Diagnostic Accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis

Abstract Background: The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for tuberculous adenitis in a tuberculosis and HIV endemic setting. Methods: We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of > 20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of ‘definite tuberculosis’ (microbiological criteria) or ‘probable tuberculosis’ (histological and clinical criteria). Results: We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had ‘definite tuberculosis’, 15 ‘probable tuberculosis’ and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24 );or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When the samples from tissue and FNA were pooled and compared to culture the sensitivity was 84% (60-97; 16/19). Conclusions: Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.

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Diagnostic Accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis

10.21203/rs.2.13145/v3 ◽

2019 ◽

Author(s):

Katherine Antel ◽

Jenna Oosthuizen ◽

Francois Malherbe ◽

Vernon J Louw ◽

Mark P Nicol ◽

...

Keyword(s):

Lymph Node ◽

Diagnostic Accuracy ◽

Rapid Test ◽

High Specificity ◽

Reference Standard ◽

Clinical Criteria ◽

Fine Needle Aspirates ◽

Microbiological Criteria ◽

Tissue Specimens ◽

Composite Reference Standard

Abstract Background: The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for tuberculous adenitis in a tuberculosis and HIV endemic setting. Methods: We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of > 20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of ‘definite tuberculosis’ (microbiological criteria) or ‘probable tuberculosis’ (histological and clinical criteria). Results: We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had ‘definite tuberculosis’, 15 ‘probable tuberculosis’ and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24 );or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When the samples from tissue and FNA were pooled and compared to culture the sensitivity was 84% (60-97; 16/19). Conclusions: Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.

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Tuberculosis diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM in vulnerable children

European Respiratory Journal ◽

10.1183/13993003.01116-2021 ◽

2021 ◽

pp. 2101116

Author(s):

Patrick Orikiriza ◽

Julianna Smith ◽

Bob Ssekyanzi ◽

Dan Nyehangane ◽

Ivan Mugisha Taremwa ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Sensitivity And Specificity ◽

Severe Malnutrition ◽

Hiv Positive ◽

Age Group ◽

Reference Standard ◽

Hiv Status ◽

Vulnerable Children ◽

Diagnostic Approaches ◽

Composite Reference Standard

BackgroundNon-sputum based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis [TB] who cannot expectorate sputum. We evaluated the diagnostic accuracy of Xpert MTB/RIF from stool and urine AlereLipoarabinomannan [LAM] test in this group of children.MethodsHospitalised children with presumptive TB and either age <2 years, HIV-positive or severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used.ResultsThe study enrolled 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. Twelve (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children. Against the microbiological reference standard the sensitivity and specificity (n/N, 95% confidence intervals) of stool Xpert MTB/RIF was 50.0% (6/12, 21.1–78.9) and 99.1% (198/200 96.4–99.9), while that of urine AlereLAM was 50.0% (6/12, 21.1–78.9) and 74.6% (147/197, 67.9–80.5) respectively. Against the composite reference standard sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and >2 years) or HIV status.ConclusionThe Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.

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2156. To Evaluate the Role of Kit-Based Loop-Mediated Isothermal Amplification (TB-LAMP) Assay in the Diagnosis of Tubercular Lymphadenitis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1836 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S731-S732

Author(s):

Neeraj Nischal ◽

Saurav Das ◽

Binit Kumar Singh ◽

Naveet Wig ◽

Manish Soneja ◽

...

Keyword(s):

Lymph Node ◽

Lamp Assay ◽

Infectious Agent ◽

Drug Susceptibility Testing ◽

Isothermal Amplification ◽

World Health ◽

Reference Standard ◽

Loop Mediated Isothermal Amplification ◽

Tubercular Lymphadenitis ◽

Composite Reference Standard

Abstract Background Tuberculosis (TB) is the leading cause of death as a single infectious agent worldwide. In 2017, there were an estimated 1.3 million TB deaths among HIV-negative people and 300,000 deaths among HIV-positive people. The rapid and accurate diagnosis of TB in lymphnode specimens remains a challenging task today. In 2016, World Health Organization endorsed a commercial molecular assay, the LoopAMP™ Mycobacterium tuberculosis complex (MTBC) detection kit (Eiken Chemical Company, Tokyo, Japan), which uses loop-mediated isothermal amplification (LAMP) for sputum samples only. No prospective studies on LAMP in diagnosis of Tubercular Lymphadenitis in adults have been done yet. Methods A prospective observational study with a total of 70 lymph-node aspirate specimens from suspected cases of Tubercular Lymphadenitis with age >18 years were selected and subjected to Ziehl–Neelsen staining, LAMP and culture in mycobacterial growth indicator tube (MGIT960). The immunochromatographic test was used to confirm MTB complex (MTBC) in culture positive samples and phenotypic drug susceptibility testing was done using MGIT-960. The composite reference standard (CRS) used in the study includes symptoms, radiological evidence and follow-up of 2 months. 2 × 2 tables were made and Sensitivity, Specificity, PPV, NPV of TB-LAMP were calculated with respect to AFB smear and composite reference standard (CRS). Results LAMP assay was able to detect MTBC in 34.3% (24/70) of lymph-node specimens. Sensitivity and specificity of the assay were 100% and 69.7%, respectively, considering smear as gold standard. On comparing with CRS, the assay showed 100% sensitivity and 100% specificity in the diagnosis of MTBC. Conclusion In our study, LAMP assay was found to be a promising tool for the diagnosis of Tubercular Lymphadenitis and could be used for rapid and cost-effective diagnosis of Tubercular Lymphadenitis in resource-limited settings. Disclosures All authors: No reported disclosures.

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Diversity in Typhoid Diagnostic Protocols And Recommendation for Composite Reference Standard

10.20944/preprints202107.0515.v2 ◽

2021 ◽

Author(s):

Bernard Igiri ◽

Stanley Irobekhian Reuben Okoduwa ◽

Shaibu Ahmed Munirat ◽

Iquo Bassey Otu-Bassey ◽

Abdullahi Bashir ◽

...

Keyword(s):

Typhoid Fever ◽

Diagnostic Accuracy ◽

Predictive Value ◽

Reference Standard ◽

Widal Test ◽

Average Percentage ◽

Public Health Burden ◽

Significant Difference ◽

Prospective Study Design ◽

Composite Reference Standard

Typhoid fever is a major public health burden which causes substantial global morbidity and mortality due to lack of decisive diagnostic protocols. The capacity of commonly use diagnostic test to validate the absence of typhoid fever is controversial. This study explores to evaluate new techniques for typhoid diagnosis and proposed a harmonised suitable standardized composite reference to be adopted. Published peer-reviewed articles indexed in PubMed, MEDLINE and Google scholar were reviewed for hospital-based studies. This study reveals new typhoid diagnostic techniques such as proteomics, serology, Rapid Diagnostic tests (RDTs), transcriptomics, genomics, and metabolomics. 34.4% of the studies use prospective study design. The study result establishes that, Widal test has a moderate diagnostic accuracy with average percentage sensitivity (52.9%), specificity (54%), positive predictive value (PPV) (56.8%) as well as negative predictive value (NPV) (55.6%) when compared with 29.4%, 28%, 29.5%, and 27.8% of Typhidot respectively. The findings showed a statistically significant difference on the sensitivity between Widal and Typhidot t (40) = 2.639, p = 0.012 at p<0.05 using independent sample t-test. When there is no perfect reference standard that has an optimal diagnostic accuracy, the need for a harmonised suitable standardized composite reference is essential. Hence, this study recommends that, peripheral blood culture with established sensitivity of 60% and Widal test with average sensitivity of 52.9% be adopted as a consensus composite reference standard for typhoid fever diagnosis in other to improve confidence in prevalence estimates.

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Diagnostic accuracy of GeneXpert MTB/RIF assay for detection of tubercular pleural effusion

PLoS ONE ◽

10.1371/journal.pone.0251618 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0251618

Author(s):

Jyoti Jain ◽

Pooja Jadhao ◽

Shashank Banait ◽

Preetam Salunkhe

Keyword(s):

Pleural Effusion ◽

Diagnostic Accuracy ◽

Tertiary Care ◽

Public Health Problem ◽

P Value ◽

Care Hospital ◽

Reference Standard ◽

Likelihood Ratios ◽

Predictive Values ◽

Composite Reference Standard

India has been engaged in tuberculosis (TB) control activities for over 50 years and yet TB continues to remain India’s important public health problem. The present study was conducted to compare the performance of GeneXpert MTB/RIF (GXpert) assay with composite reference standard in diagnosing cases of tubercular pleural effusion (TPE) and to evaluate the reliability of rifampicin resistance. A cross-sectional study was performed in a Department of Medicine of a rural teaching tertiary care hospital in central India. In all consecutive patients with pleural effusion on chest radiograph presenting to Department of Medicine, GXpert assay and composite reference standard was performed to evaluate the diagnostic accuracy of GXpert assay for detecting TPE in comparison to composite reference standard. Standard formulae were used to calculate the sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (LR+) and negative likelihood ratios (LR-). Mc-Nemar’s test was applied to compare variables. All comparisons were two-tailed. We considered the difference to be statistically significant if the P value was less than 0.05. The sensitivity of the GXpert assay in diagnosing TPE was 16.6% among 158 study participants, the specificity was 100% and diagnostic accuracy was 52.5% which was statistically significant (p value < 0.05). It had a PPV of 100% (95%CI: 88.3% - 100%) and a NPV of 47.5% (95%CI: 39.3% - 55.7%). The LR+ and LR-were 23.5 (95%CI: 1.43–38.6) and 0.83 (95%CI: 0.76–0.91) respectively. GXpert assay has a very high specificity in diagnosing TPE but has a low sensitivity. In comparison to composite reference standard Thus its clinical utility is limited when used as a standalone test. A physician’s clinical acumen in combination with routine pleural fluid analysis should be the key factor in the diagnosis of TPE in clinically and radiologically suspected patients, especially in high TB burden countries.

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Clinical evaluation of the Xpert MTB/XDR assay for rapid detection of isoniazid, fluoroquinolone, ethionamide and second-line drug resistance: A cross-sectional multicentre diagnostic accuracy study

10.1101/2021.05.06.21256505 ◽

2021 ◽

Author(s):

Adam Penn-Nicholson ◽

Sophia B Georghiou ◽

Nelly Ciobanu ◽

Mubin Kazi ◽

Manpreet Bhalla ◽

...

Keyword(s):

Drug Resistance ◽

Diagnostic Accuracy ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Foreign Affairs ◽

Second Line ◽

Reference Standard ◽

Composite Reference Standard ◽

Resistance Detection

Background The WHO End TB Strategy requires universal drug susceptibility testing and treatment of all people with tuberculosis. However, available second-line diagnostic tools are cumbersome and require sophisticated laboratory infrastructure, and ultimately less than half of those with drug-resistant tuberculosis receive appropriate treatment. Xpert MTB/XDR was developed to help overcome these limitations. Methods We assessed the diagnostic accuracy of sputum-based Xpert MTB/XDR for isoniazid, fluoroquinolone, ethionamide and second-line injectable resistance detection in adults with an Xpert MTB/RIF or Ultra Mycobacterium tuberculosis-positive result against a composite reference standard of phenotypic drug-susceptibility testing and whole genome sequencing (NCT03728725). Participants with pulmonary tuberculosis symptoms and ≥1 risk factor for drug resistance were consecutively enrolled between four clinical sites in India, Moldova and South Africa. Findings Between 31 July 2019 and 21 March 2020, we enrolled 710 patients, of which 611 (86.1%) had results from index and composite reference standard tests and were included in analysis. The sensitivity of Xpert MTB/XDR was 94% for isoniazid, 95% for fluoroquinolones, 54% for ethionamide, 73% for amikacin, 86% for kanamycin, and 61% for capreomycin resistance detection. Specificity was 98-100% for all drugs. Performance was equivalent to line-probe assays. The non-determinate rate of Xpert MTB/XDR was 2.96%. Interpretation This first prospective, multicentre clinical study of the Xpert MTB/XDR assay demonstrated high diagnostic test accuracy, meeting target product profile criteria for a next-generation drug susceptibility test. Funding German Federal Ministry of Education and Research through KfW, Dutch Ministry of Foreign Affairs, and Australian Department of Foreign Affairs and Trade.

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Performance of Xpert® MTB/RIF in diagnosing tuberculous pleuritis using thoracoscopic pleural biopsy

BMC Infectious Diseases ◽

10.1186/s12879-020-05578-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Chengjun Li ◽

Chang Liu ◽

Bingqi Sun ◽

Wei Zhang ◽

Yang Wang ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Reference Standard ◽

Pleural Biopsy ◽

Predictive Values ◽

Biopsy Specimens ◽

Biopsy Tissue ◽

Liquid Culture System ◽

Tissue Specimens ◽

Composite Reference Standard ◽

Rule Out

Abstract Background Etiological diagnosis of tuberculous pleuritis is challenging, owing to a paucity of Mycobacterium tuberculosis (MTB) in the affected region. Moreover, currently available methods, such as the detection of acid-fast bacilli and microbiological culture, are not always conducive to timely diagnosis and treatment. In this study, we evaluated the performance of Xpert® MTB/RIF assay (hereinafter referred to as “Xpert”) in detecting MTB in difficult-to-diagnose patients using suspensions of pleural biopsy tissue specimens obtained under direct thoracoscopic guidance. Methods One hundred and sixty patients with an unexplained pleural effusion were included from the Shenyang Tenth People’s Hospital and Shenyang Chest Hospital, China, between 2017 and 2018. The included patients underwent thoracoscopy under local anesthesia, with an intercostal incision of approximately 1.0 cm for biopsy. The biopsy specimens were used for pathological and etiological examinations. The Xpert test was evaluated for its sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV, respectively), against data obtained using standards: the BACTEC™ MGIT™ 960 liquid culture system and a composite reference standard (CRS). Results The sensitivity and specificity of Xpert were 68.8 and 64.6%, respectively, against the MGIT 960 culture data. The PPV and NPV of Xpert were 56.4 and 75.6%, respectively. The sensitivity of Xpert was 69.0% against the CRS data, which was significantly higher than that of MGIT 960 culture (56.6%). The PPV and NPV of Xpert against the CRS data were 100.0 and 57.3%, respectively. Conclusions Xpert is a good rule-in test but has limited value as a rule-out test for the diagnosis of tuberculosis pleuritis.

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Diversity in Typhoid Diagnostic Protocols And Recommendation for Composite Reference Standard

10.20944/preprints202107.0515.v1 ◽

2021 ◽

Author(s):

Bernard Igiri ◽

Stanley Irobekhian Reuben Okoduwa ◽

Shaibu Ahmed Munirat ◽

Iquo Bassey Otu-Bassey ◽

Abdullahi Bashir ◽

...

Keyword(s):

Typhoid Fever ◽

Diagnostic Accuracy ◽

Predictive Value ◽

Reference Standard ◽

Widal Test ◽

Average Percentage ◽

Public Health Burden ◽

Significant Difference ◽

Prospective Study Design ◽

Composite Reference Standard

Typhoid fever is a major public health burden which causes substantial global morbidity and mortality due to lack of decisive diagnostic protocols. The capacity of commonly use diagnostic test to validate the absence of typhoid fever is controversial. This study explores to evaluate new techniques for typhoid diagnosis and proposed a harmonised suitable standardized composite reference to be adopted. Published peer-reviewed articles indexed in PubMed, MEDLINE and Google scholar were reviewed for hospital-based studies. This study reveals new typhoid diagnostic techniques such as proteomics, serology, Rapid Diagnostic tests (RDTs), transcriptomics, genomics, and metabolomics. 34.4% of the studies use prospective study design. The study result establishes that, Widal test has a moderate diagnostic accuracy with average percentage sensitivity (52.9%), specificity (54%), positive predictive value (PPV) (56.8%) as well as negative predictive value (NPV) (55.6%) when compared with 29.4%, 28%, 29.5%, and 27.8% of Typhidot respectively. The findings showed a statistically significant difference on the sensitivity between Widal and Typhidot t (40) = 2.639, p = 0.012 at p<0.05 using independent sample t-test. When there is no perfect reference standard that has an optimal diagnostic accuracy, the need for a harmonised suitable standardized composite reference is essential. Hence, this study recommends that, peripheral blood culture with established sensitivity of 60% and Widal test with average sensitivity of 52.9% be adopted as a consensus composite reference standard for typhoid fever diagnosis in other to improve confidence in prevalence estimates.

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Fujifilm SILVAMP TB-LAM for the Diagnosis of Tuberculosis in Nigerian Adults

Journal of Clinical Medicine ◽

10.3390/jcm10112514 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2514

Author(s):

Patricia Comella-del-Barrio ◽

John S. Bimba ◽

Ramota Adelakun ◽

Konstantina Kontogianni ◽

Bárbara Molina-Moya ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Positive Culture ◽

Urine Samples ◽

Hiv Positive ◽

Reference Standard ◽

Negative Culture ◽

District Hospitals ◽

Good Diagnostic Accuracy ◽

Hiv Negative

There is a need for diagnostics for tuberculosis (TB) that are easy to use, able to screen non-sputum samples, and able to provide rapid results for the management of both immunocompromised and immunocompetent individuals. The Fujifilm SILVAMP TB LAM (FujiLAM) assay, a new non-sputum based point of need test for the diagnosis of TB, could potentially address most of these needs. We evaluated the performance of FujiLAM in HIV positive and HIV negative patients with presumptive TB attending three district hospitals in Nigeria. Consecutive patients were asked to provide urine samples on the spot, which were tested with FujiLAM. The results were compared against a positive culture and/or Xpert MTB/RIF as the reference standard. Forty-five patients had bacteriologically confirmed TB, and 159 had negative culture and Xpert MTB/RIF (no TB). The FujiLAM test was positive in 23 (sensitivity 65.7%, 95% CI = 48–80) HIV negative and seven (70%, 95% CI = 35–92) HIV positive patients with bacteriological confirmation of TB. FujiLAM was negative in 97 (specificity 99.0%, 95% CI = 94–100) HIV negative and 56 (93.3%, 95% CI = 83–98) HIV positive patients without TB. The FujiLAM test has good diagnostic accuracy for considering its application in both HIV positive and HIV negative patients with TB.

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