Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study
Background:
The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.
Methods and Findings:
Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102–236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%).
Conclusions:
In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal.
: Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study. PLoS Med 8(7): e32767. doi:10.1371/journal.pmed.1001067
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001067
Souhrn
Background:
The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.
Methods and Findings:
Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102–236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%).
Conclusions:
In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal.
: Please see later in the article for the Editors' Summary
Zdroje
1. LawnSDWoodR 2011 Tuberculosis in antiretroviral treatment services in resource-limited settings: addressing the challenges of screening and diagnosis. J Infect Dis In press
2. KranzerKHoubenRMGlynnJRBekkerLGWoodR 2010 Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis. Lancet Infect Dis 10 93 102
3. LawnSDKranzerKEdwardsDJMcNallyMBekkerLG 2010 Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS 24 1323 1328
4. BassettIVWangBChettySGiddyJLosinaE 2010 Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis 51 823 829
5. LawnSDMyerLBekkerLGWoodR 2006 Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. AIDS 20 1605 1612
6. MooreDLiechtyCEkwaruPWereWMwimaG 2007 Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda. AIDS 21 713 719
7. LawnSDHarriesADAnglaretXMyerLWoodR 2008 Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 22 1897 1908
8. BockNNJensenPAMillerBNardellE 2007 Tuberculosis infection control in resource-limited settings in the era of expanding HIV care and treatment. J Infect Dis 196 Suppl 1 S108 S113
9. GandhiNRMollASturmAWPawinskiRGovenderT 2006 Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368 1575 1580
10. WellsCDCegielskiJPNelsonLJLasersonKFHoltzTH 2007 HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis 196 Suppl 1 S86 S107
11. O'DonnellMRJarandJLovedayMPadayatchiNZelnickJ 2010 High incidence of hospital admissions with multidrug-resistant and extensively drug-resistant tuberculosis among South African health care workers. Ann Intern Med 153 516 522
12. ReidMJShahNS 2009 Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis 9 173 184
13. GetahunHKittikraisakWHeiligCMCorbettELAylesH 2011 Development of a standardized screening rule for tuberculosis in people livign with HIV in resource-contrained settings: individual participant data meta-analysis of observational studies. PLoS Med 8 e1000391 doi:10.1371/journal.pmed.1000391
14. World Health Organization 2010 Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings Geneva World Health Organization Available: http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf. Accessed 7 December 2010
15. LawnSDEdwardsDJKranzerKVogtMBekkerLG 2009 Urine lipoarabinomannan assay for tuberculosis screening before antiretroviral therapy diagnostic yield and association with immune reconstitution disease. AIDS 23 1875 1880
16. DawsonRMasukaPEdwardsDJBatemanEDBekkerLG 2010 Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV. Int J Tuberc Lung Dis 14 52 58
17. LawnSDWoodR 2011 Tuberculosis screening in patients starting antiretroviral therapy: stretching diagnostics to the limits. Clin Infect Dis 52 276 277
18. World Health Organization 2010 Multidrug and extensively drug-resistant TB (M/XDR-TB). 2010 global report on surveillance and response. WHO/HTM/TB/2010.3 Geneva World Health Organization Available: http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf. Accessed 18 August 2010
19. GandhiNRNunnPDhedaKSchaafHSZignolM 2010 Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 375 1830 1843
20. BoehmeCCNabetaPHillemannDNicolMPShenaiS 2010 Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 363 1005 1015
21. World Health Organization 2010 December 6 Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR-TB Geneva World Health Organization Available: http://www.who.int/tb/laboratory/roadmap_xpert_mtb_rif_rev23dec2010.pdf. Accessed 8 December 2010
22. BlakemoreRStoryEHelbDKopJBanadaP 2010 Evaluation of the analytical performance of the Xpert(R) MTB/RIF assay. J Clin Microbiol 48 2495 2501
23. HelbDJonesMStoryEBoehmeCWallaceE 2010 Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol 48 229 237
24. BoehmeCCNicolMPNabetaPMichaelJSGotuzzoE 2011 Feasibility and impact of decentralised use of Xpert MTB/RIF for the diagnosis of tuberculosis and multi-drug resistance—results from a multi-center implementation study. Lancet 377 1495 1505
25. ArmandSVanhulsPDelcroixGCourcolRLemaitreN 2011 Comparison of the Xpert MTB/RIF test with an IS6110-TaqMan real-time PCR assay for direct detection of Mycobacterium tuberculosis in respiratory and nonrespiratory specimens. J Clin Microbiol 49 1772 1776
26. MarloweEMNovak-WeekleySMCumpioJSharpSEMomenyMA 2011 Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol 49 1621 1623
27. MoureRMunozLTorresMSantinMMartinR 2011 Rapid detection of Mycobacterium tuberculosis complex and rifampin resistance in smear-negative clinical samples by use of an integrated real-time PCR method. J Clin Microbiol 49 1137 1139
28. HillemannDRusch-GerdesSBoehmeCRichterE 2011 Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol 49 1202 1205
29. VadwaiVBoehmeCNabetaPShettyAAllandD 2011 Xpert MTB/RIF, a new pillar in the diagnosis of extrapulmonary tuberculosis? J Clin Microbiol E-pub ahead of print. doi:10.1128/JCM.02319-10
30. LawnSDMyerLEdwardsDBekkerLGWoodR 2009 Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS 23 1717 1725
31. LawnSDMyerLBekkerLGWoodR 2007 Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 21 335 341
32. South Africa Department of Health 2004 The South African National Tuberculosis Control Programme: practical guidelines Pretoria South Africa Department of Health Available: http://www.kznhealth.gov.za/chrp/documents/Guidelines/Guidelines%20National/Tuberculosis/SA%20TB%20Guidelines%202004.pdf. Accessed 15 April 2010
33. Den BoonSBatemanEDEnarsonDABorgdorffMWVerverS 2005 Development and evaluation of a new chest radiograph reading and recording system for epidemiological surveys of tuberculosis and lung disease. Int J Tuberc Lung Dis 9 1088 1096
34. LawnSDMyerLOrrellCBekkerLGWoodR 2005 Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 19 2141 2148
35. LawnSDFraenzelAKranzerKCaldwellJBekkerLG 2011 Improving access to antiretroviral therapy for patients with HIV-associated tuberculosis in South Africa. S Afr Med J In press
36. GandhiNRShahNSAndrewsJRVellaVMollAP 2010 HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med 181 80 86
37. NicolM 2010 Algorithms for referral to rapid diagnostics for MDR-TB: preliminary outcomes [presentation]. International Union Against Tuberculosis and Lung Disease 41st Union World Conference on Lung Health; November 2010; Berlin, Germany. Available: http://uwclh.conference2web.com/content/227. Accessed 2 February 2011
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2011 Číslo 7
- Statinová intolerance
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Co dělat při intoleranci statinů?
- Pleiotropní účinky statinů na kardiovaskulární systém
- DESATORO PRE PRAX: Aktuálne odporúčanie ESPEN pre nutričný manažment u pacientov s COVID-19
Najčítanejšie v tomto čísle
- Individualized Cost-Effectiveness Analysis
- GeneXpert—A Game-Changer for Tuberculosis Control?
- Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study
- Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort