Paediatrics (RCH) - Research Publications
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ItemCan child pneumonia in low-resource settings be treated without antibiotics? A systematic review & meta-analysis(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: WHO guidelines recommend the use of antibiotics for all cases of pneumonia in children, despite the majority being caused by viruses. We performed a systematic review and meta-analysis to determine which children aged 2-59 months with WHO-defined fast breathing pneumonia, if any, can be safely treated without antibiotics. METHODS: We systematically searched medical databases for articles published in the last 20 years. We included both observational and interventional studies that compared antibiotics to no antibiotics in children aged 2-59 months diagnosed with fast breathing pneumonia in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, and assessed for risk of bias using the Effective Public Health Practice Project (EPHPP) framework. Overall, we included 13 studies in this review. We performed a meta-analysis of four included studies comparing amoxicillin to placebo. RESULTS: Most children with fast breathing pneumonia will have a good outcome, regardless of whether or not they are treated with antibiotics. Meta-analysis of four RCTs comparing amoxicillin to placebo for children with pneumonia showed higher risk of treatment failure in the placebo group (odds ratio OR 1.40, 95% confidence interval CI = 1.00-1.96). We did not identify any child pneumonia subgroups in whom antibiotics can be safely omitted. Limited data suggest that infants with clinically-diagnosed bronchiolitis are a particular low-mortality group who may be safely treated without antibiotics in some contexts. CONCLUSIONS: Children with WHO-defined fast breathing pneumonia in LMICs should continue to be treated with antibiotics. Future studies should seek to identify which children stand to benefit most from antibiotic therapy, and identify those in whom antibiotics may not be required, and in which circumstances.
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ItemPrevalence of pneumonia and malnutrition among children in Jigawa state, Nigeria: a community-based clinical screening study(BMJ PUBLISHING GROUP, 2022-10)OBJECTIVE: To estimate the point prevalence of pneumonia and malnutrition and explore associations with household socioeconomic factors. DESIGN: Community-based cross-sectional study conducted in January-June 2021 among a random sample of households across all villages in the study area. SETTING: Kiyawa Local Government Area, Jigawa state, Nigeria. PARTICIPANTS: Children aged 0-59 months who were permanent residents in Kiyawa and present at home at the time of the survey. MAIN OUTCOME MEASURES: Pneumonia (non-severe and severe) defined using WHO criteria (2014 revision) in children aged 0-59 months. Malnutrition (moderate and severe) defined using mid-upper arm circumference in children aged 6-59 months. RESULTS: 9171 children were assessed, with a mean age of 24.8 months (SD=15.8); 48.7% were girls. Overall pneumonia (severe or non-severe) point prevalence was 1.3% (n=121/9171); 0.6% (n=55/9171) had severe pneumonia. Using an alternate definition that did not rely on caregiver-reported cough/difficult breathing revealed higher pneumonia prevalence (n=258, 2.8%, 0.6% severe, 2.2% non-severe). Access to any toilet facility was associated with lower odds of pneumonia (aOR: 0.56; 95% CI: 0.31 to 1.01). The prevalence of malnutrition (moderate or severe) was 15.6% (n=1239/7954) with 4.1% (n=329/7954) were severely malnourished. Being older (aOR: 0.22; 95% CI: 0.17 to 0.27), male (aOR: 0.77; 95% CI: 0.66 to 0.91) and having head of compound a business owner or professional (vs subsistence farmer, aOR 0.71; 95% CI: 0.56 to 0.90) were associated with lower odds of malnutrition. CONCLUSIONS: In this large, representative community-based survey, there was a considerable pneumonia and malnutrition morbidity burden. We noted challenges in the diagnosis of Integrated Management of Childhood Illness-defined pneumonia in this context.
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ItemContinuous Positive Airway Pressure (CPAP) for severe pneumonia in low- and middle-income countries: A systematic review of contextual factors(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Continuous positive airway pressure (CPAP) may have a role in reducing the high mortality in children less than 5 years with World Health Organization (WHO) severe pneumonia. More evidence is needed to understand important contextual factors that impact on implementation, effectiveness, and safety in low resource settings. METHODS: We conducted a systematic review of Medline, Embase and Pubmed (January 2000 to August 2020) with terms of "pneumonia", "CPAP" and "child". We included studies that provided original clinical or non-clinical data on the use of CPAP in children (28 days-4 years) with pneumonia in low- or middle-income countries. We used standardised tools to assess study quality, and grade levels of evidence for clinical conclusions. Results are presented as a narrative synthesis describing context, intervention, and population alongside outcome data. RESULTS: Of 902 identified unique references, 23 articles met inclusion criteria, including 6 randomised controlled trials, one cluster cross over trial, 12 observational studies, 3 case reports and 1 cost-effectiveness analysis. There was significant heterogeneity in patient population, with wide range in mortality among participants in different studies (0%-55%). Reporting of contextual factors, including staffing, costs, and details of supportive care was patchy and non-standardised. Current evidence suggests that CPAP has a role in the management of infants with bronchiolitis and as escalation therapy for children with pneumonia failing standard-flow oxygen therapy. However, CPAP must be implemented with appropriate staffing (including doctor oversight), intensive monitoring and supportive care, and technician and infrastructure capacity. We provide practical guidance and recommendations based on available evidence and published expert opinion, for the adoption of CPAP into routine care in low resource settings and for reporting of future CPAP studies. CONCLUSIONS: CPAP is a safe intervention in settings that can provide intensive monitoring and supportive care, and the strongest evidence for a benefit of CPAP is in infants (aged less than 1 year) with bronchiolitis. The available published evidence and clinical experience can be used to help facilities assess appropriateness of implementing CPAP, guide health workers in refining selection of patients most likely to benefit from it, and provide a framework for components of safe and effective CPAP therapy. PROTOCOL REGISTRATION: PROSPERO registration: CRD42020210597.
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ItemThe utility of chest x-ray and lung ultrasound in the management of infants and children presenting with severe pneumonia in low-and middle-income countries: A pragmatic scoping review(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Chest x-ray (CXR) is commonly used (when available) to support clinical management decisions for child pneumonia and provide a reference standard for diagnosis in research studies. However, its diagnostic and technical limitations for both purposes are well recognised. Recent evidence suggests that lung ultrasound (LUS) may have diagnostic utility in pneumonia. This systematic scoping review of research on the utility of CXR and LUS in the management of severe childhood pneumonia aims to inform pragmatic guidelines for low- and middle-income countries (LMICs) and identify gaps in knowledge. METHODS: We included peer-reviewed studies published between 2000 and 2020 in infants and children aged from one month to nine years, presenting with severe pneumonia. CXR studies were limited to those from LMICs, while LUS studies included any geographic region. LUS and CXR articles were mapped into the following themes: indications, role in diagnosis, role in management, impact on outcomes, and practical considerations for LMIC settings. RESULTS: 85 articles met all eligibility criteria, including 27 CXR studies and 58 LUS studies. CXR studies were primarily observational and examined associations between radiographic abnormalities and pneumonia aetiology or outcomes. The most consistent finding was an association between CXR consolidation and risk of mortality. Difficulty obtaining quality CXR images and inter-reader variability in interpretation were commonly reported challenges. Research evaluating indications for CXR, role in management, and impact on patient outcomes was very limited. LUS studies primarily focused on diagnostic accuracy. LUS had higher sensitivity for identification of consolidation than CXR. There are gaps in knowledge regarding diagnostic criteria, as well as the practical utility of LUS in the diagnosis and management of pneumonia. Most LUS studies were conducted in HIC settings with experienced operators; however, small feasibility studies indicate that good inter-operator reliability may be achieved by training of novice clinicians in LMIC settings. CONCLUSIONS: The available evidence does not support the routine use of CXR or LUS as essential tools in the diagnosis and initial management of severe pneumonia. Further evaluation is required to determine the clinical utility and feasibility of both imaging modalities in low-resource settings.
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ItemManagement of tuberculosis infection in Victorian children: A retrospective clinical audit of factors affecting treatment completion(PUBLIC LIBRARY SCIENCE, 2022-10-13)BACKGROUND: Tuberculosis preventive treatment (TPT) is strongly recommended for children following infection with Mycobacterium tuberculosis because of their high risk of progression to active tuberculosis, including severe disseminated disease. We describe the implementation of TPT for children and adolescents with evidence of tuberculosis infection (TBI) at Victoria's largest children's hospital and examine factors affecting treatment completion. METHODS: We conducted a retrospective clinical audit of all children and adolescents aged <18 years diagnosed with latent TBI at the Royal Children's Hospital, Melbourne, between 2010 and 2016 inclusive. The primary outcome was treatment completion, defined as completing TPT to within one month of a target duration for the specified regimen (for instance, at least five months of a six-month isoniazid course), confirmed by the treating clinician. Factors associated with treatment adherence were evaluated by univariate and multivariate analysis. RESULTS: Of 402 participants with TBI, 296 (74%) met the criteria for treatment "complete". The most common TPT regimen was six months of daily isoniazid (377, 94%). On multivariate logistic regression analysis, treatment completion was more likely among children and adolescents who had refugee health screening performed (OR 2.31, 95%CI 1.34-4.00) or who were also treated for other medical conditions (OR 1.67 95%CI 1.0-2.85), and less likely among those who experienced side-effects (OR 0.32, 95%CI 0.11-0.94). However, TPT was generally well tolerated with side-effects reported in 15 participants (3.7%). CONCLUSION: Identification of factors associated with TPT completion and deficiencies in the existing care pathway have informed service provision changes to further improve outcomes for Victorian children and adolescents with TBI.
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ItemCost-effectiveness and sustainability of improved hospital oxygen systems in Nigeria(BMJ PUBLISHING GROUP, 2022-08)INTRODUCTION: Improving hospital oxygen systems can improve quality of care and reduce mortality for children, but we lack data on cost-effectiveness or sustainability. This study evaluated medium-term sustainability and cost-effectiveness of the Nigeria Oxygen Implementation programme. METHODS: Prospective follow-up of a stepped-wedge trial involving 12 secondary-level hospitals. Cross-sectional facility assessment, clinical audit (January-March 2021), summary admission data (January 2018-December 2020), programme cost data. INTERVENTION: pulse oximetry introduction followed by solar-powered oxygen system installation with clinical and technical training and support. PRIMARY OUTCOMES: (i) proportion of children screened with pulse oximetry; (ii) proportion of hypoxaemic (SpO2 <90%) children who received oxygen. Comparison across three time periods: preintervention (2014-2015), intervention (2016-2017) and follow-up (2018-2020) using mixed-effects logistic regression. Calculated cost-effectiveness of the intervention on child pneumonia mortality using programme costs, recorded deaths and estimated counterfactual deaths using effectiveness estimates from our effectiveness study. Reported cost-effectiveness over the original 2-year intervention period (2016-2017) and extrapolated over 5 years (2016-2020). RESULTS: Pulse oximetry coverage for neonates and children remained high during follow-up (83% and 81%) compared with full oxygen system period (94% and 92%) and preintervention (3.9% and 2.9%). Oxygen coverage for hypoxaemic neonates/children was similarly high (94%/88%) compared with full oxygen system period (90%/82%). Functional oxygen sources were present in 11/12 (92%) paediatric areas and all (8/8) neonatal areas; three-quarters (15/20) of wards had a functional oximeter. Of 32 concentrators deployed, 23/32 (72%) passed technical testing and usage was high (median 10 797 hours). Estimated 5-year cost-effectiveness US$86 per patient treated, $2694-4382 per life saved and $82-125 per disability-adjusted life year-averted. We identified practical issues for hospitals and Ministries of Health wishing to adapt and scale up pulse oximetry and oxygen. CONCLUSION: Hospital-level improvements to oxygen and pulse oximetry systems in Nigerian hospitals have been sustained over the medium-term and are a highly cost-effective child pneumonia intervention.
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ItemTechnology to improve reliable access to oxygen in Western Uganda: study protocol for a phased implementation trial in neonatal and paediatric wards(BMJ PUBLISHING GROUP, 2022-06)INTRODUCTION: Oxygen is an essential medicine for children and adults. The current systems for its delivery can be expensive and unreliable in settings where oxygen is most needed. FREO2 Foundation Australia has developed an integrated oxygen system, driven by a mains-powered oxygen concentrator, with the ability to switch automatically between low-pressure oxygen storage device and cylinder oxygen in power interruptions. The aim of this study is to assess the clinical impact and cost-effectiveness of expanding this system to 20 community and district hospitals and level IV facilities in Western Uganda. METHODS AND ANALYSIS: This will be a phased implementation with preintervention and postintervention comparison of outcomes. Standardised baseline data collection and needs assessment will be conducted, followed by implementation of the FREO2 Oxygen System in combination with pulse oximetry in 1-2 facilities per month over a 16-month period, with a total 23-month data collection period. The primary outcome will be the proportion of hypoxaemic children receiving oxygen pre and post oxygen system. Secondary outcomes will assess clinical, economic and technical aspects. Pre and post oxygen system primary and secondary outcomes will be compared using regression models and standard tests of significance. Useability will be quantitatively and qualitatively evaluated in terms of acceptability, feasibility and appropriateness, using standardised implementation outcome measure tools. ETHICS AND DISSEMINATION: Ethics approval was obtained from Mbarara University of Science and Technology (MUREC 1/7) and the University of Melbourne (2021-14489-13654-2). Outcomes will be presented to the involved facilities, and to representatives of the Ministry of Health, Uganda. Broader dissemination will include publication in peer-reviewed journals and academic conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12621000241831.
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ItemSystematic review of the clinical outcomes of pneumonia with a penicillin-group resistant pneumococcus in respiratory and blood culture specimens in children in low- and middle-income countries(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Streptococcus pneumoniae is one of the most common bacteria causing pneumonia and the World Health Organization (WHO) recommends first-line treatment of pneumonia with penicillins. Due to increases in the frequency of penicillin resistance, this systematic review aimed to determine the clinical outcomes of children with pneumonia in low- and middle-income countries (LMICs), with penicillin-group resistant pneumococci in respiratory and/or blood cultures specimens. METHODS: English-language articles from January 2000 to November 2020 were identified by searching four databases. Systematic reviews and epidemiological studies from LMICs that included children aged one month to 9 years and reported outcomes of pneumonia with a penicillin-resistant pneumococcus in respiratory and blood culture specimens with or without comparison groups were included. Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. A narrative synthesis of findings based on the results of included studies was performed. RESULTS: We included 7 articles involving 2864 children. One strong- and four medium-quality studies showed no difference in clinical outcomes (duration of symptoms, length of hospital stay and mortality) between those children with penicillin non-susceptible compared to susceptible pneumococci. Two weak quality studies suggested better outcomes in the penicillin-susceptible group. CONCLUSIONS: Current evidence suggests no difference in clinical outcomes of child pneumonia due to a penicillin-resistant S. pneumoniae and as such, there is no evidence to support a change in current WHO antibiotic guidelines.
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ItemReview of the role of additional treatments including oseltamivir, oral steroids, macrolides, and vitamin supplementation for children with severe pneumonia in low- and middle-income countries(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Pneumonia is a major cause of death in children aged under five years. As children with severe pneumonia have the highest risk of morbidity and mortality, previous studies have evaluated the additional benefit of adjunctive treatments such as oseltamivir, oral steroids, macrolides, and vitamin supplementation that can be added to standard antibiotic management to improve clinical outcomes. The study reviewed the evidence for the role of these additional treatments for children with severe pneumonia in low- and middle-income countries (LMICs). METHODS: Four electronic databases were searched for English-language articles between 2000 to 2020. Systematic reviews (SRs) with meta-analyses, comparative cohort studies, and randomised controlled trials (RCTs) from LMICs that reported clinical outcomes for children with severe pneumonia aged between one month to 9 years who received adjunct treatment in addition to standard care were included. Risk of bias of included SRs was assessed using AMSTAR 2, and of individual studies using the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies. RESULTS: Overall, the search identified 2147 articles, 32 of which were eligible, including 7 SRs and 25 RCTs. These studies evaluated zinc (4 SRs, 17 RCTs), Vitamin D (1 SR, 4 RCTs), Vitamin A (3 SRs, 1 RCT), Vitamin C (1 SR, 2 RCTs) and micronutrients (1 RCT). Most studies reported clinical outcomes of time to improvement, length of stay, and treatment failure (including mortality). No studies of oseltamivir, steroids, or macrolides fulfilling the inclusion criteria were identified. For zinc, pooled analyses from SRs showed no evidence of benefit. Similarly, a Cochrane review and one RCT found that Vitamin A did not improve clinical outcomes. For Vitamin D, an RCT evaluating a single high dose of 100 000 international units (IU) of vitamin D found a reduction in time to improvement, with 38%-40% documented vitamin D deficiency at baseline. However, two other studies of 1000 IU daily did not show any effect, but vitamin D status was not measured. For vitamin C, two studies found a reduction in time to symptom resolution in those with severe disease, with one reporting a shorter length of hospital stay. However, both studies were of weak quality. Most studies excluded malnourished children, and studies which included these children did not report specifically on the effect of micronutrients. CONCLUSIONS: This review found that adjunctive zinc and vitamin A, in addition to standard care, does not improve clinical outcomes in children with severe pneumonia in LMICs (strong evidence). However, a reduction in time to symptom resolution was reported with high dose vitamin D supplementation in children with documented vitamin D deficiency (strong evidence from one study) and vitamin C (weak evidence), although further research is needed, especially in underweight children.
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ItemWhich children with chest-indrawing pneumonia can be safely treated at home, and under what conditions is it safe to do so? A systematic review of evidence from low- and middle-income countries(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: WHO pneumonia guidelines recommend that children (aged 2-59 months) with chest indrawing pneumonia and without any "general danger sign" can be treated with oral amoxicillin without hospital admission. This recommendation was based on trial data from limited contexts whose generalisability is unclear. This review aimed to identify which children with chest-indrawing pneumonia in low- and middle-income countries can be safely treated at home, and under what conditions is it safe to do so. METHODS: We searched MEDLINE, EMBASE, and PubMed for observational and interventional studies of home-based management of children (aged 28 days to four years) with chest-indrawing pneumonia in low- or middle-income countries. RESULTS: We included 14 studies, including seven randomised trials, from a variety of urban and rural contexts in 11 countries. Two community-based and two hospital-based trials in Pakistan and India found that home treatment of chest-indrawing pneumonia was associated with similar or superior treatment outcomes to hospital admission. Evidence from trials (n = 3) and observational (n = 6) studies in these and other countries confirms the acceptability and feasibility of home management of chest-indrawing pneumonia in low-risk cases, so long as safeguards are in place. Risk assessment includes clinical danger signs, oxygen saturation, and the presence of comorbidities such as undernutrition, anaemia, or HIV. Pulse oximetry is a critical risk-assessment tool that is currently not widely available and can identify severely ill patients with hypoxaemia otherwise possibly missed by clinical assessment alone. Additional safeguards include caregiver understanding and ability to return for review. CONCLUSIONS: Home treatment of chest-indrawing pneumonia can be safe but should only be recommended for children confirmed to be low-risk and in contexts where appropriate care and safety measures are in place.
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