Diagnosis Of Extrapulmonary Tuberculosis Research Articles

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.

Comparing the cost-effectiveness of the MPT64-antigen detection test to Xpert MTB/RIF and ZN-microscopy for the diagnosis of Extrapulmonary Tuberculosis: An economic evaluation modelling study.

Extrapulmonary Tuberculosis (EPTB) poses challenges from patient and health system perspectives. The cost-effectiveness analysis of the Xpert MTB/RIF (Xpert) test to diagnose pulmonary tuberculosis is documented. However, there are no economic evaluations for EPTB. Considering the reported better diagnostic sensitivity of the MPT64 test, this study explored its cost-effectiveness as an alternative diagnostic test. We conducted this economic evaluation to assess the cost-effectiveness of the MPT64 test compared to Xpert and ZN microscopy for EPTB adult patients. We utilised a Markov modelling approach to capture short- and long-term costs and benefits from a health system perspective. For the model inputs, we combined data from our cohort studies in Tanzania and peer-reviewed EPTB literature. We calculated the Incremental Cost Effectiveness Ratio (ICER) by comparing the cost (in USD) of each diagnostic test and Quality Adjusted Life Years (QALYs) as health gain. We found the MPT64 test cost-effective for EPTB diagnosis and absolutely dominated ZN microscopy and Xpert using the baseline model inputs. A scenario analysis showed that the Xpert test might be the most cost-effective at its higher test sensitivity, which corresponds to using it to diagnose lymph node aspirates. The prevalence of HIV among EPTB cases, their probability of treatment, costs of ART, and the probability of the MPT64 test in detecting EPTB patients were the main parameters associated with the highest impact on ICER in one-way deterministic analysis. The most cost-effective option for EPTB at the baseline parameters was the MPT64 diagnostic test. Including the MPT64 test in EPTB diagnostic pathways for previously untreated patients can lead to better resource use. The Xpert test was the most cost-effective diagnostic intervention at a higher diagnostic test sensitivity in scenario analyses based on different sites of infection, such as for the lymph node aspirates.

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 & 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.

Diagnostic value of chemiluminescence for urinary lipoarabinomannan antigen assay in active tuberculosis: insights from a retrospective study.

This study aimed to assess the efficacy of chemiluminescence-based urinary lipoarabinomannan (LAM) antigen assay as a diagnostic tool for identifying active tuberculosis. A retrospective study was conducted on 166 Tuberculosis (TB), 22 Non-Tuberculous Mycobacteria (NTM), 69 Non-TB cases, and 73 healthy controls from Zhangjiagang First Peoples Hospital between July 2022 and November 2022. Clinical and laboratory data were collected, including urine samples for LAM antigen detection, sputum samples and pleural effusion for GeneXpert, TB-DNA, and culture. TB group exhibited a higher LAM positivity rate (P < 0.001). CD4 count and diabetes as independent factors influencing the diagnostic accuracy of LAM. The LAM assay showed a sensitivity of 50.6% and a specificity of 95.65%. Notably, LAM's sensitivity was superior to TB-DNA (50.60% vs. 38.16%, P < 0.05). LAM's PTB detection rate was 51.7%, superior to TB-DNA (P = 0.047). Moreover, in EPTB cases, the LAM detection rate was 42.11%, surpassing Gene Xpert (P = 0.042), as well as exceeding the detection rates of TB-DNA and sputum culture. LAM antigen detection using chemiluminescence has demonstrated outstanding clinical diagnostic value for active TB, especially in the diagnosis of extrapulmonary TB. The convenience of sample collection in this diagnostic approach allows for widespread application in the clinical diagnosis of active tuberculosis, particularly in cases of EPTB and sputum-negative patients.

Concordance and discordance of GeneXpert MTB/RIF and conventional culture method for diagnosis of Extra-Pulmonary Tuberculosis at a tertiary care hospital in Pakistan.

To identify concordance and discordance between GeneXpert MTB/RIF assay and gold standard bacteriologic culture for the diagnosis of Mycobacterium tuberculosis (MTB) in Extra-Pulmonary tuberculosis (EPTB) specimens in our region. This is a retrospective cross-sectional study conducted at the Indus Hospital and Health Network. Data from 1st January, 2020 to 31st December, 2021 was analyzed. A total of 1499 EPTB specimens were included for which GeneXpert was requested along with acid-fast bacteria (AFB) culture from the same specimen. Specimens were processed according to specimen type following standard operating procedures of the laboratory. Fluorescent staining was performed on all specimens along with bacteriologic culture. The GeneXpert MTB/RIF assay was carried out in exact accordance with the manufacturer's instructions. Out of 1499 EPTB specimens, 1370 (91.39%) specimens exhibited concordance between GeneXpert and conventional culture method, while 129 (8.60%) specimens showed discordance. GeneXpert exhibited sensitivity and specificity of 69.4% and 94.3% respectively in comparison to culture. GeneXpert sensitivity for the diagnosis of EPTB varied with the site involved. Lower sensitivity was observed in ascitic and pleural fluids as compared to higher sensitivity observed among urine samples and pus aspirates. However, given the quick turnaround time and ease of use, it is a helpful tool in the diagnosis of EPTB when utilized in the appropriate clinical context. Caution is advised while interpreting negative GeneXpert results in endemic settings and should be interpreted along with other supporting clinical and diagnostic features.

LOCALISATION ANOPARIETALE DE LA TUBERCULOSE. À PROPOS D’UNCAS

ntroduction: Anoperineal localization of tuberculosisis a rare clinical form with often delayed diagnosis. Wereport a case of anal mycobacterium tuberculosiscomplicated by tuberculous miliaria.Case report: A 25-year-old patient was admitted to theDepartment of Pneumology for treatment of a chronicproductive cough and Sadoul stage 2 dyspnea in acontext of fever and general deterioration. Questioningrevealed that the patient had had risky sex, had analpain and h, which he attributed to an undocumentedhaemorrhoidal disease for which he had been receivingtreatment for several months. Clinical examinationrevealed a PS of 3, fever of 38°C and SpO2 of 99% onroom air. Pleuropulmonary examination revealedbilateral basal crackles in both lung fields. Proctologicalexamination revealed a painful perianal ulceration withirregular margins and a dirty background, resting onan erythematous base. The patient tested negative forBAAR and positive for IDRT. The chest X-ray showedmicronodular opacities scattered over both lung fields.GeneXpert testing of the anal lesion was positive andsensitive. Given this clinical picture, the radiographicabnormalities and the biological data, the diagnosis ofanal tuberculosis complicated by miliaria was accepted.Anti-tuberculosis treatment was started, together withlocal treatment. After 1 month, there was a significantimprovement in symptoms. Unfortunately, the patientdied 4 months later.Conclusion: The diagnosis of extrapulmonarytuberculosis is not always easy and anal tuberculosisposes a diagnostic problem with an often dismalprognosis, as was the case in our patient.Key words: tuberculosis, delayed diagnosis, prognosisCorrespondance : Tafsir Ngary KaService de pneumologie du CHNU de FannEmail : tafsirka80@gmail.comTel : +22177686637491

Assessing risks for bovine and zoonotic tuberculosis through spatial analysis and a questionnaire survey in Fiji – A pilot study

Mycobacterium bovis causes tuberculosis in cattle and when transmitted to humans typically causes extra-pulmonary tuberculosis (EPTB). Bovine tuberculosis (bTB) has a global distribution and is controlled in most countries to protect animal and public health. Recent studies revealed that bTB is established on dairy farms in Fiji where EPTB cases have been reported in people. The aims of this pilot investigation were to look for putative zoonotic TB (EPTB) cases in people and to evaluate practices that might contribute to the persistence and transmission of M. bovis between cattle and to humans. Existing data sets were shared between the Fiji Ministry of Agriculture and Ministry of Health and a questionnaire-based survey was implemented using One Health principles. Statistically significant co-location and close proximity of EPTB cases and bovine TB affected farms were identified. The bTB infection status of farms was significantly associated with unfenced water sources where cattle grazed. Of 247 households, 65 % shared drinking water sources with cattle and 36 % consumed raw milk without boiling, while 62 % of participants reported backyard slaughter of cattle. Several participants reported current symptoms potentially suggestive of TB (chronic cough) but the impact of smoking and history of previous TB treatment could not be evaluated. Farmers had limited understanding of the practices required to prevent bTB at farm level. Further study is recommended and should include an assessment of lifetime EPTB diagnoses, classification of farms based on more recent bTB test data and molecular typing of mycobacterial isolates from humans, cattle and the environment. A targeted awareness and education approach is required to reduce the future risk of zoonotic TB and to help ensure uptake of recommendations and practices aimed at controlling and preventing bTB.

Performance of IS6110-LAMP assay for detection of Mycobacterium tuberculosis complex in blood and urine samples from patients with extrapulmonary tuberculosis

BackgroundThe diagnosis of extrapulmonary tuberculosis (EPTB) shows numerous difficulties because of non-specific symptomatology and low sensitivity of conventional methods. Loop-mediated isothermal amplification (LAMP) is a fast and low-cost technique, which can amplify under isothermal conditions an amount of target DNA copies into approximately a billion copies. ObjectiveThe present study aimed to evaluate a IS6110-LAMP system for Mycobacterium tuberculosis detection in blood and urine samples from patients with EPTB. MethodsThe collected samples (n = 122) were stratified in two groups: Group EPTB – patient samples with confirmed EPTB (n = 61); Group non-TB – patient samples without TB (n = 61). The urine samples underwent decontamination, and the components of blood samples were separated (plasma and PBMC). DNA extractions were performed in all biological samples followed by IS6110-LAMP assay technique. The detection limit was evaluated through dilution curves (1:10) using Mtb reference strain (H37Rv) genomic DNA. FindingsThe detection limit of IS6110-LAMP was 10 fg/μL (∼10–20 bacilli/μL). The IS6110-LAMP technique sensitivity and specificity were 95.65 % and 79.25 %, respectively, with a general kappa agreement index of 0.762. Main conclusionsBased on these results, IS6110-LAMP test showed considerable diagnostic parameters, being able to aid in the speed and accuracy of the final EPTB diagnosis.

GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis.

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

Diagnostic Efficacy of New Xpert Ultra for Extrapulmonary Tuberculosis Using Culture and Composite Reference Standard.

Xpert Ultra (Cepheid, USA) is recently introduced with an extra category of trace-positive results and higher sensitivity for tuberculosis (TB) diagnosis. The objective of the study was to assess the diagnostic accuracy of Xpert Ultra for extrapulmonary samples using culture and composite reference standard (CRS) as the gold standard. In a 1-year (March 2021-22) prospective observational study, samples of suspected extrapulmonary TB (EPTB) patients were subjected to Ziehl-Neelsen staining, culture, and Xpert Ultra (Cepheid, Sunnyvale, CA) tests. Relevant clinical and treatment information was noted. The diagnostic accuracy of Xpert Ultra compared with culture and CRS was calculated. Out of 1720 suspected patients of EPTB, 223 (13%), predominantly males 135 (60%), with a mean age of 41.46 ± 19.81 years, were diagnosed as TB positive following CRS criteria. The maximum cases were of pleural TB (35.4%), followed by central nervous system TB (17.9%), gastrointestinal TB (17.5%), and lymph node TB (12.1%). Of all samples, 150 (8.7%) were microbiologically confirmed, including 141 detected by Xpert ultra, 67 culture positive, and only 16 smear positive. Among the Xpert Ultra-positive samples, 35 showed trace results, including six false-positive results. Considering culture and CRS as the gold standard, the sensitivity (86.57%, 59.64%) and specificity (94.98%, 99.47%) of Xpert Ultra were calculated, respectively. Rifampicin resistance was detected in 1 (0.70%) sample. Diagnosis of EPTB is a challenge and Xpert Ultra may detect TB at a very early stage. However, it is essential to rule out false-positive results. Additional studies are needed on Xpert Ultra to interpret trace results better.

Histopathological features in the clinical specimens with tuberculosis diagnosis by BACTEC MGIT 960 culture

Diagnosis of extrapulmonary tuberculosis remains challenging in lower-middle income countries with high burden of tuberculosis (TB). This study aims to describe the histological characteristics in biopsy samples from patients with confirmed TB. This is a retrospective study of clinical biopsy specimens with positive liquid medium culture for Mycobacterium tuberculosis and histopathological examination in the National Lung Hospital in Vietnam. Among 1045 biopsy specimens with mycobacteria culture, the overall rate of growth of Mycobacteria tuberculosis in culture was 20.7% (216/1045). The positivity rates of MIGT culture among surgical biopsy specimens were 75% in bone specimen, followed by vertebral specimens (51.3%), and joint specimens (26.4%). For specimens obtained by the fine needle aspiration, the positivity rates of MIGT culture were 26.3% in lymph node and 25.3% in pleural specimen. Among specimens with culture confirmation of TB, the most common histopathoglogical suggestive finding of TB was the presence of epithelioid cell (83.3%), Langhans giant cells (75.9%), and caseous necrosis (75.5%). The high proportion of histological features suggestive of TB among the TB culture confirmed biopsy samples support for further evaluation of histological examination and its combination with other recommended rapid molecular assays in specimens with suspicion of TB.

INDEX guidelines for extra-pulmonary tuberculosis: knowledge and practice among clinicians in Bengaluru, Karnataka

Background: Extra-pulmonary tuberculosis (EPTB) remains a major problem in developing countries, which acquire diagnostic and management challenges. The study was conducted to characterize the diagnosed EPTB cases, and to understand the perspectives of clinicians on diagnosis and challenges in its management. Methods: A total of 150 EPTB patients' medical records were reviewed at two tertiary hospitals in Bengaluru, Karnataka for the period January 2017 to December 2017. The questionnaire-based interview was conducted among clinicians (n=42) during the study period. Results: The mean age and weight of EPTB patients (females (77, 51%) and males (73, 49%) were 32.5 (±17.5) years and 44.5 (±16.3) kilograms, respectively. Pleural TB (44, 29%), cervical lymph node TB (LNTB) (32, 21%) and abdominal TB (17, 11%) were the most common sites of EPTB involvement, followed by bones and joints TB (11, 7%), spine TB (10, 7%), hilar/mediastinal TB (9, 6%), tuberculoma (8, 5%), TB meningitis (6, 4%), abdominal LNTB (6, 4%), urinary TB (4, 3%) and others (3, 2%). We found GeneXpert was the basis of EPTB diagnosis in 43.3% of cases followed by acid-fast bacilli (AFB) smear microscopy (20.7%) and culture (12.5%). Of 150 EPTB suspected cases, 73% (110) were started anti-TB treatment (ATT), including 8% (12) having received ATT previously. According to LIKERT scale options, 90% of clinicians agreed GeneXpert as a promising diagnostic tool for diagnosis as compared to other microbiological (79%) and histopathological tests (55%). Conclusions: The quality of EPTB diagnosis and management practices at these institutions is satisfactory according to the principles laid down in INDEX TB guidelines or the national guidelines.

Understanding the bacillary load and host interaction to design a point-of-care test to diagnose tuberculosis

Designing of a Point-of-care test to diagnose tuberculosis (TB) is not an easy task. This viewpoint stems from the dichotomous diagnostic approach, based on the bacillary load estimated in latent tuberculosis infection (LTBI), thanks to the isoniazid chemoprophylaxis strategy, as well as the importance of imaging to differentiate between LTBI and TB. It integrates the “TB spectrum” elucidated through positron emission tomography-computed tomography scan (PET-CT) to highlight the dynamic nature of TB lesions. Additionally, it emphasizes the relevance of animal models that support this perspective, including the drainage of bacilli through foamy macrophages, which aids in understanding LTBI and its chemoprophylaxis, and the significance of lung anatomy in TB induction. Especially the role of interlobular septa and the encapsulation process and its role in lung lobe predilection impact disease progression. Moreover, it acknowledges the gender bias in TB, as its incidence is significantly higher in men across various socioeconomic circumstances, suggesting an unidentified biological mechanism. For a comprehensive approach, the impact of stress and cortisol levels is suggested as a new parameter to be considered, given their association with poverty, and social inequity, and their tendency to be higher in men. All this information has to be contemplated when designing an accurate point-of-care test. The test should encompass the complexity of TB and necessarily integrate both bacillary and host response parameters. It also should cover the diagnosis of extrapulmonary TB, and pay attention to immunosuppressed and pediatric population.

Quantification of mycobacterial proteins in extrapulmonary tuberculosis cases by nano-based real-time immuno-PCR.

Aim: Diagnosis of extrapulmonary tuberculosis (EPTB) is difficult, and a rapid and dependable diagnostic test is urgently needed. Methods: A nano-based assay, SYBR Green magnetic bead-coupled gold nanoparticle-based real-time immuno-polymerase chain reaction (MB-AuNP-RT-I-PCR) was studied for the quantitative detection of Mycobacterium tuberculosis MPT-64+CFP-10 proteins in clinically suspected EPTB patients. Results: A wide range (270fg/ml-9.9ng/ml) of MPT-64+CFP-10 was quantified by MB-AuNP-RT-I-PCR in EPTB cases, whereas magneto-ELISA demonstrated a narrow range (1.8-10ng/ml). Furthermore, high sensitivity (88.2%) and specificity (100%) were attained by MB-AuNP-RT-I-PCR in EPTB (n=51) and non-TB control (n=49) subjects, respectively. Both MB-AuNP-I-PCR/magneto-ELISA exhibited significantly lower (p<0.05-0.01) sensitivities than MB-AuNP-RT-I-PCR. Conclusion: The MB-AuNP-RT-I-PCR described hereinshows good diagnostic accuracy, which may translate into a credible diagnostic kit.

Epidemiology of extrapulmonary tuberculosis in Brunei Darussalam: a retrospective cohort study

ObjectivesWe reported the incidence and associated factors of extrapulmonary tuberculosis (EPTB).DesignA retrospective cohort study.SettingBrunei Darussalam, an intermediate tuberculosis (TB)-burden country with stagnating annual TB rates.ParticipantsAll active TB cases identified in...

Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB).

MPT51 and MPT64-based antigen detection assay for the diagnosis of extrapulmonary tuberculosis from urine samples

In view of WHO's “End-TB” strategy, we developed a non-invasive, urine-based ELISA, targeting 2 Mycobacterium tuberculosis antigens namely MPT51 and MPT64 for extrapulmonary TB (EPTB) diagnosis. Suspected EPTB patients (n = 137) [Pleural TB, Abdominal TB and Tuberculous meningitis] were categorized in “Definite” EPTB (n = 10) [Xpert-MTB/RIF and/or culture-positive], “Probable” EPTB (n = 77) and “Non-EPTB” (n = 50) groups using defined composite reference standards. ROC-curves were generated using ELISA results of “Definite” EPTB and “Non-EPTB” groups for both antigens independently and cut-off values were selected to provide 86.3% (95%CI:73.3–94.2) specificity for MPT51 and 92% (95%CI:80.8–97.8) for MPT64. The sensitivity of MPT51-ELISA and MPT64-ELISA was 70% (95%CI:34.7–93.3) and 90% (95%CI:55.5–99.7) for “Definite” EPTB group and 32.5% (95%CI:22.2–44.1) and 30.8% (95%CI:20.8–42.2) for “Probable” EPTB group, respectively. Combining the results of both ELISAs showed a 100% (95%CI:69.1–100) sensitivity in “Definite” EPTB group and 41.6% (95%CI:30.4–53.4) in “Probable” EPTB group, with an 80% (95%CI:66.3–89.9) specificity. The results demonstrated the potential of urine-based ELISAs as screening tests for EPTB diagnosis.

Accuracy of Xpert® MTB/RIF in diagnosing extrapulmonary tuberculosis in Indian children.

Background Diagnosing extrapulmonary tuberculosis (EPTB) can be challenging because of a variety of presentations. We assessed the accuracy of the Xpert MTB/RIF assay in diagnosing EPTB in children. Methods Of the 255 children diagnosed to have tuberculosis (TB) who underwent testing by the Xpert MTB/ RIF assay at the TB clinic from December 2014 to April 2017, 182 had EPTB and were included in the study. The diagnostic accuracy, specificity and sensitivity of the Xpert assay were calculated with Mycobacterium growth indicator tube (MGIT) as a reference standard. Results Lymph node TB was present in 58 (32%) children, 37 (20%) had neurological TB, 36 (20%) had bone TB, 31 (17%) had pleural TB, 15 (8%) had abdominal TB, 2 (1%) had abscess, 2 (1%) had congenital TB and disseminated TB was seen in 1 (0.4%) child. Xpert MTB/RIF assay was positive in 84 (46.2%) patients. The sensitivity and specificity of the Xpert MTB/RIF assay were 72% and 72.04%, respectively. Compared to MGIT, a kappa coefficient of 0.44 shows moderate agreement between the Xpert assay and MGIT. The sensitivity of Xpert MTB/RIF assay in abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 50% (15%-85%), 72.7% (15.9%- 86.9%), 80.8% (62.1%-91.5%), 75% (50.5%-90%) and 25% (4.6%-70%), respectively. The specificity of abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 83.3% (43.7%-97%), 69.2% (42.4%- 87.3%), 55.2% (37.6%-71.6%), 85% (64%-94.8%) and 82.6% (62.9%-93%), respectively. Forty-seven (26%) patients had drug-resistant TB (DR-TB), of which 15 (8%) were rifampicin-resistant (RR), 2 (1%) were polyresistant, 14 (8%) had multi-DR (MDR), 15 (8%) had pre-extremely DR (XDR) and 1 (1%) had XDR-TB. Of the 15 patients with MDR-TB, Xpert MTB/RIF assay detected only 10 (71%) as RR (p=0.06). Of the 15 pre-XDR cases, Xpert MTB/RIF detected only 8 (53%) as RR (p=0.02). Conclusion Xpert MTB/RIF assay is useful in the diagnosis of EPTB. It shows good concordance with MGIT. However, it may be negative in patients with DR-TB.

Diagnostic Performance of Different Laboratory Methods for the Detection of Extrapulmonary Tuberculosis.

Accurate and appropriate extrapulmonary tuberculosis (EPTB) diagnosis remains challenging due to its paucibacillary nature, requirement of invasive collection procedures, and lack of sensitive tests. This study investigated the diagnostic performance of different methods for the diagnosis of EPTB. A total of 1340 EPTB specimens were collected from presumptive EPTB patients from four different hospitals between November 2015 and March 2017. The collected specimens were tested with AFB microscopy, culture, Xpert MTB/RIF assay (Xpert), and MTBDRplus assay. Among the 1340 EPTB specimens, 49 (3.66%), 141 (10.52%), 166 (12.39%), and 154 (11.49%) were positive in AFB microscopy, culture, Xpert MTB/RIF, and MTBDRplus assay, respectively. A total of 194 (14.9%) cases were found positive in at least one of these methods. Using culture as a reference standard, the sensitivity and specificity of AFB microscopy, Xpert MTB/RIF, and MTBDRplus assay were: 27.0%/99.1%, 83.7%/96.0%, and 79.4%/96.5%, respectively. Compared to the composite reference standard, the sensitivity of culture, AFB microscopy, Xpert MTB/RIF, and MTBDRplus assay was 72.7%, 25.3%, 85.6%, and 79.4%, respectively, with a specificity of 100% for all the methods. The Xpert MTB/RIF assay showed the highest sensitivity compared to other methods. Considering the short turnaround time and promising findings, Xpert MTB/RIF assay should be integrated into national TB guidelines as a routine diagnostic test.

Diagnosis of extrapulmonary tuberculosis by ultrasound-guided biopsy: A retrospective comparison study.

To compare the diagnostic performance of laboratory assays on the ultrasound-guided core needle biopsy samples for diagnosis of extra-pulmonary tuberculosis (EPTB) in HIV-positive and HIV-negative patients. A total of 217 patients suspected to have EPTB underwent lesion biopsy from 2017 to 2020. Results of laboratory tests on the biopsy and non-biopsy samples were collected with clinical data for retrospective analysis of test utility. The calculated diagnostic accuracy of the tests was stratified according to the specimen types and HIV status. The cohort contained 118 patients with a final positive diagnosis of extrapulmonary tuberculosis (EPTB group, 54.4%) and 99 finally diagnosed as without TB (non-EPTB group, 45.6%). The risk factor for EPTB was HIV co-infection (OR 2.22, 95% CI 1.17-4.28, p = 0.014). In biopsy samples, GeneXpert (Xpert) showed higher sensitivity (96.6% [91.6-98.7], p < 0.0001) than culture (56.1% [47.0-64.9]). Regardless of HIV status, Xpert had the highest sensitivity (>95%) and specificity (nearly 100%) of any methods. In non-biopsy samples, only T-SPOT.TB (T-SPOT) showed higher sensitivity than culture (90.9% [62.3-99.5] vs 35.3% [17.3-58.7], p = 0.0037). Furthermore, the sensitivities of Xpert were lower in non-biopsy samples (60.0% [23.1-92.9], p = 0.022) than in biopsy samples (100% [86.7-100]). Even in smear-negative biopsy samples, Xpert still had higher sensitivity than culture and retained high specificity (100% [95.7-100]). Superior performance of Xpert in diagnosing EPTB was observed regardless of HIV status and specimen types. Nevertheless, the biopsy samples still substantially facilitated the accurate diagnosis of extrapulmonary tuberculosis.