UCLH Members Event: Tuberculosis Past... · 2.6 – 2.8 million y Early Hominids Archaeological record 200,000 y Modern Man Anatomy, Y-c’some, mitochondria 50 - 60,000 y Dispersal

UCLH Members Event: Tuberculosis 22nd 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

Thoracoplasty

TB Notifications in England & Wales

Where did TB come from

and why is it going away?

“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

Pleural adhesions from chronic infection 6-8 year old girl, Thebes, 1500-500 BC

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

Human origins and civilisation

2.6 – 2.8 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























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

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


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


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

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

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.

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



Improvements in social conditions: poverty and overcrowding




Registrar Generals Annual Reports

• Mortality statistics: 3 notifiable diseases





Improvements in social conditions: poverty and overcrowding




Registrar General’s Annual Reports

• Mortality stats: 3 notifiable diseases



Death rates for infants per 1000 live births, left hand scale (dots), and cholera (squares) per million, right hand scale (E&W)



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)…


1825 Elizabeth age 10 1825 Maria age 11 1849 Anne age 29 1848Emily age 30 1855 Charlotte age 38

Five siblings All died from TB None had children

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


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”


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”


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”

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


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


New Poor Law (1834)

Bentham’s Utilitarianism: ‘correct level of poor rate’

Malthus’s doctrine of population growth opposes Old Poor Law


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)


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)


Old St Pancras workhouse

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


TB in contemporary London

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

Rich world

5% of all cases

Rare cause of death


CT imaging common







Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards







Rich world

5% of all cases

Rare cause of death


CT imaging common







Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards







Rich world

5% of all cases

Rare cause of death


CT imaging common







Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards







Rich world

5% of all cases

Rare cause of death


CT imaging common






Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards







Rich world

5% of all cases

Rare cause of death


CT imaging common






Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards






Rich world

5% of all cases

Rare cause of death


CT imaging common






Low drug resistance



Poor world

95% of all cases


Treated by nurses




Overcrowded wards






Rich world

2% of all cases

Rare cause of death


CT imaging common






Low drug resistance



Poor world

98% of all cases


Treated by nurses




Overcrowded wards






TB in contemporary London

7290 cases

2nd highest rate in Western Europe

250% increase in MDR since 2000

95% increase in migrant cases

5% decrease in native cases

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Tuberculosis case reports and rates, UK, 2004-2013

Tuberculosis in the UK: 2014 report

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Office for National Statistics (ONS) Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

61

Tuberculosis case reports and rates by PHE Centre,

England, 2013 35.5

17.3

11.2

15.6

9.5

14.3

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5.1 4.6 4.8

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• Three-year average tuberculosis case rates by local area*, UK, 2011-2013

*England – Local authorities, Wales and Scotland – Health Boards, NI – Country level

© Crown copyright and database rights 2014 Ordnance Survey 100016969

London



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UK Born Non-UK Born Rate in UK Born Rate in Non-UK Born

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Tuberculosis case reports & rates by age group & place of birth,

UK, 2013


Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI),Labour Force Survey (LFS) Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

64 Tuberculosis in the UK: 2014 report

Proportion of TB cases by deprivation quintile residence, England, 2013

Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI), Index of Multiple Deprivation (IMD 2010) Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

2,962

1,871

1,006

644 427

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Most deprived 2nd quintile 3rd quintile 4th quintile Least deprived

Pro

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Deprivation Quintiles

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

NCL TB Service: region of birth 2014-5: 160 patients

Africa

Asia

Americas

Middle East

Europe

UK

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

North Central London TB Service (2014-5): clinical 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

North Central London TB Service (2014-5): social complexity

70

Most frequent countries of birth for non-UK born TB cases, UK, 2013

* Where country of birth was known; **Years

Country of birth Number of cases Percentage of cases*

Median time since entry to UK (IQR)**

India 1,615 29.8 5 (2 -13)

Pakistan 1,103 20.4 7 (2 -22)

Somalia 292 5.4 9 (4 -13)

Bangladesh 248 4.6 7 (3 -18)

Nepal 170 3.1 3 (2 -6)

Nigeria 164 3.0 7 (3 -11)

Philippines 136 2.5 8 (5 -12)

Zimbabwe 105 1.9 11 (7 -12)

Sri Lanka 95 1.8 7 (3 -13)

Kenya 84 1.6 22 (8 -37)

Romania 70 1.3 2 (0 -4)

Afghanistan 67 1.2 6 (2 -11)

Poland 66 1.2 5 (2 -7.5)

Eritrea 62 1.1 4 (2 -7)

China 56 1.0 7 (4 -11)

Others (each <1%)

1,082 20.0 5 (1 -13)

Total* 5,415 100 7 (3 -14)


Source: Enhance Tuberculosis Surveillance (ETS), Enhanced Surveillance of Mycobacterial Infections (ESMI) Data as at: May 2014. Prepared by: TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England

71

Time between entry to the UK & TB diagnosis for

non-UK born TB cases by year, UK, 2013



72

Proportion of TB case reports by site of disease, UK, 2004-2013

* With or without extra-pulmonary disease



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73

Tuberculosis case reports by site of disease, UK, 2013 Site of disease* Number of cases Percentage**

Pulmonary 4,096 52.1

Extra-thoracic lymph nodes 1,874 23.9

Unknown extra-pulmonary 931 11.9

Intra-thoracic lymph nodes 916 11.7

Pleural 673 8.6

Other extra-pulmonary 689 8.8

Gastrointestinal 432 5.5

Bone – spine 353 4.5

Bone – other 220 0.5

Miliary± 211 2.8

CNS – meningitis 172 2.7

Genitourinary 145 2.2

CNS – other 129 1.8

Cryptic 39 1.6

Laryngeal 19 0.2



*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


Treatment completion at 12 months for drug sensitive TB cases with expected treatment duration <12 months*, UK, 2003-2012

* 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


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TB outcome at 12 months for drug sensitive TB cases with expected treatment duration <12 months*, UK, 2012

Treatment outcome n %

Completed 6,438 82.8

Died 345 4.4

Lost to follow-up 307 3.9

Still on treatment 446 5.7

Stopped 79 1.0

Not evaluated** 159 2.0

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



TB outcome at 24 months for drug resistant cohort, UK, 2011*

*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

Treatment outcome n %

Completed 47 48.0

Died 4 4.1

Lost to follow-up 19 19.4

Still on treatment 22 22.4

Stopped 4 4.1

Not evaluated** 2 2.0

Total 98

Documents

UCLH Members Event: Tuberculosis Past... · 2.6 – 2.8 million y Early Hominids Archaeological record 200,000 y Modern Man Anatomy, Y-c’some, mitochondria 50 - 60,000 y Dispersal