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1. Age and sex influence antibody profiles associated with tuberculosis progression

Author

Davies, Leela R. L., Wang, Chuangqi, Steigler, Pia, Bowman, Kathryn A., Fischinger, Stephanie, Hatherill, Mark, Fisher, Michelle, Mbandi, Stanley Kimbung, Rodo, Miguel, Ottenhoff, Tom H. M., Dockrell, Hazel M., Sutherland, Jayne S., Mayanja-Kizza, Harriet, Boom, W. Henry, Walzl, Gerhard, Kaufmann, Stefan H. E., Nemes, Elisa, Scriba, Thomas J., Lauffenburger, Douglas, Alter, Galit, and Fortune, Sarah M.

Published
2024
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2. Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control

Author

Swanson, Rosemary V., Gupta, Ananya, Foreman, Taylor W., Lu, Lan, Choreno-Parra, Jose Alberto, Mbandi, Stanley Kimbung, Rosa, Bruce A., Akter, Sadia, Das, Shibali, Ahmed, Mushtaq, Garcia-Hernandez, Maria de la Luz, Singh, Dhiraj K., Esaulova, Ekaterina, Artyomov, Maxim N., Gommerman, Jennifer, Mehra, Smriti, Zuniga, Joaquin, Mitreva, Makedonka, Scriba, Thomas J., Rangel-Moreno, Javier, Kaushal, Deepak, and Khader, Shabaana A.

Published
2023
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3. RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response

Author

Penn-Nicholson, Adam, Mbandi, Stanley Kimbung, Thompson, Ethan, Mendelsohn, Simon C, Suliman, Sara, Chegou, Novel N, Malherbe, Stephanus T, Darboe, Fatoumatta, Erasmus, Mzwandile, Hanekom, Willem A, Bilek, Nicole, Fisher, Michelle, Kaufmann, Stefan HE, Winter, Jill, Murphy, Melissa, Wood, Robin, Morrow, Carl, Van Rhijn, Ildiko, Moody, Branch, Murray, Megan, Andrade, Bruno B, Sterling, Timothy R, Sutherland, Jayne, Naidoo, Kogieleum, Padayatchi, Nesri, Walzl, Gerhard, Hatherill, Mark, Zak, Daniel, and Scriba, Thomas J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Prevention, Infectious Diseases, HIV/AIDS, Lung, Tuberculosis, Rare Diseases, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Infection, Good Health and Well Being, Adolescent, Area Under Curve, Biomarkers, Cohort Studies, Female, HIV Infections, Humans, Male, Mycobacterium tuberculosis, Point-of-Care Systems, Positron-Emission Tomography, Prognosis, RNA, Bacterial, ROC Curve, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Adolescent Cohort Study team, GC6-74 Consortium, SATVI Clinical and Laboratory Team, ScreenTB Consortium, AE-TBC Consortium, RePORT Brazil Team, Peruvian Household Contacts Cohort Team, CAPRISA IMPRESS team
Abstract

Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.

Published
2020

4. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis

Author

Hamada, Yohhei, Gupta, Rishi K., Quartagno, Matteo, Izzard, Abbie, Acuna-Villaorduna, Carlos, Altet, Neus, Diel, Roland, Dominguez, Jose, Floyd, Sian, Gupta, Amita, Huerga, Helena, Jones-López, Edward C., Kinikar, Aarti, Lange, Christoph, van Leth, Frank, Liu, Qiao, Lu, Wei, Lu, Peng, Rueda, Irene Latorre, Martinez, Leonardo, Mbandi, Stanley Kimbung, Muñoz, Laura, Padilla, Elisabeth Sánchez, Paradkar, Mandar, Scriba, Thomas, Sester, Martina, Shanaube, Kwame, Sharma, Surendra K., Sloot, Rosa, Sotgiu, Giovanni, Thiruvengadam, Kannan, Vashishtha, Richa, Abubakar, Ibrahim, and Rangaka, Molebogeng X.

Published
2023
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5. Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study

Author

Penn-Nicholson, Adam, Hraha, Thomas, Thompson, Ethan G, Sterling, David, Mbandi, Stanley Kimbung, Wall, Kirsten M, Fisher, Michelle, Suliman, Sara, Shankar, Smitha, Hanekom, Willem A, Janjic, Nebojsa, Hatherill, Mark, Kaufmann, Stefan HE, Sutherland, Jayne, Walzl, Gerhard, De Groote, Mary Ann, Ochsner, Urs, Zak, Daniel E, and Scriba, Thomas J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Rare Diseases, HIV/AIDS, Tuberculosis, Clinical Research, Prevention, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Infection, Good Health and Well Being, Adolescent, Biomarkers, Child, Cohort Studies, Diagnostic Tests, Routine, Disease Progression, Female, Humans, Longitudinal Studies, Male, Point-of-Care Testing, Prognosis, Prospective Studies, Proteome, Proteomics, ACS and GC6–74 cohort study groups, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundA nonsputum blood test capable of predicting progression of healthy individuals to active tuberculosis (TB) before clinical symptoms manifest would allow targeted treatment to curb transmission. We aimed to develop a proteomic biomarker of risk of TB progression for ultimate translation into a point-of-care diagnostic.Methods and findingsProteomic TB risk signatures were discovered in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents aged 12-18 years (68% female) who participated in the Adolescent Cohort Study (ACS) between July 6, 2005 and April 23, 2007, through either active (every 6 months) or passive follow-up over 2 years. Forty-six individuals developed microbiologically confirmed TB disease within 2 years of follow-up and were selected as progressors; 106 nonprogressors, who remained healthy, were matched to progressors. Over 3,000 human proteins were quantified in plasma with a highly multiplexed proteomic assay (SOMAscan). Three hundred sixty-one proteins of differential abundance between progressors and nonprogressors were identified. A 5-protein signature, TB Risk Model 5 (TRM5), was discovered in the ACS training set and verified by blind prediction in the ACS test set. Poor performance on samples 13-24 months before TB diagnosis motivated discovery of a second 3-protein signature, 3-protein pair-ratio (3PR) developed using an orthogonal strategy on the full ACS subcohort. Prognostic performance of both signatures was validated in an independent cohort of 1,948 HIV-negative household TB contacts from The Gambia (aged 15-60 years, 66% female), longitudinally followed up for 2 years between March 5, 2007 and October 21, 2010, sampled at baseline, month 6, and month 18. Amongst these contacts, 34 individuals progressed to microbiologically confirmed TB disease and were included as progressors, and 115 nonprogressors were included as controls. Prognostic performance of the TRM5 signature in the ACS training set was excellent within 6 months of TB diagnosis (area under the receiver operating characteristic curve [AUC] 0.96 [95% confidence interval, 0.93-0.99]) and 6-12 months (AUC 0.76 [0.65-0.87]) before TB diagnosis. TRM5 validated with an AUC of 0.66 (0.56-0.75) within 1 year of TB diagnosis in the Gambian validation cohort. The 3PR signature yielded an AUC of 0.89 (0.84-0.95) within 6 months of TB diagnosis and 0.72 (0.64-0.81) 7-12 months before TB diagnosis in the entire South African discovery cohort and validated with an AUC of 0.65 (0.55-0.75) within 1 year of TB diagnosis in the Gambian validation cohort. Signature validation may have been limited by a systematic shift in signal magnitudes generated by differences between the validation assay when compared to the discovery assay. Further validation, especially in cohorts from non-African countries, is necessary to determine how generalizable signature performance is.ConclusionsBoth proteomic TB risk signatures predicted progression to incident TB within a year of diagnosis. To our knowledge, these are the first validated prognostic proteomic signatures. Neither meet the minimum criteria as defined in the WHO Target Product Profile for a progression test. More work is required to develop such a test for practical identification of individuals for investigation of incipient, subclinical, or active TB disease for appropriate treatment and care.

Published
2019

7. Transcriptomic Signatures of Progression to Tuberculosis Disease Among Close Contacts in Brazil.

Author

Mendelsohn, Simon C, Andrade, Bruno B, Mbandi, Stanley Kimbung, Andrade, Alice M S, Muwanga, Vanessa M, Figueiredo, Marina C, Erasmus, Mzwandile, Rolla, Valeria C, Thami, Prisca K, Cordeiro-Santos, Marcelo, Penn-Nicholson, Adam, Kritski, Afranio L, Hatherill, Mark, Sterling, Timothy R, Scriba, Thomas J, and Consortia, the RePORT–South Africa and RePORT–Brazil

Abstract

Background Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. Methods Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up. Results Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up. Conclusions Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR

Author

Mendelsohn, Simon C., Mbandi, Stanley Kimbung, Fiore-Gartland, Andrew, Penn-Nicholson, Adam, Musvosvi, Munyaradzi, Mulenga, Humphrey, Fisher, Michelle, Hadley, Katie, Erasmus, Mzwandile, Nombida, Onke, Tameris, Michèle, Walzl, Gerhard, Naidoo, Kogieleum, Churchyard, Gavin, Hatherill, Mark, and Scriba, Thomas J.

Published
2022
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12. Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Author

Abrahams, Charmaine, Africa, Hadn, Ahlers, Petri, Arendsen, Denis, Badimo, Tebogo, Baepanye, Kagiso, Baepanye, Kesenogile Edna, Bande, Bianca, Batyi, Nomfuneko Cynthia, Beukes, Roslyn, Bontsi, Laudicia Tshenolo, Booi, Obakeng Peter, Botha, Mari Cathrin, Braaf, Samentra, Buhlungu, Sivuyile, Carstens, Alida, Chauke, Kgomotso Violet, Chinappa, Thilagavathy, Chung, Eva, Chung, Michelle, Clarke, Ken, Cloete, Yolundi, Coetzee, Lorraine, Collignon, Marelize, Companie, Alessandro, Corris, Cara-mia, Cwaile, Mooketsi Theophillius, Cwele, Thobelani, Davids, Ilse, Davies, Isabella Johanna, De Klerk, Emilia, de Kock, Marwou, Dhlamini, Audrey Lebohang, Diamond, Bongani, Didloff, Maria, Dlamini, Celaphiwe, Dolo, Palesa, Eyre, Candice, Feni, Tebogo, Ferreira, Juanita, Ferus, Christal, Fisher, Michelle, Flinn, Marika, Fransman, Bernadine, Galane, Welseh Phindile, Geldenhuys, Hennie, Gempies, Diann, Goliath, Thelma, Govender, Dhineshree, Gregg, Yolande, Gumede, Goodness, Gwamada, Zanele, Halti, Senzo, Hassiem, Rieyaat, Herling, Roxane, Herselman, Yulandi, Hughes, Ellis, Issel, Henry, Iyemosolo, Blanchard Mbay, Jali, Zandile, Janse Van Rensburg, Bonita, Jansen, Ruwiyda, Jeleni, James Michael, Jonkane, Olebogeng, Julies, Fabio, Kafaar, Fazlin, Kasongo, Christian Mabika, Keffers, Sophie, Kekana, Boitumelo Sophy, Kekana, Sebaetseng Jeanette, Kelepu, Xoliswa, Khanyile, Lungile, Khobedi, Gomotsegang Virginia, Khomba, Gloria, Khoza, Lucky Sipho, King, Marietjie, Kolobe, Gloria Keitumetse, Kruger, Sandra, Kruger, Jaftha, Kunene, Ndlela Israel, Lakay, Sunelza, Lakhi, Aneesa, Langa, Nondumiso, Ledwaba, Hildah, Lekagane, Lerato Julia, Lekotloane, Sheiley Christina, Leopeng, Thelma, Louw, Ilze Jeanette, Luabeya, Angelique Kany Kany, Lusale, Sarah Teboso, Maatjie, Perfect Tiisetso, Mabasa, Immaculate, Mabe, Tshegofatso Dorah, Mabena, Kamogelo Fortunate, Mabuza, Nkosinathi Charles, Mabwe, Simbarashe, Madikwe, Johanna Thapelo, Madikwe, Octavia Mahkosazana, Maebana, Rapontwana Letlhogonolo, Magwasha, Malobisa Sylvester, Majola, Molly, Makhetha, Mantai, Makhethe, Lebohang, Malay, Vernon, Manzini, Vutlhari-I-Vunhenha Fairlord, Maphanga, Jabu, Maphanga, Nonhle, Market, Juanita, Maroele, Isholedi Samuel, Masibi, Omphile Petunia, Mathabanzini, July Rocky, Mathode, Tendamudzimu Ivan, Matsane, Ellen Ditaba, Mbata, Lungile, Meyer, Faheema, Mhandire, Nyasha Karen, Miga, Thembisiwe, Mkhize, Nosisa Charity Thandeka, Mkhokho, Caroline, Mkwalase, Neo Hilda, Mnqonywa, Nondzakazi, Moche, Karabo, Modisaotsile, Brenda Matshidiso, Mokgetsengoane, Patricia Pakiso, Mokone, Selemeng Matseliso Carol, Molatlhegi, Kegomoditswe Magdeline, Molefe, Thuso Andrew, Moloko, Joseph Panie, Molosi, Kabelo, Molotsi, Motlatsi Evelyn, Montwedi, Tebogo Edwin, Monyemangene, Boikanyo Dinah, Mooketsi, Hellen Mokopi, Moses, Miriam, Mosito, Boitumelo, Mosito, Tshplpfelo Mapula, Mosweu, Ireen Lesebang, Mothaga, Primrose, Motlagomang, Banyana Olga, Mouton, Angelique, Mpofu, Onesisa, Mthembu, Funeka Nomvula, Mtlali, Mpho, Ndlovu, Nhlamulo, Ngcobo, Nompumelelo, Noble, Julia, Ntamo, Bantubonke Bertrum, Ntanjana, Gloria, Ntshauba, Tedrius, Opperman, Fajwa, Padayatchi, Nesri, Papalagae, Thandiwe, Petersen, Christel, Phakathi, Themba, Phatshwane, Mapule Ozma, Plaatjie, Patiswa, Pretorius, Abe, Rameetse, Victor Kgothatso, Ramjit, Dirhona, Ratangee, Frances, Ratangee, Maigan, Sanyaka, Pearl Nomsa, Sato, Alicia, Schoeman, Elisma, Schreuder, Constance, Seabela, Letlhogonolo, Segaetsho, Kelebogile Magdeline, Sein, Ni Ni, Selepe, Raesibe Agnes Pearl, Senne, Melissa Neo, September, Alison, September, Cashwin, Serake, Moeti, Shenje, Justin, Shezi, Thandiwe, Shezi, Sifiso Cornelius, Sing, Phindile, Singh, Chandrapharbha, Sithetho, Zona, Solomons, Dorothy, Stanley, Kim, Steyn, Marcia, Stofile, Bongiwe, Stryers, Sonia, Swanepoel, Liticia, Swarts, Anne, Thaba, Mando Mmakhora, Theko, Lethabo Collen, Thembela, Philile, Thompo, Mugwena, Toefy, Asma, Toto, Khayalethu, Tsagae, Dimakatso Sylvia, Tsamane, Ayanda, Tshikovhi, Vincent, Tswaile, Lebogang Isaac, Tyambetyu, Petrus, Tönsing, Susanne, Valley, Habibullah, van der Merwe, Linda, van Rooyen, Elma, Veldsman, Ashley, Veldtsman, Helen, Vollenhoven, Kelvin, Zaca, Londiwe, Zimri, Elaine, Zulu, Mbali, Mendelsohn, Simon C, Fiore-Gartland, Andrew, Penn-Nicholson, Adam, Mulenga, Humphrey, Mbandi, Stanley Kimbung, Borate, Bhavesh, Hadley, Katie, Hikuam, Chris, Musvosvi, Munyaradzi, Bilek, Nicole, Erasmus, Mzwandile, Jaxa, Lungisa, Raphela, Rodney, Nombida, Onke, Kaskar, Masooda, Sumner, Tom, White, Richard G, Innes, Craig, Brumskine, William, Hiemstra, Andriëtte, Malherbe, Stephanus T, Hassan-Moosa, Razia, Tameris, Michèle, Walzl, Gerhard, Naidoo, Kogieleum, Churchyard, Gavin, Scriba, Thomas J, and Hatherill, Mark

Published
2021
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13. Diagnostic Performance of Host Blood Transcriptomic Signatures for Pulmonary Tuberculosis in a Multi-Cohort Study of Symptomatic Patients in Africa

Author

Muwanga, Vanessa, primary, Mendelsohn, Simon C., additional, Leukes, Vinzeigh, additional, Stanley, Kim, additional, Mbandi, Stanley Kimbung, additional, Erasmus, Mzwandile, additional, Flinn, Marika, additional, Fisher, Tarryn-Lee, additional, Raphela, Rodney, additional, Bilek, Nicole, additional, Malherbe, Stephanus T., additional, Tromp, Gerard, additional, Van der Spuy, Gian, additional, Walzl, Gerhard, additional, Chegou, Novel N., additional, and Scriba, Thomas J., additional

Published
2023
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14. Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Author

Llibre, Alba, primary, Smith, Nikaïa, additional, Rouilly, Vincent, additional, Musvosvi, Munyaradzi, additional, Nemes, Elisa, additional, Posseme, Céline, additional, Mabwe, Simbarashe, additional, Charbit, Bruno, additional, Mbandi, Stanley Kimbung, additional, Filander, Elizabeth, additional, Africa, Hadn, additional, Saint-André, Violaine, additional, Bondet, Vincent, additional, Bost, Pierre, additional, Mulenga, Humphrey, additional, Bilek, Nicole, additional, Albert, Matthew L., additional, Scriba, Thomas J., additional, and Duffy, Darragh, additional

Published
2022
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15. Host-Directed Targeting of LincRNA-MIR99AHG Suppresses Intracellular Growth of Mycobacterium tuberculosis

Author

Gcanga, Lorna, primary, Tamgue, Ousman, additional, Ozturk, Mumin, additional, Pillay, Shandre, additional, Jacobs, Raygaana, additional, Chia, Julius Ebua, additional, Mbandi, Stanley Kimbung, additional, Davids, Malika, additional, Dheda, Keertan, additional, Schmeier, Sebastian, additional, Alam, Tanvir, additional, Roy, Sugata, additional, Suzuki, Harukazu, additional, Brombacher, Frank, additional, and Guler, Reto, additional

Published
2022
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16. Host transcriptomic signatures of tuberculosis can predict immune reconstitution inflammatory syndrome in HIV patients

Author

Mbandi, Stanley Kimbung, primary, Painter, Hannah, additional, Penn‐Nicholson, Adam, additional, Toefy, Asma, additional, Erasmus, Mzwandile, additional, Hanekom, Willem A., additional, Scriba, Thomas J., additional, Lai, Rachel P.J., additional, Marais, Suzaan, additional, Fletcher, Helen A., additional, Meintjes, Graeme, additional, Wilkinson, Robert J., additional, Cotton, Mark F., additional, Pahwa, Savita, additional, Cameron, Mark J., additional, and Nemes, Elisa, additional

Published
2022
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18. Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study

Author

Mendelsohn, Simon C, primary, Fiore-Gartland, Andrew, additional, Penn-Nicholson, Adam, additional, Mulenga, Humphrey, additional, Mbandi, Stanley Kimbung, additional, Borate, Bhavesh, additional, Hadley, Katie, additional, Hikuam, Chris, additional, Musvosvi, Munyaradzi, additional, Bilek, Nicole, additional, Erasmus, Mzwandile, additional, Jaxa, Lungisa, additional, Raphela, Rodney, additional, Nombida, Onke, additional, Kaskar, Masooda, additional, Sumner, Tom, additional, White, Richard G, additional, Innes, Craig, additional, Brumskine, William, additional, Hiemstra, Andriëtte, additional, Malherbe, Stephanus T, additional, Hassan-Moosa, Razia, additional, Tameris, Michèle, additional, Walzl, Gerhard, additional, Naidoo, Kogieleum, additional, Churchyard, Gavin, additional, Scriba, Thomas J, additional, Hatherill, Mark, additional, Abrahams, Charmaine, additional, Africa, Hadn, additional, Ahlers, Petri, additional, Arendsen, Denis, additional, Badimo, Tebogo, additional, Baepanye, Kagiso, additional, Baepanye, Kesenogile Edna, additional, Bande, Bianca, additional, Batyi, Nomfuneko Cynthia, additional, Beukes, Roslyn, additional, Bontsi, Laudicia Tshenolo, additional, Booi, Obakeng Peter, additional, Botha, Mari Cathrin, additional, Braaf, Samentra, additional, Buhlungu, Sivuyile, additional, Carstens, Alida, additional, Chauke, Kgomotso Violet, additional, Chinappa, Thilagavathy, additional, Chung, Eva, additional, Chung, Michelle, additional, Clarke, Ken, additional, Cloete, Yolundi, additional, Coetzee, Lorraine, additional, Collignon, Marelize, additional, Companie, Alessandro, additional, Corris, Cara-mia, additional, Cwaile, Mooketsi Theophillius, additional, Cwele, Thobelani, additional, Davids, Ilse, additional, Davies, Isabella Johanna, additional, De Klerk, Emilia, additional, de Kock, Marwou, additional, Dhlamini, Audrey Lebohang, additional, Diamond, Bongani, additional, Didloff, Maria, additional, Dlamini, Celaphiwe, additional, Dolo, Palesa, additional, Eyre, Candice, additional, Feni, Tebogo, additional, Ferreira, Juanita, additional, Ferus, Christal, additional, Fisher, Michelle, additional, Flinn, Marika, additional, Fransman, Bernadine, additional, Galane, Welseh Phindile, additional, Geldenhuys, Hennie, additional, Gempies, Diann, additional, Goliath, Thelma, additional, Govender, Dhineshree, additional, Gregg, Yolande, additional, Gumede, Goodness, additional, Gwamada, Zanele, additional, Halti, Senzo, additional, Hassiem, Rieyaat, additional, Herling, Roxane, additional, Herselman, Yulandi, additional, Hughes, Ellis, additional, Issel, Henry, additional, Iyemosolo, Blanchard Mbay, additional, Jali, Zandile, additional, Janse Van Rensburg, Bonita, additional, Jansen, Ruwiyda, additional, Jeleni, James Michael, additional, Jonkane, Olebogeng, additional, Julies, Fabio, additional, Kafaar, Fazlin, additional, Kasongo, Christian Mabika, additional, Keffers, Sophie, additional, Kekana, Boitumelo Sophy, additional, Kekana, Sebaetseng Jeanette, additional, Kelepu, Xoliswa, additional, Khanyile, Lungile, additional, Khobedi, Gomotsegang Virginia, additional, Khomba, Gloria, additional, Khoza, Lucky Sipho, additional, King, Marietjie, additional, Kolobe, Gloria Keitumetse, additional, Kruger, Sandra, additional, Kruger, Jaftha, additional, Kunene, Ndlela Israel, additional, Lakay, Sunelza, additional, Lakhi, Aneesa, additional, Langa, Nondumiso, additional, Ledwaba, Hildah, additional, Lekagane, Lerato Julia, additional, Lekotloane, Sheiley Christina, additional, Leopeng, Thelma, additional, Louw, Ilze Jeanette, additional, Luabeya, Angelique Kany Kany, additional, Lusale, Sarah Teboso, additional, Maatjie, Perfect Tiisetso, additional, Mabasa, Immaculate, additional, Mabe, Tshegofatso Dorah, additional, Mabena, Kamogelo Fortunate, additional, Mabuza, Nkosinathi Charles, additional, Mabwe, Simbarashe, additional, Madikwe, Johanna Thapelo, additional, Madikwe, Octavia Mahkosazana, additional, Maebana, Rapontwana Letlhogonolo, additional, Magwasha, Malobisa Sylvester, additional, Majola, Molly, additional, Makhetha, Mantai, additional, Makhethe, Lebohang, additional, Malay, Vernon, additional, Manzini, Vutlhari-I-Vunhenha Fairlord, additional, Maphanga, Jabu, additional, Maphanga, Nonhle, additional, Market, Juanita, additional, Maroele, Isholedi Samuel, additional, Masibi, Omphile Petunia, additional, Mathabanzini, July Rocky, additional, Mathode, Tendamudzimu Ivan, additional, Matsane, Ellen Ditaba, additional, Mbata, Lungile, additional, Meyer, Faheema, additional, Mhandire, Nyasha Karen, additional, Miga, Thembisiwe, additional, Mkhize, Nosisa Charity Thandeka, additional, Mkhokho, Caroline, additional, Mkwalase, Neo Hilda, additional, Mnqonywa, Nondzakazi, additional, Moche, Karabo, additional, Modisaotsile, Brenda Matshidiso, additional, Mokgetsengoane, Patricia Pakiso, additional, Mokone, Selemeng Matseliso Carol, additional, Molatlhegi, Kegomoditswe Magdeline, additional, Molefe, Thuso Andrew, additional, Moloko, Joseph Panie, additional, Molosi, Kabelo, additional, Molotsi, Motlatsi Evelyn, additional, Montwedi, Tebogo Edwin, additional, Monyemangene, Boikanyo Dinah, additional, Mooketsi, Hellen Mokopi, additional, Moses, Miriam, additional, Mosito, Boitumelo, additional, Mosito, Tshplpfelo Mapula, additional, Mosweu, Ireen Lesebang, additional, Mothaga, Primrose, additional, Motlagomang, Banyana Olga, additional, Mouton, Angelique, additional, Mpofu, Onesisa, additional, Mthembu, Funeka Nomvula, additional, Mtlali, Mpho, additional, Ndlovu, Nhlamulo, additional, Ngcobo, Nompumelelo, additional, Noble, Julia, additional, Ntamo, Bantubonke Bertrum, additional, Ntanjana, Gloria, additional, Ntshauba, Tedrius, additional, Opperman, Fajwa, additional, Padayatchi, Nesri, additional, Papalagae, Thandiwe, additional, Petersen, Christel, additional, Phakathi, Themba, additional, Phatshwane, Mapule Ozma, additional, Plaatjie, Patiswa, additional, Pretorius, Abe, additional, Rameetse, Victor Kgothatso, additional, Ramjit, Dirhona, additional, Ratangee, Frances, additional, Ratangee, Maigan, additional, Sanyaka, Pearl Nomsa, additional, Sato, Alicia, additional, Schoeman, Elisma, additional, Schreuder, Constance, additional, Seabela, Letlhogonolo, additional, Segaetsho, Kelebogile Magdeline, additional, Sein, Ni Ni, additional, Selepe, Raesibe Agnes Pearl, additional, Senne, Melissa Neo, additional, September, Alison, additional, September, Cashwin, additional, Serake, Moeti, additional, Shenje, Justin, additional, Shezi, Thandiwe, additional, Shezi, Sifiso Cornelius, additional, Sing, Phindile, additional, Singh, Chandrapharbha, additional, Sithetho, Zona, additional, Solomons, Dorothy, additional, Stanley, Kim, additional, Steyn, Marcia, additional, Stofile, Bongiwe, additional, Stryers, Sonia, additional, Swanepoel, Liticia, additional, Swarts, Anne, additional, Thaba, Mando Mmakhora, additional, Theko, Lethabo Collen, additional, Thembela, Philile, additional, Thompo, Mugwena, additional, Toefy, Asma, additional, Toto, Khayalethu, additional, Tsagae, Dimakatso Sylvia, additional, Tsamane, Ayanda, additional, Tshikovhi, Vincent, additional, Tswaile, Lebogang Isaac, additional, Tyambetyu, Petrus, additional, Tönsing, Susanne, additional, Valley, Habibullah, additional, van der Merwe, Linda, additional, van Rooyen, Elma, additional, Veldsman, Ashley, additional, Veldtsman, Helen, additional, Vollenhoven, Kelvin, additional, Zaca, Londiwe, additional, Zimri, Elaine, additional, and Zulu, Mbali, additional

Published
2021
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19. Inflammatory Determinants of Differential Tuberculosis Risk in Pre-Adolescent Children and Young Adults

Author

Baguma, Richard, primary, Mbandi, Stanley Kimbung, additional, Rodo, Miguel J., additional, Erasmus, Mzwandile, additional, Day, Jonathan, additional, Makhethe, Lebohang, additional, de Kock, Marwou, additional, van Rooyen, Michele, additional, Stone, Lynnett, additional, Bilek, Nicole, additional, Steyn, Marcia, additional, Africa, Hadn, additional, Darboe, Fatoumatta, additional, Chegou, Novel N., additional, Tromp, Gerard, additional, Walzl, Gerhard, additional, Hatherill, Mark, additional, Penn-Nicholson, Adam, additional, and Scriba, Thomas J., additional

Published
2021
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20. Clinical Predictors of Pulmonary Tuberculosis Among South African Adults With HIV

Author

Mendelsohn, Simon C., primary, Fiore-Gartland, Andrew, additional, Awany, Denis, additional, Mulenga, Humphrey, additional, Mbandi, Stanley Kimbung, additional, Tameris, Michèle, additional, Walzl, Gerhard, additional, Naidoo, Kogieleum, additional, Churchyard, Gavin, additional, Scriba, Thomas J., additional, Hatherill, Mark, additional, and Team, CORTIS-HR Study, additional

Published
2021
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21. Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Author

Llibre, Alba, primary, Smith, Nikaïa, additional, Rouilly, Vincent, additional, Musvosvi, Munyaradzi, additional, Nemes, Elisa, additional, Posseme, Céline, additional, Mabwe, Simba, additional, Charbit, Bruno, additional, Mbandi, Stanley Kimbung, additional, Filander, Elizabeth, additional, Africa, Hadn, additional, Saint-André, Violaine, additional, Bondet, Vincent, additional, Bost, Pierre, additional, Mulenga, Humphrey, additional, Bilek, Nicole, additional, Albert, Matthew L, additional, Scriba, Thomas J, additional, and Duffy, Darragh, additional

Published
2020
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24. Immune correlates of tuberculosis disease and risk translate across species

Author

Ahmed, Mushtaq, primary, Thirunavukkarasu, Shyamala, additional, Rosa, Bruce A., additional, Thomas, Kimberly A., additional, Das, Shibali, additional, Rangel-Moreno, Javier, additional, Lu, Lan, additional, Mehra, Smriti, additional, Mbandi, Stanley Kimbung, additional, Thackray, Larissa B., additional, Diamond, Michael S., additional, Murphy, Kenneth M., additional, Means, Terry, additional, Martin, John, additional, Kaushal, Deepak, additional, Scriba, Thomas J., additional, Mitreva, Makedonka, additional, and Khader, Shabaana A., additional

Published
2020
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25. Prospective Validation of a Host Blood Transcriptomic Biomarker for Pulmonary Tuberculosis in People Living with HIV: A Diagnostic and Prognostic Accuracy Study

Author

Mendelsohn, Simon C., primary, Fiore-Gartland, Andrew, additional, Penn-Nicholson, Adam, additional, Mulenga, Humphrey, additional, Mbandi, Stanley Kimbung, additional, Borate, Bhavesh, additional, Hadley, Katie, additional, Hikuam, Chris, additional, Musvosvi, Munyaradzi, additional, Bilek, Nicole, additional, Erasmus, Mzwandile, additional, Jaxa, Lungisa, additional, Raphela, Rodney, additional, Nombida, Onke, additional, Kaskar, Masooda, additional, Sumner, Tom, additional, White, Richard G., additional, Innes, Craig, additional, Brumskine, William, additional, Hiemstra, Andriëtte, additional, Malherbe, Stephanus T., additional, Hassan-Moosa, Razia, additional, Tameris, Michèle, additional, Walzl, Gerhard, additional, Naidoo, Kogieleum, additional, Churchyard, Gavin, additional, Scriba, Thomas J., additional, Hatherill, Mark, additional, and Team, CORTIS-HR Study, additional

Published
2020
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26. Host-Directed Targeting of lincRNA-MIR99AHG Suppresses Intracellular Growth of Mycobacterium Tuberculosis

Author

Gcanga, Lorna, primary, Tamgue, Ousman, additional, Ozturk, Mumin, additional, Pillay, Shandre, additional, Jacobs, Raygaana, additional, Chia, Julius Ebua, additional, Mbandi, Stanley Kimbung, additional, Davids, Malika, additional, Dheda, Keertan, additional, Schmeier, Sebastian, additional, Alam, Tanvir, additional, Roy, Sugata, additional, Suzuki, Harukazu, additional, Brombacher, Frank, additional, and Guler, Reto, additional

Published
2020
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27. Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.

Author

Mulenga, Humphrey, Musvosvi, Munyaradzi, Mendelsohn, Simon C., Penn-Nicholson, Adam, Mbandi, Stanley Kimbung, Fiore-Gartland, Andrew, Tameris, Michele, Mabwe, Simbarashe, Africa, Hadn, Bilek, Nicole, Kafaar, Fazlin, Khader, Shabaana A., Carstens, Balie, Hadley, Katie, Hikuam, Chris, Erasmus, Mzwandile, Jaxa, Lungisa, Raphela, Rodney, Nombida, Onke, and Kaskar, Masooda

Subjects
TUBERCULOSIS, BIOMARKERS, RESPIRATORY infections, HIV, MESSENGER RNA
Abstract

Rationale: Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. Objectives: We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods: RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11+ participants were randomized to TPT or no TPT; RISK11- participants received no TPT. PLHIV received standard-of-care antiretroviral therapy and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by real-time quantitative PCR. Measurements and Main Results: RISK11+ status was transient in most of the 128 HIV-negative participants with longitudinal samples; more than 70% of RISK11+ participants reverted to RISK11- by 3 months, irrespective of TPT. By comparison, reversion from a RISK11+ state was less common in 645 PLHIV (42.1%). Non-HIV viral and nontuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%) than those with bacterial organisms other than TB (13.4%) or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Conclusions: Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control. [ABSTRACT FROM AUTHOR]

Published
2021
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28. Diagnostic performance of an optimized transcriptomic signature of risk of tuberculosis in cryopreserved peripheral blood mononuclear cells

Author

Matiwane, Sindile, Jaxa, Lungisa, Xoyana, Noncedo, Schreuder, Constance, Botes, Janelle, Africa, Hadn, Makhethe, Lebohang, Steyn, Marcia, Darboe, Fatoumatta, Mbandi, Stanley Kimbung, Thompson, Ethan G., Fisher, Michelle, Rodo, Miguel, van Rooyen, Michele, Filander, Elizabeth, Bilek, Nicole, Mabwe, Simbarashe, Hatherill, Mark, Zak, Daniel E., Penn-Nicholson, Adam, and Scriba, Thomas J.

Published
2018
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29. Cytomegalovirus infection is a risk factor for tuberculosis disease in infants

Author

Müller, Julius, primary, Tanner, Rachel, additional, Matsumiya, Magali, additional, Snowden, Margaret A., additional, Landry, Bernard, additional, Satti, Iman, additional, Harris, Stephanie A., additional, O’Shea, Matthew K., additional, Stockdale, Lisa, additional, Marsay, Leanne, additional, Chomka, Agnieszka, additional, Harrington-Kandt, Rachel, additional, Thomas, Zita-Rose Manjaly, additional, Naranbhai, Vivek, additional, Stylianou, Elena, additional, Mbandi, Stanley Kimbung, additional, Hatherill, Mark, additional, Hussey, Gregory, additional, Mahomed, Hassan, additional, Tameris, Michele, additional, McClain, J. Bruce, additional, Evans, Thomas G., additional, Hanekom, Willem A., additional, Scriba, Thomas J., additional, McShane, Helen, additional, and Fletcher, Helen A., additional

Published
2019
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30. Plasma Type I IFN Protein Concentrations in Human Tuberculosis

Author

Llibre, Alba, primary, Bilek, Nicole, additional, Bondet, Vincent, additional, Darboe, Fatoumatta, additional, Mbandi, Stanley Kimbung, additional, Penn-Nicholson, Adam, additional, Hatherill, Mark, additional, Rozenberg, Flore, additional, Scriba, Thomas J., additional, and Duffy, Darragh, additional

Published
2019
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32. Diagnostic performance of an optimized transcriptomic signature of risk of tuberculosis in cryopreserved peripheral blood mononuclear cells

Author

Darboe, Fatoumatta, primary, Mbandi, Stanley Kimbung, additional, Thompson, Ethan G., additional, Fisher, Michelle, additional, Rodo, Miguel, additional, van Rooyen, Michele, additional, Filander, Elizabeth, additional, Bilek, Nicole, additional, Mabwe, Simbarashe, additional, Hatherill, Mark, additional, Zak, Daniel E., additional, Penn-Nicholson, Adam, additional, Scriba, Thomas J., additional, Matiwane, Sindile, additional, Jaxa, Lungisa, additional, Xoyana, Noncedo, additional, Schreuder, Constance, additional, Botes, Janelle, additional, Africa, Hadn, additional, Makhethe, Lebohang, additional, and Steyn, Marcia, additional

Published
2018
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33. Cytomegalovirus infection is a risk factor for TB disease in Infants

Author

Muller, Julius, primary, Tanner, Rachel, additional, Matsumiya, Magali, additional, Snowden, Margaret A., additional, Landry, Bernard, additional, Satti, Iman, additional, Harris, Stephanie A., additional, O’Shea, Matthew K., additional, Stockdale, Lisa, additional, Marsay, Leanne, additional, Chomka, Agnieszka, additional, Harrington-Kandt, Rachel, additional, Thomas, Zita-Rose Manjaly, additional, Naranbhai, Vivek, additional, Stylianou, Elena, additional, Mbandi, Stanley Kimbung, additional, Hatherill, Mark, additional, Hussey, Gregory, additional, Mahomed, Hassan, additional, Tameris, Michele, additional, McClain, J. Bruce, additional, Evans, Thomas G., additional, Hanekom, Willem A., additional, Scriba, Thomas J., additional, McShane, Helen, additional, and Fletcher, Helen A., additional

Published
2017
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34. Detection of Tuberculosis Recurrence, Diagnosis and Treatment Response by a Blood Transcriptomic Risk Signature in HIV-Infected Persons on Antiretroviral Therapy.

Author

Darboe, Fatoumatta, Mbandi, Stanley Kimbung, Naidoo, Kogieleum, Yende-Zuma, Nonhlanhla, Lewis, Lara, Thompson, Ethan G., Duffy, Fergal J., Fisher, Michelle, Filander, Elizabeth, van Rooyen, Michele, Bilek, Nicole, Mabwe, Simbarashe, McKinnon, Lyle R., Chegou, Novel, Loxton, Andre, Walzl, Gerhard, Tromp, Gerard, Padayatchi, Nesri, Govender, Dhineshree, and Hatherill, Mark

Subjects
HIV-positive persons, THERAPEUTICS, HIV, TUBERCULOSIS, MYCOBACTERIUM tuberculosis, TUBERCULOSIS diagnosis, VIRAL load
Abstract

HIV-infected individuals are at high risk of tuberculosis disease and those with prior tuberculosis episodes are at even higher risk of disease recurrence. A non-sputum biomarker that identifies individuals at highest tuberculosis risk would allow targeted microbiological testing and appropriate treatment and also guide need for prolonged therapy. We determined the utility of a previously developed whole blood transcriptomic correlate of risk (COR) signature for (1) predicting incident recurrent tuberculosis, (2) tuberculosis diagnosis and (3) its potential utility for tuberculosis treatment monitoring in HIV-infected individuals. We retrieved cryopreserved blood specimens from three previously completed clinical studies and measured the COR signature by quantitative microfluidic real-time-PCR. The signature differentiated recurrent tuberculosis progressors from non-progressors within 3 months of diagnosis with an area under the Receiver-operating characteristic (ROC) curve (AUC) of 0.72 (95% confidence interval (CI), 0.58–0.85) amongst HIV-infected individuals on antiretroviral therapy (ART). Twenty-five of 43 progressors (58%) were asymptomatic at microbiological diagnosis and thus had subclinical disease. The signature showed excellent diagnostic discrimination between HIV-uninfected tuberculosis cases and controls (AUC 0.97; 95%CI 0.94–1). Performance was lower in HIV-infected individuals (AUC 0.83; 95%CI 0.81–0.96) and signature scores were directly associated with HIV viral loads. Tuberculosis treatment response in HIV-infected individuals on ART with a new recurrent tuberculosis diagnosis was also assessed. Signature scores decreased significantly during treatment. However, pre-treatment scores could not differentiate between those who became sputum negative before and after 2 months. Direct application of the unmodified blood transcriptomic COR signature detected subclinical and active tuberculosis by blind validation in HIV-infected individuals. However, prognostic performance for recurrent tuberculosis, and performance as diagnostic and as treatment monitoring tool in HIV-infected persons was inferior to published results from HIV-negative cohorts. Our results suggest that performance of transcriptomic signatures comprising interferon stimulated genes are negatively affected in HIV-infected individuals, especially in those with incompletely suppressed viral loads. [ABSTRACT FROM AUTHOR]

Published
2019
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35. Correction: Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding

Author

Vij, Shubha, primary, Kuhl, Heiner, additional, Kuznetsova, Inna S., additional, Komissarov, Aleksey, additional, Yurchenko, Andrey A., additional, Van Heusden, Peter, additional, Singh, Siddharth, additional, Thevasagayam, Natascha M., additional, Prakki, Sai Rama Sridatta, additional, Purushothaman, Kathiresan, additional, Saju, Jolly M., additional, Jiang, Junhui, additional, Mbandi, Stanley Kimbung, additional, Jonas, Mario, additional, Hin Yan Tong, Amy, additional, Mwangi, Sarah, additional, Lau, Doreen, additional, Ngoh, Si Yan, additional, Liew, Woei Chang, additional, Shen, Xueyan, additional, Hon, Lawrence S., additional, Drake, James P., additional, Boitano, Matthew, additional, Hall, Richard, additional, Chin, Chen-Shan, additional, Lachumanan, Ramkumar, additional, Korlach, Jonas, additional, Trifonov, Vladimir, additional, Kabilov, Marsel, additional, Tupikin, Alexey, additional, Green, Darrell, additional, Moxon, Simon, additional, Garvin, Tyler, additional, Sedlazeck, Fritz J., additional, Vurture, Gregory W., additional, Gopalapillai, Gopikrishna, additional, Katneni, Vinaya Kumar, additional, Noble, Tansyn H., additional, Scaria, Vinod, additional, Sivasubbu, Sridhar, additional, Jerry, Dean R., additional, O'Brien, Stephen J., additional, Schatz, Michael C., additional, Dalmay, Tamás, additional, Turner, Stephen W., additional, Lok, Si, additional, Christoffels, Alan, additional, and Orbán, László, additional

Published
2016
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36. Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding

Author

Vij, Shubha, primary, Kuhl, Heiner, additional, Kuznetsova, Inna S., additional, Komissarov, Aleksey, additional, Yurchenko, Andrey A., additional, Van Heusden, Peter, additional, Singh, Siddharth, additional, Thevasagayam, Natascha M., additional, Prakki, Sai Rama Sridatta, additional, Purushothaman, Kathiresan, additional, Saju, Jolly M., additional, Jiang, Junhui, additional, Mbandi, Stanley Kimbung, additional, Jonas, Mario, additional, Hin Yan Tong, Amy, additional, Mwangi, Sarah, additional, Lau, Doreen, additional, Ngoh, Si Yan, additional, Liew, Woei Chang, additional, Shen, Xueyan, additional, Hon, Lawrence S., additional, Drake, James P., additional, Boitano, Matthew, additional, Hall, Richard, additional, Chin, Chen-Shan, additional, Lachumanan, Ramkumar, additional, Korlach, Jonas, additional, Trifonov, Vladimir, additional, Kabilov, Marsel, additional, Tupikin, Alexey, additional, Green, Darrell, additional, Moxon, Simon, additional, Garvin, Tyler, additional, Sedlazeck, Fritz J., additional, Vurture, Gregory W., additional, Gopalapillai, Gopikrishna, additional, Kumar Katneni, Vinaya, additional, Noble, Tansyn H., additional, Scaria, Vinod, additional, Sivasubbu, Sridhar, additional, Jerry, Dean R., additional, O'Brien, Stephen J., additional, Schatz, Michael C., additional, Dalmay, Tamás, additional, Turner, Stephen W., additional, Lok, Si, additional, Christoffels, Alan, additional, and Orbán, László, additional

Published
2016
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39. Correction: Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study.

Author

Penn-Nicholson, Adam, Hraha, Thomas, Thompson, Ethan G., Sterling, David, Mbandi, Stanley Kimbung, Wall, Kirsten M., Fisher, Michelle, Suliman, Sara, Shankar, Smitha, Hanekom, Willem A., Janjic, Nebojsa, Hatherill, Mark, Kaufmann, Stefan H. E., Sutherland, Jayne, Walzl, Gerhard, De Groote, Mary Ann, Ochsner, Urs, Zak, Daniel E., Scriba, Thomas J., and ACS and GC6–74 cohort study groups

Subjects
COHORT analysis, LONGITUDINAL method, TUBERCULOSIS
Abstract

[This corrects the article DOI: 10.1371/journal.pmed.1002781.]. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study.

Author

Muwanga VM, Mendelsohn SC, Leukes V, Stanley K, Mbandi SK, Erasmus M, Flinn M, Fisher TL, Raphela R, Bilek N, Malherbe ST, Tromp G, Van Der Spuy G, Walzl G, Chegou NN, and Scriba TJ

Subjects
Humans, Female, Male, Adult, Case-Control Studies, Middle Aged, Gambia, South Africa, Ethiopia, Malawi, Uganda, Tuberculosis, Pulmonary blood, Tuberculosis, Pulmonary diagnosis, Young Adult, Mycobacterium tuberculosis genetics, Tuberculosis blood, Tuberculosis diagnosis, Tuberculosis genetics, Sensitivity and Specificity, Namibia, Sputum microbiology, Real-Time Polymerase Chain Reaction, Transcriptome
Abstract

Background: Multiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TB versus other respiratory diseases (ORD)., Methods: As part of a nested case-control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled. TB was diagnosed based on clinical, microbiological and radiological findings. Transcriptomic signatures were measured in whole blood using microfluidic real-time quantitative PCR. Diagnostic performance was benchmarked against the World Health Organization Target Product Profile (TPP) for a non-sputum TB triage test., Results: Among 579 participants, 158 had definite, microbiologically confirmed TB, 32 had probable TB, while 389 participants had ORD. Nine signatures differentiated between ORD and TB with equivalent performance (Satproedprai7: area under the curve 0.83 (95% CI 0.79-0.87); Jacobsen3: 0.83 (95% CI 0.79-0.86); Suliman2: 0.82 (95% CI 0.78-0.86); Roe1: 0.82 (95% CI 0.78-0.86); Kaforou22: 0.82 (95% CI 0.78-0.86); Sambarey10: 0.81 (95% CI 0.77-0.85); Duffy9: 0.81 (95% CI 0.76-0.86); Gliddon3: 0.8 (95% CI 0.75-0.85); Suliman4 0.79 (95% CI 0.75-0.84)). Benchmarked against a 90% sensitivity, these signatures achieved specificities between 44% (95% CI 38-49%) and 54% (95% CI 49-59%), not meeting the TPP criteria. Signature scores significantly varied by HIV status and country. In country-specific analyses, several signatures, such as Satproedprai7 and Penn-Nicholson6, met the minimal TPP criteria for a triage test in Ethiopia, Malawi and South Africa., Conclusion: No signatures met the TPP criteria in a pooled analysis of all countries, but several signatures met the minimum criteria for a non-sputum TB triage test in some countries., Competing Interests: Conflict of interest: G. Walzl and T.J. Scriba report grants from the Bill & Melinda Gates Foundation during the conduct of the study. T.J. Scriba and N.N. Chegou report grants from the South African Medical Research Council during the conduct of the study. G. Walzl reports grants from the South African National Research Foundation and EDCTP. T.J. Scriba has patents of the RISK11 (Darboe11), RISK6 (Penn-Nicholson6) and RISK4 (Suliman4) signatures issued. G. Walzl and N.N. Chegou have patents “TB diagnostic markers” (PCT/IB2013/054377), “Serum host biomarkers for tuberculosis disease” (PCT/IB2017/052142) and “Method for diagnosing TB” (PCT/IB2017/052142) granted but receive no royalties on these patents. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Published
2024
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