Tuberculosis, its epidemiology & current situation.

Tuberculosis,Tuberculosis,its epidemiology & its epidemiology &

current situationcurrent situation

Tuberculosis,Tuberculosis,its epidemiology & its epidemiology &

current situationcurrent situation

Causal Causal AgentAgentCausal Causal AgentAgent

- - Mycobacterium tuberculosisMycobacterium tuberculosis ccomplexomplex

- - M. tuberculosisM. tuberculosis - M. bovis- M. bovis - M. africanum- M. africanum - M. microti- M. microti - M. caneti- M. caneti - M. pinnipedii- M. pinnipedii - M. caprae- M. caprae

- Slow and Little Alarmant- Slow and Little AlarmantClinical Clinical PresentationPresentation

- Excessive - Excessive Delay Delay to Consult the HCto Consult the HC

- Very Late Diagnosis- Very Late Diagnosis

LongLong time to be contagious when the Cases are Diagnosed time to be contagious when the Cases are Diagnosed

- M. tuberculosis delay - M. tuberculosis delay 16-24 h16-24 h. to be divided. to be divided (60 < Estafiloc.) (60 < Estafiloc.)

Very Slow Very Slow Division CapacityDivision CapacityVery Slow Very Slow Division CapacityDivision Capacity

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Causal AgentCausal Agent

- Mycobacterium tuberculosis complex - Mycobacterium tuberculosis complex

Polyvalent Polyvalent behaviourbehaviour depending depending on medium.on medium.

■ In a tuberculosis patient, there are In a tuberculosis patient, there are different bacillary populationsdifferent bacillary populations formed of formed of bacilli in different situationsbacilli in different situations

- Location- Location

- pH- pH

- Replication rate, susceptibility to drugs, …- Replication rate, susceptibility to drugs, …

Bacillary populationsBacillary populations

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Bacillary populationsBacillary populations1. 1. RapidlyRapidly multiplying bacilli multiplying bacilli

- Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavern wall)

- Large number of bacilli → High probability of spontaneous natural mutations

Many Millions

Natural Resistant Mutants

FailureFailure

RelapsesRelapses2. 2. SlowSlow multiplication Bacilli multiplication Bacilli

- Intramacrophagic location. Acid pH. Population<105

No Naturally Resistant MutantsNo Naturally Resistant Mutants

Bacillary populationsBacillary populations

Bacillary populationsBacillary populations3. 3. IntermittentlyIntermittently growing bacilli growing bacilli

- Unfavourable conditions. Solid caseum. Extracellular

- Population <105 - Relapse capacity

No Naturally Resistant MutantsNo Naturally Resistant Mutants

RelapsesRelapses

Bacillary Bacillary populationspopulations

1. Rapidly multiplying bacilli1. Rapidly multiplying bacilli → INHINH

- Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavern wall)

- Large number of bacilli → High probability of spontaneous mutations

2. Slowly multiplying bacilli2. Slowly multiplying bacilli → PZPZ

- Intramacrophagic location. Acid pH. Population<105

3. Intermittently growing bacilli3. Intermittently growing bacilli → RIFRIF

- Unfavourable conditions. Solid caseum. Extracellular- Population <105. Relapse capacity

4. Bacilli in latent state:4. Bacilli in latent state: Not susceptible to drugs

- Reactivations and relapses

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2. 2. ReservoirReservoir. Source of Infection. Source of Infection2. 2. ReservoirReservoir. Source of Infection. Source of Infection

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ReservoirReservoirReservoirReservoir

- MAN:- MAN: * Infected, healthy* Infected, healthy

World Population:World Population: 6.100 Millions 6.100 Millions

M. TB Infection:M. TB Infection: 2.000 Millions 2.000 Millions

¡¡ Possible Reservoir MDR-TB: ¡¡ Possible Reservoir MDR-TB: 50 Millions50 Millions !! !!

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Source of InfectionSource of InfectionSource of InfectionSource of Infection

- MAN:- MAN:

* Active * Active diseasedisease

TB Cases: TB Cases: 16 million 16 million

MDR-TB Cases:MDR-TB Cases: + 500.000+ 500.000

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Mechanism of Mechanism of TransmissionTransmissionMechanism of Mechanism of TransmissionTransmission

- Fundamentally AEROGEN- Fundamentally AEROGEN

- Very Uncommon:- Very Uncommon: - Cutaneous-Mucosal- Cutaneous-Mucosal

- Urogenital- Urogenital

- Inoculation- Inoculation

- Tran placental, etc- Tran placental, etc

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TB Transmission. Contagious aerosol (droplets < 5 micras)

Greatest TB Greatest TB TransmittersTransmittersGreatest TB Greatest TB TransmittersTransmitters

1.- Persons with bad Coughs1.- Persons with bad Coughs

2.- Sputum Sm+ Patients2.- Sputum Sm+ Patients

3.- Untreated patients3.- Untreated patients4.- Patients who have just commenced treatment4.- Patients who have just commenced treatment

5.- Cases with poor response to treatment5.- Cases with poor response to treatment

Pulmonary TB (85%)

Exposure toSource of disease

Sputum Smear+

Infection

Active TB

Extra Pulmonary(15%)

10-15 persons / year 5 – 10%

Sputum Smear Negative (35%)

50%

TB Epidemiologic TB Epidemiologic CycleCycle

TB TB RiskRisk Groups Groups Relative Risk of developing TBRelative Risk of developing TB

(compared with control population, regardless of (compared with control population, regardless of PPD)PPD)

TB TB RiskRisk Groups Groups Relative Risk of developing TBRelative Risk of developing TB

(compared with control population, regardless of (compared with control population, regardless of PPD)PPD)

- HIV/AIDS 150

- Silicosis 30

- Diabetes 2 – 4.1

- Chronic renal failure / Haemodial. 10 – 25.3

- Gastrectomy 2-5

- Jejunoileal by-pass 27 - 63

- Kidney transplant 37

- Heart “ 20 - 74

- Head or neck carcinoma 16

ATS/CDC. Am J Respir Crit Care Med 2000; 161 (part 2)

M. tuberculosis Resistance M. tuberculosis Resistance Natural Resistant Mutants according to Bacillary Natural Resistant Mutants according to Bacillary

PopulationPopulation

M. tuberculosis Resistance M. tuberculosis Resistance Natural Resistant Mutants according to Bacillary Natural Resistant Mutants according to Bacillary

PopulationPopulation

INH 1 x 105-106 Bacilli

RIF 1 x 107-108 Bacilli

SM 1 x 105-106 Bacilli

EMB 1 x 105-106 Bacilli

PZ 1 x 102-104 Bacilli ?

Quinolones 1 x 105-106 Bacilli ?

Others 1 x 105-106 Bacilli ?

M. tuberculosis Resistance M. tuberculosis Resistance Bacillary Population in different TB LesionsBacillary Population in different TB Lesions

M. tuberculosis Resistance M. tuberculosis Resistance Bacillary Population in different TB LesionsBacillary Population in different TB Lesions

TB Sm+ 107-109 Bacilli

Cavitary 107-109 Bacilli

Infiltrated 104-107 Bacilli

Nodules 104-106 Bacilli

Adenopathies 104-106 Bacilli

Renal TB 107-109 Bacilli

Extrapul. TB 104-106 Bacilli

Bacteriological Fundaments

of TB Treatment

1. Drug combinations

The combination of drugs prevents the

appearance of resistance,

because it avoids the selection of

naturally resistant mutants

Selection of Natural Resistance,Selection of Natural Resistance,

Acquired and Initial ResistanceAcquired and Initial Resistance

SUSCEPTIBLESUSCEPTIBLE

to Drugsto Drugs

RESISTANTRESISTANT

to Drugsto Drugs

LatentLatent

ContagiousContagious

LatentLatent

Contagious Contagious

Develop intoDevelop into

DR TBDR TB

transmissiontransmission

acquire DR-TBacquire DR-TB acquire (M)DR-TBacquire (M)DR-TB

transmissiontransmissionDevelop Develop

into TBinto TB

Basic Concepts in TB Resistance

M.D.R.M.D.R.

M. Tuberculosis Resistance M. Tuberculosis Resistance Multidrug-resistance (MDR)Multidrug-resistance (MDR)

M. Tuberculosis Resistance M. Tuberculosis Resistance Multidrug-resistance (MDR)Multidrug-resistance (MDR)

Defined as resistance at a minimum to “INH+RIF”

It is extremely dangerous, as this TB is very difficult to cure

MDR may be:– Primary or Initial– Acquired

Will it determine Will it determine

the the futurefuture of TB? of TB?

موارد مقاوم به چند دارو

موارد حساس به دارو

250 تا 25بین میلیون تومان

000,200کمتر از تومان هزينه

%95بیش از درصد60 تا 40 اميد بهبودي

ماه6 ماه24 تا 18طول دوره

درمان

موارد100% ماه6 تا 4

% 10کمتر از موارد

به مدت کوتاه

نیاز به بستری

غالبا نارسایی تنفسی برای تمام عمر ندارد معلوليت

حفظ يك منبع آلودگي از نوع مقاوم

حذف یک منبع انتشار

يدميولوژيپا

مقايسه هزينه ، طول مدت درمان و اثر بخشي رژيم هاي درماني موجود ميان يك

بيمار مبتال به سل حساس به دارو و يك بيمار به سل مقاوم به چند دارو

LOSS OF HEALTHY LIFE DUE TO TB

Rank Condition %DALYs1 Lower respiratory infections 6.12 HIV/AIDS 6.03 Unipolar depressive disorders 4.54 Diarrhoeal diseases 4.15 Ischaemic heart disease 4.06 Childhood diseases 3.37 Cerebrovascular disease 3.18 Malaria 2.99 Road traffic accidents 2.6

10 Tuberculosis 2.5

Estimated numbers of new cases, 2006Estimated numbers of new cases, 2006

No estimate

0–999

10 000–99 999

100 000–999 999

1 000 000 or more

1000–9999

Estimated number of new TB cases (all forms)

9m cases annually>1/3 in India and China

Estimated TB incidence rate, 2006Estimated TB incidence rate, 2006

Estimated new TB cases (all forms) per 100 000 population

No estimate

0-24

50-99

300 or more

25-49

100-299World : 139/100,000

Highest TB rates per capita are in Africalinked to HIV/AIDS

Tuberculosis notification rates, 2006Tuberculosis notification rates, 2006

No report

0–24

25–49

50–99

100 or more

Notified TB cases (new and relapse) per 100 000 population

World : 82/100,000

82*100/139 = 57%

Smear+ CDR= 61%

World Health

Assembly 1991

"…attain a global target of cure of 85% sputum-positive patients under treatment and detection

of 70% of cases by the year 2000"

MILLENNIUM DEVELOPMENT GOALS (2015)MILLENNIUM DEVELOPMENT GOALS (2015)

1. Eradicate poverty and hunger2. Universal primary education3. Empower women4. Reduce child mortality5. Improve maternal health6. Combat HIV/AIDS, malaria and other diseases7. Environmental sustainability8. Global partnership for development

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Targets for global TB controlMILLENNIUM DEVELOPMENT GOALS

"to have halted and begun to reverse incidence... by 2015"

Targets for global TB controlMILLENNIUM DEVELOPMENT GOALS

"to have halted and begun to reverse incidence... by 2015"

Implementation (DOTS) Target YearCase detection 70% 2005

Treatment success 85% 2004/5

ImpactPrevalence 50% 2015

Death 50% 2015 Incidence <1 per million 2050

Estimated TB Burden I.R.IRAN – 2006

Estimated TB Burden I.R.IRAN – 2006

GlobalGlobal EMROEMRO IranIran

Prevalence RatePrevalence Rate 219/100,000219/100,000 152/100,000152/100,000 2828/100,000/100,000

Mortality RateMortality Rate 25/100,00025/100,000 20/100,00020/100,000 33/100,000/100,000

Incidence RateIncidence Rate

All formsAll forms 139/100,000139/100,000 105/100,000105/100,000 2222/100,000/100,000

SS+SS+ 62/100,00062/100,000 47/100,00047/100,000 1010/100,000/100,000

HIV prev. in new TB casesHIV prev. in new TB cases 7.7 %7.7 % 1.1 %1.1 % 1.71.7

Estimated HIV prevalence in new TB cases, 2006Estimated HIV prevalence in new TB cases, 2006

No estimate

0–4

20–49

50 or more

5–19

HIV prevalence in TB cases, (%)

World= 7.7%

MDR-TB Prevalence Rate among new cases2006

MDR-TB Prevalence Rate among new cases2006

World: 3.1%

EMRO: 2.9%

MDR-TB Prevalence Rate among Previously Treated Cases2006

MDR-TB Prevalence Rate among Previously Treated Cases2006

World: 19.3%

EMRO: 28.9%

XDR-TBXDR-TB

Extensively drug-resistant TB (XDR TB) defined as:

MDR TB with further resistance to:

•A fluoroquinolone

• One or more of the following injectable drugs:

kanamycin, amikacin, capreomycin

Source: Global XDR-TB Task Force, 7-8 October, 2006

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Ecuador

Georgia

Argentina

Bangladesh

Germany

Republic of Korea

Armenia

Russian Federation

South Africa

Portugal

Latvia

Mexico

Peru

USA

Brazil

UK

Sweden

Thailand

Chile

Spain

Islamic Republic of Iran

China, Hong Kong SAR

France

Japan

Norway

Canada

Countries with confirmed XDR-TB cases as of February 2007

Countries with confirmed XDR-TB cases as of February 2007

Estimated number of

cases

Estimated number of

deaths

1.6 million8.8 million

116,000*424,000

All forms of TB

Multidrug -resistant

TB )MDR-TB(Extensively drug-resistant TB )XDR-TB(

27,000* 16,000*

* Calculated based on several available estimates

Latest Global TB Estimates - 2005Latest Global TB Estimates - 2005

Drug susceptible TB*

*or limited resistance

Manageable with 4 drug regimen - DOTS

Resistance to H&R

Treatable with 2nd line drugs

MDR-TB

1990

XDR-TB

2006

Resistance to 2nd line drugs

Treatment options seriously restricted

Total DR ?

Resistance to all available drugs

No treatment options

Evolution of drug-resistant TBEvolution of drug-resistant TB

سلوضعيت فعلي بيماري در جمهوري اسالمي ايران

سلوضعيت فعلي بيماري در جمهوري اسالمي ايران

بيست و دو كشور داراي بيشترين بار بيماري

فراواني و ميزان بروز گزارش شده سل در كشور (1387)

فراواني و ميزان بروز گزارش شده سل در كشور (1387)

ميزان بروزگزارش شده

/ (100,000) تعداد

13.4 9742 كل اشكال سل

6.7 4885 اسمير خلط مثبت

سل ريوي

2.7 1936 اسمير خلط منفي

3.6 2606 سل خارج ريوي

وضعيت ميزان بيماريابي سل در كشور (1387)

وضعيت ميزان بيماريابي سل در كشور (1387)

CDR

) ميزان بروز/100,000)

تعدادمورد انتظار

گزارش شده

61 % 22 13.4 9742 كل اشكال سل

67% 10 6.7 4885 اسمير خلط مثبت سل

ريوي2.7 1936 اسمير خلط

منفي

3.6 2606 سل خارج ريوي

موارد 67%موجود

شناسايي و گزارش شده

.اند

موارد شناسايي نشده )گم شده(:

بيماران33%

اين موارد شناسايي نشده، كجا گم شده اند؟

روند فراواني موارد سل اسمير مثبت گزارش شده در كشور

1387 به تفكيك مليت

روند فراواني موارد سل اسمير مثبت گزارش شده در كشور

1387 به تفكيك مليت

ميزان بروز سل ريوي اسمير خلط مثبت برحسب دانشگاههاي علوم پزشكي كشور –

1387 سال

توزيع جنسي بروز سل ريوي اسمير مثبت در كشور 1387 در سال

توزيع جنسي بروز سل ريوي اسمير مثبت در كشور 1387 در سال

50%

50%

مرد زن

نتيجه درمان بيماران مبتال به سل ريوي اسمير مثبت

85 سال –جمهوری اسالمی ایران

نتيجه درمان بيماران مبتال به سل ريوي اسمير مثبت

85 سال –جمهوری اسالمی ایران

1385

83 ميزان موفقيت درمان