Endogenous reactivation cases identified by whole genome sequencing of Mycobacterium tuberculosis: Exploration of possible causes in Latvian tuberculosis patients

Abstract

Background

The recurrence of tuberculosis (TB) continues to place a significant burden on patients and TB programs worldwide. Repeated TB episodes can develop either due to endogenous reactivation of previously treated TB or exogenous reinfection with a distinct strain of Mycobacterium tuberculosis (Mtb). Determining the precise cause of the recurrent TB episodes and identifying reasons for endogenous reactivation of previously successfully treated patients is crucial for introducing effective TB control measures.

Methods

Here, we aimed to provide a retrospective individual analysis of the clinical data of pulmonary TB patients with assumed endogenous infection reactivation based on WGS results to identify the reasons for reactivation. Patient medical files were reviewed to describe the provoking factors for endogenous reactivation.

Results

In total, 25 patients with assumed endogenous TB reactivation were included in the study group, and 30 patients with one TB episode during the study period were included in the control group. There were no statistically significant differences identified between studied patient groups in patients age (t₍₅₃₎ = −1.53, p = 0.13), body mass index (t₍₅₃₎ = 0.82, p = 0.42), area of residency (χ²_(1;55) = 0.015, p = 0.9), employment status (χ²_{(1;55) =} 0.076, p = 0.78) and presence of comorbidities (χ²_(1;55) = 3.67, p = 0.78). Study group patients had statistically significantly more frequently positive sputum smear microscopy results (χ²_(1;55) = 8.72, p = 0.0031), longer time to sputum smear (t₍₃₁₎ = −2.2, p = 0.036) and sputum culture conversion (W ₍₅₅₎ = 198.5, p = 0.0029). Smoking was statistically significantly (χ²_(1;55) = 5.77, p = 0.016) more frequently represented among study group patients. The median treatment duration for drug susceptible TB was 6 months in both in the control group (IQR 6–6) and among study group patients (IQR 6–7.75). The median treatment duration for multidrug-resistant TB was 20 months (IQR 17–23) in the control group and 19 months (IQR 16–19) in the study group patients.

Conclusion

Positive SSM for acid-fast bacteria, delayed time to sputum smear and sputum culture conversion, smoking, and incomplete therapy in the study group patients with multidrug-resistant TB should be considered as potential reasons for reactivation in recurrent TB patient group in our study.