Procalcitonin in malaria: A promising but complex biomarker

Malaria remains a leading cause of acute febrile illness in endemic regions, where early differentiation between severe malaria and bacterial sepsis is frequently challenging due to overlapping clinical features. In addition, there is a lack of robust, widely validated biomarkers that reliably reflect disease severity and prognosis, limiting timely risk stratification and optimal clinical management. Procalcitonin (PCT), historically regarded as a biomarker specific to bacterial infections and commonly used to guide antibiotic stewardship, has increasingly been evaluated for its potential role in malaria. Its elevation in malaria is thought to reflect the intensity of the host inflammatory response, driven by cytokine release and high parasitemia, rather than direct pathogen specificity. Consequently, PCT should be viewed as a nonspecific host-response biomarker with possible prognostic or predictive value, complementing but not replacing pathogen-based diagnostic markers in malaria. Most investigations of PCT in malaria have focused on its utility in assessing disease severity and prognosis, particularly in nonendemic settings where clinicians have limited experience managing malaria and where PCT is often used to guide treatment decisions in imported cases. A French prospective multicenter cohort study demonstrated significantly higher PCT levels in patients with severe malaria compared with uncomplicated disease; however, plasma albumin and soluble triggering receptor expressed on myeloid cells were identified as more informative markers of severity.[1] In contrast, a study from Cameroon, an endemic region, reported comparable PCT levels in children with uncomplicated and complicated malaria, suggesting limited discriminatory value in that setting.[2] Conversely, a more recent study from India found significantly higher PCT concentrations in patients with severe Plasmodium falciparum malaria compared with uncomplicated cases, highlighting regional variability in findings.[3] A recent meta-analysis further underscored this heterogeneity, showing that although pooled mean PCT levels tended to be lower in uncomplicated malaria than in severe disease, this difference was not consistently maintained when random-effects models were applied. These findings suggest that PCT alone lacks sufficient reliability to distinguish between severe and uncomplicated malaria or to differentiate malaria from nonmalarial febrile illness. Rather, its clinical utility may lie in combination with other inflammatory, metabolic, or organ-dysfunction markers.[4] A review published in this issue likewise reported that although PCT levels are generally higher in adults with severe malaria compared with nonsevere disease, its overall diagnostic and prognostic accuracy remains variable. Considerable heterogeneity in reported sensitivity, specificity, and proposed cutoff thresholds appears to stem from differences in study design, case definitions of severity, assay methodologies, and inadequate control for confounding factors – particularly the presence of concomitant bacterial infection.[5] Collectively, the available evidence does not support the use of PCT as an independent or definitive biomarker of malaria severity. Rather, PCT may serve a supportive role in specific clinical scenarios, such as early risk stratification or in the assessment of possible bacterial co-infection in febrile patients. Future investigations should prioritize large, prospective, methodologically robust studies employing standardized laboratory techniques and uniform severity criteria. Such studies are needed to establish malaria-specific PCT cutoff values and to determine its incremental clinical utility when used in combination with other biomarkers and integrated with established clinical and laboratory parameters. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.