M. Samarkos TUBERCULOSIS IN GREECE

INTRODUCTION

Tuberculosis  Tuberculosis – Infection by Mycobacterium tuberculosis  Primary infection: at a young age, most of the times asymptomatic  Latent infection: no signs, symptoms or other findings of active disease. It follows untreated primary infection  Post-primary infection (Reactivation): It occurs years after primary infection, in 5-10% of exposed persons Conditions such as HIV, immunosuppression etc increase the probability of post-primary infection  Treatment: Combination of antituberculous drugs for >6 months.

Drug resistant tuberculosis  M. tuberculosis may develop resistance to anti-TB drugs  Multi Drug Resistant TB (MDR-TB): Resistance to INH + RIF  Extensively Drug Resistant TB (XDR-TB): Resistance to INH + RIF + Quinolones + One Injectable second line drug  Multi Drug Resistant TB  More difficult to treat  More frequent relapses  Increased mortality  Increased health-care cost (10x – 100x)  MDR-TB usually due to incomplete therapy or non-compliance

Tuberculosis incidence  The number of new cases and relapses in a given population over a time period (usually one year)  Low: <20 (25) cases/ population  High: >20 (25) cases/ population

Definitions  Migrant: a foreigner legally admitted and expected to settle in a host country.  Asylum seeker: a person wishing to be admitted to a country as a refugee and awaiting decision on their application for refugee status under relevant international instruments.  Foreign-born citizen: a person who is a national of the state in which they are present but who was born in another country.  Illegal or undocumented foreigner/migrant: a person whose entry, stay or work in a host country is illegal.  In this presentation the term “immigrant” includes all of the above

THE SIZE OF THE PROBLEM

Estimated TB incidence rates, 2010 Global Tuberculosis Control WHO

Global trends in estimated rates of TB incidence and mortality Global Tuberculosis Control WHO

Total TB notification rates/100,000 population – Europe 2009 Tuberculosis surveillance in Europe 2009, ECDC

Total TB notifications by previous treatment history and total TB case rates, Europe, 2000–200 9 Tuberculosis surveillance in Europe 2009, ECDC

Tuberculosis cases, notification rates per population and mean annual change in rates, European Region, 2005–2009 Greece: 582 cases, 5,2/ , -6,7% Romania: cases, 108,2/ , Subtotal EU/EEA: 79,665 cases, 15,8/ , -5,8% Tuberculosis surveillance in Europe 2009, ECDC

Percentage of notified TB cases of foreign origin, Europe, 2009a

Résumé  The incidence of TB in Europe is declining  In many countries (especially of the Eastern Europe) the incidence remains high  In the Scandinavian countries TB incidence is increasing  In Western Europe a significant proportion of cases (>20%) are from immigrants  In certain countries (UK, Netherlands, Sweden, Norway, Denmark, Cyprus) the majority of cases are from immigrants  In these countries the epidemiology of TB has been significantly affected by migration

DATA FOR GREECE

TB incidence in Greece Total notifications HCDPC

TB incidence in Greece Laboratory confirmed cases National Reference Laboratory for Mycobacteria Euro Surveill. 2010;15(28):pii=19614

Age distribution of notifications in Greece, ΚΕΕΛΠΝΟ

Frequency of notifications according to previous treatment status ΚΕΕΛΠΝΟ

Drug susceptibility testing data and tuberculosis resistance phenotypes rates, Greece, Euro Surveil l. 2010;15(28):pii=19614

Percentage of multidrug resistance, Greeks versus immigrants/foreign-born, Greece, Euro Surveill. 2010;15(28):pii=19614

How reliable are our data ?  “…It has to be noted however that studies estimating the number of new cases of TB using antituberculous drug consumption, suggest that there is significant underreporting of TB cases …” HCDCP (ΚΕΕΛΠΝΟ): Epidemiological data for TB in Greece,

 Retrospective study for the period  Cross-check of data from 3 Prefectural Public Health Directorates (PHD), Patras University Hospital and South-West Greece Hospital for Pulmonary Disease and Hellenic Centre for Disease Control and Prevention (HCDCP)  186 cases of TB were diagnosed in the two hospitals: 72 (38.7%) were notified to PHDs  161 TB notifications to the three PHDs (from all hospitals of the area): 112 (70%) were notified to HCDCP  Notified TB cases incidence: 3.8/100,000  Actual TB cases incidence: 9.5/100,000 Euro Surveill. 2009;14(11):pii=19152

Résumé  Notified cases TB incidence in Greece is low.  TB incidence in Greek natives is declining.  Absolute number of TB cases in immigrants tends to overcome the respective number in Greeks.  There is a significant proportion of resistance to anti-TB drugs and a small percentage of MDR (5-8%)  There is evidence of substantial underreporting of tuberculosis cases to public health authorities

TUBERCULOSIS IN IMMIGRANTS

Tuberculosis in immigrants  High incidence of TB in immigrants reflects the higher risk of exposure in their countries of origin.  Other factors may play a role  Conditions of migration  Living conditions in the host country  HIV incidence in the country of origin  High incidence of MDR/XDR-TB in immigrants  High incidence of resistance in countries of origin  Incomplete treatment in country of origin or host country

Tuberculosis in immigrants  Foreign-born individuals have increased risk of TB for up to 20 years after migration  The impact on TB epidemiology is long-term  The rate of conversion of latent to active TB is similar in the foreign-born and native populations.  Screening programs on arrival have low yield

TB in immigrants – why is it important ?  Influence on TB epidemiology of the host country  UK, Scandinavian countries  Need for more health-care resources  Risk of transmission of TB to native population ?  MDR disease

Risk of transmission of TB to native population - Data  USA: On a State level there was no correlation between TB incidence in US-born and foreign-born persons ( )  San Francisco: <2% of US-born TB cases were transmitted from foreign-born TB patients ( )  Norway: Imported TB had little influence on the transmission of M tuberculosis in the receiving low- incidence country ( ) N Engl J Med 2005;332:1071, Am J Respir Crit Care Med 1998;158:1797, Am J Respir Crit Care Med 2007;176:930

Risk of transmission of TB to native population - Data  Rhode Island, USA: TB transmission between the foreign- born and US-born population should not be neglected.  Germany: there is no significant TB transmission from TB high-prevalence immigrant autochthonous population.  Barcelona: Recent TB transmission among Spanish-born and foreign-born populations contributed significantly to the burden of TB in Barcelona  Italy: The overall impact of imported TB on public health in the low-incidence study area is relatively modest J Clin Microbiol 2011;49:834, BMC Infect Dis. 2009;9:197, CMI 2010;16:568, CMI 2010;16:1091

Risk of transmission of TB to native population – Conclusion ?  Numerous studies on the subject.  Conflicting data among studies.  More recent studies have used molecular tools to dissect the epidemiology of TB.  Some of the studies suggest that the risk of TB transmission among natives and immigrants should not be neglected.

SOLUTIONS TO THE PROBLEM

How to confront the problem ?  Early diagnosis and case finding  Develop specific strategies for immigrants  Effective treatment  Ensure access to health-care for all immigrants  Ensure follow-up  DOTS  Preventive therapy  Screening for latent infection  Infection control  Surveillance and response

Screening services in Europe  Screening units:  Units within hospital facilities  Municipal Health Service  Units in transit camps  Screening modalities  Universal use of TST in children, varying in adults  Chest x-ray in almost all studied sites One site required symptoms or TST(+) to order CXR Eur Respir J 2006;27:801

TB Screening strategies  Pre-entry / pre-migration screening  Port of arrival screening  Reception / holding / transit centre screening  Community post-arrival screening  Occasional screening  Follow-up screening

What is the best screening strategy?  Systematic review in the EU/EEA  Yield and coverage were used as indicators of screening strategy effectiveness  Median yield: 0.185% (IQR 0.10 – 0.35%)  No difference between three main strategies Port of arrival screening Reception/holding centers screening Community screening Eur Respir J 2009;34:1180

Tuberculosis screening: Problems  Screening programs using CXR  Low yield for active TB cases  Higher yield for latent TB cases  High rate of false positives  High negative predictive value  Screening programs operate on arrival  The impact of initial screening on TB epidemiology is low  TB cases in immigrants continue to accumulate in subsequent years

Tuberculosis screening: Cost  Canada: permanent resident applicants screening for TB with CXR  12,898 screened – 17 TB cases detected ( incidence 131/100,000)  Cost of detection and treatment through the screening program: 31,418 Canadian $ per case  Cost of passive diagnosis and treatment: 11,090 Canadian $ per case  Estimated cost of other screening modalities (TST, sputum culture, PCR) per TB case detected were higher than that of CXR  Sputum culture using one specimen was marginally more cost-effective than CXR

Screening in Greece  Immigrants are not regularly screened for TB  A Health Clearance Certificate is required for immigrants applying for work/residence/study permit  Chest X-ray is a requirement  Screening data from Heraclion, Crete:  1872 immigrants applying for work permit underwent chest X-ray  Only 4 had significant findings  No case of TB was detected  Occasional screening of immigrants applying for residence permit with TST – Data ? Int J Tuberc Lung Dis. 2005;9:865

National Tuberculosis Control Program  Designed in the context of the Global Plan to Stop TB (WHO)  Part of the National Action Plan for Communicable Diseases  Compulsory hospitalization or home restriction of active TB patients  Free health care for all patients with TB including undocumented immigrants (including TB medications)  Postponement of deportation of patient with active TB  Measures to improve reporting of TB cases  Controlled prescription of anti-TB drugs  Staffing of TB Clinics  MDR-TB Clinics exclusively responsible for MDR cases  € have been allocated for the period

Résumé  TB screening programs in immigrants have low yield and are not cost-effective  TB screening programs operate on arrival, therefore they miss TB cases accumulating in subsequent years  In Greece screening is associated with Work/Residence permit application  A National Tuberculosis Control Program awaits to be fully implemented

UNDOCUMENTED IMMIGRANTS

Undocumented immigrants – a difficult case  Little is known regarding demography and TB epidemiology  Netherlands 2002: 7% of TB patients were undocumented immigrant  Diagnosed with TB at a later stage, with a higher proportion of positive sputum smear and culture  Fear to be arrested  Inability to pay for health care when required  Unaware of their right to health coverage

Undocumented immigrants  Increased risk of becoming infected  Overcrowded travel  Poor housing and working conditions in the country of relocation  Inadequate nutrition and stressful living conditions  Wide disparities among countries regarding access of undocumented immigrants to health care, right to medication, legal framework regarding deportation procedure.

Working Group on Transborder Migration and TB of the International Union Against TB and Lung Disease Recommendations for TB in Undocumented Immigrants  Health authorities and/or health staff should ensure easy access to low- threshold facilities where undocumented migrants who are TB suspects can be diagnosed and treated without giving their names and without fear of being reported to the police or migration officials. Health authorities should remind health staff that they have an obligation of confidentiality.  Each country should ensure that undocumented migrants with TB are not deported until completion of treatment.  Authorities and non-governmental sectors should raise awareness among undocumented migrants about TB, emphasising that diagnosis and treatment should be free of charge and wholly independent of migratory status. Int J Tuberc Lung D is 2008;12:878

FUTURE PROSPECTS

Future control strategies  Data suggest that screening immigrants for TB is a low-yield and expensive TB control strategy  A more effective use of resources may be comprehensive contact tracing within foreign-born communities or use of Interferon-gamma Release Assays for screening.  The ideal long-term TB control strategy would be global investment to improve tuberculosis control in high-incidence countries Thorax 2010;65:178

Domestic Returns from Investment in the Control of Tuberculosis in Other Countries  Radiographic screening of legal immigrants plus current tuberculosis-control programs  Addition of either U.S.-funded expansion of the strategy of DOTS in Mexico or TST to screen legal immigrants from Mexico.  U.S.-funded efforts to expand the DOTS program in Mexico, Haiti, and the Dominican Republic could reduce tuberculosis- related morbidity and mortality among migrants to the United States, producing net cost savings for the United States N Engl J Med 2005;353:1008

Net Savings or Added Costs of Implementing a Strategy of Radiographic Screening plus Either Expansion of the DOTS Program or Tuberculin Skin Testing

The six components of the STOP TB STRATEGY 1.Pursue high-quality DOTS expansion and enhancement 2.Address TB-HIV, MDR-TB, and the needs of poor and vulnerable populations 3.Contribute to health system strengthening based on primary health care 4.Engage all care providers 5.Empower people with TB, and communities through partnership 6.Enable and promote research