Determinants of tuberculosis site among 1035 cases in Frankfurt, 2008-2023: does lineage matter?

Abstract Extrapulmonary tuberculosis (EPTB) presents with nonspecific symptoms which can pose a diagnostic challenge. Currently, there are no clear predictors for EPTB. We aimed to identify these factors for better diagnosis and disease control. We included tuberculosis cases reported in Frankfurt from 2008-2023, with available clinical and whole genome sequencing data. According to WHO criteria, cases with pulmonary or combined pulmonary and extrapulmonary symptoms were categorised as pulmonary tuberculosis, while exclusively extrapulmonary symptoms were categorised as extrapulmonary tuberculosis. We assessed the association between EPTB and M. tuberculosis lineage, comorbidities and demographic characteristics using logistic regression, calculating crude and adjusted odds ratios (aOR). Of the 1035 reported tuberculosis cases, 272 had exclusively extrapulmonary disease and 136 had both pulmonary and extrapulmonary disease. In the univariable analysis, lineages 1 and 3 were significantly associated with extrapulmonary disease compared to lineage 4. However, this association was not observed in the multivariable analysis. In the final regression model, females were more likely to develop EPTB than men (aOR: 1.65, CI: 1.19-2.27). The odds of developing extrapulmonary disease were higher among patients born in the South-East Asian (aOR: 6.48, CI: 3.72-11.43) and Eastern Mediterranean (aOR: 5.54, CI: 3.41-9.11) than in other regions. Among the comorbidities, diabetes was found to be negatively associated with extrapulmonary disease (aOR: 0.50, CI: 0.26-0.91). Our results indicate that host factors such as geographic origin and sex are stronger predictors for extrapulmonary presentation of tuberculosis than a specific lineage. We recommend increasing physicians’ awareness of the nonspecific presentation of EPTB and adapting screening programmes, particularly for patients from South-East Asian and Eastern Mediterranean regions to foster more effective tuberculosis control measures. Key messages • Our study highlights the importance of considering host factors in predicting extrapulmonary tuberculosis, indicating their stronger influence compared to specific M. tuberculosis lineages. • Increased physicians’ awareness of the nonspecific symptoms of EPTB and targeted screening programs for high-risk populations are crucial for enhancing tuberculosis control measures.