Extrapulmonary Tuberculosis

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Kangwon Choe - One of the best experts on this subject based on the ideXlab platform.

  • diagnostic usefulness of a t cell based assay for Extrapulmonary Tuberculosis in immunocompromised patients
    The American Journal of Medicine, 2009
    Co-Authors: Sunghan Kim, Kyoungho Song, Sujin Choi, Hongbin Kim, Namjoong Kim, Kangwon Choe
    Abstract:

    Abstract Background The low reactivity of the tuberculin skin test limits its clinical use in immunocompromised patients with Extrapulmonary Tuberculosis. A recently developed T-cell-based assay for diagnosing Tuberculosis infection gave promising results. However, there were few data on the usefulness of this assay for diagnosing Extrapulmonary Tuberculosis in immunocompromised patients. Methods All adult patients with suspected Extrapulmonary Tuberculosis were prospectively enrolled at 2 university-affiliated hospitals over an 18-month period. In addition to the conventional tests for diagnosing Extrapulmonary Tuberculosis, enzyme-linked immunospot (ELISPOT) assay for the interferon-γ-producing T-cell response to early secretory antigenic target-6 and culture filtrate protein-10 was performed. The final diagnoses in patients with suspected Extrapulmonary Tuberculosis were classified by clinical category. Results There were 179 patients with suspected Extrapulmonary Tuberculosis enrolled: 59 (33%) were classified as immunocompromised. Of the 179 patients, 75 (42%) were classified as Extrapulmonary Tuberculosis, including 56 confirmed Tuberculosis plus 19 probable Tuberculosis, and 97 (54%) were classified as not Tuberculosis. The remaining 7 (4%) had possible Tuberculosis and were excluded from the final analysis. The tuberculin skin test (induration size ≥10 mm) was less sensitive in immunocompromised patients (38%; 95% confidence interval [CI], 19%-59%) than in immunocompetent patients (69%; 95% CI, 54%-81%, P =.01). In contrast, the ELISPOT assay retained a high sensitivity: (88%; 95% CI, 68%-97%) in immunocompromised patients compared with 96% (95% CI, 87%-100%) in immunocompetent patients ( P =.32). Conclusion The immunosuppressive condition does not affect the diagnostic sensitivity of the ELISPOT assay for Extrapulmonary Tuberculosis.

  • diagnostic usefulness of a t cell based assay for Extrapulmonary Tuberculosis
    JAMA Internal Medicine, 2007
    Co-Authors: Sunghan Kim, Sujin Choi, Hongbin Kim, Namjoong Kim, Kangwon Choe
    Abstract:

    Background Diagnosing Extrapulmonary Tuberculosis (E-TB) remains a challenge. A recently developed Mycobacterium Tuberculosis –specific region of difference 1 gene-based assay for diagnosing Tuberculosis infection showed promising results. However, the diagnostic usefulness of this assay remains to be determined compared with tuberculin skin test (TST) in patients with suspected E-TB in clinical practice. Methods All patients with suspected E-TB were prospectively enrolled in a tertiary care hospital during a 9-month period. In addition to the conventional tests for diagnosing E-TB, the interferon γ–producing T-cell responses to early secreted antigenic target 6 and culture filtrate protein 10 by enzyme-linked immunospot (ELISPOT) assay were performed. Final diagnosis in patients having suspected E-TB was classified by clinical category. Results Seventy-two patients with suspected E-TB were enrolled; 34 (47%) had immunosuppressive conditions. Of 72 patients, 32 (44%) were classified as having E-TB, including 22 with confirmed Tuberculosis and 10 with probable Tuberculosis, and 35 (49%) were classified as not having Tuberculosis. The remaining 5 (7%) had possible Tuberculosis and were excluded from the final analysis. Chronic caseating granulomas, acid-fast bacilli stain, M Tuberculosis polymerase chain reaction, and cultures for M Tuberculosis were positive in 22 (69%), 5 (16%), 15 (47%), and 18 (56%), respectively, of 32 patients with E-TB. The sensitivity and specificity of the TST (induration size, ≥10 mm) were 47% (95% confidence interval [CI], 29%-65%) and 86% (95% CI, 70%-95%), respectively. By comparison, the sensitivity and specificity of the ELISPOT assay were 94% (95% CI, 79%-99%; P P  =.99 between TST and ELISPOT), respectively. Conclusion The ELISPOT assay is a useful adjunct test for diagnosing E-TB.

Sunghan Kim - One of the best experts on this subject based on the ideXlab platform.

  • diagnostic usefulness of a t cell based assay for Extrapulmonary Tuberculosis in immunocompromised patients
    The American Journal of Medicine, 2009
    Co-Authors: Sunghan Kim, Kyoungho Song, Sujin Choi, Hongbin Kim, Namjoong Kim, Kangwon Choe
    Abstract:

    Abstract Background The low reactivity of the tuberculin skin test limits its clinical use in immunocompromised patients with Extrapulmonary Tuberculosis. A recently developed T-cell-based assay for diagnosing Tuberculosis infection gave promising results. However, there were few data on the usefulness of this assay for diagnosing Extrapulmonary Tuberculosis in immunocompromised patients. Methods All adult patients with suspected Extrapulmonary Tuberculosis were prospectively enrolled at 2 university-affiliated hospitals over an 18-month period. In addition to the conventional tests for diagnosing Extrapulmonary Tuberculosis, enzyme-linked immunospot (ELISPOT) assay for the interferon-γ-producing T-cell response to early secretory antigenic target-6 and culture filtrate protein-10 was performed. The final diagnoses in patients with suspected Extrapulmonary Tuberculosis were classified by clinical category. Results There were 179 patients with suspected Extrapulmonary Tuberculosis enrolled: 59 (33%) were classified as immunocompromised. Of the 179 patients, 75 (42%) were classified as Extrapulmonary Tuberculosis, including 56 confirmed Tuberculosis plus 19 probable Tuberculosis, and 97 (54%) were classified as not Tuberculosis. The remaining 7 (4%) had possible Tuberculosis and were excluded from the final analysis. The tuberculin skin test (induration size ≥10 mm) was less sensitive in immunocompromised patients (38%; 95% confidence interval [CI], 19%-59%) than in immunocompetent patients (69%; 95% CI, 54%-81%, P =.01). In contrast, the ELISPOT assay retained a high sensitivity: (88%; 95% CI, 68%-97%) in immunocompromised patients compared with 96% (95% CI, 87%-100%) in immunocompetent patients ( P =.32). Conclusion The immunosuppressive condition does not affect the diagnostic sensitivity of the ELISPOT assay for Extrapulmonary Tuberculosis.

  • diagnostic usefulness of a t cell based assay for Extrapulmonary Tuberculosis
    JAMA Internal Medicine, 2007
    Co-Authors: Sunghan Kim, Sujin Choi, Hongbin Kim, Namjoong Kim, Kangwon Choe
    Abstract:

    Background Diagnosing Extrapulmonary Tuberculosis (E-TB) remains a challenge. A recently developed Mycobacterium Tuberculosis –specific region of difference 1 gene-based assay for diagnosing Tuberculosis infection showed promising results. However, the diagnostic usefulness of this assay remains to be determined compared with tuberculin skin test (TST) in patients with suspected E-TB in clinical practice. Methods All patients with suspected E-TB were prospectively enrolled in a tertiary care hospital during a 9-month period. In addition to the conventional tests for diagnosing E-TB, the interferon γ–producing T-cell responses to early secreted antigenic target 6 and culture filtrate protein 10 by enzyme-linked immunospot (ELISPOT) assay were performed. Final diagnosis in patients having suspected E-TB was classified by clinical category. Results Seventy-two patients with suspected E-TB were enrolled; 34 (47%) had immunosuppressive conditions. Of 72 patients, 32 (44%) were classified as having E-TB, including 22 with confirmed Tuberculosis and 10 with probable Tuberculosis, and 35 (49%) were classified as not having Tuberculosis. The remaining 5 (7%) had possible Tuberculosis and were excluded from the final analysis. Chronic caseating granulomas, acid-fast bacilli stain, M Tuberculosis polymerase chain reaction, and cultures for M Tuberculosis were positive in 22 (69%), 5 (16%), 15 (47%), and 18 (56%), respectively, of 32 patients with E-TB. The sensitivity and specificity of the TST (induration size, ≥10 mm) were 47% (95% confidence interval [CI], 29%-65%) and 86% (95% CI, 70%-95%), respectively. By comparison, the sensitivity and specificity of the ELISPOT assay were 94% (95% CI, 79%-99%; P P  =.99 between TST and ELISPOT), respectively. Conclusion The ELISPOT assay is a useful adjunct test for diagnosing E-TB.

Alimuddin Zumla - One of the best experts on this subject based on the ideXlab platform.

  • diagnosis of Extrapulmonary Tuberculosis using the xpert mtb rif assay
    Expert Review of Anti-infective Therapy, 2012
    Co-Authors: Stephen D Lawn, Alimuddin Zumla
    Abstract:

    Evaluation of: Tortoli E, Russo C, Piersimoni C et al. Clinical validation of Xpert MTB/RIF for the diagnosis of Extrapulmonary Tuberculosis. Eur. Respir. J. doi:10.1183/09031936.00176311 (2012) (Epub ahead of print). The Xpert® MTB/RIF assay has been CE-marked for rapid molecular diagnosis of TB in Europe and has been endorsed by the WHO as a replacement for sputum smear microscopy for diagnosis of pulmonary TB in low- and middle-income countries. However, few data are available to inform recommendations for use of the assay for testing nonsputum clinical samples when investigating suspected Extrapulmonary TB (EPTB). We review and discuss the findings of Tortoli and colleagues, who evaluated the assay used for this purpose in a large study of adults and children in Italy. They provide a per-sample analysis of 268 diagnoses of EPTB at a range of anatomic sites (sensitivity: 81.3%; 95% CI: 76.2-85.8) and data for 1206 samples in which EPTB was excluded (specificity: 99.8%; 95% CI: 99.4-100). We discuss how this paper forms an important addition to the growing body of literature demonstrating the utility of Xpert MTB/RIF for EPTB diagnosis when applied to diverse types of clinical samples

Mustafa Tehmina - One of the best experts on this subject based on the ideXlab platform.

  • Host biomarkers for monitoring therapeutic response in Extrapulmonary Tuberculosis
    'Elsevier BV', 2021
    Co-Authors: Ambreen Atiqa, Khaliq Aasia, Naqvi, Syed Zeeshan Haider, Tahir Amna, Mustafa Manal, Chaudhary, Safee Ullah, Mirza Shaper, Mustafa Tehmina
    Abstract:

    Purpose The aim of this study was to explore the utility of inflammatory biomarkers in the peripheral blood to predict response to treatment in Extrapulmonary Tuberculosis (EPTB). Methods A Luminex xMAP-based multiplex immunoassay was used to measure 40 inflammatory biomarkers in un-stimulated plasma of 91 EPTB patients (48 lymphadenitis, and 43 pleuritis) before and at 2 and 6 months of treatment. Results Overall a significant change was observed in 28 inflammatory biomarkers with treatment in EPTB patients. However, MIG/CXCL9, IP-10/CXCL10, and CCL23 decreased in all patients' groups with successful treatment at both time points. At 2 months, 29/64 (45%) patients responded partially while 35/64 (55%) showed complete regress. Among good responders, a higher number of biomarkers (16/40) reduced significantly as compared to partial responders (1/40). Almost half (14/29) of partial responders required longer treatment than 6 months to achieve satisfactory response. The levels of MIG, IP-10, MIF, CCL22 and CCL23 reduced significantly among 80, 74, 60, 71, 51% good responders, as compared to 52, 52, 52, 59, 52% partial responders, respectively. A biosignature, defined by a significant decrease in any one of these five biomarkers, corresponded with satisfactory response to treatment in 97% patients at 2 month and 99% patients at 6 months of treatment. Conclusion Change in inflammatory biomarkers correlates with treatment success. A five biomarker biosignature (MIG, IP-10, MIF, CCL22 and CCL23) could be used as an indicator of treatment success.publishedVersio

  • MPT64 antigen detection test improves diagnosis of pediatric Extrapulmonary Tuberculosis in Mbeya, Tanzania
    'Springer Science and Business Media LLC', 2021
    Co-Authors: Grønningen Erlend, Nanyaro Marywinnie, Sviland Lisbet, Ngadaya Esther, Muller William, Torres Lisete, Mfinanga Sayoki, Mustafa Tehmina
    Abstract:

    Pediatric Extrapulmonary Tuberculosis (EPTB) is a diagnostic challenge. A new immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests. The aim of this study was to implement and validate the test performance in a resource limited African setting. Presumptive pediatric (0–18 y) EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital, and followed to the end of treatment or until a final diagnosis was reached. Specimens from suspected sites of infection were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the tests was assessed using mycobacterial culture as well as a composite reference standard. 30 patients were categorized as TB cases, 31 as non-TB cases and 2 were uncategorized. In the TB group, the three most common infections were adenitis (30%), peritonitis (30%) and meningitis (20%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 92%, 88%, 87%, 92% and 90%, respectively. Mortality was equally high among TB/non-TB cases (23% vs 21%), and malnutrition was the main comorbidity among TB cases. The MPT64 test was implementable in the routine diagnostics in a low-resource setting and improved the diagnosis of pediatric EPTB.publishedVersio

  • Patient Health Seeking and Diagnostic Delay in Extrapulmonary Tuberculosis: A Hospital Based Study from Central India
    'Hindawi Limited', 2020
    Co-Authors: Purohit Manju, Purohit Rajvi, Mustafa Tehmina
    Abstract:

    Objective. We aimed to investigate the awareness, health care seeking behavior, and diagnostic delay in Extrapulmonary Tuberculosis (EPTB) in a resource-constrained setting from Central India. Setting and Method. Questionnaire based interview of 1220 EPTB patients ≥14 years of age was conducted between July 2004 and August 2012 at Ujjain charitable Hospital, Ujjain, India. Results. Only 15% of patients had ever heard about EPTB and 2-4% knew about its prevention or treatment. Only 12% patients first sought medical advice while 49% patients practiced self-medication, 28% consulted traditional healers and 11% drug store/pharmacy. The median patient delay was 8 weeks (4.6-21.4 weeks). Majority (78%) of patients visited ≥3 health centers. Thirty-eight percent patients first visited any government health facility. Majority (97%) who first visited district and primary public health center were referred to private sector for investigations and 82% patients changed the consultation to private doctor after initial visit to public hospital. The median health system delay was 7 weeks (0.6-16.4 weeks). Conclusion. Patients had very poor awareness of EPTB. Patients were referred from public to private sector in search of diagnostic facilities. Improvement of public awareness about EPTB and better public-private partnership may contribute towards reduction in diagnostic delay.publishedVersio

  • Diagnosis of Extrapulmonary Tuberculosis using the MPT64 antigen detection test in a high-income low Tuberculosis prevalence setting
    'Springer Science and Business Media LLC', 2020
    Co-Authors: Hoel, Ida M, Sviland Lisbet, Syre Heidi, Dyrhol-riise, Anne M, Skarstein Ingerid, Jebsen Peter, Jørstad, Melissa D, Wiker Harald, Mustafa Tehmina
    Abstract:

    Background Extrapulmonary Tuberculosis (EPTB) poses diagnostic challenges due to the paucibacillary nature of the disease. The immunochemistry-based MPT64 antigen detection test (MPT64 test) has shown promising results for diagnosing EPTB in previous studies performed in low-resource settings, with higher sensitivity than microscopy and culture. The aim of this study was to investigate the performance of the MPT64 test in a routine clinical setting in a high-income low TB prevalence country. Methods Extrapulmonary samples sent for TB diagnostics to microbiology and pathology laboratories at three regional tertiary care hospitals in Norway in a one-year period were included and subjected to the MPT64 test in parallel to the routine TB diagnostic tests. Results Samples from 288 patients were included and categorised as confirmed TB cases (n = 26), clinically diagnosed TB cases (n = 5), non-TB cases (n = 243) and uncategorised (n = 14), using a composite reference standard (CRS). In formalin-fixed biopsies, the sensitivity (95% CI) of the MPT64 test, microscopy, PCR-based tests pooled, and culture was 37% (16–62), 20% (4–48), 37% (16–62) and 50% (23–77), respectively, against the CRS. The MPT64 test showed a good positive predictive value (88%) and an excellent specificity (99, 95% CI 92–100) in formalin-fixed biopsies. In fine-needle aspirates, pus and fluid samples, the test performance was lower. Conclusions The MPT64 test was implementable in pathology laboratories as part of routine diagnostics, and although the sensitivity of the MPT64 test was not better than culture in this setting, the test supplements other rapid diagnostic methods, including microscopy and PCR-based tests, and can contribute to strengthen the diagnosis of EPTB in formalin-fixed biopsies in the absence of culture confirmation

  • Diagnosis of Extrapulmonary Tuberculosis using the MPT64 antigen detection test in a high-income low Tuberculosis prevalence setting
    'Springer Science and Business Media LLC', 2020
    Co-Authors: Hoel, Ida Marie, Jørstad, Melissa Davidsen, Dyrhol-riise Anne, Sviland Lisbeth, Syre Heidi, Skarstein Ingerid, Jebsen, Peter Wilhelm, Wiker, Harald G, Mustafa Tehmina
    Abstract:

    Background Extrapulmonary Tuberculosis (EPTB) poses diagnostic challenges due to the paucibacillary nature of the disease. The immunochemistry-based MPT64 antigen detection test (MPT64 test) has shown promising results for diagnosing EPTB in previous studies performed in low-resource settings, with higher sensitivity than microscopy and culture. The aim of this study was to investigate the performance of the MPT64 test in a routine clinical setting in a high-income low TB prevalence country. Methods Extrapulmonary samples sent for TB diagnostics to microbiology and pathology laboratories at three regional tertiary care hospitals in Norway in a one-year period were included and subjected to the MPT64 test in parallel to the routine TB diagnostic tests. Results Samples from 288 patients were included and categorised as confirmed TB cases (n = 26), clinically diagnosed TB cases (n = 5), non-TB cases (n = 243) and uncategorised (n = 14), using a composite reference standard (CRS). In formalin-fixed biopsies, the sensitivity (95% CI) of the MPT64 test, microscopy, PCR-based tests pooled, and culture was 37% (16–62), 20% (4–48), 37% (16–62) and 50% (23–77), respectively, against the CRS. The MPT64 test showed a good positive predictive value (88%) and an excellent specificity (99, 95% CI 92–100) in formalin-fixed biopsies. In fine-needle aspirates, pus and fluid samples, the test performance was lower. Conclusions The MPT64 test was implementable in pathology laboratories as part of routine diagnostics, and although the sensitivity of the MPT64 test was not better than culture in this setting, the test supplements other rapid diagnostic methods, including microscopy and PCR-based tests, and can contribute to strengthen the diagnosis of EPTB in formalin-fixed biopsies in the absence of culture confirmation.publishedVersio

Spyros A Kalams - One of the best experts on this subject based on the ideXlab platform.

  • increased frequency of regulatory t cells and t lymphocyte activation in persons with previously treated Extrapulmonary Tuberculosis
    Clinical and Vaccine Immunology, 2012
    Co-Authors: Alexandre S De Almeida, Christina T Fiske, Timothy R Sterling, Spyros A Kalams
    Abstract:

    ABSTRACT Extrapulmonary Tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+ T lymphocytes in general, are important in the host immune response to Mycobacterium Tuberculosis. We evaluated T lymphocytes from patients after recovery from Extrapulmonary Tuberculosis, which may reflect conditions before M. Tuberculosis infection. A case-control study was conducted among HIV-uninfected adults with previously treated Extrapulmonary Tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary Tuberculosis, (ii) close Tuberculosis contacts with M. Tuberculosis infection, and (iii) close Tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+ CD25hi CD127low FoxP3+ cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 Extrapulmonary Tuberculosis cases, 18 pulmonary Tuberculosis controls, 17 controls with M. Tuberculosis infection, and 18 controls without M. Tuberculosis infection. The median Treg cell proportion was highest among persons with previous Extrapulmonary Tuberculosis (1.23%) compared to subjects with pulmonary Tuberculosis (0.56%), latent M. Tuberculosis infection (0.14%), or no M. Tuberculosis infection (0.20%) (P = 0.001). The median proportion of CD4+ T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+ T lymphocytes from persons with previous Extrapulmonary Tuberculosis (0.79%) compared to subjects with pulmonary Tuberculosis (0.44%), latent M. Tuberculosis infection (0.14%), or no M. Tuberculosis infection (0.32%) (P = 0.005). Compared with controls, persons with previously treated Extrapulmonary Tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+ T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for Extrapulmonary Tuberculosis.