High Tuberculosis Prevalence Setting Research Articles

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Outcomes of resectable pulmonary aspergilloma and the performance gap in a high tuberculosis prevalence setting: A retrospective study

Background . Pulmonary aspergillomas develop in patients with underlying structural lung diseases. The mainstay of therapy is surgery. Objectives . To assess treatment and clinical outcomes following diagnosis of potentially resectable pulmonary aspergilloma at the Tygerberg Hospital (TBH) between January 2013 and December 2015. Methods . This was a retrospective analysis conducted at TBH. Patients were followed up between 6 and 29 months following diagnosis to analyse outcomes. Results . Fifty-nine patients presented for surgery. The mean (SD) age was 44.5 (8.8) years. Thirty-six (61.0%) were male and 13 (22.0%) were HIV-positive. A previous history of pulmonary TB was identified in 83.1% of the patients. One or both upper lobes were involved in 58 patients (98.3%) and haemoptysis was the most frequent symptom, occurring in 56 patients (94.9%). Nine patients (15.3%) were considered unfit for surgery. As of June 2016, 23 (46.0%) of the remaining 50 patients had undergone surgery and 3 (6.0%) had died before surgery was performed. The median time from multidisciplinary discussion to surgery was 190 days (interquartile range 134 - 351). Twenty patients (87.0%) underwent lobectomy and 3 (13.0%) had pneumonectomy. There was no postoperative mortality. One patient developed bleeding, persistent air leak and aspiration pneumonia postoperatively. Three patients were hospitalised for >7 days postoperatively. Following surgery, only two patients reported ongoing respiratory symptoms by day 90. Conclusion . Less than half of the patients accepted for lung resection at TBH underwent surgery. Waiting times were long (>1 year in 25%) and were associated with mortality. Barriers to prompt surgery are complex, but should be addressed urgently.

Endobronchial ultrasound experience in a high tuberculosis prevalence setting

BackgroundMost of the published endobronchial ultrasound-guided transbronchial needle aspiration (EBUS–TBNA) data are from the western countries, establishing the role of EBUS–TBNA in the diagnosis and staging of lung cancer. The etiology of mediastinal lymphadenopathy may be different in an ethnic group with a high prevalence of tuberculosis (TB). ObjectiveTo assess the etiology of mediastinal adenopathy in a high TB prevalence setting and to determine the performance of various tests in the diagnosis of tuberculous mediastinal lymphadenitis. MethodsRetrospective analysis of bronchoscopic data of patients who underwent endobronchial ultrasound (EBUS) in a tertiary care center in India. ResultsOut of 138 patients who underwent EBUS, 63 (46%) had granulomatous disease. Of the 35 patients with a diagnosis of TB, in 10 (29%), microbiology of EBUS specimens was diagnostic and in 3 (9%), this was the sole diagnostic feature. In 5 (14%) mycobacterial cultures were positive, in 6 (17%) GeneXpert for Mycobacterium tuberculosis/rifampicin resistance (Xpert MTB/RIF) was positive, and in 3 (9%) acid fast smears were positive. ConclusionIn high TB prevalence countries, EBUS diagnoses a higher number of granulomatous than malignant diseases. EBUS specimen should, therefore, be subjected also to mycobacterial smear, culture, and Xpert MTB/RIF for optimal results.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

The reliability analysis of Xpert-positive result for smear-negative and culture-negative specimen collected from bone and joint tuberculosis suspects.

The Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) has been widely used for pulmonary and extra-pulmonary tuberculosis (TB) diagnosis. In clinical practice, specimen yielding smear-negative, culture-negative but Xpert-positive results is frequently confronted. Due to the notorious possibility of contamination that molecular tests always been thought of, Xpert-positive results without bacteriological supporting evidence arouse great confusions to clinicians. A retrospective study was performed. From April 2014 to February 2015, 852 clinical specimens were Xpert-positive. The results of Xpert assay, bacteriological and pathological examinations from either the same specimens or from the specimens collected during same clinical operations were investigated. A total of 90 specimens with Xpert-positive but smear-negative and culture-negative results were recruited, and 81 of them were pus specimens collected from Bone and Joint Tuberculosis (BJTB) patients. According to the pathological examination results, 77 of the 81 pus specimens, 8 of 9 other types of specimens were confirmed as either TB or strongly suggestive of TB; three pus specimens and one biopsy tissue were also suggested TB but with less stronger evidence; only one pus specimen was not TB suggestive. Our study demonstrated that Xpert could be trusted for BJTB diagnosis even when no supporting bacteriological evidence is available in high TB prevalence settings. Our results will alleviate the confusion among clinicians in such scenarios.

Adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings

Adenosine deaminase (ADA) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (pTB) in high tuberculosis prevalence settings. We investigated the diagnostic utility of pleural ADA using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in Paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with pTB, 70 with other diagnoses) were analyzed. Median follow-up was 15.6 months. Mean [interquartile range] pleural ADA was 119 U/L [IQR: 83–143] in pTB and 24 U/L [IQR: 15–31] in non-tuberculous effusions (P<0.001). With an optimal pleural ADA cut-off value of 41.5 U/L for pTB diagnosis, sensitivity and specificity were 97.1% and 92.9%, while positive and negative predictive values were 86.8% and 98.5%, respectively. We conclude that pleural ADA activity could be integrated in the diagnostic procedures of pTB in low to medium tuberculosis prevalence settings.

The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area.

Integrated positron emission tomography/computed tomography (PET-CT) is a well-validated modality for assessing pulmonary mass lesions and specifically for estimating risk of malignancy. Tuberculosis (TB) is known to cause false-positive PET-CT findings. To investigate the utility of PET-CT in the evaluation of pulmonary mass lesions and nodules in a high TB prevalence setting. All patients referred for the evaluation of a solitary pulmonary nodule or mass and who underwent PET-CT scanning over a 3-year period were included. The PET-CT findings, including maximum standardised uptake value (SUVmax), were compared with the gold standard (tissue or microbiological diagnosis). The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for malignant disease were calculated according to the SUVmax cut-off of 2.5 and a proposed cut-off obtained from a receiver operating characteristic (ROC) curve. Forty-nine patients (mean (standard deviation) age 60.1 (10.2) years; 29 males) were included, of whom 30 had malignancy. Using an SUVmax cut-off of 2.5, PET-CT had a sensitivity, specificity, positive and negative predictive value and diagnostic accuracy for malignancy of 93.3%, 36.8%, 70.0%, 77.8% and 71.4%, respectively. After a ROC curve analysis, a suggested SUVmax cut-off of 5.0 improved the specificity to 78.9% and the diagnostic accuracy to 86.7%, with a small reduction in sensitivity to 90.0%. The diagnostic accuracy of PET-CT in the evaluation of pulmonary mass lesions using the conventional SUVmax cut-off of 2.5 was reduced in a TB-endemic area. An SUVmax cut-off of 5.0 has a higher specificity and diagnostic accuracy for malignancy, with a comparable sensitivity.

Risk of incident active tuberculosis and use of corticosteroids

To examine the association between corticosteroid use and risk of active tuberculosis (TB) disease. We conducted a population-based nested case-control study based on Taiwan's National Health Insurance Research Database between January 1999 and December 2011. Each case of incident active TB was matched to 100 controls using a risk-set sampling scheme. From a participant cohort of 1 million, 6229 cases of new active TB and 622,900 controls were identified. Current, recent, past, ever and chronic use of corticosteroids were associated with an increased risk of developing incident active TB, with adjusted rate ratios of respectively 2.76 (95%CI 2.44-3.11), 1.99 (95%CI 1.73-2.31), 1.17 (95%CI 1.06-1.29), 1.60 (95%CI 1.49-1.72), and 1.58 (95%CI 1.43-1.75). For subgroup analysis, the increased risk of TB in chronic corticosteroids users was substantially higher in subjects aged ≤70 years and female subjects. In this relatively high TB prevalence setting, we found that use of corticosteroids was associated with an increased risk of TB. Current use of corticosteroids was associated with the highest risk of TB.

The performance and limitation of T-SPOT.TB for the diagnosis of TB in a high prevalence setting.

Tuberculosis (TB) diagnosis remains difficulty. The previous reports have shown that the T-SPOT.TB assay may be a more promising diagnostic tool for TB, however, it needs a further study to evaluate the diagnostic value of T-SPOT.TB for the specific populations in a high prevalence setting. In this present study, we conducted stratified and comparable analyses to explore the clinical value and the limitation of T-SPOT.TB assay in TB diagnosis in a high TB prevalence setting, Southern China. A total of 413 subjects including 163 pulmonary TB (PTB), 39 extrapulmonary TB (EPTB), 106 non-TB pulmonary diseases (NTBPDs), 20 medical staff and 85 healthy controls were included in the study. According to T-SPOT.TB, there had a high incidence of latent TB infection (LTBI) in general population in Southern China, especially in the NTBPDS and medical staff. The T-SPOT.TB had a high performance in the diagnosis of active TB (ATB) in a lower risk of TB infection population such as the general population, however, the T-SPOT.TB for the diagnosis of ATB in the high risk of TB infection populations involving close contacts such as the patients with pulmonary diseases (PD) or medical staff isn't reliable due to the interference by LTBI. Under this condition, the value of rule-out of the assay was seemed to be better than that of rule-in. We believed that the T-SPOT.TB is suitable for screening both the EPTB and the ATB combined with diabetes mellitus (DM). However, we found that the sensitivity of T-SPOT.TB in sputum smear-negative population wasn't as high as that in smear-positive population. The T-SPOT.TB testing results should be interpreted with caution combined with subject's characteristics in a high prevalence setting.

Two-Step Tuberculin Skin Testing in School-Going Adolescents with Initial 0-4 Millimeter Responses in a High Tuberculosis Prevalence Setting in South India

BackgroundThe utility of two-step tuberculin skin testing among adolescents in high tuberculosis prevalence settings is not well established.ObjectivesTo determine the proportion and determinants of a 0-4 mm response to an initial standard tuberculin skin test (TST) and evaluating 'boosting' with repeat testing.MethodsAdolescents between 11 and 18 years attending schools/colleges underwent a TST; those with a response of between 0–4 mm had a repeat TST 1-4 weeks later.ResultsInitial TST was done for 6608/6643 participants; 1257 (19%) developed a 0-4 mm response to the initial TST. Younger age and under-nutrition were more likely to be associated with a 0-4 mm response, while the presence of BCG (Bacillus Calmette Guerin) scar and higher socio-economic class were less likely to be associated with a 0-4 mm response. On repeat testing boosting was seen in 13.2% (145/1098; ≥ 6 mm over the initial test) while 4.3% showed boosting using a more conservative cutoff of a repeat TST ≥ 10 mm with an increment of at least 6 mm (47/1098). History of exposure to a tuberculosis (TB) case was associated with enhanced response.ConclusionThe proportion of adolescents who demonstrated boosting on two-step TST testing in our study was relatively low. As a result repeat testing did not greatly alter the prevalence of TST positivity. However, the two-step TST helps identify individuals who can potentially boost their immune response to a second test, and thus, prevents them from being misclassified as those with newly acquired infection, or tuberculin converters. While two-step tuberculin skin testing may have a limited role in population- level TST surveys, it may be useful where serial tuberculin testing needs to be performed to distinguish those who show an enhanced response or boosters from those who indeed have a new infection, or converters.

Tuberculin skin test conversion among HIV patients on antiretroviral therapy in Uganda

A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence. To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART). Prospective cohort study of TST-negative, ART-naïve HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed. Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings. A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART.

Negative effect of smoking on the performance of the QuantiFERON TB gold in tube test

BackgroundFalse negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively.MethodsPatients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results.ResultsSmokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02).ConclusionsCigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.

Destructive rib lesions in an HIV sero-negative male: an unusual presentation of tuberculosis in a high tuberculosis prevalence setting

Tuberculosis (TB) of the rib is a very rare form of skeletal TB and its diagnosis may be difficult because of a low index of suspicion by clinicians. The presentation often mimics malignant disease clinically and radiologically and diagnosis may only be confirmed by tissue biopsy. We present a 32-year-old HIV-negative man who presented with a three-month history of progressively worsening pleuritic chest pain, weight loss, fatigue, anorexia and low-grade fever with night sweats. A chest computerized tomography (CT) scan showed destructive lesions in the right fourth and seventh ribs with no pulmonary lesions. A diagnosis of TB of the rib was made after surgical resection and histopathology of the affected tissue. There was significant improvement when anti-TB therapy was initiated. This case report emphasizes the importance of a high index of suspicion of TB in patients presenting with destructive bone lesions in regions with high prevalence of TB.

Evaluation of the status of tuberculosis as part of the clinical case definition of AIDS in India

Aim: To assess HIV associated tuberculosis in a high tuberculosis prevalence setting and its status in the clinical case definition of AIDS. Methods: All HIV patients attending the infectious disease...