Smear-negative Pulmonary Tuberculosis Research Articles

The first report of co-existence of pulmonary tuberculosis and lung malignancy in a kidney transplant recipient: a case report and literature review

BackgroundAlong with the medical development, organ transplant patients increase dramatically. Since these transplant patients take immunosuppressants for a long term, their immune functions are in a suppressed state, prone to all kinds of opportunistic infections and cancer. However, it is rarely reported that the kidney transplant recipients (KTRs) have pulmonary tuberculosis and lung cancer simultaneously.Case presentationA 60-year-old male was admitted because of persistent lung shadow for 2 years without any obvious symptom 8 years after renal transplant. T-SPOT test was positive but other etiological examinations for Mycobacterium tuberculosis were negative. Chest CT scan revealed two pulmonary lesions in the right upper and lower lobe respectively. 18F-fluorodesoxyglucose positron-emission tomography (FDG-PET) CT found FDG intake increased in both pulmonary consolidation lesions. CT-guided percutaneous transthoracic needle biopsy revealed lung adenocarcinoma and tuberculosis. The video-assisted thoracoscopic surgery was operated to resect the malignancy lesions. The patient received specific anti-tuberculosis therapy and was discharged. At the follow-up of 6 months post drug withdrawal, the patient was recovered very well.ConclusionsWe for the first time reported co-existence of smear-negative pulmonary TB and lung adenocarcinoma in a KTR, which highlighted the clinical awareness of co-occurrence of TB and malignancy after renal transplant and emphasized the value of biopsy and 18F-FDG-PET in early diagnosis of TB and cancer.

Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis

BackgroundThere is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells (“CD27−CD4+” and “CD27−IFN-γ+CD4+”) was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of “CD27−IFN-γ+CD4+” cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with “CD27−IFN-γ+CD4+” cells by Spearman statistical analysis.ResultsWe observed that the percentages of “CD27−IFN-γ+CD4+” cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of “CD27−IFN-γ+CD4+” cells was negatively correlated with WBC (white blood cell count) (r = − 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, “CD27−IFN-γ+CD4+” cells were significantly decreased, especially in the > 50 years group, after clinical treatment.ConclusionThe present results demonstrated that the percentage of “CD27−IFN-γ+CD4+” cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

The Role of High Resolution Computed Tomography in the Diagnosis of Suspected Sputum Smear Negative Active Pulmonary TB

Objective: To evaluate the diagnostic accuracy of high resolution CT (HrCT) for confirmatory evaluation of patients having active pulmonary TB (PTB) taking Acid-fast bacillus (AFB) culture reporting as standard parameter. Methods: In this cross-sectional (validation) analysis we included 200 patients having chest X-rays and clinical evidence of active TB and sputum smear (SS) –ve results. These patients were recruited from March-2019 to December-2019. Data of patients regarding baseline hematology investigations, sputum smear findings, and presenting symptoms was obtained. Sputum samples were obtained again for each patients, and sent for AFB culture reporting. The HrCT was performed in the radiology unit using a 64 slices CT machine. Results: The mean age of included patients was 53.61 ± 11.96 years. There 81 (40.5%) female and 119 (59.5%) male patients. The proportion of true positive (TP) cases was 79 (39.5%), true negative cases was 96 (48.0%), false positive (FP) cases 11 (5.5%) and false negative (FN) was 14 (7.0%). The HrCT was found to have sensitivity of 84.9%, specificity 89.7%, PPV 87.8% and NPV 87.3%. Conclusion: HrCT is a reliable imaging method for accurately diagnosis the active Pul. TB with a good sensitivity and specificity. In our view, HrCT can be used as a firstline imaging evaluation test for diagnosing pul. TB in suspected patients. Keywords: Pulmonary TB, Microbial culture, high resolution CT.Objective: To evaluate the diagnostic accuracy of high resolution CT (HrCT) for confirmatory evaluation of patients having active pulmonary TB (PTB) taking Acid-fast bacillus (AFB) culture reporting as standard parameter. Methods: In this cross-sectional (validation) analysis we included 200 patients having chest X-rays and clinical evidence of active TB and sputum smear (SS) –ve results. These patients were recruited from March-2019 to December-2019. Data of patients regarding baseline hematology investigations, sputum smear findings, and presenting symptoms was obtained. Sputum samples were obtained again for each patients, and sent for AFB culture reporting. The HrCT was performed in the radiology unit using a 64 slices CT machine. Results: The mean age of included patients was 53.61 ± 11.96 years. There 81 (40.5%) female and 119 (59.5%) male patients. The proportion of true positive (TP) cases was 79 (39.5%), true negative cases was 96 (48.0%), false positive (FP) cases 11 (5.5%) and false negative (FN) was 14 (7.0%). The HrCT was found to have sensitivity of 84.9%, specificity 89.7%, PPV 87.8% and NPV 87.3%. Conclusion: HrCT is a reliable imaging method for accurately diagnosis the active Pul. TB with a good sensitivity and specificity. In our view, HrCT can be used as a firstline imaging evaluation test for diagnosing pul. TB in suspected patients. Keywords: Pulmonary TB, Microbial culture, high resolution CT.

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

Role of bronchoalveolar lavage fluid and serum interleukin-27 in the diagnosis of smear-negative pulmonary tuberculosis.

Background:To evaluate the value of interleukin (IL)-27 measured in serum and bronchoalveolar lavage fluid (BALF) for the diagnosis of smear-negative pulmonary tuberculosis (TB).Methods:This was a prospective study of patients planned to undergo bronchoscopy at Wuxi No.5 People's Hospital between January 2017 and September 2018. The patients were grouped as the TB and control groups. BALF and serum IL-27 were measured by ELISA. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value and calculate the optimal cutoff values.Results:There were 40 patients in the control group and 87 in the TB group. In the TB group, 20 had positive sputum smear results and 67 were negative. The area under the ROC curve (AUC) of BALF IL-27 for pulmonary TB was 0.897 (95% CI: 0.830–0.944) (P < .001). The AUC of serum IL-27 for pulmonary TB was 0.703 (95% CI: 0.616–0.781) (P < .001). In patients with negative sputum smear results, the AUCs of BALF IL-27 and serum IL-27 for pulmonary TB was 0.882 (95% confidence interval [CI]: 0.805–0.936) (P < .001) and 0.679 (95% CI: 0.601–0.782) (P < .001), respectively.Conclusions:BALF IL-27 can be used for the diagnosis of pulmonary TB, particularly in those with a negative sputum smear result. Serum IL-27 could be an auxiliary method for TB screening.

Diagnostic challenges and Gene-Xpert utility in detecting Mycobacterium tuberculosis among suspected cases of Pulmonary tuberculosis.

The incidence of pulmonary tuberculosis (PTB) can be reduced by preventing transmission with rapid and precise case detection and early treatment. The Gene-Xpert MTB/RIF assay is a useful tool for detecting Mycobacterium tuberculosis (MTB) with rifampicin resistance within approximately two hours by using a nucleic acid amplification technique. This study was designed to reduce the underdiagnosis of smear-negative pulmonary TB and to assess the clinical and radiological characteristics of PTB patients. This cross-sectional study included 235 participants who went to the Luyang primary health care clinic from September 2016 to June 2017. The demographic data were analyzed to investigate the association of patient gender, age group, and ethnicity by chi-square test. To assess the efficacy of the diagnostic test, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. The area under the curve for sputum for both AFB and gene-Xpert was analyzed to compare their accuracy in diagnosing TB. In this study, TB was more common in males than in females. The majority (50.71%) of the cases belonged to the 25–44-year-old age group and the Bajau ethnicity (57.74%). Out of 50 pulmonary TB cases (smear-positive with AFB staining), 49 samples were positive according to the Gene-Xpert MTB/RIF assay and was confirmed by MTB culture. However, out of 185 smear-negative presumptive cases, 21 cases were positive by Gene-Xpert MTB/RIF assay in that a sample showed drug resistance, and these results were confirmed by MTB culture, showing resistance to isoniazid. In comparison to sputum for AFB, Gene-Xpert showed more sensitivity and specificity with almost complete accuracy. The additional 21 PTB cases detection from the presumptive cases by GeneXpert had significant impact compared to initial observation by the routine tests which overcame the diagnostic challenges and ambiguities.

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.

English

BACKGROUND In India, everyday more than 6000 people develop tuberculosis (TB) and more than 600 people die of TB (2 death every 5 minutes).1 World Health Organization (WHO) has recently endorsed cartridge based nucleic acid amplification test (CBNAAT) which has the potential to lead a revolution in the diagnosis of tuberculosis. This study intends to assess the performance of CBNAAT for the diagnosis of suspected smear negative pulmonary and extra pulmonary tuberculosis. METHODS The cross-sectional study was carried out in Department of Microbiology, Government Medical College, Thrissur, Kerala, India. CBNAAT was done in district tuberculosis center, Thrissur. The study was done from December 2016 to December 2017. Samples were sent for microscopy, culture and CBNAAT. RESULTS A total of 250 patients were evaluated. Majority of the specimens collected were sputum (61.2 %) followed by bronchial wash (17.6 %). Culture was positive in 48 specimens. CBNAAT was positive in 58 specimens. Both culture and CBNAAT were positive in 47 patients. CBNAAT was negative in 1 specimen but positive in culture test. CBNAAT detected an additional 10 samples. Taking culture as gold standard, culture positives were taken as true positives and culture negatives were taken as true negatives. Accordingly, true positive was 48, true negative was 202, false positive was 10 and false negative was 1. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were respectively 97.95 %, 95.2 %, 82.75 % and 99.5 %. CBNAAT missed out a sputum sample which was culture positive. CONCLUSIONS We found CBNAAT to be an important diagnostic modality especially in smear negative patients for early diagnosis and treatment of TB. Culture of mycobacteria is considered as a gold standard method, but it takes weeks to obtain a positive result and simultaneous detection of rifampicin resistance is not possible with this method. KEY WORDS Tuberculosis, Smear Negative TB, ZN Stain, AFB, Petroff’s Method, CBNAAT, RNTCP, Culture

Misdiagnosis of chronic pulmonary aspergillosis as pulmonary tuberculosis at a tertiary care center in Uganda: a case series

BackgroundDiagnosis of chronic pulmonary aspergillosis (CPA) is based on a combination of clinical symptomatology, compatible chest imaging findings, evidence of Aspergillus infection and exclusion of alternative diagnosis, all occurring for more than 3 months. Recently, a rapid, highly sensitive and specific point-of-care lateral flow device (LFD) has been introduced for the detection of Aspergillus-specific immunoglobulin (Ig)G, especially in resource-limited settings where CPA is underdiagnosed and often misdiagnosed as smear-negative pulmonary tuberculosis (PTB). Therefore, in our setting, where tuberculosis (TB) is endemic, exclusion of PTB is an important first step to the diagnosis of CPA. We used the recently published CPA diagnostic criteria for resource-limited settings to identify patients with CPA in our center.Case presentationThree Ugandan women (45/human immunodeficiency virus (HIV) negative, 53/HIV infected and 18/HIV negative), with a longstanding history of cough, chest pain, weight loss and constitutional symptoms, were clinically and radiologically diagnosed with PTB and empirically treated with an anti-tuberculous regimen despite negative microbiological tests. Repeat sputum Mycobacteria GeneXpert assays were negative for all three patients. On further evaluation, all three patients met the CPA diagnostic criteria with demonstrable thick-walled cavities and fungal balls (aspergilomas) on chest imaging and positive Aspergillus-specific IgG/IgM antibody tests. After CPA diagnosis, anti-TB drugs were safely discontinued for all patients, and they were initiated on capsules of itraconazole 200 mg twice daily with good treatment outcomes.ConclusionsThe availability of simple clinical diagnostic criteria for CPA and a LFD have the potential to reduce misdiagnosis of CPA and in turn improve treatment outcomes in resource-limited settings.

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.

Comparative Performance of Line Probe Assay (Version 2) and Xpert MTB/RIF Assay for Early Diagnosis of Rifampicin-Resistant Pulmonary Tuberculosis.

BackgroundThe emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples.MethodsA total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results.ResultsAmong culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb ) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%.ConclusionWe conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

The value of GeneXpert MTB/RIF in bronchoalveolar lavage fluid in the diagnosis of smear-negative pulmonary tuberculosis

This study aims to evaluate the diagnostic value of Xpert MTB/ RIF assay in bronchoalveolar lavage fluid (BALF) in subjects with smear-negative pulmonary tuberculosis. From January 2019 to December 2019, 197 patients with suspected pulmonary tuberculosis were recruited, and bronchoalveolar lavage fluid was collected for acid-fast staining smear, liquid culture of Mycobacterium combined drug sensitivity and Xpert MTB/RIF detection. The sensitivity, specificity, positive predictive value and negative predictive value of Xpert MTB/RIF in bronchoalveolar lavage fluid (BALF) were calculated with smear-negative pulmonary tuberculosis as the reference standard. The consistency of xpert MTB/RIF in the diagnosis of rifampicin resistance was evaluated, with the results of Mycobacterium liquid culture drug sensitivity test and drug sensitivity test as the gold standards. The results showed that among 197 suspected tuberculosis patients, 55 patients were not diagnosed with tuberculosis and 142 patients were diagnosed with smear-negative pulmonary tuberculosis. One hundred and twenty three cases (86.62%) were positive for Xpert MTB/ RIF in bronchoalveolar lavage fluid, 15 cases (10.56%) were positive by acid-fast staining smear method, and 88 cases (61.97%) were positive by the liquid culture method. The positive rate of Xpert MTB / RIF was 93.18% (82 / 88), which was higher than that of 75.93% (41 / 54) of the negative BALF mycobacterium culture (χ 2 = 8.598, P&lt;0.01). The sensitivity and specificity of Xpert MTB/RIF for rifampicin resistance were 100.00% and 97.30%, respectively. Therefore, the diagnostic value of Xpert MTB/RIF in bronchoalveolar lavage fluid for bacterialnegative pulmonary tuberculosis is superior to the acid-fast staining smear of lavage fluid and the mycobacterium culture method.

Spatial-temporal clustering of notified pulmonary tuberculosis and its predictors in East Gojjam Zone, Northwest Ethiopia.

BackgroundTuberculosis (TB) remains a key health menace in Ethiopia and its districts. This study aimed to assess the spatial-temporal clustering of notified pulmonary TB (PTB) cases in East Gojjam Zone, Northwest Ethiopia.MethodsA retrospective study was conducted among all PTB cases reported from 2013–2019. Case notification rates (CNRs) of PTB cases at Kebele (the lowest administrative unit), woreda, and zone levels were estimated. The PTB clustering was done using global Moran’s I statistics on Arc GIS 10.6. We used Kulldorff SaTScan 9.6 with a discrete Poisson model to identify statistically significant spatial-temporal clustering of PTB cases at Kebele level. Similarly, a negative binomial regression analysis was used to identify factors associated with the incidence of PTB cases at kebele level.ResultsA total of 5340 (52%) smear-positive and 4928 (48%) smear-negative PTB cases were analyzed. The overall mean CNR of PTB cases at zone, woreda and Kebele levels were 58(47–69), 82(56–204), and 69(36–347) per 100,000 population, respectively. The purely spatial cluster analysis identified eight most likely clusters (one for overall and one per year for seven reporting years) and 47 secondary clusters. Similarly, the space-time scan analysis identified one most likely and seven secondary clusters. The purely temporal analysis also detected one most likely cluster from 2013–2015. Rural residence, distance from the nearest health facility, and poor TB service readiness were factors (p-value <0.05) to PTB incidence at kebele level.ConclusionThe distribution of PTB cases was clustered. The PTB CNR was low and showed a decreasing trend during the reporting periods. Rural residence, distance from the health facilities, and poor facility readiness were factors of PTB incidence. Improving accessibility and readiness of health facilities mainly to rural and hotspot areas is vital to increase case detection and reduce TB transmission.

Chest X-ray interpretation does not complement Xpert MTB/RIF in diagnosis of smear-negative pulmonary tuberculosis among TB-HIV co-infected adults in a resource-limited setting

BackgroundChest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients.MethodsHIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard.ResultsThree hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28–39) years and CD4 count 112 (23–308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6–77.8) and 53.7% (95%CI 47.7–59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0–75.7) and 95.8% (95%CI 92.8–97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5–93.9) and 51.6% (95%CI 45.6–57.5) respectively; 86.2% (95%CI 75.3–93.5) and 48.1% (95%CI 40.7–55.6) among inpatients and 93.8% (95%CI 69.8–99.8) and 58.0% (95%CI 47.7–67.8) among outpatients respectively.ConclusionIn this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.

Sex-related differences in smear-positive pulmonary tuberculosis patients in Kuala Lumpur, Malaysia: Prevalence and associated factors.

Smear-positive pulmonary tuberculosis (PTB) is more infectious compared to smear-negative PTB and have great significance for epidemiology and infection control. The prevalence of smear-positive PTB rarely affects males and females equally. Hence, we aimed to identify the sex-related differences in the prevalence of smear-positive PTB and its associated factors in Kuala Lumpur, Malaysia. A cross-sectional study was conducted using data from the National Tuberculosis Information System (TBIS) from 1 January, 2015, to 31 December, 2019. The study population was selected using simple random sampling from the list of registered PTB patients in TBIS. The criteria for inclusion were all Malaysian adults aged ≥18 years residing in Kuala Lumpur and registered as PTB in TBIS. Factors associated with smear-positive PTB in male and female patients were determined using multiple logistic regression analysis. Overall prevalence of smear-positive PTB was 68.6%, and male patients predominated (71%). The male:female prevalence ratio of smear-positive PTB was 2.4:1. Male patients who worked as machine operators and elementary workers (adjusted odds ratio (aOR) 2.23, 95% confidence interval (CI) 1.24–4.02, p = 0.007), were self-employed (aOR 2.58, 95% CI 1.46–4.56, p = 0.001), lived in a residence categorized as ‘other’ (aOR 2.49, 95% CI 1.28–4.86, p = 0.007) and were smokers (aOR 1.37, 95% CI 1.01–1.87, p = 0.045) had higher odds for smear-positive PTB. Meanwhile, female patients with diabetes mellitus had higher odds for smear-positive PTB (aOR 1.92, 95% CI 1.05–3.54, p = 0.035), while female patients who were healthcare workers had lower odds (aOR 0.33, 95% CI 0.12, 0.94, p = 0.039). The prevalence of smear-positive PTB is higher in males compared to females. The factors associated with smear-positive PTB differed based on sex. The current TB control program, especially on smear-positive PTB, should likely be strategized and stratified by sex.

Five-year trend analysis of tuberculosis in Bahir Dar, Northwest Ethiopia, 2015-2019.

Background:Tuberculosis (TB) remains a major cause of morbidity and mortality in Ethiopia despite the increased availability of effective treatments. Trend analysis of issues and priorities affecting TB programs across different regions of the country is critical to ensure equitable and sustainable TB outcomes. We aimed to analyze the trends of TB in Bahir Dar, Northwest Ethiopia, over 5 years from 2015 to 2019.Methods:An institution-based, retrospective cross-sectional study was conducted in Bahir Dar, the capital city of the Amhara Region in Ethiopia. Five-year data and records of individual TB cases were reviewed from all public and private health-care facilities and health bureaus in Bahir Dar. Using a standard checklist adapted from the World Health Organization, data were abstracted relevant to sociodemographic characteristics of the patients, year and type of TB infection, and HIV status. SPSS version 20 software was used for data analysis.Results:Data of 4275 patients with TB were identified, of which 929 (21.7%) were smear-positive pulmonary TB, 1195 (28%) were smear-negative pulmonary TB, and 2151 (50.3%) were extrapulmonary TB patients. TB was more prevalent in the age group 15–34 years (51.2%), and females (55.5%). In the years from 2015 to 2019, the prevalence of all forms of TB was 922 (21.6%), 812 (19.0%), 843 (19.7%), 876 (20.5%), and 822 (19.2%), respectively, demonstrating a decreasing trend though inconsistent. The variables sex (adjusted odds ratio [AOR]: 1.734, 95% confidence interval [CI] [1.390–2.187]), HIV co-infection (AOR: 1.875, 95% CI [1.553–2.265]), and age <15 years (AOR: 1.372, 95% CI [1.121–1.680]) showed a significant association with TB infection.Conclusions:The prevalence of TB in Bahir Dar, Northwest Ethiopia, demonstrated a decreasing trend over the years from 2015 to 2019 but with inconsistencies. HIV co-infection significantly increased the risk of developing TB, and productive age groups and females were at the greater prevalence of TB, highlighting the importance of strengthening sustainable TB care and prevention interventions toward these groups of people.

Utility of GeneXpert Mycobacterium tuberculosis/rifampicin assay in smear-negative pulmonary tuberculosis

Background: Tuberculosis (TB) remains one of the world's deadliest communicable diseases. An alarming rise in the incidence of Mycobacterium tuberculosis (MTB) has prompted the need for rapid diagnostic techniques. Despite low sensitivity in MTB detection, sputum microscopy remains the main diagnostic method, especially in resource-limited settings. Mycobacterial culture is the gold standard method for TB diagnosis; however, the use in clinical practice is limited due to longer time, biosafety requirements, and high cost. In December 2010, the World Health Organization (WHO) 1st endorsed the usage of Xpert MTB/rifampicin (RIF) assay. The WHO recommends that GeneXpert test could be used as a follow on test to microscopy, especially in smear-negative specimens. Objectives: To assess percentage of Tuberculosis cases and Multi Drug Resistant (MDR) case detection at diagnosis using Xpert MTB/RIF assay in smear-negative pulmonary cases. Materials and Methodology: Detailed relevant clinical history and examination were carried out for 105 pulmonary TB suspect patients. Sputum acid-fast bacilli smear two samples and human immunodeficiency virus status were checked under RNTCP; chest X-ray PA view was done. Smear-negative patients were subjected to bronchoscopy and bronchoalveolar lavage (BAL)/bronchial washing. BAL/Bronchial washing was tested for GeneXpert. Interpretation and Conclusion: MTB was detected in 21 (20%) samples out of 105 samples and RIF resistance was detected in 1 (1%) sample. Most common chest x-ray abnormalities were cavity (33.3%) and consolidation (33.3%). 8 cases (38.1%) among Gene xpert positives had past history of Tuberculosis. Comorbidities were found in 5 cases (23.8%) among Gene Xpert positives. The present study concludes that using standard clinical assessment for selection, five patients need to be tested to detect one case of smear-negative TB. Smear-negative patients could benefit from Xpert, particularly in areas where no culture is available.

Histoplasmosis overlapping with HIV and tuberculosis in sub-Saharan Africa: challenges and research priorities.

Histoplasmosis, tuberculosis and HIV are all highly prevalent in sub-Saharan Africa (SSA). Co-occurrence of two or more of these infections has been reported in several populations of patients, especially those with advanced HIV infection where these opportunistic infections contribute to a significant morbidity and mortality. With a high burden of pulmonary tuberculosis (PTB) secondary to HIV in SSA, histoplasmosis is commonly misdiagnosed as smear-negative PTB in HIV patients due to similar clinical and radiological presentations. This is also partly the result of the lack of trained clinical and laboratory personnel to make a definite diagnosis of histoplasmosis. There is a low index of clinical suspicion for histoplasmosis, and cases are mostly discovered accidently and documented through case reports and case series. Similarly, the high cost and lack of fungal diagnostics in most SSA countries makes it difficult to make a diagnosis. There is a need to build local capacity for mycology so that patients are managed to improve on the index of clinical suspicion and diagnostic capabilities. Moreover, simple accurate point-of-care diagnostic tests and first-line antifungal treatment for histoplasmosis are not available in many SSA countries. This review describes the existence of co-infections of histoplasmosis, tuberculosis and HIV in SSA, highlighting the challenges and research priorities.

Diagnostic yield of bronchoalveolar lavage GeneXpert in smear-negative and sputum-scarce pulmonary tuberculosis

Background Tuberculosis remains a common public health hazard in the underdeveloped world. Initial approach to diagnosis is sputum smear staining for acid-fast bacilli, however only 40% of patients are smear positive. Aim and objectives To assess the diagnostic yield of GeneXpert in bronchoalveolar lavage in a smear negative or sputum scarce suspected case of pulmonary tuberculosis. Methods This analytical cross-sectional study included 50 patients who had clinical and radiological signs consistent with pulmonary tuberculosis and three negative Ziehl–Neelsen sputum smears or unobtainable sputum. All patients underwent fiberoptic bronchoscopy guided bronchoalveolar lavage that was sent for evaluation with GeneXpert and mycobacterial culture (Lowenstein–Jensen). Sensitivity analysis was carried out using culture as the gold standard. Results There is a statistically significant increase of positive TB cases diagnosed by bronchoalveolar lavage GeneXpert, as all cases were positive (100%) including 17 patients that were sputum scant, while all cases diagnosed by smear acid-fast bacilli were negative (100%) (P 0.05). Conclusion Bronchoalveolar lavage GeneXpert has superior diagnostic yield than acid-fast bacilli smear microscopy, and the yield is as effective as mycobacterial cultures, but much faster and time saving. It can be used as a gold standard for TB diagnosis.

Evaluation and comparison of molecular and conventional diagnostic modalities for detecting pulmonary tuberculosis in bronchoalveolar lavage fluid

ContextIn cases of sputum smear-negative and sputum-scarce (SSN/SC) pulmonary tuberculosis (PTB), bronchoalveolar lavage (BAL) fluid may be helpful in establishing diagnosis. No specific recommendations for BAL samples have yet been formulated due to limited literature. Aims1. To find a sensitive and specific protocol for same-day diagnosis of PTB using BAL in SSN/SC clinically suspected patients. 2. To evaluate the need to routinely perform MGIT for all BAL samples. Settings and DesignProspective observational study design in a tertiary care hospital in New Delhi. Methods and materialFibreoptic bronchoscopy was performed and BAL collected from 175 clinically suspected SSN/SC PTB patients. BAL samples were subjected to: ZN Stain, Xpert MTB/RIF CBNAAT, BACTEC MGIT 960 liquid culture and M. tuberculosis complex DNA Real time PCR. The results of the various diagnostic tests were analysed using a) MGIT as gold standard and b) a composite reference standard (CRS) for a final diagnosis of PTB. Statistical analysis usedMicrosoft Excel 2016 and SPSS version 21.0 were used. Sensitivity, specificity and predictive values were calculated and compared using McNemar test. A p value of <0.05 was considered statistically significant. Results34 Cases had a final diagnosis of TB as per the CRS. Using CRS, MGIT had a sensitivity of 50.0% (32.4%–67.6%). There was no statistically significant difference between sensitivities of CBNAAT and PCR; both were more sensitive than ZN stain. Sensitivity and specificity of CBNAAT was 79.4% (62.1%–91.3%) and 100.0% (97.4%–100.0%) respectively. The preferred protocol for the hospital is CBNAAT and ZN stain. There was no statistically significant difference in sensitivity by adding PCR or MGIT to this protocol. ConclusionsWe found it a good strategy to perform CBNAAT and ZN stain on BAL fluid for accurate and same-day PTB diagnosis. CBNAAT is useful for ruling PTB in even when BAL cultures are negative. It is prudent to continue to routinely perform MGIT for all BAL samples.