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  1. Article ; Online: Dolutegravir based therapy showed CD4

    Gebremedhin, Teshager / Aynalem, Melak / Adem, Mohammed / Geremew, Demeke / Aleka, Yetemwork / Kiflie, Amare

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 3297

    Abstract: Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. ... ...

    Abstract Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4
    MeSH term(s) Humans ; Acquired Immunodeficiency Syndrome/drug therapy ; Antiretroviral Therapy, Highly Active ; HIV Infections ; Prospective Studies ; Viral Load ; Pilot Projects ; CD4 Lymphocyte Count ; Anti-HIV Agents/pharmacology ; HIV-1/genetics ; CD4-Positive T-Lymphocytes ; RNA/pharmacology ; Heterocyclic Compounds, 3-Ring ; Oxazines ; Piperazines ; Pyridones
    Chemical Substances dolutegravir (DKO1W9H7M1) ; Anti-HIV Agents ; RNA (63231-63-0) ; Heterocyclic Compounds, 3-Ring ; Oxazines ; Piperazines ; Pyridones
    Language English
    Publishing date 2024-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-53282-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Helminth species-specific effects on IFN-γ producing T cells during active and latent tuberculosis.

    Kiflie, Amare / Bewket, Gezahegn / Tajebe, Fitsumbrhan / Abate, Ebba / Schӧn, Thomas / Blomgran, Robert

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 1, Page(s) e0011094

    Abstract: Background: Interferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and ... ...

    Abstract Background: Interferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-γ production by T cells in relation to disease severity during active and latent TB infection (LTBI).
    Methods: In this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-γ production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control.
    Results: Helminth infected CCs and LTBI subjects showed a significant reduction of IFN-γ+ CD4+ T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-γ+ T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-γ+ CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-γ+ T cells compared to the corresponding non-helminth infected PTB.
    Conclusion: We found a reduction in IFN-γ producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity.
    MeSH term(s) Humans ; Animals ; Latent Tuberculosis ; Interferon-gamma ; Mycobacterium tuberculosis ; Tuberculin ; Leukocytes, Mononuclear ; Tuberculosis/diagnosis ; CD4-Positive T-Lymphocytes ; Helminths ; Antigens, Bacterial
    Chemical Substances Interferon-gamma (82115-62-6) ; Tuberculin ; Antigens, Bacterial
    Language English
    Publishing date 2023-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0011094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Differential effects of asymptomatic Ascaris lumbricoides, Schistosoma mansoni or hook worm infection on the frequency and TGF-beta-producing capacity of regulatory T cells during active tuberculosis.

    Kiflie, Amare / Bewket, Gezahegn / Abate, Ebba / Schön, Thomas / Blomgran, Robert

    Tuberculosis (Edinburgh, Scotland)

    2021  Volume 131, Page(s) 102126

    Abstract: Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species- ... ...

    Abstract Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-β producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-β-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-β
    MeSH term(s) Analysis of Variance ; Animals ; Ascaris lumbricoides/pathogenicity ; Ethiopia ; Schistosoma mansoni/pathogenicity ; Schistosomiasis/complications ; Schistosomiasis/physiopathology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tuberculosis/immunology
    Language English
    Publishing date 2021-09-14
    Publishing country Scotland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2046804-0
    ISSN 1873-281X ; 1472-9792
    ISSN (online) 1873-281X
    ISSN 1472-9792
    DOI 10.1016/j.tube.2021.102126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls.

    Bewket, Gezahegn / Kiflie, Amare / Tajebe, Fitsumbrhan / Abate, Ebba / Schön, Thomas / Blomgran, Robert

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 8, Page(s) e0010721

    Abstract: Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the ... ...

    Abstract Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and QuantiFERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.
    MeSH term(s) Animals ; Coinfection ; Cytokines/immunology ; Helminthiasis/immunology ; Helminths/classification ; Humans ; Interleukin-17/immunology ; Leukocytes, Mononuclear/immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Tuberculin ; Tuberculosis/complications ; Tuberculosis/immunology ; Tumor Necrosis Factor-alpha
    Chemical Substances Cytokines ; Interleukin-17 ; Tuberculin ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2022-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Seroprevalence of HBV and HCV Among Diabetes Mellitus Patients Attending University of Gondar Hospital, Northwest Ethiopia.

    Fasil, Alebachew / Geremew, Demeke / Bewket, Gezahegn / Kiflie, Amare / Abebe, Molla / Biadgo, Belete

    Clinical laboratory

    2022  Volume 68, Issue 9

    Abstract: Background: Hepatitis B and hepatitis C viruses are common infections and main causative agents of chronic liver diseases, cirrhosis, and hepatocellular carcinoma. The liver is the major site of hormone and glucose metabolism which have deep ... ...

    Abstract Background: Hepatitis B and hepatitis C viruses are common infections and main causative agents of chronic liver diseases, cirrhosis, and hepatocellular carcinoma. The liver is the major site of hormone and glucose metabolism which have deep interconnection with diabetes. Hepatitis-B and hepatitis-C virus infection and diabetes are prevalent diseases worldwide associated with increased morbidity and mortality. High prevalence of DM, HCV, and HBV showed that there is a higher chance of coexisting in an individual. Therefore, our study tried to assess the coexistence of hepatitis viruses and diabetes mellitus among DM patients at the University of Gondar comprehensive specialized hospital.
    Methods: The hospital-based, cross-sectional study was conducted from November 01 to December 30, 2019 to as-sess the prevalence and associated factors of HBV and HCV among diabetes patients attending at University of Gondar referral hospital. Sociodemographic data was collected using a semi-structured questionnaire. Four milliliters of blood were collected using an anticoagulant free test tube for measurement of biochemical parameters and detection of hepatitis viruses. HBsAg and anti-HCV antibody detection was performed using One Step Cassette Style HBsAg Rapid Test and EUGENE® anti-HCV rapid test, respectively. Binary and multivariable logistic regression models were used to evaluate associated risk factors for the outcome variable. A p-value of < 0.05 was considered statistically significant.
    Results: A total of 288 diabetes patients were included in this study and the prevalence of HBV and HCV was 7 (2.43%) and 18 (6.25%), respectively. Hepatitis B virus showed similar prevalence for type 1 and type 2 diabetes at 2.6% and 2.3%, respectively, but HCV showed a wide variation with 17.5% and 4.3% prevalence, respectively, for both diabetes types. In a multivariable logistic regression model compared with younger age (≤ 24 years), older age ≥ 65 years (AOR: 19.545, 95% CI: 2.577 - 22.827) age groups and poor glycemic control (AOR: 18.84, 95% CI: 17.83 - 20.39) showed significant association with HBV.
    Conclusions: A considerably large number of diabetes patients tested positive for anti-HCV antibody as a marker of Hepatitis C virus infection. None of the variables showed significant association with active Hepatitis B virus infection whereas older ages (≥ 65 years) and diabetes patients with poor glycemic control showed significant association with anti-HCV antibody positivity.
    MeSH term(s) Adult ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology ; Ethiopia/epidemiology ; Glucose ; Hepacivirus ; Hepatitis B/complications ; Hepatitis B/diagnosis ; Hepatitis B/epidemiology ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis C/complications ; Hepatitis C/diagnosis ; Hepatitis C/epidemiology ; Hepatitis C Antibodies ; Hormones ; Hospitals ; Humans ; Seroepidemiologic Studies ; Young Adult
    Chemical Substances Hepatitis B Surface Antigens ; Hepatitis C Antibodies ; Hormones ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-09-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1307629-2
    ISSN 1433-6510 ; 0941-2131
    ISSN 1433-6510 ; 0941-2131
    DOI 10.7754/Clin.Lab.2022.210935
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis.

    Bewket, Gezahegn / Kiflie, Amare / Abate, Ebba / Stendahl, Olle / Schön, Thomas / Blomgran, Robert

    PLoS neglected tropical diseases

    2021  Volume 15, Issue 3, Page(s) e0009194

    Abstract: Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate ... ...

    Abstract Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.
    MeSH term(s) Adolescent ; Adult ; Animals ; Antigens, Helminth ; Case-Control Studies ; Coinfection ; Ethiopia ; Female ; Helminthiasis/immunology ; Helminthiasis/pathology ; Helminths/physiology ; Humans ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; Parasite Egg Count ; Tuberculosis, Pulmonary/immunology ; Tuberculosis, Pulmonary/pathology ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Antigens, Helminth ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2021-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0009194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Latent tuberculosis infection and associated risk factors among people living with HIV and apparently healthy blood donors at the University of Gondar referral hospital, Northwest Ethiopia.

    Tilahun, Mekdes / Shibabaw, Agumas / Kiflie, Amare / Bewket, Gezahegn / Abate, Ebba / Gelaw, Baye

    BMC research notes

    2019  Volume 12, Issue 1, Page(s) 515

    Abstract: Objective: Immuno-compromised individuals with latent tuberculosis infection (LTBI) are at an increased risk for tuberculosis reactivation compared with the general population. The aim of this study was to determine the prevalence of latent tuberculosis ...

    Abstract Objective: Immuno-compromised individuals with latent tuberculosis infection (LTBI) are at an increased risk for tuberculosis reactivation compared with the general population. The aim of this study was to determine the prevalence of latent tuberculosis infection among people living with human immunodeficiency virus (PLWH) and apparently healthy blood donors. Human Immunodeficiency Virus positive individuals and for the purpose of comparison apparently healthy blood donors were enrolled. Blood sample was collected and tested for LTBI using QuantiFeron-TB Gold In-Tube assay (QFT-GIT) and CD4+ T cell count was determined by using BD FACS count.
    Results: The overall prevalence of LTBI regardless of HIV status was 46%. The prevalence of LTBI among PLWH was 44% and that of blood donors 48%. ART naïve HIV positive patients were three times more likely to have LTBI than patients under ART treatment (P = 0.04). Data also showed statistically significant negative association between previous or current preventive INH therapy and LTBI among HIV positive cases (P = 0.005). The proportion of LTBI was slightly lower among HIV positive individuals than apparently healthy blood donors. Nevertheless, HIV positive individuals should be screened for LTBI and take INH prophylaxis.
    MeSH term(s) Adult ; Anti-Retroviral Agents/therapeutic use ; Blood Donors/statistics & numerical data ; CD4 Lymphocyte Count ; Comorbidity ; Ethiopia/epidemiology ; Female ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Hospitals, University ; Humans ; Latent Tuberculosis/diagnosis ; Latent Tuberculosis/epidemiology ; Male ; Prevalence ; Referral and Consultation ; Risk Factors ; Tuberculin Test ; Young Adult
    Chemical Substances Anti-Retroviral Agents
    Language English
    Publishing date 2019-08-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2413336-X
    ISSN 1756-0500 ; 1756-0500
    ISSN (online) 1756-0500
    ISSN 1756-0500
    DOI 10.1186/s13104-019-4548-x
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  8. Article: Minimally Invasive Microbiopsies as an Improved Sampling Method for the Diagnosis of Cutaneous Leishmaniasis.

    Churiso, Gemechu / van Henten, Saskia / Cnops, Lieselotte / Pollmann, Julia / Melkamu, Roma / Lemma, Mulualem / Kiflie, Amare / Fikre, Helina / van Griensven, Johan / Adriaensen, Wim

    Open forum infectious diseases

    2020  Volume 7, Issue 9, Page(s) ofaa364

    Abstract: Current sampling methods to diagnose cutaneous leishmaniasis are invasive and painful. An alternative and minimally invasive microbiopsy device was evaluated in a diverse range of cutaneous leishmaniasis lesions in Ethiopia. Using polymerase chain ... ...

    Abstract Current sampling methods to diagnose cutaneous leishmaniasis are invasive and painful. An alternative and minimally invasive microbiopsy device was evaluated in a diverse range of cutaneous leishmaniasis lesions in Ethiopia. Using polymerase chain reaction-based diagnosis, the microbiopsy outperformed the routine skin slit sample by detecting more patients while pain scores were significantly lower.
    Language English
    Publishing date 2020-08-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofaa364
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  9. Article ; Online: Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation.

    Aleka, Yetemwork / Ibarra-Meneses, Ana Victoria / Workineh, Meseret / Tajebe, Fitsumbrhan / Kiflie, Amare / Tessema, Mekibib Kassa / Melkamu, Roma / Tadesse, Azeb / Moreno, Javier / van Griensven, Johan / Carrillo, Eugenia / Adriaensen, Wim

    Journal of immunology research

    2020  Volume 2020, Page(s) 8385672

    Abstract: Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue ... ...

    Abstract Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-
    MeSH term(s) Adolescent ; Adult ; Cells, Cultured ; Cohort Studies ; Cytokines/metabolism ; Endemic Diseases ; Ethiopia/epidemiology ; Female ; Follow-Up Studies ; Humans ; Immunization ; Leishmania donovani/physiology ; Leishmaniasis, Visceral/epidemiology ; Leishmaniasis, Visceral/immunology ; Male ; Monitoring, Physiologic ; Pilot Projects ; Treatment Outcome ; Young Adult
    Chemical Substances Cytokines
    Language English
    Publishing date 2020-01-23
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2817541-4
    ISSN 2314-7156 ; 2314-8861
    ISSN (online) 2314-7156
    ISSN 2314-8861
    DOI 10.1155/2020/8385672
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  10. Article ; Online: Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production.

    Adem, Emebet / Tajebe, Fitsumbirhan / Getahun, Mulusew / Kiflie, Amare / Diro, Ermias / Hailu, Asrat / Shkedy, Ziv / Mengesha, Bewketu / Mulaw, Tadele / Atnafu, Saba / Deressa, Tekalign / Mathewos, Biniam / Abate, Ebba / Modolell, Manuel / Munder, Markus / Müller, Ingrid / Takele, Yegnasew / Kropf, Pascale

    PLoS neglected tropical diseases

    2016  Volume 10, Issue 3, Page(s) e0004468

    Abstract: One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole ... ...

    Abstract One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation.
    MeSH term(s) Adolescent ; Adult ; Antigens, Protozoan/immunology ; Arginase/metabolism ; Cross-Sectional Studies ; Ethiopia ; Granulocytes/immunology ; Humans ; India ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leishmaniasis, Visceral/drug therapy ; Leishmaniasis, Visceral/pathology ; Male ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Treatment Outcome ; Young Adult
    Chemical Substances Antigens, Protozoan ; Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6) ; Arginase (EC 3.5.3.1)
    Language English
    Publishing date 2016-03-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0004468
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