TB IN MIGRANT POPULATIONS Practical options chosen in neighbouring countries for screening and management

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25th Swiss Symposium on Tuberculosis Münchenwiler TB IN MIGRANT POPULATIONS Practical options chosen in neighbouring countries for screening and management SITUATION IN PARIS / FRANCE Fadi ANTOUN CENTRE DE LUTTE ANTITUBERCULEUSE, Bureau de la Prévention et des Dépistages, DASES 17 mars 2016

Many thanks to Delphine ANTOINE* for her help on epidemiological and demographic data and on the English version of this presentation. * InVS

TUBERCULOSIS IN FRANCE HISTORY

4

PARISIAN SLUMS EARLY TWENTIETH CENTURY 5

PARISIAN HEALTH VISITORS, 1950 6

TUBERCULOSIS IN FRANCE EPIDEMIOLOGICAL DATA

INTERNATIONAL IMMIGRANTS, FRANCE POPULATION LIVING IN FRANCE 2014 FIGURES TOTAL POPULATION 65.8 millions IMMIGRANTS LIVING IN FRANCE 5.9 millions UNDOCUMENTED IMMIGRANTS 300 000 500 000 POPULATION ENTERING IN FRANCE 2014 Figures IMMIGRANTS AUTHORISED TO STAY IN FRANCE AND SEEKING STAY PERMIT 215 797 ASYLUM SEEKERS 55 672 REFUGEES 12 052 Source: INSEE, homme office

IMMIGRANT FLOW FROM 2005 TO 2015 (immigrants seeking a stay permit) X1000 Source : French Immigration Office

FRENCH IMMIGRATION OFFICE, 2014 210 940 STAYS PERMIT IN FRANCE Other 742 [6%] Humanitory 20 822 [10%] Economic 19 054 [9%] Students 64 996 [31%] Familial 92 326 [44%] 24% FROM AMERICA AND EUROPA - 8% < 20 YEARS Source : French Immigration Office

TUBERCULOSIS NOTIFICATION NUMBER AND RATE France, 2000-2013 Number of cases (all forms) rate (all forms) per 100 000 8000 11.1 10.6 10.3 12 rate (TB pulmonary) per 100 000 Number of cases 7000 6000 5000 4000 3000 9.9 6714 6465 6322 6098 8.2 8.0 7.6 7.2 9.0 8.6 8.8 9.0 8.4 8.2 8.0 7.7 7.6 7.5 5578 5368 5323 5574 5758 5276 5187 4991 4975 4934 6.5 6.1 6.1 6.4 6.3 5.9 5.8 5.6 5.6 5.4 10 8 6 4 Rate per 100 000 2000 1000, 2 0 0 Year of notification Source : InVS, TB MANDATORY NOTIFICATION + INSEE (National Institute for Statistics and economy)

TUBERCULOSIS IN FRANCE, 2013 France : 65 millions inhabitants 4934 TB cases notified in 2013: rate = 7.5/100 000 Born in France 44% Foreign born 56% Homeless persons 5.4% 2,2 million inhabitants 408 TB cases (8.3% of all cases) 18/100 000 Ile de France region (Paris and suburb) 11 million inhabitants (including Paris) 1 776 TB cases (36% of all cases) 14.7/100 000 BEH, march 2015

TUBERCULOSIS NOTIFICATION RATE, 2000-2013 Ile-de-France (IdF) (Paris Overseas and suburbs) Districts (DOM) France except IdF and DOM Paris 60 50 TB rate per 100 000 40 30 20 10 0 Year of notification Source : InVS, TB MANDATORY NOTIFICATION + INSEE (National Institute for Statistics and economy) Cellule Tuberculose / CLAT 75

TUBERCULOSIS NOTIFICATION RATE BY MAIN SOCIO-DEMOGRAPHIC CHARACTERISTICS, FRANCE, 2013 Taux pour 100 000 40 60 80 100 120 140 160 180 35,6 176, 91,6 For each characteristic p<0,01 Source: InVS (Mandatory notification)

TUBERCULOSIS NOTIFICATION RATE BY PLACE OF BIRTH AND TIME SINCE ENTRY IN FRANCE, 2013 < 2 years 2-4 years 5-9 years 10 years and + 450 Rate per 100 000 400 350 300 250 200 150 100 50 0 383 267 209 127 116 87 57 50 33 26 32 33 13 20 16 18 23 5 13 19 Total Foreign born Europe * Africa Asia Other regions Place of birth Europe: without France and including Central and East Europe Sources: InVS, mandatory notification and INSEE, population census

MDR * TUBERCULOSIS STRAINS RECEIVED AT THE NATIONAL REFERENCE CENTER(CNR-MYRMA), FRANCE, 2006-2013 * TB MDR = TB Resistant to INH and RMP Source: CNR-MyrMA

TUBERCULOSIS CASES IN PARIS-2013 TB CASES HAVE DECREASED : 1200 CASES in 2003, 408 in 2013 and 324 in 2015 IN 2013 PARIS France without Paris TB incidence per 100 000 18 7 % of TB cases in foreign born % of TB cases born in sub saharan Africa % of TB cases foreign born in shelter 72% 54% 29% 20% 6% NA % of TB cases in homeless 12% 4%

TB in migrants shelters N= 26 stable since 5 Y DISTRIBUTION OF CASES BY DISTRICT INCIDENCE BY DISTRICT IN 2013 XVII N= 408 TB in deprived and very deprived conditions N=120 XVIII XIX XVI VIII VII I IX II III IV X XI XX XV VI V XII Incidence XIV XIII < 10 / 100 000 10-20 / 100 000 21-30 / 100 000 31-40 / 100 000 North and East of Paris have highest incidence

MIGRANTS MIGRANT IMPACT ON TB IN PARIS, 2013 Parisian population 2,2 Millions MIGRANTS 72 % of TB cases including 6 % in shelter (n=26)

TB CONTROL

ORGANISATION OF TB CONTROL IN FRANCE, 2016 Clinicians TREATMENT+ FOLLOW UP Notification Notification Regional health agency (ARS-DT) Anti tuberculosis control center (CLAT) InVS EPIDEMIOLOGICAL ANALYSIS CONTACT INVESTIGATION ACTIVE X RAY SCREENING ARS-DT : District Unit of regional health authority CLAT : Anti tuberculosis control center InVS : National Institute for Public Health

TUBERCULOSIS CONTROL IN FRANCE 2005 : guidelines on TB and migrants 2007 : national TB programme and change of BCG policy from universal and mandatory vaccination to voluntary and at risk groups vaccination 2013-2014 : National guidelines (High Council for public Health) 2013 : TB contact investigation 2014 : diagnostic and management of resistant TB Tuberculosis treatment IS FREE of charge for all REGIONAL HEALTH AUTORITHY (ARS) responsible for infectious disease control (of which TB) TUBERCULOSIS CENTER in charge of TB control at district level (CLAT)

NATIONAL REGULATIONS AND PRACTICE ON TB SCREENING IN MIGRANTS AS OF MARCH 2016 Type of immigrants Immigrants authorised to live in France for more than three months (except EEA residents) and seeking a stay permit Systematic medical visit : including TB Screening (Chest X Ray), vaccine, preventable diseases check ( diabetes, ) Performed in France except for immigrants seeking stay permit from Morocco, Mali, Tunisia, Turkey, Cameroon, Senegal (pre entry screening) No impact of the TB screening results on administrative process Asylum seekers Medical visit if in dedicated migrants shelter (only 20% of asylum seekers) Refugee Medical visit

RECENT FRENCH POLICY FOR IGRA USE AVIS DE LA HAS n 2015.0047/AC/SEAP du 3 juin 2015 Screening of LTBI for migrants < 15 years coming from high incidence countries including children < 5 years (2015) Quantitative presentation of results New French Pneumology Society Recommandations 2016 (not yet validated). IGRA OR TST. IGRA preferable to TST IF BCG OR RISK OF LOSS OF FOLLOW UP. INDIVIDUAL BUT NO SYSTEMATIC SCREENING OF MIGRANTS <35 YEARS COMING FROM HIGH INCIDENCE COUNTRIES

HIGH COUNCIL OF PUBLIC HEALTH REPORT 2005 French recommandations on tuberculosis and migrants Recommendations of expert group 'Tuberculosis and Migrants' Council senior public health of France, June 7, 2005 - DGS

ALGORITHM LEGAL AND ILLEGAL MIGRANTS AND ASYLUM SEAKERS* < 15 YEARS > 15 YEARS TST CHEST X RAY TST > 10 mm TST < or = 10 mm TB DISEASE TB SEQUELAE NORMAL CHEST X RAY CHEST X RAY NO FOLLOW UP TREATMENT PREVENTIVE TREATMENT RECOMMENDATION : survey (chest X Ray/year) during 2 years** NORMAL ABNORMAL * if coming from high incidence countries>50/100 000 PREVENTIVE TREATMENT TST > 10 mm without BCG TST > 15 mm with BCG or unknown BCG HEALTH ASSESSMENT AND TREATMENT ** if coming recently from very high incidence countries100/100 000

OFII 2006 NATIONAL REGULATION ON MEDICAL SCREEENING OF IMMIGRANT SEEKING A STAY PERMIT Clinical Examination Chest X-RAY for all (except <10 years) TST only for those <15 years

CONTACT INVESTIGATION IN HOMELESS PERSONS AND MIGRANT SHELTERS -2013 French Guidelines PRECARIOUS (migrant/homeless shelter) with stay duration > 3-6 months GREAT PRECARIOUS (living in street or in a shelter <3 months) USUAL SCREENING (LTBI + TB screening for those in the same room) SPECIFIC SCREENING If 2 TB in 6 months period occuring in a shelter SCREENING TB for all shelter residents with chest X RAY using mobile Unit No screening for LTBI

SPECIAL MANAGEMENT OF TB MIGRANTS IN PARIS AND SUBURBS

35 avenue Courteline 75012 Paris o Regional mission (regional public health IDF 2008-2011 Plan) implementation in 2010 Created in 1996 o Since its inception, ± 700 supported, including > 300 patients with TB treatment

More than 100 difficult TB (MDR + homeless) treated/year TB Center for inpatients with complex TB, acting as reference center for clinical advice for treatment and management of TB patients

TB SCREENING OF MIGRANTS AT ARRIVAL FRENCH IMMIGRATION OFFICE : 22 CENTERS DISPATCHED IN ALL FRENCH TERRITORY HEALTH CHECK AS PART OF PROCESS TO SEEK A STAY PERMIT RESULT OF HEALTH CHECK DO NOT IMPACT ON STAY PERMIT ISSUE UNDER THE AUTHORITY OF MINISTRY OF THE INTERIOR

LAST NATIONAL RESULTS, 2008 250 238 TB CASES /REGION N=194 TB /100 000 CHEST X-RAY = 98/10 5 200 150 100 92 91 50 42 63 34 47 44 15 11 0 AFRIQUE ASIE EUROPE MAGHREB AMERIQUE Source : French Immigration Office

FRENCH IMMIGRATION OFFICE PROSPECTIVE STUDY 2014 COLLABORATION BETWEEN PARISIAN MIGRATION OFFICE AND CONTROL CENTER OF TB

PARISIAN PROSPECTIVE STUDY : from 01-01-2014 to 30-06-2014 25 000 MIGRANTS/YEAR ABOUT 1/8 OF ALL MIGRANTS TO FRANCE 96 ABNORMAL X-RAY 11 997 MIGRANTS between 01-01-2015 and 30-06-2015 12 TB

PARISIAN PROSPECTIVE STUDY 2014 from 01-01-2014 to 30-06-2014 ABNORMAL CHEST X RAY N= 96 Region of birth (N=96) Sexe (N=96) 16 80 1 3 23 Subsaharan North Africa South America 41 20 South East Asia MEAN AGE (N=96) : 40,2 Years 8 East Europa Others (America/Canada/Mid dle East) DASES - lundi 6 mai 2013

PARISIAN PROSPECTIVE STUDY 2014 RESULTS (1) Delay Arrival in France (N=94) 104 months Consultation OFII 70 60 50 40 30 20 10 0 59 25 6 4 0-12 mois 12-24 mois 24-36 mois > 36 mois Consultation OFII (N=95) 11 days Consultation CLAT Immediate answer Consultation OFII (N=95) 22 days Consultation CLAT Final answer DASES - lundi 6 mai 2013

PARISIAN PROSPECTIVE STUDY 2014 - RESULTS (2) 11 997 MIGRANTS AND 96 ABNORMAL X-RAY TB X-Ray SEQUELA 26 TB ACTIVE OTHER X-RAY SEQUELA 12 1 SMEAR + 11 SMEAR- 8 C + 49 OTHER DIAGNOSIS 1 mandibula cancer 100 TM/100.000 X-RAY DASES - lundi 6 mai 2013

PARISIAN PROSPECTIVE STUDY 2014 - CONCLUSIONS ACTIVE TB SCREENING among MIGRANTS NEWLY ARRIVED IS AN INTERESTING STRATEGY WITH A MEAN RATE OF 100 TB/100 000 X-RAY THIS RATE IN BELOW WHAT WE EXPECTED BECAUSE OF : - LONG DELAY BETWEEN SCREENING AND ARRIVAL TIME - SCREENING OF ALL MIGRANTS INCLUDING THOSE COMING FROM LOW INCIDENCE COUNTRIES EFFICIENT COLLABORATION BETWEEN French Immigration Office And Anti-TB center IS NEEDED WITH REGULAR EVALUATION OF RESULTS MIGRANTS MUST BE SCREENED EARLIER AND ONLY THOSE COMING FROM HIGH INCIDENCE COUNTRIES (> 50/ 10 X 5)

Since 1994 mobile xray screening in Paris shelters TB ACTIVE SCREENING OF MIGRANTS IN PARIS SHELTERS - IN PARIS CITY 35 TO 40 MIGRANTS SHELTER WITH ALMOST 10 TO 12 000 REGULAR RESIDENTS AND PROBABLY TWICE THIS NUMBER (if including indocumented residents) - LOOKING MORE AND MORE LIKE «ONE STAR HOTEL» - SYSTEMATIC SCREENING ONCE /Y AND MORE IF NECESSERLY

MOBILE X-RAY APPARITUS USED UNTIL 2013 TO SCREEN SHELTER POPULATION Cellule Tuberculose/CLAT75-2016

BPD Cellule Tuberculose/CLAT75 BPD Cellule Tuberculose/CLAT 75

MOBILE X-RAY SCREENING IN PARIS / NUMBER OF CHEST X RAY AND TB CASES SCREENED IN MIGRANTS SHELTER BETWEEN 1994-2013 14000 80 Number of Chest X Ray 12000 10000 8000 6000 70 60 50 40 30 TB cases 4000 20 2000 10 0 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 n Rx en foyers migrants n TM dépistées chez migrants In 2013 : 3 416 CHEST X-RAY and 4 TB BPD Cellule Tuberculose/CLAT75 BPD Cellule Tuberculose/CLAT 75

CHEST X RAY SCREENING IN MIGRANT SHELTER 3 major periods in chest X Ray screening Chest X Ray in migrant shelter / Paris 1994-2011 1994 to 2001 : starting period efficiency 1 TM /600 XR (15% of all TB) 2002 to 2004 : epidemic period efficiency 1 TB/100 XR (40% of all TB) 2005 to 2011 : stabilisation period efficiency 1 TB/800 XR (10% of all TB ) JRVS 2013-FA BPD Cellule Tuberculose/CLAT75 Cellule Tuberculose / CLAT 75

TB CASES IN MIGRANT SHELTER, PARIS 2002 TO 2013 ALL TB CASES / TB CASES SCREENED BY MOBILE CHEST X RAY 140 129 120 TB DRS 100 90 TB Globales 80 74 60 55 48 40 20 0 30 16 7 35 3 27 36 6 8 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 MOBILE X-RAY SCREENING IS EFFICIENT IN EPIDEMIC SITUATIONS WITH MORE THAN 50% OF ALL TB SCREENED 3 22 6 32 32 33 3 2 4 26 BPD Cellule Tuberculose/CLAT75 BPD Cellule Tuberculose/CLAT 75

CONCLUSIONS IN PARIS BEFORE 2013 SYSTEMATIC ANNUAL SCREENING AFTER 2013 SCREENING in MIGRANT SHELTERS ONLY IF 2 TB occurs in 6 months period SYSTEMATIC ANNUAL SCREENING BY X-RY ALLOW 3 TB DIAGNOSIS (1 TB FOR 1000 XR)= 10 to 12% of all migrants shelter TB VERY EFFICIENT IN EPIDEMIC SITUATION WITH SEVERAL SIMULTANEOUS SCREENING IN HIGH RISK SHELTERS BPD BPD Cellule Cellule Tuberculose/CLAT75

ACTIVE SCREENING DIFFICULT COSTY ++ POOR RESULTS STRATEGIES 1-2 - 3 - CONTACT SCREENING STRATEGY (1% of CS = 1000 / 100 000 CS ) SCREENING AT OFII (French immigration office ) about 100 TM /100 000 XR) SCREENING IN MIGRANT SHELTER = 100 TB / 100 000 XR

ACTIVE SCREENING IN PARIS-2013 408 Index Cases In 2013 3.000 Contact Subject TB LTB I TB +TB prevented By treatment LTBI Contact screening French immigration Office Screening ( OFII) Active screening in migrant+homeless shelters 32 345 45 12 0 12 4+2 6 TOTAL : 63 15% of all cases Cellule Tuberculose / CLAT 75

LTBI SCREENING OF MIGRANTS -FEW DATA in France concerning LTBI among migrant or general population -No Evaluation of LTBI in migrant < 15 Y despite a National Recommendation

DATA ON LTBI IN CHILDREN < 15 YEARS OLD-FRANCE In France, LTBI in children < 15 years should be notified (since 2003) whatever the situation Definition case : based for the moment on TST result Difficulty in assessing the exhaustivity of the surveillance system From 2011 to 2013: 2361 LTBI notified in children (around 750-850 each year) Around 2/3 of LTBI in children foreign born or with foreign born parents

PARIS MIGRANTS < 15 YEARS YEAR NUMBER SCREENED LTBI TREATED 2010 306 33 2011 271 40 2012 245 40 2013 152 24 2014 244 26 - ONLY LESS THAN 25 % OF MIGRANTS < 15 Y ARE SCREENED - AROUND 10 % WITH LTBI TREATED

CONCLUSIONS AND RECOMMENDATIONS BETTER SELECTION OF MIGRANTS : COUNTRY OF BIRTH WITH TB INCIDENCE > 50 / 10 X5 SCREENING SHOULD BE PERFORMED AS SOON AS POSSIBLE AFTER ARRIVAL IN FRANCE ASYLUM SEEKER SHOULD BE INCLUDED IN THE SCREENING LTBI SCREENING IN CHILDREN < 15 Y SHOULD BE ASSESSED AND EXPANDED IN A SECOND TIME LTBI SCREENING MAY BE PROPOSED FOR ALL MIGRANTS < 35 Y NEWLY ARRIVED FROM HIGH INCIDENCE COUNTRIES

LTBI SCREENING BY IGRA /Young adults from 16 to 30 Years If we consider sub-saharan migrants in France Number of persons concerned: about 20 000 (1) Estimated number of QFT+ : 4 000 à 5 000 (20 à 25 %) (3) Number of TB avoided if LTBI treatment : 20 à 25 at 2 Years and 150 at 5 Years (2) 300 to 400 TB /10 000 To avoid 1 TB at 5 years : 133 migrants should be screened and 27 LTBI (IGRA+) should be treated (1 ) InVS mars 2009 (2) Mulder C, Van Deutekom H, et al. Role of the QuantiFERON -TB Gold In-Tube assay in screening new immigrants for tuberculosis infection. ERJ December 1, 2012;40(6):1443-1449. Gill AL, Ormerod LP, Watson JP. Positive predictive value of an interferon-gamma release assay for progression from latent to active tuberculosis in new-entrant screening. ERS 2014 (abstract) (3)-Pareek M, Bond M, and al. Community-based evaluation of immigrant tuberculosis screening using interferon gamma release assays and tuberculin skin testing : observational study and economic analysis. Thorax 2012:1-10 -Orlando G, Merli S, and al. Interferon-γ releasing assay versus tuberculin skin testing for latent tuberculosis infection in targeted screening programs for high risk immigrants. Infection 2010;38:195-204- - Askekand Winje B, Oftung F, and al. Screnning for tuberculosis among newly arrived asylum seekers : comparison of QuanTIFERON TB Gold with tuberculin skin test. BMC Infectious Diseases 2008;8:65- -Ruff L, Hardman N, and al. Comparison of QuantiFERON -TB Gold positivity rates in an English city s targeted tuberculosis screening programme of new entrants with the WHO figures for tuberculosis incidence in their countries of origin. ESCMID 2013 (abstract