Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

The expanding role of extracorporeal membrane oxygenation retrieval services in Australia.

Herein we detail the cases of three patients transferred on veno-arterial extracorporeal membrane oxygenation (VA ECMO) from a tertiary referral hospital to an ECMO centre. We highlight the benefits of such a transfer and offer this as a model of care for unwell patients likely to require a prolonged period of ECMO support.

Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

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 Maori 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.

Screening and treating pulmonary arterial hypertension in a tertiary hospital-based multidisciplinary clinic: the first 200 patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) is an increasingly recognised serious illness with insidious onset, delayed diagnosis, complex diagnostic algorithms and poor prognosis, but with recently available effective treatments. AIMS: To efficiently diagnose and to offer treatment for PAH, we established a multidisciplinary service in 2005, where patients attend a clinic staffed by specialists in cardiology, respiratory medicine, rheumatology and immunology in a tertiary referral hospital setting. METHODS: We studied the first 200 patients referred. Serology, echocardiography, lung function tests, high-resolution computed tomography, World Health Organisation Class determination and 6-min walk tests and/or right heart catheterisation were performed, as clinically indicated. RESULTS: Of the 200 patients seen, 66 had confirmed pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg) diagnosed on echocardiography ± right heart catheterisation. Of these patients, 58 had catheter-proven PAH (mean pulmonary artery pressure > 25 mmHg with mean wedge pressure < 15 mmHg). Underlying diagnoses for the confirmed PAH patients were idiopathic (32), scleroderma-associated (14), other connective tissue disease (4) and associated with congenital heart disease (8). Patients with confirmed PAH were commenced on PAH-specific therapy--initially bosentan in the majority but sildenafil, and iloprost were occasionally used initially for patient-specific reasons. Median time from when the patient first called the clinic to prescription of therapy was 16 days (interquartile range; 0-31 days). All surviving patients with PAH have attended for regular 6-monthly follow-up visits with a 100% retention rate up to 4 years. CONCLUSION: A multidisciplinary clinic can provide efficient diagnosis and rapid triage to PAH-specific therapy, if appropriate. Retention rates remain high, at follow up.

Impact of recent antibiotics on nasopharyngeal carriage and lower airway infection in Indigenous Australian children with non-cystic fibrosis bronchiectasis.

Indigenous Australian children have increased rates of bronchiectasis. Despite a lack of high-level evidence on effectiveness and antibiotic resistance, these children often receive long-term antibiotics. In this study, we determined the impact of recent macrolide (primarily azithromycin) and ß-lactam antibiotic use on nasopharyngeal colonisation, lower airway infection (>10(4) CFU/mL of bronchoalveolar lavage fluid culture) and antibiotic resistance in non-typeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Moraxella catarrhalis isolates from 104 Indigenous children with radiographically confirmed bronchiectasis. Recent antibiotic use was associated with significantly reduced nasopharyngeal carriage, especially of S. pneumoniae in 39 children who received macrolides [odds ratio (OR)=0.22, 95% confidence interval (CI) 0.08-0.63] and 26 children who received ß-lactams (OR=0.07, 95% CI 0.01-0.32), but had no significant effect on lower airway infection involving any of the three pathogens. Children given macrolides were significantly more likely to carry (OR=4.58, 95% CI 1.14-21.7) and be infected by (OR=8.13, 95% CI 1.47-81.3) azithromycin-resistant S. pneumoniae. Children who received ß-lactam antibiotics may be more likely to have lower airway infection with ß-lactamase-positive ampicillin-resistant NTHi (OR=4.40, 95% CI 0.85-23.9). The risk of lower airway infection by antibiotic-resistant pathogens in children receiving antibiotics is of concern. Clinical trials to determine the overall benefit of long-term antibiotic therapy are underway.

International retrieval of adults on extracorporeal membrane oxygenation support.

A retrieval service was established in New South Wales to provide mobile extracorporeal membrane oxygenation support to patients with severe, acute cardiac or respiratory failure. This service has also retrieved four adult patients from Nouméa, New Caledonia to Sydney on extracorporeal membrane oxygenation support, which are the first international retrievals of this type from Australia. We discuss our experience with these patients, three of whom survived to hospital discharge. However, one patient referred from New Caledonia died before extracorporeal membrane oxygenation could be established.

Retrieval of critically ill adults using extracorporeal membrane oxygenation: an Australian experience.

PURPOSE: A retrieval program was developed in New South Wales (NSW), Australia to provide extracorporeal membrane oxygenation support (ECMO) for the safe transport of adults with severe, acute respiratory or cardiac failure. We describe the development and results of this program and the impact of the 2009 H1N1 epidemic on this service. METHODS: An observational study of all patients who were retrieved on ECMO support in NSW, from March 1, 2007 to June 1, 2010, was carried out. RESULTS: Forty adult patients were retrieved on ECMO support (median age 34 years). The indications for retrieval were respiratory in 38 patients (of whom 16 were confirmed or suspected H1N1 cases) and cardiac in 2 patients. Two other patients died after referral but before ECMO support could be established. Patients were transported by road (n = 26, 65%), medical retrieval jet (n = 10, 25%) and helicopter (n = 4, 10%). The median retrieval distance was 250 km (range 12-1,960 km). Thirty-four patients (85%) survived to hospital discharge. Survival for respiratory indications was 87% (33/38 patients) and 50% (1/2 patients) for cardiac indications. There were no deaths or major morbidity associated with these retrievals. CONCLUSIONS: Patients with very severe respiratory failure, which was considered to preclude conventional ventilation for safe transfer to tertiary centres, were managed by an ECMO referral and retrieval program in NSW and had a high rate of survival. This program also enhanced the capacity of the state to respond to a surge in demand for ECMO support due to the H1N1 epidemic, although the role of ECMO in respiratory failure is not yet well defined.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia.

OBJECTIVE: To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. METHODS: We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. FINDINGS: There were 526 pneumonia events among 10,600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. CONCLUSION: There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia.

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001-2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI -43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.

Lower respiratory tract infections.

Acute lower respiratory infections (ALRI) are the major cause of morbidity and mortality in young children worldwide. ALRIs are important indicators of the health disparities that persist between Indigenous and non-Indigenous children in developed countries. Bronchiolitis and pneumonia account for the majority of the ALRI burden. The epidemiology, diagnosis, and management of these diseases in Indigenous children are discussed. In comparison with non-Indigenous children in developing countries they have higher rates of disease, more complications, and their management is influenced by several unique factors including the epidemiology of disease and, in some remote regions, constraints on hospital referral and access to highly trained staff. The prevention of repeat infections and the early detection and management of chronic lung disease is critical to the long-term respiratory and overall health of these children.

An overview of acute otitis media in Australian Aboriginal children living in remote communities.

Australian Aboriginal children experience early, persistent and severe middle ear infections. We conducted a review of the medical literature that addressed acute otitis media (AOM) in Australian Aboriginal children. Comparisons were made with the recent guidelines on the diagnosis and management of AOM prepared by the American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis media in Aboriginal children living in remote communities begins in the first 3 months of life following early bacterial colonisation. Young children with persistent signs of suppurative disease (bulging of the tympanic membrane or middle ear discharge) are probably most at risk of developing chronic suppurative otitis media.

Non-CF bronchiectasis: clinical and HRCT evaluation.

Childhood bronchiectasis not related to underlying disease is still common in some populations in affluent countries. The aims of the study were to: 1) describe demographics, 2) evaluate the effectiveness of routine investigations, and 3) determine the relationship between spirometry and radiology scoring systems, in children with chronic suppurative lung disease (CSLD) living in Central Australia. Data of children living in Central Australia aged 70%) and early hospitalisation for pneumonia were common (median age, 0.5 years). Previous admissions for pneumonia were almost universally present and significantly more common than bronchiolitis (95% CI for proportional difference, 0.4-0.51). Although the majority did not have a treatable underlying cause, investigations had significant impact on management in 12.3% of children. None of the chest HRCT scores related to any spirometry data. In conclusion, CSLD is unacceptably common in indigenous children of this region, commences early in life, and is associated with significant comorbidities. Spirometry data do not reflect the severity of lung disease in HRCT scans. While improvement in the living standards is of utmost importance, the medical management that includes thorough investigations of these children should not be neglected.

Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease.

BACKGROUND: Published data on the frequency and types of flexible bronchoscopic airway appearances in children with non-cystic fibrosis bronchiectasis and chronic suppurative lung disease are unavailable. The aims of this study were to describe airway appearances and frequency of airway abnormalities and to relate these airway abnormalities to chest high resolution computed tomography (cHRCT) findings in a cohort of children with non-cystic fibrosis chronic suppurative lung disease (CSLD). METHODS: Indigenous children with non-cystic fibrosis CSLD (>4 months moist and/or productive cough) were prospectively identified and collected over a 2.5 year period at two paediatric centres. Their medical charts and bronchoscopic notes were retrospectively reviewed. RESULTS: In all but one child the aetiology of the bronchiectasis was presumed to be following a respiratory infection. Thirty three of the 65 children with CSLD underwent bronchoscopy and five major types of airway findings were identified (mucosal abnormality/inflammation only, bronchomalacia, obliterative-like lesion, malacia/obliterative-like combination, and no macroscopic abnormality). The obliterative-like lesion, previously undescribed, was present in 16.7% of bronchiectatic lobes. Structural airway lesions (bronchomalacia and/or obliterative-like lesion) were present in 39.7% of children. These lesions, when present, corresponded to the site of abnormality on the cHRCT scan. CONCLUSIONS: Structural airway abnormality is commonly found in children with post-infectious bronchiectasis and a new bronchoscopic finding has been described. Airway abnormalities, when present, related to the same lobe abnormality on the cHRCT scan. How these airway abnormalities relate to aetiology, management strategy, and prognosis is unknown.

Acute respiratory failure secondary to chronic obstructive pulmonary disease treated in the intensive care unit: a long term follow up study.

BACKGROUND: Traditionally, patients with acute respiratory failure due to chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU) are believed to have a poor outcome. A study was undertaken to explore both hospital and long term outcome in this group and to identify clinical predictors. METHODS: A retrospective review was carried out of consecutive admissions to a tertiary referral ICU over a 6 year period. This group was then followed prospectively for a minimum of 3 years following ICU admission. RESULTS: A total of 74 patients were admitted to the ICU with acute respiratory failure due to COPD during the study period. Mean forced expiratory volume in 1 second (FEV1) was 0.74 (0.34) l. Eighty five per cent of the group underwent invasive mechanical ventilation for a median of 2 days (range 1-17). The median duration of stay in the ICU was 3 days (range 2-17). Survival to hospital discharge was 79.7%. Admission arterial carbon dioxide tension (PaCO2) and APACHE II score were independent predictors of hospital mortality on multiple regression analysis. Mortality at 6 months, 1, 2, and 3 years was 40.5%, 48.6%, 58.1%, and 63.5%, respectively. There were no independent predictors of mortality in the long term. CONCLUSIONS: Despite the need for invasive mechanical ventilation in most of the study group, good early survival was observed. Mortality in the long term was significant but acceptable, given the degree of chronic respiratory impairment of the group.

Incident sexually transmitted infections and their risk factors in an Aboriginal community in Australia: a population based cohort study.

OBJECTIVE: To identify risk factors for incident sexually transmitted infections (STI) in a remote Aboriginal community in Australia. DESIGN: A population based cohort study. SETTING: An Aboriginal community in central Australia. PARTICIPANTS: 1034 Aboriginal people aged 12-40 years, resident in the study region, seen during the period 1 January 1996 to 30 June 1998 for STI diagnosis. MAIN OUTCOME MEASURES: Incident rate of gonorrhoea, chlamydia, and syphilis per 100 person years. RESULTS: There were 313 episodes of incident gonorrhoea, 240 of incident chlamydial infection, and 17 of incident syphilis. For gonorrhoea, risk factors were age, substance abuse, and previous prevalent chlamydial infection with a rate ratio (RR) of 3.2 in people aged 15-19 years, 1.6 in people who abused alcohol, and 3.2 in women who had sniffed petrol on a regular basis. For chlamydia, risk factors were sex, age, and a previous history of STI with a RR of 2.7 in people aged 15-19 years. Similar factors were associated with an increased risk of syphilis but the associations were not statistically significant. CONCLUSION: This study identified objective predictors of incident STI which can be used to target interventions and maximise their impact. The results of this study may well have relevance to indigenous communities in other countries that are faced with high levels of STI and substance abuse.

Conjugate pneumococcal vaccines for aboriginal children in Australia.

Research indicates a high burden of pneumococcal disease and great potential benefits of conjugate vaccines in Indigenous Australian children, who should have high priority for delivery of these vaccines. Incidence of invasive pneumococcal disease in Indigenous people in central Australia is the highest reported in the world (2053 per 100,000 persons per year in those aged under two years). Acute respiratory infection is a major cause of morbidity in Indigenous children in rural and remote areas. Early pneumococcal colonisation of the nasopharynx and high rates of carriage are seen in Indigenous children, and are probably related to their high rates of ear disease. Current seven-valent conjugate vaccines are likely to cover about two-thirds of invasive isolates in Indigenous Australian children; 11-valent vaccines will cover a higher proportion. Questions remain about the best vaccine carrier protein and the likely impact of vaccine on ear disease, pneumococcal carriage and antibiotic resistance.