Age and sex specific biomarker profiling of malaria infection in Ghana: Implications for demographic-tailored clinical management

Abstract

Malaria, predominantly caused by Plasmodium falciparum in sub-Saharan Africa, drives significant haematological alterations. These alterations can serve as valuable biomarkers for disease monitoring and prognosis. However, age- and sex-specific variations in these biomarkers remain poorly characterized, limiting personalized clinical management. We evaluated the age- and sex-related differences in haematological and inflammatory biomarkers among 100 patients with microscopy-confirmed P. falciparum malaria in Ghana. A cross-sectional comparative study was conducted from January to May 2018. Full blood counts (RBC, Hb, HCT, platelets, WBC subsets) were measured using the Sysmex XS-1000i analyzer, and inflammatory indices such as platelet-monocyte ratio were calculated. Kruskal-Wallis and Mann-Whitney U tests were employed to compare variations across age groups and sexes. Spearman correlation, multivariable quantile regression, and interaction analyses examined relationships between parasite density and biomarkers, with age and sex as covariates. P-values <0.05 were considered statistically significant. Males exhibited higher RBC counts (median 4.72 vs. 4.06 × 10¹²/L, p<0.001), haemoglobin (13.75 vs. 11.10 g/dL, p<0.001), and haematocrit (38.40% vs. 31.80%, p<0.001), while females had elevated platelets (157.50 vs. 115.50 × 10⁹/L, p=0.011) and platelet-monocyte ratios (p=0.025). Younger participants (4–25 years) displayed lower RBC indices (RBC: 4.29 vs. 4.71 × 10¹²/L, p=0.008; RDW-CV: 13.10% vs. 14.20%, p=0.017) and higher lymphocyte-monocyte ratios (LMR: 2.00 vs. 1.27, p=0.006) compared to older groups. Higher parasite density was independently associated with reductions in platelet count, haematocrit, haemoglobin, mean corpuscular haemoglobin, eosinophil count, mean corpuscular volume, and platelet-monocyte ratio (all p<0.05). Significant interactions revealed that the effect of parasite density on haemoglobin and mean corpuscular haemoglobin concentration differed by sex, while its effect on systemic inflammatory response index differed by age. Significant age- and sex-specific variations in haematological and inflammatory biomarkers underscore the need for demographic-tailored reference ranges in malaria management. The independent associations between parasite density and key biomarkers, modified by demographic factors, highlight the importance of considering both parasite burden and patient demographics. These findings advocate integrating sex- and age-specific biomarkers into clinical protocols to optimize diagnostics and therapeutic strategies in endemic regions.