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.

Nasopharyngeal carriage of otitis media pathogens in infants receiving 10-valent non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10), 13-valent pneumococcal conjugate vaccine (PCV13) or a mixed primary schedule of both vaccines: A randomised controlled trial.

BACKGROUND: Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? METHODS: Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. FINDINGS: At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). CONCLUSIONS: Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

Preventative and medical treatment of ear disease in remote or resource-constrained environments.

BACKGROUND: Important ear problems can affect the outer ear, the middle ear and the inner ear. Globally, the greatest burden of disease is due to ear conditions that are associated with otorrhoea and hearing loss. METHODS: This study reviewed the literature on the prevention and treatment of common ear conditions that are most relevant to settings with high rates of ear disease and limited resources. The grading of recommendations assessment, development and evaluation ('GRADE') approach was utilised to assess interventions. RESULTS: Accurate diagnosis of ear disease is challenging. Much of the preventable burden of ear disease is associated with otitis media. Nine otitis media interventions for which there is moderate to high certainty of effect were identified. While most interventions only provide modest benefit, the impact of treatment is more substantial in children with acute otitis media with perforation and chronic suppurative otitis media. CONCLUSION: Disease prevention through good hygiene practices, breastfeeding, reducing smoke exposure, immunisation and limiting noise exposure is recommended. Children with acute otitis media with perforation, chronic suppurative otitis media, complications of otitis media, and significant hearing loss should be prioritised for medical treatment.

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.

Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012.

INTRODUCTION: Australian Indigenous children suffer a high burden of diarrhoeal disease. Nitazoxanide is an antimicrobial that has been shown to be effective against a broad range of enteropathogens. To date, its use has not been reported in the tropical Top End (northernmost part) of the Northern Territory, Australia. The objective was to describe the use of nitazoxanide at the Royal Darwin Hospital, Northern Territory, and to assess any association with the time to resolution of diarrhoea. METHODS: Eligible children (≤13 years) were identified from dispensary records as having been prescribed nitazoxanide during the audit period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal aetiology, treatment details and clinical outcomes were obtained by chart review. RESULTS: Twenty-eight children were treated with nitazoxanide, mostly for Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was evident in 27 (96%) children on admission, and 11 (41%) were underweight. Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days post-admission). For children ≥12 months, nitazoxanide was prescribed according to guidelines stipulated by the Centers for Disease Control and Prevention (CDC). Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after starting treatment. An increase in weight for length at discharge was found for all children. CONCLUSIONS: Prompt resolution of diarrhoea without adverse outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium infection in this setting. Its role in the treatment of other causes of infectious diarrhoea needs further investigation. Randomised trials will further direct its use and determine optimal dosing regimens.

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.

Can a management pathway for chronic cough in children improve clinical outcomes: protocol for a multicentre evaluation.

BACKGROUND: Chronic cough is common and is associated with significant economic and human costs. While cough can be a problematic symptom without serious consequences, it could also reflect a serious underlying illness. Evidence shows that the management of chronic cough in children needs to be improved. Our study tests the hypothesis that the management of chronic cough in children with an evidence-based management pathway is feasible and reliable, and improves clinical outcomes. METHODS/DESIGN: We are conducting a multicentre randomised controlled trial based in respiratory clinics in 5 major Australian cities. Children (n = 250) fulfilling inclusion criteria (new patients with chronic cough) are randomised (allocation concealed) to the standardised clinical management pathway (specialist starts clinical pathway within 2 weeks) or usual care (existing care until review by specialist at 6 weeks). Cough diary, cough-specific quality of life (QOL) and generic QOL are collected at baseline and at 6, 10, 14, 26, and 52 weeks. Children are followed-up for 6 months after diagnosis and cough resolution (with at least monthly contact from study nurses). A random sample from each site will be independently examined to determine adherence to the pathway. Primary outcomes are group differences in QOL and proportion of children that are cough free at week 6. DISCUSSION: The clinical management pathway is based on data from Cochrane Reviews combined with collective clinical experience (250 doctor years). This study will provide additional evidence on the optimal management of chronic cough in children. TRIAL REGISTRATION: ACTRN12607000526471.

A comprehensive approach to health promotion for the reduction of dental caries in remote Indigenous Australian children: a clustered randomised controlled trial.

AIM: To evaluate the effect of a community-oriented primary health care (CPHC) intervention on oral health behaviours of Indigenous preschool children living in remote communities of Australia's Northern Territory. METHODS: The study was a community-clustered randomised controlled trial over two years, set in 30 remote Indigenous communities in the Northern Territory of Australia. Children aged 18-47 months at baseline were enrolled in the study. The intervention included fluoride varnish applications, training of primary care workers, and health promotion for oral health at an individual, family and community level. Intervention communities received six-monthly visits over two years and control communities were visited at baseline and two years later with no contact in the intervening period. The outcome measures reported in this paper are the impact of the intervention on two secondary endpoints: oral health promotion activities in the community and personal oral health practice of children. RESULTS: The intervention did not produce any significant change in oral health behaviours, clinical measures of oral hygiene, or community programmes promoting oral health. Dental caries can be reduced but will continue to be a problem among young remote Indigenous children while they experience major social disadvantage.

Age-specific cluster of cases of serotype 1 Streptococcus pneumoniae carriage in remote indigenous communities in Australia.

Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian indigenous infants. Pneumococcal carriage surveillance detected substantial replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our aim was to review Streptococcus pneumoniae serotype 1 carriage and invasive pneumococcal disease (IPD) data for this population and to analyze serotype 1 isolates. Carriage data were collected between 1992 and 2004 in the Darwin region, one of the five regions in the Northern Territory. Carriage data were also collected in 2003 and 2005 from four regions in the Northern Territory. Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by multilocus sequence typing. In the Darwin region, 26 children were reported carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered cases of serotype 1 carriage were noted in two other regions. Cocolonization of serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive swabs). In conclusion, pneumococcal carriage studies detected intermittent serotype 1 carriage and an ST227 cluster in children in indigenous communities in the Northern Territory of Australia. There was no apparent increase in serotype 1 IPD during this time. The rate of serotype 1 cocolonization with other pneumococcal serotypes suggests that carriage of this serotype may be underestimated.

Culture-specific programs for children and adults from minority groups who have asthma.

BACKGROUND: People with asthma who come from minority groups have poorer asthma outcomes and more asthma related visits to Emergency Departments (ED). Various programmes are used to educate and empower people with asthma and these have previously been shown to improve certain asthma outcomes. Models of care for chronic diseases in minority groups usually include a focus of the cultural context of the individual and not just the symptoms of the disease. Therefore, questions about whether culturally specific asthma education programmes for people from minority groups are effective at improving asthma outcomes, are feasible and are cost-effective need to be answered. OBJECTIVES: To determine whether culture-specific asthma programmes, in comparison to generic asthma education programmes or usual care, improve asthma related outcomes in children and adults with asthma who belong to minority groups. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles. The latest search was performed in March 2007. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing the use of culture-specific asthma education programmes with generic asthma education programmes, or usual care, in adults or children from minority groups who suffer from asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently selected, extracted and assessed the data for inclusion. We contacted authors for further information if required. MAIN RESULTS: Three studies were eligible for inclusion in the review. A total of 396 patients, aged from 7 to 59 years were included in the meta-analysis of data. Use of a culture-specific programme was superior to generic programmes or usual care, in improving asthma quality of life scores in adults, pooled WMD 0.25 (95% CI 0.09 to 0.41) and asthma knowledge scores in children, WMD 3.30 (95% CI 1.07 to 5.53). There was no significant difference between groups in occurrence of asthma exacerbations, but the width of the confidence interval means that effects on exacerbation rates cannot be ruled out, rate ratio 0.93 (95% CI 0.80 to 1.10). AUTHORS' CONCLUSIONS: Culture-specific programmes for adults and children from minority groups with asthma, have been found to be more effective than generic programmes in improving some (Quality of Life and asthma knowledge) but not all asthma outcomes. This evidence is limited by the small number of included studies and the lack of reported outcomes. Further trials are required to answer this question conclusively.

Clinical pathways for chronic cough in children.

BACKGROUND: Chronic cough (a cough lasting longer than 4 weeks) is a common symptom presenting to primary care in Australia and internationally. Chronic cough costs the community, is distressing to parents, and ignoring cough may lead to delayed diagnosis and illness progression of serious underlying respiratory disease. Clinical guidelines have been shown to provide more efficient and effective patient care and can clarify clinical decision making. Cough guidelines have been designed to facilitate management of chronic cough, however treatment recommendations vary and specific clinical pathways for the treatment of chronic cough in children are important, as the cause and treatments for cough in a child vary significantly adults. Therefore, it would be beneficial to clinical practice to systematically evaluate the use of clinical pathways for the treatment of chronic cough in children. OBJECTIVES: To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. SEARCH STRATEGY: The Cochrane Register of controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The search was carried out in May 2007. SELECTION CRITERIA: All randomised controlled trials with parallel group design comparing use vs non-use of a clinical pathway for treatment of chronic cough in children. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against the pre-determined criteria for inclusion. Two reviewers independently selected the studies and it was planned that data extraction would have been done in duplicate. MAIN RESULTS: The search identified 471 potentially relevant titles but no studies met criteria for inclusion in the review. AUTHORS' CONCLUSIONS: Without further available evidence, recommendations for the use of clinical pathways for the treatment of chronic cough in children cannot be made. Until further evidence is available, the decision for further investigation and treatment for the child presenting with chronic cough should be made on an individual basis (i.e. dependent on symptoms and signs) with consideration for existing data from other Cochrane reviews on specific treatments for cough. Trials are required to provide evidence on the effectiveness of clinical pathways for the treatment of chronic cough in children.

Influenza vaccine for children and adults with bronchiectasis.

BACKGROUND: Bronchiectasis is a major cause of respiratory morbidity especially in developing countries. In affluent countries, bronchiectasis is increasingly recognised in certain subsections of communities (e.g. Aboriginal communities) as well as a coexistent disease/comorbidity and disease modifier in respiratory diseases such as COPD (reported rates of 29-50% in adults). Respiratory exacerbations in people with bronchiectasis are associated with reduced quality of life, accelerated pulmonary decline, hospitalisation and even death. Current recommendations for inactivated influenza vaccination includes adults aged 65 years and over, those in residential care and health care workers and also all adults and children with chronic illness, particularly cardiac and pulmonary diseases. OBJECTIVES: To evaluate the effectiveness of influenza vaccine as routine management in children and adults with bronchiectasis in (a) reducing the severity and frequency of respiratory exacerbations and (b) pulmonary decline SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. Pharmaceutical manufacturers of influenza were also contacted. The latest searches were performed in July 2006. SELECTION CRITERIA: All randomised controlled trials with at least one annual influenza vaccine involving children or adults with bronchiectasis. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. It was planned that two independent reviewers selected, extracted and assessed data for inclusion. MAIN RESULTS: No eligible trials were identified and thus no data were available for analysis. AUTHORS' CONCLUSIONS: There is neither evidence for, nor against, routine annual influenza vaccination for children and adults with bronchiectasis.

Pneumococcal vaccines for children and adults with bronchiectasis.

BACKGROUND: Bronchiectasis is increasingly recognized as a major cause of respiratory morbidity especially in developing countries. Even in affluent countries, bronchiectasis is increasingly seen in some community subsections (e.g. Aboriginal communities) and occurs as a comorbidity and disease modifier in respiratory diseases such as chronic obstructive pulmonary disease (COPD). Respiratory exacerbations in people with bronchiectasis is associated with reduced quality of life, accelerated pulmonary decline, hospitalisation and even death. Conjugate pneumococcal vaccine is part of the routine infant immunisation schedule in many countries. Current recommendations for additional pneumococcal vaccination include children and adults with chronic suppurative disease. OBJECTIVES: To evaluate the effectiveness of pneumococcal vaccine as routine management in children and adults with bronchiectasis in (a) reducing the severity and frequency of respiratory exacerbations and (b) pulmonary decline. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. Pharmaceutical manufacturers of pneumococcal vaccines were also contacted. The latest searches were performed in October 2006. SELECTION CRITERIA: All randomised controlled trials that utilised pneumococcal vaccine on children and adults with bronchiectasis. All types of pneumococcal vaccines were included. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data was available for analysis. One small non-randomised controlled trial in children was reported. MAIN RESULTS: No randomised controlled trials pertaining effectiveness of pneumococcal vaccine as routine management in children and adults with bronchiectasis were found. A benefit in elimination of Strep. pneumoniae in the sputum was found in a non-randomised trial in children but no clinical effect was described. AUTHORS' CONCLUSIONS: At present, there is a lack of reliable evidence to support or refute the routine use of pneumococcal vaccine as routine management in children and adults with bronchiectasis. Randomised controlled trials examining the efficacy of this intervention using various vaccine types in different age groups are needed. Until further evidence is available, it is recommended that health providers adhere to national guidelines.

Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era.

Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a diverse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.

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.

Antibiotics for the prevention of acute and chronic suppurative otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a common childhood illness. These middle ear infections may be frequent and painful. AOM may be associated with perforation of the tympanic membrane and can progress to chronic suppurative otitis media (CSOM). OBJECTIVES: To determine the effectiveness of long-term antibiotics (for longer than six weeks) in preventing any AOM, AOM with perforation and CSOM. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (January 1966 to March Week 3 2006), OLD MEDLINE (1950 to 1965), EMBASE (1990 to December 2005) and the references of relevant studies. SELECTION CRITERIA: All randomised controlled trials of long-term (longer than six weeks) antibiotics versus placebo or no treatment for the prevention of AOM, AOM with perforation, or CSOM were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data for: any AOM; episodes of AOM; any recurrent AOM; episodes of illness; any side effects; any antibiotic resistance, as well as outcomes at end of intervention (any AOM); and following cessation of intervention (any AOM). For dichotomous outcomes, the summary risk ratio (fixed and random-effects models) was calculated. For rate outcomes, the summary incidence rate ratio was calculated. MAIN RESULTS: Sixteen studies involving 1483 children met our inclusion criteria. All studies enrolled children at increased risk of AOM, and in seven studies the children were prone to otitis media. The majority of studies were high quality and most (15 studies) reported data for our primary outcomes. None reported AOM with perforation or CSOM. Long-term antibiotics reduced any episode of AOM (13 studies, 1358 children, risk ratio (RR) 0.62, 95% CI 0.52 to 0.75; random-effects model) and number of episodes of AOM (12 studies, 1112 children, incidence rate ratio (IRR) 0.48, 95% CI 0.37 to 0.62; random-effects model). Approximately five children would need to be treated long term to prevent one child experiencing AOM whilst on treatment. Antibiotics prevented 1.5 episodes of AOM for every 12 months of treatment per child. Statistical heterogeneity was explored. Long-term antibiotics were not associated with a significant increase in adverse events (11 studies, 714 children, RR 1.99, 95% CI 0.25 to 15.89; random-effects model). AUTHORS' CONCLUSIONS: For children at risk, antibiotics given once or twice daily will reduce the probability of AOM while the child is on treatment. Antibiotics will reduce the number of episodes of AOM per year from around three to around 1.5. We believe that larger absolute benefits are likely in high-risk children. These conclusions were not affected by sensitivity analyses.

Missed opportunities for a diagnosis of acute otitis media in Aboriginal children.

OBJECTIVE: Severe otitis media and its sequelae are common in rural and remote Aboriginal children. Identification of acute otitis media (AOM) is likely to reduce the number of children who go on to develop chronic suppurative otitis media and associated complications. The aim of this study was to compare the diagnoses made by researchers with that documented in the medical records of children admitted to the paediatric isolation ward of the Royal Darwin Hospital, Darwin, Northern Territory. METHODS: Children aged <8 years admitted to Royal Darwin Hospital were eligible for assessment by pneumatic otoscopy, video-otoscopy and tympanometry. A diagnosis was made for each child according to the state of their worst ear. Comparisons were made between the researcher diagnoses of ear disease and those documented in the hospital notes by medical staff. RESULTS: Thirty-one children were enrolled during 32 admissions. Most were aged <2 years, Aboriginal, and resided in remote communities. Sixty-one video-otoscopic assessments were attempted and sufficiently good images to allow diagnosis were obtained in 105 of 122 ears. Acute otitis media was diagnosed by the research team in 20 of 32 child admissions. Of 29 children who had ear examinations documented by hospital staff, only seven had a diagnosis of AOM recorded. Overall, the research team were almost three times more likely to make this diagnosis (relative risk 2.9, 95% confidence interval 1.6, 5.2). This difference was unlikely to have occurred by chance (P = 0.0002, McNemar's Chi-squared test). CONCLUSIONS: In this small study, young Aboriginal children with clear bulging of their tympanic membrane were not diagnosed with AOM by medical staff. Further training in diagnosis, including cleaning of the ear canal, may lead to more accurate assessment and appropriate recommendations for ongoing management.

Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.

Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.

Perspectives on infective ear disease in indigenous Australian children.

Australian Aboriginal children experience the highest rates of bacterial respiratory diseases reported in the literature. Neonatal acquisition of multiple bacterial pathogenic species and strains predicts persistent and severe disease throughout childhood, particularly infective ear disease. The dynamics of bacterial nasopharyngeal colonization and transmission are poorly understood. The importance of host factors, bacterial competition and co-operation in the transition from asymptomatic carriage to disease are also uncertain. Treatment outcomes are poor, possibly due to the high density of bacterial infection following early age exposure, poor compliance and increasing levels of antibiotic resistance. The relationship between antibiotic use, clinical outcomes and bacterial resistance needs to be better understood in high-risk populations if the benefits associated with treatment are to be maximized. While there is an urgent need for vaccines, the early age of infection and the high rates of transmission and bacterial antigenic diversity mean these may also be less effective than predicted from studies in low-risk populations.