HIV-related TB in Malawi: clinical trials on diagnosis, treatment and outcomes
Malawi-Liverpool-Wellcome Trust and the College of Medicine in Blantyre, Malawi host a number of School studies tackling the complex interactions of tuberculosis and HIV. TB Centre investigators working here include Liz Corbett, who is based in Blantyre, Rashida Ferrand from her base in Harare, Steve Lawn, Katherine Fielding, Clare Flach, Rebecca Harris, Ankur Gupta-Wright, Augustine Choko and Marriott Nliwasa.
Projects include four major randomised controlled trials of diagnostic interventions, which are funded by the UK Medical Research Council, Department for International Development and Wellcome Trust Global Clinical Trials Scheme, as well as the US National Institutes of Health and Helse Nord:
- HitTB – a cluster randomised controlled trial of community-level HIV self-testing with a TB incidence outcome
- CHEPETSA – a cluster randomised controlled trial comparing microscopy with molecular TB diagnosis using Xpert MTB/RIF in newly diagnosed people living with HIV
- STAMP – an individually randomised controlled trial comparing sputum with sputum plus urinary TB diagnostics in HIV positive in-patients (see page 2)
- PACTS -a household randomised controlled trial of patient-delivered TB contact screening and isoniazid preventive therapy eligibility assessment.
The site has a Biosafety Level 2 TB culture lab, which is being upgraded to Level 3 in 2016. It also undertakes comprehensive extended monitoring and evaluation of all registering TB patients in Blantyre City, which currently has 2,900 TB cases each year among a total population of 676,000. A recently developed online app (“ePAL” – the electronic Participant Locator) enables accurate collection of place of residence data, and integrates these into routine registration for identification of hotspots and assisting follow up City-wide. The centre also has a strong social science theme, for example studying masculinity as a barrier to seeking TB treatment and medical care.
TB programmes in Zambia
Zambart is a major research collaboration between the School and the University
of Zambia. Current Zambart studies include a TB vaccine trial with Aeras and GlaxoSmithKline, diagnostics studies of Quantiferon plus, a TB and meningitis study, and a study of the relationship between TB, HIV and diabetes, as well as HPTN071/ PopART which looks at TB in the context of universal test and treat for HIV.
Multi-drug resistant TB and interaction with Diabetes Mellitus in Peru
In addition to ongoing diagnostic, epidemiological and genomic studies largely focussed on multi-drug resistant TB in Peru, Centre researchers are working with partners at Universidad Peruana Cayetano Heredia (UPCH) in Lima on the EU-funded TANDEM consortium project.
The association between TB and diabetes mellitus is being investigated using established laboratory and community-based research platforms here and at partner sites in Indonesia, Romania and South Africa. Both the School and UPCH are core partners in the global TB genomics programme known as CRyPTIC, theComprehensive Resistance Prediction for Tuberculosis International Consortium, led by the University of Oxford and funded by the Bill & Melinda Gates Foundation.
HIV-related TB co-infection in Brazil
A two-year clinical trial with individual randomisation led by epidemiologists from the Oswald Cruz Foundation in Recife, Brazil and the School started in March 2014. The objective is to estimate the incremental cost-effectiveness of a protocol for screening and diagnosis of TB in HIV patients. The study includes screening by clinical algorithm, followed by diagnosis with gene Xpert MTB/RIF, sputum smear microscopy and chest X-ray.
Malawi Epidemiology and Intervention Research
Unit The Karonga Prevention Study, now part of the Malawi Epidemiology and Intervention Research Unit, is using traditional epidemiology and whole genome sequencing on long-term population-based data to find out how and where TB transmission occurs, whether some strains are more transmissible or virulent than others, and how TB interacts with HIV.