Clinical And Biomedical Tuberculosis Research Unit

Interim Unit Manager : Ms Thuli Mthiyane
E-mail: Thuli.Mthiyane@mrc.ac.za

Mandate of the unit
This unit conducts research directed at effective TB control, which spans the following five key research priorities:

• Expertise in conducting clinical trials in new drug development with the aim of simplifying TB treatment;
• Interventions directed at TB and HIV dual epidemics aimed at reducing mortality from dual infection;
• Development of new, rapid, effective, safe and fieldfriendly diagnostics;
• Research translation directed at integrating clinical research into the provincial programme; and
• A provincial surveillance programme in response to a newly unfolding extreme drug- resistant TB outbreak.

Over the past year the unit has aimed at establishing an African network of TB Researchers in addressing the strategically identifed research areas. The successful outcome of 3 applications to the European and Development Countries Clinical Trials Partnership (EDCTP) has ensured that this will take place over the next five years and provides an opportunity to contribute meaningfully to the global control strategy (WHO) which identifies the need for interventions aimed both at TB and at HIV/AIDS simultaneously. The use of HAART for the control of HIV/AIDS is seen as critical to TB control through the biological effect of interrupting HIV transmission and potentially decreasing the incidence of TB.  In the light of this, several research institutions and control programmes in Sub Saharan Africa together with the University of London and WHO have created a Consortium to provide the evidence for "optimizing and improving the management of TB in high HIV prevalent settings". We envisage through this grouping to streamline the research questions towards providing an appropriate approach to maximizing skills and institutional capacities in developing the much needed evidence to optimize care for TB and HIV co-infected patients. We also see in the group opportunities to further develop and strengthen research capacity through the admixture of skills and institutional networks and through the effect of considerable experience of WHO/TDR in developing research capability in disease endemic settings. The details of the projects under this new endeavor are outlined under the "new projects" section.

 We play a growing role in new drug development for TB treatment with the commencement of 2 clinical trials (Phase II and III) investigating  the quinolone group of drugs in a treatment shortening regimen for TB. These trials are sponsored by the European Commission and WHO TDR. Efforts have long been pursued to reduce the duration of treatment of TB with the aim of obtaining rapid sterilisation of lesions and avoid patients' failure to comply properly with long-lasting treatments. In this effort to shorten treatment of TB, a giant step was realised in the late 70s-early 80s with the (re)discovery of the effect of adjoining pyrazinamide in the intensive phase of treatment and the use of very efficient drugs like rifampicine, allowing to reduce treatment of TB from 12-18 months to 6-8 months. In an attempt to reduce further the duration of treatment, several drugs have been proposed, including the quinolones (Gillespie 1998). Fluoroquinolones have been shown to have bactericidal activity in vitro against M. tuberculosis (Garcia-Rodrigues 1993, Davies 1987, Yew 1994), which has been confirmed in animal studies models. As this class of drugs is well tolerated over extended periods, they have been proposed in the treatment of tuberculosis (Gillespie 1998). They are rapidly absorbed orally and have high availability after oral administration. They are highly concentrated in respiratory tract tissues, secretions and inside macrophages. The present research agenda seeks to assess the bacteriological and clinical efficacy of a quinolone-containing treatment shortening regimens for pulmonary TB in 2 current trials and one new trial. These 3 projects are described below (2 in the current project section and one under new projects).

The results of a dose-ranging EBA and pharmacokinetics study of the long-acting rifampicin, rifapentine will be submitted for publication soon.  The World Health Organization has acknowledged the EBA studies as important in clinical development of new drugs and it has been recommended to precede full-scale phase III trials, which are costly and could take at least 3 years to complete. This unit has been recognised internationally as a prominent centre for EBA studies, mainly because of continuous research, as reflected in various publications in this field since 1993. 

Since its inception in 1995, the unit has a relatively small operating budget, the research activity, collaborations and outputs have grown considerably. It remains strongly linked to the Nelson R Mandela School of Medicine and the Kwa-Zulu Natal Provincial Department of Health. The unit is recognized internationally as a center of excellence for the design and conduct of clinical trials.