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While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette-Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4 + T and CD8 + T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.

Background: Bovine tuberculosis (bTB) is still a prominent threat to animal health; lacking an efficient vaccine, other than BCG to get rid of tuberculosis, the most effective way for this is culling and slaughtering the infected animals. There are several cellular, serological, and molecular tests for the diagnosis of the disease but the most practical one at the field level is the double skin testing with bovine and aviary tuberculins. This is not a very specific test but is sensitive enough to identify most diseased animals; adjunct practical tests are desirable to strengthen the utility of skin tests. All lymphoid and myeloid cells participate, in diverse grades, in the immune response to tuberculosis with neutrophils playing an unintended pathologic role. The study aimed to investigate the response of neutrophils to agents present in the sera of tuberculous cows., Methods: We have developed a neutrophil-based test (N BT) to identify diseased cows within a herd suspected of having tuberculosis; a positive N BT correlates with a positive double skin test. In this test, healthy neutrophils are incubated with the sera of healthy or tuberculous cows for 3 and 6 h, and the nuclear morphologic changes are recorded and analyzed., Results: Sera from tuberculous but not from healthy cows induce nuclear alterations including pyknosis, swelling, apoptosis, and sometimes NETosis, in healthy neutrophils, and CFP 10 and ESAT 6 participate in the phenomenon., Conclusion: We propose the N BT as an auxiliary tool for substantiating the diagnosis of bTB reinforcing the PPD test outcome to help decide whether or not a cow should be sacrificed., Competing Interests: None

Tuberculosis has been present in the world's population for as long as there has been written language. It is a disease known to the ancient Egyptians, Greeks, Romans, and Hebrews, but its etiology eluded the world for thousands of years. Even after the germ theory was accepted and early scientists hypothesized a pathogen as the cause, the identity of the sleeping killer in society remained a mystery. That is until Robert Koch was able to grow and visualize Mycobacterium tuberculosis . Koch introduced his Old Tuberculin solution as a diagnostic therapy of tuberculosis (TB), with the intent to reduce the number of infected persons and stop its spread. Old Tuberculin's ability to treat TB proved minimal, but its diagnostic potential paved the way for more effective tests from von Pirquet, Calmette, Wolff-Eisner, and Mantoux. Florence Seibert set out to identify and purify the active principle in Koch's Old Tuberculin and ended up creating purified protein derivative (PPD) tuberculin which is still used as the standard for the tuberculin skin test (TST). Interferon-γ release assays (IGRAs) are a more modern diagnostic tool for detecting latent TB infection that offer some benefits (and some disadvantages) to TST. TSTs and IGRAs can determine if an individual has been infected with M. tuberculosis but are equally unable to predict progression to active tuberculosis, the diagnosis of which relies on assessment of clinical symptoms, radiographic imaging, and sample culture.

Introduction: Mantoux test aids in the diagnosis of tuberculosis (TB), however its application and interpretation are dependent on multiple factors., Methodology: A prospective study enrolling 400 children (aged 2-12) suspected to have tuberculosis. All participants received Mantoux test with two different strengths (1 TU and 5 TU) of Purified Protein Derivative (PPD) on different forearms. The test was read by two readers after 48 ± 2 and 72 ± 2 hours. Primary outcome was difference in the size of induration when read by two readers (interobserver variability). Secondary outcomes were difference in the size of induration at different intervals, with different strengths of PPD and percentage positivity of Mantoux test in TB patients., Results: Statistically significant difference was seen in the size of induration when read by two different readers, with fair to moderate agreement when read at 48 and 72 hours (1 TU: p = 0.002, k = 0.52 and p = 0.1, k = 0.73 respectively, 5 TU: p = 0.001, k = 0.39 and p = 0.0009, k = 0.33 respectively). Tendency of under-reading occurred when size of induration was close to significant level (10-14 mm). Size of induration was similar when read at 48 or 72 hours (1 TU: p = 0.9, 5 TU: p = 1.0). Mantoux positivity rate in patients with TB was more with 5 TU as compared to 1 TU (61.2% vs. 16.3%)., Conclusions: There is significant interobserver variability with a tendency to under-read around the cutoff point. The use of 5 TU PPD at 48 hours by a trained physician can aid in early and more reliable diagnosis of TB., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2018 Dimple Goel, Mukta Mantan, GR Sethi.)

This study compares purified protein derivative (PPD) screening to digital chest radiography (CXR) screening for tuberculosis (TB) in newly admitted inmates in the San Diego County Jail system. The study period lasted from 2002 to 2014, during which 45 cases of active TB were detected, a rate of 69.2 cases per 100,000 person-years. Compared to PPD, CXR reduces the median number of days active TB cases were in the general population from 44.4 to 5.2 days and the number of exposures from 1,222 to 138 persons. These results confirm that CXR remains a more effective method for preventing exposure to active TB in jail facilities., (© The Author(s) 2016.)

Background: Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS., Methods: Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip(®) ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis., Results: At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS - at the time of the IRIS episode, but also already at baseline - are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included "Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses" and "Complement System"., Conclusion: Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Tuberculosis (TB) is a zoonotic disease primarily caused by pathogens belonging to the genus of Mycobacterium. Programs of control and eradication for bovine TB include a screening using single intradermal tuberculin (SIT) test with Mycobacterium bovis (M. bovis)-purified protein derivatives (PPD-B) single or concurrent with Mycobacterium avium (M. avium)-purified protein derivatives (PPD-A). This study aimed to determine the effects of intradermal PPD-B and PPD-A test on immunerelated mRNA and microRNAs in dermal oedema exudates of water buffaloes (Bubalus bubalis). The investigation was carried out on RNA extracted from dermal oedema exudates of 36 animals, of which 24 were M. bovis positive (M. bovis+) and 12 M. avium positive (M. avium+). The lymphocyte polarization toward Th1, Th2, TReg, and Th17 lineages was addressed by measuring the abundance of the respective cytokines and transcription factors, namely TBET, STAT4, IFNγ, and IL1β for Th1; STAT5B, and IL4 for Th2; FOXP3 and IL10 for TReg; and RORC, STAT3, and IL17A for Th17. Due to the very low abundance of Th17-related genes, a digital PCR protocol was also applied. The abundance of microRNAs involved in the immune response against PPDs, including miR-122-5p, miR-148a-3p, miR30a, and miR-455-5p, was equally measured. Results showed that IFNγ (fold change = 2.54; p = 0.037) and miR-148a-3p (fold change = 2.54; p = 0.03) were upregulated in M. bovis+ as compared to M. avium+ samples. Our preliminary results supported the pivotal role of IFNγ in the local immune response related to PPD-B and highlighted the differential expression of miR-148a-3p, which downregulates the proinflammatory cytokines and the TLR4- mediated NF-κB activation, providing an anti-inflammation modulator in responses to mycobacterial infection. [ABSTRACT FROM AUTHOR]

La tuberculosis en una enfermedad infectocontagiosa, que puede cursar sin síntomas en personas sanas. El objetivo de esta investigación se basó en, analizar la relación entre las pruebas bacteriológicas, inmunológica y las radiografías de tórax y comorbilidad más frecuente en pacientes que fueron diagnosticados con tuberculosis pulmonar. Se planteó un estudio transversal analítico, se realizó una revisión de la base de datos de vigilancia epidemiológica de El Salvador de los años 2015 al 2017 del Hospital Nacional General y de Psiquiatría "Dr. José Molina Martínez"; se realizó revisión de expedientes clínicos de cada paciente para establecer las características sociodemográficas de la población y recolectar información de los resultados de las pruebas diagnósticas realizadas. Pacientes que cumplieron criterios de inclusión n=37. La información se procesó en Epi Info 4.2. Los resultados establecen que: Rayos X de tórax positivos en un 86%, prueba de baciloscopia positiva en el 62%, prueba GeneXpert positiva en el 58%; y el derivado proteico purificado (PPD) positivo en el 100% de los pacientes. Al analizar la asociación de variables se utilizó Prueba exacta de Fisher, la asociación entre Rayos X de tórax y baciloscopia da un OR de 22 con p<0.05 (p=0.016); y entre PPD y Rayos X de tórax se obtiene p<0.001 (p=0.001) El resto de las pruebas como el cultivo LJ y el GeneXpert no tuvieron asociación significativa. La prueba bacteriológica que más se asocia con los resultados radiológicos positivos es la baciloscopia y le sigue la PPD [ABSTRACT FROM AUTHOR]

Background and purpose: Tuberculosis is a contagious disease caused by mycobacterium tuberculosis. Approximately 30% of the world's population is infected, 5-10% of whom develop active tuberculosis. The aim of this study was to determine the tuberculin skin test conversion. Materials and methods: A cross-sectional study was conducted in 114 staff working in Qaemshahr Razi Hospital, 2015-2017. Demographic characteristics and the results of tuberculin skin test (TST) were recorded in a checklist. Data analysis was done in SPSS V20. Results: The participants included 15.8% males and 84.2% females (mean age: 29.42±5.03). Among the subjects, 33% had latent tuberculosis. TST was positive in 11.4% in first evaluation and 36.84% had positive TST in the second assessment. TST seroconversion was observed in 25.44%, in 61.4% the working experience was more than 10 years, and 61.5% worked in infectious department. There were significant associations between the positive result of TST and age, gender, and working experience (P=0.002, P=0.021, and P=0.01, respectively). We observed significant differences in the results of TST between the first and second evaluation (P

Abstract Background Bovine purified protein derivative (bPPD) and avian purified protein derivative (aPPD) are widely used for bovine tuberculosis diagnosis. However, little is known about their qualitative and quantitative characteristics, which makes their standardisation difficult. In addition, bPPD can give false-positive tuberculosis results because of sequence homology between Mycobacterium bovis (M. bovis) and M. avium proteins. Thus, the objective of this study was to carry out a proteomic characterisation of bPPD, aPPD and an immunopurified subcomplex from bPPD called P22 in order to identify proteins contributing to cross-reactivity among these three products in tuberculosis diagnosis. Methods Trypsin digests of bPPD, aPPD and P22 were analysed by nanoscale liquid chromatography-electrospray ionization tandem mass spectrometry. Mice were immunised with bPPD or aPPD, and their serum was tested by indirect ELISA for reactivity against these preparations as well as against P22. Results A total of 456 proteins were identified in bPPD, 1019 in aPPD and 118 in P22; 146 of these proteins were shared by bPPD and aPPD, and 43 were present in all three preparations. Candidate proteins that may cause cross-reactivity between bPPD and aPPD were identified based on protein abundance and antigenic propensity. Serum reactivity experiments indicated that P22 may provide greater specificity than bPPD with similar sensitivity for ELISA-type detection of antibodies against M. tuberculosis complex. Conclusion The subpreparation from bPPD called P22 may be an alternative to bPPD for serodiagnosis of bovine tuberculosis, since it shares fewer proteins with aPPD than bPPD does, reducing risk of cross-reactivity with anti-M. avium antibodies.

The Irish Bovine Tuberculosis (bTB) eradication programme operates under national legislation and fulfills OIE and EU trade requirements. Tuberculin purified protein derivative (PPD), a preparation obtained from the heat-treated products of growth and lysis of Mycobacterium bovis or Mycobacterium avium (as appropriate), is critical to the diagnosis of tuberculosis (TB). Standardization of Tuberculin PPD potency, the relative activity in sensitized animals compared to a reference standard, is essential to underpin the reliability of certification for international trade and to ensure that disease eradication programmes are effective and efficient. A Bovine International Standard Tuberculin PPD (BIS) was established by the WHO in 1986 and is used to determine comparative potencies of Tuberculin PPDs. Ideally, Tuberculin PPD potency should be evaluated in the species in which the tuberculin will be used but due to practical difficulties in performing potency assays in cattle, for routine PPD production, they are usually assayed in guinea pigs. Low potency tuberculin PPD is less efficient and thus inferior for bTB diagnosis. Difficulties experienced in the Irish bTB eradication programme have included the supply of sub-standard potency, and thus inferior, bovine (M. bovis) Tuberculin PPD in the late 1970s. The purpose of this paper is to outline the critical role of Tuberculin PPD assays carried out on naturally infected tuberculous cattle, as required by the OIE and under EU legislation in the quality control for the Irish Bovine Eradication Programme. Such assays ensure that the Tuberculin PPD used meets the diagnostic sensitivity and specificity requirements to underpin a successful national eradication programme.

Precise detection of latent tuberculosis infection is becoming increasingly important due to increased use of immunosuppressive drugs and the human immunodeficiency virus epidemic, which increased the risk of reactivation to active tuberculosis (TB). The Quanti-FERON® TB Gold IGRA Test has advantages over the skin test for TB, otherwise known as a Mantoux tuberculin test, for example, requires only a blood sample collection; there is no need for the patient to return to the laboratory for reading and interpretation of the results; The results are objective, do not require interpretation of the reader or interference of subjective criteria; it is an in vitro test, so there is no “booster effect” (potentiation of the tuberculin reaction); the test is not affected by prior BCG vaccination or infection with other species of mycobacteria. Limitations are described, although rare, as cross-reactions of this method with infections by some species of non-tuberculosis mycobacteria (including Mycobacterium kansasii, Mycobacterium szulgai and Mycobacterium marinum). There is still little data on the IGRA test in certain populations, such as in children, immunocompromised patients and pregnant women. In these groups, the interpretation of the test can be difficult and more studies are needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine tuberculosis (Tb) agents in milk and the pathologic changes in the tissues and organs of 100 PPD Tb-positive cows that were intended for slaughter. Milk samples were taken before slaughtering and PCR analysis was conducted to detect the Tb agent. In postmortem examinations, the lungs, liver, mammary glands, spleen, kidneys, and heart were collected for macroscopic and histopathological examinations. Out of the 100 PPD positive cows, lesions of Tb were observed in 75 cows. In the microscopic examination, Tb was identified in the lungs (51 cases), liver (61 cases), and in both the liver and lungs (37 cases). Although mammary Tb was suspected in 32 cows in macroscopic examinations, in microscopic examinations these cases were evaluated as chronic pyogenic abscesses mastitis. No Tb agents were detected by PCR analysis in milk samples taken from the cows before slaughter. Therefore, periodical milk inspections are suggested for controlling agents in milk. In some of the Tb PPD positive animals (25 cases), no changes were detected; therefore, there is a need to improve tests with higher sensitivity for the antemortem diagnosis of Tb. Moreover, people involved in the livestock sector should be trained about Tb, hygiene rules, and disease-free herds. [ABSTRACT FROM AUTHOR]

Background: Bovine purified protein derivative (bPPD) and avian purified protein derivative (aPPD) are widely used for bovine tuberculosis diagnosis. However, little is known about their qualitative and quantitative characteristics, which makes their standardisation difficult. In addition, bPPD can give false-positive tuberculosis results because of sequence homology between Mycobacterium bovis (M. bovis) and M. avium proteins. Thus, the objective of this study was to carry out a proteomic characterisation of bPPD, aPPD and an immunopurified subcomplex from bPPD called P22 in order to identify proteins contributing to cross-reactivity among these three products in tuberculosis diagnosis. Methods: Trypsin digests of bPPD, aPPD and P22 were analysed by nanoscale liquid chromatography-electrospray ionization tandem mass spectrometry. Mice were immunised with bPPD or aPPD, and their serum was tested by indirect ELISA for reactivity against these preparations as well as against P22. Results: A total of 456 proteins were identified in bPPD, 1019 in aPPD and 118 in P22; 146 of these proteins were shared by bPPD and aPPD, and 43 were present in all three preparations. Candidate proteins that may cause crossreactivity between bPPD and aPPD were identified based on protein abundance and antigenic propensity. Serum reactivity experiments indicated that P22 may provide greater specificity than bPPD with similar sensitivity for ELISAtype detection of antibodies against M. tuberculosis complex. Conclusion: The subpreparation from bPPD called P22 may be an alternative to bPPD for serodiagnosis of bovine tuberculosis, since it shares fewer proteins with aPPD than bPPD does, reducing risk of cross-reactivity with anti-M. avium antibodies. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis represents one of the very important infectious diseases in Egypt and the world. It has zoonotic importance and causes severe economic losses. Accurate and rapid diagnosis considered as the milestone for control of the disease. In this study ELISA technique was used for confirmation of positive reactors cows that tested with single intradermal tuberculin test, to detect false positive reactors. Bovine PPD and ST.CF antigens have been used as two different coating antigens for ELISA technique. 3747 cattle from dairy farms in five different governorates were subjected to the single intradermal cervical tuberculin test whereas 78 (2.24%) proved positive reactors to tuberculin. These positive reactors tested with ELISA. 64 (82.05%) animals were positive by ELISA coated with ST-CF, while by using bovine PPD as coating antigen 58 (74.35%) animals were positive. The previous results indicated that ELISA test showed higher sensitivity and specificity using ST-CF as coating antigen than in case of bovine PPD coating antigen.

Patients with an autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, uveitis or psoriasis, and treated with the anti-tumour necrosis factor (TNF) alpha inhibitors are at high risk of developing various infections including tuberculosis (TB). Serious infections are the result of the patients' immunocompromised status that is caused by the primary disease itself, as well as by previous immunosuppressive therapy. In order to decrease the risk of developing TB, prior to the introduction of the anti-TNF alpha therapy, all patients should undergo screening for TB. Experiences from the countries that have already implemented recommendations for TB screening show a significant decrease in TB occurrence in the anti-TNF alpha treated patients. The PPD skin test result is considered positive if induration is of size ≥5 mm. The BCG vaccine applied at birth has no effect on interpretation of PPD test results in adults. The diagnosis of active TB is contraindicated for the introduction of the anti-TNF alpha therapy; first, such patients should receive the TB treatment; and 6 months after the completion of the TB treatment, the introduction of the anti-TNF alpha therapy may be considered. The patients with the diagnosis of the latent TB infection (LTBI) should not immediately start with the anti-TNF alpha therapy, but they should first receive the TB chemoprophylaxis; not earlier than a month upon the introduction of the TB chemoprophylaxis, the anti-TNF alpha therapy may be introduced. The first TB follow-up screening during the anti-TNF alpha therapy is recommended 6 months after the anti-TNF alpha therapy has been introduced and the next one should be scheduled after 12 months.

Tuberculosis is the most common infectious cause of death worldwide. Young children especially infants usually are more susceptible to tuberculous infection. Disease usually develops within 1 year of infection. The present study has been conducted upon 41 children in whom Mantoux test was positive (n=41). These children were coming to our outpatient department, in a Teaching Hospital, Nizamabad, Telangana State with mild fever, cough, night sweats, anorexia, and loss of weight. The age group selected for this study was 1 to 12 year, and the period of study was from August, 2013 to December, 2015. Among the 41 children under study 13 children were 1 to 4 year and 28 were 5 to 12 year. Among the total 41 cases of Mantoux positive, 16 (39%) were found to be suffering from tuberculous disease and anti tuberculous drugs were started. In these cases 7 were 1 to 4 year (n=13), and 9 were 5 to 12 year (n=28). After 3 months follow up, all the children who were on ATT became free from their symptoms. It shows association between mantoux positivity and tuberculosis is more in children between 1 and 4 year than children between the age of 5 and 12 year. Most of the other children needed antipyretics, other symptomatic drugs and antibiotics only. But in 3 cases symptoms were not relieved either with antibiotics or with trial ATT. The factors for deciding tuberculosis are history of contact, clinical picture, CBP, ESR, chest- x- ray, Mantoux test, sputum for AFB, antibiotic trial, follow up, trial ATT. All these factors are put together and then only we will decide whether to start ATT or not. [ABSTRACT FROM AUTHOR]

Pulmonary hyalinizing granuloma (PHG) is a rare benign pulmonary nodular lesion of unknown etiology. We present a case of a 5-year-old boy who was found to have a chest mass while being evaluated for abdominal pain. He underwent a CXR and CT scan that showed popcorn calcifications in the right posterior mediastinum and within the hilum of right lung. These lesions were suspicious for benign calcified lymph nodes and follow-up chest CT after 3.5 months showed no interval changes in the calcified mediastinal masses. Extensive testing ruled out infectious diseases and malignancies. Given the unknown etiology of the lesions, he underwent VATS biopsy that demonstrated a nodular lesion characterized by a peripheral rim of fibrous tissue and central zone of necrosis and calcification, findings consistent with hyalinizing granuloma. PHG is extremely rare in pediatric age group. Although diagnosis of this condition is made by radiological and histopathological findings, it is important to rule out other causes of chest masses. Most of the patients usually have good prognosis with this rare disorder. [ABSTRACT FROM AUTHOR]

The effect of the human immunodeficiency virus (HIV) infection on IgG production against purified protein derivative (PPD) and 2,3-diacil-trehalose (SL-IV) was investigated by an enzyme-linked immunosorbent assay (ELISA) test. Comparison between the antigens showed that immunocompetent patients produce preferentially antibodies to SL-IV than to PPD (73.3% versus 63.3%). Combination of these results showed an increase of the sensitivity to 80%, which decreased over the spectrum of immunodepression caused by HIV. In the tuberculous HIV seropositive group the sensitivities of SL-IV and PPD were 36.4% versus 40% and 0% versus 22.2% in the tuberculosis/acquired immunodeficiency syndrome (TB/AIDS) group. Combination of these results gave respectively 54.5% and 20%, showing that serological tests have limited value for diagnosis of tuberculosis in HIV infected patients. High antibody levels were observed in HIV seropositive asymptomatic group, but only two individuals were positive for both antigens. In the follow up, one of them developed tuberculous lymphadenitis, indicating that further work is needed to access the value of serological tests in predicting tuberculosis in HIV infected individuals.

Summary Aiming to identify a possible biomarker that distinguishes immune cellular response of active tuberculosis from latent infection. Peripheral blood mononuclear cells (PBMCs) of pulmonary tuberculosis patients (PTB), tuberculin positive household contacts (TST+ HHC), and tuberculin negative non-household contacts (TST− Non HHC) were stimulated with PPD or CFP-10 and the percentage of CD69 + cells, proliferating precursor and IFN-γ producing CD4 + , CD8 + , CD56 + CD3 − and CD56 + CD3 + cells were compared. IL-2, IL-12p70, IL-15, IL-18 and IL-10 were measured in culture supernatants. PTB and TST+ HHC presented higher percentages of CD69 + cells, IFN-γ + and proliferating precursors in all subpopulations studied and higher IL-12p70 levels than TST− Non HHC. The increased percentage of IFN-γ producing CD56 + CD3 + cells in response to CFP-10 in PTB, compared with TST− Non HHC and the ratios between the percentage of CD56 + CD3 + cells/CD56 + CD3 − and CD8 + cells producing IFN-γ suggest that these parameters may distinguish active TB from latently infected individuals. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) cells from mouse and human play a protective role in the immune responses against the infection of Mycobacterium tuberculosis. However, the characteristic of CD3TCRvβ11 NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that the numbers of CD3TCRvβ11 NKT cells in pleural fluid mononuclear cells (PFMCs) were significantly lower than those in peripheral blood mononuclear cells (PBMCs). However, CD3TCRvβ11 NKT cells from PFMCs spontaneously expressed high levels of CD69 and CD25 and effector memory phenotypes of CD45ROCD62LCCR7. After stimulation with the antigens of M. tuberculosis, CD3TCRvβ11 NKT cells from PFMCs produced high levels of IFN-γ. Sorted CD3TCRvβ11 NKT cells from PFMCs cultured with antigen presenting cells (APCs) produced IFN-γ protein and mRNA. The production of IFN-γ could be completely inhibited by AG490 and Wortmannin. In addition, CD3TCRvβ11 NKT cells from PFMCs expressed higher levels of Fas (CD95), FasL (CD178) and perforin but lower levels of granzyme B compared with those from PBMCs. Taken together, our data demonstrated for the first time that M. tuberculosis-specific CD3TCRvβ11 NKT cells participated in the local immune responses against M. tuberculosis through the production of IFN-γ and the secretion of cytolytic molecules. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine, which plays an important role in the pathogenesis of several inflammatory diseases such as ankylosing spondylitis (AS), rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Anti-TNF-α therapy is now widely used for treatment of inflammatory diseases. An increased incidence of tuberculosis in patients under anti-TNF-α therapy has been reported. The aim of this study was to investigate the prevalence of latent tuberculosis in patients treated with an anti-TNF-α agent. Methods: Eighty three patients under anti-TNF-α treatment referring to the Rheumatology outpatient clinic enrolled in the study. Tuberculin skin test (PPD) and chest x-ray are performed. An induration of 5 mm or more is defined as latent tuberculosis. Patients with latent tuberculosis are treated with isoniazid (INH) 300 mg/day during 9 months. Results: Mean age of the 83 patients was 37.59±10.80 years; the average duration of illness was 9.82±7.08 years. The primary disease was AS (n=62), RA (n=16), and PsA (n=5). The patients were treated with different anti-TNF-α agents (etanercept n=30, adalimumab n=30, infliximab n=21, and golimumab n=2). PPD induration of 5 mm or more was measured in 63 (76%) of 83 patients. INH prophylaxis was started in 76 of the patients including 13 patients with PPD induration < 5mm due to increased risk of tuberculosis (family history, working as a health professional, history of infected with mycobacterium tuberculosis). The number of male patients (76%) with PPD induration ≥5 mm is significantly higher than the number of female patients (24%) with PPD induration ≥5 mm (p=0.026). The number of patients with AS in patients with PPD induration ≥5 mm (n=51, 81%) is significantly higher than the number of patients with AS in patients with PPD induration <5 mm (n=11, 55%) and the presence of RA in patients with PPD induration ≥5mm (n=8, 13%) is found significantly lower than in patients with PPD induration <5mm (n=8, 40%) (p=0.025). There is no statistically significant difference based on used anti-TNF-α between patients with PPD induration ≥5mm and PPD induration <5mm (p=0,369). The rate of PPD induration ≥5 mm in patients treated with infliximab is found 2.4 times more than the other anti-TNF-α agent.Conclusions: Active tuberculosis or reactivation of latent tuberculosis presents as a serious complication in patients receiving anti-TNF-α therapy. Latent tuberculosis screening and preventive tuberculosis treatment is important before the use of anti-TNF-α agent. Further studies on this subject are needed. [ABSTRACT FROM AUTHOR]

Objectives: To ascertain the status of Tuberculin Skin Test (TST) in the children aged 0-5 y who are household contacts of adults having sputum smear positive pulmonary tuberculosis and also to study the relationship of TST and Chest X-Ray (CXR) and their relevance in contact screening under RNTCP setup. Methods: This prospective hospital based clinical study was conducted at a tertiary level referral medical college in Northern India. Study subjects were 200 children ≤5 y of age who were household contacts of adults with sputum smear positive pulmonary tuberculosis. All these adult index cases were registered and taking regular treatment at RNTCP centre attached to a medical college. Demographic data collection, detailed clinical history along with clinical examination, growth assessment, TST and chest radiography (CXR) was done for every child. Results: TST was positive in 39 % children and out of these 68 % of child contacts had CXR findings suggestive of tuberculosis. This correlation was found to be highly significant ( p < 0.001), especially in children less than 1 y of age. A high percentage of clinically asymptomatic children also had positive TST and CXR consistent with definition of TB disease. Conclusions: Contact screening must be prioritized in RNTCP. Unlike presently, TST and CXR should be actively employed in RNTCP for contact screening. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of tuberculosis (TB) infection is an important component of tuberculosis control programs in many countries. Identification of persons with asymptomatic, or latent, tuberculosis infection allows for treatment of individuals at high risk for progressing to active disease so that the overall burden of tuberculosis disease is diminished. In the United States, targeted testing and treatment of latent tuberculosis infection (LTI) are major components of the Centers for Disease Control and Prevention's efforts at TB elimination. This review focuses on the comparative utility of tuberculin skin testing and interferon-gamma release assays (IGRAs) to diagnose LTI. Commercially available IGRAs have superior sensitivity and specificity compared with conventional tuberculin skin testingin some settings (particularly bacille-Calmette Guérin--vaccinated individuals). Also discussed are the performance characteristics of these tests in specific populations, including foreign-born persons from high-prevalence countries, close contacts of actively infected patients, immunocompromised populations, and health care workers. [ABSTRACT FROM AUTHOR]

The article presents abstracts of poster presentations on dermatology, including topics on newborn skin disorders in a dermatology outpatient clinic in Turkey, influence of neonatal and maternal factors on the prevalence of salmon patch, and treatment of diffuse cutaneous mastocytosis with imatinib mesylate.

Objective: To correlate the tuberculosis skin test (TST/PPD) and the interferon gamma release assay for the diagnosis of latent tuberculosis in infant Warao population, younger than fifteen years old is in the communities of Pedernales municipality, Delta Amacuro State, Venezuela, from September to November 2010. Methods: TST/PPD was applied in 473 individuals younger than fifteen years old; the positive reactors and the negative ones with confirmed TB patient contact were selected for assay with the Quanti-FERON® TB Gold In Tube test. Results: From 473 subjects with applied applied PPD, 97 of them resulted positive, 14 were negative having confirmed TB contact and 362 were negative. Quanti-FERON® TB Gold In Tube test was performed in 107 individuals (93 PPD positive plus 14 PPD negative with confirmed TB contact), 83 were positive, 21 were negative and 3 undetermined. The correlation between these two tests was calculated through kappa index, which was 0.9 and the statistical significance through Mac Nemar Chi2 test modified by Yates which was 3.25 (p>0.05). Conclusions: TST/PPD and interferon gamma release assay were concordant, almost perfectly, for the studied group. There was no statistical difference between TST/PPD and interferon gamma release assay. High latent tuberculosis prevalence was determined in these communities. [ABSTRACT FROM AUTHOR]

The diagnosis of latent and active tuberculosis in the HIV-positive population is challenged by diminished sensitivity of conventional tests, atypical presentations, and the lack of culture methods in the developing world, where the burden of co-infection is greatest. In response to these challenges, a variety of new diagnostics have emerged. These include interferon-gamma release assays for the diagnosis of latent tuberculosis (TB) infection and novel culture methods and molecular assays for the diagnosis of active tuberculosis. Although some tests (such as interferon-gamma release assays) are not clearly superior to existing diagnostics, other novel diagnostics, such as real-time polymerase chain reaction and the microscopic observed direct susceptibility assay hold much promise for prompt and accurate TB diagnosis in this population. Line-probe, nitrate reductase, and mycobacteriophage assays have also provided rapid alternatives to conventional time-consuming drug susceptibility testing and are critical to curtailing the spread of multidrug-resistant TB. [ABSTRACT FROM AUTHOR]

Wu X, Liang Y, Wang L, Wang Z, Zhang C, Yang Y, Zhang J. Latent tuberculosis infection among new recruits to the army in Beijing, China in 2009. APMIS 2011; 119: 377-84. China is a country with high latent tuberculosis infection (LTI) and has a policy of routine BCG vaccination. To monitor tuberculosis (TB) infection, a total of 907 new recruits to the army were interviewed and routinely examined by chest radiographs. They were intradermally injected with purified protein derivative (PPD) and detected with enzyme-linked immunospot (ELISPOT) assay with recombinant CFP-10/ESAT-6 (rCFP-10/ESAT-6) fusion protein, as a stimulus, from December 2009 to February 2010. The prevalence of LTI among new recruits was estimated as 50.2% and 30.7% by PPD skin test and ELISPOT assay, respectively. Of 452 PPD-negative and 455 PPD-positive volunteers, 132 (29.2%) and 146 (32.1%) were ELISPOT positive, respectively. The overall consistency between these two tests was 51.4% (466/907). Although 65.6% of PPD-positive volunteers and 27.8% of ELISPOT-positive volunteers (spot-forming cells; SFC 12.2 ± 21.2) could find the vaccination scars on their arms, 21.3% of PPD-positive volunteers and 35.9% of ELISPOT-positive volunteers (SFC 18.3 ± 34.6) could not. Thus, the TB infection rate in army recruits in China was not as high as previously reported. The results suggest that the ELISPOT technique, we presented, is an accurate method for screening TB infection in China. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis (TB) is an important infectious disease worldwide. Tuberculin skin test (TST) is the standard test for diagnosis of tuberculosis infection; Bacillus Calmette-Guerin (BCG) vaccination at birth has effects on this test The aim of this study was to determine the prevalence of positive TST cases among 7- to 11-year-old primary school children and also to follow test- positive individuals for a five-year period. Methods: TST was performed on 10.184 children aged 7-11 years sampled by cluster random method in Kermanshah, West Iran. Those who had a positive test result (i.e. an induration of 215 mm following 72 hours of injecting 0.1 ml of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis") were followed for five years to determine the presence of active TB. Also tuberculin positive rates at cut-off points of 10 mm and âl5 mm for boys and girls and at different ages were derived and compared using the chi-squared test Findings: Of 10.184 studied subjects, 830 (8.15%) cases showed positive TST. This rate was 8.7% in boys and 7.8% in girls (P=0.1). A significant linear trend was found between the tuberculin positive rates and age at all cut-off points (P<0,001), No active TB was detected during 5-year follow-up. Conclusion: The rate of positive TST cases in primary school children in Kermanshah, Iran was 8.15% with no neweases of active tuberculosis detection within five-year follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of steroid treatment on visual outcome and ocular complications in patients with presumed ocular tuberculosis. Methods: Retrospective review of patients with presumptive ocular tuberculosis. The clinical diagnosis was made based on ocular findings, positive purified protein derivative (PPD) testing of more than 15 mm induration, exclusion of other causes of uveitis and positive ocular response to anti-tuberculous therapy (ATT) within 4 weeks. Group 1 included patients who had received oral prednisone or subtenon injection of triamcinolone acetonide prior to ATT. Group 2 included patients who did not receive corticosteroid therapy prior to administration of ATT. Results: Among 500 consecutive new cases of uveitis encountered in 1997-2007 there were 49 (10%) patients with presumed ocular tuberculosis. These comprised 28 (57%) male and 21 (43%) female patients with a mean age of 45 years (range 12-76 years). Four (20%) patients in group 1 had initial visual acuity of 20 / 40 or better, in comparison to eight (28%) patients in group 2. At 1-year follow-up, six (30%) patients in group 1 had a visual acuity of 20 / 40 or better compared with 20 (69%) patients in group 2 (p = 0.007). Of 20 eyes (26%) in group 1 that had visual acuity of < 20 / 50 at 1-year follow up, 14 (70%) eyes developed severe chorioretinal lesion (p = 0.019). Conclusion: Early administration of corticosteroids without anti-tuberculous therapy in presumed ocular tuberculosis may lead to poor visual outcome compared with patients who did not receive corticosteroids prior to presentation. Furthermore, the severity of chorioretinitis lesion in the group of patients given corticosteroid prior to ATT may account for the poor visual outcome. [ABSTRACT FROM AUTHOR]

Abstract: The control of mycobacterial infection by the host depends on cell-mediated immunity (CMI), involving activated macrophages, T cells, and type 1 cytokines (Th1). Here we evaluated the capacity of antigen-induced proliferation by peripheral blood mononuclear cells (PBMCs) and the production of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12p40). The Th1 cytokine interferon-gamma (IFN–γ) and Th2 cytokines interleukin 4 (IL-4) and interleukin 5 (IL-5) in 62 pulmonary tuberculosis (TB) patients (40 Warao indigenous patients [WP] and 22 Creole nonindigenous patients [CP]) and 24 healthy controls (12 Warao indigenous controls [WC] and 12 Creole nonindigenous controls [CC]) at 24 and 48 hours in response to purified protein derivative (PPD) from Mycobacterium tuberculosis. The overall results revealed that testing of CP and CC'' PBMCs for TNF-α, IFN-γ, and IL-12p40 production was higher compared with WP and WC'' PBMCs after stimulating for 24 and 48 hours (p < 0.0001), within the WP group, the lower productions of IL-12p40 and IFN-γ significantly correlated (r 2 = 0.91, p < 0.01). Although in general there was interindividual variability in the observed responses of Th2 cytokines, especially with IL-4, there was a trend to produce higher PPD-induced IL-5 by WP'' PBMCs compared with WC'' PBMCs and CP'' PBMCs at 24 and 48 hours, respectively. High IL-5 production correlated inversely with low IFN-γ production (r 2 = −0.97, p < 0.002). In conclusion, our results suggest that PPD-induced responses observed in patients from both populations can be divided into two groups: one group that activates Creole'' PBMCs to preferentially secrete TNF-α, IL-12p40 and IFN-γ and another group that activates preferential secretion of IL-5 in Warao'' PBMCs. [Copyright &y& Elsevier]

Abstract: Tuberculosis (TB) represents one of the leading killers among all infectious disease. Protection against TB depends on the activation of T-helper type I (Th1) immune response. Carbon nanotubes (CNTs) have attracted considerable attention because of their potential applications as new nanovehicle. In the current study, tuberculin purified protein derivative (PPD) was conjugated to carboxylated single-walled carbon nanotubes (SWCNTs). Cytotoxicity of the carboxylated SWCNT and SWCNT-PPD conjugate was analyzed with MTT assay and by reactive oxygen species (ROS) and nitric oxide (NO) generation. Male BALB/c mice were immunized with BCG, PPD, SWCNT-PPD conjugate and PPD in complete Freund''s adjuvant (CFA). Induction of cellular immune response was analyzed by measuring the levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-10 and IL-5). Immunization with non-conjugated PPD or PPD in Freund''s adjuvant induced a Th2 cytokine response while immunization with BCG resulted to a mixed Th1/Th2 cytokine response. In contrast, PPD in conjugation with SWCNT generated preferentially a Th1-type cytokine response in the absence of potential cytotoxic effects. [Copyright &y& Elsevier]

Abstract: European badgers (Meles meles) are considered to be an important reservoir of infection for Mycobacterium bovis and are implicated in the transmission of tuberculosis to cattle in Ireland and Great Britain. Accurate tests are required for tuberculosis surveillance in badger populations and to provide a basis for the development of strategies, including vaccination, to reduce the incidence of the infection. In this study, we have developed an endobronchial M. bovis infection model in badgers in which we measured cell-mediated immune and serological responses for up to 24 weeks post-infection. Groups of badgers were subjected to necropsy at 6-week intervals and the gross lesion severity status compared with immune responses measured in blood samples taken throughout the course of the study. The panel of antigens included bovine and avian tuberculins (PPD) as well as single antigens, ESAT-6, CFP-10, MPB70, Rv3019c, Rv3873, Rv3878 and Rv3879, all known to be recognised by the immune system in other animal models of tuberculosis infection. Our results demonstrated that M. bovis infected badgers responded to specific antigens as early as 6 weeks post-infection, consistent with the presence of visible lesions. The data also revealed unique patterns of antigen recognition with high levels of PBMC proliferation in the presence of CFP-10 but low proliferation levels with ESAT-6. Using a multi-antigen print immunoassay (MAPIA), we were able to confirm that MPB83 is the dominant antigen recognised by serum antibodies in infected badgers. [Copyright &y& Elsevier]

A study was conducted in 2005, with students from biomedical careers (medicine, nursing and stomatology) and compared to students of a non-biomedical career (public accounts) from the Autonomous University of Aguascalientes, all enrolled on initial semesters, intermediate and the end of their studies. All students were applied five units of purified protein derivative CT68 of Mycobacterium tuberculosis, and the interpretation of the test was made within 48 to 72 hours applied, in accordance with international standards. The reading was interpreted as a negative test when the induration was less than 5 mm; negative but expected by previous vaccination with BCG when there were between 5 and 10 mm, and positive with an induration exceeding 10 mm. The differences in the mean, standard deviation and standard error of the reading is presented in the PPD of medical students between the fifth and ninth semester (50< 9 0, p <0.05) in the nursing between the fifth and seventh semester (50<70, p <0.05), and students from public accountancy between the fifth and ninth semesters (50 <09, p <0.01), with no differences in the reactivity of pupils of different semesters of stomatology. The most marked difference was presented at the reactivity exceeding 10 mm in nursing groups, with 0% in the first half to 50% in students from the last semesters, which suggests exposure to mycobacteria, and requires assessing whether that happened in strengthened response versus positive conversion to the test. It is recommended by the survey results, that the medical and nursing students in contact with patients in their clinical practice are at risk of infection, not present due to an appropriate immune response, without developing disease or even as having it as an occupational risk, to have an annual monitoring since joining with PPD to evaluate conversion to the test, as well as strengthen preventive measures against tuberculosis. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the anti-Mycobacterium tuberculosis (Mtb) immune responses of HIV patients after long-term successful HAART, presenting >500 TCD4+ cells/μl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n =14) or disease (HIV+CTB, n =17). Their lymphoproliferative and IFN-γ responses were compared with those from HIV-uninfected controls either PPD+ (HIV−PPD+, n =17) or with past history of pulmonary tuberculosis (n =15). Most HIV-infected patients presented normal PHA responses while responses to the Mtb recombinant polypeptides ESAT-6 and Ag85B were markedly reduced. Responses to a whole Mtb lysate (S-Mtb) in HIV+PPD+ patients were lower than in HIV−PPD+ controls, while in HIV+CTB patients these responses were similar to that of past-tuberculosis controls. Comparison between the two HIV groups also suggested better S-Mtb responses in those cured from tuberculosis. Thus, while immune responses to single Mtb proteins are depressed even after successful HAART, reactivity to S-Mtb is high, specially in those cured from tuberculosis, possibly as a result of the survival of higher numbers of mycobacteria-specific T cell clones during the immunosuppression phase, which may afford sufficient protection against new Mtb challenges. [Copyright &y& Elsevier]

The QuantiFERON-TB Gold (QFT-G) is a new FDA approved test for diagnosing Mycobacterium tuberculosis infection. This test detects the release of interferon-gamma (IFNγ) in whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing 2 proteins present in M. tuberculosis: early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). These antigens have greater specificity than tests using purified protein derivative (PPD) as the tuberculosis antigen. The CDC recommends that QFT-G may be used in all circumstances in which the TB skin test is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers). Advantages of the QFT-G include: no false-positive reactions from previous BCG vaccination; no cross-reactivity with non-tuberculous mycobacterium infections; and, better detection of active tuberculosis. [ABSTRACT FROM AUTHOR]

Objective: To compare a RD1-based in-house ELISPOT-interferon-γ (IFN-γ) assay with a commercial (T-SPOT.TB™) assay for the diagnosis of Mycobacterium tuberculosis (TB) infection and the efficacy of the tuberculin skin test (TST) and ELISPOT assay in detecting latent TB infection (LTBI). Design: Eighty-six subjects (65 household contacts of contagious TB-infected patients, 13 subjects with active or previous TB infection, and 8 with suspected TB infection) were consecutively recruited in the context of a surveillance program. Methods: Enrolled subjects underwent the Mantoux TST and two different ELISPOT-IFN-γ assays: an in-house assay using a pool of selected M. tuberculosis peptides (MTP) and the commercial T-SPOT.TB assay. Results: The in-house and commercial ELISPOT-IFN-γ assays showed almost complete concordance (99%) in diagnosing acute or LTBI. When comparing the efficacy of the TST with the in-house ELISPOT assay in detecting TB infection, a small agreement was observed (k=0.344, P<0.0001): 36% of the subjects with a positive TST were ELISPOT-MTP negative and 12% with a negative TST were ELISPOT-MTP positive. Furthermore, 78% of the ELISPOT-MTP negative individuals were ELISPOT- Bacillus Calmette-Guérin (BCG) positive, most of whom had received BCG vaccination. Conclusion: Our in-house ELISPOT assay based on a restricted pool of highly selected peptides is equivalent to the commercial T-SPOT.TB assay, is cheaper and is probably not confounded, unlike the TST, by BCG vaccination in our setting [ABSTRACT FROM AUTHOR]

ABSTRACT: Once considered a disease under control, tuberculosis is again increasing in prevalence. Multidrug-resistant strains have developed that make treatment more challenging than ever before. This article summarizes the latest and most important information that should help nurse practitioners develop an index of suspicion that a patient may have this debilitating disease. [Copyright &y& Elsevier]

Abstract: Early clinical trials of a potential new tuberculosis (TB) diagnostic, the Patch Test for Active TB (PTAT), used MPB64 protein that was purified from the spent medium of Bacillus Calmette–Guérin (BCG) Tokyo 172 vaccine production. The yield was poor, 0.05mg/L, and the process for purification of the protein was complex, requiring four chromatographic steps. The combination of yield and purification complexity compromised the ability to produce the PTAT diagnostic in quantities sufficient for larger clinical trials and commercialization. We report here a highly efficient method for the overexpression and purification of recombinant MPT64 from Escherichia coli (rMPT64) based upon a mild insolubility of rMPT64 following induction, and scalable anion-exchange and gel filtration chromatographies. Yields of protein were improved substantially to approximately 250mg/L, and resulted in a preparation greater than 98% pure. Quantitative release assays were developed and used with MALDI-TOF mass spectrometry to confirm the identity of rMPT64. Using a guinea pig model of active TB, we found that rMPT64 elicited a specific immune response indistinguishable from that of MPB64 purified from BCG Tokyo culture filtrates. These results describe the first efficient and scalable protocol for production of rMPT64, demonstrate its activity in an animal model of active TB, and lay the foundation of ongoing and future use of the PTAT in clinical settings. [Copyright &y& Elsevier]

Abstract: IFN-γ responses to Mycobacterium tuberculosis antigens ESAT-6 and CFP-10 have been proposed as specific markers of M. tuberculosis infection. Monokine induced by gamma interferon (MIG/CXCL9) has been shown to be expressed by IFN-γ stimulated mononuclear cells and to attract activated T-cells through the chemokine receptor CXCR3. Since MIG is induced early in the response to IFN-γ, measuring MIG may provide an interesting marker to assess downstream IFN-γ induced responses, in contrast to assays that mainly focus on quantifying production of IFN-γ per se. We, therefore, investigated MIG and IFN-γ responses to a fusion protein of ESAT-6 and CFP-10, and compared responses to the conserved mycobacterial antigen 85B (Ag85B) and purified protein derivative (PPD) of M. tuberculosis, in 29 BCG vaccinee controls and 24 TB patients. IFN-γ secreting cells were determined by ELISPOT, and MIG production was measured by ELISA and flow cytometry. Production of MIG in response to ESAT-6/CFP-10, Ag85B and PPD correlated overall with increased numbers of IFN-γ secreting cells (r =0.55, P <0.0001). A significant increase was noted among patients compared to controls in the secretion of IFN-γ and MIG following stimulation with ESAT-6/CFP-10 or PPD (P <0.05). Moreover, MIG intracellular expression was higher in TB patients compared to BCG vaccinees (P <0.05) in response to ESAT-6/CFP-10 or PPD. We conclude that MIG production correlates significantly with enhanced T-cell IFN-γ production induced by M. tuberculosis-specific antigens ESAT-6/CFP-10. These results point to MIG as a potential novel biomarker that may be helpful in assessing downstream responses induced by IFN-γ in TB. [Copyright &y& Elsevier]

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Tuberculosis (TB) continues to be a leading infectious cause of death worldwide, and it remains a serious public health problem in developing countries. To determine the prevalence of tuberculosis infection among garment workers, the authors conducted a retrospective prevalence survey of employees working in garment factories in Qatar from January 2000 to June 2003. A mass screening of garment factory workers was carried out by chest X-ray and Mantoux skin test at the Rumailah Hospital, Hamad Medical Corporation. The authors considered those workers with a purified protein derivative (tuberculin) reaction of &nvge; 15 mm to be infected with TB, or to have a latent TB infection. Workers with active TB diseases were confirmed by histopathological and mycobacteriological examinations. The authors studied a total of 2,774 garment factory workers, and they found 43% of them to be infected (reaction &nvge; 15 mm). The mean age of the infected subjects was significantly higher than that of the noninfected subjects (p < .001); 53% of the infected subjects were between 30 and 40 years of age. Indians and Pakistanis made up the most frequent nationalities among the infected subjects (50.0%), followed by Nepalis (44.1%). The prevalence rate of tuberculosis infection in garment workers was high. Overcrowding in factories and residential facilities increases the risk of TB transmission. [ABSTRACT FROM AUTHOR]

Patients with chronic renal failure are at increased risk for tuberculosis (TB). Centers for Disease Control and Prevention (CDC) have recommended annual skin testing for TB, with tuberculin-purified protein derivative (PPD), in patients with chronic renal failure. Uremia alters the macrophage function, which can lead to anergy for skin tests. The aim of this prospective study was to determine the prevalence of positive tuberculin skin test (TST) and the booster effect of TST in hemodialysis patients living in a relatively underdeveloped portion of the country. Material and Methods. Patients were recruited from Van (Yuzuncu Yil University Hospital, Yuksek Ihtisas Hospital) and the Mus State Hospital). At the time of this study, a total of 143 patients were under hemodialysis treatment in these hemodialysis centers, and among them, 124 were included in the study. Informed consent was obtained before inclusion in the study. A positive PPD was an induration of >10 mm in response to five tuberculin units of PPD (RT23-Tween 80), at 72 h. TST-negative patients received a booster TST 10 days later, ~ 10 cm away from the previous intracutaneous injection. The test dose could not be increased due to unavailability of this kind of preparation. The test was performed and interpreted in the same way. Skin testing was performed in June and December 2003. Patients with known active TB are not included in the study. Testing was not done in hospitalized patients to rule out effects of other disease states. Results. Mean age of the patients was 45.3 ± 16 (range 13–82) years. All patients were on HD treatment twice ( n : 14) or three times ( n : 110) weekly. Duration of dialysis before TST was 30 ± 17 (12–84) months. With the first test ( n : 14), 11.3% of the patients showed a positive reaction; the second test added ( n : 15) 12.1% more TST-positive patients, reaching a total of ( n : 29) 23.4% of the patients with a positive TST. The mean induration of the positive TST was 16 ± 4 mm in the first test and 15 ± 3 mm in the second. Five (17.2%) of the patients with positive PPD and two of the patients (2.1%) with negative PPD results subsequently developed active TB within 12 months. Conclusion. We found a significant booster effect in our hemodialysis patients using TST-2. Repeat PPD test with the same dosage could detect positive patients more than twofold higher. Among positive PPD patients, TB incidence is considerably high. [ABSTRACT FROM AUTHOR]