Non-Tuberculous Mycobacteria in pulmonary disease patients with presumptive tuberculosis from Ghana - The influence of environmental, pathogen, and host immune factors

• Applicant: Professor Dr. Marc Jacobsen
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 501664089

Pulmonary disease caused by Non-Tuberculous Mycobacteria (NTM) is frequently diagnosed in presumptive tuberculosis (TB) patients worldwide but the mechanisms underlying increased susceptibility to NTM remain elusive. Own preliminary studies found high prevalence of NTM pulmonary disease in different regions of Ghana and rapid-growing Mycobacterium (M.) fortuitum was the most frequent species identified. This study aims to investigate host and pathogen factors as well as the influence of environment on NTM disease pathology. Due to the reported high prevalence of M. fortuitum, a special focus will be on genetic characterization of clinical isolates and development of immune-based assays for detection of M. fortuitum infection and routes of transmission.This study is performed in tight collaboration between partners from Kumasi/Ghana (KCCR) and Düsseldorf (UKD) and includes three work packages (WPs). WP1 will identify and characterize NTM infected individuals (approx. n=100) within presumptive pulmonary TB patients (n=800) recruited in different hospitals from the Ashanti region of Ghana. Detailed anamnesis and clinical characterization will be performed to identify predisposing factors and to assess NTM disease manifestation and severity. As controls, age and sex matched i) TB patients, ii) asymptomatic NTM patients’ household contacts, iii) community controls will be recruited. Repeated sputum samples prior to and under treatment will be retrieved from all patients and peripheral blood will be taken from all study participants. WP2 will perform sputum and immune-based assays for detection of NTM infection and WP3 will characterize immunopathology underlying NTM pulmonary disease. Whole genome sequencing of M. fortuitum strains from patients will determine possible clonal dissemination (as shown for related M. abscessus) and identify specific PCR targets for established culture-independent detection of M. fortuitum in sputum samples. The immunological assays performed are well established and have been applied to characterize immunopathology of tuberculosis. These include a T-cell-based method for discrimination of infection with different mycobacterial species and comprehensive phenotyping by multi-color flow cytometry to identify key factors involved in immune protection or disease progression in NTM infection. Functional implications of identified key factors will be characterized using lentiviral-based immune modulation and in vitro anti-mycobacterial kill assays. This study will contribute to our understanding of influential factors and immunopathology in NTM pulmonary disease and the special role of neglected M. fortuitum in Sub-Saharan African countries. Clinical and basic science expertise in mycobacterial diseases is well provided at both partner institutes and the long-standing cooperation is now strengthened by a cooperation agreement between the universities.

• DFG Programme: Research Grants
• International Connection: Ghana
• Cooperation Partner: Ernest Adankwah, Ph.D.
• International Co-Applicant: Professor Dr. Richard Odame Phillips