EDCTP portfolio: Neglected infectious diseases

The ShigOraVax study is collecting essential data to advance the development of vaccines against Shigella, a key cause of diarrhoeal disease in low-income countries.

Preventing dysentery in young children

Shigella is the second most common cause of deaths from diarrhoea in children under five years of age. In 2013, Shigella infections were responsible for at least 34,000 deaths of children under five years of age, but recent use of more specific diagnostics suggests that the impact of Shigella has been significantly underestimated.

Although several Shigella vaccines are in development, their evaluation is hampered by a limited understanding of disease burden.

The challenge

The most common forms of Shigella are S. flexneri strains 2a, 3a and 6 and S. sonnei, all of which are associated with severe diarrhoeal disease. The ShigOraVax project aims to develop a whole-cell inactivated vaccine that is protective against all these strains, can be administered orally, and is cheap and easy to manufacture.

The project will first test the vaccine’s safety in European and African adults, before beginning safety studies in children in Burkina Faso. A phase II multicentre trial will be organised in Burkina Faso and Zambia.

Importantly, the project will also collect data on children with moderate to severe diarrhoea at trial sites, to generate a clearer picture of the disease burden attributable to Shigella and to provide a foundation for assessing the efficacy of the vaccine. 

The project

The ShigOraVax study will advance the development of a vaccine against one of the most common causes of severe diarrhoea in young children. It will also strengthen the capacity of Burkina Faso and Zambia to carry out vaccine research, and provide much-needed data on the Shigella disease burden in 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

Shigella is the second most common cause of deaths from diarrhoea in children under five years of age. In 2013, Shigella infections were responsible for at least 34,000 deaths of children under five years of age, but recent use of more specific diagnostics suggests that the impact of Shigella has been significantly underestimated.

Although several Shigella vaccines are in development, their evaluation is hampered by a limited understanding of disease burden.

The most common forms of Shigella are S. flexneri strains 2a, 3a and 6 and S. sonnei, all of which are associated with severe diarrhoeal disease. The ShigOraVax project aims to develop a whole-cell inactivated vaccine that is protective against all these strains, can be administered orally, and is cheap and easy to manufacture.

The project will first test the vaccine’s safety in European and African adults, before beginning safety studies in children in Burkina Faso. A phase II multicentre trial will be organised in Burkina Faso and Zambia.

Importantly, the project will also collect data on children with moderate to severe diarrhoea at trial sites, to generate a clearer picture of the disease burden attributable to Shigella and to provide a foundation for assessing the efficacy of the vaccine. 

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 ShigOraVax study will advance the development of a vaccine against one of the most common causes of severe diarrhoea in young children. It will also strengthen the capacity of Burkina Faso and Zambia to carry out vaccine research, and provide much-needed data on the Shigella disease burden in 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

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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