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TB Diagnostics*

Vinand M Nantulya

*Presentation at TAC/TAG First Africa Region TB/HIV Advocacy, 19-21 June 2006, Cape Town, South Africa

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Fundamental diagnostic: 1882

Fundamental diagnostic: 2006

Market uptake

Lack of progress in TB diagnostics

Discovery Science

Product Development

Targets & Reagents

Companies & Platforms

Performance testing

Evaluation & Approval

Need & Access

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Annual Cost of TB Diagnostic Testing

> 1.2 billion Total :

$35,119,542* NAAT

$580,955.889Mantoux

$509,406,090Xray

$376,258,898*Culture

$324,906,257Microscopy

*Manufacturers cost applied. Reimbursement cost may be higher.

Current global direct expenditures on TB diagnostic tests

The diagnostic yield of this expenditure is limited, with only 19% of all TB cases detected and reported as smear-positive.*

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Availability of diagnostic servicesAvailability of diagnostic services

Pop

ulat

ion

(mill

ions

)

Gro

ss N

atio

nal I

ndex

DS

T la

bs/1

00k

popu

latio

n

DS

T la

bs/1

00k

TB

su

spec

ts

Cu

ltu

re la

bs/1

00k

popu

latio

n

Cu

ltu

re la

bs/1

00k

TB

su

spec

ts

Mic

rosc

op

y la

bs/1

00k

popu

latio

n

Mic

rosc

op

y la

bs/1

00k

TB

sus

pect

s

Hea

lth

po

sts

/100

k po

pula

tion

Hea

lth

po

sts

/100

k T

B

susp

ects

North America 328 37,610 0.10 64.2 0.35 226.4 0.88 570 1.46 951Europe 459 22,850 0.16 34.0 0.44 95.3 0.49 106 3.89 851Japan 127 34,510Other High Income 30 18,000 0.11 15.7 0.35 49.4 0.96 135 4.33 608Total from 22 HBC 3,892 869 0.02 1.0 0.06 3.6 1.16 67 8.06 466Rest of World 1,383 0.06 1.8 0.08 2.5 1.37 41 8.87 263Total 6,219 5,500 0.04 2.2 0.11 5.8 1.12 59 7.40 388

Among 22 high burden countries there is an average of 1.12 microscopy centers per 100,000 population BUT 50% do not work due to logistical problems (missing or broken materials, strikes, lack of trained personnel) making access to microscopy difficult

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• In Lima, 22% of 259 TB patients first sought health care from pharmacists. But only 56% of TB patients were requested to submit sputum specimens and did so.

• In Chennai, 13% of 1000 patients being evaluated for symptomatic respiratory disease did not complete the diagnostic process, and 11% of patients in whom TB was detected were not notified of the diagnosis.

• In Lusaka, on the other hand, due primarily to the necessity for patients to purchase the sputum collection container, only 0.5% of patients completed the diagnostic process and only 6 of 600 patients even submitted a single sample.

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Private health expenditure in countries with high TB burdens

0

20

40

60

80

100

pri

vate

as

% o

f to

tal

exp

end

iture

Uplekar 2001

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• Although DOTS provides free diagnosis and treatment, repeated visits to health facilities are required. The cost of transportation and food, coupled with low income because of time away from work, may be more than poor TB patients or families can afford.

• A study from Malawi estimated that on average, TB patients spent US$ 13 and lost 22 days from work at the diagnosis stage alone.

• Patients presenting for diagnosis in a study in Ho Chi Minh City contacted 1.3 different health providers with an average of 2.5 visits per health care provider. Moving from one provider to the next delays treatment and involves considerable cost to the patient.

Economic barriers

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Delays to diagnosis within the health

system varied widely, but were in many

cases substantial, and could be limited by

introducing technologies that could be

used more peripherally, where patients first

seek care.

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• FIND was established in 2003 by World Health Assembly resolution

• A public / private partnership • Based in Geneva as a Swiss tax-exempt

foundation• Current portfolio includes TB, Malaria and sleeping

sickness, each run as an independent business unit

• Currently funded by Bill and Melinda Gates Foundation, but there is need for funds from public sector donors

A brief background about FIND

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FIND is pursuing a two-pronged strategy

• Develop and evaluate better diagnostic tools• Explore creative, sustainable ways to

strengthen overall quality of diagnostic services in both public and private health sector, using new tools as catalyst

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Purpose

Case Detection

Drug susceptibility testing

Latent TB Infection

Test Indications

• Detect pulmonary TB with high bacterial load (SS+)

• Detect pulmonary TB with low bacterial load (SS -, Cx +)

• Detect extra-pulmonary and pediatric TB

• Detect MDR-TB for treatment

• Detect LTBI for treatment

Priority

# 1

# 2

# 3

# 4

# 5

Priority setting

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Levels of health system

FIND’s strategy is driven by customer requirements and the different levels of health system

Few hours

Less than 1 hour

NAAT

Cultures

MicroscopyOnly 19 % (1.7 million) of new cases detected by microscopy (smear +)

5 days

15 days

1 day

2 M undetected unreported

smear + patients

45 days

5 days

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FeasibilityContract

phase Development

phaseEvaluation

phaseDemonstration

phaseGlobal Policy

2 3 654 71

Cu

stom

er R

equ

iremen

ts

Sp

ecification

s

Tactic: Milestones for Process and Outputs

PHASES

Milestones 8

National Practice

Impact

Cu

stom

er sup

po

rt d

ocu

men

t

WH

O g

uid

elines

Effectiven

ess

Efficacy

Pro

du

ct in b

ox

Effe

ctivene

ss &

Access

Registration

FINDPARTNER

Output

Access

Customer support document

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Development EvaluationFeasibility

DistrictDistrictLabLab

PeripheralPeripheralLabLab

TB Product pipeline – Status 2006

ClinicClinicHealth postHealth post

Demonstration

MGIT- MTB

SPECIATIONMGIT-DST

PHAGE RIF RESIST

REAL TIME PCRTK-MEDIA

E-NOSEFLUOR MICROSCOPEURINE LAM ELISALAMP ISOTHERMAL NATURINARY DNA DETECTION

AG DISCOVERY PROJECTS

RAPID ANTIBODY TESTFLURESCENCE STRIP METER FOR AB DETECTION

ANTIGEN LAT FLOWURINE LAM LAT FLOW

AccessAccess

FEASIBILITY DEVELOPMENT EVALUATION DEMONSTRATION POLICY

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FEASIBILITY

Bottlenecks to success

Bottleneck

Inadequate proven principles

Action

More investments in product driven discovery research

Civil society

DEVELOPMENT EVALUATION DEMONSTRATION POLICY NATIONAL PRACTICE

Bottleneck?

Reluctance or slow process

Action Strategic communication& finance activities & civil society

Bottleneck:

• Training

• Maintenance

• Trouble shooting, QC/QA

• Access for underprivileged

Action

• Involve industry, partners & civil society

• Creative solutions

Bottleneck?

Clinical, management & infrastructure capacity

Action

Continuous partner involvement including civil society

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Project sites and demonstration goals

Study sites MGIT in established

labMGIT in new lab (district level)

Impact on clinical outcome

Cost-effectiveness

ZAMSTAR: Lusaka, Cape Town

NRL in Lusaka, TB lab at Stellenbosch

Impact of MGIT for AFB- TB on care

Overall cost of MGIT for AFB- TB cases

THIBELO: gold mines in 3 regions in South Africa

NHLS laboratory in Johannesburg

Relative diagnostic yield in AFB- TB cases

Expected value of clinical information

THRio: HIV care clinics in Rio de Janeiro

TB lab in national research center

Relative diagnostic yield in AFB- TB cases

QUALYs gained by MGIT vs no culture

Tanzania: Dar es Salaam and Iringa Region

National TB Reference lab in Dar

New TB lab in Iringa TBD TBD

Eldoret: HIV care program

New TB lab in AMPATH program

TBD TBD

Cambodia: two to four provinces with TB/HIV activities

New TB labs TBD TBD

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Mbeya Medical Research Programme, TanzaniaMbeya Medical Research Programme, Tanzania