Background Malaria and typhoid fever are known to cause severe morbidity and mortality if miss-treated or left untreated. The oxidant/antioxidant and immune responses to these diseases involve a complex interplay of stress-mediating inflammatory cytokines which orchestrate a coherent response that leads to pathogen clearance and recovery. This study investigated the stress-mediated cytokine profiles in patients attending the Obala District Hospital, Yaoundé, Cameroon and diagnosed with malaria and/or typhoid fever. Methods In this cross-sectional observational study, we measured the levels of cortisol and stress-mediating inflammatory cytokines in peripheral blood samples collected from 55 malaria and/or typhoid fever patients, along with a healthy control group (n = 15) using commercial ELISA kits. The psychological stress response of the voluntary participants over the past 30 days was assessed using a 10-item Perceived Stress Scale (PSS) questionnaire. Results Our findings revealed unique stress-mediating cytokine patterns in each studied group. The baseline cortisol levels were significantly higher in all patient groups when compared to the control (p<0.001). The overall mean cortisol level in the typho-malaria group was over 2.5 times greater than that of the control (43.27µg/dl versus 17.01µg/dl). Also, the concentrations of IL-1β (p<0.01), IL-2 (p<0.0001), TNF-α (p<0.0001), IFN-γ (p<0.0001) and IL-6 (p<0.01) were significantly upregulated in patients with malaria and typhoid comorbidity, comparing to mono-infections and healthy controls. In contrast, aside from the significant increase in IFN-γ (p<0.0001) and IL-10 (p<0.01), there was no significant change in the concentration of IL-4 (p=0.11), and IL-6 (p=0.14) in the malaria group compared to the control. However, those with typhoid fever displayed a significant upregulation in IL-2 (p<0.001), IL-4 (p<0.05) and IL-10 (p<0.05). Interestingly, there was a positive correlation between perceived stress scores and IL-2 (r = 0.365, p=0.002), IFN-γ (r = 0.248, p=0.03) and IL-6 (r = 0.412, p=0.0001) in the typho-malaria group. Beside IL-6, no significant correlation was found between stress index and the other anti-inflammatory cytokines IL-4 (r = 0.204, p=0.09) and IL-10 (r = 0.153, p=0.20) in coinfected individuals. Conclusion These results suggest that stress response may play a crucial role in shaping the inflammatory landscape during malaria and typhoid fever. Understanding the immunopathogenesis of these diseases could potentially pave the way for the development of novel therapeutic strategies targeting the stress-cytokine axis.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study protocol was reviewed and approved by three different ethical review committees and regulatory authorities: the Centre Regional Ethics Committee for Human Health Research (Ref. #: 0226/CRERSHC/2022), the Centre Regional Delegation of Public Health under the ministry of Public Health (Ref. #: 1392/AAR/MINSANTE/SG/DRSPC), and the Cameroon Baptist Convention Institutional Review Board (Ref #: IRB2023-26). Written informed consent was obtained from all participants before enrollment, confidentiality and privacy was maintained, and any potential risks or adverse effects were greatly minimized.

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