INDEX TB GUIDELINE -EXTRA PULMONARY TB

1. Index TB guideline- EPTB
Dr.Akhilesh. K
Asst Professor
Pulmonary Medicine
AIMS,KOCHI

2. India accounts for 20% of all TB incidence cases in the world
Non-HBCs
20%
Pakistan
3%
Ethiopia
3%
Philippines
3%
South Africa
5%
Bangladesh
4%
Nigeria
5%
Indonesia
6%
China
14%
India
20%
Other 13 HBCs
16%
Source: WHO Global Report 2009

3. Evolution of TB Control in India
• 1950s-60s Important TB research at TRC and
NTI
• 1962 National TB Program (NTP)
• 1992 Program Review
•only 30% of patients diagnosed;
•of these, only 30% treated
successfully
• 1993 RNTCP pilot began
• 1998 RNTCP scale-up
• 2001 450 million population covered
• 2004 >80% of country covered
• 2006 Entire country covered by RNTCP

4. Impact - RNTCP
oNearly 22 million deaths have been saved since 1995.
o 45% decrease in death due to TB since 1990
o Global target of 85% cure rate and 70% of case detection
rate consistently achieved 2003 onward
o Case fatality reduced from 29% to 4% in NSP cases

5. Current views leading to change in
regime to daily regime
•High rates of “relapse” in RNTCP ~ 12 - 15%
•Increasing INH Resistance remain high( 20-40%)
SMCSI MC 22 - 03 - 2016 5

7. Magnitude of The problem
• 15%-20% of all TB cases in India in HIV negative
Immunocompetent
• >50%( 45-56%) – HIV Positive
• Usually Paucibacillary
• 75% have lymph node or pleural TB
• Occur in all age groups but incidence is higher in children /
young

8. • HIV Negative • HIV Positive

9. EPTB
Lack of
uniform
Tt
Comorbidity
&
Paucibacillar
y nature
Drug
Resistan
ce
Variable
presentatio
ns

10. AlIMS &

11. Principles
• Patient Centred approach
• Promote early diagnosis
• Access to tissue based diagnosis
• Addressing Drug resistance
• Avoiding unnecessary , invasive and costly tests.
• Access to HIV Testing
• Identify patients with concurrent active Pulmonary TB
• Ensuring effective treatment with appropriate regimen
• Promoting adherence
• Record keeping and public health promotion

12. Major questions raised by providers
• Use of tuberculin skin testing
• Role of the Xpert MTB/RIF test in diagnosing EPTB
•
• Role of other polymerase chain reaction (PCR)-based tests in diagnosing EPTB
• Empirical treatment
• Corticosteroids in EPTB
• Duration of anti-tuberculosis treatment (ATT) in EPTB
• Definition of treatment failure in terms of clinical parameters prompting
extended treatment, revised diagnosis, or consideration of drug resistance.

13. DEFINITIONS

15. Genexpert In
EPTB

16. LYMPHNODE TB
 Additional test to conventional smear microscopy, culture and
cytology in FNAC specimens.(Strong)
Quick diagnosis,Reduced stigma from overdiagnosis,R Resistnace
TB MENINGITITIS
Adjunctive test for tuberculous meningitis (TBM).
 A negative Xpert result does not rule out TBM.
Decision to give ATT should be based on clinical features and CSF
profile.( Conditional)
PLEURAL TB
 Should not be routinely used to diagnose pleural TB (Strong)

17. Steroids in
EPTB

18. TB MENINGITIS ( HIV Negative)
TBM in HIV-negative -RECOMMENDED
Duration of steroid treatment should be for at least 4 weeks, with
tapering as appropriate.(Strong)
TBM(HIV Positive)- May be used where other life-threatening
opportunistic infections are absent.
( Conditional)

19. • TB Pericarditis(HIV Negative)- Recommended for HIV-negative
patients with TB pericarditis with pericardial effusion.(Conditional)
• TB Pericarditis(HIV Positive)- Recommended for HIV-positive patients
with TB pericarditis with pericardial effusion.(Conditional)
• Pleural TB(Irrespective of HIV Status)
- Not routinely recommended in pleural TB.( Conditional)

21. Duration Of
Treatment

22. •Peripheral LN TB - 6 months ATT standard first-line regimen
(2RHZE/4RHE) is recommended for peripheral lymph node
TB.(Strong)
•Abdominal TB- 6 months ATT standard first-line regimen is
recommended for abdominal TB( Strong)
•TB Meningitis- TB meningitis should be treated with
standard first-line ATT for at least 9 months.(Conditional)

23. CNS TB

24. EPIDEMOLOGY
•Estimated 1% all cases
of TB In India
•High case fatality rate
•Long Term sequelae

25. Who should be investigated?

26. Diagnostic
Method
Selected patients Comments
Lumbar
puncture
All Lymphocytic
Pleocytosis with Low
Serum/CSF Glucose ratio
HIV testing All Integrated Counselling For
Seropositive
Chest Xray All Active /past TB
CT Brain All R/O hydrocephalus
MRI Brain Selected cases Diagnostic uncertainty

27. CSF SAMPLING

28. •Minimum 6 ml needed for adults ;3 ml for children
CSF Gram stain ,AFB Smear,TC
CSF / Serum Glucose Ratio
Mycobacterial culture ,Species identification& DST
Rule out other causes- Viral/ Cryptococcal/
Bacterial/Fungal
Genexpert-Adjunctive test. Negative Doesnot rule out
TBM .1 ml optimal for Xpert( High False Neg)
 Sensitivity-80.5% Specifcity -97.8%)
IGRA Not recommended
ADA is not useful
Diagnostic accuracy of Other PCR test highly variable

29. 2 HRZE+7 HRE
Referral – As early as
possible
Follow up till 2 years
at regular interval
DR suspect-
Poor response to
ATT/or MDR
contact
Steroids indicated
Dexa ( 0.4 mg/kg/24 hr in
divided doses) and taper

30. Alternate Regimen( Tech.Advisory Sub comitee)
 Streptomycin in IP Phase instead of Ethambutol in visual
impairment or cannot be assessed
Pyrazinamide instead of Ethambutol in CP Phase
Total Duration can be extended upto 12 months
Stopping Treatment- Clinical resolution
Residual neurological deficit should not be used as a sign of activity
Surgery-V/P Shunt

31. CNS TUBERCULOMA

32. Presumptive Tuberculoma
•Any patient presenting with seizures, headache,
fever or focal neurological deficits with
neuroimaging features consistent with a mass lesion
of inflammatory nature.

33. Diagnosis
Previous history and contact with TB case
CXR and CT for looking alt sites
HIV
 MRI – Confirmatory
CSF- May be Normal / finding of TBM
Culture – sensitivity low
PCR test validity doubtful.
Stereotactic/ open biopsy- Invasive

34. 9-12 months
Repeat MRI after 3 ,9 &12
months
Failure- If lack of reduction in
size /increase in size after 3-
6 months of Tt
Paradoxical Reaction-if
increase in size / number
after 3 months-Steroid/ ATT
Before putting second line in suspected MDR assess Risk/Benefit
ratio.
Tissue diagnosis- Sent H/P, AFB Culture,

35. SPINAL TB

36. Clinical Features
•Localised back pain>6 weeks with tenderness in
spinous process with or without fever, Wt loss with
or without spinal cord compression.
• Patient with advanced disease may have spinal
deformity, paraspinal muscle wasting
• In children failure to thrive, night cry, inability to
walk/cautious gait

37. Test Patient Comment
Chest X ray All Rule out PTB
HIV All Integrated Counselling and test
Xray Spine Limited Lesion will be delayed presentation
in CXR
( 3-6 months)
Follow up and monitoring
MRI Spine All Confirmation
Extend of Disease
Early Identification
CT Spine Selected cases Limited use in spinal cord involvement
Biopsy All P/C or Open
Send Specimen For
A)Routine and AFB Culture
B)Microscopy and AFB Smear
C)Histopathology and Cytology
Genexpert/PCR test Not Insufficient evidence

38. TREATMENT
• Start ATT if Clinico radiological evidence even if Biopsy is
not possible after assessing risk of procedure
• 2 HRZE+10 HRE ( Maximum upto 18 months of Tt)
• Surgery For Diagnosis, Spinal deformity, Neurological
Deficit

39. Follow up
• If any new signs of Neurological deficit report immediately
• Patient with Neurological Deficit weekly monitoring with
neural chart
• X ray spine every 3 months
• MRI at 6,9,12,18 following Tt Initiation
• Follow up every 6 months for 2 years after stopping
treatment
• Report to physician if any new signs after Stopping RX

40. Bone & Joint TB
• MC in Immuno suppressed and Old TB
• In the early course, aspiration of synovial fluid/ pus usually
not diagnostic but should send for Microscopy and Culture
• Biopsy of the affected structure/ sinus tract curettage /
Edge biopsy can be done and to be send for microscopy and
culture and H/P
• CBNAAT limited role
• Treatment Regimen 2 HRZE+ 10-16 HRE

41. Pleural TB

42. Chest Xray All -Confirmation/PTB
-Monitoring
HIV Test All Integrated Counselling&
test
CT Scan Selected Cases -Alternate diagnosis(CA)
-Disseminated Disease
USG Chest Selected cases Alt. To CXR
Thoracocentesis All Diagnostic only.Send for
TC,DC,Cytology,AFB
smear,Culture,protein,
sugar,LDH(S.LDH also)
Sputum AFB Selected cases CBNAAT/AFB Smear/AFB
culture
Pleural Biopsy Selected cases High yield
H/P ,AFB Culture&
Microscopy
Thoracoscopy Selected cases -More yield than Closed
Pleural Bx.
-Uncertain Diagnosis
PLEURAL FLUID CRITERIA
Exudative
High ADA
Genexpert Not
Recommended
Sensitivity-46.4%
Specificity-99.1%)
>70U/L- High
40-70 U/L- indeterminate
<40 U/L- Less likely

43. 2 HRZE+4 HRE
Steroids not
recommended
Follow up CXR after 8
weeks
General Improvement
2 weeks
Significant Improvement
6-8 weeks
Worsening initially –
Paradoxical Reaction

44. Lymph node Tuberculosis

45. Type Symptoms
Presumptive Peripheral LN TB LNE >1 cm in axilla, neck, groin+
Constitutional features
Mediastinal TB Constitutional features
Cough,fever
Hilar enlargement in CXR and/or
Mediastinal widening in CT
Chest in the absence of evidence
of active PTB
Abdominal LN TB Dull, colicky abdominal pain,
distension
Constitutional features
Abdominal LNE on USG ,CT or
MR

46. DIAGNOSIS
TEST PATIENT COMMENT
CXR All Cases Active/Old PTB
HIV All cases Integrated counselling &
tests
USG/CT chest&/or
abdomen
Selected cases Uncertain diagnosis
FNAC All Gene Xpert/AFB
Smear/AFB Culture&
DST/Cytology
Excision Biopsy Selected •If FNAC inconclusive
•Alternate diagnosis
Gene Xpert/AFB
smear/AFB Culture &
DST,Histopath

47. • Specimen should be taken before starting ATT
• Non dependant Aspiration by Z technique for superficial
LNE
• Image guided Aspiration for Deep LNE
• Abdominal LNE- CT Guided/USG Guided FNAC or Biopsy
• Mediastinal LNE- EBUS guided FNAC if facility available
Genexpert should be used as an additional test to cytology
( Strong)
Sensitivity -83.1% Specificity -93.1%

48. PERPIPHERAL LNE
2 HRZE+4 HRE
 Follow up after 4 Months
 Worsening in 1St 3 months- paradoxical reaction
 If Residual LNE ( largest LN)< 1 cm at the end of Tt- No active TB
 If largest LN>1 cm- Partial responders
Expert Group suggest additional 3 months of ATT - Biopsy / AFB
Culture if failed to respond to that
Some group suggest further ATT not needed
( insufficient data)

49. Follow up – 4 Months
If CXR s/o no improvement------------- CT Chest
WHEN TO STOP ATT?
if no improvement after 4 months of Tt documented
clinicoradiologically ( Difference of opinion)
Mediastinal LNE
2HRZE+ 4 HRE

50. Abdominal TB
Most common site -Abdomen distal
to duodenum
( Jejunum,ileum,colon,peritoneum)

51. Test Patient Comments
CXR/HIV All Rule out PTB
Integrated counselling
Ascitic fluid All Cytology,ADA,Albumin
and protein,AFB
Smear,AFB
culture,Routine C& S
USG abdomen All Ascites,Omental
thickening, Mesentric
adenopathy
USG Guided FNAC/Core
biopsy from Mesentric or
RPLN
,omentum,peritoneum
Selected Microscopy &Culture of
FNAC/Biopsy specimen
than fluid alone
Send for H/P,M/C copy,
Culture
CT/MRI Abdomen Selected Diagnostic Uncertainty
Laproscopy Selected( Cost, Invasive)  Tubercles in thickened
peritoneum,omentum and
Liver
 Fibro-adhesive
peritonitis
Targeted Diagnostic
SAAG<1.1
High protein (>2.5 g/DL)
ADA >39 IU/L
Sensitivity in Smear AFB
and AFB Culture Low
PCR – Variable accuracy
( No Recommendation)

52. Test Patients Comments
Ileocolonoscopy (
Retrograde ileoscopy)
All cases
Rule Out IBD
Sent for H/p,AFB
Culture
CT/MR enterography
/enteroclysis
Selected •Short Segment
stricture
•Necrotic Nodes
•Ileocaecal wall
thickening
UGIE Selected
Barium study Selected UGIE Contraindicated
or
Small Bowel stricture
PCR BASED -NOT RECOMMENDED – HIGHLY
VARIABLE ACCURACY

53. TREATMENT
2 HRZE+4 HRE
Extension as per
Physician’s discretion
All Presumptive GI TB
should be referred to GI
Follow Up after 3 & 6
Months
Surgery
Stricture-Endoscopic
Dilatation/Resection of stricture
P/c or Endoscopic biliary
stenting,Drainge of Liver abscess

54. UROGENITAL TB

55. SYMPTOMS
• Lower urinary symptoms
( frequency, urgency, nocturia) with dysuria and/or
hematuria for 2 weeks which has not responded with 5 day
course of antibiotics
• ( Avoid FQ if suspecting TB)
• Generalised symptoms

56. CXR/HIV/RFT All cases
Urine M/c and aerobic culture( Non
mycobactrial
Sterile pyuria( s/oTB)
Asso.TB
Bacterial infection
Early Morning Urine sample 3 -5sample needed for smear AFB and
AFB Culture. Low sensitivity ; but culture
confirmative
USG KUB All cases ( Normal in early disease; if pick
up hydronephrosis s/o TB)
IV urography ( plain Xray) Selected cases( widely available; Low
sensitivity)
Contrast enhanced CT urography Selected cases( More Sensitivity)
MR urography without contrast Selected( Expensive; but no need of
contrast, more sensitive
FNAC/Biopsy AFB Smear/ Culture & DST/H/P

57. Urethroscopy with or
without bladder biopsy
Selected cases
Biopsy Most of the cases( AFB
smear , Culture/HP), DST)

58. Diagnosis
CXR/HIV Test All Cases
USG or CT abdomen or Chest Selected cases
FNAC All( AFB Smear, Culture with
DST, Cytology, Xpert)
Excision Biopsy Selected ( If FNAC
inconclusive or alt .diagnosis)
AFB Smear,Culture&
DST,Xpert, Histopath
Genexpert Sensitivity -87-100% Specificity-92-98%

60. Cardiac Tuberculosis

61. Test Patients Comments
Chest Xray All Water Bottle Sign
HIV All
ECG All Low Voltge ,T wave
flattening
ECHO All Pericardial Effusion
CT and Cardiac
MRI
Selected

62. •Microbiological Diagnosis Poor yield
•Xpert – Not Recommended
•ADA- Contributory
• 2 HRZE+4 HRE
•FUP after 4 Months
•Steroids indicated

63. TAKE HOME MESSAGE
• Treatment of EPTB is to be individualised
• Clinician is having discretion in deciding duration of
treatment ,methods of obtaining tissue for sampling etc
• Sensitivity of Newer techniques in EPTB low so that
diagnostic utility will vary depends on site of involvement
• Further study needed in certain areas – Researches should
be encouraged