Epidemiological association of <it>Campylobacter jejuni</it> groups with pathogenicity-associated genetic markers

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni</it>, the most leading cause for bacterial gastroenteritis worldwide, shows a high genetic diversity among its isolates. Recently, we demonstrated the existence of six <it>C. jejuni</it>-groups by combining MLST with six genetic markers. These groups were further characterized by the detection of <it>cj1321-cj1326</it>, <it>fucP</it>, <it>cj0178</it>, <it>cj0755</it>/<it>cfrA, ceuE</it>, <it>pldA</it>, <it>cstII</it>, and <it>cstIII</it> in order (I.) to show further associations between these different genetic markers and MLST CCs. Moreover, different studies were able to associate several of these markers: a sialylated lipoologosaccharide (<it>cstII/III</it>⁺), the gamma-glytamyl-transpeptidase (<it>ggt</it>⁺), and the absence of a certain allele of the enterochelin-uptake-binding-protein (<it>ceuE</it>₁₁₁₆₈^-) with severe campylobacteriosis, bloody diarrhea and unpleasant outcome. Additionally more than half of human <it>Campylobacter-</it>isolates were assigned to a non-livestock clade associated with the absence of <it>cj1321-cj1326</it>. These isolates were considered as mere colonizers.</p> <p>From the combination of marker genes, the ratio of human isolates in a specific group, and clinical data (II.) it should be demonstrated to which of the previous defined groups these <it>Campylobacter</it>-subpopulations, associated with higher virulence, correspond.</p> <p>Results</p> <p>Besides the marker gene <it>pldA</it>, all new estimated genetic markers show significant differences in their distribution among the various MLST-based groups. Especially the genes for <it>cj1321-cj1326</it>, <it>fucP</it>, <it>cj0178</it>, <it>cj0755</it>/<it>cfrA</it> are widely associated with each other and split the study population into two major and seven intermediate groups substantiating the previous group-definition, whereas <it>cstII</it> and <it>cstIII</it> indicate at least three groups following an independent distribution pattern.</p> <p>Conclusions</p> <p>Based on these data a group of <it>C. jejuni</it>-isolates characterized by the presence of <it>ansB, dmsA</it>, <it>ggt,</it> and the absence of <it>cj1365c</it>, <it>cj1585c</it>, <it>cj1321-cj1326, fucP</it>, <it>cj0178</it>, <it>cj0755</it>/<it>cfrA,</it> and <it>cstII/III</it> was associated with a higher prevalence in human campylobacteriosis, bloody diarrhea as well as hospitalization and bears obviously a higher virulence for humans. In contrast to that better livestock-adapted groups characterized by the ability to utilize L-fucose and the presence of all of the five identified putative <it>C. jejuni</it> iron-uptake systems as well as <it>cj1321-cj1326</it>, <it>cj1365c, cj1585c</it>, and <it>cstII</it> and/or <it>cstIII</it> (sialylated lipoologosaccharide) is more prevalent in animal hosts and was secondary associated with less severe campylobacteriosis.</p

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group