Background. Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting... Show moreBackground. Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. Methods. We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as " clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. Results. Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH >= 7.0, and/or renal insufficiency (estimated glomerular filtration rate, <= 40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. Conclusions. Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule. Show less
This thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play... Show moreThis thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play a role in controlling latent infection. Several new highly M. tuberculosis-specific peptides mixtures were identified to optimize the sensitivity of immunodiagnostic assays. The performance of interferon-gamma-release-assays (IGRA) for detection of latent TB were evaluated. Two short-incubation IGRA, QuantiFERON-TB Gold and T-SPOTTM.TB, were found to correlate better to the level of exposure to M. tuberculosis than the tuberculin skin test (TST), indicating that these assays are very sensitive for detection of recent infections. However, short-incubation IGRA are less sensitive than prolonged-incubation IGRA and TST for detection of latent TB acquired in the past. The search for proteins that are specifically targeted by the immune system during latency led to the identification of several antigens encoded within the DosR-regulon. This set of genes of M. tuberculosis is strongly upregulated by during in vitro models of latency. These antigens, including 16kDa _-crystallin, were preferentially recognized by latently infected individuals, which suggest that T-cell responses to latency antigens are associated with natural protection against reactivation of TB, warranting their further study as vaccine candidates. Show less
