Tuberculosis Diagnosis

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Madhukar Pai - One of the best experts on this subject based on the ideXlab platform.

  • informing decision making for universal access to quality Tuberculosis Diagnosis in india an economic epidemiological model
    BMC Medicine, 2019
    Co-Authors: Hojoon Sohn, Madhukar Pai, Parastu Kasaie, Emily A Kendall, Gabriela B Gomez, Anna Vassall, David W Dowdy
    Abstract:

    India and many other high-burden countries have committed to providing universal access to high-quality Diagnosis and drug susceptibility testing (DST) for Tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster Diagnosis and reduce losses to follow-up (LTFU). We generated functions to evaluate the costs of centralized and decentralized molecular testing for Tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] − $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for Tuberculosis.

  • Impact of fluoroquinolone treatment on delay of Tuberculosis Diagnosis: A systematic review and meta-analysis
    Elsevier, 2017
    Co-Authors: Catherine A Hogan, Lekha Puri, Genevieve Gore, Madhukar Pai
    Abstract:

    Background: Fluoroquinolones are among the most commonly used antibiotics for the treatment of respiratory infections. Because fluoroquinolones show bactericidal activity against Mycobacterium Tuberculosis, there is concern that their use can delay the Diagnosis of Tuberculosis. We conducted a systematic review and meta-analysis to assess whether empiric treatment with fluoroquinolones delays the Diagnosis and treatment of Tuberculosis in patients with respiratory tract infections. Objectives: The primary objective was to assess the delay in days in the Diagnosis and treatment of Tuberculosis, among patients who received quinolones, compared to those who received non-fluoroquinolone antibiotics. Methods: We included studies of adult patients treated with fluoroquinolones prior to a confirmed Diagnosis of Tuberculosis. We performed a literature search of 7 databases (including PubMed, Embase and Cochrane Library) with no language restrictions. We calculated an unweighted mean of estimate of difference in delay across all studies. For the studies for which the estimate was available as a mean with standard deviation, a weighted average using a random effects meta-analysis model was estimated. Results: A total of 3983 citations were identified from the literature search; of these, 17 articles were selected for full-text review. A total of 10 studies were retained for the synthesis. These included 7 retrospective cohort studies and 3 case-control studies. Only one of these studies was from a high TB burden country, South Africa. The most commonly used fluoroquinolones were levofloxacin, gemifloxacin and moxifloxacin. The unweighted average of difference in delay between the fluoroquinolone group and non-fluoroquinolone group was 12.9 days (95% CI 6.1â19.7). When these differences were pooled using a random effects model, the weighted estimate was 10.9 days (95% CI 4.2â17.6). When stratified by acid-fast smear status, the delay was consistently greater in the smear-negative group. Conclusion: Although results are variable, the use of fluoroquinolones in patients with respiratory infections seems to delay the Diagnosis of TB by nearly two weeks. Consistent with the International Standards for TB Care, their use should be avoided when Tuberculosis is suspected. Keywords: Tuberculosis, Fluoroquinolones, Diagnostic dela

  • interferon γ release assays for active pulmonary Tuberculosis Diagnosis in adults in low and middle income countries systematic review and meta analysis
    The Journal of Infectious Diseases, 2011
    Co-Authors: John Z Metcalfe, Charles K Everett, Karen R Steingart, Adithya Cattamanchi, Laurence Huang, Philip C Hopewell, Madhukar Pai
    Abstract:

    Background. The diagnostic value of interferon-c release assays (IGRAs) for active Tuberculosis in low- and middle-income countries is unclear. Methods. We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary Tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. Results. Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)‐uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%‐92%) for T-SPOT and 60% (95% CI, 34%‐82%) for QFT-GIT. HSROC/ bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%‐79%]; QFT-GIT, 52% [95% CI, 41%‐62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%‐63%]; QFT-GIT, 50% [95% CI, 35%‐65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active Tuberculosis Diagnosis. Conclusions. In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active Tuberculosis Diagnosis in adults, especially in the context of HIV coinfection.

  • Tuberculosis Diagnosis time for a game change
    The New England Journal of Medicine, 2010
    Co-Authors: Peter M Small, Madhukar Pai
    Abstract:

    The effective treatment of Tuberculosis is a lifesaving intervention. The global scale-up of Tuberculosis therapy has averted 6 million deaths over the past 15 years, making it one of the greatest public health interventions of our lifetime.1 Unfortunately, by the time most patients are treated, they have already infected many others.2 This failure to interrupt transmission fuels the global epidemic so that every year there are more new cases of Tuberculosis than in the previous year.1 National Tuberculosis programs are particularly challenged by multidrug-resistant Tuberculosis. Globally, fewer than 2% of the estimated cases of multidrug-resistant disease are reported to the . . .

  • novel and improved technologies for Tuberculosis Diagnosis progress and challenges
    Clinics in Chest Medicine, 2009
    Co-Authors: Madhukar Pai, Jessica Minion, Hojoon Sohn, Alice Zwerling, Mark D Perkins
    Abstract:

    Despite a decade of success in improving cure rates for Tuberculosis (TB), Diagnosis and case detection remain a major obstacle to TB control. This article reviews the existing evidence base on TB diagnostics, describes the progress of new technologies, and ends with a review of cost-effectiveness and modeling studies on the potential effect of new diagnostics in TB control.

Adithya Cattamanchi - One of the best experts on this subject based on the ideXlab platform.

  • quality of care in childhood Tuberculosis Diagnosis at primary care clinics in kampala uganda
    International Journal of Tuberculosis and Lung Disease, 2018
    Co-Authors: Samuel Kizito, Achilles Katamba, Carina Marquez, P Turimumahoro, Irene Ayakaka, J L Davis, Adithya Cattamanchi
    Abstract:

    OBJECTIVE To assess the quality of routine childhood Tuberculosis (TB) evaluation in Kampala, Uganda. SETTING AND DESIGN This was a cross-sectional study of children aged <15 years attending six government-run clinics from November 2015 to December 2016. Clinicians completed a standardized patient record form for all child visits. We assessed the following performance indicators of TB evaluation developed based on the Desk Guide of the International Union Against Tuberculosis and Lung Disease, an evidence-based decision aid on childhood TB Diagnosis and management for clinicians: proportion screened for TB symptoms or contact history, proportion referred for laboratory evaluation if screen-positive, and proportion treated for TB if test-positive or meeting clinical criteria. RESULTS Of 24 566 consecutive children enrolled, 11 614 (47%) were fully screened for TB symptoms. Of 1747 (15%) children who screened positive, 360 (21%) had sputum examined, including 159 (44%) using smear microscopy, 244 (67%) using Xpert® MTB/RIF, and 52 (14%) using both techniques. Treatment was initiated in 18/20 (80%) children who tested positive. An additional 65 screen-positive children met the clinical criteria for TB; none were initiated on treatment. CONCLUSIONS Large gaps exist along the pathway to Diagnosis and treatment of childhood TB. There is an urgent need for enhanced implementation of evidence-based approaches to TB Diagnosis to improve outcomes in childhood TB.

  • automated Tuberculosis Diagnosis using fluorescence images from a mobile microscope
    Medical Image Computing and Computer-Assisted Intervention, 2012
    Co-Authors: Jeannette Chang, Adithya Cattamanchi, Pablo Arbelaez, Neil A Switz, Clay Reber, Asa Tapley, Lucian J Davis, Daniel A Fletcher, Jitendra Malik
    Abstract:

    In low-resource areas, the most common method of Tuberculosis (TB) Diagnosis is visual identification of rod-shaped TB bacilli in microscopic images of sputum smears. We present an algorithm for automated TB detection using images from digital microscopes such as CellScope, a novel, portable device capable of brightfield and fluorescence microscopy. Automated processing on such platforms could save lives by bringing healthcare to rural areas with limited access to laboratory-based diagnostics. Our algorithm applies morphological operations and template matching with a Gaussian kernel to identify candidate TB-objects. We characterize these objects using Hu moments, geometric and photometric features, and histograms of oriented gradients and then perform support vector machine classification. We test our algorithm on a large set of CellScope images (594 images corresponding to 290 patients) from sputum smears collected at clinics in Uganda. Our object-level classification performance is highly accurate, with average precision of 89.2% +/- 2.1%. For slide-level classification, our algorithm performs at the level of human readers, demonstrating the potential for making a significant impact on global healthcare.

  • interferon γ release assays for active pulmonary Tuberculosis Diagnosis in adults in low and middle income countries systematic review and meta analysis
    The Journal of Infectious Diseases, 2011
    Co-Authors: John Z Metcalfe, Charles K Everett, Karen R Steingart, Adithya Cattamanchi, Laurence Huang, Philip C Hopewell, Madhukar Pai
    Abstract:

    Background. The diagnostic value of interferon-c release assays (IGRAs) for active Tuberculosis in low- and middle-income countries is unclear. Methods. We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary Tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. Results. Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)‐uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%‐92%) for T-SPOT and 60% (95% CI, 34%‐82%) for QFT-GIT. HSROC/ bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%‐79%]; QFT-GIT, 52% [95% CI, 41%‐62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%‐63%]; QFT-GIT, 50% [95% CI, 35%‐65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active Tuberculosis Diagnosis. Conclusions. In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active Tuberculosis Diagnosis in adults, especially in the context of HIV coinfection.

Susan E. Dorman - One of the best experts on this subject based on the ideXlab platform.

  • quantiferon tb gold in tube implementation for latent Tuberculosis Diagnosis in a public health clinic a cost effectiveness analysis
    BMC Infectious Diseases, 2012
    Co-Authors: Maunank Shah, Danielle Dipietro, Maria Martinsevora, Vincent Marsiglia, Kathryn Miele, Howard Choi, Susan E. Dorman
    Abstract:

    Background The tuberculin skin test (TST) has limitations for latent Tuberculosis infection (LTBI) Diagnosis in low-prevalence settings. Previously, all TST-positive individuals referred from the community to Baltimore City Health Department (BCHD) were offered LTBI treatment, after active TB was excluded. In 2010, BCHD introduced adjunctive QuantiFERON-TB Gold In-Tube (QFT-GIT) testing for TST-positive referrals. We evaluated costs and cost-effectiveness of this new diagnostic algorithm.

  • programmatic impact of quantiferon tb gold in tube implementation on latent Tuberculosis Diagnosis and treatment in a public health clinic
    PLOS ONE, 2012
    Co-Authors: Maunank Shah, Danielle Dipietro, Adena Greenbaum, Sherry Ketemepi, Maria Martinsevora, Vincent Marsiglia, Susan E. Dorman
    Abstract:

    Background QuantiFERON-TB Gold In-Tube (QFT-GIT) is considered an alternative to the tuberculin skin test (TST) for the Diagnosis of Tuberculosis (TB) infection, but the programmatic impact of QFT-GIT implementation is largely unknown. In March, 2010, the Baltimore City Health Department (BCHD) introduced routine QFT-GIT testing for individuals referred to the TB program for suspected latent TB infection (LTBI).

  • impact of enhanced Tuberculosis Diagnosis in south africa a mathematical model of expanded culture and drug susceptibility testing
    Proceedings of the National Academy of Sciences of the United States of America, 2008
    Co-Authors: David Wesley Dowdy, Richard E Chaisson, Gary Maartens, Elizabeth L Corbett, Susan E. Dorman
    Abstract:

    South Africa has high rates of Tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB Diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Performing culture and DST in 37% of new cases and 85% of previously treated cases was projected to save 47,955 lives (17.2% reduction in TB mortality, 95% simulation interval (S.I.) 8.9-24.4%), avert 7,721 MDR-TB cases (14.1% reduction, 95% S.I. 5.3-23.8%), and prevent 46.6% of MDR-TB deaths (95% S.I. 32.6-56.0%) in South Africa over 10 years. Used alone, expanded culture and DST did not reduce XDR-TB incidence, but they enhanced the impact of transmission-reduction strategies, such as respiratory isolation. In South Africa, expanding TB culture and DST could substantially reduce TB, and particularly MDR-TB, mortality. Control of XDR-TB will require additional interventions, the impact of which may be enhanced by improved TB Diagnosis.

John Z Metcalfe - One of the best experts on this subject based on the ideXlab platform.

  • point of care xpert mtb rif versus smear microscopy for Tuberculosis Diagnosis in southern african primary care clinics a multicentre economic evaluation
    The Lancet Global Health, 2019
    Co-Authors: Anil Pooran, Grant Theron, Lynn S Zijenah, Duncan Chanda, Petra Clowes, Lawrence Mwenge, Farirai Mutenherwa, Paul Lecesse, John Z Metcalfe
    Abstract:

    Summary Background Rapid on-site Diagnosis facilitates Tuberculosis control. Performing Xpert MTB/RIF (Xpert) at point of care is feasible, even when performed by minimally trained health-care workers, and when compared with point-of-care smear microscopy, reduces time to Diagnosis and pretreatment loss to follow-up. However, whether Xpert is cost-effective at point of care remains unclear. Methods We empirically collected cost (US$, 2014) and clinical outcome data from participants presenting to primary health-care facilities in four African countries (South Africa, Zambia, Zimbabwe, and Tanzania) during the TB-NEAT trial. Costs were determined using an bottom-up ingredients approach. Effectiveness measures from the trial included number of cases diagnosed, initiated on treatment, and completing treatment. The primary outcome was the incremental cost-effectiveness of point-of-care Xpert relative to smear microscopy. The study was performed from the perspective of the health-care provider. Findings Using data from 1502 patients, we calculated that the mean Xpert unit cost was lower when performed at a centralised laboratory (Lab Xpert) rather than at point of care ($23·00 [95% CI 22·12–23·88] vs $28·03 [26·19–29·87]). Per 1000 patients screened, and relative to smear microscopy, point-of-care Xpert cost an additional $35 529 (27 054–40 025) and was associated with an additional 24·3 treatment initiations ([–20·0 to 68·5]; $1464 per treatment), 63·4 same-day treatment initiations ([27·3–99·4]; $511 per same-day treatment), and 29·4 treatment completions ([–6·9 to 65·6]; $1211 per completion). Xpert costs were most sensitive to test volume, whereas incremental outcomes were most sensitive to the number of patients initiating and completing treatment. The probability of point-of-care Xpert being cost-effective was 90% at a willingness to pay of $3820 per treatment completion. Interpretation In southern Africa, although point-of-care Xpert unit cost is higher than Lab Xpert, it is likely to offer good value for money relative to smear microscopy. With the current availability of point-of-care nucleic acid amplification platforms (eg, Xpert Edge), these data inform much needed investment and resource allocation strategies in Tuberculosis endemic settings. Funding European Union European and Developing Countries Clinical Trials Partnership and the South African Medical Research Council.

  • interferon γ release assays for active pulmonary Tuberculosis Diagnosis in adults in low and middle income countries systematic review and meta analysis
    The Journal of Infectious Diseases, 2011
    Co-Authors: John Z Metcalfe, Charles K Everett, Karen R Steingart, Adithya Cattamanchi, Laurence Huang, Philip C Hopewell, Madhukar Pai
    Abstract:

    Background. The diagnostic value of interferon-c release assays (IGRAs) for active Tuberculosis in low- and middle-income countries is unclear. Methods. We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary Tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. Results. Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)‐uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%‐92%) for T-SPOT and 60% (95% CI, 34%‐82%) for QFT-GIT. HSROC/ bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%‐79%]; QFT-GIT, 52% [95% CI, 41%‐62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%‐63%]; QFT-GIT, 50% [95% CI, 35%‐65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active Tuberculosis Diagnosis. Conclusions. In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active Tuberculosis Diagnosis in adults, especially in the context of HIV coinfection.

Jose De La Fuente - One of the best experts on this subject based on the ideXlab platform.

  • Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for seroDiagnosis of bovine Tuberculosis
    'Springer Science and Business Media LLC', 2018
    Co-Authors: Infantes-lorenzo, José Antonio, Risalde, María Ángeles, Moreno Inmaculada, Romero Beatriz, Jose De La Fuente, Roy Álvaro, Villar Margarita, Ibarrola Nieves, Puentes Eugenia, Lucía De ,juan
    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.This work was supported by the Ministerio de Economía, Industria y Competitividad of Spain (RTC-2016-4746-2), the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria of Spain (RTA2015-00043-C02-02) and the TAVS-CM Programme of the Comunidad de Madrid (S2013/ABI-2747), cofinanced by the FEDER fund “A way to build Europe”. Jose Antonio Infantes-Lorenzo was supported by an FPU contract-fellowship (Formación de Profesorado Universitario) from the Ministerio de Educación, Cultura y Deporte of the Spanish Government (FPU2013/6000). Alvaro Roy is the recipient of an Industrial Doctorate contract (DI-15-08110) funded by the Spanish Ministerio de Economía, Industria y Competitividad and the European Social Fund.Peer Reviewe

  • proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for seroDiagnosis of bovine Tuberculosis
    Clinical Proteomics, 2017
    Co-Authors: Jose Antonio Infanteslorenzo, Inmaculada Moreno, Maria Angeles Risalde, Alvaro Roy, Margarita Villar, Beatriz Romero, Nieves Ibarrola, Jose De La Fuente
    Abstract:

    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. 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. 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. 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.

  • Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for seroDiagnosis of bovine Tuberculosis
    BMC, 2017
    Co-Authors: José Antonio Infantes-lorenzo, Inmaculada Moreno, Alvaro Roy, Margarita Villar, Beatriz Romero, Nieves Ibarrola, Jose De La Fuente, María De Los Ángeles Risalde, Eugenia Puentes, Lucía De ,juan
    Abstract:

    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

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