J. Lucian (Luke) Davis, MD, MAS Division of Pulmonary & Critical Care Medicine

San Francisco General Hospital July 10, 2013

Maximizing the impact of smear microscopy

McGill Advanced TB Diagnostic Research Course

Roadmap

Estimated vs. Notified Cases

Case Detection Rate (%) 1995-2010

MDG target

0

20

40

60

80

100

1995 2000 2005 2010Global Africa

• TB patients are diagnosed but not reported

• TB patients do not seek care

• TB patients seek care but are not diagnosed

– Diagnostics have low sensitivity or long turn-around time – Poor TB evaluation practices

Three reasons for low case detection rates

WHO Global TB Report 2010

The TB diagnostic funnel

Seek care for symptoms of TB

Seek care at a microscopy center

Get referred for smear examination

Test smear-positive

Start treatment

All with unexplained cough

Diagnosed & treated TB patients

TB evaluation guidelines

Standard 1. All persons with otherwise unexplained productive cough lasting 2-3 weeks or more should be evaluated for tuberculosis.

Standard 2. All patients who are capable of producing sputum and suspected of having pulmonary tuberculosis should have at least two sputum specimens submitted for microscopic examination in a quality-assured laboratory.

Standard 8. All patients diagnosed with TB should receive an internationally accepted first-line treatment regimen.

Hopewell P. Lancet. 2006

International Standards for Tuberculosis Care (ISTC)

Uganda TB Surveillance Project

• Network of 6 government health centers

• Partners – Uganda Ministry of Health – Makerere University

• Electronic data collection (>100,000 visits/year)

• Web-interface to monitor indicators tied to ISTC

Patient demographics

Cough history

TB exams

TB diagnoses

TB medications

ISTC Quality Indicators

Cough >/= 2 weeks

Sputum AFB Ordered

Sputum AFB Completed

AFB Smear-Positive

TB Treatment

>/= 2 Negatives >/= 1 Positive

TB Evaluation Algorithm

Total episodes of care

Proportion Receiving ISTC-adherent Care

Indicator

1

2

3

Objective 1: “Define quality gap”

Q1 2009 (14,852 patients 365 TB suspects) Standard 1: Referred for TB testing 21% Standard 2: Completed TB testing (if referred) 71% Standard 3: Treated for TB (if smear-positive) 73% ISTC-adherent care 11%

Davis et al. AJRCCM 2011

ISTC, International Standards for TB Care

WHO smear microscopy policy, 2008

• Eliminating 3rd smear – ~33% decrease in technician time and in supply costs – ~70% increase in case detection from better microscopy

• Does not address high costs to patients Katamba A et al Int J Tuberc Lung Dis 2007 Cambanis A et al Int J Tuberc Lung Dis 2007

500 patients with possible TB 100 with AFB+ TB

1st Sputum

2nd Sputum

3rd Sputum

Number of slides examined 500 413 402

Incremental cases per slide examined 87 11 2

Number needed to diagnose AFB+ 6 38 201

Objective 2: “Understand quality gap” • Conceptual Model: Theory of Planned Behavior

• Data collection – Key informant interviews (26 interviews completed) – Field Observation

• Analysis – Transcribe interviews and field notes – Apply standard coding scheme to identify recurring themes

ISTC, International Standards for TB Care

PRECEDE framework Recurring themes

Predisposing factors (Knowledge, attitudes, beliefs, intention)

•Low motivation of staff • Inconsistent training of staff

“Some of us are trained, but some new staff are not trained.”

Enabling Factors (Factors that if addressed make it easier to initiate the desired behavior)

•Workload faced by lab staff •Multi-day sputum collection and evaluation

“When they have a cough for more than 2 weeks they are sent to the lab. But the problem is they get the first sample and sometimes, actually most times they don’t bring the second sample.”

Reinforcing Factors (Factors that if addressed make it easier to continue the desired behavior)

•Limited capacity for patient follow-up •Lack of communication and coordination between staff

“…actually at times we have met but we don’t meet [regularly], only when we realize there is a problem that’s when we communicate and say why is this happening, then we try to rectify.”

Barriers to TB evaluation

Objective 3: “Improve quality gap”

ISTC, International Standards for TB Care

p=0.005

ISTC-adherent care: 2009 Q1 – Q4

Davis et al. AJRCCM 2011 ISTC, International Standards for TB Care

ISTC-adherent care: 2009 Q1 – Q4

Q1 Q2 Q3 Q4

% getting ISTC-adherent care 11% 22% 37% 34%

New TB patients on treatment 5 13 23 21

Objective 3: “Improve quality gap”

ISTC, International Standards for TB Care

Sample performance feedback report

Trends, interpretation, goal setting

Intervention evaluation

• Design: Quasi-experimental (interrupted time series) • Sites selected to receive intervention in random order • Analysis: Logistic regression with robust standard errors

• Primary predictor: Intervention period (pre vs. post) • Co-variates: Age, gender, secular trend for time

Site 6

Site 5

Site 4

Site 3

Site 2

Site 1

Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

Post-Intervention Period

CALENDAR TIME

Intervention Control Period

Continuous quality improvement reports

Objective 3: “Improve quality gap”

ISTC, International Standards for TB Care

Same-day TB diagnosis policy

STAG: Logistical & infection control concerns

*STAG:

WHO Strategic

and Technical Advisory

Group

“More programmatic evidence needed…”

Quality impact of optimized smear microscopy

Optimized smear microscopy: Next steps?

Cattamanchi A et al Am J Respir Crit Care Med 2011

Same-day reporting

Davis JL et al. JAIDS 2012

Two WHO policies, two approaches to improving yield

Smear result indicates TB

TB treatment initiated

Smear exam ordered

Inadequate sensitivity

Pre-treatment loss to follow-up

Day 1

Day 1-2

Day 1

Xpert result indicates TB

TB treatment initiated

Xpert done

Inadequate sensitivity

Pre-treatment loss to follow-up

2011: Xpert MTB/RIF

2010: Same-day microscopy

Day 1 Day 2-3

Which has the greatest impact? 1. Same-day diagnosis 2. Regionalized Xpert, or 3. Both?

Compartmental model

Scenarios modeled

* Same-day scaled-up over 2 years to 100% population coverage † Xpert scaled-up over 2 years to 75% population coverage ¶ Xpert over 2 years to 75% coverage, same-day microscopy last 25%

Scenario Sensitivity for AFB- TB

Pre-treatment loss to follow-up

Standard Microscopy 0% 15% Same-day Microscopy* 0% 1.5% Xpert† 72% 15% Same-day Xpert¶ 72% 1.5%

Projected impact on annual TB incidence

Same-day Xpert MTB/RIF

Projected impact on TB mortality

Scenario

Cumulative Mortality # of deaths (millions)

Reduction (%)

Standard Microscopy 4.20 0 Same-day Microscopy 3.70 0.49 (12) Xpert 3.20 1.00 (24) Same-day Xpert 2.81 1.39 (33)

Same-day microscopy provides substantial incremental impact on incidence and mortality (and likely at very low cost)

Smear image

Diagnosis

Community health worker Trained microscopist

Patient District Health Center

Expanding smear access: mobile telemicroscopy

Prototype for field testing

TB bacillus. Image captured using device in direct sunlight.

• Portable, battery-powered fluorescence imaging • Diagnostic quality imaging • Sensitivity and specificity non-inferior (+/- 10%) to

standard LED fluorescence microscopy

Breslauer et al, PLoS One 2009 Tapley et al, J Clin Micro 2013

CellScope – 2nd generation

Automated detection

Mobile phone CellScope Auramine-O

iPhone 4S

Chang et al, MICCAI 2012

The TB diagnostic funnel

Seek care for symptoms of TB

Seek care at a microscopy center

Get referred for smear examination

Test smear-positive

Start treatment

All with unexplained cough

Diagnosed & treated TB patients

Summary • Microscopy offers many opportunities to improve case

detection and patient-centered TB evaluation – Increasing the delivery of high-quality diagnostic services – Shortening the diagnostic process and reducing drop-out – Reducing untreated smear-positive TB in the community

• Better services to individuals at the top of the TB diagnostic funnel will provide much greater gains for TB programs than better diagnostics at the bottom of the funnel

Acknowledgments

Adithya Cattamanchi UCSF

Achilles Katamba Makerere University

William Worodria Makerere University

David Dowdy Johns Hopkins

MIND Team, MU-UCSF Collaboration Uganda TB Surveillance Project Team

Questions?