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TB IN DENMARK AND EUROPE

VERSUS

HIGH BURDEN COUNTRIES

STOCKHOLM, SEP 1ST 2015

Troels Lillebaek

Director, Consultant, DMSc, DTM&H

International Reference Laboratory of Mycobacteriology / WHO TB Supranational Reference Laboratory Copenhagen

Statens Serum Institut, Denmark

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ESTIMATED TB INCIDENCE 2013, WHO

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WORLD´S HIGHEST INCIDENCES / 100,000

Top 10 1. Swaziland 1,327 2. South Africa 993 3. Namibia 723 4. Sierra Leone 723 5. Lesotho 632 6. Djibouti 620 7. Zimbabwe 603 8. Mozambique 548 9. Gabon 450 10. Zambia 444 tll@ssi.dk

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ASIA´S HIGHEST INCIDENCES / 100,000

1. Swaziland 1,327 2. South Africa 993 3. Namibia 723 4. Sierra Leone 723 5. Lesotho 632 6. Djibouti 620 7. Zimbabwe 603 8. Mozambique 548 9. Gabon 450 10. Zambia 444 11. Cambodia 424 tll@ssi.dk

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AMERICAS' HIGHEST INCIDENCES / 100,000

> 100 / 100,000 Haiti 222 Bolivia 131 Guyana 110 Peru 101 tll@ssi.dk

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EUROPE'S HIGHEST INCIDENCES / 100,000

> 100 / 100,000 Tajikistan 193 Moldova 161 Kazakhstan 129 Kyrgyzstan 128 Azerbaijan 113 Romania 101 Uzbekistan 101 tll@ssi.dk

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HIV IN TB CASES 2013, WHO

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NOS. MDR-TB CASES 2013, WHO

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PERSPECTIVE

The burden of TB is highest in

Asia and Africa1

95% new cases and 98% deaths occur in developing nations

22 high burden countries account for over 80% of the world’s TB cases.

Worldwide, only 4.4% of

estimated TB cases occurred in

the European Region2

1http://www.who.int/tb/publications/global_report/2009/en/

2

http://www.euro.who.int/en/what-we-do/health-

topics/communicable-

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TRUE PICTURE?

Danmark / Europe

World

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” 'I'VE GOT NOTHING TO DO TODAY BUT SMILE”

SIMON AND GARFUNKEL

Mortality (½ x incidence)

Incidence

Emerging Infectious Diseases 2002; 8:679-684.

Historical background [danish]: DK

er et af de lande i verden, som har den ældste og mest omfattende

TB-registrering. Der findes statistik over TB-mortalitet i danske byer helt tilbage fra 1876. I retsakt af 1897 blev danske læger pålagt at anmelde "svindsot", og i lov af 14. april 1905 blev TB i lunger og strubehoved anmeldelsespligtig. Siden 1921 har TB-data været samlet i et landsomfattende register. Endelig, i 1951, blev der indført anmeldelsespligt for alle former for TB. I Nationalt

Referencelaboratorium for TB & Mykobakterier på SSI er der således gode forudsætninger for at forske i tuberkulose (TB) og non-tuberkuløse mykobakterier (NTM). Ikke mindst da laboratoriet har diagnosticeret

mykobakterier i mere end 100 år.

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SCREENING FOR TB BY SPUTUM CULTURE

IN HIGH-RISK GROUPS IN COPENHAGEN, DK

SEP 2012 JUN 2014 7 x screening

11 locations where socially marginalized people gather in Copenhagen

“Spot sputum for MIC + CULT

1075 screened 36 TB cases = 3,3% 2,2% found in 1st round 97% CULT+ 19% MIC+ 57% PCR+ 78% Xray+

Copenhagen near the church ”Vor frelser Kirke”

Jensen SG et al. Screening for tuberculosis by sputum culture in high-risk groups in Copenhagen, Denmark: a novel and

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SCREENING MED SPOT DYRKNING BLANDT

SOCIALT UDSATTE, KØBENHAVNSOMRÅDET

Fig 1: Participants screened in screening round 1-7: total, new, repeat and TB cases identified.

Screened population n=1075 TB cases identified n=36 Age, years* 45.5 (SD 11.2) 46.7 (SD 10.0) Sex Male 765 (71.2 %) 28 (77.8%) Female 310 (28.8 %) 8 (22.2%) Ethnicity Danish 6 (16.7 %) Greenlandic 26 (72.2 %) Other - TB high incidence 2 (5.6 %) Other - TB low incidence 2 (5.6 %) Homeless 23 (63.9 %) Substance abuse Alcohol** 23 (63.9%)

Cannabis** 19 (52.8 %) Drugs** 4 (11.1 %) None 8 (22.2 %) One 12 (33.3 %) Two or more 16 (44.4 %) Previous TB 6 (16.7 %) HIV infection*** 0 (0.0 %)

*Age at first screening (screened population) and at diagnosis (TB cases) **Abuse of more than one substance could be reported.

*** HIV-test at time of TB diagnosis

Jensen SG et al. Screening for tuberculosis by sputum culture in high-risk groups in Copenhagen, Denmark: a novel and

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DANISH GENOTYPING DATA

N = 776 persons Male = 74% (n=572) Danish-born = 81% (n=631) Greenlandic-born = 15% (n=113) - Pulmonary-TB = 88% - AFB+ = 74%

Many socially deprived persons with records of;

- Homelessness

- Alcohol or drug abuse

- Unemployment

- Psykiatric problems

N = 7,000

Ugeskr Laeger 2012;174(44):2696-701 (oversigt kilder)

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A

C

B

Figure S2. Cases with

Mycobacterium tuberculosis

“C2/1112-15” genotype among Greenlanders in Denmark during 20 years, from 1992 through 2011, by geographical location. Many cases are located in central Copenhagen, as indicated by the largest circles in Figures 3A+C, and located in the city of Aalborg, as indicated by the largest circle in Figure 3B. The sizes of the circles are proportional to the number of cases observed.

STAMME C2/1112-15

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“SOMETHING IS ROTTEN IN THE STATE OF DENMARK” WILLIAM SHAKESPEARE Mortality (½ x incidence) Incidence • 430/100,000 Greenlanders in Denmark = equals

Zambia (no. 10 in the world)

3% TB in Danish risk groups = equals?

203/100,000 Greenlanders in Greenland = equals Tajikistan (no. 1 in Europe)

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TB IN LOW-ENDEMIC HIGH-INCOME DK

Immigrants from TB high-burden

areas

- Imported cases & reactivation

disease

- Low rates of active

transmission

Marginalized Danes & Greenlanders

- Extraordinary high rates of

active MT transmission Elderly Danes

- Reactivation disease

- Low rates of transmission

TB risk groups Denmark / Europe

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TB AGE GROUPS – NORDIC COUNTRIES

DK

N

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“SOMETHING IS ROTTEN IN THE STATE KINGDOM …”

WILLIAM SHAKESPEARE

Notification rate 1977-2012 in East Greenland, as number of notifications of tuberculosis (TB) per 100.000 inhabitants

tll@ssi.dk

Bjorn-Mortensen et al. Tuberculosis outbreak in East Greenland. Groups at risk in an isolated arctic setting. ERJ 2015 [in press].

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“SOMETHING IS ROTTEN IN THE STATE KINGDOM …”

WILLIAM SHAKESPEARE

Table 2: Incidence rates (IR) and incidence rate ratios (IRR) of TB per 100.000 person-years (PY) in East Greenland from 2008-2012 according to calendar year, gender and age at diagnosis.

Settlement of Kuummiut

Remaining East Greenland

N PY IR (95% CI) N PY IR (95% CI) IRR (95% CI) p-value1

Total 28 1668 1730 (1195-2506) 99 15360 704 (577-859) 2.48 (1.60-3.85) Year 0.1073 2008 1 351 286 (40-2029) 6 3168 197 (88-437) 1.20 (0.14-10.00) 2009 5 346 1479 (616-3554) 7 3136 210 (94-468) 7.94 (2.28-27.67) 2010 8 333 2463 (1232-4926) 21 3085 733 (473-1136) 3.71 (1.57-8.79) 2011 6 322 1944 (873-4327) 42 3013 1604 (1185-2170) 1.17 (0.49-2.80) 2012 8 313 2695 (1348-5388) 23 2958 911 (605-1371) 3.17 (1.34-7.52) Gender 0.4476 Male 13 873 1528 (887-2632) 56 7885 794 (611-1032) 2.10 (1.12-3.94) Female 15 794 1954 (1178-3241) 43 7474 610 (449-828) 2.95 (1.60-5.46) Age at diagnosis 0.0957 0-12 years - 380 - 3 3631 90 (29-280) 0.00 (0.00) 13-19 years 18 251 7389 (4656-11729) 39 2056 2210 (1614-3024) 4.08 (2.28-7.31) 20+ years 10 1036 1000 (538-1858) 57 9671 633 (486-824) 1.49 (0.74-3.00)

1Test for interaction of calendar year, gender and age at diagnosis with the effect of location.

Bjorn-Mortensen et al. Tuberculosis outbreak in East Greenland. Groups at risk in an isolated arctic setting. ERJ 2015 [in press].

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ESTIMATED TB INCIDENCE, WHO

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ROTTEN IN OTHER KINGDOMS?

Source: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20726

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LONDON “THE TB CAPITAL OF EUROPE”

Increase in nos. cases by nearly 50% since 1999 Especially, in deprived boroughs

Poor housing, inadequate ventilation, and overcrowding - conditions compared to “Victorian Britain” Poor housing conditions in Victorian London tll@ssi.dk

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OTHER LOW ENDEMIC COUNTRIES

London stabilized at 44 / 100,000 Now, urban areas outside London at 28 / 100,000

- Younger age distribution, long time in UK

Increase in many European countries

Especially urban areas

Concentrated in high-risk groups, e.g. migrants, refugees, homeless people, drug users, prisoners, and HIV-infected groups

In some areas complicated with high levels of drug-resistance.

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TB IN DENMARK AND EUROPE VERSUS

HIGH BURDEN COUNTRIES

TB-patient South-Eastern Sudan Resources?

TB-patient Denmark

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THE WHITE PLAGUE HAS RETURNED

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PATIENTER, XDR-TB

Case 1, RS (Vejle), Mand, f. 1973, Republikken Ingusjien, Rusland

MIK +++ (!)

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PATIENTER, XDR-TB

Case 2, RN (Aalborg), Mand, f. 1967, Republikken Ingusjien, Rusland

MIK +++ (!)

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IT IS NOT ROCKET SCIENCE

Passive case finding

Active case finding Contact tracing

Screening programs

In combination with treatment of latent infection

Think resistance…

Improve living conditions for the poorest

- We can afford it

- We cannot defend not doing it

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Figure

Fig 1: Participants screened in screening round 1-7:
Figure S2. Cases with  Mycobacterium tuberculosis
Table 2: Incidence rates (IR) and incidence rate ratios (IRR) of TB per 100.000 person-years (PY)  in East Greenland from 2008-2012 according to calendar year, gender and age at diagnosis

References

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