Diagnosis Of Extrapulmonary Tuberculosis Research Articles

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 & 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.

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.

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).