pLDH to identify severity in imported malaria: Implementing smartphone video analysis for rapid clinical decision-making

Malaria is the main parasitic disease-causing death in endemic and non-endemic regions. Imported malaria cases face an elevated risk of severe disease, but non-specific clinical presentations and limited clinician experience often delay diagnosis, prognosis and treatment. Quantification of parasite biomarkers by lateral flow assays (LFAs) could address this challenge. We conducted a retrospective cohort study of patients with imported Plasmodium falciparum malaria and non-malarial fevers. Using a bead-based multiplex immunoassay and commercial LFAs, we evaluated the diagnostic and severity assessment capabilities of two parasite biomarkers: Plasmodium falciparum histidine-rich protein-2 (PfHRP2) and pan-specific lactate dehydrogenase (pan-pLDH). To improve the speed and objectivity of LFA interpretation, we used smartphone-based image- and video-analysis. The bead-based immunoassay showcased an excellent diagnostic performance for PfHRP2 and pan-pLDH, while revealing PfHRP2 and pan-pLDH as promising severity biomarkers. On LFAs, PfHRP2 maintained perfect diagnostic accuracy, compared to pan-pLDH. Notably, pan-pLDH excelled in identifying severe malaria cases, outperforming PfHRP2. Smartphone-based video-analysis reduced testing time to under 6 min and maintained pan-pLDH's performance in detecting severe malaria. Our study underscores the potential of pan-pLDH as a valuable biomarker for severity assessment in imported Plasmodium falciparum malaria cases, particularly in non-endemic settings where rapid clinical decisions are critical.