IMMUNOLOGY & INFECTIONS GROUP

Local Investigators:

Prof. Richard O. Phillips
Dr. Linda Batsa Debrah

Phone: +233 209140451
E-Mail:  phillips@kccr.de

International Collaborators:

Prof. Marc Jacobsen
Dr. Julia Seyfarth

Post-Doctoral Staff:

Dr.Dorcas Ohui Owusu
Dr. Ernest Adankwah

Doctoral Students

Isaac Acheampong
Hubert Senanu Ahor

Masters Students:

Difery Minadzi
Monika Mira Vivekanandan
Wilfred Aniagyei
Joseph Fosu Arthur
Augustine Yeboah

Research Staff

Millicent Lamptey
Sumaya Mohayideen

Technical Staff (field):

Dr. Osei Sarfo-Kantanka, MBChB (KATH)
Shadrack Osei Asibey (KATH),
Agnes Owusu Boateng(KATH),

Research Projects:

Title:  Mansonella perstans effects on BCG vaccine-induced protection against childhood tuberculosis (TB) as well as TB disease severity and recovery in Ghana’

Mansonella perstans (M. perstans) is one of the most prevalent human parasites in sub-Saharan Africa with a predicted more than 100 million estimated infected individuals in endemic regions and we have recently reported that M. perstans is highly prevalent in the middle belt of Ghana. M. perstans is a vector-borne parasite transmitted by female flies (biting midges) of the genus Culicoides. M. perstans filariasis is predominantly found in rural populations and high prevalence of infections in children and adolescents in some villages in Ghana have been found. Children from these infected/affected communities have a concomitant high risk to get infected by mycobacteria, namely M. ulcerans and M. tuberculosis.

Mycobacterial diseases are a major public health problem in Africa and particularly children are susceptible to Tuberculosis and Buruli ulcer disease (BUD). Despite major efforts to eradicate these diseases, Tuberculosis is still highly prevalent. One major obstacle for disease eradication is the lack of a protective vaccine. The only available Tuberculosis vaccine M. bovis BCG only partially protects children from developing severe forms and extrapulmonary manifestations of Tuberculosis. Since BCG vaccination is widely used in sub-Saharan Africa – including Ghana – one aim is to target environmental factors that influence protective immunity (e.g., by treatment of co-infections) to improve efficacy of BCG vaccination. An initial study concerning the influence of M. perstans infections on BCG-vaccination in children detects specific changes of induced T-cell immunity when mothers were infected with M. perstans. In addition, susceptibility against Tuberculosis as well as disease course and recovery may be impeded by co-infections.

Recovery from TB requires long-term chemotherapy and shortening of treatment is a crucial factor for disease eradication. The vast majority of pulmonary TB patients present with M. tuberculosis positive sputum smear samples prior to therapy, and time to sputum conversion is a useful tool to monitor treatment efficacy. Environmental factors – including co-infections– have been shown to affect M. tuberculosis sputum burden and time to conversion. We will thus compare time to sputum conversion and disease severity between TB patients with and without M. perstans.

Primary Objective

The overall aim of this project is to investigate a possible role of M. perstans infection on TB disease manifestation and recovery time under treatment.

Secondary Objectives

To characterize disease severity and time to recovery in TB patients with and without M.
perstans co-infection

To determine the influence of M. perstans infection on risk against the development of
TB in BCG vaccinated children/adolescents

To validate candidate biomarker for TB disease severity and recovery under treatment
To validate candidate biomarker for prediction of BCG vaccine induced immune
protection against development of TB.

Expected Impact

Both the lack of a protective vaccine and long-term chemotherapy prerequisite for TB treatment are major problems for TB elimination. Clinically relevant effects on TB disease progression in BCG vaccinated children and adolescents has so far not been investigated in comprehensive studies. This study will help us to determine if M. perstans infection influences disease severity and recovery in tuberculosis patients and whether infection with M. perstans influences BCG-induced protection against disease progression in vaccinated children.

Title: Type 1 diabetes (T1D) 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. T1D onset is frequently diagnosed during childhood -predominantly between 5 and 15 years in Caucasians- whereas late onset at adolescence or adulthood is less common. In contrast, T1D patients from Sub-Saharan Africa are characterized by largely delayed disease onset of approximately 10 years as demonstrated by previous studies including our own from Ghana. External (e.g., infections, vaccination) as well as genetic factors contribute to differential onset, but the underlying immune pathology and potentially influential environmental factors are poorly defined so far.

Primary Objective

The main aim of this study is to identify the immune pathology of early versus late onset T1D and the influencing genetic and environmental factors among T1D patients in Ghana and Germany

Secondary Objectives

1.  To identify clinical, biochemical and genetic characterization of T1D patients and controls in Ghana and Germany.
2. To compare the immune phenotypic and serum parameters between patients with early, average and late onset of T1D as well as age-matched healthy controls for identification of biomarkers
3. To identify the immune genetic susceptibility and external factors that influence T1D manifestation and contribute to differential T1D onset between Ghana and Germany
4. To identify the immune pathology between T1D patients with different onset age from Germany and Ghana can reveal key influential immune mechanisms
5. To identify serum biomarkers (e.g. from Interleukin-7 promoting effector/regulatory T-cell pathways) that predict T1D onset and disease course in Ghanaian and German cohorts 

Expected Impact

Investigation of immune system key factors important for the time of T1D onset will increase our understanding of immune mechanisms in T1DM and potential immune modulating genetic and environmental factors. This will help to identify candidate immune biomarkers for immune modulatory treatment trials in order to postpone T1D onset. The strength of our project lies in the unique, well-developed T1D cohorts on two continents with contrasting environmental conditions, a sound preparation by close collaboration and documented publication record and strong cooperation partners in Ghana and within the German Center for Diabetes Research (DZD).

Adankwah, E., R. A. Arthur, D. Minadzi, D. O. Owusu, R. O. Phillips, and M. Jacobsen. 2021. “Immune Response against TB and Non-Tuberculous Mycobacterial Pulmonary Disease.” International Journal of Tuberculosis and Lung Disease 25 (3): 234–36. https://doi.org/10.5588/IJTLD.20.0678.

Adankwah, E, A Güler, E Mayatepek, R O Phillips, N Nausch, and M Jacobsen. 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.

Adankwah, E, C Lundtoft, A Güler, K.L.M.C. Franken, T H M Ottenhoff, E Mayatepek, E Owusu-Dabo, R O Phillips, N Nausch, and M Jacobsen. 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). https://doi.org/10.3389/fimmu.2019.01518.

Adankwah, Ernest, Jean De Dieu Harelimana, Difery Minadzi, Wilfred Aniagyei, Mohammed K Abass, Linda Batsa Debrah, Dorcas O Owusu, Ertan Mayatepek, Richard O Phillips, and Marc Jacobsen. 2021. “Lower IL-7 Receptor Expression of Monocytes Impairs Antimycobacterial Effector  Functions in Patients with Tuberculosis.” Journal of Immunology (Baltimore, Md. : 1950) 206 (10): 2430–40. https://doi.org/10.4049/jimmunol.2001256.

Adankwah, Ernest, Norman Nausch, Difery Minadzi, Mohammed K Abass, Kees L M C Franken, Tom H M Ottenhoff, Ertan Mayatepek, Richard O Phillips, and Marc Jacobsen. 2021. “Interleukin-6 and Mycobacterium Tuberculosis Dormancy Antigens Improve Diagnosis of  Tuberculosis.” The Journal of Infection 82 (2): 245–52. https://doi.org/10.1016/j.jinf.2020.11.032.

Adankwah, Ernest, Julia Seyfarth, Richard Phillips, and Marc Jacobsen. 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, no. April. https://doi.org/10.1038/s41423-021-00695-8.

Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

Else Kröner-Fresenius-Stiftung (EKF)

Doctor of Philosophy

Dr. Ernest Adankwah (2020): “Pathognomonic effects of human tuberculosis on host immune response in an endemic population: impact on T-cell functions and M. tuberculosis infection diagnosis”

Dr. Dorcas Ohui Owusu (2019): “Hepatitis C virus in Ghana: risk factors, genotypes and the role of T cells in spontaneous recovery”

Dr Daniel Antwi Berko (2017): “Analysis of the immune-modulatory effects of Mansonella perstans infection associated with concomitant Mycobacterium ulcerans disease and Tuberculosis infection in Ghana.”