Paediatrics (RCH) - Research Publications

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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 (INT SOC GLOBAL HEALTH, 2022-01-01)
    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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    Recommendations for treatment of childhood non-severe pneumonia
    Grant, GB ; Campbell, H ; Dowell, SF ; Graham, SM ; Klugman, KP ; Mulholland, EK ; Steinhoff, M ; Weber, MW ; Qazi, S (ELSEVIER SCI LTD, 2009-03-01)
    WHO recommendations for early antimicrobial treatment of childhood pneumonia have been effective in reducing childhood mortality, but the last major revision was over 10 years ago. The emergence of antimicrobial resistance, new pneumonia pathogens, and new drugs have prompted WHO to assemble an international panel to review the literature on childhood pneumonia and to develop evidence-based recommendations for the empirical treatment of non-severe pneumonia among children managed by first-level health providers. Treatment should target the bacterial causes most likely to lead to severe disease, including Streptoccocus pneumoniae and Haemophilus influenzae. The best first-line agent is amoxicillin, given twice daily for 3-5 days, although co-trimoxazole may be an alternative in some settings. Treatment failure should be defined in a child who develops signs warranting immediate referral or who does not have a decrease in respiratory rate after 48-72 h of therapy. If failure occurs, and no indication for immediate referral exists, possible explanations for failure should be systematically determined, including non-adherence to therapy and alternative diagnoses. If failure of the first-line agent remains a possible explanation, suitable second-line agents include high-dose amoxicillin-clavulanic acid with or without an affordable macrolide for children over 3 years of age.
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    State-of-the-art in the pneumococcal field: Proceedings of the 11(th) International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-11)
    Kwambana-Adams, BA ; Mulholland, EK ; Satzke, C ; Smith-Vaughan, H ; Brueggemann, A ; Whitney, C ; Kirkham, L-A ; Sa-Leao, R ; Vidal, J ; Graham, H ; Murdoch, D ; Paranhos-Baccala, G ; Goldblatt, D ; Pomat, WS ; Best, E ; McIntyre, P ; McVernon, J ; Weinberger, D ; Dunne, E ; Scott, JA ; Cripps, AW ; Mackenzie, G ; Madhi, S ; Torzillo, P ; Graham, S ; Kartasasmita, C ; Awori, JO ; Smith, A ; Hilty, M ; Blyth, C ; Pilishvili, T ; Hammitt, L ; Andrews, R ; Crooks, K ; Hanage, WP ; Wijburg, O ; Morpeth, S ; French, N ; Cheng, A ; Trappetti, C ; Tuomanen, E ; Rosch, J ; Arora, N ; Rodgers, G ; Yoshida, LM ; Richmond, P ; Licciardi, P ; Ferreira, DM (BMC, 2020-02-05)
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) is the premier global scientific symposium dedicated to the exchange, advancement and dissemination of the latest research on the pneumococcus, one of the world's deadliest bacterial pathogens. Since the first ISPPD was held in 1998, substantial progress has been made to control pneumococcal disease, for instance, more than half of surviving infants (78.6 million) from 143 countries now have access to the life-saving pneumococcal conjugate vaccine (PCV). The 11th ISPPD (ISPPD-11) was held in Melbourne, Australia in April 2018 and the proceedings of the symposium are captured in this report. Twenty years on from the first ISPPD, there remain many challenges and unanswered questions such as the continued disparity in disease incidence in Indigenous populations, the slow roll-out of PCV in some regions such as Asia, the persisting burden of disease in adults, serotype replacement and diagnosis of pneumococcal pneumonia. ISPPD-11 also put the spotlight on cutting-edge science including metagenomic, transcriptomic, microscopy, medical imaging and mathematical modelling approaches. ISPPD-11 was highly diverse, bringing together 1184 delegates from 86 countries, representing various fields including academia, primary healthcare, pharmaceuticals, biotechnology, policymakers and public health.
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    Impact of the change in WHO's severe pneumonia case definition on hospitalized pneumonia epidemiology: case studies from six countries
    Russell, FM ; Reyburn, R ; Chan, J ; Tuivaga, E ; Lim, R ; Lai, J ; Hoang, MTV ; Choummanivong, M ; Sychareun, V ; Dung, KTK ; de Campo, M ; Enarson, P ; Graham, S ; La Vincente, S ; Mungan, T ; von Mollendorf, C ; Mackenzie, G ; Mulholland, K (WORLD HEALTH ORGANIZATION, 2019-06-01)
    OBJECTIVE: To quantify the impact of the change in definition of severe pneumonia on documented pneumonia burden. METHODS: We reviewed existing data acquired during observational hospitalized pneumonia studies, before the introduction of the pneumococcal conjugate vaccine, in infants aged 2-23 months from Fiji, Gambia, Lao People's Democratic Republic, Malawi, Mongolia and Viet Nam. We used clinical data to calculate the percentage of all-cause pneumonia hospitalizations with severe pneumonia, and with primary end-point consolidation, according to both the 2005 or 2013 World Health Organization (WHO) definitions. Where population data were available, we also calculated the incidence of severe pneumonia hospitalizations according to the different definitions. FINDINGS: At six of the seven sites, the percentages of all-cause pneumonia hospitalizations due to severe pneumonia were significantly less (P < 0.001) according to the 2013 WHO definition compared with the 2005 definition. However, the percentage of severe pneumonia hospitalizations, according to the two definitions of severe pneumonia, with primary end-point consolidation varied little within each site. The annual incidences of severe pneumonia hospitalizations per 100 000 infants were significantly less (all P < 0.001) according to the 2013 definition compared with the 2005 definition, ranging from a difference of -301.0 (95% confidence interval, CI: -405.2 to -196.8) in Fiji to -3242.6 (95% CI: -3695.2 to -2789.9) in the Gambia. CONCLUSION: The revision of WHO's definition of severe pneumonia affects pneumonia epidemiology, and hence the interpretation of any pneumonia intervention impact evaluation.