Plasmodium vivax in vitro continuous culture: the spoke in the wheel

Abstract

Understanding the life cycle of Plasmodium vivax is fundamental for developing strategies aimed at controlling and eliminating this parasitic species. Although advances in omic sciences and high-throughput techniques in recent years have enabled the identification and characterization of proteins which might be participating in P. vivax invasion of target cells, exclusive parasite tropism for invading reticulocytes has become the main obstacle in maintaining a continuous culture for this species. Such advance that would help in defining each parasite protein’s function in the complex process of P. vivax invasion, in addition to evaluating new therapeutic agents, is still a dream. Advances related to maintenance, culture medium supplements and the use of different sources of reticulocytes and parasites (strains and isolates) have been made regarding the development of an in vitro culture for P. vivax; however, only some cultures having few replication cycles have been obtained to date, meaning that this parasite’s maintenance goes beyond the technical components involved. Although it is still not yet clear which molecular mechanisms P. vivax prefers for invading young CD71+ reticulocytes [early maturation stages (I–II–III)], changes related to membrane proteins remodelling of such cells could form part of the explanation. The most relevant aspects regarding P. vivax in vitro culture and host cell characteristics have been analysed in this review to explain possible reasons why the species’ continuous in vitro culture is so difficult to standardize. Some alternatives for P. vivax in vitro culture have also been described.

Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle

“…This contributes to the fact that Plasmodium vivax remains a significant global health problem, putting approximately one-third of the global population at risk for infection and resulting in an estimated 7.51 million reported cases in 2017 [3]. Furthermore, relative to other malaria species, P. vivax has many unique and challenging biological qualities including the presence of spontaneously reactivating dormant liver stages (hypnozoites), strong preference for invading the youngest circulating host red blood cells (reticulocytes), and the rapid development of transmissible gametocytes often before clinical symptoms present [4].…”

Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates

“…Unlike P. falciparum, scientific progress towards understanding P. vivax has been minimal, partly due to the inability to maintain continuous cultures for its propagation. Although efforts in this direction have been promising [16] a standard in vitro culture for P. vivax has not yet been established. Hence, scientists have had to rely on clinical samples and animal models [17][18][19][20][21] for the study of P. vivax, further delaying the identification of new molecules and their functional characterization.…”

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

“…Those are key questions, and answering them will be critical to develop strategies to prevent the emergence of Duffy-negative infections. No clear answer has been made yet, mainly because of the inherent difficulty in working on P. vivax as there is still no in vitro continuous culture available for this species [60,61]; however, some hypothesis can be raised on the parasite and/or human sides.…”