Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (ß ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (ß = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (ß = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (ß = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (ß = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

Helicobacter exploits integrin for type IV secretion and kinase activation.

Integrins are important mammalian receptors involved in normal cellular functions as well as pathogenesis of chronic inflammation and cancer. We propose that integrins are exploited by the gastric pathogen and type-1 carcinogen Helicobacter pylori for injection of the bacterial oncoprotein cytotoxin-associated gene A (CagA) into gastric epithelial cells. Virulent H. pylori express a type-IV secretion pilus that injects CagA into the host cell; CagA then becomes tyrosine-phosphorylated by Src family kinases. However, the identity of the host cell receptor involved in this process has remained unknown. Here we show that the H. pylori CagL protein is a specialized adhesin that is targeted to the pilus surface, where it binds to and activates integrin alpha5beta1 receptor on gastric epithelial cells through an arginine-glycine-aspartate motif. This interaction triggers CagA delivery into target cells as well as activation of focal adhesion kinase and Src. Our findings provide insights into the role of integrins in H.-pylori-induced pathogenesis. CagL may be exploited as a new molecular tool for our further understanding of integrin signalling.

Serial Changes in Exercise Capacity, NT-proBNP, and Adiponectin in Patients with Acute Coronary Syndrome before and after Phase II Rehabilitation as well as at the 12-Month Follow-Up.

BACKGROUND: Acute coronary syndrome (ACS) causes pathophysiological changes in exercise capacity, N-terminal part of pro-brain natriuretic peptide (NT-proBNP), and adiponectin that impact the course of coronary artery disease and clinical outcomes after cardiac rehabilitation (CR). However, the serial changes and the relationship between the changes in these parameters for a prolonged term remain uninvestigated. METHODS: Eighty-one patients with ACS underwent a three- or four-week CR program after acute care and were followed up for 12 months. Exercise capacity on a cycle ergometer and blood levels of NT-proBNP and adiponectin were determined before and after CR as well as at the 12-month follow-up. RESULTS: Exercise capacity increased from 100 watts (in median) before CR to 138 watts after CR and 150 watts at 12 months. The NT-proBNP level (526 pg/ml before CR) remained almost unchanged after CR (557 pg/ml) and then decreased at 12 months (173 pg/ml). The adiponectin level (14.5 µg/ml before CR) increased after CR (16.0 µg/ml) and at 12 months (17.2 µg/ml). There was no significant correlation among the changes in these parameters at each observation time point. CONCLUSION: During the observation period from before CR to the 12-month follow-up, exercise capacity, NT-proBNP, and adiponectin underwent significant changes; however, these changes were independent from each other and not correlated linearly, and they provide complementary information in clinical practice. Thus, all these parameters should be included and determined at different time points for a prolonged period of time.

Use and effects of malaria control measures in pregnancy in Lagos, Nigeria.

In Nigeria, malaria causes up to 11% of maternal mortality. Our main aim was to find out the most common mosquito control measures employed by the pregnant women in Lagos and their effects on malaria infection. The study was carried out over a period of 6 months during which trained interviewers administered questionnaires to 400 pregnant women. The prevalence of malaria was 8.4%. There was no significant association between the prevalence of malaria and age, level of education, or occupation of the participants. Pregnant women in the age range 26-30 had the mean parasite density (409.9 ± 196.80). Insecticide spray (32.8%), mosquito coil (27.5%), and insecticide-treated nets (ITN) (15.5%) were the major mosquito control measures employed by the participants while the prevalence of infection among them were 2.3%, 6.2%, and 3.2%, respectively (P<0.05). Only 18.3% of the women had taken more than one dose of intermittent preventive treatment (IPT), while another 11.8% had taken a single dose. The infection rate among them was 4.1% and 6.4%, respectively. Malaria prevalence was highest among those who had not received any dose of IPT (10%). This study showed that the use of ITN and IPT among the pregnant women were still unacceptably low. It also showed that the use of insecticide spray which was the most common malaria control measure adopted by the participants was effective despite the fact that it is not a National Malaria Control Policy. We recommend that a sustained integrated mosquito management and public education should be strengthened in Nigeria.

Varicella outbreak in Indian students in Magdeburg with detection of the African-Indian VZV clade 5.

Varicella has the highest contagiosity index of all viral diseases. We report an endemic outbreak of varicella among 4 Indian students in Magdeburg in November and December 2008. An initially severe course was observed in three of these patients with a negative vaccination status. Large vesicular skin lesions with a diameter of up to 8 mm were found in all patients. Molecular genetic tests revealed African/Indian clade 5 in 2 patients, although the European clades (i.e., clade 1 and 3) are the most common in Germany, accounting for 85 %. All patients recovered without any complications after administration of intravenous aciclovir at a dosage of 10 mg per kg body weight. Although isolated cases of varicella are not notifiable according to the German Protection against Infection Act, endemic outbreaks must be reported to the appropriate health surveillance authorities.

Cowpox infection transmitted from a domestic cat.

A 21-year-old immunocompetent woman developed a cowpox infec-tion,while working as a veterinarian's assistant in a rural area. She had never received vaccinia immunization and came in contact with a fatally-infected house cat. Under symptomatic treatment, the infection remained localized to one cheek and cleared over 3 weeks with substantial dermal-subcutaneous tissue destruction. Orthopoxvirus detection by PCR is a modern diagnostic standard, in addition to identification by negative-contrast electron microscopy. A promising therapeutic option is cidofovir, but this virostatic drug is not yet approved for the treatment of cowpox.

Expression patterns and role of the CadF protein in Campylobacter jejuni and Campylobacter coli.

Binding of Campylobacter jejuni and Campylobacter coli to host fibronectin is mediated by the 37 kDa outer membrane protein CadF. Immunoblot analysis of 58 C. jejuni and C. coli isolates of human and animal origin showed that CadF is expressed in every strain. In most C. jejuni isolates, a 37 kDa band (p37) and a less-prominent 32 kDa band (p32) reacted with the antibodies. In C. coli isolates, CadF was consistently larger with sizes of 39 kDa (p39) and 34 kDa (p34), respectively. PCR analysis and sequencing revealed the presence of a 39-bp insertion sequence in the cadF gene of C. coli strains, explaining the increased molecular size. Infection assays revealed that C. jejuni bound and invaded INT-407 epithelial cells much more efficiently than C. coli and that this difference was considerably reduced in isogenic cadF mutants. These results demonstrate that CadF is an important pathogenicity factor. The difference between CadF of C. jejuni and C. coli may potentially be exploited to discriminate these species in food and clinical specimens.

Rapid characterization of the normal and disturbed vaginal microbiota by application of 16S rRNA gene terminal RFLP fingerprinting.

Bacterial vaginosis (BV) is a prevalent infection in women of reproductive age associated with numerous sequelae, including preterm delivery, amniotic fluid infections and an increased risk of acquiring sexually transmitted diseases. The vaginal microbiota in BV patients is characterized by a shift from lactobacilli to a diverse spectrum of mostly anaerobic bacteria. In this study, terminal restriction fragment length polymorphism (T-RFLP) was used to characterize the vaginal bacterial communities from 50 women with BV and 20 healthy subjects. In the BV samples, 23 species or phylotypes from 17 genera could be identified, including Atopobium vaginae, Megasphaera sp., Lactobacillus iners, Gardnerella vaginalis and three recently described phylotypes from the order Clostridiales. The number of detected species or phylotypes was on average 6.3 per sample (range 2-14). In contrast, in normal samples, only Lactobacillus species could be identified. In conclusion, T-RFLP provides a rapid and reliable technique to investigate the diversity of the predominant vaginal microbiota and allows differentiation of the flora of BV and healthy women. As such, T-RFLP may be helpful both in the diagnosis of BV from vaginal fluids and in a better understanding of the bacterial succession involved in the aetiology of BV.

Rapid screening of clarithromycin resistance in Helicobacter pylori by pyrosequencing.

Helicobacter pylori infections can be effectively treated with clarithromycin, a macrolide, in combination with other antibiotics, such as amoxicillin, tetracycline or metronidazole. The failure of H. pylori eradication is mainly associated with macrolide-resistant strains. Three point mutations (A2142G/C, A2143G, T2182C) in the peptidyltransferase region of domain V of the 23S rRNA have been described as being associated with clarithromycin resistance. Therefore, the determination of clarithromycin resistance by pyrosequencing was evaluated. H. pylori from 81 gastric biopsies was cultured and clarithromycin resistance was determined by Etest, as well as by pyrosequencing technology (PSQ 96 system; Biotage). The respective mutations were set in relation to the MIC measured in microg ml(-1) by Etest. In this study, point mutations in positions 2142 and 2143 were associated with clarithromycin resistance. Mutations in position 2182 did not contribute to clarithromycin resistance. In addition, from 22 out of the 81 biopsies, clarithromycin resistance was determined directly without culturing H. pylori to save additional time. Identical results were obtained as compared to resistance testing with pure H. pylori strains. All results obtained by pyrosequencing were evaluated by Sanger sequencing. The data show that pyrosequencing to detect point mutation is a fast and reliable method for determining clarithromycin resistance in H. pylori, and provides the same results as the Etest.

Use of a novel coinfection system reveals a role for Rac1, H-Ras, and CrkII phosphorylation in Helicobacter pylori-induced host cell actin cytoskeletal rearrangements.

The Helicobacter pylori CagA protein induces profound morphological changes in the host cytoskeleton and cell scattering, but the signalling involved is poorly understood. Pseudomonas aeruginosa also affects host actin cytoskeleton in a variety of ways by injecting the ExoS and ExoT toxins which encode N-terminal GTPase activating protein and C-terminal ADP-ribosyltransferase (ADPRT) activities. In this study we developed a novel coinfection assay to gain new insights into CagA effector protein functions. We found that P. aeruginosa injecting either ExoT or ExoS efficiently prevented the H. pylori-induced scattering phenotype. Both the Rho-GAP and the ADPRT domains of ExoS were needed to block the H. pylori-induced actin cytoskeletal rearrangements, whereas either domain of ExoT was sufficient for this activity. This strategy revealed common pathways subverted by different pathogens, and aided in the definition of signalling cascades that control the CagA-mediated cell scattering and elongation. We identified Crk adapter proteins, Rac1 and H-Ras, but not RhoA or Cdc42, which are the ExoS and/or ExoT targets, as crucial components of the CagA-induced phenotype. In addition, we show that ADP-ribosylation of CrkII by ExoT blocks phosphorylation of CrkII at Y-221, which is also important for the CagA-induced signalling.

Differential effects of PDGF-BB on matrix metalloproteases and cytokine release in fibroblasts of Type 2 diabetic patients and normal controls in vitro.

AIMS/HYPOTHESIS: The complex process of wound healing is regulated by various growth factors. The systemic character of diabetes mellitus favors the chronification of diabetic wounds. In this study, the in vitro effects of platelet-derived growth factor (PDGF)-BB on the expression of cytokines and matrix metalloproteases (MMPs) in fibroblasts of Type 2 diabetic patients and healthy controls were investigated. METHODS: We studied six Type 2 diabetic patients (mean Hba1(c)=7.5%) and six healthy controls. For proliferation studies, cultivated fibroblasts, prepared from biopsies taken from the thigh, were stimulated with different concentrations of PDGF. After 48 h, the expression of MMPs and cytokines was measured. We analysed the mRNA expression by RT-PCR (TaqMan), tissue protein levels by zymography, and cell supernatant levels by ELISA. RESULTS: Levels of MMP-mRNA were elevated in diabetic fibroblasts compared with healthy controls. At baseline, MMP-2 protein levels were significantly increased in the fibroblast of diabetic patients (P=.019). For MMP-9, a trend towards higher levels (P=.3) was found. After incubation with PDGF, a significant reduction of MMP-9 (P=.01) and MMP-13 (P=.04) was found. Analysis of cytokine release in cell culture supernatant showed elevated levels of interleukin (IL)-8 at baseline conditions. MMP-1 and MMP-2 levels in the supernatant were concentration-dependently reduced. CONCLUSIONS: This study, for the first time, demonstrates elevated MMPs in cultivated fibroblasts (derived from intact skin and not from an open wound) of diabetic patients compared with healthy controls under in vitro conditions. Therefore, our data support the hypothesis of alterations of wound healing in diabetic patients on the cellular level, reflecting the systemic character of the disease.

Strain-specific expression profiles of virulence genes in Helicobacter pylori during infection of gastric epithelial cells and granulocytes.

Helicobacter pylori expresses a variety of known virulence-associated factors, whose expression is likely to be dependent on the ecological niche of this pathogen. Here, we compared the temporal changes in the level of virulence-associated gene transcription in H. pylori strains isolated from patients with different pathology. Our aim was to study the coordinated gene expression profiles of these virulence factors during infection of AGS gastric epithelial cells and granulocytes. Using real-time quantitative (TaqMan) RT-PCR, we determined the mRNA expression of cagA, ureA, napA, katA, vacAs1 and vacAs2 alleles in a time course up to 6 h. The expression profiles of the investigated genes vary according to the strain, and were mainly either upregulated or unchanged upon bacterial contact with AGS cells. In contrast, upon contact with granulocytes, the majority of the genes were repressed in H. pylori. The following major results were obtained: (i) genetically diverse H. pylori exhibit different mRNA expression profiles, (ii) the expression patterns were strain-specific and time-dependent and (iii) the regulation of expression profiles was host cell dependent. These data were statistically significant and suggest that contact with target cells leads to an active cross-talk between the pathogen and its host. The use of Taqman-PCR to analyse the expression of mRNA of a bacterial pathogen in response to a changing host environment enabled us to identify variable and strain-specific transcription profiles in a sensitive and reproducible manner.

Combined topical fluconazole and corticosteroid treatment for experimental Candida albicans keratomycosis.

PURPOSE: To determine the most efficient time point and concentration of topical corticosteroids in Candida albicans keratitis treated with fluconazole. METHODS: Corneas of 105 rabbits were infected with viable yeast cells of C. albicans (2.5 x 10(5)). After a 48-hour incubation period, seven groups of animals were treated for 21 days with fluconazole, with group I acting as a control, and groups II to VII receiving adjunct therapy with the corticosteroid prednisolone (5 or 10 times daily; 3, 9, or 15 days after infection). The degree of corneal infiltration, ulceration, corneal clouding, hypopyon, conjunctivitis, neovascularization, and corneal perforation was monitored over a 24-day period, as well as recultivation and resistance to fluconazole of the C. albicans pathogen. RESULTS: The control group showed the highest level of corneal clouding and neovascularization. In comparison, by day 24, the majority of groups also treated with prednisolone displayed significantly less corneal clouding and neovascularization. An immediate decrease in corneal clouding was observed in groups treated with additional low- or high-dose prednisolone from day 9 after inoculation. After additional prednisolone treatment from day 9 or 15 after inoculation, no significant difference was detected in the recultivation rate of C. albicans compared with the control. Early administration of prednisolone (day 3, low and high dose) resulted in the recultivation of significantly more C. albicans. CONCLUSIONS: Fluconazole plus adjunct high-dose prednisolone treatment was most effective when administered 9 days after infection. The delayed application of corticosteroids after treatment with antimycotic drugs in cases of fungal keratitis is therefore not contraindicated and may be beneficial in patients.

Small-sized low-density lipoproteins of subclass B from patients with end-stage renal disease effectively augment tumor necrosis factor-alpha-induced adhesive properties in human endothelial cells.

Increased prevalence of small-sized low-density lipoprotein (LDL) subclass B (diameter < 25.5 nm) possibly is involved in the multifactorial process of cardiovascular disease in patients with end-stage renal disease. Given these epidemiological observations, mechanisms underlying the combined effect of a proinflammatory insult and LDL of different subclasses (subclass A, diameter > 25.5 nm, and subclass B) in a cellular model were investigated. For this, human umbilical vein endothelial cells were preexposed to LDL, then stimulated with tumor necrosis factor-alpha (TNF-alpha). Modulatory effects of LDL phenotypes on the activation of adhesion molecules, monocyte adherence, and transcriptional activity of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) were investigated. Our data show that subclass B LDLs were metabolized through nonspecific scavenger receptors and specific LDL-receptor pathways in endothelial cells. Furthermore, LDL subclass B in comparison to subclass A more effectively enhanced monocyte recruitment and adhesive properties of endothelial cells in response to TNF-alpha. These effects appeared not to be mediated by oxidative stress-responsive NF-kappaB because modulation of this transcription factor by LDL was moderate and similar for both LDL phenotypes. Conversely, effects of LDL subclass B were considered to be caused by augmented AP-1 binding activity. In conclusion, the present model provides new clues in atherogenic mechanisms of small-sized LDLs, which sensitize vascular cells to inflammatory signals more effectively than normal-sized LDLs.

Respiratory syncytial virus: G gene genotype and disease severity.

BACKGROUND: In a hospital-based study by Martinello (2002), specific G gene genotypes of respiratory syncytial virus subgroup A virus were associated with an increased severity of illness. AIM: We sought to confirm the association of G genotypes with disease severity in a population-based study. MATERIAL AND METHODS: Ninety-one type A respiratory syncytial viruses (identified in the 1999/2000 season by polymerase chain reaction and cell culture), collected in a German multicenter study (PRI.DE) were analyzed for G gene diversity (amino acids 1-165). Disease severity was classified according to World Health Organization criteria for pneumonia in outpatients and by a bronchiolitis score (Rodriguez, 1997) in inpatients. Multiple regression analysis was used to explain disease severity. RESULTS: Three clusters were identified (cluster 1, n = 35; cluster 2,n = 35; cluster 3, n = 21). Sixty-seven patients had severe disease. After controlling for other variables, illness severity was significantly greater for cluster 2 viruses (odds ratio, 7.0; 95% confidence interval, 1.6 49), compared with viruses in other clusters. Other known risk factors (male gender, age) were not associated with disease severity. Our cluster 2 is genetically distinct from the virulent genotype in Martinello's study. DISCUSSION: Previously reported associations between G genotypes and disease severity in hospitalized patients can be generalized across the spectrum of illnesses including outpatients. The association seems not to be linked to a specific G gene structure. Rather G gene diversity in combination with the susceptibility of the host cohort may form the basis of such associations. Because of the magnitude of the effect, the underlying mechanisms warrant further investigation.

Antibiotic susceptibility of Helicobacter pylori in Germany: stable primary resistance from 1995 to 2000.

The issue of antibiotic resistance in Helicobacter pylori is of particular concern and has become an important factor leading to eradication failure. This paper reports the prevalence of primary resistance to clarithromycin, amoxicillin, metronidazole and tetracycline among H. pylori isolates in the north-eastern part of Germany. A total of 1644 clinical H. pylori isolates was investigated over a period of 6 years from 1995 to 2000. The MICs were determined by the Etest. The overall rate of primary resistance was 26.2% for metronidazole and 2.2% for clarithromycin. No significant changes in the resistance rates during the period of investigation were observed. No isolate was resistant to amoxicillin or tetracycline. PCR-RFLP analysis for the detection of point mutations associated with clarithromycin resistance was performed with 36 H. pylori isolates. The A --> G transition mutation at position 2143 was detected in 19 H. pylori isolates (52.8%), whereas the mutation at position 2142 was found in 13 isolates (36.1%).

Panel of emerging cardiac biomarkers contributes for prognosis rather than diagnosis in chronic heart failure.

BACKGROUND: As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT). METHODS: All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls. RESULTS: All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers. CONCLUSION: All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.

Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study).

BACKGROUND: Anemia has been shown to be a risk factor for coronary artery disease and mortality. The involvement of body iron stores in the development of CAD remains controversial. So far, studies that examined hemoglobin and parameters of iron metabolism simultaneously do not exist. METHODS AND RESULTS: Hemoglobin and iron status were determined in 1480 patients with stable angiographic coronary artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI: 1.51-2.78), respectively compared to their highest gender-specific quartiles. The fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation, ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69 (95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18), respectively compared to their highest gender-specific quartiles. When adjusting in addition for iron and ferritin the OR for CAD in the lowest quartiles of hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender-specific quartiles. Thus, the associations between either iron status or low hemoglobin and CAD appeared independent from each other. The sTfR was only marginally associated with angiographic CAD. CONCLUSIONS: Both low hemoglobin and iron depletion are independently associated with angiographic CAD.

Infections due to Pseudallescheria/Scedosporium species in patients with advanced HIV disease--a diagnostic and therapeutic challenge.

OBJECTIVES: The aim of this study is to highlight the importance of infections caused by members of the genera Pseudallescheria/Scedosporium in HIV-positive patients. METHODS: We describe a case of a fatal scedosporiosis in a treatment-naïve HIV patient and review all previously reported cases of pseudallescheriosis/scedosporiosis from a search of the PubMed and Deutsches Institut für Medizinische Dokumentation und Information (DIMDI) databases, applying the terms 'Pseudallescheria', 'Scedosporium', 'Allescheria', 'Monosporium', 'Petriellidium', 'boydii', 'prolificans', 'inflatum', cross-referenced with 'HIV' and 'AIDS'. RESULTS: Detection of Scedosporium and Pseudallescheria species has been reported in 22 HIV-positive patients. Fourteen isolates belonged to the Pseudallescheria boydii complex and eight to Scedosporium prolificans. Invasive scedosporiosis (IS) was proven in 54.5% of the patients. Among them dissemination was observed in 66.7%. Pseudallescheria/Scedosporium species were mainly isolated from male individuals. Patients with proven IS showed CD4+ cell counts <100/µl and a higher co-infection rate as compared to colonized patients. Patients with central nervous system (CNS) manifestations showed CD4+ cell counts <50/µl. The mortality rate for patients with proven IS was 75% and was 100% for patients with dissemination/CNS manifestations. The fatality rate for patients treated with antifungal drugs plus surgery was lower compared to patients treated with antimycotic agents alone. CONCLUSIONS: IS only occurred in HIV-positive patients with a strongly impaired immune system. The survival rates of patients with advanced HIV disease and invasive scedosporiosis can be improved by rapid diagnosis by biopsy and requires complex therapy with a combination of active antifungal drugs, surgery and supportive immune augmentation.

Phenotypic and genotypic analysis of clinical isolates Salmonella serovar Typhimurium in western Kenya.

BACKGROUND: Salmonella spp. are recognized as some of the most common causes of enteritis worldwide. This study aimed to identify clinically isolated S. Typhimurium in western Kenya and to assess antimicrobial resistance profiles and strain inter-relatedness. METHODS: The study was performed in rural Maseno, Nyanza province in Kenya, between February 2004 and June 2005. Sixty-three patients with diarrhoea and fever were recruited. S. Typhimurium isolates were confirmed using serotyping, biochemical testing, and 16S rRNA sequencing. Susceptibility to 20 antimicrobials was determined and specific resistance genes were identified by polymerase chain reaction (PCR). Strain diversity was further analyzed using pulsed-field gel electrophoresis (PFGE), fluorescence amplified fragment length polymorphism (fAFLP), and multi-locus-variable-number-tandem regions (MLVNTR). RESULTS: Twenty S. Typhimurium strains were isolated in the course of the study and their identity was confirmed by 16S rRNA gene sequencing. All 20 S. Typhimurium strains were resistant to ampicillin, streptomycin and sulfamethoxazole; ciprofloxacin resistance and phage DT104 were not detected. PFGE, plasmid profiling, and analysis of selected VNTR loci revealed further heterogeneity among the strains in the study. CONCLUSION: S. Typhimurium was commonly isolated from patients with diarrhoea and fever in Maseno. Considerable phenotypic and genotypic diversity was observed among isolates, suggesting that strains belonging to multiple lineages are responsible for disease in the study region. Multiple resistance was common and mediated by a variety of resistance genes but not by phage DT104.