Kampala, 22 Oct 2012

Ajay Thirumala

MDR TB Diagnostics

Our strategy

1. Accelerate diagnostic innovation along a value chain: ISO 13485 certification for project management and clinical trials. (Focus: TB, Malaria and HAT)

2. Leverage investment against preferential prices for low and middle income countries. (Affordable)

3. Strengthen Local Laboratory facilities to ensure new technologies are Accessible to everyone (Focus: Public Health Facilities).

4. Produce Development Partnership: Build and sustain effective partnerships- currently 200 active partners in 61 countries.

The impact of diagnostics

Reduced disease transmissionEffective disease control, including DRTBDecreased morbidity/mortalityCredible health system

Tuberculosis

The slow path to diagnosis for patients with cough:

Grzybowski, et al. Bull Int Un Tuberc 1975;50:90

More and more slow path: Drug resistant TB detection and treatment

TB

Malaria

HAT / OND

Liquid culture;

rapid speciation

Line probe assay

LED-based fluorescence microscopy

Automated NAAT (Xpert MTB/RIF)

RDT product testing Blood transfer device

mAECT production in DRC

Rapid screening test prototype developed

Implementation of WHO endorsed tests and capacity building

Round 1Round 2

Round 3

Key advancements in the diagnostics - FIND’s role

Implementation support (training, job-aids, SMS reporting)

LED-based fluorescence microscopy

Pipeline for New Diagnostics for TB and MDR-TB, July 2012

Drug resistant TB• Multidrug resistance- MDR TB

– Isoniazid and Rifampicin

• Extensively drug-resistance- XDR– MDR + fluoroquinolones and at least one of injectables: amikacin,

capreomycin or kanamycin

MDR-TB*: Uganda

Expandx TB Project • Overall grant (GLI, GDF, FIND): 90.5 Mio (incl. 2 Mio for Xp)• Funding for FIND: 21.2 Mio (including 1.5 Mio OGAC)• Duration: Dec 2008 - Dec 2013• Project goal: Expand access to MDR-TB dx in 27 countries• Key deliverables: Identify 129,000 MDR cases; Impact market

dynamics (price, # suppliers)• Progress:

– MOUs with 22/27 countries

– Initial assessments for 24/27 countries

– >10,000 MDR-TB patients diagnosed by end 2011

Expandx TB Uganda

• 2010- July: MOU with Min. of Health, Uganda• 2010- July: 1st Lab Assessment – GLI-FIND combined• 2010- Sep/Oct: Civil work initiated at Mulago Referral Hospital for

point-of-care MDR-TB lab• 2011- May: New diagnostic equipment installation at the Lab• 2011 July-Sep- Standardization of technology, trainings and

orientations to staff• 2011 Nov- Lab started testing for patients; and is provided 5 start

SLAMTA accreditation as part of NTRL

Civil works - Ward 5&6-Mulago Hospital, NTRL, Kampala, UGANDA

Main entrance

Ramp

Equipment installation

The Republic of Uganda

MINISTRY OF HEALTH

Lab showing air-extraction ducts

The Republic of Uganda

MINISTRY OF HEALTH

Tuberculosis Rapid Diagnostics Lab at Mulago

Entry door for containment roomAnteroom entry to containment room

View of containment room from anteroom

Containment room

The Republic of Uganda

MINISTRY OF HEALTH

Heating block for DNA extraction

Pre-amp room view

Microfuge-DNA extraction

Hands on trainings for LPA

Algorithm for MDR-TB diagnosis

MDR-TB suspect

Smear microscopy

Positive

LPA (rapid)

MDR (confirm on LJ)

Mono-Rif (confirm on LJ)

Non-MDR

Negative

Culture

Positive

LPA (rapid)

Negative

XpertMTB/Rif

Line Probe Assay (LPA) for detection of MDR-TB NTRL, Uganda (15th Mar 2010-18th Oct 2012)

 Year MDR* All Susceptible Total**2010 37 228 3122011 49 489 6552012 83 360 551Total 169 1077 1518

*- MDR- Patients showing resistance to both Isoniazid and Rifampicin**- Includes other than MDR drug resistant patients

GeneXpert (Xpert MTB/RIF) for Diagnosis of TB and rifampicin resistant TB

- Two hours cartridge based test. - Automated- Possible at district level.- Peripheral Lab and clinical staff can run it- Can detect Smear negative TB- problem of HIV patients

- Challenge in POC facilities-Electricity?

Details of Mfg:

Solar Panels: Dulas Solar (http://www.dulas.org.uk/index.cfm)

Solar Charge Controller: Tarom, Steca GmbH (http://www.stecasolar.com/index.php?Steca_Tarom_en)

Inverter: Local Kampala market- Chinese make

Solar batteries: Local Kampala market- Luminous India make

Technician: Local Kampala school pass-out

Capacity:

3 Gx-4 runs/ day

Expected sun-hours:

1800-2000/year

Started in:

April 2011

Approx Cost:

3600 USD

Capacity:

3 Gx-4 runs/ day

Expected sun-hours:

1800-2000/year

Started in:

April 2011

Approx Cost:

3600 USD

Local innovations: GeneXpert works with Solar power- Luwero HC IV

Early Evidence for scale up

Grant: Dutch Government

FIND March-2011

Early scale-up of Xpert for TB in HIV positive patients at six sites under NTLP

Grant: TB reach Wv2, STOP TB Partnership (0.6 million USD)

Results of Xpert roll-out in Uganda (Nov 2011 -June 2012)

Xpert siteTB

Negative

MTB positive very Low

MTB positive Low

MTB positive Medium

MTB positive High TOTAL

TASO, Entebbe 527 42 24 14 4 631

Fort Portal RRH 585 56 46 24 7 770

Jinja RRH 339 19 14 13 2 421

Lira RRH 547 62 42 27 3 738

Masaka RRH 392 34 27 16 3 539

Soroti RRH 509 60 27 23 7 703

TOTAL 2899 273 180 117 26 3802

*3 rifampicin resistance cases out 596 TB cases: two confirmed at NTRL, and one died

Thank You

23

National TB & Leprosy Program

MOH, Uganda

Two different approaches to Diagnosis of Smear Negative PTB, at a HIV-care setting in Uganda

(for Clients of Lake Victoria Islands)

HIV Positive female (36 years) patient on ARVs (CD4-115

cells/uL)

Lymphadenitis (TB)??? Advised FNA of lymph node but had no access - Smear negative PTB???

PTB, Xpert Positive. Placed on treatment same day

2 yrs& 2 months

6 months

Cured, Xpert- negative after 7 months

of Rx

HIV Positive female (26 years) patient on Septrin-CTX prophylaxis- (CD4-423 cells/uL)

PMTCT-AZT Prophylaxis

Cough-productive for 2 months

PTB, SSN-Xray suggestive-Rx same day

CD 4: 264 cells/uL; -> placed on ARVs

Defaulted for TB drugs (‘REACH” issues)

1 year

6 months

3 months

1 and half month Lack of trust in system

Delays in TB-

Dx

Transmitted TB to 3 ½ year HIV +ve Child

Lab got a Gx at this stage

Bunyaazi IslandAround 30 nautical miles south of Entebbe

Bunyaazi IslandAround 30 nautical miles south of Entebbe

Entebbe

Bunyaazi

Lake Victoria

Client visit : beneficiary of FIND-TBR Wv 2 project –Xpert MTB/RIF test

Visit 20-June-2012

(FIND, NTRL (MoH), TASO)

UGANDA