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Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN-gamma assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.

Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or ␣-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB. Tuberculosis (TB) is easily transmitted by inhalation of infectiousMycobacterium tuberculosis bacilli from the air and is one of the leading causes of death in adults between the ages of 15 and 45 years (43). The global incidence rate of TB is increasing by approximately 0.4% per year (43), driven by factors such as the human immunodeficiency virus (HIV)/ AIDS epidemic, poverty, and increasing population density. Despite the existence of effective treatment regimens, control of TB is complicated by the chronic nature of the disease. Only 5 to 10% of recently exposed individuals develop clinically active TB in the first 2 years after exposure, and this, together with the often transient nature of exposure, makes accurate tracing of recently exposed and potentially infected individuals extremely difficult.A higher percentage of exposed individuals become infected but are able to limit the growth of the mycobacteria and become latently infected. The exact incidence of latent infection remains unclear, but it is estimated that up to 2 billion people globally may harbor latent TB infections (17,22,43). Latency can only be understood as a dynamic process-an active host immune response is essential to keep the disease in the latent stage, as demonstrated by the high rate of TB recrudescence in individuals with HIV infection (8) or the reactivation of the latent infection in individuals given anti-tumor necrosis factor alpha therapy (29). The decline of the immune system due to old age or malnutrition also increases the risk of latent disease becoming clinically significant.Thus, latently infected individuals provide a highly relevant population to study what human protective immune responses against M. tuberculosis look like. However, identifying these people has been problematic in the past. The classical definition of latent infection (conversion to positivity in the purified protein derivative-ba...

IntroductionGuidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia.MethodsA prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured.ResultsOf 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bed-side characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 μg/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia.The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R2 = 0.278, P = 0.007).ConclusionsPCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.

Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.