Washington D.C., USA, 22-27 July 2012 The value of universal TB screening with GeneXpert MTB/RIF in...

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, 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


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)


• 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


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


• 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.


Methods


Xpert assay steps, Boehme 2010

TB Diagnostics: innovating to make an impactTB Diagnostics: innovating to make an impact

Fig 1: study flow diagram


• 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.


Results


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


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


192 (91%) patients had a negative Xpert result; of these 11 (5.7%) had a clinical diagnosis of TB


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.


Conclusion


• Supervisors

• SACORE

• Harare City Health Department

• Study participants

• NMRL

• BRTI TB lab staff

Acknowledgements


Washington D.C., USA, 22-27 July 2012 The value of universal TB screening with GeneXpert MTB/RIF in...

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