The WorldWide Antimalarial Resistance Network (WWARN) generates innovative resources and reliable evidence to inform the malaria community on the factors affecting the efficacy of antimalarial medicines.
The WorldWide Antimalarial Resistance Network (WWARN) is a multi-disciplinary, scientifically independent network that provides reliable evidence to inform the malaria community on the factors affecting the efficacy of antimalarial medicines. WWARN, which is part of the Infectious Diseases Data Observatory, provides high-quality analysis, customised research tools and services, and a global platform for exchanging scientific and public health information.
WWARN was founded in 2009 to provide the information necessary to prevent or alleviate antimalarial drug resistance and therefore reduce the number of people falling ill and dying from malaria.
WWARN now works with around 270 collaborators across the world to help optimise the efficacy of antimalarial medicines and treatment regimens, especially for vulnerable groups including pregnant women, infants and malnourished children. WWARN also provides evidence to inform the development of new antimalarial medicines.
The threat of artemisinin resistance
Artemisinin derivatives used in combination with other partner medicines are currently the cornerstone of malaria treatment. However, artemisinin resistance in Plasmodium falciparum malaria is the single greatest threat to efforts to control and eliminate malaria.
Resistance has been identified in Cambodia, Thailand, Vietnam, Laos and Myanmar. The spread or emergence of resistance beyond the Myanmar-Indian border, toward Africa, could derail current efforts to eliminate malaria. Assessing, mapping, and modelling the emergence or spread of artemisinin resistance is essential to limiting the impact of drug resistance on patient illness and mortality rates.
There are currently no new and approved antimalarial drugs and the drug development pipeline is a long and complex process, so it is vital to sustain the efficacy of existing artemisinin combination therapies (ACTs) until new medicines are registered and launched.
Barriers to prevention and control efforts
In the past, assessments of antimalarial resistance were based solely on the success of antimalarial drug treatments. The available data were variable in quality and reliability, and many data files were inaccessible. Geographical gaps in data, and a lack of standardisation in data collection and analysis, make it difficult to track or anticipate resistance before it becomes apparent through treatment failures and deaths.
Life-saving information that enables treatment approaches to be optimised is not always current or readily available in many countries. Furthermore, clinical trial treatment assessments are not always reliable (quality assured), correctly analysed, or made available to global policy makers, donors, pharmaceutical companies and researchers.
Poor quality medicines are also a significant barrier to malaria control and prevention efforts and threaten the lives and livelihood of millions of people globally. These include both substandard medicines – caused by errors during the manufacturing process – and falsified medicines – caused by criminal fraud. Assessing the quality of antimalarial drugs is particularly challenging due to the heterogeneity and paucity of data available.
How is WWARN responding to these challenges?
WWARN provides a unique platform for the sharing and analysis of data on antimalarial medicines. Detection of subtle changes in patient treatment outcomes can provide early warning of emerging drug resistance. This allows prompt implementation of containment efforts to help prolong the usefulness of current antimalarial medicines.
Data sharing partnerships: WWARN has developed a unique model to facilitate data sharing in the research community. The WWARN data-sharing platform is the result of a collaborative effort of more than 250 partners around the world, comprised of research institutions, governmental and non-governmental organisations, product development partnerships, and pharmaceutical companies.
Data repository: WWARN’s Data Centre contains the majority of the world’s clinical, molecular, pharmacological and drug quality clinical trial results. The Data Centre is a repository for around 80% of ACT clinical trial studies published since 2000 – data from over 120,000 patients. WWARN serves as a long-term data storage facility ensuring that this important information continues to be available to the malaria research community.
Data curation and analysis: WWARN has developed an innovative system for standardising heterogeneous data, enabling detailed analyses of large combined datasets. WWARN’s approach to data analysis provides unparalleled statistical power to answer critical public health questions that it would be impossible to answer through analysis of results from individual clinical trials.
Collaborative meta-analyses: WWARN has facilitated 20 active or published collaborative meta-analyses. These meta-analyses have made significant contributions to our understanding of the factors affecting the efficacy of antimalarial medicines. For instance, pooled analyses of artesunate-amodiaquine data showed that providing the artemisinin and amodiaquine as a single pill was more effective than treating people with two separate pills.
Tools and services: To help researchers generate high quality data, WWARN provides resources, services and training free of charge to the malaria community. For example, the WWARN Explorer enables researchers to identify gaps in clinical trial data. The WWARN Toolkit helps to build capacity in malaria endemic countries, to strengthen the collection, analysis, interpretation and dissemination of high quality research data.
Defining artemisinin resistance: WWARN has developed, validated and made available a Parasite Clearance Estimator (PCE), the only online tool currently available for assessing parasite clearance rates, a measure of artemisinin resistance. The PCE has become a standard reference tool and is being used to document the spread or emergence of resistance in the Mekong region. WWARN has developed models of the emergence and spread of known molecular markers of artemisinin resistance, including the K13 Molecular Surveyor which summarises data from over 5,000 samples from 22 countries.
Partnership projects: WWARN is a key partner in the second Tracking Resistance to Artemisinin Collaboration (TRAC II), a project that is investigating the safety, tolerability and efficacy of two Triple ACTs, and monitoring for the extension and emergence of artemisinin and partner drug resistance across Asia and Africa.
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