Epidemiologi TB - Dr. Nurjannah MPH

EPIDEMIOLOGY OF TUBERCULOSIS

Nurjannah, MD, MPHPublic Health Department

Medical FacultySyiah Kuala UniversitySeptember 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.

ExposureSubclinicalinfection

Infectioustuberculosis

Non-infectioustuberculosis

Death

Riskfactors

Riskfactors

Riskfactors

Riskfactors

A Model for the Epidemiology of Tuberculosis

Rieder HL. Infection 1995;23:1-4

Steps in the pathogenesis of TB

ExposureSub-clinicalInfection

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 Risk factors for disease given that infection has occurred ?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

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 agency’s 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 era1 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

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%

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%

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 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

Est

imat

ed T

B in

cid

ence

(p

er 1

00K

, 199

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

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

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

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 (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 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

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