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

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

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

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.

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

Patient characteristics

IP-10 profiles of smear-positive patients

over 14 days of TB chemotherapy

0

200

400

600

800

1000

1200

1400

1600

1800

day 0 day 1 day 2 day 3 day 5 day 7 day 14

IP-1

0 c

on

ce

ntr

ati

on

(p

g/m

l) IndividuaI

IP-10

profiles

Smear-

positive

geometric

mean

IP-10 profiles of smear-negative culture/Xpert

positive patients over the first 14 days of TB

chemotherapy

0

100

200

300

400

500

600

700

800

900

1000

Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

IP-1

0 c

on

ce

ntr

ati

on

(p

g/m

l) Individual

IP-10

profiles

Smear-

negative

geometric

mean

0

100

200

300

400

500

600

700

800

Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

IP-1

0 c

on

ce

ntr

ati

on

(p

g/m

l)

Smear-

negativeculture/gene

Xpert-postive

Smear-

positive

Geometric mean IP-10 concentrations for smear-

positive and smear-negative culture/Xpert-positive

patients over 14 days of TB chemotherapy

0

100

200

300

400

500

600

700

800

900

1000

day 0 day 1 day 2 day 3 day 5 day 7 day 14

IP-1

0 c

on

ce

ntr

ati

on

(p

g/m

l)

IP-10 profile of the smear-negative culture /

Xpert-negative patient over the first 14 days of

TB chemotherapy

Smear-

negative

culture/gene

Xpert-

negative

IP-10 profiles of patients with rifampicin resistant

MTB over the first 14 days of TB chemotherapy

0

100

200

300

400

500

600

Day 0 Day 1 Day 2 Day 3 Day 5 Day 7 Day 14

IP-1

0 c

on

ce

ntr

ait

ion

(p

/ml)

Individual IP-

10 profiles

Geometric

mean for rifampicin resistant

patients

Comparison between IP-10 concentrations in

patients with HIV and without HIV over 14 days of

TB chemotherapy

0

100

200

300

400

500

600

day0 day1 day2 day3 day5 day7 day14

IP-1

0 c

on

ce

ntr

ati

on

(p

g/m

l) geometric

mean forHIV +VEpatients

geometricmean forHIV-vepatients

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.

Any Questions ?