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)
    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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    Direct and indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with pneumonia from formal and informal settlements in Mongolia: an observational study
    Chan, J ; Mungun, T ; Batsaixan, P ; Ulziibayar, M ; Suuri, B ; Otgonbayar, D ; Luvsantseren, D ; Nguyen, CD ; Narangarel, D ; Dunne, EM ; Fox, K ; Hinds, J ; Nation, ML ; Pell, CL ; Mulholland, EK ; Satzke, C ; von Mollendorf, C ; Russell, FM (ELSEVIER, 2021-10)
    BACKGROUND: Within Ulaanbaatar, Mongolia, risk factors for pneumonia are concentrated among children living in informal settlements comprised of temporary shelters (gers). We used pneumococcal carriage surveillance among children from formal and informal settlements hospitalised with pneumonia to evaluate the direct and indirect effects of 13-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) pneumococcal carriage following a phased introduction of PCV13. METHODS: We enrolled and collected nasopharyngeal swabs from children 2-59 months of age presenting to hospital. Pneumococci were detected using lytA qPCR and serotyped using microarray on a random monthly selection of swabs between November 2015 and March 2019 from two districts in Ulaanbaatar. PCV13 status was determined using written records. We quantified the associations between individual PCV13 status (direct effects) and district-level PCV13 coverage (indirect effects) and VT carriage using generalised estimating equations and explored interactions by settlement type. FINDINGS: A total of 1 292 swabs from 6 046 participants were tested for pneumococci. Receipt of PCV13 and increasing PCV13 coverage independently reduced the risk of VT carriage. For each percent increase in PCV13 coverage, the adjusted odds of VT carriage decreased by 1•0% (OR 95% CI 0•983-0•996; p=0•001), with a predicted decrease in VT carriage rate from 29•1% to 13•1% as coverage reached 100%. There was a trend towards a slower decline within informal settlements (p=0•100). Adjusted PCV13 vaccine effectiveness against VT carriage was 39•1% (95% CI 11•4-58•1%, p=0•009). INTERPRETATION: Substantial indirect effects were observed following PCV13 introduction, including among children living within informal settlements. FUNDING: Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance.
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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)
    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.