Diabetes-independent increase of factor VII-activating protease activation in patients with Gram-negative sepsis (melioidosis).

BACKGROUND: The plasma protease factor VII-activating protease (FSAP) can release nucleosomes from late apoptotic cells. Nucleosomes are markers of cell death, and extracellular cell-free DNA has been suggested to play an important role in inflammation and has been demonstrated to correlate with severity and outcome in sepsis patients. OBJECTIVE: To investigate FSAP activation in patients suffering from Burkholderia pseudomallei infection (melioidosis), an important cause of Gram-negative sepsis in Southeast Asia. As diabetes mellitus (DM) is the most important risk factor for both melioidosis and sepsis, we were also able to examine the role of DM in FSAP activation in this cohort of patients. METHODS: In a prospective observational study, complexes of FSAP with α2 -antiplasmin (AP) were assayed in 44 patients with melioidosis, 34 of whom were classified as diabetic. Eighty-two healthy subjects served as controls (52 with DM and 30 without). RESULTS: FSAP-AP complex levels were markedly elevated in patients as compared with controls. The FSAP level increased by 16.82 AU mL(-1) in patients with melioidosis after adjustment for the effect of DM in the regression model. As expected, FSAP activation was correlated with nucleosome release (slope = 0.74). No difference in FSAP activation on admission was seen between survivors and non-survivors, but the extent of FSAP activation correlated with stage of the disease; repeated testing during convalescence showed a return towards normal values (day 0 vs. day 28, 4.16 AU mL(-1) , 95% confidence interval [CI] 1.42-12.22). CONCLUSION: Patients with Gram-negative sepsis caused by B. pseudomallei have abundant FSAP activation, which significantly correlates with stage of disease. The presence of DM, however, does not influence the extent of FSAP activation.

Prevalence of Trichomonas vaginalis, Mycoplasma genitalium and Ureaplasma urealyticum in men with urethritis attending an urban sexual health clinic.

We conducted a study to determine the prevalence of Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) in men with urethritis, attending an urban sexual health clinic, in order to inform screening and treatment policies. Men attending an urban sexual health clinic between June 2011 and January 2012 were evaluated. Urine samples were collected from men with urethritis and tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and TV using transcription-mediated amplification and for MG and UU using polymerase chain reaction. Eighty-three samples were analysed. The prevalence of CT was 33.7% (28/83), GC was 16.8% (14/83), TV was 3.6% (3/83), MG was 12.0% (10/83) and UU was 4.8% (4/83). Fifteen men had recurrent urethritis. Of these, three were found to have had TV, five to have had MG and none to have had UU, at initial presentation. Given the prevalence of MG in this study, there is an urgent need for further larger studies looking at optimal treatment regimens and screening strategies in urethritis.

Predictors of contact tracing completion and outcomes in tuberculosis: a 21-year retrospective cohort study.

SETTING: Birmingham, UK, 1990-2010. OBJECTIVE: To identify predictors in contacts for completion of screening and of a positive screening outcome, i.e., a diagnosis of latent tuberculous infection (LTBI) or active tuberculosis (TB). DESIGN: A retrospective cohort study of TB notifications for a European city. RESULTS: A total of 46,158 contacts were identified from 7365 index cases. Over the study period 17,471 (40.9%) failed to complete screening. Active TB or LTBI was diagnosed in 2220 (7.0%) contacts of cases of pulmonary TB (PTB) and in 222 (2.7%) contacts of cases of extra-pulmonary TB (EPTB). The proportion of contacts offered LTBI treatment increased (P < 0.001) over the study period. Age, ethnicity, sex and use of interferon-gamma release assays (IGRA) were the most important predictors of screening completion, with working age adult males who were Black or from the Indian subcontinent least likely to complete. Age, smear positivity status of the index case and IGRA usage were the most important predictors of a positive screening outcome (active TB or LTBI diagnosed). CONCLUSION: Contact tracing of both PTB and EPTB index cases is useful for active case finding. The findings of this study can be used to target screening and improve the effectiveness and efficiency of local contact tracing programmes.

The impact of diabetes on the pathogenesis of sepsis.

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones.