Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control Study
Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon...
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| Published in: | PloS one Vol. 3; no. 9; p. e3173 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
Public Library of Science
09.09.2008
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| ISSN: | 1932-6203, 1932-6203 |
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| Abstract | Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.
This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.
MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. |
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| AbstractList | Background Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. Methodology/Principal Findings This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. Conclusions/Significance MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. Background Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. Methodology/Principal Findings This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. Conclusions/Significance MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.BACKGROUNDMulti-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.METHODOLOGY/PRINCIPAL FINDINGSThis retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.CONCLUSIONS/SIGNIFICANCEMDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. BackgroundMulti-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.Methodology/principal findingsThis retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.Conclusions/significanceMDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods. |
| Audience | Academic |
| Author | O'Riordan, Philly Wilkinson, Robert J. Wall, Robert Pasvol, Geoffrey Schwab, Uli Bassett, Paul Logan, Sarah Cooke, Graham Davidson, Robert N. Flanagan, Katie L. |
| AuthorAffiliation | 2 Wellcome Centre for Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, United Kingdom University College London, United Kingdom 3 Department of Medical Microbiology, Northwick Park Hospital, Harrow, Middlesex, United Kingdom 1 Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital, Harrow, Middlesex, United Kingdom |
| AuthorAffiliation_xml | – name: 3 Department of Medical Microbiology, Northwick Park Hospital, Harrow, Middlesex, United Kingdom – name: University College London, United Kingdom – name: 1 Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital, Harrow, Middlesex, United Kingdom – name: 2 Wellcome Centre for Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, United Kingdom |
| Author_xml | – sequence: 1 givenname: Philly surname: O'Riordan fullname: O'Riordan, Philly – sequence: 2 givenname: Uli surname: Schwab fullname: Schwab, Uli – sequence: 3 givenname: Sarah surname: Logan fullname: Logan, Sarah – sequence: 4 givenname: Graham surname: Cooke fullname: Cooke, Graham – sequence: 5 givenname: Robert J. surname: Wilkinson fullname: Wilkinson, Robert J. – sequence: 6 givenname: Robert N. surname: Davidson fullname: Davidson, Robert N. – sequence: 7 givenname: Paul surname: Bassett fullname: Bassett, Paul – sequence: 8 givenname: Robert surname: Wall fullname: Wall, Robert – sequence: 9 givenname: Geoffrey surname: Pasvol fullname: Pasvol, Geoffrey – sequence: 10 givenname: Katie L. surname: Flanagan fullname: Flanagan, Katie L. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18779863$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2008 Public Library of Science 2008 Philly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Philly et al. 2008 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: OP SU CG PG KLF. Performed the experiments: OP SU LS RW. Analyzed the data: OP BP PG KLF. Wrote the paper: OP CG WJR RD BP RW PG KLF. Current address: Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa Current address: MRC Research Laboratories, Fajara, The Gambia Current address: Imperial College, London and Africa Centre for Health and Population Studies, University of KwaZulu Natal, KwaZulu Natal, South Africa |
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| References_xml | – volume: 55 start-page: 962 year: 2000 ident: ref21 article-title: Resource implications of patients with multidrug resistant tuberculosis. publication-title: Thorax doi: 10.1136/thorax.55.11.962 – volume: 953 start-page: 138 year: 2001 ident: ref7 article-title: Molecular techniques in the diagnosis of Mycobacterium tuberculosis and the detection of drug resistance. publication-title: Ann N Y Acad Sci – volume: 370(9596) start-page: 1453 year: 2007 ident: ref12 article-title: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. publication-title: Lancet – volume: 24 start-page: S121 year: 1997 ident: ref16 article-title: Drug-resistant tuberculosis: review of the worldwide situation and the WHO/IUATLD Global Surveillance Project. International Union Against Tuberculosis and Lung Disease. publication-title: Clin Infect Dis doi: 10.1093/clinids/24.Supplement_1.S121 – volume: 953 start-page: 185 year: 2001 ident: ref15 article-title: The clinical management of the drug-resistant patient. publication-title: Ann N Y Acad Sci doi: 10.1111/j.1749-6632.2001.tb11376.x – volume: 83(1–3) start-page: 44 year: 2003 ident: ref17 article-title: The global situation of MDR-TB. publication-title: Tuberculosis (Edinb) doi: 10.1016/S1472-9792(02)00058-6 – start-page: S31 year: 1996 ident: ref13 article-title: Risk Factors for drug resistance in patients with tuberculosis in England and Wales 1993–4. publication-title: Thorax – volume: 307(6918) start-page: 1539 year: 1993 ident: ref18 article-title: Screening migrants at risk of tuberculosis. publication-title: Brit Med J doi: 10.1136/bmj.307.6918.1539 – year: 2003 ident: ref2 article-title: Treatment of Tuberculosis: Guidelines for National Programmes. Third Edition. – ident: ref22 article-title: Molecular line probe assays for rapid screening of patients at risk of multi-drug resistant tuberculosis (MDR-TB). – year: 2006 ident: ref1 article-title: Focus on Tuberculosis: Annual surveillance report 2006 - England, Wales and Northern Ireland. – volume: 177(7) start-page: 787 year: 2008 ident: ref23 article-title: Rapid Molecular Screening for MDR-TB in a High Volume Public Health Laboratory in South Africa. publication-title: Am J Respir Crit Care Med doi: 10.1164/rccm.200709-1436OC – volume: 36(7) start-page: 1969 year: 1998 ident: ref8 article-title: Comparison of three molecular assays for rapid detection of rifampicin resistance in Mycobacterium tuberculosis. publication-title: J Clin Microbiol doi: 10.1128/JCM.36.7.1969-1973.1998 – volume: (1) start-page: 39 year: 1998 ident: ref19 article-title: Is new immigrant screening for tuberculosis still worthwhile? publication-title: J Infect Dis 37 – volume: 12(5) start-page: 752 year: 2006 ident: ref9 article-title: Mycobacterium Tuberculosis and Rifampicin Resistance, United Kingdom. publication-title: Emerg Infect Dis doi: 10.3201/eid1205.041339 – volume: 368 start-page: 2142 year: 2006 ident: ref4 article-title: Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis. publication-title: Lancet doi: 10.1016/S0140-6736(06)69863-2 – volume: 57(2) start-page: 152 year: 2002 ident: ref5 article-title: Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995–9. publication-title: Thorax doi: 10.1136/thorax.57.2.152 – year: 2005 ident: ref3 article-title: The UK Mycobacterial Surveillance Network Report, 1994–2003. 10 years of MycobNet. – volume: 53(1) start-page: 5 year: 2005 ident: ref11 article-title: Drug-resistent tuberculosis: A disease of target populations in Houston, Texas. publication-title: J Infect – volume: 8(8) start-page: 1012 year: 2004 ident: ref20 article-title: Costs of patients hospitalized for multidrug-resistant tuberculosis. publication-title: Int J Tuberc Lung Dis – volume: 57 start-page: 810 year: 2002 ident: ref6 article-title: A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK. publication-title: Thorax doi: 10.1136/thorax.57.9.810 – volume: 33(11) start-page: 2994 year: 1995 ident: ref10 article-title: Detection and identification of mycobacteria by DNA amplification and oligonucleotide-specific capture plate hybridization. publication-title: J Clin Microbiol doi: 10.1128/JCM.33.11.2994-2998.1995 – volume: 61 start-page: 158 year: 2006 ident: ref14 article-title: Risk factors for multidrug resistant tuberculosis in Europe: a systematic review. publication-title: Thorax doi: 10.1136/thx.2005.045963 |
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| Snippet | Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community... Background Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the... BackgroundMulti-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the... Background Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the... |
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| SubjectTerms | Acid resistance Antibiotics, Antitubercular - pharmacology Bacilli Care and treatment Case-Control Studies Control Demographics Demography Diagnosis Diagnostic systems DNA-directed RNA polymerase Drug resistance Epidemiology Female Health care Health surveillance Hospitals Humans Impact analysis Infections Infectious Diseases/Antimicrobials and Drug Resistance Infectious Diseases/Bacterial Infections Laboratories Lung diseases Male Medical diagnosis Medical personnel Medical records Medical research Medicine Microbiology Microbiology/Medical Microbiology Multidrug resistance Multidrug resistant organisms Mutation Patients Public health Retrospective Studies Ribonucleic acid Rifampin Rifampin - pharmacology Risk Risk analysis Risk Factors RNA RNA polymerase RNA Polymerase II - genetics RpoB protein Sensitivity Studies Test procedures Therapy Thorax Treatment Outcome Tuberculosis Tuberculosis, Multidrug-Resistant - diagnosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - prevention & control Tuberculosis, Multidrug-Resistant - transmission Tuberculosis, Pulmonary - diagnosis Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - prevention & control Tuberculosis, Pulmonary - transmission |
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| Title | Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control Study |
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