n this Lecture I tried my best to include all essential features about the TB disease. I hope that this will help to undergraduate Medical students for better understanding the Disease.

1. AB RAJAR
ASSOCIATE PROFESSOR
COMMUNITY HEALTH SCIENCES.
Muhammad Medical College
“Captain of men of death”
“The great white plague”.
“To dry up”

2. LEARNING OBJECTIVES.
• Introduction.
• Global Burden of Tuberculosis.
• National Burden of Tuberculosis.
• The economic and social burden of Tuberculosis.
• Epidemiological indices.
• Natural History of Tuberculosis.
• Directly observed treatment, short course (DOTS) chemotherapy.
• Childhood Tuberculosis.
• The control of Tuberculosis.

3. INTRODUCTION.
• It is a specific infectious disease caused by M.Tuberculosis,primarily
affecting the lungs but secondary can affect as:
• Intestine,
• Meninges,
• Bones,
• joints,
• Lymph glands,
• Skin
• & other tissues of the body.

4. HISTORY OF TB
• Until mid-1800s, many believed TB was hereditary
• 1865 Jean Antoine Villemin proved TB was contagious
• 1882 Robert Koch discovered M. Mycobacterium bacterium tuberculosis that
causes TB.

5. TB HISTORY TIMELINE
1840 19201860 1900 1940 1960 1980 20001880
TB cases decline1993:
due to increased funding
and enhanced TB control
efforts
1884:
First TB
sanatorium
established
in U.S.
1865:
Jean-
Antoine
Villemin
proved TB is
contagious
1943:
Streptomycin
(SM) a drug used
to treat TB is
discovered
1882:
Robert Koch discovers
M. tuberculosis
Mid-1980s:
Unexpected rise in
TB cases
1943-1952:
Two more drugs are
discovered to treat
TB: INH and PAS

6. WHO | TUBERCULOSIS
• Tuberculosis (TB) is one of the top 10 causes of death worldwide.
• In 2016, 10.4 million people fell ill with TB, and 1.7 million died from the
disease (including 0.4 million among people with HIV).
• Over 95% of TB deaths occur in low- and middle-income countries.
• Seven countries account for 64% of the total, with India leading the count,
followed by Indonesia, China, Philippines, Pakistan, Nigeria, and South
Africa.
• In 2016, an estimated 1 million children became ill with TB and 250 000
children died of TB (including children with HIV associated TB).
• TB is a leading killer of HIV-positive people: in 2016, 40% of HIV deaths
were due to TB.

7. WHO | TUBERCULOSIS
• Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health
security threat.
• WHO estimates that there were 600 000 new cases with resistance to
rifampicin – the most effective first-line drug, of which 490 000 had MDR-
TB. Globally, TB incidence is falling at about 2% per year.
• This needs to accelerate to a 4–5% annual decline to reach the 2020
milestones of the End TB Strategy.
• An estimated 53 million lives were saved through TB diagnosis and
treatment between 2000 and 2016.
• Ending the TB epidemic by 2030 is among the health targets of the
Sustainable Development Goals.

8. • 8.7 million new cases
• 13% in HIV-infected (HIV+) patients
• India/China->40%
• Africa (South Africa>Nigeria)-> 24%
• Americas-> 3%
• 1.4 million TB-related deaths
• 990,000 in HIV-uninfected (HIV-)
• 430,000 in HIV+
• One of the top three causes of death for adult females in resource-limited
settings (RLS)
TB: 2011 snapshot
WHO Global Tuberculosis Control , 2012

9. 2011 Global TB Incidence Rates:
“disease of poverty”
WHO Global Tuberculous Control , 2012

10. 2011 Global Burden of HIV/TB
Co-Infection
WHO Global Tuberculous Control , 2012

11. WHO EMRO | Tuberculosis | Programmes | Pakistan
• Pakistan, with an estimated 510 000 new TB cases emerging each
year.
• Approximately 15 000 developing drug resistant TB cases every year.
• Pakistan ranked fifth among TB high-burden countries worldwide and
it accounts for 61% of the TB burden in the WHO Eastern
Mediterranean Region. [EMRO]
• The country is also estimated to have the fourth highest prevalence of
multidrug-resistant TB (MDR-TB) globally.

12. THE ECONOMIC AND SOCIAL BURDEN OF DISEASE.
• TB primarily affects people in their most productive years of life.
• Almost 80% of TB patients are between 15 to 54 years of age.
• While 2/3 of cases are male.’
• More than 50% of female cases occurring before the age of 34 years.
• TB kills more women in reproductive age than all causes of maternal
mortality.
• 1/3 of female infertility.
• Huge number of children of TB patients either leave school or take up
employment to get help support their children.

13. TB Infection vs. TB Disease
• There is a difference between TB “infection” and TB “disease”
• TB INFECTION:
• TB germs stay in your lungs, but they do not multiply or make you sick
• You cannot pass TB germs to others
• TB DISEASE:
• TB germs stay in your lungs or move to other parts of your body, multiply,
and make you sick
• You can pass the TB germs to other people

14. FACTORS CONTRIBUTING TO THE INCREASE IN TB CASES
a. HIV epidemic
b. Increased immigration from high-prevalence countries
c. Transmission of TB in congregate settings (e.g., correctional
facilities, long term care)
d. Deterioration of the public health care infrastructure

15. NOT EVERYONE EXPOSED BECOMES INFECTED
•Probability of transmission depends on:
– Infectiousness
– Type of environment
– Length of exposure
•10% of infected persons will develop TB disease at some
point in their lives
– 5% within 1-2 years
– 5% at some point in their lives

16. PERSONS AT RISK FOR DEVELOPING TB DISEASE
• Persons at high risk for developing TB disease fall into 2
categories
a. Those who have been recently infected
b. Those with clinical conditions that increase their risk of
progressing from LTBI (latent T.B infection) to TB disease

17. INCREASED RISK FOR PROGRESSION TO TB DISEASE.
Persons more likely to progress from LTBI to TB disease include:
• HIV infected persons
• Those with history of prior, untreated TB
• Underweight or malnourished persons
• Injection drug use
• Those receiving TNF-α antagonists for treatment of rheumatoid
arthritis or Crohn’s disease
• Certain medical conditions

18. Latent TB Infection (LTBI)
•Occurs when person breathes in bacteria and it reaches the air sacs
(alveoli) of lung
• Immune system keeps bacilli contained and under control
• Person is not infectious and has no symptoms

19. TB Disease
 Occurs when immune system cannot keep bacilli contained
 Bacilli begin to multiply rapidly
 Person develops TB symptoms

20. LTBI vs TB Disease

22. EPIDEMIOLOGICAL INDICES.
• Indices or parameters are needed to measure the tuberculosis
problem in a community
• For planning and evaluation of control measures
• Indices are also required for international comparison

23. EPIDEMIOLOGICAL INDICES.
A) PREVALENCE OF INFECTION:-
• It is the percentage of individual who show a positive reaction to the
standard tuberculin test.
B) INCIDENCE OF INFECTION (ANNUAL INFECTION RATE):
• It is the percentage of population under study who will be newly
infected by M. tuberculosis.
• It reflects the annual risk of being infected in a given community.

24. EPIDEMIOLOGICAL INDICES.
C) PREVALENCE OF DISEASE (CASE RATE) :-
• It is the percentage of individuals who’s sputum is positive for
tubercle bacilli on microscopic examination.
• It is the best available practical index to estimate the number of
infectious cases or case load in a community.
D) INDICES OF NEW CASES :-
• It is the percentage of new tuberculosis cases per 1000 population
occurring during one year.

25. EPIDEMIOLOGICAL INDICES.
E) PREVALENCE OF SUSPECT CASES :-
• It is based on X- Ray examination of chest.
• Drawback of this index is that radiography cannot reveal with any
certainty.
• That’s why it has no epidemiological significance.
F) CASE DETECTION RATE:
no. of new and relapse cases in a year
estimated incidence of such cases in same year

26. EPIDEMIOLOGICAL INDICES.
G) PREVALENCE OF NEW DRUG RESISTANCE CASES :-
• The patients resistance to anti- tuberculosis drugs.
MORTALITY RATE :-
• The no. of deaths from TB per lakh population was used as the index
of the TB problem in a community.
• At present time it has no significance.

27. SOME DEFINATIONS OF TB CASES
• NEW CASES – A patient with sputum +ve PTB who has never treated
for TB or has taken anti- tuberculosis drug for less than 4 week.
• RELAPSE – A patient who return smear +ve having previously been
treated for TB and cured.
• Return after default- A patient who return sputum smear +ve after
having left treatment for at least 2 months.
• TRANSFER IN- A patient recorded in another administrative area
register and transferred into another area to continue treatment.

28. SOME DEFINATIONS OF TB CASES
• TRANSFER OUT- A patient who has been transfer to another area
registered and treatment result are not known.
• CURED– Initially smear +ve positive patient who completed treatment
and had –ve smear result on at least two occasions.
• COHORT- A group of patients in whom TB has been diagnosed and
who were registered for treatment during a specified time period.

30. NATURAL HISTORY OF TB
AGENT FACTORS
AGENT
M. TUBERCULOSIS
IS A FACULTATIVE
INTRACELLULAR
PARASITE
SOURCE OF
INFECTION
TWO SOURCES)(
COMMUNICABILITY
PATIENTS ARE REMAIN
INFECTIVE AS LONG
AS THEY REMAIN
UNTREATED
HUMAN SOURCE
MOST COMMON
SOURCE
BOVINE SOURCE
INFECTION USUALLY
BY INFECTED MILK

31. AGENT FACTORS.
• A ) AGENT:
• It was” ROBERT KOCK”discovered the causative agent MYCOBACTERIUM
TUBERCULOSIS in 1882,( an acid fast, gram positive, on-motile, aerobic, rod-
shaped organism) is a facultative intracellular parasite i.e. it is readily ingested
by phagocytes & is resistant to intracellular killing.
• TWO FORMS OF M.TUBERCULOSIS OCCURS:
• Human variety,
• Bovine variety,
• Others as..Avian type-rarely pathogenic, Murine.

32. AGENT FACTORS.
• SOURCE OF INFECTION:
• There are two sources of infection
• 1] Human source & 2] Bovine source.
• HUMAN SOURCE:
• The most common source of infection is human case whose sputum is positive for
tubercle bacilli and who has either received no treatment or has not been treated
fully.
• BOVINE SOURCE:
• The bovine source of infection is usually infected milk.
• COMMUNICABILITY:
• TB is communicable as long as the TB patient is untreated.

33. HOST FACTORS (DISTRIBUTION)
• AGE:
• TB can occur at any age but children and older people are more susceptible
due to weak immune system.
• SEX:
• No discrimination. But TB is more common in females above 35 years and
males above 45 yrs.
• NUTRITION:
• Malnutrition predisposes to TB.
• EDUCATION:
• More common in illiterate peoples.

34. HOST FACTORS (DISTRIBUTION)
• SOCIO-ECONOMIC STATUS:
• More common in persons with low socioeconomic status.
• OTHER DISEASES: ‘
• HIV/AIDS: Person with HIV is 100 times more prone to TB.Diabetes also
increases the risk.
• IMMUNITY: May be by:
I. Natural infection.
II. Vaccination with BCG.

35. DETERMINANATS OF TB.
• PRIMARY DETERMINANTS:
• The etiological agent is Mycobacterium Tuberculosis. Two types of the bacilli:
• Human variety
• Bovine variety.
• SECONDARY DETERMINANTS:
• Low socio-economic status.
• Lack of education.
• Physical environment: warm and humid environment favors the disease
spread.

36. MODE OF TRANSMISSION
• Mainly with Droplet infection within range of 30 cm,droplet nuclei
generated by sputum-positive patients with pulmonary tuberculosis.
• Dust loaded with organisms from tuberculosis patient because
mycobacterium tuberculosis can survive for years in dry sputum.
• Food Borne: Food handled by infected persons.
• Fomite Borne.
• Directly by kissing the infected person.

37. MODE OF TRANSMISSION
• TB is spread person to person
through the air via droplet nuclei
• M. tuberculosis may be expelled
when an infectious person:
• Coughs
• Sneezes
• Speaks
• Sings
• Transmission occurs when
another person inhales droplet
nuclei

38. MODE OF TRANSMISSION
• Probability that TB will be transmitted depends on:
• Infectiousness of person with TB disease
• Environment in which exposure occurred
• Length of exposure
• Virulence (strength) of the tubercle bacilli
• The best way to stop transmission is to:
• Isolate infectious persons
• Provide effective treatment to infectious persons as soon as possible

39. RESERVOIR
• Infected person.
• Infected cow/animals.
• Agent
• Reservoir
• Portal of Exit
• Mode of transmission
• Portal of Entry
• Susceptible host
Cycle of
infection

40. PORTAL OF ENTRY:
• By inhalation through nose and throat,organsims reach the alveoli
causing TB of the respiratory tract.
• By ingestion through mouth causing tuberculosis of alimentary tract
and tonsils.

41. INCUBATION PERIOD
• The time from receipt of infection to the development of a positive
tuberculin test ranges from 3 to 6 weeks, and disease process depends
upon:
• Closeness of contact
• Extent of the disease
• Sputum positivity of source case ( dose of infection).
• Host parasite relationship.
• Thus the incubation period may be weeks, months or years.

44. CONTROL OF TUBERCULOSIS
• NATIONAL CONTROL PROGRAM IN PAKISTAN:
• In 1993,WHO declared a global TB control program.
• METHODOLOGY ADOPTED.
• To carry out mass survey for detection and diagnosis of TB cases.
• To treat all new cases and already known cases.
• To carry out BCG vaccination to protect young population.
• Health education of masses regarding preventive measures.
• Training of medical and paramedical personals.

45. CONTROL OF TUBERCULOSIS
• AIMS:
I. Reducing the reservoir of infection.
II. Improving of resistance.
III. Minimizing the chance of spread.

46. CONTROL OF TUBERCULOSIS
• 1.REDUCING THE RESERVOIR OF INFECTION:
• It is carried out by:
a. Case finding.
b. Treatment.
• CASE FINDING:
 Case:
• The first step in TB control programme is early detection of sputum positive
cases.
• Target Group:
• Person having

47. CONTROL OF TUBERCULOSIS
• CASE FINDING TECHNIQUES:
I. Sputum examination.
II. Mass Miniature Radiography.
III. Tuberculin Test.
IV. X-ray Chest.

48. SPUTUM EXAMINATION CONFIRMATION BY ..
• Acid-fast bacilli are seen on sputum smear or in other body tissues or
fluids,
• By culturing M. tuberculosis from sputum or other respiratory specimens,
• Nucleic acid amplification tests are more rapid than culture and specific for
M. tuberculosis. They are also more sensitive than the acid-fast bacillus
smear but less sensitive than culture.
• (chest x-ray) radiological abnormalities.
• Or using clinical criteria in the absence of microbiologic confirmation.
• Laboratory testing should be performed when feasible to confirm the
diagnosis and to conduct drug susceptibility testing to guide treatment

49. TREATMENT
Two-Phase Chemotherapy:
I. The first is a short aggressive or intense phase, early in the course
of treatment. Lasting 1-3months---->During this phase, three or
more drugs are combined to kill of as many bacilli as possible.
II. The second or combination phase is aimed at sterilizing the smaller
number of dormant or persisting bacilli.

50. TREATMENT
• DIFFERENT REGIMENS:
(1) 6 Months Duration:
 (INITIAL PHASE 2 MONTHS)
• Ethambutol or streptomycin Isoniazid +Rifampicin+Prazinamide.
 (CONTINUATION PHASE 4MONTHS)
• Isoniazid Rifampicin.
.

51. TREATMENT CONTI…
• DIFFERENT REGIMENS:
(2) 9 Months Duration:
 (INITIAL PHASE 2 MONTHS)
• Ethambutol or streptomycin + Isoniazid +Rifampicin.
 (CONTINUATION PHASE 7 MONTHS).
• Isoniazid + Rifampicin.

52. TREATMENT CONT..
(3) 12 Months Duration:
 ( TWICE WEAKLY DOSE)
• Streptomycin 1 gm I/M
• Isoniazid +Pyridoxine orally
(DAILY DOSE):
• Isoniazid + Thioacetazone

53. NATIONAL T.B CONTROL PROGRAMME
2.IMPROVING OF RESISTANCE:
• By BCG Vaccination:(Introduced in Pakistan in 1950)
• AIM: To induce a benign artificial primary infection which will stimulate an
acquired resistance to possible subsequent infection with virulent tubercle
bacilli & thus reduce the morbidity & mortality from primary tuberculosis
among those most at risk.
• After BCG vaccination a primary infection will still take place, but the
progression or disseminated infection will be reduced.
• BCG vaccination induces cell-mediated immunity to Mycobacterium & dose
not generate Humoral immunity as do other vaccines, so it alters body’s
defenses not inducing antibody formation.

54. NATIONAL T.B CONTROL PROGRAMME
3.MINIMIZING THE CHANCES OF SPREAD:
a. Isolation.
b. Care of the patients in the home.
c. Destruction of the sputum.
d. Visit by health visitors.
e. Promoting health education.
f. Improving living standards.
g. Chemoprophylaxis with INH for one year or INH plus ethambutol
for 9 months.

55. NATIONAL T.B CONTROL PROGRAMME
• ORGANIZATIONS WORKING FOR PREVENTION OF TUBERCULOSIS.
• Field units.( attached to district headquarters)
 Tuberculin survey units.
 MMR vaccination unit
 BCG vaccination unit.
• Clinics attached with primary health units.
• Hospital and sanatoria.
• BCG vaccination units.
• Voluntary organizations.

56. Directly Observed Therapy Short course (DOTS)
• DOTS or Directly Observed Treatment Short course is the
internationally recommended strategy for TB control that has been
recognized as a highly efficient and cost-effective strategy.
• Regular supervision is required to ensure that the patient actually
takes all the drugs prescribed.DOTS may be ensure as under:
• The patients should receive every dose of their initial intensive phase
facility ( BHU,RHC,etc) with the health worker observing the patients
swallowing all the tablets.

57. Directly Observed Therapy Short course (DOTS)
• In case the patient is unable to reach the health facility, a health
worker should be designed to administer DOTS either at patient’s or
health worker’s home or work place.
• If the above two are not feasible, a respected member of the
community should be made responsible for DOST.
• If all above options fail, hospitalization of the patient should be
seriously considered at the closest available health facility.