With the emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia, it is more important than ever to monitor the efficacy of these antimalarial drugs on the African continent, where the majority of malaria deaths occur.
“There is a clear historical pattern: drug resistance often emerges in Southeast Asia and then spreads around the globe. This time, we have the opportunity to get ahead of the next wave of drug resistance,” says Dr Deus Ishengoma, a researcher with National Institute for Medical Research in Tanzania and a member of the recently-formed Plasmodium Diversity Network Africa (PDNA).
Working locally to understand parasite diversity across Africa
With artemisinin resistance not yet detected in Africa, there is an important window for scientists to collect baseline information on genetic diversity in parasite populations in different geographical regions, track known molecular markers of resistance to key partner drugs, and get the infrastructure and expertise in place so that they can respond quickly should artemisinin resistance arise in Africa.
These objectives are at the heart of the PDNA, which was founded by a cadre of African malaria research scientists who saw a need to coordinate their research.
“This type of work can only be accomplished through collaboration. We can’t get an accurate picture of drug resistance by looking in a single place,” says Abdoulaye Djimdé, Professor at the University of Science, Techniques and Technologies, Bamako in Mali, International Fellow at the Wellcome Trust Sanger Institute, UK, and the PDNA’s lead investigator. “If we combine our expertise and work systematically at multiple locations, we have the potential to transform our understanding of genetic diversity in parasite populations across the whole of Africa."
As if to illustrate the point, Dr Milijaona Randrianarivelojosia, Head of the Malaria Research Unit at the Institut Pasteur de Madagascar, describes how understanding the spread of resistance across parasites populations in other parts of Africa is an important element of malaria control on the island of Madagascar. “Following six decades of chloroquine use, the absence of mutant parasites genetically resistant to this drug is intriguing. This is strongly suggestive of low parasite introduction into the island from mainland Africa. However, we need to demonstrate in advance if parasite flow within Africa poses a risk to Madagascar, should artemisinin resistant parasites arise on the mainland.”
Madagascar is just one example. PDNA researchers are working at eleven locations across the vast continent. Each researcher is conducting their own study into local aspects of malaria. These independent studies vary in scope and address different scientific questions, for example, some researchers are on the lookout for signs of local P. falciparum resistance to artemisinin while others are examining trends in transmission or analysing local parasite population structures.
Working across all study sites is bioethicist Dr Paulina Tindana, a research fellow at the Navrongo Health Research Centre in Northern Ghana, who adds, “While each individual site has its own goals, members of the network must work together to achieve their shared mission. This collaborative effort will require the group to define overarching governance structures and data sharing policies that are respectful of individual studies and the local context where they are being undertaken. This must be done right at the beginning.”
The starting point for each of the network’s independent studies is to isolate parasite DNA directly from blood samples drawn from malaria patients, using a shared protocol. The resulting parasite DNA is then sequenced and genotyped through a collaboration with the Wellcome Trust Sanger Institute and the MalariaGEN Plasmodium falciparum Community Project. As contributors to the Community Project, PDNA researchers will receive the DNA sequence reads and quality-assured genotypes for their contributed samples. Each researcher can use this data for their local study. Additionally, all the data will be compiled into a PDNA repository. This will enable the PDNA to carry out data analysis on a large, standardised data set, the results of which could inform malaria control initiatives across Africa.
Partnering with the MalariaGEN Plasmodium falciparum Community Project has the added benefit of connecting this regional information with data on genetic variation that is being collected by researchers around the globe.
Building capacity building amongst African researchers
For many members of the PDNA, this home-grown initiative marks a step towards leadership of malaria research activities within their communities. “The PDNA connects many young African researchers not just to each other but also to more senior African researchers to work together to achieve a shared goal. This new initiative gives us an important opportunity to learn from each other’s experiences and to shape African research into the genetic diversity of malaria parasites,” says Lemu Golassa, PhD candidate at Addis Ababa University and Armauer Hansen Research Institute in Addis Ababa, Ethiopia.
This capacity building element of the PDNA fits well with the CGGH’s focus on developing research capacity for genomic data analysis in developing countries. In 2013, the CGGH saw an opportunity to use the Medical Research Council (MRC) Centenary Award funds available to them as an MRC Centre to do something a little different—and support the formation of this young network.
The Centenary Awards were intended to support MRC-funded researchers but with the blessing of the MRC, CGGH used their award to support four PDNA researchers to pursue research at study sites in Ghana, Tanzania and Cameroon. Recognising the need for an ethical framework to support this type of collaboration, the CGGH provided additional support for bioethicist Dr Paulina Tindana.
“Many of the researchers involved in the PDNA, although not necessarily MRC-funded, had tangible, longstanding relationships with the CGGH. The Centenary Award presented a unique opportunity for us to support their efforts, further the science of genomic epidemiology in Africa, and help many young researchers to get state-of-the-art technical and analytical training while retaining the closest possible links with their home institutions—for us, it was a win-win,” says Dr Victoria Cornelius, CGGH Business Manager.
In addition to supporting individual projects, CGGH provided support for a series of meetings to bring together the network members. The first network-wide meeting, held in in March 2013 in Oxford, UK, was a defining moment, as researchers came together to discuss the network’s objectives and structure. It became clear that to achieve its goals, the network would need to grow and bring on board researchers at additional study sites and CGGH supported this growth. In May 2013, the network members gathered in Accra, Ghana, for a second meeting, this time to set their scientific objectives and develop an ethics and governance framework for the coming malaria transmission season.
A third meeting took place in June 2014 at the Genome Campus in Hinxton, UK. The meeting brought together all PDNA members to review the current status of their work, progress to date, and to discuss the future directions of the network, as well as their collaboration with MalariaGEN and the Wellcome Trust Sanger Institute. In future, the members will come together again for a data analysis clinic in which various different genotyping and sampling techniques will be shared and discussed.
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