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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Bibliographic Details
Published in:PloS one Vol. 3; no. 9; p. e3173
Main Authors: O'Riordan, Philly, Schwab, Uli, Logan, Sarah, Cooke, Graham, Wilkinson, Robert J., Davidson, Robert N., Bassett, Paul, Wall, Robert, Pasvol, Geoffrey, Flanagan, Katie L.
Format: Journal Article
Language:English
Published: United States Public Library of Science 09.09.2008
Public Library of Science (PLoS)
Subjects:
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
United Kingdom > UK
England
South Africa
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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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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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0003173