A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
Katharine A. Collins, … , Joerg J. Moehrle, James S. McCarthy
Katharine A. Collins, … , Joerg J. Moehrle, James S. McCarthy
Published February 11, 2020
Citation Information: J Clin Invest. 2020;130(6):2920-2927. https://doi.org/10.1172/JCI134923.
View: Text | PDF
Clinical Research and Public Health Infectious disease

A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions

Abstract

BACKGROUND Interventions that interrupt Plasmodium vivax transmission or eliminate dormant P. vivax liver-stage parasites will be essential for malaria elimination. Development of these interventions has been hindered by the lack of P. vivax in vitro culture and could be accelerated by a safe and reproducible clinical model in malaria-naive individuals.METHODS Healthy, malaria-naive adults were enrolled in 2 studies to assess the safety, infectivity, and transmissibility of a new P. vivax isolate. Participants (Study 1, n = 2; Study 2, n = 24) were inoculated with P. vivax–infected red blood cells to initiate infection, and were treated with artemether-lumefantrine (Study 1) or chloroquine (Study 2). Primary endpoints were safety and infectivity of the new isolate. In Study 2, transmission to mosquitoes was also evaluated using mosquito feeding assays, and sporozoite viability was assessed using in vitro cultured hepatocytes.RESULTS Parasitemia and gametocytemia developed in all participants and was cleared by antimalarial treatment. Adverse events were mostly mild or moderate and none were serious. Sixty-nine percent of participants (11/16) were infectious to Anopheles mosquitoes at peak gametocytemia. Mosquito infection rates reached 97% following membrane feeding with gametocyte-enriched blood, and sporozoites developed into liver-stage schizonts in culture.CONCLUSION We have demonstrated the safe, reproducible, and efficient transmission of P. vivax gametocytes from humans to mosquitoes, and have established an experimental model that will accelerate the development of interventions targeting multiple stages of the P. vivax life cycle.TRIAL REGISTRATION ACTRN12614000930684 and ACTRN12616000174482.FUNDING (Australian) National Health and Medical Research Council Program Grant 1132975 (Study 1). Bill and Melinda Gates Foundation (OPP1111147) (Study 2).

Authors

Katharine A. Collins, Claire Y.T. Wang, Matthew Adams, Hayley Mitchell, Greg J. Robinson, Melanie Rampton, Suzanne Elliott, Anand Odedra, David Khoury, Emma Ballard, Todd B. Shelper, Leonardo Lucantoni, Vicky M. Avery, Stephan Chalon, Joerg J. Moehrle, James S. McCarthy

×

Figure 1

Study design schematic.

Options: View larger image (or click on image) Download as PowerPoint
Study design schematic. Malaria-naive volunteers were inoculated with P....
Malaria-naive volunteers were inoculated with P. vivax–infected RBCs (pRBCs) on day 0 (D0). Asexual parasitemia and gametocytemia were evaluated from day 4 and continued until the end of study. Participants in Study 1 started artemether-lumefantrine treatment on day 8 (n = 2). Participants in Study 2 started chloroquine treatment on day 8 (n = 8), day 9 (n = 1), or 10 (n = 15). For Study 2, mosquito feeding assays were performed between day 6 and day 10 by direct feeding (allowing mosquitoes to feed on participants by live bite), or by membrane feeding on venous blood. D, day relative to inoculation (day 0); pRBC: P. vivax parasite–infected RBCs.