Etiology of Clinical Community-Acquired Pneumonia in Swedish Children Aged 1-59 Months with High Pneumococcal Vaccine Coverage-The TREND Study

Abstract

(1) Immunization with pneumococcal conjugate vaccines has decreased the burden of community-acquired pneumonia (CAP) in children and likely led to a shift in CAP etiology. (2) The Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) enrolled children 1-59 months with clinical CAP according to the World Health Organization (WHO) criteria at Sachs' Children and Youth Hospital, Stockholm, Sweden. Children with rhonchi and indrawing underwent "bronchodilator challenge". C-reactive protein and nasopharyngeal PCR detecting 20 respiratory pathogens, were collected from all children. Etiology was defined according to an a priori defined algorithm based on microbiological, biochemical, and radiological findings. (3) Of 327 enrolled children, 107 (32%) required hospitalization; 91 (28%) received antibiotic treatment; 77 (24%) had a chest X-ray performed; and 60 (18%) responded to bronchodilator challenge. 243 (74%) episodes were classified as viral, 11 (3%) as mixed viral-bacterial, five (2%) as bacterial, two (0.6%) as atypical bacterial and 66 (20%) as undetermined etiology. After exclusion of children responding to bronchodilator challenge, the proportion of bacterial and mixed viral-bacterial etiology was 1% and 4%, respectively. (4) The novel TREND etiology algorithm classified the majority of clinical CAP episodes as of viral etiology, whereas bacterial etiology was uncommon. Defining CAP in children <5 years is challenging, and the WHO definition of clinical CAP is not suitable for use in children immunized with pneumococcal conjugate vaccines.

Keywords: World Health Organization; bacterial pneumonia; children; etiology; pneumococcal conjugate vaccines; respiratory infection; viral pneumonia.

Figure 1

Flowchart of the TREND etiology algorithm. Abbreviations: B. pertussis, Bordetella pertussis; CRP, C-reactive protein; h, hour; hMPV, human metapneumovirus; M. pneumoniae, Mycoplasma pneumoniae; PCR, polymerase chain reaction; PIV, parainfluenza virus; RSV, respiratory syncytial virus; TREND, Trial of Respiratory infections for Enhanced Diagnostics.

Figure 2

Real-time PCR findings according to age in nasopharyngeal aspirates of children with clinical CAP in the TREND study (n = 327). Numbers showing the total number of detected pathogens. Abbreviations: B. pertussis, Bordetella pertussis; C. pneumoniae, Chlamydophila pneumoniae; CAP, community-acquired pneumonia; H. influenzae, Haemophilus influenzae; M. pneumoniae, Mycoplasma pneumoniae; PCR, polymerase chain reaction; RSV, respiratory syncytial virus; S. pneumoniae, Streptococcus pneumoniae; TREND, Trial of Respiratory infections for Enhanced Diagnostics.

Figure 3

Etiology classification of children with clinical CAP in the TREND study in (A) the full cohort based on WHO criteria (n = 327), (B) children with physician-diagnosed CAP (ICD-10 code of J10.0, J11.0 or J12-J18) (n = 50), children (C) with (n = 60) or (D) without (n = 267) positive bronchodilator challenge and (E) children with WHO radiographic CAP (n = 25). Abbreviations: CAP, community-acquired pneumonia; WHO, World Health Organization.