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Transcript of A pilot study measuring the kinetic profile of IP-10 over ... FIS PDF/Monday... · A pilot study...
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 ?