Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics.

Laia Alsina,Maria G Basteiro,Hector D De Paz,Carmen Muñoz-Almagro,Mariona F De Sevilla,Miriam Triviño,Melania Iñigo,Manel Juan,Bernard Beall

doi:10.1371/journal.pone.0118848

Abstract

PurposeClinical, 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.MethodsAll 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.Results593 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.Conclusionsrecurrent 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.

Highlights

Streptococcus pneumoniae is a commensal organism of the human nasopharynx [1] and a major cause of morbidity and mortality worldwide
593 patients were diagnosed with invasive pneumococcal disease (IPD) and 10 patients died
23 episodes of recurrent IPD were identified in 10 patients (1.7%)

Summary

Introduction

Streptococcus pneumoniae (pneumococcus) is a commensal organism of the human nasopharynx [1] and a major cause of morbidity and mortality worldwide. In 2000, it was estimated that about 14.5 million episodes of serious pneumococcal disease and more than 800,000 deaths in children less than 5 years of age occurred [3]. Pneumococcus is the leading cause of mild infections of the upper respiratory tract (otitis media, sinusitis) [1]. Despite this high burden, the occurrence of 2 or more episodes of invasive pneumococcal disease (IPD) in the same individual one month apart, called recurrent IPD [4], is much less frequent, with an estimated rate between 2 and 4% [4]. The event of a recurrent IPD must pose the question of an underlying medical condition predisposing to this rare phenomenon

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