Ahmed Abdulridha Ameen Shlash, Abbas Hussein Obaid, Zahraa Basem
Background: Typhoid fever, caused by Salmonella Typhi. The rise of extensively drug-resistant (XDR) strains has reduced treatment options. Control depends on the Th1 immune response, especially the IL 12/IFN γ pathway. Objective: To assess antimicrobial susceptibility of S. Typhi isolates and compare serum IL 12α and IFN γ levels between typhoid patients and healthy controls in Najaf, Iraq. Methods: The cross sectional study included 30 blood culture confirmed S. Typhi patients from Najaf hospitals. Isolates were tested for antimicrobial susceptibility using VITEK 2 (AST GN card). Serum IL 12α and IFN γ were measured by ELISA in patients and 30 matched controls. Data were analyzed in SPSS. p < 0.05 was considered significant. Results: Isolates retained the highest susceptibility to imipenem (83.3%), meropenem (80.0%), and trimethoprim-sulfamethoxazole (60.0%), with low susceptibility to third-generation cephalosporins and azithromycin (≤20%). Patients and controls were well matched for age (17.6 ± 7.2 vs 18.7 ± 8.4 years, p = 0.58) and sex (56.7% male in both groups, p = 1.00). Both cytokines were significantly higher in patients than controls: IFN-γ (111.99 ± 26.55 vs 62.97 ± 11.94 ng/mL; p < 0.001) and IL-12α (382.29 ± 29.45 vs 253.56 ± 16.01 ng/L; p < 0.001). Within patients, IFN-γ and IL-12α were positively correlated (Spearman r = 0.41, p = 0.023). ROC curve analysis showed excellent discrimination between patients and controls for both markers (IL-12α AUC = 0.992; IFN-γ AUC = 0.982). Conclusions: S. Typhi isolates remained most susceptible to carbapenems, with high resistance to cephalosporins and azithromycin. Larger studies linking resistance phenotypes to cytokine responses and validating cutoffs across diverse fevers are required.