National Institute for Infectious Diseases INMI

Rome, Italy

National Institute for Infectious Diseases INMI

Rome, Italy
SEARCH FILTERS
Time filter
Source Type

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.


PubMed | University of Rome La Sapienza, P.O.I.T., L Spallanzani National Institute For Infectious Diseases Inmi, Instituto Superiore Of Sanita Iss and National Institute for Infectious Diseases INMI
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2015

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.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-, IL-2, TNF-, 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-+Th2+ or TNF-+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.We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-+Th2+ triple-positive and TNF-+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.


Petrone L.,National Institute for Infectious Diseases INMI | Cannas A.,National Institute for Infectious Diseases INMI | Aloi F.,O people | Aloi F.,St Francis Nsambya Hospital | And 12 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.


Petrone L.,National Institute for Infectious Diseases INMI | Cannas A.,National Institute for Infectious Diseases INMI | Vanini V.,National Institute for Infectious Diseases INMI | Cuzzi G.,National Institute for Infectious Diseases INMI | And 16 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2016

SETTING: Blood interferon-γ inducible protein 10 (IP-10) has been proposed as a biomarker of disease activity for both tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Urine IP-10 has been detected in adults with active TB, and its level decreases after successful anti-tuberculosis treatment. OBJECTIVE: To evaluate blood and urine IP-10 as biomarker of disease activity. DESIGN: Patients with HIV-TB and active TB were enrolled. Individuals with HIV infection only and healthy donors were included as controls. Blood and urine IP-10 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Of 39 active TB patients enrolled, 24 were HIV-infected and 15 were HIV-uninfected. Of 87 control subjects without active TB, 54 were HIV-infected and 33 were HIV-uninfected. IP-10 analysis was performed in patients with concomitant blood and urine sample collection. Blood IP-10 was associated with active TB, regardless of HIV infection status; urine IP-10 levels were increased in active TB patients, although the difference was significant in HIV-infected individuals only. Finally, in HIV-infected patients, both blood and urine IP-10 levels were inversely correlated with CD4 Tcell counts. CONCLUSION: These findings suggest that IP-10 could be used as a biomarker for disease activity (inflammation). © 2016 The Union.


PubMed | San Raffaele Scientific Institute, National Institute for Infectious Diseases INMI and National Institute For Infectious Diseases Inmi L Spallanzani
Type: | Journal: International journal of mycobacteriology | Year: 2017

Interferon (IFN)- release assays (IGRA) are designed for diagnosing tuberculosis (TB) infection. The new IGRA, QuantiFERON-TB Plus (QFT-Plus), is based on the enzyme-linked immunosorbent assay detection of IFN- after stimulation with Mycobacterium tuberculosis TB1 and TB2 antigens. TB1 elicits a cellular-mediated immune (CMI) response by CD4 T cells, and TB2 contains peptides recognized by both CD4 and CD8 T cells. The aim of the study is to characterize the CMI to QFT-Plus peptides in active TB and latent TB infection (LTBI) at baseline and during or after specific treatment (follow-up).We enrolled 7 individuals with active TB and 11 individuals with LTBI at baseline and followed them during the treatment, either for active diseases or preventive therapy. Peripheral blood mononuclear cells were stimulated with QFT-Plus antigens (TB1, TB2, and mitogen). Cytokine profile (IFN-, tumor necrosis factor-, interleukin-2) and phenotype (CD45RA, CD27) of CD4 and CD8 T cells were characterized by flow cytometry.All the individuals responded to mitogen. CD4 T-cell responses to TB1 and TB2 were similar in both individuals with active TB and those with LTBI evaluated over time. Differently, we found a higher number of TB2-associated CD8 T-cell responders in individuals with active TB than in those with LTBI. For individuals with active TB, there was no change in the specific response overtime. Differently, in individuals with LTBI, the number of CD8 responders to QFT-Plus antigens increased during preventive treatment (TB1=5/11 [45%], TB2=5/11 [45%]) compared with that at the time of enrolment (TB1=1/11 [9%], TB2=1/11 [9%]). Moreover, we analyzed the effector memory profile of T cells responding to QFT-Plus antigens. The largest component of antigen-specific CD4 T cells (65%) had a central memory (CD45RA-CD27+) phenotype at enrolment and during follow-up. In contrast, specific CD8 T cells, which were analyzed only at follow-up because they were almost absent at baseline, were characterized by a large component with nave (CD45RA+CD27+) phenotype (40%) and a minor component with central memory (25%) features.To our knowledge, this is the first report characterizing CD4 and CD8 T-cell responses of individuals with active TB and with LTBI, followed overtime, to QFT-Plus antigens by flow cytometry. The results, although preliminary, may help in identifying better tools for monitoring therapy, especially in those with LTBI undergoing preventive treatment.


PubMed | San Raffaele Scientific Institute, National Institute for Infectious Diseases INMI and National Institute For Infectious Diseases Inmi L Spallanzani
Type: | Journal: International journal of mycobacteriology | Year: 2017

Interferon (IFN)--release assays (IGRAs) are designed for the diagnosis of tuberculosis (TB) infection. The new IGRA called QuantiFERON-TB Plus (QFT-Plus) is based on enzyme-linked immunosorbent assay (ELISA) detection of IFN- following Myobacterium tuberculosis-antigen stimulation with TB1 and TB2 antigens. TB1 elicits a cell-mediated immune response by CD4 T cells and TB2 elicits a response from both CD4 and CD8 T cells. Here, we characterized variations IFN- release detected by ELISA to QFT-IT and QFT-Plus in patients with active TB and latent TB infection (LTBI) at baseline and during or after specific treatment (follow-up).We studied seven patients with active TB and 10 patients with LTBI at baseline and during treatment either for active disease or preventive therapy. IFN- release detected by ELISA to QFT-IT and QFT-Plus was concomitantly evaluated over time. Statistical analysis was performed using a nonparametrical test for a paired dataset (Wilcoxon test).All participants responded to the mitogen, with all active-TB patients responding to QFT-IT or QFT-Plus at baseline. The responses did not change over time either qualitatively (number of responders) or quantitatively (IFN- release evaluated as IU/mL). Among the LTBI group, although all participants responded to both QFT-IT and QFT-Plus and the responses did not change over time, the quantitative responses to QFT-Plus showed a different trend. Specifically, response to TB2 was significantly lower at follow-up as compared with that observed at baseline (p=0.004), whereas the response to TB1 was not significantly different (p=0.16).To our knowledge, this is the first report characterizing IFN- responses to QFT-Plus antigens in participants with active TB and LTBI over time. The data need to be confirmed in larger settings; however, we showed that monitoring IFN- release in response to TB2 can be used to evaluate preventive therapy immune changes. This can be useful also as a tool for public health control strategies in settings where preventive treatment is recommended.


PubMed | Ifakara Health Institute, Swiss Tropical and Public Health Institute, O people, St Francis Nsambya Hospital and National Institute for Infectious Diseases INMI
Type: | Journal: BioMed research international | Year: 2015

Interferon- 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.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.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.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.


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.,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.

Loading National Institute for Infectious Diseases INMI collaborators
Loading National Institute for Infectious Diseases INMI collaborators