Serum Tumour Necrosis Factor-Alpha and Interleukin-4 as Immunological Indicators of hwp1-Confirmed Candida albicans Respiratory Tract Infection: A Case-Control Study from Wasit Province, Iraq

Introduction: Candida albicans is a critical-priority fungal pathogen and an increasingly recognised cause of respiratory tract infection in hospitalised and immunocompromised patients. Tumour necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) exert opposing influences on antifungal immunity, yet their combined behaviour in molecularly confirmed respiratory candidiasis remains poorly defined. Aim of this study is to quantify serum TNF-α and IL-4 in Iraqi patients with hwp1-confirmed C. albicans respiratory infection and to evaluate their diagnostic performance. Methods: A case-control study enrolled 200 patients with respiratory tract infection and 100 age- and sex-matched healthy controls at three facilities in Al-Kut, Wasit province, Iraq, between December 2025 and April 2026. Isolates were identified by conventional mycology and the VITEK®2 Compact system, then confirmed by polymerase chain reaction targeting the hwp1 gene. Serum cytokines were measured by sandwich ELISA, and diagnostic accuracy was assessed by receiver operating characteristic analysis. Results: C. albicans was cultured from 42 patients (21.0%) and from no control (P < 0.0001); 37 isolates (88.1%) yielded the 941 bp hwp1 amplicon. TNF-α was markedly higher in patients (156.6 ± 38.20 versus 34.85 ± 14.73 ng/L) as was IL-4 (56.59 ± 17.19 versus 17.78 ± 6.783 ng/L; both P < 0.0001). Both cytokines achieved an area under the curve of 1.000 with 100% sensitivity and specificity. TNF-α correlated inversely with procalcitonin among patients (r = −0.339, P = 0.028). Conclusion: Respiratory candidiasis is accompanied by simultaneous pro-inflammatory and Th2 activation. Combined measurement of TNF-α and IL-4 with hwp1 detection warrants evaluation as a diagnostic adjunct.