Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study
Authors: John Woodford, Ashley Gillman, Peter Jenvey, Jennie Roberts, Stephen Woolley, Bridget E. Barber, Melissa Fernandez, Stephen Rose, Paul Thomas, Nicholas M. Anstey, James S. McCarthy
Journal: PLoS Medicine (2021)

Background Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum , which is known to undergo microvascular tissue sequestration, little is known about the behavior of P . vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. Methods and findings To identify organ-specific changes during the early stages of P . vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P . vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P . falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species ( n = 3 P . vivax ; n = 4 P . falciparum ). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume ( P . vivax : +28.8% [confidence interval (CI) +10.3% to +57.3%], P . falciparum : +22.9 [CI −15.3% to +61.1%]) and radiotracer uptake ( P . vivax : +15.5% [CI −0.7% to +31.7%], P . falciparum : +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P . vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow ( P . vivax : +4.6% [CI −15.9% to +25.0%], P . falciparum : +3.2% [CI −3.2% to +9.6%]) or liver ( P . vivax : +6.2% [CI −8.7% to +21.1%], P . falciparum : −1.4% [CI −4.6% to +1.8%]) following infection with either species. In participants with P . vivax , hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P . vivax infection compared to P . falciparum . The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. Conclusions PET/MRI indicated greater splenic tropism and metabolic activity in early P . vivax infection compared to P . falciparum , supporting the hypothesis of splenic accumulation of P . vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.