Now showing 1 - 10 of 43
  • Publication
    Journal Article
    Impact of swimming on chronic suppurative otitis media in Aboriginal children: a randomised controlled trial.
    (2013-07-08)
    Stephen ATN
    ;
    Leach AJ
    ;
    To measure the impact of 4 weeks of daily swimming on rates of ear discharge among Aboriginal children with a tympanic membrane perforation (TMP) and on the microbiology of the nasopharynx and middle ear. A randomised controlled trial involving 89 Aboriginal children (aged 5-12 2013s) with a TMP, conducted in two remote Northern Territory Aboriginal communities from August to December 2009. 4 school weeks of daily swimming lessons (45 minutes) in a chlorinated pool. Proportions of children with ear discharge and respiratory and opportunistic bacteria in the nasopharynx and middle ear. Of 89 children randomly assigned to the swimming or non-swimming groups, 58 (26/41 swimmers and 32/48 non-swimmers) had ear discharge at baseline. After 4 weeks, 24 of 41 swimmers had ear discharge compared with 32 of 48 non-swimmers (risk difference, - 8% (95% CI, - 28% to 12%). There were no statistically significant changes in the microbiology of the nasopharynx or middle ear in swimmers or non-swimmers. Streptococcus pneumoniae and non-typeable Haemophilus influenzae were the dominant organisms cultured from the nasopharynx, and H. influenzae, Staphylococcus aureus and Pseudomonas aeruginosa were the dominant organisms in the middle ear. Swimming lessons for Aboriginal children in remote communities should be supported, but it is unlikely that they will substantially reduce rates of chronic suppurative otitis media and associated bacteria in the nasopharynx and middle ear. However, swimming was not associated with increased risk of ear discharge and we found no reason to discourage it. Australian New Zealand Clinical Trials Registry ACTRN12613000634774.
      1385
  • Publication
    Journal Article
    Long-term azithromycin in children with bronchiectasis unrelated to cystic fibrosis: treatment effects over time.
    (2022-08-25)
    Vicendese D
    ;
    Yerkovich S
    ;
    Grimwood K
    ;
    Valery PC
    ;
    Byrnes CA
    ;
    ;
    Dharmage SC
    ;
    Chang AB
    BACKGROUND: Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis (CF) receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and those likely to most benefit remains unknown. RESEARCH QUESTIONS: (i) What is the period following its commencement when azithromycin is most effective? and (ii) What factors may modify azithromycin effects? STUDY DESIGN AND METHODS: A secondary analysis was conducted of our previous randomized controlled trial involving 89 Indigenous children with bronchiectasis unrelated to CF. Semi-parametric poisson regression identified the azithromycin efficacy period. Multivariable poisson regression identified factors that modify azithromycin effect. RESULTS: Azithromycin was associated with fewer exacerbations per child-week during weeks 4-96, with the most effective period observed between weeks 17-62. Eleven factors were associated with different azithromycin effects, four of them were significant at p<0.05 level. Compared with their counterparts, higher reduction in excerbations was observed in: children with nasopharyngeal carriage of bacterial pathogens, [incidence rate ratio, IRR=0.81 (95% confidence interval 0.57 to 1.14) versus 0.29 (0.20 to 0.44), p<0.001]; New Zealand children [IRR=0.73 (0.51 to 1.03) versus 0.39 (0.28 to 0.55), p=0.012]; and those with higher weight-for-height z-scores [interaction IRR=0.82 (0.67 to 0.99), p=0.044]. Compared with their counterparts, lower reduction was observed in those born preterm [IRR=0.41 (0.30 to 0.55) versus 0.74 (0.49 to 1.10), p=0.012]. INTERPRETATION: Regular azithromycin is best used for at least 17-weeks and up to 62-weeks as these periods provide maximum benefit for Indigenous children with bronchiectasis unrelated to CF. Several factors modified azithromycin benefits, however these traits need confirmation in larger studies before being adopted into clinical practice.
      3241
  • Publication
    Journal Article
    Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.
    (2015-11)
    Hare KM
    ;
    Grimwood K
    ;
    Chang AB
    ;
    Chatfield MD
    ;
    Valery PC
    ;
    Leach AJ
    ;
    Smith-Vaughan HC
    ;
    ;
    Byrnes CA
    ;
    Torzillo PJ
    ;
    Cheng AC
    Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.
      1346
  • Publication
    Comparative Study
    Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.
    (2015-01-16)
    Leach AJ
    ;
    Mulholland EK
    ;
    Santosham M
    ;
    Torzillo PJ
    ;
    Brown NJ
    ;
    McIntyre P
    ;
    Smith-Vaughan H
    ;
    Skull S
    ;
    Balloch A
    ;
    Andrews RM
    ;
    Carapetis J
    ;
    McDonnell J
    ;
    ;
    Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection. This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM. Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals. ACTRN12610000544077 and NCT01174849.
      1617
  • Publication
    Journal Article
    Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children.
    (2018-06-29)
    Smith-Vaughan HC
    ;
    Binks MJ
    ;
    Beissbarth J
    ;
    Chang AB
    ;
    McCallum GB
    ;
    Mackay IM
    ;
    ;
    Marsh RL
    ;
    Torzillo PJ
    ;
    Wurzel DF
    ;
    Grimwood K
    ;
    Nosworthy E
    ;
    Gaydon JE
    ;
    Leach AJ
    ;
    MacHunter B
    ;
    Chatfield MD
    ;
    Sloots TP
    ;
    Cheng AC
    Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.
      1314
  • Publication
    Journal Article
    Geographic consistency in dominant, non-typeable Haemophilus influenzae genotypes colonising four distinct Australian paediatric groups: a cohort study.
    (2016)
    Smith-Vaughan HC
    ;
    Beissbarth J
    ;
    Bowman J
    ;
    Hare KM
    ;
    Price EP
    ;
    Pickering J
    ;
    Lehmann D
    ;
    Chang AB
    ;
    ;
    Marsh RL
    ;
    Leach AJ
    Non-typeable Haemophilus influenzae (NTHi)-associated ear and respiratory diseases (including pneumonia) represent a major health burden in many parts of the world. NTHi strains retrieved from the upper airways commonly reflect those found in the lower airways. Despite growing genomic and genotyping data on NTHi, there remains a limited understanding of global and regional NTHi population structures. The aim of this study was to determine whether nasopharyngeal carriage in four Australian paediatric groups at varying risk of NTHi colonisation was dominated by the same NTHi genotypes. Genotyping data generated by PCR-ribotyping were evaluated for 3070 NTHi isolates colonising the nasopharynges of Aboriginal and non-Aboriginal children enrolled in four longitudinal studies in three separate urban and remote regions of Australia. Several NTHi PCR-ribotypes dominated in nasopharyngeal carriage, irrespective of study setting. Principal coordinates analysis confirmed a cluster of common PCR-ribotypes among all cohorts. In conclusion, we identified dominant PCR-ribotypes common to geographically disparate Australian paediatric populations. Future genomic analyses will shed further light on the precise factors underlying the dominance of certain NTHi strains in nasopharyngeal carriage.
      1261
  • Publication
    Journal Article
    Ear, nose and throat surgery: All you need to know about the surgical approach to the management of middle-ear effusions in Australian Indigenous and non-Indigenous children.
    (2017-11)
    Kong K
    ;
    Lannigan FJ
    ;
    ;
    Leach AJ
    ;
    O'Leary SJ
    Otitis media (OM) is a common condition in Australia. It represents a spectrum of diseases from otitis media with effusion (OME) to chronic suppurative otitis media. For all the OM diagnoses, Australian Indigenous children have higher rates of early onset, severe and persistent disease. OME is the most common form of OM and often occurs after an upper respiratory tract infection. It can be difficult to diagnose (and often goes unrecognised). Hearing loss is the most important complication. The middle-ear effusion impedes the movement of the tympanic membrane and causes a conductive hearing loss of around 25 dB. Around 20% will have a hearing loss exceeding 35 dB. Children with early onset, persistent, bilateral OME and hearing loss (or speech delay) are most likely to benefit from interventions. However, the impact of all the effective treatment options is modest. Giving advice about effective communication strategies for young children is always appropriate. The best evidence from randomised trials supports not using antihistamines and/or decongestants, considering a trial of antibiotics and referral for tympanostomy tubes. Despite the availability of evidence-based guidelines, giving advice about treatment is a challenge because recommendations vary according to condition, age, risk of complications and parental preference. While most children with OME can be effectively managed in primary care, we need to get children who meet the criteria for simple ear, nose and throat procedures that improve hearing on to ear, nose and throat surgery waiting lists. Long delays in hearing support may contribute to life-long social and economic disadvantage.
      1319
  • Publication
    Journal Article
    Impact of the 23-valent pneumococcal polysaccharide vaccination in pregnancy against infant acute lower respiratory infections in the Northern Territory of Australia.
    (2018-12-25)
    Binks MJ
    ;
    Moberley SA
    ;
    Balloch A
    ;
    Leach AJ
    ;
    Nelson S
    ;
    Hare KM
    ;
    Wilson C
    ;
    Nelson J
    ;
    ;
    Ware RS
    ;
    Tang MLK
    ;
    Torzillo PJ
    ;
    Carapetis JR
    ;
    Mulholland K
    ;
    Andrews RM
    Indigenous children in Australia's Northern Territory are densely colonised with the pneumococcus within weeks of birth antecedent to a high prevalence of acute lower respiratory infection (ALRI). We assessed the impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in pregnancy against infant ALRI in this setting. In an open label, allocation concealed, outcome-assessor blinded, randomised controlled trial conducted in the Northern Territory of Australia, healthy Indigenous women aged 17-39 years were randomised to receive the 23vPPV during pregnancy (n = 75; 30-36 weeks gestation), at birth (n = 75), or at 7 months post-partum (n = 77). Randomisation was stratified by community of residence. In a secondary analysis, we compared the incidence of ALRI hospitalisations and ALRI clinic presentations (ascertained from electronic medical records) among infants of pregnancy vaccinees versus infants of mothers not vaccinated in pregnancy (controls) in the first year of life. ALRI hospitalisation incidence was 12.3 per 100 child-years among infants of pregnancy vaccinees compared with 15.8 per 100 child-years among controls (hazard ratio (HR) 0.77, 95%CI 0.29-2.03). ALRI hospitalisations were more common among remote compared to urban infants (27.7 versus 8.6 per 100 child-years). Stratification by dwelling highlighted a differential antenatal vaccine effect against ALRI hospitalisations (urban HR 2.45, 95%CI 0.60-9.99; remote HR 0.21, 95%CI 0.04-1.08). ALRI clinic presentation incidence was similar among infants of pregnancy vaccinees and controls. In this small study, antenatal 23vPPV vaccination was not associated with a reduced incidence of infant ALRI hospitalisations or ALRI clinic presentations during the first year of life. A potential differential effect between urban and remote settings warrants further investigation. PneuMum; ClinicalTrials.gov NCT00714064.
      1199
  • Publication
    Journal Article
    Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001.
    (2009-08-04)
    Leach AJ
    ;
    ;
    McCallum GB
    ;
    Wilson CA
    ;
    Stubbs L
    ;
    Beissbarth J
    ;
    Jacups S
    ;
    Hare K
    ;
    Smith-Vaughan HC
    In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule. We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs) in 2003 and 2005. Nasal secretions were collected and processed according to published methods. 902 children (mean age 25 months) living in 29 communities in 2003 and 818 children (mean age 35 months) in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order) 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > or = 0.12 microg/mL) strains (15% overall) was detected in serotypes (descending order) 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > or = 2 microg/mL) strains (5% overall), was detected in serotypes (descending order) 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Pneumococcal carriage remains high (approximately80%) in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined years were 16F, 19A, 11A, 6C and 23B. Antimicrobial non-susceptibility was detected in these and 17 additional serotypes. Shifts in serotype-specific carriage suggest a need more research to clarify the association between pneumococcal vaccination and carriage at the serotype level.
      1312
  • Publication
    Journal Article
    The short-term impact of each primary dose of pneumococcal conjugate vaccine on nasopharyngeal carriage: Systematic review and meta-analyses of randomised controlled trials.
    (2016-02-03)
    Nicholls TR
    ;
    Leach AJ
    ;
    Early onset of persistent otitis media is a priority issue for Australian Indigenous populations. The objective is to determine the direct and short-term impact of one, two and three doses of any pneumococcal conjugate vaccine (PCV) formulation on nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi), the otopathogens targeted by current PCVs. We searched MEDLINE (PubMed) and CENTRAL (Cochrane Library) to 29 September 2015. We also scanned reference lists of recent reviews and contacted authors. We included randomised controlled trials (RCTs) with a PCV schedule commencing ≤3 months of age that reported controlled non-cumulative group-specific prevalence data for carriage of Spn or NTHi at age<12 months. We performed a standard risk of bias assessment. We estimated the pooled relative risk (RR) and 95% confidence interval (95%CI) for each vaccine dose on NP carriage by meta-analysis. We included 16 RCTs involving 14,776 participants. The PCVs were conjugated to diphtheria toxin CRM197, diphtheria toxoid, tetanus toxoid or NTHi protein D and varied in valency (4-13). Controls were non-PCVs, placebo or no vaccine. The earliest carriage outcome was from 2 to 9 months of age. Compared to controls, there were no significant differences between one or two doses of PCV on vaccine-type (VT) pneumococcal carriage at ∼4 and ∼6 months respectively. However, VT carriage was significantly lower at ∼7 months RR 0.67 95%CI 0.56-0.81 from 9 studies and 7613 infants and non-vaccine type (NVT) carriage was higher RR 1.23 95%CI 1.09-1.40 from 8 studies and 5861 infants. No impact on overall pneumococcal or NTHi carriage was found. The primary PCV schedule had no significant short-term impact on overall pneumococcal or NTHi NP carriage and a limited impact on VT pneumococcal carriage before the third dose.
      1237