Volume 196 Issue 5

We need high-voltage infection prevention and management, not short-sighted overuse of antibiotics. As long as human behaviour and medical practices exert unpredictable effects on the microbial environment, infectious disease will continue to challenge and surprise us. Changes in host factors (eg, immunosuppression, hospitalisation), environment ...

on behalf of the Executive Council of the Australasian Society for Infectious Diseases

Decades of population growth, globalisation and complacency are driving new epidemics. Unexpected plagues of epidemic infectious diseases have entered human history for centuries, often with devastating consequences. With good public health and the advent of new drugs, vaccines and insecticides in the middle of the 20th century ...

Duane J Gubler MS, ScD

A new series explores contemporary issues shaping medical school education Educating our future doctors has never before been such a high-stakes activity. The explosion of medical knowledge, new models of health care delivery, workforce imperatives and demands for greater social accountability are changing educational practice at an international level. Over the past decade, Australian medical schools have been at the forefront of many of these changes, as educators seek to consolidate our reputation as a provider of high-quality medical education. A major priority has been to ensure that the content of medical school programs is relevant and evidence-based. With competing demands on curriculum time, there has been a pressing need to define the core knowledge, skills and attitudes required by medical students to be practice-ready for their junior doctor years. This continues to be a complex and challenging exercise. There has been, for example, robust and at times acrimonious debate about the required depth of bioscience knowledge in entry-to-practice medical programs, in part fuelled by publication of the Australian Medical Education Study.1 Medical schools have also faced the task of extending the core curriculum to reflect changing emphases in health care delivery. Specific expertise is required to sustain new models of practice, such as interprofessional practice, effective management of the diseases of ageing, and chronic condition self-management support. The importance of laying the foundations of this expertise in medical school is increasingly being recognised, particularly within the broader context of the quality and safety movement.2 Considerable energy has also been devoted to optimising the efficiency and efficacy of medical school education.3 New theoretical models of learning, as well as the outcomes of educational research, are being used to define best practice.4 There has been an increasing emphasis on developing pedagogical approaches that help students to effectively appraise information and apply problem-solving frameworks. Substantial progress has also been made in the area of clinical skills acquisition, by applying techniques such as simulation-based learning, hypothesis-driven physical examination and deliberate practice.5 At the same time, the delivery of quality medical school education in Australia has been challenged by economic, logistic and workforce imperatives. One of the main reasons has been the need to overcome the shortage of medical practitioners, particularly in rural areas. This, combined with the expansion of the international student market, has led to a dramatic surge in medical student numbers in Australia, from 1287 in 2004 to a projected 3018 by 2014.6 The increasing demand for places has been accompanied by a growth in the number of medical schools between 2000 and 2008 from 10 to 19, with at least four other universities currently pursuing the right to establish medical programs. Significant challenges in coordinating clinical placements have arisen as a result of increasing student numbers and changing educational practices. The tertiary teaching hospital is no longer the sole provider of clinical education, and teaching now occurs in a wide variety of locations, including community settings and laboratories for simulation-based learning. Considerable effort has been required to foster consistency of curriculum delivery across these dispersed learning environments. Various bodies, such as the Australian Medical Council and Health Workforce Australia, are working to ensure medical students receive high-quality supervision as well as suitable clinical experience.7 Maintaining a well trained medical education workforce, nevertheless, remains at the heart of educating our future doctors. Several programs, such as Teaching on the run,8 are now offered to help clinical teachers enhance their expertise. Furthermore, a range of postgraduate qualifications is available for those wishing to explore the discipline in more depth or to assume leadership roles in medical education. A greater emphasis on academic development has contributed to strengthening of relationships with other areas of medical education. The continuum of learning is more clearly articulated than in the past; specifically, the Australian Curriculum Framework for Junior Doctors now provides a pivot between medical school education and vocational training.9 Medical schools are also strengthening their relationships with the wider community, in recognition of their social obligations. This has been exemplified by the development of the Indigenous Health Curriculum Framework,10 and selection procedures that aim to provide equity of access for disadvantaged applicants and shape the medical workforce so that it better serves diverse patient populations. With these developments has come a greater recognition of the need to evaluate the efficacy and cost-effectiveness of innovation in medical school education. It must be acknowledged that much of the reform in medical education has preceded rigorous inquiry, and the discipline has been rightly criticised for this.11 Accordingly, there has been a greater commitment to undertaking programmatic research and implementing strategies that feed outcomes back into educational policy and practice. In recognition of the importance of educating our future doctors, the MJA today begins a series of articles exploring the changes taking place in medical school education in Australia. For each article in this Medical Education series, there will be a one-page summary in the MJA’s print edition, and the complete text will be published on the MJA’s website (mja.com.au). doi: 10.5694/mja11.10968

Jennifer J Conn FRACP, MClinEd, BSc(Hons) · David A Ellwood MA, DPhil(Oxon), FRANZCOG(CMFM) · James M Hillis MB BS(Hons), BMedSc

The full content of this article is available by downloading the PDF.

The full content of this article is available by downloading the PDF.

Incidence rates of cancer vary over time;1 this is called a “period effect”. Incidence rates of cancer also tend to increase with age;1 this is called an “age effect”. Another time variable that is associated with the incidence of cancer is year of birth of the patient — the “cohort effect”. Many authors have used real data to emphasise the importance of cohort effects for assessing trends in incidence.2,3 Here, I present a simple, hypothetical example to illustrate the cohort effect. Consider the data shown in the Box. In this hypothetical population, the age groups are 0–29, 30–59 and 60–89 years and everyone dies on their 90th birthday. The Box contains data for three years (1940, 1970 and 2000). For each year and age group, n denotes the size of the population, P denotes the probability of being diagnosed with cancer in the year, and EI denotes the expected incidence (the expected number of new cases of cancer), which is calculated with the formula: EI = n × P In 1940, in the 0–29-year age group, there were 600 people, the probability of being diagnosed with cancer was 0.01, and the EI was thus 600 × 0.01 = 6. In the whole population, 41 of 1000 people are expected to be diagnosed with cancer. In this scenario, a wonder drug that prevents cancer was discovered in 1941. However, it must be administered in utero, so only people born since 1941 can benefit. In 1970, assume there were 100 people aged 0–29 years. In this group, the probability of being diagnosed with cancer was 0, because they were born since 1941, and the EI was 0. The 600 people, who were aged 0–29 years in 1940, were aged 30–59 years in 1970; the probability of being diagnosed with cancer in that age group was 0.05, as in 1940; so the EI was 30. In the whole population, 90 of 1000 people are expected to be diagnosed with cancer in 1970. In 2000, only those aged 60–89 years were born before 1941. Overall, 120 of 1000 people are expected to be diagnosed with cancer. Thus, in 1940 there would be 41 new cases in a population of 1000, in 1970 there would be 90 new cases in a population of 1000, and in 2000 there would be 120 new cases in a population of 1000. This trend suggests that things will be worse in 2030. In fact, the disease will disappear in 2030. A hypothetical population that illustrates the cohort effect 1940 1970 2000 Age (years) n P EI n P EI n P EI 0–29 600 0.01 6 100 0 0 300 0 0 30–59 300 0.05 15 600 0.05 30 100 0 0 60–89 100 0.20 20 300 0.20 60 600 0.20 120 0–89 1000 41 1000 90 1000 120 In this scenario, n denotes the population size, P denotes the probability of being diagnosed with cancer in the year and EI denotes the expected incidence of cancer, and a drug that prevents cancer when administered in utero was discovered in 1941.

Terence M Mills

Social networking and search engine data confer real-time advantages The population-level pattern-based nature of epidemiological research makes it well suited for computational work in general, and for machine learning in particular. The social nature of disease spread makes recent trends in social media computing specifically amenable to epidemiological research, but can computational techniques be reliable indicators and predictors of communicable disease? Previous approaches to epidemiology have had to rely on self-report mechanisms (eg, online health surveillance at www.flutracking.net), or on reports from health care services, such as the United Kingdom Health Protection Agency (HPA), the United States Centers for Disease Control (CDC) and the European Centre for Disease Prevention and Control. The recent growth in the use of social media means that people now volunteer large amounts of information on a real-time and location-specific basis. Along with this, advances in computational intelligence in the form of machine-learning and data-mining techniques have proven useful in knowledge discovery and predictions in other domains. So, how best can we make use of and interpret that vast quantity of information? The information is of two main kinds: that provided by users (status updates and microblogging, such as on Facebook and Twitter); and requests for information using search engines such as Google and Yahoo. Patterns found in this information can be interpreted by applying machine-learning and data-mining techniques. Roughly speaking, machine learning and data mining are used to make predictions based on patterns learned from data and discovering patterns in data. In the words of Tom Mitchell, “A computer program is said to learn from experience E with respect to some class of tasks T and performance measure P, if its performance at tasks in T, as measured by P, improves with experience E”.1 Researchers from the University of Bristol in the UK have been using Twitter to investigate the possibility of tracking influenza spread. They collected about 160 000 tweets per day over 24 weeks from the 54 most populated areas in the UK, in which they sought, for example, reports of sore throat, fever or headache. Reports from the HPA (based on general practitioner consultations per 100 000 citizens resulting in influenza diagnoses) were used as the “gold standard” basis for disease activity when learning to predict influenza rates. Learning and discovering patterns resulted in the ability to predict HPA flu rates with about 90% accuracy.2 The University of Iowa used a similar approach, whereby public sentiment about pandemic (H1N1) 2009 influenza and actual disease activity was tracked using Twitter posts. Using about a million influenza-related tweets and the CDC’s reported data, machine learning was used to construct a predictive model. Even though the model does not predict disease activity, it was able to estimate activity in real-time, reflecting the data in the official CDC reports. The advantage is that “real-time” is typically 1–2 weeks ahead of CDC reports.3 People do not use use Twitter to discuss their health — many use search engines to research symptoms, treatments, spread of diseases, and so on. Google conducted an experiment on monitoring search queries related to influenza. An analysis of 5 years’ worth of log-files in combination with available CDC information was used to construct a regression model for influenza surveillance, which contains the top 45 search terms. This model was used to predict the spread of influenza in the 2007–2008 influenza season. As with the University of Iowa example, the system was able to consistently estimate the percentage of the population with influenza 1–2 weeks ahead of official CDC reports.4 I have highlighted just some of the emerging work on applying clever algorithms and large amounts of computational power to vast amounts of information generated by users of search engines and social media. Despite the impressive results, these approaches are not a panacea for epidemic surveillance. There are challenges, some shared with existing techniques and some that are unique. People discussing their health on Twitter are not representative of the general population, and Twitter use is not uniform across time and geography. Demographic data provided by traditional surveillance cannot (yet) be supplied by search queries. Additionally, it is difficult to separate discussion about epidemics from actual cases. Regardless of current shortcomings, these approaches will prove to be important parts of modern medicine.

Anders Kofod-Petersen DrScient

Infectious diseases expert Peter Collignon supports tight control over food-production practices. Worldwide, increases in deaths and morbidity in humans are associated with rapid increases in rates of antibiotic resistance in bacteria. This problem is escalating more quickly in gram-negative bacteria such as ...

Peter J Collignon AM, FASM, FRCPA, FRACP

Veterinary pharmacologist Stephen Page believes that antibiotic use in animals benefits human and animal health While antibiotic use in livestock has the potential to cause harm to human health, the likelihood of harm arising from the use of antibiotics under current Australian practices is highly unlikely. There is ample independent evidence supporting the long history of appropriate use of antibiotics in Australian livestock. For example, the past six annual reports of the National Residue Survey contain the results of tests for the presence of up to 38 antibacterial agents in the edible tissues of cattle, pigs, poultry and sheep.1 Almost 400 000 assays were performed and compliance with Australian standards was at or above 99.99% for each of the four species tested. Given the high morbidity and mortality associated with many of the diseases of livestock (eg, necrotic enteritis and coccidiosis in poultry, bovine respiratory disease and mastitis in cattle, and post-weaning diarrhoea and porcine respiratory disease in pigs), prevention of infectious diseases is of fundamental importance. Judicious use of antibiotics in integrated animal health plans has an important role to play in protecting the health and welfare of animals and in contributing to the safety and quality of the food that is produced. Only 39 antibacterial agents are approved and available for use in Australian livestock, six of which are from classes with no human medical use counterpart. As an example of contemporary patterns of use, a recent survey of the use of antimicrobial agents in the Australian pig industry found most use was for control of infections with Lawsonia intracellularis, Mycoplasma hyopneumoniae and Escherichia coli and relied on sulfonamides, tetracyclines and penicillins2 — all drugs considered by the Expert Advisory Group on Antimicrobial Resistance to be of low importance to public health.3 What led the Australian Department of Health and Ageing to conclude that “Australia’s food supply is one of the safest and cleanest in the world”4? In 2008, Food Science Australia was commissioned to survey the presence of bacteria with antimicrobial resistance in samples of raw whole poultry, beef mince and pork chops collected from shops in Melbourne, Sydney, Brisbane and Perth. Among the isolates of Campylobacter jejuni, Salmonella and E. coli that were collected, no fluoroquinolone or ceftiofur resistance was identified. No Enterococcus faecium was isolated and all Enterococcus faecalis isolates were susceptible to ampicillin, penicillin and vancomycin; only one of 300 E. faecalis isolates was resistant to gentamicin. In contrast, Denmark, despite being recognised as having one of the most regulated and conservative approaches to the use of antibiotics in livestock, noted significant antibiotic resistance in their most recent antimicrobial resistance monitoring report: fluoroquinolone-resistant C. jejuni in 17% of broiler meat samples; high-level gentamicin resistance in E. faecalis from pork samples; vancomycin-resistant E. faecium in 47% of isolates from broiler chickens; extended-spectrum β-lactamase producing E. coli (ceftriaxone resistant) in 27% of broiler cloacal swabs and 9% of broiler meat samples; fluoroquinolone-resistant Salmonella enterica subspecies enterica serovar Enteritidis in 8% of sporadic cases of human salmonellosis; multiresistant Salmonella enterica subspecies enterica serovar Typhimurium definitive type 104 (DT104) in 7% of isolates from pigs; and ceftiofur-resistant E. coli in 1% of domestic pork and broiler meat samples.5 OzFoodNet (http://www.ozfoodnet.gov.au) was established by the Australian Government in 2000 to enhance surveillance of foodborne disease. It has published eight annual reports, which do not identify any cases of domestically acquired foodborne illness caused by infections with Salmonella, Campylobacter or Shiga toxin-producing E. coli complicated by antibiotic resistance of livestock origin. By contrast, a number of human cases of fluoroquinolone-resistant Campylobacter infection and S. Typhimurium DT104 infection have been described, but each originated from overseas (especially South-East Asia) or from imported food. Since 2001, the Australian Salmonella Reference Centre has tested more than 18 000 Salmonella isolates from cattle, pigs, sheep, chickens (broilers and layers), raw meat and eggs. No fluoroquinolone-resistant isolates were found and only nine isolates (most of which were submitted before 2004) were phenotypically resistant to cefotaxime at 1 g/mL. Australians should be reassured that food safety is the highest priority in livestock production. The Australian Veterinary Association is currently updating a series of guidelines for responsible use of antibiotics, the poultry industry is supporting leading edge research to develop a vaccine to prevent necrotic enteritis, and the pig industry has spent over $7 million on projects to refine and replace the use antibiotics and has committed to halving antibiotic use by 2018. Antibiotics used prudently and selectively can clearly benefit animal health and welfare, leading to overall human health benefits, not risks.

Stephen W Page BVSc(Hons), MVetClinStud, MAppSci(EnvTox)

Effective clinical practice is predicated on valid and relevant clinical science — a commodity in increasingly short supply. The pre-eminent place of clinical research has become tainted by methodological shortcomings, commercial influences and neglect of the needs of patients and clinicians. Researchers need to be more proactive in evaluating clinical interventions in terms of patient-important benefit, wide applicability and comparative effectiveness, and in adopting study designs and reporting standards that ensure accurate and transparent research outputs. Funders of research need to be more supportive of applied clinical research that rigorously evaluates effectiveness of new treatments and synthesises existing knowledge into clinically useful systematic reviews. Several strategies for improving the state of the science are possible but their implementation requires collective action of all those undertaking and reporting clinical research.

Ian A Scott FRACP, MHA, MEd · Paul P Glasziou FRACGP, PhD

Donor countries withdraw HIV funding just when compelling evidence on prevention emerges The global epidemic of HIV and AIDS started in sub-Saharan Africa, and there are now 23 million people in the region living with HIV, representing 68% of the world total. In December 2011, I participated in the 16th International Conference on HIV/AIDS and Sexually Transmitted Infections in Africa (ICASA), held in Addis Ababa, Ethiopia. The conference was full of good news about progress against HIV over the past few years, but there was also a great deal of concern about the ability to sustain the momentum. The 2011 Global HIV/AIDS Response progress report, released on 30 November, showed that the number of new HIV infections in sub-Saharan Africa declined from 2.2 million in 2001 to 1.9 million in 2010, and the number of AIDS-related deaths declined from 1.7 million in 2005 (the peak) to 1.2 million in 2010.1 The decline in AIDS deaths is mainly due to the increased availability of antiretroviral therapy (ART), and the main reason for the availability of ART in Africa is the United States President’s Emergency Plan for AIDS Relief (PEPFAR). President George W Bush established PEPFAR in 2003, and he was guest of honour at ICASA. The 5000 delegates gave him a standing ovation as he approached the podium to deliver his address. A major cause for optimism at ICASA was the recently published evidence that ART can effectively prevent transmission of HIV, a concept called “treatment as prevention”. Results from a randomised trial published in August 2011 showed that early initiation of ART for the HIV-positive partner in a serodiscordant couple reduced HIV transmission to the HIV-negative partner by 96%.2 Other studies published in 2011 have shown that use of ART by the HIV-negative partner reduces risk of HIV infection.3 This all bodes well for control of HIV in Africa — but only if there is adequate funding. Overshadowing ICASA was the spectre of cuts to foreign aid to Africa as a result of the global financial crisis. Just before ICASA, the Global Fund to Fight AIDS, Tuberculosis and Malaria announced that it was cancelling Round 11 of its funding. One of ICASA’s keynote speakers, Canada’s Stephen Lewis, was particularly scathing in his criticism of the Global Fund and its donor countries. Like previous speakers, he warned that a reduction in funding meant that people would die because of lack of access to ART. But Lewis went further. He said: “The decision on the part of the donor countries is unforgiveable ... It’s unconscionable, indefensible, outrageous. It’s murder, that’s what it is: murder.”4 While the Global Fund’s decision to cancel Round 11 was unexpected and shocking, there was, nevertheless, general recognition at ICASA that African countries need to become less dependent on donors in their efforts to control HIV and AIDS. Indeed, the theme of the conference was “Own, scale-up and sustain”. One of the advocacy groups at ICASA — these conferences tend to involve a nice mixture of scientists and activists — was lobbying hard for African governments to spend 15% of their budgets on health, as they had agreed to do in the Abuja Declaration as long ago as 2001.5 Led by its Minister of Health, Dr Tedros Adhanom Ghebreyesus, Ethiopia is one country that is taking a comprehensive approach to improving the health of its population. Dr Tedros has often been called the “world’s best health minister”. His major achievements include training and deployment of 38 000 health extension workers and an increase in medical school admissions from 250 students in 2005 to 2500 in 2012. At ICASA, he spoke of how he has used donor funding for HIV programs as a platform for strengthening the entire Ethiopian health system. There was only a handful of Australians at ICASA. I worked with HelpAge International, the World Health Organization and UNAIDS (the Joint United Nations Programme on HIV/AIDS) to convene a workshop on HIV in people aged 50 years and older, and Dr Daniel O’Brien from Geelong presented data from his work with Médecins sans Frontières on false positive results from rapid diagnostic tests for HIV. It’s a pity there weren’t more of us. Ethiopia holds a special place in Australia’s relationship with Africa. It is the site of the fistula hospital established by Australian Dr Catherine Hamlin and her husband, and also a new Australian Embassy that will soon start allocating significant funding for maternal and child health. ICASA shows that the next few years will be crucial to health in Africa. Australian doctors should contribute more to the continent with the highest burden of disease.

Robert G Cumming MB BS, MPH, PhD

Increased research in the area of complementary and alternative medicine (CAM) is urgently required, in addition to a balanced appraisal and communication of the state of evidence in the field. Current challenges for clinicians and the public in accepting purported CAM evidence concern potential selective publication of results, marked differences in product quality ...

Jerome Sarris PhD, MHSc

To the Editor: Le and Chapman’s article1 on capacity at the end of life raises a number of timely issues, given our ageing population and the autonomous rights of individuals in end-of-life decision making.2 The authors made a best-interests decision, based on the patient’s humanity and their responsibility not to let him die “alone, cold and probably in pain”, contrary to his “decision” to die what would not be “a good death”. This stance can be problematic because best interests or good death are entirely subjective, and doctors who provide treatment to a competent patient may be committing trespass.3 Thus, the question of whether he was capable of making a decision to die “a bad death” is possibly more crucial. Structured capacity assessment is beneficial for the peace of mind of clinicians, patients and family. This patient lay on the floor “because he wished to do so” — a “limited realistic choice”. He was delirious and therefore deemed incompetent. Did the delirium affect his ability to weigh the pros and cons of staying on the floor and refusing hospital admission? Assessment of capacity to consent to medical treatment involves determining whether the patient is capable of understanding the ramifications of treatment and its alternatives (including no treatment). His premorbid choices (precedent autonomy)4 of living a squalid, isolated existence and refusing treatment for some time must also be noted. Yet capacity is dynamic and can change over time. Careful capacity assessment can justify decisions made on behalf of patients.

Sharon G Reutens · Carmelle Peisah

In reply: We thank Reutens and Peisah for their response to our article.1 We agree that careful capacity assessment is of critical importance — a patient’s capacity should be assessed rather than assumed. Delirium can often affect capacity due to the impact of attentional deficit on the process of decision making.2 In our case, the patient could neither reason through the ramifications of his decision to stay on the floor nor be involved in a logical discussion as to why we had concerns about his choice. Indeed, he had not chosen to be on the floor but was there because of his fall, his delirium and his inability to rise. However, we do caution that clinicians should trust their own clinical decisions when these are based on sound assessment. Choosing not to make hard decisions for fear of litigation (eg, committing trespass) does neither the patient, the community nor our profession any favours.

Brian H Le · Michael D Chapman

To the Editor: Kapur and colleagues correctly assert that the Declaration of Montréal states that “access to pain management is a fundamental human right”.1 The Declaration was proposed by International Association for the Study of Pain (IASP) delegates to the International Pain Summit and was approved by the IASP Council. However, Kapur et al incorrectly assert that the Declaration leaves the position of diagnosis uncertain, and that “the only specific treatment modality mentioned is opioid therapy”. Article 3 of the Declaration recognises: The right of all people with pain to have access to appropriate assessment and treatment of the pain by adequately trained health care professionals.2 Footnote 6 includes the need for “educational programs regarding pain assessment and treatment in all of the health care professions”. Thus, a label of “chronic pain” does not lead to a right to opioid treatment without proper assessment and consideration of treatment options. Footnote 6 refers to a range of treatment options, such as pain medications, including opioids and other essential medications for pain, and best-practice interdisciplinary and integrative nonpharmacological therapies, with access to professionals skilled in [their] safe and effective use ...2 It would be hard to describe the carefully worded articles, obligations and footnotes of the Declaration as “dogma, moral coercion or forays into jurisprudence”.1 At its General Assembly in 2011, the World Medical Association (WMA) supported measures to improve access to pain management. Dr Mukesh Haikerwal, Chair of the WMA, said: Physicians and other health care professionals have an ethical duty to offer proper clinical assessments to patients with pain and to offer appropriate treatment.3 Further, a WMA resolution asserted that people facing pain had a right to appropriate pain management, including effective medications such as morphine. Denial of pain treatment violated the right to health and might be medically unethical.3 It is puzzling that Awerbuch feels that describing chronic pain as a disease means that “the patient becomes the sole arbiter of whether he or she is ill. The prescribing doctor has no means by which to objectively determine treatment outcomes”.4 In the article to which he refers,5 and in other reports including Australia’s National Pain Strategy,6 the “disease” of chronic pain is described in terms of physical, psychological and environmental factors that require assessment by health professionals with adequate knowledge and training. This is not just a labelling exercise.

Michael J Cousins

To the Editor: The continuing integration of genetic technologies into clinical medicine is providing opportunities for health care improvement. This has the potential to reduce health disparities between Indigenous and non-Indigenous Australians in several ways: improving our understanding of disease pathogenesis, obtaining a perspective from ...

Gareth S Baynam

To the Editor: We read with interest the recent article by Harvey and colleagues, which eloquently outlines the benefits and risks of selective oestrogen receptor modulators in the prevention of breast cancer in women at moderate-to-high risk. Another oral medication that may prove to be of benefit in reducing the risk of breast cancer is the ...

Jerry R Greenfield · Ann I McCormack

To the Editor: Recent media reports related to Ian “Molly” Meldrum1 are a timely reminder, once again, of the risk of physical injury posed by a fall from a ladder. We carried out a survey of injuries sustained in falls from ladders among patients presenting to the Royal Prince Alfred Hospital (RPAH), an inner-Sydney major trauma centre, between January 2009 and December 2011. We linked data from the hospital trauma registry with data from the New South Wales Department of Health Centre for Epidemiology and Research. The trauma registry routinely collects data on all injury-related admissions and trauma team activations. NSW Health provided data from a free-text search for the term “ladder” within the presenting problems, triage text and diagnoses in the electronic medical records of all patients who presented to the RPAH emergency department (ED) during the period studied. For comparison, we also constructed a survey of injuries sustained by pedestrians struck by a motor vehicle. We used trauma registry data, from a previous study of patients with such injuries, for 409 consecutive patients admitted during 2008–2010. The study was approved by the Sydney Local Health District Ethics Review Committee (RPAH zone). We identified 331 ED presentations related to any ladder incident. Of these, 136 were available in the trauma registry for analysis. The mean age of patients was 54 years (SD, 17 years; 95% CI, 51–57), and a significant proportion (37; 27%) were 65 years or older. No inpatient deaths were reported. The most common body regions injured were upper limb (54; 40%) and head (41; 30%). Severe head injuries were sustained by 14 patients (10%) (Box). Although the proportion of patients with major trauma (injury severity score, > 15) was consistent with previous trauma registry reports,2,3 the proportion with head injury was much higher and may be related to the older age in this cohort. One recent study suggested that the incidence of major injury from ladder falls is increasing, particularly among older people.4 Many presentations for minor injury were not captured by the trauma registry; however, unlike previous reports, we included all patients requiring initial assessment by the trauma team. The proportions with severe head injury (head Abbreviated Injury Scale score, ≥ 3), intensive care admission and major trauma were similar between patients who fell from ladders and pedestrians who were struck by motor vehicles (10% v 12%, P = 0.50; 10% v 9%, P = 0.79; 12% v 15%, P = 0.30, respectively). Based on the significant proportion of people sustaining severe head injury, new ladder-safety initiatives are required, particularly targeting those aged 65 years and over. Demographic and injury profile of patients with injuries sustained in a fall from a ladder who were admitted to an inner-Sydney trauma centre, January 2009 – December 2011 (n = 136) Variable No. (%)* 95% CI Age, years (mean, SD) 54 (17) – Male 111 (82%) 76–89 Time of incident After hours† 30 (22%) 15–29 Weekend 37 (27%) 20–35 Height of fall < 1 m 29 (21%) 14–28 1–5 m 105 (77%) 69–83 > 5 m 2 (1%) 0–5 Hospital admission 95 (70%) 62–77 Intensive care admission 14 (10%) 5–15 Length of stay in hospital, days (mean, SD) 5.4 (8.9) – Injury severity score (mean, SD) 7 (5) – Major trauma‡ 16 (12%) 6–17 Body region injured Head 41 (30%) 22–38 Severe head injury§ 14 (10%) 5–15 Upper limb 54 (40%) 31–48 Lower limb 37 (27%) 20–35 Chest 14 (10%) 5–15 Severe chest injury¶ 7 (5%) 1–9 Abdomen 3 (2%) 0–5 Vertebral column 26 (19%) 12–26 Spinal cord injury 9 (6%) 2–11 AIS = Abbreviated Injury Scale. * Unless otherwise specified. † Any time between 18:00 and 08:00. ‡ Injury severity score > 15. § Any significant intracranial bleed, oedema and/or major skull fracture; head AIS score ≥ 3. ¶ Includes flail chest, major haemothorax or pneumothorax and mediastinal injury; chest AIS score ≥ 3.

Michael M Dinh · Helen L Stark · Kendall J Bein

To the Editor: The recent article by New and colleagues1 is an important piece in the “bed-block” picture, providing insight into perceived difficulties for patients on discharge, as a result of insufficient appropriate facilities. The authors suggested that “Redistributing proposed funding for inpatient subacute beds to measures for overcoming these barriers” may improve patient flow through the whole hospital system. This idea fits well with current federal health policy that “bed equivalents” are an important aspect of innovative and flexible models of care for rehabilitation services in Australia.2 Most states are reviewing how rehabilitation services are best designed to ensure the most effective use of limited resources, both in terms of programs and workforce. Improving the coordination of programs managed by the various levels of government, across health, disability and the aged care sectors, will help overcome the barriers identified in this study. The Australasian Faculty of Rehabilitation Medicine applauds efforts to increase research on rehabilitation and patient care, and supports federal and state initiatives providing increased resources for subacute care, both within hospitals and in the community. Investment in rehabilitation services at the community level is one of the most viable solutions and will meet the needs of an ageing population. Effective community care and the proposed National Disability Insurance Scheme (http://www.ndis.gov.au), if well executed, will reduce the burden on other parts of the health and aged care sectors and help ease the burden on hospitals.

Kathleen McCarthy

To the Editor: The entertaining history of Sydney Hospital by Kappagoda1 illustrates the risk of accepting local lore as fact. The assertions that Sydney Hospital “hosted the first operation [in Australia] under general anaesthetic” and that it was “a leg amputation under chloroform” are both incorrect. The first surgical operations under general anaesthesia in Australia took place in Launceston, Tasmania, on Monday 7 June 1847, using ether administered with apparatus that had been depicted in the Illustrated London News.2,3 Two patients were successfully anaesthetised by Dr William Russ Pugh — both walked home and were completely happy with the procedure. The operation referred to by Kappagoda was reported in the Sydney Morning Herald (SMH) on Monday 28 June 1847 as having occurred “a few days back”4 — at least 2 weeks after Pugh’s patients were anaesthetised. Further, ether, not chloroform, was used in Sydney. The SMH reporter had also seen ether used to anaesthetise patients on other occasions, but these patients were undergoing dental extraction. The decision to operate may have been precipitated by a news item in the SMH on Thursday 24 June 1847. The paper reported that “The medical men at Launceston have made several successful experiments in performing surgical operations on patients who have inhaled ether.”5 To local readers, it would have been obvious that this had occurred at least several days, and possibly several weeks, before the Sydney surgery, because of the delay in transmitting news from Launceston to Sydney. Perhaps this news spurred the Sydney surgeons to act.

John D Paull

To the Editor: The first recorded use of an anaesthetic in Australia was not at Sydney Hospital, as stated by Kappagoda,1 but was at Dr John Belisario’s rooms in Spring Street, Sydney. Belisario, with Dr Charles Nathan (honorary surgeon to Sydney Infirmary), administered ether to two patients having dental extractions on 6 June 1847, and possibly to other patients a day or two earlier.2,3 The first recorded use of an anaesthetic for surgery was in Launceston, Tasmania, by Dr William Russ Pugh on 7 June 1847, when he administered ether for removal of an epulis from a woman’s jaw, followed by excision of a cataract from a man. Pugh published these cases in the Australian Medical Journal — the first medical journal in Australia, of which the Medical Journal of Australia is the direct descendant,4 and which only existed for 15 months. The Editor, Dr Isaac Aaron, was one of the first surgeons at Sydney Infirmary. Ether was the sole anaesthetic available in Australia for 10 months before chloroform was introduced. The first recorded death under ether occurred in Sydney on 9 April 1848. Two days later, on Tuesday 11 April, Nathan gave evidence in the morning at the inquest of this death and, in the afternoon, gave the first chloroform anaesthetic in Australia at Sydney Infirmary, to a young girl. The first recorded death under chloroform anaesthesia in Australia occurred on 19 July 1848 at Windsor, New South Wales.2 Sydney Infirmary, later Hospital, was closely involved in the early days of anaesthesia in Australia, both on site and through its staff, but cannot claim priority.

Michael G Cooper

Restoration of immune responses against opportunistic pathogens after commencing antiretroviral therapy (ART) may cause immune restoration disease (IRD) in about 10%–40% of HIV patients with low CD4+ T-cell counts and usually presents clinically as a type of immune reconstitution inflammatory syndrome (IRIS). IRIS may be associated ...

Martyn A H French MD, FRACP, FRCPath

Murray Valley encephalitis virus (MVEV) is a mosquito-borne virus that is found across Australia, Papua New Guinea and Irian Jaya.MVEV is endemic to northern Australia and causes occasional outbreaks across south-eastern Australia.2011 saw a dramatic increase in MVEV activity in endemic regions and the re-emergence of MVEV in ...

James Knox BSc(Med), MBBS, DTM · Raquel U Cowan MB BS, PhD · Joseph S Doyle MB BS, MSc, FRACP · Matthew K Ligtermoet MB BS, BMed Sci · John S Archer MB BS, FRACP, PhD · James N C Burrow MB BS, FRACP · Steven Y C Tong MB BS, FRACP, PhD · Bart J Currie FRACP, FAFPHM, DTM · John S Mackenzie PhD, FASM, FACTM · David W Smith MB BS, FRCPA, FACTM · Mike Catton BSc(Hons), MB ChB, FRCPA · Rodney J Moran · Craig A Aboltins MB BS(Hons), FRACP · Jack S Richards MB BS, FRACP, PhD

Objectives: To explore the burden of illness associated with infectious syndromes and to measure the associated use of antimicrobials in residential aged care facilities (RACFs).Design, setting and subjects: Retrospective analysis of data for January 2006 to December 2010 from an infection surveillance system covering residents of four co-located RACFs, with a total of 150 residential care beds, in Melbourne, Victoria.Main outcome measures: Number of episodes and incidence of health care-associated infection (HCAI); rate of antimicrobial use; prescribing concordance with McGeer criteria for infection; frequency of clinical specimen collection.Results: There were 1114 episodes of an infectious syndrome over 267 684 occupied bed-days (OBD), affording an average HCAI rate of 4.16 episodes/1000 OBD annually over 5 years (95% CI, 3.92–4.41). The mean rate of antimicrobial use was 7.07 courses/1000 OBD (range, 6.71–7.84). Around 40% of antimicrobial prescribing was for episodes that did not fulfil the McGeer criteria for clinical infection; this included about half of suspected urinary tract and upper respiratory tract infections (URTI), and about one-third of suspected lower respiratory tract and skin infections. Antimicrobials were routinely prescribed for URTI and bronchitis. Of all episodes treated with antimicrobials, 36% had documentation that a clinical specimen was obtained.Conclusions: The HCAI rate remained relatively stable over time. Routine surveillance and feedback of infection rates to the facilities did not result in a noticeable decrease of infection burden over time. It is of immediate concern that antimicrobials were being prescribed for a large proportion of suspected infections that did not meet criteria for clinical infection. Opportunities exist to further improve the use of antimicrobials in the RACF setting.

Ching Jou Lim BPharm(Hons) · Susan C McLellan RN, GradCert InfectControl, GradDipNSInfectControl · Allen C Cheng FRACP, MPH, PhD · Joanne M Culton RN, GradCert InfectControl · Sneha N Parikh BA · Anton Y Peleg* MB BS, PhD, FRACP · David C M Kong* BPharm, MPharm, PhD

Objectives: To determine incidence and trends in antibiotic resistance in Australian Salmonella enterica subspecies enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) isolates over the past 26 years.Design: A retrospective analysis of consecutive microbiologically confirmed enteric fever isolates.Participants and setting: All S. Typhi and S. Paratyphi isolates from patients diagnosed with enteric fever in Australia between 1985 and 2010.Main outcome measures: Incidence and variation in antibiotic resistance over time and according to country of origin.Results: We analysed 2551 isolates, which originated from 74 countries or regions, mainly India (33%) and Indonesia (22%). The incidence among Australian residents increased from four to five before 2003 to seven cases per million person-years after 2003. Multidrug resistance (chloramphenicol, ampicillin, trimethoprim) and nalidixic acid resistance emerged rapidly from the early 1990s, with nalidixic acid resistance increasing to 70% in 2009–2010, while multidrug resistance was relatively stable at between 4% and 11%. Nalidixic acid and multidrug resistance rates are highest in isolates from the Indian subcontinent. Some countries in South-East Asia, such as Indonesia, had very low rates of resistance; however, this varied across the region.Conclusions: Nalidixic acid resistance has become widespread in enteric fever isolates from the Indian subcontinent and some parts of South-East Asia, justifying the use of ceftriaxone or azithromycin rather than ciprofloxacin as first-line treatment. However, resistance in some countries remains rare, potentially allowing treatment to be adjusted according to country of origin.

Robert J Commons MB BS, BMedSci, DipObsGyn · Emma McBryde MB BS, FRACP, PhD · Mary Valcanis BSc, MPH · Joan Powling BAgrSc · Alan Street MB BS, FRACP · Geoff Hogg BM, BS, FRACP

Objective: To estimate the number of cancers to be diagnosed in 2025 that could be prevented solely due to changes in diet and physical activity.Design and setting: We used an Australian population-based cancer database to estimate the total number of cancers to be diagnosed in 2025, by applying published age- and sex-specific population projections to current cancer incidence rates, and multiplying the projected numbers of cancers by estimates of population-attributable fractions.Main outcome measures: Projected number of preventable cancers that would be diagnosed in 2025.Results: Our projections suggest that there will be about 170 000 Australians diagnosed with cancer in 2025. This represents an increase of about 60% on the 2007 incidence. Almost 43 000 of these cancers (low estimate, 42 295; middle, 42 657; high, 43 990) could be prevented through improvements to diet and physical activity levels, including through their impact on obesity. It is likely that this is an underestimate of the true figure. The most preventable cancer types in 2025 were estimated to be bowel cancer and female breast cancer (10 049 and 7273 preventable cases, respectively).Conclusions: About 25% of cancers, or about 43 000 cancers in 2025, can potentially be prevented through improvements in diet and physical activity. It is imperative that governments, clinicians and researchers act now if we are to reduce the significant future human and financial burden of cancer.

Peter D Baade PhD · Xingqiong Meng PhD, MD · Craig Sinclair MPPM, BEd · Philippa Youl MPH

Objective: To describe the epidemiology, clinical features and diagnosis of Mycobacterium ulcerans infection occurring on the Bellarine Peninsula in Victoria. Design, setting and patients: Analysis of prospectively collected data on all patients with confirmed M. ulcerans infection reported from the Bellarine Peninsula and managed at Barwon Health ...

Sarah C Boyd MB BS · Eugene Athan MB BS, FRACP · N Deborah Friedman MB BS, FRACP · Andrew Hughes MB BS, FRACP · Aaron Walton MB BS, FRACP · Peter Callan MB BS, FRACS · Anthony McDonald MB BS, FRACS · Daniel P O’Brien MB BS, FRACP

Objective: To compare the unprecedented 91 cases of melioidosis in the Top End of the Northern Territory of Australia from 1 October 2009 to 30 September 2010 with the 540 cases in the preceding 20 years and postulate reasons for this year of very high melioidosis incidence.Design, setting and participants: Review of prospectively collected data on all patients with culture-confirmed melioidosis at Royal Darwin Hospital, the Top End’s tertiary referral centre, since 1 October 1989.Main outcome measures: Population-based annual incidence of melioidosis; differences in epidemiology, clinical presentations and outcomes for 2009–2010 compared with the preceding 20 years.Results: In 2009–2010, the estimated population-based incidence of melioidosis was 50.2 cases per 100 000 in the Top End population overall, and 102.4 cases per 100 000 in the Top End Indigenous population. The proportion of patients acquiring melioidosis in the Darwin urban area increased from 49% in 1989–2009 to 65% in 2009–2010 (OR, 1.96; 95% CI, 1.20–3.19). Among the 49 Indigenous Australian patients with melioidosis in 2009–2010, 63% acquired the infection in Darwin, compared with 35% of Indigenous patients in the previous 20 years (OR, 3.17; 95% CI, 1.62–6.24).Conclusions: In 2009–2010, the Top End had the highest annual incidence of melioidosis documented from anywhere to date. The prominent increase in cases in Darwin was associated with above average rainfall in Darwin during December 2009 to February 2010. The increase in the proportion of Indigenous Australians who acquired melioidosis in Darwin may reflect movement of some Indigenous people into Darwin from remote communities.

Uma Parameswaran MB BS · Robert W Baird MB BS, FRACP, FRCPA · Linda M Ward BAppSci, MMedSci · Bart J Currie FRACP, FAFPHM, DTMTH

We report the first human case of babesiosis in Australia, thought to be locally acquired Clinical recordA 56-year-old man with serious hepatic, renal and bony injuries was transferred to Canberra Hospital in mid November 2010 following a motor vehicle accident. His medical history included type 1 diabetes mellitus, excessive alcohol and prescription medicine use, depression, hypertension and hypercholesterolaemia. He had no history of injecting drug use. He had been living on the south coast of New South Wales with his son. During the first 4 months of his admission he required surgery, prolonged broad-spectrum antibiotic therapy and total parenteral nutrition. He developed worsening cholestatic liver function, moderate-to-severe thrombocytopenia and fluctuating anaemia. By late March 2011, he was pancytopenic with worsening anaemia due to intravascular haemolysis, lymphopenia and severe thrombocytopenia, and required ongoing blood product transfusions. The result of an HIV test was negative. In early April, the patient was transferred to the intensive care unit because of respiratory and haemodynamic deterioration. On 10 April, intraerythrocytic parasites were incidentally identified during routine examination of blood films taken that morning. Ring-form parasites, initially thought to be a Plasmodium species, were confirmed on thick and thin films. Results of immunochromatographic tests were negative for Plasmodium falciparum; however, intravenous artesunate and primaquine therapy for presumed severe malaria was commenced. Broad-spectrum antibiotic therapy was continued. After 48 hours without clinical improvement, the parasitaemia level had increased from 1.7% to 2.6% infected red blood cells. Re-examination of the blood films and recognition that the organisms did not produce hemozoin led to the presumptive diagnosis of babesiosis infection. This was confirmed by Australian and overseas experts who viewed electronic files of the slides. The patient was then given intravenous quinine (600 mg 8-hourly) and clindamycin (600 mg 6-hourly) for babesiosis. Azithromycin and tigecycline were also added to provide additonal broad-spectrum antimicrobial cover, but clinical deterioration continued, and the levels of parasitaemia, anaemia and thrombocytopenia did not improve. He developed multiorgan failure and required haemodialysis. The parasitaemia peaked at 5.1% infected red blood cells despite ongoing blood transfusions (including 18 units of packed red cells over 8 days). As his condition was too unstable for him to undergo total red cell exchange, an exchange of 500 mL of blood was performed on 16 April. He did not recover from the multiorgan failure, and severe thrombocytopenia contributed to acute gastrointestinal bleeding. On 18 April — 5 days after commencing specific antibabesiosis therapy — he suffered a fatal asystolic arrest. Following the patient’s death, a retrospective study of the blood films taken during his hospital admission was undertaken. Ring-form parasites were detected in very low numbers back to the end of the first week of March 2011, coinciding with the development of severe thrombocytopenia. Initially, the multiple blood products that the patient received during his admission were thought to be the likely cause of his babesiosis. But blood films stored by his local pathology service and taken between September and November 2010 (ie, before his hospital admission) revealed pre-existence of the intraerythrocytic parasite and hyposplenic features. As the patient had not received blood products before his hospital admission in November 2010, the parasitaemia could not have been transfusion related. He had reported being bitten by ticks, but had been too sick to qualify this further. Due to general ill health, he had not worked or left the local area for many years. His only overseas travel had been to New Zealand almost 40 years earlier, a country with no known human babesiosis. It thus seemed unlikely that the babesiosis was acquired from overseas. The patient had lived on the south coast of New South Wales for over 30 years — on a small farm with two horses and two Staffordshire bull terriers for 25 years, and then at a house in a small town with his son and a new Staffordshire bull terrier (acquired from within Australia) for 8 years. The new Staffordshire bull terrier was their only pet and was still living at their south coast home in mid 2011. Both his son (who was asymptomatic) and his Staffordshire bull terrier underwent testing for babesiosis; the results were negative. To identify the organism and further elucidate its source, blood samples and films from the patient were examined at the Centers for Disease Control and Prevention (CDC) in Atlanta, United States, and at the School of Veterinary and Biomedical Sciences, Murdoch University, Western Australia. Both laboratories agreed that the morphological characteristics of the parasites in the blood films were consistent with a small Babesia. Intraerythrocytic organisms were mostly single and measured 1.5–2.5 m in size but were highly polymorphic; pyriform and ovoid forms predominated, bizarre amoeboid forms were also common, and an occasional tetrad (Maltese cross form) was noted (Box 1). Immunofluorescent antibody testing for Babesia microti was performed by the CDC on serum samples from the patient (positive result, with titre of 1 : 256) and his son (negative result). Complete sequencing of the 18S ribosomal RNA gene (18S rDNA) and partial sequencing of the β-tubulin gene (both amplified by polymerase chain reaction) confirmed that the organism in the patient’s blood was B. microti. At the CDC, a nested PCR that specifically amplifies a 154-base-pair fragment from the B. microti 18S rDNA was initially used to confirm the presence of B. microti in the patient’s blood. In addition, sequencing of a 1767-base-pair fragment amplified with primers Crypto FL (5'-AACCTGGTTGATCCTGCCAGTAGTCAT-3') and Crypto RN (5'-GAATGATCCTTCCGCAGGTTCACCTAC-3'), was performed to strengthen the PCR findings.1 The 18S rDNA sequence obtained was 100% similar to the GenBank entry AY693840 obtained from a B. microti isolate 18S rDNA gene. At Murdoch University, two nested sets of universal piroplasm 18S rDNA primers were used, one of which has been published.2 The patient’s son’s blood was used as a negative control. The consensus sequence was 100% homologous to known human-derived Babesia species isolates. In addition, five novel primer sets designed during this study were used to obtain a partial β-tubulin gene fragment (791 base pairs), which confirmed the presence of B. microti in the patient’s blood and showed 100% homology with North American isolates (eg, GenBank entries AB083377 and AY144722). A phylogenetic tree for this locus (produced using the maximum likelihood method) revealed clustering with isolates of B. microti obtained from the tick species Ixodes scapularis (formerly known as Ixodes dammini), humans and voles in North America. DiscussionTo our knowledge, this is the first report of a human case of babesiosis in Australia, which we believe was locally acquired. Human babesiosis is an emerging tick-borne zoonosis. The first human case was reported in Croatia in 1957.3 In 1968, Babesia divergens was identified as the cause of human babesiosis in Europe; this was soon followed by the discovery of human cases of B. microti infection in the US.4 More recently, human cases of babesiosis have emerged from Asia, Africa and South America.5-8 Since B. microti has never been detected in Australia before, its discovery as the cause of infection in this patient, who had no significant history of travel, raises intriguing questions about its natural hosts and epidemiology on this continent. Traditionally, B. microti is considered to have a Holarctic distribution, associated with a variety of small mammalian hosts (rodents, including voles, and shrews), and is transmitted by several Ixodes tick species present throughout the northern hemisphere, with humans becoming infected as accidental hosts. Recent phylogenetic analyses based on complete sequences of the genes encoding 18S ribosomal RNA, β-tubulin and the η subunit of the chaperonin-containing t-complex polypeptide 1 suggest that B. microti represents a genetically diverse species complex that comprises several geographically distinct clusters located in North America, Eurasia and Japan, and is closely related to “Babesia microti-like” species isolated from an ever-expanding range of feral and domesticated mammal hosts.9 In Australia, babesiosis is a well documented disease of cattle (Babesia bigemina and Babesia bovis) and dogs (Babesia canis, Babesia vogeli and Babesia gibsoni), and babesiosis tick vectors have been imported to the continent since European settlement.10,11 Australia also has a diverse variety of native Ixodes ticks, including Ixodes holocyclus (responsible for tick paralysis), and a few Babesia and Theileria species have been described morphologically in native marsupial hosts (but not B. microti).12 Unfortunately, a paucity of molecular studies means that the taxonomy and phylogenetic relationships of the endemic piroplasms (intraerythrocytic tick parasites, including Babesia and Theileria) are not well understood. Based on phylogenetic analysis, the isolate from this patient was most closely related to North American strains of B. microti, so it is unlikely that the piroplasm described here originated from a native Australian mammal, but not impossible. In the absence of transfusion or injecting drug history, the patient must have become infected following a tick bite. Two scenarios seem probable. The patient might have been bitten by an imported tick (contained within clothing or luggage that had recently arrived from an endemic country), but no history suggested such contact. Alternatively, a local tick might have transmitted an autochthonous infection, presumably originating from one or more species of introduced rodent. The natural history of this patient’s infection is notable. Babesia ring forms were detectable on routine blood films taken while he was an outpatient — 7 months before he died. At that time, he was asymptomatic and neither anaemic nor thrombocytopenic, but 6 months later the babesiosis became symptomatic and severe. The parasitaemia of 5.1% around the time of his death was likely to have been an underestimate of the true figure as it would have been diluted by the multiple blood products that he was receiving at the time. Asymptomatic parasitaemia is well described in babesiosis, both in the setting of primary infection and following treatment of symptomatic infection.4 It is unclear what transformed this patient’s chronic asymptomatic infection into a severe symptomatic infection that probably contributed to his death. He did have risk factors for severe babesiosis: hyposplenism, liver impairment and his age;4 however, these were present when the infection was asymptomatic months earlier. It is possible that his chronic hospitalisation, and general deconditioning from the long admission, resulted in significant immunosuppression. Severe babesiosis from B. microti is a serious condition with a case fatality rate of 5%–10%.13 Indeed, this patient’s condition did not improve despite his receiving recommended therapy once the diagnosis of babesiosis was made. Even the artesunate that he received for suspected malaria (immediately before the diagnosis) has been shown to have activity against B. microti in animal models.14 Although the animal host for B. microti is yet to be identified in Australia, the proximity of ticks, other wildlife and human populations along Australia’s eastern seaboard means that further cases may be encountered. Clinicians working in Australia should therefore be aware of the signs and symptoms of babesiosis and how to diagnose it (Box 2). Further investigation into the piroplasms of native mammals, introduced rodents and their ticks is necessary to identify the source of this infection. As transfusion-related babesiosis is well recognised in other countries,15 this case may have future implications for the screening of blood products in Australia. 1 Blood film from a 56-year-old man infected with Babesia microti, showing a tetrad form (black arrow) and single ovoid forms (white arrows) Wright stain; original magnification, 3 100. 2 Diagnosing human babesiosis in Australia When to suspect babesiosis Clinicians should suspect babesiosis in patients in Australia who have haemolytic anaemia, thrombocytopenia, fever, an influenza-like illness and a history of at least one of the following: tick bites outdoor activities putting one at risk of tick bites transfusion of blood products overseas travel to a region where babesiosis is endemic. How to proceed with the diagnosis Thick and thin blood films should be examined for intraerythrocytic parasites (three sets of films should be taken, 8–12 hours apart). If the results of blood films are negative but the diagnosis is still suspected, antibody testing of serum and molecular testing of blood (by polymerase chain reaction) can be done.

Sanjaya N Senanayake MB BS, FRACP, MAppEpid · Andrea Paparini MSc, PhD · Maya Latimer MB BS, FRACP, FRCPA · Kerrie Andriolo GradCert (DiagnosticPathology) · Alexandre J Dasilva PhD · Heather Wilson MB BS, PhD · Maniphet V Xayavong BA, MBA · Peter J Collignon MBBS, FRACP, FRCPA · Phillip Jeans MB BS, FRACS · Peter J Irwin BVetMed, PhD, FANZCVSc

Recent federal trade policy commitments could protect Australia’s tobacco control legislation and the Pharmaceutical Benefits Scheme in the Trans-Pacific Partnership Agreement negotiations In its Trade Policy Statement of April 2011, the Australian Government committed to “preserve the right of Australian governments to make laws in important public policy areas” and to reject provisions in trade agreements that could “limit its capacity to put health warnings or plain packaging requirements on tobacco products or its ability to continue the Pharmaceutical Benefits Scheme”.1 One forum in which this resolve is likely to be tested is the Trans-Pacific Partnership Agreement (TPPA) negotiations. The TPPA is a proposed regional free trade agreement between Australia, Brunei, Chile, Malaysia, Peru, Singapore, New Zealand, the United States and Vietnam — a diverse assortment of countries from several continents around the Pacific rim. The TPPA differs from existing bilateral and regional free trade agreements in its sheer size and geographic diversity. It has the potential to restrict national policy space — “the freedom, scope and mechanisms that governments have to choose, design and implement public policies to fulfil their aims”2 — on an unprecedented scale. This article explores the potential for the TPPA to constrain Australia’s national health policy space through two illustrative case studies: tobacco plain packaging and the Pharmaceutical Benefits Scheme (PBS). Investor–state dispute settlement and plain packaging of tobacco productsDuring 2011, the Australian Government introduced legislation requiring tobacco products to be packaged in plain paper (with graphic health warnings, but minimal branding). This represents an important assault on one of the last bastions of tobacco marketing — the appeal to personal identity.3 Strong tobacco control policies such as Australia’s tobacco plain packaging laws are consistent with a substantial body of scientific literature and the World Health Organization’s Framework Convention on Tobacco Control, but they can be challenged under international trade and investment agreements, which are driven by economic rather than public health goals. Philip Morris Asia (PMA) — a subsidiary of Philip Morris International (PMI) — has launched an investor–state dispute against the Australian Government over its tobacco plain packaging legislation. While several tobacco companies have taken their complaints to the High Court, PMA has also been able to pursue its case in international arbitration (where it has a greater chance of success) through an investor–state dispute settlement (ISDS) clause in a bilateral investment treaty signed between Australia and Hong Kong in the early 1990s. This is the second investor–state dispute to arise over tobacco labelling; PMI is bringing a similar case against Uruguay through a Swiss subsidiary.4 PMI has also been prominent in calling for an ISDS provision in the TPPA.4,5 Ironically, the corporate restructuring that has allowed PMI to access the Hong Kong bilateral investment treaty (PMA was made the sole shareholder in Philip Morris Australia in February 2011) has also significantly weakened its claims. This is because the investment was made with the company’s full knowledge that the plain packaging legislation was being developed.6 The government has a strong case. Nevertheless, the dispute with PMA highlights broader problems of including ISDS provisions in trade treaties, and demonstrates why it is important that they be excluded from the TPPA. The arbitration rules that govern PMA’s dispute with the Australian Government are those of the United Nations Commission on International Trade Law. The case will be decided by a tribunal made up of three members: one chosen by PMA, one chosen by Australia, and a third, mutually agreed upon, which will act as president. This method of appointing arbitrators has been described as neither independent nor impartial.7 In sharp contrast to domestic forms of adjudication, individuals can serve as a legal representative in one ISDS case and an arbitrator in another, further undermining their ability to act without bias. Furthermore, although the arbitrators will be experts in international investment law, they may have little or no experience with specific fields of public policy such as tobacco control. While the public has a stake in investor–state disputes, confidentiality is a dominant principle in investment arbitration. Hearings are rarely opened to the public unless both parties agree, and investors have opted for closed hearings in several recent cases concerning public policy. In this regard, it is commendable that the Australian Government has adopted a high standard of transparency in advance of the commencement of formal proceedings by posting PMA’s claims and their response on a public website.8 The arbitration will be expensive for Australian taxpayers, although the government may be able to recoup some of the costs if it prevails. In several investor–state disputes to date, legal fees alone have amounted to over US$4 million and in one case have exceeded US$13 million.9 There are also arbitrator’s fees, administration fees and additional costs for involving experts and witnesses. Even more significant are the awards in investor–state cases, which are widely enforceable.7 The Czech Republic was obliged to pay more than US$350 million in compensation to a Dutch investor, which according to one report meant a near doubling of the country’s public sector deficit.10 It can readily be seen how insertion of a TPPA ISDS mechanism into Australia’s national health policy space might skew legislation away from the public interest towards supranational corporate interests. This is why it is significant that the government has vowed to no longer include provisions on ISDS in the bilateral and regional trade agreements that it signs.1 Australia’s refusal to consent to ISDS in the TPPA is a significant step towards limiting the encroachment of international trade agreements into our national health policy space and retaining our sovereign right to regulate significant areas of public health policy. US proposals for medicines policy in the TPPAChallenges to Pharmaceutical Benefits Advisory Committee processesThe PBS is another area of domestic health policy that the Australian Government has committed to protect in international trade agreements. However, US TPPA negotiators are seeking substantial changes to Australia’s laws and administrative processes. Certain draft TPPA provisions relate to the PBS directly and also indirectly, by seeking to prolong pharmaceutical patents and minimise exceptions to them made in the public interest. We examine these proposals as another instance of how the TPPA may promote incursions into our national health policy space. In October 2011, a draft annex to the transparency chapter of the TPPA was leaked.11 Under the rubric of transparency and procedural fairness, this TPPA annex seeks to impose new restrictions on the operation of national pharmaceutical reimbursement and pricing schemes (Box 1). It is an annex because it is not designed to apply to the US, as it would if it was in the body of the treaty. Clause (d) of paragraph X.3 of the draft annex would require countries to reimburse pharmaceutical companies based on “competitive market-derived prices in the Party’s territory”, or other benchmarks that “appropriately recognize the value” of the patented product. This wording represents a shift away from the more science-based standard in Annex 2-C of the Australia–United States Free Trade Agreement (AUSFTA), which refers to the “objectively demonstrated therapeutic significance” of the new patented pharmaceutical (http://www.dfat.gov.au/fta/ausfta/final-text). This provision includes no mechanism for proving that prices are derived from “competitive” markets. It undermines the world-class science-based mechanisms used by the Pharmaceutical Benefits Advisory Committee (PBAC) to determine whether a new patented medicine has sufficient health innovation to be listed on the PBS (based on a determination of cost-effectiveness, as well as efficacy, quality and safety). Paragraph X.3 of the draft annex seeks to impose a new independent appeals process on determinations by government bodies such as the PBAC (Box 1). This is contrary to what was decided (after prolonged and acrimonious negotiations) under Annex 2-C of the AUSFTA, which only provides for independent expert review as a quality improvement exercise for the PBAC. The threat and the use of an independent appeals process would increase the capacity of the pharmaceutical industry to lobby against PBAC decisions and undercut their expert-informed determinations. Paragraph X.4 of the draft annex requires parties to permit pharmaceutical companies to disseminate information to health professionals and consumers via the internet — a practice that is not permitted for prescription drugs in Australia due to concerns about overprescribing. This is also contrary to Annex 2-C of the AUSFTA, which makes the direct advertising of pharmaceuticals subject to Australia’s domestic laws, regulations and procedures. There is a consensus against such advertising in the Australian national policy space, chiefly because of its capacity to increase lobbying of the medical profession for purposes of corporate gain rather than public health benefit. While the effect of US TPPA proposals on Australia’s PBS would be economically damaging and reduce the affordability of medicines in Australia, the effects on access to medicines in other TPPA countries could be far more severe, particularly for developing countries and those required to make greater changes to their domestic laws.12 Extending intellectual property rightsUS TPPA proposals on intellectual property applying to patents13,14 (Box 2) would also add to the cost of medicines overall, affecting the sustainability of the PBS. Non-government organisations have undertaken extensive analyses of these proposed provisions,12,15 and have shown areas where TPPA provisions extend patent protection beyond comparable AUSFTA patent provisions and existing Australian law.15 For example, proposed article 8.1 of the intellectual property (IP) chapter of the TPPA provides patent protection for new forms, uses or methods of using a known product, whereas article 17.9.1 of the AUSFTA does not require patent protection to be provided for new forms of existing drugs.15 Although, in practice, new forms are sometimes patented, the TPPA proposals would restrict efforts to tighten patenting standards in future. Proposed IP article 8.2 requires patenting of diagnostic, therapeutic and surgical methods, whereas article 17.9.2 of the AUSFTA allows for its exclusion.15 This change could restrict expeditious patient access to new clinical developments and substantially add to health care costs. Proposed IP article 8.7 would also eliminate pre-grant opposition to patent applications by third parties, a safeguard provided for in the Australian Patents Act 1990, which is designed to prevent unwarranted patents from being granted.15 Most concerning are the provisions for data exclusivity periods — where generic manufacturers cannot use clinical trial data to prepare and register their products for springboarding after patent expiry. Proposed IP article 9.214 provides an additional 3 years of data exclusivity for new uses of existing pharmaceutical products, on top of the 5 years of data exclusivity already permitted under article 17.10.1 of the AUSFTA. There is also a placeholder for specific provisions for biologics (medicines produced from biological products, which are not currently dealt with separately in Australia). US pharmaceutical companies are reportedly lobbying for 12 years of data exclusivity for biologics. If adopted, these proposals would lead to higher costs to the PBS (as drugs stay under patent for longer periods) and delayed entry of cheaper generic medicines into the market. The US TPPA proposals for extended intellectual property rights and data exclusivity for pharmaceutical companies would require changes to Australian laws and administrative processes. They would also conflict with the spirit of the Intellectual Property Laws Amendment (Raising the Bar) Bill 2011, which is currently before the Senate and seeks to raise patent standards and facilitate faster regulatory approval for generic medicines. ConclusionRecent Australian trade policy commitments to exclude ISDS and provisions that would affect the PBS from the TPPA are a positive step towards preserving sovereign, democratic and science-based control over our national health policy space. It is important that Australia continues to insist that future trade agreements, including the TPPA, do not extend the intellectual property privileges of patent holders, interfere with the operation of the PBS or provide foreign corporations with ISDS rights to challenge domestic public health policies. 1 Leaked United States demands for changes to schemes such as Australia’s Pharmaceutical Benefits Scheme Pharmaceutical Benefits Advisory Committee (PBAC) recommendations to be based on competitively derived market forces or systems that appropriately value patented pharmaceuticals (no mention of “objectively derived therapeutic significance” as in the Australia–United States Free Trade Agreement) Appeals process able to challenge PBAC recommendations Heightened capacity for direct-to-patient pharmaceutical advertising 2 Some United States proposals for extensions to intellectual property rights applying to patents Patent protection for new forms of existing drugs Patenting of diagnostic, therapeutic and surgical methods Elimination of pre-grant opposition Extensions to data-exclusivity periods for some drugs

Deborah H Gleeson BSc(MLS), MPH, PhD · Kyla S Tienhaara PhD · Thomas A Faunce BA LLB(Hons), BMed, PhD

Selection processes for medical schools need to be unbiased, valid, and psychometrically reliable, as well as evidence-based and transparent to all stakeholders. A range of academic and non-academic criteria are used for selection, including matriculation scores, aptitude tests and interviews. Research into selection is fraught with methodological difficulties; however, it shows positive benefits for structured selection processes. Pretest coaching and “faking good” are potential limitations of current selection procedures. Developments in medical school selection include the use of personality tests, centralised selection centres and programs to increase participation by socially disadvantaged students.

Ian G Wilson MB BS, PhD, FRACGP · Christopher Roberts MB ChB, FRACGP, PhD · Eleanor M Flynn MB BS, FRACGP, FRACMA · Barbara Griffin BPsych(Hons), PhD, MAPS

Viewing germs through biological and sociological lenses. In 1922, Simon Flexner, the director of the Rockefeller Institute in New York City, observed that “each generation receives its particular impression of epidemic diseases”. After the influenza pandemic of 1918, the postwar medical generation was trying to ...

Warwick H Anderson MD, PhD

Robert MacMahon AM, MB BS, MS, FRCS, although publicly renowned as a paediatric surgeon, was far more — teacher, innovator, a family man with a delightful sense of humour, and founding governor of the Make-A-Wish Foundation Bob was born in the Sydney suburb of Eastwood on 22 April 1931. He studied medicine at the University of Sydney, graduating in 1954. He undertook 4 years of training at the Royal Newcastle Hospital, and spent his spare time in the surf and on the rugby field for the Newcastle Wanderers. He then studied in the United Kingdom, where he decided to become a paediatric surgeon. After obtaining a Master of Science from the University of Colorado Denver, he returned to Sydney in 1965, to become the first James Fairfax Surgical Research Fellow at the Children’s Medical Research Foundation. In 1967, he was appointed inaugural Head of the Department of Paediatric Surgery at the Queen Victoria Medical Centre (later Monash Medical Centre), Melbourne. In 1970, he became Associate Professor of Paediatric Surgery at Monash University. At Monash, he developed his interest in the nutrition of premature infants, running a research program in amino acid and mineral metabolism. Between 1970 and 1975, through intravenous feeding, he increased premature infant survival from 18% to 71%. In 1974, Bob founded the Australasian Society for Parenteral and Enteral Nutrition and was its inaugural President. He served on the Monash University Human Research Ethics Committee for 40 years, and was its Chair from 1999 to 2009. He was President of the Australian and New Zealand Association of Paediatric Surgeons from 1991 to 1993. He performed the first human fetal operation in Australia and the first in-utero repair of a diaphragmatic hernia. He also pioneered in-utero laser vesicostomy and helped create the Fetal Diagnostic Unit at Monash Medical Centre. Throughout his career, Bob contributed to 10 textbooks and authored more than 60 research articles. In 2010, he was made a Member of the Order of Australia. After he retired from medicine, he enjoyed camping in the bush, surfing and golf. Bob died on 1 April 2011 from prostate cancer, and is survived by his wife Bessie and four daughters. He will be remembered for his personal integrity, enthusiasm, achievements, intellect and judgement, and his wonderful sense of humour.

Robert J Stunden

Gone viral. The germs that share our lives. Frank Bowden. Sydney: University of New South Wales Press, 2011 (216 pp, $32.95). ISBN 978174223273. FRANK BOWDEN tells a good story. As a sexual health physician and professor of medicine at the Australian National University Medical School he is well placed to provide an informative account of 15 “germs that share our life”. The anecdotes from his years of clinical and public health work in Australia make for interesting reading for both health professionals and the public. Fairfield Hospital for Infectious Diseases was, indeed, a “beautiful anachronism” in the 1980s, remembered fondly by generations of Victorian medical students who rotated through there, especially by the registrars who had the good fortune to be mentored in the science and art of general medicine and infectious diseases by Fairfield’s legendary infectious diseases physicians. Bowden provides a poignant account of his training at Fairfield during the early years of the AIDS epidemic: “There were 16 patients with AIDS on Ward 4. They were all men, all homosexual, and they were all dying”. Indigenous health has been an important part of Bowden’s career and many of the organisms he bases his stories on remain major causes of morbidity in Australia’s Indigenous population. Several controversial aspects are raised. The author is for an aggressive approach to screening and treatment of sexually transmitted infections (STIs). He laments that the success of the national donovanosis eradication campaign, which he was centrally involved in, has not been matched with similar results for other STIs, and that historically there has been opposition to the concept of mass treatment as a means to address the high rates of infectious diseases in Indigenous communities. The argument has been that a “sheep-dip approach” fails to address the primary issues of socioeconomic disadvantage, housing, health hardware, and access to health services and education. Nevertheless, the stars may be aligning finally to include the possibility of population-based treatment for infections such as syphilis, scabies, trachoma and chlamydial genitourinary infections in the setting of improved primary health care. Having to reach for the dictionary often when reading can be annoying; or it can be amusing, or even enlightening. Bowden takes the reader along from the role of necromancy in WHO decision making to the adverse impact of HIV misinformation by a pulchritudinous female surgeon. I remain baffled, however, by his allusion to the “metaphorical cojones” of cardiologists!

Bart J Currie

Incorrect statement: In: “We’ll drink to that: the 200th anniversary of the permanent Sydney Hospital” in the 16 January 2012 issue of the Journal (Med J Aust 2012; 196: 77-78), the statement “[Sydney Hospital] hosted the first operation under general anaesthetic (a leg amputation under chloroform)” was incorrect and is withdrawn. For further information, see page 315 in this issue.

Incorrect box title: In “Guide-wire fragment embolisation in paediatric peripherally inserted central catheters” in the 5 March 2012 issue of the Journal (Med J Aust 2012; 196: 250-255), there was an error in Box 2 (page 251). The labels in the title were reversed. The title should have been given as “Embolised wire fragment on chest x-ray, supine (A) and lateral (B) views”.

The work of the infectious diseases specialist spans three different domains: the pathogens that infect us, the human bodies they invade and the broader community at risk of infection.

Amanda Bryan

Most of the doctors who seek financial and personal help from a medical benevolent association have no income protection or trauma insurance.

Kath Ryan

Acute or chronic illness, like death and taxes, will come to us all. Many assume it is some way off, or that our illness will have a slow onset so that we and our families can prepare for a change in circumstances.

John de