Implementing parasite genotyping into national surveillance frameworks: feedback from control programmes and researchers in the Asia–Pacific region

Abstract

The Asia–Pacific region faces formidable challenges in achieving malaria elimination by the proposed target in 2030. Molecular surveillance of Plasmodium parasites can provide important information on malaria transmission and adaptation, which can inform national malaria control programmes (NMCPs) in decision-making processes. In November 2019 a parasite genotyping workshop was held in Jakarta, Indonesia, to review molecular approaches for parasite surveillance and explore ways in which these tools can be integrated into public health systems and inform policy. The meeting was attended by 70 participants from 8 malaria-endemic countries and partners of the Asia Pacific Malaria Elimination Network. The participants acknowledged the utility of multiple use cases for parasite genotyping including: quantifying the prevalence of drug resistant parasites, predicting risks of treatment failure, identifying major routes and reservoirs of infection, monitoring imported malaria and its contribution to local transmission, characterizing the origins and dynamics of malaria outbreaks, and estimating the frequency of Plasmodium vivax relapses. However, the priority of each use case varies with different endemic settings. Although a one-size-fits-all approach to molecular surveillance is unlikely to be applicable across the Asia–Pacific region, consensus on the spectrum of added-value activities will help support data sharing across national boundaries. Knowledge exchange is needed to establish local expertise in different laboratory-based methodologies and bioinformatics processes. Collaborative research involving local and international teams will help maximize the impact of analytical outputs on the operational needs of NMCPs. Research is also needed to explore the cost-effectiveness of genetic epidemiology for different use cases to help to leverage funding for wide-scale implementation. Engagement between NMCPs and local researchers will be critical throughout this process.

Advances and opportunities in malaria population genomics

“…The distinct genomic signatures of parasites allow investigation of the connections between parasite populations to identify previously unappreciated sources and sinks of infections and to assess whether cases in low-transmission areas are caused by local transmission or importation — scenarios that demand distinct intervention strategies and the differentiation of which has implications for achieving or maintaining official malaria elimination status. Meaningful implementation of malaria genomics approaches for public health will require careful consideration of the current operational challenges 140 , including sustainable data generation and analysis capacity, harmonization of data and analysis approaches among localities, reagent supply chains, timelines and cost, and the practical value of the information itself.…”

“…The additional cost and technical challenge associated with the storage and processing of WGS data relative to targeted genotyping panels are likely to result in a reduced return on investment in a decentralized data generation system 50 , 109 . WGS is essential for identifying new genetic variants relevant for surveillance and validating genomic methodological advancements; however, the research community has been actively evaluating the potential role of targeted sequencing and genotyping approaches to recover the most informative genomic regions for malaria genomic epidemiology 9 , 140 , 142 . On the basis of this work, we suggest that for some applications, deep (1,000×) sequencing coverage of small genomic windows — comprising the most informative 20 kb of malaria parasite genomes, such as highly diverse regions and known markers of interest — could be equally or more operationally useful than 100× sequencing coverage of the whole 23–27 Mb parasite genome and require 100-fold lower net data production per sample.…”

The changing epidemiology of Plasmodium vivax: Insights from conventional and novel surveillance tools

“…However, a better understanding of how historical and more recent migratory and epidemiological factors may have shaped local population diversity will be needed. In addition, further research is needed to assess how genetic indices can be made readily available and provide timely, actionable, and cost-effective information to malaria control programmes [ 21 ].…”

“…Given the complex and often unpredictable patterns of parasite connectivity, comprehensive genetic surveillance frameworks will be needed to understand how P . vivax parasites are spreading within and between communities [ 21 ]. The methods used to characterise parasite connectivity are also an important consideration for malaria parasites, which have an obligate stage of sexual reproduction in the mosquito midgut.…”

High proportion of genome-wide homology and increased basal pvcrt levels in Plasmodium vivax late recurrences: a chloroquine therapeutic efficacy study

“…Another difficulty is the intrinsic logistical constraints linked to TES in settings where transmission is being drastically reduced, which questions the feasibility of classical in vivo studies under these epidemiological conditions. Such limitation could potentially be overcome once a CQR marker is validated and can be implemented into molecular surveillance, similarly to the ongoing surveillance of P. falciparum artemisinin resistance in Greater Mekong Subregion based on the pfkelch-13 gene (59).…”