Global trends in tuberculosis and Importance of LTBI strategies Jean-Pierre Zellweger Swiss Lung Association
Conflicts of interest I am a retired clinician, former chief of the TB clinic at the University hospital of Lausanne, now working as a part-time consultant for a Swiss NGO (Swiss lung Association) in charge of contact investigations for TB, DOT and TB information in Switzerland I have no conflict of interest in relation with this presentation
Natural history of tuberculosis TB Concentration of M.tbc Duration of exposure + + Immune deficiency Young age Recent infection exposure 25-50% Latent infection 5-10% noeexiosure (LTBI) - - TB No infection Ventilation UV Respiratory protection Preventive treatment Ancient infection Immune defenses
Immunological events after M. tb infection Mack U, Eur Respir J 2009;33:956-73
Some basic principles The development of TB takes place in a minority of infected persons, usually within 2 years after infection Treating all persons with latent infection could in theory eradicate TB by exhausting the pool of future reactivation As only a minority of infected persons will develop TB, and preventive treatment is not easy, it is necessary to select the infected persons at highest risk of reactivation
TB elimination: old and new principles Early detection and adequate treatment of patients with active TB remains the key activity for the control of transmission within the local population Detection of persons with latent infection (LTBI) and preventive treatment of infected persons can contribute to the control of TB in a population
TB elimination: old and new principles Screening for LTBI must target the groups with the highest likelihood of infection: Contact of contagious TB Persons originating from high-incidence regions Preventive treatment must be offered in priority to the infected persons with the highest risk of reactivation: Immunodepressed persons Recent contacts Children
How frequent is LTBI? The old wisdom «One third of the world population is infected with M.tb» (WHO) is based on evaluations with tuberculin skin tests The available estimates (based on IGRAs) vary: 0.6% in young healthy adults born in US 1 8% in elderly adults in UK 2 13-20% in rural China 3 27-50% among TB contacts 4 49% in exposed health care workers in Russia 5 1 Mazurek, CID 2007;45:826 2 Hinks, BMC Inf Dis 2012;12:339 3 Gao, Lancet Inf Dis 2015;15:310 4 Zellweger, AJRCCM 2015;191: DOI.1164/rccm.201502-0232OC 5 Drobniewski, PLoS Medicine, 2007;4(2)e55
Key steps in the management of LTBI
Screening for LTBI: current position of WHO for countries with limited income and/or high incidence of TB Preventive therapy should be offered to people living with HIV and children <5 years in close contact with TB (after exclusion of active TB). Prior testing optional
Screening for LTBI: current position of WHO for high-income countries with low incidence of TB Systematic screening and preventive treatment recommended for : People living with HIV or under anti-tnf Recent contacts of pulmonary TB Immunodeficiency from other origin (organ transplantation, renal dialysis, silicosis) Screening and treatment of LTBI is optional for: Health-care workers exposed to TB Migrants from high-incidence countries Prisoners, homeless persons, users of illicit drugs Active TB has to be excluded before initiation of a preventive treatment
Transmission of TB among contacts??????
Fox, GF et al, Eur Respir J 2013;41:140-56
Development of TB after contact
Risk of TB in PLHIV Alene, KA. BMC Infect Dis 2013;13:292
Developement of TB by age category
TB risk/100 000 untreated contacts 12000 10000 8000 6000 4000 0-4 mm 5-9 mm 10-14 mm + 15 mm 2000 0 close non close casual Moran-Mendoza O, IJTLD 2007;11(9):1014-20
TST size and risk of TB in contacts 180 160 140 120 100 80 60 40 20 0 0-4 5-9 10-14 15+ household close casual 0-10 years Moran-Mendoza O, IJTLD 2007;11(9):1014-20
Additional risk of tuberculosis after infection Erkens J ERJ 2010
TB within 2 years after contact 601 contacts S+ PTB 1 TB* (*IGRA +) 358 TST neg 243 TST >5mm (40%) 5 TB (2.3%) 535 IGRA neg 66 IGRA pos (11%) 0 TB 25 prevent ttt 41 no prevent ttt Diel R, AJRCCM 2008 0 TB 6 TB (14.6%)
LTBI and TB among contacts of pulmonary TB American Journal of Respiratory and Critical Care Medicine Volume 191 Number 10 May 15 2015 European multicentric study (26 Centers in 10 countries) Follow-up during 2 years of all contacts tested with IGRAs
Tbnet study: LTBI and TB in TB contacts 1023 index cases 5020 contacts tested with IGRA 27.2% positive IGRA 4513 contacts with follow-up (89.9%) 49 TB cases among contacts 25 within 81 d after notification of index case (=prevalent) 24 after 81 d (=incident)
% Proportion of contacts with positive IGRA, by origin, age and type of contact 60 50 40 50 37 34 43 40 45 30 20 24 24 23 26 29 21 15 10 0 origin age type of contact Africa America Asia Europe
Risk of TB in contacts within 2 years, by test results and preventive therapy (PT) 1.4 1.2 1.2 1 0.8 0.8 0.6 0.4 0.2 0 0.05 0.23 0.11 0 0 ELISA ELISPOT 0 neg neg PT pos pos PT
American Journal of Respiratory and Critical Care Medicine Volume 191 Number 10 May 15 2015
Migrants in 1880: German socialists, russian anarchists, english convicts and other European poor entering in US. «Baggage the only requisite»
Screening for TB on Ellis Island, New York: the big staircase and the «cough test»
M. Sestini, World Press Photo Award 2014
Screening for TB in migrants Before entry (pre-immigration screening) At the border (port-of-entry screening) At the border (in refugee centers) Within the country (community level, for accepted migrants) Within the country (passive screening)
Screening for active TB
Screening for active TB - questionnaire
Screening by risk factors a) health questionnaire b) contacts c) origin
TB screening at the Swiss border: comparison of two systems Schneeberger Geisler, S. IJTLD 2010;14(11):1388-94
www.tb-screen.ch
Recent TB transmission and LTBI reactivation Ricks, PM, PLoS 2011; 6(11):e27405
Delay between entry in Switzerland and TB notification (833 non-swiss patients, 2009-12) Median delay: 3.02 years Asylum seekers (331 cases): 1.26 year Source: OFSP
Number of TB cases notified among asylum seekers, by years and duration of stay in CH 200 180 160 140 120 100 80 60 40 20 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 <90 days >90 days unknown Source: BAG/OFSP
LTBI in migrants The majority of TB cases notified in western countries are observed among foreign-born Screening at the border detects the currently active cases Most of the TB cases are notified AFTER the entry in the country, by reactivation from prior infection Would screening for LTBI and provision of preventive treatment decrease the risk of later reactivation?
Screening for «silent travelers»?
Proportion of migrants with latent TB infection Pareek M, Lancet Inf Dis 2011;11(6):435
Origin of migrants with a positive IGRA
TB incidence within 2 years after entry in 1468 migrants, by IGRA result and incidence in the country of origin 700 600 500 400 300 200 Incidence: <100 100-199 200+ 100 0 QFT pos (20%): infectés QFT neg (80%) (non infectés) Mulder C, ERS 2012;40:1443,
Risk of LTBI by travel conditions (400 migrants)
Cost-effectiveness of screening migrants for LTBI Screening migrants for LTBI is cost-effective if They come from a high-incidence country They are young A preventive treatment is offered and followed IGRA is the most cost-effective screening method Ref: Zammarchi L et al, BMC health service research 2015;15:412
Screening practice for LTBI in migrants Pareek M, Emerg Infect Dis 2012
Positive IGRA and risk of TB in recent migrants (UK) Screening 4511 IGRA + 1092 (24%) IGRA 3419 (76%) TB 21 LTBI 1071 TB 4 (0.01%) Prev Ther 600 No Prev Ther 471 TB 2 (0.33%) TB 3.18%) Gill, AL, ERS 2014 abstract
Cases of TB averted by LTBI screening
Screening migrants for LTBI: some problems Which migrants: asylum seekers? Foreign travelers? Undocumented migrants? Screening tool: TST vs IGRA? Follow-up: medical examination and preventive treatemnt
TB in undocumented migrants 5% of all TB cases in Belgium 7% of all TB cases in the Netherlands 7.5% of all TB cases in Geneva (CH) >10% of all TB cases in Austria
TB notification and screening in Malta Pace-Asciak A. IJTLD 2013;17(8):1065-70
Screening migrants with TST and IGRA (Norway) Winje BA, BMC Infect Dis 2008; 8:65
Is preventive treatment of migrants with LTBI possible? Young, healthy adults without symptoms Other competing priorities Duration of stay unknown Administrative, legal, financial obstacles Frequent changes in residence, unknown residence Difficult communication Cultural obstacles, representation of health and disease Structure of the local health services
Preventive treatment completion Hirsch-Moverman Y, IJTLD 2015;19(1):31-8
LTBI and completion of preventive treatment in migrant children (US) Taylor EM, J Immigr Min Health 2015;doi 10.1007/s10903-015-0273-2
Completion of preventive treatment in a group of migrants Sarivalasis, A. Swiss Medical Weekly 2013;143:w13860
Some further problems Preventive treatment of contacts of MDR-TB Is possible and cost-effective, at least in contacts of MDR-TB cases who retained quinolone sensitivity
Preventive treatment of MDR-TB contacts Bamrah,S., IJTLD 2014;18(8):912-8
Conclusions Screening for LTBI in groups with high rate of infection and preventive treatment may contribute to the control of TB TB in industrialized countries is mainly observed among foreign-born migrants Screening migrants for active disease detects a minority of (active) cases The majority of cases of TB in migrants are detected after entry by reactivation from LTBI Screening for LTBI and provision of a preventive treatment may decrease the number of future cases Prescription of preventive treatment is difficult, but not impossible (the shorter the better!)
Thank you and open the eye
The challenge Who is at risk of infection (in case of contact)? Who is at risk of TB (if infected)? How to detect persons with an increased risk of developing TB after infection? How to prevent the development of future TB (without treating unnecessarily those who have no risk)?
TB after pre-immigration screening
Risk of TB after entry in Australia
Incidence of tuberculosis after arrival among migrants to Canada, by origin 1800 1600 1540 1400 1200 1120 1000 800 710 600 400 200 0 128 35 76 65 17 17 80 240 8 47 133 179 36 53 284 overall rate first year 1-5 years after 5 years Greenaway C., Can Med Ass J 2010;doi:10.1503/cmaj.090302
Incidence of TB among migrants after entry in Canada, by incidence in the country of origin Langlois-Klassen D, Eur Respir J 2011;38:895
TB notification among undocumented migrants to Malta