Pediatric malaria in a non-endemic European setting: clinical patterns, laboratory markers, and the ambiguous role of immunity

Purpose: Pediatric malaria in non-endemic regions poses diagnostic and management challenges, particularly in the context of migration and international travel. This study aimed to characterize clinical, laboratory, and epidemiological features of pediatric malaria in a European non-endemic setting and to evaluate whether presumed immune status influences disease severity. Methods: We conducted a retrospective study of children diagnosed with malaria at a tertiary center in Milan, Italy (2004–2024). Patients were stratified by presumed immune status into Non-Immune (NI) (Italian-born) and Presumed-Immune (PI) (foreign-born or frequent travelers to endemic areas). Differences between groups were analyzed using the Mann–Whitney U and Fisher’s exact tests. Associations between laboratory markers (serum sodium, C-reactive protein [CRP], and platelet count) and clinical outcomes (length of hospital stay and fever duration) were evaluated using Spearman’s rank correlation (ρ). Results: Seventy-four cases were included (59% male; median age 9.0 years). Patients were stratified into Non-Immune (NI, 47.3%) and Presumed-Immune (PI, 52.7%) groups; the PI group was significantly older (p < 0.001). P. falciparum (62.2%) and P. vivax (27%) were the main species. Severe malaria (WHO 2015 criteria) occurred in 23% of patients, with no significant difference between NI and PI groups (p = 0.783). Spearman’s analysis showed that serum sodium levels were inversely associated with length of hospital stay (ρ = – 0.284, p = 0.020), while CRP levels correlated positively with fever duration (ρ = 0.256, p = 0.033) and strongly negatively with platelet counts (ρ = – 0.585, p < 0.001). A significant therapeutic shift occurred post-2015, with intravenous artesunate replacing quinine as the gold standard treatment for severe malaria. Conclusion: Pediatric malaria severity and biochemical profiles appeared largely independent of presumed immune status in non-endemic settings. Clinical outcomes were more closely associated with admission laboratory markers—particularly hyponatremia and elevated CRP levels-than with geographic proxies of immunity. The adoption of intravenous artesunate as first-line therapy after 2015 was associated with improved clinical management. These findings highlight the need for careful monitoring of all pediatric malaria cases, regardless of prior exposure, as traditional classifications based on presumed immunity may not reliably predict disease severity.