a brief description of tuberculosis

1. A 45 yr old male patient ,hailing from a
poor socioeconomic condition
came at OPD with complain of
• loss of wt &appetite
• evening rise of temp
• cough >3wks
• hemoptysis

2. TUBERCULOSIS
Tuberculosis
(abbreviated as TB for
tubercle bacillus or
Tuberculosis) is a
common and often
deadly infectious disease
caused by mycobacteria,
mainly Mycobacterium
tuberculosis.
Two type: Pulmonary &
Extrapulmonary

3. Epidemiology
 According to the World Health Organization (WHO), nearly 2 billion people—one
third of the world's population—have been exposed to the tuberculosis pathogen.
 Annually, 8 million people become ill with tuberculosis, and 2 million people die
from the disease worldwide.
 In 2004, around 14.6 million people had active TB disease with 9 million new cases.
 The annual incidence rate varies from 356 per 100,000 in Africa to 41 per 100,000
in the Americas.
 Tuberculosis is the world's greatest infectious killer of women of reproductive age
and the leading cause of death among people with HIV/AIDS.

4. Epidemiology (contd..)

5. Epidemiology (contd..)
Major changes in trends secondary to HIV
- 1953-1985 cases decreased from 84,304 to 22,201
- during this period cases were reactivation of old
infection and elderly
- TB and AIDS registries suggests that HIV-infected
pts account for 30-50% increase in cases of TB

6. Tuberculosis prevalence rates, 2007
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health
Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2006. All rights reserved
No report
0–24
25–49
50–99
100 or more
Notified TB cases (new and
relapse) per 100 000 population

7. AFR*
10 %
S wa z i l a nd
1%
Ni ge r i a
8 %
Ke ny a
7 %
Zi mba bwe
5 %
M oz a mbi que
5 %
Za mbi a
4 %
UR Ta nz a ni a
4 %DR Congo
4 %
Uga nda
4 %
Et hi opi a
3 %
M a l a wi
3 %
Côt e d' I v oi r e
2 %
S out h Af r i c a
19 %
Ot he r
2 1%
Brazil
AMR*
Russia
EUR*
India
SEAR*
WPR
EMR
0
5
10
15
20
Geographical distribution of
HIV-positive TB cases, 2005
For each country or region, the number of incident TB
cases arising in people with HIV is shown as a
percentage of the global total of such cases. AFR* is all
countries in the WHO African Region except those shown
separately; AMR* excludes Brazil; EUR* excludes the
Russian Federation; SEAR* excludes India.

8. WORLD TB DAY 2017: Bangladesh continues its
battle against the disease
 Bangladesh has high rates of migration and the transient population
faces poverty, overcrowding and poorly ventilated living and working
conditions, all of which allow TB to spread.
 The South-East Asia region accounts for a disproportionately high
number of global TB cases and Bangladesh is one of 22 ‘high TB-burden’
countries.
 In 2014, there were 187,005 new cases of TB in Bangladesh and it was
the leading cause of death, accounting for 81,000 fatalities.
 Ending the TB epidemic by 2030 is one of the health targets of the newly
adopted Sustainable Development Goals. WHO has set a target for a
95% reduction in deaths and a 90% reduction in TB incidence by 2035.
As World Tuberculosis Day(24th March) marks renewed efforts to ‘Unite to
end TB’, we give some insight into the disease that remains a major
public health problem for Bangladesh.

9. Incidence
 1985-1990 TB cases increased 55% in Hispanics and
27% in African Americans
 Populations at risk
- Foreign-born individuals
- Low socioeconomic status
- Cancer pts
- Celiac disease
- Cigarette smokers
- TNF-a antagonists
- Corticosteroids
- HIV

10. Case Definations…
 Smear positive TB : At least 2 sputum smear positive for AFB
initially
or
1 smear positive and 1 positive culture
or
1 smear positive and radiographic abnormality with active
pulmonary TB
 Smear negative TB : At least three negative smears but TB
suggestive symptoms and X-ray abnormality or positive
culture

11. Case Definations (contd…)
 Relapse : A pt who returns smear positive having previously
been treated for TB and declared cured after the completion
of his treatment
 Failure case : A pt who was initially smear positive , who
began treatment but remained or became smear positive
again at five months or later during the course of treatment

12. Case Definations (contd…)
 MDR TB : It is a specific form of drug-resistant TB due to a
bacillus resistant to at least isoniazid and rifampicin, the two
most powerful anti-TB drugs
 XDR-TB : It is resistance to at least Isoniazid and Rifampicin
(i.e. multidrug-resistant TB or MDR-TB), plus resistance to any
fluroquinolones, and any one of the second-line anti-TB
injectable drugs (Amikacin, Kanamycin or Capreomycin).

13. Transmission
 When people suffering from active pulmonary TB cough,
sneeze, speak, or spit, they expel infectious aerosol droplets
0.5 to 5 µm in diameter.
 A single sneeze can release up to 40,000 droplets.
 People with prolonged, frequent, or intense contact are at
particularly high risk of becoming infected, with an estimated
22% infection rate.
 A person with active but untreated tuberculosis can infect
10–15 other people per year.
 Others at risk include people in areas where TB is common.

14. Transmission

15. Transmission
 residents and employees of high-risk congregate settings,
 medically under-served and low-income populations,
 high-risk racial or ethnic minority populations,
 children exposed to adults in high-risk categories,
 patients immunocompromised by conditions such as
HIV/AIDS, people who take immunosuppressant drugs,
 and health care workers serving these high-risk clients.

16. Transmission of tb

17. Causative Organism
Genus : Mycobacteria
Species : Typical - M.Tuberculosis
- M.Laprae
Atypical – M.Bovis
-M.Africanum
-M.Microti
-M.Kansasi
-M.Scrofulacium..etc

18. M tuberculosis
 Aerobic, non-sporing, non-capsulated, non-motile rod
 On artificial media, coccoid & filamentous forms are seen with
variable morphology from one species to other
 1.2-4 μm (1-10) x 0.3-0.5 μm
 Arranged singly, in pairs or in clumps
 Cell wall contains abundance of complex lipids, some of which are
unique to mycobacteria
 Requires special media for growth.They are
 L-J Media(6 wk)
 MiddleBrook agar Media
 BACTEC(1-3 wk)
 MGIT

19. Acid Fast Bacilli

20. Pathogenesis
Reservoir: human with active tuberculosis
Primary cells infected: macrophage
Bacilli after entry into body reside principally
intracellularly inside
• monocytes,
• RE cells
• giant cells.

21. TB Pathogenesis (1)
Latent TB Infection
Once inhaled, bacteria travel to lung alveoli and establish
infection
2–12 wks after infection, immune response limits activity;
infection is detectable
Some bacteria survive and remain dormant but viable for
years (latent TB infection, or LTBI)

22. TB Pathogenesis (2)
Latent TB Infection
Persons with LTBI are
Asymptomatic
Not infectious
LTBI formerly diagnosed only with TST
Now QFT-G can be used

23. Pathology
 Production & development of lesions & their healing or
progression are determined chiefly by-
a. number of bacilli in the inoculum & their
subsequent multiplication &
b. resistance & hypersensitivty of the host
 Two principal types of lesions- exudative & productive
type

24. Exudative lesion
 Acute inflammatory reaction, with edema fluid, PMNs, &
later monocytes around tubercle bacilli
 Seen particularly in lung tissue
 Fate-
a. may heal by resolution
b. may lead to massive necrosis of tissue
c. may develop into productive type of lesion
 During exudative phase- tuberculin test become positive

25. Productive lesion
 Fully developed lesion- granuloma formation
 Granuloma- 3 zones- tubercle
a. central area of large, multinucleated giant cells
containing tubercle bacilli
b. midzone of pale epithelioid cells
c. peripheral zone of fibroblasts, lymphocytes &
monocytes
 Later central area undergoes caseation & peripheral fibrosis
 Fate-
a. caseous tubercle may break into bronchus & empty
its contents there – form a cavity
b. heal by fibrosis or calcification

26.  Upper two: granuloma with central caseation necrosis
 Lower left: granuloma without caseation
 Lower right: non-reactive TB (no granuloma)- sheets of foamy
histiocytes packed with mycobacteria

27. Spread of organism in the host
Direct extension
Lymphatic spread
Hematogenous spread
Spread by natural passages

28. Types of infection
Primary & secondary (reactivation) tuberculosis:
Primary tuberculosis: develops in previously unexposed &
therefore unsensitized person – first contract with tubercle
bacilli
Source of organism- exogenous
Acute exudative lesions rapidly spreading to lymphatics &
regional lymph nodes (hilar)
Heals rapidly or may disseminate
Lymph nodes- massive caseation that usually calcifies
Common site- base of the lung
Other organs involved- intestine, cervical lymph nodes,
meninges, bones & joints, skin etc

29. Types of infection (contd..)
Ghon’s focus: primary local lesion
Primary (Ghon) complex: Ghon’s focus, strands of
affected lymphatics & enlarged lymph nodes (hilar)
About 5% primary infection- leads to disease
Lymphohematogenous dissemination- dreaded
complication → tuberculous meningitis & disseminated
(miliary) tuberculosis
Usually occurred in childhood or in tuberculin-negative
adults
Tuberculin test become positive in 2-4 weeks after
infection

30. Sites of Involvement:
Primary : lung, Tonsil , Intestine , Skin
Secondary : Lymph node , GI Tract , Pericardium ,
CNS , Bones & Joints , Genitourinary
Rare : Thyroid Gland , Heart Muscle , Skeletal Muscle
, Pancreas .

31. Clinical feature of Pulmonary TB
• Chronic cough, often with haemoptysis
• Pyrexia of unknown origin
• Unresolved pneumonia
• Exudative pleural effusion
• Asymptomatic (diagnosis on chest X-ray)
• Weight loss, general debility
• Spontaneous pneumothorax

32.  Exudative ascites
 Mesenteric adenitis
 Intestinal obstruction
 Cranial nerve palsy
 Lymph node enlargement
 Pericardial effusion
 Constrictive pericarditis
 Monoarthritis
 Haematuria/dysuria
 Infertility in women
 Epididymitis
 Anorectal ulceration
 Headache, vomiting,
 Lymphocytic meningitis
 Hydrocephalus
 Space-occupying lesion
(tuberculoma)
 Kyphosis
 Cord compression
 Abdominal mass
 Psoas abscess
 General observation
Weight loss
Fever
Night sweats
 seizures, confusion
C/F of Extra pulmonary TB

33. Complications of TB in Chronic cases
Pulmonary
 • Massive haemoptysis
 • Cor pulmonale
 • Fibrosis/emphysema
 • Atypical mycobacterial
infection
 • Aspergilloma
 • Lung/pleural calcification
 • Obstructive airways disease
 • Bronchiectasis
 • Bronchopleural fistula
Non-pulmonary
 • Empyema necessitans
 • Laryngitis
 • Enteritis*
 • Anorectal disease*
 • Amyloidosis
 • Poncet’s polyarthritis

34. Diagnosis of TB
 Specimens required
 Pulmonary
 • Sputum* (induced with nebulised hypertonic saline if not
expectorating)
 • Bronchoscopy with washings or BAL
 • Gastric washing* (mainly used for children)
 Extrapulmonary
 • Fluid examination (cerebrospinal, ascitic, pleural,
pericardial,joint): yield classically very low
 • Tissue biopsy (from affected site): bone marrow/liver may be
diagnostic in disseminated disease

35. Diagnostic tests
 Tuberculin skin test: low sensitivity/specificity; useful only in
primary or deep-seated infection
 Stain
Ziehl–Neelsen
Auramine fluorescence
 Nucleic acid amplification
 Culture
Solid media (Löwenstein–Jensen, Middlebrook)
Liquid media (e.g. BACTEC or MGIT)
 Pleural fluid: adenosine deaminase
 Response to empirical antituberculous drugs (usually seen
after 5–10 days)

36. Baseline blood tests
 FBC,
 CRP,
 ESR,
 U&E and
 LFTs

37. Mantoux Tuberculin Skin Test
 Preferred method of skin testing for M. tuberculosis infection
 TST is useful for
Determining how many people in a
group are infected (e.g., contact
investigation)
Examining persons who have
symptoms of TB
 Multiple puncture tests (e.g., Tine Test) are inaccurate and not
recommended

38. Administering the TST
Inject 0.1 ml of 5 TU PPD
tuberculin solution
intradermally on volar
surface of forearm using
a 27-gauge needle
Observed for 30 min for
any immediate type of
reactions
Produce a wheal 6 to 10
mm in diameter in 48-72
hrs


39. Reading & interpretation
Final reading after 72 hrs (48-72 hrs)
Positive reaction : area of induration 10 mm or
more – persists for several days- indicates person
has an infection & continue to carry viable
mycobacteria
Negative reaction: no area of induration
Doubtful reaction: <10 mm
In HIV positive cases: ≥5 mm induration is
positive
Induration >15 mm: indicative of active
tuberculosis
Tuberculin negative- susceptible to tubercular
infection

40. Factors That May Cause False-Positive
TST Reactions
Nontuberculous mycobacteria
Reactions caused by nontuberculous
mycobacteria are usually  10 mm of
induration
BCG vaccination
Reactivity in BCG vaccine recipients
generally wanes over time; positive TST
result is likely due to TB infection if risk
factors are present

41. False negative tuberculin reaction
Overwhelming tuberculous infection with marked
toxaemia (disseminated or miliary tuberculosis)
Newborn & elderly
Recent viral infection (e.g measles or infectious
mononucleosis) or vaccination
Immunosuppression like AIDS
Malnutrition
Immunosuppressive therapy
Malignancy- Hodgkin’s disease
Sarcoidosis
Scarlet fever

42. Factors That May Cause False-Negative
TST Reactions (1)
Anergy
Inability to react to a TST because of a
weakened immune system
Usefulness of anergy testing in TST-
negative persons who are HIV infected
has not been demonstrated

43. Factors That May Cause False-Negative
TST Reactions (2)
Recent TB infection
Defined as 2 to 10 weeks after exposure
Very young age
Newborns

44. Factors That May Cause False-Negative
TST Reactions (3)
 Live-virus vaccination
For example, measles or smallpox
Can temporarily suppress TST reactivity
 Overwhelming TB disease
 Poor TST administration technique
For example, TST injection too shallow
or too deep, or wheal is too small

45. ADA
 Adenosine DeAminase is an enzyme.
 ADA positive means serum ADA>14U/L
 Sensitivity : 92.7%
 Specificity : 88.1%
 Advantages :
1. Quick . eg culture is lengthy
2. Accurate diagnosis.eg AFB may absent in that specific sample
3. Helps in Monitoring
4. No requirement of expertise.eg PCR require expert person.

46. Treatment

47. Tuberculosis treatment
 The standard "short" course treatment for tuberculosis (TB), is
isoniazid, rifampicin, pyrazinamide, and ethambutol for two months,
then isoniazid and rifampicin alone for a further four months. The
patient is considered cured at six months (although there is still a
relapse rate of 2 to 3%). For latent tuberculosis, the standard treatment
is six to nine months of isoniazid alone.
 If the organism is known to be fully sensitive, then treatment is with
isoniazid, rifampicin, and pyrazinamide for two months, followed by
isoniazid and rifampicin for four months. Ethambutol need not be
used.

48. Drugs (contd..)
 All first-line anti-tuberculous drug names have a
standard three-letter and a single-letter abbreviation:
1. ethambutol is EMB or E,
2. isoniazid is INH or H,
3. pyrazinamide is PZA or Z,
4. rifampicin is RMP or R,
5. Streptomycin is STM or S.

49. Drugs (contd..)
 There are six classes of second-line drugs (SLDs) used for the
treatment of TB. A drug may be classed as second-line
instead of first-line for one of two possible reasons: it may be
less effective than the first-line drugs.
1. aminoglycosides: e.g., amikacin (AMK), kanamycin (KM);
2. polypeptides: e.g., capreomycin, viomycin, enviomycin;
3. fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin,
moxifloxacin (MXF);
4. thioamides: e.g. ethionamide, prothionamide
5. cycloserine (the only antibiotic in its class);
6. p-aminosalicylic acid (PAS or P).

50. Drugs
 considered "third-line drugs"
 not very effective or because their efficacy has not been proven .
 Rifabutin is effective, but is not included on the WHO list because
for most developing countries, it is impractically expensive.
1. rifabutin
2. macrolides: e.g., clarithromycin (CLR);
3. linezolid (LZD);
4. thioacetazone (T);
5. thioridazinea;
6. arginine;
7. vitamin D;
8. R207910.

51. Dosage & Duration..

53. Adjunctive Treatment
 Pyridoxine (Vitamin B6)
The use of Pyridoxine is recommended for all adults patients started on TB treatment
to prevent peripheral neuropathy most commonly caused by Isoniazid.
Dose of Pyridoxine: 25mg daily
If patient develops peripheral neuropathy at any stage during TB treatment, the dose
can be increased to 50 – 75mg (up to maximum of 200mg) until the symptoms
subside, then reduce to 25mg daily.
 Steroids
The use of corticosteroids is recommended in extra-pulmonary tuberculosis,
particularly for TB meningitis and pericarditis. High dose steroid treatment for 2-4
weeks and the taper off gradually over several weeks depending on clinical progress is
recommended.
The response to treatment is assessed clinically.

54. Counselling of Patient
 Medication that the patient will be taking, when and how to take it, the side effects
they may experience from the medication and what to do when the side effects
develop.
 The duration of treatment; important milestones during treatment such as sputum
testing to monitor the response to treatment and changes in medication; the
importance of completing treatment
 Expected benefits of adherence
 Expected consequences of non-adherence
 Developing an adherence plan to identify barriers to treatment and address these
to ensure treatment completion
 The link to HIV and the need for an HIV test
 General health issues including how to eat a balanced diet using readily available
food, exercising, stopping smoking and reducing alcohol intake.

55. Monitoring and DOTS
 DOTS stands for "Directly Observed Therapy, Short-course" and is
a major plan in the WHO global TB eradication programme.
 The DOTS strategy focuses on five main points of action.
1. These include government commitment to control TB,
2. diagnosis based on sputum-smear microscopy tests done on patients who
actively report TB symptoms,
3. direct observation short-course chemotherapy treatments,
4. a definite supply of drugs, and
5. standardized reporting and recording of cases and treatment outcomes.

56. Prevention
TB prevention and control takes two parallel
approaches.
In the first, people with TB and their contacts are
identified and then treated.
Identification of infections often involves testing
high-risk groups for TB.
In the second approach, children are vaccinated to
protect them from TB.

57. Vaccines
 Many countries use Bacillus Calmette-Guérin (BCG) vaccine
as part of their TB control programs, especially for infants.
According to the W.H.O., this is the most often used vaccine
worldwide, with 85% of infants in 172 countries immunized in
1993.
 BCG provides some protection against severe forms of
pediatric TB
 unreliable against adult pulmonary TB,
 Currently, there are more cases of TB on the planet than at
any other time in history
 urgent need for a newer, more effective vaccine that would
prevent all forms of TB—including drug resistant strains—in
all age groups and among people with HIV.

58. 6/5/2018
58