The value of universal TB screening with GeneXpert MTB/RIF in pre-ART patients in Harare

1. 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. Mupfumi1’2, P. Mason1’2, S. Zinyowera2,3, J. Matsekete1, T. Bandason1, S. Mungofa4, R. Mutetwa1 Biomedical Training and Research Institute, Harare University of Zimbabwe College of Health Sciences National Microbiology Reference Laboratory, Harare Harare City Council

2. The global burden of TB in 2010 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%) (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)

3. TB Diagnostics: innovating to make an impact Challenges in diagnosing TB • 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

4. MTB GeneXpert® MTB/RIF Test: game changer for TB diagnosis • 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 GeneXpert System module cartridge

5. TB Diagnostics: innovating to make an impact Methods • 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.

6. TB Diagnostics: innovating to make an impact TB Diagnostics: innovating to make an impact Fig 1: study flow diagram Xpert assay steps, Boehme 2010

7. TB Diagnostics: innovating to make an impact Results • 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.

8. TB Diagnostics: innovating to make an impact Table 1: Baseline participant characteristics of pre-ART patients

9. TB Diagnostics: innovating to make an impact Table 2: characteristics of patients with clinical diagnosis of TB 192 (91%) patients had a negative Xpert result; of these 11 (5.7%) had a clinical diagnosis of TB

10. TB Diagnostics: innovating to make an impact Conclusion • 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.

11. TB Diagnostics: innovating to make an impact Acknowledgements • Supervisors • SACORE • Harare City Health Department • Study participants • NMRL • BRTI TB lab staff