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Petrone L.,L Spallanzani National Institute For Infectious Diseases Inmi | Vanini V.,L Spallanzani National Institute For Infectious Diseases Inmi | Petruccioli E.,L Spallanzani National Institute For Infectious Diseases Inmi | Ettorre G.M.,Unit of Surgery and Transplantation | And 8 more authors.
Journal of Infection | Year: 2015

Objectives: Human Cystic Echinococcosis (CE) is estimated in 2-3 million global cases. CE diagnosis and clinical management are based on imaging and serology, which lacks sensitivity and does not provide cyst stage information. This study aimed to evaluate tools for improving diagnosis by analysing the Interleukin (IL)-4-response to Antigen B (AgB) of Echinococcus granulosus. Methods: Whole blood (WB) and peripheral blood mononuclear cells were stimulated with AgB. IL-4 levels were measured by enzyme-linked immunosorbent assay. Results: WB 1-day stimulation resulted the best experimental condition for evaluating AgB IL-4-response. IL-4 levels were significantly higher in CE patients than healthy donors (. p≤0.0001). A ROC analysis showed significant area under the curve (AUC) results (AUC, 0.85; p=0.0001) identifying an IL-4 level cut-off point ≥0.39pg/mL which predicted CE with 71.4% sensitivity and 93.3% specificity. Moreover, we found that IL-4 levels were significantly increased in patients with active cysts compared to those with inactive cysts (. p≤0.0001). ROC analysis showed significant AUC results (0.94; p=0.0001) with a cut-off point of 4.6pg/mL which predicted active cysts with 84.6% sensitivity and 92% specificity. Conclusions: We found immunological correlates associated with CE and biological cyst activity. © 2014 The British Infection Association.

Nicolotti N.,National Institute for Infectious Diseases INMI | Cattel C.,Catholic University of the Sacred Heart | Gualano M.R.,University of Turin | Soriano A.,Catholic University of the Sacred Heart | And 2 more authors.
Epidemiology Biostatistics and Public Health | Year: 2013

Background: fever of unknown origin (FUO) is defined as a fever with no etiologic diagnosis after standardized investigations performed during 3 days in hospital or after at least 3 ambulatory visits. Our study aims to describe the epidemiology of classic FUO through the retrospective analysis of 902 861 admissions to a large University Hospital in Italy, to investigate its temporal trend, and to evaluate differences between young and old patients. Methods: we retrieved data records of all the admissions between the 1st January 1988 and 31st December 2007. Proportional admission rate (PAR) of FUO was calculated. Time trends of FUO admissions were analysed by joinpoint regression, with time changes expressed as Expected Annual Percent Change (EA PC). The ICD 9-CM code was used to identify the diagnosis on discharge of FUO cases. Results: in the study period 3 156 patients were admitted with a diagnosis of FUO (PAR=3.50 per 1 000). The time-trend analysis showed two joinpoints, the first in 1995 (EAPC of 307.80, 95% CI: 89.66-776.84, p=0.002), and the second in 1998 (EAPC=-8.57, 95% CI: -10.37-6.73; p<0.001). Around 22% of admissions remained without a definitive diagnosis of FUO, with this percentage being lower in patients ≥65 years compared with subjects aged 21-64. ConclusionS: FUO is a leading cause of admission to hospitals, as well as of morbidity and mortality, thus representing a challenge for diagnostic medicine and hospital care. It is necessary to develop a diagnostic methodology for FUO, so as to reduce costs of preventable hospitalizations.

Petrone L.,L Spallanzani National Institute For Infectious Diseases Inmi | Vanini V.,L Spallanzani National Institute For Infectious Diseases Inmi | Petruccioli E.,L Spallanzani National Institute For Infectious Diseases Inmi | Ettorre G.M.,P.O.I.T | And 8 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Background: Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures. Methodology/Principal Findings: We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the “active stages” group compared to the “inactive stages” group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE. Conclusions: We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence. © 2015 Petrone et al.

Petrone L.,National Institute for Infectious Diseases INMI | Cannas A.,National Institute for Infectious Diseases INMI | Aloi F.,O people | Nsubuga M.,St. Francis Nsambya Hospital | And 11 more authors.
BioMed Research International | Year: 2015

Objectives. Interferon-γ inducible protein 10 (IP-10), either in blood or in urine, has been proposed as a tuberculosis (TB) biomarker for adults. This study aims to evaluate the potential of IP-10 diagnostics in children from Uganda, a high TB-endemic country. Methods. IP-10 was measured in the blood and urine concomitantly taken from children who were prospectively enrolled with suspected active TB, with or without HIV infection. Clinical/microbiological parameters and commercially available TB-immune assays (tuberculin skin test (TST) and QuantiFERON TB-Gold In-Tube (QFT-IT)) were concomitantly evaluated. Results. One hundred twenty-eight children were prospectively enrolled. The analysis was performed on 111 children: 80 (72%) of them were HIV-uninfected and 31 (27.9%) were HIV-infected. Thirty-three healthy adult donors (HAD) were included as controls. The data showed that IP-10 is detectable in the urine and blood of children with active TB, independent of HIV status and age. However, although IP-10 levels were higher in active TB children compared to HAD, the accuracy of identifying "active TB" was low and similar to the TST and QFT-IT. Conclusion. IP-10 levels are higher in children with respiratory illness compared to controls, independent of "TB status" suggesting that the evaluation of this parameter can be used as an inflammatory marker more than a TB test. © 2015 Linda Petrone et al.

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