24 march short ntep who diagnosis of dr tb

Robert Koch
24 March,1882
Physiologists of Berlin
• Bacteria isolated from tubercular patients
Injected into
• 94 guinea pigs
• 70 rabbits
• 44 mice
• 9 cats
Caused a similar disease in all these animals

• Diagnose and treat 40 million people with TB in the period 2018 to 2022:
• 2018  7 million; thereafter 8 million every year
• Early diagnosis of TB & universal drug susceptibility testing
• Microbiological detection of TB is critical
• Most appropriate and sensitive method should be used
• Follow approved algorithm
• RT PCR assay as front line detection rather than smear
• LPA 1 & 2 for rapid detection of DR TB
• Antigen testing in Urine (HIV patients)

Specimen collection and transportation to labs
• Obtaining good quality specimens of adequate volume are critical to ensure
correct diagnosis.
• Collection of specimens: Programme recommends collection of sputum one
spot and one morning, OR
2 spot specimens collected with a gap of at least one hour
(if the patient is coming from a long distance OR s/he is unlikely to
return to give the second specimen).
Specimen collection & transportation to the laboratory

Good quality specimen:
• Volume of 2-5 ml,
• Preferably mucopurulent and not heavily blood stained or contaminated.
• Collect the specimen in a sterile container (50 ml conical tube) after
thorough rinsing of the mouth with clean water.
• Specimens should be transported to the NAAT or C-DST laboratory as soon
as possible after collection.
• If a delay is unavoidable the specimens should be refrigerated to inhibit
the growth of unwanted micro-organisms.
Good Quality Specimen

Specimen will be rejected if the following issues are observed
1. Unlabelled or mislabelled specimen
2. Specimen sent without request form.
3. Name on Specimen and request form do not match.
4. If the container is full up to the lid with the specimen due to pooling
5. Sample is not collected in an appropriate container
6. Specimen breakage or leakage
Specimens will be rejected if

Material required for packing the specimen for
transportation
• Falcon tubes (50 ml conical bottom tubes made of polypropylene) containing
the sputum samples;
• 5% phenol;
• absorbent tissues;
• packaging kit;
• permanent marker pen.
Material required for packing & transporting of
samples

Steps in performing triple packaging for the transportation of specimen
Confirm that the cap is
tightly closed
Wipe with 5% phenol wipe with tissue
paper
Write the patient details
on the Opaque area
Wrap the parafilm strip at the
joint between the cap and the
neck of the Falcon tube such
that a secure seal is formed
Primary
receptacle/
package
Absorbent
Cotton
Open the absorbent Cotton roll
and spread out the cotton roll
on the work bench; separate
the cotton into two equal
layers.
Roll the Falcon tube containing
the sample tightly in the
absorbent cotton Put this roll containing
the Falcon tube into the
Zip lock pouch
Cover the
entire tube
Roll the whole into a
tight bundle, ensuring
that there is no air in
the pouch; Secure this
bundle with the
rubber bands
Secondary
receptacle/
package
Insert the RNTCP Annexure (Form 15 A) in to
another Zip lock pouch after ensuring that the
details on the form and the sample tubes match,
with the writing facing outside. Seal the zip lock
on the pouch.
Annexure
15A
Frozen Gel
Packs
Biohazard sticker
Tertiary
receptacle/
package
1
2
3
Steps in triple packing of samples & transporting
of specimens

Figure 4.1 Technical Specifications of Transport Box for Sputum Specimen
transportation in Cool Chain
Thermocol transport box
Size:
Thickness of box-2.5 cm
Outer Dimensions:
Length-18.5cm, Breadth-13cm, Height-12 cm (without lid), Height-14 cm (with lid)
Inner Dimensions:
Length-14.5cm, Breadth-8cm, Height-12cm (without lid), Height-13cm (with inner part of lid)
No. of gel pack required:2, Weight of fully packed consignment box: 400 grams, Approximate cost of courier charges: 60-70 Rupee per box
Gel packs maintain a temperature between 12-20 Deg Celsius for up to approximately 48 hours in tightly packed thermocol boxes (average outside temperature 35˚C). If
conditioned in the deep freezer (temperature between -20 to -15˚C) for a minimum of 48 hours to a maximum of 72 hours before use. (This is onetime use box.
Thermocol boxes and gel packs are not reused)
Specification of transport box

• Two fresh specimen need to be collected at designated collection centres by
trained LT and transported in a cool chain on the same day to the nearest
CBNAAT lab for all eligible patients.
• At CBNAAT sites, based on results of RR-TB or RS-TB, the second specimen
needs to be repacked by the LT at CBNAAT site and transported to the NTEP
C-DST laboratory in a cool chain on the same day for SL-LPA and/or FL-LPA
respectively along with the updated NTEP request form
Specimen collection & Transport to laboratory

• All specimens need to be delivered to the NTEP C-DST laboratory within
48-72 hours of collection.
• Ideally, an agency (courier/speed post) should be identified for this
purpose by the concerned DTO.
• Agency may be engaged as per partnership guidelines for specimen
transportation in cool chain.
• If none is available, human carriers need to be identified from the health
system/ community to transport the specimen in bio-safe conditions
with appropriate enablers.
Specimen collection & Transport to laboratory

Materials required for Sputum transport to be supplied to
DMCs by DTO
• 50-ml conical bottom tubes (made of polypropylene material)
• the 3 layer packing materials like thermocol box,
• ice gel pack (pre-freezed at -20 degree for 48 hours),
• request for testing biological specimen form,
• polythene bags,
• tissue paper roll as absorbent,
• parafilm tapes,
• brown tape for packaging box,
• permanent marker pen,
• labels, bio-hazard sticker,
• scissors, spirit swab etc.
Material required for collection & Transport will be
provided

Critical points while specimen collection and transportation
• 50-ml conical tubes should carry a label indicating the patient’s details like
name, date of specimen collection, name of DMC/DTC, Lab. No:- XYZ,
specimen A or B;
• LT of DMC should promptly inform the specimen transport agency like a
courier/ speed post service to collect and transport the specimens;
• for every TB patient referred by MO-DMC, date of referral and transport of
sputa specimens to C-DST laboratory should be entered in respective column
of the DMC lab register (Annexure 15K) and TB notification register (Annexure
I).
• once the sputum has been transported to the C-DST laboratory, the
presumptive DR TB patient should return to continue their NTEP first-line
treatment
Critical points while collecting & transporting samples

DR-TB Diagnostic Algorithm
All notified TB patients
Presumptive TB
R resistance detected R resistance not detected
H resistance not detected
H resistance detected
• PLHIV
• EPTB
• Smear -ve/NA with X-ray
suggestive of TB including
paediatric
• Vulnerable populations
• Contact of DR TB patient
Non responder to treatment
FL – LPA$,
SL – LPA$ and
DST for Mfx(1.0), Lzd*,
Cfz*, Z*, Bdq*, Dlm*
NAAT#
FL LPA$
SL LPA$
DST for Z*
DST for Mfx (1.0) & Lzd only if FQ or Z
resistance detected
# NAAT include CBNAAT & TruNAAT
*whenever available
$ Culture isolates to be subjected to LPA for smear negative specimens
For discordance resolution – see text
• DS TB
• H mono/poly
NTEP endorsed DR TB Algorithm

The vision of the programme is to offer DST to TB patients at the earliest time in
their course of disease.
The integrated diagnostic algorithm starts with three groups of patients who are
either
1. presumptive TB,
2. notified TB or
3. non-responders to treatment.
The main objective of this algorithm
• to segregate DR TB and offer appropriate treatment based on drug resistance
status at least for resistance to R or H at the time of diagnosis of TB.
• subsequent time points when DST needs to be offered
DR-TB Diagnostic Algorithm
DR TB Diagnostic Algorithm

The left path of the algorithm
For the presumptive TB persons
• PLHIV
• EPTB
• Smear -ve/NA with X-ray suggestive of TB including paediatric
• Vulnerable populations
• Contact of DR TB patient
By virtue of using NAAT as the TB diagnostic test, the R status is also
available simultaneously along with TB detection.
Left Path of the Algorithm

Rifampicin Resistant detected
• FL LPA (for Eto)
• SL LPA and (for FQ or SLI)
• DST to Mfx (1.0), Lzd*, Cfz*, Z*, Bdq*, Dlm*(*whenever available) will be
set up on liquid culture using the decontaminated deposits only for RR TB
patients (Base line SL DST).
Rifampicin Resistance Detected
The critical concentration is defined as the lowest concentration of an
anti-TB agent in vitro that will inhibit the growth of 99% of phenotypically
wild type isolates of M. tuberculosis complex.

Gene expert
Gene Xpert
Gene Xpert
Cartridge Based Nucleic Acid Amplification Test
(CBNAAT)

• WHO endorsed Cartridge based, closed RT PCR for
• Detection of MTB &
• RIF Resistance (as surrogate for MDR TB)
• Contains Internal quality controls for
• Sample Processing (SPC)
• Probe Check (PCC)
• Amplifies a 192 bp region of MTB rpoB gene
• RIF resistance is detected by 5 overlapping molecular beacon probes
that are complementary to entire 81 bp region of RRDR of rpoB gene
Gene Xpert MTB/RIF CBNAAT

Gene Xpert Report
Gene Xpert MTB/RIF is Positive / Negative
Mycobacterium tuberculosis DNA Detected / Not Detected
Quantitation High / Medium / Low / Very Low
Rifampicin Resistance Present / Absent
Result:
MTB Quantitation Result Ct Range
High < 16
Medium 16 – 22
Low 22 – 28
Very Low  28
Rifampicin result result types, when MTB is DETECTED
 Rifampicin resistance Detected: a mutation in the rpoB gene has been detected that falls within the valid delta Ct setting.
 Rifampicin resistance Not detected: no mutation in the rpoB has been detected
 Rifampicin resistance Indeterminate: The MTB concentration was very low and resistance couldnot be detected.
Gene Xpert MTB/RIF [CBNAAT]
Result

Detection of Rifampicin Resistance
Detection of Rifampicin Resistance

Sensitivity = True positives / all affected
Specificity = True negatives / all unaffected
Smear sensitivity is 30%, culture (Gold Standard) 100% but takes 6 wks
Gene Xpert Sensitivity = 99%, Specificity 99%, TAT 2 hours
Cepheid Submission to USA FDA

323 culture & Xpert +, 63 only Culture +ve, Xpert + in 40 additional
234 of these (60.6%) smear negative
Xpert Sensitivity 83.7%; Specificity 99.1%
Sensitivity with respiratory samples 86.5%
Sensitivity with extra pulmonary samples 73.1%
Sensitivity of Microscopy alone 39.4%
Xpert improved diagnosis of Pulmonary TB by 36.5%
Xpert improved diagnosis of extra pulmonary TB by 63.4%
G. Lombardiet al. Department of Experimental, Diagnostic and Specialty Medicine –
Unit of Microbiology, Alma Mater Studiorum University of Bologna - S. Orsola-Malpighi
University Hospital, Bologna, Italy,

Gene Xpert is the best available test but is suboptimal in pauci bacilliary TB infections

Gene Xpert Ultra
Better version
131 cfu/ml 16 cfu/ml
Gene Xpert  Ultra
131 16

Gene Xpert Vs Gene Xpert Ultra
Gene Xpert Gene Xpert Ultra
Diagnosis Mtb Complex Mtb complex
Resistance Detects Rif Resistance as surrogate for MDR TB Detects Rif Resistance as surrogate for MDR TB
Amplification Single target:
rpo B core region
Multiple copy targets:
rpo B core region
Insertion sequences:
IS 6110
IS 1081
Resistance detection RT PCR,
5 probes bind to rpo B gene
Melting curve,
4 probes bind to rpo B gene
Sample size 2 ml 2 ml
PCR reaction volume 25 ul 50 ul
Assay TAT 112 minutes 65 to 87 minutes
Limits of detection 131 cfu / ml 16 cfu / ml
Cost US$ 9.98 US$ 9.98
Use Initial diagnostic tests from adults & children Initial diagnostic tests from adults & children
Special advantage Pauci-bacillary samples : from Paediatrics pts.,
EPTB like CSF, Lymph nodes, Tissues, Fluids

• 129 HIV +ve adults included in the study
• 23 were considered probable and screened for TBM
• Gene Xpert Ultra positive in 16 / 23; sensitivity 70%
• Gene Xpert positive in 10 / 23; sensitivity 43%
• MGIT Culture positive in 10 / 23; sensitivity 43%
• Recovery was best when 6 ml of CSF was subjected to Gene Xpert Ultra

Rifampicin resistance not detected
For all TB patient in Rifampicin resistant not detected
FL LPA (H mono
resistance detection)
For all H mono/poly resistance detected
SL LPA
DST for Z
For H + FQ or Z
resistance detected
DST to Mfx (1.0) & Lzd
Rifampicin Resistance Not Detected

Smear
microscopy
Smear
+Ve
LPA
Valid
results
Reported to
concerned
health facility
Invalid
results
Smear -
Ve
Liquid
culture
Specimen process algorithm at CDST lab
At the C-DST laboratory, smear microscopy is done on the second specimen
received from NAAT lab. LPA will be carried out for smear positive specimen
while smear negative specimen will be managed as mentioned
Specimen processing algorithm at
CDST Laboratory

Specimen
collection
centres
Two specimen in conical
tubes, collected, packed &
transported in cool chain
Generate Test
ID
NAAT
sites
One specimen will be
utilized to perform NAAT
and second specimen will
be transported to C-DST
lab
Update NAAT result
and create Test ID
for tests expected
at C-DST lab
C-DST lab
Second specimen will be
tested for FL and/or SL LPA
and further DST as
applicable
Update test
results
Operational process of specimen referral
Specimen handling Nikshay
Operational process of sample referral

• 1. conjugate control (line 1)
• 2. Amplification control (line 2)
• 3. TUB reaction control (line 3)
• 4. Locus control band for different target regions are
located just before the respective WT & MUT bands
must be present for assay to be considered valid
• 5. LPA is indeterminate if corresponding locus control is
missing while test is valid ( i.e CC & TUB & AC visible)
• 6. WT reaction zones comprise regions in the genome
known to have mutations leading to resistance
• 7. MUT reaction zones correspond to probes that
identify most common mutations in the gene
• 8. Resistance is DETECTED when MUT probes are
developed
• 9. If WT probes are not developed, resistance is inferred
• 10. If WT & one MUT is developed  Mixed culture

FL LPA
Wild type probe [WT#]
Mutation Probe [MUT#]
Developed
Not Developed
Targets wild type probe mutation probe
control bands CC; AC; TUB
1. rpo b gene for Rif 8 + 1 LC 4
2. kat G gene for INH 1 + 1 LC 2
3. Promoter inh A for 2 + 1 LC 4
a. Low level INH
b. Ethionamide
c. Prothenamide
FL LPA

D 516 V GAC  GTC Aspartic acid  Valine
H 526 Y CAC  TAC Histidine  Tyrosine
H 526 D CAC  GAC  Aspartic acid
S 531 L TCG  TTG Serine  Leucine

FL LPA Interpretation
Probe Result interpretation Clinical Interpretation
katG MUT1 or MUT2 developed
Mutation associated with high-level
increase in MIC detected.
Isoniazid is unlikely to be
effective even at high dose
katG WT, MUT1 and MUT2 not
developed
inhA MUT1 developed
Mutation associated with at least low-level
increase in MIC detected. Resistance to
Eto/Pto detected.
Isoniazid at high dose is likely
effective.
Ethionamide/prothionamide are
not effective.
inhA MUT2 developed
Resistance to Eto/Pto likely detected.
effective.
likely not effective.
InhA WT1, MUT1 and MUT2 not
developed
Resistance to Eto/Pto likely inferred.
InhA MUT3A developed Mutation associated with at least low-level
Resistance to Eto/Pto likely detected.
effective.
not effective.
InhA MUT3B developed
InhA WT2, MUT3A and MUT3B not
developed
increase in MIC inferred.

SL LPA
Wild type probes
MUT Probes
Developed
Not Developed
Targets wild type probe mutation probe
control bands CC; AC; TUB
gyr A 3 + 1 LC 6
gyr B 1 + 1 LC 2
rrs 2 + 1 LC 2
eis 3 + 1 LC 1
SL LPA

A 90 V GCG  GTG Alanine  Valine
S 91 P TCG  CCG Serine  Proline
D 94 A GAC  AAC Aspartic acid  Alanine
D 94 N GAC  AAC  Asparagine
D 94 Y GAC  TAC  Tyrosine
D 94 G GAC  GGC  Glycine
D 94 H GAC  CAC  Histidine

Mutations detected in SL LPA
Mutations detected in SL LPA

SL LPA Interpretation (FQ)
gyrA WT1 not developed
Resistance to Lfx inferred. Mutation associated with at least low-level
increase in MIC for Mfx inferred.
Levofloxacin is not effective.
Moxifloxacin could be used at
higher dose. The regimen
should be reevaluated based
on phenotypic DST results at
CB.
gyrA MUT1 developed Resistance to Lfx detected. Mutation associated with at least low-level
increase in MIC for Mfx detected.
gyrA MUT2 developed
gyrA WT2, MUT1 and MUT2 not
developed
increase in MIC for Mfx inferred.
gyrA MUT3A developed
Resistance to Lfx detected. Mutation associated with at least low-level
gyrA MUT3B developed
Resistance to Lfx detected. Mutation associated with high-level increase in
MIC for Mfx detected.
Levofloxacin is not effective.
Moxifloxacin is not effective.
gyrA MUT3C developed
gyrA MUT3D developed
gyrA WT3, MUT3A,
MUT3B, MUT3C, MUT3D not
developed
increase in MIC for Mfx inferred. Levofloxacin is not effective.
Moxifloxacin could be used at
higher dose. The regimen
should be reevaluated based
on phenotypic DST results at
CB.
gyrB MUT1 developed Resistance to Lfx detected. Mutation associated with at least low-level
gyrB MUT2 developed
gyrB WT, MUT1 and MUT2 not
developed
increase
in MIC for Mfx inferred.

SL LPA Interpretation (SLI)
rrs MUT1 developed Resistance to Km, Am, Cm detected Amikacin, kanamycin and capreomycin are not effective.
rrs WT1 and MUT1
not developed
Resistance to Km, Am*, Cm inferred
Kanamycin and capreomycin are likely not effective.
Phenotypic DST result should guide the choice to use
Amikacin in the treatment regimen.
rrs MUT2 developed Resistance to Km, Am, Cm detected Amikacin, kanamycin and capreomycin are not effective.
rrs WT2 and MUT2
not developed
Resistance to Km, Am, Cm inferred Amikacin, kanamycin and capreomycin are likely not effective.
eis WT1 not
developed
Resistance to Km inferred. Resistance to
Am and Cm not detected.
Amikacin and Capreomycin are likely effective. Kanamycin is
not effective.
eis MUT1 developed
Resistance to Km detected. Resistance to
Amikacin and Capreomycin are likely effective. Kanamycin is
not effective.
rrs WT2 and MUT2
not developed
Resistance to Km inferred. Resistance to
Amikacin and capreomycin are likely effective. Kanamycin
likely not effective.
eis WT3 not
developed
Resistance to Km, Am, Cm not detected Amikacin, kanamycin and capreomycin are likely effective.

Methods for drug susceptibility testing
Rapid molecular Drug Resistance Testing (DRT) -
Genotype
Nucleic Acid
Amplification Test
(NAAT)
cartridge
based Gene-
Xpert platform
chip based
TruNAAT
platform
Line Probe Assay (LPA)
First line (H &
R)
Second line
(Lfx, Mfx, Km,
Cm, Am)
Growth-based
phenotypic drug
susceptibility testing
(DST)
first-line drugs: R, H, E, Z
Second-line drugs: S, Lfx,
Mfx, Km, Cm, Am other
drugs: Lzd, Cfz, Bdq*,
Dlm* PAS etc.,
Genotypic testing is much faster than phenotypic methods.

Group A Group B Group C
Include all three if possible Include one or both Make up depending upon resistance
Levofloxacin Lfx or Clofazimine Cfz Ethambutol E
Moxifloxacin Mfx Cycloserine Cs or Delamanid Dlm
Bedaquiline Bdq Terizidone Trd Pyrazinamide Z
Linezolid Lzd Imipenem-cilastatin Ipm- Cln or
Meropenem Mpm
Amikacin Am or
Streptomycin S
Ethionamide Eto or
Prothionamide Pto
Para amino salicyclic acid PAS
What is new in TB ?
Change in classification of anti TB drugs
Second Line

What is new in TB ?
Definition of pre XDR & Updated definition of XDR-TB
• Pre-XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis)
strains that fulfil the definition of MDR/RR-TB and that are also resistant to
any fluoroquinolone
• XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis)
strains that fulfil the definition of MDR/RR-TB and that are also resistant to
any fluoroquinolone and at least one additional Group A drug

Phenotypic DST
If Mtb is RR TB
Baseline Drug Susceptibility testing
1. Moxifloxacin (1 ug/ml)
2. Linezolid
3. Clofazimine
4. Delamanid
The critical concentration is defined as the lowest concentration of an anti-TB
agent in vitro that will inhibit the growth of 99% of phenotypically wild type
isolates of M. tuberculosis complex

Speed Of Growth Of M.tuberculosis (MGIT 960 vs L J Media)
1st wk 2nd wk 3rd wk 4th wk 5th wk 6th wk
166
0
132
23
55
46
23
63
13
48
2
24
391 204
Data generated in 2007 – 08 by Dr Bansidhar Tarai under guidance of
Dr Ashok Rattan during their tenure in Religare SRL Reference Lab, Gurgaon, unpublished
Time-to-Detection in Culture Predicts Risk of
Mycobacterium tuberculosis Transmission:
Matthew K. O’Shea et al. [UK] Clinical Infectious Diseases 2014;59(2):177–85
TTD < 9 days identifies patients at high risk of transmitting tuberculosis and is superior to
sputum smear.

• 1. Molecular assays intended as initial tests for TB
• 2. Loop-mediated isothermal amplification
• 3. First-line LPAs
• 4. Second-line LPAs
• 5. Lateral flow urine lipoarabinomannan assay

• In adults with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be
used as an initial diagnostic test for TB and rifampicin-resistance detection in
sputum rather than smear microscopy/culture and phenotypic DST
• In children with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be
used as an initial diagnostic test for TB and rifampicin-resistance detection in
sputum, gastric aspirate, nasopharyngeal aspirate and stool rather than smear
microscopy/culture and phenotypic DST.
• In adults with signs and symptoms of pulmonary TB and without a prior history
of TB (≤5 years) or with a remote history of TB treatment (>5 years since end of
treatment), Xpert Ultra should be used as an initial diagnostic test for TB and for
rifampicin-resistance detection in sputum, rather than smear microscopy/culture
and phenotypic DST.
Recommendations on Xpert MTB/RIF
and Xpert Ultra as initial tests in adults
and children with signs and symptoms
of pulmonary TB

• In adults with signs and symptoms of pulmonary TB and with a prior
history of TB and an end of treatment within the last 5 years, Xpert
Ultra may be used as an initial diagnostic test for TB and for
rifampicin-resistance detection in sputum, rather than smear
microscopy/culture and phenotypic DST.
• In children with signs and symptoms of pulmonary TB, Xpert Ultra
should be used as the initial diagnostic test for TB and detection of
rifampicin resistance in sputum or nasopharyngeal aspirate, rather
than smear microscopy/culture and phenotypic DST
Recommendations on Xpert MTB/RIF
and Xpert Ultra as initial tests in adults
and children with signs and symptoms

• In adults and children with signs and symptoms of TB meningitis, Xpert MTB/RIF
or Xpert Ultra should be used in cerebrospinal fluid (CSF) as an initial diagnostic
test for TB meningitis rather than smear microscopy/culture.
• In adults and children with signs and symptoms of extrapulmonary TB, Xpert
MTB/RIF may be used in lymph node aspirate, lymph node biopsy, pleural fluid,
peritoneal fluid, pericardial fluid, synovial fluid or urine specimens as the initial
diagnostic test for respective form of extrapulmonary TB rather than smear
microscopy/culture.
• In adults and children with signs and symptoms of extrapulmonary TB, Xpert
Ultra may be used in lymph node aspirate and lymph node biopsy as the initial
diagnostic test for lymph nodes TB rather than smear microscopy/culture
Recommendations on Xpert MTB/RIF and Xpert Ultra
as initial tests in adults and children with signs and
symptoms of extrapulmonary TB

• In adults and children with signs and symptoms of extrapulmonary
TB, Xpert MTB/RIF or Xpert Ultra should be used for rifampicin-
resistance detection rather than culture and phenotypic DST.
• In HIV-positive adults and children with signs and symptoms of
disseminated TB, Xpert MTB/RIF may be used in blood, as an initial
diagnostic test for disseminated TB
Recommendations on Xpert MTB/RIF and Xpert Ultra as
initial tests in adults and children with signs and symptoms
of extrapulmonary TB

• In adults with signs and symptoms of pulmonary TB who have an Xpert
Ultra trace positive result on the initial test, repeated testing with Xpert
Ultra may not be used.
• In children with signs and symptoms of pulmonary TB in settings with
pretest probability below 5% and an Xpert MTB/RIF negative result on the
initial test, repeated testing with Xpert MTB/RIF in sputum, gastric fluid,
nasopharyngeal aspirate or stool specimens may not be used.
pretest probability 5% or more and an Xpert MTB/RIF negative result on
the initial test, repeated testing with Xpert MTB/RIF (for total of two tests)
in sputum, gastric fluid, nasopharyngeal aspirate and stool specimens may
be used.
repeated testing in adults and children with signs and
symptoms of pulmonary TB

pretest probability below 5% and an Xpert Ultra negative result on
the initial test, repeated testing with Xpert Ultra in sputum or
nasopharyngeal aspirate specimens may not be used.
pretest probability 5% or more and an Xpert Ultra negative result on
the first initial test, repeated one Xpert Ultra test (for a total of two
tests) in sputum and nasopharyngeal aspirate specimens may be
used.
repeated testing in adults and children with signs and

Recommendations on Xpert MTB/RIF and Xpert Ultra as initial tests for
pulmonary TB in adults in the general population either with signs and
symptoms of TB or chest radiograph with lung abnormalities or both
• In adults in the general population who had either signs or symptoms
of TB or chest radiograph with lung abnormalities or both, the Xpert
MTB/RIF or Xpert Ultra may replace culture as the initial test for
pulmonary TB.
• In adults in the general population who had either a positive TB
symptom screen or chest radiograph with lung abnormalities or both,
one Xpert Ultra test may be used rather than two Xpert Ultra tests as
the initial test for pulmonary TB.

• In adults and children with signs and symptoms of pulmonary TB, the
Truenat MTB or MTB Plus may be used as an initial diagnostic test for
TB rather than smear microscopy/culture.
• In adults and children with signs and symptoms of pulmonary TB and
a Truenat MTB or MTB Plus positive result, Truenat MTB-RIF Dx may
be used as an initial test for rifampicin resistance rather than culture
and phenotypic DST.
Recommendations on Truenat MTB, MTB Plus and
Truenat MTB-RIF Dx in adults and children with signs and

DST and DRT
Growth-based phenotypic drug susceptibility testing
• Culture though a highly sensitive and specific method for TB diagnosis,
requires 2-8 weeks to yield results.
• automated Liquid culture systems e.g. BACTEC MGIT 960, BacT Alert or
Versatrek etc and solid (Lowenstein Jensen) media.
Rapid molecular drug resistance testing
• LPA provides rapid diagnosis of R and H resistance as well as resistance to
FQs and SLIDs. LPA can yield results in 72 hours.
• NAAT provides accurate and rapid diagnosis of TB by detecting M.tb and R
resistance conferring mutations. The test can be performed in both
respiratory and non respiratory specimens and yields results in 2 hours.
Drug Susceptibility Testing &
Drug Resistance Testing

Choice of diagnostic technology
DR diagnostic technology Choice
NAAT/LPA First
Liquid culture isolation and LPA DST Second
Liquid culture isolation and liquid DST Third
Solid LJ media- of up to 84 days,
Liquid Culture (MGIT) up to 42 days,
LPA up to 72 hours
NAAT - 2 hours.
Testing time

Possible Resistant patterns & treatment options
Universal DST
to
individualise
DR TB
treatment

24 march short ntep who diagnosis of dr tb

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