Publications by authors named "Amare Kiflie"

5 Publications

  • Page 1 of 1

Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis.

PLoS Negl Trop Dis 2021 Mar 2;15(3):e0009194. Epub 2021 Mar 2.

Department of Biomedical and Clinical Sciences, Linköping University, Sweden.

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.
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http://dx.doi.org/10.1371/journal.pntd.0009194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954301PMC
March 2021

Minimally Invasive Microbiopsies as an Improved Sampling Method for the Diagnosis of Cutaneous Leishmaniasis.

Open Forum Infect Dis 2020 Sep 17;7(9):ofaa364. Epub 2020 Aug 17.

Unit of Neglected Tropical Diseases, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1093/ofid/ofaa364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486950PMC
September 2020

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation.

J Immunol Res 2020 23;2020:8385672. Epub 2020 Jan 23.

Unit of Neglected Tropical Diseases, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

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-, TNF-, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble antigen, we observed an early, robust, and incremental increase of IFN-, TNF-, and IP-10 levels in all patients during treatment. Moreover, based on the IFN- levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main species. The levels of IFN-, IP-10, or TNF- also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN- and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.
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http://dx.doi.org/10.1155/2020/8385672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193677PMC
February 2021

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.

BMC Res Notes 2019 Aug 16;12(1):515. Epub 2019 Aug 16.

Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences (CMHS), The University of Gondar (UOG), P.O. box 196, Gondar, Ethiopia.

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.
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http://dx.doi.org/10.1186/s13104-019-4548-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698024PMC
August 2019

Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production.

PLoS Negl Trop Dis 2016 Mar 10;10(3):e0004468. Epub 2016 Mar 10.

Department of Medicine, Imperial College London, London, United Kingdom.

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.
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http://dx.doi.org/10.1371/journal.pntd.0004468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786308PMC
March 2016