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7. 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

9. Brief Report: Differentiated Service Delivery Framework for People With Multidrug-Resistant Tuberculosis and HIV Coinfection

Author

Reis, Karl, primary, Wolf, Allison, additional, Perumal, Rubeshan, additional, Seepamore, Boitumelo, additional, Guzman, Kevin, additional, Ross, Jesse, additional, Cheung, Ying Kuen K., additional, Amico, K. Rivet, additional, Brust, James C. M., additional, Padayatchi, Nesri, additional, Friedland, Gerald, additional, Naidoo, Kogieleum, additional, Daftary, Amrita, additional, Zelnick, Jennifer, additional, and O'Donnell, Max, additional

Published
2024
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12. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Author

treatment–2017, The Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB, Ahmad, Nafees, Ahuja, Shama D, Akkerman, Onno W, Alffenaar, Jan-Willem C, Anderson, Laura F, Baghaei, Parvaneh, Bang, Didi, Barry, Pennan M, Bastos, Mayara L, Behera, Digamber, Benedetti, Andrea, Bisson, Gregory P, Boeree, Martin J, Bonnet, Maryline, Brode, Sarah K, Brust, James CM, Cai, Ying, Caumes, Eric, Cegielski, J Peter, Centis, Rosella, Chan, Pei-Chun, Chan, Edward D, Chang, Kwok-Chiu, Charles, Macarthur, Cirule, Andra, Dalcolmo, Margareth Pretti, D'Ambrosio, Lia, de Vries, Gerard, Dheda, Keertan, Esmail, Aliasgar, Flood, Jennifer, Fox, Gregory J, Fréchet-Jachym, Mathilde, Fregona, Geisa, Gayoso, Regina, Gegia, Medea, Gler, Maria Tarcela, Gu, Sue, Guglielmetti, Lorenzo, Holtz, Timothy H, Hughes, Jennifer, Isaakidis, Petros, Jarlsberg, Leah, Kempker, Russell R, Keshavjee, Salmaan, Khan, Faiz Ahmad, Kipiani, Maia, Koenig, Serena P, Koh, Won-Jung, Kritski, Afranio, Kuksa, Liga, Kvasnovsky, Charlotte L, Kwak, Nakwon, Lan, Zhiyi, Lange, Christoph, Laniado-Laborín, Rafael, Lee, Myungsun, Leimane, Vaira, Leung, Chi-Chiu, Leung, Eric Chung-Ching, Li, Pei Zhi, Lowenthal, Phil, Maciel, Ethel L, Marks, Suzanne M, Mase, Sundari, Mbuagbaw, Lawrence, Migliori, Giovanni B, Milanov, Vladimir, Miller, Ann C, Mitnick, Carole D, Modongo, Chawangwa, Mohr, Erika, Monedero, Ignacio, Nahid, Payam, Ndjeka, Norbert, O'Donnell, Max R, Padayatchi, Nesri, Palmero, Domingo, Pape, Jean William, Podewils, Laura J, Reynolds, Ian, Riekstina, Vija, Robert, Jérôme, Rodriguez, Maria, Seaworth, Barbara, Seung, Kwonjune J, Schnippel, Kathryn, Shim, Tae Sun, Singla, Rupak, Smith, Sarah E, Sotgiu, Giovanni, Sukhbaatar, Ganzaya, Tabarsi, Payam, Tiberi, Simon, Trajman, Anete, Trieu, Lisa, Udwadia, Zarir F, van der Werf, Tjip S, and Veziris, Nicolas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Tuberculosis, Lung, Antimicrobial Resistance, Prevention, Clinical Trials and Supportive Activities, Rare Diseases, Orphan Drug, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Amikacin, Antitubercular Agents, Capreomycin, Carbapenems, Clofazimine, Diarylquinolines, Drug Therapy, Combination, Fluoroquinolones, Humans, Kanamycin, Levofloxacin, Linezolid, Moxifloxacin, Recurrence, Treatment Failure, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundTreatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.MethodsIn this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration.FindingsOf 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses.InterpretationAlthough inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.FundingAmerican Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Published
2018

13. A cluster-randomized controlled trial to improve the quality of integrated HIV-tuberculosis services in primary health care clinics in South Africa

Author

Gengiah, Santhanalakshmi, Barker, Pierre M., Yende-Zuma, Nonhlanhla, Mbatha, Mduduzi, Naidoo, Shane, Taylor, Myra, Loveday, Marian, Mhlongo, Mesuli, Jackson, Clark, Nunn, Andrew J., Padayatchi, Nesri, Karim, Salim S. Abdool, and Naidoo, Kogieleum

Subjects
Tuberculosis -- Care and treatment, Clinics -- Quality management, Primary health care -- Quality management, HIV infection -- Care and treatment, Health
Abstract

Introduction: : Tuberculosis (TB) remains the most common cause of death among people living with HIV Integrating HIV and TB services reduces mortality but is sub-optimally implemented. Quality improvement (QI) methods offer a low-cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV-TB care in rural South African primary healthcare (PHC) clinics. Methods: Sixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on-site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study-appointed data capturers from all study clinics. This study's outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing. Results: The QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02-1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02-2.72; p=0.044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups. Conclusions: QI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV-TB service delivery and increase the success of future QI scale-up activities. Keywords: cluster-randomized; collaboratives; HIV-TB services; integration; primary healthcare clinics; quality improvement, 1 | INTRODUCTION In South Africa (SA), the convergence of the HIV and tuberculosis (TB) epidemics created one of the largest HIV-TB co-epidemics in the world [1]. In 2016, an [...]

Published
2021
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14. 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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17. Baseline and treatment-emergent bedaquiline resistance in drug-resistant tuberculosis: a systematic review and meta-analysis

Author

Perumal, Rubeshan, primary, Bionghi, Neda, additional, Nimmo, Camus, additional, Letsoalo, Marothi, additional, Cummings, Matthew J., additional, Hopson, Madeleine, additional, Wolf, Allison, additional, Jubaer, Shamim Al, additional, Padayatchi, Nesri, additional, Naidoo, Kogieleum, additional, Larsen, Michelle H., additional, and O'Donnell, Max, additional

Published
2023
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20. Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

Author

Chimukangara, Benjamin, Lessells, Richard J., Singh, Lavanya, Grigalionyte, Indra, Yende-Zuma, Nonhlanhla, Adams, Rochelle, Dawood, Halima, Dlamini, Linda, Buthelezi, Sibonisile, Chetty, Sheldon, Diallo, Karidia, Duffus, Wayne A., Mogashoa, Mary, Hagen, Melissa B., Giandhari, Jennifer, de Oliveira, Tulio, Moodley, Pravi, Padayatchi, Nesri, and Naidoo, Kogieleum

Published
2021
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22. The Lancet Respiratory Medicine Commission: 2019 update: epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant and incurable tuberculosis

Author

Dheda, Keertan, Gumbo, Tawanda, Maartens, Gary, Dooley, Kelly E, Esmail, Aliasgar, Murray, Megan, Furin, Jennifer, Nardell, Edward, London, Leslie, Lessem, Erica, Limberis, Jason, Theron, Grant, McNerney, Ruth, Niemann, Stefan, Dowdy, David, Van Rie, Annelies, Pasipanodya, Jotam G, Rodrigues, Camilla, Clark, Taane G, Sirgel, Frik A, Schaaf, H Simon, Chang, Kwok Chiu, Lange, Christoph, Nahid, Payam, Fourie, Bernard, Ndjeka, Norbert, Nunn, Andrew, Migliori, GB, Udwadia, Zarir F, Horsburgh, C Robert, Jr, Churchyard, Gavin J, Menzies, Dick, Hesseling, Anneke C, Seddon, James A, Low, Marcus, Keshavjee, Salmaan, Nuermberger, Eric, McIlleron, Helen, Fennelly, Kevin P, Jindani, Amina, Jaramillo, Ernesto, Padayatchi, Nesri, Barry, Clifton E, 3rd, Warren, Robin M, and Nardell, Edward A

Published
2019
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26. TB Control in South Africa

Author

Dawood, Halima, Padayatchi, Nesri, Lu, Yichen, editor, Wang, Lixia, editor, Duanmu, Hongjin, editor, Chanyasulkit, Chris, editor, Strong, Amie J., editor, and Zhang, Hui, editor

Published
2017
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31. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Author

Dheda, Keertan, Gumbo, Tawanda, Maartens, Gary, Dooley, Kelly E, McNerney, Ruth, Murray, Megan, Furin, Jennifer, Nardell, Edward A, London, Leslie, Lessem, Erica, Theron, Grant, van Helden, Paul, Niemann, Stefan, Merker, Matthias, Dowdy, David, Van Rie, Annelies, Siu, Gilman K H, Pasipanodya, Jotam G, Rodrigues, Camilla, Clark, Taane G, Sirgel, Frik A, Esmail, Aliasgar, Lin, Hsien-Ho, Atre, Sachin R, Schaaf, H Simon, Chang, Kwok Chiu, Lange, Christoph, Nahid, Payam, Udwadia, Zarir F, Horsburgh, C Robert, Jr, Churchyard, Gavin J, Menzies, Dick, Hesseling, Anneke C, Nuermberger, Eric, McIlleron, Helen, Fennelly, Kevin P, Goemaere, Eric, Jaramillo, Ernesto, Low, Marcus, Jara, Carolina Morán, Padayatchi, Nesri, and Warren, Robin M

Published
2017
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33. Mycobacterium tuberculosis Intra-Host Evolution Among Drug-Resistant Tuberculosis Patients Failing Treatment

Author

Perumal,Rubeshan, Khan,Azraa, Naidoo,Kogieleum, Ngema,Senamile L, Nandlal,Louansha, Padayatchi,Nesri, Dookie,Navisha, Perumal,Rubeshan, Khan,Azraa, Naidoo,Kogieleum, Ngema,Senamile L, Nandlal,Louansha, Padayatchi,Nesri, and Dookie,Navisha

Abstract

Rubeshan Perumal,1,2 Azraa Khan,1 Kogieleum Naidoo,1,2 Senamile L Ngema,1 Louansha Nandlal,1,2 Nesri Padayatchi,1,2 Navisha Dookie1,2 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, KwaZulu Natal, South Africa; 2South African Medical Research Council (SAMRC) – CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Durban, KwaZulu Natal, South AfricaCorrespondence: Rubeshan Perumal, Doris Duke Medical Research Institute (2nd Floor), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Private Bag X7, Congella, Durban, 4013, South Africa, Tel +27 31 260 4555, Fax +27 31 260 4566, Email Rubeshan.perumal@caprisa.orgBackground: Understanding Mycobacterium tuberculosis (Mtb) intra-host evolution of drug resistance is important for successful drug-resistant tuberculosis (DR-TB) treatment and control strategies. This study aimed to characterise the acquisition of genetic mutations and low-frequency variants associated with treatment-emergent Mtb drug resistance in longitudinally profiled clinical isolates from patients who experienced DR-TB treatment failure.Patients and Methods: We performed deep Whole Genome Sequencing on 23 clinical isolates obtained longitudinally across nine timepoints from five patients who experienced DR-TB treatment failure enrolled in the CAPRISA 020 InDEX study. The minimum inhibitory concentrations (MICs) were established on the BACTEC™ MGIT 960™ instrument on 15/23 longitudinal clinical isolates for eight anti-TB drugs (rifampicin, isoniazid, ethambutol, levofloxacin, moxifloxacin, linezolid, clofazimine, bedaquiline).Results: In total, 22 resistance associated mutations/variants were detected. We observed four treatment-emergent mutations in two out of the five patients. Emerging resistance to the fluoroquinolones was associated with 16- and 64-fold elevated levofloxacin (2– 8 mg/L) and moxifloxacin (1– 2 mg/L) MICs, respectively, resulting from the D94G/N and

Published
2023

38. INSTIs for the management of HIV-associated TB (INSIGHT study): a phase 2b study to evaluate the efficacy, safety and pharmacokinetics of a combination of bictegravir, emtricitabine and tenofovir alafenamide fumarate for the treatment of HIV-1 infection in patients with drug-susceptible tuberculosis on a rifampicin-based treatment regimen: a phase 2b open-label randomised controlled trial

Author

Naidoo, Anushka, primary, Dooley, Kelly E, additional, Naidoo, Kogieleum, additional, Padayatchi, Nesri, additional, Yende-Zuma, Nonhlanhla, additional, Perumal, Rubeshan, additional, Dorse, Gillian, additional, Boodhram, Resha, additional, and Osuala, Emmanuella Chinonso, additional

Published
2022
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44. Bedaquiline Adherence Measured by Electronic Dose Monitoring Predicts Clinical Outcomes in the Treatment of Patients With Multidrug-Resistant Tuberculosis and HIV/AIDS

Author

O'Donnell, Max R., primary, Padayatchi, Nesri, additional, Wolf, Allison, additional, Zelnick, Jennifer, additional, Daftary, Amrita, additional, Orrell, Catherine, additional, Nimmo, Camus, additional, Baldwin, Matthew, additional, Boodhram, Resha, additional, Maharaj, Bhavna, additional, Amico, K. Rivet, additional, Naidoo, Kogieleum, additional, and Friedland, Gerald, additional

Published
2022
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46. Similar Antibody Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 in Individuals Living Without and with Human Immunodeficiency Virus on Antiretroviral Therapy during the First South African Infection Wave

Author

Snyman, Jumari, Hwa, Shi Hsia, Krause, Robert, Muema, Daniel, Reddy, Tarylee, Ganga, Yashica, Karim, Farina, Leslie, Alasdair, Sigal, Alex, Ndung'U, Thumbi, Archary, Moherndran, Dullabh, Kaylesh J., Goulder, Philip, Harling, Guy, Harrichandparsad, Rohen, Herbst, Kobus, Jeena, Prakash, Khoza, Thandeka, Klein, Nigel, Kloverpris, Henrik, Madansein, Rajhmun, Marakalala, Mohlopheni, Mazibuko, Matilda, Moshabela, Mosa, Mthabela, Ntombifuthi, Naidoo, Kogie, Ndhlovu, Zaza, Nyamande, Kennedy, Padayatchi, Nesri, Patel, Vinod, Smit, Theresa, Steyn, Adrie, Wong, Emily, Snyman, Jumari, Hwa, Shi Hsia, Krause, Robert, Muema, Daniel, Reddy, Tarylee, Ganga, Yashica, Karim, Farina, Leslie, Alasdair, Sigal, Alex, Ndung'U, Thumbi, Archary, Moherndran, Dullabh, Kaylesh J., Goulder, Philip, Harling, Guy, Harrichandparsad, Rohen, Herbst, Kobus, Jeena, Prakash, Khoza, Thandeka, Klein, Nigel, Kloverpris, Henrik, Madansein, Rajhmun, Marakalala, Mohlopheni, Mazibuko, Matilda, Moshabela, Mosa, Mthabela, Ntombifuthi, Naidoo, Kogie, Ndhlovu, Zaza, Nyamande, Kennedy, Padayatchi, Nesri, Patel, Vinod, Smit, Theresa, Steyn, Adrie, and Wong, Emily

Abstract

Background: There is limited understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis in African populations with a high burden of infectious disease comorbidities such as human immunodeficiency virus (HIV). The kinetics, magnitude, and duration of virus-specific antibodies and B-cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. Methods: We longitudinally followed SARS-CoV-2-infected individuals in Durban, KwaZulu-Natal, South Africa, and characterized SARS-CoV-2 receptor-binding domain-specific immunoglobulin (Ig) M, IgG, and IgA weekly for 1 month and at 3 months post-diagnosis. Thirty of 72 (41.7%) were PLWH, 25/30 (83%) of whom were on antiretroviral therapy (ART) with full HIV suppression. Plasma neutralization was determined using a live virus neutralization assay, and antibody-secreting cell population frequencies were determined by flow cytometry. Results: Similar seroconversion rates, time to peak antibody titer, peak magnitude, and durability of anti-SARS-CoV-2 IgM, IgG, and IgA were observed in people not living with HIV and PLWH with complete HIV suppression on ART. In addition, similar potency in a live virus neutralization assay was observed in both groups. Loss of IgA was significantly associated with age (P =. 023) and a previous diagnosis of tuberculosis (P=.018). Conclusions: Similar antibody responses and neutralization potency in people not living with HIV and PLWH on stable ART in an African setting suggest that coronavirus disease 2019 (COVID-19) natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.

Published
2022

48. Adherence Measured Using Electronic Dose Monitoring is Associated with Emergent Antiretroviral Resistance and Poor Outcomes in People with Human Immunodeficiency Virus/AIDS and Multidrug-Resistant Tuberculosis

Author

Bateman, Mark, primary, Wolf, Allison, additional, Chimukangara, Benjamin, additional, Brust, James C M, additional, Lessells, Richard, additional, Amico, Rivet, additional, Boodhram, Resha, additional, Singh, Nalini, additional, Orrell, Catherine, additional, Friedland, Gerald, additional, Naidoo, Kogieleum, additional, Padayatchi, Nesri, additional, and O’Donnell, Max R, additional

Published
2022
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