Paediatrics (RCH) - Research Publications

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    Which 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.
    Wilkes, C ; Graham, H ; Walker, P ; Duke, T ; ARI Review group, (International Global Health Society, 2022-08-31)
    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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    Aetiology of childhood pneumonia in low- and middle-income countries in the era of vaccination: a systematic review.
    von Mollendorf, C ; Berger, D ; Gwee, A ; Duke, T ; Graham, SM ; Russell, FM ; Mulholland, EK ; ARI review group, (International Global Health Society, 2022-07-23)
    Background: This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries. Methods: We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830]. Results: We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis. Conclusions: Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.
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    Childhood pneumonia in humanitarian emergencies in low- and middle-income countries: A systematic scoping review
    Chen, SJ ; Walker, PJB ; Mulholland, K ; Graham, HR (INT SOC GLOBAL HEALTH, 2022-01-01)
    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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    Quality of care for children with acute respiratory infections in health facilities: A comparative analysis of assessment tools
    Quach, A ; Tosif, S ; Graham, SM ; von Mollendorf, C ; Mulholland, K ; Graham, H ; Duke, T ; Russell, FM (INT SOC GLOBAL HEALTH, 2022-01-01)
    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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    A Prospective Evaluation of the Symptom-Based Screening Approach to the Management of Children Who Are Contacts of Tuberculosis Cases
    Triasih, R ; Robertson, CF ; Duke, T ; Graham, SM (OXFORD UNIV PRESS INC, 2015-01-01)
    BACKGROUND: Child tuberculosis contact screening and management can enhance case finding and prevent tuberculosis disease. It is universally recommended but rarely implemented in tuberculosis-endemic settings. The World Health Organization (WHO)-recommended symptom-based screening approach could improve implementation but has not been prospectively evaluated. METHODS: We conducted a cohort study of children who were close contacts of pulmonary tuberculosis patients in Indonesia from August 2010 to December 2012. We performed clinical assessment, tuberculin skin test, and chest radiography in all eligible children irrespective of symptoms at baseline. Mycobacterial culture and Xpert MTB/RIF assay were performed on sputum from children with persistent symptoms of suspected tuberculosis. Children were managed according to WHO guidelines and were prospectively followed for 12 months. RESULTS: A total of 269 child contacts of 140 index cases were evaluated. At baseline, 21 (8%) children had tuberculosis diagnosed clinically; an additional 102 (38%) had evidence of infection without disease. Of children with any tuberculosis-related symptoms at baseline, 21% had tuberculosis diagnosed compared with none of the asymptomatic children (P < .001). After 12 months of follow-up, none of the 99 eligible young child contacts (<5 years) who received isoniazid preventive therapy (IPT) had developed disease compared with 4 of 149 (2.6%) asymptomatic older children who did not receive IPT. CONCLUSIONS: Symptom-based screening is an effective and simple approach to child tuberculosis contact management that can be implemented at the primary healthcare level.
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    Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial
    Chisti, MJ ; Salam, MA ; Smith, JH ; Ahmed, T ; Pietroni, MAC ; Shahunja, KM ; Shahid, ASMSB ; Faruque, ASG ; Ashraf, H ; Bardhan, PK ; Sharifuzzaman, ; Graham, SM ; Duke, T (ELSEVIER SCIENCE INC, 2015-09-12)
    BACKGROUND: In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. METHODS: This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07-0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11-2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07-0·89; p=0·022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. FUNDING: International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.
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    Assessing the quality of care for children attending health facilities: a systematic review of assessment tools
    Quach, A ; Tosif, S ; Nababan, H ; Duke, T ; Graham, SM ; Were, WM ; Muzigaba, M ; Russell, FM (BMJ PUBLISHING GROUP, 2021-10-01)
    INTRODUCTION: Assessing quality of healthcare is integral in determining progress towards equitable health outcomes worldwide. Using the WHO 'Standards for improving quality of care for children and young adolescents in health facilities' as a reference standard, we aimed to evaluate existing tools that assess quality of care for children. METHODS: We undertook a systematic literature review of publications/reports between 2008 and 2020 that reported use of quality of care assessment tools for children (<15 years) in health facilities. Identified tools were reviewed against the 40 quality statements and 510 quality measures from the WHO Standards to determine the extent each tool was consistent with the WHO Standards. The protocol was registered in PROSPERO ID: CRD42020175652. RESULTS: Nine assessment tools met inclusion criteria. Two hospital care tools developed by WHO-Europe and WHO-South-East Asia Offices had the most consistency with the WHO Standards, assessing 291 (57·1%) and 208 (40·8%) of the 510 quality measures, respectively. Remaining tools included between 33 (6·5%) and 206 (40·4%) of the 510 quality measures. The WHO-Europe tool was the only tool to assess all 40 quality statements. The most common quality measures absent were related to experience of care, particularly provision of educational, emotional and psychosocial support to children and families, and fulfilment of children's rights during care. CONCLUSION: Quality of care assessment tools for children in health facilities are missing some key elements highlighted by the WHO Standards. The WHO Standards are, however, extensive and applying all the quality measures in every setting may not be feasible. A consensus of key indicators to monitor the WHO Standards is required. Existing tools could be modified to include priority indicators to strengthen progress reporting towards delivering quality health services for children. In doing so, a balance between comprehensiveness and practical utility is needed. PROSPERO REGISTRATION NUMBER: CRD42020175652.
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    A mixed-methods evaluation of adherence to preventive treatment among child tuberculosis contacts in Indonesia
    Triasih, R ; Padmawati, RS ; Duke, T ; Robertson, C ; Sawyer, SM ; Graham, SM (INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2016-08-01)
    BACKGROUND: Tuberculosis (TB) can be prevented using isoniazid preventive therapy (IPT) among child contacts. However, the benefits of IPT depend on adherence to at least 6 months of daily treatment. A greater understanding of the barriers to and facilitators of adherence to IPT in resource-poor settings is required to optimise the benefits. METHODS: We prospectively evaluated adherence to IPT and its associated factors among child contacts (age 0-5 years) eligible for IPT. We undertook in-depth interviews with care givers and a focus group discussion with health care workers, which were thematically analysed to explore barriers to and facilitators of adherence from the perspective of both care givers and health workers. RESULTS: Of 99 eligible children, 49 (49.5%) did not complete 6 months of IPT. Children whose care giver collected their IPT medications from primary health centres were more likely to have incomplete adherence than those who collected them from hospitals (aOR 2.9, 95%CI 1.1-7.8). Thematic analyses revealed major barriers to and facilitators of adherence: regimen-related, care giver-related and health care-related factors, social support and access. Many of these factors are readily modifiable. CONCLUSION: Providing information about IPT and improving accessibility for care givers to receive IPT at the primary health care facility should be priorities to facilitate implementation.
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    A Prospective Study of the Prevalence of Tuberculosis and Bacteraemia in Bangladeshi Children with Severe Malnutrition and Pneumonia Including an Evaluation of Xpert MTB/RIF Assay
    Chisti, MJ ; Graham, SM ; Duke, T ; Ahmed, T ; Ashraf, H ; Faruque, ASG ; La Vincente, S ; Banu, S ; Raqib, R ; Salam, MA ; Nicol, MP (PUBLIC LIBRARY SCIENCE, 2014-04-02)
    BACKGROUND: Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. METHODS: We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. RESULTS: 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94) and 92% (95% CI: 87-95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. CONCLUSION AND SIGNIFICANCE: TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.
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    An evaluation of chest X-ray in the context of community-based screening of child tuberculosis contacts
    Triasih, R ; Robertson, C ; de Campo, J ; Duke, T ; Choridah, L ; Graham, SM (INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2015-12-01)
    BACKGROUND: There are no published data on the critical review of chest X-ray (CXR) findings of children in the context of community-based contact screening. OBJECTIVES: To describe the quality, findings and inter-observer agreement of CXRs in child TB contacts in Indonesia. METHODS: We performed antero-posterior (AP) and lateral CXR in children who had had close contact with a pulmonary TB case. The CXRs were interpreted independently by four reviewers. RESULTS: A total of 530 CXRs of 265 children were reviewed. Most (63%) of the children were asymptomatic at the time of CXR. Only 60% of the CXRs were reported as moderate to good quality by all reviewers, and inter-observer agreement on quality was slight to moderate (weighted κ = 0.16-0.35) for AP view. The majority of the CXRs were reported as normal (range 65-77%), with fair to moderate inter-observer agreement (κ = 0.25-0.46). Hilar lymphadenopathy (6-16%) was the most common CXR abnormality reported with poor inter-observer agreement (κ = -0.03 to 0.25). CONCLUSION: The CXRs of child TB contacts investigated in the community were characterised by low quality, low agreement and low yield. Our findings support guidelines that CXR is not routinely indicated in asymptomatic child TB contacts in this setting.