Tuberculosis

TUBERCULOSIS – History,
Epidemiology & Prevention
Dr. Animesh Gupta
MBBS, MD, FDM, FAGE
Assistant Professor
Dept. Of Community Medicine, SIMS & RC, Mangalore
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Dr. Animesh Gupta Tuberculosis

History of TB
Historically known by a variety
of names, including:
Consumption
Wasting disease
White plague
TB was a death sentence for
many
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Vintage image circa 1919
Image credit: National Library of Medicine

History of TB
Scientific Discoveries in 1800s
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Until mid-1800s, many
believed TB was hereditary
1865- Jean Antoine-Villemin
proved TB was contagious
1882- Robert Koch discovered
M. tuberculosis, the bacterium
that causes TB
Mycobacterium tuberculosis
Image credit: Janice Haney Carr

History of TB
SANATORIUMS
Before TB antibiotics, many
patients were sent to
sanatoriums
Patients followed a
regimen of bed rest, open
air, and sunshine
TB patients who could not
afford sanatoriums often
died at home
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Sanatorium patients resting outside

TB Management Early 19th Century5
Pre-antibiotic era: before 1940s (e.g., cod liver oils, bed rest, fresh air)Dr. Animesh Gupta Tuberculosis

TB History Timeline
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1840 19201860 1900 1940 1960 1980 20001880
1993: TB cases decline due to
increased funding and
enhanced TB control efforts
Mid-1970s: Most TB
sanatoriums in U.S.
closed
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

Introduction
Tuberculosis (TB) is an infectious bacterial
disease caused by Mycobacterium tuberculosis,
which most commonly affects the lungs.
It is transmitted from person to person via
droplets
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Global burden of TB
 In 2016
 10.4 million – New TB cases
 1.8 million died from the disease (0.4 million – HIV +ve)
 4,80,000 people developed MDR-TB
 1,73,000 deaths from MDR-TB.
60% of the new TB cases: India, Indonesia, China,
Nigeria, Pakistan, and South Africa.
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Source: GLOBAL TUBERCULOSIS REPORT 2017 - WHO

Incidence of TB- SEAR10

Estimated burden of TB in India
Number (Lakhs)
Incidence 28
Mortality 4.8
HIV among estimated incident TB patients 1.1
Mortality of HIV- TB Patients 0.37
MDR-TB among notified pulmonary TB patients 1.3
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Source : Annual TB 2017 Report, SEARO- WHO (www.tbcindia.gov.in)Dr. Animesh Gupta Tuberculosis

Epidemiological Factors
 Agent factors
a. Agent
✓ M. tuberculosis
- Faculative intracellular
- Strains – Human & bovine
✓ Atypical myobacteria
- Photochromogens – M. kansasii
- Scotochromogens – M. scrofulaceum
- Non photochromogens – M. intercellulare
- Rapid growers – M.fortuitum
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Epidemiological Factors….
b) Source of infection
▪ Human source – Sputum +ve case
▪ Bovine source – infected milk
c) Communicability
▪ Person is infective as long as they remain
untreated
▪ Effective treatment – reduces infectivity – 48 hrs
13

Host Factors
Age-
 All ages
Sex-
 Male>Female, No heredity
Nutrition-
 Malnutrition predispose to TB
Immunity-
 CMI
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Social Factors
➢ Poor quality of life
➢ Poor housing
➢ Overcrowding
➢ Population explosion
➢ Large families
➢ Poverty, Illiteracy, Ignorance
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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
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TB Transmission
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Dots in air represent droplet nuclei containing
M. tuberculosis

TB 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
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Incubation Period
▪ 3-6 weeks
▪ Depends upon- closeness of contact, extent
of disease, sputum positivity, immunity of the
individual
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Pathogenesis
▪ Primary TB
▪ Ghon’s focus
▪ Primary complex
▪ Secondary TB

Epidemiological indices
To measure the problem in a community
Planning and evaluation of control measures
Required for international comparisons
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Epidemiological indices……
a) Prevalence of infection
Percentage of individuals who show a positive
reaction to the standard tuberculin test.
b) Incidence of infection
Percentage of population under study who will
be newly infected by Mycobacterium
tuberculosis among the non infected of the
preceding survey during the course of one
year.
c) Prevalence of disease or case rate
Percentage of individuals whose is positive for
tubercle bacilli on microscopic examination
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Epidemiological indices……
d) Incidence of new cases
Percentage of new cases (confirmed by
bacteriological examination)Per 1,000
population occurring in one year
e) Prevalence of drug resistant cases
Those patients excreting tubercle bacilli
resistant to anti tubercular drugs
f) Mortality rate
Number of deaths from TB every year
per1000 or 100000 population
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Clinical Features
▪ Cough with expectoration > 2 weeks
▪ Evening rise temperature
▪ Loss of weight
▪ Hemoptysis
▪ Chest pain
▪ Failure to thrive
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Clinical Feature24

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Laboratory Diagnosis
▪ Sputum examination- 2 sputum samples
-At what time ?
▪ Chest X-ray
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Diagnosis27

Dr P V Benjamin
FATHER OF ANTI-TB MOVEMENT IN INDIA
Era of conventional chemotherapy
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TB Chemotherapy: The Effective TB
Control
 First-line Drugs
Isoniazid (INH) Rifampicin
(RMP), Pyrazinamide (PZA),
Streptomycin, Ethambutol
 Second-line
PAS, Kanamycin, Cycloserine,
Ethionamide, Thiacetazone,
Ciprofloxacin/Ofloxacin, Rifapentine,
Amikacin, Viomycin, Capreomycin.
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1944
Streptomycin
1946
PAS
1952
Isoniazid
1963
Rifampicin

Treatment
 Anti-tuberculosis drugs should be
✓ highly effective
✓ free from side effects
✓ easy to administer
✓ reasonably cheap
Classification-
 Bactericidal drugs
Rifampicin, INH, Streptomycin, Pyrazinamide
 Bacteriostatic drugs
Ethambutol, Thioacetazone
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Treatment (DOTS Regimens)
Category of
Treatment
Type of Patient Regimen*
Category I All new pulmonary (smear-positive
and negative), extra pulmonary and
‘others’ TB patients.
2H3R3Z3E3+
4H3R3
Category II TB patients who have had more than
one month anti-tuberculosis
treatment previously
Relapse , Failure, Treatment After Default,
Others
2H3R3Z3E3S3 +
1H3R3Z3E3 +
5H3R3E3
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Childhood TB
 The newer weight bands are 6-8 kg, 9-12 kg, 13-16 kg, 17-
20 kg, 21-24 kg and 25-30 kg.
 Chemoprophylaxis for children under 6 years: isoniazid
(5mg/kg) for 6 months
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Rifampicin 10-12 mg/kg (max 600 mg/day)
Isoniazid 10 mg/kg (max 300 mg/day)
Ethambutol 20-25mg/kg (max 1500
mg/day)
Pyrazinamide 30-35mg/kg (max 2000
mg/day)
Streptomycin 15 mg/kg (max 1gm/day)Dr. Animesh Gupta Tuberculosis

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Drug-Resistant TB
Caused by M. tuberculosis
organisms resistant to at least
one TB treatment drug
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)
Resistant means drugs can no
longer kill the bacteria
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Drug-Resistant TB…
Primary
Resistance
Caused by person-to-person
transmission of drug-resistant
organisms
Secondary
Resistance
Develops during TB treatment:
• Patient was not
given appropriate
treatment regimen
OR
• Patient did not
follow treatment regimen as
prescribed
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Drug-Resistant TB….
Mono-resistant Resistant to any one TB treatment
drug
Poly-resistant Resistant to at least any 2 TB drugs
(but not both isoniazid and rifampin)
Multidrug
resistant
(MDR TB)
Resistant to at least isoniazid and
rifampin, the 2 best first-line TB
treatment drugs
Extensively
drug resistant
(XDR TB)
Resistant to isoniazid and rifampin,
PLUS resistant to any fluoroquinolone
AND at least 1 of the 3 injectable
second-line drugs (e.g., amikacin,
kanamycin, or capreomycin)
36

Drug Resistant TB Treatment
For MDR-TB : Daily DOT includes (6-9m) Kanamycin,
Levofloxacin, Cycloserine, Ethionamide,
Pyrazinamide, and Ethambutol. (18m) Levofloxacin,
Cycloserine, Ethionamide, Ethambutol
For XDR-TB : (6-12m) Capreomycin, PAS (Para-
Aminosalicylate Sodium), Moxifloxacin, High dose
INH, Clofazimine, Linezolid, and Amoxy- Clavulanic
Acid. (18m) all the above drugs except
Capreomycin
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Newer Diagnostics
CXR (Digital; Computer Aided Detection for TB)
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NEWER DIAGNOSTICS
 Sputum smear microscopy (LED FM)
 Automated staining tool and slide
processors (RAL STAINER)
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Automated slide reader
(TBDx system)
Automated slide reader

• Fluorescence in situ
hybridization (FISH)
• Liquid culture plateforms
(MGIT 960, BacT/Alert 3D
120)
NEWER DIAGNOSTICS..40

Notifiable Disease41

http://nikshay.gov.in42

Recent advances in Treatment
Daily drug treatment – 5 states- Maharashtra,
Bihar, Kerala, Himachal Pradesh and Sikkim -
February 2016.
Introduction of new anti TB drug under RNTCP-
Bedaquiline
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Bedaquiline
Introduction of new anti TB drug under RNTCP
 highly bound to plasma proteins and hepatically
metabolized.
 Extended half-life : present in the plasma up to 5.5
months post stopping BDQ.
 No cross-resistance with existing first- and second-line
anti-TB drugs
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Criteria For Patients To Receive
Bedaquiline
 Adults aged > 18 years having pulmonary MDR-TB.
 MDR TB with resistance to Second line injectable drugs or
Fluroquinolones.
 XDR TB
 Treatment failures of MDR/XDR TB or MDR TB
 Females should not be pregnant, or should be using
effective non-hormone-based birth control methods.
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Bedaquiline
 Dosage:
400 mg daily – 2 weeks followed by
 200mg 3 times a week – 3 to 24 weeks
 All patients would be counselled and managed indoor
for a mandatory period of 2 weeks to complete the
initial 2 weeks of BDQ doses.
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References
1. A brief history of tuberculosis control in India. Geneva, Switzerland: World Health
Organisation; 2010.
2. Revised National TB Control Program : Annual Status Report 2016. New Delhi:
Central TB Division, 2017.
3. Global Tuberculosis Report 2016, WHO
4. http://www.who.int/tb/strategy/stop_tb_strategy/en/
5. http://www.who.int/topics/tuberculosis/en
6. Park Textbook of Preventive & Social Medicine, 23rd Edition
7. Tuberculosis: Current Situation, Challenges and Overview of its Control Programs in
India: Journal of Global Infectious Disease 2011 Apr-Jun; 3(2): 143–150
8. TB INDIA 2017, Revised National TB Control Programme, Annual Status Report 2017
(Available from: http://www.tbcindia.nic.in/Pdfs/TB%20INDIA%202014.pdf)
9. TB EliminationTreatment of Multidrug-Resistant Tuberculosis: Bedaquiline.
(Available from :
https://www.cdc.gov/tb/publications/factsheets/treatment/multidrug-resistant-
tuberculosis-bedaquiline )
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World TB Day – 24th March 2017
THANK YOU
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Tuberculosis

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