UCLH Members Event: Tuberculosis

Transcription

1 UCLH Members Event: Tuberculosis 22 nd June 2015 Dave Moore, London School of Hygiene & Tropical Medicine & UCLH Phil Gothard, Hospital for Tropical Diseases, UCLH Al Story, TB Find & Treat Service, UCLH

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4 Thoracoplasty

5 TB Notifications in England & Wales

6 Where did TB come from and why is it going away?

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8 Phthisis was the most considerable of the diseases which then prevailed and the only one which proved fatal to many persons. Hippocrates Book I, Of the Epidemics

9 Pleural adhesions from chronic infection 6-8 year old girl, Thebes, BC

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11 Vac tomb, Hungary, 1808 Mummified body 36 year old man Died after haemorrhage from mouth Microscopic appearance of chest material Strongly PCR+ for M tuberculosis

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14 Human origins and civilisation million y Early Hominids Archaeological record 200,000 y Modern Man Anatomy, Y-c some, mitochondria 50-60,000 y Dispersal East Rapid (1km/y) coastal express Mitochondrial DNA, tool archaeology 20-40,000 y Dispersal North Slow founder effect West from Asia not via the Nile

15 Human origins and civilisation million y Early Hominids Archaeological record 200,000 y Modern Man Anatomy, Y-c some, mitochondria 50-60,000 y Dispersal East Rapid (1km/y) coastal express Mitochondrial DNA, tool archaeology 20-40,000 y Dispersal North Slow founder effect West from Asia not via the Nile

16 Human origins and civilisation million y Early Hominids Archaeological record 200,000 y Modern Man Anatomy, Y-c some, mitochondria 50-60,000 y Dispersal East Rapid (1km/y) coastal express Mitochondrial DNA, tool archaeology 20-40,000 y Dispersal North Slow founder effect West from Asia not via the Nile

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18 Where did M tuberculosis come from? Co-evolution of pre-mtb from soil with early hominids (2-3 million years) Mycobacterium prototuberculosis = Most recent common ancestor Evolutionary bottleneck 20-40,000 y ago Sequence data show it was located in E Africa

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20 Human origins and civilisation Hunter gatherers => bottleneck for highly virulent pathogens Neolithic society (10,000 years ago) => Settled agriculture Denser population Ecological disruption (cultivation) Economic and political inequality Nutritional narrowing

21 Human origins and civilisation Hunter gatherers => bottleneck for highly virulent pathogens Neolithic society (10,000 years ago) => Settled agriculture Denser population Ecological disruption (cultivation) Economic and political inequality Nutritional narrowing

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23 TB caused 1 in 4 of all deaths in C18th and early C19th

24 TB caused 1 in 4 of all deaths in C18th and early C19th

25 Changing incidence: 1850 to 1910 Death rates for tuberculosis per million per annum, left hand scale (dots) and all causes per million, right hand scale (squares), for England and Wales.

26 Changing incidence: 1850 to 1910 TB rates have fallen steadily since 1850 Improvements in social conditions: poverty and overcrowding? Comparison of social factors with tuberculosis and other diseases of poverty (cholera, dysentery, infant mortality) Registrar Generals Annual Reports Mortality statistics: 3 notifiable diseases Census data: housing & size of resident population Statistics: average real earnings

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28 Changing incidence: 1850 to 1910 TB rates have fallen steadily since 1850 Improvements in social conditions: poverty and overcrowding Comparison of social factors with tuberculosis and other diseases of poverty (cholera, dysentery, infant mortality) Registrar Generals Annual Reports Mortality statistics: 3 notifiable diseases Census data: housing & size of resident population Statistics: average real earnings

29 Changing incidence: 1850 to 1910 TB rates have fallen steadily since 1850 Improvements in social conditions: poverty and overcrowding Comparison of social factors with tuberculosis and other diseases of poverty (cholera, dysentery, infant mortality) Registrar General s Annual Reports Mortality stats: 3 notifiable diseases Census data: housing & size of resident population Statistics: average real earnings

30 Changing incidence: 1850 to 1910 Death rates for infants per 1000 live births, left hand scale (dots), and cholera (squares) per million, right hand scale (E&W)

31 Changing incidence: 1850 to 1910

32 Changing incidence: 1850 to 1910 Fall in TB mortality far exceeds improvement in social conditions Why? TB affects young adults, and kills children Reduced fertility of TB-susceptible families Relative increase in TB-resistant population Hypothesis BCG & Rx remove this selective pressure Modern population may be more susceptible No decline in white population incidence (late C20)

33 1825 Elizabeth age Maria age Anne age Emily age Charlotte age 38 Five siblings All died from TB None had children

34 Changing incidence: 1850 to 1910 Fall in TB mortality far exceeds improvement in social conditions Why? TB affects young adults, and kills children Reduced fertility of TB-susceptible families Relative increase in TB-resistant population Hypothesis BCG & Rx remove this selective pressure Modern population may be more susceptible

35 Alternative hypotheses for decline in mortality Thomas McKeown & RG Record (1962) progressive improvement in the standard of living Sir Stanley Woodwark (1938) together with rickets, scuvy and gout disease the influence of diet can clearly be traced Sir Arthur Newsholme (1923) reduced exposure to infection brought about by the segregation of consumptives in Poor Law Infirmaries

36 Alternative hypotheses for decline in mortality Thomas McKeown & RG Record (1962) progressive improvement in the standard of living Sir Stanley Woodwark (1938) together with rickets, scuvy and gouty disease the influence of diet can clearly be traced Sir Arthur Newsholme (1923) reduced exposure to infection brought about by the segregation of consumptives in Poor Law Infirmaries

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38 Alternative hypotheses for decline in mortality Thomas McKeown & RG Record (1962) progressive improvement in the standard of living Sir Stanley Woodwark (1938) together with rickets, scuvy and gout disease the influence of diet can clearly be traced Sir Arthur Newsholme (1923) reduced exposure to infection brought about by the segregation of consumptives in Poor Law Infirmaries

39 Alternative hypotheses for decline in mortality VH Springett (1952) 1) Reduction in number of persons infected ISOLATION (AND VACCINATION) 2) Reduction in number of infected persons developing disease HOST DENFENCE 3) Reduction in those with TB who die from the disease TREATMENT

40 Alternative hypotheses for decline in mortality VH Springett (1952) 1) Reduction in number of persons infected ISOLATION (AND VACCINATION) 2) Reduction in number of infected persons developing disease HOST DEFENCE 3) Reduction in those with TB who die from the disease TREATMENT

41 Alternative hypotheses for decline in mortality New Poor Law (1834) Bentham s Utilitarianism: correct level of poor rate Malthus s doctrine of population growth opposes Old Poor Law

42 Alternative hypotheses for decline in mortality New Poor Law (1834) TB disease of young and productive => destitute No longer allowed to receive alms at home Workhouses admit sick paupers and become public hospitals Workhouse expansion 1860s onwards London 1869: 28,600 inmates 11,000 sick (39%) (cf 4000 general hospital beds)

43 Alternative hypotheses for decline in mortality New Poor Law (1834) TB disease of young and productive => destitute No longer allowed to receive alms at home Workhouses admit sick paupers and become public hospitals Workhouse expansion 1860s onwards London 1869: 28,600 inmates 11,000 sick (39%) (cf 4000 general hospital beds)

44 Old St Pancras workhouse

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46 Alternative hypotheses for decline in mortality 1834 Phase 1 Initial New Poor Law Segregation 1870 Phase 2 Expansion of workhouses Koch s discovery (WW1) 1920 Phase 3 7x expansion in TB beds Sputum microscopy Artificial pnuemothorax => smear negative 1950 Phase 4 Chemotherapy

47 TB in contemporary London

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51 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Empirical 4-drug therapy (eth) Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 98% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Empirical 4-drug therapy (strep) Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

52 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Empirical 4-drug therapy (eth) Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Empirical 4-drug therapy (strep) Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

53 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Empirical 4-drug therapy (eth) Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Empirical 4-drug therapy (strep) Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

54 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Empirical 4-drug therapy (eth) Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Empirical 4-drug therapy (strep) Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

55 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Empirical 4-drug therapy (strep) Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

56 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

57 Rich world 5% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 95% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

58 Rich world 2% of all cases Rare cause of death Treated by doctors / MDT CT imaging common Bronchoscopy if smear negative Extensive microbiology Hospital isolation facilities Enthusiastic contact tracing Completion rates >95% Low drug resistance Targeted DOT in practice HIV co-infection unusual Poor world 98% of all cases Common cause of death Treated by nurses CXR is too expensive Limited sputum microscopy No drug susceptibility testing Overcrowded wards Limited contact tracing Completion rates <75% High drug resistance (expensive) Universal DOTS in theory HIV co-infection common

59 TB in contemporary London 7290 cases 2 nd highest rate in Western Europe 250% increase in MDR since % increase in migrant cases 5% decrease in native cases

60 Number of cases Rate (per 100, 000) Tuberculosis case reports and rates, UK, , , , , , , , , , , Year Number of cases Rate per 100,000 Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 60 Tuberculosis in the UK: 2014 report

61 Number of Cases Rate (per 100,000) Tuberculosis case reports and rates by PHE Centre, England, , ,000 2,500 Number of cases Rate per 100, ,000 1,500 1, PHE Centre Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England Tuberculosis in the UK: 2014 report

62 Three-year average tuberculosis case rates by local area*, UK, *England Local authorities, Wales and Scotland Health Boards, NI Country level London Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 62 Tuberculosis in the UK: 2014 report Crown copyright and database rights 2014 Ordnance Survey

63 Number of cases Rate (per 100,000) Tuberculosis case reports & rates by age group & place of birth, UK, , ,100 1, Age group (years) UK Born Non-UK Born Rate in UK Born Rate in Non-UK Born Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI),Labour Force Survey (LFS) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 63 Tuberculosis in the UK: 2014 report

64 Proportion of TB cases (%) Proportion of TB cases by deprivation quintile residence, England, , , , Most deprived 2nd quintile 3rd quintile 4th quintile Least deprived Deprivation Quintiles Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Index of Multiple Deprivation (IMD 2010) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 64 Tuberculosis in the UK: 2014 report

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66 North Central London TB Service (2014-5): patients by country of birth 160 cases 76% born overseas 49 countries Somalia 14 India 12 Eritrea 11 Bangladesh 6 Pakistan 5 Philippines 5 Turkey 5

67 NCL TB Service: region of birth : 160 patients Africa Asia Americas Middle East Europe UK

68 North Central London TB Service (2014-5): clinical complexity 41 (26%) in hospital 16 (10%) spinal 65 (41%) pulmonary 24 (15%) smear positive 10 (6%) cavities 9 (6%) HIV+ 4 (3%) Isoniazid resistant 1 (0.6%) MDR

69 North Central London TB Service (2014-5): social complexity 15 (9%) not registered with a GP 30 (19%) with adherence risk factors Homeless 18 Drug use 10 Mental Health 9 Prison 8 Alcohol 4 26 (16%) on DOT 42 (26%) enhanced case management

70 Most frequent countries of birth for non-uk born TB cases, UK, 2013 Country of birth Number of cases * Where country of birth was known; **Years Percentage of cases* Median time since entry to UK (IQR)** India 1, (2-13) Pakistan 1, (2-22) Somalia (4-13) Bangladesh (3-18) Nepal (2-6) Nigeria (3-11) Philippines (5-12) Zimbabwe (7-12) Sri Lanka (3-13) Kenya (8-37) Romania (0-4) Afghanistan (2-11) Poland (2-7.5) Eritrea (2-7) China (4-11) Others (each <1%) 1, (1-13) Total* 5, (3-14) Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 70 Tuberculosis in the UK: 2014 report

71 Time between entry to the UK & TB diagnosis for non-uk born TB cases by year, UK, 2013 Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 71 Tuberculosis in the UK: 2014 report

72 Proportion of cases (%) Proportion of TB case reports by site of disease, UK, Year Pulmonary* Extra-pulmonary only * With or without extra-pulmonary disease Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 72 Tuberculosis in the UK: 2014 report

73 Tuberculosis case reports by site of disease, UK, 2013 Site of disease* Number of cases Percentage** Pulmonary 4, Extra-thoracic lymph nodes 1, Unknown extra-pulmonary Intra-thoracic lymph nodes Pleural Other extra-pulmonary Gastrointestinal Bone spine Bone other Miliary ± CNS meningitis Genitourinary CNS other Cryptic Laryngeal *With or without disease at another site **Percentage of cases with known site of disease (8751) ± For Scotland cases, this includes both cryptic and miliary site CNS-Central Nervous System Total percentage exceeds 100% due to infections at more than one site Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 73 Tuberculosis in the UK: 2014 report

74 Proportion of cases (%) Treatment completion at 12 months for drug sensitive TB cases with expected treatment duration <12 months*, UK, Year * Excludes initial and amplified to rifampicin resistant TB and MDR-TB cases and MDR-TB treated cases and those with CNS, spinal, miliary or cryptic disseminated TB Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 74 Tuberculosis in the UK: 2014 report

75 TB outcome at 12 months for drug sensitive TB cases with expected treatment duration <12 months*, UK, 2012 Treatment outcome n % Completed 6, Died Lost to follow-up Still on treatment Stopped Not evaluated** Total 7,774 * Excludes initial and amplified to rifampicin resistant TB and MDR-TB cases and MDR-TB treated cases and those with CNS, spinal, miliary or cryptic disseminated TB ** Not evaluated includes missing, unknown and transferred out Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England 75 Tuberculosis in the UK: 2014 report

76 TB outcome at 24 months for drug resistant cohort, UK, 2011* Treatment outcome n % Completed Died Lost to follow-up Still on treatment Stopped Not evaluated** Total 98 *Excludes initial and amplified to rifampicin resistant TB and MDR-TB cases and MDR-TB treatment cases ** Not evaluated includes missing, unknown and transferred out 76 Tuberculosis in the UK: 2014 report

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