Washington D.C., USA, 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

Washington D.C., USA, 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 ( million)

Washington D.C., USA, 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, 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

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

Washington D.C., USA, 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, 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 N Mean weight, kg -SD Median CD4, cells/µl –IQR >350 cells/µl < cells/µl< < cells/µl< <50 cells/µl TB symptoms Cough>2weeks Fever Night sweats Weight loss Chest pain TB history TB contact

Washington D.C., USA, 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

Washington D.C., USA, 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

Washington D.C., USA, 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