Search

Your search keyword '"Warren, Robin M."' showing total 884 results
Start Over Author "Warren, Robin M."
884 results on '"Warren, Robin M."'

6. Bedaquiline: what might the future hold?

Author

Shaw, Emily S, Stoker, Neil G, Potter, Jessica L, Claassen, Helgard, Leslie, Alasdair, Tweed, Conor D, Chiang, Chen-Yuan, Conradie, Francesca, Esmail, Hanif, Lange, Christoph, Pinto, Lancelot, Rucsineanu, Oxana, Sloan, Derek J, Theron, Grant, Tisile, Phumeza, Voo, Teck Chuan, Warren, Robin M, Lebina, Limakatso, and Lipman, Marc

Published
2024
Full Text
View/download PDF

7. Variants in Bedaquiline-Candidate-Resistance Genes: Prevalence in Bedaquiline-Naive Patients, Effect on MIC, and Association with Mycobacterium tuberculosis Lineage

Author

Rivière, Emmanuel, Verboven, Lennert, Dippenaar, Anzaan, Goossens, Sander, De Vos, Elise, Streicher, Elizabeth, Cuypers, Bart, Laukens, Kris, Ben-Rached, Fathia, Rodwell, Timothy C, Pain, Arnab, Warren, Robin M, Heupink, Tim H, and Van Rie, Annelies

Subjects
Tuberculosis, Antimicrobial Resistance, Vaccine Related, Biodefense, Genetics, Biotechnology, Infectious Diseases, Emerging Infectious Diseases, Prevention, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Antitubercular Agents, Diarylquinolines, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Phylogeny, Prevalence, Tuberculosis, Multidrug-Resistant, antibiotic resistance, antimicrobial resistance, bedaquiline, drug-resistant tuberculosis, epidemiology, phenotypic drug susceptibility testing, phylogeny, tuberculosis, whole-genome sequencing, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract

Studies have shown that variants in bedaquiline-resistance genes can occur in isolates from bedaquiline-naive patients. We assessed the prevalence of variants in all bedaquiline-candidate-resistance genes in bedaquiline-naive patients, investigated the association between these variants and lineage, and the effect on phenotype. We used whole-genome sequencing to identify variants in bedaquiline-resistance genes in isolates from 509 bedaquiline treatment naive South African tuberculosis patients. A phylogenetic tree was constructed to investigate the association with the isolate lineage background. Bedaquiline MIC was determined using the UKMYC6 microtiter assay. Variants were identified in 502 of 509 isolates (98.6%), with the highest (85%) prevalence of variants in the Rv0676c (mmpL5) gene. We identified 36 unique variants, including 19 variants not reported previously. Only four isolates had a bedaquiline MIC equal to or above the epidemiological cut-off value of 0.25 μg/mL. Phylogenetic analysis showed that 14 of the 15 variants observed more than once occurred monophyletically in one Mycobacterium tuberculosis (sub)lineage. The bedaquiline MIC differed between isolates belonging to lineage 2 and 4 (Fisher's exact test, P = 0.0004). The prevalence of variants in bedaquiline-resistance genes in isolates from bedaquiline-naive patients is high, but very few (

Published
2022

9. Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study

Author

Reeve, Byron W P, Ndlangalavu, Gcobisa, Mishra, Hridesh, Palmer, Zaida, Tshivhula, Happy, Rockman, Loren, Naidoo, Selisha, Mbu, Desiree L, Naidoo, Charissa C, Derendinger, Brigitta, Walzl, Gerhard, Malherbe, Stephanus T, van Helden, Paul D, Semitala, Fred C, Yoon, Christina, Gupta, Rishi K, Noursadeghi, Mahdad, Warren, Robin M, and Theron, Grant

Published
2024
Full Text
View/download PDF

10. Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

Author

Bisimwa, Bertin C, Nachega, Jean B, Warren, Robin M, Theron, Grant, Metcalfe, John Z, Shah, Maunank, Diacon, Andreas H, Sam-Agudu, Nadia A, Yotebieng, Marcel, Bulabula, André NH, Katoto, Patrick DMC, Chirambiza, Jean-Paul, Nyota, Rosette, Birembano, Freddy M, Musafiri, Eric M, Byadunia, Sifa, Bahizire, Esto, Kaswa, Michel K, Callens, Steven, and Kashongwe, Zacharie M

Subjects
Tuberculosis, Infectious Diseases, Prevention, Clinical Research, Rare Diseases, Biodefense, Emerging Infectious Diseases, Vaccine Related, Antimicrobial Resistance, Infection, Good Health and Well Being, Adult, Cross-Sectional Studies, Democratic Republic of the Congo, Humans, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Rifampin, Sensitivity and Specificity, Tuberculosis, Multidrug-Resistant, GenoType MTBDRplus assay, drug resistance, rpoB mutations, inhA mutations, DRC, inhA mutations, rpoB mutations, GenoType MTBDRplus assay, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

BackgroundRifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC).MethodsWe conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy.ResultsAmong 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively.ConclusionsIn this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Published
2021

13. Author Correction: Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase

Author

Ezewudo, Matthew, Borens, Amanda, Chiner-Oms, Álvaro, Miotto, Paolo, Chindelevitch, Leonid, Starks, Angela M, Hanna, Debra, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Kohl, Thomas Andreas, Warren, Robin M, Crook, Derrick, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, McNerney, Ruth, Cirillo, Daniela M, Schito, Marco, Rodwell, Timothy C, and Posey, James

Subjects
Microbiology, Biological Sciences, Infection, Good Health and Well Being
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

14. Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana.

Author

Wang, Qiao, Modongo, Chawangwa, Allender, Christopher, Engelthaler, David M, Warren, Robin M, Zetola, Nicola M, and Shin, Sanghyuk S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Tuberculosis, Emerging Infectious Diseases, Rare Diseases, Vaccine Related, Biodefense, Prevention, Intellectual and Developmental Disabilities (IDD), Infectious Diseases, Antimicrobial Resistance, Brain Disorders, HIV/AIDS, Down Syndrome, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Antitubercular Agents, Botswana, Female, High-Throughput Nucleotide Sequencing, Humans, Isoniazid, Male, Microbial Sensitivity Tests, Middle Aged, Mycobacterium tuberculosis, Phenotype, Sensitivity and Specificity, Tuberculosis, Multidrug-Resistant, Young Adult, HIV infections, next-generation sequencing, diagnostics, drug-resistant tuberculosis, heteroresistance, single-molecule overlapping reads, Microbiology, Pharmacology and Pharmaceutical Sciences, Medical microbiology, Pharmacology and pharmaceutical sciences
Abstract

Multidrug-resistant tuberculosis (TB) is an alarming threat, and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated the sensitivity and specificity of targeted DS versus phenotypic drug susceptibility testing (pDST) among patients starting first-line anti-TB therapy in Botswana. Overall, we found high concordance between DS and pDST. Lower sensitivity of DS, which targets established high-confidence resistance variants, was observed for detecting isoniazid resistance among HIV-infected patients.

Published
2019

15. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis

Author

Walker, A Sarah, Steyn, Adrie J C, Lalvani, Ajit, Baulard, Alain, Christoffels, Alan, Mendoza-Ticona, Alberto, Trovato, Alberto, Skrahina, Alena, Lachapelle, Alexander S, Brankin, Alice, Piatek, Amy, Gibertoni Cruz, Ana, Koch, Anastasia, Cabibbe, Andrea Maurizio, Spitaleri, Andrea, Brandao, Angela P, Chaiprasert, Angkana, Suresh, Anita, Barbova, Anna, Van Rie, Annelies, Ghodousi, Arash, Bainomugisa, Arnold, Mandal, Ayan, Roohi, Aysha, Javid, Babak, Zhu, Baoli, Letcher, Brice, Rodrigues, Camilla, Nimmo, Camus, NATHANSON, Carl-Michael, Duncan, Carla, Coulter, Christopher, Utpatel, Christian, Liu, Chunfa, Grazian, Clara, Kong, Clare, Köser, Claudio U, Wilson, Daniel J, Cirillo, Daniela Maria, Matias, Daniela, Jorgensen, Danielle, Zimenkov, Danila, Chetty, Darren, Moore, David AJ, Clifton, David A, Crook, Derrick W, van Soolingen, Dick, Liu, Dongxin, Kohlerschmidt, Donna, Barreira, Draurio, Ngcamu, Dumisani, Santos Lazaro, Elias David, Kelly, Ellis, Borroni, Emanuele, Roycroft, Emma, Andre, Emmanuel, Böttger, Erik C, Robinson, Esther, Menardo, Fabrizio, Mendes, Flavia F, Jamieson, Frances B, Coll, Francesc, Gao, George Fu, Kasule, George W, Rossolini, Gian Maria, Rodger, Gillian, Smith, E Grace, Meintjes, Graeme, Thwaites, Guy, Hoffmann, Harald, Albert, Heidi, Cox, Helen, Laurenson, Ian F, Comas, Iñaki, Arandjelovic, Irena, Barilar, Ivan, Robledo, Jaime, Millard, James, Johnston, James, Posey, Jamie, Andrews, Jason R, Knaggs, Jeff, Gardy, Jennifer, Guthrie, Jennifer, Taylor, Jill, Werngren, Jim, Metcalfe, John, Coronel, Jorge, Shea, Joseph, Carter, Joshua, Pinhata, Juliana MW, Kus, Julianne V, Todt, Katharina, Holt, Kathryn, Nilgiriwala, Kayzad S, Ghisi, Kelen T, Malone, Kerri M, Faksri, Kiatichai, Musser, Kimberlee A, Joseph, Lavania, Rigouts, Leen, Chindelevitch, Leonid, Jarrett, Lisa, Grandjean, Louis, Ferrazoli, Lucilaine, Rodrigues, Mabel, Farhat, Maha, Schito, Marco, Fitzgibbon, Margaret M, Loembé, Marguerite Massinga, Wijkander, Maria, Ballif, Marie, Rabodoarivelo, Marie-Sylvianne, Mihalic, Marina, WILCOX, Mark, Hunt, Martin, ZIGNOL, Matteo, Merker, Matthias, Egger, Matthias, O'Donnell, Max, Caws, Maxine, Wu, Mei-Hua, Whitfield, Michael G, Inouye, Michael, Mansjö, Mikael, Dang Thi, Minh Ha, Joloba, Moses, Kamal, SM Mostofa, Okozi, Nana, ISMAIL, Nazir, Mistry, Nerges, Hoang, Nhung N, Rakotosamimanana, Niaina, Paton, Nicholas I, Rancoita, Paola M V, Miotto, Paolo, Lapierre, Pascal, Hall, Patricia J, Tang, Patrick, Claxton, Pauline, Wintringer, Penelope, Keller, Peter M, Thai, Phan Vuong Khac, Fowler, Philip W, Supply, Philip, Srilohasin, Prapaporn, Suriyaphol, Prapat, Rathod, Priti, Kambli, Priti, Groenheit, Ramona, Colman, Rebecca E, Ong, Rick Twee-Hee, Warren, Robin M, Wilkinson, Robert J, Diel, Roland, Oliveira, Rosangela S, Khot, Rukhsar, Jou, Ruwen, Tahseen, Sabira, Laurent, Sacha, Gharbia, Saheer, Kouchaki, Samaneh, Shah, Sanchi, Plesnik, Sara, Earle, Sarah G, Dunstan, Sarah, Hoosdally, Sarah J, Mitarai, Satoshi, Gagneux, Sebastien, Omar, Shaheed V, Yao, Shen-Yuan, Grandjean Lapierre, Simon, Battaglia, Simone, Niemann, Stefan, Pandey, Sushil, Uplekar, Swapna, Halse, Tanya A, Cohen, Ted, Cortes, Teresa, Prammananan, Therdsak, Kohl, Thomas A, Thuong, Nguyen T T, Teo, Tik Ying, Peto, Timothy E A, Rodwell, Timothy C, William, Timothy, Walker, Timothy M, Rogers, Thomas R, Surve, Utkarsha, Mathys, Vanessa, Furió, Victoria, Cook, Victoria, Vijay, Srinivasan, Escuyer, Vincent, Dreyer, Viola, Sintchenko, Vitali, Saphonn, Vonthanak, Solano, Walter, Lin, Wan-Hsuan, van Gemert, Wayne, He, Wencong, Yang, Yang, Zhao, Yanlin, Qin, Youwen, Xiao, Yu-Xin, Hasan, Zahra, Iqbal, Zamin, Puyen, Zully M, Farhat, Maha R, Posey, James, Peto, Timothy EA, Nathanson, Carl-Michael, Zignol, Matteo, Walker, Ann Sarah, and Ismail, Nazir

Published
2022
Full Text
View/download PDF

16. The Hidden Epidemic of Isoniazid-Resistant Tuberculosis in South Africa.

Author

Klopper, Marisa, van der Merwe, Charnay J., van der Heijden, Yuri F., Folkerts, Megan, Loubser, Johannes, Streicher, Elizabeth M., Mekler, Kate, Hayes, Cindy, Engelthaler, David M., Metcalfe, John Z., and Warren, Robin M.

Subjects
WHOLE genome sequencing, ISONIAZID, TUBERCULOSIS, GENOTYPES, PHENOTYPES
Abstract

Rationale: Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. Objectives: To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa. Methods: Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment. We performed isoniazid phenotypic and genotypic drug susceptibility testing, including FluoroTypeMTBDR, Sanger sequencing, targeted next-generation sequencing, and whole-genome sequencing. Results: We analyzed baseline isolates from 766 patients with rifampin-susceptible TB. Of 89 patients (11.7%) who were found to have Hr-TB, 39 (44%) had canonical katG or inhA promoter mutations; 35 (39%) had noncanonical katG mutations (including 5 with underlying large deletions); 4 (5%) had mutations in other candidate genes associated with isoniazid resistance. For 11 (12.4%), no cause of resistance was found. Conclusions: Among patients with rifampin-susceptible TB who were diagnosed using first-line molecular TB assays, there is a high prevalence of Hr-TB. Phenotypic drug susceptibility testing remains the gold standard. To improve the performance of genetic-based phenotyping tests, all isoniazid resistance–associated regions should be included, and such tests should have the ability to identify underlying mutations. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

18. Mixed Mycobacterium tuberculosis-Strain Infections Are Associated With Poor Treatment Outcomes Among Patients With Newly Diagnosed Tuberculosis, Independent of Pretreatment Heteroresistance.

Author

Shin, Sanghyuk S, Modongo, Chawangwa, Baik, Yeonsoo, Allender, Christopher, Lemmer, Darrin, Colman, Rebecca E, Engelthaler, David M, Warren, Robin M, and Zetola, Nicola M

Subjects
Antimicrobial Resistance, Rare Diseases, Infectious Diseases, Tuberculosis, Orphan Drug, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adult, Antitubercular Agents, Botswana, Female, Genotype, Humans, Male, Middle Aged, Mycobacterium tuberculosis, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Young Adult, Next-generation sequencing, drug-resistant tuberculosis, diagnostics, HIV infections, treatment outcome, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

BackgroundHeteroresistant Mycobacterium tuberculosis infections (defined as concomitant infection with drug-resistant and drug-susceptible strains) may explain the higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections while controlling for pretreatment heteroresistance in a population-based sample of patients with tuberculosis starting first-line tuberculosis therapy in Botswana.MethodsWe performed 24-locus mycobacterial interspersed repetitive unit-variable number tandem-repeat analysis and targeted deep sequencing on baseline primary cultured isolates to detect mixed infections and heteroresistance, respectively. Drug-sensitive, micro-heteroresistant, macro-heteroresistant, and fixed-resistant infections were defined as infections in which the frequency of resistance was

Published
2018

19. Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase

Author

Ezewudo, Matthew, Borens, Amanda, Chiner-Oms, Álvaro, Miotto, Paolo, Chindelevitch, Leonid, Starks, Angela M, Hanna, Debra, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Kohl, Thomas Andreas, Warren, Robin M, Crook, Derrick, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, McNerney, Ruth, Cirillo, Daniela M, Schito, Marco, Rodwell, Timothy C, and Posey, James

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Microbiology, Clinical Sciences, Human Genome, Tuberculosis, Antimicrobial Resistance, Rare Diseases, Biotechnology, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Antitubercular Agents, Bacterial Proteins, Drug Resistance, Multiple, Bacterial, Genome, Bacterial, Genotype, Humans, Knowledge Bases, Mutation, Mycobacterium tuberculosis, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Tuberculosis, Multidrug-Resistant, Whole Genome Sequencing
Abstract

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis.

Published
2018

25. Latent Tuberculosis Infection Is Associated with an Enrichment of Short-Chain Fatty Acid-Producing Bacteria in the Stool of Women Living with HIV

Author

Moodley, Suventha, primary, Kroon, Elouise, additional, Naidoo, Charissa C., additional, Nyawo, Georgina R., additional, Wu, Benjamin G., additional, Naidoo, Selisha, additional, Chiyaka, Tinaye L., additional, Tshivhula, Happy, additional, Singh, Shivani, additional, Li, Yonghua, additional, Warren, Robin M., additional, Hoal, Eileen G., additional, Schurr, Erwin, additional, Clemente, Jose C., additional, Segal, Leopoldo N., additional, Möller, Marlo, additional, and Theron, Grant, additional

Published
2024
Full Text
View/download PDF

26. Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study

Author

Cox, Helen, Salaam-Dreyer, Zubeida, Goig, Galo A, Nicol, Mark P, Menardo, Fabrizio, Dippenaar, Anzaan, Mohr-Holland, Erika, Daniels, Johnny, Cudahy, Patrick G T, Borrell, Sonia, Reinhard, Miriam, Doetsch, Anna, Beisel, Christian, Reuter, Anja, Furin, Jennifer, Gagneux, Sebastien, and Warren, Robin M

Published
2021
Full Text
View/download PDF

31. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis

Author

Miotto, Paolo, Tessema, Belay, Tagliani, Elisa, Chindelevitch, Leonid, Starks, Angela M, Emerson, Claudia, Hanna, Debra, Kim, Peter S, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Denkinger, Claudia M, Fleming, Joy, Warren, Robin M, Crook, Derrick, Posey, James, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Murray, Megan, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, Ranganathan, Uma Devi K, McNerney, Ruth, Ezewudo, Matthew, Cirillo, Daniela M, Schito, Marco, Köser, Claudio U, and Rodwell, Timothy C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Tuberculosis, HIV/AIDS, Antimicrobial Resistance, Genetics, Rare Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Bacterial Proteins, DNA, Bacterial, Data Interpretation, Statistical, Drug Resistance, Multiple, Bacterial, Genotype, Humans, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Phenotype, Sequence Analysis, DNA, Systematic Reviews as Topic, Tuberculosis, Multidrug-Resistant, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology
Abstract

A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.

Published
2017

32. Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance.

Author

Metcalfe, John Z, Streicher, Elizabeth, Theron, Grant, Colman, Rebecca E, Penaloza, Renee, Allender, Christopher, Lemmer, Darrin, Warren, Robin M, and Engelthaler, David M

Subjects
Humans, Mycobacterium tuberculosis, Tuberculosis, Multidrug-Resistant, Isoniazid, Fluoroquinolones, Rifampin, DNA Gyrase, DNA-Directed RNA Polymerases, Bacterial Proteins, Antitubercular Agents, Drug Resistance, Multiple, Bacterial, High-Throughput Nucleotide Sequencing, drug-resistant tuberculosis, gyrA, heteroresistance, rpoB, rrs, Biodefense, Infectious Diseases, Prevention, Rare Diseases, Antimicrobial Resistance, Vaccine Related, Tuberculosis, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract

Multidrug-resistant tuberculosis (TB) presents a major public health dilemma. Heteroresistance, the coexistence of drug-resistant and drug-susceptible strains or of multiple drug-resistant strains with discrete haplotypes, may affect accurate diagnosis and the institution of effective treatment. Subculture, or passage of cells onto fresh growth medium, is utilized to preserve Mycobacterium tuberculosis cell lines and is universally employed in TB diagnostics. The impact of such passages, typically performed in the absence of drug, on drug-resistant subpopulations is hypothesized to vary according to the competitive costs of genotypic resistance-associated variants. We applied ultradeep next-generation sequencing to 61 phenotypically rifampin-monoresistant (n = 17) and preextensively (n = 41) and extensively (n = 3) drug-resistant isolates with presumptive heteroresistance at two time points in serial subculture. We found significant dynamic loss of minor-variant resistant subpopulations across all analyzed resistance-determining regions, including eight isolates (13%) whose antibiogram data would have transitioned from resistant to susceptible for at least one drug through subculture. Surprisingly, some resistance-associated variants appeared to be selected for in subculture.

Published
2017

36. A machine-learning based model for automated recommendation of individualized treatment of rifampicin-resistant tuberculosis.

Author

Verboven, Lennert, Callens, Steven, Black, John, Maartens, Gary, Dooley, Kelly E., Potgieter, Samantha, Cartuyvels, Ruben, Laukens, Kris, Warren, Robin M., and Van Rie, Annelies

Subjects
CLINICAL decision support systems, WHOLE genome sequencing, LITERATURE reviews, RIFAMPIN, DIGITAL technology, HIGH-income countries
Abstract

Background: Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. Methods: We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. Results: Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. Conclusions: Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of patients with RR-TB, especially those with 'difficult-to-treat' forms of RR-TB. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

37. The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

Author

Wijk, Marie, Gausi, Kamunkhwala, Malatesta, Samantha, Weber, Sarah E, Court, Richard, Myers, Bronwyn, Carney, Tara, Parry, Charles D H, Horsburgh, C Robert, White, Laura F, Wiesner, Lubbe, Warren, Robin M, Uren, Caitlin, McIlleron, Helen, Kloprogge, Frank, Denti, Paolo, and Jacobson, Karen R

Subjects
ALCOHOL drinking, SUBSTANCE abuse, PHARMACOKINETICS, TUBERCULOSIS, ETHAMBUTOL, ISONIAZID
Abstract

Background In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics. Objectives To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB. Methods We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates. Results The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27–48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%. Conclusion No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

38. Decentralized Care for Rifampin-Resistant Tuberculosis, Western Cape, South Africa

Author

Leavitt, Sarah V., Jacobson, Karen R., Ragan, Elizabeth J., Bor, Jacob, Hughes, Jennifer, Bouton, Tara C., Dolby, Tania, Warren, Robin M., and Jenkins, Helen E.

Subjects
Decentralization (Management) -- Analysis -- Health aspects, Tuberculosis -- Care and treatment, Public health administration -- Methods, Health
Abstract

South Africa has a high tuberculosis (TB) prevalence, complicated by multidrug resistance to rifampin and isoniazid (1). In 2018, multidrug-resistant (MDR) and rifampin-resistant (RR) TB accounted for 3.4% of new [...]

Published
2021
Full Text
View/download PDF

40. Subtracting the background: Reducing cell-free DNA's confounding effects on Mycobacterium tuberculosis quantitation and the sputum microbiome

Author

Naidoo, Charissa C., primary, Venter, Rouxjeane, additional, Codony, Francesc, additional, Agustí, Gemma, additional, Kitchin, Natasha, additional, Naidoo, Selisha, additional, Monaco, Hilary, additional, Mishra, Hridesh, additional, Li, Yonghua, additional, Clemente, Jose C., additional, Warren, Robin M., additional, Segal, Leopoldo N., additional, and Theron, Grant, additional

Published
2024
Full Text
View/download PDF

41. Analysis of the limitedM. tuberculosisaccessory genome reveals potential pitfalls of pan-genome analysis approaches

Author

Marin, Maximillian G., primary, Wippel, Christoph, additional, Quinones-Olvera, Natalia, additional, Behruznia, Mahboobeh, additional, Jeffrey, Brendan M., additional, Harris, Michael, additional, Mann, Brendon C., additional, Rosenthal, Alex, additional, Jacobson, Karen R., additional, Warren, Robin M., additional, Li, Heng, additional, Meehan, Conor J., additional, and Farhat, Maha R., additional

Published
2024
Full Text
View/download PDF

43. Human whole genome sequencing in South Africa

Author

Glanzmann, Brigitte, Jooste, Tracey, Ghoor, Samira, Gordon, Richard, Mia, Rizwana, Mao, Jun, Li, Hao, Charls, Patrick, Douman, Craig, Kotze, Maritha J., Peeters, Armand V., Loots, Glaudina, Esser, Monika, Tiemessen, Caroline T., Wilkinson, Robert J., Louw, Johan, Gray, Glenda, Warren, Robin M., Möller, Marlo, and Kinnear, Craig

Published
2021
Full Text
View/download PDF

49. 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
Full Text
View/download PDF

50. Distinct serum biosignatures are associated with different tuberculosis treatment outcomes

Author

Ronacher, Katharina, Chegou, Novel N., Kleynhans, Léanie, Djoba Siawaya, Joel F., du Plessis, Nelita, Loxton, André G., Maasdorp, Elizna, Tromp, Gerard, Kidd, Martin, Stanley, Kim, Kriel, Magdalena, Menezes, Angela, Gutschmidt, Andrea, van der Spuy, Gian D., Warren, Robin M., Dietze, Reynaldo, Okwera, Alphonse, Thiel, Bonnie, Belisle, John T., Cliff, Jacqueline M., Boom, W. Henry, Johnson, John L., van Helden, Paul D., Dockrell, Hazel M., and Walzl, Gerhard

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results