General Medicine & Global Health (GMGH) is a university-based research group at the Cape Heart Institute of the University of Cape Town and at the Department of Internal Medicine of the University Hospital Zurich/University of Zurich, established in 2019 by Associate Professor Friedrich Thienemann. Our mission is to improve global health through research, education and health services in partnership with institutions in our communities in Africa.
We study the convergence of non-communicable and infectious diseases in order to better understand the interaction of both with the aim to optimise current therapies to improve treatment outcomes. Our focus is on the world's biggest killers tuberculosis (TB), HIV/AIDS, cardiovascular and lung diseases, and diabetes – all major causes of morbidity, mortality, poverty, and inequality in low- and middle-income countries.
In order to achieve the above, we aim to strengthen local research capacity through training, collaboration, networking, good governance, effective leadership, support and mentoring with the goal to produce research excellence and to develop the next generation of global leaders in health. Our team develops regular health education programs to uplift our communities to live healthier lives.
The GMGH research lab is based at the Institute of Infectious Disease and Molecular Medicine (IDM) and is led by Professor Reto Guler. The Guler lab aims to identify targets for pathogen and host-directed drug therapy for TB; this includes the identification of statins and host non-coding RNAs as host-directed drug therapy for TB and the role of epigenetics in host immunity to TB. Further research includes investigating Minor Groove Binders as novel anti-mycobacterial agents and non-ionic surfactant vesicles as a drug delivery system for TB.
Protocol title: Preventing TB relapse and chronic lung disease: A proof-of-concept, double-blinded, randomized, placebo-controlled trial to evaluate the safety and efficacy of atorvastatin to reduce inflammation after TB treatment completion in HIV-infected and HIV-uninfected adults measured by FDG-PET/CT.
The primary objective is to compare persistent lung inflammation measured by total lung glycolysis on FDG-PET/CT after 12 weeks of 40 mg atorvastatin and placebo. If successful this trial will have proven that statins as Host Directed Therapy can be safe and effective adjunctive therapy to TB treatment in general. Further efficacy trials can be undertaken to translate the results into reduced TB relapse rates and reduced post-TB chronic lung disease. ClinicalTrials.gov Identifier: NCT04147286
Visit the StatinTB website.
PredictTB is a five-year project financed by a variety of international funders and implemented by American, African, Asian and European partners, that aims to shorten the treatment times of TB in drug-sensitive patients through individualized therapy. Coordinated by Prof. Clifton Barry from the US National Institutes of Health and Prof. Gerhard Walzl from Stellenbosch University in South Africa. The consortium implemented a prospective, randomized, no inferiority phase 2b clinical trial, enrolling and following-up 620 patients with drug sensitive pulmonary TB in five collaborating sites in Cape Town, South Africa and four sites in Henan Province, China. Over the five years, the project team will evaluate a set of criteria to reduce TB treatment times using data from scans, assays and cultures to evaluate inflammation and lung pathology, to test for the sustained presence of bacteria and to determine which patients are eligible for shortened treatment. In a sub-study, we investigate the potential of lung MRI to better understand complex lung lesions in TB (virtual biopsy study). ClinicalTrials.gov Identifier: NCT02821832
Visit the PredictTB website.
Protocol title: Cardiac assessment using cardiac MRI to better understand long-term morbidity and mortality after successful tuberculosis treatment (Cardiac Imaging After TB, CIA-TB)
The main focus of national TB control programs has been the DOTS strategy – directly observed treatment, short-course – which was an integral part of the End TB strategy by the World Health Organization. "DOTS quickly makes the infectious cases non-infectious and breaks the cycle of transmission". To achieve this, DOTS ensures that every TB patient achieves treatment success within a six-month course of TB treatment; at the end of this treatment, patients are currently discharged from their TB clinics as "cured" or "treatment completed". But TB is a lifelong disease: long-term morbidity and mortality after successful TB treatment are increasingly recognised with associated long-term functional impairment. To date, most research has focused on pulmonary function and data on cardiovascular long-term sequelae following TB treatment is lacking. In CAI-TB we investigate cardiac inflammation, fibrosis and function using cardiovascular magnetic resonance imaging (CMR) and coronary CT (CCT) after TB treatment.
From a global perspective, cardiovascular disease in HIV may result from cardiac involvement upon presentation of opportunistic infections in the presence of advanced immunosuppression, be a consequence of HIV-induced immune activation or derive from antiretroviral therapy-associated dyslipidemia and insulin resistance. HIV-associated cardiomyopathy and HIV-associated pulmonary hypertension are the most common cardiac manifestations in HIV. This study is investigating cardiovascular disease in a healthy HIV-infected cohort in Cape Town using Echocardiography and cardiac biomarkers.
HREC REF: 337/2013
Epidemiology, etiology, management and outcome data for various forms of pulmonary hypertension (PH) in Africa are scarce. A prospective, multinational cohort registry of 220 consecutive patients (97% of African descent) from nine specialist centers in four African countries. The antecedents, characteristics and management of newly diagnosed PH plus 6-month survival were studied. We are currently investigating the contribution of HIV to the burden of PH in Africa and are in planning of PAPUCO II. Co-Principal investigators are Prof. Karen Sliwa-Hahnle and Prof. Friedrich Thienemann.
HREC REF 337/2013
Protocol title: Targeting non-coding RNAs as host-directed drug therapy for tuberculosis
Tuberculosis (TB) kills more than one million people each year globally. Therefore, there is an urgent need to develop new, alternative drug treatments. In this study, we aim to identify host factors and pathways that are subverted by Mycobacterium tuberculosis (Mtb) to increase its persistence and survival within macrophages. Using genome-wide transcriptome analysis in Mtb-infected macrophages using the powerful CAGE technology, we have previously identified differentially expressed ncRNAs (miRNAs and lncRNAs) in M1/M2 polarized macrophages. Our identified ncRNAs are likely to represent novel targets by Mtb to evade host protective killing functions that permit the bacteria to survive within macrophages. Our aim is to functionally validate these differentially expressed ncRNAs in Mtb-infected human PBMCs, using chemically engineered antisense oligonucleotides (gapmers). Our objective is to validate our identified ncRNAs and associated pathways in human PBMCs infected in-vitro with Mtb. Differences in pathogen burden, phagosomal maturation, autophagy, host cytokine responses and killing effector functions will investigate the involvement of the selected ncRNAs in possible host protective or detrimental response against TB. The most promising ncRNAs will be further validated for their target genes by computational approaches and other methods, including dual-luciferase reporter assay and RNA immunoprecipitation. The expected outcomes are to identify new host drug targets to combat TB. Such results are expected to have a critical positive translational impact. As such, targeting these new host ncRNAs as a therapy to efficiently eliminate Mtb is less likely to induce multi-drug resistance than conventional antibiotic treatments. This study is a collaboration with colleagues at the National Institutes of Health (NIH).
Chris Barnard Building
UCT Faculty of Health Sciences
Cape Town, South Africa