EPIDEMIOLOGY OF

TUBERCULOSIS
Nurjannah, MD, MPH
Public Health Department
Medical Faculty
Syiah Kuala University
September 16, 2010
Banda Aceh
Why do a TB lecture?
Because, as you will see, it is one of
the most important, readily
preventable infectious disease in the
world, yet it still kills and sickens
millions each year.
That makes it worth doing something
about!
OBJECTIVES:
General concepts in TB Epidemiology
Epidemiological indicators of TB
Global epidemiological trends of TB
TB situation in South East Asia
Prospects of TB control

Why do we need to study
Epidemiology of TB?
What is Epidemiology ?
Epi - among ; Demos - People ; Logos - Study
DEFINITION
Epidemiology is the study of the -
Frequency
Distribution - time, place & person
Determinants - physical, biological, social,
behavioral & cultural of health problems & health
related events and application of this study to control
health problems.
Aims of Epidemiology ?
To describe natural history of disease
Describe distribution and relative importance
Measure frequency
To define risk groups
To evaluate interventions
To describe trends
To predict future trends and changes in
disease presentation.
Elements to Understanding TB
Agent Individual Community
Interventions
Control
Think TB
Cough
Sputum
Haemoptysis
Fever
Loss of weight
Chest pain
Etc., etc., etc.
Exposure
Subclinical
infection
Infectious
tuberculosis
Non-infectious
tuberculosis
Death
Risk
factors
Risk
factors
Risk
factors
Risk
factors
A Model for the Epidemiology of Tuberculosis
Rieder HL. Infection 1995;23:1-4
Steps in the pathogenesis of TB
Exposure
Sub-clinical
Infection
Non-Infectious
Infectious
Death
Risks of exposure
More common in developing countries.
In developed countries is more frequent
among immigrants, drug users, HIV,
homeless, and those living in inner cities
(eg. Slum area).


Risk factors of exposure
Socioeconomic Status
Poverty
Crowding living conditions
Reduce access to health care
Migration
Population density (rural vs. urban)
Nutritional status


Descriptive epidemiology
Age-specific incidence varies over
countries and socioeconomic conditions:
Elders in Developed countries
Young adults in developing countries*
Higher among males than females
Access to diagnosis
Health services notification process


* Mainly those in their most productive years of life


Risk of Infection with tubercle bacilli

Probability of infection depends on:
Number of droplets nuclei in air
Duration of exposure of a susceptible
individual to that droplet
Airborne transmission (risk of
infection)
Risk of infection is exogenous
To be transmissible through air, agent
must remain buoyant in the air.
Velocity of a droplet falling to the ground
depends on: surface and diameter.
For example: in moisture-saturated air
droplets would fall to the ground from a
height of 2 meters. in less than 10 sec.
Liquid droplets tend to evaporate,
diminishing their size.

The duration of time droplets remain in
unsaturated air is proportional to its size.
Very small droplets evaporate immediately
Large drops settle rapidly and reach ground
without evaporation.
Droplets with a size less than 0.1 mm. are
more likely to reach alveoli and then
produce infection.
Droplets higher than 5 mm will not
produce infection.

TB Infection
Droplet nuclei containing
mycobacteria inhaled
Usually deposited in the lower lobes
Air circulation and ventilation
Volume of air into which the bacilli are
expelled determines the probability that a
susceptible individual becomes infected
Ventilation dilutes the concentration of
infectious droplets nuclei
Surgical masks are of low efficiency
because they do not filter particles higher
than 5 mm, and do not seal mouth and
nose.
Characteristics of an infectious
patient
Patient must be able to produce airborne
infectious droplets.
It requires some 5,000 bacilli in 1 ml. of
sputum to yield positive a smear, and
10,000 to identify a smear as positive with
a 95% probability.
Patients with a positive smear are by far
more infectious than those with a negative
one and positive culture.
Probability of becoming infected varies
depending on the distance between source
and receptor.

Reduction of Infection
Reducing expulsion of infectious materials
from source cases such a covering the
mouth and nose during coughing and the
most efficient treatment.
Host immune response
Tuberculin
Tuberculin test
Sensitivity of test is well characterized
Specificity unpredictable.
The influence of BCG vaccination on the
results of tuberculin skin testing is related
to the time elapsed since vaccination.
Risk of infection
The risk of becoming infected is largely exogenous in
nature:
Characteristics of the source
Environment
Duration of exposure
(most likely young adults)

The risk of developing tuberculosis is largely
endogenous, determined by the integrity of the
cellular immune system (most likely elders)

The importance of any risk factor in public health is
determined by both the strength of the association
and the prevalence of the risk factor in the
population.
Risk factors
HIV/AIDS
Fibrotic lesions
Silicosis
Immuno suppresive treatment
Haemodialysis
Underweight
Diabetes
Infecting dose
Age (adolescents and > 60)
Genetic factors
Blood groups (higher in blood groups AB or B
than O or A)
Hemophilia

Environmental Factors
Smoking
Alcohol abuse
Injecting drug users
Nutrition
Malnutrition
Diet (vegetarian)
Vitamin D deficiency
Medical conditions
Silicosis (25 times higher)
Diabetes (3 times higher)
Malignant lymphomas (neck and head)
Renal failure (10-15 times higher)
Gastrectomy (5 times higher)
Jejunoileal bypass (association reported
but unknown prevalence)
Corticosteroid treatment (controversial)
Pregnancy
No solid evidence
However, there are indications that post-
partum period might double the risk of
progression to TB
Factors associated with the etiology of the
agent
Infecting dose effect
Drug resistance
Infection with M. bovis.
Re-infection
All persons who have been treated can be
re-infected
Immunologic memory wanes


Note: It has been noted that those who already have been infected
may have a lower risk of developing the disease than those who are
not.
Mortality
TB mortality risk factors
Site (higher in positive smear)
Type of disease (association to)
Timeliness of diagnosis
Appropriate diagnosis
Mistake in reading X-rays
Mistake in interpreting signs and symptoms
Delayed diagnosis
Quality of treatment
Each war and economic unrest usually results in
an increase of mortality

Factors determining characteristics
of mortality
Age-specific differences in mortality
Difference in mortality in each cohort
group
Difference at particular periods or events
Impact of HIV infection
Endogenous re-activation of persons who
became infected with HIV
Progression from infection in persons with pre-
existing HIV infection
Transmission to the general population from
persons who develop TB because of their HIV
infection
The lifetime risk of dually infected persons to
develop TB is about 30%
Higher probability of extra-pulmonary TB
What is the most important
risk factor for TB?
Risk factors for disease given that
infection has occurred ?
[Relative Risk of
remotely acquired
infection = 1]
(0.2% per year)
Risk factor Relative Risk
AIDS 200
HIV Infection 30-40
Silicosis 30
Recent Infection 20
Under-nutrition 2-5
Diabetes mellitus 2-5


Incidence of TB in South Africa per 1000
population
0
5
10
15
20
25
30
General population
Gold miners
I J TLD,3(9),1999,791-798
Other High Risk Groups
Populations in war / civil unrest
Refugees and migrants
Slum dwellers
Homeless people/Foot path
dwellers
Smoking
Prisoners

TB in prisons
Studies in Thailand
* TB incidence 90 times higher in prisons
* High HIV sero-positivity in TB cases
* High levels of drug resistance
* RFLP studies signify role of recent
transmission
Determinants of death?

* Severity of illness
* Smear positivity
* delay in diagnosis
* quality of treatment
* drug susceptibility pattern

Epidemiological
indicators of TB
Enumerate epidemiological
indicators of TB you know of?
Definitions: Patients with TB
TB infection
TB bacilli live inside the person, but the bacilli
do not cause pathological destruction of
organs
No signs or symptoms of disease
TB disease
TB bacilli progressively invade an organ(s)
Signs and symptoms of disease appear
Definitions: Patients with TB
Pulmonary TB
Disease involves the lung parenchyma
Smear-positive: visible TB bacilli in sputum
Smear-negative: no visible TB bacilli in
sputum
Extra-pulmonary TB
Disease involving an organ other than the
lung parenchyma
Includes pleural TB

Definitions: TB Epidemiology
Incidence
Number of persons that develop new TB disease
within a specific time period, specific geographic area
Divided by number of persons at risk for TB disease
(includes persons with and without TB infection)
Prevalence
Number of persons that develop new TB disease plus
the number of persons that already have disease
(existing cases + incident cases)
Divided by number of persons from which the
population of cases arose
Definitions: TB Epidemiology
Annual risk of infection
Probability in a given year that a person will
develop TB infection
Notification rate
Number of persons notified to a public health
agency per 100,000 population
Most widely used statistic
Not the same as the incidence rate, because
depends on persons who seek medical care,
receive TB diagnosis, have public health report
form complete, meet agencys definition of a case
Definitions: TB Epidemiology
Treatment success rate
Number of new, smear-positive TB patients cured or
completing treatment divided by all new, smear-
positive TB patients enrolled in a DOTS program
International goal is > 85% success rate
Case detection rate
Number of TB patients notified in public health
surveillance divided by estimated TB incidence
Estimated TB incidence based on annual risk of
infection and other studies
International goal is > 70% case detection rate
Risk of infection and infectious
cases
Pre-chemotherapy era
1 infectious sources infected 20 persons during the 2-year
period the case remained infectious before death or
spontaneous bacteriological conversion.
When intervention introduced
Duration of infectiousness reduced
Transmission decreased
Relation between prevalence and incidence disturbed.
In countries with inadequate case management, the number
of infectious patients may remain essentially the same after 2
years, because the principal impact of such an intervention
lies with a reduction of case fatality at the expense of keeping
infectious cases alive.
Infection increases with HIV and immunocompetent host

2 cases
of TB
1 Infectious case
20 contacts

1 Non-infectious
-_-_-
Each case leads to two cases
Risk of Infection Among Contacts as a Function of the Proximity of Contact
Risk of Infection from Exposure
Exposure to:
Persons who cough
Persons with sputum positive for acid-fast bacilli
Persons not on TB treatment
Persons just started on TB treatment
Persons with a poor response to TB treatment
Close contact, for long amounts of time, outside of
natural sunlight (e.g., UV light)
Example: a slum dwelling with many persons living
in a small space with very little sunlight
Exposure to tubercule bacilli
Number of incident cases
Duration of infectiousness
Number of case-contact/time
Population density
Family size
Difference in climatic conditions
Age of sources of infection
Gender
Housing characteristics

DISEASE SURVEY METHODOLOGY


Sampling of representative population
House to house registration
Screening:
- X-ray of all above five years of age
- Symptomatic screening
X-ray pictures read by two independent readers and by
an umpire reader
Sputum specimens (2/3) collected from persons with
abnormal X-ray shadows & / or chest symptomatics
Sputum examination by direct microscopy (and culture).
Disease mortality rates
* Community based prospective studies

* Death certification
Other Epidemiological
indicators of Tuberculosis
* Ratio of prevalence and incidence
* Age distribution of cases
* Case fatality rates
* Force of MDR cases
* Disability adjusted life years (DALY)

Epidemiological trends of
TB
Tuberculosis Mortality in Three European Cities,
Modeled From Available Data, 1750 - 1950
Year
1750 1800 1850 1900 1950
D
e
a
t
h
s

p
e
r

1
0
0
,
0
0
0
0
200
400
600
800
1000
Grigg ERN. Am Rev Tuberc Pulm Dis 1958;78:151-72
London
Stockholm
Hamburg
Tuberculosis Mortality Rates in Germany, 1892 - 1940
Year
1890 1900 1910 1920 1930 1940
D
e
a
t
h
s

p
e
r

1
0
0
,
0
0
0
0
50
100
150
200
250
Redeker F. In: Handbuch der Tuberkulose (Hein J, et al, eds) 1958;1:473
Secular Trend in Annual Risk of Infection,
Selected European Countries
Calendar year
1900 1920 1940 1960 1980
P
e
r

c
e
n
t

r
i
s
k

(
l
o
g

s
c
a
l
e
)
0.01
0.1
1
10
N
o
r
w
a
y
Poland
S
lo
v
e
n
ia
F
r
a
n
c
e
N
e
t
h
e
r
l
a
n
d
s
E
n
g
la
n
d
a
n
d
W
a
le
s
Waaler H, et al. Bull Int Union Tuberc 1975;50:5-61
Sutherland I, et al. Bull Int Union Tuberc 1971;45:75-114
Lotte A, et al. Int J Epidemiol 1973;2:265-82
Sutherland I, et al. Tubercle 1983;64:241-253
Styblo K, et al. Bull Int Union Tuberc 1969;42:5-104
Vynnycky E, et al. Int J Tuber Lung Dis 1997;1:389-96
Slope reference:
% decline / year
Serbia
0%
5%
10%
15%
Centers for Disease Control and Prevention. Reported Tuberculosis in the United States 1996:1997:5
Centers for Disease Control and Prevention. MMWR 1998;47:253-7
Reported Tuberculosis Cases in the United States, 1953 - 1997
Year of notification
1950 1960 1970 1980 1990 2000
N
u
m
b
e
r

o
f

c
a
s
e
s

(
l
o
g

s
c
a
l
e
)
20000
40000
80000
Annual Risk of Tuberculous Infection
WHO South-East Asia Region
Year
50 60 70 80
R
i
s
k

o
f

i
n
f
e
c
t
i
o
n

(
%
)
(
l
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g

s
c
a
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e
)
0.1
0.2
0.5
1
2
5
Slope reference:
% decline / year
Cauthen GM. WHO Document 1988;WHO/TB/88.154:1-34
India
Indonesia
Thailand
1%
5%
10%
How does HIV pandemic
influence TB epidemic
Higher rate of progression from latent
infection to disease (5-10% per year
compared to 10% per year among HIV
negative)

Previously HIV infected persons when
exposed to TB rapidly develop the disease.

Excess cases due to the above lead to
increased transmission of infection

Higher case fatality due to HIV infection
Evidence of association between
HIV and TB
* Increase in TB in areas worst affected by HIV
* Higher increase in age group affected by HIV.
* 50 to 70% AIDS cases develop TB in South East Asia
Region.
* HIV positiv higher among TB cases than general
population.
- Northern Thailand: HIV positivity in TB cases : 40%
- Malawi : 75%

Total population
Infected with
M. tuberculosis
Infected with HIV
Determinants for the Frequency of HIV-Associated Tuberculosis in a Community
Prevalence of infection with
M. tuberculosis
Prevalence and incidence
of HIV infection
Overlap of the two respective
population segments
Impact of HIV Infection on Tuberculosis Notifications
in Chiang Rai, Thailand, 1985 - 1994
Year of notification
85 90 95
N
o
.

o
f

c
a
s
e
s

(
l
o
g

s
c
a
l
e
)
200
300
400
500
All cases
HIV-neg cases
Yanai H, et al. AIDS 1996;10:527-31
TB trends in Africa
(countries with high HIV rates)
0
50
100
150
200
250
300
350
1980 1985 1990 1995 2000
S
t
a
n
d
a
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d
i
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e
d

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e
Estimated TB incidence vs
HIV prevalence
0
200
400
600
800
0,0 0,1 0,2 0,3 0,4
HIV prevalence, adults 15-49 years
E
s
t
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B

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i
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,

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9
9
9
)
20% of all patients in Russia have MDR TB
TB morbidity rates in Russia
0
10
20
30
40
50
60
70
80
90
1970 1980 1990 1997 1998 1999
p
e
r

l
a
k
h

p
o
p
.
0
5
10
15
20
25
30
35
1987 1997
%
Case fatality rates in Russia
Increase in CFR attributable to increase in drug resistance cases
Global picture
> 2 billion people (about 1/3 of the world population)
are estimated to be infected with TB.
The prevalence of active infection was 14.4 million,
with prevalence rate of 219/100,000 persons.
The incidence of new cases was estimated to be 9.2
million, with incidence rate of 139/100,000.
12 of the 15 countries with the highest estimated TB
incidence are in Africa, where the TB incidence rate
was 363/100,000.
1.7 million deaths from TB worldwide, a death rate of
25/100,000.
The highest rates (100/100,000 or higher) are
observed in sub-Saharan Africa, India, China, and
the islands of Southeast Asia.
Intermediate rates of tuberculosis (26 to 100
cases/100,000) occur in Central and South America,
Eastern Europe, and northern Africa.
Low rates (less than 25 cases per 100,000
inhabitants) occur in the United States, Western
Europe, Canada, Japan, and Australia.
Approximately 95 percent of TB cases occur in
developing countries.
Approximately 1 in 14 new TB cases occur in
individuals who are infected with HIV
Epidemiological situation of
TB in South East Asian
countries
TB in South-East Asia
WPR
25%
AFR
18%
EMR
8%
EUR
6%
AMR
5%
SEAR
38%
Incidence: 3 mill
Deaths : 1 mill (1500/day)

India, Bangladesh, Indonesia, Myanmar & Thailand
contribute 95% of regional burden
HIV-TB in SEAR

* Second largest number of HIV positives (30%)
* 6 million HIV positives in SEAR
India :4 mill
Thailand :1 mill
Myanmar :0.5 mill
* Low sero-positivity in Bangladesh, Maldives,
Bhutan, Indonesia and Sri lanka
* Nepal : Low in antenatal women, high among
IDUs.



Incidence of all
cases
Country Pop. in
million
Global
rank
%
contribution
Total
(000)
Rate
/100000
India 1045 1 20 1761 168
Indonesia 217 3 6 557 256
Bangladesh 144 5 4 318 221
Thailand 62 19 1 80 128
Myanmar 49 22 1 75 154
Country wise Epidemiology situation
Country wise Epidemiology situation - Continued
Incidence of ss + Country
Total
(000)
Rate
/100000
Prevalence
(ss +)
/100000
TB
Mortality/
100000
HIV +
TB
cases
%
cases
MDR
India 787 75 156 37 4.6
(0.4-28)
3.4
Indonesia 250 115 272 59 0.6 0.7
Bangladesh 143 99 188 520 0.1 1.4
Thailand 35 57 254 86 24 0.5
Myanmar 33 68 83 26 11 1.5
Country DOTS
population
coverage
(%) - 2002
Treatment
success (%)
2001
cohort
DOTS detection
rate
(ss +) - 2002 (%)
India 52 85 31
Indonesia 98 86 30
Bangladesh 95 84 34
Thailand 100 56 47
Myanmar 88 81 73
What is meant by control ?
To move from high to low endemicity or
elimination
Objectives of TB control
programmes
Decrease transmission of infection by:-
- Rapidly identifying cases
- Adequate treatment
Decrease deaths due to TB.
Cure of maximum number of cases.
To prevent relapse.
To prevent emergence of drug resistance.
To reduce TB in children by preventive
treatment.
HIV prevention and control is
of major importance towards
TB control