Transcript Epidemiologic Basis of Tuberculosis Control Slides from the web site http://www.tbrieder.org Compiled by: Hans L Rieder.

Epidemiologic Basis of Tuberculosis Control
Slides from the web site http://www.tbrieder.org
Compiled by:
Hans L Rieder
The five core modules of The Union’s
International Tuberculosis Courses
The DOTS Strategy of the national tuberculosis program
Intervention strategies
Etiologic
agent
Individual
Community
Bacteriologic
basis
Clinical
presentation
Epidemiologic
basis
Types of Approaches to the
Epidemiology of Tuberculosis
o Etiologic epidemiology
o Descriptive (administrative)
epidemiology
o Predictive epidemiology
A Model for the Epidemiology of Tuberculosis
Risk
factors
Risk
factors
Risk
factors
Risk
factors
Infectious
tuberculosis
Exposure
Subclinical
infection
Death
Non-infectious
tuberculosis
Rieder HL. Infection 1995;23:1-4
Exposure to
M. tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
A pragmatic definition of “relevant” exposure
An exposure leading with a reasonably measurable risk to
acquisition of infection with M tuberculosis, thus:
Outdoors
Indoors
Proximity highly relevant
Proximity largely irrelevant
Risk factors for exposure to
M. tuberculosis
o
Incidence of infectious tuberculosis
o
Duration of infectiousness
o
Number of contacts with susceptibles
per unit of time of infectiousness
Age-adjusted median age (years)
Change in the Median Age of Tuberculosis Patients,
Finland, Among Males and Females, 1954 - 1995
70
60
50
Males
40
Females
30
60
70
80
90
Year of notification
Härö AS. Tuberculosis and Respiratory Diseases Yearbook 1998;24:101-3
Infection with
M. tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Risk of Infection Given Exposure:
Largely Exogenous Factors
Particles
Volume
Particles:
Volume:
Exposure time:
x
Exposure time
Production of infectious droplet nuclei
Volume of air and ventilation
Time of inhaling air with droplet nuclei
Falling and Evaporation Times of Droplets of Varying Diameters
Droplet diameter (mm)
Falling time (seconds)
0.00
0.05
0.10
0.15
0.20
1
To evaporation
2
To ground
(2m)
3
Wells WF. Am J Hyg 1934;20:611-8
Production of Infectious
Droplets and Droplet Nuclei
o Aerosolization
o Site and form of disease
Number of droplets expelled by different
aerosol-producing maneuvers
Number of droplets
50000
40000
30000
20000
10000
0
Coughing
Talking
Singing
Loudon RG, et al. Am Rev Respir Dis 1968;98:297-300
Cumulative Percentage of Droplets Expelled During
Aerosol-Producing Maneuvres, by Droplet Size
Cumulative percentage
100
80
60
Coughing
40
Singing
20
Talking
0
1
3
5 7 10
100
1000
Droplet diameter (micrometers)
Loudon RG, et al. Am Rev Respir Dis 1968;98:297-300
Tuberculous Infection Among Close Contacts (Children <15 yr)
by Bacteriologic Status of Index Case
70
s+/c+
s+/c+ Smear-positive / culture-positive
Per cent infected
60
s+/c+
50
s-/c+
Smear-negative / culture-positive
s-/c-
Smear-negative / culture-negative
40
30
s+/c+
s-/c+
s-/c-
20
10
s-/c+
s-/c-
s-/c+
s-/c-
0
Bedfordshire
1948 - 1952
Rotterdam
1967 - 1969
Saskatchewan
1966 - 1971
Shaw JB, et al. Am Rev Respir Dis 1954;69:724-32
van Geuns HA, et al. Bull Int Union Tuberc 1975;50:107-21
Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106
Fraction of cases / infected
Sensitivity of Direct Sputum Smear Examination
in Identifying Pulmonary Tuberculosis and Transmitters
1.0
0.8
Fraction due to
smear-neg cases
Smear-neg
Culture-pos
0.6
Fraction due to
smear-pos cases
0.4
0.2
Smear-pos
Culture-pos
0.0
Cases of
pulmonary
tuberculosis
Infected
contacts
< 15 yr
Calculated from data from:
Grzybowski S, et al. Bull Int Union Tuberc Lung Dis 1975;50:90-106
Tuberculosis Among Primary Health Care Attendees
with Prolonged Cough, Harare, Zimbabwe, 2003 (?)
90
27
207
454
100
sm - / cul -
Per cent
80
sm - / cul +
TB -
TB -
60
smear pos
40
20
TB +
TB +
0
HIV negative
HIV positive
Munyati SS, et al. Clin Infect Dis 2005;40:1818-27
Prevalence of Infection Among Childhood Contacts <5yr
by Characteristic of Bacteriologically Confirmed Source
490/1,012
Per cent infected
50
40
30
Cough +
Sputum +
71/286
20
10
0
Cough +
Sputum -
24/244
Cough Sputum -
Hertzberg G. Acta Tuberc Scand 1957;38(S-1):1-146
Tuberculous Infection in Young High-Risk Contacts
by Isoniazid Susceptibility of Index' Strain
Per cent infected
40
30
20
10
0
INH-resistant
INH-susceptible
Snider DE, Jr, et al. Am Rev Respir Dis 1985;132:125-32
Interval Between Acquisition of Infection and Observable
Immunologic Response, Faroe Islands, 1939 to 1947
Cumulative per cent
100
80
Exposure < 24 hrs
Exposure >= 24 hrs
Maximum to minimum
60
Median
40
20
0
0
20
40
60
Days since exposure
Poulsen A. Acta Tuberc Scan 1954;24:311-46
Clearance of Air
o Dispersion of bacilli
o Survival of bacilli
Killing of BCG by Sunlight and in Open Sky Without
Direct Exposure to Direct Rays of the Sun
Number of colonies
(log scale)
107
106
105
104
103
Skyshine
102
Sunlight
101
05 15 30
60
240
Exposure time (minutes)
Edwards LB, et al. Bull World Hlth Organ 1952;5:333-6
Prevalence of Tuberculous Infection by Proximity of Contact
to a Smear-Positive Case, Jinan, China, 1993-1996
Per cent infected
40
30
20
10
0
Household
intimate
Household
regular
Household
sporadic
Community
member
Extent of contact
Lutong L, et al. Int J Tuberc Lung Dis 2000;4:275-7
Risk of Infection Among Contacts as a Function of Exposure Duration
Infection with
M. tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Descriptive epidemiology of
tuberculous infection
o Methodological issues in determining
prevalence of tuberculous infection
o Prevalence of tuberculous infection
Standardization of the
Tuberculin Skin Test
o Standardization of tuberculin
o Standardization of administration
o Standardization of reading
Original PPD-S Produced by Florence Seibert
No. 23
No. 24
Picture courtesy: Brennan MJ, Anderson C, Quander J.
United States Food and Drug Administration, November 29, 2001
Cumulative Percentage of Children Reacting to Increasing Doses
of Tuberculin, Among Healthy Children and Tuberculosis Patients
5 TU PPD-S
Per cent reacting
100
Tuberculosis patients
80
60
Healthy children
40
20
0
10-9
10-8
10-7
10-6
10-5
10-4
10-3
10-2
10-1
100
Dose of tuberculin (mg)
Furcolow ML, et al. Public Health Rep 1941;56:1082-1100
Comparison of Tuberculin PPD-S and PPD RT23 in
Eskimo Children and United States Navy Recruits
20
Eskimo children
2 TU PPD RT23
15
10
Per cent reacting
5 TU PPD-S
5
0
20
US Navy recruits
2 TU PPD RT23
15
10
5
5 TU PPD-S
0
0
5
10
15
20
25
30
Induration (mm)
Comstock GW, et al. Bull World Health Organ 1964;31:161-170
Mantoux C. La Presse Médicale 1910;2:10-15
Tuberculin Skin Test Reaction Sizes Among
Aboriginals with a BCG Scar, Alberta, Canada
Fraction reacting
0.20
0.15
0.10
0.05
0.00
0
10
20
30
Induration (mm)
Enarson DA. Int J Tuberc Lung Dis 1998;2(suppl 1):S16-S22
Distribution of Reaction Sizes to 5 TU Tuberculin PPD-S
in 5,544 Tuberculosis Patients, United States
Per cent reacting
20
15
10
5
0
0
5
10
15
20
25
30
Induration (mm)
Edwards LB, et al. Am Rev Respir Dis 1969;99(4, part 2 of 2):1-132
Distribution of Tuberculin Skin Test Reaction Sizes Among
Healthy Children Compared with Tuberculosis Patients, Djibouti
0.10
Children
Patients
Fraction reacting
0.08
0.06
0.04
0.02
0.00
0
10
20
30
Induration (mm)
Trébucq A et al. Int J Tuberc Lung Dis 2005:9:1097-1104
Tuberculin Skin Test Reaction Size Distribution
in Two Tuberculin Surveys, Korea 1965 and 1995
1965
Fraction reacting
0.06
0.04
0.02
0.00
0
5
10
15
20
25
Fraction reacting
0.06
30
1995
0.04
0.02
0.00
0
5
10
15
20
25
30
Induration (mm)
Korean Institute of Tuberculosis 1966:1-181
Korean National Tuberculosis Institute 1996:1-180
Sensitivity to M. intracellulare in the United States
Edwards LB, et al. Am Rev Respir Dis 1969;(No 4, part 2):13
Recovery of M. avium complex from Savannah River
Floodplain (USA) Soil Samples, as a Function of Soil pH
CFU / mg soil
400
300
200
100
0
4.0
4.5
5.0
5.5
6.0
6.5
7.0
pH
Brooks RW, et al. Am Rev Respir Dis 1984;130:630-3
A distribution of tuberculin skin test reaction sizes
Number of reactors
1000
800
600
400
200
0
0
5
10
15
20
25
30
Induration (mm)
Original data: Narain R, et al. Bull World Health Org 1963;29;641-64
Number of reactors
Tuberculin Skin Test Reaction Sizes, Observed, Mixture,
Cross-Reaction, and Tuberculous Infection Distribution
Infection
yes
no
1000
Test
800
pos
neg
a
c
b
d
a+b
c+d
total
a+c
b+d
N
Cut-off
total
600
P = 0.448
400
200
b
c
0
0
5
10
15
20
25
30
Induration (mm)
Original data: Narain R, et al. Bull World Health Org 1963;29;641-64
Waning of tuberculin skin test reaction following
BCG strain 1173 p2 among Korean school children
Per cent reacting
40
After 5 years
30
After 1 year
20
After 9 weeks
10
0
0
5
10
15
20
25
Induration (mm)
Kim SJ. Tuberc Respir Dis (Korea) 1988;35:6-12
Probability of Tuberculous Infection Among US Navy Recruits
by Tuberculin Skin Test Size and History of Contact
Probability of Infection
100
History of contact
80
60
40
No history of contact
20
0
0
5
10
15
20
25
Induration (mm)
Rust P, et al. Am J Epidemiol 1975;101:311-22
Comparative Results of Tuberculin Test, QuantiFERON Test,
and T-SPOT.TB Test, among Contacts, by BCG Vaccination
BCG+
Proportion reacting (%)
80
BCG60
BCG-
BCG+
40
BCGBCG+
20
0
Tuberculin
Test
T-SPOT.TB
Test
QFN-G-IT
Test
Dominguez J, et al. Clin Vacc Immunol 2008;15:168-71
The Litmus Test: Case Incidence Given a Test Result
Incidence per 100,000 p-yr
Incidence Case Rate Among Household Contacts of SmearPositive Tuberculosis, by Intitial Tuberculin and IGRA Test, Gambia
2000
Mx: Mantoux
ES: Elispot
1500
1000
0.8-1.3%!
500
100
MxES-
Mx-
ES-
Mx+
Mx+
ES-
Mx- Mx+
ES+
ES+ ES+
Mx+
or
ES+
Hill PC, et al. PLoS One 2008;3(1): e1379. doi:10.1371/journal.pone.0001379
Fate of M tuberculosis in calcified lesions
Pulmonary
Author
Lymphatic
Lesions
Sterile
Lesions
Sterile
10
9
16
10
Rabinowitch
-
-
30
19
Koenigsfeld
21
17
18
13
Schroeder
40
40
61
60
Opie
92
77
91
70
-
-
17
17
27
16
-
-
Anders
-
-
58
50
Saenz
44
33
-
-
Total
234
192
291
239
Schmitz
Griffith
Rubinstein
Percentage sterile
82.1
82.1
Canetti G. Paris: Vigot Frères, 1939, 305 pp
Age-Specific Prevalence of Tuberculous Infection
in Healthy Children, Paris, 1910
100
Per cent reacting
80
60
40
20
0
0
5
10
15
Age (years)
Mantoux C. Presse Méd 1910;2:10-13
Male-to Female Ratio in Prevalence of Tuberculous,
Infection by Age, India 1961-1962 and Denmark, 1950-52
Male-to-female ratio
1.8
1.6
1.4
India
1.2
Denmark
1.0
0.8
0
5
10 15
25
35
45
55
Age (years)
National Tuberculosis Institute Bangalore. Bull World Health Organ 1974;51:473-88
Groth-Petersen E, et al. Bull World Health Organ 1959;21:5-49
Prevalence of Tuberculous Infection by Age and Profession,
Norway, 1927-1928
Per cent infected
100
Working class
80
60
Farmers
40
20
0
0
10
20
30
40
50
Age (years)
Heimbeck J. Tidskrift Norske Laegeforening 1928;48:945-61
Urban-to-Rural Ratio of Age-Specific
Tuberculous Infection, Zanzibar and Korea
Urban-to-rural ratio
2.5
Zanzibar
2.0
1.5
Korea
1.0
0
10
20
30
40
Age (years)
Korean Institute of Tuberculosis, 1966
Roelsgaard E, et al. Bull World Health Organ 1964;30:459-518
Prevalence of infection (%)
Prevalence of tuberculosis infection by age and socioeconomic
status in Heidleberg, Trondheim, and Hué, 1910 - 1920
60
Trondheim
(Norway)
50
Hué
(Viet Nam)
40
30
Heidelberg
(Germany)
20
Poor
Rich
10
0
0
5
10
15
20
25
30
Age (years)
d'Arcy Hart P. Br Med Res Council Spec Ser 1932;No 164:5-132
Frequency of Large Tuberculin Skin Test Reactions Among
High School Students, Washington County, USA, 1963
Reactors per 1,000
25
Education
of parents
Housing characteristics
Persons per room
20
15
10
5
0
12+ yr
< 12 yr
<1
1+
Kuemmerer JM, et al. Am Rev Respir Dis 1967;96:885-92
Prevalence of infection (%)
Age-Specific Prevalence of Tuberculous Infection,
Cross-Sectional Surveys, Rural Zurich, Switzerland
100
1920
1953/54
80
1967
1978
60
40
1990
(modeled)
20
0
0
10
20
30
40
50
60
Age (years)
Zuberbühler JG. Thesis, University of Zürich, 1981:1-121
Hofer S. Thesis, University of Zürich 1982;1-45
Haefliger E. Prax Klin Pneumol 1982;36:335-64
Haefliger E. Therapiewoche Schweiz 1989;5:855-66
Rieder HL, et al. Schweiz Med Rundschau 1990;79:675-9
Prevalence of tuberculous infection, by age and sex,
Korea, 1965-1995, analysis by mixture analysis
100
Prevalence (%)
Males
1965
80
60
7
19
40
8
19
1995
5
5
20
0
0
5
10
100
20
80
1965
30
1995
60
40
25
X Data
Females
Prevalence (%)
15
19
75
8
19
5
20
0
0
5
10
15
20
25
30
Age (years)
Neuenschwander BE, et al. Int J Tuberc Lung Dis 2000;4:719-29
Infection with
M. tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Algebraic Derivation of the Average Annual Risk of Infection from Prevalence
Notation:
b
Calendar year cohort was born
a
Age of cohort at calendar time survey was conducted
Pb+a
R
Prevalence of infection in cohort at time of survey
Average annual risk of infection between calendar time b and calendar
time b+a
At birth:
1 – Pb
=
1
At age = 1:
1 – Pb+1
=
1 (1 – R)1
At age = 2:
1 – Pb+2
=
1 (1 – R)1 (1 – R)2
1 – Pb+a
=
1 (1 – R)1 (1 – R)2 … (1 – R)a
1 – Pb+a
=
(1 – R)a
(1 – Pb+a)1/a
=
(1 – R)
R
=
1 – (1 – Pb+a)1/a
…
At age = a:
Risk or incidence of infection
Difference between Calculated Annual Risk
and Actual Annual Incidence of Infection
Inci
den
ce 1
Calculated risk
ce
n
e
d
i
c
In
b
2
b+(a/2)
Calendar time
b+a
Annual Risk of Tuberculous Infection in
Low-Income Countries of Five WHO Regions
4
Afghanistan
Risk of infection (%)
Legend:
Africa
3
Americas
Thailand
2
Gambia
Lesotho
Korea
Pakistan
Philippines
Botswana
China
Samoa
Malaysia
Libya
Kuwait
0
70
Eastern Mediterranean
Western Pacific
Tanzania
1
Argentina
South-East Asia
Algeria
Bahrain
75
80
85
Year
Cauthen GM, et al. WHO Document 1988;WHO/TB/88.154:1-34
Secular Trend in Annual Risk of Infection, Selected European Countries
Engl
and
Per cent risk (log scale)
10
and
W ale
Serbia
Slo
s
Slope reference:
% decline / year
Poland
ven
i
a
0%
1
No
rw
ay
Fr
an
5%
10%
0.1
Ne
t
15%
ce
he
rla
nd
s
0.01
1900
1920
1940
1960
1980
Calendar year
Waaler H, et al. Bull Int Union Tuberc 1975;50:5-61
Sutherland I, et al. Tubercle 1983;64:241-253
Styblo K, et al. Bull Int Union Tuberc 1969;42:5-104
Sutherland I, et al. Bull Int Union Tuberc 1971;45:75-114
Vynnycky E, et al. Int J Tuber Lung Dis 1997;1:389-96
Lotte A, et al. Int J Epidemiol 1973;2:265-82
Age-specific prevalence of prior infection with M tuberculosis
Modeled from Cauthen data, Western Europe, 1990
Per cent population / infected
20
15
10
5
0
0
20
40
60
80
100
5-year age groups
Data courtesy: ten Dam HG, World Health Organization, 1990
Annual Risk of Tuberculous Infection WHO Eastern Mediterranean Region
Risk of infection (%)
(log scale)
5
Legend:
Algeria
Afghanistan
Bahrain
Kuwait
Libya
Pakistan
Syria
2
1
Slope reference:
% decline / year
0.5
1%
5%
0.2
10%
0.1
40
50
60
70
80
Year
Cauthen GM. WHO Document 1988;WHO/TB/88.154:1-34
Annual Risk of Tuberculous Infection
WHO African Region (Except Algeria)
Risk of infection (%)
(log scale)
5
2
1
Slope reference:
% decline / year
0.5
1%
Legend:
5%
0.2
Botswana
Burundi
Cameroon
Ethiopia
10%
0.1
40
50
60
70
Gambia
Lesotho
Nigeria
Tanzania
80
Year
Cauthen GM. WHO Document 1988;WHO/TB/88.154:1-34
Age-specific prevalence of prior infection with M tuberculosis
Modeled from Cauthen data, Southern Africa, 1990
Per cent population / infected
20
15
10
5
0
0
20
40
60
80
100
5-year age groups
Data courtesy: ten Dam HG, World Health Organization, 1990
Annual Risk of Tuberculous Infection WHO South-East Asia Region
Risk of infection (%)
(log scale)
5
2
1
Slope reference:
% decline / year
0.5
1%
Legend:
5%
India
0.2
10%
Indonesia
Thailand
0.1
40
50
60
70
80
Year
Cauthen GM. WHO Document 1988;WHO/TB/88.154:1-34
Age-specific prevalence of prior infection with M tuberculosis
Modeled from Cauthen data, Southeast Asia, 1990
Per cent population / infected
20
15
10
5
0
0
20
40
60
80
100
5-year age groups
Data courtesy: ten Dam HG, World Health Organization, 1990
The Epidemiologic Situation of Tuberculosis and Economic Realities
Annual risk of infection (%)
Current level
Annual decline
Health
resource
availability
I Industrialized
0.01 – 0.1
> 10
Excellent
II Middle-income Latin
America, West Asia, North
Africa
0.5 – 1.5
5 – 10
Good
III Middle-income East and
Southeast Asia
1.0 – 2.5
<5
Good
IV Sub-Saharan Africa, Indian
subcontinent
1.0 – 2.5
0–3
Poor
Country or area
Kochi A. Tubercle 1991;72:1-6
Incidence, Point Prevalence, and Period Prevalence
Year 1
Year 2
In year 3:
Incidence:
Point prevalence, March 15:
Period prevalence year 3:
Year 3
Year 4
12 cases
24 cases
288 person-months
Incidence, Point Prevalence, and Period Prevalence
Year 1
Year 2
In year 3:
Incidence:
Point prevalence, March 15:
Period prevalence year 3:
Year 3
Year 4
12 cases
6 cases
72 person-months
Tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Lifetime Risk of Pulmonary Tuberculosis, Adjusted
for Age, by Calendar Time, England and Wales
20
All pulmonary
Per cent
15
10
5
Smear-positive pulmonary
0
1900
1920
1940
1960
1980
Year
Vynnycky E, et al. Am J Epidemiol 2000;152:247-63
Average annual case rate (per 100,000)
Incidence of Tuberculosis Among Initial Reactors,
by Age when Tuberculosis was First Diagnosed
400
300
200
100
0
0
5
10
15
20
25
30
35
40
Age (years)
Comstock GW, et al. Am J Epidemiol 1974;99:131-8
Percentage of Eskimos with 5mm or more Induration
to 5 TU PPD-S, by Sex and Age, Alaska, 1957
Per cent positive reactors
100
80
60
Female
Male
40
20
0
0
10
20
30
40
50
60
Age group (years)
Comstock GW, et al. Am Rev Respir Dis 1967;95:935-43
Male-to-Female Ratios of Tuberculosis Among Eskimos,
Adjusted for Tuberculous Infection, 1958-1964
Male-to-female ratio
1.6
1.4
1.2
1.0
0.8
0
10
20
30
40
50
60
Age group (years)
Calculated from: Comstock GW, et al. Public Health Rep 1959;74:621-34
Comstock GW, et al. Am Rev Respir Dis 1967;95:935-43
Cases per 1,000 reactors
Incidence of Tuberculosis During Follow-up in Placebo
Groups of Preventive Chemotherapy and BCG Trials
12
10
8
6
4
2
Preventive
therapy trial
BCG trial
0
0
5
10
15
20
Year of observation
Ferebee SH. Adv Tuberc Res 1969;17:28-106
D'Arcy Hart P, et al. Br Med J 1977;2:293-5
Risk of Tuberculosis Among Tuberculin-Positive,
HIV Infected Persons in Three Selected Studies
Risk per 100 person-yr
18
16
14
12
10
8
6
4
2
0
New York City
Italy
Spain
Selwyn PA, et al. N Engl J Med 1989;320:545-50
Antonucci G, et al. JAMA 1995;274:143-8
Guelar A, et al. AIDS 1993;7:1345-9
Risk of Tuberculosis Among HIV Infected, TuberculinPositive Persons, by CD4+ Lymphocyte Count
Tuberculosis incidence per
100 person-yr (log scale)
30
10
5
2
1
< 0.20
0.20 - 0.35
> 0.35
CD4+ lymphocyte count x 109 / L
Antonucci G, et al. J Am Med Assoc 1995;274:143-8
Cumulative Percentage Tuberculosis-Free by Category
of Silicosis Among Gold Miners, South Africa
Per cent disease-free
100
Category 0
90
Category 1
80
Category 2
70
60
Category 3
50
0
1
2
3
4
5
6
7
Year of observation
Cowie RL. Am J Respir Crit Care Med 1994;150:1460-2
Age-Specific Relative Risks for Incident Tuberculosis
Among Diabetics, Korea, 1988 - 1990
All bacteriologically
confirmed cases
30
Relative risk
(log scale)
Smear-positive cases
10
3
1
30
40
50
60
70
Age (years)
Kim SJ, et al. Tuber Lung Dis 1995;529-33
Relative Odds for Tuberculosis Among Male
Smokers, Aged 30 Years and Older, Great Britain
95% upper
confidence interval
6
Odds ratio
5
4
3
95% lower
confidence interval
2
1
0
10
20
30
40
Number of cigarettes smoked per day
Edwards JH. Br J Prev Soc Med 1957;11:10-11
200
150
100
Fe
m
e
al
M
Cases per 1 million observation years
Incidence of Infectious Tuberculosis by (Age-Adjusted) Body
Mass Index, 15+ Years Old, by Sex, Norway,1963 - 1975
ale
50
0
2.1
2.3
2.5
2.7
2.9
3.1
Body mass index (g/cm2 )
Tverdal A. Eur J Respir Dis 1986;69:355-62
Cases per 1,000 population
Incidence of Bacteriologically Confirmed Tuberculosis
After Measles Outbreak, Greenland 1962
50
Measles
40
30
20
10
No measles
0
0
5 10 15 20
40
60
Age group (years)
Krebs Lange P. Scand J Respir Dis 1970;51:256-67
Cases per 1,000 person-years
(log scale)
Example of Risk Differences in Individuals
Following Infection with M. tuberculosis
??
1000
100
10
1
Long-standing
infection
Recent
infection
SuperUnderlying
imposed HIV infection
HIV infection
Selected Risk Factors for Tuberculosis Given Infection
Referent: Infection> 7 yr past
Infection <1 yr past
HIV infection
Fibrotic lesions
Silicosis
Carcinoma of head or neck
Hemophilia
Immunosuppressive treatment
Hemodialysis
Underweight
Diabetes
Smoking, heavy
Gastrectomy
Jejunoileal bypass
Infecting dose
1
2
5
10
20
50
100
Relative risk / odds (log scale)
Rieder HL. Epidemiologic basis of tuberculosis control. Paris: 1999
Tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Improved Notification of Tuberculosis in Two London Hospitals
Per cent cases notified
100
Chest medicine
Other medical specialty
Surgical specialty
90
Other / unknown
80
70
60
50
1985-89
1992-93
Brown JS, et al. Br Med J 1995;310:974
Reported Tuberculosis Cases in the United States, 1953 - 2008
Number of cases (log scale)
80000
40000
20000
10000
1950
1960
1970
1980
1990
2000
2010
Year of notification
Centers for Disease Control and Prevention
Reported Tuberculosis in the United States, 1953-2008
Evaluating the Relative Annual Change
Year
No. of
cases
X
A
X+1
B
X+2
C
X+3
D
Relative change
B
-1
A
C
-1
B
D
-1
C
Tuberculosis - United States, First 39 Weeks, 1985
+5
Per cent change
0
1985 vs 1984
1984 vs 1983
-10
-20
"..., additional investigations will determine the extent to which
the national morbidity may be due to HTLV-III/LAV infection."
-30
0
4
8
12
16
20
24
28
32
36
40
44
48
52
Reporting week
CDC. Morb Mortal Wkly Rep 1985;34:625-7
Raw data courtesy: Alan B Bloch, 11 Oct 1994
Changes in Tuberculosis Notifications in
Western Europe From One to the Next Year
Per cent change
+ 40
+ 20
0
- 20
- 40
- 60
1976
1978
1980
1982
1984
1986
1988
1990
1992
Year of notification
Raviglione MC, et al. Bull World Health Organ 1993;71:297-306
Tuberculosis Notification Rates Among Males,
Cross-Sectional Observations, Finland 1954 -1994
1954
Notifications per 100,000
(log scale)
500
1964
100
1974
50
1984
10
5
1994
1
0.5
0
20
40
60
80
Age (years)
Härö AS. Tuberc Respir Dis Yearbook 1998;24:1-151
Tuberculosis Notification Rates Among Males,
by Birth Cohort, Finland 1954 -1994
1902
1954
196
100
4
197
1912
4
4
19
52
10
194
2
32
19
50
198
1892
1922
1994
62
19
Notifications per 100,000
(log scale)
500
5
1
1972
0.5
0
20
40
60
80
Age (years)
Härö AS. Tuberc Respir Dis Yearbook 1998;24:1-151
Tuberculosis Notification Rates Among Males,
by Birth Cohort, Finland 1954 -1994
1902
1892
1912
100
19
52
10
194
2
32
19
50
1922
62
19
Notifications per 100,000
(log scale)
500
5
1
1972
0.5
0
20
40
60
80
Age (years)
Härö AS. Tuberc Respir Dis Yearbook 1998;24:1-151
Tuberculosis Notification Rates Among Females,
by Birth Cohort, Finland 1954 -1994
500
Notifications per 100,000
(log scale)
19
194
100
50
1952
2
22
1912
193
1902
1892
1954
2
1994
10
196
5
2
1972
1
0.5
0
20
40
60
80
Age (years)
Härö AS. Tuberc Respir Dis Yearbook 1998;24:1-151
Age-adjusted median age (years)
Change in the Median Age of Tuberculosis Patients,
Finland, Among Males and Females, 1954 - 1995
70
60
50
Males
40
Females
30
60
70
80
90
Year of notification
Härö AS. Tuberculosis and Respiratory Diseases Yearbook 1998;24:101-3
Median Age of Tuberculosis Patients with Culture-Confirmed
Pulmonary Tuberculosis in Korean Prevalence Surveys, 1970-1995
58
56
Median age (yrs)
54
52
50
48
46
44
42
40
38
1965
1970
1975
1980
1985
1990
1995
2000
Year of survey
Data courtesy: Kim SJ, Sep 13, 2001
Male-to-Female Rate Ratio in the Incidence of Pulmonary
Tuberculosis, Denmark (other than Copenhagen), 1921 - 1953
Male-to-female rate ratio
(log scale)
1.6
1.3
1
0.7
1920
1930
1940
1950
Year of report
Groth-Petersen E, et al. Bull World Health Organ 1959;21:5-49
Incidence of Pulmonary Tuberculosis Among Married
Men, by Residence, Denmark, 1960 - 1968
Incidence per 100,000
Capital
60
40
Rural
districts
20
0
20
40
60
80
Age (years)
Christensen O. Scand J Respir Dis 1978(suppl):21-7
Cases per 100,000
Association of Housing Density and Tuberculosis in
Canadian First Nations Communities, Canada, 1997-99
150
100
50
0
0.4
1.0
1.2 +
Persons per room
Clark M, et al. Int J Epidemiol 2003;31:940-5
Relationship between estimated tuberculosis incidence
rates 2004 and per capita gross domestic product 2005
Tuberculosis cases
per 100,000 (log scale)
1,000
India
500
China
200
100
50
United
Kingdom
20
10
5
2.5
100
200
500
1,000 2,000
5,000 10,000 20,000 50,000
GDP (in US$) per head (log scale)
Janssens JP, Rieder HL. Eur Respir J 2008;32:1415-6
Global Migration
o Foreign labor
o Asylum seekers, refugees
o Internally displaced persons
Foreign Born-to-Canada Born Risk Ratios
for Tuberculosis in Canada, 1970 - 1972
Risk ratio (log scale)
16
8
4
Philippines
India
Portugal
Greece
2
Hungary
1
Canada
United States
0.5
China
Finland
Yugoslavia
Austria
United Kingdom and Germany
Benelux
Enarson D, et al. Am Rev Respri Dis 1979;119:11-8
Reported Tuberculosis Cases in Denmark,
by Country of Origin, 1973 - 1999
Reported cases (log scale)
800
Born in Denmark
400
200
Born abroad
100
50
1975
1980
1985
1990
1995
2000
Year of notification
Lillebaek T, et al. J Clin Microbiol 2001;855-61
Lillebaek T. Personal communication, June 11, 2001
Number of notified cases
Interval Between Entry or Re-Entry to Britain and
Notification of Tuberculosis Among Asians in London
40
30
20
10
0
No visit to Asia
(time from entry)
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22
40
30
20
10
0
Visit to Asia
(time from entry)
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22
40
30
20
10
0
Visit to Asia
(time from re-entry)
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22
Years after entry / re -entry
McCarthy OR. Br J Dis Chest 1984;78:248-53
Nosocomial Tuberculosis Outbreak in a
Impact of HIVHospital
on the Epidemiology
of Tuberculosis
in Verona, Italy
Direct:
Indirect:
0
20
o
Reactivation of tuberculous infection acquired
before HIV infection
HIV pos
Personnel
patients
o Progression of tuberculous infection
acquired
after HIV infection
o40 Transmission
the 120
population
60
80 to
100
140 not
160infected
180 with
200
HIV
Days after occurrence
of
index
case
Sutherland I. Br Comm Dis Rep 1990:10
di Perri G, et al. Lancet 1989;2:1502-4
Cases per 100,000 population
(log scale)
A Tuberculosis Tale of Two Countries
Tanzania
150
100
50
30
20
10
Switzerland
5
1940
1950
1960
1970
1980
1990
2000
Year of notification
Data courtesy:
Helbling P, Federal Office of Public Health, Switzerland, May 26, 2008
Egwaga SM, National Tuberculosis / Leprosy Programme, Tanzania, November 19, 2007
Notifications of Tuberculosis, by Type of Disease,
Tanzania, 1979 - 2008
Smear-positive
Smear-negative
Extrapulmonary
Number of cases
(log scale)
25000
10000
5000
2500
Relapses
1000
500
250
1980
1985
1990
1995
2000
2005
Year of notification
Tanzania NTLP / IUATLD. Progress Report 1996;No. 36
Tanzania NTLP / KNCV. Report 2003;No. 12
Egwaga S. Personal communication, 9 Nov 2009
Changes in tuberculosis notification rates,
Cape Town, South Africa, 1996-2004
3000
Cases per 100,000
2500
2003-2004
2000
1500
1996-1997
1000
500
0
0
10
20
30
40
50
60
10-year age groups
Lawn SD, et al. Clin Infect Dis 2006;42:1040-7
Per cent with tuberculosis
Tuberculosis among AIDS Patients, by Race / Ethnicity,
Florida, United States, 1981 - 1986
30
20
10
0
White, non- Hispanic
Black
Hispanic
American
Haitian
Rieder HL, et al. Arch Intern Med 1989;149:1268-73
Determinants for the Frequency of HIV-Associated Tuberculosis in a Community
Total population
Prevalence and incidence of
infection with M. tuberculosis
Infected with
M. tuberculosis
Prevalence and incidence
of HIV infection
Overlap of the two respective
population segments
Infected with HIV
Age-specific notification rates of sputum smear-positive
tuberculosis, females, Vietnam, 2000 versus 2008
Cases per 100,000
population (log scale)
400
300
2000
200
2008
100
50
30
Children up to age 14 years excluded
15
25
35
45
55
65
Age group (years)
Data courtesy: Vietnam NTP, International
Tuberculosis Course, Hanoi, 31 August 2009
Age-specific notification rates of sputum smear-positive
tuberculosis, males, Vietnam, 2000 versus 2008
Cases per 100,000
population (log scale)
400
300
2000
2008
200
100
50
Children up to age14 years excluded
30
15
25
35
45
55
65
Age group (years)
Data courtesy: Vietnam NTP, International
Tuberculosis Course, Hanoi, 31 August 2009
Epidemiologic Definitions of Contributors to
Tuberculosis Morbidity
Tuberculosis resulting from:
Recent infection
Primary tuberculosis: a ‘recent’ infection acquired
within the previous five years, leading to tuberculosis
Distant infection and
recent infection
Exogenous tuberculosis: a ‘distant’ infection five
years or more previously and a ‘recent’ infection,
either of them leading to tuberculosis
Distant infection
Endogenous tuberculosis: a ‘distant’ infection, but
no ‘recent’ infection, leading to tuberculosis
Sutherland I, et al. Tubercle 1982;63:255-68
Proportion of Tuberculosis Cases Attributable to Primary Infection, Exogenous
Reinfection, or Endogenous Reactivation, Among Males, by Age, Netherlands
Per cent of all cases
100
Primary
80
15 to 19 years old
60
15- to 19-year-old
40
20
Endogenous
Exogenous
0
1950
1955
1960
1965
1970
100
Per cent of all cases
60 to 64 years old
Endogenous
80
60
60- to 64-year-old
40
20
Exogenous
Primary
0
1950
1955
1960
1965
1970
Year
Sutherland I, et al. Tubercle 1982;63:255-68
A transmission model of tuberculosis from Hong Kong
Wu P, et al. PLoS One 2010;5(5): e10468:doi:10.1371/journal.pone.0010468
Cases per 100,000 population
(log scale)
Estimated Tuberculosis Incidence by WHO Region
1990 versus 2006
AFR
300
200
SEAR
Total
100
WPR
EMR
50
EUR
AMR
30
1990
2006
World Health Organization
WHO Doc 2008;WHO/HTM/TB/2008.393:191
Estimated Number of Incident Tuberculosis
Cases in the World, by WHO Region, 2007
Southeast Asia
Africa
Western Pacific
Eastern Mediterranean
Europe
Total: 9.3 million incident cases
Americas
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Number of cases (in million)
World Health Organization. WHO/HTM/TM/2009.411;2009:1-303
Tuberculosis
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Cases per 100,000 (log scale)
Projected Tuberculosis Incidence among Males
in Finland, Years 2000 and 2010
400
Observed in
birth cohorts
100
Observed in
year 2000
30
10
3
2000
Projected from
2010
birth cohorts
1
20
30
40
50
60
70
80
Age (years)
Härö AS. Tuberc Respir Dis Yearbook 1988;18:66
Parkkali L. Personal communication, October 11, 2005
Tuberculosis Death
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Risk Factors for Death from
Tuberculosis
o
Site and form of tuberculosis
o
Patient’s and doctor’s delay
Cumulative Case Fatality from Untreated Sputum
Smear-Positive Pulmonary Tuberculosis
100
United Kingdom
Sweden
Per cent dead
80
Denmark
60
40
20
0
0
2
4
6
8
10
12
14
16
18
20
Years after first admission
Thompson BC. Br Med J 1943;2:721
Berg G. Acta Tuberc Scand 1939;(suppl):1-207
Buhl K, et al. Bull World Health Organ 1967;37:907-25
Fate of Untreated Pulmonary Tuberculosis in Sanatorium
Patients, Long-Term Follow-Up, Barmelweid, Switzerland
100
"Open" tuberculosis
Per cent dead
80
60
40
"Closed" tuberculosis
20
0
0
2
4
6
8
10
12
14
16
18
Years after first admission
Krebs W. Beitr Klin Tbk 1930;74:345-79
Male-to-Female Case Fatality from Pulmonary
Tuberculosis, Denmark, 1935 and 1940 Combined
Male-to-female ratio
(log scale)
1.4
1.3
1.2
1.1
1
0.9
Small
numbers
0.8
0
5
15 20 25
35
45
55
65
Age group (years)
Groth-Petersen E, et al. Bull World Health Organ 1959;21:5-39
Age-Specific Frequency of Death from Pulmonary Tuberculosis
by Amount of Drugs Taken, North Arcot District, India, 1986 - 1988
< 50%
Per cent dead
60
50 - 79%
40
80 - 100%
20
0
15
25
45
65
Age group (years)
Datta M, et al. Tuber Lung Dis 1993;74:180-6
Proportion of Tuberculosis Cases Diagnosed at
Death, by Age, United States, 1985 - 1988
Per cent diagnosed at death
20
15
10
5
0
0
15
25
35
45
55
65
75
85
100
Age (years)
Rieder HL, et al. Chest 1991;100:678-81
Prevalence of HIV Infection Among Tuberculosis Patients and
Deaths Among Tuberculosis Patients on Treatment, Malawi
Per cent (log scale)
80
Prevalence of HIV infection
among tuberculosis patients
40
20
Proportion of tuberculosis
patients dying on treatment
10
5
1986
1988
1990
1992
1994
1996
1998
Year
Mukadi YD, et al. AIDS 2001;15:143-52
Mycobacterium tuberculosis Bacteremia in
Febrile Patients in Dar es Salaam, Tanzania
25
HIV pos
Per cent
20
15
survived
10
5
died
HIV neg
0
Archibald LK, et al. Clin Infect Dis 1998;26:290-6
Tuberculosis Death
o Etiologic epidemiology
o Descriptive epidemiology
o Predictive epidemiology
Tuberculosis Mortality in Three European Cities,
Modeled From Available Data, 1750 - 1950
Deaths per 100,000
1000
London
Stockholm
Hamburg
800
600
400
200
0
1750
1800
1850
1900
1950
Year
Grigg ERN. Am Rev Tuberc Pulm Dis 1958;78:151-72
Male-to-female ratio
Reported Male-to-Female Tuberculosis Deaths
Ratio, The Netherlands, 1925 - 1955
1.3
1.2
1.1
1.0
0.9
1925
1930
1935
1940
1945
1950
1955
Reporting year
Data courtesy: Nagelkerke N. August 18, 2005
300
187
6
200
191
6
100
189
6
186
6
18
46
185
6
36
18
Deaths per 100,000
Mortality from Respiratory Tuberculosis Among Males,
Cross-Sectionally and by Birth Cohort, Switzerland
1901
1921
188
6
1941
1961
1926
1906
30
40
1981
0
0
10
20
Age (years)
50
60
70
80
What did chemotherapy
do?
Mortality from Respiratory Tuberculosis Among Males,
Cross-Sectionally and by Birth Cohort, Switzerland
Deaths per 100,000
1901
1921
200
185
187
200
1941
100
191
100
189
186
46
6
6
1901
1921
6
188
6
1941
6
6
1961
1981
Mortality
from Respiratory Tuberculosis Among Males,
0
Cross-Sectionally
and
by Birth
Cohort,
Switzerland
0
10
20
30
40
50
60
70
80
Age (years)
300
1906
30
191
10
30
40
1981
0
0
10
20
50
60
70
Male respiratory tuberculosis
mortality
36
46
0.3
Three ways of looking at the same data from
Switzerland
Chemotherapy!
0.1
0
10
20
30
80
6
3
19
1906
75
1896
1926
1
1961
1926
Age (years)
100
19
Deaths per 100,000
(log scale)
18
300
36
300
18
Deaths per 100,000
Mortality from Respiratory Tuberculosis Among Males,
Cross-Sectionally and by Birth Cohort, Switzerland
40
Age (years)
50
60
70
80
300
183
6
1846
1901
185
6
200
06
19
Deaths per 100,000
Mortality from Respiratory Tuberculosis Among Females,
Cross-Sectionally and by Birth Cohort, Switzerland
100
1926
1921
1941
1866
18
96
188
6
1876
1961
1981
1916
0
0
10
20
30
40
Age (years)
50
60
70
80
Which estimate do you like best - or, if you have no data: MODEL!
Deaths (millions)
4
3
Murray
Kochi
Dolin
2
Corbett
WHO report
1
0
1990
1995
2000
2005
Year for estimate
Murray C J L, et al. Bull Int Union Tuberc Lung Dis 1990;65(1):6-24
Kochi A. Tubercle 1991;72:1-6
Dolin P J, et al. Bull World Health Organ 1994;72:213-20
Corbett E L, et al. Arch Intern Med 2003;163:1009-21
World Health Organization. World Health Organization Document 2008;WHO/HTM/TB/2008.393:1-294
Dr. Karel Styblo, Developer of the DOTS Strategy, in Somalia
Picture courtesy: Liisa Parkkali
Dr. Karel Styblo, Developer of the DOTS Strategy, in Somalia
Picture courtesy: Liisa Parkkali
Arata Kochi
Director of the WHO
Tuberculosis Programme
1988-2000
“…The art of epidemiologic reasoning is to
draw sensible conclusions from imperfect
data…”
Comstock GW. Am J Epidemiol 1990;131:206