Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analyses
3. Results
3.1. Patients Characteristics
3.2. Clinical and Diagnostic Differences Between Isolated Pulmonary and Extrapulmonary/Disseminated Tuberculosis: A Comparative Analysis
3.3. Diagnostic Yield and Procedures in Extrapulmonary/Disseminated Tuberculosis
3.4. Diagnostic Performance of Microbiological MTB Detection Methods Across Various Specimen Types
4. Discussion
- Enhanced Diagnostic Strategies:
- Improved Treatment Approaches:
- Strengthening Follow-up:
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient Characteristics (n = 194) | ||
---|---|---|
General characteristics | Age, years, median (min, max) | 41 (16–89) |
Gender, male, total (%) | 121 (62.4%) | |
Country of origin, absolute (%) | Germany | 50 (25.8) |
Other than Germany ** | 144 (74.2) | |
WHO geographic regions of origin | Europe | 93 (47.9%) |
Africa | 34 (17.5%) | |
Eastern Mediterranean | 32 (16.5%) | |
Southeast Asia | 18 (9.3) | |
Americas | 2 (1%) | |
Unknown | 15 (7.7%) | |
Pre-existing conditions, absolute (%) | Diabetes mellitus | 19 (9.8%) |
Cardiac disease | 42 (21.6%) | |
Pulmonary disease | 28 (14.4%) | |
HIV infection | 18 (9.3) | |
Replicating hepatitis C infection | 8 (4.1) | |
Replicating hepatitis B infection | 5 (2.6) | |
Solid organ transplantation | 7 (3.6) | |
Hematologic disease | 6 (3.1) | |
Autoimmune disease | 16 (8.2) | |
Immunosuppressive therapy | 36 (18.6) | |
Site of TB infection, absolute (%) | Isolated pulmonary manifestation | 98 (50.5%) |
Disseminated infection (more than one site of inception) | 41 (21.1%) | |
Lymph node | 31 (16%) | |
Bone and joint | 10 (5.2%) | |
Abdominal | 5 (2.6%) | |
Urogenital | 2 (1%) | |
Intestinal | 2 (1%) | |
Cardiac | 2 (1%) | |
Soft tissue | 2 (1%) | |
Cerebral/meningitis | 1 (0.5%) | |
Tuberculosis drug resistance, absolute (%) | MDR tuberculosis | 10 (5.2) |
Pre-XDR tuberculosis | 3 (1.5) | |
XDR tuberculosis | 3 (1.5) | |
Therapy outcome | Not evaluated (lost to follow-up) | 119 (61.3) |
Sustained treatment success | 55 (28.4%) | |
Deceased | 3 (1.5%) | |
Therapy ongoing | 17 (8.8%) |
Isolated Pulmonary Tuberculosis (n = 98) | Extrapulmonary/Disseminated Tuberculosis (n = 96) | p-Value | |
---|---|---|---|
Age, years, median (min–max) | 44.5 (16–85) | 35 (18–89) | 0.24 |
Gender, male, total (%) | 66 (67.3%) | 55 (57.3%) | 0.15 |
Country of origin Germany, absolute (%) | 31 (31.6%) | 19 (19.7%) | 0.049 |
Symptomatic disease | 64 (65.3%) | 82 (85.4%) | 0.001 |
Diagnosed through contact tracing | 34 (34.7%) | 14 (14.6%) | 0.001 |
Time interval from first physician contact until TB diagnosis (weeks), median (min–max) | 1 (1–8) | 1 (1–208) | 0.013 |
Detection of drug resistance (PCR and/or culture) | 16 (16.3%) | 18 (18.8%) | 0.66 |
TB diagnosis (Smear) | 98 (100%) | 96 (100%) | n.d. |
Microscopy positive | 40 (40.8%) | 13 (13.5%) | <0.001 |
Positive MTB NAAT | 73 (74.5%) | 28 (29.2%) | <0.001 |
Culture positive | 68 (69.4%) | 25 (26.0%) | <0.001 |
Disease-associated complications | 16 (16.3%) | 41 (42.7%) | <0.001 |
Hepatotoxic side effect of tuberculostatic medication | 4 (4.1%) | 10 (10.4%) | 0.1 |
Hemoptysis | 2 (2%) | 0 (0%) | 0.5 |
Pancreatitis | 0 0%) | 2 (2.1%) | 0.24 |
Ileus | 0 (0%) | 1 (1%) | 0.5 |
TBC bacteriaemia | 2 (2%) | 9 (9.4%) | 0.03 |
Paradoxical immune reaction | 0 (0%) | 8 (8.3%) | 0.003 |
Required surgery | 0 (0%) | 11 (11.5%) | <0.001 |
Hemophagocytic lymphohistiocytosis | 0 (0%) | 2 (2.1%) | 0.24 |
Organ transplantation | 5 (5.1) | 2 (2.1%) | 0.45 |
Hematologic disease | 4 (4.1%) | 2 (2.1%) | 0.68 |
Autoimmune disease | 8 (8.2%) | 8 (8.3%) | 1 |
Immunosuppressive therapy | 18 (18.4) | 18 (18.8) | 0.95 |
HIV infection | 10 (10.2%) | 8 (8.3%) | 0.81 |
CD4+ cell count (cells/µL) (IQR) | 264.0 (84.75–442.0) | 126.5 (44.25–225.75) | 0.21 |
Antiretroviral therapy | 6 (60%) | 1 (12.5%) | 0.04 |
Hep. C infection | 7 (7.1%) | 5 (5.2%) | n.d. |
Hep. C RNA detectable | 4 (57.1%) | 4 (80%) | n.d. |
Hep. B infection | 8 (8.2%) | 12 (12.5%) | n.d. |
Hep. B DNA detectable | 1 (12.5%) | 4 (33%) | n.d. |
Drug resistance | 16 (16.3%) | 18 (18.8%) | 0.66 |
TBC medical treatment | 95 (96.9%) | 93 (96.9) | 1.0 |
Standard treatment (Rif, Iso, PZA, Etb) | 74 (75.5%) | 71 (74%) | 0.8 |
Therapy outcome | 0.24 | ||
Not evaluated (Lost to follow-up) | 65 (66.3%) | 53 (55.2%) | |
Sustained Treatment Success | 23 (23.5%) | 32 (33.3%) | |
Deceased | 3 (3.1%) | 1 (1%) | |
Therapy ongoing | 7 (7.1%) | 10 (10.4%) |
Extrapulmonary/Disseminated Tuberculosis (n = 92) | |
---|---|
More than one procedure is required for microbiological pathogen confirmation | 40 (43.5%) |
Histological analysis | 68 (73.9%) |
Detection of epithelioid granulomas | 59 (86.8%) |
NAAT on formalin-fixed specimens | 55 (59.8%) |
NAAT positive for MTB DNA | 44 (80%) |
TB culture done | 78 (84.8%) |
TBC culture positive | 56 (71.8%) |
Microscopic analysis on native (no formalin fixation) specimens | 78 (84.8%) |
Detection of acid-fast bacilli | 22 (28.2%) |
NAAT on native (no formalin fixation) specimens | 78 (84.8%) |
NAAT positive for MTB DNA | 59 (75.6%) |
Specimen | MTB Culture Positive | PCR Primary Specimen Positive | Microscopy Primary Specimen Positive |
---|---|---|---|
Lymph node (n = 31) | 24 (77.4%) | 27 (87.1%) | 8 (25.8%) |
Bone biopsy (n = 15) | 13 (86.7%) | 9 (60%) | 4 (26.7%) |
Soft tissue biopsy (n = 8) | 4 (50%) | 8 (100%) | 4 (50%) |
Colon biopsy (n = 5) | 3 (60%) | 4 (80%) | 2 (40%) |
Bone marrow biopsy (n = 2) | 1 (50%) | 0 (0%) | 0 (0%) |
Brain biopsy (n = 4) | 1 (25%) | 2 (50%) | 0 (0%) |
Urine (n = 4) | 4 (100%) | 4 (100%) | 3 (75%) |
Stool (n = 2) | 0 (0%) | 1 (50%) | 0 (0%) |
Liver biopsy (n = 2) | 1 (50%) | 0 (0%) | 0 (0%) |
Ascites (n = 1) | 1 (100%) | 1 (100%) | 0 (0%) |
Blood culture (n = 2) | 2 (100%) | 2 (100%) | 0 (0%) |
Pericard (n = 2) | 2 (100%) | 1 (50%) | 0 (0%) |
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Wilmink, J.; Vollenberg, R.; Olaru, I.D.; Fischer, J.; Trebicka, J.; Tepasse, P.-R. Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center. Infect. Dis. Rep. 2025, 17, 39. https://doi.org/10.3390/idr17030039
Wilmink J, Vollenberg R, Olaru ID, Fischer J, Trebicka J, Tepasse P-R. Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center. Infectious Disease Reports. 2025; 17(3):39. https://doi.org/10.3390/idr17030039
Chicago/Turabian StyleWilmink, Jonas, Richard Vollenberg, Ioana D. Olaru, Julia Fischer, Jonel Trebicka, and Phil-Robin Tepasse. 2025. "Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center" Infectious Disease Reports 17, no. 3: 39. https://doi.org/10.3390/idr17030039
APA StyleWilmink, J., Vollenberg, R., Olaru, I. D., Fischer, J., Trebicka, J., & Tepasse, P.-R. (2025). Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center. Infectious Disease Reports, 17(3), 39. https://doi.org/10.3390/idr17030039