Epidemiology of TBand its control
Dr. V. K. ChadhaSr. Epidemiologist
National TB Institute
Bangalore
I. General concepts in TB Epidemiology
II. Epidemiological indicators of TB and their estimation
III. Global epidemiological trends of TB
IV. TB situation in South East Asia
- presentations by Country participants
V. Prospects of TB control
Why do we need to study Epidemiology of TB?
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.
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,
behavioural & cultural
of health problems & health related events and
application of this study to control health problems.
ExposureSubclinicalinfection
Infectioustuberculosis
Non-infectioustuberculosis
Death
Riskfactors
Riskfactors
Riskfactors
Riskfactors
A Model for the Epidemiology of Tuberculosis
Rieder HL. Infection 1995;23:1-4
Risk of exposure ?* Incidence / prevalence of infectious TB in
the community
* Duration of infectiousness
* opportunities for case - contact interactions
-Urban/Rural
-No. of individuals in the house holds
Risk of Infection ?
* No. of infectious droplets produced
* Volume of shared air space
* Length of exposure
* Ventilation
* Climatic conditions
Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106
Tuberculous Infection Among Children by Type ofContact and Bacteriologic Status of Index Case,
British Columbia and Saskatchewan, 1966 - 1971
Pe
r ce
nt
infe
cte
d
0
5
10
15
20
25
30
35
40Close
Casual Close
Casual
Smear + Smear -
Household transmission of TB- important epidemiological factor
• Case control study in Malawi
TB among contacts
Cases 770 56/2766
Controls 918 11/3203P<0.001
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
What is the most important risk factor for TB?
Example of Risk Differences in IndividualsFollowing Infection with M. tuberculosis
Cas
es p
er 1
,000
per
son-
year
s(lo
g sc
ale)
1
10
100
1000
Long-standinginfection
Recentinfection
Super-imposed
HIV infection
UnderlyingHIV infection
??
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 populationGold miners
IJTLD,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 and their estimation
Enumerate epidemiological indicators of TB you know of?
Epidemiological indicators of tuberculosis ?
* Prevalence of infection
* Incidence (average annual risk) of infection
(ARI)
* Prevalence of disease
* Incidence of disease
* Tuberculosis mortality rates
How to estimate prevalence of infection?
Estimating prevalence of infectionEstimating prevalence of infection
* Study population-sampling
* Registration of eligible age group
- house-to-house / school based.
* Informed consent.
* Examination for BCG scar.
* Tuberculin testing with 1TU/2TU PPD RT23 with tween 80.
* Reading of reaction sizes appx. 72 hours later.
What is the rationale behind tuberculin surveys in children ?
• Extent or recent transmission
• Study trends in TB epidemiology
(Ultimate aim of control programme is to replace older more infected cohorts with younger less infected cohorts)
Analysis of tuberculin surveyction size % of
childrenReaction size % of
children1 mm 16 mm2 mm 17 mm3 mm 18 mm4 mm 19 mm5 mm 20 mm6 mm 21 mm7 mm 22 mm8 mm 23 mm9 mm 24 mm10 mm 25 mm11 mm 26 mm12 mm 27 mm13 mm 28 mm14 mm 29 mm15 mm 30 mm
Frequency Distribution of Tuberculin SkinTest Reaction Sizes, Korea 1975
Induration (mm)
0 5 10 15 20 25 30
Fra
ctio
n re
actin
g
0.00
0.05
0.10
0.15
Korean Institute of Tuberculosis 1976:1-116
0
5
10
15
20
25
30
35
40
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
Reaction in mm
Perc
enta
ge
Frequency distribution of tuberculin reaction sizes among children aged 1-9 years - Kota
N = 3870
Estimation of incidence of infection?
Dual skin testing at two different periods -Conversion -Boosting
Compute average annual risk of infection
(ARTI) = 1-(1-P)1/A
A RT I
• Key epidemiological indicator in developing countries.
• It is the probability of acquiring new tuberculosis infection or re-infection over the course of one year.
A R I expresses the overall impact of various factors influencing the transmission of tubercle bacilli !
- Load of infectious cases
- Efficiency of case finding
- Efficiency of treatment programme
ARI identifies the regions of high transmission
It provides an indirect estimate of size of sources
of infection
Any change in disease burden and programme
implementation is first reflected in the change in
ARI
It holds the key to the study of epidemiological
trends which are more important than exact
estimates of disease prevalence
How to estimate prevalence of disease?
DISEASE SURVEY METHODOLOGYDISEASE SURVEY METHODOLOGY
Sampling of representative population
House to house registration
Screening:
- MMR 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).
How to estimate disease incidence?
Relationship between ARTI and incidence of disease
Styblo derived the following relationship from data of pre- chemotherapy
• Every one percent of ARTI corresponds to 50 new smear positive cases per 100,000 population per year
Relationship between ARI & Incidence of smear positive cases of Pulmonary Tuberculosis
(Indian studies)
Incidence / 100,000pop for every one
percent of ARI
NTI Longitudinalstudy (1961 – 1968)
53
BCG Prevention Trial 42-74 (57)
Relation between ARI and Incidence !
* Situation : Disease incidence remains same
but the risk of infection declines
Q 1. When is this situation likely?
Q 2. What is the impact on equation
(relationship) ?
What happens to the equation in high HIV settings?
The equation is dependent more on number of infections generated per case and not merely on incidence
Disease mortality rates !
* Community based prospective studies
* Death certification
ESTIMATION OF ANNUAL RISK OF TUBERCULOUS INFECTION IN DIFFERENT ZONES OF INDIA
-A CROSS SECTIONAL STUDY
2000-2003
Districts selected for National Sample Survey -ARI
The proportion of children with BCG scar by zone
North Zone 45.3%
South Zone 64.3%
West Zone 52.0%
East Zone 51.5%
The estimated prevalence of infection and ARTI by zone
ZonePrevalence
of infectionARTI
North10.3%
(8.4-12.2)
1.9%
(1.5-2.2)
West9.3%
(6.8-11.8)
1.8%
(1.3-2.3)
South6.1%
(4.9-7.2)
1.1%
(0.9-1.3)
East6.9%
(5.5-8.2)
1.3%
(1.0-1.6)
( ) : 95% C.I.
Prevalence of infecton by zone and stratum (1-9 years)
9.1
4.5
7.8
6.5
14.1
9.8
12.6
9.0
10.3
6.1
9.3
6.9
0
2
4
6
8
10
12
14
16
North South West East
%
Rural Urban Zone
Does higher ARTI in urban areas indicate higher incidence of
smear positive cases
Programme inputs The survey findings provide baseline estimates of ARI for
- evaluation of TB Control Measures.
- Study of epidemiological trends in years to
come High rate of ARI indicates high load of infectious cases of TB in
most parts of India. Prolonged and sustained efforts required to control TB.
There are significant inter-regional differences in tuberculosis situation.
Intensification of TB control services in urban areas with higher ARI rates to be taken up on priority basis.
Case finding expectations cannot be applied uniformly all over the country
Other Epidemiological indicators of Tuberculosis
* Ratio of prevalence and incidence
* Age distribution of cases
* Case fatality rates
* Force of MDR cases
* TBM notification rates
* 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
Dea
ths
per
100,
000
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
Dea
ths
per
100,
000
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
Per
cen
t ris
k (lo
g sc
ale)
0.01
0.1
1
10
Norway
PolandSlovenia
FranceNetherlands
England and Wales
Waaler H, et al. Bull Int Union Tuberc 1975;50:5-61Sutherland I, et al. Bull Int Union Tuberc 1971;45:75-114Lotte A, et al. Int J Epidemiol 1973;2:265-82
Sutherland I, et al. Tubercle 1983;64:241-253Styblo 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%
TB trends in EuropeMedian age in Finland
39.4
31.1
55.7
65.1
0
10
20
30
40
50
60
70
Males Females
19541986
TB trends in EuropeNetherlands
Year ARI Median Age
1950 0.53% 28.9 year
1980 0.21% 43.7 year
Global drug resistance surveillance
D.R. among newcases
D.R. amongpreviously treatedcases
1994-96 1.4% 13%
1996-99 1.0% 9.3%
Centers for Disease Control and Prevention. Reported Tuberculosis in the United States 1996:1997:5Centers 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
Num
ber
of c
ases
(lo
g sc
ale)
20000
40000
80000
Annual Risk of Tuberculous InfectionWHO South-East Asia Region
Year
50 60 70 80
Ris
k of
infe
ctio
n (%
)(lo
g sc
ale)
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%
Trends in ARI-Chingleput
At intake in 1969 : 1.8%After 4 years in 1973 : 1.8%After 10 years : 1.9%After 15 years : 1.7%
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 SEAR.
* HIV positivity higher among TB cases than
general population.
-Northern Thailand: HIV positivity in TB cases :
40%
: Malawi : 75%
Total population
Infected withM. 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 Notificationsin Chiang Rai, Thailand, 1985 - 1994
Year of notification
85 90 95
No.
of c
ases
(lo
g sc
ale)
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
Sta
nd
ard
ize
d n
oti
fic
ati
on
ra
te
Estimated TB incidence vs HIV prevalence
0
200
400
600
800
0.0 0.1 0.2 0.3 0.4HIV prevalence, adults 15-49 years
Esti
mat
ed
TB
inci
de
nce
(p
er
100K
, 199
9)
Notification Rates of Sputum Smear-Positive Tuberculosis,by Age, Tanzania Mainland, 1984 and 1995
Age group (years)
0 15 25 35 45 55 65
Not
ifica
tions
per
100
,000
0
50
100
150
200
Tanzania NTLP / IUATLD. Progress Report 1996;No. 36
1995
1984
20% of all patients in Russia have MBR TB
TB morbidity rates in Russia
0
10
20
30
40
50
60
70
80
90
1970 1980 1990 1997 1998 1999
per l
akh
pop.
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
Culture Positive cases, Prevalence:Incidence - Chingleput
0
1.5
3
4.5
1968-70 1971-73 1973-75 1976-78 1979-81 1981-83
Average - 3.4
(3.6 for smear pos)
In your opinion, what should be the practical methods of monitoring epidemiological trends in any given community
Global picture
• 3rd largest cause of death (2.8%) and loss of DALYs in 15-59 year age group
• Incidence all cases - 8.8 million (2002)-141/100000
• in 22 HBCs - 7.0 million (80%)
• Smear + - 3.9 (63/100000) million
• Case notifications of smear positive cases increasing @ 4% per year- 5% in eastern Europe and 7% in high HIV African countries.
Epidemiological situation of TB in South East Asian countries
Format for Country presentationsEstimated incidence of New smearpositive casesLatest estimates of ARTI
Population mortality rates
Any information on disease trends
HIV sero-prevalence among TBcasesMDR in new cases
MDR in previosly treated cases
Any other epidemiologicalinformation eg, age sex distributionof cases, TB in prisoners etc.
TB in South-East Asia
WPR25%
AFR18%
EMR8%
EUR6%
AMR5%
SEAR38%
Incidence: 3 millDeaths : 1 mill (1500/day)
India, Bangladesh, Indonesia, Myanmar & Thailand contribute 95% of regional burden
HIV-TB in SEAR
* Second largest number of HIV positives after SSA
SSA:60% SEAR: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.
TB situation in India
Prevalence of sputum positive pulmonary TB
Area Year Preval. Rate per 1000 pop.
National Sample Survey 1955-58 4
Tumkur 1960-611979
4.14.4
Rural Bangalore 1960-611967-681974-751984-86
4.13.93.24.4
Chingleput 1968-711973-751979-811984-861999-2001
10.78.97.76.96.9
Raichur 1988-89 10.7
Morena, M.P. 1991-94 12.7
A R T I i n I n d i a
0
0.5
1
1.5
2
2.5
3
3.5
4
Tum
kur D
istt,
1960
-61
Tum
kur D
istt,
1972
-73
Rura
l Ban
galo
re, 1
961
Rura
l Ban
galo
re, 1
970
Bang
alor
e(Ru
ral),
197
7-78
Bang
alor
e Ru
ral,
1984
Per
i urb
an B
anga
lore
, 199
2
Bang
alor
e Ci
ty, 1
997
Chin
glep
ut, T
N 1
969
Chin
glep
ut, T
N 1
979
Chin
glep
ut, T
N 1
984
Car N
icob
ar Is
land
, 198
6
Triv
andr
um, 1
991-
92
Bika
ner
Raj
, 199
2
Mor
ena,
MP,
1989
Tiru
vallu
r, 19
99-2
001
Nor
th Z
one-
Indi
a 20
00-0
2
Wes
t Zon
e-In
dia
2000
-02
Sout
h Zo
ne-In
dia
2000
-02
East
zon
e In
dia
2001
-03
Annu
al R
isk
of I
nfec
tion
(%)
INCIDENCE OF PULMONARY INCIDENCE OF PULMONARY TUBERCULOSIS IN INDIATUBERCULOSIS IN INDIA
Study Period Method Incidence
1961-62 1.361962-64 0.80
Bangalore RuralAge 5years 1964-68
Repeated Surveys1.04
Def : Culture +ve
1968-71 3.83
1976-78 2.30
BCG.TRIAL,ChingleputAge > 15 years
1981-83
Repeated Surveys,passive case
finding , selectivecase finding 3.00
Def: Culture positive &/or Microsopy +ve
CMC – VelloreAge> 10 yrs
1981-83 Active case finding 1.10
Def:Smear +ve
HIV Sero-prevalence among TB Cases
Year of study % HIV +ve
Govt Hospital Tanjavur, TN 1999 8.9
General Hospital, Pune, MH 2000 28.8
TB & Chest Hospital,Goa 2000 10.9
AIIMS, Delhi 2000-02 9.4
Medical College, Lucknow 2000-01 4.3
Medical College, Aligarh 2000-01 2.8
Multi Drug Resistance in new TB cases
Year of study % MDR
23 districts of Tamilnadu 1997 3.4
DOT centres, Bangalore 1999 2.2
DTP centres, Raichur, Karnataka 1999-2000 2.5
Wardha, Maharashtra 2000-01 0.5
Jabhalpur, Madhya Pradesh 2001-02 1.0
Hoogli, West Bengal 2000-01 3.0
Mayurbhanj, Orissa 2000-02 0.7
Multi Drug Resistance in previously treated TB cases
Year of study % MDR
TB Sanatorium, Chennai, TN 1997-2000 54.8
DOT centres, Tiruvallur, TN 1999-2000 18.3
State TB Centre, Ahmedabad, GJ 2000-01 33.0
ARI in other countries
2.32.2 2.2
1.5
1
2
2.6
1.1
0.9
0.6
0.3
2
0
0.5
1
1.5
2
2.5
3
Series1
Incidence of allcases
Country Pop. inmillion
Globalrank
%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 +CountryTotal(000)
Rate/100000
Prevalence(ss +)
/100000
TBMortality/
100000
HIV +TB
cases
%casesMDR
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 DOTSpopulationcoverage
(%) - 2002
Treatmentsuccess (%)
– 2001cohort
DOTS detectionrate
(ss +) - 2002 (%)
India 52 85 31
Indonesia 98 86 30
Bangladesh 95 84 34
Thailand 100 56 47
Myanmar 88 81 73
Progress of DOTS in high burdened countries
High treatment success (>70%)Low treatment
successCase detection under
DOTS 10-49%>50%
Brazil, Russia,South Africa,Uganda
Afghanisthan,Bangladesh, China,Euthopia, India,Indonesia, Kenya,Mozambique, Nigeria,Pakistan, Tanzania,Zimbabwe
Cambodia, Cango,Myanmar, Philipines,Thailand, Vietnam
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.• IEC - Purpose ?
2 cases of TB
1 Infectious case
20 contacts
1 Non-infectious
-_-_-
Each case leads to two cases
How does DOTS strategy help control TB?
DOTS
• Decreases deaths
• Decreases duration of infectiousness
• Increased case detection plus high cure rate decreases transmission of infection that will ultimately lead to decline in incidence.
• Prevents emergence of MDR
A good programme like DOTS reduces disease burden
• Case fatility rate reduced to <5% compared to 60%-70% in a few years among untreated cases.
• Cure of every case under DOTS with about 4 months diagnostic delay prevents 0.7 new smear positive cases.(further prevention possible by reducing diagnostic delay)
• Preventive treatment to each child prevents 0.03 new case and 0.007 deaths.
How does a poor programme worsen the TB situation
• Poor programme with low cure rate (<50%) and low detection rate worsen TB situation by decreasing case fatility rates leading to increased prevalence and transmission of infection.
HIV prevention and control is of major importance towards TB
control
Priority to smear positive cases
• To reduce transmission of infection. A good DOTS programme would reduce transmission of infections by about 73%
• Cost per DALY highest for treating smear positive cases.
The Cuba example
• Very low levels of MDR in Cuba
• Cuba is a low HIV country
HIV-TB Vs. DOTS - TB trends in Tanzania
0
10
20
30
40
50
60
70
80
90
100
1978-82 1983-87 1988-92 1993-97
0
0.2
0.4
0.6
0.8
1
1.2
smear positivenotif icationrate/ 100,000popTreatmentcompletionrates
ARI
• Increased case detection will decrease transmission rapidly provided cure rates are high.
• It has been estimated that achievement of 70% case detection and 85% cure rate by 2010 will result in greatest benefits in cases and deaths averted in regions with highest burden - South East Asia, Africa and Western Pacific.
• Longer the time taken to reach targets, incidence will decrease more slowly.
• The proportion of deaths averted by DOTS would be greater than the proportion of cases– Non curative treatment can prevent death without
eliminating infectiousness.
– Programme will treat non-infectious cases also
Control TB since every breadth counts (World TB day 2004 theme)
Business as usual will not eliminate TB
It is time for business unusual
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