SMS reminders to improve the uptake and timeliness of the primary immunisation series in infants: a multi-centre randomised controlled trial.

Background: Immunisation timeliness continues to present challenges to achieving optimal vaccine coverage in infancy, particularly in disadvantaged groups and Australian First Nations infants. We aimed to determine whether a tailored, educational SMS reminder improves the timeliness of immunisation in infants up to seven months of age. Methods: A pragmatic, three-arm, parallel-group, randomised controlled trial of immunisation reminders was conducted in two First-Nations-specific primary health care centres and two public hospital antenatal clinics in South East Queensland, Australia. Live-born infants of mothers enrolled during pregnancy were randomised at birth and followed to eight months of age. One group received a simple SMS reminder at two weeks before, the week of, and two weeks after the due date for immunisation at two, four and six months of age. The second group received a tailored SMS with an educational message at two weeks before and on the date immunisations were due; those not immunised two weeks following the due date were offered support to immunise the baby. Controls received no intervention or contact until the baby turned seven months of age. The primary outcome was the proportion of infants age-appropriately vaccinated at seven months of age as recorded on the Australian Immunisation Register. Secondary outcomes included vaccination status at three and five months of age. Results: Between 30 May 2016 and 24 May 2018, one hundred and ninety-six infants (31% First Nations infants) were randomised. At seven months of age, 54/65 (83.1%) infants in the educational SMS ± additional support group (ESMS±S) were age-appropriately immunised, compared to 45/64 (70.3%) in the simple SMS group and 45/67 (67.2%) in controls. Differences were most marked at five months of age: ESMS±S 95.5%; simple SMS 73.4%; controls 75.8%. The difference between the ESMS±S group and the other two groups at seven months of age was no longer apparent when those who received additional support beyond the SMS were assumed to have not been vaccinated if that support had not been received. Discussion: A tailored SMS reminder system using an educational message and with provision of additional support to mothers is more effective in improving immunisation timeliness in infants at three and five months of age than a simple message and no intervention. The additional support was required at seven months of age in order to achieve higher coverage in the ESMS±S group.

Risk Factors for Chronic Cough in Young Children: A Cohort Study.

Background and Objective: Data on the predictors of chronic cough development in young children are scarce. Our primary objective was to examine the factors associated with young children developing a chronic cough, with a focus on childcare attendance. Methods: A secondary analysis of data collected in a prospective cohort study of children presenting to three emergency departments and three primary healthcare centers in southeast Queensland, Australia. Eligible children where those aged <6-years presenting with cough and without known underlying chronic lung disease other than asthma. Children were followed for 4 weeks to ascertain cough duration. The primary outcome was persistent cough at day-28. Logistic regression models were undertaken to identify independent predictors of chronic cough including sensitivity analyses that accounted for children with unknown cough status at day-28. Results: In 362 children, 95 (26.2%) were classified as having chronic cough. In models that included only children for whom cough status was known at day-28, symptom duration at enrolment, age <12 months [adjusted odds ratio (aOR) 4.5, 95% confidence interval (CI) 1.1, 18.7], gestational age (aOR 3.2, 95%CI 1.4, 7.9), underlying medical conditions (aOR 2.6, 95% CI 1.3, 5.5), a history of wheeze (aOR 2.6, 95% CI 1.4, 4.8) and childcare attendance (aOR 2.3, 95% CI 1.2, 4.4) were independent predictors of chronic cough. Amongst childcare attendees only, 64 (29.8%) had chronic cough at day-28. The strongest predictor of chronic cough amongst childcare attendees was continued attendance at childcare during their illness (aOR = 12.9, 95% CI 3.9, 43.3). Conclusion: Gestational age, underlying medical conditions, prior wheeze and childcare attendance are risk factors for chronic cough in young children. Parents/careers need to be aware of the risks associated with their child continuing to attend childcare whilst unwell and childcare centers should reinforce prevention measures in their facilities.

Effectiveness of a chronic cough management algorithm at the transitional stage from acute to chronic cough in children: a multicenter, nested, single-blind, randomised controlled trial.

BACKGROUND: Chronic (lasting at least 4 weeks) cough in children is an important cause of morbidity. An algorithmic approach to the management of coughs in children evaluated in observational studies and a randomised controlled trial (RCT) enrolled children referred with median cough duration of 16 weeks to specialist centres. We investigated whether applying an evidence-based cough management algorithm in non-specialist settings earlier, once cough persisted for more than 4 weeks, improved cough resolution compared with usual care. METHODS: We undertook a multicentre, single-blind RCT nested within a prospective cohort study of children (<15 years) in Australia presenting to three primary care or three hospital emergency departments with an acute respiratory illness with cough. Children were excluded if they had a known diagnosis of an underlying chronic medical condition (excluding asthma) or had an immunosuppressive illness or were taking immunomodulating drugs for more than 2 weeks in the preceding 30 days, or had severe symptoms requiring inpatient hospitalisation. Children were followed up for 8 weeks; those with a persistent cough at day 28 were randomly assigned to the cough management algorithm or to usual care. Randomisation was stratified by reason for presentation, study site, and cough duration (4 weeks to <6 weeks vs ≥6 weeks) using computer-generated permuted blocks (block size of four) with a 1:1 allocation. The primary outcome was the proportion of children with cough resolution at day 56 (defined as resolved if the child did not cough for at least 3 days and nights since day 28 or a more than 75% reduction in their average day and night cough score). Absolute risk differences (RDabsolute) were calculated by modified intention-to-treat analysis (ITT). This trial is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12615000132549. FINDINGS: Between July 7, 2015, and Oct 31, 2018, 1018 children were screened, 509 were enrolled in the cohort study, and of 115 children in the ITT analysis, 57 were randomly assigned to the intervention group and 58 to the control group. Children had a median age of 1·6 years (IQR 1·0-4·5); 45 (39%) of 115 were Indigenous, and 59 (51%) were boys. By day 56, 33 (58%) of 57 children in the intervention group achieved cough resolution compared with 23 (40%) 58 in the control group; cough resolution was unknown in 12 (21%) of 57 children receiving the intervention and in 13 (22%) of 58 receiving the control. The RDabsolute assuming children with an unknown cough outcome were still coughing at day 56 was 18·3% (95% CI 0·3-36·2); the number needed-to-treat for benefit was five (95% CI 3-364); the adjusted odds ratio was 1·5 (95% CI 1·3-1·6), favouring the intervention group. INTERPRETATION: This study suggests an evidence-based cough management algorithm improves cough resolution in community-based children in the early phases of chronic cough. However, larger studies to confirm these findings in primary care are required. FUNDING: National Health and Medical Research Council.

The clinical, immunological and microbiological impact of the 10-valent pneumococcal-Protein D conjugate vaccine in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: A multi-centre, double-blind, randomised controlled trial.

We aimed to determine the efficacy of the 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to <18-years with recurrent protracted bacterial bronchitis (rPBB), chronic suppurative lung disease (CSLD) or bronchiectasis. In a multi-centre, double-blind randomised controlled trial, children received two doses, 2-months apart of the 10vPHiD-CV or quadrivalent meningococcal-ACYW135 conjugate vaccine. Active surveillance for acute exacerbations, respiratory symptoms and antibiotic use was undertaken through to 12-months after the second vaccine dose (clinical cohort only). Serum, saliva and nasopharyngeal swabs were collected to measure immunological and microbiological effects (immunology cohort). Between December 2012 and August 2015, 62 children were enrolled onto the clinical protocol (1 excluded from clinical analyses due to unblinding), while 74 contributed to the immunology cohort (overall mean age = 6.8-years (standard deviation = 3.7), 42 (56.8%) male). The absolute risk difference comparing the 10vPHiD-CV group (n = 31 children) to the MenACYW135 group (n = 30 children) for acute exacerbations was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0, 0.9). Compared to the MenACYW135 group, children who received the 10vPHiD-CV were less likely to have respiratory symptoms in each fortnight of surveillance (incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and required fewer short-course (<14-days duration) antibiotics (IDR 0.81, 95% CI 0.61, 1.09). The vaccine was immunogenic and no serious adverse events related to the vaccine were reported. In conclusion, 10vPHiD-CV might have a future role in managing children with rPBB, CSLD and bronchiectasis, but larger multicentre trials are needed to confirm or refute findings from this preliminary study.

Effectiveness of a cough management algorithm at the transitional phase from acute to chronic cough in Australian children aged <15†years: protocol for a randomised controlled trial.

INTRODUCTION: Acute respiratory infections (ARIs) are leading causes of hospitalisation in Australian children and, if recurrent, are associated with increased risk of chronic pulmonary disorders later in life. Chronic (>4 weeks) cough in children following ARI is associated with decreased quality-of-life scores and increased health and societal economic costs. We will determine whether a validated evidence-based cough algorithm, initiated when chronic cough is first diagnosed after presentation with ARI, improves clinical outcomes in children compared with usual care. METHODS AND ANALYSIS: A multicentre, parallel group, open-label, randomised controlled trial, nested within a prospective cohort study in Southeast Queensland, Australia, is underway. 750 children aged <15 years will be enrolled and followed weekly for 8 weeks after presenting with an ARI with cough. 214 children from this cohort with persistent cough at day 28 will be randomised to either early initiation of a cough management algorithm or usual care (107 per group). Randomisation is stratified by reason for presentation, site and total cough duration at day 28 (<6 and ≥6 weeks). Demographic details, risk factors, clinical histories, examination findings, cost-of-illness data, an anterior nasal swab and parent and child exhaled carbon monoxide levels (when age appropriate) are collected at enrolment. Weekly contacts will collect cough status and cost-of-illness data. Additional nasal swabs are collected at days 28 and 56. The primary outcome is time-to-cough resolution. Secondary outcomes include direct and indirect costs of illness and the predictors of chronic cough postpresentation. ETHICS AND DISSEMINATION: The Children's Health Queensland (HREC/15/QRCH/15) and the Queensland University of Technology University (1500000132) Research Ethics Committees have approved the study. The study will inform best-practice management of cough in children. TRIAL REGISTRATION NUMBER: ACTRN12615000132549.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial.

BACKGROUND: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. METHODS: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. DISCUSSION: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12612000034831.