Child health

In reply: Information made available by South Australia’s Child Death and Serious Injury Review Committee is similar to that in other Australian states that have a Child Death Review Committee; all produce an annual report of circumstances related to child deaths, including child drowning. While we are aware of these reports, for our study of child drowning, individual case details were required that cannot be extracted from compiled summaries in annual reports. By contrast, the National Coroners Information System (NCIS) provides access to original documents for individual drowning cases. Details for South Australian child drownings in the NCIS database were very limited, although at no point in our article did we infer that this information is not collected in SA; rather we stated that that coroners findings were only available for 38.1% of cases in the NCIS, and that autopsy and toxicology reports are not routinely uploaded.1 Further, the recently revised position paper of the National Drowning Prevention Alliance (NDPA) states that neither a single device nor a single solution can prevent child drownings, and recommended that caregivers, aquatic facility owners, managers and operators use “layers of protection” to aid in child drowning prevention.2 We certainly agree that the ongoing promulgation of well researched public health campaigns is an important layer in the prevention of child drowning, although, to date, no published studies have investigated the effectiveness or rigorously evaluated Australian aquatic death prevention campaigns (such as Keep Watch, Kids Alive — Do The Five, SafeWaters and Play it Safe by the Water). However, the NDPA did identify that supervision is the one layer that should be ever-present, regardless of what other layers are used.2

Lauren A Petrass · Jennifer D Blitvich · Caroline F Finch

No-fault compensation, based on the ethical principle of redistributive justice, should form a cornerstone of Australia’s immunisation strategy Australia has an enviable reputation for its publicly funded vaccine program — a program that has benefited Australian children and adults over many years. In 2010, the National Immunisation Program funded 12 vaccines, twice as many as a decade previously. To monitor outcomes from this program, the Australian Childhood Immunisation Register, which commenced data collection in 1996, provides a detailed record of vaccine uptake by children.1 Funding for the register and for incentives to general practitioners to improve vaccine uptake are part of the total budget for Australia’s vaccine program, estimated to exceed $400 million annually.2,3 One area for improvement in the vaccine program is monitoring of adverse events following immunisation (AEFI). Another would be the introduction of a no-fault compensation scheme for serious adverse events which can be confidently attributed to vaccination. An investigation into the unexpectedly high number of febrile convulsions in children aged less than 5 years after they had received the influenza vaccine in 2010 — in some cases, with devastating consequences4 — provided a forceful reminder that timely vaccine safety monitoring is needed in Australia.5 More active adverse event surveillance is certain to uncover more AEFI but many of these will only be coincidental, while others will be of a transient or relatively trivial nature. On rare occasions, a serious AEFI with long-term sequelae will be recognised. A decision will then need to be made on whether the vaccine was responsible for that serious event. The World Health Organization defines four categories of serious AEFI: hospital admission or prolongation of an existing hospital admission; permanent disability; any event that is life threatening; or death.6 Using these criteria, 8% (193/2396) of the AEFI reported by passive surveillance in Australia in 2009 were judged to be serious.7 However, unlike many countries where compensation schemes exist for adverse events attributed to a vaccine, Australia has no routine approach to making the assessment of attribution. Parents of children or adults who believe they deserve compensation for a serious adverse event that they attribute to a vaccine are therefore required to make their case through the adversarial legal system. This requires the demonstration that an individual or an organisation was at fault. However, fault is often difficult to demonstrate and an adverse event may be caused by vaccination through no fault of the vaccine manufacturer, the regulator or the person who administered the vaccine. We have previously argued that a Queensland child who developed transverse myelitis after receiving oral polio vaccine was an example of an adverse event following vaccination where no fault was attributable to any party.8,9 Despite detailed epidemiological evidence that was consistent in this case with the causal criteria for an AEFI promulgated by the Institute of Medicine of the National Academies in the United States,8 and despite laboratory evidence showing that the polio virus recovered from this child was similarly pathogenic to a polio virus that has been accepted as causing vaccine-associated paralytic polio,9 the polio expert committee concluded that the evidence was insufficient to support a causal relationship between the oral polio vaccine and transverse myelitis. As causality has not been accepted, this child has received no compensation. The general principles associated with this case raise a number of pertinent questions for Australia. First, should a child who may have been injured by a vaccine, which was endorsed and paid for by the community, be compensated by the community when the serious adverse event may be attributed to the vaccine? Second, what are the criteria for accepting an attributable relationship between receipt of the vaccine and a subsequent adverse event? Third, what is the best method for financing a compensation scheme? Each question may highlight a potential barrier to the implementation of a no-fault AEFI compensation scheme in Australia. By 2010, 19 countries around the world had implemented no-fault AEFI compensation, implicitly answering “yes” to the question of whether the community owes a duty of care to an individual injured by a vaccine.10 There is also a strong ethical argument for this position, based on the concept of redistributive justice. Any person who is injured while helping to protect the community — for instance, by contributing to herd immunity, such that there are sufficiently many people immunised to prevent widespread disease transmission within the community — should not bear the consequences of injury alone. In essence, the community owes a debt of gratitude to that person. Temporal association of an adverse event with receipt of a vaccine does not establish causality and the underlying notion of causation used in most compensation schemes is similar to that used in epidemiology.10 The World Health Organization has published guidelines on causality for an AEFI.11 An adverse event considered to be very likely or certainly due to a vaccine would comprise a “Clinical event with a plausible time relationship to vaccine administration, and which cannot be explained by concurrent disease or other drugs or chemicals”.11 To simplify and expedite determinations of causality in the US, a vaccine injury table is used to predetermine causality if a vaccine injury is included in the table.10 However, determining causation is a complex issue. Recognising this, most countries have a designated committee, comprising medical and legal members, which deliberates on the attributable relationship between receipt of the vaccine and subsequent adverse event.10 Concerns about funding a no-fault compensation scheme is another of the probable barriers to its implementation in Australia. Schemes are currently funded by one of four methods: a vaccine levy; compensation for AEFI as part of a much broader injury compensation scheme; specific AEFI compensation funded through general tax revenue; and funding in association with industry.10 Funding through a vaccine levy has been self-sustaining in the US. Despite compensation payments having been made to 2580 claimants since 1989, the compensation fund there has a surplus of about US$3 billion.12,13 No-fault vaccine-injury compensation programs are based on the premise that any adverse event attributable to vaccination is not due to the fault of a specific individual or organisation, but due to an unavoidable risk that is acknowledged as being associated with vaccines. Germany has been operating a no-fault AEFI compensation scheme for 50 years.10 France restricts its compensation to serious AEFI, since these are likely to have long-term implications for the injured party.10 Restricting compensation to events with long-term consequences, above a nominated clinical threshold, may be an acceptable model for Australia. We have previously argued that Australia should follow the lead of other advanced countries and implement a no-fault compensation scheme.14 We continue to argue that such a scheme, based on the ethical principle of redistributive justice, should form a cornerstone of Australia’s immunisation strategy. Disclaimer The views expressed are those of the authors and have not been endorsed by any institution or organisation with which the authors are affiliated or by any committees of which the authors are members.

Heath A Kelly BSc, MB BS, MPH · Clare Looker MB BS, MPH · David Isaacs MD, FRACP, FRCPCH

To the Editor: Young children are at increased risk of severe influenza compared with the general population. Routine vaccination of children using trivalent influenza vaccine (TIV) is recommended in the United States and Canada. The Western Australian government, with support from vaccine manufacturers, has been providing TIV free of charge to all children aged 6–59 months since 2008.1 In 2010, high fevers and an increased incidence of convulsions were observed in children aged < 5 years after administration of TIV. Most reports of adverse events were from WA, owing to higher uptake of vaccination associated with the free vaccination program. The national influenza vaccination program for children aged < 5 years was subsequently suspended,2 and high rates of fever and convulsions were confirmed.2,3 The majority of adverse events occurred after administration of Fluvax or Fluvax Junior (CSL Biotherapies). More than 50% of parents of children who were administered Fluvax or Fluvax Junior reported high fever after vaccination. The incidence of febrile convulsions after vaccination with Fluvax and Fluvax Junior was 4.4 per 1000 doses, significantly higher than expected.3,4 Fluvax and Fluvax Junior are not recommended for children aged < 5 years in the Australian 2011 influenza vaccination program.5 In response to these events, WA Health established an online registry for vaccine-associated adverse events — the Western Australian Vaccine Safety Surveillance (WAVSS). Health professionals are required and members of the public encouraged to report adverse events. In addition, a prospective safety study of the 2011 TIV in children aged < 5 years has commenced at Princess Margaret Hospital for Children and the WA Central Immunisation Clinic. From 15 March to 29 April 2011, 2227 doses of TIV were administered to children aged < 5 years in WA (2130 doses of Vaxigrip [Sanofi Pasteur]; 97 doses of Influvac [Solvay]). Adverse events in four children aged < 5 years have been reported via WAVSS: two with elevated temperature (≥38°C yet < 39.5°C) within 24 hours of vaccination, one with vomiting and diarrhoea after vaccination, and one with fever (not specified) and convulsions 4 days after vaccination (this child had a respiratory tract infection at the time of vaccination). All four children were administered other vaccines with TIV. In the safety study, 144 children were enrolled between 15 March and 29 April 2011. Adverse events after vaccination were reported in 10 children (7%), two of whom received other vaccines in addition to TIV. All 10 children had fever reported, and one child had a temperature > 39.5°C. Two children developed vomiting. No convulsions were reported and none of the children who had adverse events required assistance from a health care professional. These data demonstrate that the significant adverse events that occurred after administration of TIV in 2010 have not been observed in WA during early 2011. Ongoing surveillance is underway and will continue. Poor uptake of influenza vaccination in Australian children is likely to result in increased influenza-related hospitalisation, morbidity and mortality. Data such as those reported here are required to reassure the community of the safety of this vaccination program before the expected start of the 2011 influenza season.

Christopher C Blyth · Tracy Y Markus · Paul V Effler · Peter C Richmond

To the Editor: The Medicare item for annual child health checks (CHCs) for Aboriginal and Torres Strait Islanders involves taking a comprehensive health-related history from the antenatal period onwards, recording growth parameters, performing a medical examination, identifying new diagnoses and commencing management, which may include advice, referral, vaccinations and treatment. The CHC has had little evaluation as a primary health care tool in the urban setting; indeed, outside remote regions, it has barely been taken out of the toolbox. Although 76% of Aboriginal and Torres Strait Islander people live in urban or regional areas,1 we are unaware of any published research on CHCs outside remote areas. We therefore aimed to evaluate the role of the CHC for 0–14-year-olds at Inala Indigenous Health Service, an urban primary care service in a suburb of Brisbane. Ethics approval was obtained from the University of Queensland’s Behavioural and Social Sciences Ethical Review Committee and Metro South Health Service District Human Research Ethics Committee at the Princess Alexandra Hospital. The local Inala Elders Aboriginal and Torres Strait Islander Corporation supported the project. Descriptive statistical analysis was conducted using Stata, version 10 (StataCorp, College Station, Tex, USA). Of 867 eligible children, we completed 786 CHCs from May 2007 to December 2009. We excluded 245 “subsequent” CHCs (31%) in children who had already had a CHC in the study period, and 109 of the remaining 541 (20%) that were not accompanied by a research consent form, leaving 432 CHCs available for analysis. The children (234 male [54%]) were Aboriginal (394, 91%), Torres Strait Islander (9, 2%) or both (29, 7%). Reported health risk factors included living in households with a smoker (75%), parental unemployment (67%), exposure to domestic violence (29%), never having been breastfed (32%) and not having teeth brushed twice daily (46%), although more than half the children (57%) exercised at least 30 minutes every day. New diagnoses made at the CHC (40%) were primarily dental caries (36%) or conditions involving the skin (18%) or ears (10%). During the CHC, 63% of parents were given health advice, 24% of children were referred for follow-up and 22% were vaccinated (Box). From May 2006 (when CHCs were introduced) to June 2009, 4610 Indigenous CHCs were reported by Australia’s 54 metropolitan Divisions of General Practice, comprising just 4.3% of the eligible population.2 This contrasts with the 14 500 CHCs (89% coverage) completed in prescribed remote areas by the Northern Territory Emergency Response (NTER).3 A recent report highlights the low number of CHCs performed outside the NTER and the lack of timely follow-up within the NTER to address detected health problems. The report concluded: “It’s clearly time to reconsider this failed health policy”.4 However, a distinction should be drawn between the NTER CHCs — usually performed by “fly-in, fly-out” teams who are not in a position to provide ongoing care — and a CHC program embedded in a local clinic as a cornerstone of usual health care. In the wake of the NTER, the then National Aboriginal Community Controlled Health Organisation chairperson, Dr Mick Adams, said, “This is not to say that we do not want more child health checks [but we reject] the present way of doing them”.5 Strengths of our study include the high proportion of our clinic’s eligible population who had CHCs (541/867, 62%). Although our practice comprises only 0.8% of Australia’s urban Indigenous children, our service completed 10% of the CHCs done in Australian metropolitan areas to June 2009.2 Because the study was limited to the day of the CHC, we were unable to evaluate whether referrals resulted in attendances. Further research is required to document the success of follow-up resulting from CHCs, including referral attendance rates. We have found that the Indigenous CHC, performed within the patient’s usual primary care service, provides an important opportunity to make new diagnoses and to identify and initiate management of health risk factors. The CHC is an underused tool worth dusting off in primary care. Health risk factors (reported by parent or carer), new diagnoses and interventions from child health checks of 432 Aboriginal and Torres Strait Islander participants attending Inala Indigenous Health Service, May 2007 – December 2009* Variable No. (%) Variable No. (%) Maternal substance use during pregnancy Adolescent (12–14-year-olds) behaviour (n = 65) Tobacco (n = 432) 156 (36%) Consumes alcohol (n = 54) 5 (9%) Alcohol (n = 432) 70 (16%) Current smoker (n = 54) 4 (7%) Cannabis (n = 431) 36 (8%) Sexually active (n = 51) 3 (6%) Intravenous drugs (n = 431) 16 (4%) New diagnosis resulting from health check Household characteristics Any new diagnosis (n = 432) 174 (40%) Household with a smoker (n = 416) 312 (75%) Dental caries (n = 345) 124 (36%) Unemployed parent (n = 432) 288 (67%) Skin condition, all causes (n = 432) 77 (18%) Single parent caring for child (n = 432) 194 (45%) Ear condition‡ (n = 432) 43 (10%) Stressful event impacting on household (n = 432) 180 (42%) Overweight (n = 332) 83 (25%) Households with six or more residents (range, 6–12) (n = 408) 149 (37%) Obese (n = 332) 36 (11%) History of domestic violence exposure (past or current) (n = 432) 124 (29%) Interventions (n = 432) Perinatal characteristics Any health/lifestyle advice 270 (63%) Premature birth (gestation < 37 weeks) (n = 336) 45 (13%) Nutrition advice 119 (28%) Perinatal complication (n = 432) 170 (39%) Learning/behavioural advice 54 (13%) Never breastfed (n = 339) 110 (32%) Physical activity advice 54 (13%) Childhood health behaviour Smoking cessation advice 42 (10%) Watch electronic media ≥ 60 min/day (n = 237) 183 (77%) Alcohol consumption advice 33 (8%) Teeth not brushed twice daily (n = 360) 165 (46%) Any referral (n = 432) 103 (24%) Suboptimal physical activity† (n = 215) 92 (43%) Paediatrician referral 31 (7%) Parental/carer concerns about child’s behaviour (n = 264) 81 (31%) Dental referral 26 (6%) Parental/carer concerns about child’s learning (n = 276) 82 (30%) Audiology referral 17 (4%) Dietitian referral 13 (3%) Vaccinations given on the day of the check (n = 432) 96 (22%) * Denominators vary because of missing data. † ≤ 30 min/day for < 7 days a week. ‡ Defined as having signs (eg, perforation, bulging) or a diagnosis (eg, otitis media, otitis externa) of ear disease in at least one ear.

Justin J Coleman · Geoffrey K Spurling · Deborah A Askew · Noel E Hayman

The Thoracic Society of Australia and New Zealand has updated its guidelines on corticosteroid use in childhood asthma The understanding of childhood asthma has increased substantially since the publication of the Thoracic Society of Australia and New Zealand (TSANZ) position statement The role of corticosteroids in the management of childhood asthma in 2002.1 In particular, recognition of the need for separate asthma management guidelines for children aged 5 years or younger has increased,2 and considerably more clinical research evidence on the role of asthma medications in children has become available. The 2010 revision of the TSANZ position statement provides updated recommendations on the roles of inhaled corticosteroids, oral corticosteroids, leukotriene receptor antagonists and combination medications (inhaled corticosteroids plus long-acting β-agonists) in childhood asthma management based on recently published evidence.3 The role of leukotriene receptor antagonists in the management of childhood asthma has also been addressed in detail in a recent National Asthma Council Australia information paper.4 The National Asthma Council Australia provides a comprehensive overview of the role of preventive treatment in childhood asthma in its Asthma management handbook 2006.5 It advocates a stepwise approach to drug therapy that is based on asthma severity. If control is not achieved using initial preventer therapy, it is important to review the diagnosis of asthma — particularly in children aged 5 years or younger — as many children with recurrent cough are mislabelled as having asthma6 and different wheezing phenotypes require different treatment approaches.2 Before escalating the level of preventer therapy, it is also essential to check the child’s inhaler technique and adherence to treatment. Step-down treatment (“back titration”) is advocated once control has been achieved and sustained for at least 3 months. Two placebo-controlled studies of montelukast have established the efficacy and safety of this medication and form the basis of its current Pharmaceutical Benefits Scheme listing for children with frequent intermittent or mild persistent asthma.3,4 Compared with placebo, regular montelukast therapy produces a modest reduction in exacerbation risk in children with viral-induced wheezing.3,4 An additional benefit of montelukast therapy is its proven efficacy for protecting against exercise-induced bronchoconstriction,3,4 being more effective than long-acting β-agonists without development of the tolerance seen with long-acting β-agonists.3 This information led to the current Pharmaceutical Benefits Scheme listing of montelukast for children aged 6–14 years who have ongoing activity-related asthma despite inhaled corticosteroid treatment. The effectiveness of prophylactic inhaled corticosteroids in persistent childhood asthma is well established.3 In contrast, regular inhaled corticosteroid treatment for intermittent, viral-induced wheezing does not reduce rates of hospitalisation, use of oral corticosteroids, or frequency and duration of acute episodes.3 Systemic effects of inhaled corticosteroids in children are well documented; they include impaired linear growth, adrenal suppression, and effects on bone mineralisation.3 Although the clinical significance of these adverse effects is uncertain, factors such as individual susceptibility, severity of asthma, age, pubertal status, total dose, and dose delivery may affect risk of systemic toxicity. Although it is common to add a long-acting β-agonist to inhaled corticosteroids (as a single combination inhaler) there are few paediatric studies examining this practice, and these suggest that, while the combination improves lung function, it does not reduce exacerbation risk — in fact, it may increase it.3 These recent studies support the current National Asthma Council recommendations of reserving the addition of long-acting β-agonists for children with asthma that is not adequately controlled by 200–250 μg/day fluticasone propionate or equivalent doses of other inhaled corticosteroids,3 and highlight the potential role of montelukast as an alternative add-on therapy. The use of long-acting β-agonists is not, however, recommended for children aged 5 years or younger.2,3 Our recommendations for preventer treatment in childhood asthma are summarised in the Box. Children with infrequent intermittent asthma require no preventer therapy. Current evidence suggests that non-steroidal preventers should be trialled first in children with frequent intermittent or mild persistent asthma, while inhaled corticosteroids are indicated as first-line preventer treatment in children with moderate–severe persistent asthma. Long-acting β-agonists or montelukast are add-on options in children with persistent symptoms despite adequate inhaled corticosteroid treatment. In terms of acute asthma management, oral corticosteroids improve outcomes in children presenting to hospital with acute asthma, but the efficacy of oral corticosteroids for children aged 5 years or younger with acute, mild–moderate, viral-induced wheezing has been questioned.3 Based on current evidence, we recommend oral corticosteroids be reserved for children with moderate–severe acute asthma exacerbation and children with an incomplete response to β-agonists. However, in children aged 5 years or younger (particularly those with intermittent, viral-induced wheezing) the use of oral corticosteroids should be limited to those with severe wheeze who require hospital admission; an initial dose of 2 mg/kg prednisolone (maximum 60 mg) is recommended, followed by daily doses of 1 mg/kg if required. Although a 3-day course is generally sufficient, a more prolonged course may be indicated in severe cases. There is some evidence for the benefit of intermittent inhaled corticosteroids and leukotriene receptor antagonists in acute asthma, but oral corticosteroids remain the treatment of choice — particularly for more severe episodes, because of ease of administration, low cost and greater proven efficacy in severe acute asthma. The need for recurrent systemic corticosteroid therapy requires reassessment of the child’s interval therapy, particularly in cases of persistent asthma, and specialist referral. Preventer therapy for children who have frequent intermittent or persistent asthma symptoms* FP = fluticasone propionate. BDP–HFA = beclomethasone dipropionate – hydrofluoroalkane. BUD = budesonide. CIC = ciclesonide. * Modified from the Asthma management handbook 2006 with permission from the National Asthma Council Australia.5 † Long-acting β-agonists not recommended for children aged 5 years or younger.

Peter P Van Asperen MB BS, MD, FRACP · Craig M Mellis MPH, MD, FRACP · Peter D Sly MD, DSc, FRACP · Colin F Robertson MSc, MD, FRACP

Objective: To audit general paediatric outpatient practice in Australia, including consultation characteristics and management patterns, diagnoses, factors associated with diagnoses, and billing practices.Design, setting and participants: In October – November 2008, members of the Australian Paediatric Research Network (APRN; a national network of paediatricians established to facilitate multisite secondary care research) were invited to prospectively complete brief standardised data collection forms for 100 consecutive patients or all patients during a 2-week period, whichever came first.Main outcome measures: Length of consultation and type of diagnoses made; proportions recorded as having medications, investigations or referral; odds ratios for factors associated with diagnoses; and proportions of Medicare items billed.Results: Of 300 APRN members, 199 (66%) completed data forms for 8345 consultations in which 15 375 diagnoses were made (mean, 1.8 diagnoses per consultation); 46.0%, 30.9% and 22.8% of consultations involved 1, 2 and ≥ 3 diagnoses, respectively. New and review consultations lasted a mean of 41 (SD, 20) and 26 (SD, 15) minutes, respectively. The most common diagnoses were attention deficit hyperactivity disorder (18.3%), baby checks (9.1%), and learning difficulties (7.5%). Patients seen in 47.5% of consultations had medications (eg, prescriptions, vaccinations) recorded, and patients in 27.2% of consultations were referred elsewhere, usually to a subspecialist or psychologist (31.6% and 26.6% of referrals, respectively). Male sex of the child and owning a Health Care Card were associated with most developmental–behavioural diagnoses. Paediatricians tended to bill for single disease/non-complex consultations, even when seeing a child with multiple problems.Conclusions: Australian paediatricians see children with a range of diagnoses that are often multiple and complex. Our findings provide directions for future secondary care research, and may inform workforce planning and paediatricians’ training requirements.

Harriet Hiscock MB BS, FRACP, MD · Gehan Roberts MB BS, FRACP, PhD · Daryl Efron MB BS, FRACP, MD · Jillian R Sewell MB BS, FRACP · Hannah E Bryson BA(Hons) · Anna M H Price BA(Hons) · Frank Oberklaid MD, FRACP, DCH · Michael South FRACP, MD, FCIM · Melissa A Wake MB ChB, FRACP, MD

Ronald Nicolson O’Reilly was born on 18 January 1921 in Winton, Queensland. Raised in Winton and Barcaldine, he went to Brisbane Boys’ College, and then studied medicine at the University of Queensland, graduating in 1945. Ron completed his residency at Brisbane General Hospital and established a general practice in suburban Chermside. He soon realised that his vocation was with children, and undertook training in paediatrics at the Royal Children’s Hospital in Melbourne. He was very highly regarded in Melbourne as a clinician and researcher, but in 1957, Ron returned to Brisbane, where he worked as a physician and then Deputy Medical Superintendent at the Royal Children’s Hospital. In 1961, he received his doctorate from the University of Melbourne for his thesis on bronchiectasis. In 1962, Ron was appointed Senior Visiting Paediatrician at the Royal Children’s Hospital, where he remained until mandatory retirement at age 60 in 1981. He also entered private practice on Wickham Terrace, which he continued until he was in his seventies. In 1975, Ron became a Member of the Royal Australasian College of Physicians and, in 1978, a Fellow. Ron was an outstanding teacher and clinician, and he cared for many doctors’ children — an expression of the respect held for him. He served on the boards of the Asthma Foundation of Queensland, Montrose Home for Crippled Children, Xavier Home, Tufnell Home, and St Helen’s Hospital as it evolved into the Wesley Hospital. Ron retired from practice in 1994 to live on Bribie Island, where he became very active in the Bribie Island Environmental Protection Association. His wife Elva, who had been a great support in his work, predeceased him by 22 years. Ron died on 13 September 2010, soon after suffering a massive stroke. He is survived by his son Graham, daughter Annise, and several grandchildren who appreciated his wise and gentle counsel. For those of us who came under his influence, memories of an excellent clinician and stimulating teacher will endure. He did not seek honours or awards but deserved many.

D Barry Appleton

Objectives: To examine the experience of fear, the fear response, and factors affecting fear in adolescents undergoing school-based human papillomavirus (HPV) vaccination.Design, participants and setting: A purposive sampling strategy and qualitative methods, including observation and face-to-face interviews. Focus groups comprised adolescent girls who were involved in HPV vaccination in 2007 at schools in Sydney, New South Wales. Individual interviews were conducted with parents, teachers and vaccination nurses.Results: Data from observing vaccination days at three schools and from interviewing 130 adolescents in 20 focus groups, 38 parents, 10 teachers and seven nurses were included in the analysis. All participants discussed the issue of fear and distress experienced by adolescent girls in relation to HPV vaccination. Observations corroborated the focus group and interview data. Our results indicated that fear was promoted by witnessing the fear reactions of peers; perceived judgement by peers; lack of information or misinformation; and being vaccinated later in the day. Fear was moderated by procedural factors, the support of peers, appropriate knowledge, and nurses’ distraction techniques or approach. Fear also affected acceptance of HPV vaccination.Conclusions: Fear of HPV vaccination was a near universal experience among adolescents in the school setting and was often associated with significant distress that had an adverse impact on the vaccination process. School vaccination could be improved by proactively managing fear and distress.

Diana M Bernard MPH · Spring C Cooper Robbins PhD · Kirsten J McCaffery PhD · Caroline M Scott MHlthSc(Nurs) · S Rachel Skinner PhD, FRACP

Newborn screening (NBS) programs are a well established and cost-effective method for early identification of genetic disorders. However, a raft of legal questions surrounds the collection, storage, ownership and secondary use of NBS cards. The absence of clear legal rules governing NBS programs in Australia means that there are few straightforward answers to these questions. A series of controversial incidents have exposed this uncertainty in Australia, and remarkably similar controversies have occurred in the United States and European Union. We review the situation, using Victoria as a case study. We also make the case for a dedicated regulatory regime for NBS programs, arguing that the lack of such a regime threatens public trust and the robust operation of NBS programs in Australia. New rules would likely introduce stricter requirements for informed consent at the point of blood collection than has been the norm to date. However, the scope for use of cards in research could expand rather than contract, and it may be possible to reduce the risk that vast card archives will need to be destroyed in response to future public outcries.

Diana M Bowman BSc, LLB, PhD · David M Studdert LLB, ScD, MPH

Objectives: To establish how frequently supervision was explicitly identified as a factor in coroner-certified unintentional drowning deaths of children in Australia, and to determine the percentage of cases where failure of supervision may have been a contributing factor; also, to identify the proportion of cases with coroners’ recommendations relating to supervision and unintentional child drownings.Design and setting: Retrospective case-series analysis of unintentional drowning deaths of children (aged 0–14 years) in Australia from 1 July 2000 to 30 June 2009, based on data from the National Coroners Information System (NCIS).Main outcome measures: Number of unintentional child drownings and the extent to which supervisory factors were formally reported by coroners as a contributing factor; proportion of cases with coroners’ findings that also had coroners’ recommendations.Results: 339 relevant child drownings were identified within the 9-year period. Supervision (or lack thereof) was identified as a contributing factor in 71.7%. However, specific detail about the nature and extent of supervision varied across these cases. The availability of text documents describing the findings (police reports, coroners’ findings, autopsy reports, toxicology reports), and the level of detail within these documents, also varied considerably across jurisdictions. Despite almost half (47.2%) of the closed cases having coroners’ findings attached, only 15% of these also included specific coroners’ recommendations.Conclusion: Lack of adequate supervision, or lack thereof, is a significant problem associated with fatal drownings of children in Australia. There is a need to improve the standard and consistency of information contained in text documents within the NCIS to provide more useful information for preventing child drowning deaths.

Lauren A Petrass BEd(PE)(Hons), GradDip(Outdoor · Jennifer D Blitvich MPE, DipEd, PhD · Caroline F Finch BSc, MSc, PhD

Objective: To examine age and sex differences in the leading causes of prevalent disability in young Australians.Design, setting and participants: We analysed data from the 2003 Australian Burden of Disease and Injury Study, which estimated the prevalent disability burden attributable to 170 diseases and injuries, for younger adolescents (10–14 years), older adolescents (15–19 years) and young adults (20–24 years).Main outcome measures: The broad categories of disease and injury that are the main contributors to prevalent disability and the 10 leading disease and injury causes of prevalent disability, according to sex and age group.Results: Total prevalent disability rates are lowest in younger adolescents and highest in young adults. Mental disorders are the largest “contributor” to disability in young Australians, and anxiety and depressive disorders are the leading single cause. In young males, autism and attention deficit hyperactivity disorder cause similar levels of disability as do anxiety and depression. In young females, eating disorders are the second leading cause of mental disorder disability. Alcohol use disorders and schizophrenia make important contributions to disability in young adult males. Asthma is the most prominent cause of physical disability in all three age groups.Conclusions: There are substantial changes in both the pattern and level of disability burden across the three age groups that we studied. The increase in total prevalent disability that occurs from early adolescence to young adulthood should focus attention on the delivery of accessible and youth friendly health care as well as the effectiveness of transitions from child health services to adult health services.

Rebecca R S Mathews MPH · Wayne D Hall PhD · Theo Vos PhD · George C Patton MD, FRANZCP · Louisa Degenhardt PhD

To the Editor: Rahman and colleagues suggest that iodine deficiency in Victoria increased between 2001 and 2006, based on the findings of thyroid-stimulating hormone (TSH) levels in neonates at routine newborn screening.1 Indeed, their data as presented suggest a doubling of the percentage of mothers with iodine deficiency to over 9% during that period. This could be correct. Certainly, as they state, there is much evidence to suggest that there is mild iodine deficiency in Australia. However, there are caveats about the data they report which are not mentioned. Data from New South Wales do not show this trend. While they do suggest a degree of mild iodine deficiency, there was no increase in the percentage of neonates with TSH levels > 5 mIU/L of whole blood from 2002 to 2009 (Box), although the average age at sampling falls slightly (from 2.96 to 2.32 days) over this period. The World Health Organization has defined iodine sufficiency as being indicated, inter alia, when more than 3% of newborns aged 3–4 days have a TSH level > 5 mIU/L of whole blood.2 Factors that affect the TSH level in a newborn screening program include the precise age at sampling, and any changes to the method of TSH analysis used. In a Swiss study assessing the efficacy of iodine supplementation, there was a small but significant decrease in the TSH level from Day 3 to Day 4 of age.3 This is unsurprising: following the TSH surge in the first hours after birth, TSH levels decline gradually to a steady level at about Day 7.4 There could well have been a trend to earlier sampling in Victoria, within the bounds of the 2–4 days of age assay that Rahman and colleagues mention, over the period studied, but these crucial data are not given. The dried blood spot TSH assay method is not described either. A change in any aspect of the methodology; for example, if the manufacturer modified the antibody used, may produce a small, clinically insignificant but numerically significant, change in results. If the data presented by Rahman and colleagues for Victoria do not have these biases, then the situation warrants further investigation, but whatever is happening in Victoria seems not to be replicated over the border. Percentage of newborns with thyroid-stimulating hormone (TSH) level > 5 mIU/L of whole blood, detected by routine newborn screening in New South Wales, by year Year Newborns with TSH level > 5 mIU/L 2002 3.80% 2003 3.68% 2004 3.87% 2005 5.02% 2006 4.48% 2007 3.56% 2008 3.92% 2009 4.00%

Bridget M Wilcken · Veronica C Wiley

In reply: The methods used for blood sample collection and analysis remained unchanged during our data collection period. One source of thyroid-stimulating hormone (TSH) calibrators and reagents was used over the study period by a single laboratory covering all of Victoria. Material from the United States Centers for Disease Control and Prevention was used for external quality assurance, ensuring that the results were in agreement with those of other laboratories. The per cent coefficient of variation over the period ranged from 10% to 20%. The table of neonatal TSH values for New South Wales provided by Wilcken and Wiley further demonstrates the value of using TSH levels as a screening tool for population iodine status, even with a decreasing mean age of sample collection. While we dealt with the effect of sample collection time in our published article,1 here we present a table illustrating analysis of the Victorian neonatal TSH values for samples collected at 48, 72 and 96 hours after birth (Box). The percentage of elevated TSH values increased from 2001 to 2006 at each collection time and, although the percentage of elevated TSH values decreased with increasing age, these values were still indicative of iodine deficiency. Iodine status varies between regions. The National Iodine Nutrition Study (NINS) found both South Australia and Queensland iodine sufficient, while the neighbouring states of NSW and Victoria were iodine deficient.2 The results also indicated that iodine status was worse in Victoria than in NSW; therefore, we might expect similar differences in TSH values. We are now in the process of analysing Victorian TSH values for 2007 to 2010. Percentage of newborns with thyroid-stimulating hormone (TSH) level > 5 mIU/L for blood samples collected at 48, 72 and 96 hours after birth, Victoria, 2001–2006 Sample collection time (h) Percentage of neonates with TSH > 5 mIU/L according to birth year 2001 2002 2003 2004 2005 2006 48 5.73% 6.83% 8.47% 10.58% 11.86% 13.53% 72 4.20% 5.15% 6.87% 7.01% 9.13% 9.38% 96 2.49% 3.21% 4.37% 3.78% 5.98% 5.34%

Ashequr Rahman · Gayle S Savige · Nicholas J Deacon · Ivan Francis · Janice E Chesters

To the Editor: O’Leary and Major1 have opened debate on the issues raised by the New South Wales-wide introduction of the Clinical Excellence Commission Between the Flags (BTF) observation charts, which incorporate escalation thresholds for vital signs and other criteria. In the BTF charts, “yellow” zone criteria trigger a clinical review and “red” zone criteria, a rapid response.2 Evidence shows that deterioration can be recognised early, reducing serious consequences.3,4 O’Leary and Major trialled a subset of the draft BTF paediatric calling criteria in the context of triage in an emergency department, applying them retrospectively and comparing the actual triage decision with the one that would have been made using the BTF criteria alone. They also examined patient disposition for patients falling within the yellow and red zones. They concluded that “the physiological parameters ... are not suitable as a triage tool in the paediatric emergency department, do not replace an experienced triage nurse, and are a poor predictor of disposition”.1 We are not surprised by this conclusion. The Australasian Triage Scale is designed to assess a patient’s urgency based on presenting problem and general appearance, possibly combined with physiological observations.5 Trialling a subset of vital signs, on their own, against the triage process, although interesting, is unlikely to demonstrate a strong correlation in decision making for the following reasons. The BTF vital signs observations are designed for use in the context of a “track and trigger system” in a general ward, to monitor trends, not as a substitute for the triage process. Vital sign observations on their own contribute little to triage decisions. Triage decisions are poor predictors of disposition (eg, up to 67% of triage Category 2 patients are discharged home from the emergency department) (Sydney South West Area Health Service emergency department data for July 2010, for Campbelltown, Liverpool and Royal Prince Alfred hospitals). On their own, we would expect vital signs to be poorer predictors of disposition outcome than triage decisions, which have the benefit of information on presenting problem and general appearance. Context for vital sign observations has a major influence on their interpretation. We recommend that more work be done on the value of the BTF vital signs criteria as a complement, not alternative, to triage processes.

Charles H Pain · Clifford F Hughes · Marino Festa · Jodie Ekholm · Matthew O’Meara

Clinical records Patient 1 A 7-month-old boy presented with a 24-hour history of restlessness, tachypnoea, poor feeding and vomiting. An abdominal ultrasound was thought to show possible intussusception. The infant’s medical history, including the perinatal period, was unremarkable. His body weight was normal (9 kg). There was no family history of note, and the family denied giving him medications (including complementary or alternative treatment) apart from paracetamol. He appeared lethargic, with minimal motor and verbal response, although this improved when a low blood sugar level (2.0 mmol/L; reference range [RR], 3.0–5.5 mmol/L) was corrected. Test results of arterial blood gas levels showed a well compensated anion-gap metabolic acidosis, with a lactate level elevated to 7.8 mmol/L (RR, < 2.0 mmol/L); pH, 7.38 (RR, 7.35–7.43); partial pressure of carbon dioxide (PaCO2), 14 mmHg (RR, 32–45 mmHg); partial pressure of oxygen (PaO2), 129 mmHg (RR, 69–116 mmHg); plasma bicarbonate (HCO3), 8 mmol/L (RR, 22–32 mmol/L); base equivalent (BE), − 7 (RR, − 2 to + 2); sodium, 142 mmol/L (RR, 135–145 mmol/L); potassium, 4.9 mmol/L (RR, 3.6–5.1 mmol/L); and chloride (Cl), 113 mmol/L (RR, 95–105 mmol/L). Initial urinalysis showed a specific gravity of 1.025 (RR, 1.015–1.025), pH of 6.0 (RR, 5.0–8.0) and elevated ketones (80 mg/L; RR, 5–30 mg/L), but was otherwise normal. Results of a repeat abdominal ultrasound were normal. Apart from persistent tachypnoea, hyperpnoea and periods of appearing lethargic and less interactive, the infant’s vital signs and results of a physical examination were unremarkable. The unexplained anion-gap metabolic acidosis persisted. Metabolic investigations showed a mild transaminitis (serum aspartate aminotransferase [AST], 568 U/L and alanine aminotransferase [ALT], 946 U/L [RR for both, < 45 U/L]) and hyperammonaemia (plasma ammonia, 183 µmol/L [RR, < 50 µmol/L]). Accordingly, extra intravenous (IV) dextrose was administered (increased to 9.3 mg/kg/min); a urine specimen was sent for urgent mass spectroscopy; and oral administration of a cocktail of vitamins (biotin, B12, riboflavin and carnitine) was commenced, as well as IV bolus doses and then continuing infusions of sodium benzoate and arginine. At this time, the working diagnosis was of an organic acidaemia or urea cycle defect with decompensation, caused by intercurrent illness. Over the following 8 hours, with these measures in place, the transaminitis and hyperammonaemia improved marginally, but the infant’s conscious state deteriorated and he required endotracheal intubation. Once intubated, hyperventilation to a PaCO2 blood level of about 20 mmol/L was continued and the patient was prepared for haemofiltration. The urine spectroscopy result showed salicylate metabolites, and blood testing showed a quantitated salicylate level of 1.44 mmol/L (therapeutic range, 1.1–2.2 mmol/L). A regimen of aggressive urinary alkalinisation, as well as potassium supplementation, was commenced using IV sodium bicarbonate 2 mmol/kg/h and potassium chloride 5 mmol/h. During the next 12 hours, the metabolic acidaemia resolved: the elevated serum lactate and plasma ammonia levels normalised, and the patient became more interactive and responsive. The following day, detailed examination of the contents of the family’s home medicine cupboard revealed Bonjela teething gel (Reckitt Benckiser [8.7% choline salicylate]), which the family admitted to using on the infant’s gums frequently over the preceding 2 months. Based on an average application of two to three tubes of Bonjela (15 g per tube) per week over 2 months, it was estimated that he received about 60 mg/kg/day of choline salicylate. Urine alkalinisation with IV sodium bicarbonate was continued for a total of about 36 hours, during which the serum salicylate level fell to < 3 mg/dL (< 0.22 mmol/L) and all other biochemical parameters were within normal limits. Seventy-two hours later, he was discharged from hospital, with normal neurological examination results. Patient 2 A 13-month-old girl was referred to the hospital outpatients department with failure to thrive. She had a normal gestational and delivery history, and her initial growth parameters were on the third centiles for height and weight. When the infant was aged 9 months, her weight started to fall away from the third centile. She was said to have a good appetite and normal stools. Her parents denied she had a history of medication use. A clinical examination revealed a happy, active, non-dysmorphic girl. Results of initial investigations of her failure to thrive were normal (including serum levels of electrolytes, calcium, magnesium, phosphate, thyroid-stimulating hormone and thyroxine; liver function tests; serological tests for coeliac disease; full blood count and film; stool microscopy and examination for cysts, ova and pathogens; and karyotype analysis). The exception was an arterial blood gas test result, which showed a mixed metabolic acidosis and respiratory alkalosis (pH, 7.46; PaCO2, 25 mmHg; PaO2, 147 mmHg; HCO3, 13 mmol/L; BE, − 7) and mild hyperchloraemia (Cl, 110 mmol/L). Ammonia was slightly elevated at 67 mol/L. Urine spectroscopy surprisingly showed a high concentration of salicylate metabolites. On further questioning, the parents admitted to giving the child Bonjela gel for teething frequently over several months and, on occasion, to using up to a whole tube of Bonjela at night to settle her to sleep. The result of a quantitated blood salicylate test done 4 days after admission was 0.2 mmol/L. Traces of phenol were also found on the urine spectroscopy and a search of the family’s house revealed a phenol-based cleaning agent used daily in the house. The significance of this finding was uncertain. There were no other dermatological, gastrointestinal or central nervous system symptoms suggestive of chronic phenol exposure. Bonjela use was stopped, results of a repeat urine spectroscopy were clear, and subsequent levels of blood gases normal. The patient made a good recovery and her normal growth pattern resumed. Choline salicylate is a non-acetyl salicylate medicament. Compared with aspirin (acetylsalicylic acid), it has effective anti-inflammatory properties but less analgesic andantiplatelet action. The case of Patient 1 is a valuable reminder of the potential toxicity of chronic salicylate intake at dosages close to those recommended for over-the-counter teething gels (see following). Our accounts of both patients show the value of taking detailed medication histories for people presenting with unexplained intoxication. Medication histories should include patients’ exposure not only to prescribed or over-the-counter medications, but also topical, dermal or mucosal applications, and any complementary or alternative preparations. Checking contents of the home medicine cupboard may be necessary if further clarity is required. The account of Patient 2 graphically shows the potential for chronic salicylate intoxication to be subtle and difficult to diagnose. Since the late 1970s, chronic poisoning is the most frequently encountered form of salicylate intoxication.1 During chronic aspirin intake, major hepatic elimination pathways become saturated, extending the half-life of salicylate.2,3 Orally ingested salicylate usually has a serum half-life of 2–4 hours at low doses, and this may increase to as high as 12 hours when used at higher anti-inflammatory doses.4 For Patient 1, an elimination half-life of about 28 hours was estimated from serial retrospective measurement of salicylate levels over 18 hours before urine alkalinisation. Salicylates are metabolised more slowly in neonates than in those with mature liver function.5 The pathophysiology of chronic salicylate intoxication involves an uncoupling of oxidative phosphorylation and interference in carbohydrate, lipid and amino acid metabolism. The toxicities manifested by Patient 1 are attributable to these processes. He was initially hypoglycaemic, with documented elevation of serum lactate and pyruvate levels, as well as having evidence of secondary lipolysis and increased ketone body formation. Salicylates inhibit hepatic aminotransferases, which increases blood amino acid levels and can produce aminoaciduria.6 Salicylates also impair the urea cycle both indirectly, by inhibiting the respiratory chain, and directly, by suppressing production of ornithine transcarbamylase; these effects explain both patients’ hyperammonaemia.7 The clinical manifestations of salicylate intoxication are protean, with acute intoxication more commonly causing gastrointestinal symptoms, and chronic intoxication presenting with central nervous system symptoms.8 In children, neurological impairment, metabolic acidosis, and hypoglycaemia are common findings of chronic salicylate poisoning. These symptoms were all observed in Patient 1, and the classic combination of metabolic acidosis and respiratory alkalosis was present in Patient 2. Central nervous system disturbances include hyperventilation, agitation, tremor, altered behaviour, memory deficits and altered conscious state. Serum levels of salicylate between 1.1 and 2.2 mmol/L are considered therapeutic for treatment of inflammatory conditions; in acute intoxication, a level of more than 3.6 mmol/L is likely to indicate severe intoxication. Chronic salicylate intoxication occurs with lower serum concentrations because, over time, a larger amount of salicylate is distributed to tissues, such as those of the central nervous system. Therefore, in chronic intoxication, an initial serum salicylate concentration is of limited value.2 Mortality is much higher in chronic intoxication than a single ingested overdose.8 Early diagnosis and aggressive supportive treatment such as induced alkaline diuresis and haemodialysis are paramount in the management of symptomatic salicylate poisoning. Acidaemia enhances salicylate transfer into brain tissue. Alkalinising the serum raises the blood pH above that of the brain pH and shifts salicylate from tissues to the plasma. In addition, alkalinising the urine enhances renal excretion of salicylate.4 Lessons from practice Chronic salicylate intoxication in infants may be subtle but potentially life-threatening. Significant inadvertent salicylate poisoning from over-the-counter preparations can occur. All salicylate-containing products should have an appropriate warning label. Warnings are not present on packaging of several salicylate-containing teething gels that are marketed for infants in Australia and New Zealand. It is noteworthy that there is little evidence supporting the use of choline salicylate-containing gels to relieve the discomfort of teething. There is stronger support for other measures: paracetamol or ibuprofen for pain or fever; teething gels that contain local anaesthetic; and non-pharmacological options such as cold teething rings.9 Ours is not the first report of significant salicylate intoxication secondary to the application of teething gel containing choline salicylate.10-12 In 2002, the United Kingdom’s Commission on Human Medicines issued unequivocal advice that salicylate-containing products are contraindicated in children and young people under the age of 16 years except on specific medical advice.13 The Bonjela teething gel that is sold within the UK no longer contains salicylate — the analgesic component is now lignocaine, although the manufacturer continues to market salicylate-containing products for adults. As of April 2009, the Medicines and Healthcare Products Regulatory Agency in England had received three reports of adverse reactions in children associated with the use of topical oral gel containing choline salicylate.14 It is important to appreciate that dosing of this gel directly from the tube is potentially inaccurate, increasing its risks of causing chronic toxicity. The package labelling instructs the carer “to cover the tip of the index finger” with the gel and then apply it to the affected area up to a maximum of six times daily. Commentators have suggested that “... according to manufacturers’ recommendation of one application every 3 hours, one third of a tube could be utilised in 24 hours”.4 The mother of Patient 1 admitted using two to three 15 g tubes per week over a long period. This equates to twice the minimum daily dose reported to have caused toxicity following chronic ingestion.7 The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) states that salicylate intoxication by unintentional overdose of teething gel has been reported “on a number of occasions” to the NZ National Poisons Centre.15 In Australia, the Therapeutic Goods Administration regards teething gels as “therapeutic goods” and therefore, in our view, these gels should be subject to the requirement that labels of over-the-counter aspirin-containing products include a warning statement.16 Warnings are not present on packaging of several salicylate-containing teething gels that are marketed for infants in Australia and NZ. It is important that nurses, doctors, pharmacists and families are aware of the potential risk.

Gary D Williams MB BS, FRACP, FCICM · Edwin P Kirk MB BS, PhD, FRACP · Callum J Wilson MB ChB, FRACP · Caroline A Meadows BM BS, MRCP(Paeds), MRCPCH · Betty S Chan MB BS, PhD, FACEM

To the Editor: About 5% of Australians of Asian, African, Middle Eastern or Mediterranean descent have glucose-6-phosphate dehydrogenase (G6PD) deficiency.1 Affected babies can develop massive haemolysis within hours of exposure to clothes stored with mothballs containing naphthalene. It has long been known that this results in severe jaundice, which may lead to kernicterus2 and profound brain damage, for which the cost is either a lifetime of dependency and very expensive care, or death. We are aware of three cases of kernicterus in babies with G6PD deficiency in Australia in the past 3 years, one of which was associated with exposure to naphthalene in mothballs. One baby died. The exact incidence of severe neonatal jaundice and kernicterus in Australia is unknown, but it is the subject of an ongoing study funded by the Cerebral Palsy Foundation and coordinated through the Australian Paediatric Surveillance Unit. In Australia, packages of naphthalene mothballs must carry a warning that the product is harmful to children. However, clinical directors of neonatal units that comprise the Australian and New Zealand Neonatal Network have unanimously agreed that warning labels give insufficient protection. They have called on the Australian Pesticides and Veterinary Medicines Authority (APVMA) to act in harmony with the European Union, which banned the sale of mothballs containing naphthalene in 2008,3 following a report by the European Chemicals Bureau.4 The adverse risk–benefit ratio for naphthalene provides strong justification for its withdrawal. A submission to this effect has been lodged with the APVMA. Some mothballs contain paradichlorobenzene, a chemical related to naphthalene and associated with haemolysis. Less toxic products that protect clothes against moths exist. Department stores in the United Kingdom have replaced moth repellents containing naphthalene with products containing natural substances, such as sandalwood and lavender. Between 2004 and 2010, the New South Wales Poisons Information Centre reported that it received about one call per week concerning children exposed to naphthalene in moth repellents (Box). The Victorian Poisons Information Centre reported 53 calls in 2008.5 While acknowledging the importance of raising awareness of the dangers of naphthalene, we believe that the safest course is prevention — that is, an Australia-wide ban of mothballs containing naphthalene. Readers who wish to report cases of naphthalene toxicity are encouraged to contact APVMA at aerp@apvma.gov.au. Number of calls to the New South Wales Poisons Information Centre reporting children exposed to napthalene in moth repellents, 2004–2010 Year Number of calls 2004 55 2005 59 2006 65 2007 67 2008 73 2009 45 2010 71 Total (average) 435 (62) Source of data: Judith Kirby, Department Head, NSW Poisons Information Centre, personal communication.

on behalf of the Advisory Committee of the Australian and New Zealand Neonatal Network

The medical and psychosocial needs of children and adolescents differ from those of adults, and this should be reflected in the care they receive in all areas of a health service. Children and adolescents must be accommodated separately to adults to ensure that their unique needs are met and risks of harm are minimised. The Standards for the care of children and adolescents in health services have been developed by a working group of clinicians, health service providers and consumer advocates based on a combination of available research evidence, published best practice guidelines and multidisciplinary expert consensus. Stakeholder input was obtained through invitations to comment, and pilot testing of the Standards was conducted in six metropolitan, regional and rural hospitals. The Standards provide detailed recommendations in the areas of recognising rights; the provision of child-, adolescent- and family-friendly health service facilities; the availability of child- and adolescent-specific equipment; and the importance of appropriately trained staff. To facilitate implementation and allow ongoing performance monitoring, the Standards have been developed for use alongside the Australian Council on Healthcare Standards Evaluation and Quality Improvement Program. The Standards provide a vehicle to ensure patient safety and to facilitate the provision of high-quality care for children and adolescents in Australian health services.

Melissa K Hill BSc(Hons), PhD · Marjorie Pawsey MB BS, DPH · Anne Cutler MEd(Health) · Joanna L Holt BSc, MHP · Sharon R Goldfeld FRACP, FAFPHM, PhD

CorrectionOmitted acknowledgement: In “Twenty-five years of treatment for childhood acute lymphoblastic leukaemia in Western Australia: how do we compare?” in the 15 November 2010 issue of the Journal (Med J Aust 2010; 193: 585-589), it was not acknowledged that Professor M K Bulsara and Professor K Hird of the School of Medicine, University of Notre Dame, Fremantle, WA contributed to the design and analysis of the study. The html and pdf versions of this article were corrected on 12 Jan 2011.

Hannah Forward · Guicheng C Zheng · Catherine H Cole

Human infection with Rickettsia felis has been reported in most parts of the world, and R. felis has recently been confirmed in cat fleas in Western Australia. The clinical presentations of R. typhi and R. felis are similar, and in the past, the incidence of R. felis infection may have been underestimated. We describe the first reported cases of probable human R. felis infection in Australia. Two adults and three children in Victoria contracted a rickettsial disease after exposure to fleas from kittens. Molecular testing of fleas demonstrated the presence of R. felis but not R. typhi. Clinical recordsPatient B, a previously well 9-year-old girl, was admitted to a children’s hospital in Melbourne, Victoria, in April 2009 with severe abdominal pain, fevers to 39°C and a non-pruritic erythematous macular rash, initially present on the trunk and then spreading to the upper limbs and face (Box 1). The patient described a prodrome of 5 days of fever and malaise, with occasional vomiting and diarrhoea. She had been appropriately vaccinated, had no drug allergies, and did not regularly take any medication. On initial examination, the girl appeared unwell, with pitting oedema of the ankles and a generalised macular rash. There was no hepatosplenomegaly or significant lymphadenopathy. Initial laboratory test results indicated leukopenia (white blood cell count, 3.0 × 109/L [reference range (RR), 4.5–13.5 × 109/L]), lymphopenia (lymphocytes, 0.42 × 109/L [RR, 1.5–6.5 × 109/L]), thrombocytopenia (platelet count, 38 × 109/L [RR, 150–400 × 109/L]), hyponatraemia (Na+, 133 mmol/L [RR, 135–145 mmol/L]), hypoalbuminaemia (serum albumin, 19 g/L [RR, 33–47 g/L]), and elevated transaminase levels (aspartate aminotransferase, 168 IU/L [RR, < 55 IU/L]; alanine aminotransferase, 177 IU/L [RR, < 55 IU/L]). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Urine and blood cultures were ordered, as well as serological tests for a range of infectious diseases. The patient lived with her parents and two siblings in suburban Melbourne on a hobby farm next to a wooded reserve notable for stagnant water and mosquitoes. The family had many pets, including a dog, goat, ducks, budgerigars, mice and a domesticated rat. They had never travelled outside Australia, and had not recently had visitors from overseas. About 3 weeks before the onset of the illness, the family had acquired a pair of kittens (Cat 1 and Cat 2) from a farm in Lara, a rural suburb in Victoria, and had given Cat 2 to a neighbour. Patient B had ongoing persistent fever and severe abdominal pain. Her platelet count remained low, and her hepatic function, coagulopathy, hyponatraemia and hypoalbuminaemia worsened. On Day 3 of her admission, she developed pulmonary oedema and required a short stay in the intensive care unit, during which she received azithromycin, albumin and frusemide, as well as intensive supportive therapy and monitoring. She was given intravenous immunoglobulin (IVIG) 2 g/kg for possible Kawasaki disease but showed no response. Also on Day 3 of Patient B’s hospitalisation, her 8-year-old sister (Patient C) presented with fevers to 40°C, mild abdominal pain and a rash on her torso. On examination, she appeared to be well, but had florid facial flushing, a macular rash spreading to the limbs, tender cervical lymph nodes and a mildly tender abdomen. Patient C’s initial laboratory test results indicated mild leukopenia (white blood cell count, 4.5 × 109/L) and hyponatraemia (Na+, 132 mmol/L). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Over 48 hours she became thrombocytopenic (platelet count, 77 × 109/L), with worsening abdominal pain and hyponatraemia (Na+, 132 mmol/L), and elevated alanine aminotransferase (75 IU/L). She was given IVIG 2 g/kg for possible Kawasaki disease. Her condition improved rapidly. On Day 7 of Patient B’s hospitalisation, Patient D, the girls’ 4-year-old brother, presented with a fever of 39.6°C and five erythematous macules on his legs and trunk. He was otherwise well. Laboratory test results for Patient D showed leukopenia (white blood cell count, 4.0 × 109/L), with no other abnormalities. He was admitted for observation without treatment. The three siblings were discharged home on Day 11 of Patient B’s hospitalisation, without definitive diagnoses. Patients C and D had episodes of fever for 1 week, but remained well otherwise. A phone review on Day 18 found that the three children were well and afebrile. However, their maternal grandmother (Patient E) had had 3 days of fever and rigors and had been admitted to another hospital for observation. On advice from the children’s doctor, Patient E’s treating doctor administered doxycyline and her condition subsequently improved. It was also discovered that the neighbour who had been given Cat 2 (Patient A) had become unwell 2 days before Patient B, with a non-specific febrile illness that had settled by the time Patient B was admitted to hospital. She was therefore the initial case in the cluster. All patients had had extensive close contact with one or both of the cats. The children’s parents had minimal contact with the cats and were asymptomatic. The family reported that both cats had flea (Ctenocephalides felis) infestations when they acquired them. Cat 1 no longer had fleas after having been treated topically with insecticide, but its serum was tested for typhus-group rickettsial species. Because it was unwell, Cat 2 had been euthanased before blood samples could be taken. As collecting fleas from the two kittens was not possible, fleas from other cats of the group into which they were born, including the kittens’ mother, were collected for molecular analysis to identify any rickettsial species they carried. Serological testing was performed using indirect microimmunofluorescence assay (IFA).1,2 Initial serological analysis (in April 2009) for the presence of both spotted-fever-group and typhus-group rickettsial antibodies was undertaken on Patients B and C. The results showed the presence of typhus-group but not spotted-fever-group rickettsial antibodies. A month later (May 2009), serological testing was repeated for Patients B and C, and initial testing was done for Patients D, E and A. The tests showed rising typhus-group rickettsial antibody titres in patients B, C and E and high titres in patients A and D. In addition, Patient C showed clear evidence of seroconversion (Box 2), while both parents were negative for rickettsial antibodies. Serological testing undertaken on Cat 1 also showed the presence of typhus-group rickettsial antibodies (Box 2). DNA was extracted from the serum of Patient C (buffy coat [white cell layer] was not available), and Cat 1, and from pooled and crushed cat fleas that were collected from cats in the group that Cat 1 and Cat 2 had come from. A rickettsial real-time polymerase chain reaction (PCR) test was performed on the extracted DNA samples.3 The fleas, but not the patient’s or cat’s serum, were positive for rickettsial DNA. A 1077 base-pair fragment of the rickettsial citrate synthase gene was amplified and sequenced.4 This sequence was compared with the validated rickettsial species5 and showed closest phylogenetic similarity to Rickettsia felis, with a sequence similarity of 99.7% (1074/1077 base pairs). Rickettsia typhi DNA was not detected in the cat fleas. The citrate synthase gene (gltA) sequence analysis using the neighbour-joining algorithm is shown in Box 3. DiscussionThe five patients described here are the first reported cases of probable human R. felis infection in Australia, and the analyses provide the first molecular evidence of R. felis in cat fleas in Victoria. It has been previously detected in cat and dog fleas in Western Australia by molecular analysis.6 Human infection with R. felis has been reported in most other parts of the world.7-10 While genetically a member of the spotted-fever rickettsia group, R. felis behaves clinically and serologically like a typhus-group rickettsia and is transmitted by fleas. Antibodies induced by R. felis react with typhus-group rickettsiae in serological tests, rather than with spotted-fever-group rickettsiae. A petechial rash is an infrequent sign of infection, and a macular or maculopapular rash is present in only 50% of patients (Box 1). The high attack rate and severity of infection noted in this cluster may be due to the heavy flea infestation that was reported. Resolution without therapy is well described in rickettsial infection. Only two patients (B and C) received antimicrobial therapy with known activity against rickettsial species. The five patients showed a strong positive result for the presence of typhus-group antibodies. Patient C’s clear seroconversion was consistent with recent acute R. felis or R. typhi infection.7 While exposure to either R. felis or R. typhi could have led to Cat 1 producing typhus-group antibodies, only R. felis DNA was detected in the cat fleas. It is common for blood from cats infected with R. felis to be negative for rickettsial DNA,8 as in this case. Cat 1 still had antibodies to R. felis but either had cleared the infection, or the organism was present in tissues other than peripheral blood. In a previous experimental exposure of cats to R. felis-positive fleas, 13 of 16 cats were positive by serological testing using IFA, but only five of the 16 were positive by PCR.11 The human cases reported in this study were only identified serologically, and as the clinical presentations of R. typhi and R. felis are similar, R. typhi cannot be completely ruled out as the causative agent. However, given the molecular data from the cat fleas, R. felis is the more likely causative agent. In the past, the incidence of R. felis infection in patients with raised typhus group antibody levels may have been underestimated, with the causative agent probably reported as R. typhi when it may have been R. felis — a confusion that has been seen in other studies.8,9 1 Widespread erythematous macular rash, Patient B 2 Serology results of five seropositive patients and a cat exposed to rickettsial infection, 2009 Patient/ cat Sex, age in years Day of onset* Status in family Rickettsia group Serum antibody titre April May June A F, 63 − 2 Neighbour SFG nd < 1/128 nd TG nd 1/16 384 nd B F, 9 1 Child SFG 1/128 1/128 nd TG 1/1024 1/8192 nd C F, 8 3 Child SFG 1/128 1/256 nd TG < 1/128 1/16 384 nd D M, 4 7 Child SFG nd 1/128 nd TG nd 1/16 384 nd E F, 59 15 Grandmother SFG nd < 1/128 < 1/128 TG nd 1/1024 1/2048 Cat 1 F, < 1 na Pet SFG nd nd < 1/128 TG nd nd 1/512 na = not applicable. nd = not done. SFG = spotted-fever group (ie, Rickettsia australis and R. honei). TG = typhus group (ie, R. prowazekii and R. typhi). * Compared with Patient B’s admission (Day 1). 3 Condensed phylogenetic tree comparing the DNA fragment sequenced in this analysis (“Rickettsia felis [Lara]”) with validated rickettsial species Relationship of a 1077 base-pair fragment of the gltA gene of Rickettsia felis (Lara) among other validated rickettsial species, with the core spotted-fever-group rickettsiae truncated. The tree was prepared using the neighbour-joining algorithm.* Bootstrap values are indicated at each node. The scale bar represents a 2% nucleotide divergence. * Molecular Evolutionary Genetics Analysis (MEGA) software, version 4.0, 2007 [free internet download].

Molly Williams MB BS · Leonard Izzard BSc, PhD · Stephen R Graves MB BS, PhD, FRCPA · John Stenos BSc, PhD · Julian J Kelly MB BS, FRACP

To the Editor: We would like to report the deaths of three young children in Australia as a result of hanging from bicycle helmets. Our aim is to draw attention to this rare but entirely preventable cause of childhood death. Helmets are required to be worn when bicycles are ridden, and have been the subject of mandatory standards since 1989.1 A number of accidental deaths have, however, been reported in the United States, Scandinavia and Canada as a result of young children becoming suspended by their bicycle helmets while playing on playground equipment. This has led to a series of warnings about not allowing children to wear helmets in playgrounds.2,3 The National Coroners Information System (NCIS)4 is an electronic database containing information on coronial cases from all Australian states and territories since 2001. We undertook a review of the NCIS for all deaths of children in Australia that were associated with bicycle helmets from 2001 to 2009. Three cases of deaths due to hanging were identified; these involved a 2-year-old boy who was suspended by his helmet strap between a bunk bed and a wall (in 2003), a 3-year-old boy who was suspended by his helmet strap when he tried to climb out of a home window (in 2007), and a 5-year-old boy who was suspended from an overhead clothesline while jumping on a trampoline (in 2009). These cases show that accidental hanging is still occurring among young children who wear bicycle helmets while engaging in activities other than bicycle riding. Importantly, hanging from bicycle helmets can occur in places other than playgrounds, sometimes by quite unusual mechanisms. Although such deaths are rare,5 it is important for parents and child carers to ensure that bicycle helmets are only worn by children for their intended purpose, and not during other activities.

Roger W Byard · Allan Cala · Donald Ritchey · Noel Woodford

“Child deaths are falling, but not quickly enough to reach the target.” “Most maternal deaths could be avoided.” The Millennium Development Goals Report, 20101 “Where we are now in terms of health service delivery should be measured against where we have come from and not where we ideally should be. A lot of progress has been made.” Mary L Nannono, Permanent Secretary at Uganda’s Ministry of Health, 20082 The Millennium Development Goals (MDGs) report published in June 20101 shows that the targets to reduce maternal and child deaths will not be met, particularly in sub-Saharan Africa. Uganda is an east African country committed to achieving MDG 4 (the goal to improve child survival) and MDG 5 (the goal to improve maternal health). In recent years, there has been much work to improve Ugandan antenatal and neonatal care, scaling up emergency obstetric care services and child health policies. However, progress remains slow and, at current standards, Uganda is unlikely to attain the MDG 4 and 5 objectives (Box).3 Why has there been insufficient progress? What happens when mothers and children come to hospital? I am an Australian doctor training in paediatrics under the Royal Australasian College of Physicians. I also intend to train in anaesthesia. I decided to take a year-long break from the training scheme to do humanitarian aid work in a developing country, and I am now coming to the end of a 6-month sabbatical in Uganda. This personal perspective on paediatric and obstetric care provision in Uganda aims to illustrate some of the stumbling blocks in practice that are limiting progress towards the MDGs in maternal and child health. My time in Uganda was divided between the obstetric operating theatre of the National Referral Hospital in Kampala, and responsibility for a paediatric ward in rural Uganda at a not-for-profit mission hospital, run jointly by the local Catholic diocese and an international non-government organisation. Every morning on arrival at the obstetric theatre I was greeted by women waiting, lining up in the entrance hall or lying on plastic sheets on the floor of the ward, contracting in pain. All needed emergency caesarean sections. However, each woman waited in turn for her operation or spontaneous delivery, whichever came first. When her turn came, the patient would walk into theatre and struggle onto the operating table with minimal assistance, pausing only for a grunt or grimace during a contraction. My first day at the Kampala hospital theatre was particularly disappointing — six emergency caesarean sections resulted in two fresh stillbirths, one macerated stillbirth and two admissions to the special-care baby unit. We hand-ventilated one baby for an hour because there was no mechanical ventilator. Later that afternoon, the baby stabilised on continuous positive airway pressure, but died overnight. My colleagues and I decided to undertake a 1-month audit to review maternal and neonatal outcomes: were there avoidable delays for emergency caesarean sections, and could anything be done about them? The maternal mortality rate in my sample of 435 was 1%, the stillbirth rate was close to 7% (equivalent to the hospital’s 1968 rates14) and mothers waited on average for 5 hours for the emergency procedure. Reasons for delays included staff unavailability, a lack of running water, a non-functional autoclave (and hence no sterile drapes and gowns), and no spinal needles or drugs for spinal anaesthesia. As a result of the audit, the hospital expedited the building of two new obstetric and gynaecological operating theatres and undertook to ensure that highly qualified and experienced staff ran them. Mothers are advised to bring a delivery pack when they come to hospital — not a dressing gown, slippers and baby clothes, but their own cannulae, sterile swabs, suture materials and 10 packets of sterile gloves, in case the hospital supply runs out. During my second week, a woman in her seventh pregnancy joined the section queue. Her indication for surgery was obstructed labour at 38 weeks gestation, with a “poor obstetric history” that translated as six previous stillbirths. She waited patiently in line but when it was her turn there were no gloves in stock and she had brought only one packet. She waited while women with gloves had their procedures. Her blank emotionless expression when the surgeons told her over the drapes that her baby was stillborn will remain with me forever. How can this hospital function as a comprehensive emergency obstetric care provider when caesarean section priority relates to the number of gloves the patient can supply rather than the underlying urgency of surgery? My responsibility for a 23-bed children’s ward (often with two to three patients per bed) in rural Uganda also brought me many challenges. At this hospital, one difficult day started with a mother in obstructed labour who delivered her baby with shoulder dystocia. During our attempt to resuscitate the baby, there was a power failure and, as there was no fuel for the back-up generator, the oxygen concentrator did not work. The oxygen cylinders were empty, so there was no oxygen in the hospital. Sadly, we were unable to save the baby. The same day, a 4-day-old twin died of jaundice because our phototherapy machine was broken and the parents could not afford to travel to another hospital. Then the mother decided to discharge herself from hospital with her surviving twin, also jaundiced and on intravenous antibiotics, and consult a traditional healer. I remember a 3-year-old patient referred from a larger regional centre to our rural hospital for a blood transfusion because there was “no blood available”. The child’s haemoglobin level was 2 g/dL and she was in severe respiratory distress. I was confused by the cross-match form and unit number noted in her case notes, yet the clearly documented reason for transfer was “no blood available”. The mother reported that, while she and her daughter were at the regional centre, another child, as sick as her own, had arrived whose need for the blood, already crossed-matched for our patient, was decided to be the more urgent because his or her mother could contribute money. As health care practitioners, we make decisions that are generally evidence based and (hopefully) in the patient’s best interests. A premature neonate, with a gestational age of 27 weeks, had been labelled a “fighter” after surviving 3 days on only a whiff of oxygen. This was going to be a success story for Africa — the survival of a premature baby. One night, a 6-month-old boy presented in severe respiratory distress when the oxygen concentrator was away being repaired and the only oxygen cylinder that wasn’t empty (it was one-quarter full) was with the fighter, who hadn’t tolerated a trial on room air. Reluctant to take oxygen away from her, I told the mother of the boy that I had done all I could. He died 3 hours later and I could hear the mother wailing from my room. The next day, the condition of the fighter on oxygen therapy suddenly deteriorated and I was unable to revive her. Had I made the wrong decision? Hindsight is a torment for one’s conscience. However, the oxygen dilemma prompted us to adapt the oxygen tubing so that two children could receive low-flow oxygen at the same time. When I received my first Ugandan arrest call, I ran to the bedside. Almost 5 minutes after I arrived, the suction and some monitoring equipment appeared. Oxygen was not available until later and we also had to wait for resuscitation drugs. The outcome was poor, both for the patient and my confidence. After my third resuscitation call, I didn’t run any more. I walked “mpola mpola” (slowly, slowly) with the rest of the team — arrests are difficult to manage without basic equipment, and usually fatal because of delayed treatment. So far I have painted a somewhat bleak picture, but there were good days and successes. A 6-week-old girl was brought in severely malnourished, weighing 2 kg with sepsis and malaria. The good Samaritan who had picked her up as a newborn from the roadside after the mother abandoned her was feeding her cow’s milk. After antibiotics, antimalarials and commencing our formula feeding program, the child gained weight and even started to smile. Also heartening, and something that has constantly amazed me, is the resilience and good humour of the staff, who do their best with what is available. However, when I read in the local newspaper that the World Health Organization’s Making Pregnancy Safer program is to be extended, and more mothers will be encouraged to give birth in hospital, I remember all the critical events that I have witnessed. Surely this advice will not lead to improved outcomes while there is such a disparity between demand and supply, between concept and reality. Reliable running water and electricity; hospital supplies like basic disposables, oxygen, and blood for transfusion; and adequate staffing and staff training are essential requirements for emergency obstetric and paediatric care. My story highlights that if basic hospital facilities were improved and some systemic delivery deficiencies overcome, more progress towards the MDGs 4 and 5 in Uganda and all of sub-Saharan Africa would be made. Ensuring that 90 per cent of African mothers and newborns have access to the essential interventions already written into policy would cost a very affordable US$1.39 per capita.15 What are the Millennium Development Goals for maternal and child health and where does Uganda stand in achieving them? Millennium Development Goal (MDG) 4 aspires to a global target of a two-third reduction by 2015 in the mortality rate of children aged under 5 years. For Uganda, this means a decrease to below 56 deaths per 1000 live births; however, the rate only declined from 186 to 135 deaths per 1000 live births during the period 1990 to 2008.4 Globally, neonatal mortality accounts for 38 per cent of deaths in children aged under 5 years; hence, a substantial reduction in neonatal deaths is necessary if this goal is to be attained.5 A 2006 Ugandan survey reported a perinatal mortality rate (comprising the stillbirth rate and early neonatal mortality rate) of 36.3 per 1000 pregnancies.6 This amounts to 44 500 newborns dying and 45 100 stillborn babies each year.7 Childbirth is the time of greatest lifetime risk of mortality for a mother and her baby. Intrapartum complications account for an estimated 42% of the world’s 358 000 annual maternal mortality rate (MMR). Sub-Saharan Africa contributes 57% to the world’s annual MMR.8 The first target of MDG 5 is to reduce the MMR by three-quarters before 2015, equivalent to a reduction to 131 deaths per 100 000 live births in Uganda — the estimated MMR is currently 435 deaths per 100 000 live births.9 A 2005 study estimated the MMR at 645 deaths per 100 000 live births at the National Referral Hospital, my workplace.10 Many obstetric and newborn complications can be prevented or successfully managed with prompt interventions. The Lancet Newborn Survival Series demonstrated that skilled clinical care could effect a reduction in neonatal mortality rates of up to 72 per cent.11 Timely identification and management of childbirth complications is paramount, and while more mothers and newborns die during this period than at any other, coverage and quality of care often remains inadequate in resource-limited settings.12 It is also important to note that with gross under-reporting (deaths at home or en route to hospital are often not recorded), the true figures are undoubtedly substantially higher. However, Uganda’s slow progress towards MDGs 4 and 5 has put the spotlight firmly on maternal and child health delivery. The government has responded by developing a national roadmap to accelerate the reduction of maternal and child mortality and morbidity. It has been placed high on the political agenda and, with the country’s upcoming elections in February 2011, all major political parties in the country are promising to make maternal and child health a priority. In addition, the World Bank in May 2010 released a new 5-year action plan to help poor countries reduce their maternal and child deaths. Uganda is one of the sub-Saharan African countries targeted. There is hope that, with time, Uganda will achieve the aim of the United Nations 2009 global consensus on maternal, newborn and child health: to have “every pregnancy wanted, every birth safe and every newborn and child healthy”.13 “All needed an emergency caesarean section. However, each woman waited in turn for her operation or spontaneous delivery, whichever came first.” “My responsibility for a 23-bed children’s ward (often with two to three patients per bed) in rural Uganda also brought me many challenges.” Communication, Ugandan style!

Katie M Moynihan MB BS, DCH

The ethics of pediatric research. David S Wendler. Oxford: Oxford University Press, 2010 (337 pp). ISBN 9780199730087. AS HEAD of the Unit on Vulnerable Populations, Department of Bioethics, NIH Clinical Center, in the United States, David Wendler continues to contribute to the rich debate on issues surrounding ethical research involving vulnerable populations, including children, who cannot give informed consent. This particular work was written while Wendler was a Faculty Fellow in Ethics at the Safra Center for Ethics at Harvard University, and is the result of over 10 years of research. A balanced and engaging analysis of the justifications for the ethical acceptability of non-beneficial paediatric research is critical, if we are to undertake ethically sound translational research in vulnerable populations to improve medical care. Scholars in clinical research ethics and, potentially, clinicians engaged in paediatric research should find this book of interest and value. Each well structured chapter includes brief summaries of the arguments presented in the chapters immediately preceding and succeeding it. Wendler is particularly helpful when he explores the ways in which concepts such as “social value”, “human interests and causes”, “wellbeing” and a “better life” influence the moral status of non-beneficial paediatric research. Additional diligence is called for by all parties where substitute consent is required. This topic could have received further critique as part of the two insightful and extended chapters on the contributions of participants. Acknowledging the shared responsibilities of clinicians, researchers, substitute decisionmakers, bioethicists, human research ethics committee members, regulators and publishers in ensuring good clinical research practice is essential for a sound examination of key issues. The book is relevant to an Australian audience, with reference to comparative regulatory frameworks here, the US, Canada and elsewhere. The book is well within reach of most budgets and would be a worthwhile addition to medical and social science libraries.

Jennifer M Fleming

Objectives: To compare survival among the subgroup of children with acute lymphoblastic leukaemia (ALL) who were treated at Princess Margaret Hospital for Children (PMH) in Perth, Western Australia, over 25 years under 15 consecutive protocols of the Children’s Cancer Group (CCG) with survival for the entire cohort of children in multiple centres treated under CCG protocols in that period; and to highlight the benefits of membership of a large cooperative research group conducting multicentre randomised controlled trials.Design, participants and setting: Retrospective review of the outcomes of all 311 children with newly diagnosed ALL treated at PMH between 1983 and 2008.Main outcome measures: 4-year event-free survival; and 10-year overall survival.Results: Four-year event-free survival for the entire PMH cohort increased from 66% (SE, 6%) for 1983–1987 to 88% (SE, 6%) for 2002–2005, while overall survival over the same period improved from 78% (SE, 5%) to 94% (SE, 4%). Comparisons of outcomes of children treated at PMH with those of the entire CCG cohort, protocol by protocol, revealed similar outcomes.Conclusion: Outcomes of children treated at PMH over the 25-year period are equivalent to those of the larger CCG cohort.

Hannah Forward MB BS(Hons) · Guicheng C Zheng PhD · Catherine H Cole MB BS, FRACP, FRCPA

We report the first Australian case of treatment of infant botulism with a human botulinum antitoxin developed in the United States by the California Department of Public Health. Our patient’s clinical improvement was rapid, and although the product is expensive, cost-analysis supports the economical viability of its use. In future cases of suspected infant botulism, we recommend that Australian clinicians promptly obtain and administer this antitoxin to their patient. Clinical recordA 5-month-old girl who was fully breastfed presented to the emergency department at a tertiary children’s hospital with poor feeding and lethargy. She was afebrile and mildly dehydrated, with a poor suck and a weak cry. Laboratory testing revealed a normal full blood examination and mild derangement of electrolytes consistent with dehydration. Blood cultures were sterile, and cerebrospinal fluid examination was normal. Formal neurological examination revealed bilateral ptosis, low muscle tone, globally reduced muscle strength and no gag reflex. Deep tendon reflexes were absent, and pupillary reflexes were preserved. Nerve conduction velocities and electromyography were normal. Further history revealed no recent ingestion of honey and no passage of bowel motions for 10 days. She had not received oral polio vaccine and had no history of overseas travel. The patient was transferred to the hospital’s paediatric intensive care unit (PICU), where we established a working diagnosis of infant botulism, pending confirmatory investigations. The patient was electively intubated and ventilated on Day 3 of her hospital admission. Faecal fluid was obtained per rectum for a mouse toxin bioassay. We telephoned the California Department of Public Health’s Infant Botulism Treatment and Prevention Program (IBTPP) in the United States to purchase BabyBIG (botulism immune globulin [intravenous human]) (Massachusetts Public Health Biologic Laboratories and Cangene Corporation, Boston, Mass, USA), which we received 48 hours later. A single infusion of BabyBIG was administered on Day 7 of the child’s admission to hospital, with no adverse consequences. The product cost US$43 500. The diagnosis of infant botulism was confirmed by the mouse bioassay, with growth of toxin B-producing Clostridium botulinum from faeces. The child was extubated on Day 10 of her PICU admission, discharged from the PICU on Day 16, and discharged home on full enteral feeds on Day 24. Follow-up physiotherapy showed gross motor delay with postural weakness, which had resolved by 2 months after discharge. DiscussionThis is the first case of infant botulism in Australia in which BabyBIG has been used (personal communication, Dr Stephen Arnon, Chief, IBTPP, California Department of Public Health, 21 March 2009). While an uncommon disease, Australia has had about one case per year since 1999.1 Infant botulism arises from ingestion of C. botulinum spores and growth of the organism in the gastrointestinal tract, producing botulinum toxin, which binds irreversibly to receptors at the neuromuscular junction, producing flaccid paralysis. Ingestion of honey is a classic risk factor, although frequently no specific source of the infection is found. Intensive supportive care is required until muscular function recovers — a process which takes weeks to months, usually with extended hospitalisation and artificial ventilation. BabyBIG was developed by the California Department of Public Health and registered with the US Food and Drug Administration (FDA).2 The product is derived from serum donations from individuals immunised with pentavalent botulinum toxoid, a vaccine developed by the US military. Purification and preparation of the product is in line with FDA licensing requirements for processing human plasma, including screening of donors and testing plasma for transmissible diseases. The product comes as a lyophilised powder of immunoglobulin G, stabilised with 5% sucrose and 1% human albumin, and contains neutralising antibodies against botulinum toxins A and B. The product has a half-life of about 28 days, and a single infusion is calculated to neutralise all absorbed botulinum toxin for at least 6 months. BabyBIG was initially assessed in a randomised, double-blind, placebo-controlled trial conducted between 1993 and 1997.3 The trial involved 129 Californian infants with botulism, treated on Days 0–3 of hospital admission, and showed significant decreases in duration of ventilation (by 2.6 weeks [P = 0.01]), length of PICU stay (by 3.2 weeks [P < 0.001]), length of hospital stay (from 5.7 weeks down to 2.6 weeks, [P < 0.001]), and mean hospital costs per patient (of US$88 600 [P < 0.0001]). Subsequent open-label, US-wide use of the product on 382 infants showed similar results in the 366 infants who received BabyBIG within 7 days of admission.3 The product was initially only available to infants in North America, but since 2003 has been exported internationally on a case-by-case basis. A subsequent review has shown that only 5% (32) of 681 cases treated with BabyBIG since 2003 have been misdiagnoses, with no adverse events occurring as a consequence of the infusion in any infants.4 Although the cost of the treatment is substantial, evidence has shown the intervention to be economically sound. In our case, a conservative estimate of costs saved just from reduced requirement for intensive care ranged from A$28 000 to A$117 600, based on an estimate of A$4000 per intensive care day. The social and emotional benefits of early discharge and recovery to the child and her family are obvious. In cases of suspected infant botulism, we recommend that Australian intensive care physicians and paediatricians promptly obtain and administer BabyBIG to their patient. All experience to date encourages pre-emptive treatment without waiting for confirmation by diagnostic testing. Despite long distances in sourcing the product, with good communication, this process can provide a timely, safe, effective and cost-saving treatment for infant botulism.

Meryta L A May MB BS, FRACP, FRCPA · Michael A Corkeron MB BS, FANZCA, FCICM · Mark Stretton MB BS, FRACP

Passive surveillance cannot be relied on as the sole means of surveillance On 22 April 2010, use of seasonal trivalent influenza vaccine in children aged 5 years and under was suspended across Australia, pending an investigation into an apparent increase in reports of adverse events following immunisation (AEFI).1 This unprecedented halt to a national immunisation initiative followed Western Australia’s decision to place a moratorium on the use of this vaccine in young children after observing a spike in emergency department presentations for high fever and febrile convulsions after vaccination.2 A subsequent investigation by the Therapeutic Goods Administration indicated that febrile convulsions related to the vaccine were reported from all jurisdictions except the Northern Territory.2 The apparent rate of febrile convulsions following vaccination was 5–9 per 1000 doses administered, about 50 times higher than that reported following measles–mumps–rubella vaccination.2,3 A recent review, requested by the Minister for Health in WA, has highlighted significant deficiencies in AEFI surveillance.4 In Australia, the current mechanism for identifying AEFI nationally is passive surveillance. Passive surveillance relies on health providers and the public recognising and reporting suspected AEFI to state or federal health authorities. The constraints that are inherent to passive surveillance, including under-reporting and biased reporting, are compounded by the diverse approaches to surveillance that are employed throughout Australia, as illustrated by a fourfold difference in AEFI reporting rates per 100 000 population between jurisdictions.5,6 Adding to concerns about variable sensitivity across the state systems is the inevitable delay in collection, aggregation and analysis of AEFI reports forwarded to the national authority. A number of the issues evident during the response to the vaccine-associated reactions were recognised 5 years earlier during the National Vaccine Safety Workshop.7 A clear set of recommendations for improving adverse event surveillance was identified at the time, but many of the recommendations have not been adequately addressed. Robust postmarketing surveillance is vital for influenza vaccines because seasonal trivalent influenza vaccine does not require clinical trial data to demonstrate safety before release — it is assumed that safety is not altered by the annual change in the combination of vaccine strains. While past experience suggests that this is true, history also indicates that future vaccine scares are inevitable and we should plan accordingly.8 Trivalent influenza vaccine, in particular, highlights the need for postmarketing surveillance to be linked with the capacity for rapid review and response, because a large proportion of the vaccine is administered over a short period before the onset of the influenza season each year. The way forward is to establish a coordinated, uniform approach to AEFI reporting, coding, collation and analysis. A standing vaccine safety monitoring group which includes key stakeholders — representing the regulators, state and national immunisation programs and vaccine safety and epidemiology experts — needs to be urgently established. The inability of the existing surveillance systems to detect the early signal of an increased incidence of febrile convulsions, within 24 hours of receiving 2010 seasonal trivalent influenza vaccine, demonstrates that passive surveillance cannot be relied on as the sole means of surveillance. Complementary active surveillance systems which can methodically detect potential AEFI signals, quickly establish rates and establish causality should be developed. The Australian Childhood Immunisation Register is uniquely placed to contribute to vaccine safety surveillance through data linkage with hospital morbidity and emergency department datasets, as demonstrated by a recent study from South Australia.3 Sentinel surveillance in four tertiary care Australian paediatric hospitals has been shown to be an effective mechanism of surveillance for specific AEFI.9 Implementing active AEFI surveillance systems will require sustainable funding, but this will be a small fraction of the cost expended on vaccines and vaccine delivery and could be resourced by levying a surcharge per vaccine dose sold, similar to methods adopted elsewhere to support compensation for vaccine-associated injuries.10 Central to any system of vaccine safety monitoring are issues of governance; specifically, transparency in decision making. Other countries currently provide full disclosure and web access to de-identified AEFI reports and open access to the deliberations of expert committees.11,12 This engenders public trust in immunisation programs, and similar strategies should be considered in Australia. The vast majority of Australian parents, vaccine recipients and health care providers trust public health authorities to assess and monitor vaccine safety. This is critical to ensure that the benefits of vaccination outweigh any potential risks. In the aftermath of the 2010 seasonal trivalent influenza vaccine experience, maintaining the public’s trust requires that we get started on building the fully functional, standard-of-care AEFI surveillance system that Australia deserves. Vaccine safety should be an integral component of the National Immunisation Strategy, which should include strategies for comprehensive and complementary passive and active systems of surveillance.

Michael S Gold MB ChB, MD, FRACP · Paul Effler MD, MPH · Heath Kelly BSc, MB BS, MPH · Peter C Richmond MB BS, MRCP, FRACP · Jim P Buttery MB BS, FRACP, MSc