Index TB guideline- EPTBDr.Akhilesh. K

Asst Professor, Pulmonary Medicine

India accounts for 20% of all TB incidence cases in the world

Non-HBCs20%

Pakistan3%

Ethiopia3%

Philippines3%

South Africa5%

Bangladesh4%

Nigeria5%

Indonesia6%

China14%

India20%

Other 13 HBCs16%

Source: WHO Global Report 2009

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

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

SMCSI MC 22 - 03 - 2016 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%)

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

• HIV Negative • HIV Positive

EPTB

AlIMS &

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

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.

DEFINITIONS

Genexpert In EPTB

LYMPHNODE TB Additional test to conventional smear microscopy, culture and

cytology in FNAC specimens.(Strong)Quick diagnosis,Reduced stigma from overdiagnosis,R Resistnace

TB MENINGITITISAdjunctive 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)

Steroids in EPTB

TB MENINGITIS ( HIV Negative)

TBM in HIV-negative -RECOMMENDEDDuration 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)

• 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)

Duration Of Treatment

• 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)

CNS TB

EPIDEMOLOGY

• Estimated 1% all cases of TB In India

• High case fatality rate• Long Term sequelae

Who should be investigated?

Diagnostic Method

Selected patients Comments

Lumbar puncture

All LymphocyticPleocytosis 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

CSF SAMPLING

• 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

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 indicatedDexa ( 0.4 mg/kg/24 hr in divided doses)

and taper

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 resolutionResidual neurological deficit should not be used as a sign of activity

Surgery-V/P Shunt

CNS TUBERCULOMA

Presumptive Tuberculoma

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

DiagnosisPrevious 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

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,

SPINAL TB

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

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 ConfirmationExtend of DiseaseEarly Identification

CT Spine Selected cases Limited use in spinal cord involvement

Biopsy All P/C or Open Send Specimen For A)Routine and AFB CultureB)Microscopy and AFB SmearC)Histopathology and Cytology

Genexpert/PCR test Not Insufficient evidence

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

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

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

Pleural TB

Test Patients CommentsChest 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 CXRThoracocentesis 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

ExudativeHigh ADA

Genexpert Not Recommended

Sensitivity-46.4%Specificity-99.1%)

>70U/L- High

40-70 U/L- indeterminate

<40 U/L- Less likely

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

Lymph node Tuberculosis

Type Symptoms

Presumptive Peripheral LN TB LNE >1 cm in axilla, neck, groin+ Constitutional features

Mediastinal TB Constitutional featuresCough,feverHilar enlargement in CXR and/orMediastinal widening in CT Chest in the absence of evidence of active PTB

Abdominal LN TB Dull, colicky abdominal pain, distensionConstitutional features Abdominal LNE on USG ,CT or MR

DIAGNOSIS

TEST PATIENT COMMENTCXR 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

• 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%

PERPIPHERAL LNE2 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)

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 LNE2HRZE+ 4 HRE

Abdominal TB

Most common site -Abdomen distal to duodenum( Jejunum,ileum,colon,peritoneum)

Test Patient Comments

CXR/HIV All Rule out PTBIntegrated 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 aloneSend for H/P,M/C copy, Culture

CT/MRI Abdomen Selected Diagnostic UncertaintyLaproscopy Selected( Cost, Invasive) Tubercles in thickened

peritoneum,omentum and Liver Fibro-adhesive peritonitisTargeted Diagnostic sample increase yield

SAAG<1.1High protein (>2.5 g/DL)

ADA >39 IU/L

Sensitivity in Smear AFB and AFB Culture Low

PCR – Variable accuracy( No Recommendation)

Test Patients Comments

Ileocolonoscopy ( Retrograde ileoscopy)

All casesRule 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 orSmall Bowel stricture

PCR BASED -NOT RECOMMENDED – HIGHLY VARIABLE ACCURACY

TREATMENT

2 HRZE+4 HREExtension as per Physician’s

discretion

All Presumptive GI TB should be referred to GI

Follow Up after 3 & 6 Months

SurgeryStricture-Endoscopic

Dilatation/Resection of strictureP/c or Endoscopic biliary stenting,Drainge of Liver

abscess

UROGENITAL TB

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

CXR/HIV/RFT All cases

Urine M/c and aerobic culture( Non mycobactrial

Sterile pyuria( s/oTB)Asso.TBBacterial 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

Urethroscopy with or without bladder biopsy

Selected cases

Biopsy Most of the cases( AFB smear , Culture/HP), DST)

Diagnosis

CXR/HIV Test All CasesUSG or CT abdomen or Chest Selected casesFNAC 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%

Cardiac Tuberculosis

Test Patients CommentsChest Xray All Water Bottle SignHIV AllECG All Low Voltge ,T wave

flatteningECHO All Pericardial EffusionCT and Cardiac MRI

Selected

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

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