Dr Jean-Bertin Bukasa Kabuya

Zambia

EDCTP portfolio: Career Development Fellowships

Dr Jean-Bertin Bukasa Kabuya aims to improve standard intermittent presumptive treatment outcomes by introducing a rapid test for SP-resistant parasites at the first antenatal care visit.

Preventing malaria in pregnancy while avoiding the development of further drug-resistance

Malaria in pregnancy (MIP) may result in serious clinical consequences for mother and child. In moderate- to high-transmission areas of sub-Saharan Africa, the World Health Organization (WHO) recommends the use of long-lasting insecticidal nets (LLINs) together with Intermittent Preventive Treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) and/or treatment of confirmed cases.

However, there are concerns that IPTp-SP efficacy is becoming less as a consequence of the ever-increasing parasite resistance to SP. Continued use of SP for IPTp would result in further reduction of IPTp-SP efficacy and compromise the prevention of MIP-associated adverse outcomes. As SP needs to remain the recommended antimalarial drug for IPTp, the challenge is to devise strategies to prevent and treat which avoid furthering SP-resistance of the parasite.

The challenge

Reducing SP interaction with the already mutated parasite would prevent further selection of mutated parasites, reduce resistance to SP and improve its efficacy. This may be achieved by introducing at the first antenatal care (ANC) visit, a malaria Rapid Diagnostic Testing (mRDT). Mothers testing positive will then be treated with a fully effective antimalarial drug before being administered SP; mothers testing negative will receive SP as per current recommendations.

Therefore, Dr Kubuya proposed to compare the current IPTp-SP treatment with IPTp-SP in combination with an mRDT and treatment at the first ANC visit (IPTp-SP+) in terms of efficacy at clearing peripheral maternal parasitaemia and prevention of adverse outcomes associated with MIP. Volunteer mothers not infected with HIV and meeting the inclusion criteria will be recruited for this clinical trial. Relevant socio-demographic and clinical information is collected and blood samples are taken for haemoglobin and malaria molecular testing at enrolment, days 14, 28, 42 and 63, and at delivery. In addition, cord blood and a placental biopsy will be collected, and babies’ haemoglobin will be measured to determine malaria parasitology and histopathology.

The project

Data from this study may directly help MIP leaders to review current practice for the prevention of malaria in pregnancy. Positive outcomes will expand the available medical interventions for this special population and contribute to averting resistance to SP.

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 in pregnancy (MIP) may result in serious clinical consequences for mother and child. In moderate- to high-transmission areas of sub-Saharan Africa, the World Health Organization (WHO) recommends the use of long-lasting insecticidal nets (LLINs) together with Intermittent Preventive Treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) and/or treatment of confirmed cases.

However, there are concerns that IPTp-SP efficacy is becoming less as a consequence of the ever-increasing parasite resistance to SP. Continued use of SP for IPTp would result in further reduction of IPTp-SP efficacy and compromise the prevention of MIP-associated adverse outcomes. As SP needs to remain the recommended antimalarial drug for IPTp, the challenge is to devise strategies to prevent and treat which avoid furthering SP-resistance of the parasite.

Reducing SP interaction with the already mutated parasite would prevent further selection of mutated parasites, reduce resistance to SP and improve its efficacy. This may be achieved by introducing at the first antenatal care (ANC) visit, a malaria Rapid Diagnostic Testing (mRDT). Mothers testing positive will then be treated with a fully effective antimalarial drug before being administered SP; mothers testing negative will receive SP as per current recommendations.

Therefore, Dr Kubuya proposed to compare the current IPTp-SP treatment with IPTp-SP in combination with an mRDT and treatment at the first ANC visit (IPTp-SP+) in terms of efficacy at clearing peripheral maternal parasitaemia and prevention of adverse outcomes associated with MIP. Volunteer mothers not infected with HIV and meeting the inclusion criteria will be recruited for this clinical trial. Relevant socio-demographic and clinical information is collected and blood samples are taken for haemoglobin and malaria molecular testing at enrolment, days 14, 28, 42 and 63, and at delivery. In addition, cord blood and a placental biopsy will be collected, and babies’ haemoglobin will be measured to determine malaria parasitology and histopathology.

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.

Data from this study may directly help MIP leaders to review current practice for the prevention of malaria in pregnancy. Positive outcomes will expand the available medical interventions for this special population and contribute to averting resistance to SP.

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.