TUBERCULOSIS IN GREECE
M. Samarkos
INTRODUCTION
Tuberculosis
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Tuberculosis – Infection by Mycobacterium tuberculosis
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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
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Conditions such as HIV, immunosuppression etc increase the probability of
post-primary infection
Treatment: Combination of antituberculous drugs for >6 months.
Drug resistant tuberculosis
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M. tuberculosis may develop resistance to anti-TB drugs
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Multi Drug Resistant TB
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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
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
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The number of new cases and relapses in a given
population over a time period (usually one year)
 Low:
<20 (25) cases/100.000 population
 High: >20 (25) cases/100.000 population
Definitions
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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 2011 - WHO
Global trends in estimated rates of TB incidence and mortality
Global Tuberculosis Control 2011 - 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, 2000–2009
Tuberculosis surveillance in Europe 2009, ECDC
Tuberculosis cases, notification rates per 100 000 population
and mean annual change in rates, European Region, 2005–2009
Greece: 582 cases, 5,2/100.000, -6,7%
Romania: 23267 cases, 108,2/100.000,
Subtotal EU/EEA: 79,665 cases, 15,8/100.000, -5,8%
Tuberculosis surveillance in Europe 2009, ECDC
Percentage of notified TB cases of foreign origin, Europe, 2009a
Tuberculosis surveillance in Europe 2009, ECDC
Résumé
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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 2004-2009
Total notifications
HCDPC
TB incidence in Greece 1995-2009
Laboratory confirmed cases
National Reference Laboratory for Mycobacteria
Euro Surveill. 2010;15(28):pii=19614
Age distribution of notifications in Greece,
2004-2009
ΚΕΕΛΠΝΟ
Frequency of notifications according to previous treatment
status
ΚΕΕΛΠΝΟ
Drug susceptibility testing data and tuberculosis resistance phenotypes rates,
Greece, 1995-2009
Euro Surveill. 2010;15(28):pii=19614
Percentage of multidrug resistance, Greeks versus immigrants/foreign-born,
Greece, 1995-2009
Euro Surveill. 2010;15(28):pii=19614
How reliable are our data ?
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“…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, 2004-2009
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Retrospective study for the period 2000-2003
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
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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
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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
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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
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Tuberculosis in immigrants
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Foreign-born individuals have increased risk of TB for up
to 20 years after migration
 The
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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 ?
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Influence on TB epidemiology of the host country
 UK,
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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
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USA: On a State level there was no correlation between
TB incidence in US-born and foreign-born persons
(1986-1993)
San Francisco: <2% of US-born TB cases were
transmitted from foreign-born TB patients (1991-1995)
Norway: Imported TB had little influence on the
transmission of M tuberculosis in the receiving lowincidence country (1994-2005)
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
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Rhode Island, USA: TB transmission between the foreignborn 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 ?
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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 ?
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Early diagnosis and case finding
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Effective treatment
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Ensure access to health-care for all immigrants
Ensure follow-up
DOTS
Preventive therapy
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Develop specific strategies for immigrants
Screening for latent infection
Infection control
Surveillance and response
Screening services in Europe
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Screening units:
 Units
within hospital facilities
 Municipal Health Service
 Units in transit camps
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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
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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?
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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
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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
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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
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Tuberculosis screening: Cost
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Canada: permanent resident applicants screening for TB with
CXR
12,898 screened – 17 TB cases detected ( incidence
131/100,000)
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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
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Sputum culture using one specimen was marginally more cost-effective
than CXR
Screening in Greece
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Immigrants are not regularly screened for TB
A Health Clearance Certificate is required for immigrants applying
for work/residence/study permit
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Screening data from Heraclion, Crete:
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Chest X-ray is a requirement
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
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Designed in the context of the Global Plan to Stop TB (WHO)
Part of the National Action Plan for Communicable Diseases 2008-12
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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
4.059.566 € have been allocated for the period 2008-2012.
http://www2.keelpno.gr/blog/?p=681
Résumé
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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
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Little is known regarding demography and TB epidemiology
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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
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Undocumented immigrants
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Increased risk of becoming infected
Overcrowded travel
 Poor housing and working conditions in the country of relocation
 Inadequate nutrition and stressful living conditions
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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
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Health authorities and/or health staff should ensure easy access to lowthreshold 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 Dis 2008;12:878
FUTURE PROSPECTS
Future control strategies
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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
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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 tuberculosisrelated 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
http://www.who.int/tb/strategy/en/index.html