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  • American Society for Microbiology  (3)
  • 1
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 9, No. 3 ( 2021-12-22)
    Kurzfassung: Interferon-γ-inducible protein 10 (IP-10) has been suggested as a marker for targeted viral load (VL) monitoring during antiretroviral treatment (ART). We aimed to determine the kinetics of IP-10 during the initial year of ART, with particular regard to the impact of tuberculosis (TB) co-infection on IP-10 secretion. Longitudinal plasma IP-10 levels were quantified in 112 treatment-naive HIV-positive adults at Ethiopian health centers, through enzyme-linked immunosorbent assay (ELISA) using samples obtained before and during the initial 12 months of ART. All participants underwent bacteriological TB investigation before starting ART. In virological responders (VRs; defined as VL  〈  150 copies/ml with no subsequent VL ≥ 1,000 copies/ml), IP-10 kinetics were analyzed using linear regression models. Among 91/112 (81.3%) participants classified as VRs, 17 (18.7%) had concomitant TB. Median baseline IP-10 was 650 pg/ml (interquartile range [IQR], 428–1,002) in VRs. IP-10 decline was more rapid during the first month of ART (median 306 pg/ml/month) compared with later time intervals (median 7-48 pg/ml/month, P   〈  0.001 in each comparison). Although VRs with TB had higher IP-10 levels at baseline (median 1106 pg/ml [IQR, 627–1,704]), compared with individuals without TB (median 628 pg/ml [IQR, 391–885] ; P  = 0.003), the rate of IP-10 decline during ART was similar, regardless of TB-status. During the initial year of ART, IP-10 kinetics followed a biphasic pattern in VRs, with a more rapid decline in the first month of ART compared with later time intervals. Baseline IP-10 was higher in individuals with TB versus individuals without TB, but the kinetics during ART were similar. IMPORTANCE To reach the goal of elimination of HIV as public health threat, access to antiretroviral treatment (ART) has to be further scaled up. To ensure viral suppression in individuals receiving ART, novel and robust systems for treatment monitoring are required. Targeting viral load monitoring to identify individuals at increased likelihood of treatment failure, using screening tools, could be an effective use of limited resources for viral load testing. Interferon-γ-inducible protein 10 (IP-10), a host inflammation mediator, has shown potential for this purpose. Here, we have investigated IP-10 kinetics in Ethiopian adults with HIV during the initial year after ART initiation. IP-10 levels decreased in parallel with viral load during ART, and prevalent tuberculosis at ART initiation did not influence IP-10 kinetics. This study shows satisfactory performance for IP-10 as a surrogate marker for viral load in persons starting ART, with no influence of concomitant tuberculosis.
    Materialart: Online-Ressource
    ISSN: 2165-0497
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2021
    ZDB Id: 2807133-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 59, No. 10 ( 2021-09-20)
    Kurzfassung: Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis . We investigated M. tuberculosis -specific interferon-γ responses in women followed longitudinally during pregnancy and postpartum. Interferon-γ levels (stimulated by M. tuberculosis antigens [TB1 and TB2] and mitogen included in the QuantiFERON-TB Gold Plus assay) were measured in blood from pregnant HIV-negative women identified from a prospective cohort at Ethiopian antenatal care clinics. Longitudinal comparisons included women without active tuberculosis (TB) with M. tuberculosis -triggered interferon-γ responses of ≥ 0.20 IU/ml, sampled on two and/or three occasions (1st/2nd trimester, 3rd trimester, and 9 months postpartum). Among 2,093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of M. tuberculosis -stimulated interferon-γ responses. Median M. tuberculosis -triggered interferon-γ concentrations were higher at 3rd than those at the 1st/2nd trimester (in 38 women with samples available from these time points; TB1: 2.8 versus 1.6 IU/ml, P  = 0.005; TB2: 3.3 versus 2.8 IU/ml, P  = 0.03) and postpartum (in 49 women with samples available from these time points; TB1: 3.1 versus 2.2 IU/ml, P  = 0.01; TB2: 3.1 versus 2.3 IU/ml, P  = 0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3rd than those at 1st/2nd trimester (in 32 women with samples available from these time points: 21.0 versus 34.9 IU/ml, P  = 0.02). Results were similar in 22 women sampled on all 3 occasions. In HIV-negative women, M. tuberculosis -stimulated interferon-γ responses were higher during the 3rd trimester than those at earlier stages of pregnancy and postpartum, despite decreased mitogen-triggered responses. These findings suggest increased M. tuberculosis -specific cellular responses due to dynamic changes of latent TB infection during pregnancy.
    Materialart: Online-Ressource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2021
    ZDB Id: 1498353-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Infection and Immunity, American Society for Microbiology, Vol. 88, No. 12 ( 2020-11-16)
    Kurzfassung: Cell (CD3 + T cell and CD68 + macrophages), cytokine (interferon gamma-positive [IFN-γ + ] and tumor necrosis factor alpha-positive [TNF-α + ]), and effector molecule (inducible nitric oxide synthase-positive [iNOS + ]) responses were evaluated in the lymph nodes and tissues of cattle naturally infected with Mycobacterium bovis . Detailed postmortem and immunohistochemical examinations of lesions were performed on 16 cows that were positive by the single intradermal cervical comparative tuberculin (SICCT) test and that were identified from dairy farms located around the city of Addis Ababa, Ethiopia. The severity of the gross lesion was significantly higher ( P  = 0.003) in M. bovis culture-positive cows ( n  = 12) than in culture-negative cows ( n  = 4). Immunohistochemical techniques showed that in culture-positive cows, the mean immunolabeling fraction of CD3 + T cells decreased as the stage of granuloma increased from stage I to stage IV ( P   〈  0.001). In contrast, the CD68 + macrophage, IFN-γ + , TNF-α + , and iNOS + immunolabeling fractions increased from stage I to stage IV ( P   〈  0.001). In the early stages, culture-negative cows showed a significantly higher fraction of CD68 + macrophage ( P  = 0.03) and iNOS + ( P  = 0.007) immunolabeling fractions than culture-positive cows. Similarly, at advanced granuloma stages, culture-negative cows demonstrated significantly higher mean proportions of CD3 + T cells ( P   〈  0.001) than culture-positive cows. Thus, this study demonstrates that, following natural infection of cows with M. bovis , as the stage of granuloma increases from stage I to stage IV, the immunolabeling fraction of CD3 + cells decreases, while the CD68 + macrophage, IFN-γ + , TNF-α + , and iNOS + immunolabeling fractions increases.
    Materialart: Online-Ressource
    ISSN: 0019-9567 , 1098-5522
    RVK:
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2020
    ZDB Id: 1483247-1
    Standort Signatur Einschränkungen Verfügbarkeit
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