Paediatrics (RCH) - Research Publications
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ItemSystematic review on the impact of the pneumococcal conjugate vaccine ten valent (PCV10) or thirteen valent (PCV13) on all-cause, radiologically confirmed and severe pneumonia hospitalisation rates and pneumonia mortality in children 0-9 years old(INT SOC GLOBAL HEALTH, 2023)BACKGROUND: There is an ongoing need to assess the impact of pneumococcal conjugate vaccines (PCVs) to guide the use of these potentially valuable but under-utilized vaccines against pneumonia, which is one of the most common causes of post-neonatal mortality. METHODS: We conducted a systematic review of the literature on PCV10 and PCV13 impact on all-cause, radiologically confirmed and severe pneumonia hospitalisation rates as well as all-cause and pneumonia-specific mortality rates. We included studies that were published from 2003 onwards, had a post-licensure observational study design, and reported on any of our defined outcomes in children aged between 0-9 years. We derived incidence rates (IRs), incidence rate ratios (IRRs) or percent differences (%). We assessed all studies for risk of bias using the Effective Public Health Practice Project (EPHPP) quality assessment tool. RESULTS: We identified a total of 1885 studies and included 43 comparing one or more of the following hospitalised outcomes of interest: all-cause pneumonia (n = 27), severe pneumonia (n = 6), all-cause empyema (n = 8), radiologically confirmed pneumonia (n = 8), pneumococcal pneumonia (n = 7), and pneumonia mortality (n = 10). No studies evaluated all-cause mortality. Studies were conducted in all WHO regions except South East Asia Region (SEAR) and low- or middle-income countries (LMICs) in the Western Pacific Region (WPR). Among children <5 years old, PCV impact ranged from 7% to 60% for all-cause pneumonia hospitalisation, 8% to 90% for severe pneumonia hospitalisation, 12% to 79% for radiologically confirmed pneumonia, and 45% to 85% for pneumococcal confirmed pneumonia. For pneumonia-related mortality, impact was found in three studies and ranged from 10% to 78%. No obvious differences were found in vaccine impact between PCV10 and PCV13. One study found a 17% reduction in all-cause pneumonia among children aged 5-9 years, while another found a reduction of 81% among those aged 5-17 years. A third study found a 57% reduction in all-cause empyema among children 5-14 years of age. CONCLUSION: We found clear evidence of declines in hospitalisation rates due to all-cause, severe, radiologically confirmed, and bacteraemic pneumococcal pneumonia in children aged <5 years, supporting ongoing use of PCV10 and PCV13. However, there were few studies from countries with the highest <5-year mortality and no studies from SEAR and LMICs in the WPR. Standardising methods of future PCV impact studies is recommended.
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ItemThe impact of the introduction of ten- or thirteen-valent pneumococcal conjugate vaccines on antimicrobial-resistant pneumococcal disease and carriage: A systematic literature review(INT SOC GLOBAL HEALTH, 2023)BACKGROUND: A systematic review in 2019 found reductions in antimicrobial resistance (AMR) of pneumococcal vaccine serotypes following pneumococcal conjugate vaccine (PCV) introduction. However, few low- or middle-income countries were included as not many had introduced higher valent PCVs (PCV10 or PCV13). The aim of our review is to describe AMR rates in these samples following the introduction of PCV10 or PCV13. METHODS: We conducted a systematic literature review of published papers that compared AMR for invasive pneumococcal disease (IPD), otitis media (OM) and nasopharyngeal carriage (NPC) samples following introduction of PCV10 or PCV13 to the pre-PCV period. Included studies published from July 2017 to August 2020 had a post-licensure observational study design and reported on our defined outcomes: IPD, OM, NPC and other (sputum or mixed invasive and non-invasive pneumococcal) isolates from people of all ages. Rates of AMR in the pre- and post-period were extracted. RESULTS: Data were extracted from 31 studies. Among IPD isolates, penicillin AMR rates following PCV10 or PCV13 introduction declined in 32% (n = 9/29) of included studies, increased in 34% (n = 10/29) and showed no change in 34% (n = 10/29). Cephalosporins AMR declined in 32% (n = 6/19) of studies, increased in 21% (n = 4/19) and showed no change in 47% (n = 9/19). Macrolides AMR declined in 33% (n = 4/12) of studies, increased in 50% (n = 6/12), and showed no change in 17% (n = 2/12). AMR to other antibiotics (including multidrug resistance) declined in 23% (n = 9/39) of studies, increased in 41% (n = 16/39) and showed no change in AMR in 36% (n = 14/39). There were no obvious differences between AMR; in setting which used PCV10 vs PCV13, according to time since PCV introduction or by World Bank income status of the respective country. The only study including OM isolates found no change in penicillin resistance. There were few studies on AMR in NPC (four studies), OM (one study) or other isolates (five studies). The results followed similar patterns to IPD isolates. CONCLUSIONS: We observed considerable heterogeneity in the findings between and within studies, e.g. no evidence of reduction in amoxicillin AMR with an increase in macrolides AMR. Reasons for such diverse findings include the period covered by different studies and variation in other pressures towards AMR.
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ItemWhat are the risk factors for death among children with pneumonia in low- and middle-income countries? A systematic review(INT SOC GLOBAL HEALTH, 2023)BACKGROUND: Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an individual and population level. This review aimed to identify the most important risk factors for mortality among children aged under ten years with pneumonia. METHODS: We systematically searched MEDLINE, EMBASE, and PubMed for observational and interventional studies reporting risk factors for mortality in children (aged two months to nine years) in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, assessed risk of bias using the EPHPP framework, and extracted data on demographic, clinical, and laboratory risk factors for death. We synthesized data descriptively and using Forest plots and did not attempt meta-analysis due to the heterogeneity in study design, definitions, and populations. FINDINGS: We included 143 studies in this review. Hypoxaemia (low blood oxygen level), decreased conscious state, severe acute malnutrition, and the presence of an underlying chronic condition were the risk factors most strongly and consistently associated with increased mortality in children with pneumonia. Additional important clinical factors that were associated with mortality in the majority of studies included particular clinical signs (cyanosis, pallor, tachypnoea, chest indrawing, convulsions, diarrhoea), chronic comorbidities (anaemia, HIV infection, congenital heart disease, heart failure), as well as other non-severe forms of malnutrition. Important demographic factors associated with mortality in the majority of studies included age <12 months and inadequate immunisation. Important laboratory and investigation findings associated with mortality in the majority of studies included: confirmed Pneumocystis jirovecii pneumonia (PJP), consolidation on chest x-ray, pleural effusion on chest x-ray, and leukopenia. Several other demographic, clinical and laboratory findings were associated with mortality less consistently or in a small numbers of studies. CONCLUSIONS: Risk assessment for children with pneumonia should include routine evaluation for hypoxaemia (pulse oximetry), decreased conscious state (e.g. AVPU), malnutrition (severe, moderate, and stunting), and the presence of an underlying chronic condition as these are strongly and consistently associated with increased mortality. Other potentially useful risk factors include the presence of pallor or anaemia, chest indrawing, young age (<12 months), inadequate immunisation, and leukopenia.
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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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