Smear-negative Pulmonary Tuberculosis Patients Research Articles

Clinical and Imaging Characteristics of Smear Negative Pulmonary Tuberculosis Patients: A Comparative Study.

Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia.

Significance of serum copper zinc ratio in smear negative pulmonary tuberculosis cases in Rohilkhand region

Tuberculosis being a highly contagious chronic pulmonary and systemic disease is explicit cause of morbidity and mortality worldwide. There is a direct relationship between zinc and copper in maturation of immunity, Cu/Zn ratio in serum serves to assess levels of oxidative stress in infectious diseases and thus could be used as a diagnostic tool in early diagnosis of smear negative tuberculosis. To study and evaluate significance of serum Cu and Zn concentration and Cu/Zn ratio in smear negative pulmonary tuberculosis patients in comparison to apparently healthy controls. Observational case control study was carried out on patients attending IPD and OPD, Department of Pulmonary Medicine, RMCH. Fifty cases of smear negative PTB patients(group A) was taken and compared with fifty age and sex matched apparently healthy controls(group B). Serum Cu and Zn were estimated in both groups by colorimetric method using EM Chem5Plus V2 Semi autoanalyzer. Data is presented as mean ± SD. Comparison of serum levels of the parameters between the two groups was performed by Student’s‘t’ test. The p value &amp;#60;0.05 was considered as statistically significant. We found serum Zinc to be significantly lower in group I than group II(p&amp;#60;0.00), serum Copper &amp; Cu/Zn ratio to be significantly higher in group I than II(p&amp;#60;0.00). The results suggests that early estimation of serum Cu, Zn &amp; Cu/Zn ratio serves as useful diagnostic marker for smear negative pulmonary TB cases though more extensive multicentric study will provide more insights.

Development of a new cellular immunological detection method for tuberculosis based on HupB protein induced IL-6 release test.

As a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein. HupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings. Cytokine's screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis. This study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.

Diagnostic Yield of Direct Smear, Concentrated Smear, Liquid Culture, and GeneXpert by Sputum Induction in Smear-Negative Pulmonary Tuberculosis Patients

Background: Spontaneous sputum smear gave negative results in clinically and radiologically suspected pulmonary tuberculosis (TB) patients. Hence, the study aimed to evaluate the diagnostic yield of induced sputum with direct smear, concentrated smear, liquid culture, and GeneXpert. Materials and Methods: This cross-sectional study was conducted on clinically and radiographically suspected TB patients who were sputum smear-negative; 88 sputum smear-negative patients underwent sputum induction, and the samples were tested for direct smear, concentrated smear, liquid culture, and GeneXpert. Descriptive analysis was carried out for frequency and proportion for categorical variables and mean and standard deviation for quantitative variables. Diagnostic yield was calculated for each test. Data analyzed using coGuide software, V.1.03. Results: The mean age of the study population was 46.87 ± 15.09 years, and male participants were the majority. The diagnostic yield of induced sputum was 19.29% compared to a direct smear. Diagnostic yield was 59.25%, 80.70%, and 94.73% for concentrated smears, liquid culture, and GeneXpert, respectively. Conclusion: Induced sputum gave a high diagnostic yield in smear-negative pulmonary TB. With induced sputum, GeneXpert gave maximum yield compared to direct smear, concentrated smear, and liquid culture.

Effect of sputum quality and role of Xpert® MTB/ RIF assay for detection of smear-negative pulmonary tuberculosis in same-day diagnosis strategy in Addis Ababa, Ethiopia.

BackgroundThere is limited information on the performance of the Xpert® MTB/RIF test for diagnosis of smear-negative pulmonary tuberculosis (SNPT) and rifampicin resistance (RR) in the same-day diagnosis approach. The effects of sputum quality and other factors affecting the Xpert performance are also under-investigated.ObjectiveThis study aimed to determine the performance of the Xpert® MTB/RIF test for detection of SNPT and RR in the same-day diagnosis strategy and the effect of sputum quality and other factors on its performance.MethodsA cross-sectional study was conducted from August 2017 to January 2018 across 16 health facilities in Addis Ababa, Ethiopia. Two spot sputum samples were collected from 418 presumptive SNPT patients, tested with Xpert® MTB/RIF, then compared to tuberculosis culture. Additionally, culture isolates were tested for RR by BACTEC MGIT™ 960 drug susceptibility testing (DST) and MTBDRplus version 2.ResultsThe Xpert® MTB/RIF test detected 24 (5.7%) SNPT cases, with a sensitivity of 92.3% (75.9% – 97.9%) and specificity of 99.2% (97.8% – 99.7%) compared with tuberculosis culture. Xpert® MTB/RIF also detected three (11.58%) RR strains with 100.0% concordance with BACTEC MGIT™ 960 DST and MTBDRplus results. Three blood-stained SNPT samples were positive by Xpert (30.0%), which was 6.9 times higher compared to salivary sputum (odds ratio: 6.9, 95% confidence interval: 1.36–34.96, p = 0.020).ConclusionThe performance of the Xpert® MTB/RIF to detect SNPT and RR in same-day diagnosis is high. However, SNPT positivity varies among sputum qualities, and good sample collection is necessary for better test performance.

Persistent expression of activation markers on Mycobacterium tuberculosis-specific CD4 T cells in smear negative TB patients.

T cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB. In this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa. Levels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month. After six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.

Prevalence of chronic pulmonary aspergillosis and the antifungal drug resistance of Aspergillusspp. in pulmonary tuberculosis patients in Uzbekistan.

The aim of our study was to determine the prevalence of chronic pulmonary aspergillosis in pulmonary tuberculosis patients and the antifungal resistance of Aspergillus spp. isolates in Uzbekistan. Chronic pulmonary aspergillosis was detected in 11.4% and 20.0% of smear-positive and smear-negative pulmonary tuberculosis patients, respectively.

Mycobacterium tuberculosis antigen-specific T-cell responses in smear-negative pulmonary tuberculosis patients.

Despite recent improvements in microbial detection, smear-negative TB remains a diagnostic challenge. In this study, we investigated the potential discriminatory role of polychromatic flow cytometry of M. tuberculosis antigen-specific T cells to discriminate smear-negative TB from health controls with or without latent TB infection, and non-TB respiratory illnesses in an endemic setting. A cross-sectional study was conducted on HIV negative, newly diagnosed smear-positive PTB (n = 34), smear-negative/GeneXpert negative PTB (n = 29) patients, non-TB patients with respiratory illness (n = 33) and apparently healthy latent TB infected (n = 30) or non-infected (n = 23) individuals. The expression of activation (HLA-DR, CD-38), proliferation (Ki-67), and functional (IFN-γ, TNF-α) T-cell markers using polychromatic flow cytometry was defined after stimulation with PPD antigens. Sputum samples were collected and processed from all patients for Mtb detection using a concentrated microscopy, LJ/MGIT culture, and RD9 typing by PCR. Our study showed CD4 T cells specific for PPD co-expressed activation/proliferation markers together with induced cytokines IFN-γ or TNF-α were present at substantially higher levels among patients with smear-positive and smear-negative pulmonary TB than among healthy controls and to a lesser extent among patients with non-TB illness. Our study conclude that smear-negative TB can be distinguished from non-TB respiratory illness and healthy controls with a flow cytometric assay for PPD-specific T cells co-expressing activation/proliferation markers and cytokines.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

BackgroundRecent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.MethodsFour SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.ResultsWe found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.ConclusionNEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

Accuracy of GeneXpert in Diagnosis of Smear Negative Tuberculosis: A Cross-Sectional Study

Objective: This study was aimed to compare the diagnostic accuracy of GeneXpert in smear negative as compared to smear positive pulmonary tuberculosis patients.&#x0D; Methods: This comparative cross sectional study was undertaken at Health Research Institute (National Institute of Health) TB Research Centre, Pulmonology King Edward Medical University Lahore, Pakistan. A total of 101 patients in each smear negative and positive groups were included. After taking the informed consent a predesigned questionnaire was used to collect the data.&#x0D; Results: A total of 202 patients consisting of 94 (46.5%) male and 108 (53.5%) females with mean age of patients as 39.83±18.14 years were included in this study. Highest proportion of 45% patients remained to be in age range of 18-35 years. Culture presented the highest accuracy of 96.1% with sensitivity, specificity and positive predictive value of 95.9%, 100%, and 100% respectively while GeneXpert remained to be 94.6%, 94.9%, 80%, and 99.5% respectively in this study.&#x0D; Conclusion: Accuracy of GeneXpert is excellent in diagnosis of smear positive pulmonary tuberculosis patients and very well in diagnosing smear negative pulmonary TB patients and a great addition in early and definite diagnosis of TB and keeps the ability to confirm around 75% smear negative pulmonary tuberculosis.

Who to Involve and Where to Start Integrating Tuberculosis Screening into Routine Healthcare Services: Positive Cough of Any Duration as the First Step for Screening Tuberculosis in Ethiopia.

BackgroundRecent country surveys have shown an unacceptably high prevalence of confirmed tuberculosis (TB) even among those with a low duration of cough, and more than 50% of those with bacteriologically confirmed pulmonary tuberculosis (PTB) do not report symptoms that correspond to presumptive TB. Furthermore, there has been an increase in the incidence of smear-negative PTB patients who can serve as a source of infection. We investigated whether screening people who sought healthcare for cough of any duration can increase TB case detection in Ethiopia, and compiled the lessons learned and recommendations.MethodsWe carried out a facility-based study in Ethiopia. All consenting participants who sought any healthcare at the outpatients department, and healthcare facilities for reproductive and child health, anti-retroviral therapy, and diabetes were screened for cough of any duration, and those with cough underwent further investigations using chest radiography (CXR) (except for pregnant women, patients on anti-retroviral therapy, and diabetic patients) and microbiological tests. Confirmed cases were linked to TB treatment following the country’s standard guidelines.ResultsWe screened 195,713 people who sought healthcare for cough of any duration. Of these, 2647 reported cough symptom of any duration, of whom 1853 underwent further diagnostic tests as they fulfilled the criteria for presumptive TB. Overall, 309/1853 (16.7%) were diagnosed with PTB and linked to TB treatment. Screening by cough of any duration and/or CXR improved TB case finding, and engaging all health teams (administrative and supportive staff, as well as healthcare providers) in the TB screening and diagnosis significantly improved the process.ConclusionScreening for TB using cough of any duration and/or CXR for any patient who sought healthcare has the potential to increase both the number of presumptive TB cases and the number of patients diagnosed with and treated for TB in Ethiopia. Such initiatives require strong engagement of facility staff, regular maintenance and calibration of TB diagnostic equipment, and uninterrupted reagent supplies.

Diagnostic Value of Bronchoalveolar Lavage Examination in Sputum Negative Patients for AFB in Suspected Pulmonary Tuberculosis

Background: Pulmonary tuberculosis (PTB) is one of the most common infections worldwide, more commonly among the developing countries like Bangladesh. So its early detection and prompt treatment was a challenge and the burden of diagnostic challenge was higher if the patients smear negative for Acid Fast Bacilli (AFB). Objective: Evaluate the diagnostic value of Bronchoalveolar lavage (BAL) for diagnosis of suspected Pulmonary Tuberculosis (PTB) whose sputum for AFB smear neagtive. Materials and Methods: A cross-sectional observational reserach was undertaken where 50 patients were included on the basis of specific inclusion and exclusion criteria. All patients who had negative smear for AFB but highly suspected for PTB underwent fibreoptic bronchoscopy to collect Bronchoalveolar lavage (BAL) fluid for diagnostic testing in the form of BAL for AFB and mycobacterial culture in Lowenstein Jensen medium. Results: The Male predominacy 29 (58%) was obserevd among the smear negative PTB patients. Clinically more than seventy percent (72%) presents with fever then cough with sputum and haemoptysis 62% and 32% respectively. Radiological cavitation 33 (66%) was the most common x-ray findings. After analysis of BAL for AFB about 31 (62%) patient found positive and on culture about mycobacterial growth found in 29 (58%) patients. Conclusion: Bronchoalveolar lavage had a superior diagnostic value in patients with smear negative suspected pulmonary tuberculosis. KYAMC Journal.2021;12(02): 84-87

The Diagnostic Potential of CB NAAT in Detecting Drug Resistance in Smear-Negative Pulmonary Tuberculosis Patients: A Retrospective Study

The Diagnostic Potential of CB NAAT in Detecting Drug Resistance in Smear-Negative Pulmonary Tuberculosis Patients: A Retrospective Study

Clinical and CT characteristics of Xpert MTB/RIF-negative pulmonary tuberculosis.

PurposeTo determine the diagnostic accuracy of the Xpert MTB/RIF assay in patients with smear-negative pulmonary tuberculosis (TB) and to assess clinical and CT characteristics of Xpert-negative pulmonary TB.Material and methodsWe retrospectively reviewed the records of 1,400 patients with suspected pulmonary TB for whom the sputum Xpert MTB/RIF assay was performed between September 1, 2014 and February 28, 2020. Clinical and CT characteristics of smear-negative pulmonary TB patients with negative Xpert MTB/RIF results were compared with positive results.ResultsOf 1,400 patients, 365 (26.1%) were diagnosed with pulmonary TB and 190 of 365 patients (52.1%) were negative for sputum acid-fast bacilli. The diagnosis of pulmonary TB was based on a positive culture, positive Xpert MTB/RIF or the clinical diagnoses of patients treated with an anti-TB medication. The sensitivity, specificity, positive predictive and negative predictive values of sputum Xpert MTB/RIF for smear-negative pulmonary TB were 41.1%, 100%, 100%, and 90.1%, respectively. Finally, 172 patients with smear-negative pulmonary TB who underwent chest CT within 2 weeks of diagnosis were included to compare Xpert-positive (n = 66) and Xpert- negative (n = 106) groups. Patients with sputum Xpert-negative TB showed lower positive rates for sputum culture (33.0% vs. 81.8%, p<0.001) and bronchoalveolar lavage culture (53.3% vs. 84.6%, p = 0.042) than in Xpert-positive TB. Time to start TB medication was longer in patients with Xpert-negative TB than in Xpert-positive TB (11.3±16.4 days vs. 5.0±8.7 days, p = 0.001). On chest CT, sputum Xpert-negative TB showed significantly lower frequency of consolidation (21.7% vs. 39.4%, p = 0.012), cavitation (23.6% vs. 37.9%, p = 0.045), more frequent peripheral location (50.9% vs. 21.2 p = 0.001) with lower area of involvement (4.3±4.3 vs. 7.6±6.4, p<0.001). Multivariate analysis revealed peripheral location (odds ratios, 2.565; 95% confidence interval: 1.157–5.687; p = 0.020) and higher total extent of the involved lobe (odds ratios, 0.928; 95% confidence interval: 0.865–0.995; p = 0.037) were significant factors associated with Xpert MTB/RIF-negative TB. Regardless of Xpert positivity, more than 80% of all cases were diagnosed of TB on chest CT by radiologists.ConclusionThe detection rate of sputum Xpert MTB/RIF assay was relatively low for smear negative pulmonary TB. Chest CT image interpretation may play an important role in early diagnosis and treatment of Xpert MTB/RIF-negative pulmonary TB.

Challenges in morphological diagnosis of tuberculosis

TB is the seventh leading cause of death worldwide and third leading cause of death among women in the 15–44 age group1. However, in 2010, the number of multidrug-resistant tuberculosis (MDR-TB) cases rose to 650,000 worldwide, with more than 150,000 deaths. All of the well-known widely available methods such as chest X-ray, culture in liquid and solid media should be accompanied with the modern and more accurate methods such as chest CT and molecular diagnostic tests which proved the necessity of usage with high sensitivity and accuracy, especially in smear-negative pulmonary TB patients and patients with the multi drug resistant forms.

Trends of tuberculosis case detection, mortality and co-infection with HIV in Ghana: A retrospective cohort study.

In an era of renewed commitment to accelerate the declines in Tuberculosis (TB) incidence and mortality, there is the need for National Tuberculosis Programmes (NTPs) to monitor trends in key indicators across a geographical location and to provide reliable data for direct measurement of TB incidence and mortality. In this context, we explored the trends of TB case detection, mortality and HIV co-infection, and examined the predictors of TB deaths in Ten districts of the Volta region of Ghana. We conducted a retrospective cohort study of all TB cases registered from 2013 to 2017 in 10 districts of the Volta Region of Ghana. Case detection rate (CDR) was computed as the ratio of the number of new and relapse TB case notified to NTP to the number of estimated incident TB cases in a given year. Case fatality rates were estimated using data from 2012-2016 cohort of TB patients. Simple and multiple logistic regression were used to identify predictors of TB deaths with odds ratios and 95% confidence intervals estimated. Overall, there were 3,735 new and relapse TB patients who commenced anti-TB treatment during the period, representing the case detection rate of 40.1% with district variations. The CDR remained stable during the 5 years. Of the total cases, HIV status was documented for 3,144 (84.2%), among whom, 712 (22.6%) were HIV positive. The TB/HIV co-infection was more prevalent among children under 15 years of age (30.1%), males (30.6%), treatment after lost to follow-up patients (33.3%), and smear-negative pulmonary TB patients (29.1%). The prevalence of TB/HIV co-infection did not significantly change over the years. The overall case fatality rate was 13% (n = 486), with considerable variation among HIV-positives and HIV-negative TB patients (21.8% and 11% respectively) (p<0.001) and among districts. TB/HIV co-infection, sputum smear-negative pulmonary TB and district of anti-TB treatment predicted TB mortality. TB case detection rate was low and remained stable during the study period, whereas co-infection with HIV and mortality rates were quite high, indicating the need for feasible strategies such as active case finding to improve case detection, and improved case management to reduce mortality.

Diagnostic performance of non-invasive, stool-based molecular assays in patients with paucibacillary tuberculosis

Timely diagnosis of paucibacillary tuberculosis (TB) which includes smear-negative pulmonary TB (PTB) and extra-pulmonary TB (EPTB) remains a challenge. This study was performed to assess the diagnostic utility of stool as a specimen of choice for detection of mycobacterial DNA in paucibacillary TB patients in a TB-endemic setting. Stool samples were collected from 246 subjects including 129 TB patients (62 PTB and 67 EPTB) recruited at TB hospital in Delhi, India. Diagnostic efficacy of stool IS6110 PCR (n = 228) was measured, using microbiologically/clinically confirmed TB as the reference standard. The clinical sensitivity of stool PCR was 97.22% (95% confidence interval (CI), 85.47-99.93) for detection of Mycobacterium tuberculosis in stool samples of smear-positive PTB patients and 76.92% (CI, 56.35–91.03) in samples from smear-negative PTB patients. Overall sensitivity of PCR for EPTB was 68.66% (CI, 56.16–79.44), with the highest sensitivity for stool samples from patients with lymph node TB (73.5%), followed by abdominal TB (66.7%) and pleural effusion (56.3%). Stool PCR presented a specificity of 95.12%. The receiver operating characteristic curve also indicated the diagnostic utility of stool PCR in TB detection (AUC: 0.882). The performance characteristic of the molecular assay suggests that stool DNA testing has clinical value in detection of TB.

Evaluation of GeneXpert MTB/RIF as a diagnostic tool in patients with sputum smear-negative TB in a high HIV burden region in Nigeria.

There are challenges in the diagnosis of TB in people with smear-negative pulmonary TB (SNPTB) in resource-limited settings. We evaluated the diagnostic usefulness of Xpert MTB/RIF compared with TB culture among SNPTB. The study was a cross-sectional study among patients with SNPTB. The Xpert MTB/RIF tests and sputum culture (using Lowenstein-Jensen medium) were performed. Sensitivity and specificity were calculated. Of 150 patients studied, the sensitivity and specificity of GeneXpert MTB/RIF were 81.8 and 97.4%, respectively. The sensitivity and specificity of Xpert MTB/RIF assay was comparative with culture in SNPTB patients.

Diagnosing sputum smear negative pulmonary tuberculosis patients by transbronchial biopsy and bronchoalveolar lavage smear.

Pulmonary tuberculosis is one of the leading causes of infectious disease related mortality. Transbonchial biopsy and bronchoalveolar lavage smear obtained by bronchoscopy provides greater quantity of material for analysis, thus increases the chances of diagnosing the disease. Objectives: To diagnose sputum smear negative pulmonary tuberculosis patients by Transbronchial Biopsy and Bronchoalveolar smear keeping bronchoalvelar lavage culture as gold standard. To calculate and compare the diagnostic accuracy of transbronchial biopsy and bronchoalveolar lavage smear in sputum negative patients. Study Design: Cross-sectional validation study. Setting: Department of histopathology, Foundation University Medical College, Islamabad and Department of Pulmonology and Microbiology, Fauji Foundation Hospital, Rawalpindi. Period: From May 2016 to May 2017. Materials &amp; Methods: It comprised 96 patients who underwent bronchoscopy. Transbronchial biopsy, bronchoalveolar lavage smear preparation and bronchoalveolar lavage culture was performed on specimens of all patients. Results: Out of 96 patients 22 (22.91%) patients were actually having tuberculosis whereas 74 (77%) had only clinical and radiological suspicion of tuberculosis. The mean age of patients was 43 years with a standard deviation of ±19.1 .The age range was 12-80 years. The sensitivity, specificity, positive predictive value, negative predictive value and true positives of transbronchial biopsy were 68.1%, 77%, 46.8%, 89% and15.62% while the values for bronchoalveolar lavage were 50%, 97.29%, 84.6%, 86.7% and 11.45% respectively. Thus, the diagnostic accuracy calculated for transbronchial biopsy and bronchoalveolar lavage was 75% and 13.54% respectively. Conclusions: Bronchoscopy should be done in all sputum negative tuberculosis patients having strong clinical and radiological suspicion to obtain transbronchial biopsy and bronchoalveolar lavage for timely diagnosis, treatment and prevention of disease transmission as well as to avoid empirical treatment and its side effects in patients having no tuberculosis. The diagnostic accuracy of transbronchial biopsy is almost 5 times more compared to bronchoalveolar lavage smear.

Application of CBNAAT (Xpert MTB/RIF assay) in new smear negative pulmonary tuberculosis patients.

Presumptive pulmonary tuberculosis (PTB) patients whose sputum are detected to be smear negative for acid fast bacilli (AFB) present a significant challenge for a treating physician. Initiating these patients on anti tuberculous treatment (ATT) on empirical basis is not a good strategy as many were found to be sputum culture for tuberculosis negative on further evaluation according to many previous studies. In India due to resource limited settings and lack of knowledge about newest diagnostic modalities patients are often initiated only on the basis of characteristic clinical symptoms and chest radiographic abnormalities. This study was conducted to identify the advantage of application of sputum cartridge based nucleic acid amplification test (CBNAAT) in sputum AFB smear negative presumptive pulmonary TB patients. Our study concluded that clinical symptoms and radiological characteristics cannot differentiate TB patients from non-TB patients. Treating patients only on empirical basis would have resulted in unnecessary treatment of 41 patients.