Non-capsulated and capsulated Haemophilus influenzae in children with acute otitis media in Venezuela: a prospective epidemiological study

<p>Abstract</p> <p>Background</p> <p>Non-typeable <it>Haemophilus influenzae </it>(NTHi) and <it>Streptococcus pneumoniae </it>are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age.</p> <p>Methods</p> <p>Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes).</p> <p>Results</p> <p>Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (<it>S. pneumoniae, H. influenzae, S. pyogenes </it>or <it>M. catarrhalis</it>) was cultured from 65.9% (60/91) of episodes. <it>H. influenzae </it>(55.5%; 35/63 episodes) and <it>S. pneumoniae </it>(34.9%; 22/63 episodes) were the most frequently reported bacteria. Among <it>H. influenzae </it>isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for <it>H. influenzae </it>was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six <it>H. influenzae </it>positive samples (66.7%) from recurrent episodes.</p> <p>Conclusions</p> <p>We found <it>H. influenzae </it>and <it>S. pneumoniae </it>to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.</p

Community mobilisation with women's groups facilitated by Accredited Social Health Activists (ASHAs) to improve maternal and newborn health in underserved areas of Jharkhand and Orissa: study protocol for a cluster-randomised controlled trial

Background: Around a quarter of the world's neonatal and maternal deaths occur in India. Morbidity and mortality are highest in rural areas and among the poorest wealth quintiles. Few interventions to improve maternal and newborn health outcomes with government-mandated community health workers have been rigorously evaluated at scale in this setting.The study aims to assess the impact of a community mobilisation intervention with women's groups facilitated by ASHAs to improve maternal and newborn health outcomes among rural tribal communities of Jharkhand and Orissa.Methods/design: The study is a cluster-randomised controlled trial and will be implemented in five districts, three in Jharkhand and two in Orissa. The unit of randomisation is a rural cluster of approximately 5000 population. We identified villages within rural, tribal areas of five districts, approached them for participation in the study and enrolled them into 30 clusters, with approximately 10 ASHAs per cluster. Within each district, 6 clusters were randomly allocated to receive the community intervention or to the control group, resulting in 15 intervention and 15 control clusters. Randomisation was carried out in the presence of local stakeholders who selected the cluster numbers and allocated them to intervention or control using a pre-generated random number sequence. The intervention is a participatory learning and action cycle where ASHAs support community women's groups through a four-phase process in which they identify and prioritise local maternal and newborn health problems, implement strategies to address these and evaluate the result. The cycle is designed to fit with the ASHAs' mandate to mobilise communities for health and to complement their other tasks, including increasing institutional delivery rates and providing home visits to mothers and newborns. The trial's primary endpoint is neonatal mortality during 24 months of intervention. Additional endpoints include home care practices and health care-seeking in the antenatal, delivery and postnatal period. The impact of the intervention will be measured through a prospective surveillance system implemented by the project team, through which mothers will be interviewed around six weeks after delivery. Cost data and qualitative data are collected for cost-effectiveness and process evaluations

Human Placental-Specific Epipolymorphism and its Association with Adverse Pregnancy Outcomes

Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic “on-or-off” pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%–25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such “epipolymorphism” in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy

Sterilization of hydrogen peroxide resistant bacterial spores with stabilized chlorine dioxide

Bacillus pumilus SAFR-032 spores isolated from a clean room environment are known to exhibit enhanced resistance to peroxide, desiccation, UV radiation and chemical disinfection than other spore-forming bacteria. The survival of B. pumilus SAFR-032 spores to standard clean room sterilization practices requires development of more stringent disinfection agents. Here, we report the effects of a stabilized chlorine dioxide-based biocidal agent against spores of B. pumilus SAFR-032 and Bacillus subtilis ATCC 6051. Viability was determined via CFU measurement after exposure. Chlorine dioxide demonstrated efficacy towards sterilization of spores of B. pumilus SAFR-032 equivalent or better than exposure to hydrogen peroxide. These results indicate efficacy of chlorine dioxide delivered through a stabilized chlorine dioxide product as a means of sterilization of peroxide- and UV-resistant spores.This work is supported by the National Institutes of Health (1R01GM090064-01), a NASA EPSCoR Research Infrastructure Development (RID) grant NN07AL49A, and the University of Oklahoma.Ye