1912–2012: a century of research on Plasmodium vivax in vitro culture

• Thus far, no reliable protocol for Plasmodium vivax in vitro culture has been established.
• Low P. vivax density in patients is a major obstacle for starting a culture.
• Successful invasion and drug tests are important advances in P. vivax research.
• Stem cell-derived reticulocytes could be a reliable source of target cells.
• An international consortium for concerted efforts on P. vivax culture is needed.

The development of a continuous Plasmodium vivax blood cycle in vitro was first attempted 100 years ago. Since then, and despite the use of different methods, only short-term cultures have been achieved so far. The available literature has been reviewed in order to provide a critical overview of the currently available knowledge on P. vivax blood cycle culture systems and identify some unexplored ways forward. Results show that data accumulated over the past century remain fragmented and often contradictory, making it difficult to draw conclusions. There is the need for an international consortium on P. vivax culture able to collect, update, and share new evidence, including negative results, and thus better coordinate current efforts towards the establishment of a continuous P. vivax culture.