World TB Day 24th March 2015
Institute of Child Health, London
New TB diagnostics
and rollout
Ruth McNerney
TB Alert
Conflict of interest statement
I have no financial interest in the sale of any
diagnostic test.
Mention of specific companies or products does not
imply endorsement or recommendation.
Views expressed are my own and do not represent
TB ALERT or any other organisation.
TB diagnosis
diagnosis is a is
complicated
journey
TB
a long journey
Poverty
Lack of
awareness
Lack of
trained staff
Lost results
Social
exclusion
Cost
Lack of
access
Stigma
Delayed
Dx
Lack of
reagents/kits
Inadequate
specimen
Lack of
robustness
Poor sensitivity/
Inconvenience Confounding
specificity
conditions
TB pathogenesis is not straight forward
Infection
Controlled
or latent
infection
Infection
Primary
disease
Post-primary
disease
(reactivation)
Infection
Disease
Quiescence
or cure
Host response and symptoms vary by stage of
disease, site of disease, bacterial lineage, preexposure and confounding conditions . . .
Diagnostics Product Development Pathway
Clinical performance:
sensitivity/specificity
Clinical trials: impact,
cost effectiveness
Diagnostics Product Development Pathway
Clinical performance:
sensitivity/specificity
Clinical trials: impact,
cost effectiveness
GeneXpert rollout
GeneXpert Rollout
www.who.int/tb/laboratory/mtbrifrollout/en/
Robustness?
HEAT DUST POWER
GeneXpert instrument failure rates:
India 18 sites: 32% of modules replaced within 10 months
Nine country study: more than half of modules failed within 3 months
Feasibility of decentralised deployment of Xpert MTB/RIF test at lower level of health system in India.
Raizada et al PLoS One 2014; 9(2): e89301.
Results from early programmatic implementation of Xpert MTB/RIF testing in 9 countries. Creswell et al. BMC
Infect Dis 2014; 14: 2.
Costs of installation?
Nigeria: infrastructure improvements of between
USD 2,622 and USD 9,716 per lab
Abdurrahman et al The hidden costs of installing Xpert machines in a
tuberculosis high-burden country: Experiences from Nigeria. The Pan African
Medical Journal 2014, 18, 277
Published clinical trials to determine impact
Sample Outcome
size
Indicator
Study
Design
Setting
Theron
et al
2014
Randomized,
parallel-group,
multicentre
South Africa,
Tanzania, Zambia,
Zimbabwe
1,502
Time to treatment
Morbidity at 2 & 6m
Cox et al
2014
Pragmatic
prospective
clusterrandomized
South Africa
1,945
Confirmed cases
Treatment at 3m
Mortality at 6m
Durovni
et al
2014
Stepped-wedge
Brazil
cluster randomized
trial 14 sites
24,227
Time to treatment
TB notification rates
424
Time to treatment
Mortality at 3m
Mupfumi Single-centre
et al
pragmatic
2014
randomized
controlled
ART-associated TB
Zimbabwe
N.B Clinical trials to investigate impact on patients with drug resistant disease not available
Key points
• Xpert MTB/RIF detected more cases of pulmonary
tuberculosis than smear microscopy
• Faster access to treatment was achieved with
Xpert MTB/RIF than with smear microscopy
• Case notification rates were not increased by
implementation of Xpert MTB/RIF when used at the
point of care in health clinics.
• Implementation of XpertMTB/RIF for diagnosis had
no impact on patient morbidity or mortality
• Further inventions are needed to control TB
e.g. Community based initiatives
NB Clinical trials to investigate impact on patients with drug resistant disease not available
Time from sample collection to treatment initiation
Study
Xpert
test site
Theron
Days to treatment (range)
Xpert
No Xpert
Clinic
0 (0-5)
1 (0-6)
Cox
Clinic
4 (2-8)
8 (2-27)
Durovni
Clinic
8 (5-9)
11 (8-14)
Mupfumi
Referral lab
5 (3-13)
8 (3-23)
Do high rates of empirical treatment undermine the potential effect of new
diagnostic tests for tuberculosis in high burden settings? Theron et al 2014
Lancet Infect Dis 2014; 14:527–532.
Suboptimal specificity of Xpert MTB/RIF among treatment-experienced
patients. Metcalfe et al 2015 Eur Respir J.
What next for
TB diagnostics?
We urgently need
affordable rapid tests
that can be used to
screen for active TB and
differentiate from latent
infection.
http://www.wethewomen.org
We need better tests for
children and nonpulmonary forms of TB.
These tests do not exist
for TB (yet).
http://www.soulwinning.info/hm/starting.htm
Novel technologies in development
Several projects utilising nanotechnology
POC NAAT
African pouch rats
Raman spectroscopy
Breath analysis
www.smithsdetection.com
Coming soon . . .
NAAT (nucleic acid amplification tests)
Test
XpertTB/RIF*
Cepheid Inc, USA
Amplification
reaction
Polymerase Chain
Reaction
Operational features




EasyNAT
Ustar Biotechnologies
Ltd, China
Cross Priming
Amplification
TrueNat
Molbio Diagnostics
Pvt. Ltd, India
Polymerase Chain
Reaction

VerePLEX Lab-On-Chip Polymerase Chain
Veredus Laboratories, Reaction
Singapore

Genedrive
Epistem Ltd, UK


Polymerase Chain
Reaction
* New versions in development



Automated sample
extraction
RMP resistance
Isothermal 65°C
Instrument free visual
output
Instrument free DNA
extraction
Miniaturised chipbased
Semi-automated DNA
extraction
Microarray
technology
RMP & INH resistance
plus 9 NTMs.
Paper based DNA
extraction technology
RMP resistance
Time
(min)
<90
Stage of
development
Released to
market
<90
Released to
market
<60
Released to
market
<180
Released for
research use
60
Field trials
TB diagnosis isis
a complicated
journey
Diagnosis
a long journey
Poverty
Lack of
awareness
Lack of
trained staff
Lost results
Social
exclusion
Cost
Lack of
access
Stigma
Delayed
Dx
Lack of
reagents/kits
Inadequate
specimen
Lack of
robustness
Poor sensitivity/
Inconvenience Confounding
specificity
conditions
Thank you for your attention
www.tbalert.org