1. 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. Mupfumi 1’2, P. Mason 1’2, S. Zinyowera 2,3, J. Matsekete 1, T. Bandason 1, S. Mungofa 4, R. Mutetwa 1 1.Biomedical Training and Research Institute, Harare 2.University of Zimbabwe College of Health Sciences 3.National Microbiology Reference Laboratory, Harare 4.Harare City Council Abstract #: THAB0104 TB Diagnostics: innovating to make an impact

2. 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)

3. 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

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

5. 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

6. Washington D.C., USA, 22-27 July 2012www.aids2012.org Xpert assay steps, Boehme 2010 TB Diagnostics: innovating to make an impact Fig 1: study flow diagram

7. 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

8. 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 impact characteristicAll patients% or IQR or SD TB diagnosed % or IQ or SDNon-TB% or IQR or SDp-value N212311518185 Mean weight, kg -SD59.111.855.99.359.612.1 Median CD4, cells/µl –IQR16377-25613957-21017280-258 >350 cells/µl942674 200< cells/µl<350793872372410.26 50< cells/µl<200884217557140 <50 cells/µl33165 2816 TB symptoms Cough>2weeks51451239 220.04 Fever12258258197540.005 Night sweats10449227182450.004 Weight loss148691890130670.04 Chest pain10345147082430.02 TB history TB contact492382641230.70

9. Washington D.C., USA, 22-27 July 2012www.aids2012.org Characteristic Clinical TB (n=11) n (%) Non TB (n=181) n (%) p-value Cough8 (73)77 (43)0.05 Fever10 (91)97 (54)0.02 Night sweats6 (55)82 (45)0.55 Chest pain7 (64)75 (41)0.15 Weight loss9 (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

10. Washington D.C., USA, 22-27 July 2012www.aids2012.org  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

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org Supervisors SACORE Harare City Health Department Study participants NMRL BRTI TB lab staff Acknowledgements TB Diagnostics: innovating to make an impact