title: Etiology of community acquired pneumonia among children in India: prospective, cohort study.
abstract: BACKGROUND
  Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap.
  
  
  METHODS
  We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens.
  
  
  RESULTS
  We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae-3, CMV-3, S. aureus-2, H. influenzae-2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality.
  
  
  CONCLUSIONS
  The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.
authors.affiliation: Department of Pediatrics, PGIMER, Chandigarh, India.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mathew
authors.affiliation: Department of Pediatrics, PGIMER, Chandigarh, India.
authors.forename: Sunit
authors.initials: S
authors.lastname: Singhi
authors.affiliation: Department of Medical Microbiology, PGIMER, Chandigarh, India.
authors.forename: Pallab
authors.initials: P
authors.lastname: Ray
authors.affiliation: Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hagel
authors.affiliation: Dept of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Shanie
authors.initials: S
authors.lastname: Saghafian-Hedengren
authors.affiliation: Department of Pediatrics, PGIMER, Chandigarh, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Dept of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ygberg
authors.affiliation: Department of Radiodiagnosis and Imaging, PGIMER Chandigarh, India.
authors.forename: Kushaljit Singh
authors.initials: KS
authors.lastname: Sodhi
authors.affiliation: Xcyton Diagnostics Pvt Ltd, Bangalore, India.
authors.forename: B V Ravi
authors.initials: BV
authors.lastname: Kumar
authors.affiliation: Dept of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson