Publications

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

EDCTP portfolio: Emerging diseases

The AdjustEBOVGP-Dx project is developing and testing a rapid point-of-care diagnostic to detect Ebola virus and to distinguish Ebola from a close relative, Marburg virus.

Rapid detection of Ebola infection

Ebola and Marburg viruses cause severe viral haemorrhagic fevers with a high fatality rate. However, during the early stages of infection, symptoms are similar to other tropical infectious diseases.

Current diagnostic tools for Ebola and its relatives are costly, require laboratory facilities, and are too slow to support effective clinical care and disease control. Point-of-care tests have recently been developed for Ebola but these do not detect its relatives such as Marburg virus.

The challenge

Monoclonal antibodies have been developed that recognise a structure, known as filovirus glycoprotein (GP), which is common to a range of viruses in the Ebola family. However, these antibodies have not been able to detect GP in samples from infected patients, probably because GP is biochemically modified after it is made.

The AdjustEBOVGP-Dx project is exploring whether a range of biochemical treatments can strip away these modifications, enabling monoclonal antibodies to access GP. It is developing a prototype point-of-care diagnostic that will combine this biochemical pretreatment with monoclonal antibody-based detection of GP.

The prototype will then be tested in the ongoing Ebola outbreak in the Democratic Republic of the Congo.

The project

The AdjustEBOVGP-Dx project could provide a new tool to support the early detection of and rapid response to Ebola virus infections. Importantly, it would also be the first diagnostic able to identify infections with both Ebola and Marburg virus, another lethal viral infection with epidemic potential.

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

Ebola and Marburg viruses cause severe viral haemorrhagic fevers with a high fatality rate. However, during the early stages of infection, symptoms are similar to other tropical infectious diseases.

Current diagnostic tools for Ebola and its relatives are costly, require laboratory facilities, and are too slow to support effective clinical care and disease control. Point-of-care tests have recently been developed for Ebola but these do not detect its relatives such as Marburg virus.

Monoclonal antibodies have been developed that recognise a structure, known as filovirus glycoprotein (GP), which is common to a range of viruses in the Ebola family. However, these antibodies have not been able to detect GP in samples from infected patients, probably because GP is biochemically modified after it is made.

The AdjustEBOVGP-Dx project is exploring whether a range of biochemical treatments can strip away these modifications, enabling monoclonal antibodies to access GP. It is developing a prototype point-of-care diagnostic that will combine this biochemical pretreatment with monoclonal antibody-based detection of GP.

The prototype will then be tested in the ongoing Ebola outbreak in the Democratic Republic of the Congo.

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.

The AdjustEBOVGP-Dx project could provide a new tool to support the early detection of and rapid response to Ebola virus infections. Importantly, it would also be the first diagnostic able to identify infections with both Ebola and Marburg virus, another lethal viral infection with epidemic potential.

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