Paediatrics (RCH) - Research Publications
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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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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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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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ItemChildhood pneumonia in humanitarian emergencies in low- and middle-income countries: A systematic scoping review(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Humanitarian emergencies increase many risk factors for pneumonia, including disruption to food, water and sanitation, and basic health services. This review describes pneumonia morbidity and mortality among children and adolescents affected by humanitarian emergencies. METHODS: We searched MEDLINE, EMBASE, and PubMed databases for publications reporting pneumonia morbidity or mortality among children aged 1 month to 17 years in humanitarian emergencies (eg, natural disaster, armed conflict, displacement) in low- and middle-income countries (LMICs). RESULTS: We included 22 papers published between January 2000 and July 2021 from 33 countries, involving refugee/displaced persons camps (n = 5), other conflict settings (n = 14), and natural disaster (n = 3). Population pneumonia incidence was high for children under 5 years of age (73 to 146 episodes per 100 patient-years); 6%-29% met World Health Organization (WHO) criteria for severe pneumonia requiring admission. Pneumonia accounted for 13%-34% of child and adolescent presentations to camp health facilities, 7%-48% of presentations and admissions to health facilities in other conflict settings, and 12%-22% of admissions to hospitals following natural disasters. Pneumonia related deaths accounted for 7%-30% of child and adolescent deaths in hospital, though case-fatality rates varied greatly (0.5%-17.2%). The risk for pneumonia was greater for children who are: recently displaced, living in crowded settings (particularly large camps), with deficient water and sanitation facilities, and those who are malnourished. CONCLUSION: Pneumonia is a leading cause of morbidity and mortality in children and adolescents affected by humanitarian emergencies. Future research should address population-based pneumonia burden, particularly for older children and adolescents, and describe contextual factors to allow for more meaningful interpretation and guide interventions.
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ItemQuality of care for children with acute respiratory infections in health facilities: A comparative analysis of assessment tools(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: Severe childhood pneumonia requires treatment in hospital by trained health care workers. It is therefore important to determine if health facilities provide quality health services for children with acute respiratory infections (ARI), including pneumonia. Using established indicators from WHO to measure quality of care (QoC) as a reference standard, this review aims to evaluate how well existing tools assess QoC for children presenting to health facilities with ARI. METHODS: Existing assessment tools identified from a published systematic literature review that evaluated QoC assessment tools for children (<15 years) in health facilities for all health conditions were included in this ARI-specific review. 27 ARI-specific indicators or "quality measures" from the WHO "Standards for improving quality of care for children and young adolescents in health facilities" were selected for use as a reference standard to assess QoC for children presenting to health facilities with ARI symptoms. Each included assessment tool was evaluated independently by two paediatricians to determine how many of the WHO ARI quality measures were assessable by the tool. The assessment tools were then ranked in order of percentage of ARI quality measures assessable. RESULTS: Nine assessment tools that assessed QoC for children attending health facilities were included. Two hospital care tools developed by WHO had the most consistency with ARI-specific indicators, assessing 22/27 (81.5%) and 20/27 (74.1%) of the quality measures. The remaining tools were less consistent with the ARI-specific indicators, including between zero to 16 of the 27 quality measures. The most common indicators absent from the tools were assessment of appropriate use of pulse oximetry and administration of oxygen, how often oxygen supply was unavailable, and mortality rates. CONCLUSIONS: The existing WHO hospital-based QoC assessment tools are comprehensive but could be enhanced by improved data quality around oxygen availability and appropriate use of pulse oximetry and oxygen administration. Any tools, however, should be considered within broader assessments of QoC, rather than utilised in isolation. Further adaptation to local settings will improve feasibility and facilitate progress in the delivery of quality health care for children with ARI. REGISTRATION: The protocol of the original systematic review was registered in PROSPERO ID: CRD42020175652.
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ItemThe effectiveness of the 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People's Democratic Republic: An observational hospital-based test-negative study(ELSEVIER, 2020-09)BACKGROUND: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. METHODS: A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. FINDINGS: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. INTERPRETATION: PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. FUNDING: Funded by the Bill & Melinda Gates Foundation.