New Entrant TB Screening Dr. John P. Watson Consultant Respiratory Physician

New Entrant TB Screening - Why?

3 Tuberculosis case reports & rates by place of birth, UK, 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 Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

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

New Entrant TB Screening – How?

Pre-entry CXR

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

Limitations 500 diagnosed within 1 year of arrival 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. 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 UK total 7892 cases in 2013 At best, reduce incidence by 3.3% At best, reduce incidence by 3.3%

Yield of pre-entry screening cases of TB detected per year cases of TB detected per year 2013 increased to increased to 130 Rate 188/100,000 (0.19%) 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 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:

LTBI in new entrants Most TB in overseas born Most TB in overseas born Most have been here > 1 year – opportunity to identify LTBI before develop active disease Most have been here > 1 year – opportunity to identify LTBI before develop active disease Most in age group eligible for chemoprophylaxis 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 Norway asylum seekers, 72% BCG 912 asylum seekers, 72% BCG 29% Quantiferon Pos 29% Quantiferon Pos TST ≥ 6mm : TST ≥ 6mm : 460(50%) 460(50%) Detect 88% of Pos IGRA Detect 88% of Pos IGRA TST ≥ 15mm: TST ≥ 15mm: 141 (15%) 141 (15%) Detect 39% of pos IGRA Detect 39% of pos IGRA Winje BA et al. BMC Infect Dis. 2008; 8: 65. 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 Children Pregnant women Pregnant women Sub-Saharan Africa Sub-Saharan Africa East Timor East Timor NICE 2006: CG33

Problems with NICE 2006: Who to screen? LTBI testing limited to Africa (+East Timor) LTBI testing limited to Africa (+East Timor) TB incidence Gambia: 173/10 5 TB incidence Gambia: 173/10 5 TB incidence Philippines: 292/10 5 TB incidence Philippines: 292/10 5 Largest number of TB cases in UK in overseas born from Asia. Largest number of TB cases in UK in overseas born from Asia. 42% Pakistan, India & Bangladesh 42% Pakistan, India & Bangladesh <50% from Africa <50% from Africa

22 Most frequent countries of birth for non-UK born TB cases, UK, 2013 * Where country of birth was known; **Years Tuberculosis in the UK: 2014 report Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May 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” “High incidence countries” Defined in NICE as >40/100,000 Defined in NICE as >40/100,000 NICE 2011: CG117

Problems with NICE 2011: Who to screen? Logic of 40/100,000 threshold Logic of 40/100,000 threshold People moving from Libya (TB incidence 40/10 5 ) to London (TB incidence 44.4/10 5 ) should be screened People moving from Libya (TB incidence 40/10 5 ) to London (TB incidence 44.4/10 5 ) should be screened Should we screen all “immigrants” to Yorkshire or Manchester from London? Should we screen all “immigrants” to Yorkshire or Manchester from London? Yield low – is it cost effective? Yield low – is it cost effective?

The problem in Leeds Rising incidence of TB, predominantly among arrivals to UK in previous 2-3 years Rising incidence of TB, predominantly among arrivals to UK in previous 2-3 years NICE guidance for new entrant Xrays NICE guidance for new entrant Xrays Massive resource implication Massive resource implication Lack of logic in who to screen for LTBI Lack of logic in who to screen for LTBI GP registrations: 6-8x more new entrants than previously identified by Port Health. GP registrations: 6-8x more new entrants than previously identified by Port Health. No increase in resources No increase in resources

Rising Immigration

TB SCREENING

2007 Leeds Pilot Limit to countries with TB incidence >200 Limit to countries with TB incidence >200 No TST except children No TST except children Nurse led community based clinic Nurse led community based clinic Simple symptom questions + QFT for all >16yrs Simple symptom questions + QFT for all >16yrs QFT neg – informed by letter, no further action QFT neg – informed by letter, no further action QFT pos - invited for CXR and medical review QFT pos - invited for CXR and medical review If no active TB, <35 – Rx for LTBI If no active TB, <35 – Rx for LTBI

Leeds immigrant screening results 2007 Leeds NICE 2006 Number screened Number screened LTBI diagnosed105 83* LTBI diagnosed105 83* active TB 0 0 active TB 0 0 Total cost £9 781£ Total cost £9 781£ Cost per LTBI diagnosed£93.18£160.81* Cost per LTBI diagnosed£93.18£160.81* *Assuming no false negative TST Hardy et al, Thorax 2010;65:178-80

Leeds 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 (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 Multicentre study “Real life” screening situation 2009 “Real life” screening situation 2009 Leeds, Westminster, Blackburn Leeds, Westminster, Blackburn New entrants, screened with IGRA New entrants, screened with IGRA QuantiFERON TB Gold In Tube QuantiFERON TB Gold In Tube Pareek M, et al. Lancet Infect Dis 2011;11:

Results Total screened: 1229 Total screened: 1229 Age Age <1636( 3%) <1636( 3%) (48%) (48%) (49%) (49%) Female:51% Female:51% Previous BCG: 83% Previous BCG: 83% Indian subcontinent: 60% Indian subcontinent: 60% Sub-Saharan Africa: 20% Sub-Saharan Africa: 20%

Results (continued) IGRA Results IGRA Results Positive245(20%) Positive245(20%) Negative982(80%) Negative982(80%) Indeterminate 2 (0.2%) Indeterminate 2 (0.2%) Positive result associated with: Positive result associated with: Increasing TB incidence in country of origin (p<0.01) Increasing TB incidence in country of origin (p<0.01) TB incidence <150/10 5 : 13% TB incidence <150/10 5 : 13% TB incidence >150/ 10 5 : 21.5% TB incidence >150/ 10 5 : 21.5% Increasing age (p<0.0001) Increasing age (p<0.0001) Active TB: 5 cases. Active TB: 5 cases.

Cost effectiveness Couuntries with TB incidence> 150/10 5 ICER £20,819 per case prevented Couuntries with TB incidence> 150/10 5 ICER £20,819 per case prevented More effective and less cost than NICE 2006 More effective and less cost than NICE /10 5 prevents more disease than higher threshold. 150/10 5 prevents more disease than higher threshold. Detect 92% positive IGRA Detect 92% positive IGRA NICE 2006 protocol would miss 71% of LTBI NICE 2006 protocol would miss 71% of LTBI

Assumptions for cost calculations Pos Quantiferon – untreated has 5% risk of TB within 20 years Pos Quantiferon – untreated has 5% risk of TB within 20 years Chemoprophylaxis reduces risk by 60% Chemoprophylaxis reduces risk by 60%BUT

The Big But Blackburn New entrants yr with pos TST: 16% active TB after 15 years Blackburn New entrants yr with pos TST: 16% active TB after 15 years Choudhury et al, Public Health 2014;36:390-5 Choudhury et al, Public Health 2014;36:390-5 Norway asylum seekers: Norway asylum seekers: Pos QFT: Active TB 3.3% in months Pos QFT: Active TB 3.3% in months Winje BA et al. BMC Infect Dis. 2008; 8: 65. Winje BA et al. BMC Infect Dis. 2008; 8: 65. ERS 2014 new data 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! As soon as possible! Before leaving home country? Before leaving home country? Problem of adequate resources for testing and treatment Problem of adequate resources for testing and treatment Verification of test results / treatment Verification of test results / treatment Distorts priority in high burden countries from case finding and holding of active TB Distorts priority in high burden countries from case finding and holding of active TB Risk of reinfection prior to travel to UK Risk of reinfection prior to travel to UK Not practical for asylum seekers / war zones Not practical for asylum seekers / war zones

New Entrants: When to screen? At airport At airport Experience of port of entry CXR not promising Experience of port of entry CXR not promising Follow up of results? Follow up of results? Asylum seekers: reception centre Asylum seekers: reception centre On arrival in destination place of residence On arrival in destination place of residence GP registration GP registration Social Housing / school entry/ work permit / university registration Social Housing / school entry/ work permit / university registration

New Entrant TB Screening: Conclusions Why: Top reduce the incidence of TB in UK Why: Top reduce the incidence of TB in UK Who: New entrants from countries with TB incidence > 150/10 5 Who: New entrants from countries with TB incidence > 150/10 5 How: Single step IGRA How: Single step IGRA When: As soon as possible after arrival in UK When: As soon as possible after arrival in UK But can it make a difference? But can it make a difference?