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Mycobacterial Diseases
Mycobacterial Diseases Research Directorate(MDRD)
About MDRD
Research
Researchers at MDRD
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About MDRD
The Mycobacterial Diseases Research Directorate (MDRD) is mandated to conduct research on two major fields: Tuberculosis (TB) and Leprosy.
The mission of MDRD is to generate scientific evidences in both TB and leprosy contributing towards diagnosis, prevention and control of the diseases.
Basic Biomedical Research
Understanding and characterizing the Host-pathogen interactions
Epidemiology of the diseases
Molecular epidemiology of the circulating strains, drug resistance patterns
Co-infections
Biomarker search for
Diagnostics
Vaccines
drug targets
Operational Research
Research
Major Research projects
1. An integrated approach to unraveling susceptibility to tuberculosis in Africa
(TBGEN-Africa )
Africa has the highest level of genetic diversity amongst all human populations. It also has the highest level of genetic diversity amongst populations of the pathogen that causes tuberculosis (TB).
The project proposed that the long history of co-evolution of host and pathogen genomes contributes to the diverse outcome following MTB infection, as reflected in the variable percentage of individuals progressing to active TB and varying efficiencies of ongoing transmission.
To test this hypothesis:
The distribution of MTB genotypes alongside the genotypes of genetically-distinct human populations in four African countries will be mapped.
Comparison of paired host and bacterial genomes will identify loci that have co-evolved.
This information will have fundamental importance in understanding the influence of host genetics on disease susceptibility and will highlight novel factors that impact on TB pathogenesis and pathology including the influence of HIV-induced immunosuppression.
Ethiopia, Eritrea, Sudan and Cameroon are members of the consortium and AHRI leads the project.
Funding: Wellcome Trust through African Academy of Sciences (AAS) as part of the H3Africa Consortium.
For further reading: tbgen.ahri.gov.et（http://tbgen.ahri.gov.et）
2. Immune Signatures to Characterize Progression from Latent TB Infection to Active TB Disease (Ethiopia) (Tuberculosis Research Units Network (TBRU) Ethiopia)
The Tuberculosis Research Units Network (TBRU-N) is a consortium project involving partners from USA and other parts of the world to study the role of antigen specific T cell responses in the control of tuberculosis (TB). AHRI is involved in this consortium to study the spectrum of
Mycobacterium tuberculosis (Mtb)-antigen specific immune responses in contacts of pulmonary TB patients, which ultimately contribute to the development of tools that help identifying people who are at higher risk of progression to active TB and make priorities for preventive interventions. The study is an observational study, involving contacts of pulmonary TB patients and conducted at selected health facilities in Addis Ababa, Ethiopia. This collaborative project is funded by NIH.
For more information : http://tbru.emory.edu/
3. AHRI-APOPO Tuberculosis Research Project
This project, being conducted under a partnership agreement between AHRI and APOPO (a non-profit organization that trains and deploys detection rats for humanitarian purposes; www.apopo.org) has two wings:
(A) enhanced TB case finding in Addis Ababa and
(B) improved TB/HIV screening in Ethiopian prisons. Special features of the project are the research into the use of TB detection rats (African giant pouched rats, bred and trained in Tanzania) as a TB diagnostic tool, and the improvement of services along the TB care cascade in line with the global efforts to “Find. Treat All” and ending TB.
4. SeroSelectTB
Evaluation of the feasibility, accuracy, and effect of a rapid point-of-care serological triage test for active TB (SeroSelectTB) in high burden, HIV-endemic African settings: a multi-centre, parallel group, randomized, controlled trial.
Objective: to qualify the performance of SeroSelectTB and determine the extent to which the test reduces diagnostic delay and expedites treatment.
Funding: EDCTP; the leading institute is NIPH
5. Post Exposure Prophylaxis for leprosy (PEP4LEP )
“Chemoprophylaxis for leprosy: comparing the effectiveness and feasibility of a skin camp intervention to a health centre based intervention; An implementation trial in Mozambique, Ethiopia and Tanzania” (PEP4LEP)
The general objective of the project is to contribute towards interrupting the transmission of M. leprae by identifying the most effective and feasible method for screening of people at risk of developing leprosy and administering chemoprophylaxis (a single dose rifampicin; SDR) in Ethiopia, Mozambique, and Tanzania.
Funding: EDCTP & LRI, and leading institute is NLR
6. Microbiological and epidemiological aspects of tuberculosis during pregnancy
The project aims to investigate the impact of pregnancy on the immune control of latent TB infection.
7. C-type lectin receptor expression by helminth or HIV infection: setting the threshold for sensing of mycobacteria
The project aims at understanding the underlying mechanisms of immunity to M.tb by worm infections in the human system at the level of CLR expression. Specifically, the effect of maternal helminth infection on CLR expression in mothers and newborns will be investgated, which will address how intrauterine exposure of the infant to type 2 immune environment affects their response to BCG vaccination.CLR expression and functional analyses will be complemented with a broader analysis of immunological gene expression and epigenetic histone modifications.
Collaborator: Universitats Klinikum Erlangen
Funding : DFG, German Research Foundation
8. Characterization of innate and adaptive immune responses to mycobacterial antigens in house-hold contacts of Tuberculosis patients (IRTBHHC).
Objectives: to evaluate TB antigen specific immune responses in house hold contacts of TB patients, and correlations with the ability to inhibit mycobacterial growth and with epigenetic modifications in innate immune cells.
Funding: TBGEN Africa, EDCTP, OWSD-UNESCO, NIH/Fogarty Global Centre Infectious Diseases
For further reading : https://ahri.gov.et/irtbhhc/
9. Exploring epigenetic alterations of cellular immunity in MDR TB with relevance for new therapy using epigenetic and immune modulating drugs
The objective of this project is to study immune checkpoint molecules and epigenetic alterations in DS-TB and MDR-TB
10. Active case detection of leprosy and tracing household contacts in hotspot areas
One of the priority areas in leprosy research is early detection of leprosy. The delay in leprosy case diagnosis and the presence of asymptomatic individuals at high risk of developing leprosy are the causes for increased disability among newly diagnosed patients and for ongoing transmission of leprosy in the population.
The recent strategy of WHO and national control program is to conduct active case detection and contact tracing activities in hot-spot sites. We have conducted ACF and contact tracing in West Arsi zone (Kokosa wereda) and in East Hararghe zone (Fedis wereda). The activity includes KAP assessment, training of HEW and TBL focal persons in leprosy management, house to house survey and close follow up of contacts and laboratory based assessments.
Researchers at MDRD
Dr. Kidist Bobosha (MSc, PhD) Senior researcher and Director of MDRD Email: kidist.bobosha@ahri.gov.et Tel: +251 911 672286 Skype: boboshak
Dr. Liya Wassie, (MSc, PhD) Senior researcher and TB Team Leader Email: liya.wliya.wassie@ahri.gov.et asie@ahri.gov.et Tel: +251 911 664975 Skype: lilisho
Dr. Berhanu Seyoum, (MSc, PhD) Senior researcher Email: berhanu.seyoum@ahri.gov.et Tel: +251 911 677774
Martha Zewdie (MSc, PhD) Postdoctoral fellow- TBGEN Africa PI of IRTBHHC project looking at protective immunity and epigenetic modifications of innate immune cells
Meseret Habtamu Mekonnen (MSc, PhD) Postdoctoral fellow C-type lectin receptor expression by helminth or HIV infection: setting the threshold for sensing of mycobacteria Email: meseret.habtamu@ahri.gov.et Tel: +251 921623485
Negussie Beyene (PhD, MPH) Head, AHRI-APOPO Research project Email: negussie.beyene@apopo.org Tel: +251 911 391166 Skype: negbene
Publication
MDRD publications 2021
Begna Tulu, Aboma Zewede, Mulugeta Belay, Miserach Zeleke, Mussie Girma, Metasebia Tegegn, Fozia Ibrahim, David A. Jolliffe, Markos Abebe, Taye Tolera Balcha, Balako Gumi, Henny M. Martineau, Adrian R. Martineau, Gobena Ameni. Epidemiology of Bovine Tuberculosis and Its Zoonotic Implication in Addis Ababa Milkshed, Central Ethiopia. Front Vet Sci. 2021; 8: 595511. doi: 10.3389/fvets.2021.595511
Hygon Mutavhatsindi, Gian D. van der Spuy, Stephanus T. Malherbe, Jayne S. Sutherland, Annemieke Geluk, Harriet Mayanja-Kizza, Amelia C. Crampin, Desta Kassa, Rawleigh Howe, Adane Mihret, Jacob A. Sheehama, Emmanuel Nepolo, Gunar Günther, Hazel M. Dockrell, Paul L. A. M. Corstjens, Kim Stanley, Gerhard Walzl, Novel N. Chegou, the AE-TBC ScreenTB Consortia. Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease. Front Immunol. 2021; 12: 607827 doi: 10.3389/fimmu.2021.607827
Birhan Alemnew, Soren T. Hoff, Tamrat Abebe, Markos Abebe, Abraham Aseffa, Rawleigh Howe, Liya Wassie. Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection. BMC Immunol. 2021; 22: 9. PMCID: PMC7842038 doi: 10.1186/s12865-021-00400-4
Meseret Gebre, Lindsay Hatzenbuehler Cameron, Getachew Tadesse, Yohannes Woldeamanuel, Liya Wassie. Variable Diagnostic Performance of Stool Xpert in Pediatric Tuberculosis: a systematic review and meta-analysis. Open Forum Infectious Diseases, ofaa627. https://doi.org/10.1093/ofid/ofaa627
Drug Resistance Conferring Mutation and Genetic Diversity of Mycobacterium tuberculosis Isolates in Tuberculosis Lymphadenitis Patients; Ethiopia. Sosina Ayalew, Teklu Wegayehu, Hawult Taye, Liya Wassie, Selfu Girma, Stefan Berg, Adane Mihret. Infect Drug Resist. 2021; 14: 575–584. Published online 2021 Feb 15. doi: 10.2147/IDR.S298683 PMCID: PMC7894881
MDRD publications Jan- Dec, 2020
Tekle Airgecho Lobie, Yimtubezinash Woldeamanuel, Daniel Asrat, Demissew Beyene, Magnar Bjørås, Abraham Aseffa. Genetic diversity and drug resistance pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in the Benishangul Gumuz region and its surroundings, Northwest Ethiopia. PLoS ONE 15(4): e0231320.
M. Habtamu, G. Abrahamsen, A. Aseffa, E. Andargie, S . Ay a l e w, M. Abebe and A. Spurkland. High-throughput analysis of T cell–monocyte interaction in human tuberculosis. Clinical and Experimental Immunology (2020), 1–13
Abiyu Mekonnen1, Jeffery M. Collins, Eveline Klinkenberg, Dawit Assefa, Abraham Aseffa, Gobena Ameni and Beyene Petros. Tuberculosis knowledge and attitude among non-health science university students needs attention: a cross-sectional study in three Ethiopian universities. BMC Public Health (2020) 20:631
Melaku Tilahun, Ezra Shimelis, Teklu Wogayehu, Gebeyehu Assefa, Getachew Wondimagegn, Alemayehu Mekonnen, Tsegaye Hailu, Kidist Bobosha, Abraham Aseffa. Molecular detection of multidrug resistance pattern and associated gene mutations in M. tuberculosis isolates from newly diagnosed pulmonary tuberculosis patients in Addis Ababa, Ethiopia. Plos One; Aug 4, 2020 . doi: 10.1371/journal.pone.0236054
Kedir Urgesa, Kidist Bobosha, Berhanu Seyoum , Biftu Geda, Fitsum Weldegebreal, Adane Mihret, Rawleigh Howe, Mirgissa Kaba, Abraham Aseffa. Knowledge of and Attitude Toward Leprosy in a Leprosy Endemic District, Eastern Ethiopia: A Community-Based Study. Risk Manag Healthc Policy. Aug 10, 2020 doi: 10.2147/RMHP.S254625
Fregenet Tesfaye a,g,*, Erik Sturegård a,c, John Walles a,d, Niclas Winqvist a, Taye Tolera Balcha a, Sara Karlson b, Daba Mulleta e, Per-Erik Isberg f, Marianne Jansson b, Per Bj¨orkman a,h. Alternative biomarkers for classification of latent tuberculosis infection status in pregnant women with borderline Quantiferon plus results. Tuberculosis Sep 2020 doi.org/10.1016/j.tube.2020.101984
Mahlet Birku, Girmay Desalegn, Getachew Kassa, Aster Tsegaye, Markos Abebe. Effect of pregnancy and HIV infection on detection of latent TB infection by Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube assay among women living in a high TB and HIV burden setting. Int J Infect Dis. 2020 Dec; 101: 235–242. Published online 2020 Oct 9. doi: 10.1016/j.ijid.2020.09.1452
Solomon Abebe Yimer, Shewit Kalayou, Håvard Homberset, Alemayehu Godana Birhanu, Tahira Riaz, Ephrem Debebe Zegeye, Timo Lutter, Markos Abebe, Carol Holm-Hansen, Abraham Aseffa, Tone Tønjum. Lineage-Specific Proteomic Signatures in the Mycobacterium tuberculosis Complex Reveal Differential Abundance of Proteins Involved in Virulence, DNA Repair, CRISPR-Cas, Bioenergetics and Lipid Metabolism. Front Microbiol. 2020; 11: 550760. doi: 10.3389/fmicb.2020.550760
Gary Napier, Susana Campino, Yared Merid, Markos Abebe, Yimtubezinash Woldeamanuel, Abraham Aseffa, Martin L. Hibberd, Jody Phelan, Taane G. Clark. Robust barcoding and identification of Mycobacterium tuberculosis lineages for epidemiological and clinical studies. Genome Med. 2020; 12: 114. doi: 10.1186/s13073-020-00817-3
Getnet Abie Mekonnen, Adane Mihret, Mekdes Tamiru, Elena Hailu, Abebe Olani, Abde Aliy, Melaku Sombo, Matios Lakew, Balako Gumi, Gobena Ameni, James L. N. Wood, Stefan Berg. Genotype Diversity of Mycobacterium bovis and Pathology of Bovine Tuberculosis in Selected Emerging Dairy Regions of Ethiopia. Front Vet Sci. 2020; 7. doi: 10.3389/fvets.2020.553940
MDRD publications Jan- Dec, 2019
Mekonnen B, Mihret A , Getahun M, Hailu T, Sidiki S, V Kelley H, Scordo JM,Hunt WG, Pan X, Balada-Llasat JM, Gebreyes W, Evans CA, Aseffa A , Torrelles JB,Wang SH, Abebe T. Evaluation of the tuberculosis culture color plate test for rapid detection of drug susceptible and drug-resistant Mycobacterium tuberculosis in a resource-limited setting, Addis Ababa, Ethiopia. PLoS One. 2019 May 28;14(5):e0215679. doi: 10.1371/ journal.pone.0215679. eCollection 2019. PubMed PMID: 31136575.
Olsson O, Björkman P, Jansson M, Balcha TT, Mulleta D, Yeba H, Valfridsson C, Carlsson F, Skogmar S. Plasma Profiles of Inflammatory Markers Associated WithActive Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals. Open Forum Infect Dis. 2019 Jan 31;6(2):ofz015. doi: 10.1093/ofid/ofz015. eCollection 2019 Feb.