Roll out plan of the Xpert MTB/RIF system

and its impact in the Rwanda TB Program

Dr UMUBYEYI NYARUHIRIRA Alaine, MPH, PhD

Senior Lecturer - NUR

Senior Lecturer - NUR

Lab technical Advisor, ICAP – Columbia University

Workshop on the implementation and roll out of Xpert

MTB/RIF system For rapid diagnosis of TB and MDRTB

Geneva, 7-8 April, 2011

DIAGNOSIS OF PULMONARY TB

COUGH fever, night sweats , weight loss

Sputum smear microscopy HIV Test

Smear-positive (at least 1 smear)

Smear-negative

and HIV+

Smear-negative

and HIV- /not done

Amoxicillin for 7 days

Request as quick as possible: • 2d sputum smear microscopy

(rapid culture if available) • Chest X-ray • Clinical evaluation • HIV evaluation (CD4, stage) • Amoxicillin for 7 days

> 2 weeks

If danger signs (respiratory frequency >30 per minute, pulse >120/min, fever >39°C, unable to walk, confusion), give injectable ampicillin and refer to the hospital *

No improvement: 2d sputum smear

microscopy

Improvement: IEC: consult if cough resume

Smear positive

• Smear negative

• CXR and clinic suggestive of

TB • Medical

decision

• Smear negative

• CXR not suggestive of TB

• No improvement

TB treatment • Culture and DST if retreatment

If HIV+ • Enrol at HIV clinic • Cotrimoxazole and Pyridoxin

• Clinical evaluation • HIV evaluation (CD4, stage)

• Investigate other diseases

• Re-evaluate for TB

Smear positive

Smear negative

• CXR and clinic suggestive of TB

• Medical decision

Chest X-Ray

CXR not suggestive

of TB

Investigate

other diseases

*At hospital arrival: do sputum examination, CXR, HIV test, clinical evaluation and continue antibiotics. If HIV+, smear negative, CXR suggestive of TB and no improvement after 3-5 days, start TB treatment

et pas d’amélioration après 3-5 jours, traiter pour TB. Do not give Fluoroquinolones (Ciprofloxacin) in case of TB suspicion

Current laboratory algorithm for TB Lab diagnosis in Rwanda as from October 2010

Impact of using HAIN test in reducing the TAT [for TB pulmonary cases] to

obtain DST 1st line results at NRL (Kigali) – Study period (From October 2009

to December 2010)

TAT of results

according to

method (days)

DST Methods

120

140

160

# o

f te

sts

perf

orm

ed

DST 1st line TAT comparison by method :

Classical (LJ solid culture) vsMolecular (HAIN PCR test)

method (days)

Solid

culture

LJ

HAIN

from

Culture

HAIN

from

sputum

Median 79 49 3

Max 151 103 9

Min 47 20 1

0

20

40

60

80

100

120

DST/LJ Hain from Culture Hain from sputum

# o

f te

sts

perf

orm

ed

DST method

Mediane

max

min

Median time between DST 1st line results and start up

of treatment for TB pulmonary cases

- Empiric treatment are not considered here - In 2005 until mid 2006, DST result date was not reported

86 days

56 days56 days

29 days

13,5 days11 days

2006 (n=22) 2007 (n=76) 2008 (n=61) 2009 (n=62) 2010 (n=89)

Patients recruitment for GeneXpert validation

1. TB suspected cases

• Any HIV+ TB suspect

• Any symptomatic household contact of a MDR-TB patient

• HIV neg with smear-negative and TB suspected cases who were

investigated according to the TB algorithm (CXR, antibiotics,

clinical evaluation) and still remain TB suspect. clinical evaluation) and still remain TB suspect.

• TB suspects among prisoners

• TB suspects among health care workers.

2. Smear-positive TB cases at higher risk for drug resistance:

• Patients previously treated: relapse, after default, after failure

• Any patient who has a smear-positive control during treatment

(C2, C3, etc)

DIAGNOSIS OF PULMONARY TB FOR GENEXPERT SITES COUGH > 2 weeks

HIV+: Fever or night sweats > 3wks, weight loss > 3kg within the last 4 wks

HIV + HIV- severely ill patients

Mtb+/R+ Mtb+/R- Sm-

If danger signs (respiratory frequency >30 per minute, pulse >120/min, fever >39°C, unable to walk, confusion), give injectable ampicillin and refer to the hospital *

HIV – with low risk or DR TB

GENEXPERT/MICROSCOPY/CULTURE MICROSCOPY

Mtb-/R-

HIV test

Mtb+/R+

Mtb+/R-

Sm-

Amoxicillin

for 7 days

Request as quick as possible: • Chest X-ray • Clinical evaluation and available

investigations (FNA, Abdo UV, lab) • HIV evaluation (CD4, stage) • Amoxicillin for 7 days or continue

injectable (severely ill patients)

No improvement: 2d sputum smear

microscopy

Improvement:

IEC

2d line TB Rx

•TB unlikely:

investigate other diseases Re-evaluate for TB

Sm+

Sm- • CXR and clinic suggestive of TB

• Medical decision to treat for TB

Sm+

CXR

1st line TB Rx

Mtb-/R-

1st line TB Rx

•Severely ill, no

improved after 3 days: treat for TB

Low MDR

risk

High MDR

risk

Any

positive

control

Still TB suspect: GENEXPERT/MICROSCOPY/CULTURE

MDR risk

assessment

2 Sputum collection > 1.5 ml

On site: Sputum 1 At NRL / CHUK:

-Aliquot Sputum 1

- Sputum 2

Smear ZN / LED

Gene Xpert MTB /

RIF

NACL-NaOH

Smear / Auramine

Summary of the sample processing steps

Culture – LJ (Gold Standard)

Liquid culture - MGIT

GeneXpert MTB / RIF

All positive cultures

- MPT64 (Capilia TB)

-MGIT – SIRE

-DST - LJ proportion method (Gold Standard)

-Genotype MTBDR Plus assay (HAIN)

SITE SELECTION CRITERIA FOR

GENEXPERT

• Workload (6 sites have been selected)

• TB detection and Positivity rate (> 5%)

• TB-HIV and MDR-TB burden (>10%)

• Accessibility (transportation system network operational)

Data from 2010Data from 2010 CHUK MUHIMA KABGAYI RWINKW. KICUKIRO BIRYOGO

# TB suspects 983 806 1235 710 648 431

# positive TB suspects 128 91 76 44 95 80

% Positivity rate 13% 11% 6% 6% 15% 19%

# HIV+ TB suspects 96 352 190 161 65 72

% HIV+ TB suspects 10% 44% 15% 23% 10% 17%

MDR-TB patients confirmed 4 6 3 1 2 3

SELECTED SITES FOR GENEXPERT

10

Specimen Transportation in the Lab Network

NRL , CHUK, (CHUB in near future)

Feedback

Tests performed and feedback sent

twice per week to different levels by

TRAC NET, phone call and courier

11

DH Laboratories

HC Laboratories

Samples sent for CD4 count,

Hematology, clinical chemistry

and QC

Daily basis with motorbike

Feedback

Samples sent for specialized

analysis ( DBS, VL Tb culture, DST

and epidemic disease)

Samples sent for specialized

analysis ( DBS, VL Tb culture, DST

and epidemics diseases)

TRAC NET, phone call and courier

Next steps / challenges

• Support NRL in collaboration with FIND to clarify

procurement mechanisms (6 machines, kits,

consumables, installation, maintenance, etc…)

• Development of the training tools

• Support NRL to develop a quality control program in

collaboration with FIND/ WHO, GLI etc…

• Ensure running costs and sustainability

Aknowledgment

• TB Unit/TRAC-Plus, NRL

Dr Michel Gasana

Dr Martine Toussaint

Dr Odette Mukabayire

Mr John Gatabazi

TB Lab team at NRL

• CDC

• ICAP/Columbia University

Dr Jessica Justman

Dr Bereket Alemayehu

Dr Stephania Koblavi-Deme

Dr Ruben Sahabo

Dr Greet Vandebriel

Mr Elisaphan Munyaseza• CDC

David Mc Alistair

Dave Lawrence

• GFATM

Dr Daniel Ngamije

• World Bank

Mrs Miriam Schneidman

Supported by PEPFAR