Sputum Smear-negative Tuberculosis Research Articles

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.

Trends of Tuberculosis Disease from 2013-2018 in Bale Zone, Oromia Region, Ethiopia. Retrospective Review.

Tuberculosis is a common global public health problem. Ethiopia is among the thirty top Tuberculosis burden countries. Trends of tuberculosis disease in general and at the district level in the Bale Zone have not been assessed and no adequate information existed for informed decision-making. This study was to describe the trends and physical distribution of the tuberculosis disease in the Bale Zone from 2013 to 2018. We reviewed the reported data of tuberculosis from 2013 to 2018 in March 2019 and extracted data of tuberculosis from the Bale Zone health information system database. Analysis of the six-year data of tuberculosis was conducted after the data was cleaned and checked for completeness. We recruited a total of 11, 268 tuberculosis cases. The proportions of sputum smear-positive tuberculosis (SS+), sputum smear-negative tuberculosis (SS-), and extra-pulmonary tuberculosis (EPTB) cases were 40.4%, 29.6% and 30%, respectively. Of all cases, 81.9% are aged greater than 15 years. Prevalence of all types of tuberculosis was 0.005%, 0.127%, 0.133%, 0.136%, 0.131% and 0.093% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively. The death rate from positive pulmonary tuberculosis was 0%. 2.74, 2.10, 2.06, 1.04, and 2.75 in 2013, 2014, 2015, 2016, 2017 and 2018, respectively. The highest average prevalence rate was 198, 152 and 142 per 100,000 populations in Berbere, Rayitu, and Gura-Dhamole Woreda, respectively. The proportion of sputum smear-positive tuberculosis was high in the Bale Zone. Bale Zone should give more attention to the Tuberculosis program to tackle sputum smear positive. We recommended researchers investigate further research to identify determinants in districts with a high prevalence rate of tuberculosis.

Диагностика туберкулеза легких при недоказанном бактериовыделении (обзор литературы)

The authors analyzed 31 scientific publications, which highlighted modern methods to the diagnosis of bacteriologically unconfirmed pulmonary tuberculosis (PTB). In the article, such clinical cases are classified into two groups due to the absence of the tuberculosis causative agent. This approach can serve as a justification for choosing optimal and appropriate additional methods and techniques for diagnosing bacteriologically unconfirmed PTB. Given the fact that bacterial excretion is determined by traditional microbiological methods (microscopic and cultural) in sputum, the literature review presents data on additional measures for obtaining biological material for the etiological diagnosis of tuberculosis, using molecular genetic methods for detecting Mycobacterium tuberculosis DNA. Besides, the article shows the diagnostic significance of immunological and serological tests for the tuberculosis diagnosis, as well as modern methods to the X-ray results interpretation, using mathematical methods that evaluate the dynamic X-ray imaging. A special place in the bacteriologically unconfirmed PTB diagnosis is occupied by the description of biopsy material using artificial intelligence. That is, the integration of medicine and information technology achievements allows us having a source of additional information that should help the doctor diagnose tuberculosis in difficult clinical cases. KEYWORDS: tuberculosis, oligobacillar forms of tuberculosis, sputum smear-negative tuberculosis, diagnosis, bacteriologically unconfirmed, diagnostic material, immunological methods, radiation methods, mathematical methods. FOR CITATION: Tyulkova T.E., Lugovkina T.K., Kutuzova D.M., Khabibullina N.F. Diagnosis of bacteriologically unconfirmed pulmonary tuberculosis (literature review). Russian Medical Inquiry. 2022;6(7):387–392 (in Russ.). DOI: 10.32364/2587-6821-2022-6-7-387-392.

Association of Tumor Necrosis Factor α Inhibitor Use with Diagnostic Features and Mortality of Tuberculosis in the United States, 2010-2017.

BackgroundAn elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF-α inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described.MethodsWe analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010–2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF-α inhibitors.ResultsOf 70 129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P < .001). Patients receiving TNF-α inhibitors were less likely to have acid-fast bacilli noted on sputum smear microscopy (25.6% vs 39.1%, P = .04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P < .001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF-α inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95–2.26]).ConclusionsClinicians evaluating TNF-α inhibitor–treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear–negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF-α inhibitor therapy before TB diagnosis was noted.

Clinico-radiological and bronchoscopic predictors of microbiological yield in sputum negative tuberculosis in Pakistan.

To determine association of clinico-radiological factors and radiological activity with diagnostic yield in sputum-smear negative tuberculosis (TB). Prospective observational study in the Military Hospital Rawalpindi (Pakistan) from July to December 2018. Adult patients having no contraindications to bronchoscopy were included. HIV positive patients and those on anti-tuberculosis therapy for more than one week were excluded. High-resolution computed tomography (HRCT) findings were classified based on active and inactive tuberculosis features. Washings were sent for acid-fast bacillus (AFB) smear, GeneXpert assay and cultures. Out of 215 patients, 42.3% (91) were diagnosed with microbiological or histological evidence of TB. On univariate analysis, cavitation (p-value <0.001), soft-tissue nodules (p-value 0.04), and endobronchial mucosal changes (p-value 0.02) were associated with culture positivity. Presence of cavitation (OR= 4.10; CI= 2.18,7.73; p-value<0.001) was the only independent predictor of microbiological yield. Diagnostic yield was 70%, 50%, 12.5% and 8.6% in patients with definitely active, probably active, indeterminate and inactive tuberculosis HRCT features respectively. Sensitivity, specificity, positive predictive value and negative predictive value of HRCT active TB were 95.38% (95% CI 87.10-99.04), 48.00 % (95% CI 39.78-56.30), 44.29% (95% CI 40.31-48.33), 96.00 % (95%CI 88.70-98.66) respectively. There was no significant association between age groups, smoking status and gender with diagnosis of tuberculosis in our study. Radiological activity and certain visualized bronchoscopic changes were associated with good diagnostic performance and can be used as predictive factors in diagnosis of active smear negative tuberculosis.

A Retrospective Cross-Sectional Study of the Utility of Cartridge-Based Nucleic Acid Amplification Test in Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in People Living with HIV in Second Highest HIV Prevalent State in India

Abstract Introduction Tuberculosis (TB) in people living with human immunodeficiency virus (PLHIV) is difficult to diagnose due to fewer organisms in sputum and extrapulmonary samples. Sputum culture takes 4 to 8 weeks for growth of the mycobacteria. Delayed treatment for TB in PLHIV leads to increased mortality. This study evaluated cartridge-based nucleic acid amplification test (CBNAAT) as a diagnostic tool for diagnosis of pulmonary TB (PTB) and extrapulmonary TB (EPTB) in PLHIV in the second most HIV prevalent state in India and for comparing its efficacy between Ziehl–Neelsen (ZN) staining sputum smear–positive and sputum smear–negative TB. Methods This cross-sectional study was conducted in RIMS, Imphal, with 167 PLHIV patients, age 15 years or older, having signs and symptoms of TB. Appropriate samples for sputum microscopy and CBNAAT were sent. Conclusion The overall sensitivity of sputum smear for acid-fast bacillus (AFB) was found to be 30.71% and that of CBNAAT was 38.57%. Sensitivity of CBNAAT for sputum smear–positive and sputum smear–negative TB was 100 and 11.3%, respectively. Sensitivity of ZN smear for AFB of EPTB sample was 48.1% and that of CBNAAT was 59.25%. In both PTB and EPTB, CBNAAT showed an increase in diagnosis of microbiologically confirmed PTB cases by 7.8 and 11.1%, respectively, over and above the cases diagnosed by ZN smear microscopy. Rifampicin resistance was detected in five patients. We conclude that CBNAAT is a rapid test with better sensitivity in diagnosis of PTB and EPTB in PLHIV, compared with ZN smear microscopy. It detects rifampicin resistance for multidrug-resistant TB and helps in early treatment intervention.

Combined tests with Xpert MTB/RIF assay with bronchoalveolar lavage fluid increasing the diagnostic performance of smear-negative pulmonary tuberculosis in Eastern China.

Tuberculosis (TB) remains a global public health threat. Misdiagnosis and delayed therapy of sputum smear-negative TB can affect the treatment outcomes and promote pathogen transmission. The application of Xpert MTB/RIF assay in bronchoalveolar lavage fluid (BALF) has been recommended but needs clinical evidence. We carried out a prospective study in the Nanjing Public Health Medical Center from September 2018 to August 2019. Pulmonary tuberculosis (PTB) patients were enrolled in the study if they had negative results of sputum smear. We compared the performance of Xpert MTB/RIF assay in sputum and BALF using sputum culture as the reference. In addition to this, we applied parallel tests using sputum culture, sputum-based Xpert MTB/RIF assay and BALF-based Xpert MTB/RIF assay to jointly detect smear-negative PTB using clinical diagnosis as the reference. With mycobacterial culture as the reference standard, Xpert MTB/RIF of BALF showed a higher sensitivity (14/16, 87.5%), but a relatively lower specificity (57/92, 62.0%). Xpert MTB/RIF of sputum showed relatively lower sensitivity (6/10, 60.0%) and higher specificity (63/88, 71.6%). Compared with sputum culture, Xpert MTB /RIF assay reduced the median detection time of MTB from 30 to 0 days, which significantly shortened the diagnosis time of the smear-negative TB patients. Among the combined detections, the positive detection proportion was improved with significant differences comparing with sputum culture only, from 11.1% (10/90) to 46.7% (42/90) (P < 0.05). Our study showed Xpert MTB/RIF in BALF had a better performance in detecting MTB of smear-negative patients.

Delays in HIV and TB diagnosis and treatment initiation in co-infected patients in Colombia.

We investigated the delays in the diagnosis of tuberculosis and/or HIV, their treatment initiation, and factors associated with each delay. All drug-susceptible tuberculosis cases diagnosed in 2014 and 2015 in Colombia, with a confirmed diagnosis of HIV were included. A total of 1909 patients were registered with tuberculosis/HIV co-infection. Seventy-nine percent of patients were men, 50% had sputum smear-negative tuberculosis, culture was done in 50% of cases, 68.5% had &lt;200 CD4 cell count at diagnosis, and 35% had concurrent tuberculosis/HIV diagnosis. Delays in the tuberculosis diagnosis were identified in 54.8% of the patients, and delays in tuberculosis and HIV treatment initiation in 41.8% and 27.4%, respectively. The risk factors associated with delay in tuberculosis diagnosis were age between 15–34 and ≥45 years, and those patients who received tuberculin skin test. The risk factor associated with antiretroviral therapy initiation delay was previously-treated tuberculosis patients after failure. It is necessary to implement strategies for early detection and treatment initiation of HIV and to use rapid test for tuberculosis diagnosis in this population.

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.

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.

Comparison of induced sputum and bronchial washings for CBNAAT in diagnosing sputum smear negative pulmonary tuberculosis

Introduction: Tuberculosis is one of the most infectious public health problems for decades and has also become difficult to diagnose in recent times due to association with immunocompromised status. With the advent of the newer diagnostic technique like CBNAAT, can providing positive results even in less number of tuberculos bacilli in specimen samples. The present study was aimed to compare induced sputum and bronchial washings for CBNAAT in diagnosing sputum smear negative tuberculosis. Materials and Methods: A prospective, observational study was conducted in the Department of Pulmonary Medicine, Maharaja Institute of Medical Sciences (MIMS), Vizianagaram, Andhra Pradesh, India. A total of 43 patients with sputum negative tuberculosis were enrolled and induced sputum and BAL fluid for CBNAAT sent for analysis under RNTCP in district hospital. Results: Male patients (67.45%) were more compared to the females (32.55%). Majority belongs to 51-60 years with mean age group of 49.18 years. Most common X- ray presentation was infiltration followed by consolidation. Induced sputum CBNAAT was positive in only 07 patients compare d to bronchial washings CBNAAT in 27 patients. Conclusions: As CBNAAT can diagnose rapidly and prevent transmission and mortality in smearnegative in pulmonary tuberculosis patients, all smear-negative and immunocompromised patients should be subjected to CBNAAT. CBNAAT detects pulmonary TB in PLHIV with greater efficacy than sputum microscopy, also helping in early diagnosis in less than 2 hours, so that early therapy can be started, thus decreasing the incidence of MDR-TB and associated its mortality. Keywords: Bronchial washings, CBNAAT, Induced sputum, Pulmonary tuberculosis, Smear negative.

The characteristics of spatial-temporal distribution and cluster of tuberculosis in Yunnan Province, China, 2005\u20132018

BackgroundTuberculosis (TB) makes a big challenge to public health, especially in high TB burden counties of China and Greater Mekong Subregion (GMS). The aim of this study was to identify the spatial-temporal dynamic process and high-risk region of notified pulmonary tuberculosis (PTB), sputum smear-positive tuberculosis (SSP-TB) and sputum smear-negative tuberculosis (SSN-TB) cases in Yunnan, the south-western of China between years of 2005 to 2018. Meanwhile, to evaluate the similarity of prevalence pattern for TB among GMS.MethodsData for notified PTB were extracted from the China Information System for Disease Control and Prevention (CISDCP) correspond to population information in 129 counties of Yunnan between 2005 to 2018. Seasonally adjusted time series defined the trend cycle and seasonality of PTB prevalence. Kulldorff’s space-time scan statistics was applied to identify temporal, spatial and spatial-temporal PTB prevalence clusters at county-level of Yunnan. Pearson correlation coefficient and hierarchical clustering were applied to define the similarity of TB prevalence among borders with GMS.ResultThere were a total of 381,855 notified PTB cases in Yunnan, and the average prevalence was 59.1 per 100,000 population between 2005 to 2018. A declined long-term trend with seasonality of a peak in spring and a trough in winter for PTB was observed. Spatial-temporal scan statistics detected the significant clusters of PTB prevalence, the most likely cluster concentrated in the northeastern angle of Yunnan between 2011 to 2015 (RR = 2.6, P < 0.01), though the most recent cluster for PTB and spatial cluster for SSP-TB was in borders with GMS. There were six potential TB prevalence patterns among GMS.ConclusionThis study detected aggregated time interval and regions for PTB, SSP-TB, and SSN-TB at county-level of Yunnan province. Similarity prevalence pattern was found in borders and GMS. The localized prevention strategy should focus on cross-boundary transmission and SSN-TB control.

Diagnosis of tuberculosis through breath test: A systematic review

BackgroundBreath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. MethodsTo estimate the diagnostic accuracy of breath test with electronic-nose and other devices against culture or other tests for TB, we screened multiple databases until January 6, 2019. FindingsWe included fourteen studies, with 1715 subjects in the analysis. The pooled sensitivity and specificity of electronic-nose were 0.93 (95% CI 0.82–0.97) and 0.93 (95% CI 0.82–0.97), respectively, and no heterogeneity was found. The sensitivity and specificity of other breath test devices ranged from 0.62 to 1.00, and 0.11 to 0.84, respectively. InterpretationThe low to moderate evidence of these studies shows that breath tests can diagnose TB accurately, however, to give a real-time test result, additional development is needed. Research should also focus on sputum smear negative TB, children, and the positioning of breath testing in the diagnostic work flow. FundingThe authors received no specific funding for this work.

Role of BAL fluid CBNAAT for diagnosis of tuberculosis: Our experience at a tertiary care Hospital

Background: Sputum smear negative tuberculosis can be a diagnostic challenge and there can be a dilemma in initiation of treatment, CBNAAT is one important test which gives quick results within hours plus an additional information about resistance with rifampicin, in sputum negative or non-expectorating patients brochoalveoloarlavagae can be useful, if tested for CBNAAT made available via fiberoptic bronchoscopy. Materials and Methods: Clinico-radiological suspects of pulmonary tuberculosis who showed clinical symptoms and radiological opacities consistent with tuberculosis who were sputum negative or not expectorating sputum were included in this study with exclusion patients in whom bronchoscopy was contraindicated, smear and CBNAAT examination was done of the obtained sample. The data was then analyzed.Results: in our study of 100 patients 57 were males and 43 were females, the most common lesion detected in imaging was consolidation 44% of patients followed by cavitary lesions at 27 %. Out of 100 patients who were clinicoradiologically suspected for PTB who underwent bronchoscopy 45 were diagnosed PTB out of which 32 tested positive for CBNAAT, no rifampicin resistance was detected in those cases. Conclusion: CBNAAT obtained from broncho-alveolar samples can be of great value especially when there is a physicians dilemma to start antitubercular treatment, as there are also other conditions mimicking tuberculosis both radiologically and clinically. Hence, BAL results with CBNAAT can help to arrive at a conclusion.

Detection of Mycobacterium tuberculosis in AFB smear-negative sputum specimens through MTB culture and GeneXpert® MTB/RIF assay.

Tuberculosis (TB) is an important public health issue around the globe which is a chronic infectious disease and is still one of the major challenges for developing countries. The emergence of drug-resistant TB makes the condition worse and there is an urgent need of fast, highly sensitive diagnostic methods. This study was undertaken to evaluate the performance of GeneXpert® MTB/RIF assay and MTB culture for the detection of Mycobacterium tuberculosis (MTB) in sputum smear-negative pulmonary TB/drug-resistant tuberculosis (DR-TB) suspects. A total of 168 sputum smear-negative TB suspects were recruited for the study. Among the suspected TB cases, 52.98% were male and 47.02% were females with the mean age of 42 ± 17.6 years. All the sputum specimens collected from the study population were subjected to Ziehl–Neelsen (ZN) smear microscopy, GeneXpert MTB/RIF assay, and MTB culture. The results revealed that, out of 168 acid-fast bacilli (AFB)/ZN smear microscopy–negative sputum specimens, 48 (28.57%) and 58 (34.52%) were detected MTB positive by GeneXpert MTB/RIF assay and MTB culture, respectively, while 120 (71.43%) and 110 (65.48%) suspected TB cases were confirmed negative by GeneXpert MTB/RIF assay and MTB culture, respectively. The study concluded that GeneXpert assay was found to be a rapid and accurate tool for MTB detection in smear-negative sputum specimens. GeneXpert has advantage over ZN smear microscopy and MTB culture as it detects MTB and rifampicin resistance simultaneously within 2 h with minimal biohazards.

Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV.

BackgroundApproaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.MethodsConsecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening.ResultsThe median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients.ConclusionsDirect measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.

Diagnosis of Pulmonary Tuberculosis by Measurement of ADA, CEA and PCR in Bronchoalveolar Lavage and Compare with Smear and Culture of BK in the Patient with Pulmonary Infiltration

Background: Pulmonary tuberculosis ( TB) is one of the problems in diagnosis and management of patients with pneumonia and pleural effusion. Bronchoscopy and bronchoalveolar lavage (BAL) can help us in the differential diagnosis. Tumor markers are substances that are produced by cancer or other cells of the body in response to diseases. These substances can be found in the blood, urine, or body fluids, for example in bronchoalveolar lavage of some patients with pulmonary diseases. CEA is a tumor marker that can help us for diagnosis and monitoring of peripheral lung cancer. ADA has been shown to rise in the BAL of patients with TB. Because the sputum smear negative TB patients have been a diagnostic challenge for health professionals this study was designed to determine the diagnostic value of ADA & CEA & PCR in BAL fluid and then compare the relationship of these markers with sputum and clinical finding in diagnosis of pulmonary tuberculosis. Material and Method: A cross sectional study conducted in Shahrekord Hajar hospital where 100 patients were enrolled in our study (62 females, 38 males). These patients were admitted to hospital and bronchoscopy with BAL was performed, then fluid was analysed for ADA, CEA, PCR and sputum smear for TB. Result: From 100 patients who were evaluated in this study 9 patients had TB, 39 patients had pneumonia, 11 patients had primary lung malignancy, 9 patients had metastases to lung and 8 patients had bronchitis. In Patients with TB the level of ADA was not significantly elevated in BAL. ADA increased significantly in patients with pneumonia (P: 0/95). In patients with metastases to lung and primary lung cancer and a combination of both groups compared to other patients without malignancy there was no relationship between CEA. PCR was positive in TB and other patients, but significantly increased in TB. (p=0/021) Discussion: Although it was thought that CEA may be elevated in BAL of patients with malignancy and ADA in tuberculosis we did not find a correlation in these patients. This study showed that ADA and CEA levels in BAL fluid does not help us in diagnosis of TB or cancer. It may have afalse positive in pneumonia, COPD and other diseases, but PCR for TB may assist in TB diagnosis but not alone.

Study on Culture Positivity among Sputum Smear Negative Tuberculosis Suspects attending the National Tuberculosis Centre, Nepal

Background: Globally, more than half of all TB cases are not detected. If they are not diagnosed and get treatment infection transmission may continue and patients suffer and may eventually die. Pulmonary TB either smear positive or negative is normally diagnosed by Ziehl-Neelsen stained sputum smear examination microscopy. Since the culture is the gold standard, evaluation of smear negative TB cases by this method is likely to detect more cases.&#x0D; Objectives: The objective of this study is to find out culture positivity among smear negative patients.&#x0D; Methods: All the three sputum samples reported negative by Ziehl-Neelsen microscopy from a total of 138 new TB suspected cases more than 15 years of age at NTC Laboratory. Nepal were cultured on Lowenstein-Jensen media. Tubes showing sufficient growth (culture positive) were recorded and all the culture positive results were informed to NTC. The culture positive samples were processed for DST on first line drugs using proportion method.&#x0D; Results: The culture positivity rate was 5.1% (7 of 138 cases) All the positive cultures were processed for DST on first line anti-TB drugs and none showed resistance of the total 138 suspected Tuberculosis patients, 94 (68.1%) were males and 44 were females (31.9%) with male: female ratio 1:047. The mean age of the total patients were 30.69. Nearly 42% of them belonged to 31-50 years. Mean age of the male patients was significantly higher than total of the female (p&lt;.001).&#x0D; Conclusions: Seven smear negative cases among the total of 138 suspected TB patients attending NTC were culture positive. Similar study has to be done in other parts of the country.

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.

Yield of tuberculosis among household contacts of tuberculosis patients in Accra, Ghana

BackgroundThe End TB Strategy calls for systematic screening of selected high-risk groups including contacts of tuberculosis (TB) cases to facilitate early TB case detection. Contact investigation is not usually routinely practiced in low TB burden countries, such as Ghana, with consequent paucity of data on the yield of TB case detection from such interventions. This study’s objective was to document the outcomes and feasibility of implementing contact investigation activities under programmatic conditions in Ghana.MethodsRetrospective analyses were conducted of abstracted data from the National TB Program, following a contact investigation intervention for TB cases diagnosed in 10 facilities in Accra from June 2010 to December 2014. Various proportions and yield from number of contacts needed to screen (NNS) and number needed to test (NNT) to detect a TB case were assessed.ResultsOverall, out of the 8519 listed contacts of 3267 index cases, 8166 (96%) were screened and 614 (7.5%) were identified as presumptive TB. Out of these, 438 (71%) underwent sputum smear microscopy/evaluation and 53 TB cases were diagnosed. Of these, 56.6% were males, and 49% had sputum smear-positive TB, 38% had sputum smear-negative TB, and 7% had extra-pulmonary TB. The NNS and NNT to detect a TB case of all forms were 154 and 8, respectively. The proportion of TB cases with contacts listed and proportion of contacts screened annually were 88–96% and 83–100%, respectively. The proportion of presumptive TB cases tested and proportion of TB cases diagnosed among contacts tested that were 100% and 36%, respectively, in 2010 dropped to 40% and 14%, respectively, by 2014.ConclusionsThe study demonstrates that contact identification and prioritization components of a contact investigation were feasible, but overall yield of TB cases may have been lower due to the declining rate of clinical evaluation of presumptive TB contacts over time. Addressing barriers to accessing appropriate diagnostic tests may enhance yield from contact investigation in Ghana.