Improving the health of First Nations children in Australia

Regular monitoring and supportive federal and state public policy are critical to closing the gap in child health

Health and wellbeing of children and young people are the keys to human capability of future generations. Human capability includes the capacity to participate in economic, social and civil activities and be a valued contributor to society;1 it means that not only can you usefully live, work and vote, but you can be a good parent to your children. Thus there is no better investment that the state can make than to influence factors that will enhance the health and wellbeing of children and youth.

There were an estimated 200 245 First Nations2 children aged 0–14 years in Australia in 2011, comprising 4.9% of the total child population and 35% of the total First Nations population.3 With such a high proportion of children compared with the non-Aboriginal population, the First Nations population is much younger, with fewer adults per child to care for them. An Australian Research Alliance for Children and Youth report adds to evidence from the most recent Australian Institute of Health and Welfare report on the health of Australia’s children to document the growing divide between the health of First Nations and other Australian children.3,4

Child health indicators include mortality rates (Box, A), prevalence of chronic conditions, indicators of early development (including rates of dental decay [Box, B]), promotion of early learning (eg, adults reading to children in preschool years) and school readiness assessed with the Australian Early Development Index (Box, C).3 Risk factors for poor child health include: teenage pregnancies; smoking and alcohol exposure during pregnancy; pregnancy outcomes such as stillbirths, low birthweight and preterm births; the proportion of children aged 5–14 years who are overweight or obese; and the proportion of children aged 12–15 years who are current smokers. In addition, indicators of the level of safety and security of children — including rates of accidental injury, substantiated reports of child abuse and neglect, evidence of children as victims of violence, and indicators of homelessness and crime — further highlight how poorly Aboriginal children fare during childhood.

Owing to significant gaps in available data, Australia is not included in UNICEF reports relevant to First Nations children, including The children left behind: a league table of inequality in child well-being in the world’s rich countries.5 This report is important for many First Nations children who experience conditions near the bottom because it focuses on closing the gap between the bottom and the middle:

We should focus on closing the gap between the bottom and the middle not because that is the easy thing to do, but because focusing on those who do not have the chance of a good life is the most important thing to do.5

While there has been progress, particularly in educational outcomes, the gap in healthy child development in safe and secure environments is disturbing. It has resulted from of a variety of complex social circumstances, due to colonisation, marginalisation and forced removals. To effectively and successfully interrupt and reverse these generational traumas on today’s children, careful and sensitive First Nations-led programs are required. Programs in Canada and Australia have shown that the major protective and healing effects of strong culture are immensely powerful, even in urban situations, which highlights the value of strong government support for such programs in Australia. For example, putting First Nations children and youth into cultural programs is more effective than incarceration for preventing recidivism, and increased recognition of Aboriginal cultures in school curricula increases rates of high school completion by First Nations students.6

Drawing on our own and overseas data,7 we believe that Australian services have failed to close the gap in child health because they have been developed without involving or engaging First Nations people. When participatory action research methods are used, as has been done with Inuit communities in Nunavut in Canada,8 the use and success of services are dramatic. Such strategies lead to higher levels of local employment, higher self-esteem, and reduced mental illness and substance misuse among First Nations people. British Columbian data on First Nations youth suicide rates have shown that the lowest rates in Canada were in communities with strong culture and Aboriginal control of services (eg, health, education and community safety).9 This means that a major rethink of services for First Nations people is needed, and that centralised policy applied to multiple diverse communities is unlikely to work. Although the policy content of what needs to be done can be developed centrally based on existing evidence (eg, alcohol in pregnancy causes brain damage, early childhood environments are vital to help children to be ready for school, complete immunisation prevents infections, and avoiding sweet drinks prevents obesity and dental decay), development and implementation of services need to be done locally and with community involvement. A great example of this is the strategy to overcome fetal alcohol spectrum disorders (FASD) that was developed by Aboriginal women June Oscar and Emily Carter and the First Nations people of Fitzroy Valley. This comprehensive and effective strategy has enabled the community to think and act beyond the stigma of FASD — community members drove the design and implementation of programs to prevent FASD, and they created opportunities and support mechanisms to enable the best possible treatment for children with FASD.10

Building on the Australian Research Alliance for Children and Youth report,4 we need a consistent national framework for monitoring health status and an understanding of the impact of federal and state policies on First Nations children. Recent policies with the potential to affect First Nations children include: the Northern Territory intervention, the loosening of alcohol restrictions in the Northern Territory, policies aimed at addressing overrepresentation of Aboriginal children in child protection reporting, housing policies (including evictions and the transfer of public housing properties to ownership and management by non-government organisations), policies that have changed financial support for single parents, education policies aimed at assessing school readiness and other policies aimed at closing the gap in health. The effects of these policies on First Nations children need to be considered in regular assessments of public policy, with the needs of children prioritised over competing interests.

The exciting thing is that we now have a growing number of Aboriginal health care providers and other university-trained professionals to employ to make services effective. We have equity in medical student intakes which augurs well for future progress in this critical area. The dream of having appropriate, culturally safe policies, programs and services for our First Nations children can become a reality if it is supported and promoted by all levels of government.

Child health indicators that show a divide between First Nations and other Australian children*

SES = socioeconomic status. LBOTE = language background other than English. * Adapted with permission from A picture of Australia’s children 2012.3 † Developmentally vulnerable on one or more Australian Early Development Index domains.

Conflicting information from TGA versus FDA may undermine compliance with use of medication

To the Editor: Conflicting information about treatments is known to undermine compliance with the use of medications.1 The education of patients and caregivers that accompanies prescribing should therefore be as consistent as possible. Clients may conduct research on the internet into particular medicines and try to corroborate “what the doctor said”. In the case of the use of clonidine in children, publicly available information is conflicting. The websites of two regulatory agencies, the Therapeutic Goods Administration (TGA) in Australia and the Food and Drug Administration (FDA) in the United States, give conflicting information on using this α-2 adrenergic agonist. Doctors in Australia may refer patients to the TGA website for information on clonidine, but in doing so will only provide information on the use of clonidine for hypertension. However, paediatricians and child and adolescent psychiatrists may use clonidine (following guidance used in other countries) in children and adolescents for diverse beneficial effects in managing attention deficit-hyperactivity disorder (ADHD), outside its TGA-approved use.2

The TGA’s consumer medical information (CMI)3 and product information (PI)4 for clonidine state:

Catapres is not recommended for use in children and teenagers up to 18 years of age. Serious side effects have been observed when clonidine, the active ingredient
in Catapres, is used with methylphenidate in children
with ADHD. Therefore, Catapres in this combination is not recommended.3

The use and the safety of clonidine in children and adolescents has little supporting evidence . . . and therefore can not be recommended for use in this population.4

The Pharmaceutical Benefits Scheme website has hyperlinks to both PI and CMI on the website
of the TGA.

A problem arises if a client seeks information about prescribed medication from other jurisdictions such as the US. In their statistical review and evaluation of clonidine, the FDA states, based on most recent evidence, that:

CLONICEL [the trade name for clonidine in the US] is efficacious, as a monotherapy and as an add-on to a psychostimulant, in the treatment of subjects (6-17 years-old) with ADHD.5

Therefore compliance with medication regimens may be undermined by conflicting information from the TGA and FDA. Clinicians need to be aware of the differences in information and recommendations disseminated by authoritative sources and be prepared when they counsel patients. Perhaps the TGA should review its CMI and PI to reflect recent evidence that clonidine, with the necessary cautions, can be safely prescribed to some selected children and adolescents.

Impact of swimming on chronic suppurative otitis media in Aboriginal children: a randomised controlled trial

Rates of chronic suppurative otitis media (CSOM) among Aboriginal children living in remote areas in Australia are the highest in the world.1 ,2 A survey of 29 Aboriginal communities in the Northern Territory found that 40% of children had a tympanic membrane perforation (TMP) by 18 months of age.3 About 50%–80% of Aboriginal children with CSOM suffer from moderate to severe hearing loss.4,5 This occurs while language and speech are developing and may persist throughout primary school.

There is evidence suggesting that the recommended treatment for ear discharge (twice-daily cleaning and topical ciprofloxacin) can produce cure rates of 70%–90%.6–8 However, a study of Aboriginal children with CSOM in the NT found that less than 30% of children had resolution of ear discharge after 8 weeks of similar treatment.9 This study suggested that ongoing treatment for long periods was difficult for many Aboriginal families living in underresourced and stressful conditions. When children in high-risk communities do not receive appropriate medical treatment for ear disease, using swimming pools to limit levels of ear discharge and possibly reduce bacterial transmission becomes an attractive option.

Traditionally, children with perforated eardrums have been restricted from swimming because of fears of infection. However, it is hypothesised that swimming helps cleanse discharge from the middle ear, nasopharynx and hands and that this benefit may outweigh the risk of introducing infection. Several observational studies have examined the relationship between swimming and levels of skin and ear disease among Aboriginal children.10–14 In a cross-sectional survey, close proximity to a swimming area was associated with reductions of up to 40% in otitis media.10 Two systematic reviews have found that swimming without ear protection does not affect rates of recurrent ear discharge in children with tympanostomy tubes (grommets).15,16 Despite these findings, surveys indicate uncertainty among clinicians regarding water precautions for children with grommets.17–19

Our aim was to conduct a randomised controlled trial (RCT) to better understand the impact of swimming on children with CSOM, and to address a lack of data on ear discharge in older Aboriginal children (aged 5–12 years) with CSOM. We also aimed to obtain microbiological profiles of the nasopharynx and middle ear to help elucidate the cleansing hypothesis.

Methods

Study design

Between August and December 2009, we conducted an RCT examining the impact of 4 weeks of daily swimming in a chlorinated pool on TMPs in Aboriginal children. The Human Research Ethics Committee of the Northern Territory Department of Health and Families and the Menzies School of Health Research approved the study.

Participants and setting

Participants were from two remote Aboriginal communities in the NT. Resident Aboriginal children aged 5–12 years who were found at baseline ear examination to have a TMP were eligible for the trial. Children with a medical condition that prohibited them from swimming were excluded.

Randomisation and blinding

A random sequence stratified by community and age (< 8 years or ≥ 8 years) was generated using Stata version 8 (StataCorp). The allocation sequence was concealed from all investigators. The clinical assessment was performed without knowledge of the group allocation, and laboratory staff were also blinded to group allocation and clinical data.

Intervention

Children in the intervention group swam in a chlorinated pool for 45 minutes, 5 days a week, for 4 weeks. Swimmers did not wear head protection (cap or earplugs) and went underwater frequently. Children in the control group were restricted from swimming for 4 weeks.

Clinical assessments

Participants’ ears were examined in the week before and the week after the intervention using tympanometry, pneumatic otoscopy and digital video otoscopy. Criteria for diagnosis were:

Otitis media with effusion: intact and retracted non-bulging tympanic membrane and type B tympanogram
Acute otitis media without perforation: any bulging of the tympanic membrane and type B tympanogram
Acute otitis media with perforation: middle ear discharge, and perforation present for less than 6 weeks or covering less than 2% of the pars tensa of the tympanic membrane
Dry perforation: perforation without any discharge
CSOM: perforation (covering > 2% of the pars tensa) and middle ear discharge.

Children with a perforation were examined a second time with a video otoscope. The degree of discharge was graded as nil, scant (discharge visible with otoscope, but limited to middle ear space), moderate (discharge visible with otoscope and present in ear canal), or profuse (discharge visible without otoscope). Drawings of the eardrum and perforations were made, with estimates of the position and size of the perforation as a percentage of the pars tensa. Examiners reviewed the videos in Darwin to confirm the original diagnoses of perforations.

Swab collection and microbiology

Swabs were taken from the nasopharynx and middle ear at both the baseline and final ear examinations. All swabs were cultured on selective media for respiratory bacteria. The bacteria specifically targeted were Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus. Ear discharge swabs were also cultured for Streptococcus pyogenes (Group A Streptococcus), Pseudomonas aeruginosa and Proteus spp.

Swabs stored in skim-milk tryptone glucose glycerol broth20 were thawed and mixed, and 10 μL aliquots were cultured on the following plates: full chocolate agar, 5% horse blood agar containing colistin and nalidixic acid, and chocolate agar with bacitracin, vancomycin, and clindamycin (Oxoid Australia). Ear discharge swabs were also cultured on MacConkey agar plates. Blood plates were incubated at 37°C in 5% CO2, and MacConkey plates at 35°C in air. Bacterial isolates were identified according to standard laboratory procedures.

The density of each of the bacteria on each plate was categorised as: 1) < 20; 2) 20–49; 3) 50–100; 4) > 100 or confluent in the primary inoculum; 5) as for 4, but colonies also in second quadrant of the plate; 6) as for 5, but colonies also in third quadrant; 7) as for 6, but colonies also in fourth quadrant. Dichotomous measures for bacterial load were categorised as low density (< 100 colonies) or high density (≥ 100 colonies).

Outcome measures

Clinical measures

The primary outcome measure was the proportion of children with otoscopic signs of ear discharge in the canal or middle ear space after 4 weeks. Final ear examinations took place 12 hours to 2.5 days after the participants’ last scheduled swim. Prespecified subgroup comparisons were: younger (5–7 years) versus older (8–12 years) children; children who had been prescribed topical antibiotics versus those who had not; degrees of discharge; and smaller (< 25%) versus larger (≥ 25%) perforations.

Microbiological measures

For the nasopharynx, we determined the proportions of children with S. pneumoniae, H. influenzae, M. catarrhalis, any respiratory pathogen (S. pneumoniae, H. influenzae, M. catarrhalis) and S. aureus. For the middle ear, we determined the proportions of children with S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, Group A Streptococcus, P. aeruginosa and Proteus spp.

Statistical methods and analyses

All participants allocated to a group contributed a clinical outcome for analysis, including children lost to follow-up, whose diagnoses were assumed not to have changed from baseline. Children lost to follow-up were excluded from assessments of microbiological outcomes. Risk differences (RDs) between the study groups were calculated with 95% confidence intervals. The Mann–Whitney U test was used to compare median perforation sizes of the study groups.

Sample size

We hypothesised that 90% of children not swimming would have ear discharge at 28 days and that swimming could reduce this proportion. We specified that a 25% difference between the two groups would be clinically important. Our aim was to recruit a sample of 100 children to provide 80% power to detect a substantial difference of 25% between the two groups.

Results

Parental consent was obtained for 89 eligible children: 41 children in the swimming group and 48 children in the non-swimming group (Box 1). At 4-week follow-up, final ear examinations were conducted on 82 children (36 swimmers and 46 non-swimmers).

At baseline, the study groups were similar in age, sex, perforation size, the presence and degree of ear discharge, and the prevalences of ear diagnoses (Box 2). Although there were no statistically significant differences in the baseline prevalence of bacteria in the nasopharynx or middle ear, swimmers had lower rates of H. influenzae in the nasopharynx and higher rates of S. aureus in both the nasopharynx and middle ear. Of the 89 children, 58 (26 swimmers and 32 non-swimmers) had ear discharge at baseline.

At 4-week follow-up, 56 children had ear discharge: 24 of 41 swimmers compared with 32 of 48 non-swimmers (RD, − 8%; 95% CI, − 28% to 12%). Excluding children lost to follow-up, 21 of 36 swimmers had ear discharge compared with 31 of 46 non-swimmers (RD, − 9%; 95% CI, − 30% to 12%).

Between baseline and 4-week follow-up, there was no statistically significant change in the prevalence of bacteria in the nasopharynx (Box 2). P. aeruginosa infection in the middle ear increased in swimmers, compared with no change in non-swimmers. Non-typeable H. influenzae isolated from ear discharge increased in both groups. Overall, the dominant organisms were S. pneumoniae and H. influenzae in the nasopharynx, and H. influenzae, S. aureus and P. aeruginosa in the middle ear.

Per-protocol analysis of swimmers attending > 75% of swimming classes and non-swimmers adhering to swimming restrictions > 75% of the time indicated that 16 of 24 swimmers had ear discharge at 4-week follow-up, compared with 29 of 44 non-swimmers (RD, 1%; 95% CI, − 23% to 23%).

Rates of discharge were significantly lower in children who were prescribed ciprofloxacin and in children with smaller perforations (Box 3).

Of the 89 children, 65 had no change from their original diagnosis (by child’s worst ear) at 4-week follow-up. Ear discharge failed to resolve in 31 of the 35 participants with moderate to profuse ear discharge at baseline (Box 3). Seven of the 89 children had a perforation that healed (Box 4).

Discussion

We found that regular swimming in a chlorinated pool for 4 weeks did not aid resolution of ear discharge in Aboriginal children with CSOM. At the end of the trial, rates of ear discharge were similar between swimmers and non-swimmers. Our microbiological data also suggest that swimming is unlikely to be effective in removing discharge from the middle ear and nasopharynx, with rates and densities of organisms generally comparable between swimmers and non-swimmers, with little change during the study. Among swimmers, there was an increase in P. aeruginosa middle ear infection, but this was not correlated with new episodes of ear discharge.

Our study is the first RCT to examine the effects of swimming on Aboriginal children with CSOM and also addresses the need for more RCTs examining the impact of swimming on children with grommets. Further, the microbiological data enabled an assessment of the effect of regular swimming on infection in the nasopharynx and middle ear. Other strengths include the blinding of examiners, prespecified subgroup analysis and a follow-up rate of more than 90%.

Our study also has some limitations. We planned to randomly assign 100 children and anticipated that 90% of participants would have ear discharge at follow-up, but we had only 89 participants and 63% with discharge at follow-up, meaning the study was underpowered. Some difficulties were encountered in recruiting children who did not attend school in one community. The possibility of contamination among non-swimmers was also a concern. Parents and school and pool staff assisted in ensuring that non-swimmers did not swim at the pool or at any other water sites, and alternative activities were provided for non-swimmers after school, as this was a popular swimming time. Attendance at swimming and activity classes were monitored, and two portable media players were offered as incentives to children with the highest attendance.

The lack of objective measures for the degree of discharge, perforation size and bacterial density may have contributed to measurement error. It is unlikely that these limitations would prevent a large clinical effect being identified. However, our small sample size means that modest benefits or harms associated with daily swimming may still be possible.

Our results are not consistent with research from two remote communities in Western Australia, which found that rates of TMPs among Aboriginal children halved from about 30% to 15% after swimming pools were installed.11 The potential to improve on our results with longer exposure to swimming is possible. However, the WA study did not follow individual children, and after 5 years the reductions were sustained in only one community.14 Further, the likelihood of significant clinical improvements over a longer period is not supported by our microbiological data. A recent South Australian study also found that the installation of swimming pools in six communities did not affect rates of TMPs among children.12

While swimming may remove some ear and nasal discharge, there is evidence to suggest that cleansing practices alone will not cure CSOM. A Cochrane review of studies conducted in developing countries found that wet irrigation or dry mopping was no more effective than no treatment in resolving ear discharge in children with CSOM (odds ratio, 0.63; 95% CI, 0.36–1.12).21 The review recommended that aural cleansing should be conducted in conjunction with topical antibiotic therapy.21 Future studies could look at the effectiveness of swimming in combination with the application of topical antibiotic therapy.

Over the 4 weeks of our intervention, rates of H. influenzae middle ear infection substantially increased in both swimmers (from 35% to 70%) and non-swimmers (from 50% to 65%). Previous topical antibiotic trials of Aboriginal children (aged 1–16 years) have reported lower baseline rates of H. influenzae in the middle ear, ranging from 5% to 25%.6,9 In contrast, a vaccination trial of Aboriginal infants aged < 24 months found H. influenzae in 85% of new perforations.22 The high levels of H. influenzae ear and nasopharyngeal infection may mean that there is a role for the use of oral antibiotics in combination with topical antibiotics to treat Aboriginal children with CSOM. There may also be benefits from vaccines against H. influenzae in Aboriginal children at high risk of progressing to CSOM.

Simultaneous hand contamination and nasal carriage of S. pneumoniae and H. influenzae is a reliable indicator of TMP in Aboriginal children under 4 years of age.23 Future research could examine rates of hand contamination in relation to swimming, particularly targeting younger children (aged 2–5 years), who are most likely to transmit otitis media bacteria to infants.

In conclusion, it seems unlikely that regular swimming in pools will resolve ear discharge and heal TMPs in the short term. We also found no clear indication that swimming reduces rates of respiratory and opportunistic bacteria in the nasopharynx or middle ear. However, we did not find swimming to be associated with an increased risk of ear discharge. We would not support the practice of restricting children with a TMP from swimming unless it was documented that ear discharge developed directly after swimming (for that particular child). More RCTs are needed to assess more modest (or longer-term) effects of swimming on middle ear disease in Aboriginal children. The combination of swimming and ciprofloxacin treatment may also produce better clinical outcomes and should be investigated.

1 Flowchart of participants through the trial

TMP = tympanic membrane perforation.

2 Participant characteristics at baseline and 4-week follow-up

Baseline

Follow-up

Swimmers
(n = 41)

Non-swimmers (n = 48)

Swimmers
(n = 41)

Non-swimmers (n = 48)

Risk difference
(95% CI)*

Mean age in years (SD)

8.9 (2.4)

8.6 (1.9)

—

Male

27 (66%)

31 (65%)

—

Ear diagnosis

n = 41

n = 48

n = 41†

n = 48†

Bilateral closed tympanic membranes

—

1/41 (2%)

6/48 (13%)

− 10% (− 23% to 2%)

Unilateral dry TMP

11/41 (27%)

11/48 (23%)

11/41 (27%)

5/48 (10%)

16% (0 to 33%)

Bilateral dry TMPs

4/41 (10%)

5/48 (10%)

5/41 (12%)

5/48 (10%)

2% (− 12% to 17%)

Unilateral wet TMP

12/41 (29%)

13/48 (27%)

10/41 (24%)

12/48 (25%)

− 1% (− 18% to 18%)

Wet TMP and dry TMP

2/41 (5%)

2/48 (4%)

5/41 (12%)

5/48 (10%)

2% (− 12% to 17%)

Bilateral wet TMPs

12/41 (29%)

17/48 (35%)

9/41 (22%)

15/48 (31%)

− 9% (− 27% to 10%)

Median size of TMP as percentage of pars tensa (IQR)

20% (8%–38%)

18% (6%–40%)

15% (4%–32%)

20% (5%–49%)

P = 0.39

Any ear discharge (primary outcome)

26/41 (63%)

32/48 (67%)

24/41 (59%)

32/48 (67%)

− 8% (− 28% to 12%)

Moderate or profuse discharge

16/41 (39%)

19/48 (40%)

20/41 (49%)

25/48 (52%)

− 3% (− 24% to 17%)

Nasopharyngeal bacteria

n = 41

n = 46‡

n = 35‡

n = 41‡

Streptococcus pneumoniae

28/41 (68%)

33/46 (72%)

19/35 (54%)

27/41 (66%)

− 12% (− 33% to 1%)

Non-typeable Haemophilus influenzae

17/41 (41%)

28/45 (62%)

21/35 (60%)

30/41 (73%)

− 13% (− 34% to 8%)

Moraxella catarrhalis§

17/40 (43%)

17/46 (37%)

6/35 (17%)

14/41 (34%)

− 17% (− 36% to 3%)

Any respiratory pathogen

28/41 (68%)

41/46 (89%)

24/35 (69%)

37/41 (90%)

− 22% (− 40% to − 4%)

Staphylococcus aureus

8/41 (20%)

5/46 (11%)

9/35 (26%)

4/41 (10%)

16% (− 1% to 34%)

At least one high-density respiratory pathogen§

17/35 (49%)

23/43 (53%)

16/35 (46%)

16/41 (39%)

7% (− 15% to 28%)

Middle ear bacteria

n = 24‡

n = 30‡

n = 23‡

n = 32‡

Streptococcus pneumoniae§

1/24 (4%)

4/30 (13%)

0/23

2/32 (6%)

− 6% (− 20% to 9%)

Non-typeable Haemophilus influenzae

8/23 (35%)

14/28 (50%)

16/23 (70%)

20/31 (65%)

5% (− 21% to 29%)

Moraxella catarrhalis§

0/22

0/29

1/21 (5%)

0/31

5% (− 4% to 14%)

Staphylococcus aureus

8/24 (33%)

5/30 (17%)

8/23 (35%)

4/32 (13%)

22% (0 to 45%)

Group A Streptococcus

3/24 (13%)

1/30 (3%)

5/23 (22%)

2/32 (6%)

15% (− 3% to 37%)

Pseudomonas aeruginosa

3/24 (13%)

10/30 (33%)

10/23 (43%)

10/32 (31%)

12% (− 13% to 37%)

Proteus spp.

3/24 (13%)

2/30 (7%)

2/23 (9%)

2/32 (6%)

2% (− 13% to 22%)

TMP = tympanic membrane perforation. IQR = interquartile range. * Unless otherwise indicated. † Includes children lost to follow-up, whose diagnoses were assumed not to have changed from baseline. ‡ Denominators are reduced due to children lost to follow-up, children refusing to have swab taken, or swab being damaged in transportation. § Some plates were contaminated by Proteus spp.

3 Children with ear discharge at final ear examination, by subgroup at baseline

Overall

Swimmers

Non-swimmers

Risk difference (95% CI)

All children with ear discharge at final ear examination

56/89 (63%)

24/41 (59%)

32/48 (67%)

− 8% (− 28% to 12%)

Subgroup

Aged 5–7 years

14/24 (58%)

6/11 (55%)

8/13 (62%)

− 7% (− 44% to 31%)

Aged 8–12 years

42/65 (65%)

18/30 (60%)

24/35 (69%)

− 9% (− 31% to 15%)

Not prescribed topical ciprofloxacin

46/67 (69%)

20/30 (67%)

26/37 (70%)

− 4% (− 26% to 18%)

Prescribed topical ciprofloxacin

10/22 (45%)

4/11 (36%)

6/11 (55%)

− 18% (− 54% to 23%)

Nil discharge

9/31 (29%)

3/15 (20%)

6/16 (38%)

− 18% (− 47% to 15%)

Scant discharge

16/23 (70%)

5/10 (50%)

11/13 (85%)

− 35% (− 66% to 4%)

Moderate or profuse discharge

31/35 (89%)

16/16 (100%)

15/19 (79%)

− 21% (− 1% to 44%)

Small (< 25%) perforation

19/49 (39%)

9/24 (38%)

10/25* (40%)

− 3% (− 29% to 24%)

Large (≥ 25%) perforation

35/38 (92%)

15/17 (88%)

20/21 (95%)

− 7% (− 31% to 13%)

* Perforation size was not estimated for two children in the non-swimming group at baseline.

4 Change in diagnosis (by child’s worst ear) from baseline to final ear examination

Outcome	Overall (n = 89)	Swimmers (n = 41)	Non-swimmers (n = 48)

Dry TMP to closed tympanic membrane	4 (5%)	1 (2%)	3 (6%)
Dry TMP to dry TMP	18 (20%)	11 (27%)	7 (15%)
Dry TMP to wet TMP	9 (10%)	3 (7%)	6 (13%)
Wet TMP to closed tympanic membrane	3 (3%)	0	3 (6%)
Wet TMP to dry TMP	8 (9%)	5 (12%)	3 (6%)
Wet TMP to wet TMP	47 (53%)	21 (51%)	26 (54%)
Improved	15 (17%)	6 (15%)	9 (19%)
Same	65 (73%)	32 (78%)	33 (69%)
Got worse	9 (10%)	3 (7%)	6 (13%)

TMP = tympanic membrane perforation.

Challenges of transition to adult health services for patients with rare diseases

What can be done for young people stuck in “health care limbo” when they leave paediatric services?

The teenage years are a time of transition, when young people must adapt to enormous physiological and emotional changes but also need time to aspire to the future. Young people living with chronic complex disease have dreams, but their challenges are amplified as they face transition from paediatric to adult health services and begin to take charge of their own complex health care needs.1

Young people need the assistance of adult health services to deal with adult issues: sexual health, fertility, drug and alcohol use, mental health, lifestyle-related disease and issues related to disability, employment, education and training. For most of their lives, young people with chronic diseases have been engaged in a paediatric, family-centred multidisciplinary model of care. They need preparation and support to move into adult services, which are more specialised, less integrated, and centred more on the individual than on the family.1,2 Failed transition leads to poor engagement with health services and adverse health outcomes.2

Despite a number of policy initiatives to provide age-appropriate and stage-appropriate care for adolescents and the development of disease-specific transition pathways (eg, for cystic fibrosis, spina bifida and diabetes),1,3–5 transition is fraught for young people living with chronic and complex diseases, especially rare diseases.

Providing disease-specific clinics for every rare disease is unrealistic; there are almost 10 000 rare genetic diseases alone. Most rare diseases have their onset in childhood, are chronic, complex, disabling and require frequent, specialist care throughout the life span.6 This necessitates access to multiple doctors, allied health workers, pathology and pharmacy services.7 Better recognition of rare diseases and increasing survival rates have led to a greater demand for transition services from this group and we must respond to their needs.

Regardless of which chronic and complex disease they have, these young people face similar problems with the transition to adult care:

inadequate preparation
difficulty finding appropriate adult health services
inadequately coordinated specialist adult services
unwillingness of general practitioners to take on complex cases
inadequate resources to coordinate the transition process
lack of psychological support.

These issues were affirmed in the recent Forum for Young People Living with Rare Disease, attended by 15 young people and 15 parents or carers representing a wide variety of rare chronic conditions: Ehlers–Danlos syndrome, Klippel–Trenaunay syndrome, narcolepsy, cataplexy, Phelan–McDermid syndrome, Duchenne muscular dystrophy, Rasmussen’s encephalitis, congenital panhypopituitarism, hypochondroplasia and other skeletal dysplasias.8

Forum participants called for:

comprehensive preparation for transition, involving the family and adult services
timing of transition according to developmental stage and maturity, not age
flexibility from adult specialists to allow parents and carers to attend some consultations
clinics that treat many different rare chronic conditions
GP clinics that are competent and confident to coordinate care and refer appropriately
accessible transition coaches or coordinators.

One 18-year-old with a rare syndrome said:

I’m still transitioning, but it’s been a trial. I’m too old for paediatrics but too difficult a case for adult services to treat. I am worried about my health . . . I don’t know who will treat me properly if I end up in hospital.

As most rare chronic diseases are initially diagnosed and treated in childhood, much of the expertise resides with paediatricians, and often there is simply nowhere to transition to. We need to address this imbalance by supporting education on chronic complex diseases in young people — both for medical students and through continued medical education. The ongoing development of the specialty of Adolescent Medicine will support this.

Multidisciplinary clinic models catering for young adults could be adapted to cater simultaneously for many different rare diseases.5 Such innovative models provide economic efficiencies,9 facilitate communication among the many health professionals involved in care and ease access for patients. Establishing clinics that involve both adult and paediatric specialists enables sharing of expertise and provides a practical training platform. Incentives beyond the current Medicare rebates are needed to support specialist GP clinics willing to look after young people with rare chronic diseases. Trapeze, a primary health transition service, has been established in New South Wales, although its current focus is limited to diabetes and respiratory disease.10

Young people living with rare chronic disease have the right to equitable access to appropriate health care. We need a network of appropriately trained and well resourced transition coordinators to facilitate linkages between young people and health and psychological services and peer support.8 Evaluation of existing transition services and clinics to inform future service needs should be a priority. Successful transition requires more than a referral letter. It is a process that takes time and requires a coordinated system-based approach.

Salicylate elimination diets in children: is food restriction supported by the evidence?

When a food is identified as causing allergic symptoms, that food will usually be removed from the diet. However, inappropriate use of extensive food elimination can be harmful. Salicylate elimination or “low salicylate” diets — which remove foods deemed to contain natural salicylates — can be particularly restrictive, especially as they are often implemented with restriction of other foods such as those containing amines, glutamates, synthetic food additives, gluten and dairy. These diets appear to be commonly used in New South Wales, but to our knowledge are not widely used outside of the state or in other countries. We discuss our own experiences with children who were referred for care to the allergy clinics of three public hospitals, and who had previously used these diets, and review the evidence for using low salicylate diets in treating a variety of disease indications.

For which conditions are low salicylate diets prescribed in Sydney?

We sought to identify the indications for which salicylate elimination is prescribed in Sydney by conducting a retrospective case note review of children attending the allergy clinics of the two main children’s hospitals, Sydney Children’s Hospital and the Children’s Hospital at Westmead, as well as a major regional allergy clinic at Campbelltown Hospital, between 1 January 2003 and 31 December 2011. We confirmed any missing details through a single telephone conversation between an immunologist or allergist and the child’s carer. Approval for the study was obtained from the South Eastern Sydney Local Health District, Human Research Ethics Committee – Northern Sector.

We identified 74 children who had at some point in their lives been on a low natural salicylate diet. The most common indication for initiation of the diet, reported by the patient’s carer, was eczema in 34/74, followed by a behavioural abnormality (eg, attention deficit hyperactivity disorder [ADHD] or unsettled infant behaviour) in 17/74 and gastrointestinal disturbances (eg, abdominal pain or gastro-oesophageal reflux disease) in 12/74 (Box).

What is the evidence supporting the role of low salicylate diets for these indications?

We reviewed the literature using MEDLINE and PubMed, combining search terms “salicylate”, “elimination diet” or “exclusion diet” with “food allergy”, “food intolerance”, “eczema”, “atopic dermatitis”, “chronic urticaria”, “ADHD”, “behaviour” or “gastrointestinal”. We found no evidence in the peer-reviewed literature to suggest a role for salicylates in any of the diseases for which the diet is prescribed.

In the absence of an overt type I hypersensitivity clinical response, food is an uncommon precipitant of eczema. A 2008 Cochrane review concluded that, with the exception of egg exclusion in patients who have positive specific IgE antibodies to egg, there is little evidence to support restriction of tolerated foods in eczema.1

On the other hand, there is good evidence that food exclusion can ameliorate the hyperkinesis symptoms of ADHD, with numerous studies showing a benefit for broad-based food exclusion diets.2 However, a recent randomised controlled trial suggests that much of this effect is caused by artificial food additives, and we were unable to identify any peer-reviewed evidence that natural salicylates can cause hyperactive behaviour.3 One published letter referred to challenge with salicylates precipitating behavioural symptoms, however the authors did not stipulate whether the challenge substance was natural salicylate or acetylsalicylic acid (aspirin)4 — aspirin being known to cause significant symptoms when natural salicylates have no effect.5

Finally, while foods are well known to cause a variety of gastrointestinal symptoms, from coeliac disease to irritable bowel syndrome, there is no good peer-reviewed evidence that natural salicylates cause any gastrointestinal symptoms.

Do salicylate elimination diets cause harm?

Although food elimination diets used to treat allergy have been associated with side effects including micronutrient deficiency,6–8 protein or energy malnutrition,9 eating disorders,10 food aversion,11 and the development of allergic reactions including fatal anaphylaxis to the excluded food on reintroduction,12,13 we were unable to identify any evidence regarding the safety or otherwise of salicylate elimination diets in children. This is of concern given that many of the patients attending our clinics had started the diets at a young age (median, 24 months; range, 6 weeks to 15 years), and continued for an extended period (> 1 year in 30/61 children).

Among our patients, where details were available, we identified a high occurrence of possible adverse outcomes among children who had been on low salicylate diets, with 31 out of 66 children suffering one or more possible adverse events. Symptoms and problems experienced included weight loss or failure to thrive in 13/66 children, eating disorders (including three cases of anorexia nervosa) in 4/66, specific nutrient deficiency in 2/66 (one case of vitamin C deficiency, one case of protein, iron and zinc deficiency), food aversion in 6/66, alopecia in 2/66 and unplanned weaning in 3/66. Four out of 13 mothers who went on the diet to benefit their breastfeeding infant suffered significant weight loss, which they perceived as problematic.

While we acknowledge that our cohort has an inherent selection bias and that without a control group it is not possible to attribute the reported events to the diet, we are concerned that all adverse events were reported to have occurred after initiation of the diet.

Also, beyond the possible adverse events noted in our patients, we are additionally concerned about the use of broad-based empirical food elimination in early life, with increasing evidence suggesting that food elimination at this time predisposes to the development of food allergy to the excluded foods, particularly among children with eczema, which was the largest group identified here.14,15

Who prescribes salicylate elimination diets?

Among those patients where details were available, 47/69 were prescribed the diet through medical allergy services, with general paediatricians 7/69 and dietitians 7/69 prescribing less frequently, while 8/69 parents obtained the diet from friends or from the internet. We do not prescribe the diets in our practice.

In order to assess whether the diet was more widely used elsewhere, we surveyed overseas allergists. An online survey of members of the editorial boards of major European and North American allergy journals produced 23/125 responses, with none of the responding experts employing the diet for ADHD, and only 1/23 using a form of salicylate exclusion for eczema.

Does the available research support a role for natural salicylates in any disease causation?

As discussed above, there is no peer-reviewed evidence to support the use of low salicylate diets in treating eczema, behavioural symptoms or gastrointestinal symptoms.

One disease where the role of natural salicylates has been studied in more detail is aspirin-sensitive asthma, where doses of natural salicylic acid 10 times higher than the aspirin dose have no effect.5 The lack of importance of natural salicylates in this disease is well established in clinical practice, as reflected by the evidence-based clinical decision support website, UpToDate (http://www.uptodate.com/home), which states that “dietary salicylates do not cause symptoms in NSAID [non-steroidal anti-inflammatory drug] sensitive patients”.16

A second disease where low salicylate diets have been trialled is chronic idiopathic urticaria (CIU); however, while there is some evidence that synthetic food additives may play a role in a small proportion of adult CIU cases,17 the peer-reviewed evidence that salicylates play any role in this disease is largely limited to studies that used aspirin as the challenge substance.18 On the other hand, there are several reasons to question the idea that salicylate-containing foods play any role in CIU. First is the recent discovery that half of childhood CIU is autoimmune in nature, resulting from autoantibodies against the high-affinity IgE receptor.19 Second, evidence suggests that those few foods said to contain salicylates that may precipitate CIU (eg, tomatoes, wine, herbs) probably do so not because of their salicylate content, but because they contain volatile aromatic chemicals (eg, alcohol, ketones and aldehydes).20 Third, there is evidence that the foods removed in low salicylate diets may not actually contain significant levels of salicylates, with one group suggesting that many “high salicylate foods” contain no aspirin and only tiny amounts of natural salicylates.21

Finally, it is important to discuss local research on salicylate intolerance performed in the early-to-mid 1980s. Most of that work focused on CIU, with a lesser focus on a number of other symptom complexes.4,22–24 The research involved placing patients on diets that removed foods containing salicylates, using food challenge to identify which constituents were responsible for any perceived improvement.22,24 However, teasing out which component of these broad-based elimination diets were responsible for any perceived benefit is difficult, given that the diets removed many food constituents, including those now known to cause symptoms, such as artificial food additives,3,17,25 and because the challenge substance was commonly aspirin,22,24 although sodium salicylate was said to have been used in some work.22 Moreover, most of the clinical data appeared in a non-peer-reviewed format,22 or with incomplete methodological details in review format in peer-reviewed journals.4,23 These non-peer-reviewed findings of disease associations of natural salicylates have not been reproduced by other investigators, and a recent British textbook of food hypersensitivity concluded “there are no effective diagnostic tests for salicylate intolerance, and no studies showing the efficacy of dietary exclusion”.26

Can salicylate elimination diets be recommended for use in children?

The use of low salicylate diets in children is not supported by current evidence or by expert opinion. There is also no evidence that these diets are safe, in particular for infants and their breastfeeding mothers, and for those at risk of developing eating disorders. While our retrospective case note review is insufficient to prove any risk associated with the diets, it is concerning that harm may occur when children and adolescents are placed on such restrictive diets, particularly if they stay on them for long periods.

We would invite any proponents and prescribers of the diet to produce evidence of the efficacy and safety for the disorders in which they consider such a restrictive diet is indicated. Pending such evidence, we cannot recommend the use of salicylate elimination diets.

Characteristics of 74 children prescribed salicylate elimination diets

Characteristic

No. of children/total*

Age at initiation of diet

Infancy (1 year or less)

26/67

Early childhood (1–3 years)

22/67

Childhood (4–10 years)

10/67

Adolescence (11–18 years)

9/67

Duration of diet

< 1 month

5/61

1 month to 6 months

17/61

> 6 months to 1 year

9/61

> 1 year

30/61

Indication for diet

Eczema

34/74

Behaviour (including ADHD)

17/4

Gastrointestinal complaints

12/74

Failure to thrive

4/74

Acute allergic reaction

3/74

Anaphylactoid reaction

2/74

Urinary urgency

1/74

Headache

1/74

Adverse events

Failure to thrive or weight loss

13/66

Food aversion

6/66

Eating disorder

4/66†

Infant weaned early

3/66

Alopecia

2/66

Nutrient deficiency

2/66

Constipation

1/66

Total children with adverse events

31/66

Breastfeeding mothers with complications of diet

4/13

Prescribed by

Medical allergy clinics

47/69

Dietitian

7/69

Paediatrician

7/69

Friend or internet

8/69

ADHD = attention deficit hyperactivity disorder. * Varying denominators reflect the completeness of available data. † Including three cases of anorexia nervosa.

Burns from motorcycle exhausts among children in New South Wales: a continuing problem

To the Editor: Burns remain a common occurrence among children, with scalds accounting for 55% of these injuries in Australia and New Zealand.1 Although a less frequent mechanism, contact burns now account for up to 30% of all burns among children.1,2 The Burns Unit (BU) at the Children’s Hospital at Westmead serves the paediatric population of New South Wales and the Australian Capital Territory. Recently, our BU has identified a rise in the number of contact burns from motorcycle exhausts among children.

Following Sydney Children’s Hospitals Network Human Research Ethics Committee approval, we performed a retrospective case series review of children ≤ 16 years of age who were referred to our BU between 1 January 2008 and 31 December 2011 and who had sustained contact burns from the exhausts of either adult or children’s motorcycles.

Over the 4-year study period, there were 96 children with motorcycle exhaust contact burns, 75 (78%) of whom were male. The mean age was 8.6 years. Forty-five (47%) of the burns occurred in backyards; 16 (17%) occurred on farms; 14 (15%) occurred in sport and recreation areas; seven (7%) occurred in driveways; seven (7%) occurred on public roads; and in seven cases (7%), the location was unknown. Only 53 (55%) of the children had adequate first aid. Of the 41 children (43%) admitted to hospital, all required skin grafting (Box). The mean length of stay was 2.4 days. Out of the total of 96 children, wound infections occurred in seven (7%), and three (3%) had a history of prior burns.

A previous study from our institution first identified concerns relating to children sustaining contact burns from exhaust systems.3 Despite this, the incidence of children sustaining motorcycle exhaust burns appears to be increasing.2,3 Between 2008 and 2012, an average of 24 children per year presented to our BU with motorcycle exhaust burns, compared with 15 per year in our earlier study.2

These results indicate that there remains a need to educate the community and health professionals regarding the dangers of motorcycle exhausts. We suggest that there should be implementation of widespread advocacy for the use of protective clothing. Consideration should also be given to the introduction of legislation requiring the modification of all motorcycle exhausts, particularly those designed for children, to reduce the incidence of contact burns in this population.

Box

Burn injury to the right leg of a 13-year-old boy secondary to contact with a motorcycle exhaust: (A) on presentation; (B) as a laser Doppler image showing a deep-dermal/full-thickness burn centrally (blue); and (C) after skin grafting.

Challenges in regulating influenza vaccines for children

Lessons need to be drawn from the assessment and licensing of influenza vaccines in previous years

In April 2010, Australia suspended paediatric influenza vaccinations as a result of febrile convulsions associated with seasonal trivalent influenza vaccine (TIV). Epidemiological investigations have established that the increase in febrile reactions was limited to one of three brands of TIV used in Australia that year — CSL Biotherapies Fluvax or Fluvax Junior (CSL TIV), registered as Afluria in the United States and Enzira in the United Kingdom.1–3 Health authorities in Australia estimated that the risk of febrile convulsions in children aged 6 months to 4 years after vaccination with CSL 2010 TIV ranged from 3–10 per 1000 vaccinated.1,3 This figure is remarkable because TIV has an excellent safety record in children and before 2010 was only rarely associated with febrile convulsions. The largest published population-based study found only one febrile convulsion after TIV vaccination of 45 356 children aged 6–23 months,4 giving a risk estimate of 2.2 convulsions per 100 000. Nonetheless, age-related differences in the reactogenicity of influenza vaccines and the potential for influenza vaccines to cause febrile reactions in children had been recognised for decades.5 Reviewing the regulatory history of the CSL influenza vaccine for children (Box) suggests there may be opportunities for improving the licensure of paediatric influenza vaccines.

Licensure of CSL Fluvax for children

In 2002, Australia’s Therapeutic Goods Administration (TGA) registered the thiomersal-free CSL TIV Fluvax for use in persons aged 6 months and older.6 Between 2004 and 2005, CSL TIV was approved for paediatric use in Sweden, the UK and Denmark despite a European Public Assessment Report which indicated that, at the time of initial registration in Europe, “no controlled clinical studies had been conducted in infants, young children, or young adolescents”.7 The assessment also acknowledged that the extent of CSL TIV use among paediatric populations at the time was “not well understood”.7

The first paediatric study of CSL TIV began in March 2005 as a post-licensure commitment to the Swedish Medical Products Agency.7,8 Conducted in Australia, the study involved vaccinating 298 children less than 9 years of age with two doses of the 2005 formulation of TIV.9 In the following year, 273 of the children received a “booster” dose using the 2006 TIV formulation, which had different influenza A(H3N2) and B vaccine virus antigens.9,10 The study results, published in 2009, showed a marked difference between the risk of reported fever, depending on the annual formulation of the CSL TIV administered.9 Among children less than 3 years of age, the proportion experiencing fever was 22.5% after vaccination with the CSL 2005 TIV formulation and 39.5% after vaccination with the 2006 formulation.9 For children aged 3–8 years, the proportions experiencing fever were also elevated in 2006, rising from 15.6% and 8.2% for doses 1 and 2 in 2005, respectively, to 27.0% after vaccination with the 2006 TIV formulation.9 Reanalysis of the published data shows that the increase in the proportion of children with fever after vaccination in 2006 compared with either vaccine dose in 2005 was statistically significant for both age groups (P < 0.05). In addition, two serious adverse events were reported from this study. Both reports were of fever and vomiting on the evening of vaccination with CSL 2006 TIV, with one of the children also experiencing a febrile convulsion — a clinical picture similar to the adverse events subsequently associated with CSL TIV in 2010.3,6,9

2007 US FDA finding: paediatric safety not established

In March 2007, CSL submitted a biologics license application (BLA) to the US Food and Drug Administration (FDA) requesting approval to market TIV for adults in the US. To enhance the safety database, CSL also provided the FDA with data from the 2005–2006 Australian paediatric study. The FDA concluded that the Australian paediatric study had not identified any unusual safety concerns,8 although a separate assessment by FDA statisticians conducted later noted the small sample size and lack of comparator arm, and stated “this study was not designed to test any hypothesis”.11 In September 2007, the FDA wrote that “ . . . the pediatric study was not controlled for safety. Therefore, at this time the data will not be considered for approval in a pediatric population”.8 Accordingly, the prescribing information for the CSL TIV formulation distributed in the US for 2008–2009 stated that the “safety and effectiveness in the pediatric population have not been established”.12

The US Pediatric Research Equity Act of 2003 requires that clinical studies are conducted in children for biological products under development.8,13 As part of the accelerated approval of CSL TIV for adults in the US, CSL agreed to conduct the first randomised controlled trial of CSL TIV in children, which was scheduled to begin in August 2009 (CSLCT-USF-07-36).8

In the interim, two developments prompted the FDA to reassess the paediatric indication for CSL TIV without waiting for the results from this study. The first was a decision in 2008 by the Advisory Committee on Immunization Practices to expand the recommendation for annual influenza vaccination to include children 5 to < 18 years of age.6 The second was the onset of the influenza A(H1N1) pandemic in April 2009. Accelerated approval of CSL’s seasonal influenza vaccine for children would facilitate licensure of CSL’s monovalent pandemic vaccine for children because

an approved pediatric indication [for CSL TIV] would permit approval of the H1N1 vaccine in children as a strain change as has been done for adults, and would obviate the need for an Emergency Use Authorization in the pediatric population.6

While acknowledging the limitations of the existing data, the FDA concluded that “due to constraints related to the influenza shortage in 2004 and current concerns related to the circulating H1N1 pandemic swine flu strain, less stringent criteria for submission for BLA is acceptable”.11 Ultimately, the FDA determined that “extenuating circumstances have changed the risk benefit ratio for the pediatric indication” and recommended that CSL TIV “be granted approval in children 6 months to < 18 years of age because of newly recognized potential clinical benefit that outweigh known risks”.6

Data emerge from the first controlled trial of the CSL TIV in children

The paediatric trial of CSL 2009–2010 TIV compared with a US-licensed comparator (NCT00959049) was completed in May 2010, just weeks after suspension of childhood influenza vaccinations in Australia. Data from this unpublished study are available on the US National Institutes of Health website, albeit without statistical analysis.14 Independent examination of the data showed that children aged 6 months to < 3 years who received a first dose of CSL TIV experienced fever (≥ 37.5°C axillary or ≥ 38.0°C oral) nearly three times as often as those receiving the comparator (37% v 14%, respectively; P < 0.00005).14 In addition, children in this age cohort were significantly more likely to experience severe fever (> 39.5°C axillary or > 40.0°C oral; P < 0.05), irritability (P < 0.00005), loss of appetite (P < 0.005), or severe nausea/vomiting (P < 0.005) after receiving a first dose of CSL TIV compared with those receiving the comparator vaccine. Children aged 3 to < 9 years who received a first dose of CSL TIV were significantly more likely to experience fever (22% v 9%, respectively; P < 0.0005) and malaise (29% v 13%; P < 0.0005).14 The seasonal TIV formulation used for this trial was antigenically distinct to the formulation subsequently associated with severe febrile reactions in Australia in 2010 (specifically, the 2009–2010 northern hemisphere vaccine did not contain pandemic 2009 H1N1 strain antigens and used a different H3N2 vaccine strain).10 Taken together, data from this study and the experience in Australia in 2010 indicate that, compared with other contemporaneous TIVs, CSL TIV was associated with a higher risk of fever in children over two consecutive manufacturing seasons using different H1N1 and H3N2 viral strains.3,14 The findings from the 2005–2006 Australian study extend this observation, suggesting that CSL TIV may have been associated with a high risk of fever in children, at least intermittently, in other years.9

In hindsight, it would appear that the US decision to grant a paediatric indication for CSL TIV in 2009 without the benefit of data from a controlled paediatric clinical trial may have led to an optimistic assessment of the risks and benefits of this vaccine. The CSL TIV associated with severe febrile reactions in the southern hemisphere in 2010 was antigenically equivalent to that distributed in the northern hemisphere for the 2010–2011 influenza season.10 If Australia had not identified the safety signal in April 2010 — an event which led directly to health authority recommendations in the US and UK that CSL TIV not be administered to children aged < 5 years for the upcoming 2010–2011 influenza season — it is possible that febrile adverse reactions associated with this formulation might have been observed among children in those countries.15,16

It is nearly 3 years since the use of CSL TIV in young children was suspended, and laboratory investigations undertaken by CSL have not yet identified a definitive cause of the adverse reactions.17 CSL has acknowledged, however, that the increase in febrile adverse events in children in 2010 may have been due, at least in part, to “differences in the manufacturing processes used to manufacture CSL TIVs compared to other licensed TIVs on the market”.17 Suboptimal virus splitting or other mechanisms related to CSL’s use of deoxycholate have been suggested as possible contributing factors.18

Last year a joint working group of the Australian Technical Advisory Group on Immunisation and the TGA reviewed data on adverse events associated with different TIV brands among persons over 10 years of age and concluded that “the safety profile of many currently registered inactivated influenza vaccines is likely to differ and evidence to support this exists”.19 This observation underscores that assumptions regarding the safety of influenza vaccines may not be transferable across brands.

Lessons learned

CSL TIV was licensed for use in children in a number of countries without the benefit of data from controlled paediatric clinical trials. The results of the only paediatric randomised controlled trial to date, conducted 7 years after thiomersal-free Fluvax was licensed for children in Australia, and Australia’s experience in 2010 demonstrate the risks inherent with this approach. Ideally, adequately powered, controlled paediatric studies should be conducted before a vaccine is licensed for children.20 Regulatory decisions on a paediatric indication for a vaccine can be challenging and are even more difficult if the safety profile of the vaccine has not been established. If circumstances do not permit a rigorous assessment of a vaccine’s safety before licensure, as could be argued for the US in 2009 with an influenza pandemic approaching, this important caveat should be communicated to providers and consumers. In addition, given that the antigenic composition of influenza vaccines often changes from year to year, comprehensive postmarketing surveillance for adverse events is essential to maintain public trust and ensure the long-term success of paediatric influenza vaccination programs.21

Influenza vaccine and serious febrile reactions in children: timeline of key events

2002	Nov	Australia registers thiomersal-free CSL Fluvax trivalent influenza vaccine (TIV) for use in infants and young children
		No prior paediatric safety or efficacy studies of Fluvax have been conducted
2004	Oct	Sweden licenses CSL TIV for use in children aged 6 months or older
		CSL makes a postapproval commitment to conduct a paediatric study
2005	Mar	The first paediatric study of CSL Fluvax commences with 298 children
	Apr	The United Kingdom licenses CSL TIV for use in children aged 6 months or older
	Jun–Dec	Denmark and the Netherlands license CSL TIV for use in children aged over 6 months
2006	Jun	The first paediatric study of CSL Fluvax finishes
		Two study participants experience serious adverse events “possibly” related to the vaccine; one is a febrile seizure
2007	Sep	United States Food and Drug Administration (FDA) gives CSL TIV accelerated approval for adults
		FDA determines that safety and effectiveness of CSL TIV in the paediatric population have not been established
		CSL commits to a paediatric trial using another US-licensed TIV as a control
2008	Mar	US expands influenza vaccinations to include all children 5–18 years of age
2009	Apr	World Health Organization signals that an influenza pandemic is imminent
	Sep	First randomised controlled trial of CSL TIV in children begins in the US
	Nov	FDA licenses CSL TIV for children citing pandemic and vaccine shortage concerns
2010	Apr	CSL 2010 TIV is associated with febrile seizures in up to 1 in 100 vaccinated children in Australia
		Australia temporarily suspends all influenza vaccinations for children aged < 5 years
	Jul	UK recommends not using CSL TIV in children < 5 years for the 2010–2011 season
	Jul	Australia recommends not using 2010 CSL TIV for children < 5 years
	Aug	US recommends not using CSL TIV in children < 5 years for the 2010–2011 season
2011	Jul	Results from first randomised controlled trial of CSL TIV in children become publicly available
		CSL 2009–2010 TIV is associated with higher risk of fever and other adverse events than the US-licensed TIV comparator
2012	Oct	CSL publishes laboratory investigations, but the cause of the adverse events in 2010 remains undetermined

Australian national birthweight percentiles by sex and gestational age, 1998–2007

Typographical errors in tables of birthweight percentiles: In “Australian national birthweight percentiles by sex and gestational age, 1998–2007”, in the 3 September 2012 issue of the Journal (Med J Aust 2012; 197: 291-294; doi: 10.5694/mja11.11331), there were two errors in Box 3 and one in Box 4 (page 293). In Box 3, the 25th percentile for boys with a gestational age of 34 weeks should be 2100 g, not 200 g, and the 3rd percentile for boys with a gestational age of 36 weeks should be 2015 g, not 015 g. In Box 4, the 97th percentile for girls with a gestational age of 31 weeks should be 2146 g, not 246 g.

The corrected birthweight percentile tables are available online (https://www.mja.com.au/journal/2012/197/5/australian-national-birthweight-percentiles-sex-and-gestational-age-1998-2007).