Diagnosis Of Extrapulmonary Tuberculosis Research Articles

"Sensitivity of GeneXpert Ultra in the Diagnosis of Extrapulmonary Tuberculosis in a Tertiary Hospital Setup of South India”

"Sensitivity of GeneXpert Ultra in the Diagnosis of Extrapulmonary Tuberculosis in a Tertiary Hospital Setup of South India”

Diagnostic accuracy of truenat MTB plus for the detection of pulmonary and extrapulmonary tuberculosis

BackgroundThe diagnosis of Tuberculosis (TB) has been a challenge till the advent of rapid molecular diagnostic tests. The traditional diagnostic tests have its own limitations with regard to its performance or the turnaround time. Truenat MTB Plus assay, a battery-operated molecular assay developed in India has been introduced for its use in pulmonary TB (PTB). However, the diagnostic accuracy of the assay is not well studied in comparison with Mycobacterial culture, especially for extrapulmonary TB (EPTB). AimWe aimed at evaluating the diagnostic accuracy of Truenat MTB Plus assay for both PTB and EPTB comparing with culture for adult population. MethodsThe specimens from presumptive PTB and EPTB patients were processed for Truenat MTB Plus assay, solid or liquid culture and AFB staining. The electronic data of all the specimen reports collected retrospectively were analysed for the sensitivity and specificity. ResultsOut of the 736 samples which had valid culture reports, 364 (49.4 %) were respiratory and 372 (50.6 %) were extrapulmonary specimens. The test positivity rate for smear microscopy, Truenat MTB Plus assay and culture was 3.7 % (27), 8.2 % (60), 7.1 % (52) respectively. Of the 60 Truenat MTB Plus positive patients with TB, 33 (55 %) were PTB and 27 (45 %) were EPTB. We estimated overall sensitivity and specificity of Truenat MTB Plus as 90 % (95 % CI: 73.4–97.8) and 98. 2 (95 % CI:96–99.3) respectively for the detection of PTB. The overall sensitivity and specificity for EPTB was 81.8 % (95 % CI: 59.7–94.8) and 97.4 % (95 % CI: 95.1–98.8) respectively. ConclusionsTruenat MTB Plus assay has comparable diagnostic accuracy with other molecular assays. The Truenat MTB Plus assay can be used for the diagnosis of PTB and EPTB, especially in resource limited settings.

Role of GeneXpert in the diagnosis of extrapulmonary tuberculosis.

The World Health Organization endorsed the cartridge-based nucleic acid amplification test Xpert MTB/RIF (GXP) for the diagnosis of tuberculosis (TB). Studies about GXP efficiency in extrapulmonary TB (EPTB) are scarce. Hence, we decided to study the role of GXP in EPTB. This prospective observational study, conducted in the pulmonary medicine department of a tertiary care hospital after ethics committee permission, recruited 200 EPTB patients. The diagnosis of TB was achieved with the help of clinico-radiological correlation with microbiological test positivity. Acid-fast bacilli (AFB) culture was treated as the comparative gold standard. Patients who had no or incomplete data were excluded from the study. Data was analyzed to calculate the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of TB and the detection of rifampicin resistance. The majority of cases were women (126 patients: 63%). The mean age was 23.71 years. On GXP, 130 (65%) had detected mycobacterium tuberculosis (MTB), and 70 (35%) did not. Adding AFB culture data, 168 (81.5%) showed microbiological evidence of TB, and 32 (18.5%) were negative. On the drug susceptibility test, 131 cases were rifampicin-sensitive, 32 were rifampicin-resistant TB, and in 5 cases, data was unavailable. The most common extrapulmonary site of involvement was the lymph node, with 94 patients (47%). The most common lymph node involved was the cervical lymph node, with 70 patients (74.5%). The sensitivity, specificity, positive predictive value, and negative predictive value of GXP in EPTB collectively were 76.68%, 86.48%, 96%, and 45.7%, respectively. GXP is useful for the rapid detection of EPTB and the identification of rifampicin resistance, especially in a high-prevalence country like India.

Prevalence of extrapulmonary tuberculosis among people living with HIV/AIDS in Southeast Asia: a systematic review and meta-analysis.

The dual burden of human immunodeficiency virus (HIV) and tuberculosis (TB) impacts people living with HIV (PLHIV) coinfected with TB. Although some primary studies have been reported on the burden of extrapulmonary TB (EPTB) among PLHIV in Southeast Asia (SEA), there is no systematic review or meta-analysis that attempts to summarize the available literature. Therefore, this review aims to summarize the prevalence of EPTB/HIV co-infection in SEA using meta-analysis based on a systematic review of published articles and gray literature. A comprehensive 3-stage methodology was adopted to conduct a thorough literature search, encompassing both published and gray literature. Data sources such as MEDLINE and Web of Science were searched for articles reporting data from SEA between 2010 and 2022. Findings were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and were sourced using a predefined search strategy from different databases. The Joanna Briggs Institute prevalence studies checklist was employed for critical appraisal. The meta-analysis of proportions was carried out using the "metaprop" function in R software (version 4.3.1) to generate pooled estimates. Effects were summarized using random-effects models, and sources of heterogeneity were explored through I2, utilizing subgroup and sensitivity analyses. Publication bias was assessed using funnel plots and pertinent statistical tests, including Egger's regression analysis. A total of 474 studies were initially identified in our search. After the removal of duplicates and a meticulous screening process of titles and abstracts, along with the application of exclusion criteria, 22 studies comprising 34,740 PLHIV were included in the final meta-analysis. The summary effect or pooled proportion estimate of EPTB among PLHIV was found to be 18% [95% confidence interval (CI): 15,22; heterogeneity: τ2=0.0056; degrees of freedom=21, p<0.001; I2=99%]. Our study showed that there was a diverse range of prevalence of EPTB among PLHIV in the SEA region, which ranged from 5% (95% CI: 4.0-7.0) in South Korea to 48% (95% CI: 41.0-55.0) in Thailand. Our systematic review and meta-analysis indicate a notably higher prevalence of EPTB among PLHIV. Early diagnosis of EPTB is crucial to mitigating associated morbidity and mortality. Therefore, a thorough medical history and comprehensive physical examination are imperative in assessing PLHIV, aiming to promptly identify and rule out EPTB. After a diligent evaluation, appropriate diagnostic measures and tailored management strategies should be promptly instituted.

Targeted nanopore sequencing using clinical specimens for the rapid diagnosis of extrapulmonary tuberculosis

BackgroundThe clinical presentation of extrapulmonary tuberculosis (EPTB) is atypical and it is easily confused with other diseases such as common infections, making prompt diagnosis a great challenge. This study aimed to evaluate the accuracy of targeted nanopore sequencing (TNS) in the diagnosis of EPTB. The diagnostic accuracy of TNS using different types of extrapulmonary specimens was also evaluated.MethodsWe reviewed the clinical data of patients with suspected EPTB for whom TNS was conducted and who were hospitalized at our center. The true positive, false positive, false negative, and true negative values were determined. Indices of diagnostic accuracy were computed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for TNS and acid-fast bacilli (AFB) culture, and compared with those from clinical diagnosis.Results149 patients were included in the analysis. The overall sensitivity, specificity, PPV, NPV, and AUC of TNS for the diagnosis of EPTB were 86.4%, 87.5%, 97.3%, 55.3%, and 0.87, respectively. For diagnosis by AFB culture, these values were 25.6%, 100.0%, 100.0%, 20.5%, and 0.63, respectively. The most common specimens used were lymph node tissue, cerebrospinal fluid, pleural effusion, and pleural tissue. The diagnostic accuracy of TNS using all types of extrapulmonary specimens was good.ConclusionsTNS demonstrates good diagnostic accuracy in the rapid diagnosis of EPTB and this was true across different types of extrapulmonary specimens.

Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London. Evidence before this study: Blood RNA biomarker signatures and CRP measurements have emerged as potential triage tests for TB, but evidence is mostly limited to their performance in pulmonary TB. Microbiological diagnosis of extrapulmonary TB (EPTB) is made challenging by the need for invasive sampling to obtain tissue from the site of disease. This is compounded by lower sensitivity of confirmatory molecular tests for EPTB compared to their performance in pulmonary disease. We performed a systematic review of diagnostic accuracy studies of blood RNA biomarkers or CRP measurements for EPTB, which could mitigate the need for site-of-disease sampling for the diagnosis of TB. We searched PubMed up to 1 st August 2023, using the following criteria: "extrapulmonary [title/abstract] AND tuberculosis [title/abstract] AND biomarker [title/abstract]". Although extrapulmonary TB was included in several studies, none focused specifically on EPTB or included an adequate number of EPTB cases to provide precise estimates of test accuracy. Added value of this study: To the best of our knowledge, we report the first diagnostic accuracy study of blood RNA biomarkers and CRP for TB among people with EPTB syndromes. We examined the performance of seven previously identified blood RNA biomarkers as triage tests for TB lymphadenitis and TB pericarditis compared to a microbiology reference standard among people referred to hospital for invasive sampling in a high TB and HIV prevalence setting. Multiple blood RNA biomarkers showed comparable diagnostic accuracy to that previously reported for pulmonary TB in both EPTB disease cohorts, irrespective of HIV status. All seven blood RNA biomarkers showed superior diagnostic accuracy to CRP for both lymphadenitis and pericarditis, but failed to meet the combined >90% sensitivity and >70% specificity recommended for a blood-based diagnostic triage test by WHO. Nonetheless, in decision curve analysis, an approach of using the best performing blood RNA biomarker to trigger confirmatory microbiological testing showed superior clinical utility in clinical services seeking to reduce the number needed to test (using invasive confirmatory testing) to less than 4 for each EPTB case detected. If acceptable to undertake invasive testing in more than 4 people for each true case detected, then a test-all approach will provide greater net benefit in this TB/HIV hyperendemic setting.Implications of all the available evidence: Blood RNA biomarkers show some potential as diagnostic triage tests for TB lymphadenitis and TB pericarditis, but do not provide the level of accuracy for blood-based triage tests recommended by WHO for community-based tests. CRP has inferior diagnostic accuracy to blood RNA biomarkers and cannot be recommended for diagnostic triage among people with EPTB syndromes referred for invasive sampling.

Insights into changing patterns of extrapulmonary tuberculosis in North India

PurposeTuberculosis is one of the dreadful infections and India contributes to substantial burden of TB cases globally. Though majority of cases are pulmonary, extra-pulmonary tuberculosis (EPTB) share significant burden, more in HIV-positive persons. Despite the striking burden, very few studies have been conducted in India and present study was undertaken to determine trends of EPTB at our tertiary care centre. MethodsThis was a retrospective study conducted over a period of 4 years 3 months. Diagnosis of EPTB was based on suspected clinical features, with positive micobiological evidence with cartridge based nucleic acid amplification test (CBNAAT) with/without microscopy. ResultsA total of 10,560 samples (pulmonary and extra-pulmonary) were received during the study period, of which 3972 were extrapulmonary. Of these, a total of 18% were noted to be positive for EPTB. Trend of positivity revealed highest burden in 2018 and a decline was noted over the years, however, rise in cases was noted in 2022. Pleural, meningitis, musculoskeletal, peritoneal and pericardial TB was more common in males, while lymphadenitis was more common in females (p value: <0.0001). Pleural TB (31%) was the most common presentation, followed by lymphadenitis. A gradual decline in lymphadenitis was noted with significantly increasing trend only for musculoskeletal TB. Rifampicin resistance was detected in 7.45% of positive samples, of which the maximum rate of resistance was noted in lymph node aspirates (11.11%), followed by musculoskeletal and pleural samples. ConclusionThe present study showed a gradual decline in positivity of EPTB cases over the years. Younger productive age group with more propensity to transmit infection was the most commonly affected, with pleural TB as the most common presentation. Rare presentations of EPTB also contributed major share. Higher rates of resistance underline requisite to strengthen ongoing programs, to achieve the End TB strategy by 2025.

Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by 18FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study)

BackgroundTuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB (EPTB) has received little attention. Diagnosis of EPTB remains challenging due to the invasive procedures required for sample collection. Spinal TB (STB) accounts for 10% of EPTB and often leads to lifelong debilitating disease due to devastating spinal deformation and compression of neural structures. Little is known about the extent of disease, although both isolated STB and a disseminated form of STB have been described. In our Spinal TB X cohort study, we aim to describe the clinical phenotype of STB using whole-body 18FDG-PET/CT, identify a specific gene expression profile for different stages of dissemination and compare findings to previously described gene expression signatures for latent and active pulmonary TB.MethodsA single-centre, prospective cohort study will be established to describe the distributional pattern of STB detected by whole-body 18FDG-PET/CT and gene expression profile of patients with suspected STB on magnetic resonance imaging (MRI) at point of diagnosis, six months, and 12 months. Blood biobanking will be performed at these time points. Specimens for microbiology will be obtained from sputum/urine, from easily accessible sites of disease (e.g., lymph nodes, abscess) identified in the first 18FDG-PET/CT, from CT-guided biopsy and/or surgery. Clinical parameters and functional scores will be collected at every physical visit. Data will be entered into RedCap® database; data cleaning, validation and analysis will be performed by the study team. The University of Cape Town Ethics Committee approved the protocol (243/2022).DiscussionThe Spinal TB X cohort study is the first prospective cohort study using whole-body 18FDG-PET/CT scans in patients with microbiologically confirmed spinal tuberculosis. Dual imaging techniques of the spine using 18FDG-PET/CT and magnetic resonance imaging as well as tissue diagnosis (microbiology and histopathology) will allow us to develop a virtual biopsy model. If successful, a distinct gene-expression profile will aid in blood-based diagnosis (point of care testing) as well as treatment monitoring and would lead to earlier diagnosis of this devastating disease.Trial registration: The study has been registered on ClinicalTrials.gov (NCT05610098).

Utility of CBNAAT (GeneXpert MTB/RIF assay) in rapid diagnosis of extrapulmonary tuberculosis in a hepatobiliary tertiary center

Objectives Newer diagnostic techniques like cartridge-based nucleic acid amplification techniques (CB NAAT) need to be evaluated for extrapulmonary tuberculosis (EPTB), as being a paucibacillary condition, it is often underdiagnosed with conventional methods. We conducted this study to assess the utility of CB NAAT (GeneXpert MTB/RIF assay) in rapid diagnosis of extrapulmonary tuberculosis. Material and Methods Liver disease patients admitted from June 2019 to June 2020 were investigated for EPTB based on clinical and radiological suspicion. EPTB was diagnosed based on one of the following: (i) histological evidence of caseating granulomas; (ii) smear positivity for acid-fast bacilli; (iii) CB NAAT (GeneXpert MTB/RIF assay, Cepheid, USA). Results A total of 290 EPTB specimens received in the laboratory were included. The extrapulmonary samples that were received included body fluids (n = 143) which included pleural fluid, ascitic fluid, drain fluids, and pus aspirates, followed by biopsies (n = 82), lymph nodes (n = 43), urine (n = 19), and CSF (n = 3). GeneXpert MTB/RIF assay was positive in 10.3% (n = 30) samples, whereas negative in 89.7% (n = 260) samples. The overall sensitivity of GeneXpert MTB/RIF assay was 61.36% (95% CI 46.62%–74.28%), specificity 89.29% (95% CI 72.8%–96.29%), positive predictive value (PPV) 90% (95% CI 74.38%–96.54%), and negative predictive value (NPV) 59.52% (95% CI 44.49%–72.96%). Conclusion The GeneXpert MTB/RIF assay is a valuable tool for extrapulmonary tuberculosis. In addition to other tests like smear, culture GeneXpert MTB/RIF assay helps in the confirmation of diagnosis. Rapid diagnosis of tuberculosis with overall good sensitivity and specificity makes it a beneficial test.

Pott’s disease and scrofuloderma as presentation of clinically extrapulmonary tuberculosis in 15 years old girl: a case report

Backgrounds: Extrapulmonary tuberculosis (TB) accounts for 15–20% of all tuberculosis cases, with the lymph node being the most commonly affected organ. Spinal tuberculosis and scrofuloderma are rare manifestations of extrapulmonary TB and constitute less than 5% of the cases. Establishing the diagnosis is a challenge. Eradication and prevention of sequelae complicate further management of the disease. This study aims to describe the clinical manifestation and the management of spondylitis tuberculosis and scrofuloderma in a child. Case presentation: A 15-year-old girl came with a chief complaint of lower extremities weakness for a week following monthly chronic low back pain. She also reported a painless lesion on her back with no sign of acute inflammation. She also complained of intermittent fever with night sweats and lost 3 kilos of body weight in the last two months. From physical examination, we found a kyphotic posture and severe malnutrition. Skin examination revealed an open wound on her right lower back, size 4x3 cm, with no sign of inflammation. The tuberculin skin test was positive with 15 mm induration. The spinal magnetic resonance imaging revealed destruction of the vertebral corpus thoracal segment, hyperintense sacrum, and right ileum bone with a cold abscess, suggesting spondylitis TB. A wound biopsy with hematoxylin-eosin stain concluded chronic granulomatous inflammation and showed multinucleated giant cell Langhans-type, suggestive of cutaneous tuberculosis. Microbiology examination (PCR GeneXpert) from wound biopsy and ziehl neelsen stain failed to detect Mycobacterium tuberculosis. The patient was diagnosed with Pott’s disease and scrofuloderma. Anti-tuberculous therapy commenced, and the patient responded well after several months of treatment. Conclusions: The diagnosis of extrapulmonary TB manifests as spinal tuberculosis, and scrofuloderma could be made from clinical manifestation and imaging.

Diagnosing adult and pediatric extrapulmonary tuberculosis by MPT64 antigen detection with immunohistochemistry and immunocytochemistry using reproduced polyclonal antibodies.

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Immunohistochemistry or immunocytochemistry has been used to diagnose tuberculosis (TB) by detection of MPT64 antigen from various extrapulmonary specimens and has shown good diagnostic performance in our previous studies. The test can distinguish between disease caused by Mycobacterium tuberculosis (Mtb) complex and nontuberculous mycobacteria and can be applied on formalin-fixed paraffin-embedded tissue. As the antibodies previously used were in limited supply, a new batch of polyclonal antibodies was developed for scale-up and evaluated for the first time in this study. Our aim was to assess the diagnostic accuracy of the MPT64 test with reproduced antibodies in the high burden settings of Pakistan and India. Patients were enrolled prospectively. Samples from suspected sites of infection were collected and subjected to histopathologic and/or cytologic evaluation, routine TB diagnostics, GeneXpert MTB/RIF (Xpert), and the MPT64 antigen detection test. Patients were followed until the end of treatment. Based on a composite reference standard (CRS), 556 patients were categorized as TB cases and 175 as non-TB cases. The MPT64 test performed well on biopsies with a sensitivity and specificity of 94% and 75%, respectively, against a CRS. For cytology samples, the sensitivity was low (36%), whereas the specificity was 81%. Overall, the MPT64 test showed higher sensitivity (73%) than Xpert (38%) and Mtb culture (33%). The test performed equally well in adults and children. We found an additive diagnostic value of the MPT64 test in conjunction with histology and molecular tests, increasing the yield for EPTB. In conclusion, immunochemical staining with MPT64 antibodies improves the diagnosis of EPTB in high burden settings and could be a valuable addition to routine diagnostics.

Comments and Illustrations of Ultrasound Findings in Extrapulmonary Tuberculosis Manifestations.

This review describes the appearance of extrapulmonary tuberculosis manifestations in comprehensive and multiparametric ultrasound imaging. The aim is to increase awareness of typical ultrasound findings regarding extrapulmonary tuberculosis, correlate those with pathological features, and facilitate differential diagnosis. Point of care ultrasound protocols can be used as a screening method in high-risk populations, although the negative findings do not exclude tuberculosis. Conversely, the diagnosis of extrapulmonary tuberculosis can never be made using ultrasound alone, as many ultrasound findings in extrapulmonary tuberculosis are non-specific. However, ultrasound-based sampling techniques can significantly facilitate the collection of samples for microbiological or molecular proof of tuberculosis, as well as facilitating the establishment of alternative diagnoses.

Assessing the utility of Truenat in extrapulmonary tuberculosis diagnosis – A NRL’s experience

BackgroundDiagnosis of extra pulmonary TB (EPTB) remains a big challenge. While data on utility of Xpert testing in EPTB diagnosis is enormous, there is limited data on Truenat MTB testing. AimIn this study we aimed to evaluate the usefulness of Truenat in EPTB diagnosis. Materials and methodsThe study included patients suspected and/or treated for EPTB located from Chennai district during the year 2021–2022. All processed EPTB samples were subjected to smear microscopy, culture and Truenat MTB testing. ResultsOf the 195 samples tested, 38 (19.4%) samples were positive for EPTB by any one of the diagnostic methods (smear, culture, microscopy). Out of these 38, 16 (42.1 %) were positive for MTB by Truenat and negative by Culture, 12 (31.5%) were positive by culture but negative by Truenat and 8 (21%) were positive by both Truenat and/or smear and culture. The sensitivity and specificity of the test was calculated with the composite reference standard (Culture (exclusion of colonies as positives), clinical conditions, and smear) and was found to be 60% and 100% respectively. ConclusionTruenat MTB test is a cost-effective rapid molecular test that can be used only for the diagnosis of presumptive EPTB and not on follow-up samples.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

ObjectiveTo evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis (EPTB). MethodsThis study was conducted at the Shanghai Public Health Clinical Center. A total of 115 patients underwent ultrasound-guided puncture biopsy, followed by MGIT 960 culture (culture), smear, GeneXpert MTB/RIF (Xpert), and histopathological examination. These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria: liquid culture and composite reference standard (CRS). ResultsWhen CRS was used as the reference standard, the sensitivity and specificity of culture, smear, Xpert, and histopathological examination were (44.83%, 89.29%), (51.72%, 89.29%), (70.11%, 96.43%), and (85.06%, 82.14%), respectively. Based on liquid culture tests, the sensitivity and specificity of smear, Xpert, and pathological examination were (66.67%, 72.60%), (83.33%, 63.01%), and (92.86%, 45.21%), respectively. Histopathological examination showed the highest sensitivity but lowest specificity. Further, we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80% and a specificity of 89.29%. ConclusionUltrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB. Compared with culture, smear, and Xpert, histopathological examination showed higher sensitivity but lower specificity. The combination of histopathology with Xpert showed the best performance characteristics.

Usefulness of Xpert MTB/RIF Ultra for rapid diagnosis of extrapulmonary tuberculosis in Tunisia

Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis. The purpose of this study was to assess the accuracy of Xpert MTB/RIF Ultra (Cepheid, USA) for rapid diagnosis of EPTB in Tunisia. Eight hundred and forty-seven extrapulmonary samples collected from 2017 to 2021, were subjected to Xpert MTB/RIF Ultra. Microscopy and culture were performed for all the specimens. The accuracy of Xpert Ultra was evaluated in comparison to the culture. Xpert Ultra diagnosed EPTB with a global sensitivity of 80.66% (74.3–85.75) and specificity of 70.87% (67.31–74.20). The molecular test was most accurate when performed in cerebrospinal fluids, bones and joints and cutaneous specimens showing a sensitivity of 100% and a specificity ranging from 70.60 to 91.11%. In lymph node samples comprising aspirates and biopsies, the sensitivity of Xpert Ultra was high 87.50% (77.23–93.53), however, the specificity was 51.08% (44.67–57.46). For pleural samples, the Xpert Ultra sensitivity was 77.50% (68.34–84.68) ranging from 71.43 to 80% in pleural biopsies and fluids respectively. The specificity in all pleural specimens was 79.56% (74.40–83.91). Xpert Ultra showed promise in the diagnosis of EPTB. The performances varied according to the site of the disease. The test may be more valuable if used in combination with other diagnostic modalities.

The diagnostic performance of Xpert MTB/RIF Ultra on Pericardial, Pleural and Ascitic cohort study fluids for diagnosis of extra-pulmonary Tuberculosis at a referral hospital in Malawi.

Extra-pulmonary tuberculosis (EPTB) accounts for 15% of the 1.4 million patients with TB notified in 2019. EPTB carries a high risk of mortality and so early diagnosis and treatment are important to reduce this risk. Diagnosis of EPTB in low- and middle-income countries is challenging. This study investigated the diagnostic performance of Xpert MTB Ultra for the diagnosis of EPTB (pericardial, pleural, and ascitic fluid) in adults at a referral hospital in Malawi. Adults with suspected extra-pulmonary TB were screened for evidence of extra-pulmonary fluid and tested for TB using Xpert MTB Ultra, mycobacterial culture, and a Focused Abdominal Sonography in HIV-associated TB (FASH scan). The diagnostic performance of the Xpert MTB Ultra was compared to mycobacterial culture and a composite reference standard defined as a positive FASH scan or a positive mycobacterial culture or a clinical TB diagnosis (constitutional symptoms not otherwise explained with response to empirical TB treatment). There were 174 patients recruited: 99/174 (57%) pleural, 70/174 (40%) ascitic and 5/174 (3%) pericardial. Overall, 10/174 (6%) had bacteriologically confirmed TB and 30/174 (17%) were started on TB treatment based on a positive FASH scan or a clinical TB diagnosis. The sensitivity and specificity of Xpert ultra compared to culture was 83% (95%CI:36%-100%) and 98% (95%CI:94%-99%), respectively. Compared to the composite reference standard, the sensitivity of Xpert Ultra was 17% (95%CI:7%-34%) and specificity was 98% (95%CI:94%-100%). Xpert MTB Ultra provides good diagnostic performance on pleural, pericardial and ascitic fluid with reference to mycobacterial culture. Improved EPTB diagnostic tests are required to improve patient outcomes. We recommend larger multi-centre studies to corroborate our findings.

Diagnostic accuracy of the IFN-γ release assay using RD1 immunodominant T-cell antigens for diagnosis of extrapulmonary tuberculosis.

The diagnosis of extrapulmonary tuberculosis (EPTB) poses a significant challenge, with controversies surrounding the accuracy of IFN-γ release assays (IGRAs). This study aimed to assess the diagnostic accuracy of RD1 immunodominant T-cell antigens, including ESAT-6, CFP-10, PE35, and PPE68 proteins, for immunodiagnosis of EPTB. Twenty-nine patients with EPTB were enrolled, and recombinant PE35, PPE68, ESAT-6, and CFP-10 proteins were evaluated in a 3-day Whole Blood Assay. IFN-γ levels were measured using a Human IFN-γ ELISA kit, and the QuantiFERON-TB Gold Plus (QFT-Plus) test was performed. Predominantly, the patients were of Afghan (62%, n=18) and Iranian (38%, n=11) nationalities. Eighteen individuals tested positive for QFT-Plus, accounting for 62% of the cases. The positivity rate for IGRA, using each distinct recombinant protein (ESAT-6, PPE68, PE35, and CFP-10), was 72% (n=21) for every protein tested. Specifically, among Afghan patients, the positivity rates for QFT-Plus and IGRA using ESAT-6, PPE68, PE35, and CFP-10 were 66.7%, 83.3%, 83.3%, 77.8%, and 88.9%, respectively. In contrast, among Iranian patients, the positivity rates for the same antigens were 54.5%, 54.5%, 54.5%, 63.6%, and 45.5%, respectively. In conclusion, our study highlights the potential of IGRA testing utilizing various proteins as a valuable diagnostic tool for EPTB. Further research is needed to elucidate the underlying factors contributing to these disparities and to optimize diagnostic strategies for EPTB in diverse populations.

Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of ‘trace’ results

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021–January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as ‘trace’ category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but ‘trace’ results should be interpreted with caution.

Advances in the detection of extrapulmonary tuberculosis: A comprehensive narrative review

Tuberculosis (TB) is a highly infectious disease with high prevalence in the economically poor countries in the world with pulmonary and extrapulmonary manifestations. Though major involvement is pulmonary but extrapulmonary tuberculosis burden is quite high &amp; requires a very strong index of suspicion with exhaustive workup for diagnosis. Due to delayed diagnosis and treatment, Extrapulmonary Tuberculosis (EPTB) seems to be more dangerous than Pulmonary Tuberculosis (PTB). EPTB can manifest itself in almost all parts of the body, producing a wide range of symptoms, making its detection tough. Early detection and timely treatment are necessary to prevent the worsening of the symptoms. Newer diagnostic tests like CBNAAT, RT-PCR, and gene sequencing have been introduced over recent years to improve the quality of assessment of this disease. While traditional diagnostic tests like culture, microscopy, and tuberculin tests take days to months to yield results, CBNAAT gives results in only 2 hours, thus making the prognosis better. However, their access is still limited to majorly developed and developing countries, being costlier than the traditional methods. This review focuses on various diagnostic procedures available for the diagnosis of EPTB.