TB, BCG and other things. Chris Conlon Infectious Diseases Oxford

Transcription

1 TB, BCG and other things Chris Conlon Infectious Diseases Oxford

2 Epidemiology Latent TB IGRA BCG

3 >50/ <50/ AFGHANISTAN BANGLADESH BOTSWANA BRUNEI DARUSSALAM BURUNDI CAMEROON CHINA CONGO ERITREA ETHIOPIA GAMBIA GHANA HONG KONG INDIA INDONESIA IRAQ KENYA KOREA, REPUBLIC OF LITHUANIA MALAWI MALAYSIA MYANMAR NEPAL NIGERIA PAKISTAN PHILIPPINES RUSSIAN FEDERATION RWANDA SOMALIA SOUTH AFRICA SRI LANKA SUDAN THAILAND TIMOR-LESTE UGANDA VIETNAM ZAMBIA ZIMBABWE FIJI FRANCE IRELAND ITALY JAMAICA LIBYAN ARAB JAMAHIRIYA MAURITIUS POLAND PORTUGAL PUERTO RICO SAINT HELENA SAUDI ARABIA SINGAPORE TURKEY UNITED STATES

4 Three-year average TB rates by local authority district, England, London Tuberculosis in England: 2015 report Contains Ordnance Survey data Crown copyright and database right Contains National Statistics data Crown copyright and database right Source: Enhanced Tuberculosis Surveillance (ETS), Office for National Statistics (ONS) Data extracted: March Prepared by: TB Section, National Infection Service, Public Health England

5 TB case notifications and rates, England, Number of cases 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1, Rate (per 100, 000) Year Number of cases Rate per 100,000 I 95% CI Tuberculosis in England: 2015 report Source: Enhanced Tuberculosis Surveillance (ETS), Office for National Statistics (ONS) Data extracted: March Prepared by: TB Section, National Infection Service, Public Health England 5

6 TB case notifications and rates by place of birth, England, Number of cases 7,000 6,000 5,000 4,000 3,000 2,000 1, Rate (per 100,000) Year UK born Non-UK born Rate UK born Rate Non-UK born I 95% CI (too narrow to be visible) I 95% CI 0 Tuberculosis in England: 2015 report 6 Source: Enhanced Tuberculosis Surveillance (ETS), Labour Force Survey (LFS) Data extracted: March Prepared by: TB Section, National Infection Service, Public Health England

7 Rate of TB by deprivation decile, England, Rate (per 100,000) Most deprived 10% of population Deprivation decile I 95% CI Least deprived 10% of population Tuberculosis in England: 2015 report 7 Source: Enhanced Tuberculosis Surveillance (ETS), Index of Multiple Deprivation (IMD 2010) Data extracted: March Prepared by: TB Section, National Infection Service, Public Health England

8 MTB Pathogenesis of TB Alveolar macrophage MTB multiplies in cell lymph blood lungs Contains MTB heals Disease increased bacterial load Necrosis (caseation) granuloma T cell activation Macrophage fusion (giant cells)

9 Latent TB versus Active TB Latent TB Common, especially in the tropics May reactivate but most never do Treatment of latent TB reduces risk Active TB Usually results in disease with symptoms Risk of spread to others Case-finding important: reduce transmission

10 Risk of developing TB In people who are tuberculin skin test positive: HIV negative: 10% lifetime risk HIV positive: 10% annual risk 50% of HIV positive people develop TB Major interaction Dual infection increasingly common

11 TB diagnosis Latent TB Evidence of Delayed-type hypersensitivity (DTH) Positive Mantoux test (tuberculin skin test) Disease Uses PPD purified protein derivative Positive IGRA Interferon-gamma release assay More specific and probably more sensitive Microscopy and culture of the organism

12 IGRA vs TST

13 Bacille Calmette-Guerin Modified from Mycobacterium bovis Lots of passages through animals Many different strains in use Immune responses variable Many trials to assess efficacy Most done in bygone era Methods, controls, assessments variable

14 What does M. tuberculosis have that BCG does not? The RD1 genomic segment of M. tuberculosis is absent from all strains of BCG and most environmental mycobacteria

15 Q: What does M. tuberculosis have that BCG doesn t? A: RD1 contains the genes for ESAT6 and CFP10 M. bovis M. tuberculosis RD1 was lost from BCG early on RD1 is present in all strains of M. tuberculosis BCG BCG BCG M. tuberculosis

16 Meta-analysis: BCG trials

17 Protection against TB meningitis and miliary TB

18 Variation in BCG efficacy

19 BCG protection from infection (Trials using IGRA after exposure)

20 Problems remaining with BCG Variable efficacy Best data come from infants and young kids Environmental factors Seems more efficacious at higher latitudes Depends on previous mycobacterial exposure

21 The future Decreasing use in the UK Probably only for those at highest risk Population: infants from high prevalence countries Healthcare: those working in TB clinics / wards Medical students I suspect requirement will drop DNA vaccines: no evidence of effect so far

22 Pragmatic for Medical, Dental and Nursing Students Screen for latent TB at entry Tuberculin or IGRA IGRA probably more cost-effective CXR for any that are positive Refer to TB service locally Majority: Annual questionnaire about symptoms Could be electronic