Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics.
OBJECTIVE
Clinical, immunological and microbiological characteristics of recurrent invasive pneumococcal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions.


METHODS
All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection.


RESULTS
593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 children). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with reinfection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapy treatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder.


CONCLUSIONS
recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection.
Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Functional Unit of Immunology, Hospital Sant Joan de Déu and Hospital Clinic. Barcelona, Spain.
Laia
L
Alsina
Department of Pediatrics, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Maria G
MG
Basteiro
Department of Molecular Microbiology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Hector D
HD
de Paz
Department of Molecular Microbiology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Melania
M
Iñigo
Department of Pediatrics, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Mariona F
MF
de Sevilla
Department of Pediatrics, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Miriam
M
Triviño
Immunology Service, Hospital Clinic and Instituto de Investigaciones Biomédicas August Pi y Sunyer (IDIBAPS), Barcelona, Spain; Functional Unit of Immunology, Hospital Sant Joan de Déu and Hospital Clinic. Barcelona, Spain.
Manel
M
Juan
Department of Molecular Microbiology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Carmen
C
Muñoz-Almagro
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D019041:L-Selectin / Q000378:metabolism; D008024:Ligands; D008297:Male; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014611:Vaccination
D016207:Cytokines; D008024:Ligands; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D019041:L-Selectin