Sputum Smear-negative Patients Research Articles

Comparison of 3 diagnostic methods for pulmonary tuberculosis in suspected patients with negative sputum smear or no sputum.

To explore the diagnostic value of 3 methods for sputum smear-negative and non-sputum patients with suspected pulmonary tuberculosis (TB). This prospective study enrolled sputum smear-negative and non-sputum patients with suspected TB admitted to Jiangxi Chest Hospital between January 2020 and December 2022. The 3 methods were bronchoalveolar lavage fluid (BALF)-acid-fast bacillus (AFB) smear, GeneXpert MTB/RIF, and gene chip for Mycobacterium strain identification. The diagnostic performance of the 3 tests was evaluated with BALF Mycobacterium culture + BALF-AFB smear + GeneXpert MTB/RIF + Gene chip as the gold standard. A total of 456 samples were collected from 114 patients with suspected TB. Twenty-four patients were diagnosed with TB. The combination of GeneXpert MTB/RIF and gene chip for Mycobacterium strain identification yielded the highest area under the receiver operating characteristics curve (AUC) of 0.953 and had sensitivity of 90.57%, specificity of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 92.42%, accuracy of 95.61%. GeneXpert MTB/RIF achieved AUC of 0.906, sensitivity of 81.13%, specificity of 100%, PPV of 100%, NPV of 85.92%, accuracy of 91.23%. BALF-AFB smear had AUC of 0.519, sensitivity of 3.77%, specificity of 100%, PPV of 100%, NPV of 54.46%, and accuracy of 55.26%. The combination of GeneXpert MTB/RIF and gene chip for Mycobacterium strain identification yielded the highest κ of 0.911, while BALF-AFB smear had the lowest κ value of 0.040. For TB in sputum smear-negative and non-sputum patients using BALF Mycobacterium culture + BALF-AFB smear + GeneXpert MTB/RIF + Gene chip as the gold standard, BALF-AFB smear showed low diagnostic performance, while, though GeneXpert MTB/RIF and gene chip had good diagnostic performance, combining GeneXpert MTB/RIF and gene chip improved the diagnostic value to a great extent.

The role of Xpert MTB/RIF using bronchoalveolar lavage fluid in active screening: insights from a tuberculosis outbreak in a junior school in eastern China.

Tuberculosis (TB) outbreaks in schools present a public health challenge. In order to effectively control the spread of transmission, timely screening, accurate diagnosis and comprehensive epidemiological investigations are essential. In July 2021, a TB outbreak occurred in a junior high school in Y City, Zhejiang Province. Students and faculty were screened for TB by symptom screening, chest radiography, and tuberculin skin test during four rounds of contact screenings. For sputum smear-negative and sputum-scarce patients, bronchoscopy was used to collect BAL samples for Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF). Whole-genome sequencing and bioinformatics analysis were performed on isolates to identify the strains of MTB isolates and predict drug resistance. Between July 2021 and November 2021, a total of 1,257 students and faculty were screened for TB during screenings. A total of 15 students (1.2% of persons screened) aged 15 years were diagnosed with TB. Eighty percent (12/15) of the cases were laboratory-confirmed (10/12 [83%] Xpert MTB/RIF-positive, 2/12 [17%] culture-positive). Most cases (12/15 [80%]) were in students from Class 2. All cases were asymptomatic except for the index case who had symptoms for more than two months. Seven MTB isolates were collected and belonged to lineage 2. Our findings demonstrated the potential of Xpert MTB/RIF using BAL as a screening tool in school TB outbreaks for sputum smear-negative and sputum-sparse suspects, which may not only rapidly improves diagnostic accuracy, but also facilitates epidemiological investigations and homology analysis.

The elevated expression of LAG-3 on CD8+T cells correlates with disease severity of pulmonary TB

ObjectiveLymphocyte-activation gene 3 (LAG-3) plays an important role in regulating T-cell responses and inducing peripheral tolerance. Our aim in this study was to investigate the relationship between LAG-3 and active tuberculosis (ATB) and the impact of LAG-3 blockade on CD8+T cells. MethodsFlow cytometry was used to detect the expression of LAG-3 on CD4+T and CD8+T cells in the peripheral blood and bronchoalveolar lavage fluid from ATB patients and to explore the relationship between LAG-3 and ATB. ResultsThe expression of LAG-3 on CD4+T and CD8+T cells in ATB patients was increased (P < 0.001), and CD8+T cells with high expression of LAG-3 were associated with sputum culture results (P < 0.05). We further analyzed the relationship between the expression of LAG-3 in CD8+T cells and the severity of tuberculosis and found that the expression of LAG-3 on CD8+T cells in smear-positive tuberculosis patients was significantly higher than that in sputum smear-negative tuberculosis patients (P < 0.05). LAG-3 expression on CD8+T cells was negatively correlated with the presence of lung lesions (P < 0.05). After stimulation with a tuberculosis-specific antigen, the expression of LAG-3 on tuberculosis-specific CD8+T cells was also upregulated, and LAG-3-expressing CD8+T cells showed reduced production of IFN-γ, decreased activation, and lower proliferation, while the function of CD8+T cells was restored when LAG-3 signaling was blocked. ConclusionsThis study further explored the relationship between immune exhaustion caused by LAG-3 and immune escape of Mycobacterium tuberculosis and revealed that the elevated expression of LAG-3 on CD8+T cells correlates with functional defects of CD8+T cells and the severity of pulmonary TB.

Role of Bronchoalveolar Lavage (BAL) Gene Xpert in Diagnosis of PTB in Sputum Smear Negative Patients

The aim of this study was to assess the diagnostic efficacy of Xpert MTB/RIF assay in bronchoalveolar lavage (BAL) in the diagnosis of pulmonary tuberculosis in sputum-smear negative patients. This observational case series study was conducted in a tertiary base institute of Bangladesh from July 2017 to June 2019. All patients with suspected pulmonary tuberculosis who were sputum-smear negative, irrespective of age and gender were included in this study. BAL fluid thus obtained and examined the smear for acid fast bacilli (AFB) and Xpert MTB/RIF assay. The sensitivity, specificity and accuracy values were calculated for smear AFB and Xpert MTB/RIF assay. Xpert MTB/RIF was identified 33 (36.7%) of 90 patients on bronchoalveolar lavage fluid in the final analysis. AFB Fluid culture was positive in 28 (31.2%) cases. The sensitivity and specificity of Xpert MTB/RIF assay was 85.7%, and 85.5% respectively. The positive likelihood ratio was 5.90, and the negative likelihood ratio was 0.167. The accuracy was 85.56%. Xpert MTB/RIF on BAL fluid can be recommended as a fruitful diagnostic tool for mycobacterium pulmonary tuberculosis especially in sputum smear negative, and culture negative patients.&#x0D; CBMJ 2023 January: Vol. 12 No. 01 P: 60-66

Diabetes Mellitus and its Association with Body Mass Index in Sputum Positive Tuberculosis Patients in a Tertiary Health Care Centre

Background: Tuberculosis is a chronic infectious disease that causes pulmonary tuberculosis and also affectsother tissues of the body. People with diabetes mellitus and those who are underweight have an increased risk ofgetting active tuberculosis. The objectives of the study were to estimate the prevalence of diabetes mellitus and todetermine its association with Body Mass Index in tuberculosis patients.Methods: In the present record-based cross-sectional study, 100 sputum smear positive tuberculosis patients 18years and older who attended the out-patient department of Pulmonary Medicine from 1/6/2020 to 31/12/2022were included and sputum smear negative patients were excluded. Data entry and analysis was done in MicrosoftExcel. Percentages were calculated and association between diabetes mellitus and Body Mass Index of the studypopulation was assessed by chi square test.Conclusion: The prevalence of diabetes mellitus in tuberculosis patients was almost double than that of thegeneral population of India and its association with underweight was found to be statistically significant. Soproper screening of all patients of tuberculosis for diabetes mellitus is necessary for early diagnosis and treatment.Health education and counselling are equally important

Diagnosis of the Sputum Smear Positive and Sputum Smear Negative Pulmonary Tuberculosis - The Role of High - Resolution Computed Tomography of Chest

BACKGROUND&#x0D; Mycobacterium tuberculosis complex causes pulmonary tuberculosis (PT) which is a major public health problem worldwide and endemic in India. PT diagnosis is done by high-resolution computed tomography (HRCT) which has high sensitivity and specificity.&#x0D; METHODS&#x0D; At a tertiary hospital, this cross-sectional study was conducted for 3 years. Patients presenting with productive cough with or without haemoptysis, shortness of breath, fever with night sweats or weight loss were suspected of having tuberculosis and underwent HRCT. PT was defined as the presence of consolidation, centrilobular nodules, and branching nodules with a tree in bud appearance with or without lymphadenopathy and pleural effusion on HRCT.&#x0D; RESULTS&#x0D; In this study, a total of 118 patients with a mean age of 51.85 ± 16.86 years were included. 64 (54.2%) were males and 54 (45.76%) were females out of 118 patients. Sputum smear was negative in a total of 66 (55.9%) patients and positive in 52(44.06%) patients. 84.26% was the diagnostic accuracy of HRCT in diagnosing PT with sensitivity, specificity, PPV and NPV of 84.28%, 83.33%, 78.98%, and 99.02%, respectively. HRCT had diagnostic accuracy, sensitivity, specificity, PPV and NPV of 86.40%, 89.46%, 83.42%, 94.14% and 72.43%, respectively in sputum smear positive patients. Whereas it was 83.87%, 91.54%, 75.40%, 64.57%, and 92.14%, respectively in sputum smear negative patients.&#x0D; CONCLUSIONS&#x0D; In diagnosing sputum smear-positive and sputum smear-negative PT, HRCT has high sensitivity. The specificity of HRCT was high in diagnosing sputum smear-positive PT, whereas in case of sputum smear-negative PT it was slightly low.

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.

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.

Role of Gene Xpert in smear negative pulmonary tuberculosis

BackgroundTuberculosis is a major health problem contributing to significant morbidity and mortality. Early diagnosis and treatment is the key for TB control. Sputum microscopy is a rapid and inexpensive test but due to low and variable sensitivity, many cases can be missed. Culture is considered to be the gold standard but is time consuming. Gene Xpert is a novel and rapid cartridge based nucleic acid amplification test (CBNAAT) that can be used for prompt diagnosis. AimTo compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gene Xpert with culture in diagnosing tuberculosis in sputum smear negative patients. MethodsThe study is a prospective observational study conducted from December 2017 to January 2019 on 189 patients, who were sputum smear negative but had signs and symptoms suggestive of tuberculosis. Their respiratory samples were taken (either sputum or bronchoalveolar lavage) and sent for Gene Xpert. The results were compared with culture, which was taken as the gold standard, and diagnostic accuracy was assessed. ResultA total of 189 patients were included in the study. In 25 patients sputum was taken and in 164 patients BAL was taken (which included 22 patients in whom sputum Gene Xpert was negative but there was high clinical suspicion of tuberculosis). The sensitivity, specificity, PPV and NPV of Gene Xpert in diagnosing smear negative pulmonary tuberculosis was found to be 96.3%, 81.3%, 87.5% and 94.2% respectively. ConclusionGene Xpert can be used as a rapid diagnostic tool in patients who are sputum smear negative but have clinical features highly suggestive of tuberculosis. It additionally helps in detecting rifampicin resistance. But every Gene Xpert positive case does not necessarily mean an active disease, therefore, past history of tuberculosis along with radiological signs of disease activity are to be considered. In case of negative Gene Xpert but high clinico-radiological suspicion of TB, patients should be followed up on regular intervals, while awaiting their culture.

Access to quality diagnosis and rational treatment for tuberculosis: real-world evidence from China\u2013Gates Tuberculosis Control Project Phase III

BackgroundChina has successfully reduced tuberculosis (TB) incidence rate over the past three decades, however, challenges remain in improving the quality of TB diagnosis and treatment. In this paper, we assess the effects of the implementation of “China National Health Commission (NHC) and Gates Foundation TB Prevention and Control Project” on the quality of TB care in the three provinces.MethodsWe conducted the baseline study in 2016 and the final evaluations in 2019 in the 12 selected project counties. We obtained TB patients’ information from the TB Information Management System and reviewed medical records of TB cases in the TB designated hospitals. We compared TB diagnosis and treatment services with the national practice guideline and used Student’s t-test and Pearson χ2 tests or Fisher’s exact tests to compare the difference before and after the project implementation.ResultsThe percentage of sputum smear-negative (SS–) patients taking culture or rapid molecular test (RMT) doubled between 2015 and 2018 (from 35% to 87%), and the percentage of bacteriologically confirmed pulmonary TB cases increased from 36% to 52%. RMT has been widely used and contributed an additional 20% of bacteriologically confirmed TB cases in 2018. The percentage of TB patients taking drug susceptibility tests (DST) also doubled (from 40% in 2015 to 82% in 2018), and the proportion of TB patients receiving adequate diagnosis services increased from 85% to 96%. Among all SS– TB patients, over 86% received the recommended diagnostic services at the end of the study period, an improvement from 75% prior to the project implementation. However, the proportion of TB patients treated irrationally using second-line anti-TB drugs (SLDs) increased from 12.6% in 2015 to 19.9% in 2018. The regional disparities remained within the project provinces, albeit the gaps between them narrowed down for almost all indicators.ConclusionsThe quality of TB diagnosis services has been improved substantially, which is attributable to the coverage of new diagnosis technology. However, irrational use of SLDs remains a concern after the project implementation.Graphic abstract

Utility of Bronchoalveolar Lavage in the Diagnosis of Sputum Negative Pulmonary Tuberculosis

INTRODUCTION: Sputum smear examination for acid fast bacilli (AFB) by Ziehl-Neelsen stain (ZN stain) is the initial approach to the diagnosis of pulmonary tuberculosis (PTB). But 50% of the cases are reported to be sputum smear negative. This study was aimed to investigate the diagnostic yield of fibreoptic bronchoscopy (FOB) guided bronchoalveolar lavage (BAL) in patients suspected to have tuberculosis. The sample was tested for Mycobacterium tuberculosis using the XpertMTB/RIF assay, which is a new test that detects Mycobacterium tuberculosis complex and resistance to rifampin in less than two hours.&#x0D; MATERIAL AND METHODS: This is a prospective cross sectional study carried out on 58 sputum smear negative patients who were clinically suspected to have pulmonary tuberculosis from April 2017 to January 2019. All patients are subjected to FOB, BAL and BAL specimens were stained for AFB and also sent for Xpert (MTB)/RIF.&#x0D; RESULTS: Among 58 patients enrolled for the study 26 patients were positive for acid fast bacilli (AFB) through BAL stain and Xpert (MTB)/RIF combined.&#x0D; CONCLUSION: FOB guided BAL is a reliable, alternative and rapid method for diagnosing smear negative pulmonary tuberculosis with minimal complications.

Role of cartridge based nucleic acid amplification test in bronchoscopy guided bronchial wash specimens in sputum smear negative PTB patients attending government general hospital, Kakinada

Tuberculosis is a global health burden still causing large mortality and morbidity. According to WHO’s 2018 Global TB Report two main routes for reducing TB incidence and death are- diagnosis and treatment. The main challenging issue with TB is to obtain a rapid and accurate diagnosis for initiating early treatment. Sometimes patient with active pulmonary tuberculosis fail to produce adequate sputum resulting in increase of false-negatives. Sputum-smear negative pulmonary tuberculosis is highly infectious and remains a diagnostic challenge. Fiber-optic bronchoscopy is an important tool for early detection and confirmation of sputum smear-negative and sputum-scarce PTB as it provides high-quality biological samples like bronchoalveolar lavage (BAL) fluid. The aim of the present study was to evaluate role of in Gene Xpert MTB/RIF on bronchoscopic specimens in sputum smear negative patients with suspicion of PTB. A prospective observational study was done on 100 patients with clinical suspicion of PTB who either have a negative sputum smear microscopy or unable to produce qualitative sputum attending outpatient and admitted in Pulmonology department, Government General Hospital, Kakinada.Out of 100 patients, 47 were diagnosed and confirmed as pulmonary tuberculosis of which bronchial specimens smear positive were 5(10.6%),bronchial specimens smear negative but CBNAAT positive were 42(89.3%). At last as CBNAAT has dual diagnostic advantage of detecting rifampicin resistance, about 5 cases were detected as rifampicin resistance. CBNAAT/RIF assay on BAL specimen provides an accurate diagnosis of PTB in patients with sputum smear negative results or those who cannot expectorate sputum and superior to sputum smears in detecting rifampicin resistance.

Diagnostic Accuracy of High-Resolution Computed Tomography of Chest in Diagnosing Sputum Smear Positive and Sputum Smear Negative Pulmonary Tuberculosis.

IntroductionPulmonary tuberculosis (PTB) is caused by species of organisms in the Mycobacterium tuberculosis complex. It is a major public health problem worldwide and is endemic in Pakistan. Various clinical and biochemical markers exist for its diagnosis. Radiology has an important role in the diagnosis of PTB. Initially, a chest radiograph is warranted for PTB evaluation. High-resolution computed tomography (HRCT) also has high sensitivity and specificity for PTB diagnosis. Features of primary TB include consolidation, lymphadenopathy, pleural effusion and miliary nodules whereas post-primary TB include apical consolidation, nodules and cavitation. The aim of this study was to determine the diagnostic accuracy of HRCT chest in diagnosing sputum smear positive and smear negative PTB.MethodsA cross-sectional study was conducted at a large tertiary care teaching hospital. A retrospective review of medical records of patients who underwent HRCT chest and sputum acid-fast bacillus (AFB) direct smear and AFB culture for suspicion of PTB was undertaken. All HRCT chest examinations were performed on multislice computed tomography (CT) scanner. On HRCT, PTB was defined as the presence of consolidation, centrilobular nodules, branching nodules with tree in bud appearance with or without lymphadenopathy and pleural effusion. Diagnostic accuracy of HRCT including sensitivity, specificity, positive and negative predictive values was calculated using 2 x 2 table, taking findings of AFB culture as a gold standard.ResultsA total of 108 patients were included in this study with a mean age of 51.85 ± 16.86 years. Diagnostic accuracy of HRCT in diagnosing PTB was found to be 84.26% with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 89.09%, 79.25%, 81.67%, and 87.50%, respectively. In sputum smear positive patients, HRCT has diagnostic accuracy, sensitivity, specificity, PPV and NPV of 87.50%, 88.57%, 84.62%, 93.94%, and 73.33%, respectively. In sputum smear negative patients, HRCT has diagnostic accuracy, sensitivity, specificity, PPV and NPV of 81.67%, 90.00%, 77.50%, 66.67%, and 93.94%, respectively.ConclusionHRCT has high sensitivity in diagnosing sputum smear positive and sputum smear negative PTB. The specificity of HRCT in diagnosing sputum smear positive PTB was high, whereas it was slightly low in diagnosing sputum smear negative PTB. Overall diagnostic accuracy of HRCT was high in diagnosing PTB.

Treatment outcomes and associated factors of tuberculosis patients on directly observed treatment (short course) in a tertiary hospital in Port Harcourt, Nigeria

Introduction: Although concerted efforts have been implemented to achieve tuberculosis (TB) prevention and control, varying outcomes have been reported in several quarters, despite the implementation of the directly observed treatment short-course (DOTS) strategy in virtually all parts of the world. It was considered necessary to assess the treatment outcomes of TB patients on DOTS strategy and the associated factors against the World Health Organization (WHO) target at the University of Port Harcourt Teaching Hospital (UPTH) Port Harcourt, to stimulate improvements in efforts toward patients care in the hospital and elsewhere. Methods: A health facility-based review of patients' records (January 1, 2014–December 31, 2018) at the TB Clinic of UPTH was carried out using a validated data record sheet. Patients undergoing treatment were excluded. Data were analyzed with the SPSS software version 20. Outcome frequencies were summarized, and the Pearson's Chi-square test was used to determine the association between the outcome and independent variables at P ≤ 0.05 statistical significance level. Results: Overall, 174 (25.7%) had completed treatment, 181 (26.7%) were cured, 95 (14.0%) died, 70 (10.3%) transferred out, 45 (6.6%) defaulted, 49 (7.2%) were not evaluated, 44 (6.5%) were lost to follow-up, and 8 (1.2%) failed treatment. There was a 17.6% decline in the proportion of patients that completed treatment from 35.9% in 2014 to 18.3% in 2018. On the contrary, there was an increase in the proportion of patients that were cured, from 14.1% in 2014% to 26.1% in 2018. Conclusions: The treatment success rate for TB in the hospital was below the WHO benchmark of 85% cure rate throughout the period under review. Basic reforms in the service delivery processes that specifically targets groups at risk (male patients, sputum smear-negative TB patients, and patients with human immunodeficiency virus/TB co-infection) with drug adherence counselling, defaulter tracing arrangements, and emphasis on drug-susceptibility testing are recommended to improve treatment outcomes.

Protection of healthcare workers against transmission of Mycobacterium tuberculosis in hospitals: a review of the evidence.

BackgroundEmployees in contact with infectious tuberculosis (TB) patients in healthcare facilities of low-incidence countries are still at considerable risk of acquiring TB infections. However, formal precautions recommended on the protection of healthcare workers may not only vary from country to country but also within a single country. The objective of this study was to compare current guidelines with respect to hospital infection control of TB, focusing on common shared priorities and discrepancies between sets of recommendations.MethodsFive types of procedures captured in guidelines of the World Health Organization, the United States of America, the United Kingdom and Germany are compared and the underlying evidence is discussed.ResultsUncontroversially, personal protection by respirators in the TB ward and during aerosol-generating procedures is key to reducing Mycobacterium tuberculosis exposure. However, there is no consensus on the types of masks that should be worn in different situations. Closely connected to this, there is considerable uncertainty with respect to the optimal date of removing sputum smear-negative and multidrug-resistant TB patients from isolation. Indeed, the use of notable new tools for this purpose, such as the highly sensitive PCR tests recommended by the World Health Organization for detecting TB/multidrug-resistant TB, have yet to be sufficiently incorporated into TB guidelines. Perceptions differ, too, as to whether long-term control measures for M. tuberculosis infections in healthcare workers by serial testing for latent TB infection should be established and, if so, how testing results should be interpreted.ConclusionsAlthough the current recommendations on protection of healthcare workers are otherwise homogeneous, there are considerable discrepancies that have important implications for daily practice.

Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosis.

Based on current WHO guidelines, hospitalized tuberculosis (TB) and HIV co-infected patients with CD4 count <100 cells/mm3 who are urine lipoarabinomannan (LAM) positive should be initiated on TB treatment. This recommendation is conditional, and data are limited in sputum smear-negative patients from TB endemic countries where the LAM test is largely inaccessible. Other potential benefits of LAM, including reduction in antibiotic usage have, hitherto, not been explored. We consecutively enrolled newly-admitted seriously-ill HIV-infected patients (n=187) with suspected TB from three hospitals in KwaZulu-Natal, South Africa. All patients were empirically treated for TB as per the WHO 2007 smear-negative TB algorithm (patients untreated for TB were not recruited). Bio-banked urine, donated prior to anti-TB treatment, was tested for TB-infection using a commercially available LAM-ELISA test. TB sputum and blood cultures were performed. Data from 156 patients containing CD4 count, urine-LAM, sputum and blood culture results were analysed. Mean age was 37 years, median CD4-count was 75 cells/mm3 [interquartile range (IQR), 34-169 cells/mm3], 54/156 (34.6%) were sputum culture-positive, 12/54 (22.2%) blood-culture positive, and 53/156 (34.0%) LAM-positive. Thus, LAM sensitivity was 55.6% (30/54). The study design did not allow for calculation of specificity. Urine-LAM positivity was associated with low CD4 count (P=0.002). Ninety-point-six percent (48/53) of LAM-positive patients received antibiotics [15/48 (31.3%), 23/48 (47.9%) and 10/48 (20.8%) received one, two or three different antibiotics respectively], while the duration of antibiotic therapy was more than 5 days in 26 of 46 (56.5%) patients. Urine LAM testing in sputum smear-negative severely-ill hospitalized patients with TB-HIV co-infection and advanced immunosuppression, offered an immediate rule-in diagnosis in one-third of empirically treated patients. Moreover, LAM, by providing a rapid alternative diagnosis, could potentially reduce antibiotic overusage in such patients thereby reducing health-care costs and facilitating antibiotic stewardship.

Pre-treatment loss to follow-up and treatment delay among bacteriologically-confirmed tuberculosis patients diagnosed in Mandalay Region, Myanmar

BackgroundPre-treatment loss to follow-up (PTLFU) among tuberculosis (TB) patients is a global public health problem, because such patients are highly infectious and experience high mortality. There is no published evidence on this issue from Myanmar.ObjectiveTo determine PTLFU and treatment delays (> 7 days duration between the date of diagnosis and starting anti-TB treatment) and their associated demographic, clinical, and health system-related factors among bacteriologically confirmed (sputum smear-positive and/or Xpert-positive) TB patients diagnosed in public health facilities of the Mandalay Region between January and June 2017.MethodThis was a cohort study involving secondary analysis of routine programme data. Every bacteriologically confirmed TB patient in the laboratory register was tracked for at least 3 months in the treatment register. Patients neither found in the treatment register nor referred out for treatment were considered PTLFU.ResultsOf the 1365 bacteriologically confirmed patients diagnosed, 1051 (77%) started on anti-TB treatment, 200 (15.6%) were referred for treatment to health facilities outside the study area, and 114 (8.4%, 95% CI 7.0%–9.9%) did not initiate anti-TB treatment (PTLFU). PTLFU was significantly higher in those with TB/HIV co-infected (18%), sputum smear-negative but Xpert MTB-positive patients (31%), and patients diagnosed at a moderate- or high-volume facility (> 50 patients tested form TB during the study period) (~ 10%). Of the 940 patients with dates recorded, 46 (5%) had a treatment delay of more than 7 days. Patients aged 45–64 years had higher risk of treatment delay compared to those aged 15–44 years. About 97% of records did not have a phone number recorded.ConclusionPTLFU and treatment delay were relatively low in the Mandalay Region. While this is reassuring, urgent steps must be taken to address those that are lost, which includes improving documentation of phone numbers to improve ‘trackability’, instituting proactive measures to trace patients lost in the care pathway, and introducing an indicator in the national tuberculosis programme (NTP) monthly report to monitor and review PTLFU. Patient subgroups with higher PTLFU should receive priority attention.

Evaluation of Smear Negative Pulmonary Tuberculosis Before and After Antibiotic Use: The Case of Four Public Health Centers of Addis Ababa, Ethiopia

Background: Diagnosis of pulmonary tuberculosis in sputum smear-negative patients is challenging in today ’ s medical practice. As a result, Diagnosis of SNPT mostly supported on clinical and radiographic elements in our country set up. Methods: A prospective cross-sectional study on the burden of smear-negative pulmonary tuberculosis from a total of 220 suspected pulmonary tuberculosis patients conducted in four public health centers of Addis Ababa, Ethiopia between May 25, 2017, and September 30, 2017. Study participants sputum sample were screened for acid-fast bacilli by direct smear microscopy two times before and after antibiotic administration and demographic data was taken. All smear negative morning sputum samples were further processed for culture using solid Lowenstein-Jensen medium at the St. Peter TB Specialized Hospital TB laboratory. Statistical analysis was done to predict the burden of smearnegative pulmonary tuberculosis. Results: 206 (93.6%) patients with suspected pulmonary tuberculosis have had negative smear results for acid-fast bacilli. 16 (7.76%) and 14 (6.8%) patients whose smears were negative for acid-fast bacilli found to be positive for Mycobacterium culture before and after taking broad-spectrum antibiotics respectively. Abnormal chest X-ray findings were observed in 25 (54.3%) out of 46 patients. Night sweat and weight loss have shown a significant association with culture-confirmed SNPT. Conclusion: The study showed 92.2% smear-negative pulmonary tuberculosis cases were still etiologically unexplained by culture. Therefore, there is a need to improve practice on sputum sample collection, processing and using other existing better diagnostic approaches for the diagnosis of SNPT in the Ethiopian setting to avoid a missed diagnosis of patients.

Role of Bronchoscopy in the Diagnosis of Pulmonary Tuberculosis in Sputum Smear Negative Patients

Role of Bronchoscopy in the Diagnosis of Pulmonary Tuberculosis in Sputum Smear Negative Patients

Transmission of Mycobacterium tuberculosis From Patients Who Are Nucleic Acid Amplification Test Negative.

Among adults with signs and symptoms of pulmonary tuberculosis (TB), recognition of transmissible TB has implications for airborne infection isolation and public health activities. Sputum smear-negative TB patients account for around one-fifth of tuberculosis transmission. The tuberculosis transmission risk of TB patients with negative results on nucleic acid amplification test (NAAT) of respiratory specimens has not been established. We sought to estimate the tuberculosis transmission risk of NAAT-negative TB patients. We retrospectively reviewed Maryland TB program data collected from 2004 to 2009, during which time NAAT using the Mycobacterium Tuberculosis Direct Test (MTD) was performed routinely. Patients with sputum Mycobacterium tuberculosis (M.tb) isolates having matching genotypes were assigned to clusters. Transmission sequence was approximated by collection order of individuals' first culture-positive specimens. Minimum transmission risks of NAAT (MTD)-negative TB patients and of smear-negative TB patients were estimated based on individuals' positions within clusters. Among 809 patients with culture-confirmed TB, M.tb genotypes were available for 782 (96.7%). For NAA-negative TB patients, the minimum transmission risk estimate was 5.1% (95% CI 0-11.4). For smear-negative TB patients, the minimum transmission risk estimate was 11.2% (95% CI 7.2-15.3). Minimum transmission risk of NAAT-negative TB patients was lower than that of smear-negative TB patients. However, transmission risk of NAA-negative TB patients appears to not be negligible.