Potential Immunological Biomarkers for Detection of Mycobacterium tuberculosis Infection in a Setting Where M. tuberculosis Is Endemic, Ethiopia.

PubMed

Teklu, Takele; Kwon, Keehwan; Wondale, Biniam; HaileMariam, Milkessa; Zewude, Aboma; Medhin, Girmay; Legesse, Mengistu; Pieper, Rembert; Ameni, Gobena

2018-04-01

Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate Mycobacterium tuberculosis infection outcomes in a setting where it is endemic, Ethiopia. Whole blood from 90 participants was stimulated using the ESAT-6/CFP-10 antigen cocktail. The interferon gamma (IFN-γ)-based QuantiFERON diagnostic test was used to distinguish between LTBI and uninfected control cases. Forty cytokines/chemokines were detected from antigen-stimulated plasma supernatants (SPSs) and unstimulated plasma samples (UPSs) using human cytokine/chemokine antibody microarrays. Statistical tests allowed us to identify potential biomarkers that distinguish the TB, LTBI, and healthy control groups. As expected, the levels of IFN-γ in SPSs returned a high area under the receiver operating characteristic curve (AUC) value comparing healthy controls and LTBI cases (Z = 0.911; P < 0.001). The SPS data also indicated that interleukin 17 (IL-17) abundance discriminates LTBI from healthy controls (Z = 0.763; P = 0.001). RANTES and MIP-1β were significantly elevated in SPSs of TB-infected compared to healthy controls ( P < 0.05), while IL-12p40 and soluble tumor necrosis factor receptor II (sTNF-RII) were significantly increased in active TB cases compared to the combined LTBI and control groups ( P < 0.05). Interestingly, quantitative changes for RANTES were observed using both SPSs and UPSs, with P values of 0.013 and 0.012, respectively, in active TB versus LTBI cases and 0.001 and 0.002, respectively, in active TB versus healthy controls. These results encourage biomarker verification studies for IL-17 and RANTES. Combinations of these cytokines may complement IFN-γ measurements to diagnose LTBI and distinguish active TB from LTBI cases. Copyright © 2018 American Society for Microbiology.

Quantiferon-TB Gold Plus is a More Sensitive Screening Tool than Quantiferon-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facility.

PubMed

Chien, Jung-Yien; Chiang, Hsiu-Tzy; Lu, Min-Chi; Ko, Wen-Chien; Yu, Chong-Jen; Chen, Yen-Hsu; Hsueh, Po-Ren

2018-05-23

We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon-gamma release assays, i.e. QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results of QFTs during reproducibility analysis were classified as definite, possible and not LTBI, respectively). Two hundred and forty-four residents were enrolled and 229 subjects were included into analysis. The median age was 80 years (range, 60-102 years old) and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results of QFT-GIT and QFT-Plus, respectively, and 215 (93.9%) subjects showed agreement results. Using composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%. The sensitivity of QFT-GIT decreased gradually with age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% vs. 89.4%, P =0.013) and similar specificity (95.1% vs. 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs. Copyright © 2018 American Society for Microbiology.

Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis

PubMed Central

2014-01-01

Background There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. Methods This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. Results There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. Conclusions We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests. PMID:24904240

Poor agreement between interferon-gamma release assays and the tuberculin skin test among HIV-infected individuals in the country of Georgia.

PubMed

Chkhartishvili, Nikoloz; Kempker, Russell R; Dvali, Natia; Abashidze, Lela; Sharavdze, Lali; Gabunia, Pati; Blumberg, Henry M; Del Rio, Carlos; Tsertsvadze, Tengiz

2013-11-01

Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48-72 hrs with ≥ 5 mm induration considered positive. Between 2009-2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/μl (IQR: 124-412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (κ = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (κ = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (κ = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved

Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.

PubMed

Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia

2015-08-01

Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Latent tuberculosis infections in hard-to-reach drug using population-detection, prevention and control.

PubMed

Hwang, Lu-Yu; Grimes, Carolyn Z; Beasley, R Palmer; Graviss, Edward A

2009-12-01

Interferon-gamma release assays (IGRAs) need be evaluated for effectiveness as screening tests for tuberculosis (TB) infection in drug users. These tests have demonstrated improved sensitivity and specificity, but have not been studied in drug users. These one step blood tests are intended to replace the tuberculin skin test (TST), which is difficult to use and requires 48 hour follow-up, so they are expected to be particularly suitable for risk groups, like drug users, in whom follow-up is problematic. Drug users have traditionally been identified as being at increased risk for acquiring TB disease. The results of our pilot study using the TST and simpler and more sensitive interferon-gamma release assays showed that about 45% of current drug users in Houston tested have at least one test positive for latent tuberculosis infection (LTBI). These preliminary data suggest that there is an important reservoir of LTBI in drug using populations, and the risk of progression to active TB disease with other infections is great. However, LTBI in drug using populations has not been studied in depth and deserves further investigation. We need to evaluate the validity of IGRAs for detection of latent TB infection, the factors associated with LTBI, the incidence and risk for developing active TB disease in drug users and the effectiveness of early treatment of LTBI. We believe that using better tuberculosis screening tools will allow us to more accurately measure the prevalence of latent TB infection and incidence of active TB disease in drug using populations and develop more effective TB prevention and treatment interventions in the community.

Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection.

PubMed

Mukai, Shigeto; Shigemura, Katsumi; Yamamichi, Fukashi; Kitagawa, Koichi; Takami, Nozomi; Nomi, Masashi; Arakawa, Soichi; Fujisawa, Masato

2017-01-01

There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. One hundred and forty new employees during 2008-2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011-2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.

The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

PubMed

Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

2016-01-01

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.

Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil.

PubMed

Teixeira de Siqueira-Filha, Noemia; Militao de Albuquerque, Maria de Fatima; Cunha Rodrigues, Laura; Legood, Rosa; Costa Santos, Andreia

2018-03-15

The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV). Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882. Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB. RBR-22t943, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Label-Free Quantitative Proteomics Identifies Novel Plasma Biomarkers for Distinguishing Pulmonary Tuberculosis and Latent Infection.

PubMed

Sun, Huishan; Pan, Liping; Jia, Hongyan; Zhang, Zhiguo; Gao, Mengqiu; Huang, Mailing; Wang, Jinghui; Sun, Qi; Wei, Rongrong; Du, Boping; Xing, Aiying; Zhang, Zongde

2018-01-01

The lack of effective differential diagnostic methods for active tuberculosis (TB) and latent infection (LTBI) is still an obstacle for TB control. Furthermore, the molecular mechanism behind the progression from LTBI to active TB has been not elucidated. Therefore, we performed label-free quantitative proteomics to identify plasma biomarkers for discriminating pulmonary TB (PTB) from LTBI. A total of 31 overlapping proteins with significant difference in expression level were identified in PTB patients ( n = 15), compared with LTBI individuals ( n = 15) and healthy controls (HCs, n = 15). Eight differentially expressed proteins were verified using western blot analysis, which was 100% consistent with the proteomics results. Statistically significant differences of six proteins were further validated in the PTB group compared with the LTBI and HC groups in the training set ( n = 240), using ELISA. Classification and regression tree (CART) analysis was employed to determine the ideal protein combination for discriminating PTB from LTBI and HC. A diagnostic model consisting of alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein 1 (AGP1), and E-cadherin (CDH1) was established and presented a sensitivity of 81.2% (69/85) and a specificity of 95.2% (80/84) in discriminating PTB from LTBI, and a sensitivity of 81.2% (69/85) and a specificity of 90.1% (64/81) in discriminating PTB from HCs. Additional validation was performed by evaluating the diagnostic model in blind testing set ( n = 113), which yielded a sensitivity of 75.0% (21/28) and specificity of 96.1% (25/26) in PTB vs. LTBI, 75.0% (21/28) and 92.3% (24/26) in PTB vs. HCs, and 75.0% (21/28) and 81.8% (27/33) in PTB vs. lung cancer (LC), respectively. This study obtained the plasma proteomic profiles of different M.TB infection statuses, which contribute to a better understanding of the pathogenesis involved in the transition from latent infection to TB activation and provide new potential diagnostic

Latent tuberculosis infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwan.

PubMed

Huang, Y-W; Shen, G-H; Lee, J-J; Yang, W-T

2010-11-01

Both the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) may be used to detect Mycobacterium tuberculosis infection. A positive reaction to either test can indicate latent tuberculosis infection (LTBI). These tests can be used to study the rate of infection in contacts of multidrug-resistant tuberculosis (MDR-TB) patients. To evaluate the transmission status of MDR-TB patients in Taiwan by examining their close contacts and to compare the efficiency of TST and QFT-GIT. Chest radiographs, TST and QFT-GIT were performed in household contacts of confirmed MDR-TB patients to determine their infection status. A total of 78 close contacts of confirmed MDR-TB patients were included in the study. The majority of the MDR-TB patients were parents of the close contacts and lived in the same building; 46% of the subjects were TST-positive and 19% were QFT-GIT-positive, indicating LTBI that was likely to develop into active MDR-TB. There was a lack of consistency between TST and QFT-GIT results in subjects with previous bacille Calmette-Guérin vaccination. Household contacts of MDR-TB patients are likely to develop LTBI; thus, follow-up and monitoring are mandatory to provide treatment and reduce the occurrence of active infection.

Specificity of the Tuberculin Skin Test and the T-SPOT."TB" Assay among Students in a Low-Tuberculosis Incidence Setting

ERIC Educational Resources Information Center

Talbot, Elizabeth A.; Harland, Dawn; Wieland-Alter, Wendy; Burrer, Sherry; Adams, Lisa V.

2012-01-01

Objective: Interferon-[gamma] release assays (IGRAs) are an important tool for detecting latent "Mycobacterium tuberculosis" infection (LTBI). Insufficient data exist about IGRA specificity in college health centers, most of which screen students for LTBI using the tuberculin skin test (TST). Participants: Students at a low-TB incidence college…

Prevalence and factors associated with latent tuberculosis infection in an indigenous population in the Brazilian Amazon.

PubMed

Malacarne, Jocieli; Rios, Diana Patricia Giraldo; Silva, Cosme Marcelo Furtado Passos da; Braga, José Ueleres; Camacho, Luiz Antonio Bastos; Basta, Paulo Cesar

2016-01-01

Recent studies have shown a high incidence and prevalence of latent tuberculosis infection (LTBI) in indigenous populations around the World. We aimed to estimate the prevalence and annual risk of infection (ARI) as well as to identify factors associated with LTBI in an indigenous population from the Brazilian Amazon. We conducted a cross-sectional study in 2011. We performed tuberculin skin tests (TSTs), smears and cultures of sputum samples, and chest radiographs for individuals who reported cough for two or more weeks. Associations between LTBI (TST ≥5mm) and socio-demographic, clinical, and epidemiological characteristics were investigated using Poisson regression with robust variance. Prevalence ratio (PR) was used as the measure of association. We examined 263 individuals. The prevalence of LTBI was 40.3%, and the ARI was 2.4%. Age ≥15 years [PR=5.5; 95% confidence interval (CI): 3.5-8.6], contact with tuberculosis (TB) patients (PR=3.8; 95% CI: 1.2-11.9), previous TB history (PR=1.4; 95% CI: 1.2-1.7), and presence of Bacillus Calmette-Guérin (BCG) scar (PR=1.9, 95% CI: 1.2-2.9) were associated with LTBI. Although some adults may have been infected years prior, the high prevalence of infection and its strong association with age ≥15 years, history of TB, and recent contact with TB patients suggest that the TB transmission risk is high in the study area.

Tuberculosis infection among young nursing trainees in South India.

PubMed

Christopher, Devasahayam J; Daley, Peter; Armstrong, Lois; James, Prince; Gupta, Richa; Premkumar, Beulah; Michael, Joy Sarojini; Radha, Vedha; Zwerling, Alice; Schiller, Ian; Dendukuri, Nandini; Pai, Madhukar

2010-04-29

Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB) patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India. Among 535 nursing students enrolled in 2007, 468 gave consent to participate, and 436 underwent two-step tuberculin skin testing (TST). A majority (95%) were females, and almost 80% were under 22 years of age. Detailed TB exposure information was obtained using interviews and clinical log books. Prevalence of latent TB infection (LTBI) was estimated using Bayesian latent class analyses (LCA). Logistic regression analyses were done to determine the association between LTBI prevalence and TB exposure and risk factors. 219 of 436 students (50.2%, 95% CI: 45.4-55.0) were TST positive using the 10 mm or greater cut-off. Based on the LCA, the prevalence of LTBI was 47.8% (95% credible interval 17.8% to 65.6%). In the multivariate analysis, TST positivity was strongly associated with time spent in health care, after adjusting for age at entry into healthcare. Our study showed a high prevalence of LTBI even in young nursing trainees. With the recent TB infection control (TBIC) policy guidance from the World Health Organization as the reference, Indian healthcare providers and the Indian Revised National TB Control Programme will need to implement TBIC interventions, and enhance capacity for TBIC at the country level. Young trainees and nurses, in particular, will need to be targeted for TBIC interventions.

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection.

PubMed

Kim, Ji Yeun; Park, Joung Ha; Kim, Min-Chul; Cha, Hye Hee; Jeon, Na-Young; Park, Seong Yeon; Kim, Min-Jae; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-08

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB. Copyright © 2018. Published by Elsevier Ltd.

Snapshot of Quantiferon TB gold testing in Northern Mexico.

PubMed

González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

2011-12-01

Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection.

PubMed

Wu, Jing; Wang, Sen; Lu, Chanyi; Shao, Lingyun; Gao, Yan; Zhou, Zumo; Huang, Heqing; Zhang, Ying; Zhang, Wenhong

2017-01-01

Cytokines play an important role in cell-mediated immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokine profile specifically associated with active tuberculosis (ATB) patients, subjects with latent tuberculosis infection (LTBI) and non-infected individuals remains to be determined. We enrolled a total of 92 subjects including patients with ATB (n = 25), LTBI (n = 36) and healthy controls (HC, n = 31) to investigate the cytokine production by peripheral blood mononuclear cells after Mtb purified protein derivative (PPD) stimulation which was evaluated by a beads-based multiplex assay system. The production of IL-1β, IL-2, IL-6, IL-10, IL-17, G-CSF, IFN-γ, IP-10, MIP-1α and TNF-α was abundantly induced by PPD in all three groups. The levels of IL-2, IL-10, IFN-γ, IP-10 and TNF-α were significantly higher in LTBI group than in ATB group. The combination of PPD-stimulated IL-2 and IL-10 accurately identified 84.0% of ATB and 88.9% of LTBI. We validated the use of PPD-stimulated IL-2 and IL-10 test combined with T-SPOT.TB test in a cohort of 44 subjects with TB suspicion. The sensitivity and specificity of the combined test were 83.3% and 92.3%, respectively. The PPD-stimulated IL-2/IFN-γ ratio (p < 0.001) in LTBI subjects was significantly higher than in active TB patients. Our study identified cytokine patterns characteristic of ATB and LTBI. Cytokines such as IL-2 and IL-10 may serve as biomarkers for distinguishing ATB from LTBI and healthy control and may contribute to intervention and improvement in TB diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Within-Subject Interlaboratory Variability of QuantiFERON-TB Gold In-Tube Tests

DTIC Science & Technology

2012-09-06

QuantiFERONH-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection...viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test...release assays (IGRAs) are designed to detect both latent Mycobacterium tuberculosis infection (LTBI) and infections manifesting as active

Diagnosis and therapeutic approach of latent tuberculosis infection.

PubMed

Domínguez, José; Latorre, Irene; Santin, Miguel

2018-05-01

Detection and treatment of latent tuberculosis infection (LTBI) is an essential measure for tuberculosis (TB) control in low-incidence countries. However, such strategy is limited by the low predictive ability of the diagnostic tests for the development of active TB among infected people and the long-term and toxic treatment regimens. The in vitro interferon-gamma release assays are more specific and sensitive than the tuberculin skin test (TST), and enable a better selection of cases requiring treatment. Nonetheless, their capacity to predict development of TB is still poor. In addition, treatment regimens for LTBI are long, and compliance rates are low. This review discusses the use of the available diagnostic tests and the new approaches to the diagnosis of LTBI, as well as its management in different clinical scenarios. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing

PubMed Central

Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.

2012-01-01

Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of

A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program.

PubMed

Wingate, La'Marcus T; Coleman, Margaret S; de la Motte Hurst, Christopher; Semple, Marie; Zhou, Weigong; Cetron, Martin S; Painter, John A

2015-12-01

This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases

The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy.

PubMed

Jung, Yu Jung; Woo, Hye In; Jeon, Kyeongman; Koh, Won-Jung; Jang, Dong Kyoung; Cha, Hoon Suk; Koh, Eun Mi; Lee, Nam Yong; Kang, Eun-Suk

2015-01-01

We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring. Before starting TNF-α antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-α antagonist therapy. At the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8% (k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-α antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection. This study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden.

Identifying components for programmatic latent tuberculosis infection control in the European Union

PubMed Central

Sandgren, Andreas; Vonk Noordegraaf-Schouten, Jannigje M; Oordt-Speets, Anouk M; van Kessel, Gerarda B; de Vlas, Sake J; van der Werf, Marieke J

2016-01-01

Individuals with latent tuberculosis infection (LTBI) are the reservoir of Mycobacterium tuberculosis in a population and as long as this reservoir exists, elimination of tuberculosis (TB) will not be feasible. In 2013, the European Centre for Disease Prevention and Control (ECDC) started an assessment of benefits and risks of introducing programmatic LTBI control, with the aim of providing guidance on how to incorporate LTBI control into national TB strategies in European Union/European Economic Area (EU/EEA) Member States and candidate countries. In a first step, experts from the Member States, candidate countries, and international and national organisations were consulted on the components of programmatic LTBI control that should be considered and evaluated in literature reviews, mathematical models and cost-effectiveness studies. This was done through a questionnaire and two interactive discussion rounds. The main components identified were identification and targeting of risk groups, determinants of LTBI and progression to active TB, optimal diagnostic tests for LTBI, effective preventive treatment regimens, and to explore the potential for combining LTBI control with other health programmes. Political commitment, a solid healthcare infrastructure, and favourable economic situation in specific countries were identified as essential to facilitate the implementation of programmatic LTBI control. PMID:27589214

Tuberculosis and latent tuberculous infection screening of migrants in Europe: comparative analysis of policies, surveillance systems and results.

PubMed

Kunst, H; Burman, M; Arnesen, T M; Fiebig, L; Hergens, M-P; Kalkouni, O; Klinkenberg, E; Orcau, À; Soini, H; Sotgiu, G; Zenner, D; de Vries, G

2017-08-01

Migration patterns into and within Europe have changed over the last decade. In 2015, European Union (EU) countries received over 1.2 million asylum requests, more than double the number registered in the previous year. This review compares the published literature on policies for tuberculosis (TB) and latent tuberculous infection (LTBI) screening in EU and European Free Trade Association (EFTA) countries with the existing TB/LTBI screening programmes for migrants in 11 EU/EFTA countries based on a survey of policy and surveillance systems. In addition, we provide a systematic review of the literature on the yield of screening migrants for active TB and LTBI in Europe. Published studies provide limited information about screening coverage and the yield of screening evaluations in EU/EFTA countries. Furthermore, countries use different screening strategies and settings, and different definitions for coverage and yield of screening for active TB and LTBI. We recommend harmonising case definitions, reporting standards and policies for TB/LTBI screening. To achieve TB elimination targets, a European platform for multi-country data collection and analysis, sharing of countries' policies and practices, and harmonisation of migrant screening strategies is needed.

Stratification by interferon-γ release assay level predicts risk of incident TB.

PubMed

Winje, Brita Askeland; White, Richard; Syre, Heidi; Skutlaberg, Dag Harald; Oftung, Fredrik; Mengshoel, Anne Torunn; Blix, Hege Salvesen; Brantsæter, Arne Broch; Holter, Ellen Kristine; Handal, Nina; Simonsen, Gunnar Skov; Afset, Jan Egil; Bakken Kran, Anne Marte

2018-04-05

Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[The clinical application of quantiferon TB-2G: its usefulness and limitations].

PubMed

Sato, Shigeki; Nagai, Hideaki

2011-02-01

under exceptional circumstances. (1) How do we manage kidney transplant recipients with latent tuberculosis infection?: Norihiko GOTO (Transplant Surgery, Nagoya Daini Red Cross Hospital) It is unclear whether QuantiFERON-second generation (QFT-2G) is useful for diagnostic screening and follow up of latent tuberculosis infection (LTBI) in immunosuppressed kidney transplant (KTx) recipients. The QFT-2G assay that included response to mitogen stimulation was performed before and 6 months after KTx. Non responder was 0 (0%) at baseline, 3 (3%) at 6 months. Response to mitogen stimulation was 9.7 +/- 5.3 IU/mL at baseline vs. 10.4 +/- 5.0 IU/mL at 6 months after KTx (p = 0.29). QFT-2G is a useful screening test for LTBI and active tuberculosis (TB) even during maintenance of immunosuppression of KTx. (2) QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients for assessing latent tuberculosis infection prior treatment of anti-tumor necrosis factor antibody: Shogo BANNO (Division of Rheumatology and Nephrology, Department of Internal Medicine, Aichi Medical School of Medicine) To determine the positive rate of LTBI in RA patients using the QFT-2G test, we divided RA patients into two groups: with or without old TB findings by chest CT. With a cutoff level set at 0.35 IU/ml, the positive rate of QFT-2G in LTBI was detected only 5.8%, when setting cutoff at 0.1 IU/ml (lower cutoff level), 23.1% was detected in LTBI patients. The positive TST results were significantly increased in non-LTBI patients compared than in LTBI patients. The QFT-2G test was not affected by the treatment of MTX, and the incidence of indeterminate result was low. The QFT-2G was useful compared to TST before administration of TNF inhibitors in RA patients, because of superior specificity of QFT-2G. (3) Clinical parameters that influence the sensitivity of T-cell assays: Haruyuki ARIGA (National Hospital Organization Tokyo National Hospital) The detection of tuberculosis (TB) infection in

Assessment of the influence of direct tobacco smoke on infection and active TB management

PubMed Central

Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A.

2017-01-01

Background Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). Objective In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. Methods A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer’s instructions. Results In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs’ false-negative results (aOR: 3.35; 95%CI:1.47–7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02–3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97–22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Conclusions Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke. PMID:28837570

Assessment of the influence of direct tobacco smoke on infection and active TB management.

PubMed

Altet, Neus; Latorre, Irene; Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A; Domínguez, Jose

2017-01-01

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions. In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95%CI:1.47-7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02-3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97-22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity

PubMed Central

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina

2017-01-01

Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB. PMID:28182700

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity.

PubMed

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina; Cardona, Pere-Joan

2017-01-01

Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB.

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

PubMed Central

Anderson, Suzanne T.; Bangani, Nonzwakazi; Banwell, Claire M.; Brent, Andrew J.; Crampin, Amelia C.; Dockrell, Hazel M.; Eley, Brian; Heyderman, Robert S.; Hibberd, Martin L.; Kern, Florian; Langford, Paul R.; Ling, Ling; Mendelson, Marc; Ottenhoff, Tom H.; Zgambo, Femia; Wilkinson, Robert J.; Coin, Lachlan J.; Levin, Michael

2013-01-01

Background A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X.; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John Z.; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

2014-01-01

SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers. PMID:24396134

Screening for latent and active tuberculosis infection in the elderly at admission to residential care homes: A cost-effectiveness analysis in an intermediate disease burden area.

PubMed

Li, Jun; Yip, Benjamin H K; Leung, Chichiu; Chung, Wankyo; Kwok, Kin On; Chan, Emily Y Y; Yeoh, Engkiong; Chung, Puihong

2018-01-01

Tuberculosis (TB) in the elderly remains a challenge in intermediate disease burden areas like Hong Kong. Given a higher TB burden in the elderly and limited impact of current case-finding strategy by patient-initiated pathway, proactive screening approaches for the high-risk group could be optimal and increasingly need targeted economic evaluations. In this study, we examined whether and under what circumstance the screening strategies are cost-effective compared with no screening strategy for the elderly at admission to residential care homes. A decision analytic process based on Markov model was adopted to evaluate the cost-effectiveness of four strategies: (i) no screening, (ii) TB screening (CXR) and (iii) TB screening (Xpert) represent screening for TB in symptomatic elderly by chest X-ray and Xpert® MTB/RIF respectively, and (iv) LTBI/TB screening represents screening for latent and active TB infection by QuantiFERON®-TB Gold In-Tube and chest X-ray. The target population was a hypothetical cohort of 65-year-old people, using a health service provider perspective and a time horizon of 20 years. The outcomes were direct medical costs, life-years and quality-adjusted life-years (QALYs) measured by incremental cost-effectiveness ratio (ICER). In the base-case analysis, no screening was the most cost-saving; TB screening (CXR) was dominated by TB screening (Xpert); LTBI/TB screening resulted in more life-years and QALYs accrued. The ICERs of LTBI/TB screening were US$19,712 and US$29,951 per QALY gained compared with no screening and TB screening (Xpert), respectively. At the willingness-to-pay threshold of US$50,000 per QALY gained, LTBI/TB screening was the most cost-effective when the probability of annual LTBI reactivation was greater than 0.155% and acceptability of LTBI/TB screening was greater than 38%. In 1,000 iterations of Monte Carlo simulation, the probabilities of no screening, TB screening (CXR), TB screening (Xpert), and LTBI/TB screening to be

Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.

PubMed

Fox, G J; Anh, N T; Nhung, N V; Loi, N T; Hoa, N B; Ngoc Anh, L T; Cuong, N K; Buu, T N; Marks, G B; Menzies, D

2017-03-01

Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB (MDR-TB) and drug-susceptible TB are not well understood. To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB ('new TB'). Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm. A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0). Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.

Risk factors for latent tuberculosis infection in close contacts of active tuberculosis patients in South Korea: a prospective cohort study.

PubMed

Lee, Seung Jun; Lee, Seung Hun; Kim, You Eun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Jang Rak; Hwang, Young Sil; Kim, Hee Jin; Menzies, Dick

2014-11-18

The diagnosis and treatment of latent tuberculosis infection (LTBI) have become mandatory to reduce the burden of tuberculosis worldwide. Close contacts of active TB patients are at high risk of both active and LTBI. The aim of this study is to identify the predominant risk factors of contracting LTBI, persons in close contact with TB patients were recruited. This study also aimed to compare the efficacy of the tuberculin skin test (TST) and QuantiFERON(®)-TB GOLD (QFT-G) to diagnose LTBI. Close contacts of active pulmonary TB patients visiting a hospital in South Korea were diagnosed for LTBI using TST and/or QFT-G. The association of positive TST and/or QFT-G with the following factors was estimated: age, gender, history of Bacillius Calmette-Guerin (BCG) vaccination, history of pulmonary TB, cohabitation status, the acid-fast bacilli smear status, and presence of cough in source cases. Of 308 subjects, 38.0% (116/305) were TST positive and 28.6% (59/206) were QFT-G positive. TST positivity was significantly associated with male gender (OR: 1.734; 95% CI: 1.001-3.003, p =0.049), history of pulmonary TB (OR: 4.130; 95% CI: 1.441-11.835, p =0.008) and household contact (OR: 2.130; 95% CI: 1.198-3.786, p =0.01) after adjustment for confounding variables. The degree of concordance between TST and QFT-G was fair (70.4%, κ =0.392). A prevalence of LTBI among close contacts of active pulmonary TB patients was high, and prior TB history and being a household contact were risk factors of LTBI in the study population.

Multi-level barriers to LTBI treatment: a research note.

PubMed

Hill, Linda; Blumberg, Elaine; Sipan, Carol; Schmitz, Katharine; West, Joshua; Kelley, Norma; Hovell, Melbourne

2010-08-01

This study describes the barriers to effective and timely LTBI treatment encountered in a research study on INH adherence in Latino adolescents. Participant study logs were reviewed, results of continuing medical education pretests for medical providers were examined, and participating medical facilities were contacted in order to construct a profile of multi-level barriers to LTBI treatment. A total of 285 TST positive Latino (96%) high school students were recruited into the trial. We encountered a lack of understanding of the gravity of tuberculosis infection among both the public and providers of health care. Parents and adolescents cited competing priorities, transportation problems and financial constraints as reasons for non-compliance. Improved education of the public and physicians is needed regarding the gravity of the disease and the value of treatment, as well as public and financial support for LTBI treatment by both the government and the medical community.

Effect of Pregnancy on Interferon Gamma Release Assay and Tuberculin Skin Test Detection of Latent TB Infection Among HIV-Infected Women in a High Burden Setting.

PubMed

LaCourse, Sylvia M; Cranmer, Lisa M; Matemo, Daniel; Kinuthia, John; Richardson, Barbra A; Horne, David J; John-Stewart, Grace

2017-05-01

Peripartum immunologic changes may affect latent tuberculosis infection (LTBI) diagnostic performance among HIV-infected women. HIV-infected women were serially tested with tuberculin skin test (TST) and interferon gamma release assay [QuantiFERON TB Gold In-tube (QFT)] in pregnancy and 6 weeks postpartum in Kenya. Prevalence, sensitivity and agreement, and correlates of QFT/TST positivity were assessed. Quantitative QFT mitogen and Mycobacterium tuberculosis antigen (Mtb-Ag) responses were compared by peripartum stage. Incidence of test conversion at 6 weeks postpartum was evaluated in baseline TST-/QFT- women. Among 100 HIV-infected women, median age was 26 years, median CD4 was 555 cells per cubic millimeter, and 88% were on antiretrovirals. More women were QFT+ than TST+ in both pregnancy (35.4% vs. 13.5%, P = 0.001) and postpartum (29.6% vs. 14.8%, P < 0.001). Among 18 consistently QFT+ women, 8 (44%) converted from TST- to TST+, with improved test agreement postpartum (56.9%, κ = 0.20 to 82.4%, κ = 0.60). Three initially QFT-/TST- women had test conversion (TST+ and/or QFT+), suggesting new infection (incidence 13.4/100 person-years). Mean QFT mitogen (4.46 vs. 7.64 IU/mL, P < 0.001) and Mtb-Ag (1.03 vs. 1.54 IU/mL, P = 0.03) responses were lower among all women retested in pregnancy vs. postpartum, and specifically among persistently QFT+ women (Mtb-Ag: 3.46 vs. 4.48 IU/mL, P = 0.007). QFT indeterminate rate was higher in pregnancy (16%) compared with postpartum (0%) because of lower mitogen response. QFT identified >2-fold more women with LTBI compared with TST in pregnancy and postpartum. Lower QFT Mtb-Ag and mitogen responses in pregnancy compared with postpartum suggest that pregnancy-associated immunologic changes may influence LTBI test performance.

Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling.

PubMed

Korthals Altes, Hester; Kloet, Serieke; Cobelens, Frank; Bootsma, Martin

2018-01-01

While tuberculosis (TB) represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation-either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995-2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting

Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling

PubMed Central

Kloet, Serieke; Cobelens, Frank; Bootsma, Martin

2018-01-01

While tuberculosis (TB) represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation–either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995–2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting

Regulatory T Cells Subvert Mycobacterial Containment in Patients Failing Extensively Drug-resistant TB Treatment.

PubMed

Davids, Malika; Pooran, Anil S; Pietersen, Elize; Wainwright, Helen C; Binder, Anke; Warren, Robin; Dheda, Keertan

2018-02-09

The advent of extensively (XDR-TB) and totally drug-resistant TB, with limited or no treatment options, has facilitated renewed interest in host directed immunotherapy, particularly for therapeutically destitute patients. However, the selection and utility of such approaches depend upon understanding the host immune response in XDR-TB, which hitherto remains unexplored. To determine the host immunological profile in patients with XDR-TB, compared to drug-sensitive TB, using peripheral blood and explanted lung tissue. Blood and explanted lung tissue were obtained from patients with XDR-TB (n=31), drug-sensitive TB (DS-TB, n=20) and presumed latent-TB infection (LTBI, n=20). T-cell phenotype (Th1/Th2/Th17/Tregs) was evaluated in all patient groups, and Treg function assessed in XDR-TB non-responders by co-culturing PPD pre-primed effector T-cells with H37Rv-infected monocyte-derived macrophages, with or without autologous Tregs. Mycobacterial containment was evaluated by counting colony-forming units. Patients failing XDR-TB treatment had an altered immuno-phenotype characterized by a substantial increase in the frequency (median; IQR) of CD4+CD25+FoxP3+ regulatory T-cells (11.5; 5.9-15.2) compared to DS-TB (3.4 %; 1.6-5.73; p < 0.001) and presumed LTBI (1.8 % 1.2-2.3; p < 0.001), which was unrelated to disease duration. Tregs isolated from XDR-TB patients suppressed T-cell proliferation (up to 90%) and subverted containment of H37Rv-infected monocyte-derived macrophages (by 30%; p= 0.03) by impairing effector T-cell function through a mechanism independent of direct cell-to-cell contact, IL-10, TGF-beta and CTLA-4. Collectively, these data suggest that Tregs may be contributing to immune dysfunction, and bacterial persistence, in patients with XDR-TB. The relevant cellular pathways may serve as potential targets for immunotherapeutic intervention.

Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital.

PubMed

Janagond, Anand Bimari; Ganesan, Vithiya; Vijay Kumar, G S; Ramesh, Arunagiri; Anand, Prem; Mariappan, M

2017-01-01

Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette-Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs

Intention of physicians to implement guidelines for screening and treatment of latent tuberculosis infection in HIV-infected patients in The Netherlands: a mixed-method design.

PubMed

Evenblij, Kirsten; Verbon, Annelies; van Leth, Frank

2016-09-01

All newly diagnosed HIV-infected patients in the Netherlands should be screened for latent tuberculosis infection (LTBI) and offered preventive therapy if infected without evidence of active tuberculosis. This guideline, endorsed by the national professional body of HIV physicians is in line with international recommendations, and based on the increased risk of progression from LTBI to active tuberculosis in HIV-infected patients. The objective of the study is to assess the intention of HIV physicians to implement this national guideline. A mixed method design triangulating results from two surveys among all (n = 80) HIV physicians in The Netherlands and qualitative interviews among 11 Dutch HIV physicians performed in 2014. The majority of physicians used a risk-stratification approach based on individual a priori risk of tuberculosis to identify HIV-infected patients for LTBI screening, rather than screening all new HIV-infected patients. The intended and actual provision of preventive treatment was low, due to expressed doubts on the accuracy of diagnostic tools for LTBI. Interviewees reported that the guidelines did not match their clinical experience and lacked evidence for the recommendations. Screening for and treatment of LTBI was approached at a patient-level only. None of the interviewees referred to potential public health implications of the guidelines. Intended implementation of the national HIV-TB guidelines in the Netherlands is poor, due to a disconnect between clinical practice and evidence-based recommendations in the guideline. There is an urgent need to reconcile the views of HIV-physicians, public health experts, and guideline committee members, regarding the best strategy to address HIV-TB co-infection in the Netherlands.

Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa

PubMed Central

Sutherland, Jayne S.; Lalor, Maeve K.; Black, Gillian F.; Ambrose, Lyn R.; Loxton, Andre G.; Chegou, Novel N.; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P.; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R.; Parida, Shreemanta K.; Boom, W. Henry; Thiel, Bonnie A.; Crampin, Amelia C.; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Kaufmann, Stefan H. E.

2013-01-01

Background Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. Methods We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. Results There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST- and TST+ contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST+ contacts (LTBI) compared to TB and TST- contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Conclusions Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

PubMed

Sutherland, Jayne S; Lalor, Maeve K; Black, Gillian F; Ambrose, Lyn R; Loxton, Andre G; Chegou, Novel N; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R; Parida, Shreemanta K; Boom, W Henry; Thiel, Bonnie A; Crampin, Amelia C; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H M; Dockrell, Hazel M; Kaufmann, Stefan H E

2013-01-01

Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study.

PubMed

Ncayiyana, Jabulani R; Bassett, Jean; West, Nora; Westreich, Daniel; Musenge, Eustasius; Emch, Michael; Pettifor, Audrey; Hanrahan, Colleen F; Schwartz, Sheree R; Sanne, Ian; van Rie, Annelies

2016-11-08

South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI RESULTS: The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0-14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01-1.05), male gender (OR = 2.70, 95 % CI = 1.55-4.70), marital status (OR = 2.00, 95 % CI = 1.31-3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04-4.31). The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty.

Prevalence and associated risk factors of latent tuberculosis infection among undergraduate and postgraduate dental students: A retrospective study.

PubMed

Lamberti, Monica; Muoio, Maria Rosaria; Westermann, Claudia; Nienhaus, Albert; Arnese, Antonio; Ribeiro Sobrinho, Antônio Paulino; Di Giuseppe, Gabriella; Garzillo, Elpidio Maria; Crispino, Vincenzo; Coppola, Nicola; De Rosa, Alfredo

2017-03-04

To estimate the prevalence of latent tuberculosis (TB) infection (LTBI) in Italian dental students exposed to the same occupational risks as dental health care personnel and to evaluate potential risk factors, a cross-sectional study was conducted on undergraduate and postgraduate students. After clinical evaluation, students were given a tuberculin skin test; in those found positive, an interferon-γ release assay (IGRA) was conducted. Of the 281 students enrolled, 10 were only TST positive; 8 were TST or/and IGRA positive. We found that participants testing positive at TST and/or IGRA, a group in which the risk of false LTBI positives is minimal, were older and had been studying longer. Although the prevalence of LTBI among dental students in our study was low, a risk of acquiring a work-related infection exists even in a country with a low incidence of TB. Thus, dental students should be screened to catch LTBI early on.

Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection.

PubMed

Dobler, Claudia C; Bosnic-Anticevich, Sinthia; Armour, Carol L

2018-01-01

The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds) and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk-benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters.

Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection

PubMed Central

Bosnic-Anticevich, Sinthia; Armour, Carol L.

2018-01-01

The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds) and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk–benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters. PMID:29577042

Prevalence of latent tuberculosis infection in healthcare workers at a hospital in Naples, Italy, a low-incidence country.

PubMed

Lamberti, Monica; Muoio, Mariarosaria; Arnese, Antonio; Borrelli, Sharon; Di Lorenzo, Teresa; Garzillo, Elpidio Maria; Signoriello, Giuseppe; De Pascalis, Stefania; Coppola, Nicola; Nienhaus, Albert

2016-01-01

Healthcare workers (HCWs) are at higher risk than the general population of contracting tuberculosis (TB). Moreover, although subjects with latent TB infection (LTBI) are asymptomatic and are not infectious, they may eventually develop active disease. Thus, a fundamental tool of TB control programs for HCWs is the screening and treatment of LTBI. From January 2014 to January 2015, hospital personnel at Azienda Ospedaliera Universitaria, Naples, Italy, were screened for TB. To this end, a tuberculin skin test (TST) was administered as an initial examination, unless when contraindicated, in which case the QuantiFERON® TB-Gold (QFT) assay was performed. Moreover, QFT was carried out on all TST-positive cases to confirm the initial result. Of 628 personnel asked to participate, 28 (4.5%) denied consent, 533 were administered TST as the baseline examination, and 67 were tested only with QFT. In the TST group, 73 (13.2%) individuals were found positive, 418 (78.4%) were negative, and 42 (7.9%) were absent for the reading window; QFT confirmed the result in 39 (53.4%) TST-positive individuals. In the QFT-only group, 44 (65.7%) individuals were found positive. All TST- and/or QFT-positive subjects were referred for chest X-ray and examination by an infectious diseases specialist. None were found to have active TB, and were thus diagnosed with LTBI. Although Italy is a low-incidence country regarding TB, our findings suggest that the prevalence of LTBI in HCWs may be relatively high. As a result, active screening for TB and LTBI is needed for these workers.

Monitoring latent tuberculosis infection diagnosis and management in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; de Vries, Gerard; Cobelens, Frank; van den Hof, Susan

2016-05-01

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events.In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation.Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events.Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40-60%. Copyright ©ERS 2016.

Advances in diagnosis and treatment of latent tuberculosis infection.

PubMed

Chapman, Helena J; Lauzardo, Michael

2014-01-01

In the United States, latent tuberculosis infection (LTBI) affects between 10 and 15 million people, of whom 10% may develop active tuberculosis disease. People at increased risk for tuberculosis reactivation include recent immigrants from countries with a high incidence of tuberculosis, children younger than age 5, people who have been infected with Mycobacterium tuberculosis within the past 2 years, or people with immunosuppression for a variety of reasons. Appropriate diagnosis and treatment of LTBI are critical for controlling and eventually eliminating tuberculosis as a public health problem. Although the tuberculin skin test is the traditional diagnostic measure for LTBI, reduced specificity has promoted the development and utilization of the interferon-γ release assays as an in vitro blood test with specific antigens to M. tuberculosis (QuantiFERON-TB Gold In-Tube test and the T.SPOT-TB test are commercially available). Despite the rise of the new diagnostic tests, however, there is still no gold standard for diagnosing LTBI, and epidemiologic risks and comorbidities need to be taken into account before initiating therapy. Current diagnostic tests combined with recommended treatment regimens are valuable tools that, when used correctly, promise to hurry the elimination of tuberculosis. © Copyright 2014 by the American Board of Family Medicine.

Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico

PubMed Central

Oren, Eyal; Alatorre-Izaguirre, Gabriela; Vargas-Villarreal, Javier; Moreno-Treviño, Maria Guadalupe; Garcialuna-Martinez, Javier; Gonzalez-Salazar, Francisco

2015-01-01

Nearly one-third of the world’s population is infected with latent tuberculosis (LTBI). Tuberculosis (TB) rates in the border states are higher than national rates in both the US and Mexico, with the border accounting for 30% of total registered TB cases in both countries. However, LTBI rates in the general population in Mexican border states are unknown. In this region, LTBI is diagnosed using the tuberculin skin test (TST). New methods of detection more specific than TST have been developed, although there is currently no gold standard for LTBI detection. Our objective is to demonstrate utility of the Quantiferon TB gold In-Tube (QFT-GIT) test compared with the TST to detect LTBI among border populations. This is an observational, cross-sectional study carried out in border areas of the states of Nuevo Leon and Tamaulipas, Mexico. Participants (n = 210) provided a TST and blood sample for the QFT-GIT. Kappa coefficients assessed the agreement between TST and QFT-GIT. Participant characteristics were compared using Fisher exact tests. Thirty-eight percent of participants were diagnosed with LTBI by QFT-GIT. The proportion of LTBI detected using QFT-GIT was almost double [38% (79/210)] that found by TST [19% (39/210)] (P < 0.001). Concordance between TST and QFT-GIT was low (kappa = 0.37). We recommend further studies utilizing the QFT-GIT test to detect LTBI among border populations. PMID:26484340

Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico.

PubMed

Oren, Eyal; Alatorre-Izaguirre, Gabriela; Vargas-Villarreal, Javier; Moreno-Treviño, Maria Guadalupe; Garcialuna-Martinez, Javier; Gonzalez-Salazar, Francisco

2015-01-01

Nearly one-third of the world's population is infected with latent tuberculosis (LTBI). Tuberculosis (TB) rates in the border states are higher than national rates in both the US and Mexico, with the border accounting for 30% of total registered TB cases in both countries. However, LTBI rates in the general population in Mexican border states are unknown. In this region, LTBI is diagnosed using the tuberculin skin test (TST). New methods of detection more specific than TST have been developed, although there is currently no gold standard for LTBI detection. Our objective is to demonstrate utility of the Quantiferon TB gold In-Tube (QFT-GIT) test compared with the TST to detect LTBI among border populations. This is an observational, cross-sectional study carried out in border areas of the states of Nuevo Leon and Tamaulipas, Mexico. Participants (n = 210) provided a TST and blood sample for the QFT-GIT. Kappa coefficients assessed the agreement between TST and QFT-GIT. Participant characteristics were compared using Fisher exact tests. Thirty-eight percent of participants were diagnosed with LTBI by QFT-GIT. The proportion of LTBI detected using QFT-GIT was almost double [38% (79/210)] that found by TST [19% (39/210)] (P < 0.001). Concordance between TST and QFT-GIT was low (kappa = 0.37). We recommend further studies utilizing the QFT-GIT test to detect LTBI among border populations.

Prevalence of tuberculosis infection in healthcare workers of the public hospital network in Medellín, Colombia: a Bayesian approach.

PubMed

Ochoa, J; León, A L; Ramírez, I C; Lopera, C M; Bernal, E; Arbeláez, M P

2017-04-01

A latent tuberculosis infection (LTBI) prevalence survey was conducted using tuberculin skin test (TST) and Quantiferon test (QFT) in 1218 healthcare workers (HCWs) in Medellín, Colombia. In order to improve the prevalence estimates, a latent class model was built using a Bayesian approach with informative priors on the sensitivity and specificity of the TST. The proportion of concordant results (TST+,QFT+) was 41% and the discordant results contributed 27%. The marginal estimate of the prevalence P(LTBI+) was 62·1% [95% credible interval (CrI) 53·0-68·2]. The probability of LTBI+ given positive results for both tests was 99·6% (95% CrI 98·1-99·9). Sensitivity was 88·5 for TST and 74·3 for QFT, and specificity was 87·8 for TST and 97·6 for QFT. A high LTBI prevalence was found in HCWs with time-accumulated exposure in hospitals that lack control plans. In a context of intermediate tuberculosis (TB) incidence it is recommended to use only one test (either QFT or TST) in prevalence surveys or as pre-employment tests. Results will be useful to help implement TB infection control plans in hospitals where HCWs may be repeatedly exposed to unnoticed TB patients, and to inform the design of TB control policies.

Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls.

PubMed

Zewdie, Martha; Howe, Rawleigh; Hoff, Søren T; Doherty, T Mark; Getachew, Nahom; Tarekegne, Azeb; Tessema, Bamlak; Yamuah, Lawrence; Aseffa, Abraham; Abebe, Markos

2016-09-01

Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers. The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4(+)CD25(+/hi) T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4(+)CD25(+)FOXP3(+)CD127(lo) Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4(+)CD25(+)FOXP3(+)CD127(lo)CD45RO(+)Ki-67(+)) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO(+)Ki-67(-)) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5-21.9) of Tregs to 9.3% (7.0-12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls

PubMed Central

Zewdie, Martha; Howe, Rawleigh; Hoff, Søren T.; Doherty, T. Mark; Getachew, Nahom; Tarekegne, Azeb; Tessema, Bamlak; Yamuah, Lawrence; Aseffa, Abraham; Abebe, Markos

2016-01-01

SUMMARY Background Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. Method We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers. Results The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4+CD25+/hi T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4+CD25+FOXP3+CD127lo Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4+CD25+FOXP3+CD127loCD45RO+Ki-67+) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO+Ki-67−) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5–21.9) of Tregs to 9.3% (7.0–12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection. PMID:27553411

High prevalence of latent tuberculosis infection among injection drug users in Tijuana, Mexico.

PubMed

Garfein, R S; Lozada, R; Liu, L; Laniado-Laborin, R; Rodwell, T C; Deiss, R; Alvelais, J; Catanzaro, A; Chiles, P G; Strathdee, S A

2009-05-01

We studied prevalence and correlates of latent tuberculosis infection (LTBI) among injection drug users (IDUs) in Tijuana, Mexico, where tuberculosis (TB) is endemic. IDUs aged > or =18 years were recruited via respondent-driven sampling (RDS) and underwent standardized interviews, human immunodeficiency virus (HIV) antibody testing and LTBI screening using Quanti-FERON((R))-TB Gold In-Tube, a whole-blood interferon-gamma release assay (IGRA). LTBI prevalence was estimated and correlates were identified using RDS-weighted logistic regression. Of 1020 IDUs, 681 (67%) tested IGRA-positive and 44 (4%) tested HIV-positive. Mean age was 37 years, 88% were male and 98% were Mexican-born. IGRA positivity was associated with recruitment nearest the US border (aOR 1.64, 95%CI 1.09-2.48), increasing years of injection (aOR 1.20/5 years, 95%CI 1.07-1.34), and years lived in Tijuana (aOR 1.10/5 years, 95%CI 1.03-1.18). Speaking some English (aOR 0.38, 95%CI 0.25-0.57) and injecting most often at home in the past 6 months (aOR 0.68, 95%CI 0.45-0.99) were inversely associated with IGRA positivity. Increased LTBI prevalence among IDUs in Tijuana appears to be associated with greater drug involvement. Given the high risk for HIV infection among Tijuana's IDUs, interventions are urgently needed to prevent HIV infection and treat LTBI among IDUs before these epidemics collide.

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

PubMed Central

Dutta, Noton K.

2014-01-01

SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI. PMID:25184558

Latent tuberculosis infection screening prior to biological treatment in Tunisian patients.

PubMed

Slouma, Marwa; Mahmoud, Ines; Saidane, Olfa; Bouden, Selma; Abdelmoula, Leila

2017-10-01

The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Chemokines additional to IFN-γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.

PubMed

Nonghanphithak, Ditthawat; Reechaipichitkul, Wipa; Namwat, Wises; Naranbhai, Vivek; Faksri, Kiatichai

2017-07-01

Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ® -TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (70.8%) and specificity (74.4%); CXCL10 showed high sensitivity (87.5%) and specificity (78.9%). Compared to IFN-γ alone, IFN-γ combined with CXCL10 significantly improved (p < 0.001) the sensitivity and specificity to discriminate between ATB and HC (97.9% sensitivity and 94.9% specificity) and between ATB and LTBI (89.6% sensitivity and 71.1% specificity). Levels of CCL2 were very significantly lower (p < 0.0001) in EC compared to HC groups and hence CCL2 is a useful marker for EC. This study demonstrated the potential application of profiling using multiple chemokines for differentiating among the various M. tuberculosis infection possibilities. We also present evidence to support the EC phenomenon based on the decrease of CCL2 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk factors for failure to complete a course of latent tuberculosis infection treatment in Salvador, Brazil.

PubMed

Machado, Almério; Finkmoore, B; Emodi, K; Takenami, I; Barbosa, T; Tavares, M; Reis, M G; Arruda, S; Riley, L W

2009-06-01

Although treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) control in countries such as the United States, it is not widely practiced in most TB-endemic countries. To examine the practice of and adherence to LTBI treatment in a high-risk population in Brazil. We followed household contacts (HHCs) of patients hospitalized with pulmonary TB in Salvador, Brazil, for 6 months after they initiated LTBI treatment with isoniazid (INH). HHCs were asked to return to the hospital once a month for 6 months for follow-up visits and INH refills. Of 101 HHCs who initiated LTBI treatment, 54 (53.5%) completed the 6-month regimen. The risk of treatment non-completion was significantly higher in HHCs who reported side effects to INH (RR 2.69, 95%CI 1.3-5.8, P = 0.01), and in those who had to take two buses for a one-way trip to the hospital (RR 1.8, 95%CI 1.01-3.3, P = 0.04). Of the 101 HHCs, 29 (28.7%) did not return for any follow-up visits; these HHCs were significantly more likely to have a 2-bus commute to the hospital compared to HHCs who completed treatment (OR 20.69, 95%CI 2.1-208.4, P = 0.01). Nearly 50% of HHCs at high risk for developing TB completed a 6-month course of LTBI treatment. Completion of LTBI treatment was most affected by medication intolerance and commuting difficulties for follow-up visits.

TB in healthcare workers in the UK: a cohort analysis 2009-2013.

PubMed

Davidson, Jennifer A; Lalor, Maeve K; Anderson, Laura F; Tamne, Surinder; Abubakar, Ibrahim; Thomas, H Lucy

2017-07-01

To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure. Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth. 2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients. The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Revisiting the natural history of tuberculosis. The inclusion of constant reinfection, host tolerance, and damage-response frameworks leads to a better understanding of latent infection and its evolution towards active disease.

PubMed

Cardona, Pere-Joan

2010-02-01

Once Mycobacterium tuberculosis infects a person it can persist for a long time in a process called latent tuberculosis infection (LTBI). LTBI has traditionally been considered to involve the bacilli remaining in a non-replicating state (dormant) in old lesions but still retaining their ability to induce reactivation and cause active tuberculosis (TB) once a disruption of the immune response takes place. The present review aims to challenge these concepts by including recent experimental data supporting LTBI as a constant endogenous reinfection process as well as the recently introduced concepts of damage-response and tolerance frameworks to explain TB induction. These frameworks highlight the key role of an exaggerated and intolerant host response against M. tuberculosis bacilli which induces the classical TB cavity in immunocompetent adults once the constant endogenous reinfection process has resulted in the presence of bacilli in the upper lobes, where they can grow faster and the immune response is delayed. This essay intends to provide new clues to understanding the induction of TB in non-immunosuppressed patients.

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

Screening contacts of patients with extrapulmonary TB for latent TB infection.

PubMed

Humphreys, Anna; Abbara, Aula; Williams, Sion; John, Laurence; Corrah, Tumena; McGregor, Alastair; Davidson, Robert N

2018-03-01

2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply that contacts of extrapulmonary TB do not require screening for latent TB infection. At our high TB prevalence site, we identified 189 active cases of TB for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and 10.7% of the contacts of extrapulmonary TB had active or latent TB infection. This supports screening contacts of extrapulmonary TB at our site and presents a way to access high-risk individuals. We propose to continue to screen the contacts of our patients with extrapulmonary TB and recommend other TB units audit their local results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

PubMed Central

Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

2011-01-01

Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

[USE OF QuantiFERON® TB-GOLD IN-TUBE IN A CONTACT INVESTIGATION TO DETERMINE THE ONSET OF TUBERCULOSIS WITH OR WITHOUT LATENT TUBERCULOSIS INFECTION TREATMENT].

PubMed

Matsumoto, Kenji; Komukai, Jun; Tsuda, Yuko; Furukawa, Kanae; Saito, Kazumi; Hirota, Satoshi; Koda, Shinichi; Kasai, Sachi; Shimouchi, Akira

2016-02-01

QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis. Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases. (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001). Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G

Risk of developing tuberculosis disease among persons diagnosed with latent tuberculosis infection in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; Cobelens, Frank; van den Hof, Susan

2016-11-01

Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands. Copyright ©ERS 2016.

Heparin-Binding Haemagglutinin, a New Tool for the Detection of Latent Mycobacterium tuberculosis Infection in Hemodialysis Patients

PubMed Central

Dessein, Rodrigue; Corbière, Véronique; Nortier, Joëlle; Dratwa, Max; Gastaldello, Karine; Pozdzik, Agnieszka; Lecher, Sophie; Grandbastien, Bruno; Locht, Camille; Mascart, Françoise

2013-01-01

Background Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients. Methods On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA). Results Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT. Conclusions The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT. PMID:23940693

HIV and TB co-infection in Indian context.

PubMed

Mahyoub, E M; Garg, Suneela; Singh, M M; Agarwal, Paras; Gupta, V K; Gupta, Naresh

2013-01-01

This study was carried out in a Anti-Retroviral Therapy Clinic and TB center of a tertiary level hospital to find out socio-demographic correlates of HIV/TB individuals and risk factors of HIV/TB co-infection in Indian context. It is a case-control study comprising 420 subjects, 3 groups of 140 each. For a case group of HIV-TB co-infected subjects, two control groups, one comprising HIV patients (not having TB), and the other TB patients (not having HIV). Majority 267 (63.6%) males, 100 (71.4%) in case group (HIV/ TB), 74 (52.9%) in control group 1 (TB) and 93 (66.4%) in control group 2 (HIV). Mean (+/-SD) age of case-group was 34.91 (+/- 8.57) years. New TB cases were 213 (76.1%), more among control-group 1, compared to case-group. Multivariate analysis showed that risk of co-infection was 1.94 times higher among individuals aged >35 years. Difference statistically significant amongst those who were not on ART than who were on ART (p < 0.001). Those with CD4 counts <200 had 1.85 times risk of TB. Smokers had 1.92 times risk of TB. Co-infection higher in males, in age group 35-44 years, urban area, lower educational status and lower socioeconomic class. Current history of smoking significantly associated with co-infection. HIV status during TB infection was detected in 1/4th of study subjects. History of TB symptoms in family significantly associated with co-infection.

National position statement for the management of latent tuberculosis infection.

PubMed

Stock, David

2017-09-01

The primary role of any tuberculosis (TB) control program is to ensure the prompt identification and effective treatment of active disease. The host immune system often succeeds in containing the initial (or primary) infection with Mycobacterium tuberculosis (Mtb), but may fail to eliminate the pathogen. The persistence of viable organisms explains the potential for the development of active disease years or even decades after infection. This is known as latent tuberculosis infection (LTBI) although, rather than a distinct entity, this probably represents part of a dynamic spectrum. Individuals with LTBI are asymptomatic and it is therefore clinically undetectable. The World Health Organization (WHO) estimates that one-third of the global population has been infected with Mtb, with highest prevalence of LTBI in countries/regions with the highest prevalence of active disease. In 2013, 88% of 1322 notifications in Australia were in the overseas-born population (incidence 19.5 per 100,000 v. 1.0 per 100,000), with this proportion rising over the course of the last decade. Combined with epidemiological evidence of low local transmission, this strongly implies that the vast majority resulted from reactivation of latent infection acquired prior to immigration. Contrasting trends in TB incidence in other developed countries probably reflect differences in policy regarding LTBI. The diagnosis and treatment of LTBI represents an important opportunity for intervention by jurisdictional TB control programs. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or

Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits.

PubMed

Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H

2017-01-01

Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects

Persistent latent tuberculosis reactivation risk in United States immigrants.

PubMed

Walter, Nicholas D; Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Estimate reactivation and imported TB in an immigrant cohort. We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1-9. High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival.

Latent Tuberculosis Infection and Occupational Protection among Health Care Workers in Two Types of Public Hospitals in China

PubMed Central

Zhou, Feng; Zhang, Li; Gao, Lei; Hao, Yibin; Zhao, Xianli; Liu, Jianmin; Lu, Jie; Li, Xiangwei; Yang, Yu; Chen, Junguo; Deng, Ying

2014-01-01

Objective To determine the impact factors of latent tuberculosis infection (LTBI) and the knowledge of TB prevention and treatment policy among health care workers (HCWs) in different types of hospitals and explore the strategies for improving TB prevention and control in medical institutions in China. Methods A cross-sectional study was carried out to evaluate the risk of TB infection and personnel occupational protection among HCWs who directly engage in medical duties in one of two public hospitals. Each potential participant completed a structured questionnaire and performed a tuberculin skin test (TST). Factors associated with LTBI were identified by logistic regression analysis. Results Seven hundred twelve HCWs completed questionnaires and 74.3% (n = 529) took the TST or had previous positive results. The TST-positive prevalence was 58.0% (n = 127) in the infectious disease hospital and 33.9% (n = 105) in the non-TB hospital. The duration of employment in the healthcare profession (6–10 years vs. ≤5 years [OR = 1.89; 95% CI = 1.10, 3.25] and>10 vs. ≤5[OR = 1.80; 95% CI = 1.20, 2.68]), type of hospital (OR = 2.40; 95% CI = 1.59, 3.62), and ever-employment in a HIV clinic or ward (OR = 1.87; 95% CI = 1.08, 3.26)were significantly associated with LTBI. The main reasons for an unwillingness to accept TST were previous positive TST results (70.2%) and concerns about skin reaction (31.9%). Conclusion A high prevalence of TB infections was observed among HCWs working in high-risk settings and with long professional experiences in Henan Province in China. Comprehensive guidelines should be developed for different types of medical institutions to reduce TB transmission and ensure the health of HCWs. PMID:25157814

Predictors of discordant tuberculin skin test and QuantiFERON®-TB Gold In-Tube results in various high-risk groups.

PubMed

Weinfurter, P; Blumberg, H M; Goldbaum, G; Royce, R; Pang, J; Tapia, J; Bethel, J; Mazurek, G H; Toney, S; Albalak, R

2011-08-01

Persons in whom targeted testing for latent tuberculosis infection (LTBI) is recommended in Seattle, Washington; Atlanta, Georgia; and central North Carolina, United States. To compare the performance of an interferon-gamma release assay (QuantiFERON®-TB Gold In-Tube [QFT-GIT]) with the tuberculin skin test (TST) among foreign-born, homeless, human immunodeficiency virus (HIV) infected and substance abuse persons tested for LTBI. A cross-sectional study requiring participants to have a blood test, a TST and data collected. Of 1653 persons, 19.5% were TST-positive and 14.0% were QFT-GIT-positive. Overall concordance was moderate (kappa 0.53; 95%CI 0.47-0.58). Compared to concordant positive results, TST+/QFT-GIT- discordance was associated with HIV infection and sex, while TST-/QFT-GIT+ discordance was associated with HIV and inversely associated with foreign birth. Compared to concordant negative results, TST-/QFT-GIT+ discordance was associated with foreign birth and age ≥50 years, while TST+/QFT-GIT-discordance was associated with foreign birth, age 30-49 years, being Black and inversely associated with HIV. HIV infection was significantly associated with indeterminate QFT-GIT results. QFT-GIT may be an improvement over the TST for diagnosing LTBI in foreign-born and older persons, and may be as useful as the TST in HIV-infected persons. The sensitivity of both tests may be low in HIV-infected persons.

Diagnosis of latent tuberculosis and prevention of reactivation in rheumatic patients receiving biologic therapy: international recommendations.

PubMed

Iannone, Florenzo; Cantini, Fabrizio; Lapadula, Giovanni

2014-05-01

To review the official international recommendations on the management of latent tuberculosis infection (LTBI) in patients with rheumatic diseases undergoing biologic therapy. A systematic search of all clinical practice recommendations on the diagnosis and treatment of LTBI in rheumatic patients eligible for starting biologic drugs published between January 2002 and March 2013. For the diagnosis of LTBI, based on positivity of tuberculin skin test (TST), interferon-γ release assay (IGRA) is also available. Most recommendations advise using both TST and IGRA, especially in case of Bacillus Calmette-Guérin vaccination, to screen patients before commencing biologic drugs. There is a general consensus that evaluation of the global risk of TB infection is a crucial point and that patients with LTBI must receive chemoprophylaxis prior to biologic therapy. However, recommendations on the need for rescreening for activation of LTBI or new TB infection while patients are being treated are inadequate. Nevertheless, the main concern is poor compliance with TB recommendations of rheumatologists in clinical practice, which seems to be the main cause of the occurrence of active TB in rheumatic patients receiving biologic therapy. Notwithstanding some differences, mainly related to regional TB incidence, international recommendations strongly suggest careful screening for LTBI before starting biologic therapy. However, the critical point is implementing dissemination and awareness of the recommendations among rheumatologists to improve adherence in real life.

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

PubMed Central

Chegou, Novel N.; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G.; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard

2017-01-01

Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings. PMID:28415587

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB.

PubMed

Awoniyi, Dolapo O; Baumann, Ralf; Chegou, Novel N; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard

2017-06-06

Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.

Persistent Latent Tuberculosis Reactivation Risk in United States Immigrants

PubMed Central

Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Rationale: Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Objectives: Estimate reactivation and imported TB in an immigrant cohort. Methods: We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001–2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Measurements and Main Results: Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2–9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1–9. Conclusions: High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival. PMID:24308495

Poor agreement between diagnostic tests for latent tuberculosis infection among HIV-infected persons in Hong Kong.

PubMed

Leung, Chi Chiu; Chan, Kenny; Yam, Wing Cheong; Lee, Man Po; Chan, Chi Kuen; Wong, Ka Hing; Ho, Pak Leung; Mak, Ida; Tam, Cheuk Ming

2016-10-01

The tuberculin skin test (TST), T-Spot.TB (T-Spot) and QuantiFERON-TB Gold-In Tube (QFT) were compared in diagnosing latent tuberculosis infection (LTBI) among human immunodeficiency virus (HIV)-infected persons. Human immunodeficiency virus-infected persons without previous history of tuberculosis or LTBI were simultaneously tested by TST, T-Spot and QFT annually and followed up for tuberculosis. Among 110 HIV-infected subjects with 85% previous TST screening coverage, 75% on anti-retroviral therapy, well-preserved median CD4 count (414/μL) and low median viral load (<75/μL), baseline TST, T-Spot and QFT were positive in 5.5%, 5.6% and 4.9%, respectively, with almost complete discordance of positive results. Among 91 (83%), 66 (60%) and 26 (24%) subjects successfully undergoing the first, second and third annual retesting, TST, T-Spot and QFT were, respectively, positive in 11/123 (8.9%), 13/173 (7.5%) and 21/182 (11.5%) on retesting, with similar discordance of positive results. There was no significant association with the concurrent CD4 count or viral load. Conversion occurred in 11/123 (8.9%), 8/160 (5.0%) and 18/168 (10.7%) of TST, T-Spot and QFT, respectively, and none was associated with changes in CD4 count or viral load. More than half of the positive T-SPOT and QFT results reverted to negative on follow-up. None of these tests picked up the single case of culture-confirmed tuberculosis observed after 798 person-years of follow-up. Major discordance in positive results, high reversion rates and low tuberculosis incidence among test-positive subjects cast serious doubt on the utility of the currently available LTBI tests in the annual screening of HIV-infected persons in an intermediate tuberculosis burden area. © 2016 Asian Pacific Society of Respirology.

Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model.

PubMed

Moses, Mark W; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M; Banaei, Niaz; Kik, Sandra V; Metcalfe, John; Pai, Madhukar; Dowdy, David

2016-07-29

Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8-25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0-2.6%) or 4.1% (95%UR: 3.7-4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3-84.6%) to 54.8% (95%UR: 44.6-64.5%) or 61.5% (95%UR: 51.6-70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections.

Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model

PubMed Central

Moses, Mark W.; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M.; Banaei, Niaz; Kik, Sandra V.; Metcalfe, John; Pai, Madhukar; Dowdy, David

2016-01-01

Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8–25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0–2.6%) or 4.1% (95%UR: 3.7–4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3–84.6%) to 54.8% (95%UR: 44.6–64.5%) or 61.5% (95%UR: 51.6–70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections. PMID:27469388

[An analysis of latent tuberculosis infection among patients with rheumatic diseases].

PubMed

Huang, A F; Luo, Y; Zhao, Y; Liu, Y

2016-04-01

To investigate the incidence of latent tuberculosis infection (LTBI) in patients with rheumatic diseases in order to find evidence for the prevention of mycobacterium tuberculosis (MTB) in these patients. From January 2013 to July 2015, 759 patients with rheumatic diseases and 38 health controls were enrolled. All of them underwent interferon-gamma release assays(T-SPOT.TB)to screen for LTBI. Incidence of MTB infection was evaluated in different groups and test was used for statistical analysis between groups. The incidences of LTBI in patients and health controls were 27.27%(207/759) and 10.53%(4/38), respectively. In 2013, 24.66%(73/296) (standardized infection rate 23.37%) patients with rheumatic diseases were positive for LTBI screening test. In 2014 and 2015, the percentages were 32.02%(73/296) (standardized infection rate was 32.15%) and 25.96%(73/228) (standardized infection rate was 28.46%), respectively, which was statistically significant in these 3 groups (P=0.004). the infection rate in 2014 tended to be higher than that in 2013 (P=0.001). There were 30.24%(88/291) male and 25.43%(119/468)female patients who were considered as LTBI. But the difference was not significant between genders. The infection rates between patients older than 60 years old and less was significantly different, which were 45.65%(42/92) and 24.74%(165/667), respectively (P=0.000). As far as diseases were concerned including rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis and other rheumatic diseases, the incidences were 33.93%(57/168), 22.06%(45/204), 25.73%(44/171) and 28.24%(61/216) respectively, without statistical significance. The incidence of LTBI is high in patients with rheumatic diseases. Attention should be paid especially to elderly patients and rheumatoid arthritis patients who have relatively higher rates of LTBI. Careful monitoring and prevention measures are suggested to take in these patients.

Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers

PubMed Central

Esterhuyse, Maria M.; Weiner, January; Caron, Etienne; Loxton, Andre G.; Iannaccone, Marco; Wagman, Chandre; Saikali, Philippe; Stanley, Kim; Wolski, Witold E.; Mollenkopf, Hans-Joachim; Schick, Matthias; Aebersold, Ruedi; Linhart, Heinz; Walzl, Gerhard

2015-01-01

ABSTRACT An estimated one-third of the world’s population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. PMID:26374119

Latent tuberculosis infection among sailors and civilians aboard U.S.S. Ronald Reagan--United States, January-July 2006.

PubMed

2007-01-05

Crews aboard ships live and work in crowded, enclosed spaces. Historically, large tuberculosis (TB) outbreaks and extensive transmission of Mycobacterium tuberculosis have occurred on U.S. Navy ships. On July 13, 2006, smear- and culture-positive, cavitary, pulmonary TB was diagnosed in a sailor aboard the aircraft carrier U.S.S. Ronald Reagan; the patient, aged 32 years, had a negative human immunodeficiency virus test. The M. tuberculosis strain cultured was susceptible to all first-line TB medications. The sailor was born in the Philippines, had latent tuberculosis infection (LTBI) diagnosed in 1995 shortly after enlisting in the U.S. Navy, and completed the 6-month daily isoniazid course that was standard treatment at that time (current treatment standard is 9 months). This report describes the contact investigation conducted by the U.S. Navy and CDC and demonstrates the importance of timely diagnosis of TB, identification and treatment of new LTBI, and cooperation among local, state, and federal agencies during large contact investigations.

Guards in Prisons: A Risk Group for Latent Tuberculosis Infection.

PubMed

Arroyave, Luisa; Keynan, Yoav; Sanchez, Deny; López, Lucelly; Marin, Diana; Posada, Maryluz; Rueda, Zulma Vanessa

2018-05-04

To determine the prevalence and incidence of LTBI among prison guards and to the risk factors associated with infection. Two male prisons in Medellín and Itaguí, Colombia. A cohort study was conducted in adult prison guards that consented to participate. Exclusion criteria included: previous or current active TB, or conditions that preclude TST administration. We screened 194 guards and completed 155 TST administrations. The prevalence of LTBI was 55.8% in prison one, and 39.1% in prison two. The risk factors associated with LTBI diagnosis included drug use at least once in a lifetime (PR: 1.75; 95% CI 1.42-2.15) and male sex (PR: 2.16; 95% CI 1.01-4.62). The cumulative incidence of TST conversion over 6 months was 3.2%. All conversions occurred in prison 1. Our findings suggest an occupational risk for LTBI prevalence and incidence among guards (different prevalence and incidence according to the prison they work).

Combination of gene expression patterns in whole blood discriminate between tuberculosis infection states

PubMed Central

2014-01-01

Background Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB. Methods We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts. Results The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts. Conclusions Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. PMID:24885723

Evaluation of Immigrant Tuberculosis Screening in Industrialized Countries

PubMed Central

Pareek, Manish; Baussano, Iacopo; Abubakar, Ibrahim; Dye, Christopher

2012-01-01

In industrialized countries, tuberculosis (TB) cases are concentrated among immigrants and driven by reactivation of imported latent TB infection (LTBI). We examined mechanisms used to screen immigrants for TB and LTBI by sending an anonymous, 18-point questionnaire to 31 member countries of the Organisation for Economic Co-operation and Development. Twenty-nine (93.5%) of 31 responded; 25 (86.2%) screened immigrants for active TB. Fewer countries (16/29, 55.2%) screened for LTBI. Marked variations were observed in targeted populations for age (range <5 years of age to all age groups) and TB incidence in countries of origin of immigrants (>20 cases/100,000 population to >500 cases/100,000). LTBI screening was conducted in 11/16 countries by using the tuberculin skin test. Six countries used interferon-γ release assays, primarily to confirm positive tuberculin skin test results. Industrialized countries performed LTBI screening infrequently and policies varied widely. There is an urgent need to define the cost-effectiveness of LTBI screening strategies for immigrants. PMID:22931959

Investigation of Mycobacterium tuberculosis transmission aboard the U.S.S. Ronald Reagan, 2006.

PubMed

Buff, Ann M; Deshpande, Swati J; Harrington, Theresa A; Wofford, Taylor S; O'Hara, Timothy W; Carrigan, Kenichi; Martin, Nicholas J; McDowell, Jackie C; Ijaz, Kashef; Jensen, Paul A; Lambert, Lauren A; Moore, Marisa; Oeltmann, John E

2008-06-01

Pulmonary tuberculosis (TB) was diagnosed in a sailor aboard the U.S.S. Ronald Reagan; an investigation was conducted to determine a screening strategy for 1,172 civilian passengers who were aboard during a temporary guest rider program. Sailors were screened for latent TB infection (LTBI) and TB disease. A case-control study was conducted among sailors to determine factors associated with new LTBI. No secondary TB disease was identified; 13% of close contacts had new LTBI. Factors associated with new LTBI among sailors were having been born outside the United States (adjusted odds ratio = 2.80; 95% confidence interval, 1.55--5.07) and being a carrier air wing member (adjusted odds ratio = 2.89; 95% confidence interval, 1.83--4.58). Among 38 civilian passengers berthed near the patient, 1 (3%) had LTBI. The investigation results indicated that Mycobacterium tuberculosis transmission was minimal and eliminated unnecessary TB screening for 1,134 civilians which saved public health resources.

Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States

PubMed Central

Shepardson, D.; Marks, S. M.; Chesson, H.; Kerrigan, A.; Holland, D. P.; Scott, N.; Tian, X.; Borisov, A. S.; Shang, N.; Heilig, C. M.; Sterling, T. R.; Villarino, M. E.; Mac Kenzie, W. R.

2017-01-01

SUMMARY SETTING A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES To assess the cost-effectiveness of 3HP compared to 9H. DESIGN A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21 525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease. PMID:24200264

Immigrant screening for latent tuberculosis in Norway: a cost-effectiveness analysis.

PubMed

Haukaas, Fredrik Salvesen; Arnesen, Trude Margrete; Winje, Brita Askeland; Aas, Eline

2017-05-01

The incidence of tuberculosis (TB) disease has increased in Norway since the mid-1990s. Immigrants are screened, and some are treated, for latent TB infection (LTBI) to prevent TB disease (reactivation). In this study, we estimated the costs of both treating and screening for LTBI and TB disease, which has not been done previously in Norway. We developed a model to indicate the cost-effectiveness of four different screening algorithms for LTBI using avoided TB disease cases as the health outcome. Further, we calculated the expected value of perfect information (EVPI), and indicated areas of LTBI screening that could be changed to improve cost-effectiveness. The costs of treating LTBI and TB disease were estimated to be €1938 and €15,489 per case, respectively. The model evaluates four algorithms, and suggests three cost-effective algorithms depending on the cost-effectiveness threshold. Screening all immigrants with interferon-gamma release assays (IGRA) requires the highest threshold (€28,400), followed by the algorithms "IGRA on immigrants with risk factors" and "no LTBI screening." EVPI is approximately €5 per screened immigrant. The costs for a cohort of 20,000 immigrants followed through 10 years range from €12.2 million for the algorithm "screening and treatment for TB disease but no LTBI screening," to €14 million for "screening all immigrants for both TB disease and LTBI with IGRA." The results suggest that the cost of TB disease screening and treatment is the largest contributor to total costs, while LTBI screening and treatment costs are relatively small. Increasing the proportion of IGRA-positive immigrants who are treated decreases the costs per avoided case substantially.

New and Noteworthy in Tuberculosis Diagnostics and Treatment.

PubMed

Swindells, Susan

2018-06-01

People with HIV infection with latent tuberculosis (TB) infection (LTBI) are at a 10-fold greater risk of developing active disease. Interferon gamma release assays and tuberculin skin testing have approximately 65% to 70% specificity for diagnosing LTBI in HIV-infected patients. LTBI can be successfully treated with isoniazid preventive therapy and early antiretroviral therapy (ART). Rapid molecular diagnostics have approximately 88% sensitivity and 98% specificity for identifying active TB. ART should be started early in patients with TB. A number of ART regimens are recommended in co-treatment that minimize the risk of drug-drug interactions. Although progress has been made, better diagnostics and TB regimens with lower risks of drug-drug interactions and shorter treatment durations are still needed. This article summarizes a presentation by Susan Swindells, MBBS, at the Ryan White HIV/AIDS Program Clinical Care Conference held in San Antonio in August 2017.

Prevalence of latent tuberculosis infection and associated risk factors among 3,374 healthcare students in Italy.

PubMed

Lamberti, Monica; Muoio, Mariarosaria; Monaco, Maria Grazia Lourdes; Uccello, Rossella; Sannolo, Nicola; Mazzarella, Gennaro; Garzillo, Elpidio Maria; Arnese, Anonio; La Cerra, Giuseppe; Coppola, Nicola

2014-01-01

The risk of tuberculosis (TB) in healthcare personnel (HCP) is related to its incidence in the general population. Healthcare students involved in clinical training could be exposed to occupational risks similar to those that HCP face. The prevalence of latent tuberculosis infection (LTBI) among undergraduate healthcare students with different working seniority in Italy was analysed. A cross-sectional study under a screening programme for LTBI among undergraduate and postgraduate students attending Medical School at the Second University of Naples was conducted between January 2012 and December 2013 with clinical evaluations, tuberculin skin testing (TST) and, in positive TST students, Interferon-γ release assays (IGRA). Putative risk factors for LTBI were assessed by means of a standardised questionnaire. 3,374 students attending the Medical School of the Second University of Naples were submitted to a screening programme for TBC. 3,331 performed TST as a first-level test and 43 performed a Quantiferon test (QFT). 128 students were TST-positive and continued the diagnostic work with QFT, which was positive in 34 students. Of the 43 subjects who took the QFT as a first-level test only 1 was positive. In 35 students positive to the QFT test we formulated the diagnosis of LTBI by clinical and radiographic results. A correlation was found between age, non-Italian born persons, studying age, post-medical school status and LTBI. The prevalence of LTBI among healthcare students in our study was very low. In countries with a low incidence of TB, the screening programmes of healthcare students can be useful for early identification and treatment of sporadic cases of LTBI.

Predictors of latent tuberculosis infection treatment completion in the US private sector: an analysis of administrative claims data.

PubMed

Stockbridge, Erica L; Miller, Thaddeus L; Carlson, Erin K; Ho, Christine

2018-05-29

Factors that affect latent tuberculosis infection (LTBI) treatment completion in the US have not been well studied beyond public health settings. This gap was highlighted by recent health insurance-related regulatory changes that are likely to increase LTBI treatment by private sector healthcare providers. We analyzed LTBI treatment completion in the private healthcare setting to facilitate planning around this important opportunity for tuberculosis (TB) control in the US. We analyzed a national sample of commercial insurance medical and pharmacy claims data for people ages 0 to 64 years who initiated daily dose isoniazid treatment between July 2011 and March 2014 and who had complete data. All individuals resided in the US. Factors associated with treatment completion were examined using multivariable generalized ordered logit models and bivariate Kruskal-Wallis tests or Spearman correlations. We identified 1072 individuals with complete data who initiated isoniazid LTBI treatment. Treatment completion was significantly associated with less restrictive health insurance, age < 15 years, patient location, use of interferon-gamma release assays, non-poverty, HIV diagnosis, immunosuppressive drug therapy, and higher cumulative counts of clinical risk factors. Private sector healthcare claims data provide insights into LTBI treatment completion patterns and patient/provider behaviors. Such information is critical to understanding the opportunities and limitations of private healthcare in the US to support treatment completion as this sector's role in protecting against and eliminating TB grows.

Prevalence of latent tuberculous infection among adults in the general population of Ca Mau, Viet Nam.

PubMed

Marks, G B; Nhung, N V; Nguyen, T A; Hoa, N B; Khoa, T H; Son, N V; Phuong, N T B; Tin, D M; Ho, J; Fox, G J

2018-03-01

The study was conducted in a randomly selected sample of persons aged 15 years living in Ca Mau Province, southern Viet Nam. To estimate the prevalence of latent tuberculous infection (LTBI) in the general adult population of this province of Viet Nam. The secondary objective was to examine age and sex differences in prevalence. A cross-sectional survey was conducted in a cluster-random sample of the population. Clusters were subcommunes. The presence of LTBI was assessed using the QuantiFERON®-TB Gold In-Tube test system. QuantiFERON tests were performed among 1319 persons aged 15 years (77.7% of those selected). The overall prevalence of positive tests was 36.8% (95%CI 33.4-40.3). The prevalence of a positive test was lower in females than in males (31.0% vs. 44.7%, OR 0.57, 95%CI 0.45-0.72, P < 0.0001). The prevalence of positive tests increased with increasing age quintile (P < 0.0001). More than one third of the general adult population in a province in southern Viet Nam have evidence of LTBI. Although LTBI prevalence is higher in males, the sex difference is not as great as that for TB notification rates.

Tuberculosis after liver transplantation in a large center in New York City: QuantiFERON® -TB Gold-based pre-transplant screening performance and active tuberculosis post-transplant.

PubMed

Hand, Jonathan; Sigel, Keith; Huprikar, Shirish; Hamula, Camille; Rana, Meena

2018-04-01

Pre-transplant screening for latent tuberculosis infection (LTBI) is a complex consideration that varies by institution. Inconsistent performance of interferon-gamma release assay (IGRA) further complicates screening. Data regarding LTBI screening outcomes and test characteristics in a large, foreign-born pre-transplant population within the United States are limited. In this retrospective study, patients who received QuantiFERON ® -TB Gold (QFT) prior to liver transplantation (LT) were included. Characteristics of patients were compared by QFT result, and predictors of indeterminate results were evaluated. Similar comparisons were performed between patients who developed active TB and those who did not. Of 148 patients screened, the rate of positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148), and 59% (88/148), respectively. An indeterminate QFT result was more than 16 times more likely in patients with a Model for End-stage Liver Disease score >25 (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and more than 4 times when performed in our institution's lab compared with commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence was 1102/100 000 transplant cases. No patient who developed active TB had a positive QFT. All were born outside of the United States (P = .06) and had pre-transplantation chest imaging demonstrating granulomatous disease (P = .006). Our experience further highlights the challenges of LTBI screening prior to LT and suggests that QFT may be a poor predictor of active TB in higher risk pre-transplant populations. Candidates should be screened as early as possible to optimize QFT performance, and local epidemiological data should be used to create institution-specific screening protocols in areas with large populations from TB-endemic regions. Management should consider TB risk factors, QFT, and imaging instead of reliance on QFT testing alone. © 2018 John Wiley

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

PubMed

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

PubMed Central

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. PMID:29320502

Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States.

PubMed

Miller, Thaddeus L; Hilsenrath, Peter; Lykens, Kristine; McNabb, Scott J N; Moonan, Patrick K; Weis, Stephen E

2006-04-01

Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non state-law mandated one in terms of cost, morbidity, treatment, and disease averted. We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of 14,350 US dollars and 34,761 US dollars per TB case, respectively. Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than state-law mandated targeted testing for TB among jailed inmates.

Tuberculosis as a force health protection threat to the United States military.

PubMed

Sanchez, Jose L; Sanchez, Joyce L; Cooper, Michael J; Hiser, Michelle J; Mancuso, James D

2015-03-01

Tuberculosis (TB) is a communicable disease that poses a threat to force health protection to the U.S. military. The rate of TB disease in the military is low; however, there are unique challenges for its control in this setting. As a low-risk population, TB testing in the U.S. military can be scaled back from the universal testing approach used previously. Reactivation of latent TB infection (LTBI) present at accession into service is the most important factor leading to TB disease; therefore, its diagnosis and treatment among recruits should be given a high priority. Deployment and overseas military service is an uncommon but important source of TB infection, and rigorous surveillance should be ensured. Case management of TB disease and LTBI can be improved by the use of cohort reviews at the service and installation levels and case finding and delays in the diagnosis of TB disease can be improved by education of providers, as well as increased use of molecular diagnostic tests. Program outcomes can be improved by making LTBI treatment compulsory, offering shorter treatment regimens, and increasing accountability through oversight and evaluation. The diagnosis of LTBI can be improved by implementing targeted testing in all settings and reducing confirmatory interferon-gamma release assay testing. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients.

PubMed

Nouhin, Janin; Pean, Polidy; Madec, Yoann; Chevalier, Mathieu F; Didier, Celine; Borand, Laurence; Blanc, François-Xavier; Scott-Algara, Daniel; Laureillard, Didier; Weiss, Laurence

2017-05-01

Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment. Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time. At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)). None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Potential of DosR and Rpf antigens from Mycobacterium tuberculosis to discriminate between latent and active tuberculosis in a tuberculosis endemic population of Medellin Colombia.

PubMed

Arroyo, Leonar; Marín, Diana; Franken, Kees L M C; Ottenhoff, Tom H M; Barrera, Luis F

2018-01-08

Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB. PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches. IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally

Prognostic score to predict mortality during TB treatment in TB/HIV co-infected patients.

PubMed

Nguyen, Duc T; Jenkins, Helen E; Graviss, Edward A

2018-01-01

Estimating mortality risk during TB treatment in HIV co-infected patients is challenging for health professionals, especially in a low TB prevalence population, due to the lack of a standardized prognostic system. The current study aimed to develop and validate a simple mortality prognostic scoring system for TB/HIV co-infected patients. Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 through 12/2016, age ≥15 years, HIV(+), and outcome being "completed" or "died", we developed and internally validated a mortality prognostic score using multiple logistic regression. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve (AUC). The model's good calibration was determined by a non-significant Hosmer-Lemeshow's goodness of fit test. Among the 450 patients included in the analysis, 57 (12.7%) died during TB treatment. The final prognostic score used six characteristics (age, residence in long-term care facility, meningeal TB, chest x-ray, culture positive, and culture not converted/unknown), which are routinely collected by TB programs. Prognostic scores were categorized into three groups that predicted mortality: low-risk (<20 points), medium-risk (20-25 points) and high-risk (>25 points). The model had good discrimination and calibration (AUC = 0.82; 0.80 in bootstrap validation), and a non-significant Hosmer-Lemeshow test p = 0.71. Our simple validated mortality prognostic scoring system can be a practical tool for health professionals in identifying TB/HIV co-infected patients with high mortality risk.

Rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?

PubMed

Alfarisi, Omamah; Alghamdi, Wael A; Al-Shaer, Mohammad H; Dooley, Kelly E; Peloquin, Charles A

2017-10-01

One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them. Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.

Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

PubMed

Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

2018-03-01

B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.

PubMed

Agaya, Janet; Nnadi, Chimeremma D; Odhiambo, Joseph; Obonyo, Charles; Obiero, Vincent; Lipke, Virginia; Okeyo, Elisha; Cain, Kevin; Oeltmann, John E

2015-12-01

To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01). Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers. © 2015 John Wiley & Sons Ltd.

Profiling the human immune response to Mycobacterium tuberculosis by human cytokine array.

PubMed

Chen, Tao; Li, Zhenyan; Yu, Li; Li, Haicheng; Lin, Jinfei; Guo, Huixin; Wang, Wei; Chen, Liang; Zhang, Xianen; Wang, Yunxia; Chen, Yuhui; Liao, Qinghua; Tan, Yaoju; Shu, Yang; Huang, Wenyan; Cai, Changhui; Zhou, Zhongjing; Yu, Meiling; Li, Guozhou; Zhou, Lin; Zhong, Qiu; Bi, Lijun; Zhao, Meigui; Guo, Lina; Zhou, Jie

2016-03-01

Tuberculosis (TB) continues to be one of the most serious infectious diseases in the world, however, no effective biomarkers can be used for rapid screening of latent tuberculosis infection (LTBI) and active TB. In this study, serum cytokines were screened and tested as potential biomarker for TB diagnosis. Cytokine array was used to track the cytokine profile and its dynamic change after TB infection. The different expressions of cytokines were confirmed by ELISA assay. ROC curve analyses were used to evaluate the efficacy of a cytokine or cytokine combination for diagnosis. Eotaxin-2, ICAM-1, MCSF, IL-12p70, and IL-11 were significantly higher in the LTBI individuals. I-309, MIG, Eotaxin-2, IL-8, ICAM-1, IL-6sR, and Eotaxin were significantly higher in active TB patients. ROC curve analyses gave AUCs of 0.843, 0.898, and 0.888 for I-309, MIG, and IL-8, respectively, and 0.894 for the combination panel in active TB diagnosis. IFN-γ/IL-4 and IL-2/TNF-α ratios exhibit dynamic changes in the healthy control and LTBI to different stages of active TB. Serum cytokines, including I-309 and MIG, IL-8, Extoxin-2, ICAM-1 and combinations of cytokines, including IFN-γ/IL-4 and IL-2/TNF-α, can be used as serum biomarkers for LTBI and active TB screening, thus indicating prospective clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

PubMed

Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

PubMed Central

Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review

PubMed Central

Greenaway, Christina; Pareek, Manish; Abou Chakra, Claire-Nour; Walji, Moneeza; Makarenko, Iuliia; Alabdulkarim, Balqis; Hogan, Catherine; McConnell, Ted; Scarfo, Brittany; Christensen, Robin; Tran, Anh; Rowbotham, Nick; van der Werf, Marieke J; Noori, Teymur; Pottie, Kevin; Matteelli, Alberto; Zenner, Dominik; Morton, Rachael L.

2018-01-01

Background Migrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit. PMID:29637889

Tuberculosis prevalence in an urban jail: 1994 and 1998.

PubMed

White, M C; Tulsky, J P; Portillo, C J; Menendez, E; Cruz, E; Goldenson, J

2001-05-01

Despite a continuing decline in tuberculosis (TB) in the US, jails remain a high-risk setting for the identification of active and latent TB infection (LTBI). The purpose of this study was to document the change in TB prevalence in the San Francisco City and County Jail. Two period prevalence analyses were done, for 1994 and 1998. The sample included all persons booked into jail during the two years. The rates of inmates screened and the prevalence of active TB and LTBI by sex and ethnicity were compared using computerized records. Prevalence of active TB was 72.1 per 100000 jail population for 1998, and did not change significantly from 1994. In 1998 one third of active TB cases were found through jail screening. Latinos represented respectively 20.1% and 17.7% of those booked in 1994 and 1998, but 43.0% and 41.7% of inmates with LTBI. In 1998, being Latino (odds ratio 2.9) and male (odds ratio 1.6) were most strongly associated with LTBI. Screening for TB among jail inmates is an increasingly valuable clinical and epidemiological tool for case-finding and for identifying persons who would benefit from preventive therapy.

Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons

PubMed Central

2014-01-01

Background Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia’s largest prison. Methods From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Results Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other

Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons.

PubMed

Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Altice, Frederick L

2014-01-10

Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia's largest prison. From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other potential confounding factors

Is Universal Screening Necessary? Incidence of Tuberculosis among Tibetan Refugees Arriving in Calgary, Alberta.

PubMed

Lim, Rachel; Jarand, Julie; Field, Stephen K; Fisher, Dina

2016-01-01

Background . Canadian policy requires refugees with a history of tuberculosis (TB) or abnormal chest radiograph to be screened after arrival for TB. However, Tibetan refugees are indiscriminately screened, regardless of preimmigration assessment. We sought to determine the incidence of latent (LTBI) and active TB, as well as treatment-related outcomes and associations between preimmigration factors and TB infection among Tibetan refugees arriving in Calgary, Alberta. Design . Retrospective cohort study including Tibetan refugees arriving between 2014 and 2016. Associations between preimmigration factors and incidence of latent and active TB were determined using Chi-square tests. Results . Out of 180 subjects, 49 percent had LTBI. LTBI was more common in migrants 30 years of age or older ( P = 0.009). Treatment initiation and completion rates were high at 90 percent and 76 percent, respectively. No associations between preimmigration factors and treatment completion were found. A case of active TB was detected and treated. Conclusion . Within this cohort, the case of active TB would have been detected through the usual postsurveillance process due to a history of TB and abnormal chest radiograph. Forty-nine percent had LTBI, compared to previously quoted rates of 97 percent. Tibetan refugees should be screened for TB in a similar manner to other refugees resettling in Canada.

A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children.

PubMed

Verhagen, Lilly M; Zomer, Aldert; Maes, Mailis; Villalba, Julian A; Del Nogal, Berenice; Eleveld, Marc; van Hijum, Sacha Aft; de Waard, Jacobus H; Hermans, Peter Wm

2013-02-01

Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). Our data justify the further exploration of our signature set as biomarkers

A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children

PubMed Central

2013-01-01

Background Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. Results We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). Conclusions Our data justify the further exploration of our

Detection of interleukin-2 is not useful for distinguishing between latent and active tuberculosis in clinical practice: a prospective cohort study.

PubMed

Santin, M; Morandeira-Rego, F; Alcaide, F; Rabuñal, R; Anibarro, L; Agüero-Balbín, R; Casas-Garcia, X; Pérez-Escolano, E; Navarro, M D; Sánchez, F; Coira-Nieto, A; Trigo-Daporta, M; Martinez-Meñaca, A; Gonzalez-Cuevas, A; López-Prieto, M D; Domínguez-Castellano, A; Jové, N

2016-12-01

Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON ® -TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort. A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. . Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p <0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered. Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Preventing Infectious Pulmonary Tuberculosis Among Foreign-Born Residents of the United States

PubMed Central

Katz, Dolly; Ghosh, Smita; Blumberg, Henry; Tamhane, Ashutosh; Sevilla, Anna; Reves, Randall

2015-01-01

Objectives. We described risk factors associated with infectious tuberculosis (TB) and missed TB-prevention opportunities in foreign-born US residents, who account for almost two thirds of the nation’s TB patients. Methods. In a cross-sectional study at 20 US sites of foreign-born persons diagnosed with TB in 2005 through 2006, we collected results of sputum smear microscopy for acid-fast bacilli (a marker for infectiousness) and data on visa status, sociodemographics, TB-related care seeking, and latent TB infection (LTBI) diagnosis opportunities. Results. Among 980 persons with pulmonary TB who reported their visa status, 601 (61%) were legal permanent residents, 131 (13.4%) had temporary visas, and 248 (25.3%) were undocumented. Undocumented persons were more likely than permanent residents to have acid-fast bacilli–positive smears at diagnosis (risk ratio = 1.3; 95% confidence interval = 1.2, 1.4). Of those diagnosed 1 year or more after arrival, 57.3% reported LTBI screening opportunities; fewer than 25% actually were. Undocumented persons reported fewer LTBI screening opportunities and were less likely to be tested. Conclusions. Progress toward TB elimination in the United States depends upon expanding opportunities for regular medical care and promotion of LTBI screening and treatment among foreign-born persons. PMID:26180947

Occupational Screening for Tuberculosis and the Use of a Borderline Zone for Interpretation of the IGRA in German Healthcare Workers

PubMed Central

Schablon, Anja; Nienhaus, Albert; Ringshausen, Felix C.; Preisser, Alexandra M.; Peters, Claudia

2014-01-01

Introduction Healthcare workers (HCWs) in low incidence countries with contact to patients with tuberculosis (TB) are considered a high-risk group for latent TB infection (LTBI) and therefore are routinely screened for LTBI. The German Occupational TB Network data is analyzed in order to estimate the prevalence and incidence of LTBI and to evaluate putative risk factors for a positive IGRA and the performance of IGRA in serial testing. Methods 3,823 HCWs were screened with the Quantiferon Gold in Tube (QFT) at least once; a second QFT was performed on 817 HCWs either in the course of contact tracing or serial examination. Risk factors for a positive QFT were assessed by a questionnaire. Results We observed a prevalence of LTBI of 8.3%. Putative risk factors for a positive QFT result were age >55 years (OR 6.89), foreign country of birth (OR 2.39), personal history of TB (OR 6.23) and workplace, e.g. internal medicine (OR 1.40), infection ward (OR 1.8) or geriatric care (OR 1.8). Of those repeatedly tested, 88.2% (721/817) tested consistently QFT-negative and 47 were consistently QFT-positive (5.8%). A conversion was observed in 2.8% (n = 21 of 742 with a negative first QFT) and a reversion occurred in 37.3% (n = 28 of 75 with a positive first QFT). Defining a conversion as an increase of the specific interferon concentration from <0.2 to >0.7 IU/ml, the conversion rate decreased to 1.2% (n = 8). Analogous to this, the reversion rate decreased to 18.8% (n = 9). Discussion In countries with a low incidence of TB and high hygiene standards, the LTBI infection risk for HCWs seems low. Introducing a borderline zone from 0.2 to ≤0.7 IU/ml may help to avoid unnecessary X-rays and preventive chemotherapy. No case of active TB was detected. Therefore, it might be reasonable to further restrict TB screening to HCWs who had unprotected contact with infectious patients or materials. PMID:25541947

Usefulness of QuantiFERON®-TB Gold test in psoriatic patients under treatment with tumour necrosis factor blockers.

PubMed

Saraceno, Rosita; Specchio, Francesca; Chiricozzi, Andrea; Sarmati, Loredana; Amicosante, Massimo; Chimenti, Maria Sole; Chimenti, Sergio

2014-02-01

Infliximab is a human/mouse chimeric anti-tumour necrosis factor (TNF)-α antibody that is effective in the management of psoriasis. Anti-TNF treatments may reactivate latent tuberculosis infection (LTBI); therefore, screening for LTBI is mandatory before starting any anti-TNF-α therapy. The aim of this study is to evaluate the usefulness of the QuantiFERON®-TB Gold (QFT-G) test in psoriatic patients under treatment with infliximab. A retrospective study had been performed on patients affected by psoriasis who had been treated with infliximab from 2003 to 2012 at a single centre. QFT-G was tested by a standard TB enzyme-linked immunosorbent assay, based on detection of interferon-γ release from sensitized leucocytes exposed to the synthetic Mycobacterium tuberculosis antigens at baseline and every 6 months until the end of treatment. A total of 140 patients were included. At baseline, 7 QFT-G tests were positive and 133 tests were negative. Of the 133 patients, 11 (8%) who were negative at baseline became QFT-G test positive during treatment. Of those 11 patients, 5 had a reversion during treatment. Of the 133 patients, 122 (92%) who were negative at baseline remained negative. It was found that the development of positive QFT-G tests, observed in 8% treated with infliximab, was not associated with pulmonary or extra-pulmonary tuberculosis.

Performance of QuantiFERON®-TB Gold In-Tube assay in children receiving disease modifying anti-rheumatic drugs.

PubMed

Gabriele, Francesca; Trachana, Maria; Simitsopoulou, Maria; Pratsidou-Gertsi, Polixeni; Iosifidis, Elias; Pana, Zoi Dorothea; Roilides, Emmanuel

2017-10-01

To evaluate the performance of the Quantiferon ® -TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Agreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay was increased by a factor of 27.6 (P=0.002), whereas there was no positive TST. There was a significant difference in the mitogen-induced IFN-γ secretion among various treatments (P=0.038). TNF-α inhibitors were associated with increased mitogen-induced IFN-γ secretion compared to monotherapy with conventional DMARDs (P=0.008). All children screened prior to anti-TNF-α treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up. QFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment. Drug regimen might influence the mitogen-induced IFN-γ secretion and the effect of TNF-α inhibitors might vary according to the specific agent administered.

Use of IFN-γ and IP-10 detection in the diagnosis of latent tuberculosis infection in patients with inflammatory rheumatic diseases.

PubMed

Villar-Hernández, Raquel; Latorre, Irene; Mínguez, Sonia; Díaz, Jéssica; García-García, Esther; Muriel-Moreno, Beatriz; Lacoma, Alicia; Prat, Cristina; Olivé, Alex; Ruhwald, Morten; Mateo, Lourdes; Domínguez, José

2017-10-01

Biologic agents are used against rheumatic diseases, however, they increase the risk of developing severe infections and diseases such as tuberculosis. We aimed to determine the benefits of IP-10 detection to diagnose latent tuberculosis infection (LTBI) in patients with inflammatory rheumatic diseases on different immunosuppressive drug regimens, and compare these results with IFN-γ detection. We included 64 patients with inflammatory rheumatic diseases. We used QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB to detect IFN-γ production, and an in-house ELISA for IP-10 detection from the previous QFN-G-IT stimulated samples. We assessed the combined use of IFN-γ release assays (IGRAs) and IP-10 test, and analyzed the influence of immunotherapy on the tests performance. We obtained 34.9% positive results by T-SPOT.TB, 25.0% by QFN-G-IT and 31.3% by IP-10 test. The combined use of IGRAs and IP-10 detection increased significantly the amount of positive results (p < 0.0001). Treatment intake had no significant effect on in vitro tests (p > 0.05). IP-10 and IFN-γ detection is comparable and their combined use could increase the number of positive results in the diagnosis of LTBI in rheumatic patients. The tested assays were not influenced by rheumatoid immunosuppressive therapy. Thus, IP-10 could be of use in the development of new and improved LTBI diagnostic tools. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Frequent Detection of Latent Tuberculosis Infection among Aged Underground Hard Coal Miners in the Absence of Recent Tuberculosis Exposure

PubMed Central

Ringshausen, Felix C.; Nienhaus, Albert; Schablon, Anja; Torres Costa, José; Knoop, Heiko; Hoffmeyer, Frank; Bünger, Jürgen; Merget, Rolf; Harth, Volker; Schultze-Werninghaus, Gerhard; Rohde, Gernot

2013-01-01

Background Miners are at particular risk for tuberculosis (TB) infection due to exposure to silica dust and silicosis. The objectives of the present observational cohort study were to determine the prevalence of latent TB infection (LTBI) among aged German underground hard coal miners with silicosis or chronic obstructive pulmonary disease (COPD) using two commercial interferon-gamma release assays (IGRAs) and to compare their performance with respect to predictors of test positivity. Methods Between October 2008 and June 2010, miners were consecutively recruited when routinely attending pneumoconiosis clinics for an expert opinion. Both IGRAs, the QuantiFERON®-TB Gold In-Tube (QFT) and the T-SPOT®.TB (T-SPOT), were performed at baseline. A standardized clinical interview was conducted at baseline and at follow-up. The cohort was prospectively followed regarding the development of active TB for at least two years after inclusion of the last study subject. Independent predictors of IGRA positivity were calculated using logistic regression. Results Among 118 subjects (mean age 75 years), none reported recent exposure to TB. Overall, the QFT and the T-SPOT yielded similarly high rates of positive results (QFT: 46.6%; 95% confidence interval 37.6–55.6%; T-SPOT: 61.0%; 95% confidence interval 52.2–69.8%). Positive results were independently predicted by age ≥80 years and foreign country of birth for both IGRAs. In addition, radiological evidence of prior healed TB increased the chance of a positive QFT result fivefold. While 28 subjects were lost to follow-up, no cases of active TB occurred among 90 subjects during an average follow-up of >2 years. Conclusions Considering the high prevalence of LTBI, the absence of recent TB exposure, and the currently low TB incidence in Germany, our study provides evidence for the persistence of specific interferon-gamma responses even decades after putative exposure. However, the clinical value of current IGRAs among our

Challenges in Obtaining Estimates of the Risk of Tuberculosis Infection During Overseas Deployment.

PubMed

Mancuso, James D; Geurts, Mia

2015-12-01

Estimates of the risk of tuberculosis (TB) infection resulting from overseas deployment among U.S. military service members have varied widely, and have been plagued by methodological problems. The purpose of this study was to estimate the incidence of TB infection in the U.S. military resulting from deployment. Three populations were examined: 1) a unit of 2,228 soldiers redeploying from Iraq in 2008, 2) a cohort of 1,978 soldiers followed up over 5 years after basic training at Fort Jackson in 2009, and 3) 6,062 participants in the 2011-2012 National Health and Nutrition Examination Survey (NHANES). The risk of TB infection in the deployed population was low-0.6% (95% confidence interval [CI]: 0.1-2.3%)-and was similar to the non-deployed population. The prevalence of latent TB infection (LTBI) in the U.S. population was not significantly different among deployed and non-deployed veterans and those with no military service. The limitations of these retrospective studies highlight the challenge in obtaining valid estimates of risk using retrospective data and the need for a more definitive study. Similar to civilian long-term travelers, risks for TB infection during deployment are focal in nature, and testing should be targeted to only those at increased risk. © The American Society of Tropical Medicine and Hygiene.

Strengthening TB infection control in specialized health facilities in Romania--using a participatory approach.

PubMed

Turusbekova, N; Popa, C; Dragos, M; van der Werf, M J; Dinca, I

2016-02-01

In 2012, the tuberculosis (TB) notification rate among Romanian TB facility doctors and nurses was 7.2 times higher than in the general population. This indicates that transmission is ongoing inside TB facilities and that TB infection control measures are insufficient. To help prevent nosocomial TB transmission a project was implemented that aimed at providing nationwide tailor-made technical assistance in TB infection control (TB-IC) in TB treatment facilities, including the development of TB infection control plans. The objective of the present article is to describe the implementation of the project and to discuss successes and challenges. The project was an implementation study using two methods of evaluation: (1) a cross sectional questionnaire study; and (2) collection of information, during the training, on challenges related to infection control and to the project implementation. The project team developed a TB facility infection control (TB-IC) plan template, together with the Romanian experts. The template was discussed and agreed upon with the experts at a meeting and thereafter distributed by email to all TB facilities. Afterwards, a training of trainers (TOT) seminar was organized which included the provision of information about different training methods, as well as information about TB-IC. The TOT was followed by training for key TB-IC providers. Information about use of the TB-IC template was gathered through a self-administered questionnaire sent to all participants of the expert meeting and the training (42 people). Additionally, non-systematized discussions were held on broader challenges in TB-IC implementation during the training. Within the project 42 key TB-IC service providers were trained in TB-IC, including 9 who were trained at a TOT seminar. The trainees were specialists working at the national level, such as country TB coordinators, or at the TB facility level: TB doctors, epidemiologists, laboratory specialists and maintenance

Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California.

PubMed

Armenta, R F; Collins, K M; Strathdee, S A; Bulterys, M A; Munoz, F; Cuevas-Mota, J; Chiles, P; Garfein, R S

2017-04-01

Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

PubMed Central

Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

2012-01-01

Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

TB-HIV co-infection among pregnant women in Karnataka, South India: A case series.

PubMed

Suresh, Shastri; Sharath, Burugina N; Anita, Shet; Lalitha, Ravindra; Prasad, Tripathy J; Rewari, Bharat B

2016-01-01

Tuberculosis (TB) is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus (HIV)-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme (RNTCP) and the National AIDS Control Programme (NACP) in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women (for an incidence of 5.4 per million pregnancies). The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI.

PubMed

Bliven-Sizemore, E E; Sterling, T R; Shang, N; Benator, D; Schwartzman, K; Reves, R; Drobeniuc, J; Bock, N; Villarino, M E

2015-09-01

Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

Tuberculosis incidence in prisons: a systematic review.

PubMed

Baussano, Iacopo; Williams, Brian G; Nunn, Paul; Beggiato, Marta; Fedeli, Ugo; Scano, Fabio

2010-12-21

Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population. A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0-61.8) and 23.0 (IQR: 11.7-36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%-17.9%) and 6.3% (IQR: 2.7%-17.2%) in high- and middle/low-income countries, respectively. The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors' Summary.

Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

PubMed

Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

2016-01-01

Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (<200/μL, 200-500/μL, >500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P<0.001). Immunologically, HIV-1+ATB group showed significantly lower numbers of ESAT-6-/CFP-10-specific IFN-γ+ T cells than HIV-1+LTB group. Consistently, PPD-specific IFN-γ+CD4+/CD8+ T effector cells in HIV-1+ATB group were significantly lower than those in HIV-1+LTB group (P<0.001). Hierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

Performance of the QuantiFERON-TB Gold Assay Among HIV-infected Children With Active Tuberculosis in France.

PubMed

Hormi, Myriam; Guérin-El Khourouj, Valérie; Pommelet, Virginie; Jeljeli, Mohamed; Pédron, Béatrice; Diana, Jean-Sébastien; Faye, Albert; Sterkers, Ghislaine

2018-04-01

Data regarding the use of QuantiFERON to assist the diagnosis of active tuberculosis (TB) in HIV-infected children are limited, especially in countries with low incidence of TB/HIV coinfection. QuantiFERON results were analyzed in 63 HIV-infected children who presented to our hospital in Paris, France. Seventeen HIV-uninfected children with active TB (4 culture-confirmed) were included for comparison. The 63 HIV-infected children (median age: 11 yr) had 113 QuantiFERON tests. Thirty-four (54%) were born in sub-Saharan Africa. Vertical HIV transmission was documented for 50 of 52 (96%) and stage III HIV-infection for 30 of 50 children (60%). Over the study period, active TB was diagnosed in 7 of 63 HIV-infected children (3 culture-confirmed). Additional ongoing or previous opportunistic infections were present in 4 of 7. QuantiFERON results were positive in 2 of 7 HIV-infected children with active TB (sensitivity: 29%) and 16 of 17 HIV-uninfected children with active TB (sensitivity: 94%). At initial QuantiFERON testing of the 63 HIV-infected children, 8 (13%) had positive results (1, active TB; 5, latent TB; 2, previous TB) and 51 (81%) had negative results. Of 33 children with repeat testing after an initially positive or negative result, the only change was one conversion from a negative to a positive result at the onset of active TB. The 4 children (6%) with indeterminate quantiFERON results had a concomitant opportunistic infection. Results of repeat testing after clinical stabilization were negative in all 4. QuantiFERON testing performed poorly for active TB diagnosis in this series of children with advanced HIV infection.

IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment.

PubMed

Yang, Qianting; Cai, Yi; Zhao, Wei; Wu, Fan; Zhang, Mingxia; Luo, Kai; Zhang, Yan; Liu, Haiying; Zhou, Boping; Kornfeld, Hardy; Chen, Xinchun

2014-12-01

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study.

PubMed

Efsen, A M W; Schultze, A; Miller, R F; Panteleev, A; Skrahin, A; Podlekareva, D N; Miro, J M; Girardi, E; Furrer, H; Losso, M H; Toibaro, J; Caylà, J A; Mocroft, A; Lundgren, J D; Post, F A; Kirk, O

2018-01-01

Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5-74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Testing for TB Infection

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

The impact of a public health department's expansion from a one-step to a two-step refugee screening process on the detection and initiation of treatment of latent tuberculosis.

PubMed

Einterz, E M; Younge, O; Hadi, C

2018-06-01

To determine, subsequent to the expansion of a county health department's refugee screening process from a one-step to a two-step process, the change in early loss to follow-up and time to initiation of treatment of new refugees with latent tuberculosis infection (LTBI). Quasi-experimental, quantitative. Review of patient medical records. Among 384 refugees who met the case definition of LTBI without prior tuberculosis (TB) classification, the number of cases lost to early follow-up fell from 12.5% to 0% after expansion to a two-step screening process. The average interval between in-country arrival and initiation of LTBI treatment was shortened by 41.4%. The addition of a second step to the refugee screening process was correlated with significant improvements in the county's success in tracking and treating cases of LTBI in refugees. Given the disproportionate importance of foreign-born cases of LTBI to the incidence of TB disease in low-incidence countries, these improvements could have a substantial impact on overall TB control, and the process described could serve as a model for other local health department refugee screening programs. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

PubMed

Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming

2016-08-01

Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment.

Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model

PubMed Central

Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie

2018-01-01

Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800

Tuberculosis screening of migrants to low-burden nations: insights from evaluation of UK practice.

PubMed

Pareek, M; Abubakar, I; White, P J; Garnett, G P; Lalvani, A

2011-05-01

Tuberculosis (TB) primarily occurs in the foreign-born in European countries, such as the UK, where increasing notifications and the high proportion of foreign-born cases has refocused attention on immigrant (new entrant) screening. We investigated how UK primary care organisations (PCOs) screen new entrants and whether this differs according to TB burden in the PCOs (incidence < 20 or ≥ 20 cases per 100,000 per annum). An anonymous, 20-point questionnaire was sent to all 192 UK PCOs asking which new entrants are screened, who is screened for active TB/latent TB infection (LTBI) and the methods used. Descriptive analyses were undertaken. Categorical responses were compared using the Chi-squared test. 177 (92.2%) out of 192 PCOs responded; all undertook screening action in response to abnormal chest radiographs, but only 107 (60.4%) screened new entrants for LTBI. Few new entrants had active TB diagnosed (median 0.0%, interquartile range (IQR) 0.0-0.5%) but more were identified with LTBI (median 7.85%, IQR 4.30-13.50%). High-burden PCOs were significantly less likely to screen new entrants for LTBI (OR 0.26, 95% CI 0.12-0.54; p<0.0001). Among PCOs screening for LTBI, there was substantial deviation from national guidance in selection of new entrant subgroups and screening method. Considerable heterogeneity and deviation from national guidance exist throughout the UK new entrant screening process, with high-burden regions undertaking the least screening. Forming an accurate picture of current front-line practice will help to inform future development of European new entrant screening policy.

A Systematic Review of the Epidemiology, Immunopathogenesis, Diagnosis, and Treatment of Pleural TB in HIV- Infected Patients

PubMed Central

Aljohaney, A.; Amjadi, K.; Alvarez, G. G.

2012-01-01

Background. High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients. Objective. To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients. Methods. A literature search from 1950 to June 2011 in MEDLINE was conducted. Results. Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients. Conclusions. Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB. PMID:22474483

Appetite and tuberculosis: is the lack of appetite an unidentified risk factor for tuberculosis?

PubMed

Hernández-Garduño, Eduardo; Pérez-Guzmán, Carlos

2007-01-01

Different risk factors have been identified as associated with tuberculosis (TB), an important and common one is malnutrition, however, the causes of malnutrition have not been studied in detail, the lack of food and poverty are among the most frequent in developing countries but others are yet to be identified. We hypothesized that chronic lack of appetite can be one of the causes of malnutrition associated to TB and therefore be a potential independent risk factor for latent tuberculosis infection (LTBI) or TB disease. If this is true, contact subjects with LTBI who have poor appetite will be at higher risk for getting the disease and people with the disease will be at risk for poor treatment outcomes.

The prevalence of human immunodeficiency virus infection among TB patients in Port Harcourt Nigeria

PubMed Central

Erhabor, O; Jeremiah, Z A; Adias, T C; Okere, CE

2010-01-01

The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with tuberculosis (TB) undergo testing for human immunodeficiency virus (HIV) infection after counseling. In this study, we investigated the prevalence of HIV infection among 120 patients diagnosed with microbiologically proven TB aged 18 to 54 years with a mean age of 39.5 years (standard deviation 6.75). The subjects studied were 36 male (30%) and 84 females (70%). Enzyme-linked immunosorbent assay methods were used to screen for HIV infection among the subjects. Of the 120 TB patients tested 30 (25%) were positive for HIV infection. The prevalence of HIV was higher in females 24 (80%) compared to males 6 (20%) and among singles (66.7%) compared to married subjects (33.3%) (χ2 = 83.5 and χ2 = 126.2, respectively P = 0.001). HIV-1 was the predominant viral subtype. HIV prevalence was significantly higher in subjects in the 38–47 year and 28–37 year age groups (both 40%) followed by the 18–28 year age group (20%) (χ2 = 42.6, P = 0.05). The mean CD4 lymphocyte count of the HIV-infected TB subjects was significantly lower (195 ± 40.5 cells/μL) compared to the non-HIV infected (288 ± 35.25 cells/μL P = 0.01). This study has shown a high prevalence of HIV among TB patients. Reactivation of TB among people living with HIV can be reduced by TB preventive therapy and by universal access to antiretroviral therapy. PMID:22096379

Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

PubMed Central

Kammüller, Michael; Tsai, Tsen-Fang; Griffiths, Christopher EM; Kapoor, Nidhi; Kolattukudy, Pappachan E; Brees, Dominique; Chibout, Salah-Dine; Safi Jr, Jorge; Fox, Todd

2017-01-01

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections. PMID:28868144

National roll-out of latent tuberculosis testing and treatment for new migrants in England: a retrospective evaluation in a high-incidence area

PubMed Central

Loutet, Miranda G.; Burman, Matthew; Jayasekera, Nivenka; Trathen, Duncan; Dart, Susan; Kunst, Heinke; Zenner, Dominik

2018-01-01

Latent tuberculosis infection (LTBI) screening is an important intervention for tuberculosis (TB) elimination in low-incidence countries and is, therefore, a key component of England's TB control strategy. This study describes outcomes from a LTBI screening programme in a high-incidence area to inform national LTBI screening in England and other low-incidence countries. We conducted a retrospective cohort study of LTBI screening among eligible migrants (from high-incidence countries and entered the UK within the last 5 years), who were identified at primary-care clinics in Newham, London between August 2014 and August 2015. Multivariable logistic regression was used to identify factors associated with LTBI testing uptake, interferon-γ release assay (IGRA) positivity and treatment uptake. 40% of individuals offered LTBI screening received an IGRA test. The majority of individuals tested were 16–35 years old, male and born in India, Bangladesh or Pakistan. Country of birth, smoking status and co-morbidities were associated with LTBI testing uptake. IGRA positivity was 32% among those tested and was significantly associated with country of birth, age, sex and co-morbidities. This study identifies factors associated with screening uptake, IGRA positivity and treatment uptake, and improves understanding of groups that should be supported to increase acceptability of LTBI testing and treatment in the community. PMID:29326327

Tuberculin reactivity in bacille Calmette-Guérin vaccinated populations: a compilation of international data.

PubMed

Joos, T J; Miller, W C; Murdoch, D M

2006-08-01

The effect of previously administered bacille Calmette-Guérin (BCG) vaccine on subsequent tuberculin skin tests (TSTs) complicates screening for latent tuberculosis infection (LTBI) in foreign-born persons. To determine the usefulness of the TST as a screening test for LTBI in foreign-born persons. A literature search was performed of published studies that compared tuberculin reactivity amongst BCG-vaccinated and non-vaccinated groups. The percentages of positive reactors in the two groups were then used to calculate a prevalence ratio. The prevalence ratio varied with the age of the groups tested and the incidence of TB in their countries of origin. The TST performed poorly in vaccinated persons of all ages from countries of low TB incidence, but was a useful screen for LTBI in vaccinated adults from countries of high and intermediate incidence. The test performed poorly as a screening method for vaccinated children under 2 years of age. Its usefulness in vaccinated children aged 2-14 years varied considerably. The usefulness of the TST as a screening method for LTBI depends on the age of the patient and the incidence of TB in their country of origin.

Comparison of the tuberculin skin test and the QuantiFERON-TB Gold test in detecting latent tuberculosis in health care workers in Iran

PubMed Central

2016-01-01

OBJECTIVES: The tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT) are used to identify latent tuberculosis infections (LTBIs). The aim of this study was to determine the agreement between these two tests among health care workers in Iran. METHODS: This cross-sectional study included 177 tuberculosis (TB) laboratory staff and 67 non-TB staff. TST indurations of 10 mm or more were considered positive. The Student’s t-test and the chi-square test were used to compare the mean score and proportion of variables between the TB laboratory staff and the non-TB laboratory staff. Kappa statistics were used to evaluate the agreement between these tests, and logistic regression was used to assess the risk factors associated with positive results for each test. RESULTS: The prevalence of LTBIs according to both the QFT and the TST was 17% (95% confidence interval [CI], 12% to 21%) and 16% (95% CI, 11% to 21%), respectively. The agreement between the QFT and the TST was 77.46%, with a kappa of 0.19 (95% CI, 0.04 to 0.34). CONCLUSIONS: Although the prevalence of LTBI based on the QFT and the TST was not significantly different, the kappa statistic was low between these two tests for the detection of LTBIs. PMID:27457062

The epidemiology of childhood tuberculosis in the Netherlands: still room for prevention

PubMed Central

2014-01-01

Background The occurrence of tuberculosis (TB) among children has long been neglected as a public health concern. However, any child with TB is a sentinel event indicating recent transmission. Vaccination, early case finding and treatment of those latently infected with TB can prevent cases, severe morbidity and unnecessary death. Method The objective of the study was to describe the occurrence of TB events among children in the Netherlands which may be avoided through preventive measures. For this purpose we performed a trend analysis of routine Dutch TB and LTBI (surveillance data in 1993–2012 and a descriptive analysis of children with TB and with LTBI diagnosed in 2005–2012). Results Overall childhood TB incidence has declined over the last two decades from 3.6 in 1993 to 1.9 per 100,000 children in 2012. The decline was stronger among Dutch-born children compared to foreign-born children. In 2005–2012 64% of childhood TB cases were detected through active case finding. Foreign-born children with TB were less likely to be detected through active case finding, when not detected through post-entry TB screening. Childhood TB diagnosis was culture confirmed in 68% of passively detected cases and 12% of actively detected cases. Of 1,049 children with LTBI started on preventive treatment in 2005–2012, 90% completed treatment. In 37% of all childhood TB cases there was at least one ‘missed opportunity’ for prevention. Thirty nine percent of child TB patients eligible for BCG were not vaccinated. Conclusion Children with TB in the Netherlands are generally detected at an early stage and treatment completion rates are high. However, more TB cases among children can be prevented through enhancing TB case finding and screening and preventive treatment of latent TB infection among migrant children, and improving the coverage of BCG vaccination among eligible risk groups. PMID:24885314

The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

PubMed

Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

2016-03-23

Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.

Barriers and outcomes: TB patients co-infected with HIV accessing antiretroviral therapy in rural Zambia.

PubMed

Chileshe, Muatale; Bond, Virginia Anne

2010-01-01

The vulnerabilities that underlie barriers faced by the rural poor whilst trying to access and adhere to "free" antiretroviral treatment (ART) demand more attention. This paper highlights barriers that poor rural Zambians co-infected with tuberculosis (TB) and HIV and their households faced in accessing ART between September 2006 and July 2007, and accounts for patient outcomes by the end of TB treatment and (more sporadically) beyond October 2009. The analysis draws on findings from wider anthropological fieldwork on the converging impact of TB, HIV and food insecurity, focusing for the purpose of this paper on ethnographic case-studies of seven newly diagnosed TB patients co-infected with HIV and their six households (one household had two TB patients). Economic barriers included being pushed into deeper poverty by managing TB, rural location, absence of any external assistance, and mustering time and extended funds for transport and "special food" during and beyond the end of TB. In the case of death, funeral costs were astronomical. Social barriers included translocation, broken marriages, a sub-ordinate household position, gender relations, denial, TB/HIV stigma and the difficulty of disclosure. Health facility barriers involved understaffing, many steps, lengthy procedures and inefficiencies (lost blood samples, electricity cuts). By the end of TB treatment, outcomes were mixed; two co-infected patients had died, three had started ART and two had yet to start ART. The three on ART underwent a striking transformation in the short term. By October 2009, two more had died and three were doing well. The study advocates nutritional support and other material support (especially transport funds) for co-infected TB patients until ART is accessed and livelihood regained. More prompt diagnosis of TB and reducing steps and increasing the reach of the ART programme in rural areas are also recommended.

Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

PubMed

Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

2013-01-01

High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

Hypovitaminosis D increases TB co-infection risk on HIV patients

NASA Astrophysics Data System (ADS)

Gayatri, Y. A. A. A.; Sukmawati, D. D.; Utama, S. M.; Somia, I. K. A.; Merati, T. P.

2018-03-01

Tuberculosis is causes of mortality and morbidity in patients with HIV. Hypovitaminosis D, a defective cell-mediated immune response to Mycobacterium tuberculosis infection has been extensively described in HIV patients, but studies assessing the role of vitamin D in TB-HIV co-infection are lacking. We, therefore, conducted a 1:1 pair- matched case-control study to verify hypovitaminosis D possible risk factor of TB- HIV co- infection. Consecutive HIV patients starting ARV and sex, age and CD4 cell count matched were by recruiting. Tuberculosis has confirmed by thepresence of acid-fast bacilli in sputum or mycobacterium detected in specimens culture/Gene Xpert/PCR. Vitamin D levels were by measuring direct chemiluminescent immunoassay on a LIAISON®25OH analyzer. The study comprised 25 cases and 25 controls, median (interquartile range) 25(OH)D3 serum concentration were 19.80 (12.15-27.45) ng/mL in cases and 33.30 (27.2-39.4) ng/mL in controls (P<0.001). After adjustment for potential confounders included anemia, smoking,and low BMI, with multivariate logistic regression analysis, hypovitaminosis Dindependently associated with the development of active tuberculosis in HIV patients.(OR 26.154 (90% CI: 4.371-156.541); p <0.001). The finding indicates that hypovitaminosis D was a risk factor of TB-HIV co-infection.

Prevalence and Factors Associated with Tuberculosis Treatment Success among TB/HIV Co-Infection in North-East Malaysia.

PubMed

Jalal, Tengku Mardhiah Tengku; Abdullah, Sarimah; Wahab, Farhanah Abd; Dir, Sharina; Naing, Nyi Nyi

2017-12-01

One of the six strategies developed by WHO, in order to stop Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to determine the prevalence of successful TB treatment and factors associated with TB treatment success among TB/HIV co-infection patients in North-East Malaysia. A cross-sectional study was carried out in the a-year period from 2003 to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The outcome of interest was treatment success as defined by Ministry of Health (MOH) when the patients was cured or completed TB treatment. Out of 1510 total TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having treatment success. A majority of TB/HIV co-infection cases were male (91.1%). Fifty-eight percent the patients were drug addicts and 6% were having positive tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39, 95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63, 4.19) were significantly associated with the treatment success of TB/HIV co-infection patients. Other factors such as age, comorbid, sputum smear and x-ray findings were not significantly factors in this study. Female patients and those with negative tuberculin test should be emphasised for successful tuberculosis treatment.

Missed opportunities to prevent tuberculosis in foreign-born persons, Connecticut, 2005-2008.

PubMed

Guh, A; Sosa, L; Hadler, J L; Lobato, M N

2011-08-01

Factors that influence testing for latent tuberculosis infection (LTBI) among foreign-born persons in Connecticut are not well understood. To identify predictors for LTBI testing and challenges related to accessing health care among the foreign-born population in Connecticut. Foreign-born Connecticut residents with confirmed or suspected tuberculosis (TB) disease during June 2005-December 2008 were interviewed regarding health care access and immigration status. Predictors for self-reported testing for LTBI after US entry were determined. Of 161 foreign-born persons interviewed, 48% experienced TB disease within 5 years after arrival. One third (51/156) reported having undergone post-arrival testing for LTBI. Although those with established health care providers were more likely to have reported testing (aOR 4.49, 95%CI 1.48-13.62), only 43% of such persons were tested. Undocumented persons, the majority of whom lacked a provider (53%), were less likely than documented persons to have reported testing (aOR 0.20, 95%CI 0.06-0.67). Hispanic permanent residents (immigrants and refugees) and visitors (persons admitted temporarily) were more likely than non-Hispanics in the respective groups to have reported testing (OR 5.25, 95%CI 1.51-18.31 and OR 7.08, 95%CI 1.30-38.44, respectively). The self-reported rate of testing for LTBI among foreign-born persons in Connecticut with confirmed or suspected TB was low and differed significantly by ethnicity and immigration status. Strategies are needed to improve health care access for foreign-born persons and expand testing for LTBI, especially among non-Hispanic and undocumented populations.

Methodological considerations for economic modelling of latent tuberculous infection screening in migrants.

PubMed

Shedrawy, J; Siroka, A; Oxlade, O; Matteelli, A; Lönnroth, K

2017-09-01

Tuberculosis (TB) in migrants from endemic to low-incidence countries results mainly from the reactivation of latent tuberculous infection (LTBI). LTBI screening policies for migrants vary greatly between countries, and the evidence on the cost-effectiveness of the different approaches is weak and heterogeneous. The aim of this review was to assess the methodology used in published economic evaluations of LTBI screening among migrants to identify critical methodological options that must be considered when using modelling to determine value for money from different economic perspectives. Three electronic databases were searched and 10 articles were included. There was considerable variation across this small number of studies with regard to economic perspective, main outcomes, modelling technique, screening options and target populations considered, as well as in parameterisation of the epidemiological situation, test accuracy, efficacy, safety and programme performance. Only one study adopted a societal perspective; others adopted a health care or wider government perspective. Parameters representing the cascade of screening and treating LTBI varied widely, with some studies using highly aspirational scenarios. This review emphasises the need for a more harmonised approach for economic analysis, and better transparency in how policy options and economic perspectives influence methodological choices. Variability is justifiable for some parameters. However, sufficient data are available to standardise others. A societal perspective is ideal, but can be challenging due to limited data. Assumptions about programme performance should be based on empirical data or at least realistic assumptions. Results should be interpreted within specific contexts and policy options, with cautious generalisations.

Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection

PubMed Central

Hirsch, Christina S; Baseke, Joy; Kafuluma, John Lusiba; Nserko, Mary; Mayanja-Kizza, Harriet; Toossi, Zahra

2016-01-01

Background CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3+ CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3+ CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known. Methods Pleural fluid mononuclear cells (PFMC) from HIV/TB co-infected patients with pleural TB were characterized by immune-staining and FACS analysis for surface markers CD4, CD127, CCR5, CXCR4, HLA-DR and intracellular expression of Foxp3, HIVp24, IFN-γ and Bcl-2. Whole PFMC and bead separated CD4+CD25+CD127− T cells were assessed for HIV-1 LTR strong stop (SS) DNA by real-time PCR, which represents viral DNA post cell entry and initiation of reverse transcription. Results High numbers of HIV-1 p24 positive Foxp3+ and Foxp3+CD127− CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4+Foxp3+CD127− T cells displayed high expression of the cellular activation marker, HLA-DR. Further, expression of the HIV-1 co-receptors, CCR5 and CXCR4, were higher on CD4+Foxp3+T cells compared to CD4+Foxp3− T cells. Purified CD4+CD25+CD127− T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4+Foxp3+T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4+CD25+CD127− T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24+ Foxp3+ CD4+T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24+ Foxp3− CD4 T cells, and Foxp3+ CD4+T cells without HIV-p24 expression. Conclusion Foxp3+ CD4 T cells in PFMC from HIV/TB co-infected subjects are predisposed to productive HIV-1 infection and have survival advantage as compared to Foxp3 negative CD4 T cells. PMID:28124031

The Prevalence Rate of Tuberculin Skin Test Positive by Contacts Group to Predict the Development of Active Tuberculosis After School Outbreaks.

PubMed

Kim, Hee Jin; Chun, Byung Chul; Kwon, AmyM; Lee, Gyeong-Ho; Ryu, Sungweon; Oh, Soo Yeon; Lee, Jin Beom; Yoo, Se Hwa; Kim, Eui Sook; Kim, Je Hyeong; Shin, Chol; Lee, Seung Heon

2015-10-01

The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. The mean duration of follow-up was 3.9±0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ≥ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.

CD137 is a Useful Marker for Identifying CD4+ T Cell Responses to Mycobacterium tuberculosis.

PubMed

Yan, Z-H; Zheng, X-F; Yi, L; Wang, J; Wang, X-J; Wei, P-J; Jia, H-Y; Zhou, L-J; Zhao, Y-L; Zhang, H-T

2017-05-01

Upregulation of CD137 on recently activated CD8 + T cells has been used to identify rare viral and tumour antigen-specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD137 for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4 + T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD137 + CD4 + T cells. We initially enrolled 31 active tuberculosis (TB) patients, 31 individuals with latent TB infection (LTBI) and 25 healthy donors. The intracellular CD137 and interferon-γ (IFN-γ) production by CD4 + T cells was simultaneously detected under unstimulated and CFP10-stimulated (culture filtrate protein 10, a Mtb-specific antigen) conditions. In unstimulated CD4 + T cells, we found that the CD137 expression in the TB group was significantly higher than that in the LTBI group. Stimulation with CFP10 largely increased the CD4 + T cell CD137 expression in both the TB and LTBI groups. After CFP10 stimulation, the frequency of CD137 + CD4 + T cells was higher than that of IFN-γ + CD4 + T cells in both the TB and LTBI groups. Most of the CFP10-activated IFN-γ-secreting cells were CD137-positive, but only a small fraction of the CD137-positive cells expressed IFN-γ. An additional 20 patients with TB were enrolled to characterize the CD45RO + CCR7 + , CD45RO + CCR7 - and CD45RO - subsets in the CD137 + CD4 + T cell populations. The Mtb-specific CD137 + CD4 + T cells were mainly identified as having an effector memory phenotype. In conclusion, CD137 is a useful marker that can be used for identifying Mtb-reactive CD4 + T cells by flow cytometry. © 2017 The Foundation for the Scandinavian Journal of Immunology.

FACTORS ASSOCIATED WITH TB/HIV CO-INFECTION AMONG DRUG SENSITIVE TUBERCULOSIS PATIENTS MANAGED IN A SECONDARY HEALTH FACILITY IN LAGOS, NIGERIA.

PubMed

Adejumo, Olusola A; Daniel, Olusoji J; Otesanya, Andrew F; Adegbola, Adebukola A; Femi-Adebayo, Temitope; Bowale, Abimbola; Adesola, Sunday; Kuku, Olugbenga O; Otemuyiwa, Kehinde O; Oladega, Shafaatu N; Johnson, Eze O; Falana, Ayodeji A; Dawodu, Olusola; Owuna, Henry; Osoba, Ganiyat; Dacosta, Adetokunbo

2017-01-01

This study assessed factors associated with TB/HIV co-infection among TB patients managed in a secondary health facility in Lagos Nigeria. A retrospective review of treatment cards of patients seen at a secondary referral hospital between January 1 2014 and December 31 2014 was conducted. Treatment outcomes and factors associated with TB/HIV co-infection were assessed. Of the 334 records of patients reviewed, the proportion of patients with TB/HIV co-infection was 21.6%. The odds of having TB/HIV co-infection was 2.7 times higher among patients above 40 years than patients less than 25 years (AOR 2.7 95% CI 1.1 - 6.5, p =0.030). In addition, the odds of having TB/HIV co-infection was 3.3 higher among extra-pulmonary TB cases (AOR 3.3; 95% CI 1.2 - 9.5; p = 0.026) and 2.1 times higher among retreated patients (AOR 2.1; 95% CI 1.1 - 3.9; p = 0.017) than pulmonary TB and new patients respectively. The chance of having TB/HIV co-infection was 2.7-fold more in patients with poor treatment outcomes than patients with treatment success (AOR 2.7; 95%CI 1.3 - 5.4; p =0.006). TB/HIV co-infection rate was high in the study area. There is need to put measures in place to improve treatment outcomes of TB/HIV co-infected patients.

Different Patterns of Cytokines and Chemokines Combined with IFN-γ Production Reflect Mycobacterium tuberculosis Infection and Disease

PubMed Central

Hu, Shizong; Jin, Dongdong; Chen, Xinchun; Jin, Qi; Liu, Haiying

2012-01-01

Background IFN-γ is presently the only soluble immunological marker used to help diagnose latent Mycobacterium tuberculosis (M.tb) infection. However, IFN-γ is not available to distinguish latent from active TB infection. Moreover, extrapulmonary tuberculosis, such as tuberculous pleurisy, cannot be properly diagnosed by IFN-γ release assay. As a result, other disease- or infection-related immunological biomarkers that would be more effective need to be screened and identified. Methodology A panel of 41 soluble immunological molecules (17 cytokines and 24 chemokines) was tested using Luminex liquid array-based multiplexed immunoassays. Samples, including plasma and pleural effusions, from healthy donors (HD, n = 12) or patients with latent tuberculosis infection (LTBI, n = 20), pulmonary tuberculosis (TB, n = 12), tuberculous pleurisy (TP, n = 15) or lung cancer (LC, n = 15) were collected and screened for soluble markers. Peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) were also isolated to investigate antigen-specific immune factors. Principal Findings For the 41 examined factors, our results indicated that three patterns were closely associated with infection and disease. (1) Significantly elevated plasma levels of IL-2, IP-10, CXCL11 and CXCL12 were present in both patients with tuberculosis and in a sub-group participant with latent tuberculosis infection who showed a higher level of IFN-γ producing cells by ELISPOT assay compared with other latently infected individuals. (2) IL-6 and IL-9 were only significantly increased in plasma from active TB patients, and the two factors were consistently highly secreted after M.tb antigen stimulation. (3) When patients developed tuberculous pleurisy, CCL1, CCL21 and IL-6 were specifically increased in the pleural effusions. In particular, these three factors were consistently highly secreted by pleural fluid mononuclear cells following M.tb-specific antigen

Value of the tuberculin skin testing and of an interferon-gamma release assay in haemodialysis patients after exposure to M. tuberculosis

PubMed Central

2012-01-01

Background Patients with end-stage renal disease (ESRD) and Mycobacterium tuberculosis infection pose a high risk of developing active TB disease. It is therefore important to detect latent TB infection (LTBI) to be able to offer treatment and prevent progression to TB disease. We assessed the value of the tuberculin skin test (TST) and of an interferon-gamma release assay (Quantiferon®-TB Gold in-Tube, QFT) for diagnosing LTBI in ESRD patients, after prolonged exposure to a highly contagious TB case in a haemodialysis unit. As a high number of patients presented erythema without induration in the TST response, this type of reaction was also analysed. Method The TST and QFT were simultaneously performed twelve weeks after the last possible exposure to a bacilliferous TB patient. If the first TST (TST-1) was negative, a second TST (TST-2) was performed 15 days later to detect a booster response. A comparison was made between the TST responses (including those cases with erythema without induration) and those for the QFT. The correlation with risk of infection and the concordance between tests were both analysed. Results A total of 52 patients fulfilled the inclusion criteria. Overall, 11 patients (21.2%) had a positive TST response: 3 for TST-1 and 8 for TST-2, and 18 patients (34.6%) showed a positive QFT response (p = 0.065). Erythema without induration was found in 3 patients at TST-1 and in a further 9 patients at TST-2. The three patients with erythema without induration in TST-1 had a positive TST-2 response. Concordance between TST and QFT was weak for TST-1 (κ = 0.21); it was moderate for overall TST (κ = 0.49); and it was strong if both induration and erythema (κ = 0.67) were considered. Conclusions In patients with ESRD, erythema without induration in the TST response could potentially be an indicator of M. tuberculosis infection. The QFT shows better accuracy for LTBI diagnosis than the TST. PMID:22905901

FACTORS ASSOCIATED WITH TB/HIV CO-INFECTION AMONG DRUG SENSITIVE TUBERCULOSIS PATIENTS MANAGED IN A SECONDARY HEALTH FACILITY IN LAGOS, NIGERIA

PubMed Central

Adejumo, Olusola A.; Daniel, Olusoji J.; Otesanya, Andrew F.; Adegbola, Adebukola A.; Femi-Adebayo, Temitope; Bowale, Abimbola; Adesola, Sunday; Kuku, Olugbenga O.; Otemuyiwa, Kehinde O.; Oladega, Shafaatu N.; Johnson, Eze O.; Falana, Ayodeji A.; Dawodu, Olusola; Owuna, Henry; Osoba, Ganiyat; Dacosta, Adetokunbo

2017-01-01

Background: This study assessed factors associated with TB/HIV co-infection among TB patients managed in a secondary health facility in Lagos Nigeria. Materials and Methods: A retrospective review of treatment cards of patients seen at a secondary referral hospital between January 1 2014 and December 31 2014 was conducted. Treatment outcomes and factors associated with TB/HIV co-infection were assessed. Results: Of the 334 records of patients reviewed, the proportion of patients with TB/HIV co-infection was 21.6%. The odds of having TB/HIV co-infection was 2.7 times higher among patients above 40 years than patients less than 25 years (AOR 2.7 95% CI 1.1 – 6.5, p =0.030). In addition, the odds of having TB/HIV co-infection was 3.3 higher among extra-pulmonary TB cases (AOR 3.3; 95% CI 1.2 – 9.5; p = 0.026) and 2.1 times higher among retreated patients (AOR 2.1; 95% CI 1.1 – 3.9; p = 0.017) than pulmonary TB and new patients respectively. The chance of having TB/HIV co-infection was 2.7-fold more in patients with poor treatment outcomes than patients with treatment success (AOR 2.7; 95%CI 1.3 – 5.4; p =0.006). Conclusion: TB/HIV co-infection rate was high in the study area. There is need to put measures in place to improve treatment outcomes of TB/HIV co-infected patients. PMID:28670643

TB infection prevention and control experiences of South African nurses - a phenomenological study

PubMed Central

2011-01-01

Background The tuberculosis (TB) epidemic in South Africa is characterised by one of the highest levels of TB/HIV co-infection and growing multidrug-resistant TB worldwide. Hospitals play a central role in the management of TB. We investigated nurses' experiences of factors influencing TB infection prevention and control (IPC) practices to identify risks associated with potential nosocomial transmission. Methods The qualitative study employed a phenomenological approach, using semi-structured interviews with a quota sample of 20 nurses in a large tertiary academic hospital in Cape Town, South Africa. The data was subjected to thematic analysis. Results Nurses expressed concerns about the possible risk of TB transmission to both patients and staff. Factors influencing TB-IPC, and increasing the potential risk of nosocomial transmission, emerged in interconnected overarching themes. Influences related to the healthcare system included suboptimal IPC provision such as the lack of isolation facilities and personal protective equipment, and the lack of a TB-IPC policy. Further influences included inadequate TB training for staff and patients, communication barriers owing to cultural and linguistic differences between staff and patients, the excessive workload of nurses, and a sense of duty of care. Influences related to wider contextual conditions included TB concerns and stigma, and the role of traditional healers. Influences related to patient behaviour included late uptake of hospital care owing to poverty and the use of traditional medicine, and poor adherence to IPC measures by patients, family members and carers. Conclusions Several interconnected influences related to the healthcare system, wider contextual conditions and patient behavior could increase the potential risk of nosocomial TB transmission at hospital level. There is an urgent need for the implementation and evaluation of a comprehensive contextually appropriate TB IPC policy with the setting and

Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test.

PubMed

Bukhary, Zakeya A; Amer, Soliman M; Emara, Magdy M; Abdalla, Mohammad E; Ali, Sahar A

2018-01-01

Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. Cross-sectional prospective. Multiple non-tertiary care hospitals. HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods. The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. 520 subjects. Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. A second step TST was not feasible within 2-3 weeks. None.

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.

PubMed

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2017-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study.

PubMed

Ronald, Lisa A; Campbell, Jonathon R; Balshaw, Robert F; Romanowski, Kamila; Roth, David Z; Marra, Fawziah; Cook, Victoria J; Johnston, James C

2018-02-26

Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. We included all individuals ( n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18-64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized. © 2018 Joule Inc. or its licensors.

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study

PubMed Central

Ronald, Lisa A.; Campbell, Jonathon R.; Balshaw, Robert F.; Romanowski, Kamila; Roth, David Z.; Marra, Fawziah; Cook, Victoria J.; Johnston, James C.

2018-01-01

BACKGROUND: Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. METHODS: We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. RESULTS: Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18–64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. INTERPRETATION: These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized. PMID:29483329

The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis

ClinicalTrials.gov

2012-08-28

To Compare the Serum Apoptosis-associated Markers Between Patients With Active TB and Patients With LTBI; To Evaluate the Efficiency of Apoptosis-associated Markers to Differentiate Potential of Active TB From LTBI

TB & HIV: the deadly intersection.

PubMed

MacDougall, D S

1999-05-01

About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.

Cost-effectiveness of initiating antiretroviral therapy at different points in TB treatment in HIV-TB co-infected ambulatory patients in South Africa

PubMed Central

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Karim, Salim Abdool

2015-01-01

Objective Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV co-infected patients. In patients with CD4+ counts <50cells/mm3, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost effectiveness of starting ART at various time points during TB treatment in patients with CD4+ counts ≥50cells/mm3. Methods In the SAPiT trial, 642 HIV-TB co-infected patients were randomized to three arms, either receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct healthcare costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. Results For patients with CD4+ count≥50cells/mm3, median monthly variable costs per patient were $116, $113 and $102 in Arms-1, -2 and -3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2 and 19 deaths in 172 patients in Arm-3. While the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Conclusions Initiation of ART after the completion of the intensive phase of TB treatment is cost effective for patients with CD4+ counts≥50cells/mm3. PMID:26167618

Risk factors for treatment default in close contacts with latent tuberculous infection.

PubMed

Fiske, C T; Yan, F-X; Hirsch-Moverman, Y; Sterling, T R; Reichler, M R

2014-04-01

1) To characterize risk factors for non-completion of latent tuberculous infection treatment (LTBIT), and 2) to assess the impact of LTBIT regimens on subsequent risk of tuberculosis (TB). Close contacts of adults aged ⩾15 years with pulmonary TB were prospectively enrolled in a multi-center study in the United States and Canada from January 2002 to December 2006. Close contacts of TB patients were screened and cross-matched with TB registries to identify those who developed active TB. Of 3238 contacts screened, 1714 (53%) were diagnosed with LTBI. Preventive treatment was recommended in 1371 (80%); 1147 (84%) initiated treatment, of whom 723 (63%) completed it. In multivariate analysis, study site, initial interview sites other than a home or health care setting and isoniazid preventive treatment (IPT) were significantly associated with non-completion of LTBIT. Fourteen TB cases were identified in contacts, all of whom initiated IPT: two TB cases among persons who received ⩾6 months of IPT (66 cases/100 000 person-years [py]), and nine among those who received 0-5 months (median 2 months) of IPT (792 cases/100 000 py, P < 0.001); data on duration of IPT were not available for three cases. Only 53% (723/1371) of close contacts for whom IPT was recommended actually completed treatment. Close contacts were significantly less likely to complete LTBIT if they took IPT. Less than 6 months of IPT was associated with increased risk of active TB.

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253.

PubMed

Shiboski, C H; Chen, H; Ghannoum, M A; Komarow, L; Evans, S; Mukherjee, P K; Isham, N; Katzenstein, D; Asmelash, A; Omozoarhe, A E; Gengiah, S; Allen, R; Tripathy, S; Swindells, S

2014-06-01

To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3). Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2-4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22-48) and the specificity 85% (95%CI 81-88). We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding.

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis

PubMed Central

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P.; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2018-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI), and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection. PMID:29379507

Performance of tests for latent tuberculosis in different groups of immunocompromised patients.

PubMed

Richeldi, Luca; Losi, Monica; D'Amico, Roberto; Luppi, Mario; Ferrari, Angela; Mussini, Cristina; Codeluppi, Mauro; Cocchi, Stefania; Prati, Francesca; Paci, Valentina; Meacci, Marisa; Meccugni, Barbara; Rumpianesi, Fabio; Roversi, Pietro; Cerri, Stefania; Luppi, Fabrizio; Ferrara, Giovanni; Latorre, Irene; Gerunda, Giorgio E; Torelli, Giuseppe; Esposito, Roberto; Fabbri, Leonardo M

2009-07-01

Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown. Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (kappa = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (kappa = 0.16) or QFT-IT (kappa = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001). Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

Difference Between Latent TB Infection and Active TB Disease

MedlinePlus

... chest x-ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment ...

Addressing knowledge gaps and prevention for tuberculosis-infected Indian adults: a vital part of elimination.

PubMed

DeLuca, Andrea; Dhumal, Gauri; Paradkar, Mandar; Suryavanshi, Nishi; Mave, Vidya; Kohli, Rewa; Shivakumar, Shri Vijay Bala Yogendra; Hulyolkar, Vidula; Gaikwad, Archana; Nangude, Ashwini; Pardeshi, Geeta; Kadam, Dileep; Gupta, Amita

2018-05-02

India plans to eliminate tuberculosis (TB) by 2025, and has identified screening and prevention as key activities. Household contacts (HHCs) of index TB cases are a high-risk population that would benefit from rapid implementation of these strategies. However, best practices for TB prevention and knowledge gaps among HHCs have not been studied. We evaluated TB knowledge and understanding of prevention among tuberculin skin-test (TST) positive HHCs. While extensive information is available in other high-burden settings regarding TB knowledge gaps, identifying how Indian adult contacts view their transmission risk and prevention options may inform novel screening algorithms and education efforts that will be part of the new elimination plan. We approached adult HHC to administer a questionnaire on TB knowledge and understanding of infection. Over 1 year, 100 HHC were enrolled at a tertiary hospital in Pune, India. The study population was 61% (n = 61) female, with a mean age of 36.6 years (range 18-67, SD = 12). Education levels were high, with 78 (78%) having at least a high school education, and 23 (24%) had at least some college education. Four (4%) of our participants were HIV-infected. General TB knowledge among HHC was low, with a majority of participants believing that you can get TB from sharing dishes (70%) or touching something that has been coughed on (52%). Understanding of infection was also low, with 42% believing that being skin-test positive means you have disease. To assess readiness for preventive therapy, we asked participants whether they are at a higher risk of progressing to active disease because of their LTBI status. Fifty-four (55%) felt that they are at higher risk. Only 8% had heard of preventive therapy. Our TB knowledge survey among HHCs with evidence of recent exposure found that knowledge is poor and families are confused about transmission in the household. It is imperative that the Indian program develop tools and incentives

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

PubMed Central

Shiboski, C. H.; Chen, H.; Ghannoum, M. A.; Komarow, L.; Evans, S.; Mukherjee, P. K.; Isham, N.; Katzenstein, D.; Asmelash, A.; Omozoarhe, A. E.; Gengiah, S.; Allen, R.; Tripathy, S.; Swindells, S.

2014-01-01

SUMMARY OBJECTIVE To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm3. Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2–4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22–48) and the specificity 85% (95%CI 81–88). CONCLUSION We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding. PMID:24903939

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

PubMed

Emerson, C; Lipke, V; Kapata, N; Mwananyambe, N; Mwinga, A; Garekwe, M; Lanje, S; Moshe, Y; Pals, S L; Nakashima, A K; Miller, B

2016-07-01

Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo.

PubMed

Kaboru, Berthollet Bwira; Ogwang, Brenda A; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-09-01

HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases' control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region.

Environmental aspects related to tuberculosis and intestinal parasites in a low-income community of the Brazilian Amazon

PubMed Central

Cardoso, Biatriz Araújo; Fonseca, Fabio de Oliveira; de Moraes, Antonio Henrique Almeida; Martins, Ana Caroline Guedes Souza; Oliveira, Nissa Vilhena da Silva; Lima, Luana Nepomuceno Gondim Costa; Dias, George Alberto da Silva; Saad, Maria Helena Féres

2017-01-01

ABSTRACT We carried out a cross-sectional study from January to December 2015 on 1,425 inhabitants from a floating population in the Brazilian Amazon (Murinin district, Pará State) to describe the population-based prevalence of tuberculosis (TB) from 2011 to 2014, recent TB contacts (rCts) latently infected with Mycobacterium tuberculosis (LTBI) , the coverage of the local health network, socio-environmental factors, and frequency of intestinal parasitic infection (IPI). We found that the sanitary structure was inadequate, with latrines being shared with other rooms within the same accommodation; well water was the main source of water, and 48% of families had low incomes. The average rate of TB was 105/100, 000 inhabitants per year; one third of TB patients had been household contacts of infected individuals in the past, and 23% of rCts were LTBI. More than half (65%) of 44% of the stools examined (representing 76% of the housing) had IPIs; the highest prevalence was of fecal-oral transmitted protozoa (40%, Giardia intestinalis ), followed by soil-transmitted helminths (23%). TB transmission may be related to insufficient disease control of rCts, frequent relocation, and underreporting. Education, adopting hygienic habits, improving sanitation, provision of a treated water supply and efficient sewage system, further comprehensive epidemiological surveillance of those who enter and leave the community and resources for basic treatment of IPIs are crucial in combating the transmission of these neglected diseases. PMID:28793025

Environmental aspects related to tuberculosis and intestinal parasites in a low-income community of the Brazilian Amazon.

PubMed

Cardoso, Biatriz Araújo; Fonseca, Fabio de Oliveira; Moraes, Antonio Henrique Almeida de; Martins, Ana Caroline Guedes Souza; Oliveira, Nissa Vilhena da Silva; Lima, Luana Nepomuceno Gondim Costa; Dias, George Alberto da Silva; Saad, Maria Helena Féres

2017-08-07

We carried out a cross-sectional study from January to December 2015 on 1,425 inhabitants from a floating population in the Brazilian Amazon (Murinin district, Pará State) to describe the population-based prevalence of tuberculosis (TB) from 2011 to 2014, recent TB contacts (rCts) latently infected with Mycobacterium tuberculosis (LTBI) , the coverage of the local health network, socio-environmental factors, and frequency of intestinal parasitic infection (IPI). We found that the sanitary structure was inadequate, with latrines being shared with other rooms within the same accommodation; well water was the main source of water, and 48% of families had low incomes. The average rate of TB was 105/100, 000 inhabitants per year; one third of TB patients had been household contacts of infected individuals in the past, and 23% of rCts were LTBI. More than half (65%) of 44% of the stools examined (representing 76% of the housing) had IPIs; the highest prevalence was of fecal-oral transmitted protozoa (40%, Giardia intestinalis ), followed by soil-transmitted helminths (23%). TB transmission may be related to insufficient disease control of rCts, frequent relocation, and underreporting. Education, adopting hygienic habits, improving sanitation, provision of a treated water supply and efficient sewage system, further comprehensive epidemiological surveillance of those who enter and leave the community and resources for basic treatment of IPIs are crucial in combating the transmission of these neglected diseases.

Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection.

PubMed

Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Dheda, Keertan

2017-05-12

Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

PubMed Central

Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-01-01

Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis

PubMed Central

Petruccioli, Elisa; Scriba, Thomas J.; Petrone, Linda; Hatherill, Mark; Cirillo, Daniela M.; Joosten, Simone A.; Ottenhoff, Tom H.; Denkinger, Claudia M.; Goletti, Delia

2016-01-01

New approaches to control the spread of tuberculosis (TB) are needed, including tools to predict development of active TB from latent TB infection (LTBI). Recent studies have described potential correlates of risk, in order to inform the development of prognostic tests for TB disease progression. These efforts have included unbiased approaches employing “omics” technologies, as well as more directed, hypothesis-driven approaches assessing a small set or even individual selected markers as candidate correlates of TB risk. Unbiased high-throughput screening of blood RNAseq profiles identified signatures of active TB risk in individuals with LTBI, ≥1 year before diagnosis. A recent infant vaccination study identified enhanced expression of T-cell activation markers as a correlate of risk prior to developing TB; conversely, high levels of Ag85A antibodies and high frequencies of interferon (IFN)-γ specific T-cells were associated with reduced risk of disease. Others have described CD27−IFN-γ+CD4+ T-cells as possibly predictive markers of TB disease. T-cell responses to TB latency antigens, including heparin-binding haemagglutinin and DosR-regulon-encoded antigens have also been correlated with protection. Further studies are needed to determine whether correlates of risk can be used to prevent active TB through targeted prophylactic treatment, or to allow targeted enrolment into efficacy trials of new TB vaccines and therapeutic drugs. PMID:27836953

Malnutrition associated with unfavorable outcome and death among South African MDR-TB and HIV co-infected children.

PubMed

Hicks, R M; Padayatchi, N; Shah, N S; Wolf, A; Werner, L; Sunkari, V B; O'Donnell, M R

2014-09-01

Pediatric multidrug-resistant tuberculosis (MDR-TB) is complicated by difficult diagnosis, complex treatment, and high mortality. In South Africa, these challenges are amplified by human immunodeficiency virus (HIV) co-infection; however, evidence on treatment outcomes among co-infected children is limited. Using conventional and new pediatric definitions, to describe treatment outcomes and identify risk factors for unfavorable outcome and mortality in children aged <15 years with MDR-TB or extensively drug-resistant TB (XDR-TB) in KwaZulu-Natal, South Africa. Retrospective cohort study in a regional TB referral hospital. From January 2009 to June 2010, 84 children (median age 8 years, IQR 4-12) with MDR-TB (n = 78) or XDR-TB (n = 6) initiated treatment. Sixty-four (77%) were HIV-positive and 62 (97%) received antiretroviral therapy. Sixty-six (79%) achieved favorable treatment outcomes. Overall mortality was 11% (n = 9) at 18 months after initiation of treatment. Malnutrition (aOR 27.4, 95%CI 2.7-278.7) and severe radiographic findings (aOR 4.68, 95%CI 1.01-21.9) were associated with unfavorable outcome. New pediatric outcome definitions increased the proportion classified as cured. It is possible to successfully treat pediatric MDR-TB-HIV even in resource-poor settings. Malnutrition is a marker for severe TB-HIV disease, and is a potential target for future interventions in these patients.

Effect of vitamin A and vitamin C supplementation on oxidative stress in HIV and HIV-TB co-infection at Lagos University Teaching Hospital (LUTH) Nigeria.

PubMed

Makinde, Oluwamayowa; Rotimi, Kunle; Ikumawoyi, Victor; Adeyemo, Titilope; Olayemi, Sunday

2017-06-01

HIV and TB infections are both associated with elevated oxidative stress parameters. Anti-oxidant supplementation may offer beneficial effects in positively modulating oxidative stress parameters in HIV and HIV-TB infected patients. We investigated the effects of vitamin A and C supplementation on oxidative stress in HIV infected and HIV-TB co-infected subjects. 40 HIV/TB co-infected and 50 HIV mono-infected patients were divided into 2 equal groups. Participants provided demographic information and blood was collected to determine oxidative stress parameters before and after vitamin A (5000 IU) and C (2600 mg) supplementation for 1 month. There was a significantly (p < 0.05) higher level of Malondialdehyde (MDA) at baseline for HIV infected subjects compared with HIV-TB co-infected subjects. There was a significantly (p < 0.05) lower level of MDA and higher level of Catalase (CAT) in subjects administered supplementation compared to subjects without supplementation for the HIV infected group. There was a significantly lower level of Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and higher level of MDA after one month of supplementation compared with baseline levels for HIV/TB co infected subjects. A similar result was also obtained for the HIV mono-infected groups which had a significantly lower level of SOD, MDA and CAT compared to the baseline. There was a significantly lower level of GSH and SOD, and higher level of MDA after supplementation compared with the baseline for HIV/TB co-infected subjects. Comparing the indices at baseline and post no-supplementation in HIV/TB co-infection showed no significant differences in the oxidative stress parameters. HIV/TB co-infection and HIV mono-infection seems to diminish the capacity of the anti-oxidant system to control oxidative stress, however exogenous anti-oxidant supplementation appears not to have beneficial roles in positively modulating the associated oxidative stress.

Tuberculosis in healthcare workers – a narrative review from a German perspective

PubMed Central

2014-01-01

Introduction Despite the decline of tuberculosis in the population at large, healthcare workers (HCW) are still at risk of infection. Methods In a narrative review the TB risk in HCW and preventive measures are described, with the focus on epidemiology and Occupational Safety and Health (OSH) regulations in Germany. Results There is an increased risk of infection not only in pneumology and laboratories with regular contact with tuberculosis patients or infectious materials. Epidemiological studies have also verified an increased risk of infection from activities that involve close contact with patients’ breath (e.g. bronchoscopy, intubation) or close contact with patients in need of care in geriatric medicine or geriatric nursing. In occupational disease claim proceedings on account of tuberculosis, the burden of proof can be eased for insured persons who work in these or other comparable fields. Forgoing evidence of an index person as a source of infection has led to a doubling of the rate of cases of tuberculosis recognised as an occupational disease and has halved the duration of occupational disease claim proceedings in Germany. For several years now, it has been possible to use the new interferon-y release assays (IGRAs) to diagnose a latent tuberculosis infection (LTBI) with significantly greater validity than with the traditional tuberculin skin test (TST). However, variability of the IGRAs around the cut-off poses problems especially in serial testing of HCWs. At around 10%, LTBI prevalence in German healthcare workers is lower than had been assumed. It can make sense to treat a recent LTBI in a young healthcare worker so as to prevent progression into active tuberculosis. If the LTBI is occupational in origin, the provider of statutory accident insurance can cover the costs of preventive treatment. However, little is known about disease progression in HCWs with positive IGRA sofar. Conclusion TB screening in HCWs will remain an important issue in the

Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression.

PubMed

Coppola, Mariateresa; Arroyo, Leonar; van Meijgaarden, Krista E; Franken, Kees Lmc; Geluk, Annemieke; Barrera, Luis F; Ottenhoff, Tom H M

2017-09-01

Tuberculosis (TB) occurs in only 3-10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved remain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. IgG levels against ESAT6/CFP10, Rv0440, Rv0867c, Rv1737c, Rv2029c, Rv2215, Rv2389c, Rv3616c and Mtb purified protein derivative (PPD) were higher in TB patients than in endemic and non-endemic controls. The only exception was Rv1733c that was preferentially recognized by antibodies from endemic controls compared to TB patients and non-endemic controls, suggesting a potential correlation with control of TB infection and progression. In patients, IgG levels against Ag85B and Rv2029c correlated with Mtb loads, while immunoglobulins against Rv0440 differed between genders. Our results support the potential role of certain Mtb antigen-(Rv1733c) specific antibodies in the control of TB infection and progression, while other Mtb antigen-specific antibodies correlate with TB disease activity and bacillary loads. The findings for Rv1733c agree with previous T-cell results and have implications for including antibody-mediated immunity in designing new strategies to control TB. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence and treatment of latent tuberculosis infection among newly arrived refugees in San Diego County, January 2010-October 2012.

PubMed

Bennett, Rachel J; Brodine, Stephanie; Waalen, Jill; Moser, Kathleen; Rodwell, Timothy C

2014-04-01

We determined the prevalence and treatment rates of latent tuberculosis infection (LTBI) in newly arrived refugees in San Diego County, California, and assessed demographic and clinical characteristics associated with these outcomes. We analyzed data from LTBI screening results of 4280 refugees resettled in San Diego County between January 2010 and October 2012. Using multivariate logistic regression, we calculated the associations between demographic and clinical risk factors and the outcomes of LTBI diagnosis and LTBI treatment initiation. The prevalence of LTBI was highest among refugees from sub-Saharan Africa (43%) and was associated with current smoking and having a clinical comorbidity that increases the risk for active tuberculosis. Although refugees from sub-Saharan Africa had the highest prevalence of infection, they were significantly less likely to initiate treatment than refugees from the Middle East. Refugees with postsecondary education were significantly more likely to initiate LTBI treatment. Public health strategies are needed to increase treatment rates among high-risk refugees with LTBI. Particular attention is required among refugees from sub-Saharan Africa and those with less education.

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report.

PubMed

Field, Stephen K; Escalante, Patricio; Fisher, Dina A; Ireland, Belinda; Irwin, Richard S

2018-02-01

Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than

New insights on the nature of latent tuberculosis infection and its treatment.

PubMed

Cardona, Pere-Joan

2007-03-01

Nowadays, there is no conclusive theory explaining the latent tuberculosis infection (LTBI). LTBI is reviewed herein as a standard progression of M. tuberculosis in the context of the usual microaerobiosis present in the host's tissues and displaying their main virulent factors: slow metabolism; cell wall thickness and ability to induce intragranulomatous necrosis. Therefore, latent bacilli (LB) would be generated by the irruption of specific immunity forcing bacilli to remain in a stationary phase (SP) inside the necrotic tissue. This tissue is crucial because it maintains a stable LB population and prolongs the production of foamy macrophages which facilitate the LB escape to the alveolar spaces. In the alveolar spaces, LB will regrow and, once freed in this privileged space, they will induce new granulomas -less developed because they are better controlled by immunity. This explains the ability of LB to face the chance to be drained as a consequence of the constant cellular turnover, and to survive for a long time in the lung. This activity also supports the hypothesis that generation of active TB highly depends on the probability of the LB regrowth in a favorable zone (i.e., in the pulmonary apex). This "dynamic" hypothesis faces a more classic one (or "static") essentially based on the presence of a "resuscitation" factor that would reactivate "dormant" bacilli in old lesions in the apex. Current possibilities for LTBI treatment are reviewed according to this "dynamic hypothesis", from the standard chemotherapy to the introduction of therapeutic vaccines and anti-inflammatory treatments.

Prevalence and Treatment of Latent Tuberculosis Infection Among Newly Arrived Refugees in San Diego County, January 2010–October 2012

PubMed Central

Bennett, Rachel J.; Brodine, Stephanie; Waalen, Jill; Moser, Kathleen; Rodwell, Timothy C.

2014-01-01

Objectives. We determined the prevalence and treatment rates of latent tuberculosis infection (LTBI) in newly arrived refugees in San Diego County, California, and assessed demographic and clinical characteristics associated with these outcomes. Methods. We analyzed data from LTBI screening results of 4280 refugees resettled in San Diego County between January 2010 and October 2012. Using multivariate logistic regression, we calculated the associations between demographic and clinical risk factors and the outcomes of LTBI diagnosis and LTBI treatment initiation. Results. The prevalence of LTBI was highest among refugees from sub-Saharan Africa (43%) and was associated with current smoking and having a clinical comorbidity that increases the risk for active tuberculosis. Although refugees from sub-Saharan Africa had the highest prevalence of infection, they were significantly less likely to initiate treatment than refugees from the Middle East. Refugees with postsecondary education were significantly more likely to initiate LTBI treatment. Conclusions. Public health strategies are needed to increase treatment rates among high-risk refugees with LTBI. Particular attention is required among refugees from sub-Saharan Africa and those with less education. PMID:24524534

Factors associated with good TB infection control practices among primary healthcare workers in the Free State Province, South Africa.

PubMed

Engelbrecht, Michelle; Janse van Rensburg, André; Kigozi, Gladys; van Rensburg, Hcj Dingie

2016-11-04

Despite the availability of TB infection control guidelines, and good levels of healthcare worker knowledge about infection control, often these measures are not well implemented. This study sought to determine the factors associated with healthcare workers' good TB infection control practices in primary health care facilities in the Free State Province, South Africa. A cross-sectional self-administered survey among nurses (n = 202) and facility-based community healthcare workers (n = 34) as well as facility observations were undertaken at all 41 primary health care facilities in a selected district of the Free State Province. The majority of respondents were female (n = 200; 87.7 %) and the average age was 44.19 years (standard deviation ±10.82). Good levels of knowledge were recorded, with 42.8 % (n = 101) having an average score (i.e. 65-79 %) and 31.8 % (n = 75) a good score (i.e. ≥ 80 %). Most respondents (n = 189; 80.4 %) had positive attitudes towards TB infection control practices (i.e. ≥ 80 %). While good TB infection control practices were reported by 72.9 % (n = 161) of the respondents (i.e. ≥75 %), observations revealed this to not necessarily be the case. For every unit increase in attitudes, good practices increased 1.090 times (CI:1.016-1.169). Respondents with high levels of knowledge (≥80 %) were 4.029 (CI: 1.550-10.469) times more likely to have good practices when compared to respondents with poor levels of knowledge (<65 %). The study did not find TB/HIV-related training to be a predictor of good practices. Positive attitudes and good levels of knowledge regarding TB infection control were the main factors associated with good infection control practices. Although many respondents reported good infection control practices - which was somewhat countered by the observations - there are areas that require attention, particularly those related to administrative controls and the use of personal

Infection control in home-based care for people living with HIV/AIDS/TB in South Africa: an exploratory study.

PubMed

Akintola, Olagoke; Hangulu, Lydia

2014-01-01

The majority of HIV and AIDS patients in sub-Saharan African countries receive health care services at home. Yet research on infection control in home-based care settings is virtually non-existent. This study explored infection control practices in home-based care in a South African province with a high HIV/TB prevalence. We conducted interviews with 10 managers of home-based care organizations and 10 focus group discussions with 80 volunteer caregivers working in high HIV/TB prevalent communities in South Africa. Findings show that volunteers had insufficient training on infection control. Materials necessary for the maintenance of hygiene and protective equipment were in short supply and the protective equipment supplied was of poor quality. Home-based care patients lived in crowded and poor conditions, and family members were negatively disposed to the use of protective devices. Together, these factors put volunteers and family caregivers at risk of infection with HIV and TB. Health policy should address the training of volunteer caregivers and the regular supply of good quality materials to ensure effective infection control. It is also important to educate families on infection control. Finally, there is a need to integrate HIV and TB control at the community level.

Distance Learning Course for Healthcare Professionals: Continuing Education in Tuberculosis.

PubMed

Cabral, Vagner Kunz; Valentini, Dirceu Felipe; Rocha, Marcos Vinícius Vieira; de Almeida, Carlos Podalírio Borges; Cazella, Sílvio Cesar; Silva, Denise Rossato

2017-12-01

Continuing education of healthcare workers (HCWs) is an essential strategy for the control of tuberculosis (TB) transmission, enabling HCWs in early detection and appropriate treatment of TB cases. We developed a distance learning (DL) course on TB for nurses. We conducted a quasi-experimental before and after study to evaluate the DL community at the participant's learning level. In addition, to evaluate the DL community at the level of participant satisfaction, a cross-sectional study was carried out after the course. Nurses involved in active inpatient or outpatient care of patients were recruited to participate in the study. Sixty-six participants started and completed the course and they were included in the analysis. The overall mean pretest and post-test scores were 10.3 ± 2.2 and 11.4 ± 2.7, respectively. Participants increased their knowledge to a statistically significant degree (p < 0.0001). At baseline, the frequency of correct answers was very low in some questions: number of people infected by Mycobacterium tuberculosis in the world (10.6%); number of TB cases in Brazil (36.4%); contagiousness of latent TB infection (LTBI) (28.8%); and definition of active case finding (45.5%). Course feedback was mostly positive, with majority of users saying they were satisfied or totally satisfied. A brief DL course on TB was associated with some improvement in knowledge among nurses. The baseline knowledge was low regarding TB epidemiologic data, concepts on LTBI, and active case finding. This finding emphasizes the need to further improve the competencies and knowledge of nurses.

Medical Surveillance Monthly Report. Volume 20, Number 5

DTIC Science & Technology

2013-05-01

a diagnosis of latent tuberculosis infection (LTBI). Although only pulmonary TB is reportable in the U.S. military,14 extra- pulmonary cases were...I G U R E 1 . Numbers of cases and rates of pulmonary tuberculosis (TB), active component, U.S. Armed Forces, and expected age-adjusted rates of... pulmonary tuberculosis in the general U.S. population, based on U.S. military population standard, 1998-2012a aData not available from the CDC in 2012

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

PubMed Central

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L. C. M.; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M. Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H. M.; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates. PMID:25339944

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.

PubMed

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L C M; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H M; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

Predicting tuberculosis risk in the foreign-born population of British Columbia, Canada: study protocol for a retrospective population-based cohort study

PubMed Central

Ronald, Lisa A; Campbell, Jonathon R; Balshaw, Robert F; Roth, David Z; Romanowski, Kamila; Marra, Fawziah; Cook, Victoria J; Johnston, James C

2016-01-01

Introduction Improved understanding of risk factors for developing active tuberculosis (TB) will better inform decisions about diagnostic testing and treatment for latent TB infection (LTBI) in migrant populations in low-incidence regions. We aim to examine TB risk factors among the foreign-born population in British Columbia (BC), Canada, and to create and validate a clinically relevant multivariate risk score to predict active TB. Methods and analysis This retrospective population-based cohort study will include all foreign-born individuals who acquired permanent resident status in Canada between 1 January 1985 and 31 December 2013 and acquired healthcare coverage in BC at any point during this period. Multiple administrative databases and disease registries will be linked, including a National Immigration Database, BC Provincial Health Insurance Registration, physician billings, hospitalisations, drugs dispensed from community pharmacies, vital statistics, HIV testing and notifications, cancer, chronic kidney disease and dialysis treatment, and all TB and LTBI testing and treatment data in BC. Extended proportional hazards regression will be used to estimate risk factors for TB and to create a prognostic TB risk score. Ethics and dissemination Ethical approval for this study has been obtained from the University of British Columbia Clinical Ethics Review Board. Once completed, study findings will be presented at conferences and published in peer-reviewed journals. An online TB risk score calculator will also be created. PMID:27888179

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test.

PubMed

Altet-Gómez, N; De Souza-Galvao, M; Latorre, I; Milà, C; Jiménez, M A; Solsona, J; Cantos, A; Zamora, J J; Ruiz-Manzano, J; Ausina, V; Domínguez, J

2011-05-01

The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥ 5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.

Latent Tuberculosis Infection Testing Practices in Long-Term Care Facilities, Boston, Massachusetts.

PubMed

Reddy, Divya; Walker, Jacob; White, Laura F; Brandeis, Gary H; Russell, Matthew L; Horsburgh, Charles R; Hochberg, Natasha S

2017-06-01

To describe latent tuberculosis infection (LTBI) testing practices in long-term care facilities (LTCFs). Retrospective cohort study. Three Boston-area LTCFs. Residents admitted between January 1 and December 31, 2011. Resident demographic characteristics, comorbidities, LTCF stay, and LTBI testing and treatment. Data for 291 LTCF residents admitted in 2011 were reviewed. Of the 257 without a history of LTBI and with documentation of testing, 162 (63%) were tested; 114 of 186 (61%) with a stay less than 90 days and 48 of 71 (68%) with a stay of 90 days or longer were tested. Of 196 residents with data on prior LTBI testing, 39 (19.9%) had LTBI; 12 of these (30.8%) were diagnosed at the LTCF. Hispanic participants were more likely than black participants to undergo LTBI testing (adjusted odds ratio (aOR) = 2.4, P = .003). Having a length of stay of less than 90 days (aOR = 0.7, P < .001) and history of illicit drug use (aOR = 0.7, P < .001) were associated with lower odds of LTBI testing. One-fifth of LTCF residents had LTBI, but testing was not always performed. The high prevalence of LTBI in older adults combined with the risk of an outbreak if a case of tuberculosis occurs in a LTCF make LTBI testing and treatment an important prevention opportunity. The importance of LTBI testing in LTCFs needs to be reinforced. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

PubMed

Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

2017-09-15

Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Epidemiology of HIV-TB in Asia.

PubMed

Narain, Jai P; Lo, Ying-Ru

2004-10-01

Tuberculosis (TB) has, for centuries, continued to remain a public health problem of enormous importance, particularly in the developing world, taking a heavy toll of those at their prime of life. The emergence of human immunodeficiency virus (HIV infection) and its close association with TB poses an even greater challenge to the health systems in general and TB programmes in particular, in African and Asian countries. HIV is considered to be the most potent risk factor for progression to active TB among those infected both with TB and HIV; as a result, TB is the most common life threatening opportunistic infection associated with HIV, and biggest cause of death among patients with acquired immunodeficiency syndrome (AIDS). In areas hard-hit by HIV, TB is increasing, leading to greater case load, thereby overstretching the already fragile health infrastructure. The deadly relationship between HIV and TB, each potentiating the effect of the other, requires a clearly defined strategy taking into consideration the natural history of the co-infection and its progression to clinical TB (and AIDS). It is clear that the only way to fight this is by bringing the two programmes to join forces and work creatively and innovatively. The strategy should include not only preventing HIV through community-based behavioural interventions and limiting progression to clinical TB through the use of isoniazid preventive therapy, but also early diagnosis and treatment of HIV-associated TB and AIDS using DOTS strategy and combination antiretroviral therapy respectively. The strategy probably would not succeed unless both the programmes are first strengthened before attempting to forge collaboration based on mutual strengths and comparative advantages. In addition, mobilizing national and international response, building partnerships and mobilizing resources will help a great deal in mounting an appropriate and effective response to HIV/TB in the Asian context.

Tuberculosis among Dislocated North Koreans Entering Republic of Korea since 1999

PubMed Central

Choi, Chang-Min; June, Jung-Hee; Kang, Cheol-In; Park, Jung-Tak; Oh, Soo-Yon; Lee, Jin-Beom; Lee, Chang-Hoon; Yim, Jae-Joon

2007-01-01

The collapse of North Korea's public health system has increased the development of tuberculosis (TB) in its populace. This study investigated the prevalence of active and latent TB infection (LTBI) in such people who have settled in the Republic of Korea since 1999. From 1999 to August 2006, 7,722 dislocated North Koreans entered the Republic of Korea and all were screened immediately for active TB. Demographic and clinical characteristics were reviewed from the official records of the Settlement Support Office for Dislocated North Koreans, based in the Ministry of Unification. Of 7,722 participants, 87 (1.13%) were diagnosed with active TB from 1999 to August 2006. Of these, 78 (90%) had pulmonary TB. Checking for the presence of a Bacille Calmette-Guérin (BCG) scar and tuberculin skin test has been performed in all dislocated North Koreans since November 2005. Of 1,112 participants, BCG vaccination scars were found in 67.4%. The tuberculin-positive rate using two tuberculin unit doses of the purified protein derivative RT23 (≥10 mm in diameter) was 81.5%. The prevalence of active TB and LTBI in dislocated North Koreans was high. Because this group bears a disproportionate burden of TB, we need to initiate a specific control programme and to plan for the impact of this disease in the Republic of Korea. PMID:18162707

Tuberculosis among dislocated North Koreans entering Republic of Korea since 1999.

PubMed

Choi, Chang Min; June, Jung Hee; Kang, Cheol In; Park, Jung Tak; Oh, Soo Yon; Lee, Jin Beom; Lee, Chang Hoon; Yim, Jae Joon; Kim, Hee Jin

2007-12-01

The collapse of North Korea's public health system has increased the development of tuberculosis (TB) in its populace. This study investigated the prevalence of active and latent TB infection (LTBI) in such people who have settled in the Republic of Korea since 1999. From 1999 to August 2006, 7,722 dislocated North Koreans entered the Republic of Korea and all were screened immediately for active TB. Demographic and clinical characteristics were reviewed from the official records of the Settlement Support Office for Dislocated North Koreans, based in the Ministry of Unification. Of 7,722 participants, 87 (1.13%) were diagnosed with active TB from 1999 to August 2006. Of these, 78 (90%) had pulmonary TB. Checking for the presence of a Bacille Calmette-Guerin (BCG) scar and tuberculin skin test has been performed in all dislocated North Koreans since November 2005. Of 1,112 participants, BCG vaccination scars were found in 67.4%. The tuberculin-positive rate using two tuberculin unit doses of the purified protein derivative RT23 (> or =10mm in diameter) was 81.5%. The prevalence of active TB and LTBI in dislocated North Koreans was high. Because this group bears a disproportionate burden of TB, we need to initiate a specific control programme and to plan for the impact of this disease in the Republic of Korea.

Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

PubMed Central

Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

2014-01-01

Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

Prevalence of latent Mycobacterium tuberculosis infection in prisoners

PubMed Central

de Navarro, Pedro Daibert; de Almeida, Isabela Neves; Kritski, Afrânio Lineu; Ceccato, Maria das Graças; Maciel, Mônica Maria Delgado; Carvalho, Wânia da Silva; de Miranda, Silvana Spindola

2016-01-01

ABSTRACT Objective: To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. Methods: This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. Results: A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Conclusions: Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system. PMID:27812634

Latent Tuberculosis Infection in an Urban Cohort: Screening and Treatment for Latent TB in an Urban Setting

PubMed Central

Morano, Jamie P.; Walton, Mary R.; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

2013-01-01

Background Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Methods Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2523 completed tuberculin skin tests (TST’s) resulted in 357 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes 1) initiation of isoniazid preventative therapy (IPT) and 2) completion of 9-months IPT. Results Of 357 new LTBIs, 86.3% (n=308) completed screening CXRs: 90.3% (n=278) were normal and 0.3% (n=1) with active tuberculosis. Of those completing CXR screening, 44.0% (n=135) agreed to IPT: 69.6% (n=94) selected DOT, and 30.4% (n=41) selected SAT. Initiating IPT was correlated with undocumented status (AOR=3.43; p<0.001) and being born in a country of highest and third highest tuberculosis prevalence (AOR=14.09; p=0.017 and AOR=2.25; p=0.005, respectively). Those selecting DOT were more likely to be Hispanic (83.0% vs 53.7%; p<0.0001), undocumented (57.4% vs 41.5%; p=0.012), have stable housing (p=0.002), employed (p<0.0001), uninsured (p=0.014), no prior cocaine or crack use (p=0.013) and no recent incarceration (p=0.001). Completing 9-months of IPT was correlated with no recent incarceration (AOR 5.95; p=0.036) and younger age (AOR 1.03; p=0.031). SAT and DOT participants did not significantly differ for IPT duration (6.54 vs 5.68 months; p=0.216) nor 9-month completion (59.8% vs 46.3%; p=0.155). Conclusions In an urban mobile healthcare sample, screening completion for LTBI was high with nearly half initiating IPT. Undocumented, Hispanic immigrants from high prevalence tuberculosis countries were more likely to self-select DOT at the mobile outreach clinic, potentially because of more culturally, linguistically, and logistically accessible services and self-selection optimization

TB Is Back.

ERIC Educational Resources Information Center

Natale, Jo Anna

1992-01-01

The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PubMed Central

Benjamin, Ronald; Banerjee, Atoshi; Sunder, Sharada Ramaseri; Gaddam, Sumanlatha; Valluri, Vijaya Lakshmi; Banerjee, Sharmistha

2013-01-01

Background Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy. Methodology/Principal Findings We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio. Conclusion/Significance With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. PMID:23936398

Evaluation of screening methods for identification of patients with chronic rheumatological disease requiring tuberculosis chemoprophylaxis prior to commencement of TNF-α antagonist therapy.

PubMed

Singanayagam, Aran; Manalan, Kavina; Sridhar, Saranya; Molyneaux, Philip L; Connell, David W; George, Peter M; Kindelerer, Anne; Seneviratne, Suranjith; Lalvani, Ajit; Wickremasinghe, Melissa; Kon, Onn Min

2013-10-01

Patients undergoing tumour necrosis factor (TNF)-α antagonist therapy are at increased risk of latent tuberculosis infection (LTBI) reactivation. The aim of this study was to determine the optimum available screening strategy for identifying patients for tuberculosis (TB) chemoprophylaxis. We conducted a prospective observational study of consecutive adults with chronic rheumatological disease referred for LTBI screening prior to commencement of TNF-α antagonist therapy. All patients included had calculation of TB risk according to age, ethnicity and year of UK entry, as described in the 2005 British Thoracic Society (BTS) guidelines and measurement of tuberculin skin test (TST) and T.Spot.TB. There were 187 patients included in the study, with 157 patients (84%) taking immunosuppressants. 137 patients would require further risk stratification according to the BTS algorithm, with 110 (80.3%) classified as being at low risk of having LTBI. There were 39 patients (35.5%) who were categorised as low risk but were either TST and/or T.Spot positive and would not have received chemoprophylaxis according to the BTS algorithm. Combination of all three methods (risk stratification and/or positive T.Spot and/or positive TST) identified 66 patients out of 137 who would potentially be offered chemoprophylaxis, which was greater than any single test or two-test combination. Performing both a TST and T.Spot in patients on immunosuppressants prior to commencement of TNF-α antagonist therapy gives an additional yield of potential LTBI compared with use of risk stratification tables alone. Our results suggest that use of all three screening modalities gives the highest yield of patients potentially requiring chemoprophylaxis.

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa.

PubMed

Engelbrecht, M C; Kigozi, N G; Chikobvu, P; Botha, S; van Rensburg, H C J

2017-07-10

South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count >350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an

Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization.

PubMed

Vajravelu, Ravy K; Osterman, Mark T; Aberra, Faten N; Roy, Jason A; Lichtenstein, Gary R; Mamtani, Ronac; Goldberg, David S; Lewis, James D; Scott, Frank I

2017-12-19

QuantiFERON-TB Gold (QFTG) is a blood test used to diagnose latent tuberculosis infection (LTBI) prior to TNF-α inhibitor (anti-TNF) initiation. We sought to determine factors associated with indeterminate QFTG results in inflammatory bowel disease (IBD) patients and whether indeterminate results are associated with IBD-related morbidity. This nested case-control study included IBD patients who underwent QFTG testing. Cases were patients with indeterminate QFTG and controls were those with negative QFTG. The association of demographic and clinical data with indeterminate QFTG result was assessed using logistic regression. We examined the clinical impact of indeterminate QFTG results on risk of hospitalization and delay in anti-TNF initiation using inverse probability-of-treatment weighting (IPTW) regression. We identified 411 patients with QFTG testing (320 negative, 80 indeterminate, and 11 positive results). No patient with an indeterminate result subsequently had LTBI. Systemic corticosteroid use (OR, 4.4; 95% CI, 2.0-9.6) and hospitalization at the time of QFTG (OR, 3.8; 95% CI, 1.9-7.7) were associated with indeterminate QFTG, while immunomodulator use was nearly statistically significant (OR, 3.1; 95% CI, 0.9-9.8) and anti-TNF use was not (OR, 0.9; 95% CI, 0.2-4.6). After IPTW adjustment, indeterminate QFTG was associated with a 23.1% (95% CI, 8.2%-37.9%) greater probability of delay in anti-TNF initiation beyond 30 days and an 11.9% (95% CI, 0.6%-23.1%) greater probability of hospitalization within 60 days. Systemic corticosteroid use and hospitalization were associated with an indeterminate QFTG result. Indeterminate QFTG results were associated with delayed anti-TNF initiation and subsequent hospitalization. © 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana

PubMed Central

Campa, Adriana; Baum, Marianna K; Bussmann, Hermann; Martinez, Sabrina Sales; Farahani, Mansour; van Widenfelt, Erik; Moyo, Sikhulile; Makhema, Joseph; Essex, Max; Marlink, Richard

2017-01-01

Background Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH. Methods A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009. The study had a factorial design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT group and the placebo group. Those participants with prior or current active TB were excluded, as were participants with advanced HIV disease (CD4 <250 cells/μL) or who had already qualified for ART. HIV-positive adults (N=878) were followed monthly for study pill dispensation, every 3 months for CD4 cell count and every 6 months for viral load during 24 months or until they were started on ART. Results The participants' characteristics were not significantly different among the four groups at baseline. Supplementation with Se alone (hazard ratio =0.20, 95% confidence interval: 0.04, 0.95, P=0.043) and the two combined SE groups (Se and Se+MVT) had significantly lower risk of developing incident TB disease compared with placebo in multivariate adjusted models (hazard ratio=0.32, 95% confidence interval: 0.11, 0.93, P=0.036). Multivitamins alone did not affect the incidence of TB. Isoniazid preventive therapy was received by 12.2% of participants, a rate that was not significantly different among the four study arms (P=0.122) and the newly diagnosed cases. Conclusion Se supplementation, alone and with MVT, decreased the incidence of TB disease in PLWH who were ART-naïve. Supplementation with these micronutrients should be considered in HIV infection, prior to ART, in areas where TB and malnutrition are endemic. PMID:29187783

Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

PubMed

Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

2014-04-01

Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

HIV screening among TB patients and level of antiretroviral therapy and co-trimoxazole preventive therapy for TB/HIV patients in Hawassa University Referral Hospital: a five year retrospective study.

PubMed

Simieneh, Asnake; Hailemariam, Mengistu; Amsalu, Anteneh

2017-01-01

Initiation of antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) is recommended for tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected patients to prevent opportunistic infection. The aim of this study was to assess the prevalence of HIV among TB patients and initiation of ART and provision of CPT for TB/HIV co-infected patients in Hawassa university referral hospital. A five year document review was done on 1961 TB patients who are registered at TB clinic of Hawassa university referral hospital from September 2009 to august 2014. Data were collected using checklist. Data analysis was done by using SPSS version 20 software. Bivariate and multivariate logistic regression analysis was used to determine the predictors of TB/HIV co-infection. Among 1961 TB patients diagnosed in the hospital, 95% (1765) were screened for HIV. Of these, 13.9% (246) were HIV positive. Out of 246 TB/HIV co-infected patients 31.7% (78/246) and 37.4% (92/246) were enrolled to start ART and CPT respectively. Roughly the trends of TB/HIV co-infection decreased with increased linkage to CPT, while linkage to ART was not regular across the year. The rate of TB/HIV co-infection was significantly associated with type of TB. Although, trend of HIV among TB patients has decreased across the year, only a minority of co-infected patients was linked to start ART and CPT. Therefore, screening of all TB patients for HIV and linkage of co-infected patients to HIV care to start ART and CPT should be strengthened in-line with the national guidelines.

Evaluation of health-care providers' knowledge of childhood tuberculosis in Lima, Peru.

PubMed

Chiang, Silvia S; Cruz, Andrea T; Del Castillo, Hernán; Contreras, Carmen; Becerra, Mercedes C; Lecca, Leonid

2015-02-01

As most national tuberculosis programmes (NTPs) focus on adult tuberculosis (TB), NTP providers may not appreciate differences in the pathophysiology and presentation of childhood TB. This study aimed to identify strengths and weaknesses in knowledge of childhood TB among the 326 NTP providers in Lima Ciudad and Lima Este--two of the Peruvian capital's four health districts. 310 providers--103 physicians, 106 nurses, 101 nursing technicians--accepted personal invitations to complete self-administered surveys, which included 14 childhood TB questions grouped into five sections: transmission, symptoms, diagnosis, prevention and treatment. Physicians were asked ten additional questions targeting their NTP diagnostic and management responsibilities. All three groups scored 97-99% on the transmission section and 83-85% on the treatment section; however, no group scored above 66% on any other section. Fewer than 50% of nurses and technicians recognised young children's high risk of extrapulmonary TB, extrapulmonary TB symptoms or the causes of false negative tuberculin skin tests. Twenty-three per cent of physicians correctly identified gastric aspirate culture sensitivity, and 42% the radiographical findings of pulmonary TB. Less than two-thirds of providers recognised the definition of latent TB infection (LTBI), young children's high risk of progression from LTBI to disease or indications for isoniazid preventive therapy. Providers at the frontline of Peru's TB control efforts demonstrated weaknesses in the areas of extrapulmonary disease, diagnosis and prevention. These knowledge gaps are likely to have resulted in delayed or missed diagnoses and lost opportunities for prevention. Educational interventions targeting NTP personnel may improve childhood TB care and outcomes.

Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist.

PubMed

Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

2009-01-01

The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants were university students diagnosed with LTBI. The authors conducted a retrospective review of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken, characteristics of completers versus noncompleters, average time to treatment completion, and reported adverse drug events. The 9-month completion rate was 59%, and the 6-month completion rate was 67%. Among those not completing treatment, 15.2% experienced fatigue and 2.2% experienced a rash (p=.04 and p=.03, respectively). LTBI clinics are a unique niche for community pharmacies and can provide individualized patient care to ensure LTBI treatment adherence, monitoring for disease progression, and safety of INH.

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2015-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland requires the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, including development, implementation and monitoring of the implementation of procedures into practice, aiming at limiting the dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staff with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include reporting all of the recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as an occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides principles of financing of individual benefits available for the insured TB patients as well as those not insured.

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2011-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland provides for the duty of the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, involving development, implementation and monitoring of practical implementation of procedures aiming at limiting dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staffs with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include notification of all recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides for principles of financing of individual benefits available for the insured TB patients and those not insured.

[Clinical and radiological study of Suruí indigenous children and adolescents, Amazon Region, Brazil].

PubMed

Basta, Paulo Cesar; Rios, Diana Patrícia Giraldo; Alves, Luiz Carlos Corrêa; Sant' Anna, Clemax Couto; Coimbra Junior, Carlos Everaldo Alvares

2010-01-01

The average incidence coefficient of tuberculosis in Suruí Indians from Rondônia was 2.500/100.000 inhabitants in 1991-2002. About 50% of these cases were reported in children < 15 years-old. This study aimed to describe the clinical and radiological characteristics of children and adolescents identified as TB case contacts. A score system for the diagnosis of childhood TB was used and the procedures adopted by local health services were in accordance with national guidelines. 52 chest X-rays of 37 indigenous subjects were analyzed; of these, 51.9% were abnormal. Some X-rays showed more than two lesions, making a total of 36 independent events. Infiltrates (38.9%), calcifications (38.9%), cavitations (11.1%) and atelectasis/pleural effusion (11.1%) were observed. Among the abnormal images, 22.2% were probably indicated active TB and 33.3% showed sequelae. Confrontation with the guidelines revealed 52.6% of divergent procedures. The presence of latent tuberculosis infection (LTBI) and active TB between children and adolescents are indicators of active and progressive transmission of Mycobacterium tuberculosis. The X-rays showed high frequencies of infiltrates and calcifications, which are compatible with primary infection in early childhood. However, these lesions are not different from those observed among other groups and do not suggest immune deficiencies. The divergences presented show that the best moment for the treatment of LTBI went unnoticed by local personnel. In conclusion, the use of a score system is fundamental for the correct diagnosis of TB in childhood, as is conducting bacilloscopy and sputum culture in adolescents able to expectorate.

Isoniazid Completion Rates for Latent Tuberculosis Infection among College Students Managed by a Community Pharmacist

ERIC Educational Resources Information Center

Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

2009-01-01

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants: Participants were university students diagnosed with…

Molecular signatures distinguishing active from latent tuberculosis in peripheral blood mononuclear cells, after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD) or Candida: a preliminary report.

PubMed

Stern, Joel N H; Keskin, Derin B; Romero, Viviana; Zuniga, Joaquin; Encinales, Liliana; Li, Changlin; Awad, Carlos; Yunis, Edmond J

2009-01-01

Purified protein derivative (PPD) or tuberculin skin testing is used to identify infected individuals with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immunity to Mtb. In the present study, we compared PBMC cultures in the presence of tuberculin or Candida antigens using cytokine bead arrays and RNA microarrays. Measurements of different cytokines and chemokines in supernatants of PMBC cultures in the presence of PPD showed increased levels of interferon (IFN)-gamma in active tuberculosis infection (ATBI) and latent TB infected (LTBI) compared to controls, and increased levels of TNF-alpha in ATBI compared with LTBI. Also, we found increase of IL-6 in cultures of PPD positive and controls but not in the cultures with Candida. We also report the molecular signature of tuberculosis infection, in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFNbeta1), a chemokine (HCC-4) a chemokine receptor (CxCR5), two interleukin receptors (IL-1R2 and IL-18R1), and three additional ones (TRAF5, Smad2, CIITA, and NOS2A). By contrast, IL-17 and IGFBP3 were significantly up-regulated in LTBI. And, STAT4, GATA3, Fra-1, and ICOS were down-regulated in ATBI but absent in LTBI. Conversely, TLR-10, IL-15, DORA, and IKK-beta were down-regulated in LTBI but not in ATBI. Interestingly, the majority of the up-regulated genes found in ATBI were found in cultures stimulated with tuberculin (PPD) or Candida antigens, suggesting that these pathogens stimulate similar immunological pathways. We believe that the molecular signature distinguishing active from latent tuberculosis infection may require using cytokine bead arrays along with RNA microarrays testing cell cultures at different times following in vitro proliferation assays using several bacterial antigens and PPD.

The role of chronic hepatitis in isoniazid hepatotoxicity during treatment for latent tuberculosis infection.

PubMed

Bliven, E E; Podewils, L J

2009-09-01

To examine chronic viral hepatitis (CVH) as a risk factor for hepatotoxicity during isoniazid (INH) treatment for latent tuberculosis infection (LTBI). A search of MEDLINE (1966-May 2008) was conducted using the terms 'tuberculosis', 'antitubercular', 'therapeutics', 'treatment', 'prevention', 'prophylaxis', 'hepatitis', 'toxic hepatitis', 'hepatotoxic', 'liver' and 'injury'. Peer-reviewed, English-language articles describing the relationship between a history of CVH and occurrence of hepatotoxicity during LTBI treatment were selected. We limited CVH diagnoses to reports with positive serological test or biopsy for hepatitis B or C. Risk ratios and 95% confidence intervals were abstracted or derived. We reviewed 486 abstracts, and 11 studies met the selection criteria. Populations included in the studies were the general population (n = 6) and transplant recipients (n = 5). The variability in study designs and case finding practices precluded performing a quantitative meta-analysis. Two studies of former or current drug users reported a consistent, positive association between chronic hepatitis C infection and INH hepatotoxicity. Other risk ratios did not significantly or consistently show any association between CVH in patients treated for LTBI and the development of INH hepatotoxicity. Owing to the limited number of published papers, CVH was not established as a risk factor for INH hepatotoxicity during LTBI treatment. Controlled studies are needed to define the safety and tolerability of LTBI treatment in those with CVH and to provide an evidence base for recommendations for LTBI treatment in persons with CVH.

Human ULK1 Variation and Susceptibility to Mycobacterium tuberculosis Infection.

PubMed

Horne, David J; Graustein, Andrew D; Shah, Javeed A; Peterson, Glenna; Savlov, Meg; Steele, Sergio; Narita, Masahiro; Hawn, Thomas R

2016-10-15

Unlike tuberculosis, few studies have evaluated a host genetic basis for variability in susceptibility to latent Mycobacterium tuberculosis infection (LTBI). We performed a candidate gene association study of autophagy-related genes and LTBI. We enrolled close contacts of individuals with pulmonary tuberculosis, assessed LTBI status, and determined clinical and sociodemographic risk factors for LTBI. In participants who self-identified as Asian or black, we compared haplotype-tagging single-nucleotide polymorphisms (SNPs) in ULK1 and GABARAP between cases (n = 143) and controls (n = 106). Using CRISPR/Cas9 in U937 monocytes, we investigated the effect of ULK1 deficiency on cytokine expression, autophagy, and M. tuberculosis replication. In Asian participants, we identified 2 ULK1 SNPs (rs12297124 and rs7300908) associated with LTBI. After adjustment for population admixture and clinical risk for LTBI, each rs12297124 minor allele conferred 80% reduction in LTBI risk (odds ratio, 0.18; 95% confidence interval, .07-.46). Compared with controls, ULK1-deficient cells exhibited decreased tumor necrosis factor secretion after stimulation with Toll-like receptor ligands and M. tuberculosis whole-cell lysate, increased M. tuberculosis replication, and decreased selective autophagy. These results demonstrate a strong association of rs12297124, a noncoding ULK1 SNP, with LTBI and a role for ULK1 regulation of TNF secretion, nonspecific and M. tuberculosis-induced autophagy, and M. tuberculosis replication in monocytes. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Diabetes Mellitus and Latent Tuberculosis Infection: A Systemic Review and Metaanalysis

PubMed Central

Lee, Meng-Rui; Huang, Ya-Ping; Kuo, Yu-Ting; Luo, Chen-Hao; Shih, Yun-Ju; Shu, Chin-Chung; Wang, Jann-Yuan; Ko, Jen-Chung; Yu, Chong-Jen

2017-01-01

Abstract Background. Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Methods. We included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale. Results. Thirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50–38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06–1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI. Conclusions. Diabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics. PMID:27986673

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

PubMed

Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

2015-10-01

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Towards tuberculosis elimination: an action framework for low-incidence countries.

PubMed

Lönnroth, Knut; Migliori, Giovanni Battista; Abubakar, Ibrahim; D'Ambrosio, Lia; de Vries, Gerard; Diel, Roland; Douglas, Paul; Falzon, Dennis; Gaudreau, Marc-Andre; Goletti, Delia; González Ochoa, Edilberto R; LoBue, Philip; Matteelli, Alberto; Njoo, Howard; Solovic, Ivan; Story, Alistair; Tayeb, Tamara; van der Werf, Marieke J; Weil, Diana; Zellweger, Jean-Pierre; Abdel Aziz, Mohamed; Al Lawati, Mohamed R M; Aliberti, Stefano; Arrazola de Oñate, Wouter; Barreira, Draurio; Bhatia, Vineet; Blasi, Francesco; Bloom, Amy; Bruchfeld, Judith; Castelli, Francesco; Centis, Rosella; Chemtob, Daniel; Cirillo, Daniela M; Colorado, Alberto; Dadu, Andrei; Dahle, Ulf R; De Paoli, Laura; Dias, Hannah M; Duarte, Raquel; Fattorini, Lanfranco; Gaga, Mina; Getahun, Haileyesus; Glaziou, Philippe; Goguadze, Lasha; Del Granado, Mirtha; Haas, Walter; Järvinen, Asko; Kwon, Geun-Yong; Mosca, Davide; Nahid, Payam; Nishikiori, Nobuyuki; Noguer, Isabel; O'Donnell, Joan; Pace-Asciak, Analita; Pompa, Maria G; Popescu, Gilda G; Robalo Cordeiro, Carlos; Rønning, Karin; Ruhwald, Morten; Sculier, Jean-Paul; Simunović, Aleksandar; Smith-Palmer, Alison; Sotgiu, Giovanni; Sulis, Giorgia; Torres-Duque, Carlos A; Umeki, Kazunori; Uplekar, Mukund; van Weezenbeek, Catharina; Vasankari, Tuula; Vitillo, Robert J; Voniatis, Constantia; Wanlin, Maryse; Raviglione, Mario C

2015-04-01

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. The content of this work is ©the authors or their employers. Design and

Towards tuberculosis elimination: an action framework for low-incidence countries

PubMed Central

Lönnroth, Knut; Migliori, Giovanni Battista; Abubakar, Ibrahim; D'Ambrosio, Lia; de Vries, Gerard; Diel, Roland; Douglas, Paul; Falzon, Dennis; Gaudreau, Marc-Andre; Goletti, Delia; González Ochoa, Edilberto R.; LoBue, Philip; Matteelli, Alberto; Njoo, Howard; Solovic, Ivan; Story, Alistair; Tayeb, Tamara; van der Werf, Marieke J.; Weil, Diana; Zellweger, Jean-Pierre; Abdel Aziz, Mohamed; Al Lawati, Mohamed R.M.; Aliberti, Stefano; Arrazola de Oñate, Wouter; Barreira, Draurio; Bhatia, Vineet; Blasi, Francesco; Bloom, Amy; Bruchfeld, Judith; Castelli, Francesco; Centis, Rosella; Chemtob, Daniel; Cirillo, Daniela M.; Colorado, Alberto; Dadu, Andrei; Dahle, Ulf R.; De Paoli, Laura; Dias, Hannah M.; Duarte, Raquel; Fattorini, Lanfranco; Gaga, Mina; Getahun, Haileyesus; Glaziou, Philippe; Goguadze, Lasha; del Granado, Mirtha; Haas, Walter; Järvinen, Asko; Kwon, Geun-Yong; Mosca, Davide; Nahid, Payam; Nishikiori, Nobuyuki; Noguer, Isabel; O'Donnell, Joan; Pace-Asciak, Analita; Pompa, Maria G.; Popescu, Gilda G.; Robalo Cordeiro, Carlos; Rønning, Karin; Ruhwald, Morten; Sculier, Jean-Paul; Simunović, Aleksandar; Smith-Palmer, Alison; Sotgiu, Giovanni; Sulis, Giorgia; Torres-Duque, Carlos A.; Umeki, Kazunori; Uplekar, Mukund; van Weezenbeek, Catharina; Vasankari, Tuula; Vitillo, Robert J.; Voniatis, Constantia; Wanlin, Maryse; Raviglione, Mario C.

2015-01-01

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. PMID:25792630

Predicting tuberculosis risk in the foreign-born population of British Columbia, Canada: study protocol for a retrospective population-based cohort study.

PubMed

Ronald, Lisa A; Campbell, Jonathon R; Balshaw, Robert F; Roth, David Z; Romanowski, Kamila; Marra, Fawziah; Cook, Victoria J; Johnston, James C

2016-11-25

Improved understanding of risk factors for developing active tuberculosis (TB) will better inform decisions about diagnostic testing and treatment for latent TB infection (LTBI) in migrant populations in low-incidence regions. We aim to examine TB risk factors among the foreign-born population in British Columbia (BC), Canada, and to create and validate a clinically relevant multivariate risk score to predict active TB. This retrospective population-based cohort study will include all foreign-born individuals who acquired permanent resident status in Canada between 1 January 1985 and 31 December 2013 and acquired healthcare coverage in BC at any point during this period. Multiple administrative databases and disease registries will be linked, including a National Immigration Database, BC Provincial Health Insurance Registration, physician billings, hospitalisations, drugs dispensed from community pharmacies, vital statistics, HIV testing and notifications, cancer, chronic kidney disease and dialysis treatment, and all TB and LTBI testing and treatment data in BC. Extended proportional hazards regression will be used to estimate risk factors for TB and to create a prognostic TB risk score. Ethical approval for this study has been obtained from the University of British Columbia Clinical Ethics Review Board. Once completed, study findings will be presented at conferences and published in peer-reviewed journals. An online TB risk score calculator will also be created. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

PubMed Central

Lala, Sanjay G.; Little, Kristen M.; Tshabangu, Nkeko; Moore, David P.; Msandiwa, Reginah; van der Watt, Martin; Chaisson, Richard E.; Martinson, Neil A.

2015-01-01

Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed

Cost effectiveness of interferon-gamma release assay for tuberculosis screening using three months of rifapentine and isoniazid among long-term expatriates from low to high incidence countries.

PubMed

Kowada, Akiko

Long-term expatriates from low to high tuberculosis (TB) incidence countries get high rates of active TB and latent TB infection (LTBI). TB screening for expatriates is important for occupational health. Interferon-gamma release assays are more accurate than tuberculin skin test (TST). Rifapentine plus isoniazid for 3 months (3HP) is as effective as 9 months of isoniazid (9H) with a higher treatment-completion rate. Decision trees and Markov models were constructed using a societal perspective on a lifetime horizon. The target population was a hypothetical cohort of 30 year-old expatriates. Seven strategies; TST with 3HP or 9H, QuantiFERON ® -TB Gold In-Tube (QFT) with 3HP or 9H, T-SPOT ® .TB (TSPOT) with 3HP or 9H and chest X-ray examination (CXR) were modeled. The main outcome measure of effectiveness was quality-adjusted life-years (QALYs) gained. QFT with 3HP yielded the greatest benefits with the lowest cost ($US 674.8; 25.95660 QALYs [year 2012 values]). CXR was the least cost-effective ($US 13,666.8; 24.62917 QALYs). Cost-effectiveness was sensitive to adherence rate of 3HP and QFT specificity, but not to BCG vaccination rate. Entry LTBI screening using QFT treated with 3HP is recommended on the basis of cost effectiveness among long-term expatriates from low to high incidence countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diabetes and pre-diabetes among household contacts of tuberculosis patients in India: is it time to screen them all?

PubMed

Shivakumar, S V B Y; Chandrasekaran, P; Kumar, A M V; Paradkar, M; Dhanasekaran, K; Suryavarshini, N; Thomas, B; Kohli, R; Thiruvengadam, K; Kulkarni, V; Hannah, L E; Sivaramakrishnan, G N; Pradhan, N; Dolla, C; Gupte, A; Ramachandran, G; DeLuca, A; Meshram, S; Bhardawaj, R; Bollinger, R C; Golub, J; Selvaraj, K; Gupte, N; Swaminathan, S; Mave, V; Gupta, A

2018-06-01

Pre-diabetes mellitus (pre-DM) and DM increase the risk of developing tuberculosis (TB). Screening contacts of TB patients for pre-DM/DM and linking them to care may mitigate the risk of developing TB and improve DM management. To measure the prevalence of pre-DM/DM and associated factors among the adult household contacts (HHCs) of pulmonary TB patients. Between August 2014 and May 2017, adult HHCs of newly diagnosed adult PTB patients in Pune and Chennai, India, had single blood samples tested for glycosylated haemoglobin (HbA1c) at enrolment. DM was defined as previously diagnosed, self-reported DM or HbA1c 6.5%, and pre-DM as HbA1c between 5.7% and 6.4%. Latent tuberculous infection (LTBI) was defined as a positive tuberculin skin test (5 mm induration) or QuantiFERON® Gold In-Tube (0.35 international units/ml). Of 652 adult HHCs, 175 (27%) had pre-DM and 64 (10%) had DM. Forty (64%) HHCs were newly diagnosed with DM and 48 (75%) had poor glycaemic control (HbA1c 7.0%). Sixty-eight (22%) pre-DM cases were aged 18-34 years. Age 35 years, body mass index 25 kg/m2, chronic disease and current tobacco smoking were significantly associated with DM among HHCs. Adult HHCs of TB patients in India have a high prevalence of undiagnosed DM, pre-DM and LTBI, putting them at high risk for developing TB. Routine DM screening should be considered among all adult HHCs of TB.

Tuberculosis in the immigrant population in Italy: state-of-the-art review.

PubMed

Scotto, Gaetano; Fazio, Vincenzina; Lo Muzio, Lorenzo

2017-09-01

Although the incidence of tuberculosis (TB) has been decreasing in the European Union/European Economic Area (EU/EEA) in recent decades, specific subgroups of the population, such as immigrants, remain at high risk of the disease. Immigration from areas of high incidence is thought to have fuelled the resurgence of TB in areas of low incidence. Indeed, while immigrants have a high risk of acquiring TB prior to migration, after migration they are exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty, stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse and limited access to health care. In Italy as well, TB has increasingly become a disease for specific population subgroups such as immigrants and in urban settings often driven by reactivation of imported latent TB infection (LTBI). In this paper we present an analysis of the national scientific literature from recent years in order to estimate the burden of TB in foreign-born populations, to establish the burden of TB in migrants by gender, age group and country of origin as well as other relevant subgroups, and evaluate the clinical manifestations of latent or active tuberculosis and treatment response.

Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age.

PubMed

Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

2016-01-01

Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age.

Granulysin-Expressing CD4+ T Cells as Candidate Immune Marker for Tuberculosis during Childhood and Adolescence

PubMed Central

Mueller, Henrik; Faé, Kellen C.; Magdorf, Klaus; Ganoza, Christian A.; Wahn, Ulrich; Guhlich, Ute; Feiterna-Sperling, Cornelia; Kaufmann, Stefan H. E.

2011-01-01

Background Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. Methods Peripheral blood mononuclear cells (PBMC) from children and adolescents (1–17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4+ CD45RO+ memory T cells. Results CD4+ CD45RO+ T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSElowCD4+CD45RO+) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4+ T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. Conclusions Our data suggest granulysin expression by CD4+ memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence. PMID:22216262

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

PubMed

Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-06-01

To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Biologics and mycobacterial diseases].

PubMed

Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

ERIC Educational Resources Information Center

Migrant Clinicians Network, Inc., Austin, TX.

A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

Low Yield of Chest Radiography in a Large Tuberculosis Screening Program1

PubMed Central

Pollock, Nira R.

2010-01-01

Purpose: To assess the frequency and spectrum of abnormalities on routine screening chest radiographs in the pre-employment evaluation of health care workers with positive tuberculin skin test (TST) results. Materials and Methods: The institutional review board approved this HIPAA-compliant retrospective study and waived the need for written informed patient consent. Chest radiographic reports of all 2586 asymptomatic individuals with positive TST results who underwent pre-employment evaluation between January 1, 2003, and December 31, 2007, were evaluated to determine the frequency of detection of evidence of active tuberculosis (TB) or latent TB infection (LTBI) and the spectrum of imaging findings. All chest radiographs interpreted as positive were reviewed by an experienced board-certified radiologist. If there was a discrepancy between the two readings, a second experienced radiologist served as an independent and final arbiter. Any follow-up chest radiographs or computed tomographic images that had been acquired by employee health services or by the employee’s private physician as a result of a suspected abnormality detected at initial screening were also evaluated. Results: Of the 159 (6.1%) chest radiographic examinations that yielded abnormal results, there were no findings that were consistent with active TB. There were 92 cases of calcified granulomas, calcified lymph nodes, or both; 25 cases of apical pleural thickening; 16 cases of fibrous scarring; and 31 cases of noncalcified nodules. All cases of fibrous scarring involved an area smaller than 2 cm2. All noncalcified nodules were 4 mm in diameter or smaller, with the exception of one primary lung malignancy and one necrotizing granuloma (negative for acid-fast bacilli) that grew Mycobacterium kansasii on culture. Conclusion: Universal chest radiography in a large pre-employment TB screening program was of low yield in the detection of active TB or increased LTBI reactivation risk, and it provided

Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

PubMed Central

Pitabut, Nada; Sakurada, Shinsaku; Tanaka, Takahiro; Ridruechai, Chutharut; Tanuma, Junko; Aoki, Takahiro; Kantipong, Pacharee; Piyaworawong, Surachai; Kobayashi, Nobuyuki; Dhepakson, Panadda; Yanai, Hideki; Yamada, Norio; Oka, Shinichi; Okada, Masaji; Khusmith, Srisin; Keicho, Naoto

2013-01-01

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. PMID:23801887

PEPFAR support for the scaling up of collaborative TB/HIV activities.

PubMed

Howard, Andrea A; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L

2012-08-15

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

PEPFAR Support for the Scaling Up of Collaborative TB/HIV Activities

PubMed Central

Howard, Andrea A.; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D.; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L.

2014-01-01

The US President’s Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR’s TB/HIV programming is based on the World Health Organization 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR’s support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy (IPT), intensified case finding and infection control. Issues to be addressed by future programming include accelerating implementation of IPT, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation. PMID:22797735

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

PubMed Central

Myers, Amy J.; Jarvela, Jessica; Flynn, JoAnne; Rutledge, Tara; Bonfield, Tracey

2016-01-01

Immune cells of the distal airways serve as “first responders” of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD4+cells but more CD8+ and CD4+CD8+ double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease). Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung. PMID:27509488

Dual skin tests with Mycobacterium avium sensitin and PPD to detect misdiagnosis of latent tuberculosis infection.

PubMed

Larson, E M; O'Donnell, M; Chamblee, S; Horsburgh, C R; Marsh, B J; Moreland, J D; Johnson, L S; von Reyn, C Fordham

2011-11-01

A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

Tuberculosis and infection control.

PubMed

Karim, Kelvin

Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings.

A systematic review of economic models used to assess the cost-effectiveness of strategies for identifying latent tuberculosis in high-risk groups.

PubMed

Auguste, Peter; Tsertsvadze, Alexander; Court, Rachel; Pink, Joshua

2016-07-01

Timely diagnosis and treatment of latent tuberculosis infection (LTBI) through screening remains a key public health priority. Although globally it is recommended to screen people at high risk of developing TB, the economic evidence underpinning these recommendations is limited. This review critically appraised studies that had used a decision-analytical modelling framework to estimate the cost-effectiveness of interferon gamma release assays (IGRAs) compared to tuberculin skin test (TST) for detecting LTBI in high risk populations. A comprehensive search of MEDLINE, EMBASE, NHS-EED was undertaken from 2009 up to June 2015. Studies were screened and extracted by independent reviewers. The study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and the Philips' checklist, respectively. A narrative synthesis of the included studies was undertaken. Ten studies were included in this review. Two economic evaluations were conducted in a child population, six in an immunocompromised population and two in a recently arrived population from a country with a high incidence of TB. Most studies (n = 7) used a decision tree structure with Markov nodes. In general, all models were clearly described in terms of reporting quality, but were subject to limitations to structure and model inputs. Models have not elaborated on their setting or the perspective of the studies was not consistent with their analyses. Other concerns were related to derivation of prevalence, test accuracy and transition probabilities. Current methods available highlight limitations in the clinical effectiveness literature, model structures and assumptions, which impact on the robustness of the cost-effectiveness results. These models available are useful, but limited on the information that can be used to inform on future cost-effectiveness analysis. Until consideration is given on deriving the performance of tests used to identify LTBI that progresses to

Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting.

PubMed

Mathad, Jyoti S; Bhosale, Ramesh; Sangar, Vikrant; Mave, Vidya; Gupte, Nikhil; Kanade, Savita; Nangude, Ashwini; Chopade, Kavita; Suryavanshi, Nishi; Deshpande, Prasad; Kulkarni, Vandana; Glesby, Marshall J; Fitzgerald, Daniel; Bharadwaj, Renu; Sambarey, Pradeep; Gupta, Amita

2014-01-01

Targeted screening for latent TB infection (LTBI) in vulnerable populations is a recommended TB control strategy. Pregnant women are at high risk for developing TB and likely to access healthcare, making pregnancy an important screening opportunity in developing countries. The sensitivity of the widely-used tuberculin skin test (TST), however, may be reduced during pregnancy. We performed a cross-sectional study comparing the TST with the QuantiFERON Gold In-tube (QGIT) in 401 HIV-negative women presenting antepartum (n = 154), at delivery (n = 148), or postpartum (n = 99) to a government hospital in Pune, India. A subset of 60 women enrolled during pregnancy was followed longitudinally and received both tests at all three stages of pregnancy. The QGIT returned significantly more positive results than the TST. Of the 401 women in the cross-sectional study, 150 (37%) had a positive QGIT, compared to 59 (14%) for the TST (p<0.005). Forty-nine (12%) did not have their TST read. Of 356 who had both results available, 46 (13%) were concordant positive, 91 (25%) were discordant (12 (3%) TST+/QGIT-; 79 (22%) TST-/QGIT+), and 206 (57%) concordant negative. Comparison by stage of pregnancy revealed that QGIT percent positivity remained stable between antepartum and delivery, unlike TST results (QGIT 31-32% vs TST 11-17%). Median IFN-γ concentration was lower at delivery than in antepartum or postpartum (1.66 vs 2.65 vs 8.99 IU/mL, p = 0.001). During postpartum, both tests had significantly increased positives (QGIT 31% vs 32% vs 52%, p = 0.01; TST 17% vs 11% vs 25%, p<0.005). The same trends were observed in the longitudinal subset. Timing and choice of LTBI test during pregnancy impact results. QGIT was more stable and more closely approximated the LTBI prevalence in India. But pregnancy stage clearly affects both tests, raising important questions about how the complex immune changes brought on by pregnancy may impact LTBI screening.

Added value of interferon-gamma release assays in screening for tuberculous infection in the Netherlands.

PubMed

Erkens, C G M; Dinmohamed, A G; Kamphorst, M; Toumanian, S; van Nispen-Dobrescu, R; Alink, M; Oudshoorn, N; Mensen, M; van den Hof, S; Borgdorff, M; Verver, S

2014-04-01

Interferon-gamma release assays (IGRAs) are reported to be more specific for the diagnosis of latent tuberculous infection (LTBI) than the tuberculin skin test (TST). The two-step procedure, TST followed by an IGRA, is reported to be cost-effective in high-income countries, but it requires more financial resources. To assess the added value of IGRA compared to TST alone in the Netherlands. Test results and background data on persons tested with an IGRA were recorded by the Public Municipal Health Services in a web-based database. The number of persons diagnosed with LTBI using different screening algorithms was calculated. In those tested with an IGRA, at least 60% of persons who would have been diagnosed with LTBI based on TST alone had a negative IGRA. Among those with a TST reaction below the cut-off for the diagnosis of LTBI, 13% had a positive IGRA. For 41% of persons tested with an IGRA after TST, the IGRA influenced whether or not an LTBI diagnosis would be made. With the IGRA as reference standard, a high proportion of persons in low-prevalence settings are treated unnecessarily for LTBI if tested with TST alone, while a small proportion eligible for preventive treatment are missed. Incremental costs of the two-step strategy seem to be balanced by the improved targeting of preventive treatment.

Migration, TB control and elimination: Whom to screen and treat.

PubMed

Rendon, A; Centis, R; Zellweger, J-P; Solovic, I; Torres-Duque, C A; Robalo Cordeiro, C; de Queiroz Mello, F C; Manissero, D; Sotgiu, G

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease. Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

BUTIMBA: Intensifying the Hunt for Child TB in Swaziland through Household Contact Tracing

PubMed Central

Alonso Ustero, Pilar; Golin, Rachel; Anabwani, Florence; Mzileni, Bulisile; Sikhondze, Welile; Stevens, Robert

2017-01-01

Background Limited data exists to inform contact tracing guidelines in children and HIV-affected populations. We evaluated the yield and additionality of household contact and source case investigations in Swaziland, a TB/HIV high-burden setting, while prioritizing identification of childhood TB. Methods In partnership with 7 local TB clinics, we implemented standardized contact tracing of index cases (IC) receiving TB treatment. Prioritizing child contacts and HIV-affected households, screening officers screened contacts for TB symptoms and to identify risk factors associated with TB. We ascertained factors moderating the yield of contact tracing and measured the impact of our program by additional notifications. Results From March 2013 to November 2015, 3,258 ICs (54% bacteriologically confirmed; 70% HIV-infected; 85% adults) were enrolled leading to evaluation of 12,175 contacts (median age 18 years, IQR 24–42; 45% children; 9% HIV-infected). Among contacts, 196 TB cases (56% bacteriologically confirmed) were diagnosed resulting in a program yield of 1.6% for all forms of TB. The number needed to screen (NNS) to identify a bacteriologically confirmed TB case or all forms TB case traced from a child IC <5 years was respectively 62% and 40% greater than the NNS for tracing from an adult IC. In year one, we demonstrated a 32% increase in detection of bacteriologically confirmed child TB. Contacts were more likely to have TB if <5 years (OR = 2.0), HIV-infected (OR = 4.9), reporting ≥1 TB symptoms (OR = 7.7), and sharing a bed (OR = 1.7) or home (OR = 1.4) with the IC. There was a 1.4 fold increased chance of detecting a TB case in households known to be HIV-affected. Conclusion Contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting potential to integrate TB

Concordance between the tuberculin skin test and interferon gamma release assay (IGRA) for diagnosing latent tuberculosis infection in patients with systemic lupus erythematosus and patient characteristics associated with an indeterminate IGRA.

PubMed

Cho, H; Kim, Y W; Suh, C-H; Jung, J-Y; Um, Y-J; Jung, J-H; Kim, H-A

2016-10-01

We investigated the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB gold (QFT-G) assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with systemic lupus erythematosus (SLE). Furthermore, we evaluated the factors associated with indeterminate results in the QFT-G assay in patients with SLE. We enrolled 136 patients with SLE prospectively, and compared them to 66 patients with rheumatoid arthritis (RA). In addition to the TST, QFT-G assay, patients' medications, and Bacillus Calmette-Guérin (BCG) vaccination status were also investigated. A positive TST or QFT-G assay result without an active tuberculosis lesion on chest x-ray was considered to indicate a diagnosis of LTBI. The prevalence of LTBI was 26.5% in patients with SLE and 30.3% in patients with RA. The agreement between the TST and QFT-G assay was fair in SLE patients, but poor in RA patients. BCG vaccination was one factor associated with discordance between TST and QFT-G. Older age and higher SLE Disease Activity Index (SLEDAI) score were associated with a negative TST/positive QFT-G result in patients with SLE. Higher SLEDAI score and increased glucocorticoid dose were associated with an indeterminate result in the QFT-G assay for patients with SLE. Agreement between the QFT-G assay and TST in patients with SLE was found to be fair. However, BCG vaccination status, age, and SLEDAI score are all factors that could result in discordance between the two tests. Indeterminate results from the QFT-G assay may be caused by a higher SLEDAI score or increased glucocorticoid dose. © The Author(s) 2016.

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.

PubMed

Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F

2016-01-01

Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

PubMed

Igari, Hidetoshi; Watanabe, Akira; Ichimura, Yasunori; Sakurai, Takayuki; Taniguchi, Toshibumi; Ishiwada, Naruhiko

2017-04-01

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities.

PubMed

Tuite, Ashleigh R; Gallant, Victor; Randell, Elaine; Bourgeois, Annie-Claude; Greer, Amy L

2017-01-13

In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density. The outcomes of interest were incident TB infections and total diagnosed active TB disease over a 10- year time period. Model-projected incidence in the absence of additional interventions was highly variable (range: 33-369 cases) over 10 years. Compared to the 'no additional intervention' scenario, reducing the time between onset of active TB disease and initiation of treatment reduced both the number of new TB infections (47% reduction, relative risk of TB = 0.53) and diagnoses of active TB disease (19% reduction, relative risk of TB = 0.81). Expanding general population screening was also projected to reduce the burden of TB, although these findings were sensitive to assumptions around the relative amount of transmission occurring outside of households. Other potential interventions examined in the model (school-based screening, rapid contact tracing, and reduced household density) were found to have limited effectiveness. In a region of northern Canada experiencing a significant TB burden, more rapid treatment initiation in active TB cases was the most impactful intervention evaluated. Mathematical modeling can provide guidance for allocation of limited resources in a way that minimizes disease transmission and protects population health.

Tuberculosis Knowledge, Awareness, and Stigma Among African-Americans in Three Southeastern Counties in the USA: a Qualitative Study of Community Perspectives.

PubMed

Royce, Rachel A; Colson, Paul W; Woodsong, Cynthia; Swinson-Evans, Tammeka; Walton, Wanda; Maiuri, Allison; DeLuca, Nickolas

2017-02-01

To inform strategies to address the tuberculosis (TB) excess among US-born African-Americans, we sought to understand the TB experience in the most highly affected southeastern communities. We conducted semi-structured interviews and focus groups in three communities with a TB excess-urban (Georgia and Tennessee) and rural (North Carolina). Participants from five groups provided diverse perspectives-African-Americans: patients with TB disease or latent TB infection (LTBI), or at high risk of contracting TB; and local community leaders and TB program staff. Few differences emerged between sites. Many participants demonstrated low levels of knowledge and awareness and held many misconceptions about TB. Patients expressed a preference for verbal communication of medical information. Patients reported fear of stigmatization and shunning, but few experienced discrimination. Patient trust for TB program staff was high, though community leaders often assumed the opposite. The findings will help guide interventions to improve knowledge and awareness regarding TB, including specific attention to the role of public and private health care providers in dispelling persistent misinformation about TB. The insight from these communities will help build the scientific foundation required to effectively eliminate health inequities.

Evaluation of the performance of two tuberculosis interferon gamma release assays (IGRA-ELISA and T-SPOT.TB) for diagnosing Mycobacterium tuberculosis infection.

PubMed

Wang, Linchuan; Tian, Xu-Dong; Yu, Yan; Chen, Wei

2018-04-01

The IGRA-ELISA and T-SPOT.TB are widely used in China. The aim of the study was to evaluate the performance of the two assays in diagnosis Mycobacterium tuberculosis infection. Of the 3727 patients in the study, 204 underwent testing using both the T-SPOT.TB and IGRA-ELISA, 1794 were tested using the T-SPOT.TB only, and 1729 were tested using the IGRA-ELISA only. The positive rate and consistency of the two assays were analyzed, and their sensitivity and specificity for diagnosing active tuberculosis were compared. There were no significant differences in the positive rate between the T-SPOT.TB test (25.8%) and IGRA-ELISA (28.6%), p = .065. The two assays were highly consistent, with a kappa value of 0.852 (p < .0001) and a total coincidence rate of 92.7%. For the diagnosis of active tuberculosis, the sensitivity and specificity values of the T-SPOT.TB test were 82.9% (107/129) and 78.6% (1309/1665), respectively, and those of IGRA-ELISA were 81.7% (94/115) and 75.2% (1214/1614), respectively. There were no significant differences in sensitivity (p > .05), but the specificity of the T-SPOT.TB test was slightly higher than that of IGRA-ELISA (p = .023). Both in terms of diagnosing M. tuberculosis infection and ruling out active tuberculosis, the performance of the IGRA-ELISA-a simple, almost labor-free assay that allows simultaneous processing of a very large number of samples-was well-matched with that of T-SPOT.TB test. However, IGRAs cannot be used as the only test to diagnose active tuberculosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk factors associated with latent tuberculosis infection in Mexican American children.

PubMed

Young, Janine; O'Connor, Mary E

2005-06-01

To determine risk factors that are associated with the presence of latent tuberculosis infection (LTBI) in Mexican American children. In this prospective cohort study, we administered tuberculin skin tests (TSTs) and a tuberculosis (TB) risk factor questionnaire to children who were aged 1 to 18 years in immigrant families at a Denver inner-city community health center and elementary school-based health center. Information requested on the questionnaire included child demographics, child and parent birth location, Bacille Calmette-Guérin (BCG) vaccination, and a history and the duration of child and family travel to and visitors from countries where TB is endemic. TST results were read at 48 to 72 hours and were interpreted as positive at 5- and 10-mm induration, depending on risk factor history. All participants received $5 coupons on return for TST reading. Of 584 children enrolled, 96% returned for TST evaluation, median age was 4 years, 48.6% were male, 98.5% were Latino, 66.3% were born in the United States, and 33% were born in Mexico. Overall, 12.4% of children had positive TSTs. For all children in the study, a positive TST was associated with birth in Mexico and no BCG received (adjusted odds ratio [OR]: 15.7; 95% confidence interval [CI]: 1.5-165.2), birth in Mexico and received BCG (adjusted OR: 29; 95% CI: 12.7-66.1), birth in the United States and received BCG (adjusted OR: 9.1; 95% CI: 2.4-34.1), and child travel to Mexico (adjusted OR: 2.8;95% CI: 1.5-5.4). Risk factors for having a positive TST in the 387 children who were born in the United States were travel to Mexico (unable to calculate the OR because all had traveled to Mexico), older age (median: 6 years; adjusted OR: 1.2/year; 95% CI: 1.02-1.40), and a history of BCG vaccination (adjusted OR: 8.2; 95% CI: 2.0-34.0). For the 195 children who were born in Mexico, logistic regression of the following variables showed that none of the variables remained in the model: child age, gender, BCG

Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless Populations in the United States: a meta-analysis.

PubMed

Parriott, Andrea; Malekinejad, Mohsen; Miller, Amanda P; Marks, Suzanne M; Horvath, Hacsi; Kahn, James G

2018-04-12

Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of

Outbreak column 21: Tuberculosis (TB): Still a nosocomial threat.

PubMed

Curran, Evonne T

2018-05-01

This outbreak column explores the epidemiology and infection prevention guidance on tuberculosis (TB) in the UK. The column finds that, at present, national guidance leaves UK hospitals ill-prepared to prevent nosocomial TB transmission. Reasons for this conclusion are as follows: (1) while TB is predominantly a disease that affects people with 'social ills', it has the potential to infect anyone who is sufficiently exposed; (2) nosocomial transmission is documented throughout history; (3) future nosocomial exposures may involve less treatable disease; and (4) current UK guidance is insufficient to prevent nosocomial transmission and is less than that advocated by the World Health Organization and the Centers for Disease Control and Prevention.

Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis among TB suspects in a rural community in Southwest Ethiopia

PubMed Central

2012-01-01

Background In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB) is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium tuberculosis isolates in Southwest Ethiopia. Methods A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the Mycobacterium tuberculosis isolates. Results Majority of the TB suspects were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7%) belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six new spoligotype patterns of Mycobacterium tuberculosis, not present in the international database (SpolDB4) were identified. None of the rural residents was HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV. Conclusion The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate in Ethiopia. A large

A world of cities and the end of TB

PubMed Central

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-01-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

Voices of decision makers on evidence-based policy: A case of evolving TB/HIV co-infection policy in India.

PubMed

Reddy, K Srikanth; Sahay, Seema

2016-01-01

This study explores decision makers' perspectives on evidence-based policy (EBP) development using the case of TB/HIV co-infection in India. Twelve in-depth interviews were conducted with purposively selected key national and international policy decision makers in India. Verbatim transcripts were processed and analysed thematically using QSR (NUD*IST 6). The decision makers were unequivocal in recognizing the TB/HIV co-infection as an important public health issue in India and stated the problem to be different than Africa. The need of having a "third programme" for co-infection was not felt. According to them, the public health management of this co-infection must be within the realm of these two programmes. The study also emphasized on decision makers' perspectives on evidence and the process of utilization of evidence for decision-making for co-infection. Study findings showed global evidence was not always accepted by the decision makers and study shows several examples of decision makers demanding local evidence for policy decisions. Decision makers did make interim policies based on global evidence but most of the time their mandate was to get local evidence. Thus, operations research/implementation science especially multi-centric studies emerge as important strategy for EBP development. Researcher-policy maker interface was a gap where role of researcher as aggressive communicator of research findings was expected.

Layered rare-earth hydroxide (LRH, R = Tb, Y) composites with fluorescein: delamination, tunable luminescence and application in chemosensoring for detecting Fe(iii) ions.

PubMed

Su, Feifei; Guo, Rong; Yu, Zihuan; Li, Jian; Liang, Zupei; Shi, Keren; Ma, Shulan; Sun, Genban; Li, Huifeng

2018-04-17

We demonstrate a novel example of tunable luminescence and the application of the delaminated FLN/OS-LRH composites (LRHs are layered rare-earth hydroxides, R = Tb, Y; FLN is the fluorescein named 2-(6-hydroxy-3-oxo-(3H)-xanthen-9-yl)benzoic acid; OS is the anionic surfactant 1-octane sulfonic acid sodium) in detecting Fe(iii) ions. The FLNxOS1-x species (x = 0.02, 0.05, 0.10, and 0.20) are intercalated into the LTbyY1-yH layers (y = 1, 0.9, 0.7, 0.5, 0.3, 0.1 and 0) by ion exchange reactions to yield the composites FLNxOS1-x-LTbyY1-yH. In the solid state, the LYH composites display green emission (564 nm) arising from the organic FLN, while in LTbH composites, the luminescence of the Tb3+ in the layers (545 nm) and the FLN in the interlayers is co-quenched. In the delaminated state in formamide (FM), FLNxOS1-x-LTbH composites display green to yellowish-green luminescence (540-574 nm) following the increasing FLN/OS ratio; while the FLN0.02OS0.98-LTbyY1-yH composites show green emission at ∼540 nm. The fluorescence lifetimes of the composites (4.22-4.63 ns) are comparable to the free FLN-Na, and the quantum yields (31.62-78.70%) of the composites especially that (78.70%) of the FLN0.02OS0.98-LYH are much higher than that (28.40%) of free FLN-Na. The recognition ability of the FLN0.02OS0.98-LYH composite for metal cations is researched. The delaminated FLN0.02OS0.98-LYH colloidal suspension exhibits high selectivity for Fe3+ over other ions (Mg2+, Al3+, Ni2+, Co2+, Cu2+, Zn2+, Mn2+, Pb2+, and Cd2+) with fluorescence quenching, which can work as a kind of turn-off fluorescence sensor for the detection of Fe3+. The detection limit of Fe3+ is determined to be 2.58 × 10-8 M and the quenching constant (Ksv) is 1.70 × 103 M-1. This is the first work on LRH materials working as a chemosensor for recognising metal cations. It provides a new approach for the design of LRH materials to be applied in fluorescence chemosensing.

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

PubMed

Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S

2014-10-01

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

The prevalence of HIV among adults with pulmonary TB at a population level in Zambia.

PubMed

Chanda-Kapata, Pascalina; Kapata, Nathan; Klinkenberg, Eveline; Grobusch, Martin P; Cobelens, Frank

2017-03-29

Tuberculosis and HIV co-infection is one of the main drivers of poor outcome for both diseases in Zambia. HIV infection has been found to predict TB infection/disease and TB has been reported as a major cause of death among individuals with HIV. Improving case detection of TB/HIV co-infection has the potential to lead to early treatment of both conditions and can impact positively on treatment outcomes. This study was conducted in order to determine the HIV prevalence among adults with tuberculosis in a national prevalence survey setting in Zambia, 2013-2014. A countrywide cross sectional survey was conducted in 2013/2014 using stratified cluster sampling, proportional to population size for rural and urban populations. Each of the 66 countrywide clusters represented one census supervisory area with cluster size averaging 825 individuals. Socio-demographic characteristics were collected during a household visit by trained survey staff. A standard symptom-screening questionnaire was administered to 46,099 eligible individuals across all clusters, followed by chest x-ray reading for all eligible. Those symptomatic or with x-ray abnormalities were confirmed or ruled out as TB case by either liquid culture or Xpert MTBRif performed at the three central reference laboratories. HIV testing was offered to all participants at the survey site following the national testing algorithm with rapid tests. The prevalence was expressed as the proportion of HIV among TB cases with 95% confidence limits. A total of 265/6123 (4.3%) participants were confirmed of having tuberculosis. Thirty-six of 151 TB survey cases who accepted HIV testing were HIV-seropositive (23.8%; 95% CI 17.2-31.4). The mean age of the TB/HIV cases was 37.6 years (range 24-70). The majority of the TB/HIV cases had some chest x-ray abnormality (88.9%); were smear positive (50.0%), and/or had a positive culture result (94.4%). None of the 36 detected TB/HIV cases were already on TB treatment, and 5/36 (13

Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

MedlinePlus

... Task Force Tuberculosis: The Connection between TB and HIV Recommend on Facebook Tweet Share Compartir Order this ... if I am infected with both TB and HIV? If you have HIV, it is important to ...

Multidrug-Resistant Tuberculosis (MDR TB)

MedlinePlus

... prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts. Ask about administrative and ...

Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

PubMed Central

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients. PMID:26075241

Immunoendocrine interactions during HIV-TB coinfection: implications for the design of new adjuvant therapies.

PubMed

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo; Quiroga, Maria Florencia

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB.

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Sun, Huishan; Gao, Mengqiu; Du, Fengjiao; Xing, Aiying; Du, Boping; Sun, Qi; Wei, Rongrong; Gu, Shuxiang; Zhang, Zongde

2015-04-01

To investigate the risk factors for false-negative T-SPOT.TB results in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic characters and clinical laboratory findings were compared between true-positive and false-negative T-SPOT.TB groups. Of 1928 suspected TB patients, 774 (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11-4.58], over-weight (BMI ≥ 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92) were independent risk factors for false-negative T-SPOT.TB results in PTB patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed an independent association with false-negative T-SPOT.TB results. Careful interpretation of negative T-SPOT.TB results is necessary in older patients with suspected PTB or EPTB, and in PTB patients who are over-weight or have had longer periods of illness before hospitalization. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparison of interferon-γ release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers.

PubMed

de Souza, Fernanda Mattos; do Prado, Thiago Nascimento; Pinheiro, Jair dos Santos; Peres, Renata Lyrio; Lacerda, Thamy Carvalho; Loureiro, Rafaela Borge; Carvalho, Jose Américo; Fregona, Geisa; Dias, Elias Santos; Cosme, Lorrayne Beliqui; Rodrigues, Rodrigo Ribeiro; Riley, Lee Wood; Maciel, Ethel Leonor Noia

2014-01-01

An interferon-γ release assay, QuantiFERON-TB (QFT) test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care work (HCW) in Brazil. A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5 mm and ≥10 mm as cut-off points. We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k = 0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group, risk factors for discordance in the TST+/QFT- group with TST cut-off of ≥5 mm included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years [OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of ≥10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly associated with the TST+/QFT- group. No statistically significant associations were found among the TST-/QFT+ discordant group with either TST cut-off value. Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed.

Tuberculosis Screening by Tuberculosis Skin Test or QuantiFERON®-TB Gold In-Tube Assay among an Immigrant Population with a High Prevalence of Tuberculosis and BCG Vaccination

PubMed Central

Painter, John A.; Graviss, Edward A.; Hai, Hoang Hoa; Nhung, Duong Thi Cam; Nga, Tran Thi Thanh; Ha, Ngan P.; Wall, Kirsten; Loan, Le Thien Huong; Parker, Matt; Manangan, Lilia; O’Brien, Rick; Maloney, Susan A.; Hoekstra, R. M.; Reves, Randall

2013-01-01

Rationale Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth. Objectives 1. Compare the sensitivity of QuantiFERON ®-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR. Methods We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR. Results The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15–19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants. Conclusions During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.  PMID:24367546

A world of cities and the end of TB.

PubMed

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-03-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care

PubMed Central

Jackson-Morris, A.; Fujiwara, P. I.; Pevzner, E.

2016-01-01

SUMMARY The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a ‘syndemic’ due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the ‘MPO-WER’ package recommended by the World Health Organization’s Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID:26260816

Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

PubMed

Kerrigan, Deanna; Tudor, Carrie; Motlhaoleng, Katlego; Lebina, Limakatso; Qomfu, Cokiswa; Variava, Ebrahim; Chon, Sandy; Martinson, Neil; Golub, Jonathan E

2018-04-16

Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

PubMed

Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

2015-12-01

Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

Implementation of tuberculosis infection control measures in designated hospitals in Zhejiang Province, China: are we doing enough to prevent nosocomial tuberculosis infections?

PubMed Central

Chen, Bin; Liu, Min; Gu, Hua; Wang, Xiaomeng; Qiu, Wei; Shen, Jian; Jiang, Jianmin

2016-01-01

Objectives Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Design Cross-sectional survey using observation and interviews. Setting All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Primary and secondary outcome measures Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. Results The TB-designated hospitals treated a median of 3030 outpatients (IQR 764–7094) and 279 patients with confirmed TB (IQR 154–459) annually, and 160 patients with TB (IQR 79–426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. Conclusions TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission

HIV screening among TB patients and co-trimoxazole preventive therapy for TB/HIV patients in Addis Ababa: facility based descriptive study.

PubMed

Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

Agents of change: The role of healthcare workers in the prevention of nosocomial and occupational tuberculosis.

PubMed

Nathavitharana, Ruvandhi R; Bond, Patricia; Dramowski, Angela; Kotze, Koot; Lederer, Philip; Oxley, Ingrid; Peters, Jurgens A; Rossouw, Chanel; van der Westhuizen, Helene-Mari; Willems, Bart; Ting, Tiong Xun; von Delft, Arne; von Delft, Dalene; Duarte, Raquel; Nardell, Edward; Zumla, Alimuddin

2017-03-01

Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired well-being in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection (LTBI) can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Using a mathematical model to evaluate the efficacy of TB control measures.

PubMed Central

Gammaitoni, L.; Nucci, M. C.

1997-01-01

We evaluated the efficacy of recommended tuberculosis (TB) infection control measures by using a deterministic mathematical model for airborne contagion. We examined the percentage of purified protein derivative conversions under various exposure conditions, environmental controlstrategies, and respiratory protective devices. We conclude that environmental control cannot eliminate the risk for TB transmission during high-risk procedures; respiratory protective devices, and particularly high-efficiency particulate air masks, may provide nearly complete protection if used with air filtration or ultraviolet irradiation. Nevertheless, the efficiency of these control measures decreases as the infectivity of the source case increases. Therefore, administrative control measures (e.g., indentifying and isolating patients with infectious TB) are the most effective because they substantially reduce the rate of infection. PMID:9284378

Interleukin 1-beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in ART-treated HIV infected patients

PubMed Central

Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R.; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndung’u, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum

2016-01-01

Background Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. Methods Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points prior to TB recurrence were stimulated with ligands for Toll like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multi-color flow cytometry and intracellular cytokine staining was used to detect IL-1β, TNF-α, IL-12 and IP10 responses from monocytes and myeloid dendritic cells (mDCs). Results Elevated production of IL-1β from monocytes following TLR-2, TLR-4 and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs respectively). Conclusion Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB. PMID:27654812

HIV and intestinal parasites in adult TB patients in a teaching hospital in Northwest Ethiopia.

PubMed

Kassu, Afework; Mengistu, Getahun; Ayele, Belete; Diro, Ermias; Mekonnen, Firew; Ketema, Dereje; Moges, Feleke; Mesfin, Tsehay; Getachew, Assefa; Ergicho, Bahiru; Elias, Daniel; Wondmikun, Yared; Aseffa, Abraham; Ota, Fusao

2007-10-01

The level of HIV infection and intestinal parasitoses among TB patients was assessed in a hospital-based cross-sectional study involving 257 patients in Gondar, Ethiopia. In TB patients, our study reported co-infection with HIV (52.1%) and intestinal parasites (40.9%) The high prevalence of HIV and intestinal parasites indicates an increased morbidity inTB patients and emphasized the importance of continued HIV sero-surveillance, stool analysis and treatment.

Potential economic viability of two proposed rifapentine-based regimens for treatment of latent tuberculosis infection.

PubMed

Holland, David P; Sanders, Gillian D; Hamilton, Carol D; Stout, Jason E

2011-01-01

Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.

Performance of TB immunodiagnostic tests in Eurasian badgers (Meles meles) of different ages and the influence of duration of infection on serological sensitivity

PubMed Central

2009-01-01

Background In parts of Great Britain and Ireland, Eurasian badgers (Meles meles) constitute a reservoir of Mycobacterium bovis infection and a potential source of infection for cattle. In vitro diagnostic tests for live badgers are an important component of strategies to control TB in this species. Immunological tests have been developed for badgers, although little is known about the influence of the age of the animal on test performance. To address this, we evaluated the performance of three immunological tests for badgers with respect to the age of the animal: the Brock Test and BrockTB STAT-PAK® serological tests and the recently developed interferon-gamma enzyme immunoassay (IFNγ EIA). Data published elsewhere suggested that seropositivity was associated with more progressive forms of TB in the badger. To gain further evidence for this, we used longitudinal data from a well-studied population of badgers to test for an association between the sensitivity of the Brock Test and the duration of TB infection. Results Sensitivity of the two serological tests was approximately 54% for both cubs and adults. Sensitivity of the IFNγ EIA was lower in cubs (57%) compared with adults (85%) when a common cut-off value was used to define test positivity. Taking data from the cubs alone, the IFNγ EIA cut-off value could be adjusted to increase the sensitivity to 71% with no loss in specificity. As a general observation, specificity of all tests was higher in cubs, although only significantly so in the case of the Brock Test. Using logistic regression analysis to adjust for age, sensitivity of the Brock Test was significantly lower at first culture positive event (58%), but increased to >80% as infection progressed. Conclusion These data suggest that serodiagnosis could be a valuable tool for detecting a higher proportion of badgers with the greatest probability of transmitting infection. The age category of the badger appeared to exert little influence on the performance

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide.

PubMed

Das, Mrinalini; Isaakidis, Petros; Van den Bergh, Rafael; Kumar, Ajay M V; Nagaraja, Sharath Burugina; Valikayath, Asmaa; Jha, Santosh; Jadhav, Bindoo; Ladomirska, Joanna

2014-01-01

Management of multidrug-resistant TB (MDR-TB) patients co-infected with human immunodeficiency virus (HIV) is highly challenging. Such patients are subject to long and potentially toxic treatments and may develop a number of different psychiatric illnesses such as anxiety and depressive disorders. A mental health assessment before MDR-TB treatment initiation may assist in early diagnosis and better management of psychiatric illnesses in patients already having two stigmatising and debilitating diseases. To address limited evidence on the baseline psychiatric conditions of HIV-infected MDR-TB patients, we aimed to document the levels of depressive symptoms at baseline, and any alteration following individualized clinical and psychological support during MDR-TB therapy, using the Patient Health Questionnaire-9 (PHQ-9) tool, among HIV-infected patients. This was a retrospective review of the medical records of an adult (aged >15 years) HIV/MDR-TB cohort registered for care during the period of August 2012 through to March 2014. A total of 45 HIV/MDR-TB patients underwent baseline assessment using the PHQ-9 tool, and seven (16%) were found to have depressive symptoms. Of these, four patients had moderate to severe depressive symptoms. Individualized psychological and clinical support was administered to these patients. Reassessments were carried out for all patients after 3 months of follow-up, except one, who died during the period. Among these 44 patients, three with baseline depressive symptoms still had depressive symptoms. However, improvements were observed in all but one after 3 months of follow-up. Psychiatric illnesses, including depressive symptoms, during MDR-TB treatment demand attention. Routine administration of baseline mental health assessments by trained staff has the potential to assist in determining appropriate measures for the management of depressive symptoms during MDR-TB treatment, and help in improving overall treatment outcomes. We recommend

Multidrug-resistant Mycobacterium tuberculosis in HIV-Infected Persons, Peru

PubMed Central

Campos, Pablo E.; Suarez, Pedro G.; Sanchez, Jorge; Zavala, David; Arevalo, Jorge; Ticona, Eduardo; Nolan, Charles M.; Hooton, Thomas M.

2003-01-01

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima-Peru and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%)of 965 patients who were HIV-negative or of unknown HIV status (p < 0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB. PMID:14720398

Implementation of tuberculosis infection control measures in designated hospitals in Zhejiang Province, China: are we doing enough to prevent nosocomial tuberculosis infections?

PubMed

Chen, Bin; Liu, Min; Gu, Hua; Wang, Xiaomeng; Qiu, Wei; Shen, Jian; Jiang, Jianmin

2016-03-03

Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Cross-sectional survey using observation and interviews. All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. The TB-designated hospitals treated a median of 3030 outpatients (IQR 764-7094) and 279 patients with confirmed TB (IQR 154-459) annually, and 160 patients with TB (IQR 79-426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission rates of patients with TB. Published by the BMJ Publishing Group Limited. For permission to

Structural and biophysical characterization of Rv3716c, a hypothetical protein from Mycobacterium tuberculosis.

PubMed

Gopalan, A; Deka, G; Prabhavathi, M; Savithri, H S; Murthy, M R N; Raja, A

2018-01-01

Latent tuberculosis (TB) is the main hurdle in reaching the goal of "Stop TB 2050". Tuberculin skin and Interferon-gamma release assay tests used currently for the diagnosis of TB infection cannot distinguish between active disease and latent tuberculosis infection (LTBI) and hence new and sensitive protein markers need to be identified for the diagnosis. A protein Rv3716c from Mycobacterium tuberculosis (MtbRv3716c) has been identified as a potential surrogate marker for the diagnosis of LTBI. Here, we present characterization of MtbRv3716c (∼13 kDa) using both biophysical and X-Ray crystallographic methods. EMSA study showed that MtbRv3716c binds to double stranded DNA. X-ray diffraction data collected on a crystal of MtbRv3716c at 1.9 Å resolution was used for structure determination using the molecular replacement method. Significant electron density was not observed for the N-terminal 21 and C-terminal 41 residues in the final electron density map. The C- terminal disordered region is proline rich and displays characteristics of intrinsically disordered proteins. Although the crystal asymmetric unit contained a protomer, a tight dimer could be generated by the application of the crystal two-fold symmetry parallel to the b axis. Packing of dimers in the crystal is mediated by a cadmium ion (Cd 2+ ) occurring at the interface of two dimers. Molecular packing analysis reveals large cavities that are probably occupied by the disordered segments of the N- and C-termini. Structural comparison with other homologous hypothetical DNA binding proteins (PDB codes: 1PUG, 1YBX) highlights structural features that might be significant for DNA binding. Copyright © 2017 Elsevier Inc. All rights reserved.

Serial testing of refugees for latent tuberculosis using the QuantiFERON-gold in-tube: effects of an antecedent tuberculin skin test.

PubMed

Baker, Cristina A; Thomas, William; Stauffer, William M; Peterson, Phillip K; Tsukayama, Dean T

2009-04-01

Screening for latent tuberculosis infection (LTBI) in refugee populations immigrating to low-incidence countries remains a challenge. We assessed the characteristics of the QuantiFERON-Gold In-Tube (QFT-GIT) compared with the tuberculin skin test (TST) in 198 refugees of all ages from tuberculosis-endemic countries. Diagnostic agreement between the first QFT-GIT and simultaneous TST was 78% (kappa = 0.56) and between serial QFT-GITs was 89% (kappa = 0.76). In serial QFT-GIT testing, 70% of subjects had an increased QFT-GIT value, perhaps the result of an antecedent TST in the setting of previous TB exposure. This boosting seemed to become less prevalent with time from TST and occurred less frequently in those with negative first QFT-GIT readings. Despite small changes in the quantitative results caused by nonspecific variation and boosting, the diagnostic result of the QFT-GIT was reliable. The QFT-GIT shows the potential to replace the TST for LTBI screening in refugees from tuberculosis-endemic areas.

Screening for Latent Tuberculosis in the Patient With Moderate to Severe Psoriasis Who Is a Candidate for Systemic and/or Biologic Therapy.

PubMed

Martínez-López, A; Rodriguez-Granger, J; Ruiz-Villaverde, R

2016-04-01

Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

PubMed

Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

2016-01-01

India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Tuberculosis and HIV co-infection in Vietnam.

PubMed

Trinh, Q M; Nguyen, H L; Do, T N; Nguyen, V N; Nguyen, B H; Nguyen, T V A; Sintchenko, V; Marais, B J

2016-05-01

Tuberculosis (TB) and human immunodeficiency virus (HIV) infection are leading causes of disease and death in Vietnam, but TB/HIV disease trends and the profile of co-infected patients are poorly described. We examined national TB and HIV notification data to provide a geographic overview and describe relevant disease trends within Vietnam. We also compared the demographic and clinical profiles of TB patients with and without HIV infection. During the past 10 years (2005-2014) cumulative HIV case numbers and deaths increased to 298,151 and 71,332 respectively, but access to antiretroviral therapy (ART) improved and new infections and deaths declined. From 2011-2014 routine HIV testing of TB patients increased from 58.9% to 72.5% and of all TB patients diagnosed with HIV in 2014, 2,803 (72.4%) received ART. The number of multidrug resistant (MDR)-TB cases enrolled for treatment increased almost 3-fold (578 to 1,532) from 2011-2014. The rate of HIV co-infection in MDR and non-MDR TB cases (51/1,532; 3.3% vs 3,774/100,555; 3.8%; OR 0.77, 95% CI 0.7-1.2) was similar in 2014. The care of TB/HIV co-infected patients have shown sustained improvement in Vietnam. Rising numbers of MDR-TB cases is a concern, but this is not "driven" by HIV co-infection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modeling socio-demography to capture tuberculosis transmission dynamics in a low burden setting

PubMed Central

Ajelli, Marco; Yang, Zhenhua; Merler, Stefano; Furlanello, Cesare; Kirschner, Denise

2011-01-01

Evidence of preferential mixing through selected social routes has been suggested for the transmission of tuberculosis (TB) infection in low burden settings. A realistic modelization of these contact routes is needed to appropriately assess the impact of individually targeted control strategies, such as contact network investigation of index cases and treatment of latent TB infection (LTBI). We propose an age-structured, socio-demographic individual based model (IBM) with a realistic, time-evolving structure of preferential contacts in a population. In particular, transmission within households, schools and work-places, together with a component of casual, distance-dependent contacts are considered. We also compared the model against two other formulations having no social structure of contacts (homogeneous mixing transmission): a baseline deterministic model without age structure and an age-structured IBM. The socio-demographic IBM better fitted recent longitudinal data on TB epidemiology in Arkansas, USA, which serves as an example of a low burden setting. Inclusion of age structure in the model proved fundamental to capturing actual proportions of reactivated TB cases (as opposed to recently transmitted) as well as profiling age-group specific incidence. The socio-demographic structure additionally provides a prediction of TB transmission rates (the rate of infection in household contacts and the rate of secondary cases in household and workplace contacts). These results suggest that the socio-demographic IBM is an optimal choice for evaluating current control strategies, including contact network investigation of index cases, and the simulation of alternative scenarios, particularly for TB eradication targets. PMID:21906603

Tuberculosis Vaccines and Prevention of Infection

PubMed Central

Day, Tracey A.; Scriba, Thomas J.; Hatherill, Mark; Hanekom, Willem A.; Evans, Thomas G.; Churchyard, Gavin J.; Kublin, James G.; Bekker, Linda-Gail; Self, Steven G.

2014-01-01

SUMMARY Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation. PMID:25428938

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB.

PubMed

Chegou, Novel N; Sutherland, Jayne S; Malherbe, Stephanus; Crampin, Amelia C; Corstjens, Paul L A M; Geluk, Annemieke; Mayanja-Kizza, Harriet; Loxton, Andre G; van der Spuy, Gian; Stanley, Kim; Kotzé, Leigh A; van der Vyver, Marieta; Rosenkrands, Ida; Kidd, Martin; van Helden, Paul D; Dockrell, Hazel M; Ottenhoff, Tom H M; Kaufmann, Stefan H E; Walzl, Gerhard

2016-09-01

User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease. We prospectively enrolled individuals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum samples using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB. Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-γ, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training sample set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site. We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

When students become patients: TB disease among medical undergraduates in Cape Town, South Africa.

PubMed

Van der Westhuizen, Helene-Mari; Dramowski, Angela

2017-05-24

Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate. Quantitative and qualitative data collected from the questionnaire and semi-structured interviews were analysed with descriptive statistics and a framework approach to identify emerging themes. Twelve individuals (10 female) reported a diagnosis of TB: pulmonary TB (n=6), pleural TB (n=3), TB lymphadenitis (n=2) and TB spine (n=1); 2/12 (17%) had drug-resistant disease (DR-TB). Mean diagnostic delay post consultation was 8.1 weeks, with only 42% of initial diagnoses being correct. Most consulted private healthcare providers (general practitioners (n=7); pulmonologists (n=4)), and nine underwent invasive procedures (bronchoscopy, pleural fluid aspiration and tissue biopsy). Substantial healthcare costs were incurred (mean ZAR25 000 for drug-sensitive TB, up to  ZAR104 000 for DR-TB). Students struggled to obtain treatment, incurred high transport costs and missed academic time. Students with DR-TB interrupted their studies and experienced severe side-effects (hepatotoxicity, depression and permanent ototoxicity). Most participants cited poor TB infection-control practices at their training hospitals as a major risk factor for occupational TB. Undergraduate medical students in Cape Town are at high risk of occupationally acquired TB, with an unmet need for comprehensive occupational health services and support.