TB: The Coventry perspective

Dr Thekli GeeUniversity Hospitals Coventry & Warwickshire

Outline

TB in Coventry:

• Epidemiology

• Resources

• New diagnostic approaches

Epidemiology

Occurrence

• Nearly a third of the world’s population is infected with TB

• TB kills almost 3 million people per year.

Tuberculosis notifications England & Wales

1913 - 2006

Source: Statutory Notifications of Infectious Diseases (NOIDs)

chemotherapy

BCG vaccination

Coventry TB rate by year 1999-2006

Rate per 100,000 population

0

5

10

15

20

25

30

35

1999 2000 2001 2002 2003 2004 2005 2006

rate

Coventry PCT

West Midlands

England & Wales

Linear (Coventry PCT)

Coventry 2007

Tuberculosis case reports and rates by region/country,

England, Wales and Northern Ireland, 2006

Coventry 2007

Coventry

Why Is TB Increasing?

Why Is TB Increasing?

Multiple contributing factors:• Homelessness• Intravenous drug use• HIV infection• Drug-resistant strains of TB• Reduced TB control and treatment resources• Immigration from high TB prevalence areas

Tuberculosis case reports by place of birth and ethnic group, England, Wales and Northern Ireland, 2001 - 2006

Changing populations

• Coventry City council – 1215 asylum seekers on housing list

• Coventry refugee centre– 8000 asylum seekers & refugees

registered– 1571 registered at Meridian Health Centre

Changing populations

• Afghanistan• Iraq• Iran

• Burundi• Democratic Republic of

Congo • Ethiopia• Eritrea• Somalia• Sudan• Zimbabwe

Resources

Increasing numbers of TB cases

Increased demand on TB services

Impact on resources

• Hospital & community TB services– TB clinic– TB nurse time

• Infection control– Isolation facilities– TB incidents

• Occupational health– Pre-employment screening– HCW contacts

• Laboratory services

Impact on resources

• Hospital & community TB services– TB clinic– TB nurse time

• Infection control– Isolation facilities– TB incidents

• Occupational health– Pre-employment screening– HCW contacts

• Laboratory services

TB incidents at UHCW NHS Trust

• 23 incidents in since January 2007

– 18 Patients• Not isolated early enough / at all during admission• Mostly medical wards• 2 Cardiothoracic ward• 1 haematology day unit

– 5 Health care workers• 3 qualified nurses• 1 nursing student• Ward host

Impact on resources

• Hospital & community TB services– TB clinic– TB nurse time

• Infection control– TB incidents – Isolation facilities

• Occupational health– Pre-employment screening– Annual reminders– HCW contacts

• Laboratory services

2007

Impact on resources

• Hospital & community TB services– TB clinic– TB nurse time

• Infection control– TB incidents – Isolation facilities

• Occupational health– Pre-employment screening– Annual reminders– HCW contacts

• Laboratory services

2006

TB national strategy2004

2006

2007

2007

Controlling TB:

1. Diagnosing primary cases

2. Treating active disease

3. Preventing transmission

4. Identifying secondary cases

5. Controlling latent infection

Current diagnostic test for latent TB

• Diagnosis of latent TB relies on the tuberculin skin test.

• 101 years old– Developed 1907 by

Charles Mantoux

• The oldest diagnostic test still in use.

The skin test enters its 6th decade of use. (Canada 1957)

Tuberculin skin tests

• Mantoux test

• Heaf test

48-72 hours later

No longer available

Tuberculin skin tests• Poor specificity:

– antigenic cross-reactivity • BCG • environmental mycobacteria

• Poor sensitivity: – 75-90% in active disease

• lower in disseminated TB and HIV infection

• Need for return visit – 50% DNA rate

• Operator variability – inoculation & reading

• Painful inflammation & scarring• Boosting effect if used repeatedly

New approaches

TB Interferon- release assays

(TIGRA)

• Principle of TIGRA – Detect IFN- produced by effector T-cells

that recognise M. tuberculosis proteins

ESAT-6 & CFP-10• Absent in BCG• Absent in most non-tuberculous Mycobacteria

– Exceptions: M. marinum, M. kansasii

Two Tests available

T-Spot.TB®

Detects individual effector T-cells that produce IFN- in response to M.tuberculosis antigens

Enzyme linked immunospot technique (ELISPOT).

QuantiFERON Gold®

Measures IFN- in the supernatant of the antigen stimulated cells

Enzyme linked immunosorbant assay technique (ELISA)

T-Spot.TB® Quantiferon Gold®

Sensitivity

Immunocompetent 83-97% 70-89%

Immunocompromised

+ malnourished

+ children

<1% indeterminate results 20-24% indeterminate results

T-Spot.TB® Quantiferon Gold®

Sensitivity

Immunocompetent 83-97% 70-89%

Immunocompromised

+ malnourished

+ children

<1% indeterminate results 20-24% indeterminate results

Specificity 99.99% 98%

T-Spot.TB® Quantiferon Gold®

Sensitivity

Immunocompetent 83-97% 70-89%

Immunocompromised

+ malnourished

+ children

<1% indeterminate results 20-24% indeterminate results

Specificity 99.99% 98%

Cost

(including labour etc)

£55-60

per test

£30

per test

T-Spot.TB® Quantiferon Gold®

Sensitivity

Immunocompetent 83-97% 70-89%

Immunocompromised

+ malnourished

+ children

<1% indeterminate results 20-24% indeterminate results

Specificity 99.99% 98%

Cost

(including labour etc)

£55-60

per test

£30

per test

Problems •Must process within 8 hours of venepuncture

•Expertise in cell separation

•Must process within 8 hours of venepuncture

-in tube assay?

•Not reliable enough in the Immunocompromised & children

Method - T-Spot.TB®

• Specimens must be processed within 8 hours of venepuncture

-ve

+ve

ELISPOT

ELISPOT Reader

Role of TIGRAs

• Detection of latent TB:– TB contacts– Healthcare workers

• New employment screens• Following TB exposure incidents

– Before starting immunosuppression• anti-TNF-α drugs e.g infliximab• Pre-transplantation

• Detection of active extra-pulmonary TB– If difficult to diagnose by conventional methods– Closely competing diagnoses e.g. Sarcoid vs TB

Contact tracing:When to use a TIGRA

– NICE:• Following positive Mantoux test

– Most cost effective– May miss some cases

– CDC• In place of Mantoux test

– Shifts burden of work from TB nurses to lab

Business case

• Laboratory service– 5 day to 6 day service– Warwickshire wide (Network)

• TIGRA– Tspot.TB– Microbiology / Immunology

Summary

• TB increasing in Coventry

• Increased demand on resources

• New approaches considered– e.g. TIGRAs