Objectives: IFN gamma-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated... Show moreObjectives: IFN gamma-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated antigens may improve immune-based tests.Methods: Multiplex cytokine analyses was done in culture supernatants after 6-day in vitro restimulation with M. tuberculosis IGRA and latency-associated antigens (i.e. Rv2628, Rv1733) in tuberculosis patients (n = 22) and asymptomatic contacts (AC)s (n = 20) from Ghana.Results: Four cytokines (i.e. IFN gamma, IP-10, IL-22 and IL-6) were significantly increased after IGRA-antigen specific restimulation. IFN gamma, IP-10, and IL-22 correlated positively and showed no differences between the study groups whereas IGRA-antigen induced IL-6 was significantly higher in tuberculosis patients. Using adjusted IGRA criteria, IL-6 showed the highest sensitivity for detection of tuberculosis patients (91%) and ACs (85%) as compared to IFN gamma, IP-10, and IL-22. Rv2628 and Rv1733 restimulation induced significantly higher IFN gamma, IP-10, and IL-22 concentrations in ACs. Combined antigen/cytokine analyses identified study group specific patterns and a combination of Rv2628/Rv1733 induced IFN gamma with IGRA-antigen induced IL-6 was optimal for classification of tuberculosis patients and ACs (AUC: 0.92, p<0.0001).Conclusions: We demonstrate the potency of alternative cytokines, especially IL-6, and latency-associated antigens Rv1733/Rv2628 to improve detection of M. tuberculosis infection and to classify tuberculosis patients and healthy contacts. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Show less
Conclusions: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker... Show moreConclusions: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Show less
Conclusion: These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with... Show moreConclusion: These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Show less
Haverkamp, M.H.; Vosse, E. van de; Dissel, J.T. van 2014
Objective: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1 -> 3)-beta-D-glucan (beta-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV... Show moreObjective: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1 -> 3)-beta-D-glucan (beta-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients. Methods: HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum beta-D-glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum beta-D-glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. Results: In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum beta-D-glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients beta-D-glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. Conclusions: The level of serum beta-D-glucan-but not AdoMet - was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring. (C) 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Show less
Nieuwkoop, C. van; van't Wout, J.W.; Spelt, I.C.; Becker, M.; Kuijper, E.J.; Blom, J.W.; ... ; Dissel, J.T. van 2010
Objective: Home-based treatment of acute pyelonephritis (AP) is generally reserved for young non-pregnant women who lack co-morbidity. This study, focusing on the elderly and patients with co... Show moreObjective: Home-based treatment of acute pyelonephritis (AP) is generally reserved for young non-pregnant women who lack co-morbidity. This study, focusing on the elderly and patients with co-morbidity, evaluates the Dutch primary care guideline that recommends referral to hospital only in case of suspected deterioration to severe sepsis or failure of antibiotic treatment, irrespective of patient's age, sex or co-morbidity. Methods: A prospective observational cohort study including consecutive non-pregnant adults with AP. Clinical and microbiological outcome measures of non-referred patients from 35 primary health care centres (PHC) were compared to patients referred to two affiliating emergency departments (EDs). Results: Of 395 evaluable patients, 153 were treated by PHCs and 242 referred to EDs. The median age was 63 years [IQR 43-77], 34% were male, 58% had co-morbidity; all comparable between the PHC and ED group. Referred ED patients were more likely to have signs of sepsis and to have been pre-treated with antibiotics. Bacteraemia was present in 10% of patients in the PHC group and 27% in the ED group (RR 2.83; 95% CI: 1.64-4.86, p < 0.001). Eight (5%) PHC patients were admitted during outpatient treatment but otherwise no major complications occurred. Clinical failure rates at 30 days were similar between PHC patients and ED patients; 9% and 10% respectively. Mortality rates of PHC patients versus ED patients were 1% versus 5% at 30 days (p = 0.058) and 1% versus 7% at 90 days (p = 0.007). Complicated outcome occurred in 6% of the PHC patients versus 12% in the patients referred to ED (p = 0.067). Conclusion: In a health care system with a well-organized primary care system and clear guideline, the outcome of adults with acute pyelonephritis, including men, the elderly and patients with co-morbidity, selected for oral antibiotic treatment at home did not lead to major complications. (C) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved. Show less
Kruif, M.D. de; Limper, M.; Sierhuis, K.; Wagenaar, J.F.P.; Spek, C.A.; Garlanda, C.; ... ; Gorp, E.C.M. van 2010
Objectives: The long pentraxin PTX3 is a promising marker of disease severity in severely ill patients. In order to identify patients warranting critical care as quickly as possible, we... Show moreObjectives: The long pentraxin PTX3 is a promising marker of disease severity in severely ill patients. In order to identify patients warranting critical care as quickly as possible, we investigated the value of PTX3 as a biomarker for disease severity in patients presenting with fever at the emergency department. Methods: Levels of PTX3 were measured in 211 febrile patients at the emergency and the levels were linked to markers of disease severity including admittance to a special care unit, bloodstream infection and congestive heart failure. Results: In comparison to median baseline levels of 2.30 ng/ml (interquartile range 1.66-3.67 ng/ml), levels of PTX3 were significantly elevated in patients admitted to the intensive/medium care unit (median value 44.4 ng/ml, interquartile range 13.6-105.9 ng/ml) and in patients referred to the ward (median value 14.2 ng/ml, interquartile range 7.01-25.1 ng/ml). In addition, PTX3 was associated with duration of hospital stay and acute congestive heart failure. The levels were predictive for bloodstream infection (AUC = 0.71; 95% CI 0.62-0.81). Conclusions: PTX3 may be a useful marker for differentiation of patients with severe disease in patients presenting with fever to the emergency department. (C) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved. Show less
