For more than a decade now, the WHO has recommended a single low-dose of primaquine be added to the standard treatment of acute, uncomplicated Plasmodium falciparum in areas with low malaria transmission. So far, however, this recommendation has not been implemented consistently across sub-Saharan Africa.
Blocking malaria transmission with primaquine
When administered in a single low dose, with standard antimalarial treatment, called artemisinin-based combinations, primaquine blocks the transmission of malaria between humans and mosquitoes. This is referred to its gametocytocidal activity i.e., killing the sexual forms of the malaria parasites. These male and female forms are taken up by mosquitoes where they mate to produce the forms that then infect humans. If deployed on a wide scale, single low-dose primaquine should benefit communities and play an instrumental role in eliminating malaria.
Strategy and global vision
WHO recommendations
Map of implementing countries
Prequalification
The prequalification system within the WHO allow for newly developed medicines to be marketed via an accelerated registration system, enabling medicines to get to patients faster and more efficiently. By developing medicines and prequalifying them with the WHO, treatments will be marketed via the accelerated registration system for prequalified finished products in WHO partner countries.
Proper dosage guidelines and pediatric formulations play a critical role in ensuring patients know take their medicine for the full duration of their treatment and that properly take their medicine. To ensure adherence to SLDPQ by all patients of all ages, especially children, practical and acceptable dosages and galenic forms must be available. This can be achieved by developing child-friendly formulations, optimising dosing regimens and packaging and assessing their acceptability to patients and their carers.
This initial research and development work needs to be managed in partnership with a drug manufacturer, which is willing and has the capacity to scale up, manufacture to international quality standards, market the finished products, and distribute them in endemic countries through malaria control programmes.
Overview of our strategy
The IMPRIMA project is based on the implementation of several complementary work packages (clinical, community/sociological and political), and capacity building, in three endemic African countries with different malaria epidemiologies, namely, Burkina Faso, Madagascar and Burundi. It aims to generate data demonstrating the safety, acceptability and impact at community level of taking SLDPQ.
IMPRIMA follows on from the “Developing Paediatric Primaquine” project, funded by the EDCTP2 programme (www.dpp-project.org), that aims to develop and clinically validate paediatric forms of primaquine.
The strong commitment of the IMPRIMA consortium players is key to its success and a fundamental step towards eliminating malaria in Africa. At the same time, an important underlying theme is strengthening the technical capabilities of the teams in the field to, particularly, monitor the development of malaria resistance to artemisinin and the partner drugs.
The complementary nature of the partners in the IMPRIMA consortium, the integration of the clinical, sociological, political and educational aspects, plus the diversity of the different epidemiological contexts are valuable elements that should see the successful implementation of the project and its reception by control programmes and the wider malaria community.
The clinical study will generate substantial, real-life evidence on the safety and acceptability of SLDPQ in large number of patients and assess, over two years, whether transmission is reduced and the effect on drugs resistance. The social and political studies, which will also include training activities, will complement the clinical evidence.
All in all, IMPRIMA aims to instill confidence in the strategy of deploying SLDPQ and its acceptance by communities and policy makers at country and international level.
Timeframe
4-year project from April 2023 to 2027
- One year of preparation
- Two years for field operations
- Final year to take stock and prepare the toolboxes.
DDP & Imprima projects
Complementarity and safety
The flavoured primaquine tablets used in the IMPRIMA project are pharmaceutically certified. The batches intended for the DPP and IMPRIMA clinical trials have been issued with certificates of analysis and they meet international standards of quality (Appendices : investigation document and certificate of analysis). All the technical information required for import permit applications in the three countries has been collected.
Funding
The European and Developing Countries Clinical Trials Partnership (EDCTP) is a public-public partnership between countries in Europe and sub-Saharan Africa, supported by the European Union, which aims to support international collaborative research and accelerate the development of new clinical interventions to prevent or treat poverty-related infectious diseases in sub-Saharan Africa. These includes HIV, tuberculosis, malaria, neglected, emerging and re-emerging infectious diseases and antimicrobial resistance.
The European Union’s EDCTP3 global health program, in partnership with African countries, has selected the IMPRIMA project (101103213) to implement SLDPQ. This project is an important step in the fight against malaria.
Consortium
In 2012, the WHO recommended adding single low dose primaquine (target dose 0.25 mg/kg) to block malaria transmission. The lack of suitable formulations and evidenced-based dosing regimens to implement this recommendation has given rise to research projects dedicated to fill this gap.
Accordingly, the Developing Paediatric Primaquine (DPP) and Implementing Primaquine in Africa (IMPRIMA) consortia were crated and received EDCTP funding. These projects, which are committed to the fight against malaria, have been forged like-minded partners.
The IMPRIMA consortium sees itself as a forerunner in building bridges between academic research and the socio-medical, political and economic spheres in order to effectively influence drug policy. In the field of research, professions and innovations are interdependent; the intellectual output of university centres and research institutes feeds closely into advances in the world of healthcare professionals. The ecosystems created between professions and regions will enable university engineers to work effectively with healthcare professionals in the field.
UNISTRA
The University of Strasbourg is a French multidisciplinary research university located in Strasbourg (Alsace), with 35 faculties and 71 laboratories (research units) in five major fields of study (Arts, Humanities, Languages/Law, Economics, Management and Political Science/Human and Social Sciences/Sciences, Technology/Health).
Health and Social Sciences are jointly involved in the Imprima project via the Faculty of Medicine and its Bacteriology and Parasitology Institutes, which are home to Research Unit 3073, dedicated to the study of Arthropod host pathogens and vector interactions. It is within this unit that the Malaria Genetics and Resistance Team (MEGATEAM) conducts cross-disciplinary research studies, from fundamental to applied aspects, in order to develop and deploy new tools to minimise the impact of malaria in Africa, monitor the evolution of Plasmodium falciparum resistance to antimalarial drugs and understand human-parasite interactions.
Within the Faculty of Social Sciences, the Institute of Ethnology and the Interdisciplinary Laboratory in Cultural Studies (LinCS UMR 7069) are carrying out the socio-anthropological study among populations involved in the fight against malaria in southern countries.
Oxford University
The University of Oxford (United Kingdom) is internationally recognised for excellence in research. It is organised into four academic divisions, which include departments, faculties and other centres.
Under the Division of Medical Sciences, the Nuffield Department of Clinical Medicine (NDM) is a major research and teaching department whose mission is to transform scientific discoveries into clinical impact. The Centre for Tropical Medicine and Global Health brings together research groups based in Asia and Africa and at two Oxford sites. Their research ranges from clinical studies to behavioural sciences; skills development is an integral part of all their activities. Like the other units in the Wellcome Trust’s Asia and Africa Programmes, the Mahidol and Oxford Universities Research Unit Tropical Health Network (MORU) based in Thailand conducts world-renowned research into tropical diseases. Established in 1979 by researchers at Mahidol University in Bangkok, the unit conducts targeted clinical public health research to discover and develop appropriate, practical and accessible interventions that improve the health of people living in resource-limited countries.
Leiden University
Leiden Law School is the oldest law faculty in the Netherlands, renowned for its excellence in legal research, and its strong focus on global challenges and interdisciplinary collaboration. The African Studies Centre Leiden (ASCL) is the oldest multidisciplinary research centre focused on the African continent in the Netherlands. The Leiden University Network for Health in Africa (LUNHA) Hub, founded in 2022, brings together Leiden Law School, the ACSL and Leiden University Medical Centre (LUMC), serving as a bridge between disciplines and leveraging a wide range of academic expertise to address urgent public health challenges and planetary crises on the African continent. As a consortium partner in the IMPRIMA project, the LUNHA Hub contributes its expertise in international law, public health and global health governance, supporting IMPRIMA country partners in their advocacy and policy development.
CNARP
Founded in 1976, the Centre National d’Application de Recherches Pharmaceutiques (CNARP) is one of nine National Research Centres under the supervision of Madagascar’s Ministry of Higher Education and Scientific Research. The institution currently has 86 employees, including 25 researchers.
The CNARP’s mission is to support the development and implementation of national scientific and technical research policy by focusing on defining, guiding, promoting and coordinating research into any product with therapeutic properties.
The centre is structured into six standard research departments, making it a benchmark in the pharmaceutical production chain. These are the extraction and chemistry, pharmacodynamics, clinical experimentation, galenics and production departments. The role of the clinical experimentation department is clinical and human health research. As such, the team in this department is one of the members of the IMPRIMA project consortium and provides leadership for WP3, the social component of the project.
GRAS
The Groupe de Recherche Action en Santé (GRAS) is a private institute based in Burkina Faso, active in the field of health research since 2008. GRAS has a multidisciplinary scientific staff with recognised expertise in clinical trials. Over the past decade, GRAS has conducted more than 25 clinical trials, including vaccine studies in malaria, pneumococcal disease, Ebola and typhoid fever. GRAS is currently a member of several global consortia working to develop new treatments or vaccines against these diseases. It benefits from the support of several national and international technical and financial partners, such as EDCTP. The institution is under the supervision of the Ministry of Higher Education, Scientific Research and Innovation (MESRSI).
INSP
Burundi’s National Institute of Public Health (INSP) is under the supervision of the Ministry of Health and began its activities in 1999. Initially, the INSP consisted only of the Training Department and the Administrative and Financial Department. In 2002, the Laboratories Department opened its doors to serve as the National Public Health Reference Laboratory. In addition to biological analyses, the laboratory carries out quality control of medicines and water. In 2006, the INSP was expanded to include a Research and Epidemiology Department, in order to fulfil the three missions set out in the founding decree :
- Initial training, further training and specialisation in public health
- Promoting and carrying out applied public health research
- Carrying out medical biology analyses and quality control of medicines, water, food and the environment.
The INSP’s mission is to give the entire Burundian population, especially the most vulnerable, access to quality preventive, curative and promotional care based on choices informed by scientific evidence. Fully committed to the fight against malaria and to the IMPRIMA project, the INSP is also involved in clinical research and in training healthcare staff.
ReMeD
ReMeD, Réseau Médicaments & Développement, is a French NGO set up nearly 30 years ago by humanitarian pharmacists to improve the availability, access, quality and use of medicines in developing countries. To achieve this, ReMeD deploys networks to facilitate the exchange of information, training and awareness-raising. Its missions are based on the principles of knowledge and transmission in order to :
- Gather and share information between public health players in countries in the North and South
- Alert, raise awareness and question public authorities and civil society
- Promote pharmaceutical expertise in the field.
Its vast international network of pharmaceutical professionals is based mainly in French-speaking African countries, and its members include experts from pharmaceutical councils, health departments, hospital pharmacist networks and the West African Economic and Monetary Union (WAEMU).