Publications

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

Dr Kingsley Badu

Ghana

EDCTP portfolio: Career Development Fellowships

Dr Kingsley Badu evaluates the possible role of infectious-bite biomarker PSOP24-377 in tracking malaria transmission intensity to improve control efforts.

Biomarkers for malaria detection and population level surveillance

The tools used in measuring malaria transmission intensity have different sensitivities at different geographical scales over time and space. This reflects changes in vector exposure, parasite infections and the dynamics of changing human immunity. Therefore, the intrinsic sensitivity of tools to detect short term changes in transmission is highly desirable. Accurate data on transmission intensity will be crucial for directing control efforts, developing and testing new interventions, as well as predicting the effects of these interventions under various conditions.

However, current tools have limitations in sensitivity at low-level transmission or lack the inherent ability to track short-term changes. Changes measured by traditional tools reflect either parasite or vector exposure but not both. The challenge is to develop an ‘ideal’ tool for tracking malaria transmission intensity. It should reflect both exposure to the vector, parasite infection and human immunity, detect short-term changes and be applicable at both individual and population level.

The challenge

Sporozoite and ookinete proteins have been identified as a promising marker for an infectious bite as human immune response correlates with seasonal vector and parasite exposure and thus. The role of infectious-bite markers to detect short-term changes in malaria transmission has not been thoroughly studied.

Dr Badu proposed to evaluate candidate biomarkers to address the current challenges regarding tools to measure malaria transmission. It is hoped that these biomarkers will prove to be sensitive for the identification of transmission hotspots, vulnerable populations and inform focused interventions to speed up malaria elimination. Using longitudinal community cohorts, under varying transmission levels, Dr Badu is studying the dynamics of antibody response to candidate biomarkers in comparison to other salivary proteins to validate infectious-bite markers.

The project

The research capacity of the fellow will be enhanced for protein chemistry, bioinformatics and project management. Moreover, standard infectious-bite markers developed in the study may be applied in other parts of Africa.

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

The tools used in measuring malaria transmission intensity have different sensitivities at different geographical scales over time and space. This reflects changes in vector exposure, parasite infections and the dynamics of changing human immunity. Therefore, the intrinsic sensitivity of tools to detect short term changes in transmission is highly desirable. Accurate data on transmission intensity will be crucial for directing control efforts, developing and testing new interventions, as well as predicting the effects of these interventions under various conditions.

However, current tools have limitations in sensitivity at low-level transmission or lack the inherent ability to track short-term changes. Changes measured by traditional tools reflect either parasite or vector exposure but not both. The challenge is to develop an ‘ideal’ tool for tracking malaria transmission intensity. It should reflect both exposure to the vector, parasite infection and human immunity, detect short-term changes and be applicable at both individual and population level.

Sporozoite and ookinete proteins have been identified as a promising marker for an infectious bite as human immune response correlates with seasonal vector and parasite exposure and thus. The role of infectious-bite markers to detect short-term changes in malaria transmission has not been thoroughly studied.

Dr Badu proposed to evaluate candidate biomarkers to address the current challenges regarding tools to measure malaria transmission. It is hoped that these biomarkers will prove to be sensitive for the identification of transmission hotspots, vulnerable populations and inform focused interventions to speed up malaria elimination. Using longitudinal community cohorts, under varying transmission levels, Dr Badu is studying the dynamics of antibody response to candidate biomarkers in comparison to other salivary proteins to validate infectious-bite markers.

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 research capacity of the fellow will be enhanced for protein chemistry, bioinformatics and project management. Moreover, standard infectious-bite markers developed in the study may be applied in other parts of Africa.

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