Predictors of Bacterial Meningitis in Resource-Limited Contexts: An Angolan Case

BACKGROUND: Despite the great morbidity and mortality that childhood bacterial meningitis (BM) is experiencing in Africa, diagnosis of BM in resource-limited contexts is still a challenge. Several algorithms and clinical predictors have been proposed to help physicians in decision-making but a lot of these markers used variables that are calculable only in well-equipped laboratories. Predictors or algorithm based on parameters that can be easily performed in basic laboratories can help significantly in BM diagnosis, even in resource-limited settings, rural hospitals or health centers. RESULTS: This retrospective study examined 145 cerebral-spinal fluid (CSF) specimens from children from 2 months to 14 years. CSF specimens were divided into two groups, according to the presence or not of a clinical diagnosis of BM. For each specimen, CSF aspect, CSF white blood cells (WBC) count, CSF glucose and protein concentration were analyzed and statistical analysis were performed. CSF WBC count ≥10/µl is no more a valuable predictor of BM. CSF protein concentration ≥50 mg/dl has a better sensitivity for BM diagnosis and when used with CSF glucose concentration ≤40 mg/dl, can help to diagnose correctly almost all the BM cases. An algorithm including CSF protein concentration, glucose concentration and WBC count has been proposed to rule out BM and to correctly diagnose it. CONCLUSIONS: In resource-limited health centers, the availability of a combination of easy-to-obtain parameters can significantly help physicians in BM diagnosis. The prompt identification of a BM case can be rapid treated or transferred to adequate structures and can modify the outcome in the patient

Indinavir/Low-dose Ritonavir Containing HAART in HIV-1 Infected Children has Potent Antiretroviral Activity, but is Associated with Side Effects and Frequent Discontinuation of Treatment

We here present the study results of 21 HIV-1 infected children who were treated with indinavir plus low-dose ritonavir and two nucleoside reverse transcriptase inhibitors (NRTIs) for 48 weeks. Although this q12h HAART regimen had potent antiretroviral activity, it was frequently associated with side effects and discontinuation of therapy

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

Assessment of a Novel Automatic Real-Time PCR Assay on the Cobas 4800 Analyzer as a Screening Platform for Hepatitis C Virus Genotyping in Clinical Practice : Comparison with Massive Sequencing

The unequivocal identification of hepatitis C virus (HCV) subtypes 1a/1b and genotypes 2 to 6 is required for optimizing the effectiveness of interferon-free, direct-acting antiviral therapies. We compared the performance of a new real-time HCV genotyping assay used on the Cobas 4800 system (C4800) with that of high-resolution HCV subtyping (HRCS). In total, 502 samples were used, including 184 samples from chronic HCV patients (from routine laboratory activity during April 2016), 5 stored samples with double HCV genotype infections for testing the limitations of the method, and 313 samples from a screening protocol implemented in our hospital (from May to August 2016) based on the new method to further determine its genotyping accuracy. A total of 282 samples, including 171 from April 2016 (the 13 remaining had too low of a viral load for HRCS), 5 selected with double infections, and 106 from screening, were analyzed by both methods, and 220 were analyzed only by the C4800. The C4800 correctly subtyped 125 of 126 1a/1b samples, and the 1 remaining sample was reported as genotype 1. The C4800 correctly genotyped 38 of 45 non-1a/1b samples (classified by HRCS), and it reported the remaining 7 samples as indeterminate. One hundred two of 106 non-1a/1b genotype samples that were identified using the C4800 for screening were confirmed by HRCS. In the 4 remaining samples, 3 were correctly reported as genotype 1 (without defining the subtype) and 1 was reported as indeterminate. None of the samples were misgenotyped. Four of 7 samples with double HCV infections were correctly genotyped by the C4800. Excluding the 5 selected double-infected samples, the C4800 showed 95.7% concordant results for genotyping HCVs 2 to 6 and 1a/1b subtyping, and 99.2% concordance for subtyping 1a/1b single infections in clinical samples. To improve laboratory workflow, we propose using the C4800 as a first-line test for HCV genotyping and 1a/1b classification, followed by transferring non-1a/1b samples to a center where HRCS is available, if further characterization is needed

Brain abscess in Korean children: A 15-year single center study

PurposeA brain abscess is a serious disease of the central nerve system. We conducted this study to summarize the clinical manifestations and outcomes of brain abscesses.MethodsA retrospective chart review of pediatric patients diagnosed with brain abscesses from November 1994 to June 2009 was performed at Samsung Medical Center, Seoul, Korea.ResultsTwenty-five patients were included in this study. On average, 1.67 cases per year were identified and the median age was 4.3 years. The common presenting clinical manifestations were fever (18/25, 72%), seizure (12/25, 48%), altered mental status (11/25, 44%), and signs of increased intracranial pressure (9/25, 36%). A total of 14 (56%) patients had underlying illnesses, with congenital heart disease (8/25, 32%) as the most common cause. Predisposing factors were identified in 15 patients (60%). The common predisposing factors were otogenic infection (3/25, 12%) and penetrating head trauma (3/25, 12%). Causative organisms were identified in 64% of patients (16/25). The causative agents were S. intermedius (n=3), S. aureus (n=3), S. pneumoniae (n=1), Group B streptococcus (n=2), E. coli (n=1), P. aeruginosa (n=1), and suspected fungal infection (n=5). Seven patients received medical treatment only while the other 18 patients also required surgical intervention. The overall fatality rate was 16% and 20% of patients had neurologic sequelae. There was no statistical association between outcomes and the factors studied.ConclusionAlthough uncommon, a brain abscess is a serious disease. A high level of suspicion is very important for early diagnosis and to prevent serious consequences

Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 × 108 colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1–. There was a significant reduction in the elimination half-life by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasma-concentration-time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits

Plant-expressed Fc-fusion protein tetravalent dengue vaccine with inherent adjuvant properties.

Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi-Pasteur Denvaxia vaccine does not protect children under the age of nine and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant-expression to produce a humanised and highly immunogenic Poly-Immunoglobulin G Scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralising antibodies and evidence of cell-mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen-specific CD4+ and CD8+ T cell proliferation, IFN-γ and antibody production. The purified polymeric fraction of dengue PIGS (D-PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low affinity Fcγ receptors on antigen-presenting cells. These results show that the plant-expressed D-PIGS have the potential for translation towards a safe and easily scalable single antigen based tetravalent dengue vaccine. This article is protected by copyright. All rights reserved

Hospital-based, prospective, multicentre surveillance to determine the incidence of intussusception in children aged below 15 years in Germany

<p>Abstract</p> <p>Background</p> <p>A new vaccine against Rotavirus (RV) gastroenteritis was introduced in Germany in 2006. In 1997 the first RV vaccine was withdrawn due to an increased incidence in intussusception (IS). Thus, an accurate estimation of the incidence of IS is important for post-licensure surveillance.</p> <p>Methods</p> <p>IS-Data were obtained from the 'Erhebungseinheit für seltene pädiatrische Erkrankungen Deutschland' (ESPED, German surveillance unit for rare pediatric diseases) collaborations' central register where all cases of intussusception in Germany for the years 2006 and 2007 are collected (n = 1200). In order to obtain an unbiased estimate of the incidence, it is necessary to determine the population under risk out of which these cases originated, and the proportion of real cases not reported to the registry (underreporting). In order to assess underreporting, a random sample of 31 hospitals was re-assessed by an outside reviewer. The estimation of incidence was done using a single Maximum-Likelihood (ML) estimator based on data from both the registry and the sample.</p> <p>Results</p> <p>The uncorrected observed incidence was calculated to be 26.6/100,000 child-years for children below 1 year old, 23.8 for those below 2 years old, and 5.2 for those below 15 years old. The review revealed a mean reporting quota of about 41% and the ML approach yielded an incidence of 51.5/100,000 child-years (95%CI [41.7;61.1]) for children below 2 years of age.</p> <p>Conclusions</p> <p>While substantial under-reporting led to very conservative estimates of the IS incidence, the approach described here allows an accurate estimation of IS incidence including corresponding confidence bands. Therefore, ML estimation is a straightforward instrument to derive stable, unbiased estimates in epidemiological studies with incomplete data.</p

Simulated effect of pneumococcal vaccination in the Netherlands on existing rules constructed in a non-vaccinated cohort predicting sequelae after bacterial meningitis

BACKGROUND: Previously two prediction rules identifying children at risk of hearing loss and academic or behavioral limitations after bacterial meningitis were developed. Streptococcus pneumoniae as causative pathogen was an important risk factor in both. Since 2006 Dutch children receive seven-valent conjugate vaccination against S. pneumoniae. The presumed effect of vaccination was simulated by excluding all children infected by S. pneumoniae with the serotypes included in the vaccine, from both previous collected cohorts (between 1990-1995). METHODS: Children infected by one of the vaccine serotypes were excluded from both original cohorts (hearing loss: 70 of 628 children; academic or behavioral limitations: 26 of 182 children). All identified risk factors were included in multivariate logistic regression models. The discriminative ability of both new models was calculated. RESULTS: The same risk factors as in the original models were significant. The discriminative ability of the original hearing loss model was 0.84 and of the new model 0.87. In the academic or behavioral limitations model it was 0.83 and 0.84 respectively. CONCLUSION: It can be assumed that the prediction rules will also be applicable on a vaccinated population. However, vaccination does not provide 100% coverage and evidence is available that serotype replacement will occur. The impact of vaccination on serotype replacement needs to be investigated, and the prediction rules must be validated externally