XDR MTBRIF Operational Considerations

8/11/2019 XDR MTBRIF Operational Considerations

1/23

Xper

Operational c

Workshop fo

Hotel Starling,

7 -

Christoph

TB Diagnostics and Laboratory

MTB/RIF

nsiderations

Early Implementers

Geneva, Switzerland

April 2011

r Gilpin PhD MPH

trengthening Unit, Stop TB Department


2/23

WHO policies 20

Year Technolo

Before 2007ZN microsc

Solid cultu

a) early diagnosis & care; b) sme

detection

2007 Liquid cultureRapid speci

2008Line Probe A

(1st line, R

2009LED-based

Conditional

2009

In-house D(MODS, CRI,

Endorsed

2010

Automated N

(TB, R)

7-2011

y Turnaround time Sensitivitygain

py

re

2-3 days

30-60 daysBaseline

r-negative TB; c) rapid MDR/XDR

DSTtion

15-30 days +10% comparedto LJ

ssay

H)2-4 days

At this time forS+ only

FM 1-2 days +10% comparedto ZN

TNRA)

15-30 days 1st line only

AAT90 minutes

+40% comparedto ZN


3/23

Characteristics and labWHO-approved technol

Diagnostic toolor method Laboratoryservice

level

Time to detection of MDR

Direct Indirect

Microscopy Peripheral

Intermediate

Central

n/a n/a

Solid culture &

DST

Central

Intermediate

n/a 9 - 12 weeks

Commercial Central n/a 3 - 5 weeks

liquid culture &

DST

Intermediate

Non-commercial

culture & DST

MODS

NRA

CLI

Central

Intermediate

2 21 days

6 9 days

n/a

3 4 weeks

7 11 weeks

3 5 weeks

(liquid culture)

7 10 weeks

(solid culture)

Line probe

assay

SM posSM neg

Central

Intermediate

24-48hrsn/a 3 5 weeks

Adapted from: World Health Organization, Stop TB PartnershipWorking Group. New Laboratory Diagnostic Tools for TuberculosAdapted from: World Health Organization, Stop TB PartnershipWorking Group. New Laboratory Diagnostic Tools for Tuberculos

ratory requirements ofgies

Equipment Consumables Trainingneeds Infrastructure(Risk category)

+ + Minimal +

+ ++ Moderate ++

+++ +++ Extensive +++

++

+

+

++

++

++

Extensive

Moderate

Extensive

++

++

+++

+++ ++ Moderate

+++++

etooling Task Force, Stop TB Partnership New Diagnosticss Control. 2009. Available at: http://www.stoptb.org/retooling.

etooling Task Force, Stop TB Partnership New Diagnosticss Control. 2009. Available at: htt

p://www.stoptb.org/retooling.


4/23

Positioning in tiered health sy

(

)

D

C

tem

C / D

15/ 30

A / 2C / D

30 / 60

C / D

15 / 30

D

(D, A, C)

AA +40% /2

ED +10%

23


5/23

Xpert MTB/RIF does not replconventional smear, culture

Conventional smear, culture, DST

Required to perform culture and DSTrifampicin

MTB/RIF and who have rifampicin sushould be monitored during treatmenmicroscopy

Patients with TB and rifampicin resist

MTB/RIF and placed on MDR-TB tremonitored by sputum smear and cultguidelines

Molecular tests, including Xpert MTB

patient monitoring as these tests alsoviable bacilli.

ace the need forand DST

ill still be required

for drugs other than

sceptible TB diseasewith sputum smear

ance confirmed by Xpert

tment should bere as per current WHO

RIF, are not suitable for

detect DNA from non-

5


6/23

Practical consideration

Storage requirements

Packaging for cartridges is bulky

Requires storage space for cartridgmonths

s: operational

es (at 2-28C), shelf life maximum 18

6


7/23


Sample preparation and testing Testing capacity of 4 module syste

(depending on working hours), each t

.

15

Transfer sample

Once cartridge is ready, test sho

Handling Time

s: operational

per working day is 15-20 tests

est takes approx.2hr

Insert the cartridge andstart the test

7

ld be loaded within 30 minutes.

2 MINUTES


8/23


Stable electricity supply needs to

UPS devices 400V or battery pack

Can be provided by Cepheid fo

Local purchase may be better

rov es on y an n er m so u A power solution is needed whi

completed

Generators may be additionally ne

Fuel as needed

s: operational

e established.

approx. USD 500

n or s or power cu s ch ensures the tests run until

ded

8


9/23


Infrastructure requirements

Xpert MTB/RIF testing require bio-saf

conditions similar to the conventionalsmear microscopy sample processin

testing

max. 30C

Consistent with other laboratory ecomputers etc.

Need a secure environment to guardtheft

s: operational

ety

sputumor

quipment,

against

9


10/23


Quality control measures (internal)

The sample processing control (SPC) con

a dry spore cake that is included in each carMTB.

Verifies that lysis of MTB has occurr

Detects specimen associated inhibiti SPC should be positive in a negativ SPC can be negative or positive in SPC passes if it meets assigned ac

The Probe Check Control is a check underThe system measures the fluorescence signrehydration, reaction-tube filling, probe integPCC passes if it meets assigned acceptanc

s: operational

tains non-infectious spores in the form of

ridge to verify adequate processing of

d if the organisms are present.

on of the real-time PCR assay.sample andpositive sample.eptance criteria.

aken before the start of the PCR reaction.l from the probes to monitor beadity and dye stability.criteria.

10


11/23


What testing capacity is necessary?One 4 module system per working day is

5 20 80 Samples per

s: operational

15-20 tests (depending on working hours)

11

500-1000 shift


12/23

Interpretation:Xpert MTB/RIF - Positive result

12


13/23

Interpretation:Xpert MTB/RIF - Positive result

13


14/23

Interpretation:Xpert MTB/RIF - Nega ive result

14


15/23

Interpretation:Xpert MTB/RIF - Invali result

15


16/23

Interpretation:Xpert MTB/RIF Uninte

INVALID

result indicates that the SPC failed

processed or PCR was inhibited.

ERROR

aborted possibly due to the reactio

probe integrity problem was detect

limits were exceeded or there was

NO RESULT

indicates that insufficient data wer

stopped a test that was in progres

pretable results

. The sample was not properly

16

n tube being filled improperly, a reagent

ed, or because the maximum pressure

a GeneXpert module failure.

collected. For example, the operator

.


17/23

GeneXpert maintenanc

Maintenance at user level:

Cartridge bay disinfection (on

Manual Self-Test: Checks for hnecessary).

Module calibration

Must be performed once a year

Calibration must be performed

Performs a thermal and optical

Why calibration?

Verifies that the system perfor

Ensures reading at correct wav

are sufficient

Avoids costly repairs and wast

requirements

e a month)

rdware failure problems (as

or every 2000 module runs

remotely by manufacturer

calibration of the module

s within a set of specifications.

length and temperature ramping

d cartridges17


18/23

GeneXpert maintenanc

Module calibration req

:

irements

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19/23

Xpert MTB/RIF training

Minimal training is needed

Xpert MTB/RIF is a complex yet us

Computer training support shouldimplementation site

-

implementation sites such as Sout

On-line technical support availablemanufacturer

Video demonstrations

needs

r-friendly technology

be assessed at each

Africa.

through skype with the

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20/23

Xpert MTB/RIF Qualit

What is needed?

A panel of unknown samples to

When should this be done?

At time of installation and follo

ow many samp es

Panels should comprise approsamples spiked with heat killed

Who will manufacture the QA mate

One SRL will be supported to e

stability and suitability for use i

How will users access the QA mat

A panel set could be shipped wfollowing calibration by the ma

Assurance

be tested using the Xpert MTB/RIF

ing module calibration

. 5 unknown artifical sputumorganisms.

ial?

tablish and validated panel

n the GeneXpert

rial?

ith each instrument and or modulesufacturer

20


21/23

Practical considerationand eligible countries*

Afghanistan Chile Ghana Libya P

Albania China Grenada Lithuania P

Algeria Colombia Guatemala Macedonia P

Angola Comoros Guinea Madagascar P

Antigua and

Barbuda

Congo, Democratic

Republic of the Guinea-Bissau Malawi P

ArgentinaCongo, Republic ofthe Guinea, Equatorial Malaysia P

Armenia Costa Rica Haiti Maldives P

Azerbaijan Cote d'Ivoire Honduras Mali R

Bangladesh Croatia India Mauritania R

e arus u a n ones a aur us

Belize Djibouti Iraq Mexico S

Benin Dominica JamaicaMicronesia,Federated States of S

Bolivia Dominican Republic Jordan MoldovaSG

Bosnia andHerzegovina Ecuador Kazakhstan Mongolia S

Botswana Egypt Kenya Montenegro S

Brazil El Salvador Kiribati Morocco S

Bulgaria Eritrea Korea, North Mozambique S

Burkina Faso Estonia Kosovo Myanmar (Burma) S

Burundi Ethiopia Kyrgyzstan Namibia Si

Cambodia Fiji Laos Nauru S

Cameroon Gabon Latvia Nepal S

Cabo Verde Gambia, The Lebanon Nicaragua SCentral AfricanRepublic Gaza and West Bank Lesotho Niger S

Chad Georgia Liberia Nigeria S

: preferential pricing

akistan Sudan, South

alau Suriname

anama Swaziland

apua New Guinea Syria

araguay Tajikistan

eru Tanzania

hilippines Thailand

omania Timor-Leste

ussia Togo

an a onga

aint Kitts and Nevis Tunisia

aint Lucia Turkmenistan

aint Vincent & therenadines Tuvalu

amoa Uganda

ao Tome and Principe Ukraine

enegal Uruguay

erbia Uzbekistan

eychelles Vanuatu

ierra Leone Venezuela

olomon Islands Vietnam

omalia Western Sahara

outh Africa Yemen

ri Lanka Zambia

udan Zimbabwe

GeneXpert System4 module

with desktop 17000 $

with laptop 17500 $

Cartridge 16.86 $

21

*as of 19.02.2011


22/23

Practical considerationrunning costs

A

4 (E

)

B

C

D

E A

C

A

/

/1 / 1

/

( 10%)

A

(,

)

: installation and

$17,500.00 >60% E/

$1,000.00 D

$500.00 ,

$200.00 ,

$1,800.00 C

$16.86 75% E

250

15

3750 *

375 10%

$5,000.00 C

$5,000.00 D

$19,200.00 A+B+C+D

$71,347.50 E+*(+)

$,. +++22


23/23


Summary

Doesnt eliminate need for conventi

Requires stable electricity supply

Has range of ambient operating tem

Testing capacity of 4 module syste

(depending on working hours, each t

Requires annual calibration

Xpert MTB/RIF testing require bio-safconventional sputum smear microsco

: operational

nal smear, culture, DST

eratures max. 30C(under revision)

- ,

per working day is 15-20 tests

st 100 min.)

ety conditions similar to thepy sample processing or testing

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XDR MTBRIF Operational Considerations

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