Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

Prof. Dorothy Yeboah-
Manu

South Africa

EDCTP portfolio: Senior Fellowships

Professor Dorothy Yeboah-Manu is assessing how diabetes affects TB disease and responses to treatment.

Understanding the impact of diabetes on TB

Professor Yeboah-Manu has developed a wide-ranging programme of research on mycobacterial infections affecting Ghana and other African countries. These include landmark studies on a TB-causing bacterium, Mycobacterium africanum, restricted to parts of West Africa. Professor Yeboah-Manu was awarded the Royal Society’s Africa Prize in 2018.

In her EDCTP Senior Fellowship, Professor Yeboah-Manu is generating additional information on the interplay between diabetes and TB. She is recruiting patients newly diagnosed with TB, who will undergo testing on their glycaemic control; patients will be categorised as either normal, having impaired glucose control or with full-blown diabetes.

Clinical and demographic data will also be collected, and patients will be tested again after 2, 5 and 6 months of treatment. Professor Yeboah-Manu will also examine interactions between anti-TB and diabetes drugs, monitor TB drug susceptibility, and culture and genotype M. tuberculosis isolates.

The challenge

Professor Wendy Burgers has developed an extensive programme of research on the impact of HIV infection on the immune system. As well as HIV vaccine development, her work also has important implications for HIV–TB co-infections.

TB is increasingly seen as encompassing a spectrum from quiescent infection through to active disease. It would be highly advantageous to know who was at risk of progressing to active disease, but development of biomarkers to identify such individuals is held back by a lack of understanding of the drivers of disease. As HIV infection tilts the scales in favour of active disease, studying HIV–TB co-infections may reveal critical disruptions that drive TB disease. 

In her EDCTP Senior Fellowship, Professor Burgers is focusing on a class of immune cells called Th22 cells, which produce the cytokine interleukin-22 (IL-22). The numbers of Th22 cells are greatly reduced in HIV infections, and there is some evidence that IL-22 plays a protective role in respiratory infections.

To shed more light on their possible role in TB, Professor Burgers is carrying out a detailed investigation of Th22 cell responses during TB disease and treatment, after HIV infection and during antiretroviral therapy. Th22 cell responses in these different disease states will be compared with those of other immune cell populations potentially involved in TB disease.

The project

Professor Yeboah-Manu’s Senior Fellowship project will yield important information on how diabetes affects TB disease and its treatment. The findings will have important implications for the management of TB patients. With diabetes becoming increasingly common in sub-Saharan Africa – three-quarters of diabetes patients live in low-income countries – the results are very timely.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Professor Yeboah-Manu has developed a wide-ranging programme of research on mycobacterial infections affecting Ghana and other African countries. These include landmark studies on a TB-causing bacterium, Mycobacterium africanum, restricted to parts of West Africa. Professor Yeboah-Manu was awarded the Royal Society’s Africa Prize in 2018.

In her EDCTP Senior Fellowship, Professor Yeboah-Manu is generating additional information on the interplay between diabetes and TB. She is recruiting patients newly diagnosed with TB, who will undergo testing on their glycaemic control; patients will be categorised as either normal, having impaired glucose control or with full-blown diabetes.

Clinical and demographic data will also be collected, and patients will be tested again after 2, 5 and 6 months of treatment. Professor Yeboah-Manu will also examine interactions between anti-TB and diabetes drugs, monitor TB drug susceptibility, and culture and genotype M. tuberculosis isolates.

Professor Wendy Burgers has developed an extensive programme of research on the impact of HIV infection on the immune system. As well as HIV vaccine development, her work also has important implications for HIV–TB co-infections.

TB is increasingly seen as encompassing a spectrum from quiescent infection through to active disease. It would be highly advantageous to know who was at risk of progressing to active disease, but development of biomarkers to identify such individuals is held back by a lack of understanding of the drivers of disease. As HIV infection tilts the scales in favour of active disease, studying HIV–TB co-infections may reveal critical disruptions that drive TB disease. 

In her EDCTP Senior Fellowship, Professor Burgers is focusing on a class of immune cells called Th22 cells, which produce the cytokine interleukin-22 (IL-22). The numbers of Th22 cells are greatly reduced in HIV infections, and there is some evidence that IL-22 plays a protective role in respiratory infections.

To shed more light on their possible role in TB, Professor Burgers is carrying out a detailed investigation of Th22 cell responses during TB disease and treatment, after HIV infection and during antiretroviral therapy. Th22 cell responses in these different disease states will be compared with those of other immune cell populations potentially involved in TB disease.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Professor Yeboah-Manu’s Senior Fellowship project will yield important information on how diabetes affects TB disease and its treatment. The findings will have important implications for the management of TB patients. With diabetes becoming increasingly common in sub-Saharan Africa – three-quarters of diabetes patients live in low-income countries – the results are very timely.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M