Systemic T-Cell Activation and Exhaustion Phenotypes in Pediatric Patients Correlated with Malarial and Intestinal Helminthic Co-Infections in Bauchi State, Nigeria
DOI:
https://doi.org/10.33003/fjs-2026-1012-5222Keywords:
Co-infection, Helminthiasis, Malaria, PediatricAbstract
In sub-Saharan Africa, concurrent infections with Plasmodium falciparum and soil-transmitted helminths (STHs) present a complex immunological challenge to the developing pediatric immune system. Immunophenotyping of cellular response profiles during co-infection remains scarce within Northern Nigeria. This study evaluated the phenotypic shifts in circulating CD4+ and CD8+ T-cell activation and exhaustion markers among children co-infected with malaria and helminthic infection in Bauchi State. A cross-sectional survey conducted among 442 pediatric participants (aged 5–12 years) stratified into four cohorts: uninfected controls (n=120), P. falciparum mono-infection (n=115), helminth mono-infection (n=105), and co-infected (n=102). Parasitological validation was via light microscopy, Kato-Katz concentration, and multiplex PCR. Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed using multi-color flow cytometry to quantify activation (CD38/HLA-DR) and exhaustion (PD−1/Tim−3) marker expression. Co-infected children exhibited lower geometric mean malarial densities compared to malaria mono-infected peers (2,450 vs. 5,890 parasites/μL, p=0.002). Prevalence of STHs indicated Ascaris lumbricoides 54.9%, Hookworm 32.4%, and Trichuris trichura 12.7%. However, dual activation markers (CD38+HLA-DR+) were higher among co-infected cohort on both CD4+ (18.9%) and CD8+ (34.5%) T-cells (p<0.001). Cellular exhaustion defined by dual expression of PD−1+Tim−3+, peaked sharply in co-infected patients (CD8+:15.4%), supassed malaria (6.2%) and helminth (5.9%) mono-infections (p<0.001). Multivariate logistic regression identified co-infection as a dominant independent predictor of advanced T-cell exhaustion (AOR=4.12, 95% CI: 2.34–7.28). Chronic co-parasitism suppresses acute malarial replication but induces robust systemic T-cell hyper-activation, accelerating progression toward functional cellular exhaustion.
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Copyright (c) 2026 Kyauta Mallam Thomas, Anthony John, Tabitha Silas, Mispha Titus, David Ochiobi, Moses Ashem, Ezekiel Bitet, Joshua Gyang
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