Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

Pediatric parapneumonic empyema (PPE) has been increasing in several countries including Spain. Streptococcus pneumoniae is a major PPE pathogen; however, antimicrobial pretreatment before pleural fl uid (PF) sampling frequently results in negative diagnostic cultures, thus greatly underestimating the contribution of pneumococci, especially pneumococci susceptible to antimicrobial agents, to PPE. The study aim was to identify the serotypes and genotypes that cause PPE by using molecular diagnostics and relate these data to disease incidence and severity. A total of 208 children with PPE were prospectively enrolled; blood and PF samples were collected. Pneumococci were detected in 79% of culture-positive and 84% of culture-negative samples. All pneumococci were genotyped by multilocus sequence typing. Serotypes were determined for 111 PPE cases; 48% were serotype 1, of 3 major genotypes previously circulating in Spain. Variance in patient complication rates was statistically signifi cant by serotype. The recent PPE increase is principally due to nonvaccine serotypes, especially the highly invasive serotype 1. P leural effusions occur in at least 40% of children hospitalized with bacterial pneumonia. Occasionally, the infectious agent invades the pleura to cause pediatric paraneumonic empyema (PPE) (1), characterized by the presence of pus. Although rarely associated with fatalities in industrialized countries, PPE often results in prolonged hospitalization and surgical intervention, and patients are at risk for serious and long-lasting illness (2,3).An increasing incidence of PPE has been reported in several countries since the mid-1990s (2-6), but it is not clear why. Streptococcus pneumoniae is the most frequently found microorganism in most recent reports. However, conventional microbiologic culture methods have low sensitivity, usually because of antimicrobial pretreatment before sterile-site sampling. Consequently, the contribution of antimicrobial drug-susceptible serotypes might be higher than reported estimates. Molecular and antigen detection-based techniques, including direct molecular typing of culture-negative pleural fl uid (PF) samples (7), can be useful adjuncts in defi ning the contributory role of different microorganisms and pneumococcal serotypes to PPE etiology (4,8).Our study's goal was to prospectively investigate the molecular epidemiology of pneumococcal PPE among children admitted to 3 of the largest tertiary-care pediatric hospitals in Spain. There were 4 objectives: 1) identify the serotypes and multilocus sequence typing (MLST) genotypes causing PPE and determine whether a temporal change in the circulating genotypes could explain the recent increase; 2) determine whether the causal genotypes were only associated with PPE or also caused other invasive pneumococcal disease (IPD) in the same population, or were carried by healthy children; 3) compare serotypes and genotypes recovered from northern and southern Spain in the context of regional differences in 7-valent pneumococcal conjugat...

BackgroundOver 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)—the gold standard for cause of death determination—are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed.Methods and findingsIn this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56–0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18–0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction.ConclusionsThe MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.

Pneumococcal parapneumonic empyema is an increasingly common complication in children. Conventional microbiological cultures indicate bacterial causes in as few as 8% of cases; therefore, there is a vital need for new molecular methods of detection and diagnosis. The development and clinical evaluation of real-time PCR-based assays to detect the pneumococcal capsular wzg gene of all serotypes tested are reported here, and 24 of them have been identified in clinical specimens. Using real-time PCR assays with highly specific TaqMan MGB probes that target DNA sequences within the capsular polysaccharide gene cluster, it was possible to differentiate serotypes 1, 3, 5, 4, 6A, 6B, 7F/A, 8, 9V/A/N/L, 14, 15B/C, 18C/B, 19A, 19F/B/C, 23F and 23A. These assays showed high sensitivity (five to ten pneumococcal DNA equivalents) and they were validated with 175 clinical isolates of known serotypes. The clinical value of this approach was demonstrated by analysis of 88 culture-negative pleural fluids from children diagnosed with parapneumonic empyema in three Spanish hospitals. Pneumococcal DNA was detected in 87.5% of pleural fluids, and serotypes 1, 7F and 3 were responsible for 34.3%, 16.4% and 11.9%, respectively, of cases of parapneumonic empyema in children. Such molecular methods are critical for the diagnosis of invasive pneumococcal disease and continued epidemiological surveillance in order to monitor serotype vaccine effectiveness.

Human cytomegalovirus (HCMV) has been reported to reshape the NK-cell receptor (NKR) distribution, promoting an expansion of CD94/NKG2C + NK and T cells. The role of NK cells in congenital HCMV infection is ill-defined. Here we studied the expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the NKG2C gene deletion in children with past congenital infection, both symptomatic (n = 15) and asymptomatic (n = 11), including as controls children with postnatal infection (n = 11) and noninfected (n = 20). The expansion of NKG2C + NK cells in HCMV-infected individuals appeared particularly marked and was associated with an increased number of LILRB1 + NK cells in cases with symptomatic congenital infection. Increased numbers of NKG2C + , NKG2A + , and CD161 + T cells were also associated to HCMV infection. The NKG2C deletion frequency was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous NKG2C +/+ genotype appeared associated with increased absolute numbers of NKG2C + NK cells. Moreover, HCMV-infected NKG2C +/+ children displayed higher absolute numbers of NKG2A + and total NK cells than NKG2C +/− individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK-cell compartment in children, revealing a modulatory influence of NKG2C copy number. Eur. J. Immunol. 2012. 42: 3256-3266 Immunity to infection 3257 lifelong latent state, occasionally undergoing reactivation, but may have a pathogenic role in immunodeficient and immunosuppressed patients [1][2][3]. Moreover, HCMV has been associated with atherosclerosis, lymphoproliferative disorders, and glioblastoma, as well as with an accelerated immunosenescence and a shorter lifespan [4][5][6][7]. Vertical transmission of HCMV during pregnancy is considered the most common cause of congenital infection worldwide, affecting ∼0.2-2% of infants and potentially causing fetal lesions [8][9][10]. Though most infected newborns are asymptomatic, ∼10% display a variety of clinical disorders [8,11] potentially leading to important sequelae such as mental retardation and deafness. The type of maternal infection (i.e., primary versus reactivation/reinfection) conditions the risk of congenital infection and the pregnancy stage at which transmission occurs is related to clinical severity [12][13][14][15][16]. Maternal antibodies with neutralizing activity are transferred to the fetus predominantly during the third trimester of gestation and may prevent congenital CMV disease [17]. Among other factors, fetal immune immaturity may determine the outcome of congenital infection [18,19]. An effective defense against HCMV requires the participation of T and NK cells, and the virus has developed different immune evasion strategies [20]. Patients with congenital HCMV infection have been shown to display mature CD8 + T-cell responses [21,22], and an expansion and differentiation of a specific TcR γδ + cell subset has been recently reported [23]. In contrast, information on the role of...

There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.

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In Morocco, the epidemiological profile of paediatric acute respiratory infections is markedly shifted towards wheezing-related diseases and thus resembles that of high-income countries. However, the high associated CFRs found in this study call for an improvement in preventive and clinical management strategies.