1. TB: The Coventry perspective
Dr Thekli Gee
University Hospitals Coventry & Warwickshire

2. Outline TB in Coventry: Epidemiology Resources
New diagnostic approaches

3. Epidemiology

4. Occurrence
Nearly a third of the world’s population is infected with TB
TB kills almost 3 million people per year.
In the mid-1980s, a resurgence of outbreaks in the U.S. brought renewed attention to TB. Since 1985, the incidence of TB in the general population has increased 14% reversing a 30 year downward trend. In 1993, over 25,000 new cases of TB were reported in the U.S. During 1994 and 1995, however, there was a decrease in TB cases in the U.S. likely due to increased awareness and efforts in prevention and control of TB.

5. Tuberculosis notifications England & Wales 1913 - 2006
chemotherapy
BCG vaccination
Source: Statutory Notifications of Infectious Diseases (NOIDs)

6. Coventry TB rate by year 1999-2006
2007
Rate per 100,000 population 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)

7. Tuberculosis case reports and rates by region/country, England, Wales and Northern Ireland, 2006
Coventry
2007

8. Coventry

9. Why Is TB Increasing?
These factors contribute to the growing increase in TB cases.

10. 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
These factors contribute to the growing increase in TB cases.

11. Tuberculosis case reports by place of birth and ethnic group, England, Wales and Northern Ireland,

12. Changing populations Coventry City council Coventry refugee centre
1215 asylum seekers on housing list
Coventry refugee centre
8000 asylum seekers & refugees registered
1571 registered at Meridian Health Centre

13. Changing populations Afghanistan Iraq Iran Burundi
Democratic Republic of Congo
Ethiopia
Eritrea
Somalia
Sudan
Zimbabwe

14. Resources Increasing numbers of TB cases 
Increased demand on TB services

15. Impact on resources Hospital & community TB services Infection control
TB clinic
TB nurse time
Infection control
Isolation facilities
TB incidents
Occupational health
Pre-employment screening
HCW contacts
Laboratory services

16. Impact on resources Hospital & community TB services Infection control
TB clinic
TB nurse time
Infection control
Isolation facilities
TB incidents
Occupational health
Pre-employment screening
HCW contacts
Laboratory services

17. 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

18. Impact on resources Hospital & community TB services Infection control
TB clinic
TB nurse time
Infection control
TB incidents
Isolation facilities
Occupational health
Pre-employment screening
Annual reminders
HCW contacts
Laboratory services
2007

19. Impact on resources Hospital & community TB services Infection control
TB clinic
TB nurse time
Infection control
TB incidents
Isolation facilities
Occupational health
Pre-employment screening
Annual reminders
HCW contacts
Laboratory services
2006

20. TB national strategy
2004
2007
2006
2007

21. Controlling TB: Diagnosing primary cases Treating active disease
Preventing transmission
Identifying secondary cases
Controlling latent infection
We began by looking at some of the reasons why a guideline on TB was produced. TB is a growing problem in England and Wales, and without proper treatment and contact tracing the spread of the disease will increase. This is a particular risk when drug resistant strains are being treated, or if incomplete treatment leads to an increase in multidrug-resistant strains.
The guideline affect patients in hospitals and prison services as well as in the community. Staff involved in implementing it will need appropriate training, and confidence in their ability to perform their roles. Successful implementation will involve many different teams and services working together, and each one has an important role to play.
The TB guideline deals with activities undertaken by different professionals in the NHS, with multiple aims: to diagnose primary cases, to identify secondary cases, to treat active disease, to control latent infection, and to prevent further transmission. The combined result of these activities should be to curb and reverse the increase in TB incidence seen in England and Wales in recent years

22. 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)

23. Tuberculin skin tests Mantoux test Heaf test 48-72 hours later
No longer available

24. Tuberculin skin tests Poor specificity: Poor sensitivity:
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

25. New approaches

26. TB Interferon-g release assays (TIGRA)
Principle of TIGRA
Detect IFN-g 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

27. Two Tests available T-Spot.TB® QuantiFERON Gold®
Detects individual effector T-cells that produce IFN-g in response to M.tuberculosis antigens
Enzyme linked immunospot technique (ELISPOT).
QuantiFERON Gold®
Measures IFN-g in the supernatant of the antigen stimulated cells
Enzyme linked immunosorbant assay technique (ELISA)

28. T-Spot.TB®
Quantiferon Gold®
Sensitivity
Immunocompetent
83-97%
70-89%
Immunocompromised
+ malnourished
+ children
<1% indeterminate results
20-24% indeterminate results

29. 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%

30. 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

31. <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%
Cost
(including labour etc)
£55-60
per test
£30
Problems
Must process within 8 hours of venepuncture
Expertise in cell separation
-in tube assay?
Not reliable enough in the Immunocompromised & children

32. Method - T-Spot.TB®
Specimens must be processed within 8 hours of venepuncture

34. ELISPOT
-ve
+ve

35. ELISPOT Reader

36. 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

37. 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

38. Business case Laboratory service TIGRA 5 day to 6 day service
Warwickshire wide (Network)
TIGRA
Tspot.TB
Microbiology / Immunology

39. Summary TB increasing in Coventry Increased demand on resources
New approaches considered
e.g. TIGRAs