Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiotaResearch in context
Mischa H. Koenen,
Ruben C.A. de Groot,
Wouter A.A. de Steenhuijsen Piters,
Mei Ling J.N. Chu,
Kayleigh Arp,
Raïza Hasrat,
Ad C.J.M. de Bruijn,
Silvia C. Estevão,
Erhard van der Vries,
Jeroen D. Langereis,
Marianne Boes,
Debby Bogaert,
Annemarie M.C. van Rossum,
Wendy W.J. Unger,
Lilly M. Verhagen
Affiliations
Mischa H. Koenen
Center of Translational Immunology, UMC Utrecht, Utrecht, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Ruben C.A. de Groot
Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC University Medical Center Rotterdam – Sophia Children's Hospital, Rotterdam, the Netherlands
Wouter A.A. de Steenhuijsen Piters
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Center for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Mei Ling J.N. Chu
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Kayleigh Arp
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Raïza Hasrat
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Ad C.J.M. de Bruijn
Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC University Medical Center Rotterdam – Sophia Children's Hospital, Rotterdam, the Netherlands
Silvia C. Estevão
Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC University Medical Center Rotterdam – Sophia Children's Hospital, Rotterdam, the Netherlands
Erhard van der Vries
Department of Research & Development, GD Animal Health, Deventer, the Netherlands
Jeroen D. Langereis
Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
Marianne Boes
Center of Translational Immunology, UMC Utrecht, Utrecht, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Debby Bogaert
Center for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands
Annemarie M.C. van Rossum
Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, Erasmus MC University Medical Center Rotterdam – Sophia Children's Hospital, Rotterdam, the Netherlands
Wendy W.J. Unger
Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC University Medical Center Rotterdam – Sophia Children's Hospital, Rotterdam, the Netherlands
Lilly M. Verhagen
Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, the Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pediatric Infectious Diseases and Immunology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author. Department of Pediatric Infectious Diseases and Immunology, Amalia Children's Hospital, Radboud University Medical Center, PO Box 9101, Geert Grooteplein Zuid 32, Nijmegen 6500 HB, the Netherlands.
Summary: Background: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors. Methods: We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing. Findings: Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06–0.37]) and total IgG deficiency (OR 0.15 [0.02–0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09–0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74–1608.11]) compared to non-carriers. Interpretation: M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members. Funding: Wilhelmina Children’s Hospital Research Fund, ‘Christine Bader Stichting Irene KinderZiekenhuis’, Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).
