Abstract
Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falciparum induced blood stage malaria (IBSM) infection, and compared results to individuals with P. vivax infection, in whom coma is rare. Seven healthy, malaria-naïve participants underwent imaging at baseline, and at early symptom onset a median 9 days following inoculation (n = 4 P. falciparum, n = 3 P. vivax). Participants with P. falciparum infection demonstrated marked lability in radiotracer uptake across all regions of the brain, exceeding expected normal variation (within subject coefficient of variation (wCV): 14.4%) compared to the relatively stable uptake in participants with P. vivax infection (wCV: 3.5%). No consistent imaging changes suggestive of microvascular dysfunction were observed in either group. Neuroimaging in early IBSM studies is safe and technically feasible, with preliminary results suggesting that differences in brain tropism between P. falciparum and P. vivax may occur very early in infection.
| Original language | English |
|---|---|
| Article number | 5696 |
| Pages (from-to) | 1-8 |
| Number of pages | 8 |
| Journal | Scientific Reports |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 2022 |
Bibliographical note
Funding Information:We would like to thank Louise Campbell and Peta Gray from HIRF for their help co-ordinating the imaging of participants and Dr Manoj Bhatt at the Department of Nuclear Medicine, RBWH for serving as the imaging medical monitor. Marita Prior at the Department of Radiology, RBWH for her help co-ordinating reporting of imaging, study staff at Q-Pharm Pty Ltd for their help co-ordinating IBSM participant exploratory study involvement, Medicines for Malaria Venture for encouraging investigator-initiated studies and all participants for volunteering their time.
Funding Information:
This project was supported by a HIRF Seed Funding Grant, Metro North Hospital and Health Service (J.W) and by the Australian National Health and Medical Research Council (J.S.M #1,135,955, #1,037,304, #1,132,975, and N.M.A #1,135,820, 1,098,334). The clinical trials contributing participants were funded by the Australian National Health and Medical Research Council (J.S.M #1,132,975), the Bill and Melinda Gates Foundation (J.S.M OPP1111147) and the Global Health Innovative Technology Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
