1. suPAR and sICAM-1 as Immune Markers for Treatment Response in Ethiopian TB patients with and without HIV co-infection Wegene T. Mekasha ICASA, Addis Ababa Dec 6, 2011

2. Contents Introduction Objectives Materials and Methods Result and Discussion Conclusion and recommendation Collaborators

3. Introduction TB is one of the major cause of morbidity and mortality 1/3 of the world population is infected Only 5-10% develop active disease 8.8 millions incidence, 13% were TB+HIV+ 1.1 million HIV- & 350, 000 HIV+ mortality Ethiopia ranked 7 th from 22 high TB burdened countries – 82, 950 estimated TB incidence WHO 2011 Global TB report

4. Intro Challenges in TB control – Diagnosis, Vaccine, treatment MDR & XDR Biomarkers A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to a therapeutic intervention" (Biomarkers definition working group 2001).

5. Intro….. Values of biomarkers Diagnostics, drug development, clinical trials, and therapeutic assessment strategies Proposed biomarkers Table-1Table-1 Selected markers suPAR and sICAM-1 – Non-specific immune markers – Expressed in immune cells like macrophages, endothelial cells, monocytes, dendritic cells, etc.

6. Objectives General Objective To assess the prospective of suPAR and sICAM-1 as immune markers for Tb disease and treatment response in TB patients with and without HIV co- infection Specific objectives To evaluate the level of suPAR and sICAM-1 in TB cases at baseline relative to healthy controls To evaluate any association of the level of suPAR and sICAM-1 with the response to anti-TB treatment. To assess the impact of HIV co-infection on the level of suPAR and sICAM-1 in TB/HIV patients

7. Methods Study design Prospective cohort Study population 105 study participants enrolled are TB+HIV- TB+HIV+ cases & controls (TB-HIV-) Inclusion/exclusion criteria – Age 15-60, volunteer HIV testing, live in Addis, consented – With chronic illness, on steroid therapy, currently or previously on ART and pregnant

8. Methods…. Laboratory tests – 155 specimens (105 baseline and 50 six month follow-up) – CD4: FACSCallibur, BD, USA – Hematology: CelDyn 3700, – Viral load: Easy Q, BioMuruex, France – Biomarkers testing: quantitative ELISA s sICAM-1 : Quantikine sICAM, R &D systems (USA) sUPAR : suPARnostic, ViroGetes (Denmark) Data analysis- Stata v 11.0

9. Result and discussion

10. Result…. Baseline characteristics – Sex= 57.3% female, 42.7% male TB+HIV-TB+HIV+Control Age28 (15-52) 34 (22-56) 26 (9-43) BMI 0m 18.37 (12.19-23.44) 18.90 (12.61-25.61) 21.42 (17.72-25.96) WBC 0m5.9 (2.3-9.4) 5.14 (2.78-10) 4.5 (2.2-9.4) CD4 0m445 (134-890) 146 (17-894) 762 (90-1567)

11. Result….. Level of suPAR at baseline

12. Result….. Level of sICAM-1 at baseline

13. Result….. Level of suPAR after 6m of Anti-TB Rx Raras & Chazin, 2010

14. Result….. Level of suPAR after 6m of Anti-TB Rx

15. Result….. Level of sICAM-1 after 6m of Anti-TB Rx Demir et al 2002, Amiri et al 2004

16. Result….. Level of sICAM-1 after 6m of Anti-TB Rx

17. Result... VariableMean (range)TB+HIV-TB+HIV+Control BMI 0m19.94 (12.14-25.96) 18.37 (12.19-23.44) 18.90 (12.61-25.61) 21.42 (17.72-25.96) BMI 6m20.25 (15.06-27.69) 20.35 (16.23-27.69) 16 (15.06-25.44) WBC 0m4.99 (2.2- 10.0) 5.9 (2.3-9.4)5.14 (2.78-10)4.5(2.2-9.4) WBC 6m4.83 (2.25-9.0) 5.36 (2.25-9.0) 3.95 (2.26-6.66) CD4 0m582 (17-1567)445 (134-890)146(17-894)762(90-1567) CD4 6m505 (18-1335)697 (265-1335) 198 (18-658)

18. Conclusion and recommendation Both suPAR and sICAM-1 level in TB+HIV- & TB+HIV+ cases were significantly higher than Control group at baseline Both markers declined significantly after TB Rx in both TB+HIV- & TB+HIV+ groups but remained higher than controls The findings showed that the potential of suPAR and sICAM-1 as diagnostic and treatment monitoring biomarkers in TB patients with and without HIV co- infection Addressing latent TB cases and including microbiological examinations are recommended for further studies

19. Collaborators Desta Kassa Yodit Alemayehu G/Medhin G/Egziabher Amelework Alemu Tsehaynesh Messele

20. Thank you Amesegenalehu