EDCTP portfolio: Neglected infectious diseases

The PREPARE study is speeding up the development of vaccines that protect women, newborns and young infants against group B streptococci.

Preventing stillbirths and neonatal meningitis

Group B streptococci are carried by a third of adults and one in five pregnant women, in the digestive system or lower vaginal tract. They usually cause no problems, but they can be transmitted to babies in the womb or during birth. Because of their immature immune systems, babies are at greater risk of invasive disease such as meningitis and septicaemia, and group B streptococci can also cause stillbirth.

There are an estimated 410,000 cases of serious infection each year, leading to 147,000 stillbirths and infant deaths globally. The highest burden is in Africa, which accounts for 64% of stillbirths and infant deaths.

The challenge

The PREPARE study aims to facilitate the development of vaccines against group B streptococci. Although serious – one in ten babies with an infection are likely to die, and half of those who survive meningitis will have long-term impairments – it is relatively rare, so large-scale phase III trials are difficult to conduct.

The PREPARE study is partnering with manufacturers to test two experimental vaccines, in women with and without HIV. To facilitate trials, the project will collect data on group B streptococcal infections and pregnancy outcomes in 70,000 women attending a hospital in Uganda. A biobank of blood samples will also be created, so links between antibody production and protection against group B streptococci-associated disease in mothers and babies can be investigated. 

The project

The PREPARE study will generate important data on the efficacy of experimental vaccines against group B streptococci, but will also provide additional evidence on disease burden in sub-Saharan Africa and on the immune responses linked to protection. A deeper understanding of the latter could provide a more convenient way to assess the efficacy of vaccines, to inform licensing decision-making and accelerate the introduction of a vaccine.

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

Group B streptococci are carried by a third of adults and one in five pregnant women, in the digestive system or lower vaginal tract. They usually cause no problems, but they can be transmitted to babies in the womb or during birth. Because of their immature immune systems, babies are at greater risk of invasive disease such as meningitis and septicaemia, and group B streptococci can also cause stillbirth.

There are an estimated 410,000 cases of serious infection each year, leading to 147,000 stillbirths and infant deaths globally. The highest burden is in Africa, which accounts for 64% of stillbirths and infant deaths.

The PREPARE study aims to facilitate the development of vaccines against group B streptococci. Although serious – one in ten babies with an infection are likely to die, and half of those who survive meningitis will have long-term impairments – it is relatively rare, so large-scale phase III trials are difficult to conduct.

The PREPARE study is partnering with manufacturers to test two experimental vaccines, in women with and without HIV. To facilitate trials, the project will collect data on group B streptococcal infections and pregnancy outcomes in 70,000 women attending a hospital in Uganda. A biobank of blood samples will also be created, so links between antibody production and protection against group B streptococci-associated disease in mothers and babies can be investigated. 

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 PREPARE study will generate important data on the efficacy of experimental vaccines against group B streptococci, but will also provide additional evidence on disease burden in sub-Saharan Africa and on the immune responses linked to protection. A deeper understanding of the latter could provide a more convenient way to assess the efficacy of vaccines, to inform licensing decision-making and accelerate the introduction of a vaccine.

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.

Contact us

For more information, please contact us or leave a message using this form.
Please enter your name
Please enter a correct e-mail address
Please enter a comment
Thank you! Your message has been sent.
Something went wrong while submitting the form. Try again.

Share this publication

Forward this page by e-mail or share it directly on social media.

Search

Enter a search term to search the EDCTP publications.
Minimal length to search is 3 characters

This publication uses cookies

We use functional and analytical cookies to improve our website. In addition, third parties place tracking cookies to display personalised advertisements on social media. By clicking accept you consent to the placement of these cookies.