Areas Of High Tuberculosis Prevalence Research Articles

Spatially-targeted tuberculosis screening has limited impact beyond household contact tracing in Lima, Peru: A model-based analysis.

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened.

Endosonographic characteristics of mediastinal lymph nodes for predicting malignancy in high tuberculosis burden settings: a study of 774 subjects

ABSTRACT Background Whether sonographic features of mediastinal lymph nodes can differentiate malignancy from tuberculosis remains unclear. Research design and methods We retrospectively identified subjects with a confirmed diagnosis of tuberculosis or malignancy on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Our primary objective was to compare the endosonographic characteristics of lymph nodes on EBUS between tuberculosis and malignancy. Our secondary objective was to assess the diagnostic performance of endosonographic characteristics in predicting malignancy. Results We included 774 subjects (1,498 lymph nodes) with a confirmed diagnosis of tuberculosis (n = 497) or malignancy (n = 277). Distinct lymph node margins (84.1% vs. 93.8%, P < 0.001) and coagulation necrosis sign (11.2% vs. 29.8%, P < 0.001) were less common in malignancy than tuberculosis. The absence of central hilar structure had the highest sensitivity (92.1%) for malignancy. Endosonographic characteristics had poor specificity for malignancy(round shape and coagulation necrosis sign, 77.3% and 70.2%. In multivariate analysis, coagulation necrosis sign was associated with a lower odds of malignancy (odds ratio 0.45 [95% confidence intervals, 0.21–0.95]). Conclusions Endosonographic characteristics, such as round shape and the coagulation necrosis sign, are not specific for malignancy in high tuberculosis prevalence areas.

Is serology a realistic approach for monitoring red deer tuberculosis in the field?

Tuberculosis (TB) is a zoonotic mycobacterial infection with great importance in human health, animal production, and wildlife conservation. Although an ambitious eradication programme in cattle has been implemented for decades, TB-free status has not yet been achieved in most of Spain, where animal TB persists in a multi-host system of domestic and wild hosts, including the red deer (Cervus elaphus). However, information on long time series and trends of TB prevalence in wildlife is scarce. The diagnosis of TB in wild red deer is often based on gross pathology and bacteriological culture confirmation, although recently serological assays have been developed to detect anti- Mycobacterium tuberculosis Complex (MTC) antibodies. Particularly, protein complex P22 has demonstrated to yield good specificity and sensitivity in the serological diagnosis of MTC for red deer, as well as cattle, goats, sheep, pigs, wild boar, and European badger. Thus, the objective of the present study was to compare the performance of the P22-ELISA with TB-compatible lesion detection, as well as to assess the potential application of each technique for determining spatiotemporal trends and risk factors of MTC infection in wild red deer from low and high TB prevalence areas of Spain over the last two decades. We tested 5095 sera from 13 wild populations by indirect ELISA using P22 as antigen. Mean seroprevalence (13.22%, CI95: 12.32–14.18) was compared with the prevalence of macroscopic TB-compatible lesions (6.94%, CI95: 6.18–7.79). The results evidenced a poor agreement between both techniques (K < 0.3), although generalized TB-lesions and anti-P22 antibodies showed a positive association (χ² = 9.054, P = 0.004). Consequently, TB-lesion based prevalence and seroprevalence cannot be considered as equivalent for TB surveillance in red deer. Regarding the spatiotemporal trend of TB in red deer in Spain, we observed a North-South gradient of TB occurrence [North: 1.23% (CI95: 0.77–1.97) of TB-lesions and 12.55% (CI95: 10.91–14.41) of P22-ELISA; Centre: 7.10% (CI95: 6.04–8.33) and 8.74% (CI95: 7.57–10.08); South: 21.04% (CI95:17.81–24.69) and 23.09% (CI95: 19.73–26.84), respectively]. Overall, there was a stability over time, with higher prevalence in adults belonging to densely populated sites. We conclude that the P22-ELISA alone is not sufficiently reliable for TB surveillance in red deer at large spatiotemporal scales. Instead, we recommend combining gross pathology and P22-ELISA.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Shared use of mineral supplement in extensive farming and its potential for infection transmission at the wildlife-livestock interface

Recently, the survival of Mycobacterium bovis on livestock mineral blocks has been confirmed, but little is known about its implication in the transmission of animal tuberculosis (TB) under field conditions. The objective of this study was to describe the shared use of mineral supplements in four extensive beef cattle farms from a high TB prevalence area in South Central Spain, to identify the main factors explaining their use, and characterize its potential role for the transmission of Mycobacterium tuberculosis Complex (MTC). This is relevant to design control measures at the wildlife-livestock interface. Animal activity was monitored by camera-trapping at 12 mineral supplementation points during spring and fall. Additionally, swabs were periodically taken from the mineral substrates and analyzed by PCR searching for MTC DNA. Cattle, pig, goat, sheep, wild boar, and red deer were all recorded licking on mineral supplementation points. Livestock species were the main users and presented a diurnal use pattern. Wild ungulates presented a nocturnal-crepuscular use pattern, with scarce overlapping with livestock. Wild boar presence was positively related to cattle presence at mineral supplementation points, whereas red deer presence was higher in supplemental points closer to forested areas and in farms without hunting pressure. We recorded 266 indirect wildlife-livestock interactions (i.e., two consecutive visits that occurred within 78 h), all of them derived from 21 unique wildlife visits. All the analyzed swabs resulted negative to MTC DNA. Comparing to other environmental sources of MTC in our study area, mainly water ponds, this research evidenced that mineral blocks are less attractive to wildlife. However, the potential for interspecific transmission of MTC or other pathogens cannot be discarded. The risk for interaction at mineral supplementation points and further transmission can be prevented by implementing specific measures in the context of integral biosecurity plans at the wildlife-livestock interface, which are proposed.

THE CASE OF THE FUNGUS IN THE HONEYCOMB

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Aspergillomas are fungal balls that typically develop in pre-existing pulmonary cavities such as those caused by tuberculosis, sarcoidosis, histoplasmosis, cystic fibrosis and lung abscesses but are rarely associated with UIP. Aspergillomas are typically distributed as either multiple bilateral pulmonary aspergillomas or as an isolated aspergilloma. The most commonly reported cases of aspergillomas have been found in post-tuberculosis cavities, accounting for 11 to 17% of cases, with an increased incidence in areas of high tuberculosis prevalence. For this reason, aspergillomas are typically found in the upper lobes with lower/middle lobe findings often associated with other cavitary pulmonary diseases. CASE PRESENTATION: We present an unusual case of multiple, unilateral aspergillomas in a non-immunocompromised patient with usual interstitial pneumonia (UIP). Patient is a 73-year-old female with seropositive rheumatoid arthritis (not on immunosuppressive therapy) who was evaluated for weight loss and minor hemoptysis. Chest CT showed classic bibasilar honeycomb changes typical of UIP. There were nodular opacities within the honeycomb changes suggestive of mycetomas seen exclusively in the right lung base. These were subsequently identified as aspergillomas by correlating the chest CT with bronchoscopic cultures that grew A. fumigatus. The patient’s symptoms resolved spontaneously after 6 months without treatment for either aspergillomas or UIP. At follow up after 2 years, the patient remained symptom free without further episodes of hemoptysis and her weight was stable. DISCUSSION: This case is a unique presentation for several reasons. First, aspergillomas are rarely associated with UIP. Second, multiple aspergillomas usually occur in immunocompromised patients whereas our patient was not immunocompromised. Third, despite the bilateral distribution of honeycombing in this patient, the aspergillomas were strictly unilateral. Finally, whereas aspergillomas are usually upper lobe predominant, our patient’s aspergillomas were localized to the right lower lobe. CONCLUSIONS: Chronic aspergillomas increase the risk of local tissue invasion which may result in potentially life-threatening hemoptysis. Fortunately, this patient’s hemoptysis spontaneously resolved and she subsequently remained asymptomatic. Such a presentation should be kept in mind when taking care of similar patients. Reference #1: Kumar N, Mishra M, Singhal A, Kaur J, Tripathi V. Aspergilloma coexisting with idiopathic pulmonary fibrosis: A rare occurrence. J Postgrad Med 2013;59:145-8 Reference #2: Moodley L, Pillay J, Dheda K. Aspergilloma and the surgeon. J Thorac Dis. 2014;6(3):202-9. Reference #3: Regis Gothard Bopaka, Hasna Jabri, Wiam El Khattabi, Hicham Afif European Respiratory Journal 2015 46: PA2650; DISCLOSURES: No relevant relationships by Nina Chan, source=Web Response No relevant relationships by Peter Sloane, source=Web Response

One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis

BackgroundTuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.MethodsWe conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.ResultsA total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, −0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P=0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).ConclusionsA 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.)

Improving detection of tuberculosis among household contacts of index tuberculosis patients by an integrated approach in Myanmar: a cross-sectional study

BackgroundContact tracing for tuberculosis (TB) is a recommended measure to improve the case detection rate; however, actual implementation in Myanmar is limited and low detection rates have been reported. Household contacts of a known index TB case are at high risk of infection, thus a more strategic action for contact tracing is required to achieve the goal of the World Health Organization End TB Strategy. This study aimed to assess TB case detection rates among household contacts by an integrated approach and identify risk factors for TB.MethodsA cross-sectional study was conducted in Mandalay City, Myanmar. Household contacts of index TB cases who had been receiving treatment for at least 3 months were prospectively investigated by an integrated approach which included modification of screening methods and active facilitation of screening investigations as follows. Initial chest x-ray (CXR) was performed for all contacts at the responsible facilities followed by sputum specimen collection for those aged ≥15 years and gene Xpert MTB/RIF examination. Transportation of all household contacts to health facilities and transportation of sputum samples for smear and gene Xpert MTB/RIF examination at centers were arranged by the research team to ensure that all household contacts received all investigations. Risk factors for TB among household contacts were identified by multiple logistic regression models.ResultsOf 174 household contacts, 115 were ≥ 15 years and 59 were < 15 years. The percentage of TB cases detected among the household contacts was 13.8%. There were 14 (12.2%) positive TB cases among the 115 contacts aged ≥15 years while 10 (16.9%) of those aged < 15 years had clinical signs and symptoms of TB with an abnormal CXR. Risk factors among household contacts for TB were being a caretaker of an index case, active and passive smoking, and drinking alcohol.ConclusionsThe integrated approach of TB contact tracing by special arrangement for CXR, sputum and gene Xpert MTB/RIF examination yielded a high TB detection rate in a high TB prevalence area. Logistic and financial administration is needed to strengthen contact tracing. Further research on high-risk household contacts should be considered for increasing TB detection rates.

Two-stage revision arthroplasty for Mycobacterium Tuberculosis periprosthetic joint infection: An outcome analysis.

BackgroundMycobacterium tuberculosis periprosthetic joint infection (TBPJI) is a rare complication of hip/knee joint arthroplasty. The outcomes of hip/knee TBPJI treatment are still unreported. The objective of this study was to investigate the outcomes of hip/knee TBPJI following treatment with two-stage exchange arthroplasty.Materials and methodsFrom 2003 to 2013, 11 patients with TBPJI (six hips and five knees) were treated with two-stage exchange arthroplasty at our institution. We collected and analyzed variables including demographic data, comorbidities, microbiological data, duration of symptoms, and types of antibiotic used in bone cement.ResultsAt the most recent follow-up, the success rate of two-stage exchange arthroplasty was 63.3% (7 of 11). All five knee treatments resulted in infection eradication and successful prosthesis reimplantation. However, only two hip TBPJI treatments resulted in successful outcomes; two patients died and two experienced chronic infection. Overall, secondary bacterial infections were common in patients with TBPJI (5 of 11 cases, 45.5%). Streptomycin in bone cement increased the success rate (83.33% vs. 40%).ConclusionMore than one third of the patients treated with two-stage exchange arthroplasty for TBPJI showed infection relapse or uncontrolled infection. Streptomycin-loaded interim cement spacers appeared to help ensure successful treatment. Routine M. tuberculosis culture is recommended when treating TBPJI in areas of high tuberculosis prevalence.

Isoniazid for preventing tuberculosis in HIV-infected children.

BackgroundTuberculosis (TB) is an important cause of illness and death in HIV‐positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV‐negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV‐positive children.ObjectivesTo summarise the effects of TB preventive treatment versus placebo in HIV‐positive children with no known TB contact on active TB, death, and reported adverse events.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017.Selection criteriaWe included trials of HIV‐positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo.Data collection and analysisTwo review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE.Main resultsWe included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow‐up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV‐positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported.In HIV‐positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups.Authors' conclusionsIsoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV‐positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. .12 April 2019Up to dateAll studies incorporated from most recent searchAll eligible published studies found in the last search (17 Feb, 2017) were included

Enhanced laboratory capacity development: a boost for effective tuberculosis control in resource-limited settings

Both routine and research tuberculosis (TB) laboratory capacity urgently need to be expanded in large parts of Sub-Saharan Africa. In 2009, the Centre de Recherches Médicales de Lambaréné (CERMEL) took a strategic decision to expand its activities by building TB laboratory capacity to address research questions and to improve routine diagnostic and treatment capacity. Over the past 7 years, a standard laboratory has been developed that is contributing significantly to TB diagnosis, treatment, and control in Gabon; training has also been provided for TB research staff in Central Africa. CERMEL has a cordial relationship with the Gabon National TB Control Programme (PNLT), which has culminated in a successful Global Fund joint application. This endeavour is considered a model for similar developments needed in areas of high TB prevalence and where TB control remains poor to date.

A combination of the QuantiFERON-TB Gold In-Tube assay and the detection of adenosine deaminase improves the diagnosis of tuberculous pleural effusion

The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remains difficult despite the availability of numerous diagnostic tools. The current study aimed to evaluate the performance of the whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional laboratory biomarkers in differential diagnosis of TPE and MPE in high tuberculosis prevalence areas. A total of 117 patients with pleural effusions were recruited, including 91 with TPE and 26 with MPE. All of the patients were tested with QFT-GIT, and the conventional biomarkers in both blood and pleural effusion were detected. The level of antigen-stimulated QFT-GIT in the whole blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33 IU/mL, P<0.0001). The sensitivity and specificity of QFT-GIT for the diagnosis of TPE were 93.0% and 60.0%, respectively. Among the biomarkers in blood and pleural effusion, pleural adenosine deaminase (ADA) was the most prominent biomarker, with a cutoff value of 15.35 IU/L. The sensitivity and specificity for the diagnosis of TPE were 93.4% and 96.2%, respectively. The diagnostic classification tree from the combination of these two biomarkers was 97.8% sensitive and 92.3% specific. Ultimately, the combination of whole blood QFT-GIT with pleural ADA improved both the specificity and positive predictive value to 100%. Thus, QFT-GIT is not superior to pleural ADA in the differential diagnosis of TPE and MPE. Combined whole blood QFT-GIT and pleural ADA detection can improve the diagnosis of TPE.

Regional and temporal characteristics of bovine tuberculosis of cattle in Great Britain

Bovine tuberculosis (TB) is a chronic disease in cattle that causes a serious food security challenge to the agricultural industry in terms of dairy and meat production. Spatio-temporal disease analysis in terms of time trends and geographic disparities of disease dynamics can provide useful insights into the overall efficiency of control efforts as well as the relative efficiency of different management measures towards eradication. In GB, Scotland has had a risk based surveillance testing policy under which high risk herds are tested frequently, and in September 2009 was officially declared as TB free. Wales have had an annual or more frequent testing policy for all cattle herds since January 2010, while in England several herds are still tested every 4 years except some high TB prevalence areas where annual testing is applied. Time series analysis using publicly available data for total tests on herds, total cattle slaughtered, new herd incidents, and herds not TB free, were analysed globally for GB and locally for the constituent regions of Wales, Scotland, West, North, and East England. After detecting trends over time, underlying regional differences were compared with the testing policies in the region. Total cattle slaughtered are decreasing in Wales, Scotland and West England, but increasing in the North and East English regions. New herd incidents, i.e., disease incidence, are decreasing in Wales, Scotland, West English region, but increasing in North and East English regions. Herds not TB free, i.e., disease prevalence, are increasing in West, North, and East English regions, while they are decreasing in Wales and Scotland. Total cattle slaughtered were positively correlated with total tests in the West, North, and East English regions, with high slopes of regression indicating that additional testing is likely to facilitate the eradication of the disease. There was no correlation between total cattle slaughtered and total tests on herds in Wales indicating that herds are tested frequent enough in order to detect all likely cases and so control TB. The main conclusion of the analysis conducted here is that more frequent testing is leading to lower TB infections in cattle both in terms of TB prevalence as well as TB incidence.

Concomitant tuberculosis and lung cancer diagnosed by bronchoscopy.

South Granada Health Area (SGHA), Spain. To describe the characteristics of concomitant tuberculosis (TB) and lung cancer cases. A total of 319 TB cases diagnosed between January 2003 and December 2010 were evaluated and identified using a prospective database. During this period, samples of bronchial secretions were obtained from all patients who underwent fibreoptic bronchoscopy (FBS) as part of a TB screening programme. A descriptive study was conducted. Concomitant TB and lung cancer were diagnosed in 15 cases (4.7% of total TB cases). The most common radiographic finding was atelectasis (53.3%), and the most common histological type was epidermoid carcinoma (60%). Lung cancer stage was advanced (III-IV) in 60% of the cases. The association between TB and lung cancer found in the SGHA after implementing a TB screening programme was higher than in other studies. This suggests that it would be advisable to perform acid-fast bacilli smear and mycobacterial culture of bronchial aspirates in all patients with presumed lung cancer, particularly in high TB prevalence areas.

103. Tuberculosis and Biologics: Real-World Experience from High Tuberculosis Prevalence Area

103. Tuberculosis and Biologics: Real-World Experience from High Tuberculosis Prevalence Area

Genotypic characteristics of Mycobacterium tuberculosis isolated from household contacts of tuberculosis patients in the Philippines

BackgroundThe Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household.MethodsMycobacterium tuberculosis isolates from household contacts of tuberculosis patients in the Philippines were characterized using restriction-fragment-length polymorphism analysis, spoligotyping, and mycobacterial interspersed repetitive units – variable number tandem repeats typing (12-loci) to determine their utility in elucidating transmission in an area of high tuberculosis prevalence. Drug susceptibility patterns for these isolates were also determined.ResultsSpoligotyping and MIRU-VNTR typing results matched in 10 (62.5%) of 16 index patient-household contact pairs while IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index patient-household contact pairs had identical drug susceptibility results.ConclusionsStrain typing of M. tuberculosis isolates from household contacts in the Philippines indicates that transmission of strains does not necessarily occur directly from the index patient living in close proximity in the same household but rather that community-based transmission also frequently occurs. Accurate susceptibility testing of all isolates is necessary to insure optimal care of both the index patients and any culture-positive household contacts.

Occurrence of Nontuberculous Mycobacterial Pulmonary Infection in an Endemic Area of Tuberculosis

The majority of investigations of the epidemiology of nontuberculous mycobacteria (NTM) have focused on highly developed nations with a low prevalence of tuberculosis. In contrast, the Para state of north Brazil represents an area of high tuberculosis prevalence and increasing NTM incidence. Toward the goal of understanding the dynamics of infection by all Mycobacterium species, we report patient characteristics and the identification of NTM strains isolated from sputum samples from patients that were residents of Para, a state in the Amazon region, Northern of Brazil, over the period January 2010 through December 2011 (2 years). The 29 NTM patients comprised 13.5% of positive mycobacterial cultures over the 2-year period. A major risk factor for NTM pulmonary disease was previous tuberculosis (76%). Further, the average age of NTM patients (52 years) was significantly higher than that of tuberculosis patients (39 years) and more were female (72.4% vs. 37.4%). Unlike other Brazilian states, NTM pulmonary patients in Para were infected with a different spectrum of mycobacteria; primarily the rapidly growing Mycobacterium massiliense and Mycobacterium simiae complex.

Improved diagnostic power by combined interferon-gamma release assay and nested-PCR in tuberculous pleurisy in high tuberculosis prevalence area

The conventional acid fast bacilli (AFB) smear and Mycobacterium tuberculosis (M.tb) culture of pleural effusion and tuberculin skin test (TST) in tuberculous pleurisy are unable to meet clinical needs because of their low sensitivities and specificities. To evaluate the diagnostic accuracies of QuantiFERON TB Gold In-Tube test (QFT-GIT) and nested-PCR in tuberculous pleurisy, we conducted a cross-sectional study in regions of China with a high tuberculosis (TB) epidemic. Seventy-eight participants were enrolled: 58 TB patients with diagnosis of confirmed or probable tuberculous pleurisy and 20 non-TB patients with a diagnosis of other non-TB diseases. The positive rates of AFB smear and M.tb culture in the pleural effusion were 5.8% (2/42) and 10.6% (5/47), respectively. The sensitivity and specificity of QFT-GIT were 93.1% (54/58) and 90.0% (18/20), whereas those of TST were 68.5% (37/54) and 86.7% (13/15), respectively; the sensitivity of QFT-GIT was significantly higher than TST (P=0.013). The sensitivity and specificity of M.tb-specific nested-PCR in pleural effusion were 94.8% (55/58) and 90.0% (18/20), respectively, with a turnaround time of 7h. Furthermore, combined QFT-GIT and nested-PCR detection improves the specificity to 100% with a sensitivity of up to 90.0%. This combination of immunoassay and molecular detection holds promise for the clinical diagnosis of tuberculous pleurisy.

Atypical pleural tuberculosis presenting as an isolated pleural tuberculoma

Pleural tuberculosis is the most common extrapulmonary manifestation of tuberculosis, and is generally characterized by an effusion. The effusion is usually unilateral and residual pleural thickening or calcification is also observed in some cases. Manifestations of multiple pleural tuberculomas without associated effusion and history of tuberculosis or antituberculous therapy are rare and an isolated pleural tuberculoma is exceedingly rare. Herein, we report the first documented case of an isolated pleural tuberculoma, diagnosed by chest CT and pathological findings. Although rare, an isolated pleural tuberculoma should be added to the differential diagnosis of focal nodular pleural tumors, particularly in areas of high tuberculosis prevalence.

Pulmonary immune-compartment-specific interferon gamma responses in HIV-infected individuals with active tuberculosis (TB) in an area of high TB prevalence.

There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNγ) response to M. tuberculosis, particularly in settings of high tuberculosis (TB) prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs) in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNγ response to purified protein derivative (PPD) and early secretory antigen 6 (ESAT6) in induced sputa (ISp) and blood samples from HIV-infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNγ in response to PPD in their induced sputa samples than individuals with non-active TB (control group). This difference was not reflected in the peripheral blood, even within the CD27− CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNγ secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNγ secretion across the spectrum of TB disease.