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While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n = 34) or EV (n = 278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P < 0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P < 0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P = 0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P < 0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P = 0.004) as well as lower C-reactive protein (CRP) levels (P = 0.006) and neutrophil counts (P < 0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age. [ABSTRACT FROM AUTHOR]

Abstract Background China's immunization program is one of the oldest and largest in the world. Rates of vaccine-preventable diseases (VPD) are comparable to those in high-income countries. The program's evolution has been characterized by ambitious target setting and innovative strategies that have not been widely described. Methods We reviewed national and provincial health department archives; analyzed disease surveillance, vaccination coverage, and serosurvey data from 1950 through 2016; and, conducted in-depth interviews with senior Chinese experts involved early VPD control efforts. Results Widespread immunization began in the 1950s with smallpox, diphtheria, and Bacillus-Calmette Guerin vaccines, and in the 1960s with pertussis, tetanus, polio, measles, and Japanese encephalitis (JE) vaccines. The largest drops in absolute VPD burden occurred in the 1970s with establishment of the Rural Cooperative Medical System and a cadre of trained peasant health workers whose responsibilities included vaccinations. From 1970 to 1979, incidence per 100,000 population dropped 48% from 3.3 to 1.75 for diphtheria, 50% from 152.2 to 49.4 for pertussis, 77% from 2.5 to 0.6 for polio, 60% from 450.5 to 178.3 for measles, and 72% from 18.0 to 5.1 for JE, averting an average of 4 million VPD cases each year. Until the early 1980s, vaccines were delivered through annual winter campaigns using a coordinated ' rush-relay' system to expedite transport while leveraging vaccine thermostability. Establishment of the cold chain system during in the 1980s allowed bi-monthly vaccination rounds and more timely vaccination resulting in rates of diphtheria, pertussis, measles and meningitis falling over 90% from 1980 to 1989, while polio and JE rates fell 40–50%. In the 1990s, progress stalled as financing for public health was weakened by broad market reforms. Large investments in public health and immunizations by the central government since 2004 has led to further declines in VPD burden and increased equity. During 2011–2016, the incidence per 100,000 population was <2.0 for measles and <0.2 for pertussis, JE, meningococcal meningitis, and hepatitis A. From 1992 to 2014, the prevalence of chronic hepatitis B infection in children <5 years fell from 9.7% to 0.3%, a 97% decline. China was certified polio-free in 2000 and diphtheria was last reported in 2006. Conclusions Long-term political commitment to immunizations as a basic right, ambitious targets, use of disease incidence as the primary metric to assess program performance, and nationwide scale-up of successful locally developed strategies that optimized use of available limited resources have been critical to China's success in controlling vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Background Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for inflammatory diseases. We evaluated the levels of LRG, interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the cerebrospinal fluid (CSF) of children with meningitis. Methods CSF samples from 10 patients with bacterial meningitis (BM) and 10 with aseptic meningitis (AM) were evaluated. Samples from 10 patients with febrile status (FS) were used as controls. LRG levels were measured using a two-site enzyme immunoassay. IL-6 and TNF-α levels were measured using a multiplex bead-based assay. CSF examination of patients with BM at the convalescent stage was also conducted. Results LRG and TNF-α levels in patients with BM, and IL-6 levels in patients with BM and AM showed significant increase compared with those in FS. Patients with BM at the convalescent stage showed significantly diminished LRG and IL-6 levels. LRG and IL-6 levels in CSF were indicated to be effective predictors for BM (LRG, AUC = 0.91; IL-6, AUC = 0.85). Only LRG levels showed a significant difference between patients with BM and AM (AUC = 0.78, P  = 0.034). Conclusions LRG level could be a sensitive inflammatory biomarker for inflammatory diseases of the central nervous system, comparable with IL-6 level. [ABSTRACT FROM AUTHOR]

Introduction Widespread introduction of pneumococcal conjugated vaccines (PCVs) impacted on invasive pneumococcal disease (IPD). However, IPD reduction may not be similar in all outcomes within IPD. We assessed PCV7/PCV13 impact on pneumococcal meningitis, bacteremic pneumonia (BP) and other (non-meningitis, non-pneumonia) IPD episodes in children <5 years in Israel. Methods A prospective, population-based, active nationwide surveillance. All pneumococcal invasive episodes with positive blood/CSF cultures, July 2000 through June 2016, were included. Three sub-periods were defined: pre-PCV (2000–2008), PCV7 (2009–2011) and PCV13 (2014–2016). Incidence rate ratios (IRRs) were calculated. Results Overall, 4321 episodes were recorded; 456 (10.6%) meningitis, 1478 (34.2%) pneumonia and 2387 (55.2%) other-IPD. In the pre-PCV period, proportion of serotypes in PCV13, but not in PCV7 (mainly serotypes 1, 5 and 19A) was higher in BP (43.3%) compared with other-IPD episodes (32.8%, p < 0.001) and similar to that of meningitis (37.6%, p = 0.1). The proportion of episodes in children <12 months was higher in meningitis (52.1%) compared with pneumonia (23.2%) and other-IPD episodes (39.5%; p < 0.001 for both). The declines of the 3 entities were not similar; Meningitis rate non-significantly declined by 24% (IRR = 0.76; 95% CI 0.57–1.01), while BP and other-IPD rates significantly declined by 57% and 70%, respectively. In contrast to other entities, BP did not decline significantly after PCV7 introduction but started to decline only after PCV13 introduction. Rates of meningitis, pneumonia and other-IPD caused by PCV13-serotypes (VT13) substantially declined by 88%, 95% and 97%, respectively, comparing PCV13 and the pre-PCV periods. However, diseases caused by non-VT13 increased by 256%, 302% in meningitis and pneumonia, respectively, but only 116% in other-IPD. Conclusions Following PCV7/PCV13 introduction, rates of episodes caused by VT13 were substantially reduced in all 3 groups. However, differences in age distribution, serotype replacement and specific serotype decrease suggest different pathogenesis and host susceptibility between the 3 entities. [ABSTRACT FROM AUTHOR]

Cronobacter is a group of opportunistic pathogen responsible for necrotizing enterocolitis, meningitis and septicaemia especially to infant and neonate, with high lethality ranging in 40%–80%. Some of them are able to survive in infant milk formula and still possesses capability of pathogenicity and virulence, biofilm formation, and high resistance to elevated osmotic pressure, low pH, heat, oxidation and desiccation. The genus Cronobacter consists of a diverse group of Gram-negative bacteria and comprises seven species: C. sakazakii , C. turicensis , C. malonaticus , C. universails , C. muytjensii , C. condiment and C. dublinensis with the three subspecies dublinensis , lausannensis and lactatidi . Sub-lethal treatments on Cronobacter strains including heat shock, acid shock, ethanol shock and desiccation would enhance its tolerance to adverse environments. Here, we discuss the stress resistance, rapid detection and disinfection methods of Cronobacter spp. in recent literature. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children. Methods Children younger than 15 years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded. Results One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007–April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010–April 2015). When both periods were compared, a 62% (95% CI: 45–75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p = 0.0001), mainly due to an 83% (95% CI: 30–96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC > 0.5 μg/L) decreased from 27% to 8%, (p = 0.02). Mean patient ages rose from 28.7 months to 38.5 months (p < 0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study. Conclusions Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15 years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed. [ABSTRACT FROM AUTHOR]

Background: A substantial reduction in bacterial meningitis has occurred in the UK following successful implementation of immunisation programmes. Most childhood meningitis in developed countries is now caused by viruses. Long-term trends in paediatric viral meningitis in England have not previously been reported. The objective of this study is to report on epidemiological trends over time in childhood viral meningitis in England.Methods: In this population-based observational study, we used routinely collected hospital discharge records from English National Health Service hospitals from 1968-2011 to analyse annual age-specific admission rates for viral meningitis, including specific viral aetiologies, in children younger than 15 years.Findings: We analysed hospital discharge records from Jan 1, 1968, to Dec 31, 2011. Hospital admission rates for viral meningitis from Jan 1, 1968, to Dec 31, 1985, varied annually, with a mean of 13·5 admissions per 100 000 children aged less than 15 years, per year (95% CI 13·0-14·0). Admission rates declined during the late 1980s, and the mean number of admissions from 1989-2011 was 5·2 per 100 000 per year (5·1-5·3). This decrease was entirely in children aged 1-14 years. Admission rates for infants aged less than 1 year increased since 2005, to 70·0 per 100 000 (63·7-76·2) in 2011, which was driven by an increase in admission of infants aged 90 days or less. In 1968-85, the majority of cases in children were in those aged 1-14 years (22 150 [89%] of 24 920 admissions). In 2007-11, 1716 (72%) of 2382 cases were in infants. Admissions for mumps-related meningitis almost disappeared following introduction of the measles-mumps-rubella (MMR) vaccine in 1988. Admissions with a specified viral aetiology have increased since 2000.Interpretation: Trends in viral meningitis admissions have changed substantially over the past 50 years, and probably reflect the impact of the MMR vaccine programme and the use of more sensitive diagnostic techniques.Funding: None. [ABSTRACT FROM AUTHOR]

Objective To investigate the long-term effectiveness of transmastoid lateral semicircular canal approach (TMLSCCA) to repair cerebrospinal fluid (CSF) leakage in children associated with recurrent meningitis and severe congenital inner malformation. Method A retrospective study was conducted in a university hospital, academic medical center. Fifteen children with recurrent meningitis, secondary to severe congenital inner ear malformation, were included in the study. All of them had CSF associated otorrhea and treated using TLSCCA to repair CSF otorrhea by packing the vestibule with muscle and fascia. Observation of the status of postoperative CSF leakage, recurrence of meningitis and complication were conducted. Results None of the cases had recurrent meningitis and CSF leakage after their TLSCCA procedure in the follow-up period of 1–8.5 years. One case presented with transient facial nerve paralysis and completely recovered 3 months later. Conclusion TLSCCA for CSF otorrhea in children with recurrent meningitis secondary to congenital inner ear malformation is an alternative approach that offers some advantages. [ABSTRACT FROM AUTHOR]

Objective Pediatricians are well aware of the immediate risks of bacterial meningitis in children. However, the long-term outcome of the disease has not been extensively studied. We aimed: (i) to evaluate the duration and quality of the long-term follow-up of children diagnosed with bacterial meningitis in a general pediatric department, (ii) to estimate the incidence of sequelae at the various stages of follow-up, and (iii) to compare our data with that of other studies. Methods We conducted a retrospective study and included 34 children (3 months–15 years) who had been hospitalized for bacterial meningitis in the pediatric department of a University Hospital between January 1st, 2001 and December 31st, 2013. Results Overall, 32% of patients presented with sequelae and 15% with seizures. Only one patient presented with hearing loss, but 23.5% of patients did not have any hearing test performed. Seven patients had a neuropsychological assessment performed and no severe neuropsychological sequela was observed in this group. The average follow-up duration increased during the study period (from 23 to 49 months). The long-term follow-up modalities observed in other studies were highly variable. Assessing the incidence and severity of sequelae was therefore difficult. Conclusion A standardized follow-up should be implemented by way of a national surveillance network of children presenting with bacterial meningitis. [ABSTRACT FROM AUTHOR]

Background Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. Objectives To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. Study design This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. Results Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p = 0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p = 0.030), and significantly more in HPeV-1 than HPeV-3 infected children ( p < 0.001). Conclusions EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection. [ABSTRACT FROM AUTHOR]

Background Bacterial meningitis is a life threatening disease that can be triggered by a CSF leak through an inner ear malformation. Early identification of the specific type of cochleovestibular dysplasia and the associated risk of meningitis is of vital importance. Objectives The objective of this review is to collect and discuss available data on the association between inner ear malformations and meningitis in children. Methods Electronic databases were crosschecked for obtaining relevant papers published in the last 20 years, and further cases were identified by hand searching through the references. Demographic data were extracted from full texts, together with information on the severity of hearing impairment, the type of inner ear anomaly, the site of cerebrospinal fluid leak, the number of recurrent meningitis episodes. Results Sixty-seven cases of meningitis related to inner ear malformation have been identified among 45 papers. Mean age at presentation is 3.60 ± 3.00 (range 0.1–14) years. Average diagnostic delay from the first episode of meningitis is 3.44 ± 3.41 (range 0.00–10.00) years. The number of meningitis episodes that occurred before the correct diagnosis and definitive surgical treatment is 3.27 ± 1.81 (range 1.00–10.00). Unilateral hearing impairment affects 70% of patients. Six patients had normal hearing at presentation. Two children are dead from inner-ear-malformation-related meningitis among reviewed reports. Conclusion A high number of paediatric patients carrying inner ear malformations, especially when associated with unilateral hearing impairment, could be at risk to develop recurrent bacterial meningitis. Universal newborn hearing screening programs should prompt a diagnostic work-up even in the case of unilateral hearing impairment, in order to prevent inner ear malformation-related meningitis. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of invasive infections among newborns in industrialized countries, with two described syndromes: early-onset disease (EOD) and late-onset disease (LOD). Since the introduction in many countries of intrapartum antibioprophylaxis (IAP), the incidence of EOD has dramatically decreased, whereas that of LOD remains unchanged. We describe the clinical and bacteriological characteristics of 438 GBS neonatal invasive infections notified to the French National Reference Centre for Streptococci in France from 2007 to 2012. Clinical data were retrieved from hospitalization reports or questionnaires. Capsular type, assignment to the hypervirulent clonal complex (CC)17 and antibiotic susceptibility profiles were determined. One hundred and seventy-four (39.7%) and 264 (60.3%) isolates were responsible for EOD, including death in utero , and LOD, respectively. EOD was associated with bacteraemia ( n = 103, 61%) and LOD with meningitis ( n = 145, 55%). EOD was mainly due to capsular polysaccharide (CPS) III isolates ( n = 99, 57%) and CPS Ia isolates ( n = 40, 23%), and CPS III isolates were responsible for 80% ( n = 211) of LOD cases. CC17 accounted for 80% ( n = 121) of CPS III isolates responsible for meningitis ( n = 151; total cases of meningitis, 188). Bad outcome risk factors were low gestational age and low birthweight. LOD represents almost 60% of cases of neonatal GBS disease in France and other countries in which IAP has been implemented. This observation reinforces the need to develop new prevention strategies targeting CC17, which is predominant in GBS neonatal infections. [ABSTRACT FROM AUTHOR]

Infectious meningitis is a large public health concern, especially in children and immunocompromised patients. Although the epidemiology of meningitis has shown significant decline in past decades, partly due to the introduction of vaccines, outbreaks are still reported worldwide. Diagnosis of meningitis is of critical importance, and it is considered to be one of the most urgent of the microbiological medical emergencies. In order to improve the treatment strategy, various diagnostic methods have been developed to detect the presence of infectious agents that cause meningitis, as well as their antibiotic resistance patterns. This article aims to enhance the understanding of meningitis and to highlight the most current updates that describe outbreaks of meningitis and the subsequent investigations. We also describe the current diagnosis and treatment options. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) is an asymptomatic colonizer of human mucosal surfaces that is responsible for sepsis and meningitis in neonates. Bacterial persistence and pathogenesis often involves biofilm formation. We previously showed that biofilm formation in medium supplemented with glucose is mediated by the PI-2a pilus. Here, biofilm formation was tested in cell culture medium supplemented with human plasma. GBS strains were able to form biofilms in these conditions unlike Group A Streptococcus (GAS) or Staphylococcus aureus . Analysis of mutants impaired for various surface components revealed that the GBS capsule is a key component in this process. [ABSTRACT FROM AUTHOR]

Background Enterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization. Objectives To assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM. Study design Observational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A = no PCR or negative PCR ( n = 17), group B = positive real-time PCR ( n = 20), and group C = positive GXEA ( n = 22). Clinical, laboratory and health-care costs data were compared. Results Clinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60 h (IQR (interquartile range) 44–87) in group B to 5 h (IQR 4–11) in group C ( p < 0.0001). Median duration of antibiotics was 1 (IQR 0–6), 1 (0–1.9), and 0.5 days (single dose) in groups A, B, and C, respectively ( p < 0.001). Median length of hospitalization was 4 days (2.5–7.5), 2 (1–3.7), and 0.5 (0.3–0.7), respectively ( p < 0.001). Median hospitalization costs were $5458 (2676–6274) in group A, $2796 (2062–5726) in group B, and $921 (765–1230) in group C ( p < 0.0001). Conclusions Rapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs. [ABSTRACT FROM AUTHOR]

Summary Background Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. Methods We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. Findings 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0–26·1) and probability of survival without neurological sequelae was 36·7% (27·9–46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6–64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5–100·0), CSF lymphocytosis (97·9%, 51·9–100·0), fever (89·8%, 79·8–95·2), and hydrocephalus (86·1%, 68·6–94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0–15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8–59·2). Interpretation Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. Funding None. [ABSTRACT FROM AUTHOR]

Summary: Neisseria meningitidis is an important cause of invasive bacterial infection in children worldwide. Although serogroup C meningococcal disease has all but disappeared in the past decade as a direct result of immunisation programmes in Europe, Canada, and Australia, meningitis and septicaemia caused by serogroup B meningococci remain uncontrolled. A vaccine (4CMenB) has now been licensed for use in the European Union, comprising three immunogenic antigens (identified with use of reverse vaccinology) combined with bacterial outer-membrane vesicles. The vaccine has the potential to reduce mortality and morbidity associated with serogroup B meningococci infections, but uncertainty remains about the breadth of protection the vaccine might induce against the diverse serogroup B meningococci strains that cause disease. We discuss drawbacks in the techniques used to estimate coverage and potential efficacy of the vaccine, and their effects on estimates of cost-effectiveness, both with and without herd immunity. For parents, and clinicians treating individual patients, the predicted benefits of vaccination outweigh existing uncertainties if any cases can be prevented, but future use of the vaccine must be followed by rigorous post-implementation surveillance to reassess its value to health systems with directly recorded epidemiological data. [Copyright &y& Elsevier]

Abstract: Objective: To determine the association of bacteria embedded within a fibrous matrix in the middle and inner ear in infants with tympanogenic meningitis. Methods: Thirty-one cases with meningitis from the human temporal bone collection at the University of Minnesota were screened to select those with tympanogenic meningitis. Inclusion criteria for tympanogenic meningitis were acute meningitis with histopathological evidence of chronic otitis media, and no other source of infection. The presence of labyrinthitis and pathologic changes such as granulation tissue, fibrosis, cholesterol granuloma, cholesteatoma, tympanic membrane perforation, tympanosclerosis, and the type of effusion were noted. The extent and location of bacteria embedded in a fibrous matrix were also explored. Results: Seventeen temporal bones, from nine cases that included two females and seven males, ranging in age from five to twenty-three months, met our criteria of tympanogenic meningitis. Eighty two percent of these temporal bones had bacteria within the fibrous matrices (BFM). BFM were located in one anatomical region in one temporal bone and multiple anatomic regions in sixteen temporal bones. The most common locations were the areas near the oval and round windows. They were also commonly seen in the epitympanum, facial recess, and supratubal recess. BFM within the inner ear were observed in the scala tympani and modiolus in the middle and basal turns of the cochleae of nine temporal bones. In one of these temporal bones, BFM were seen in the internal auditory canal. Labyrinthitis was seen in all ears. The tympanic membrane was intact in all cases. BFM were not seen in three temporal bones from two patients. In one case only one side was available for study. Conclusions: Our findings show an association between the presence of BFM in the ear with chronic pathologic changes and tympanogenic meningitis. Potential pathways of bacteria from the middle ear include hematogeous spread and/or direct spread to dura through the tympanic tegmen, and/or to the inner ear through the oval and round windows, and from there to the modiolus and the meninges. Chronic pathologic changes in the middle ear behind an intact tympanic membrane and the lack of ear symptoms may result in potentially serious sequelae and complications in infant age groups. There should be a heightened awareness of this condition. [Copyright &y& Elsevier]

Objective: We evaluated the levels of cerebrospinal fluid concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-8 in bacterial meningitis in children. Methods: The study included children up to 14 years of age admitted to a pediatric ward with fever, headache, vomiting, and seizures. The diagnosis of bacterial meningitis was based on clinical features: physical examination, blood and cerebrospinal fluid cytochemical findings, Gram stain, and bacterial culture. The cerebrospinal fluid levels of tumor necrosis factor-α, interleukin-6, and interleukin-8 were measured in 57 children with bacterial meningitis, 15 with viral meningitis, and 15 controls by enzyme-linked immunosorbent assay methods. Results: The mean concentrations of cerebrospinal fluid, tumor necrosis factor-α, interleukin-6, and interleukin-8 were 1108 ± 183, 652 ± 287, and 442 ± 120 pg/mL, respectively, in children with bacterial meningitis and were significantly increased in those in the viral meningitis group (tumor necrosis factor-α : 711 ± 105, IL-6 : 272 ± 161, IL-8 : 175 ± 62 pg/mL; P < 0.001) or control (390 ± 37, 59 ± 17, 19 ± 13 pg/mL, respectively, P < 0.001). At optimum cutoff level based on the receiver operating characteristic curve, cerebrospinal fluid cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-8) showed sensitivity and specificity of 100% for the diagnosis of bacterial meningitis. For differentiation of bacterial from viral meningitis, cerebrospinal fluid level of tumor necrosis factor-α, IL-6, and IL-8 showed sensitivity and specificity of 94.7% and 86.7%, 80.7% and 53.3%, and 89.5% and 86.7%, respectively. Conclusion: The increased concentration of cerebrospinal fluid tumor necrosis factor-α, interleukin-6, and interleukin-8 in children with meningitis suggests a role in the pathogenesis of bacterial meningitis and these levels might prove to be useful in children whose diagnosis is in question. [ABSTRACT FROM AUTHOR]

Abstract: Background: Acute meningitis is a relatively common phenomenon in children. Identifying which children are most likely to have bacterial meningitis vs. self-limiting aseptic meningitis is important, as these children require investigation and antibiotic treatment. Objective: Our aim was to systematically identify and review the quality and performance of published clinical prediction rules (CPRs) for children with suspected bacterial meningitis. Methods: Medline and Embase were searched for CPRs involving children 0–18 years of age with suspected bacterial meningitis, with cerebral spinal fluid (CSF) culture used as the reference diagnostic standard. CPR quality was assessed using 17 previously published items. CPR performance was evaluated using sensitivity, negative likelihood ratio, and the treatment frequency that would result if the rule was used. Results: Eleven studies involving 6675 children with acute meningitis fulfilled all inclusion criteria and were entered in the study. They all describe the derivation or validation of six unique CPRs. A rigorously developed, high-performing, and well-validated CPR ready for clinical use to guide which children with suspected bacterial meningitis should be hospitalized and treated with intravenous antibiotics and which can be safely discharged home was not identified. Areas for quality improvement for future CPR studies include prospective validation using standardized inclusion criteria, adequate blinding, predictor reproducibility assessment, and meticulous follow-up of outcomes. The Bacterial Meningitis Score had the highest quality and performance and is the best candidate for prospective validation. Conclusions: Until consistently high methodological quality and diagnostic performance are demonstrated through prospective validation, caution is warranted in the routine clinical use of existing CPRs for children with suspected bacterial meningitis. [Copyright &y& Elsevier]

Abstract: Background: Infections caused by human enteroviruses (EVs) are often asymptomatic or mild, although they may cause more severe illnesses as meningitis and acute flaccid paralysis. EVs have globally posed a threat to children, and outbreaks of aseptic meningitis and hand, foot and mouth disease are frequently reported. Objective: To identify EV strains circulating among healthy children in a small community in Limbe, Cameroon two years apart. Study design: Species and EV types were obtained by partial 5′UTR-VP4 and VP1 sequencing of RNA from stool samples collected in October 2009 and September 2011 from 150 children in Cameroon. Results: In all, 74 children (49%) were infected with 28 different types of EV. There were 29 (54%) infected children in 2009, and 45 (47%) in 2011. There was a significant difference between detected species of EV, with 15 (47%) children infected with EV-A in 2009, and 22 (71%) with EV-B in 2011 (p =0.0001). In 2009, one child was infected by a divergent EV, which was most similar to EV-A90. Based on the complete VP1 sequence, it was shown to be a new EV designated EV-A119. Conclusion: The current study shows a high heterogeneity of circulating EV types among children in Limbe, Cameroon, and a previously not described shift in predominating EV species. [Copyright &y& Elsevier]

Abstract: Background: Human parechoviruses (HPeVs) have recently been recognized as important viral pathogens causing sepsis-like illness and meningitis in children, but the data on these infections in Korea is limited. Klassevirus is emerging as a novel etiologic agent of acute gastroenteritis, but its role in meningitis remains unclear. Objectives: To understand the epidemiology of HPeVs and klassevirus in sepsis-like illness and meningitis through the detection and typing of the virus in cerebrospinal fluid (CSF) samples. Study design: One hundred and eighty-three CSF samples collected from 183 patients ranging in the age group 1 day to 15 years were tested by using a RT-PCR assay for HPeV, EV and klassevirus. Amplification products of the VP3/VP1 and 3D region of the HPeV, and VP1 region of the EV were sequenced to identify the type. Results: A total of 12 HPeV positive samples (6.5%) were detected from 183 CSF samples and all the samples were typed as HPeV-3. EVs were detected in 39 patients (21.3%) in which echovirus 25 and CVA6 were frequently detected, but mixed infection of HPeV-3 and EV was not observed. Klassevirus was not detected in the study population. Most of the HPeV-3 positive patients were under 3 months of age. HPeV-3 infection was detected mostly in the summer season. The VP3/VP1 gene of the 12 Korean strains clustered most closely to the Japan strain (AB759192) and the 3D gene of the Korean strains also clustered to the Japan strain, which showed no evidence of recombination. Conclusions: To our knowledge, this is the first report on the detection of HPeV-3 from CSF samples in Korea, which suggests the necessity of routine screening for this virus in young infants with sepsis-like illness and meningitis. [Copyright &y& Elsevier]

Abstract: Background: In Lyme disease–endemic areas, many children with aseptic meningitis are hospitalized while awaiting Lyme serology results. Although Lyme serology takes several days, an enteroviral polymerase chain reaction (EV PCR) test takes only a few hours to return results. Objective: Our aim was to measure the impact of EV PCR testing on duration of stay for children evaluated for Lyme meningitis. Methods: A retrospective cohort study was performed with children evaluated for Lyme meningitis at 3 Emergency Departments located in Lyme disease–endemic areas. We defined Lyme meningitis using the Centers for Disease Control and Prevention criteria (either positive Lyme serology test result or an erythema migrans rash). The duration of stay was compared by EV PCR test result (positive, negative, and not obtained). Results: There were 423 study patients identified, 117 (28%) of whom had Lyme meningitis and 209 (49%) had an EV PCR test performed. Median length of stay varied by the EV PCR test status: children with a positive EV PCR test (n = 103; 28 h; interquartile range 17–48 h), those with a negative EV PCR test (n = 106; 72 h; interquartile range 48–120 h), and those who did not have an EV PCR test obtained (n = 214; 48 h; interquartile range 24–96 h; p ≤ 0.001). Conclusions: Rapid EV PCR testing could assist clinical decision making by Emergency Physicians, avoiding potentially unnecessary hospitalization and parenteral antibiotics for children at low risk of Lyme meningitis. [Copyright &y& Elsevier]

Abstract: The true incidence of acute otitis media (AOM) in neonates and infants younger than three months is unknown. In this population organisms causing AOM may disseminate leading to bacteremia, sepsis, and meningitis [1]. Objectives: To describe the clinical presentation, associated severe infections, bacteriologic etiology, and antibiotic resistance patterns of organisms isolated from the middle ear of infants younger than three months that were not vaccinated against Streptococcus pneumoniae. Methods: Otomicroscopy was performed in all children to confirm the suspected diagnosis of AOM. When purulent effusion retained in the middle ear was diagnosed, tympanocentesis and culture of middle-ear fluid was performed by conventional methods. Serotyping was done using the Quellung technique. Results: From May 2, 2009 to February 28, 2010, 52 infants met the inclusion criteria. Thirty-six were male (69.2%) and 16 were female (30.8%). From these 52 patients, 76 samples were obtained for culture. Bilateral acute suppurative otitis media was diagnosed in 24 (46.2%) infants. Of all infants, 18 (34.6%) had been treated with antibiotics before tympanocentesis. Eight patients (44.4%) had negative middle-ear fluid cultures. Sixty bacterial pathogens were isolated from the middle-ear fluid of 43 patients. Mixed infections were recorded in 14/52 patients (26.9%). Nine cultures were negative (17.3%), of which eight were from patients that had previously been treated with antibiotics. S. pneumoniae was isolated from middle-ear aspirates of 26/52 (50%) patients with acute suppurative otitis media. Twenty-two out of the 26 isolates were susceptible (84.7%) and four were intermediately susceptible to penicillin (15.3%). Streptococcus pyogenes was isolated in 3/52 (5.8%) and Haemophilus influenzae in 18/52 patients (34.6%). Five (27.8%) of these were beta-lactamase producers. Blood cultures, cerebrospinal fluid, and urine cultures were negative. Parenteral antimicrobial treatment was indicated in 29/52 (56%). Conclusions: S. pneumoniae is the most frequent pathogen to cause AOM in this age group. Empirical treatment with amoxicillin or ceftriaxone should be considered depending on clinical suspicion of severe invasive infection. [Copyright &y& Elsevier]

Abstract: Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×106 cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis. [Copyright &y& Elsevier]

Summary: Neonatal meningococcal meningitis are rare, but serious by their high mortality and squealer of severe psychomotor and sensor neural. We report four cases of meningococcal meningitis collected in neonatology and neonatal resuscitation service CHU Hassan II of Fez, from 1st January 2003 to 31st December 2006. The aim of our work is to reassess the frequency of this pathology and analyze its transmission in the neonatal period. Neonatal meningococcal meningitis accounts for 12% of all neonatal meningitis collected in our service and 0.7% of neonatal infections during the study period. Three patients aged respectively H2, H17 and j2 life so the transmission path is most likely the placenta. The fourth patient is older than 12 days, which suggests the likelihood of exogenous transmission. The clinical picture is variable and atypical disorders tone is found in three patients representing the most constant sign. Direct examination of the CSF has identified the germ in three cases and the fourth by soluble Ag. The third generation cephalosporins were the treatment of choice for our patients. The evolution was favorable and complications are encountered in only one patient. [Copyright &y& Elsevier]

Background and Aims: Streptococcus pneumoniae constitutes one of the main causes of sepsis, bacteremia and meningitis (pneumococcal invasive disease – PID), and pneumonia in infants and small children. Antipneumococcal vaccination in Mexico is expected to be a useful strategy to reduce morbimortality due to this cause. We undertook this study to determine the prevalence of PID and pneumonia and the PCV vaccination status of affected children as well as serotype distribution and antimicrobial susceptibility of pneumococcal strains responsible for PID in infants and small children in Mexico. Methods: From March 2010–June 2011, a prospective multicenter study was carried out in four states in Mexico to determine the prevalence of bacteremia, meningitis, septic arthritis and pneumonia due to S. pneumoniae and other microorganisms in children from 28 days–59 months of age. Isolated pneumococcal strains were serotyped and their antimicrobial resistance determined. Results: During the study period, 545 children were diagnosed with bacteremia, meningitis, septic arthritis or pneumonia; 46.7% of these clinical entities occurred among children <12 months of age. Community-acquired pneumonia was the most prevalent disease. It was possible to identify a causal microorganism in 55 cases, from which 80% were S. pneumoniae. Fifteen percent of patients with PID died. The most prevalent pneumococcal serotypes were 19A, 35B, 19F and 6A. 10.2% of nonmeningeal strains were resistant to meropenem and 82% were resistant to TMP/SMX. Conclusions: This study shows that pneumococcus was the most common bacteria isolated in the studied population, although epidemiological and laboratory-based surveillance still needs improvement. [Copyright &y& Elsevier]

Abstract: Tubercular meningitis constitutes an important cause of morbidity and mortality in developing countries, and various factors determine its outcome. We studied demographic and clinical profiles of childhood tubercular meningitis, and identified predictors of outcome. This prospective study was performed in 65 children aged ≤18 years, hospitalized with a diagnosis of tubercular meningitis. Boys outnumbered girls. Most patients presented with a poor clinical grade. Headache and vomiting comprised common features. Cerebrospinal fluid was characterized by predominant lymphocytosis. Many patients were diagnosed for Mycobacterium tuberculosis via polymerase chain reaction. Hydrocephalus comprises a common finding via computed tomography. Low Glasgow Coma Scores, seizures, basal exudates, and infarcts predict outcomes. Children with headaches, fevers, and altered sensorium should be investigated promptly for tubercular meningitis. Timely intervention may lead to early diagnoses and reductions in morbidity and mortality. [Copyright &y& Elsevier]

Abstract: Bacterial meningitis is one of the most serious infections in infants and children, with considerable morbidity and mortality. Despite the spreading of conjugated vaccines against Haemophilus influenzae type b (Hib), the most important pneumococcal serotypes and serogroup C meningococcus has reduced the incidence of this infection in developed countries, it still remains a global public health problem and an important cause of mortality and disability. Whether corticosteroids should be used as a complementary therapy to antibacterials is still not clear because of the disparate findings from clinical trials and clinical evidence. The aim of this review is to analyze the available evidence on the impact of corticosteroid therapy in infants and children with bacterial meningitis in developed countries in order to define whether they should be added routinely in the empiric therapy of such disease. Our analysis concluded that in high-income countries dexamethasone has shown good results to prevent hearing loss in Hib meningitis if administered before or at the same time as the first dose of antibiotics. Dexamethasone should be evaluated in pneumococcal meningitis: it may be less beneficial in children with delayed presentation to medical attention and may be unfavourable in case of cephalosporin-resistant pneumococci. On the contrary, there is no evidence to recommend the use of corticosteroids in meningococcal meningitis. Further studies that take into account the epidemiologic changes of recent years, consider enrolment based on the onset of symptoms and evaluate outcomes such as hearing loss and neurologic sequelae with advanced techniques are urgently needed. [Copyright &y& Elsevier]

Abstract: We present a 10-year-old boy with a greater than 5-year history of cerebrospinal fluid rhinorrhea. He experienced nine episodes of bacterial meningitis and underwent four surgical repairs, including two endoscopic repairs via the lateral nasal cavity, a craniotomy repair via forehead epidural, and endoscopic repair in combination with a ventriculoperitoneal shunt. The first three surgeries failed, but the fourth was successful, with no recurrence during 2.5 years of follow-up. We suggest that ventriculoperitoneal shunts be considered for refractory recurrent cerebrospinal fluid rhinorrhea, particularly in patients after multiple failures of conventional surgical repair, to reduce intracranial hypertension caused by long-term chronic cerebrospinal fluid compensatory production. [Copyright &y& Elsevier]

Cronobacter sakazakii is a Gram-negative opportunistic pathogen that causes necrotizing enterocolitis, sepsis, and meningitis in premature infants. The genetic basis of C. sakazakii virulence is poorly understood. In this study, the putative LysR-type transcriptional regulator (LTTR) gene (ESA_01081 homolog) was characterized as a possible regulator for C. sakazakii pathogenesis. An in-frame deletion mutant of the ESA_01081 homolog and its cognate complementation strain were constructed and characterized for pathogenesis (adhesion/invasion potentials to human intestinal cells and in vivo rat pup challenge assay), biofilm formation, resistance to oxidative stress and induction of IL-8 secretion. LTTR-deficient C. sakazakii ATCC 29544 exhibits significantly attenuated phenotypes in all the properties tested, except adhesion. Our data strongly suggest that the putative gpESA_01081 homolog, plays an important regulatory role in diverse biological processes including the virulence of C. sakazakii. This is the first report of a functional global regulator in C. sakazakii. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18 (Suppl. 5): 25-36 Abstract Pneumococcal conjugated vaccines have been recommended in children for over a decade in many countries worldwide. Here we review the development of pneumococcal vaccines with a focus on the two types currently available for children and their safety record. We discuss also the effect of vaccines, including the 13-valent pneumococcal conjugate vaccine, on invasive pneumococcal diseases in children, particularly bacteraemia, pneumonia and meningitis, as well as on mucosal disease and carriage. In regions where immunization was implemented in young children, the number of invasive pneumococcal diseases decreased significantly, not only in the target age group, but also in younger and much older subjects. Challenges and future perspectives regarding the development of new 'universal' vaccines, which could bypass the current problem of serotype-specific protection in a context of serotype replacement, are also discussed. [ABSTRACT FROM AUTHOR]

Summary: Children are among the subjects most frequently affected by tuberculous meningitis (TBM) due to their relative inability to contain primary Mycobacterium tuberculosis infection in the lung. TBM is a devastating disease with about 30% mortality among the most severe cases; moreover, 50% of survivors have neurological sequelae despite an apparently adequate administration of antibiotics. Early diagnosis and prompt treatment are crucial for reducing the risk of a poor outcome. However, especially in children, the best and most rapid way to confirm the diagnosis is controversial; the optimal choice, dose, and treatment duration of anti-tuberculosis drugs are not precisely defined, and the actual importance of adjunctive therapies with steroids and neurosurgery has not been adequately demonstrated. This review is an effort to discuss present knowledge of the diagnosis and treatment of pediatric TBM in order to offer the best solution to address this dramatic disease. In conclusion, we stress that new studies in children are urgently needed because data in the early years of life are more debatable than those collected in adults. In the meantime, when treating a child with suspected TBM, the most aggressive attitude to diagnosis and therapy is necessary, because TBM is a devastating disease. [ABSTRACT FROM AUTHOR]

Abstract: Pott''s puffy tumor is a rare entity, described as a subperiosteal abscess associated with underlying cranial osteomyelitis. It is more commonly seen in the adolescent age group and may result from frontal sinusitis or trauma. We present a case of a 5-year-old male with forehead swelling, meningitis, and brain abscess communicating between epidural and subdural spaces. Treatment included 8 weeks antibiotic therapy with broad spectrum coverage of anerobic and aerobic organisms. Initial surgical approach included soft tissue incision and drainage of abscess, right frontal sinus trephine, and right endoscopic sinus surgery. One week after his initial procedure, he returned to OR for right pterional craniotomy for drainage of multiple intracranial abscesses. Total inpatient care was 4 weeks duration, and a full recovery was achieved with no long term neurological sequelae. We include an updated review of the literature of pediatric Pott''s puffy tumor in children less than 10 years of age. [Copyright &y& Elsevier]

Summary: Background: New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis. Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow β-lactam infusion. We investigated whether these treatments had benefits in children with bacterial meningitis. Methods: We did a prospective, double-blind, single-centre study with a two-by-two factorial design in Luanda, Angola. 723 participants aged 2 months to 13 years were randomly assigned two 12 h intravenous infusions, without loading doses, of 125 mg/kg bodyweight cefotaxime (total dose 250 mg/kg) given over 24 h, or 250 mg/kg bodyweight cefotaxime given as four boluses, one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo. Two primary endpoints, death or severe neurological sequelae and deafness, were analysed by intention to treat. The study was registered as ISRCTN62824827. Findings: 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups. Causative agents were identified in 63% of cases and were mostly Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Death or severe neurological sequelae were seen in 340 (47%) of 723 children and deafness in 45 (12%) of 374 tested, both distributed similarly across treatment groups. In a predefined subgroup analysis of death or any sequelae, by causative agent, a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis (infusion plus placebo, odds ratio 0·18, 95% CI 0·03–0·90, p=0·04). A similar effect was seen for children receiving cefotaxime infusion plus paracetamol, but the difference was not significant (OR 0·22, 95% CI 0·04–1·09, p=0·06). A post-hoc analysis suggested that cefotaxime infusion plus paracetamol lowered mortality at least during the first 3 days, irrespective of cause. Interpretation: Although no tested regimen improved the final outcomes of these very ill children, studies of longer courses of β-lactam infusion plus paracetamol seem warranted. Funding: The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat. [Copyright &y& Elsevier]

Abstract: Early meningococcal disease (MD) diagnosis is difficult. We assessed rapid molecular testing of respiratory specimens. We performed genotyping of respiratory swabs, blood, and cerebrospinal fluid from children with suspected disease and nasal swabs (NSs) from matched controls. Thirty-nine of 104 suspected cases had confirmed disease. Four controls were carriers. Throat swab ctrA and porA testing for detection of disease gave a sensitivity of 81% (17/21), specificity of 100% (44/44), positive predictive value (PPV) of 100% (17/17), negative predictive value (NPV) of 92% (44/48), and relative risk of 12. NS ctrA and porA testing gave a sensitivity of 51% (20/39), specificity of 95% (62/65), PPV of 87% (20/23), NPV of 77% (62/81), and relative risk of 4. Including only the 86 NSs taken within 48 h of presentation, the results were sensitivity of 60% (18/30), specificity of 96% (54/56), PPV of 90% (18/20), NPV of 82% (54/66), and relative risk of 5. Swab type agreement was excellent (kappa 0.80, P < 0.001). There was exact phylogenetic agreement from different specimen sites for individuals. Carried genosubtypes were P1.7 and P1.21-7. Prehospital rapid molecular testing of easily obtained respiratory specimens could accelerate diagnosis of MD. [Copyright &y& Elsevier]

Abstract: Studies of clonality and clinical profile of serotype 19A invasive pneumococcal disease in children (IPD-19A) are worthy after PCV7 introduction. A prospective, hospital-based surveillance of IPD-19A, culture and/or PCR confirmed, was performed in 2007–2009 in Madrid (all 22 hospitals with pediatric departments). Sixty-two cases were found: 90.3% in children <5 years, 87.1% in <36 months, and 74.2% in ≤18 months. Clinical presentations: meningitis (22.6%), primary bacteremia (19.4%), secondary bacteremia to otic foci (SBOF; 17.7%), bacteremic pneumonia (17.7%), pediatric parapneumonic empyema (PPE; 17.7%) and others (4.8%). Presentations by age: meningitis (35.7%), SBOF (28.6%) and primary bacteremia (21.4%) in children <12 months, bacteremic pneumonia, PPE and primary bacteremia (26.3% each) in 12–23 months, and bacteremic pneumonia (33.3%) and PPE (26.6%) in ≥24 months. Sequence types ST276 and ST320 represented 83.0% isolates, all oral-penicillin/erythromycin non-susceptible. In nonmeningeal isolates, non-susceptibility to parenteral penicillin/cefotaxime was 0%/17.6% (ST276) and 93.8%/75.0% (ST320). Non-susceptibility in ST276 and ST320, prevalence of these STs among 19A isolates, and serotype 19A prevalence among IPDs, indicate the importance of 19A inclusion in PCV13 for IPD-19A prevention and for reducing 19A nasopharyngeal carriage, thus preventing 19A otitis (one-third of 19A bacteremia in this study were from otic origin). [Copyright &y& Elsevier]

No data exist on the prevalence of meningitis in a first episode of seizures with fever in the Indian population. We investigated the prevalence of bacterial meningitis in children aged 6-18 months presenting with a first episode of seizures with fever, and we assessed clinical predictors of bacterial meningitis in these patients. We analyzed clinical and investigative profiles of 497 children, aged 6-18 months, admitted to pediatric casualty wards with a diagnosis of first febrile seizures. Lumbar puncture was performed in 199 (40.04%) infants. The prevalence of meningitis was 2.4% in children with first febrile seizures, 0.86% in simple febrile seizures, and 4.81% in complex febrile seizures. Duration of seizures more than 30 minutes, the presence of postictal drowsiness, and neurologic deficits were predictive of meningitis, with neurologic deficits as the most reliable. These predictors should be assessed in larger prospective studies. [ABSTRACT FROM AUTHOR]

Abstract: Within the framework of our work in CAMSP “deafness”, we accomodate and deal with very young deaf children. In this context, we are interested in the precursors of the oral language, with the emergence of this one as with the styles of interaction, which will accompany and support this process in particular among our young patients with cochlear implants. Our reflexion and our observations fall under a double theoretical prospect, at the same time neuroscientific and psychodynamic. Starting from a clinical situation of deafness acquired following a meningitis at 3 months old, we engaged in filmed consultations to follow to readiest the linguistic evolution of a young patient. Thus, we filmed several weeks a dyad mother/young girl with cochlear implants in free situation of interaction during about 15min, like ourselves in interaction with this young girl for the same length of time and with a material identical to each meeting. These filmed recordings began starting from the third adjustment from the prostheses, the young girl being then 13-month-old and profiting from a double cochlear implants (ears left and right-hand side). From these meetings of observation “shared” with the mother accompanied sometimes by the speech therapist, sometimes of the psychologist, we tried to release the precursors and the emergence of the language in this small deaf girl with cochlear implants. We propose to you to expose yourselves the first results of this research task action anchored in the private clinic of the young child in CAMSP. [Copyright &y& Elsevier]

Abstract: A 2-month-old girl developed meningitis, ventriculitis and brain abscess in the course of Citrobacter koseri infection. She was successfully treated with the combined use of antibiotics, intra-cavitary urokinase and surgery, thus avoiding the development of hydrocephalus and of ventricular loculation. C. koseri is a Gram-negative pathogen with a strong predilection for the neonatal brain. Brain abscesses develop in roughly 77% of cases, causing severe neurological sequels in one-half and death in one-third of patients. The authors aim to report the role of neurosurgical treatment for managing the severe complications that may arise in the course of C. koseri brain infection and the use of urokinase for preventing the development of loculated hydrocephalus. [Copyright &y& Elsevier]

Abstract: We investigated the correlation between memory impairment and hippocampal brain-derived neurotrophic factor (BDNF) levels in adult rats submitted to experimental meningitis (Streptococcus pneumoniae) in the neonatal period. Sixty days after inoculation the animals were submitted to the behavior tasks and hippocampal BDNF protein were evaluated. In the meningitis group, there was impairment in habituation and avoidance memory and a decrease in the BDNF levels. The decrease in hippocampal BDNF levels correlated to impairment in memory in adult animals submitted to experimental meningitis in the neonatal period. [Copyright &y& Elsevier]

Summary: Bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The introduction of the protein conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has changed the epidemiology of bacterial meningitis. Suspected bacterial meningitis is a medical emergency and needs empirical antimicrobial treatment without delay, but recognition of pathogens with increasing resistance to antimicrobial drugs is an important factor in the selection of empirical antimicrobial regimens. At present, strategies to prevent and treat bacterial meningitis are compromised by incomplete understanding of the pathogenesis. Further research on meningitis pathogenesis is thus needed. This Review summarises information on the epidemiology, pathogenesis, new diagnostic methods, empirical antimicrobial regimens, and adjunctive treatment of acute bacterial meningitis in infants and children. [Copyright &y& Elsevier]

Abstract: Enterobacter sakazakii is an emerging foodborne pathogen that causes neonatal meningitis and sepsis, with mortality rates of 40–80%. This study was conducted to determine the effect of organic acids on inhibiting the survival and the growth of E. sakazakii in laboratory media and several liquid foods. Inhibitory effects and the minimum inhibitory concentration (MIC) of nine acids (hydrochloric, lactic, malic, formic, phosphoric, propionic, citric, tartaric, and acetic acid) against E. sakazakii were determined by the agar disc diffusion test and broth dilution methods. Out of nine acids tested, five acids (malic, formic, propionic, citric, and acetic acid) showed antibacterial activity against one or more E. sakazakii stains. And, propionic and acetic acid were found to be the most effective with the lowest MIC values of 16–31 and 31–63mM against E. sakazakii, respectively. Therefore, these two acids were selected for further testing in liquid foods (Sun-Sik, baby food, grape juice and apple juice). Regarding foods tested, grape juice itself has an inhibitory effect and reduced or maintained levels of E. sakazakii during storage. However, 10mM of propionic and acetic acid in Sun-Sik and apple juice, and 100mM of propionic and acetic acid in baby foods were necessary to eliminate E. sakazakii in each food type, respectively. These results suggest that organic acids such as propionic and acetic acid may possibly be used as preservatives to inhibit E. sakazakii in liquid foods. [Copyright &y& Elsevier]

Summary: Skin abnormalities in the spinal lumbosacral region of infants are not infrequent. Physicians should look for underlying spinal malformations. We report 2 cases of dermal sinus in infants revealed by severe, acute meningitis. The dermal sinus is an abnormal tract between the skin and underlying neural structures, most often located in the lumbosacral region. It may end blindly in the subcutaneous tissues, or it may extend into the medullary space. The diagnosis should be suspected in patients with other skin findings: localized hypertrichosis, subcutaneous lipomas, hyperpigmented lesions, etc. It must be distinguished from the very frequent coccygeal pits (4% of newborns), which require no treatment. Magnetic resonance imaging should be done every time the diagnosis is suspected. Recurrent bacterial meningitis or meningitis caused by unusual bacteria is frequently associated with dermal sinus. A variety of neurologic abnormalities have been described: sensory changes, motor weakness, reflex changes, abnormal bowel and bladder function, etc. Infants generally have few neurologic symptoms, such as delayed walking or sphincter control. Orthopaedic abnormalities are rare. The dermal sinus tract needs to be detected at an early stage in order to avoid these complications, which can be prevented by early surgery. [Copyright &y& Elsevier]

Abstract: The epidemiology of bacterial meningitis has changed since the last French consensus in 1996, mainly because of more frequent Haemophilus influenzae b and pneumoccocus vaccination. A research PubMed and Cochrane databases was performed for articles published within the past 12 years, mentioning the diagnosis, surveillance, and follow-up of presumed bacterial meningitis in children. Sixty-one references were included among the 1606 on PubMed and 50 on the Cochrane databases. Additional articles (n =35) were identified using the references of selected articles. The definition of bacterial meningitis was reviewed, particularly when the causal agent was not identified. Clinical and biological criteria for the diagnosis and the place of brain imaging were updated. Guidelines available after the common use of Haemophilus influenzae vaccination were analyzed with their level of evidence. Initial surveillance data and risk factors associated with death or poor outcome were reviewed. The short and long-term follow-up was also analyzed to identify the proper follow-up for children. [Copyright &y& Elsevier]

Abstract: Bacterial meningitis remains a major cause of death and neurological and hearing sequels. In adults, the death rate ranges from 16 to 37% in meningitis due to Pneumococcus pneumoniae and neurological sequels occur in 30 to 52% of survivors. In childhood, the prognosis is better, with a death rate ranging from 2 to 15%, higher for Pneumococcus pneumoniae. Seventy-five percent of children survive without any sequel, 15% with hearing disorders (up to 30% with Pneumococcus), and rarely (3–4%) present with mental retardation, motor deficit, or epilepsy. In addition to the type of germ, the risk of sequels is six times higher in case of Pneumococcus, several factors of poor prognosis are described on admission: degree of coma, neurological deficit, cranial nerve palsy, high protein level, high erythrocytes count and low leukocytes count in CSF (less than 600 or 1000 leukocytes per microliter). Any neurological complication such as epilepsy, stroke, brain edema, hydrocephalus, or hemodynamic failure will be correlated to a poor outcome. Hearing must be tested within 15 days, followed by audiologic consultation and MRI focused on labyrinthis to detect early onset cochlear ossification. One year after meningitis, behavior and cognitive skills must be assessed, including IQ, memory, attention and executive functions, adaptive abilities, to set up specific educative and teaching strategies. [Copyright &y& Elsevier]

Abstract: The epidemiology of acute community-acquired bacterial meningitis in children in industrialized nations was greatly modified because of recommended vaccination against Haemophilus influenzae b, Streptococcus pneumoniae (SP) and in some countries against Neisseria meningitidis (Nm) group C. However, most cases of bacterial meningitis are caused by SP and Nm most frequently group B, which validates the first intention use of cefotaxime or ceftriaxone combined or not with vancomycin according to the probability of pneumococcal resistance. [Copyright &y& Elsevier]

Abstract: Only few epidemiological studies evaluate the role of ENT infections in meningitis. A retrospective review of data shows that the frequency of ENT infections is estimated at 25% in adults and children. Meningitis may occur during otological and nasosinusal infections. Acute otitis media and mastoiditis are the most common ear infections responsible for meningitis. Chronic otitis (cholesteatoma) are rarely involved. In case of acute rhinosinusitis, frequently responsible frontal and ethmoidal locations are investigated by nasal endoscopy and CT scan. A CSF leak originating mostly from anterior skull base or middle ear, either posttraumatic or spontaneous, may also be associated with meningitis. The management of ENT infections begins with antibiotics. Drainage may be discussed when identification of the bacteria is needed or if the medical treatment seems inefficient. In case of a CSF leak, closure of the defect is performed according to its location and size after evaluation by imaging (CT scan, MRI). [Copyright &y& Elsevier]

Abstract: The use of dexamethasone (DXM) as adjunctive therapy for bacterial meningitis (BM) in infants and children has remained controversial for 20 years. In spite of solid pathophysiological arguments, the limited number of patients, methodological flaws in clinical studies taken individually and pooled into meta-analyses, and the emergence of pneumococcal cephalosporin-resistance did not allow to reach a consensus on the effectiveness of DXM in the prevention of neurological sequelae, in the course of non Haemophilus influenzae b (Hib) BM. A recent meta-analysis conducted with an adequate number of patients (2750 patients including 2074 infants and children below 15 years of age) demonstrated that DXM prevented mortality and sequelae in adults with pneumococcal meningitis and suggested that this efficacy could also apply to infants and children. Data from the active surveillance networks of pediatric BM and pneumococcal resistance in France suggested that DXM anti-inflammatory effect on antibiotic CSF penetration would not have a significant impact on the bactericidal efficacy if recommended dosages of cefotaxime (300mg/kg per day) and vancomycin (60mg/kg per day) were used. DXM could be considered in the early treatment of pneumococcal BM in infants and children in industrialized countries. But there is no proven efficacy of DXM in meningococcal meningitis in infants and children. [Copyright &y& Elsevier]

Abstract: The potential severity of meningitis in infants and children requires an optimized initial empirical therapy, mainly based on direct cerebro spinal fluid (CSF) examination, and rapid therapeutic adaptation according to bacterial identification and susceptibility. Combination treatment including cefotaxim (300mg/kg per day) or ceftriaxone (100mg/kg per day) and vancomycine (60mg/kg per day) remains the standard first line if pneumococcal meningitis cannot be ruled out. A simple treatment with third generation cephalosporin can be used for Neisseria meningitidis or Haemophilus influenzae meningitis, aminoglycosides must be added in case of Enterobacteriacae, mainly before 3 months of age. Second line antibiotic therapy is adapted according to the clinical and bacteriological response on Day 2. When the minimal inhibitory concentration (MIC) of pneumococcal strain is less than 0.5mg/L, third generation cephalosporin should be continued alone for a total of 10 days. In other cases, a second lumbar puncture is necessary and the initial regimen, with or without rifampicin combination, should be used for 14 days. Amoxicillin during 3 weeks, associated with gentamycin or cotrimoxazole is recommended for listeriosis. [Copyright &y& Elsevier]