Plasma haem oxygenase-1 and interleukin-6 as adjunct host biomarkers associated with malaria

Malaria pathogenesis involves both parasite burden and host inflammatory and oxidative stress responses that contribute to haematological alterations. Full blood count (FBC)-derived indices have been explored as accessible surrogate biomarkers, reflecting systemic inflammatory changes; however, they provide limited mechanistic insight into underlying haem-driven oxidative stress pathways. Haem oxygenase-1 (HO-1) reflects cellular responses to free haem, while interleukin-6 (IL-6) mediates systemic inflammation. However, their combined role in relation to parasitaemia and haematological alterations in endemic populations remains insufficiently defined. This study evaluated plasma HO-1 and IL-6 as complementary host-response biomarkers in a hospital-based malaria-endemic population.

This cross-sectional study was conducted at Covenant University Medical Centre (CUMC), Canaanland, Ota, Ogun State, Nigeria. A total of 647 individuals were screened, and 304 participants with complete microscopy and haematological data were retained in the analytical cohort (152 microscopy-positive and 152 microscopy-negative). An integrated biomarker subset of 40 participants with matched plasma samples and complete laboratory data was used for ELISA, correlation, and receiver operating characteristic (ROC) analyses. Group comparisons used Mann-Whitney U and Kruskal-Wallis tests, categorical variables were compared using chi-square or Fisher exact tests, and associations were assessed using Spearman correlation.

In the analytical cohort, microscopy-positive participants had lower haemoglobin, haematocrit, red-cell count, mean cell indices, and platelet counts, together with higher temperature and white-cell counts than microscopy-negative participants (all p< 0.001 for the major contrasts). Fever and anaemia were also substantially more frequent in microscopy-positive participants. In the biomarker subset, IL-6 was significantly higher in malaria-positive participants than malaria-negative participants (median 141.28 vs 106.58 pg/mL; p = 0.027), whereas HO-1 showed a non-significant upward shift (230.98 vs 193.73 ng/mL; p = 0.131). IL-6 correlated positively with HO-1 (rho = 0.702, p< 0.001), parasitaemia (rho = 0.387, p = 0.015), and temperature (rho = 0.432, p = 0.006), and negatively with haemoglobin (rho = -0.417, p = 0.008). ROC analysis showed moderate discriminatory performance for IL-6 and lower performance for HO-1. IL-6 yielded an AUC of 0.709 (95% CI 0.531-0.874), with sensitivity of 72.7% and specificity of 76.5% at the Youden-optimal threshold. HO-1 yielded an AUC of 0.641 (95% CI 0.440-0.826), while the combined IL-6 + HO-1 model yielded an AUC of 0.687 (95% CI 0.461-0.886).

IL-6 showed better discriminatory performance than HO-1 in this cohort, while HO-1 demonstrated only modest and non-significant differences between groups. These findings suggest that IL-6 may be a more informative adjunct inflammatory marker in malaria, whereas the role of HO-1 requires further validation in larger studies.