Distinctive Risk Factor Profiles for Extrapulmonary Tuberculosis: A Case-Control Study in a High-Risk Region of Iran – 2024 - 2025

Background: The differential risk factors associated with extrapulmonary tuberculosis (EPTB) compared to pulmonary tuberculosis (PTB) remain inadequately characterized, particularly in high-burden and culturally distinct settings such as Sistan, Iran. Objectives: This study aimed to identify and compare the demographic and clinical determinants of EPTB and PTB in this understudied region. Methods: A case-control study was conducted from January 2024 to March 2025. A total of 400 patients (200 confirmed EPTB cases and 200 PTB cases) were randomly selected from health centers in Zabol. Data on demographic characteristics, site of infection, smoking status, alcohol consumption, diabetes history, immunosuppressive drug use, and BCG vaccination status were extracted from electronic medical records. Multivariate logistic regression analysis was used to identify independent factors associated with EPTB. Data were analyzed using SPSS version 22. Results: The mean age of EPTB patients was significantly lower than that of PTB patients (42.38 ± 17.49 vs. 49.71 ± 18.85 years, P < 0.001). Female gender (aOR = 3.27, 95% CI: 2.02 - 5.29, P < 0.001) and smoking (aOR = 1.84, 95% CI: 1.15 - 2.97, P = 0.012) were identified as independent risk factors for EPTB. Conversely, increasing age was found to be a protective factor (aOR = 0.98 per year, 95% CI: 0.96 - 0.99, P < 0.001). Lymphatic involvement was the most common EPTB site (49.5%). No significant associations were found for alcohol consumption, diabetes, immunosuppressive drug use, or BCG vaccination status with EPTB presentation. Conclusions: This study reveals a distinctive risk profile for EPTB in Southeast Iran, characterized by younger age, female gender, and smoking. The findings challenge some global narratives regarding risk factors such as diabetes and highlight the importance of regional context. Public health strategies, including targeted screening and awareness programs for young women, should be prioritized to improve early diagnosis and management of EPTB in this high-risk population.