Cerebral malaria is a complication of Plasmodium falciparum infection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We show by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) by Plasmodium parasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for ECM.
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Article Synopsis
- Malaria has surged in sub-Saharan Africa due to disruptions from the Covid-19 pandemic, leading to severe cases like cerebral malaria and acute kidney injury.
- A 22-year-old male from Chad, who presented with confusion and had a history of travel to an endemic area, was initially misdiagnosed but later confirmed to have malaria with severe symptoms.
- Successful treatment included intravenous artesunate and hemodialysis, and the patient was discharged after 20 days, highlighting the need for quick diagnosis and effective management of malaria complications.
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