A pilot study measuring the kinetic profile of IP-10 over the first 14 days of PTB chemotherapy

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1 A pilot study measuring the kinetic profile of IP-10 over the first 14 days of PTB chemotherapy Dr Rachel Saunders Dr Matthew Blakiston Liverpool School of Tropical Medicine

2 Background TB is responsible for 1.4 million deaths annually Difficulties in managing and controlling TB are contributed to by the limitations of current diagnostic methods, particularly in low resource areas, Sputum smear microscopy 50% sensitivity CXR Findings non-specific Sputum culture Delayed results, infrastructure requirements Xpert MTB/RIF Cost, lower accuracy in smear neg. cases IGRAs Do not differentiate latent from active TB HIV co-infection complicates diagnosis Smear negative PTB is a particular diagnostic challenge

3 Interferon-γ inducible protein-10 (IP-10) Chemokine secreted by monocytes in response to multiple signals, but T lymphocyte derived IFN-γ is the main driver MTB infection elevates IP-10 blood levels Single measurements are higher in active TB than LTBI and other inflammatory conditions, but not by enough to give a usable specificity IP-10 levels are higher than IFN-γ and less influenced by HIV related CD4 T cell depletion IP-10 levels decrease with successful treatment of PTB, although have not been evaluated during the first week of chemotherapy The change in IP-10 with anti-tb therapy is theoretically TB specific

4 Aim Establish the serum IP-10 profile during the early phase of PTB chemotherapy - Smear positive and negative PTB cases - In an highly TB endemic area, with high rates of HIV co-infection Why Identification of an early change in IP-10 may pave the way for investigation of an IP-10 treat then test diagnostic approach for smear negative PTB.

5 Methods Exploratory longitudinal study in Abuja, Nigeria, in May-July 2013 New PTB suspects 18 years old Had sputum smear examination performed New patient intensive phase treatment regime PTB status was established using sputum culture and/or Xpert MTB/RIF Serial monitoring of IP-10 was performed with serum samples taken on treatment days 0, 1, 2, 3, 5, 7, and 14 Serum IP-10 measured in duplicate using a sandwich ELISA

6 Patient characteristics

7 IP-10 concentration (pg/ml) IP-10 profiles of smear-positive patients over 14 days of TB chemotherapy IndividuaI IP-10 profiles Smearpositive geometric mean day 0 day 1 day 2 day 3 day 5 day 7 day 14

8 IP-10 concentration (pg/ml) IP-10 profiles of smear-negative culture/xpert positive patients over the first 14 days of TB chemotherapy Individual IP-10 profiles Smearnegative geometric mean 0 Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

9 IP-10 concentration (pg/ml) Geometric mean IP-10 concentrations for smearpositive and smear-negative culture/xpert-positive patients over 14 days of TB chemotherapy Smearnegative culture/gene Xpert-postive Smearpositive Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

10 IP-10 concentration (pg/ml) IP-10 profile of the smear-negative culture / Xpert-negative patient over the first 14 days of TB chemotherapy Smearnegative culture/gene Xpertnegative day 0 day 1 day 2 day 3 day 5 day 7 day 14

11 IP-10 concentraition (p/ml) IP-10 profiles of patients with rifampicin resistant MTB over the first 14 days of TB chemotherapy Individual IP- 10 profiles Geometric mean for rifampicin resistant patients 0 Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

12 IP-10 concentration (pg/ml) Comparison between IP-10 concentrations in patients with HIV and without HIV over 14 days of TB chemotherapy geometric mean for HIV +VE patients geometric mean for HIV-ve patients 0 day0 day1 day2 day3 day5 day7 day14

13 Conclusions Drug sensitive PTB cases show a significant decrease in IP-10 concentration over the course of early chemotherapy. The IP-10 concentrations in Rifampicin resistant MTB patients increase between day 0 and 14 of chemotherapy. HIV negative patients have lower IP-10 concentrations than HIV positive patients and demonstrate a faster rate of decline over the course of therapy. A larger study to explore a treat-to-test strategy would be feasible.

14 Any Questions?