were nominated. Subsequently, serotyping characterised the salmonella as Salmonella enterica serotype Rubislaw (S. Rubislaw), the first recorded instance of infection with this serotype in the ACT. S. Rubislaw has been isolated from various non-human sources in Australia: native animals and birds, feral goats, kangaroos and water supplies from the northern regions of Australia, and also captive snakes and lizards, including bearded dragons in South Australia in 2008 and New South Wales in 2009 (National Enteric Pathogens Surveillance Scheme [NEPSS], September 2009, unpublished data). The infant’s mother was re-interviewed and revealed that the family kept a 4-year-old pet eastern bearded dragon (Pogona barbata) (Figure). The mother reported that she cared for the lizard, fed it and cleaned its terrarium. The reptile was not permitted to roam the house but was removed from the terrarium on occasion to be held by the mother. There was no report of direct contact between the infant and lizard, and only rare contact with other children. The family was advised about the high Salmonella carriage in reptiles and the risk to young children. Environmental samples were collected from the terrarium (lizard faeces, drinking water, bark, swabs of the terrarium environment) and the household vacuum cleaner filter. S. Rubislaw was isolated from all these environmental samples. After being advised of these results, the family of the infant felt an unacceptable risk remained and the lizard was euthanased. Salmonellosis is frequently classified as a foodborne disease because contaminated food, mainly of animal origin, is the predominant mode of transmission.1 In the United States, “exotic pets” such as reptiles have become popular and reptile-associated salmonellosis has emerged as a public health problem.2-5 In Australia, although accurate figures on pet reptile ownership and reptile-associated disease are difficult to obtain, the risk to human health must be considered. International evidence suggests reptile-associated Salmonella infections are more likely to be associated with invasive disease, more commonly lead to hospitalisation and more frequently involve infants and younger children than do other Salmonella infections.4 The particular susceptibility of children to disease transmission from reptiles kept in the family home may be due to greater exposure to the contaminated reptile and greater host vulnerability.5 Much of the available evidence regarding risk in children comes from case–control studies conducted in the US.2,5 There have also been numerous reports of sporadic cases of invasive disease and hospitalisation of children and infants with salmonellosis linked to reptiles.3 A fatal case of S. Rubislaw meningitis in a 3-week-old baby was linked to a pet water dragon in England.6 It has been estimated that 90% of reptiles are colonised with Salmonella, which is shed intermittently in their faeces.7 Such high rates of colonisation suggest Salmonella are commensal organisms of the gastrointestinal tracts of these animals.4 There are over 2500 Salmonella serotypes, with most (including S. Rubislaw) belonging to S. enterica subspecies I.8 Serotypes of S. enterica subspecies I cause most Salmonella infections in humans and other warm-blooded animals. By contrast, over half of the S. enterica serotypes reported from reptiles in Australia belong to subspecies IIIa, IIIb and IV, which are rare in humans (NEPSS, unpublished data). Salmonella carried by reptiles can be transmitted either through handling a reptile, or indirectly by contact with an object contaminated by a reptile or its faeces.5 The droppings of free-roaming reptiles may result in widespread contamination of the home environment. The hands of younger children are readily contaminated, while infants may be indirectly infected via their parents or siblings. Ultimately, bacteria are transferred to the mouth and ingested. Hand washing may not eliminate the risk of infection. As the entire surface of a reptile may be contaminated, so may be the clothes and skin (beyond the hands) of the handler.9 Between nine and 19 human cases of S. Rubislaw were reported annually in Australia from 2000 to 2009 (NEPSS, unpublished data), predominantly from the northern tropical regions. Two-thirds of patients were aged less than 5 years (and most often less than 1 year), suggesting the importance of contact with environmental sources. We suspect the Australian public may not be familiar with reptile-associated salmonellosis. In the US, public health authorities have advocated the prohibition of the sale or gifting of reptiles without written point-of-sale education being provided by pet-store owners.3 Australian states and territories vary in their regulation of reptile ownership. NSW pet stores are not permitted to buy or sell reptiles or even to have them on their premises, whereas commercial reptile dealing occurs in Victoria, SA, the Northern Territory and ACT.10 In the ACT, eastern bearded dragons are classified as Category A reptiles (licence exempt), under the Nature Conservation Act 1980, and can be kept by individuals without prior experience in keeping such animals. Within the ACT there is no compulsion for pet stores, breeders or reptile keepers to inform prospective reptile owners or members of the public of possible risks to human health associated with reptile ownership or contact. We recommend that owners and prospective owners of reptiles be better informed of the risks to human health, particularly the threat to children. Lessons from practice Some Salmonella serotypes that occupy specific environmental niches infect humans through environmental sources rather than foods. Clinicians managing a young child with salmonellosis should ask parents or guardians about contact with household pets, including lizards, snakes, turtles and fish. Investigating individual cases of unusual infections can shed light on novel and evolving public health risks. Reptile-associated salmonellosis may become a more significant issue for medical practitioners and public health authorities in Australia. Parents and guardians should be advised about the risks (including invasive salmonellosis) that pet reptiles may pose to infants and young children.

Cameron R M Moffatt BBusHealthAdmin, MPH, MAppEpid · Antony R Lafferty MB ChB, FRACP · Sara Khan MB BS · Radomir Krsteski BApplSc, DipApplSc · Mary Valcanis BSc, MPH, MASM · Joan Powling BAgrSc · Mark Veitch MB BS, MAppEpid, FAFPHM

To the Editor: Infections caused by multiresistant gram-negative organisms are difficult to treat. Carbapenems are often used as a last resort but even these are under threat with the emergence of acquired metallo-b-lactamases worldwide, including Australia,1,2 India, China and Europe. We report the first case of a Providencia rettgeri producing the blaNDM-1 (New Delhi metallo-b-lactamase) type of metallo-b-lactamase in Australia. A man from Canberra, aged in his mid 50s, had elective plastic surgery in India in September 2009. This was complicated by a hypoxic brain injury, after which the patient spent 4 weeks in an intensive care unit. He was subsequently transferred to Canberra for ongoing hospital care. A urinary catheter specimen collected on admission in November 2009 showed a heavy growth of multidrug-resistant P. rettgeri and Pseudomonas aeruginosa. The P. rettgeri was resistant to all b-lactam antibiotics, including meropenem, as well as to all aminoglycosides, ciprofloxacin, tigecycline and colistin. The P. aeruginosa was resistant to all antipseudomonal antibiotics except for colistin (tigecycline was not tested as it has low or no antipseudomonal action). The patient was not given antibiotic therapy but the indwelling urinary catheter was changed and contact precautions were put in place. Both organisms were sent for molecular testing, which showed that the P. rettgeri had 100% homology with blaNDM-1.3 The patient cleared the organisms after 2 months, and since then has received ongoing inpatient care in the rehabilitation unit. The first NDM-1 type of metallo-β-lactamase was found in Klebsiella pneumoniae isolated from a Swedish patient who had recent medical contact in India.3 Data from the United Kingdom’s Antibiotic Resistance Monitoring and Reference Laboratory suggest that isolates with the NDM-1 enzyme have recently been repeatedly imported to the UK from the Indian subcontinent. There may now be circulation of these resistant isolates in the UK because some infected patients have no identifiable overseas links. Hospitals have been urged to be vigilant for multiresistant gram-negative bacteria in patients with recent hospital contact in the Indian subcontinent as well as the Eastern Mediterranean.4 Identification of an Enterobacteriaceae organism carrying blaNDM-1 is very concerning. No antibiotic may be available to treat patients who develop serious infection with such organisms, and there is the added concern regarding cross-infection in health care facilities. The plasmid carrying blaNDM-1 also contains genes that confer resistance to several other antibiotics.3 It appears likely that, in the near future, the NDM-1 enzyme will become a very successful metallo-b-lactamase globally. Patients infected with multiresistant gram-negative bacteria have entered the “post-antibiotic era”.

Geethanie A T P Fernando · Peter J Collignon · Jan M Bell

To the Editor: We report the case of a 19-year-old female veterinary student who presented with a 2-week history of a rapidly growing mass on the lateral side of the deltoid area of her left arm. On examination, the mass was soft, freely movable, slightly warm and non-tender. There was no regional lymphadenopathy. The patient was afebrile, with no signs of systemic illness. Ultrasound showed a 3.2 × 2.3 × 1 cm, low-echogenic, lobulated lesion in the subcutaneous fat, with surrounding increased echogenicity suggestive of inflammation. Magnetic resonance imaging showed a poorly defined lesion throughout the deep and superficial fascia, with infiltration into the underlying deltoid muscle (Box 1). A provisional diagnosis of sarcoma was made, but an ultrasound-guided core biopsy sample showed non-necrotising epithelioid granulomas (Box 2). Two weeks after presentation, the patient noticed a smaller raised lump, about 1 cm in diameter, on the volar aspect of her left forearm. Four months before presentation, following negative results of both Q fever serological testing and a Q fever skin test administered on the volar aspect of her left forearm (at the site of the smaller lump), the patient had received a Q-VAX (CSL, Melbourne, Vic) vaccination in the left deltoid (at the site corresponding to the larger mass). Three months after this, and about 3 weeks before the deltoid mass first appeared, the patient received a Fluvax (CSL, Melbourne, Vic) influenza vaccination at the same left-deltoid site as the Q fever vaccination. This raises the possibility that the influenza vaccination may have been associated with the subsequent Q fever granuloma reaction. Q fever, a disease caused by the zoonotic rickettsial organism Coxiella burnetii, is an occupational hazard for many Australians in animal-related professions. The disease is characterised by an acute, self-limiting febrile illness, with pneumonia and hepatitis being infrequent complications. In 2001, an Australian national Q fever vaccination program was initiated, which led to a 50% decline in the incidence of Q fever.1 Side effects are normally rare and minor; during 2001–2004, only 86 adverse reactions were reported from about 49 000 vaccinations.2 Development of non-necrotising granulomas following Q fever vaccination is uncommon, with only six cases previously described.3-5 To explore the possibility of a causal association between influenza vaccination, Q fever vaccination, and development of a granuloma, we traced four of these six patients with Q fever granuloma by contacting the authors of the previous reports. One patient had been vaccinated against influenza 2 months before the time of Q fever vaccination, and another had influenza vaccination afterwards (as in our case). Of the five cases (including our case) for which clinical history was available, three had a temporal association between influenza vaccination and Q fever vaccination, followed by the development of the non-necrotising granuloma. The indurated lesion at the separate Q fever skin-test site on the volar forearm, found in two other patients5 as well as ours, supports the notion of a systemic immune reaction rather than simply a local reaction at the vaccination site. The Naranjo score in this case was 7, indicating a “probable” adverse drug reaction. Although the granuloma was self-limited in all known cases, this case shows that there is significant risk of misdiagnosis on clinical grounds. It seems prudent to be aware of the possible association between these two vaccinations. Magnetic resonance images of lesion Axial (top) and coronal T1-weighted fat-saturated post-contrast (bottom) images demonstrate a poorly defined enhancing lesion (red arrows) in the subcutaneous fat, which superficially infiltrates and extends in a plaque-like manner in relation to the underlying deltoid muscle (white arrows). 2 Ultrasound-guided core biopsy sample of lesion The core biopsy of fibroadipose tissue shows numerous well formed non-necrotising epithelioid granulomas (arrows). The granulomas are composed of epithelioid histiocytes and a few multinucleated giant cells, surrounded by numerous lymphocytes (a mixture of B and T cells, with a greater proportion of T cells). (Original magnification × 100; haematoxylin–eosin stain.)

Deborah Burnett · Leslie Burnett

To the Editor: In her editorial, Christiansen states that the 2010 edition of Therapeutic guidelines: antibiotic (version 14) is very likely to recommend 24 hours of antibiotic prophylaxis for cardiac surgery,1 rather than the present regimen, which recommends that patients having routine cardiac surgery be given a large dose of cephazolin at induction, with a second dose if the operation is prolonged for more than 3 hours, and no doses after surgery.2 The only evidence presented in support of this proposed change is a single randomised controlled trial that purported to show a higher rate of surgical site infections after a single dose of cephazolin, than after a prolonged, multidose regimen.3 The study was flawed, for two reasons. First, cephazolin was not given until 20–30 minutes after induction of anaesthesia, which is likely to have been too late, because, as Christiansen points out, β-lactams should be given 30–60 minutes before incision.1 Second, the trial was analysed on a per-protocol, rather than an intention-to-treat basis, and 189 of the 1027 participants (18%) were excluded, so the findings may be seriously biased.4 Three other trials have compared one or two doses of a cephalosporin with multiple doses of the same antibiotic in patients having cardiac surgery; none found that multiple doses were superior, although all three were small studies with faults in their design.5-7 In 1998, McDonald and colleagues published a detailed review of single versus multiple doses of antimicrobial prophylaxis for major surgery. The analysis was in response to a suggestion by Christiansen and others that single-dose antibiotic prophylaxis may be inadequate for patients undergoing vascular surgery.8 McDonald and colleagues pointed out that the recommendation for single-dose surgical prophylaxis in Therapeutic guidelines: antibiotic (version 13),2 is based on microbiological first principles, published studies reporting efficacy, convenience of administration, reduced antibiotic resistance and toxicity, and relatively low cost. Their careful analysis of 28 randomised trials, in which the same antimicrobial was used in each arm, showed no advantage from the administration of multiple doses; the odds ratio for infection was 1.06 (95% CI, 0.89–1.25). There is no microbiological reason to suppose that the crucial interaction between contaminating bacteria and the prophylactic antibiotic in the heart is any different from that in the lung, biliary tree, uterus, bowel, prostate or bone.8 In the absence of such evidence, there is no sound reason to change the current, long-standing Therapeutic guidelines: antibiotic2 recommendation.

Frank Shann

In reply: Professor Shann raises three issues regarding the recommendation for 24 hours’ prophylaxis for cardiac surgery. First, he states that the trial1 on which this recommendation was made was flawed, because “cephazolin was not given until 20–30 minutes after induction of anaesthesia, which is likely to have been too late”. The trial included patients having coronary artery surgery and/or cardiac valve replacement, and, for these procedures, the time between induction of anaesthesia and surgical incision is about 60–75 minutes, as patients require the placement of intravenous lines and preparation for coronary artery bypass surgery. Antibiotic administration is recommended 30–60 minutes before incision, thus, administration 30 minutes after induction provides optimal serum concentrations at incision, in patients undergoing cardiac surgery. Second, the per-protocol analysis is perhaps less than ideal, but the demographics, clinical characteristics and operative data were comparable for the patients included in the analysis. Third, as stated by Professor Shann, the three earlier studies2-4 were either very small or flawed in design. The McDonald systematic review5 included 28 studies, only two of which were on cardiac surgery, both being the earlier flawed studies2,3 quoted above. The Therapeutic guidelines: antibiotic review process involves a rigorous, evidence-based assessment with input from experts in the field. The medical community of Australia can have every confidence that the recommendations made are current and evidence-based.

Keryn J Christiansen

To the Editor: We describe here some of the difficulties in managing and investigating outbreaks of viral respiratory infection in aged care facilities (ACFs) in the context of an influenza pandemic. This adds to the previous report on logistics in a hospital setting.1 On 12 June 2009, NSW Health received a call from a surveillance officer in a remote town regarding a possible pandemic (H1N1) 2009 influenza outbreak in an ACF. On 9 June, a 77-year-old female resident had become unwell, without specific symptoms of influenza-like illness. From 7 to 10 June, nine of the other 27 residents developed influenza-like illness. On 10 June, nasal swabs were taken from the 10 unwell residents by the local general practitioner for influenza nucleic acid testing (NAT). On 12 June, the index case tested positive for pandemic influenza, while the other residents tested negative. Due to concern that there might be a pandemic influenza outbreak in the facility, the index case and the nine residents with influenza-like illness were given oseltamivir (75 mg twice a day for 5 days) from 13 June; the other 18 residents and the 27 staff were given oseltamivir prophylaxis (75 mg daily for 10 days). A formal outbreak investigation and further laboratory testing (NAT, serological testing) revealed a dual outbreak dominated by rhinovirus (10 cases), with two cases of pandemic influenza and one case of untyped influenza A. All 28 residents and 26 of the 27 staff had received seasonal influenza vaccine in early 2009. This outbreak illustrates that more than one respiratory virus may co-circulate in ACFs during winter outbreaks of respiratory infection. We followed Department of Health and Ageing policy guidelines for oseltamivir use in ACFs2 and the facility was closed to visitors from 12 to 18 June. However, as all residents had received seasonal influenza vaccination, and given that older people are generally at lower risk of pandemic (H1N1) 2009 influenza,3 we could have had a higher threshold for oseltamivir use. The total estimated cost of treatment and prophylaxis was $2750 (55 residents and staff at $50/person) for oseltamivir alone. Co-infection with respiratory viruses may be more common than thought in ACFs; a recent Canadian study found two and three different pathogens in 15% and 4% of respiratory infection outbreaks, respectively, from a total of 83 outbreaks (of which 91% occurred in long-term care facilities).4 If many ACF outbreaks have more than one respiratory virus involved, laboratory investigations should take a multiplex approach that covers common respiratory viruses. As many patients as practical (at least five) should be swabbed and tested to guide treatment, prophylaxis and other investigations. Community influenza surveillance should ideally include information on sensitivity to oseltamivir, and on other circulating respiratory viruses.

Gulam Khandaker · Bridget Doyle · Dominic E Dwyer · Robert Booy

To the Editor: It is a naïve public health physician who predicts ahead of time how many people will die in a disease outbreak. Such doctors have short careers. What Collignon calls the “wrong and exaggerated” expert predictions1 of mortality from the recent influenza pandemic are based on the numbers that the World Health Organization advised governments to use in planning for pandemics.2 They are derived from a sensible calculation: plan for a situation considerably better than the 1918–1919 pandemic but somewhat worse than the 1957 or 1968 pandemics. The problem in Australia is not so much the pandemic plans produced through the time-honoured process of ad-hoc, temporary federal government committees for implementation by multiple, variously organised state and territory authorities. The real problem is producing a consistent, flexible response to any developing national infectious disease emergency. No other nation tries to do that without having a national authority, made up of full-time professionals with a fair degree of independence from the political process. The United States has its Centers for Disease Control and Prevention (http://www.cdc.gov); the United Kingdom its Health Protection Agency (http://www.hpa.org.uk); and, perhaps the most pertinent example, Canada has its Public Health Agency (http://www.phac-aspc.gc.ca), established in the aftermath of the SARS (severe acute respiratory syndrome) outbreak. The European Union has set up a supranational European Centre for Disease Prevention and Control (http://www.ecdc.europa.eu). A plan can only ever hope to put in place all the resources needed for a response, but a flexible, consistent, science-based and targeted national response to infectious and other health emergencies requires a professional national authority.

Rodney C Givney

To the Editor: Treatment of critically ill pregnant women is challenging, and information on medication use during pregnancy is scant. We describe the case of a pregnant woman who required extracorporeal membrane oxygenation (ECMO), prolonged sedation and paralysis to treat acute respiratory distress syndrome secondary to pandemic (H1N1) 2009 influenza. A 34-year-old pregnant woman (G2P1) at 21 weeks’ gestation presented to a metropolitan hospital with level 1 intensive care unit facilities. She had known Grade 2 placenta praevia, a 5-day history of influenza-like symptoms, and no history of asthma, chronic disease or recent travel. On examination, she was severely hypoxic (PaO2, 27 mmHg on 15 L/min O2), conscious, tachypnoeic and speaking in single words. A chest x-ray showed extensive bilateral infiltrates (Box). She needed urgent endotracheal intubation but remained hypoxic despite maximal intensive mechanical ventilation. The patient was transferred to St Vincent’s Hospital, Sydney, where venovenous ECMO was commenced on arrival. Her oxygenation status improved and remained satisfactory. Mechanical ventilation was reduced (tidal volume, < 6 mL/kg; peak pressure, < 30 cm H2O) to avoid ventilator-induced lung injury. The patient required very high doses of morphine, fentanyl, midazolam, propofol, dexmedetomidine, cisatracurium and heparin during ventilation and ECMO. In addition, empirical treatment with oseltamivir (150 mg twice a day, Days 1–8), azithromycin and ceftriaxone was started on admission, before a bronchoalveolar lavage specimen tested positive for influenza A and pandemic influenza. Furthermore, a multiresistant Escherichia coli caused ventilator-associated pneumonia, which was treated with meropenem (1 g three times a day, Days 17–30). ECMO was discontinued on Day 19, when lung function had improved. No other organ failure developed. On Day 21, a tracheostomy was performed for severe weakness and weaning failure. The patient was weaned from the ventilator on Day 35 and was discharged home 2 weeks later, after making a full recovery. She gave birth by caesarean section at 35 weeks’ gestation. The baby was in good health and the patient recovered well — both left hospital 3 days after the birth. Information on the use of medication in pregnant women who require intensive care is limited, especially the use of neuraminidase inhibitors.1 We found little evidence on the safety of long-term use of neuromuscular blockers and sedation in pregnancy, with or without ECMO.2 Most literature on this topic describes short-term use of neuromuscular blockers and sedation. Dexmedetomidine has a short postmarketing history, and has therefore had limited use. Data from Australia and New Zealand indicate that 9% of patients admitted to an intensive care unit with pandemic influenza are pregnant. An estimated inhospital mortality rate of more than 16% in this population indicates the severity of the infection.3,4 Single-organ lung failure is a common feature of complicated pandemic influenza, and venovenous ECMO should be considered in these circumstances.2,4,5 Our case demonstrates that ECMO and the drugs necessary for its use can be used during pregnancy in a patient with influenza-associated acute respiratory distress syndrome, and that survival of the patient and fetus is possible. Chest x-ray of a pregnant woman with influenza-associated acute respiratory distress syndrome showing extensive bilateral infiltrates

Susan A Welch · Leone N Snowden · Hergen Buscher

Objective: To compare bloodstream infection (BSI) rates, pathogens and mortality among Indigenous and non-Indigenous adults in central Australia.Design, participants and setting: Retrospective study of adult patients (aged ≥ 15 years) admitted to Alice Springs Hospital (ASH) between 1 January 2001 and 31 December 2005. Patients were followed up until 30 June 2008.Main outcome measures: Admission-based and population-based BSI rates and mortality rates for Indigenous and non-Indigenous adults.Results: During the study period, there were 824 BSI episodes (Indigenous, 753; non-Indigenous, 71). The admission-based BSI rate for Indigenous patients was 26.5 (95% CI, 26.4–26.6) per 1000 adult admissions, compared with 5.2 (95% CI, 5.1–5.2) per 1000 adult admissions for non-Indigenous patients (infection rate ratio [IRR], 5.13 [95% CI, 5.10–5.18]). The population-based BSI rate was 1354.7 (95% CI, 1256.3–1460.8) per 100 000 persons per year among Indigenous patients and 69.9 (95% CI, 55.1–88.6) per 100 000 persons per year among non-Indigenous patients (IRR, 19.4 [95% CI, 15.1–24.9]). These differences were not explained by higher comorbidity levels among Indigenous patients. Human T-cell lymphotropic virus type 1 and Strongyloides stercoralis infected 43% and 35%, respectively, of Indigenous patients tested. The risk of death during the follow-up period was 32.1% for Indigenous and 13.4% for non-Indigenous patients (hazard ratio [HR], 2.69 [95% CI, 1.38–5.25]; P = 0.004). Mortality rates were higher among Indigenous patients who had more than a single BSI (HR, 1.86 [95% CI, 1.32–2.62]; P < 0.001). The mean age at death was 48.5 years (SD, 16.2 years) for Indigenous patients and 75.1 years (SD, 18.7 years) for non-Indigenous patients (P < 0.001).Conclusion: Indigenous adults living in central Australia experience BSI rates that are among the highest reported in the world. These are associated with a high risk of death, and are a likely consequence of the poor socioeconomic circumstances of Indigenous people.

Lloyd J Einsiedel PhD, FRACP · Richard J Woodman PhD

Objective: To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life.Design: A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Immunisation Register.Participants and setting: All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age.Main outcome measures: Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol).Results: Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% CI, 416.2–437.2). Incidence rates were two times higher (relative risk, 2.12; 95% CI, 1.98–2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6–7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% CI, 0.60–2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI.Conclusions: Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.

Kerry-Ann F O’Grady GDipPH, MAppEpid, PhD · Paul J Torzillo AM, MB BS, FRACP, FJFICM · Anne B Chang FRACP, MPHTM, PhD

Objective: To describe the impact of pandemic (H1N1) 2009 influenza (nH1N1) on Indigenous people in the Top End of the Northern Territory at community, hospital and intensive care unit (ICU) levels. Design, setting and participants: We analysed influenza notifications for the Top End from 1 June to 31 August 2009, as well as data on patients admitted through Top End emergency departments with an influenza-like illness. In addition, data on patients with nH1N1 who were admitted to Royal Darwin Hospital (RDH) and the RDH ICU were prospectively collected and analysed.Main outcome measures: Age-adjusted notification rates for nH1N1 cases, Top End hospital admission rates for patients with nH1N1 and RDH ICU admission rates for patients with nH1N1, stratified by Indigenous status.Results: There were 918 nH1N1 notifications during the study period. The age-adjusted hospital admission rate for nH1N1 was 82 per 100 000 (95% CI, 68–95) estimated resident population (ERP) overall, with a markedly higher rate in the Indigenous population compared with the non-Indigenous population (269 per 100 000 versus 29 per 100 000 ERP; adjusted incidence rate ratio, 12 [95% CI, 7.8–18]). Independent predictors of ICU admission compared with hospitalisation were hypoxia (adjusted odds ratio [aOR], 4.5; CI, 1.5–13.1) and chest x-ray infiltrates (aOR, 4.3; CI, 1.5–12.6) on hospital admission.Conclusions: Pandemic (H1N1) 2009 influenza had a disproportionate impact on Indigenous Australians in the Top End, with hospitalisation rates higher than those reported elsewhere in Australia and overseas. These findings have implications for planning hospital and ICU capacity during an influenza pandemic in regions with large Indigenous populations. They also confirm the need to improve health and living circumstances and to prioritise vaccination in this population.

Shaun M Flint MB BS, BSc, FRACP · Joshua S Davis MB BS, DTM · Jiunn-Yih Su MB, MPH · Erin P Oliver-Landry MB BS, BSc · Benjamin A Rogers MB BS, FRACP · Aaron Goldstein MB BS · Jane H Thomas BN, GradDipPH · Uma Parameswaran MB BS · Colin Bigham MB BS, MRCP, FRCA · Kevin Freeman BSc · Paul Goldrick FCICM, FANZCA, FFARCSI · Steven Y C Tong MB BS, FRACP

To the Editor: Aboriginal and Torres Strait Islander people were more at risk of hospitalisation, admission to intensive care units and death during the 2009 influenza A pandemic than non-Indigenous Australians.1 We conducted a descriptive analysis of our response to the pandemic at Winnunga Nimmityjah Aboriginal Health Service (Winnunga) — an Aboriginal community controlled health service in Canberra, Australian Capital Territory, which provides comprehensive primary health care to more than 3500 patients per year. Data were sourced from the Winnunga electronic patient record system, pathology laboratories and ACT Health. The Winnunga Board approved this analysis and report for publication. In May 2009, we implemented the pre-existing Winnunga influenza pandemic plan, working closely with ACT Health and the ACT Division of General Practice. We enhanced infection control, implemented influenza testing procedures, initiated electronic data collection and obtained oseltamivir from the ACT stockpile to dispense on site. We adapted ACT Health pandemic protocols to create a flow chart appropriate for Winnunga, with approval from the ACT Chief Health Officer. This involved using clinical discretion to decide whether to dispense oseltamivir to Aboriginal and Torres Strait Islander people with mild illness, and included the provision to supply prophylactic oseltamivir to high-risk household contacts, especially in overcrowded households. A plan was made to open an on-site influenza clinic, but this was not necessary. Increased testing for influenza commenced in late May. The first patient with pandemic (H1N1) 2009 influenza was identified on 1 July (Box). Of the 168 nasal swabs tested for influenza by polymerase chain reaction analysis, 52 (31%) were positive for pandemic (H1N1) 2009 influenza. In addition, six Winnunga patients tested positive at other locations. In late July, testing guidelines changed and laboratory testing was no longer recommended for most patients with influenza-like illness.2 Consequently, we did not identify test-positive cases past the beginning of August. The actual number of cases of pandemic influenza that occurred in Winnunga patients is unknown. Of the 58 patients who tested positive, 54 were Aboriginal and/or Torres Strait Islander, 28 were male, and 47 were ACT residents. The mean age was 22 years (range, 0–62 years), 31 patients were aged under 20 years and four patients were pregnant. There was one overnight hospitalisation. During July, Winnunga accounted for 8% (44/551) of all notified pandemic influenza cases in the ACT — more than expected based on patient numbers alone. However, more testing may have been done at Winnunga than at other organisations because of our high-risk population. In July and August, 13% (204/1604) of all presenting patients at Winnunga had an influenza-like illness. There were 229 recorded episodes of influenza-like illness between May and November with a sharp peak in July and a smaller peak in August (Box). Oseltamivir dispensing commenced 1 week before identification of the first patient who tested positive, and corresponded with episodes of influenza-like illness (Box). A total of 107 courses of oseltamivir were dispensed to 33 children and 74 adults. Clinical risk factors other than Aboriginal and Torres Strait Islander status were recorded for 47 of these patients. Oseltamivir dispensed to Winnunga patients at other locations was not included in our analysis. We do not know whether oseltamivir made a difference in reducing severity of disease or preventing hospitalisations in our patients. During July and August 2009, pandemic influenza created an increased workload at Winnunga. Although there were some staff absences due to pandemic influenza, these were short and did not significantly affect clinical functions. Pandemic influenza in patients was also not as severe as planned for. A more severe pandemic would place a significant burden on our already busy Aboriginal medical service. A pre-existing influenza pandemic plan, internal public health capacity, good working relationships with local health agencies, on-site dispensing and service-specific protocols were important features of our response to the 2009 pandemic. Vaccination for influenza is being strongly promoted at Winnunga in 2010. Influenza-like illness, influenza testing, tests positive for pandemic (H1N1) 2009 influenza, and courses of oseltamivir dispensed at Winnunga Nimmityjah Aboriginal Health Service, May to November 2009

Ana Herceg · Peter G Sharp · Christine G Arthur · Julie A Tongs

Objective: To evaluate the assessment and treatment outcomes of a prison hepatitis service.Design and setting: A retrospective, observational cohort study of prison inmates who attended hepatitis clinics from 1996 to 2005 at correctional centres in New South Wales.Patients: Inmates who attended the clinics, including a nested case–control series of patients who received antiviral treatment and age- and sex-matched patients who did not receive treatment.Main outcome measures: Demographic and clinical characteristics of patients who attended the service; correlates of selection for antiviral treatment; and clinical and virological outcomes of treatment.Results: Of the 1043 inmates who attended the clinics, 851 were men (82%) and 994 (95%) were referred for HCV infection; the mean age for this group was 33 years (range, 18–74 years). In the case–control series (185 treated and 186 untreated patients), selection for treatment was not biased by culturally and linguistically diverse background, current methadone treatment or psychiatric status. In the treated group, 76 of 138 genotyped patients had a genotype that is predictive of favourable treatment response, and a small minority of those with available liver biopsy results had established cirrhosis (7/119 patients). Of treated patients for whom complete follow-up data were available, 55% achieved sustained virological response and 100% adhered to therapy. In addition, treatment episodes were not especially complicated.Conclusion: Although the prison population has high rates of injecting drug use and poor mental health, imprisonment offers an opportunity for assessment and treatment of chronic HCV infection.

Leng Boonwaat RN, MPH · Paul S Haber BSc, MD, FRACP · Michael H Levy MB BS, MPH, FAFPHM · Andrew R Lloyd MB BS, MD, FRACP

To the Editor: In their recent article, Beaman and Leung raised a number of important and pertinent issues about what we can learn from the influenza pandemic of 2009.1 However, we would like to correct a number of misconceptions on their part, including claims that Western Australia’s central public reference laboratory, PathWest Laboratory Medicine WA, (i) unreasonably favoured polymerase chain reaction (PCR) testing over antigen testing; (ii) rationed and prioritised testing primarily because of inability to cope with the high demand; (iii) rarely achieved the benchmark turnaround time of 48 hours; and (iv) spent excessive time processing a large number of specimens, of which 96% were reported as negative. State reference laboratories had to provide tests that would best guide individual patient management and the most effective use of hospital beds, as well as informing the public health response. The decision to avoid antigen detection tests was supported by the World Health Organization from the beginning of the pandemic2 and confirmed by subsequent published data showing that PCR testing was more reliable than antigen testing.3,4 Inaccurate test results hinder rather than help the pandemic response,5 especially in the early stages. From very early in the pandemic, we prioritised samples from hospitalised patients, health care workers, people at higher risk of severe disease and cases of special public health importance. For these urgent samples we aimed for, and largely achieved, a 48-hour turnaround time. Beaman and Leung did not allow for the substantial delays in transport and processing of samples before testing, which contributed 2–3 days to the turnaround time. A similar experience was reported in Victoria.6 This has highlighted the need to improve the way in which samples are handled at all stages between collection and testing. Rationing of services was a decision made in consultation with our public health colleagues, to ensure sustainable testing capacity for essential clinical and public health needs. In the end, PathWest tested 24 310 samples, representing 92.8% of the samples received, which included all of the high-priority and/or critical samples. It is misleading to suggest that a 96% negative rate was inefficient, and is a misunderstanding of the purpose of testing in the different phases of the pandemic. In the early phases, the yield of positive test results was expected to be low, as there was active case-finding at a time when no or very little virus was present in Australia. Across the course of the pandemic, the positive rate at our laboratory was 23% overall and 40% during the peak week. The response of public and private laboratories to the pandemic throughout Australia was impressive, and has now been the subject of state and national debriefings to identify potential improvements and the highest priorities for action. As part of that, we should all look at how we could improve our own laboratory’s performance and how we could make the best contribution to dealing with future pandemics and other emerging infectious diseases, both as individuals and as members of organisations. We would like to take this opportunity to acknowledge all the people within and outside laboratories who made a huge effort to save lives and reduce the impact of the pandemic.

David W Smith · David J Speers · Rodney A Bowman

To the Editor: The recent article by Davis and colleagues reported that the SMART-COP score underestimates the severity of pneumonia in tropical northern Australia, but can be improved by using locally relevant additions.1 The authors’ revised scoring system, SMARTACOP, increased the score for an albumin level < 35 g/L and added Aboriginal or Torres Strait Islander status as a variable. While these additions are useful, the reason for adding ethnicity was not fully clarified. A factor overlooked was low serum 25-hydroxyvitamin D [25(OH)D] levels among dark-skinned Australians.2 Smoking, identified as a marginally insignificant risk factor,1 is also associated with lower serum 25(OH)D levels.3 Vitamin D enhances the innate immune system through induction by 1,25-dihydroxyvitamin D of cathelicidin and defensins, which combat several types of bacterial and viral infections including upper respiratory tract infections.4 In the 1918–1919 influenza pandemic in the United States, many deaths were due to pneumonia that occurred as a complication of influenza infection. An ecological study found that indices for levels of vitamin D production from solar ultraviolet-B irradiance explained 50% of the variance in pandemic case-fatality rates among 12 communities.5 The mechanisms proposed for the beneficial effect of vitamin D were reduced proinflammatory cytokine production, which would reduce damage to the epithelial lining of the lungs, and induction of cathelicidin and defensins to fight the secondary bacterial pneumonia infection. If sera are available for those included in the Australian SMART-COP study,1 they could be analysed for 25(OH)D levels to test this hypothesis.

William B Grant

In reply: We thank Grant for his interest in our study on pneumonia severity assessment in tropical Australia. Our revised scoring system included increased weighting for hypoalbuminaemia, as well as adding a point for Indigenous status, because these two factors had the strongest association with the need for intensive respiratory or vasopressor support on univariate analysis.1 Unlike vitamin D status, these and the other factors included in the scoring system are readily available measures that can be used in the clinical setting to rapidly predict the need for intensive support. The scoring system was not intended to identify underlying aetiology or risk factors for severe pneumonia. For example, Indigenous status is likely to be a surrogate measure for undiagnosed comorbidities, lack of access to health care, and socioeconomic disadvantage. We agree that vitamin D is important in immune function and that the levels of insufficiency that result in impaired resistance to infection are not well defined.2 Most data on vitamin D deficiency in dark-skinned populations in Australia come from temperate areas,3,4 and the reference offered by Grant to support the concern about vitamin D deficiency does not cite any data from Australian populations north of southern Queensland.5 Further studies are needed on the prevalence of vitamin D deficiency in Indigenous Australians in tropical areas, and the additional contribution of vitamin D deficiency independent of known risk factors of severity and outcome.

Joshua S Davis · Allen C Cheng · Bart J Currie · Nicholas M Anstey

Incorrect figure: In “Early evidence for direct and indirect effects of the infant rotavirus vaccine program in Queensland” in the 3 August 2009 issue of the Journal (Med J Aust 2009; 191: 157-160), there was an error in Box 1 (Lambert et al). Under “(a) Notifications”, the values for the 5–19-years and 20–64-years age groups should have been reversed. Box 1, with the corrected figure, is reproduced here. 1 Percentage change in rotavirus notifications, tests performed* and tests positive* after introduction of a publicly funded infant rotavirus vaccination program in Queensland in July 2007 * Testing performed by Queensland Health Clinical and Statewide Services. † Percentage change in the number of rotavirus notifications in 2007 and 2008 compared with the number in 2006. ‡ Percentage change in the number of rotavirus tests performed in 2007 and 2008 compared with mean annual age group-specific values from 2000 to 2006. § Percentage change in the proportion of tests positive for rotavirus in 2007 and 2008 compared with age group-specific values from 2000 to 2006.

Stephen B Lambert · Cassandra E Faux · Lisa Hall · Frances A Birrell · Karen V Peterson · Christine E Selvey · Theo P Sloots · Michael D Nissen · Keith Grimwood

Two Australian blood donors were diagnosed with relapsing Plasmodium vivax malaria 5 and 15 months, respectively, after their most recent travel to a malaria-endemic country. Common features included travel to Papua New Guinea (specifically, the Kokoda Trail); full compliance with recommended malaria chemoprophylaxis; and negative results on malaria antibody testing at the time of donation. Although all fresh blood components from the two donors issued on the basis of these negative results were recalled before transfusion, these cases underscore the increased potential for relapse of P. vivax in donors returning from malaria-endemic countries, as well as the inability to identify the potential for relapse using current malarial screening tests. Clinical recordPatient 1A 63-year-old man donated blood to the Australian Red Cross Blood Service (the Blood Service) 12s7 days after returning from an organised trek on the Kokoda Trail, Papua New Guinea (PNG). An enzyme immunoassay (EIA) for Plasmodium falciparum and Plasmodium vivax antibodies was non-reactive at donation. Twenty-six days later, the donor’s wife notified the Blood Service that her husband had been admitted to hospital with fever and rigors; he was subsequently diagnosed with P. vivax malaria based on visible P. vivax parasites in a blood film (13 800 parasites/μL), and a positive result on a (non-P. falciparum) malarial antigen test (Box). He was successfully treated with primaquine. After his discharge from hospital, he was interviewed by a Blood Service medical officer and reported that he had no history of malaria; complied fully with malarial prophylaxis (doxycycline 100 mg daily, starting 2 days before entering PNG and finishing 14 days after returning home); had 2 months of lethargy after his return and developed febrile symptoms 20 days after donation; and had not travelled outside Australia after his donation. He also reported that seven of his 15 trekking companions were diagnosed with malaria after the trek. Patient 2A 39-year-old man donated blood 13 months after returning from PNG. He had made three previous donations, the first 5 months after returning from PNG, all testing negative for malarial antibodies. During the trip, the donor walked the Kokoda Trail and complied fully with prophylaxis (atovaquone–proguanil, 250 mg/100 mg daily, starting 1 day before and finishing 7 days after travel). He did not recall any recognisable malarial symptoms during the trek, but noted that a trekking companion had malaria on return to Australia. Approximately 66 days after his latest donation, the donor notified the Blood Service that he had recently been admitted to hospital with a febrile illness subsequently diagnosed as non-P. falciparum malaria; P. vivax was later confirmed from the blood film (0.5% parasitaemia) (Box). He was treated with atovaquone–proguanil (250 mg/100 mg four times daily for 3 days), made a full recovery and was discharged from hospital. He later confirmed that he had not travelled outside Australia after his return from PNG. Results of diagnostic testing of the two donors are summarised in the Box. DiscussionMalaria is transmitted predominantly through the bite of an infected female Anopheles mosquito, but, because the parasite invades and multiplies in red blood cells (RBCs), it can also be transmitted by transfusion of any blood component containing RBCs.1 Although malaria is not endemic in Australia, between 500 and 900 cases are notified annually, constituting an ongoing risk of transfusion-transmitted malaria (TTM).2 However, this risk is well controlled — the most recent recorded case of TTM occurred in 1991, involving a donor infected with P. falciparum.3 Notably, the transfusion recipient died, an outcome observed in about 10% of TTM cases caused by P. falciparum.4 To minimise TTM risk in Australia, each potential donor is asked questions to elicit if he or she has spent time in malaria-endemic countries or is at risk of having had malaria. Those identified at risk of infection are tested with an EIA for P. falciparum and P. vivax antibodies (Malaria EIA, NewLabs, Newmarket, United Kingdom). When the EIA is negative, the RBC component of the donation is considered for transfusion if at least 4 months have elapsed since the donor’s risk exposure. The 4-month waiting period minimises the possibility of false-negative test results that arise from testing within the putative 7–14-day “window period” before a complete antibody response is detectable. The Blood Service implemented serological testing of donors for malaria in 2005, replacing the previous strategy of restricting manufacture of fresh blood components from at-risk donations (ie, donations from people who had visited malaria-endemic countries in the previous 12 months or from those who had resided in an endemic country for a cumulative total of 6 months or more in the previous 3 years).5 While effectively minimising the risk of TTM, the older strategy resulted in significant loss of transfusible components (estimated in 2001 at about 5% of the Blood Service’s annual RBC production). This loss was considered unacceptable in the face of mounting demands on supplies of blood and blood products. The feasibility of serologically testing at-risk donors to reduce the period of restriction and consequent component loss had been established in Europe, where serum tests had been implemented in France6 and the UK.7 Furthermore, the use of a validated antibody test to reinstate donors after a minimum of 4 months is permitted by the applicable regulatory standard used by Australia.8 The predominant TTM risk is associated with so-called “semi-immune” individuals born or resident for extended periods in malaria-endemic countries.9 In the semi-immune person, the infection may take the form of an “equilibrium” in which very low parasite loads (generally undetectable by microscopy, and even polymerase chain reaction [PCR] testing) coexist with malarial antibodies without producing overt symptoms. Most recently recorded cases of TTM have resulted from the failure to detect and exclude the RBC-containing components of donations from semi-immune donors infected with P. falciparum.4,6 When parasite loads are extremely low, even the best plasmodial PCR assay is unable to interdict all potentially infectious donations, given that a transfusion contaminated with as few as 10 parasites can transmit infection.1 This underpins the rationale for antibody-based testing as the optimum donor-screening test, underscored by the Australian regulatory standard’s explicit exclusion of the use of molecular tests to screen donors.8 Another potential TTM risk is that both P. vivax and Plasmodium ovale have a hypnozoite form that can persist in the liver and lead to relapses after successful treatment of the primary infection.10 The interval from primary infection to relapse ranges from 1 month to 4 years.11,12 Chemoprophylactic agents are prescribed based on their efficacy against blood-stage parasites, but they are, with the exception of terminal (ie, postexposure) primaquine prophylaxis, ineffective against hypnozoites.13 Thus, they cannot prevent relapse but may delay its onset.11 Our two cases were strikingly similar, and the evidence strongly implicates PNG (specifically, the Kokoda Trail) as the site of primary infection for both. This is consistent with published evidence showing that, among non-immune travellers and soldiers returning to Australia, those from PNG and neighbouring countries were more likely to have relapsing malaria.13-15 These two cases of apparent relapse associated with P. vivax malaria in non-immune donors are, to our knowledge, the first reported cases detected by antibody testing. Further, they were unexpected because the perceived TTM risk is predominantly associated with P. falciparum infected semi-immune individuals. This either indicates that malarial antibody titres in individuals harbouring hypnozoites decline to undetectable levels 4 months or more after infection or, alternatively, that levels of parasitaemia during a “suppressed” primary infection may be too low to stimulate a significant antibody response. Thus, the current testing strategy cannot be relied on to discriminate donors at risk of relapse. This should not be seen as a reason to reject antibody testing per se, as no other available laboratory test for parasitaemia can reliably identify these individuals. Notably, the strongly positive EIA results in samples taken from the two donors at the time of admission to hospital support a robust antibody response and are consistent with the high sensitivity of the Newmarket EIA observed in samples taken from patients with acute disease.1 The TTM risk posed by relapsing P. vivax infection occurs during the asymptomatic period because symptomatic individuals would be prevented from donating. Although not precisely known, this period is expected to be short, perhaps several days. The TTM risk posed by our two patients was contained. One RBC component had been issued (Patient 1), based on its non-reactive malarial antibody test result, 20 days before symptom onset. This was successfully recalled, avoiding any potential risk to recipients. Considering the 20-day period between donation and symptom onset, it is highly likely that the donation was made before the onset of parasitaemia and, therefore, the RBC component would not have been infectious. No fresh blood components from Patient 2 were issued. What do these two cases suggest about the safety of the current Blood Service testing strategy? They certainly raise concern given that their late detection could have resulted in transfusion of potentially infectious blood components. However, such cases appear to be exceedingly rare — these are the only two reported in Australia in more than 4 years of testing. Furthermore, the contribution of such cases to overall TTM risk appears to be minute, as no TTM cases have been reported since testing began We recently published a comprehensive review that supports the existing strategy — it concluded that the current TTM risk was less than 1 in 3.3 million and had not measurably increased after implementing the testing strategy.16 Importantly, the Blood Service achieved this level of safety while recovering over 70 000 fresh blood components that would otherwise have been unavailable annually. Nonetheless, recognising the limitations of the testing strategy and the imperative to reduce recipient risk where possible, the Blood Service is considering mitigation options. As these two cases suggest travel to PNG carries a disproportionately high risk, the Blood Service is considering the feasibility of excluding donors returning from PNG from the testing protocol, and restricting fresh component production from their donations for appropriate periods of time. Blood testing for relapsing Plasmodium vivax in the two patients Place Time Pf/Pv antibody EIA* Pf/Pv antigen ICT† PCR‡ Blood film Patient 1 Sample 1 Blood Service At donation (127 days after return from PNG) Non-reactive (S/Co 0.28) Not tested Not tested Sample 2 Blood Service At hospital admission (26 days after donation) Reactive (S/Co 4.2, 3.6§) Positive Pf band negative Pan malaria positive Plasmodial DNA detected (4415 parasites/μL) Pv parasites visible (13 800 parasites/μL) Sample 3 Blood Service In hospital after treatment (33 days after donation) Reactive (S/Co 4.8, 3.7§) Negative DNA not detected Patient 2 Sample 1 Blood Service At donation (13 months after return from PNG) Non-reactive (S/Co 0.27) Not tested Not tested Sample 2 Hospital At hospital admission (66 days after donation) Reactive (S/Co > 19, 18.8§) Positive Pf band negative Pan malaria positive Plasmodial DNA detected (1861 parasites/μL) Pv parasites visible (0.5% parasitaemia) Blood Service = Australian Red Cross Blood Service. EIA = enzyme immunoassay. ICT = immuno-chromatographic test. PCR = polymerase chain reaction. PNG = Papua New Guinea. Pf = Plasmodium falciparum. Pv = Plasmodium vivax. S/Co = sample-to-cut-off ratio (this test relates to the level of antibodies in each sample compared with a predetermined cut-off level). * Malaria EIA, NewLabs, Newmarket, United Kingdom. † Binax NOW Malaria assay, Inverness Medical, United States. ‡ artus malaria RG PCR, Qiagen, Hilden, Germany. § Two values were reported because repeat testing usually requires a double check to ensure accuracy.

Clive R Seed BSc · Jacqueline T Coughlin MB BS, FRACGP · Anne M Pickworth MB BS · Robert J Harley MB BS, BMus, FRACGP · Anthony J Keller FRACP, MRCPath, FRCP

An Eritrean-born man observed over an extended period had upper gastrointestinal symptoms, fever, hepatosplenomegaly and pancytopenia in the setting of advanced HIV infection and poor adherence to antiretroviral therapy. Despite thorough investigation, it was not until a repeat gastroscopic examination and gastric biopsy were performed 18 months after initial presentation that Leishmania infection was diagnosed. The species was identified by polymerase chain reaction assay as L. donovani. Physicians managing HIV-infected patients from regions where Leishmania is endemic should consider visceral leishmaniasis, even in patients who have not lived in a Leishmania-endemic region for many years. Clinical recordA 42-year-old Eritrean-born man who had previously lived in Sudan arrived in Australia in 1995. He had not travelled overseas since that time. He was diagnosed with HIV infection in 1996. He presented in 2005 with a 2-month history of odynophagia, dysphagia and vomiting. The patient was non-adherent to antiretroviral therapy and his CD4 count was 40 cells/μL (reference range [RR], 410–1590 cells/μL). He had low-grade fever, hepatosplenomegaly and pancytopenia (haemoglobin level, 118 g/L [RR, 130–180 g/L]; white cell count, 3.2 × 109/L [RR, 4.0–11.0 × 109/L]; and platelet count, 111 × 109/L [RR, 150–400 × 109/L]). A computed tomography scan confirmed hepatosplenomegaly, but there was no intra-abdominal or pelvic lymphadenopathy. A bone marrow biopsy showed hypercellular marrow with no granulomas or malignancy. Bone marrow fungal and mycobacterial culture and a polymerase chain reaction (PCR) assay for parvovirus DNA were negative. No abnormality was visible on gastroscopic examination. Histological examination of oesophageal biopsies showed chronic inflammation, but no fungal elements were detected by fungal stains, and fungal cultures were negative. A herpes multiplex PCR assay (capable of detecting herpes simplex virus types 1 and 2, cytomegalovirus and varicella-zoster virus) was negative. No Leishmania amastigotes (the non-flagellate, intracellular form of Leishmania) were identified. Symptoms improved after treatment with omeprazole and a period of improved adherence to antiretroviral therapy. Odynophagia, dysphagia, weight loss, intermittent fever and mild pancytopenia recurred and continued over the next 18 months. Despite changes to the antiretroviral therapy regimen and efforts to improve adherence, the patient’s CD4 count remained below 50 cells/μL and the HIV viral load was consistently > 750 000 copies/mL. A repeat gastroscopic examination 18 months after initial presentation demonstrated pseudomembrane formation over the upper stomach, and histological examination of a gastric biopsy showed a florid inflammatory cell infiltrate. Within histiocytes, numerous intracellular organisms 1–3 μm in diameter were identified as Leishmania amastigotes (Box). A PCR assay confirmed the presence of L. donovani, leading to a diagnosis of visceral leishmaniasis (VL) in the setting of advanced HIV infection. Induction treatment was commenced with daily liposomal amphotericin B 4 mg/kg for 1 week, followed by weekly doses for a further 4 weeks. The odynophagia, dysphagia and pancytopenia resolved over the following 4 months. Secondary prophylaxis with monthly doses of liposomal amphotericin B continued, but the patient missed three doses over the next 6 months and symptoms recurred. When repeat endoscopy, biopsy and histology showed that Leishmania was still present, therapy was recommenced and the symptoms resolved. Further unsuccessful attempts were made to optimise the antiretroviral therapy regimen. After 12 months of intermittent adherence to treatment, the patient again developed symptoms. He subsequently returned to East Africa and was lost to follow-up. DiscussionLeishmaniasis is a protozoal infection caused by species of the genus Leishmania, an intracellular parasite transmitted by sandflies of the genus Phlebotomus. Clinical presentations include visceral, cutaneous and mucocutaneous forms, depending on the infecting species and the strength of the host’s cell-mediated immunity. The Leishmania donovani complex, composed of L. donovani and L. infantum/chagasi, is responsible for most cases of VL. Where co-infection with HIV is present, deteriorating immune function may delay the clinical presentation of VL for many years after the initial infection.1 Although documented in 70 countries, most cases of VL occur in southern Asia (particularly north-eastern India, Nepal, and Bangladesh) and East Africa (mostly Sudan, Ethiopia and Eritrea). In these regions, L. donovani is the predominant species. About 15 000 to 20 000 cases of VL occur annually in Sudan, particularly in the eastern region bordering Ethiopia and Eritrea, and VL–HIV co-infection rates are as high as 29%–40%.2-4 In southern Europe, especially in urban coastal regions, where the less virulent L. infantum is the predominant organism, high rates of VL–HIV co-infection have also been described.5 The usual incubation period of VL is 2–6 months, but a proportion of patients will remain asymptomatic after primary infection, and immunosuppression can lead to reactivation of the disease many years later. The classic presentation of VL includes fever, weight loss, hepatosplenomegaly, pancytopenia and hypergammaglobulinaemia. HIV co-infection does not dramatically alter this presentation.6,7 Gastrointestinal tract involvement is evident in 7%–40% of VL–HIV co-infected patients, and may be accompanied by odynophagia, dysphagia, chronic diarrhoea, malabsorption or abdominal pain.6,8 Most patients with HIV who present with VL are in a state of advanced immunodeficiency: up to two-thirds of patients with concomitant HIV and L. donovani infection have CD4 counts < 200 cells/μL.3 Serological tests for VL are of low sensitivity and thus have limited diagnostic value for VL–HIV co-infected patients.2 Demonstration of amastigotes in tissue or blood is the preferred method of diagnosis. Examination of a bone marrow smear is often the most useful diagnostic test (sensitivity, 67%–94%),2,4,8 and aspirates from other sites can be considered depending on the clinical presentation. A PCR assay for Leishmania DNA may improve the diagnostic yield and allow identification to a species level. Treatment of VL in patients with underlying HIV infection is associated with lower cure rates, higher rates of drug toxicity, higher relapse rates and greater mortality than treatment of VL in immunocompetent patients.2,9 Optimal treatment regimens have not yet been developed, as there is a paucity of clinical data on patients with VL–HIV co-infection. Treatment options include pentavalent antimonials such as sodium stibogluconate, standard and lipid formulations of amphotericin B, miltefosine, paromomycin and pentamidine.2,9 Although liposomal amphotericin B has not been formally assessed in VL–HIV co-infected patients, it has the highest therapeutic index of all antileishmanial drugs and a superior safety profile, making it the first choice for treatment in resource-rich countries. Although there has been recent interest in miltefosine because of its oral administration, an Ethiopian study showed that miltefosine was less effective than intramuscular sodium stibogluconate for treating HIV-infected patients.10 Maintenance secondary prophylaxis and initiation of effective antiretroviral therapy is required to prevent relapse.9 In a study conducted in a resource-limited setting in Ethiopia, antiretroviral therapy was shown to reduce the risk of VL relapse by about 50%.3 The increasing rate of VL–HIV co-infection in Africa and India is a major concern, but so far, very few cases have been reported in Australia. The case described here highlights the importance of considering the diagnosis of VL in a patient with immunodeficiency and a history of travel to, or residence in, a Leishmania-endemic region; the value of tissue biopsy combined with PCR testing; and the need for ongoing secondary prophylaxis and immune restoration. Section of gastric biopsy showing a florid inflammatory cell infiltrate and numerous Leishmania amastigotes Amastigotes appear as non-flagellate, intracellular, ovoid bodies (1–3 μm in diameter) within histiocytes (haematoxylin and eosin stain, original magnification × 300).

Samuel C Hume MB BS(Hons), FRACP · Craig A Aboltins MB BS(Hons), FRACP · Karin A Thursky MB BS, FRACP, MD · John R Daffy MB BS, FRACP · Peter A Stanley MB BS, FRACP

To the Editor: A 59-year-old woman presented with acute bilateral deafness, ataxia, and pyrexia. She had no significant past medical history and was taking no medications or antibiotics. Examination revealed normal tympanic membranes. Audiology and fundoscopy were not performed. Full blood examination results, electrolyte levels and renal function were normal. A plain chest x-ray was unremarkable, but a computed tomography scan showed lobar consolidation. The patient had microscopic haematuria but no pyuria, and negative urine culture. Blood cultures were repeatedly negative. She was commenced on a third-generation cephalosporin, as well as corticosteroids on suspicion of vasculitis. Her condition improved initially, but relapsed on weaning from the steroids. Further history-taking revealed that 3 weeks before the onset of her illness, the patient’s pet budgerigar had a prolonged diarrhoeal illness and subsequently died. On suspicion of Chlamydophila infection, she was commenced on doxycycline, and the fever resolved within 24 hours. Doxycycline was continued for 14 days, and the patient remained well thereafter. Her hearing returned to normal over 3 days. Autoimmune markers, and serological tests for Legionella species, Mycoplasma species and respiratory viruses were negative. However, her Chlamydophila psittaci IgG titre was > 512 and Chlamydophila pneumoniae IgG titre was > 2048, consistent with a recent infection with either C. psittaci or C. pneumoniae. Convalescent serological tests were not performed. To our knowledge, acute hearing loss has been reported only four times as an extrapulmonary feature of Chlamydophila infection. Puolakkainen and colleagues reported the case of a 49-year-old man who presented with otitis media in one ear and sudden deafness in the other after a severe influenza-like illness thought to be due to psittacosis.1 Crosse performed a retrospective study that looked at the clinical and epidemiological features of cases in which there was a fourfold rise in C. psittaci titre. One patient developed deafness, although no further detail was given.2 Brewis and McFerran reported the case of a 61-year-old pig farmer with sudden bilateral hearing loss associated with C. psittaci pneumonia. The hearing loss resolved with antibiotics and prednisolone.3 Finally, Darougar et al reported the case of a 15-year-old girl who presented with chronic relapsing sensorineural hearing loss, uveitis, keratitis and vertigo.4 In this case, chlamydial antibody titres were raised, and C. psittaci was isolated from the conjunctiva. She had no respiratory involvement. Her only animal exposure was to a cat with conjunctivitis, which tested negative for chlamydial and viral infections. Interestingly, Dünne et al have recently found an epidemiological association between sensorineural hearing loss and elevated C. pneumoniae IgA titres.5 This case represents further evidence that acute deafness may be a component of atypical pneumonias, and especially of Chlamydophila infection.

Andrew F Whyte · Richard Yu

What did we do well in the first year of pandemic (H1N1) 2009, and what can we do better? In Mexico in April 2009, a new H1N1 influenza strain appeared to be associated with a high mortality rate. This fuelled fears that a highly virulent virus would quickly spread internationally and cause millions of deaths. Appropriately heightened surveillance and controls were put in place, and Australia activated its “well-rehearsed plan for response to pandemic influenza”.1 Across the country by mid May, we had in place accurate polymerase chain reaction (PCR) testing for “swine flu”, improved public awareness of infection control and good public health surveillance. By September, Australia was among the first countries with a vaccine available. Now, a year after the virus first emerged, what have we learnt and how could our pandemic response be improved in the future? Swine flu did spread rapidly internationally. However, by late May, data from the United States spring showed that case-fatality rates were lower than those from seasonal influenza (< 0.1%).2 But what would happen in the Australian winter? By mid June, we knew that case-fatality rates here were also low.3 Despite this knowledge, many costly interventions continued, including border control, widespread use of antivirals, school closures and contact tracing, but with little evidence that these made much difference to the overall rate or spread of the virus. Appropriately, when it became obvious that the spread of the virus could not be controlled, the national pandemic plan was modified. A new phase, “Protect”, was adopted on 17 June,1,4 with a greater focus on treating and caring for those patients who were more vulnerable to severe outcomes. The word “pandemic” can evoke needless fear and panic. This term would be best used when a virus not only spreads widely but also has increased virulence — this latter aspect is currently not considered in the World Health Organization definition.5 Virulence needs to be measured quickly and accurately. Pandemic plans seem to assume a case-fatality rate of 1% or more. However, a different approach could be better for a virus such as swine flu with a mortality of 0.01% or less — predetermined responses that take into account different levels of virulence, not just the spread of a virus. The US has such a grading system (similar to that used for hurricane severity),6 but it was not used to guide this public health response. “Real-time” viral spread and activity can be followed with remarkable accuracy using Google Flu Trends.7 In the Australian community, the effects of the pandemic (H1N1) 2009 influenza virus were “at most like influenza circulation in a season of moderate seasonal activity”.8 Rates of absenteeism from work and school were similar to those seen in the winter of 2007.1 The 191 associated deaths were substantially fewer than the 3000 estimated yearly deaths from seasonal influenza in Australia.1,4,9 Although there may have been additional influenza-associated deaths that were not diagnosed by laboratory testing, [a] broader measure of all Australian deaths resulting from influenza or pneumonia currently indicates that there have been fewer such deaths than in other influenza or winter seasons.1 Some groups, such as Indigenous peoples and pregnant women, were more vulnerable. Pregnant women had a tenfold higher rate of severe complications than others of the same age.8 Astute clinicians in Melbourne found that pregnant women with complications were often IgG2-deficient. Thus, we now potentially have a marker that identifies those at much greater risk from influenza and also new, related therapeutic options (using gamma globulin).10 Intensive care units (ICUs) in Australia managed to cope with the larger numbers of generally younger influenza patients, but had major problems and were, worryingly, very stretched.1,4 This demonstrated the lack of spare capacity in our hospitals and ICUs — a problem most apparent every winter. Australia’s population mortality rate from swine flu was 0.9 per 100 000.1,4 If a more virulent virus with a 1% case-fatality rate infected 30% of the population, our hospitals and ICUs could not cope, and we would have to find other ways of managing the problem. Despite the widespread use of costly oseltamivir stockpiles in Australia and elsewhere, there were no obvious effects in terms of slowing or altering the overall epidemic. Antivirals probably benefit individuals who are at high risk of complications, but in the general population the benefits may be marginal.11 In addition, the recommendations for who should receive antivirals changed with the different declared phases of the pandemic (eg, from “Contain” to “Protect” phases). This led to confusion for both clinicians and the general public — were antivirals to be used to reduce transmission by ill patients, limit disease severity by stopping sick patients getting sicker, or for prophylaxis? Testing for swine flu was problematic. Most of those infected had only mild disease, but demand for testing was high. Rapid influenza tests had poor sensitivity, and no specific serological tests were available. PCR was the only reliable form of testing, but it is relatively expensive and labour-intensive. Thus, testing was often not available. Testing was also commonly centralised, which meant results were not readily available in a timely fashion, even for ill patients in many hospitals. Vaccines were also problematic. Australia was one of the first countries to manufacture and distribute a vaccine for pandemic (H1N1) 2009. However, it only became available after the epidemic finished around the end of September, in multidose vials containing thiomersal, and when a large proportion of the population may have been already immune (from recent infection or prior immunity). In vaccine trials, Australian participants had higher-than-expected levels of pre-vaccination cross-reactive antibodies.1 Thirty per cent of children aged > 3 years and 27% of adults aged 18–65 years had protective antibody levels, with 62% of adults having detectable antibodies.12,13 Older people are likely to have even higher pre-existing immunity, given their relatively lower rate of pandemic (H1N1) 2009 infection last winter. In the future, it could be worthwhile to consider another approach to vaccination. Currently, effective vaccines are usually only available “after the horse has bolted”. Because of poor matching, seasonal influenza vaccine efficacy varies from 50% to 80%.14 New vaccines that are safe and more effective, but that only have to be given once every 5–10 years and protect against a variety of influenza strains, could be a useful development. Large amounts of public money and resources were spent on antivirals and vaccines in Australia during the pandemic (H1N1) 2009 outbreak. Pandemic vaccines cost over $120 million here, widely reported and mass immunisation delivery costs for 20 million doses would likely be another $500 million. We also saw that infections spread easily. If people are sick, they should not be at work, school or travelling on public transport. Disproportionate fear generated by media reports resulted in many people presenting to emergency departments or medical practices when they had mild illness and should have stayed at home to recover on their own. However, we do need the ability to quickly assess those in risk groups or those whose condition deteriorates. This may require a phone triage system. Health care workers would then only need to directly assess the much smaller numbers of patients who may need antimicrobials or hospital admission or who are severely ill. Front-line general practitioners and other clinicians faced extreme difficulties because of deficiencies in implementing parts of the pandemic plan.15 This involved resource supply failures, time-consuming administrative burdens, delays in receiving laboratory test results and approval for provision of oseltamivir to patients, and a lack of clear communication about policy changes as the situation progressed.15 We could learn to adapt better as circumstances change and improve consultation with front-line clinicians in any future planning. The core components of current pandemic planning are influenza vaccination and antivirals. This may not be the best approach. Simple infection control measures such as hand hygiene and barrier methods (gloves, masks, isolation) reduce the spread of respiratory viruses.16 In the 1918–1919 pandemic, the vast majority of deaths were probably from bacterial complications rather than the influenza virus itself.17 Effective prevention, treatment and vaccines against bacteria are therefore potentially more effective in preventing deaths. The swine flu outbreak has provided lessons for all of us in the community — clinicians, health officials, politicians and patients. Despite our efforts to contain this virus with pandemic plans, the pandemic (H1N1) 2009 strain behaved like seasonal influenza and spread rapidly throughout the population, and then stopped just as rapidly. We need to devise better ways to decrease the spread of viruses and to identify and treat the small proportion of people infected with influenza who are likely to develop serious disease or complications. Most importantly, we need to establish better trigger points that take virulence as well as virus spread into account before we roll out pandemic plans.

Peter J Collignon FASM, FRACP, FRCPA

Objective: To assess the views, needs and intended behaviour of general practitioners and practice nurses (PNs) regarding pandemic influenza.Design, setting and participants: A postal survey of GPs and PNs in four Divisions of General Practice in New South Wales, selected to represent a diverse sample of practices from inner-city, semi-urban and rural areas. The study was undertaken from 1 February to 1 April 2009.Main outcome measures: GPs’ and PNs’ responses to survey statements assessing their awareness and perceived personal risk, intended behaviour in the event of a pandemic, and expectations surrounding antivirals, vaccine and personal and family protection.Results: Of 390 general practice staff who were sent the survey, 139 (36%) completed it. Most respondents felt confident that they possessed the necessary knowledge (71.5%, 98/137) and skills (73.7%, 101/137) to provide patient care during an influenza pandemic. Although 38.7% (53/137) stated that they would visit quarantined symptomatic patients, 41.6% (57/137) were unsure. More than half the respondents (53.2%, 74/139) stated that they would require access to vaccination and antivirals for their family as well as themselves before they would attend symptomatic patients at the general practice.Conclusion: These findings provide evidence of the need to ensure that general practice staff have access to personal and family protection to encourage an adequate response to a pandemic situation.

Holly Seale BSc, MPH, PhD · Kirsten F Ward BHSc · Nick Zwar MB BS, FRACGP, PhD · Debbie Van · Julie Leask BSc, MPH, PhD · C Raina MacIntyre MB BS, FRACP, PhD