@article{4427,
  keywords = {Humans, Bacteria, United States, Child, Metagenomics, Cohort Studies, Prospective Studies, Critical Illness, Respiration, Artificial, Haemophilus influenzae, Moraxella catarrhalis, Respiratory Syncytial Virus, Human, Respiratory Tract Infections},
  author = {Alexandra Tsitsiklis and Christina Osborne and Jack Kamm and Kayla Williamson and Katrina Kalantar and Gytis Dudas and Saharai Caldera and Amy Lyden and Michelle Tan and Norma Neff and Victoria Soesanto and J Kirk Harris and Lilliam Ambroggio and Aline Maddux and Todd Carpenter and Ron Reeder and Chris Locandro and Eric Sim{\~o}es and Matthew Leroue and Mark Hall and Athena Zuppa and Joseph Carcillo and Kathleen Meert and Anil Sapru and Murray Pollack and Patrick McQuillen and Daniel Notterman and J Michael Dean and Matt Zinter and Brandie Wagner and Joseph DeRisi and Peter Mourani and Charles Langelier},
  title = {Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics.},
  abstract = { <p><b>BACKGROUND: </b>Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.</p><p><b>METHODS: </b>We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.</p><p><b>FINDINGS: </b>Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92\%) children with LRTI, with respiratory syncytial virus (127 [46\%]), Haemophilus influenzae (70 [25\%]), and Moraxella catarrhalis (65 [24\%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52\%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68\%) children without LRTI, with rhinovirus (30 [25\%]) being most prevalent. Respiratory syncytial virus (p<0{\textperiodcentered}0001), H influenzae (p=0{\textperiodcentered}0006), and M catarrhalis (p=0{\textperiodcentered}0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.</p><p><b>INTERPRETATION: </b>These findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.</p><p><b>FUNDING: </b>US National Institutes of Health and CZ Biohub.</p> },
  year = {2022},
  journal = {Lancet Microbe},
  volume = {3},
  pages = {e284-e293},
  month = {2022 Apr},
  issn = {2666-5247},
  doi = {10.1016/S2666-5247(21)00304-9},
  language = {eng},
}