EDCTP projects supported through its Emergency Funding Mechanism and standard calls for proposals are strengthening African research capacity to respond to and manage disease outbreaks, whilst contributing data to aid the national and continental response to epidemics. The RE-BCG-COV-19 project showed that revaccination with the TB vaccine BCG failed to protect healthcare workers in South Africa against SARS-CoV-2 infection or related severe COVID-19 disease, consistent with results of the BRACE trial in Australia, Brazil, and Europe, and confirming the WHO statement that there is no evidence that BCG protects people against infection with COVID-19 virus. Results of the PEAU-EBOV-RDC study following survivors of the 2018 Ebola outbreak have shown that life-saving monoclonal antibodies as an emergency treatment might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease, which could increase the risk of reinfection or reactivation. This study has led to calls for research funding for long-term follow-up of Ebola survivors to provide data to inform future epidemic response.

In 2021, WHO verified elimination of Human African Trypanosomiasis (HAT) in Côte d’Ivoire, an achievement that drew heavily on the work of the EDCTP-funded DiTECT-HAT project. This project has been evaluating three different testing strategies for HAT, each of which would have a distinct role to play in achieving and sustaining elimination. As well its contribution to Côte d’Ivoire’s success in 2021, the DiTECT-HAT project’s work is highly relevant to other countries targeting HAT elimination.

In December 2023, the EMA adopted a positive scientific opinion of the use of Fexinidazole Winthrop as a first oral treatment for T.b. rhodesiense sleeping sickness, an acute and lethal form of this parasitic disease found in Eastern and Southern Africa. The trial for treatment of T.b. rhodesiense with Fexinidazole Winthrop in Malawi and Uganda was supported by EDCTP through the HAT-r-ACC consortium.

This positive scientific opinion today paves the way for the update of World Health Organization (WHO) guidelines on sleeping sickness, as well as the extended indication and distribution of fexinidazole in African countries where T.b. rhodesiense is prevalent.

Through the Pediatric Praziquantel Consortium (PZQ4PSAC) project, EDCTP and the Japan-based Global Health Innovative Technology (GHIT) fund supported a phase III trial of arpraziquantel, an orally dispersible treatment based on praziquantel, a drug widely used in schistosomiasis mass drug administration programmes. In December 2023, the European Medicines Agency (EMA) adopted a positive scientific opinion for arpraziquantel to treat schistosomiasis in preschool-aged children. The positive scientific opinion considered all supporting evidence, including the results of the pivotal phase III trial in Côte d’Ivoire and Kenya – which showed excellent efficacy of arpraziquantel, achieving cure rates of 90% or above, and was safe and well tolerated by young children affected by schistosomiasis.

Through the EDCTP-funded ADOPT project, the Consortium is preparing the ground for the large-scale delivery of this new treatment in endemic countries, expected to start in 2024.

The DIAMA project, which brings together groups in nine sub-Saharan African countries, is focusing on the diagnosis and management of patients with multidrug-resistant TB (MDR-TB). Three DIAMA sites generated field data on Cepheid’s Xpert MTB/XDR cartridge, which can rapidly detect resistance to second-line drugs such as isoniazid and fluoroquinolones used in the WHO-recommended regimen for rifampicin-resistant TB. This information was considered in the latest revision of WHO guidance on TB detection. The consortium has also shared data with WHO that contributed to the 2023 rapid communication on use of targeted next-generation sequencing for diagnosis of drug-resistant tuberculosis. The Rapid Communication is released in advance of updated WHO consolidated guidelines (soon expected) for diagnosis of TB to inform national TB programmes and other stakeholders of key changes expected in the available options for detection of TB drug resistance and to allow for rapid transition and planning at the country level.

Malaria during pregnancy can cause serious maternal and newborn health issues, especially in women living with HIV. The World Health Organization recommends daily doses of the antibiotic co-trimoxazole to prevent malaria in pregnant women living with HIV residing in areas with high malaria transmission. However, its efficacy in sub–Saharan Africa is threatened because malaria parasites are becoming increasingly resistant to the drug. 

Two EDCTP-funded studies, IMPROVE-2 and MAMAH, showed that the addition of the antimalarial drug dihydroartemisinin–piperaquine (DP) to daily co-trimoxazole substantially reduces the risk of malaria infection in pregnancy.

EDCTP has helped to advance the implementation and use of RTS,S/AS01, the first malaria vaccine recommended by WHO, by supporting several post-registration studies, including the Malaria Vaccine Pilot Evaluation-Case Control (MVPE-CC) project which is assessing the safety of RTS,S in routine use, the feasibility of reaching children with the recommended four-dose schedule, and the impact of the vaccine at population level to inform global policy recommendation. The RTS,S/AS01 vaccine is in high demand but supplies are currently limited, and additional malaria vaccines are urgently needed. An EDCTP-funded phase II trial found that a second malaria vaccine, R21/Matrix-M, was highly efficacious, meeting WHO’s preferred 75% efficacy target. The results of a phase III multicentre trial were equally encouraging. In October 2023, WHO recommended the vaccine for the prevention of malaria in children, and in December 2023, R21/Matrix-M malaria vaccine was added to WHO’s list of prequalified vaccines.

For almost two decades, the CHAPAS Consortium has been conducting clinical trials to improve treatment options for children living with HIV in sub-Saharan Africa. Data from EDCTP-funded CHAPAS–1 and CHAPAS–3 projects supported licensing applications for child-friendly formulations and provided evidence in support of WHO recommendations on updated treatment options. The results of the CHAPAS–4 study, designed to identify an optimal second-line treatment for children with HIV, found that newer antiretroviral combinations including tenofovir alafenamide (TAF) and dolutegravir (DTG) were superior to older second-line options for children living with HIV. These results reinforce the current WHO recommendation of DTG-based regimens being the preferred second-line regimen for children. They also provide new evidence for use of TAF in second-line combinations for children. Results from sub-studies looking at drug levels in blood samples from CHAPAS-4 are expected to contribute to the evidence for simplified weight-band dosing of these drugs for children. It will also help with the development of new formulations such as dispersible fixed-dose drug combination minipills of TAF+FTC, with or without DTG, which will make taking medication easier for children.

Central Nervous System (CNS) infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. The results of the DREAMM study published in The Lancet HIV in October 2023 showed that DREAMM implementation interventions and strategies substantially reduced all-cause 2-week mortality from 49% to 24% among people living with HIV presenting to public hospitals in Africa with suspected HIV-related infection of the CNS. Health system engineering combined with a multidisciplinary approach driven by local leadership proved a powerful means for enacting quality care.

The AMBITION-cm study has shown that a simplified treatment for cryptococcal meningitis, one of the major causes of death of people living with HIV, is as good as existing treatments and has fewer serious side effects. The treatment could potentially save costs as well. The findings have already had an impact on policy. In April 2022, WHO issued a rapid guidance update that strongly recommended use of single high-dose amphotericin B for the treatment of cryptococcal meningitis in people living with HIV.