2nd part of the presentation. It was presented in the Department of Respiratory medicine, Bsmmu

1. Clinical features,
Diagnosis and
Management of
Tuberculosis

3. Features of primary TB:Features of primary TB:
Infection (4-8 weeks):Infection (4-8 weeks):
• Influenza like illnessInfluenza like illness
• Skin test conversionSkin test conversion
• Primary complexPrimary complex
DiseaseDisease::• Lymphadenopathy– hilar, ParatrachealLymphadenopathy– hilar, Paratracheal
• Pleural effusionPleural effusion
• Endo-bronchialEndo-bronchial
• MiliaryMiliary
• PericarditisPericarditis
• Meningitis

4. Hypersensitivity:Hypersensitivity:
• Erythema nodosumErythema nodosum
• Phlyctenular conjunctivitisPhlyctenular conjunctivitis
• DactylitisDactylitis

6. Clinical Features of pulmonary TB:Clinical Features of pulmonary TB:
1)1) Chronic cough often with haemoptysisChronic cough often with haemoptysis
2)2) PUO (pyrexia of unknown origin)PUO (pyrexia of unknown origin)
3)3) Unresolved pneumoniaUnresolved pneumonia
4)4) Exudative pleural effusionExudative pleural effusion
5)5) Asymptomatic-diagnosed on CXR (P/AAsymptomatic-diagnosed on CXR (P/A
view)view)
6)6) Weight loss, general debilityWeight loss, general debility
7)7) Spontaneous pneumothoraxSpontaneous pneumothorax

7. Chronic complications of pulmonaryChronic complications of pulmonary
tuberculosis:tuberculosis:
• PulmonaryPulmonary
1)1) Massive haemoptysisMassive haemoptysis
2)2) Cor-pulmonaleCor-pulmonale
3)3) Fibrosis / EmphysemaFibrosis / Emphysema
4)4) Lung / Pleural calcificationLung / Pleural calcification
5)5) BronchiectasisBronchiectasis
6)6) Broncho pleural fistulaBroncho pleural fistula
7)7) Atypical Mycobacterial infectionAtypical Mycobacterial infection
8)8) AspergillomaAspergilloma

8. Non Pulmonary
1. Laryngitis
2. Enteritis
3. Anorectal disease
4. Amyloidosis
5. Empyma necessitans

9. Features of cryptic tuberculosisFeatures of cryptic tuberculosis
• Age-over 60 years.Age-over 60 years.
• Intermittent low grade PUO.Intermittent low grade PUO.
• Unexplained weight loss, generalUnexplained weight loss, general
debility.debility.
• Normal CXRNormal CXR
• Blood dyscrasias- LeukaemoidBlood dyscrasias- Leukaemoid
reactionreaction
• Negative Tuberculin skin testNegative Tuberculin skin test
• Confirmation by biopsy of liver orConfirmation by biopsy of liver or
bone marrow .bone marrow .

10. Extra Pulmonary
Tuberculosis

13. Diagnosis of
Tuberculosis

15. Tools ofTools of Diagnosis of Tuberculosis
1.1. CBC-ESR is increased (positive value only)CBC-ESR is increased (positive value only)
2.2. Sputum-for AFBSputum-for AFB
3.3. Chest X-rayChest X-ray
4.4. Tuberculin skin testTuberculin skin test
5.5. Culture ofCulture of the bacilii
6.6. Molecular TestMolecular Test
7.7. FNAC and BiopsyFNAC and Biopsy

16. AFB smear Specimens:
Sputum: Rinse mouth with water before collection. Collect only
exudative material brought up from lung after a deep productive
cough. On an average 2 consecutive sputum sample should be
collected
Pulmonary specimen: Sputum*, Tracheal aspirate, Gastric lavage,
BAL .
Extra pulmonary specimen : CSF, Aspirated fluid in case of Bone
and Joint infection, Body fluids, Urine, Aspirated or draining pus,
Surgically excised tissue, Endometrial tissue etc.

17. Staining of Sputum Smear Of AFB
a) Ziehl-Neelsen staining:
Advantage: - cheap – rapid
- Easy to perform
- High predictive value > 90%
- Specificity of 98%
Disadvantages:
- sputum needs to contain at least 5000 AFB/ml.
Less than 1000 bacilli/ml then chance of finding AFB is less
than 10%
- Young children, elderly & HIV infected persons
may not produce cavities & sputum containing AFB.
- It is less sensitive than culture (50 80%)‑

18. Reporting of AFB
Number of AFB seen Report
None No AFB
1-2/300 fields +/--
1-9/100 fields 1+
1-9/ 10f ields 2+
1-9/ field 3+
>9/ field 4+

19. Typical AFB- Ziehl Neelsen stain

20. b) Immune fluroscence staining or Auramine-
Rodamine staining:
Advantages:
- More sensitive
- Rapid
Disadvantages:
- Hazards of dye toxicity
- more expensive
- must be confirmed by Z-N stain

21. Acid Fast Bacilli under
Fluorescent Microscope
Dr.T.V.Rao MD 21

22. Chest X-Ray
• Chest x-ray findings do not specifically indicate
pulmonary tuberculosis because there are other chest
diseases which may show the same changes in x-ray
and there is no specific pattern of presentation of
tuberculosis on x-ray.
• Chest X-ray findings suggestive of pulmonary
tuberculosis in patients with smear-negative microscopy
should always be supported by clinical findings.
• A qualified physician should decide on the diagnosis of
TB based on x-ray techniques.

24. Tuberculin test (Mantoux test)
• The test is based on the fact that persons infected with
tubercle bacilli develop hypersensitivity to the proteins of
the organism.
• Reagents in tuberculin test:
– Purified Protein Derivatives (PPD):
It is a purified preparation of tuberculoprotein.

25. • Method: Mantoux test
• It is usually performed by intradermal injection of 0.1 ml
(5TU) of PPD on the flexor aspect of the fore arm. 1 TU
contain .00002 mg of PPD.
• Interpretation of Skin test
 Reading is taken 48 to 72 hours after injection
 Reading is based on induration
 Diameter of induration is measured transversely to the
long axis of the fore arm and recorded in mm

26. • Results:
• a. An induration more than 10 mm indicate positive test
• Opinion: These person has been exposed to M.tuberculosis or NTM
and has been sensitized. It may not indicate active disease.
• b. An induration between 5 to 10 mm is doubtful reaction
Opinion: 1. BCG vaccination
2. NTM infection
3. Old tuberculous infection
• c. An induration less than 5 mm is considered negative
Opinion: The person is not exposed to M.tuberculosis
• Such result are repeated with 10 to 25 TU dose

27. Causes of false negative skin test
Injection of PPD in the deeper layer
2. Improper storage and handling of PPD reagent
3. Acute viral infection
4. Immunosuppression by disease ( Sarcoidosis, lymphoma,
AIDs- if CD4 count < 200 cells/ml) or Drugs
5. Severe TB (25% of cases negative)
6. Newborn and elderly
7. Malnutrition
Causes of false positive skin test
1. Hypersensitivity to NTM
2. During convalescence from measles and influenzae
3. BCG vaccination

28. Culture
• Media used:
a) Liquid Media such as; Middle brook 7H9
and 7H12.
b) Solid media such as Lowenstein Jensen
Media.
Commonest used media is Lowenstein
Jensen media

30. • Most modern system of culture:
-BACTEC system: It contains Middle brook 7H12
+ Antibiotics such as Polymyxin B, Azlocyclin,
Nalidixic acid, Trimethoprim and Amphotericin B
(PANTA) to prevent growth of the contaminated
bacteria and fungi.
-MGIT system( Mycobacterial growth indicator
tube)
It is the most modern system of M.tuberculosis
detection.

32. Other Diagnostic Methods
• ADA: Adenosine deaminase (also known as
adenosine aminohydrolase, or ADA) is
an enzyme involved in purine metabolism. It is
needed for the breakdown of adenosine from
food and for the turnover of nucleic acids in
tissues.
• Present in virtually all mammalian cells, its
primary function in humans is the development
and maintenance of the immune system.
However, the full physiological role of ADA is not
yet completely understood

33.  ADA determination in body fluids (spinal, pleural, ascitic,
pericardial) for the diagnosis of tuberculous meningitis , tuberculous
pleurisy peritoneal TB and pericardial TB has a high positive
predictive value, especially in high endemic countries.
 Pleural fluid elevated adenosine deaminase (ADA) concentrations
> 45 to 60 U/L is 100 percent sensitive and 95 to 97 percent for
TBPE. Specificity is increased when the lymphocyte to neutrophil
ratio is greater than 0.75.
 High ADA levels occasionally occur in other conditions, including
rheumatoid effusion, empyema, mesothelioma, lung cancer,
parapneumonic effusion, and hematologic malignancies.
 Pleural effusions with an ADA level <40 U/L are rarely caused by
TB.

34. Molecular Techniques
• Xpert MTB/RIF and the Hain ( Line prob
Assay) are molecular tests have been
introduced in Bangladesh. These tests
can confirm whether a patient has TB with
or with out Rifampicin resistance in one
day in case of Hain test and in two hours
in case of gene x-pert.

35. • The Xpert MTB/Rif test is a cartridge-based fully automated NAAT (nucleic
acid amplification test) for TB case detection and rifampicin resistance
testing, suitable for use in disease-endemic countries.
• It purifies, concentrates, amplifies (by rapid, real-time PCR) and identifies
targeted nucleic acid sequences in the TB genome, and provides results
from unprocessed sputum samples in less than 2 hours, with minimal
hands-on technical time.
• Although molecular amplification is already a proven technology in TB
diagnosis, other existing test methods are too complex for routine and
widespread use in developing countries. The need for sample processing
and DNA extraction adds another level of complexity to implementation in
settings where resources are limited.

37. Disadvantages:
• The machine requires a stable and uninterrupted
electrical power supply and is linked to a
computer for data analysis.
• The instrument requires at least annual
calibration which presently needs to be
performed by a trained technician using
specialized calibration equipment.
• It can not differentiate between dead and alive
bacilli

38. FNAC and Biopsy
• These are special tests for confirmation of
extra-pulmonary tuberculosis and should
be performed by concerned specialists.

39. Treatment of Tuberculosis

40. • Treatment of TB is not an easy task.
• Simply prescribing of anti TB drugs just
can’t cure a patient & may create problem
for the nation.
• It requires - motivation of the patients
- compliance of taking drugs

42. Ancient TB Treatment
The Italian physician Carlo Forlanini (1847-1918)
discovered that the collapse of the affected lung
tended to have a favorable impact on the outcome
of the disease. He proposed to reduce the lung
volume by artificial pneumothorax methods that
were applied worldwide after 1913.
• Artificial pneumothorax - pleural cavities were
filled with gas or filtered air
• Bilateral pneumothorax - only parts of the lungs
were collapsed in such a way that the patient could
still live a relatively normal live.

43. Ancient TB Treatment
• Thoracoplasty - ribs from one side of
the thorax were removed in order to
collapse the infected portion of the lung
permanently.
• Gold Therapy - Holger Mollgaard
(1885-1973) from Copenhagen
introduced the compound sanocrysin in
1925, which is a double thiosulphate of
gold and sodium. But it was too toxic
even in low doses.

44. Evolution of Anti-TB Drugs
• 1944 - streptomycin (SM) and paraaminosalicylic (PAS) were
discovered
• 1950 - the first trial was performed by SM & PAS as
Mono/combined therapy.
• 1952- Isoniazid (INH), was added to the previous combination
for 18-24 months.
• 1960- Ethambutol (EMB) substituted PAS, and the treatment
course was reduced to 18 months.
• 1970-the introduction of Rifampicin (RIF) into the combination
treatment was shortened to 9 months.
• 1980- Pyrazinamide (PZA) was introduced into the
antituberculosis treatment, reduced to 6 months.

45. Case Definitions
• Case definition is necessary for-
Correct patient registration and reporting
Correct choice of appropriate standard regimen
Patient follow-up
Cohort analysis including determining trends in
proportions of different types of patients.

48. Aims of Treatment
 To cure the patient of TB
 To prevent death from active TB or its late effects
 To prevent relapse of TB
 To decrease transmission of TB to others
 To prevent the development of acquired drug resistance

49. Basic Principles of TB treatment
Appropriate combination of drugs to kill
different bacterial population
Drugs are given for the required duration
to kill the bacilli
Drugs are given in the correct dosage to
achieve the therapeutic effect

50. Fixed Dose Combination
Advantages:
 Less prescription error
 Ingestion of less amount of drugs and thus improving
patient adherence
 Less occurrence of drug resistance
Disadvantages:
If severe side effects occur then all drugs have to be
stopped and patient has to continue treatment with
single drug excluding the drugs which might responsible
for the treatment.

52. Treatment Phases
• Effective chemotherapy consists of two phases:
a) The initial or intensive phase administered daily for two months in
new cases and three months in re treatment cases. The aim of this
phase is to reduce and eliminate the multiplying bacilli rapidly
without allowing the development of acquired resistance to
prescribed drugs. During the intensive phase, the infectious
patient quickly become non-infectious( within approximately two
weeks)
b) The continuation phase is essential to eliminate the remaining
bacterial population ( mainly persisters). Drugs are administered
daily for the rest of the treatment duration according to the
category.

58. 2nd Line Anti TB Drugs
• Amoniglycosides –kanamycin, Amikacin,
Capromycin
• Thiomides – Ethionamide, Prothionamide.
• Cycloserine.
• Para amino salicylic acid (PASA)
• Clarithromycin and Azithromycin
• Ofloxacin or Ciprofloxacin.
• Thioacetazone

59. Role of Steroids in Tuberculosis
1.1. In tuberculosis of serous sacs, like peritonitis,In tuberculosis of serous sacs, like peritonitis,
pericarditis, pleural effusion, to prevent fibrosispericarditis, pleural effusion, to prevent fibrosis
and adhesions and to hasten absorption ofand adhesions and to hasten absorption of
fluid.fluid.
2.2. In tuberculous meningitis to prevent morbidityIn tuberculous meningitis to prevent morbidity
and mortality due to adhesion.and mortality due to adhesion.
3.3. In genitourinary and gastrointestinal TB toIn genitourinary and gastrointestinal TB to
prevent the development of strictures andprevent the development of strictures and
perforation.perforation.
4.4. Seriously ill patients to buy time forSeriously ill patients to buy time for
chemotherapy to become effective.chemotherapy to become effective.
5.5. To control drug hypersensitivity reactionTo control drug hypersensitivity reaction
6.6. Adrenal TBAdrenal TB

60. Anti TB Therapy in Special
Situations
• Pregnancy: SM avoid{3(HRZE)/5(HR)E
• Breast feeding: baby prophylaxis with INH for 3
months beyond non-infectious period or upto 6
months which ever takes longer.
• OCP: higher dose (50 μg) or another method
• Liver disorders: hepatotoxicity is as Z>I>R. No
problem with carrier, past acute hepatitis, alcohol
consumption; but increase risk of hepato-toxic
effects. In established chronic liver diseae the
regimen is 2SHE/10HE.
• In acute hepatitis defer treatment or 3SE/6HR or
12SE.
• CLD: 2SHER/6HR
• Renal Failure: 2HRZ/6HR, thioacetazone is not
recommended.

61. BCG Vaccination
• Bacillus Calmette Guerin or BCG vaccine
contains live attenuated M.bovis bacteria.
It basically gives cellular immunity against
mycobacteria as its an intracellular
organism. It’s a type of artificial active
immunity.
Efficacy: 20-80% ( average 70%)

62. • Advantages:
The vaccine induces a cell mediated immunity
and prevents serious complications of TB
• Disadvantages:
Do not provide 100% protection.
Doesn’t give life long immunity
Chance of disseminated Bcg infection

63. Drug Resistant Tuberculosis

65. Diagnosis Of MDR TB
High index of suspicion.
Worsening symptoms with after
improvement with anti-TB drugs,
(Normally patient becomes smear
negative by 2nd
weeks, asymptomatic by 1
month, culture negative by 2 months and
in 90% cases by 3 months.)
Contact of MDR TB patient.
Treatment failure cases.
Culture positive after 3 months of
treatment.

66. Management Of MDR TB
• Detail history of previous anti-TB drugs.
• Patient’s motivation.
• Use of 2nd
line drugs.
• Prolonged therapy with time-to-time
monitoring.
• Multiple drugs should be used.

69. If TB Is Not Adequately and
Effectively Treated, Then This
Will Happen:

71. THANK YOU