Abstract
Basic science holds enormous power for revealing the biological mechanisms of disease and, in turn, paving the way toward new, effective interventions. Recognizing this power, the 2011 Research Agenda for Malaria Eradication included key priorities in fundamental research that, if attained, could help accelerate progress toward disease elimination and eradication. The Malaria Eradication Research Agenda (malERA) Consultative Panel on Basic Science and Enabling Technologies reviewed the progress, continuing challenges, and major opportunities for future research. The recommendations come from a literature of published and unpublished materials and the deliberations of the malERA Refresh Consultative Panel. These areas span multiple aspects of the Plasmodium life cycle in both the human host and the Anopheles vector and include critical, unanswered questions about parasite transmission, human infection in the liver, asexual-stage biology, and malaria persistence. We believe an integrated approach encompassing human immunology, parasitology, and entomology, and harnessing new and emerging biomedical technologies offers the best path toward addressing these questions and, ultimately, lowering the worldwide burden of malaria.
Highlights
Summary pointsThe recent development of multiple in vitro systems for studying malaria biology has helped deepen our understanding of the disease
Since the first agenda for malaria eradication was published in 2011 [1], there have been many significant developments in basic science, including an enhanced understanding of parasite biology as well as mosquito biology (Table 1). Some of these advances could not have been predicted 5 years ago, such as the use of mouse models engrafted with human liver to advance the biology of liver-stage parasites and the development of powerful genome-editing capabilities based on clustered regularly interspaced short palindromic repeats/associated protein-9 nuclease (CRISPR/Cas9) technology
We focus here on these and other crucial areas—deficiencies in basic science research and the lack of enabling technologies—that currently limit our progress towards malaria elimination and eradication
Summary
The recent development of multiple in vitro systems for studying malaria biology has helped deepen our understanding of the disease. Research remains hampered by a lack of in vitro models that can probe key aspects of malaria (e.g., gametocyte development in Plasmodium vivax, fertilization, ookinete biology, parasite–midgut interactions, human hepatocyte infection) and generate biological materials (i.e., infectious sporozoites) for laboratory study. Developing the necessary cell lines and other in vitro culture tools to propel these studies represent important areas for future research. With the emergence of widespread insecticide resistance in mosquito populations, there is a strong need to bring basic research in mosquito biology back into the malaria. Important areas of future research include the use of gene-drive strategies and other gene-manipulation technologies; metabolomics-based approaches for biomarker discovery; structural vaccinology, novel technology platforms, and the use of novel adjuvants to improve vaccine design; and high-throughput approaches to facilitate drug discovery and screening
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