Clinical Manifestations of Tuberculosis and its Management by Dr. Saman Kularatne, Consultant Chest Physician/ Chest Hospital Welisara, Sri Lanka

1. Clinical Manifestations of
Tuberculosis and its Management
Dr. Saman Kularatne

2. PTB

3. PTB

4. Pt. with RA and PTB

5. TUBERCULOSIS
• Mycobacterium tuberculosis
• Mycobacterium bovis
• Mycobacterium africanum

6. 7
HistoryHistory
• 2500 - 1000 B.C.- Bacillus - Egyptian Mummies
• 1720 - Benjamin Masters
- TB - Caused by minute living beings.
- Infectious nature
• 1845 - Curable Disease
• 1882 - Robert Koch - discovered the TB Bacillus.
• 1944 - Discovery of Anti Tuberculous Drugs

7. In the World
-----1/3 is infected
-----8 million people develop TB every
year ( 95% in developing
countries)
-----2 million people die of TB
every year
-----TB is the biggest killer in HIV

8. 13
Sites of AttackSites of Attack
80 %
PREDOMINENTLY
LUNGS
BRAIN
EYES
LIVER
INTESTINE
SPINE

9. TUBERCULOSIS -Transmission

11. 14
Pathogenesis
Primary Infection:
Lympnodes
Ghons Focus
Immune response Dose of bacilli

12. 15
Outcome of Primary Infection.
• No clinical disease 90 % Mx - Test positive
• Hypersensitivity reactions
eg: erythema nodosum
phlyctenular conjunctivitis
dactylitis
Primary
complex
• Pulmonary & pleural complications
eg: tuberculos pneumonia
lobar collapse
pleural effusion..
• Disseminated disease
eg: lymphadenopathy
milliary disease

13. Post primary TB
• Primary TB------months / Years later
(Pulmonary / Extra pulmonary)
• Re infection (Pulmonary)

14. Categories with increased risk of
infection
• Household contacts of a sputum positive pt
• Underprivileged populations living in crowded
improvised dwellings
• Workers accommodated in crowded inadequately
ventilated dormitories, boarding houses.
• Refugees
• Prisoners
• Those living in mental health institutions
• Health care workers

15. Factors that accelerate progression from
infection to disease
• Malnutrition
• Conditions leading to immune deficiency such
as HIV infection, poorly controlled DM, CRF,
malignancies, those on immunosuppressive
drugs, long term steroids
• Elderly people
• Smokers, drug addicts, alcoholics

16. Untreated PTB
The natural history after 5 years
• 50% will be dead
• 25% will be healthy (self-cured)
• 25% will remain ill with chronic, infectious
TB

17. Symptoms of PTB
Cough > 2 weeks
Fever / night sweats
Wt. Loss / LOA
Haemoptysis
Chest pain / SOB

18. TB Investigations
• Sputum microscopy (AFB)
• CXR
• AFB culture
• Histology
• Mx.test
• PCR / ADA / Interferon - gamma

19. Sputum microscopy (AFB)

20. Sputum microscopy (AFB)
Ziehl-Neelsen Stain (the "ZN")
Stain with heated strong
carbol-fuchsin Decolorise with
acid/alcohol
Counterstain with
malachite green
Mycobacteria appear
as "ribbons of pink
against the blue of
normality"

21. AFB smear

26. 28
Tuberculin Skin TestTuberculin Skin Test
• Limited Value if TB prevalence is high
Results:
0 - 9 mm - Negative
> 10mm - Positive
> 20mm - Strongly Positive

27. Positive Mx without clinical disease
• Primary TB infection
• B.C.G. vaccination
• Past TB infection
• Exposure to environmental mycobacteria

28. Negative Mx with clinical disease
• Acute severe form of TB
• HIV infection
• Malnutrition
• Viral infections such as measles, and
chickenpox
• Malignancies
• Immunosuppressive drugs and long term
steroids

29. Tuberculin Test
• Does not measure immunity
• Does not indicate the presence or extend of
Tuberculosis disease
• Only indicates infection

30. Definitions
• PTB + ve
– At least 2 AFB +ve or
– At least 1 + ve / CXR compatible active PTB or
– At least 1 + ve / +ve culture for MTB
• PTB – ve
– At least 3 AFB – ve
– CXR compatible with active PTB
– No response a course of broad-spectrum antibiotics
– Decision made by a clinician to treat with ATT
or
– Initial AFB – ve but culture + ve

31. • EPTB
– TB of any organ of the body other than the
lung parenchyma. ( including pleural
effusions and hilar lymphadenitis )

32. • NEW
– A patient who has never taken treatment for TB
Or
– Who has taken ATT for less than one month
• Relapse
– A pt previously treated for TB who has been declared
cured or treatment completed, and is diagnosed with
bacteriologically positive (smear or culture) TB.

33. • Treatment after failure
– A pt. on treatment with Cat 1 who remains smear
positive at the end of 5 month or later during the
course of treatment.
• Treatment after default
– A pt. who returns to treatment, with positive
bacteriology, following interruption of treatment
for two months or more.

34. • Transfer in
– A pt already registered in one district and
transferred to another district for continuation of
treatment

35. • Other
– A pt. who does not fit into anyone of the above
definitions
• A pt who has been taking treatment for TB for more
than 4 wks without been registered with NTP.
• A pt. smear negative PTB or EPTB who may have
relapsed but without any bacteriological evidence

36. • Chronic
– Patient remaining sputum positive after
completing a fully supervised re-treatment
regimen.

37. • Sp. AFB Culture
– For diagnosis (eg. Sp. –ve PTB, Pleural effusion,
TBM )
– Possible Drug Resistance
• Relapses
• Defaulters
• Delayed converters
• Prisoners
• MDR contacts

38. • A population of TB bacilli in a TB pt.
– 1). Metabolically active, continuously growing
bacilli inside cavities.
– 2). Intra cellular dormant forms – bacilli inside
macrophages.
– 3). Extra cellular dormant forms
• A). Bacilli which undergo occasional spurts of
metabolism (semi dormant).
• B).Dormant bacilli, which gradually die on their own.

39. • Mode of action of ATT
– H, R, E, PAS – active against metabolically active
bacilli.
– R – has a special action against the semi dormant
forms.
– Z – acts in an acid environment inside cells e.g.
macrophages.
– So far there is no drug ,which can act on dormant
bacilli.

40. 1ST line anti-TB drugs
• Rifampicin 10mg/kg (R)
• INAH 5mg/kg (H)
• Pyrazinamide 20-30mg/kg (Z)
• Ethambutol 15mg/kg (E)
• Streptomycin 15mg/kg (S)

41. FDC
• RHZE • RH

42. FDC (Fixed-Dose Combination)
• FDC (RHEZ) – (150mg, 75mg, 275mg
400mg )
• FDC (RHE ) - ( 150mg, 75mg, 275mg )
• FDC ( RH ) - ( 150mg, 75mg )

43. Cat 1
• New smear possitive or
negative, EPTB
• 2HRZE
• 4HR
(TBM, Miliary, Neuro.
• 7HR )

44. Cat 2
• Relapse, Treatment
failure, Return after
default
• 2HRZES
• 1HRZE
• 5HRE

45. Fixed dose combination drugs FDC
<35kg 35-54kg 55-70kg >70kg
RHZE 2 3 4 5
RHE 2 3 4 5
RH 2 3 4 5

46. Minor side effects
• Anorexia, nausea and abdominal pain
• Joint pain
• Numbness and tingling sensation
• Urticaria after ingestion of red fish

47. Major side effects
• Dermatitis
• Hepatitis
• Optic neuritis - (Ethambutol)
• Vertigo, dizziness deafness - (Strepto.)
• Peripheral Neuropathy - (INAH)
• Shock, Purpura acute renal failure, heamolytic
anaemia - (Rifampicin)

48. Rifampcin
• Common side effects
– G-I symptoms
– Hepatitis
– Reduced effect of OCP,
Antepileptic drugs, oral
hypogycaemic drugs and
theophyllines
• Rare side effects
– ARF, shock,
thrombocytopenia, skin
rash, ‘Flu syndrome’
(with intermitent doses),
pseudomembranous
colitis, pseudo adrenal
crisis.

49. INAH
• Common side effects
– Peripheral neuropathy
– Hepatitis
– Histamine reaction after
ingestion of red fish e.g.,
bala,kelawalla
• Rare side effects
– Convulsions, pellagra,
joint pains,
agranulocytosis, lupoid
reaction, skin rash

50. Pyrazinamide
• Common side effects
– Joint pains
– Hepatitis
• Rare side effects
– G-I symptoms, skin
rashes, sideroblastic
aneamia

51. Ethambutol
• Common side effects
– Optic neuritis
• Rare side effects
– Skin rash, joint pains,
peripheral neuropathy.

52. Streptomycin
• Common side effects
– Auditory and vestibular
damage (also to the
foetus)
– Renal damage
• Rare side effects
– Skin rash

54. Advice to Pt
– When to take ATT
– Urine color - Rifampicin
– Foods
– Contraceptives
– Epilepsy
– LOA / Vomiting - Hepatitis
– Rashes
– Unsteady gait - Strepto.

55. • PTB
– +ve
– - ve
• Follow up
• EPTB
– Pleural effusion
– Lymphadenitis
– CNS TB
– Others - Eye

56. Follow up Sputum
• Cat 1 Smear positive
PTB)
• Cat 1 (Smear negative
PTB)
• End of 2nd month (end
of 3rd month if +ve at
the end of 2nd)
• End of 5th month
• End of treatment
• End of 2nd month
• End of treatment

57. Follow up Sputum
• Cat 2
– Relapse
– Tx after failure
– Tx after default (smear-
positive)
• End of 3rd month (end
of 4th month if +ve at
the end of 3rd)
• End of 5th month
• End of treatment

58. Sp. – ve - Follow up
• Symptoms
• Rpt CXRs
• Wt.
• (ESR)
• Sp. AFB
• Decide further investigations
• Trace AFB Culture

60. TB Pleural effusion
• ? Diagnosis confirmed – Ct. ATT
• Clinical assessment / Wt.
• CXR
• ESR
• ? Need further investigations

62. TB Lymphadenitis
• ? Diagnosis confirmed with a Biopsy
• ?Associated malignancy
• Clinical assessment / Wt. / Node size
• ESR /CRP

65. TB Meningitis
• Clinical assessment / complications
• ? Steroides 1mg/kg – 1 month
• Eye

66. Pregnancy and TB
• Most ATT drugs are safe
except streptomycin (oto-toxicity)
----Pyridoxine 10mg/d
----Vit. K to the Infant at birth (risk of post- natal
haemorrhage)

67. New born baby of a sp. +ve mother
• If the mother is smear negative, and the infant
has no evidence of congenital TB, BCG is
given.
• If the mother is smear positive at the time of
delivery, infant should be carefully examined
for evidence of active disease.
– If congenital TB suspected – ATT
– If well – prophylactic INAH 5mg/kg for 3 months.
BCG is withheld.

68. • Mx after 3 month
– If negative and the child is well, INAH stopped BCG
is given.
– If positive, carefully examination of the child for
active disease is done including a CXR.
– If active disease is diagnosed- full course of ATT
– If normal, INAH is continued up to six months and
BCG is given

69. Old TB

70. Dermatological reactions
• If only pruritus and no rash – symptomatic
treatment only
• If skin rash +, stop all ATT and wait till the rash
resolves. ( may need steroids )
• Drug challenge with the anti TB drug least likely
to be responsible for the reaction.
– H – 50mg---300mg---300mg
– R – 75mg---300mg---full dose
– P – 250mg---1gm--- full dose
– E – 100mg---500mg---Full dose
– S – 125mg---500mg--- full dose

71. Drug induced hepatitis
• Ideally base-line LFTs in all.
• Ask for nausea, vomiting
• If drug induced hepatitis is diagnosed, all ATT
should be stopped and LFT repeated weekly
• Re introduction of ATT
– H - 50mg, increase to full dose over 2-3 days and ct.
for another 2-3 days
– R – 75mg, increase to full dose over 2-3 days and ct.
for another 2-3 days
– S – 250mg, increase to full dose over 2-3 days and ct.
for another 2-3 days

72. Alternative drug regimen
–2SHE / 10HE
–2HRE / 7HR

75. Prevention of TB
----BCG vaccination
protects from Primary infection
----Case detection and treatment
----Chemoprophylaxis
Primary
Secondary
----Improving standards of living

77. Thank you
Dr. Saman Kularatne