1. Dr Justin O’Grady

2. Zambia is a high burden TB and high HIV setting 44,154 TB cases notified in 2010 – incidence of 462/100,000 pop Approx 48% of pulmonary TB cases in Zambia are smear negative

3. TB diagnostics in Zambia Current standard method for TB diagnosis is sputum microscopy Culture only available in a few reference labs country- wide

4. GeneXpert and Xpert MTB/RIF test Fully automated closed system Performs both sample preparation and real-time PCR Xpert MTB/RIF detects the Mtb complex while simultaneously detecting RIF resistance Results in less than 2 hours 98.2% and 72.5% sensitive on smear-positive and smear- negative TB patients respectively - 99.2% specific (Boehme et al 2010 NEJM)

5. GeneXpert Figure 1: GeneXpert machine, Xpert cartridge and sonicator

6. Pros Cons Robust Accurate Simple to use Rapid (2hours) Detects both MTC and RIF resistance Operation over a wide temperature and humidity range Low risk of infection Possible application for EPTB – lymph node aspirates, gastric lavage, urine, CSF etc Expensive requires calibration and maintenance relatively short shelf life of tests usefulness of RIF resistance testing in absence of MDR-TB drugs false positive RIF results requires continuous electrical power supply problems with cartridge disposal Xpert MTB/RIF

7. Xpert MTB/RIF G4

8. Cross-sectional study of 6 adult inpatient wards (3 male) Aims: To determine the overall burden of TB, sub-clinical TB, MDR-TB and TB co-morbidities with communicable and non communicable diseases (CDs and NCDs) in patients, regardless of admission diagnosis, admitted to the inpatient medical wards at UTH To evaluate the performance of Xpert MTB/RIF test in this patient population ADAT adult inpatient TB study

9. Adult inpatient TB study Figure 2: Patient recruitment flow diagram

10. Adult inpatient TB study Table 1: Age, HIV, gender and admission diagnosis statistics from both study cohort and general population

11. Adult inpatient TB study Table 2: Prevalence of culture positive TB in patients with communicable and non communicable diseases

12. Adult inpatient TB study Sub-clinical TB: asymptomatic TB or TB without sufficient symptoms to warrant investigation under Zambia National TB Programme Guidelines 13.3% (21/158) of culture confirmed TB positive patients had sub-clinical TB 3.85% (21/546) of patients not considered TB suspects, were positive Extrapolating from our data: 2.6% of all admissions to the inpatient wards at UTH may have sub-clinical TB

13. Adult inpatient TB study WHO estimates that there are only 1,100 (2% of TB cases) MDR-TB cases in Zambia each year 18/158 (11%) culture confirmed TB cases were MDR-TB Data would suggest MDR-TB is a bigger problem than previously thought in Zambia UTH is a tertiary referral hospital, therefore a higher MDR-TB prevalence would be expected

14. Table 3: Accuracy, specificity and sensitivity of the Xpert MTB/RIF assay Adult inpatient TB study

15. Conclusions There is a significant prevalence of TB co-morbidity with communicable and non communicable diseases at UTH Sub-clinical TB may be a very significant manifestation of TB in HIV positive and HIV negative inpatients in Zambia MDR-TB may be a bigger problem in Zambia than previously reported Xpert MTB/RIF performs well in a high TB/HIV prevalence setting detecting an additional 56 TB cases compared to smear

16. Future work ADAT paediatric, maternal and prison Xpert studies Rapid identification of respiratory tract infections (RID- RTI) EU FP7 application Bacteria, viruses, fungi and drug resistance detection Automated system for sample prep and detection Multiplex PCR followed by microarray based detection Xpert empyema study

17. Acknowledgements Professor Alimuddin Zumla (UCL) Dr Peter Mwaba (Zambia) Dr Matthew Bates (Zambia) UNZA-UCLMS Project staff, UTH, Lusaka, and UCL, London Funding Agencies EuropeAid (Brussels) EDCTP (Netherlands)

19. THANK YOU