Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study

Summary Background Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. Methods We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. Findings 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24–0·31; median age 5 months [IQR 3–9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04–0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4–6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4–7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33–92·54), respiratory syncytial virus (8·05, 4·21–15·38), or influenza virus (4·13, 2·06–8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae , and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sp