Dr John Lusingu

Tanzania

EDCTP portfolio: Senior Fellowships

Professor Faith Osier has created an international network to map the malaria parasite diversity across Africa – a key step in the development of more effective malaria vaccines.

Towards improved vaccines for malaria

Malaria vaccine development has proven hugely challenging. Following decades of work, the first vaccine of proven efficacy, RTS,S/AS01, is beginning to be implemented in Africa.

However, RTS,S/AS01 is of limited efficacy and requires four doses. Alternatives are still urgently needed to improve malaria control and to support the drive towards elimination. One key priority is severe malaria, which in Africa predominantly affects children under 5 years of age, which can be rapidly fatal without prompt treatment.

The challenge

Dr John Lusingu was one of the researchers involved in the clinical trials evaluating RTS,S/AS01. He is aiming to build on this experience to advance the development of other vaccine candidates and to build the capacity for malaria research and vaccine field trials in Tanzania.

In his EDCTP Senior Fellowship, Dr Lusingu is focusing on a highly variable malaria parasite protein known as PfEMP1, which is found on the surface of infected red blood cells and promotes binding of infected cells to blood vessel walls. Antibodies against PfEMP1 are associated with protection against malaria, but because it is such a highly variable protein, it takes time for people to develop a repertoire of protective antibodies. However, there is also evidence that protection against specific forms of malaria – such as malaria in pregnancy and severe malaria in children – could develop relatively quickly when antibodies against specific PfEMP1 variants are generated. 

Dr Lusingu’s research is focusing on PfEMP1 variants that bind to a protein on blood vessel walls known as endothelial protein C receptor (EPCR), which Dr Lusingu and his colleagues in Denmark have found is associated with severe malaria in children. A vaccine blocking binding to EPCR could therefore reduce the risk of one of the most deadliest manifestations of malaria.

The project

Dr Lusingu’s fellowship will build capacity for vaccine-related research, with the aim of developing a vaccine suitable for pregnant women and young children, those most vulnerable to severe malaria. It will also establish a field site in Korogwe, Tanzania, able to carry out field-based studies on candidate vaccines. Dr Lusingu’s fellowship will also facilitate the training of junior researchers (two master’s and two PhD students).

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

Malaria vaccine development has proven hugely challenging. Following decades of work, the first vaccine of proven efficacy, RTS,S/AS01, is beginning to be implemented in Africa.

However, RTS,S/AS01 is of limited efficacy and requires four doses. Alternatives are still urgently needed to improve malaria control and to support the drive towards elimination. One key priority is severe malaria, which in Africa predominantly affects children under 5 years of age, which can be rapidly fatal without prompt treatment.

Dr John Lusingu was one of the researchers involved in the clinical trials evaluating RTS,S/AS01. He is aiming to build on this experience to advance the development of other vaccine candidates and to build the capacity for malaria research and vaccine field trials in Tanzania.

In his EDCTP Senior Fellowship, Dr Lusingu is focusing on a highly variable malaria parasite protein known as PfEMP1, which is found on the surface of infected red blood cells and promotes binding of infected cells to blood vessel walls. Antibodies against PfEMP1 are associated with protection against malaria, but because it is such a highly variable protein, it takes time for people to develop a repertoire of protective antibodies. However, there is also evidence that protection against specific forms of malaria – such as malaria in pregnancy and severe malaria in children – could develop relatively quickly when antibodies against specific PfEMP1 variants are generated. 

Dr Lusingu’s research is focusing on PfEMP1 variants that bind to a protein on blood vessel walls known as endothelial protein C receptor (EPCR), which Dr Lusingu and his colleagues in Denmark have found is associated with severe malaria in children. A vaccine blocking binding to EPCR could therefore reduce the risk of one of the most deadliest manifestations of malaria.

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 Lusingu’s fellowship will build capacity for vaccine-related research, with the aim of developing a vaccine suitable for pregnant women and young children, those most vulnerable to severe malaria. It will also establish a field site in Korogwe, Tanzania, able to carry out field-based studies on candidate vaccines. Dr Lusingu’s fellowship will also facilitate the training of junior researchers (two master’s and two PhD students).

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

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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