Invasive group A, C and G streptococcal disease in western Norway: virulence gene profiles, clinical features and outcomes

AbstractInvasive group A streptococcal (iGAS) disease is endemic in Norway, but data on invasive group C and group G streptococcal (iGCS/GGS) disease are lacking. We investigated the characteristics of iGAS and iGCS/GGS infections in western Norway from March 2006 to February 2009. Clinical information was retrospectively obtained from medical records. GAS and GCS/GGS isolates were emm typed and screened for the presence of 11 superantigen (SAg) genes and the gene encoding streptococcal phospholipase A2 (SlaA). GCS/GGS isolates were also subjected to PCR with primers targeting speGdys. Sixty iGAS and 50 iGCS/GGS cases were identified, corresponding to mean annual incidence rates of 5.0 per 100 000 and 4.1 per 100 000 inhabitants, respectively. Skin and soft tissue infections were the most frequent clinical manifestations of both iGAS and iGCS/GGS disease, and 14 iGAS patients (23%) developed necrotizing fasciitis. The 30-day case fatality rates of iGAS and iGCS/GGS disease were 10% and 2%, respectively. emm1, emm3 and emm28 accounted for 53% of the GAS isolates, and these types were associated with severe clinical outcome. SAg gene and SlaA profiles were conserved within most of the GAS emm types, although five profiles were obtained within isolates of emm28. stG643 was the most prevalent GCS/GGS emm type, and speGdys was identified in 73% of the GCS/GGS isolates. Neither GAS SAg genes nor SlaA were detected in GCS/GGS. Our findings indicate a considerable burden of both iGAS and iGCS/GGS disease and a high frequency of necrotizing fasciitis caused by GAS in our community

Dissecting early regulatory relationships in the lamprey neural crest gene network

The neural crest, a multipotent embryonic cell type, originates at the border between neural and nonneural ectoderm. After neural tube closure, these cells undergo an epithelial–mesenchymal transition, migrate to precise, often distant locations, and differentiate into diverse derivatives. Analyses of expression and function of signaling and transcription factors in higher vertebrates has led to the proposal that a neural crest gene regulatory network (NC-GRN) orchestrates neural crest formation. Here, we interrogate the NC-GRN in the lamprey, taking advantage of its slow development and basal phylogenetic position to resolve early inductive events, 1 regulatory step at the time. To establish regulatory relationships at the neural plate border, we assess relative expression of 6 neural crest network genes and effects of individually perturbing each on the remaining 5. The results refine an upstream portion of the NC-GRN and reveal unexpected order and linkages therein; e.g., lamprey AP-2 appears to function early as a neural plate border rather than a neural crest specifier and in a pathway linked to MsxA but independent of ZicA. These findings provide an ancestral framework for performing comparative tests in higher vertebrates in which network linkages may be more difficult to resolve because of their rapid development

Forecasting exchange rate volatility: GARCH models versus implied volatility forecasts

This study investigates whether different specifications of univariate GARCH models can usefully forecast volatility in the foreign exchange market. The study compares in-sample forecasts from symmetric and asymmetric GARCH models with the implied volatility derived from currency options for four dollar parities. The data set covers the period 2002 to 2012. We divide the data into two periods one for the period 2002 to 2007 which is characterised by low volatility and the other for the period 2008 to 2012 characterised by high volatility. The results of this paper reveal that the implied volatility forecasts significantly outperforms the three GARCH models in both low and high volatility periods. The results strongly suggest that the foreign exchange market efficiently prices in future volatility

Nosocomial outbreak of neonatal Salmonella enterica serotype Enteritidis meningitis in a rural hospital in northern Tanzania

BACKGROUND: Clinicians at Haydom Lutheran Hospital, a rural hospital in northern Tanzania noted an unusually high case-fatality rate of pediatric meningitis and suspected an outbreak of an unknown agent or an organism resistant to the empirical therapy. METHODS: We established a provisional microbiology laboratory to investigate the suspected outbreak. Blood and spinal fluid specimens were taken from children below the age of seven years with suspected meningitis. The blood and spinal fluid specimens were inoculated in commercial blood culture bottles and locally prepared Thayer-Martin medium in slanted tubes, respectively. The bacterial isolates were sent to Norway for further investigation, including susceptibility testing and pulsed-field gel-electrophoresis (PFGE). RESULTS: Among 24 children with suspected meningitis and/or septicemia, five neonates had meningitis caused by Salmonella enterica serotype Enteritidis, all of whom died. Two children had S. Enteritidis septicemia without meningitis and both survived. Genotyping with PFGE suggested a clonal outbreak. The salmonella strain was resistant to ampicillin and sensitive to gentamicin, the two drugs commonly used to treat neonatal meningitis at the hospital. CONCLUSION: The investigation reminds us that nontyphoidal salmonellae can cause meningitis associated with very high case-fatality rates. Resistance to multiple antimicrobial agents increases the risk of treatment failure and may have contributed to the fatal outcome in all of the five patients with salmonella meningitis. The investigation indicated that the outbreak was nosocomial and the outbreak subsided after hygienic measures were instituted. Establishing a provisional microbiological laboratory is a valuable and affordable tool to investigate and control outbreaks even in remote rural areas

Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™ this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium

Выявление и идентификация карантинных объектов на хризантеме в Республике Карелия

BACKGROUND: Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection. METHODS: This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines. RESULTS: We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization. INTERPRETATIONS: Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report

BACKGROUND: Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. CASE PRESENTATION: Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. CONCLUSION: The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy

PCR Targeting Plasmodium Mitochondrial Genome of DNA Extracted from Dried Blood on Filter Paper Compared to Whole Blood.

Monitoring mortality and morbidity attributable to malaria is paramount to achieve elimination of malaria. Diagnosis of malaria is challenging and PCR is a reliable method for identifying malaria with high sensitivity. However, blood specimen collection and transport can be challenging and obtaining dried blood spots (DBS) on filter paper by finger-prick may have advantages over collecting whole blood by venepuncture. DBS and whole blood were collected from febrile children admitted at the general paediatric wards at a referral hospital in Dar es Salaam, Tanzania. DNA extracted from whole blood and from DBS was tested with a genus-specific PCR targeting the mitochondrial Plasmodium genome. Positive samples by PCR of DNA from whole blood were tested with species-specific PCR targeting the 18S rRNA locus, or sequencing if species-specific PCR was negative. Rapid diagnostic test (RDT) and thin blood smear microscopy was carried out on all patients where remnant whole blood and a blood slide, respectively, were available. Positivity of PCR was 24.5 (78/319) and 11.2% (52/442) by whole blood and DBS, respectively. All samples positive on DBS were also positive on Plasmodium falciparum species-specific PCR. All RDT positive cases were also positive by DBS PCR. All but three cases with positive blood slides were also positive by DBS. In this study, PCR for malaria mitochondrial DNA extracted from whole blood was more sensitive than from DBS. However, DBS are a practical alternative to whole blood and detected approximately the same number of cases as RDTs and, therefore, remain relevant for research purposes