the value of universal tb screening with genexpert mtb/rif in pre-art patients in harare
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TB Diagnostics: innovating to make an impact. Abstract #: THAB0104. The value of universal TB screening with GeneXpert MTB/RIF in pre-ART patients in Harare. L. Mupfumi 1’2 , P. Mason 1’2 , S. Zinyowera 2,3 , J. Matsekete 1 , T. Bandason 1 , S. Mungofa 4 , R. Mutetwa 1 - PowerPoint PPT PresentationTRANSCRIPT
Washington D.C., USA, 22-27 July 2012www.aids2012.org
The value of universal TB screening with GeneXpert MTB/RIF in pre-ART patients in Harare
L. Mupfumi1’2, P. Mason1’2, S. Zinyowera2,3, J. Matsekete1, T. Bandason1, S. Mungofa4, R. Mutetwa1
1. Biomedical Training and Research Institute, Harare2. University of Zimbabwe College of Health Sciences3. National Microbiology Reference Laboratory, Harare
4. Harare City Council
Abstract #: THAB0104 TB Diagnostics: innovating to make an impact
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Estimated number of
cases
Estimated number of
deaths
1.1 million(range 0.9–1.1 million)
12 million(range 11–14 million)All forms of TB
HIV-associated TB 1.8 million (15%)(1.3–1.6 million)
350,000 (24%)
The global burden of TB in 2010
(25% of HIV deaths worldwide are due to TB - more than 76% burdern in Africa )Orphaned children
parental TB deaths
9,7 million (0.85-11 million)
Washington D.C., USA, 22-27 July 2012www.aids2012.org
• 25% undiagnosed TB in patients initiating ART, associated with high mortality within 3-6 months of ART (Basset 2010; Moore 2007; Lawn 2006)
• Smear microscopy, the first line diagnostic tool performs suboptimally in patients entering ART care.
• Culture has long turnaround times limiting utility in pre-ART patient management.
• Chest radiography has reduced specificity in HIV infected patients
TB Diagnostics: innovating to make an impact
Challenges in diagnosing TB
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Workflow • sputum• simple 1-step external sample prep. procedure• time-to-result < 2 h • throughput: > 16 tests / day / module• integrated controls• true random access
Performance• specific for MTB• sensitivity better than smear, similar to culture• 99.5% and 71% sensitive in smear positive and smear negative TB respectively• detection of rif-resistance via rpoB gene
cartridge
GeneXpert Systemmodule
MTB
GeneXpert® MTB/RIF Test: game changer for TB diagnosis
Washington D.C., USA, 22-27 July 2012www.aids2012.org
• Over a 5-month period, 229 HIV positive adults (>18yrs) recruited regardless of symptoms at an ART initiation hospital in Harare
• Two sputum samples, collected spontaneously or after induction with 6% NaCl (Mucoclear™) in patients failing to produce sputum, were tested with Xpert and cultured.
• Patients were reviewed at 1 and 3 months post recruitment by a study doctor; chest x-rays were taken at both reviews and samples for culture obtained if still symptomatic.
TB Diagnostics: innovating to make an impact
Methods
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Xpert assay steps, Boehme 2010
TB Diagnostics: innovating to make an impactTB Diagnostics: innovating to make an impact
Fig 1: study flow diagram
Washington D.C., USA, 22-27 July 2012www.aids2012.org
• 229 patients were recruited into the study, 54% females, median age 37 years (IQR 31-44)
93% (212/229) were symptomatic; 50% (107/212) were coughing, 28% (59) had fever ,16% (28) reported weight loss.
GeneXpert diagnosed 9% (95% CI 6-14%) of cases; of these 15 % (3/20) was from non-coughers
Sputum induction was carried out in 32 patients and contributed 14% (3/20) of microbiological TB.
TB Diagnostics: innovating to make an impact
Results
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Table 1: Baseline participant characteristics of pre-ART patients
TB Diagnostics: innovating to make an impactcharacteristic All patients % or IQR or SD TB
diagnosed% or IQ or SD Non-TB % or IQR or SD p-value
N 212 31 15 181 85
Mean weight, kg -SD 59.1 11.8 55.9 9.3 59.6 12.1
Median CD4, cells/µl –IQR 163 77-256 139 57-210 172 80-258
>350 cells/µl 9 4 2 6 7 4
200< cells/µl<350 79 38 7 23 72 41 0.26
50< cells/µl<200 88 42 17 55 71 40
<50 cells/µl 33 16 5 16 28 16
TB symptoms
Cough>2weeks 51 45 12 39 39 22 0.04
Fever 122 58 25 81 97 54 0.005
Night sweats 104 49 22 71 82 45 0.004
Weight loss 148 69 18 90 130 67 0.04
Chest pain 103 45 14 70 82 43 0.02
TB history
TB contact 49 23 8 26 41 23 0.70
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Characteristic Clinical TB (n=11)n (%)
Non TB (n=181)n (%)
p-value
Cough 8 (73) 77 (43) 0.05
Fever 10 (91) 97 (54) 0.02
Night sweats 6 (55) 82 (45) 0.55
Chest pain 7 (64) 75 (41) 0.15
Weight loss 9 (82) 121 (67) 0.30
Table 2: characteristics of patients with clinical diagnosis of TB
TB Diagnostics: innovating to make an impact
192 (91%) patients had a negative Xpert result; of these 11 (5.7%) had a clinical diagnosis of TB
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We have shown in this study a high prevalence of undiagnosed TB in pre-ART patients with advanced immunodeficiency. These are patients who benefit from prompt diagnosis of TB and initiation on ART to prevent mortality.
Sputum induction in patients unable to expectorate made a significant contribution to TB diagnosis.
A two step screening algorithm of Xpert testing and chest radiography is beneficial in pre-ART patients.
TB Diagnostics: innovating to make an impact
Conclusion
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• Supervisors
• SACORE
• Harare City Health Department
• Study participants
• NMRL
• BRTI TB lab staff
Acknowledgements
TB Diagnostics: innovating to make an impact