Abstract

BackgroundBacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). ObjectivesTo systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children. Data sourcesMEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science. Study eligibility criteriaStudies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls. ParticipantsChildren under 5 years with and without acute LRTI. MethodsThree reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel–Haenszel fixed- or random-effects models. ResultsMost 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 log10 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. ConclusionsDetection 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.

Highlights

  • Over the past two decades, widespread introduction of conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has contributed to a global reduction in the incidence and severity of lower respiratory tract infection (LRTI) [1,2]

  • S. pneumoniae is recognized as the leading bacterial cause of LRTI in children [2,4], several large recent studies have not found evidence of an association between upper respiratory tract (URT) carriage and LRTI [12,13]

  • Our meta-analysis did not identify a significant association, after excluding studies reporting more antibiotic treatment prior to sampling in cases than controls, we found a positive association between S. pneumoniae URT colonization and LRTI

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Summary

Introduction

Over the past two decades, widespread introduction of conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has contributed to a global reduction in the incidence and severity of lower respiratory tract infection (LRTI) [1,2]. 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. 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 1.04e1.90). High density colonization with S. pneumoniae (>6.9 log 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.

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