Infectious diseases pose a major burden on the healthcare systems, particularly in developing countries. Tuberculosis, caused by the species in the Mycobacterium tuberculosis complex, is the leading cause of death due to an infectious agent, just behind HIV/AIDs. Despite the variety of diagnostic and treatment methods available, challenges still exist in the elimination of mycobacterial infections, particularly tuberculosis. Moreover, the efforts of the healthcare systems are thwarted by the development of drug-resistant strains. This poses the need for further research in reliable, quick, and easy-to-use diagnostics; novel treatment options; as well as effective monitoring of patients under therapy.
Type 1 diabetes (T1D), an autoimmune disease characterized by a lack of insulin secretion due to the partial or complete destruction of the pancreatic islet cells, is increasing in incidence worldwide. The destruction of the cells is believed to be a result of environmental (infections/vaccinations) or genetic factors. However, the primary trigger for the onset of Type 1 diabetes as well as the underlying immunological mechanisms remain elusive.
Our research interest primarily focuses on understanding the immune pathways responsible for disease pathogenesis. A special focus is on immune biomarkers and their potential to be used in the clinical translation of infectious and autoimmune diseases, particularly tuberculosis and type 1 diabetes.

1. Mansonella perstans effects on BCG vaccine-induced protection against childhood tuberculosis (TB) as well as TB disease severity and recovery in Ghana and Cameroon.

M. perstans is one of the most prevalent human parasites in sub-Saharan Africa. The Culicoides species are speculated to be the transmitting vector of M. perstans. However, knowledge of the exact Culicoides species in which infective larvae of M. perstans develop will help provide insights into the effect of bio-ecological niches in the prevalence of M. perstans infection. This will further enable public health action in reducing transmission and research into appropriate therapeutic strategies. Infection with M. perstans affects hosts’ immunity against mycobacterial diseases including TB and Buruli Ulcer. However, the immune modulatory effects of M. perstans infection on TB disease severity and recovery under treatment are not well understood. Previous studies have demonstrated that M. perstans infection induces regulatory immune cells and impairs the efficacy of BCG vaccination in protecting against active TB infection. To validate previous findings, studies assessing the effects of filarial infections, particularly M. perstans, in BCG-induced protection of high-risk and close contacts of active TB patients are warranted.
Furthermore, there is a paucity of reliable methods to determine disease severity and monitor tuberculosis treatment response. Identification of plasma biomarkers of T-cell function as well as T cell-specific markers associated with tuberculosis infection, treatment, and recovery will enable monitoring of TB patients under therapy and reduce unfavorable treatment outcomes.
Our research focuses on addressing these research gaps to gain a deeper insight into the transmitting vector of M. perstans, regulatory effects of M. perstans infection on Tuberculosis disease pathogenesis, and BCG-vaccine-induced protection of children contact of active TB patients. In addition, it will facilitate the identification of reliable biomarkers of tuberculosis disease severity and treatment response.

Principal Investigators:
Prof. Richard Odame Phillips
Prof. Marc Jacobsen

2.Type 1 Diabetes in Ghana and Germany – Immune pathology of early versus late disease onset and influencing genetic and environmental factors

Type 1 Diabetes (T1D) is an autoimmune disease with continuously increasing incidence and worldwide distribution. The onset of T1D in Caucasians is predominantly in childhood between 5 and 15 years, however, T1D patients from Sub-Saharan Africa have a delayed disease onset. Differences in age of onset are largely associated with genetic factors; polymorphisms of class II HLA genes encoding DQ and DR account for familial aggregation of T1D. However, previous studies have demonstrated a low concordance rate of T1D susceptibility in monozygotic twins raising concerns about the influence of environmental factors including infections and vaccination. Nevertheless, the underlying immune pathology, potentially influential environmental factors, and the precise cause of T1D onset are poorly defined so far. Aberrant effector and regulatory T cell activity have been observed in T1D patients. An increased effector and a reduced regulatory T cell function led to infiltration of autoreactive CD4+ T cells around the pancreatic islet β cells, eventually causing their destruction and loss of function. To date, there is a lack of established evidence of T cell-related differences between early and late-onset T1D.
This project aims to investigate the role of differential immune pathology and external factors for early or late T1D onset in patient cohorts from Ghana and Germany. This will enable us to identify biomarkers of immune pathology and influential external factors contributing to differences in the early onset age in German T1D patients as well as to the delayed T1D onset in Ghana.

Principal Investigators:
Prof. Richard Odame Phillips,
PD Dr. Julia Seyfarth,
Prof. Marc Jacobsen

3.Non-Tuberculous Mycobacteria in pulmonary disease patients with presumptive tuberculosis from Ghana (NOTe-ME)

Overview

Summary of Project Aims: This proposed study is intended to contribute to the detection of NTM infections and to characterize the underlying immunological mechanisms of non-Tuberculous Mycobacteria (NTM) susceptibility. This study comprises two work packages (WPs). WP1 includes clinical characterization of presumptive tuberculosis patients and identification of NTM pulmonary diseases by sputum analyses. Further, NTM characterization by whole genome analyses for identification of diagnostic test targets will be performed and serum samples stored. WP2 includes comparison of immune response between NTM and M. tuberculosis complex caused disease and latent infection. Establishment of immune assay for support of   diagnosis will be aimed for.

Principal Investigators:

Prof. Richard Phillips

Prof. Marc Jacobsen

Dr. Ernest Adankwah

Funder: German Research Foundation (DFG)

Project period: November 1, 2022-December 31, 2026

Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana

Universitätsklinikum Düsseldorf, Germany

Agogo Presbyterian Hospital, Agogo, Ghana

Atebubu Municipal Hospital, Atebubu, Ghana

St Matthias Catholic Hospital, Yeji, Ghana

Sene District Hospital, Sene, Ghana

Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana

University Hospital, KNUST

Kumasi South Hospital

2022–2025   DFG-Project (JA 1479/14-1), Title: Non-Tuberculous Mycobacteria in pulmonary disease patients with presumptive tuberculosis from Ghana – The influence of environmental, pathogen, and host immune factors (NoTe_Me)

2018–2023   DFG-Project (JA 1479/9-1), Title: Mansonella perstans effects on BCG vaccine-induced protection against childhood tuberculosis (TB) as well as TB disease severity and recovery in Ghana and Cameroon (MaPTB)

2017–2020      Manchot Graduate School, Molecules of Infection (MOI)-3, Title: Biomarkers of T-cell immunity against multi-drug resistant Mycobacterium tuberculosis strains

2013–2017   DFG-Project (JA 1479/7-1), Title: Title: The effects of Mansonella perstans infections on concomitant mycobacterial infections and BCG vaccination efficacy in Ghana, Cameroon, and Benin (MaP2Co)

2013–2016   Manchot Graduate School, Molecules of Infection (MOI)-2, Title: Characterization of T-cell interactions with macrophages in an in vitro M. tuberculosis infection model. (MaP2Co)

2009–2016      German tuberculosis relief association (DAHW), Principal Investigator; miRNAs in latent M. tuberculosis infection

2009–2012   DFG-Project (JA 1479/3-1), Title: Immune polarization in childhood TB and helminth coinfection

2010–2011   EU Framework 7 Programme Theme 1: Health, Correlates of Protection, Title: Identification and development of vaccine candidates for Buruli Ulcer Disease (BuruliVac)

1. Jonathan Kofi Adjei, Wilfred Aniagyei, Ernest Adankwah, Julia Seyfarth, Ertan Mayatepek, Daniel Antwi Berko, Nancy Ackam, Max Efui Annani-Akollor, Samuel Asamoah Sakyi, Yaw Ampem Amoako, Dorcas Owusu, Marc Jacobsen, Richard Odame Phillips “Memory B-cells are enriched in the blood of patients with acute Buruli ulcer disease: a prospective observational study” BMC Infect Dis 23, 393 (2023) Jun. https://doi.org/10.1186/s12879-023-08370-1
2. Hubert Senanu Ahor, Rebecca Schulte, Ernest Adankwah, Jean De Dieu Harelimana, Difery Minadzi, Isaac Acheampong, Monika M. Vivekanandan, Wilfred Aniagyei, Augustine Yeboah, Joseph F. Arthur, Millicent Lamptey, Mohammed K. Abass, Francis Kumbel, Francis Osei-Yeboah, Amidu Gawusu, Linda Batsa Debrah, Dorcas O. Owusu, Alexander Debrah, Ertan Mayatepek, Julia Seyfarth, Richard O. Phillips, Marc Jacobsen “Monocyte pathology in human tuberculosis is due to plasma milieu changes and aberrant STAT signalling” Immunology May 2023;1–13. https://doi: 10.1111/imm.13659

3. Owusu DO, Adankwah E, Aniagyei W, Acheampong I, Minadzi D, Yeboah A, Arthur JF, Lamptey M, Vivekanandan M, Abass MK, Kumbel F, Yeboah FO, Gawusu A, Debrah LB, Debrah A, Mayatepek E, Seyfarth J, Phillips RO and Jacobsen M. “BCG vaccinated children with contact to tuberculosis patients show delayed conversion of Mycobacterium tuberculosis specific IFNγ release” 2023 Vaccines Apr 11;4 https://doi.org/10.3390/vaccines11040855

4. Monika M Vivekanandan, Ernest Adankwah, Wilfred Aniagyei, Isaac Acheampong, Augustine Yeboah, Joseph F Arthur, Millicent NK Lamptey, Mohammed K Abass, Amidu Gawusu, Francis Kumbel, Francis Osei-Yeboah, Linda Batsa Debrah, Dorcas O Owusu, Alexander Debrah, Ertan Mayatepek, Julia Seyfarth, Richard O Phillips, Marc Jacobsen “Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients”. Infection. Feb 2023 51(1):169-79

5. Aniagyei W, Adjei JK, Adankwah E, Seyfarth J, Mayatepek E, Berko DA, Sakyi SA, Debrah LB, Debrah AY, Hoerauf A, Owusu DO, Phillips RO and Jacobsen M. “Doxycycline Treatment of Mansonella perstans–Infected Individuals Affects Immune Cell Activation and Causes Long-term T-cell Polarization”. Clinical Infectious Diseases. Feb 2023 1;76(3):e1399-407

6. Monika M. Vivekanandan, Ernest Adankwah, Wilfred Aniagyei, Isaac Acheampong, Difery Minadzi, Augustine Yeboah, Joseph F. Arthur, Millicent Lamptey, Mohammed K. Abass, Francis Kumbel, Francis Osei-Yeboah, Amidu Gawusu, Linda Batsa Debrah, Dorcas O. Owusu, Alexander Debrah, Ertan Mayatepek, Julia Seyfarth, Richard O. Phillips and Marc Jacobsen “Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment”. Infection. Jan 2023 18:1-1. https://doi.org/10.1007/s15010-023-01977-1

7. Jacobsen M, Adjei JK, Aniagyei W, Adankwah E, Seyfarth J, Mayatepek E, Antwi-Berko D, Sakyi SA, Debrah AY, Debrah LB, Owusu DO, Richard O Phillips “T-cell responses against Mycobacterium ulcerans and Mycobacterium tuberculosis protein extracts identify children with Buruli ulcer disease”. Journal of the Pediatric Infectious Diseases Society. Dec 2022;11(12):575-7.

8. Harelimana JD, Ahor HS, Benner B, Hellmuth S, Adankwah E, Minadzi D, Aniagyei W, Abass MK, Debrah LB, Owusu DO, Mayatepek E. “Characterization of Interleukin 7 receptor regulation in monocytes and mediated antimycobacterial immune responses” European Journal of Immunology 2022 Sep 52(6): 90-91

9. Vivekanandan MM, Adankwah E, Aniagyei W, Acheampong I, Yeboah A, Arthur JF, Lamptey MN, Abass MK, Gawusu A, Kumbel F, Osei-Yeboah F. Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients. Infection. 2022 Jun 27

10. Aniagyei W, Adjei JK, Adankwah E, Seyfarth J, Mayatepek E, Berko DA, Sakyi SA, Debrah LB, Debrah AY, Hoerauf A, Owusu DO. Doxycycline treatment of Mansonella perstans infected individuals affects immune cell activation and causes long-term T-cell polarization. Clinical Infectious Diseases. 2022 Jun 3.

11. Adankwah, E., Arthur, R. A., Minadzi, D., Owusu, D. O., Phillips, R. O., & Jacobsen, M. (2021). Immune response against TB and non-tuberculous mycobacterial pulmonary disease. International Journal of Tuberculosis and Lung Disease, 25(3), 234–236. https://doi.org/10.5588/IJTLD.20.0678

12. Adankwah, E, Güler, A., Mayatepek, E., Phillips, R. O., Nausch, N., & Jacobsen, M. (2020). CD27 expression of T-cells discriminates IGRA-negative TB patients from healthy contacts in Ghana. Microbes and Infection, 22(1), 65–68. https://doi.org/10.1016/j.micinf.2019.07.003

13. Adankwah, Ernest, Harelimana, J. D. D., Minadzi, D., Aniagyei, W., Abass, M. K., Batsa Debrah, L., Owusu, D. O., Mayatepek, E., Phillips, R. O., & Jacobsen, M. (2021). Lower IL-7 Receptor Expression of Monocytes Impairs Antimycobacterial Effector Functions in Patients with Tuberculosis. Journal of Immunology (Baltimore, Md. : 1950), 206(10), 2430–2440. https://doi.org/10.4049/jimmunol.2001256

14. Adankwah E, Lundtoft C, Güler A, Franken KLMC, Ottenhoff THM, Mayatepek E, Owusu-Dabo E, Phillips RO, Nausch N, Jacobsen M. (2019). Two-Hit in vitro T-Cell stimulation detects mycobacterium tuberculosis infection in QuantiFERON negative tuberculosis patients and healthy contacts from Ghana. Frontiers in Immunology, 10(JUL), 1–12. https://doi.org/10.3389/fimmu.2019.01518

15. Adankwah, Ernest, Nausch, N., Minadzi, D., Abass, M. K., Franken, K. L. M. C. M. C., Ottenhoff, T. H. M. M., Mayatepek, E., Phillips, R. O., & Jacobsen, M. (2021). Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of The Journal of Infection, 82(2), 245–252. https://doi.org/10.1016/j.jinf.2020.11.032

16. Adankwah, Ernest, Seyfarth, J., Phillips, R., & Jacobsen, M. (2021). Aberrant cytokine milieu and signaling affect immune cell phenotypes and functions in tuberculosis pathology: What can we learn from this phenomenon for application to inflammatory syndromes? Cellular and Molecular Immunology, 18(April), 2062–2064. https://doi.org/10.1038/s41423-021-00695-8

17. Güler, A., Lopez Venegas, M., Adankwah, E., Mayatepek, E., Nausch, N., & Jacobsen, M. (2020). Suppressor of cytokine signalling 3 is crucial for interleukin-7 receptor re-expression after T-cell activation and interleukin-7 dependent proliferation. European Journal of Immunology, 50(2), 234–244. https://doi.org/10.1002/eji.201948302

18. Harelimana, J. D. D., Ahor, H. S., Benner, B., Hellmuth, S., Adankwah, E., Minadzi, D., Aniagyei, W., Lamptey, M. N. K., Arthur, J., Yeboah, A., Abass, M. K., Debrah, L. B., Owusu, D. O., Mayatepek, E., Seyfarth, J., Phillips, R. O., & Jacobsen, M. (2022). Cytokine-induced transient monocyte IL-7Ra expression and the serum milieu in European Journal of Immunology, 52(6), 958–969. https://doi.org/10.1002/eji.202149661

19. Harling, K., Adankwah, E., Güler, A., Afum-Adjei Awuah, A., Adu-Amoah, L., Mayatepek, E., Owusu-Dabo, E., Nausch, N., & Jacobsen, M. (2019). Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients. Cellular & Molecular Immunology, 16(3), 275–287. https://doi.org/10.1038/cmi.2018.5

20. Vivekanandan, M. M., Adankwah, E., Aniagyei, W., Acheampong, I., Yeboah, A., Arthur, J. F., Lamptey, M. N. K., Abass, M. K., Gawusu, A., Kumbel, F., Osei-Yeboah, F., Debrah, L. B., Owusu, D. O., Debrah, A., Mayatepek, E., Seyfarth, J., Phillips, R. O., & Jacobsen, M. (2022). Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients. Infection. https://doi.org/10.1007/s15010-022-01870-3

21. Lundtoft, C., Seyfarth, J., Oberstrass, S., Rosenbauer, J., Baechle, C., Roden, M., Holl, R. W., Mayatepek, E., Kummer, S., Meissner, T., & Jacobsen, M. (2019). Autoimmunity risk- and protection-associated IL7RA genetic variants differentially affect soluble and membrane IL-7Rα expression. Journal of Autoimmunity, 97, 40–47. https://doi.org/10.1016/j.jaut.2018.10.003

22. Seyfarth, J., Förtsch, K., Ahlert, H., Laws, H.-J., Karges, B., Deenen, R., Köhrer, K., Mayatepek, E., Meissner, T., & Jacobsen, M. (2017). Dominant TNFα and impaired IL-2 cytokine profiles of CD4(+) T cells from children with type-1 diabetes. Immunology and Cell Biology, 95(7), 630–639. https://doi.org/10.1038/icb.2017.24

23. Seyfarth, J., Lundtoft, C., Förtsch, K., Ahlert, H., Rosenbauer, J., Baechle, C., Roden, M., Holl, R. W., Mayatepek, E., Kummer, S., Meissner, T., & Jacobsen, M. (2018). Interleukin-7 receptor α-chain haplotypes differentially affect soluble IL-7 receptor and IL-7 serum concentrations in children with type 1 diabetes. Pediatric Diabetes, 19(5), 955–962. https://doi.org/10.1111/pedi.12665

24. Seyfarth, J., Mütze, N., Antony Cruz, J., Kummer, S., Reinauer, C., Mayatepek, E., Meissner, T., & Jacobsen, M. (2019). CD4(+) T-Cells With High Common γ Chain Expression and Disturbed Cytokine Production Are Enriched in Children With Type-1 Diabetes. Frontiers in Immunology, 10, 820. https://doi.org/10.3389/fimmu.2019.00820
25. Seyfarth, J., Sarfo-Kantanka, O., Rosenbauer, J., Phillips, R. O., & Jacobsen, M. (2019). Type-1 diabetes onset age and sex differences between Ghanaian and German urban populations. In Journal of diabetes (Vol. 11, Issue 12, pp. 1002–1004). https://doi.org/10.1111/1753-0407.12978

1. Richard Phillips –  Group Coordinator: KNUST Ghana
2. Ernest Adankwah – Post Doc, Lecturer-KNUST
3. Julia Seyfarth –   Collaborator, University of Duesseldorf
4. (Mrs.) Dorcas Owusu –  Post Doc, Lecturer-KNUST
5. Isaac Acheampong –  PhD candidate
6. Rejoice Arthur – PhD Candidate
7. Difery Minadzi –  MPhil, PhD candidate
8. Joseph Arthur – MPhil candidate
9. Augustine Yeboah – Senior Research Assistant 
10. Millicent Lamptey – Research Assistant,
11. Ms. Sumaya Mohayideen  – Research Assistant, 
12. Margaret Ampadu Sasu – Research Assistant, 
13. Linda Amoakoa – Research Assistant,