Invasive pneumococcal disease in children can reveal a primary immunodeficiency.
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.
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.
Jean
J
Gaschignard
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.
Corinne
C
Levy
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.
Maya
M
Chrabieh
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York.
Bertrand
B
Boisson
Pediatric Unit, Grenoble Hospital, Grenoble, France.
Cécile
C
Bost-Bru
Pediatric Intensive Care Unit, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris Paris (APHP), France.
Stéphane
S
Dauger
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Emergency and Infectious Diseases Unit, Centre Hospitalier Régional Universitaire, UDSL, Lille, France.
François
F
Dubos
Pediatric Intensive Care Unit, Kremlin Bicêtre Hospital, APHP, Kremlin Bicêtre, France.
Philippe
P
Durand
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Jean Verdier Hospital, APHP, Bondy, France.
Joël
J
Gaudelus
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Necker Hospital, APHP, Paris, France.
Dominique
D
Gendrel
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Nantes Hospital, Nantes, France.
Christèle
C
Gras Le Guen
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric and Neonatal Intensive Care Units, Armand Trousseau Hospital, Paris, France.
Emmanuel
E
Grimprel
Pediatric Unit, Montpellier Hospital, Montpellier, France.
Gaël
G
Guyon
Pediatric Onco-Hematology Unit, Angers Hospital, Angers, France.
Catherine
C
Jeudy
Pediatric Unit, Montpellier Hospital, Montpellier, France.
Eric
E
Jeziorski
Pediatric Intensive Care Unit, CHRU, Lille University Hospital, UDSL, Lille, France.
Francis
F
Leclerc
Pediatric and Neonatal Intensive Care Units, Armand Trousseau Hospital, Paris, France.
Pierre-Louis
PL
Léger
Pediatric Intensive Care Unit, Necker Hospital.
Fabrice
F
Lesage
Pediatric Unit, Robert Debré Hospital, APHP, Paris, France.
Mathie
M
Lorrot
Pediatric Onco-Hematology Unit, Angers Hospital, Angers, France.
Isabelle
I
Pellier
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Intensive Care Unit, Rouen Hospital, Rouen, France.
Didier
D
Pinquier
Groupe de Pathologie Infectieuse Pédiatrique, France Pediatric Unit, Jean Verdier Hospital, APHP, Bondy, France.
Loïc
L
de Pontual
Pediatric Intensive Care Unit, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris Paris (APHP), France.
Philippe
P
Sachs
Pediatric Intensive Care and Onco-Hematology Units, Nantes Hospital, Nantes, France.
Caroline
C
Thomas
Pediatric Intensive Care Unit, Kremlin Bicêtre Hospital, APHP, Kremlin Bicêtre, France.
Pierre
P
Tissières
Pediatric Intensive Care Unit, Hôpital Femme Mère Enfant, Lyon, France.
Frédéric V
FV
Valla
Pediatric Intensive Care Unit, Hôpital Hautepierre, Strasbourg, France.
Philippe
P
Desprez
Immunology Laboratory, Georges Pompidou European Hospital, APHP, Paris.
Véronique
V
Frémeaux-Bacchi
Groupe de Pathologie Infectieuse Pédiatrique, France National Reference Center for Pneumococci, Microbiology Laboratory, Georges Pompidou European Hospital, APHP, Paris, France.
Emmanuelle
E
Varon
Laboratory Medicine, University Hospitals Leven and Experimental Laboratory Immunology, Department Microbiology and Immunology, Catholic University Leuven, Belgium.
Xavier
X
Bossuyt
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.
Robert
R
Cohen
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.
Laurent
L
Abel
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.
Jean-Laurent
JL
Casanova
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.
Anne
A
Puel
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.
Capucine
C
Picard
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005602:France; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000276:immunology*; D011446:Prospective Studies
Streptococcus pneumonia; complement deficiency; innate deficiency; primary antibody deficiency; primary immunodeficiency