New Entrant TB Screening

Dr. John P. WatsonConsultant Respiratory Physician

New Entrant TB

Screening - Why?

3

Tuberculosis case reports & rates by place of birth, UK, 2004-2013

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Labour Force Survey (LFS)Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

2004 2005 2006 2007 2008 2009 2010 2011 2012 20130

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84 86 86 8284

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Tuberculosis case reports & rates by age group & place of birth, UK, 2013

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI),Labour Force Survey (LFS)Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

New Entrant TB

Screening – How?

Pre-entry CXR

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Figure 1.8: Non UK-born tuberculosis case reports by time since entry to the UK to tuberculosis diagnosis, UK, 2012

Source: Enhanced Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)

Data as at July 2013                    

Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England      

7 Tuberculosis in the UK: 2013 report

8

Proportion of TB case reports by site of disease, UK, 2004-2013

* With or without extra-pulmonary disease

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

2004 2005 2006 2007 2008 2009 2010 2011 2012 20130

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Limitations

500 diagnosed within 1 year of arrival

52% pulmonary = 260 cases detectable by CXR – assuming that CXR abnormal up to 12 months before presentation with symptoms.

UK total 7892 cases in 2013 At best, reduce incidence by 3.3%

Yield of pre-entry screening

70-80 cases of TB detected per year 2013 increased to 130 Rate 188/100,000 (0.19%)

Public Health England: Tuberculosis in the UK: 2014 report

11

Time between entry to the UK & TB diagnosis for non-UK born TB cases by year, UK, 2013

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS)Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

TUBERCULOSIS

CXR on arrival?

Meta-anylsis TB diagnosis yield by CXR screening Total TB 0.35% Continent of origin

Europe 0.24% Africa 0.65% Asia 1.12%

Arshad et al. Eur Respir J 2010; 35:1336-1345

LTBI in new entrants

Most TB in overseas born Most have been here > 1 year –

opportunity to identify LTBI before develop active disease

Most in age group eligible for chemoprophylaxis

Screening for LTBI - how

TST IGRA

2 step test: TST, followed by IGRA if positive to improve specificity

Which test for LTBI in new entrants?

Norway 2005-6 912 asylum seekers, 72% BCG 29% Quantiferon Pos TST ≥ 6mm :

460(50%) Detect 88% of Pos IGRA

TST ≥ 15mm: 141 (15%) Detect 39% of pos IGRA

Winje BA et al. BMC Infect Dis. 2008; 8: 65.

New Entrant TB

Screening - Who?

New Entrants: Who to screen for LTBI?

NICE 2006

Children Pregnant women Sub-Saharan Africa East Timor

NICE 2006: CG33

Problems with NICE 2006: Who to screen?

LTBI testing limited to Africa (+East Timor) TB incidence Gambia: 173/105

TB incidence Philippines: 292/105

Largest number of TB cases in UK in overseas born from Asia. 42% Pakistan, India & Bangladesh <50% from Africa

22

Most frequent countries of birth for non-UK born TB cases, UK, 2013

* Where country of birth was known; **Years

Country of birth Number of cases

Percentage of cases*

Median time since entry to UK (IQR)**

India 1,615 29.8 5 (2 -13)

Pakistan 1,103 20.4 7 (2 -22)

Somalia 292 5.4 9 (4 -13)

Bangladesh 248 4.6 7 (3 -18)

Nepal 170 3.1 3 (2 -6)

Nigeria 164 3.0 7 (3 -11)

Philippines 136 2.5 8 (5 -12)

Zimbabwe 105 1.9 11 (7 -12)

Sri Lanka 95 1.8 7 (3 -13)

Kenya 84 1.6 22 (8 -37)

Romania 70 1.3 2 (0 -4)

Afghanistan 67 1.2 6 (2 -11)

Poland 66 1.2 5 (2 -7.5)

Eritrea 62 1.1 4 (2 -7)

China 56 1.0 7 (4 -11) Others (each <1%)

1,082 20.0 5 (1 -13)

Total* 5,415 100 7 (3 -14)

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI)Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

New Entrants: Who to screen for LTBI?

NICE 2011 “High incidence countries” Defined in NICE as >40/100,000

NICE 2011: CG117

Problems with NICE 2011:

Who to screen? Logic of 40/100,000 threshold

People moving from Libya (TB incidence 40/105) to London (TB incidence 44.4/105) should be screened

Should we screen all “immigrants” to Yorkshire or Manchester from London?

Yield low – is it cost effective?

The problem in Leeds - 2006

Rising incidence of TB, predominantly among arrivals to UK in previous 2-3 years

NICE guidance for new entrant Xrays Massive resource implication

Lack of logic in who to screen for LTBI

GP registrations: 6-8x more new entrants than previously identified by Port Health.

No increase in resources

Rising Immigration

New Immigrants Registering with GP in Leeds 2000 - 2007

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Countries w ith TB Incidence >40 per100,000

Countries w ith TB Incidence >160 per100,000

TBSCREENIN

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2007 Leeds Pilot

Limit to countries with TB incidence >200

No TST except children Nurse led community based clinic Simple symptom questions + QFT

for all >16yrs QFT neg – informed by letter, no

further action QFT pos - invited for CXR and

medical review If no active TB, <35 – Rx for LTBI

Leeds immigrant screening results 2007

Leeds NICE 2006

Number screened 280 275 LTBI diagnosed 105 83* active TB 0 0 Total cost £9 781 £13 346 Cost per LTBI diagnosed £93.18 £160.81*

*Assuming no false negative TST

Hardy et al, Thorax 2010;65:178-80

Leeds 2008 - 2012 Based on 2007 pilot New Entrants identified by GP

registration data Funding improved to move threshold

down to 160/100,000 to include India and Pakistan

Screened 2884 684 (23.7%) IGRA positive Chemoprophylaxis completion rate

89% Audit of 184 patients in 2009

Problem – high rate of non attendance for screening

Yield of IGRA for new entrant screening

Multicentre study “Real life” screening situation 2009 Leeds, Westminster, Blackburn New entrants, screened with IGRA

QuantiFERON TB Gold In Tube

Pareek M, et al. Lancet Infect Dis 2011;11:435-44.

Results

Total screened: 1229 Age

<16 36 ( 3%) 16-25 589 (48%) 26-35 604 (49%)

Female: 51% Previous BCG: 83% Indian subcontinent: 60% Sub-Saharan Africa: 20%

Results (continued)

IGRA Results Positive 245 (20%) Negative 982 (80%) Indeterminate 2 (0.2%)

Positive result associated with: Increasing TB incidence in country of

origin (p<0.01) TB incidence <150/105 : 13% TB incidence >150/ 105: 21.5%

Increasing age (p<0.0001) Active TB: 5 cases.

Cost effectiveness

Couuntries with TB incidence> 150/105 ICER £20,819 per case prevented

More effective and less cost than NICE 2006

150/105 prevents more disease than higher threshold. Detect 92% positive IGRA

NICE 2006 protocol would miss 71% of LTBI

Assumptions for cost calculations

Pos Quantiferon – untreated has 5% risk of TB within 20 years

Chemoprophylaxis reduces risk by 60%

BUT

The Big But Blackburn 1989-2001 New entrants

16-34 yr with pos TST: 16% active TB after 15 years

Choudhury et al, Public Health 2014;36:390-5

Norway asylum seekers: Pos QFT: Active TB 3.3% in 23-32 months

Winje BA et al. BMC Infect Dis. 2008; 8: 65.

ERS 2014 new data

If 15% Active TB after 20 years

cost to prevent 1 case of TB: not £20,819, but……

£3,040

LTBI

New Entrant TB

Screening - When?

New Entrants: When to screen?

As soon as possible! Before leaving home country?

Problem of adequate resources for testing and treatment

Verification of test results / treatment Distorts priority in high burden

countries from case finding and holding of active TB

Risk of reinfection prior to travel to UK Not practical for asylum seekers / war

zones

New Entrants: When to screen?

At airport Experience of port of entry CXR not

promising Follow up of results?

Asylum seekers: reception centre On arrival in destination place of

residence GP registration Social Housing / school entry/ work

permit / university registration

New Entrant TB Screening:

Conclusions Why: Top reduce the incidence of TB

in UK Who: New entrants from countries

with TB incidence > 150/105

How: Single step IGRA When: As soon as possible after

arrival in UK

But can it make a difference?

?