Jean Gaschignard1, Corinne Levy2, Maya Chrabieh3, Bertrand Boisson4, Cécile Bost-Bru5, Stéphane Dauger6, François Dubos7, Philippe Durand8, Joël Gaudelus9, Dominique Gendrel10, Christèle Gras Le Guen11, Emmanuel Grimprel12, Gaël Guyon13, Catherine Jeudy14, Eric Jeziorski13, Francis Leclerc15, Pierre-Louis Léger16, Fabrice Lesage17, Mathie Lorrot18, Isabelle Pellier14, Didier Pinquier19, Loïc de Pontual9, Philippe Sachs6, Caroline Thomas20, Pierre Tissières8, Frédéric V Valla21, Philippe Desprez22, Véronique Frémeaux-Bacchi23, Emmanuelle Varon24, Xavier Bossuyt25, Robert Cohen2, Laurent Abel26, Jean-Laurent Casanova27, Anne Puel3, Capucine Picard28. 1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France Groupe de Pathologie Infectieuse Pédiatrique, France. 2. Groupe de Pathologie Infectieuse Pédiatrique, France Association Clinique et Thérapeutique Infantile du Val de Marne, Saint-Maur, France Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France. 3. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France. 4. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York. 5. Pediatric Unit, Grenoble Hospital, Grenoble, France. 6. Pediatric Intensive Care Unit, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris Paris (APHP), France. 7. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Emergency and Infectious Diseases Unit, Centre Hospitalier Régional Universitaire, UDSL, Lille, France. 8. Pediatric Intensive Care Unit, Kremlin Bicêtre Hospital, APHP, Kremlin Bicêtre, France. 9. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Jean Verdier Hospital, APHP, Bondy, France. 10. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Necker Hospital, APHP, Paris, France. 11. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Nantes Hospital, Nantes, France. 12. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric and Neonatal Intensive Care Units, Armand Trousseau Hospital, Paris, France. 13. Pediatric Unit, Montpellier Hospital, Montpellier, France. 14. Pediatric Onco-Hematology Unit, Angers Hospital, Angers, France. 15. Pediatric Intensive Care Unit, CHRU, Lille University Hospital, UDSL, Lille, France. 16. Pediatric and Neonatal Intensive Care Units, Armand Trousseau Hospital, Paris, France. 17. Pediatric Intensive Care Unit, Necker Hospital. 18. Pediatric Unit, Robert Debré Hospital, APHP, Paris, France. 19. Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Intensive Care Unit, Rouen Hospital, Rouen, France. 20. Pediatric Intensive Care and Onco-Hematology Units, Nantes Hospital, Nantes, France. 21. Pediatric Intensive Care Unit, Hôpital Femme Mère Enfant, Lyon, France. 22. Pediatric Intensive Care Unit, Hôpital Hautepierre, Strasbourg, France. 23. Immunology Laboratory, Georges Pompidou European Hospital, APHP, Paris. 24. Groupe de Pathologie Infectieuse Pédiatrique, France National Reference Center for Pneumococci, Microbiology Laboratory, Georges Pompidou European Hospital, APHP, Paris, France. 25. Laboratory Medicine, University Hospitals Leven and Experimental Laboratory Immunology, Department Microbiology and Immunology, Catholic University Leuven, Belgium. 26. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York. 27. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York Pediatric Hematology-Immunology Unit, Necker-Enfants Malades Hospital, Paris, France Howard Hughes Medical Institute, New York, New York. 28. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France Pediatric Hematology-Immunology Unit, Necker-Enfants Malades Hospital, Paris, France Center for the Study of Primary Immunodeficiencies, APHP, Necker Hospital, Paris, France.
Abstract
BACKGROUND: About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. METHODS: We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. RESULTS: We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). CONCLUSIONS: Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.
BACKGROUND: About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. METHODS: We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. RESULTS: We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). CONCLUSIONS:Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.
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