EDCTP portfolio: Senior Fellowships
index
Dr Mareli Claassens is investigating how best to identify cases of drug-resistant TB in Namibia.
Searching out drug-resistant TB
More than 500,000 new cases of multidrug-resistant (MDR) TB occur each year, around 10% of which are extremely drug resistant (XDR) TB. Namibia is classified as a high TB burden country, with 11,000 new cases a year; 3.9% of new cases and 8.7% of previously treated cases are MDR-TB.
It is vital that cases of drug-resistant TB are identified in a timely fashion, so that patients can be started on the most appropriate treatment but also to limit the spread of drug-resistant strains. This requires an active case-finding strategy – going out into the community to identify cases rather than waiting them to appear at health facilities.
The challenge
In her Senior Fellowship, Dr Mareli Claassens aims to develop a clearer picture of drug-resistant TB in Namibia, to investigate the feasibility of targeted case finding to improve TB control, and to develop a TB transmission model to explore the potential impact of case-finding interventions.
Her work will focus on two areas of Namibia thought to be hotspots for transmission of drug-resistant TB, including disadvantaged ethnic minority populations. A wide range of clinical, epidemiological, laboratory and social networking data will be collected to characterise drug-resistant TB cases in these regions and how they are being spread. Through a collaboration with Research Center Borstel in Germany, this work will take advantage of the power of whole genome sequencing to reveal pathways of transmission of drug-resistant TB strains.
These results, plus a systematic review of the literature, will be used to identify a potential strategy for active case finding. Interventions will be tested in a feasibility study focusing on transmission hotspots, households and hospitals.
Data from the drug-resistant TB mapping exercise and from Namibia’s national TB programme will feed into a model of drug-resistant TB transmission, which will be used to explore the potential impact of case-finding interventions. This strand of work will include a health economic component to provide data on the likely cost-effectiveness of targeted case-finding interventions.
The project
Dr Claassens’ research will generate a deeper understanding of drug-resistant TB in Namibia and establish the feasibility and likely costs of locally appropriate case-finding interventions. The findings will contribute to more effective control of drug-resistant TB in Namibia. In addition, it will build local capacity in whole-genome sequencing and further develop Dr Claassens’ research career, facilitating her addition to the faculty at the University of Namibia.
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
More than 500,000 new cases of multidrug-resistant (MDR) TB occur each year, around 10% of which are extremely drug resistant (XDR) TB. Namibia is classified as a high TB burden country, with 11,000 new cases a year; 3.9% of new cases and 8.7% of previously treated cases are MDR-TB.
It is vital that cases of drug-resistant TB are identified in a timely fashion, so that patients can be started on the most appropriate treatment but also to limit the spread of drug-resistant strains. This requires an active case-finding strategy – going out into the community to identify cases rather than waiting them to appear at health facilities.
In her Senior Fellowship, Dr Mareli Claassens aims to develop a clearer picture of drug-resistant TB in Namibia, to investigate the feasibility of targeted case finding to improve TB control, and to develop a TB transmission model to explore the potential impact of case-finding interventions.
Her work will focus on two areas of Namibia thought to be hotspots for transmission of drug-resistant TB, including disadvantaged ethnic minority populations. A wide range of clinical, epidemiological, laboratory and social networking data will be collected to characterise drug-resistant TB cases in these regions and how they are being spread. Through a collaboration with Research Center Borstel in Germany, this work will take advantage of the power of whole genome sequencing to reveal pathways of transmission of drug-resistant TB strains.
These results, plus a systematic review of the literature, will be used to identify a potential strategy for active case finding. Interventions will be tested in a feasibility study focusing on transmission hotspots, households and hospitals.
Data from the drug-resistant TB mapping exercise and from Namibia’s national TB programme will feed into a model of drug-resistant TB transmission, which will be used to explore the potential impact of case-finding interventions. This strand of work will include a health economic component to provide data on the likely cost-effectiveness of targeted case-finding interventions.
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.
Dr Claassens’ research will generate a deeper understanding of drug-resistant TB in Namibia and establish the feasibility and likely costs of locally appropriate case-finding interventions. The findings will contribute to more effective control of drug-resistant TB in Namibia. In addition, it will build local capacity in whole-genome sequencing and further develop Dr Claassens’ research career, facilitating her addition to the faculty at the University of Namibia.
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