The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis

BACKGROUND: Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). OBJECTIVES: To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children. DATA SOURCES: MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls. PARTICIPANTS: Children under 5 years with and without acute LRTI. METHODS: Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel–Haenszel fixed- or random-effects models. RESULTS: Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23–2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17–3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04–1.90). High density colonization with S. pneumoniae (>6.9 log(10) copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive. CONCLUSIONS: Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.