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Transcript
Diagnosis of pulmonary
tuberculosis
PULMONARY
TUBERCULOSIS
2
Inhalation of myc. tuberculosis
proliferation in alveoli
Spread via the lymphatic system
The infection is
contained. Hypersensitivity
to tuberculoprotein
positive skin test
possible reactivation in the futur:
=Post primary TB
Proliferation of the infection
hilar nodes enlargment
bronchus, alveolar, pleural
involvment
=Primary TB
Hematogenous dissemination: pulmonary miliary
and extra-pulmonary TB
The diagnosis of pulmonary TB:
The usual ways in the context of a developing
country:
* Microsopic examination of sputums for research
of acid fast bacillus. (AFB)
Reminder: Acid-fastness is a physical property of some bacteria referring to
their resistance to decolorization by acids during staining procedures
Less frequent:
* Chest radiography
* Skin test with tuberculine
* Biopsy specimen and anatomo-pathology (pleural
biopsy, endoscopic biopsy…)
The diagnosis of pulmonary TB (2)
More sophisticated ways in developed countries
 culture + Antibiogram: useful for
multi-resistant TB
 Molecular genetic methods: Polymerase
chain reaction usefull for diagnosis of TB and
resistance to rifampicin and isoniazid
5
Main bacteriological techniques (1)
Microsopic examination of
sputum for research of acid fast
bacillus by Ziehl coloration or
auramine
 this examination detects
contagious patients, who have a
pulmonary tuberculosis (TPM+).
It is a screening for patients who
cough and spit and who have a
sufficient quantity of bacilli in
sputum to be detected: > 5000/ ml
These patients are the most
contaminating patients
But TPM- are numerous
•
« pauci-bacillar » cases : < 5000 bacilli per ml in
sputum:-Nodular tuberculosis (non-excavated)
-miliary
- tubercular adenopathy
- extra-pulmonary cases (EPT)
•
Too weak patients who cannot produce sufficient
sputum for bacterial analysis or are not cooperating
(salivary sputum…)
• Treatment has begun before screening
• Technical error in the research of AFB.
In cases of TPM- the physician must decid of TB treatment
on clinical and radiological datas
 But radiological aspects of TB are numerous and not always
specific
Nodules : TPMInfiltrates: TPM-/+
Cavities: TPM+
Pneumoniae: generally TPM+
Miliary:
TPMPleural effusion: TPMAdenopathies: TPMSéquella (inactive or not :TPM- / M+)
Differential diagnosis are numerous, especially in case of
Coinfection with HIV
Infiltrat AFB+/-
Cavities
AFB +
Milliary
AFB © OFCP
TB pneumonia AFB+ +
TB adenopathies VIH-
AFB -
Péricarditis TB
AFB -
The efficiency of the microscopic
examination increases with the repetition
of the samples ( Al Zahrani and coll. Int j. tuber. Lung dis. Sept 2005)
Sample
number
Positive
sample with
Ziehl %
positive
culture
1
66
93
2
76
97
3
84
99
4
85
100
10
Main bacteriological techniques
(2)
❏ culture
• The culture by the classical method
(Lowenstein culture medium):
– A bit difficult, rather high cost, delayed
results (1 to 2 months after the initial
sample),
– Especially useful for tuberculosis with few
bacilli which cannot be diagnosed by direct
microscopic examination: TPM- and EPT
11
Main bacteriological techniques
(3)
❏ Other forms of culture
• The gelose culture medium (Middlebrook medium)
3 to 4 weeks (instead of 4 to 6 with the traditional
method).
• The liquid culture medium:
– radioactive medium (Bactec system)
– non-radioactive medium (MGIT)
Can detect bacilli in 8 to 14 days.
12
❏ Molecular genetic methods:
PCR ( Polymerase Chain Reaction)
• genomic amplification technique: specific
DNA probes can identify different
mycobacteria.
• Advantage: Results in 24 to 48 h, very
good specificity (97% to 98%).
• Result in les than 2 hours with system X pert MTB/RIF Test
• Disadvantage: low sensitivity in
comparison to the culture (+/-80%), high
cost, but progress with more recent
systems (Accuprobe ®, Genprobe®)
13
X pert MTB/RIF Test
1 Sputum liquefaction
and inactivation with
2:1 sample reagent
4
Sample
automatically
filtered and
washed
2 Transfer of
2 ml material
into test cartridge
5
Ultrasonic lysis
of filter-captured
organisms to
release DNA7
6
DNA molecules
mixed with dry
PCR reagents7
7
Seminested
real-time
Amplification
and detection
in integrated
reaction tube
8
Printable
test result
3 Cartridge inserted into
MTB-RIF test platform
(end of hands-on work)
Résults in less than 2 hours
❏ Sensitivity tests: antibiograms
• Indirect antibiogram: after obtaining colonies with
culture (results 2 to 3 months after initial
sample).
• Direct antibiogram, only possible if the initial
sample contains very many bacili.
(results in 4 - 6 weeks)
. Difficult technique, high cost, delayed results.
• Routinely, this test is not necessary for treatment
of the majority of patients.
• It is very useful if there is any suspicion of
resistance
15
Some questions
Q1. What is the role of the chest x-ray
in the national TB program (1)?
Rich and developped countries: respiratory
symptoms
 chest radiography(x-ray)
Developing countries: The chest x-ray is not
recommended in first intention
(recommandations of OMS and
UICTMR)
 If TPM+: TB treatment without chest x-ray
If TPM- x 3 and persistance of symptoms after
non-specific antibiotic, the national program
recommands chest x-ray
17
Q1. What is the role of the chest xray in the national TB program (2)
• The radiography cannot make, as microscopy, a definite
diagnosis of TB, because radiological aspects of TB are
varied and often non-specific.
• But some images are very indicative of TB. Some others
images must invoke differential diagnosis.
• The chest radiography is essential for TPM(-) TB .
It is necessary for the physicians to be able to make
a correct analysis
>>> TPM- diagnosis is often made in excess, with a
useless treatment and failure to spot or diagnose
another pathology .
Disagreement between clinician and radiologist
about the analysis of the chest radiography
Evaluation
Detection of a cavity
Pulmonary abnormality
Adenopathy
Pulmonary calcification
Deterioration between 2 chest
x-rays
Deciding whether an
abnormality is TB or not TB
Percentage of
disagreement
28%
34%
60%
42%
30%
45%
19
3 distinct situations:
• The chest x-ray strongly suggests TB.
• The chest x-ray does not remotely suggest
TB
• The chest x-ray could suggest TB, but
differential diagnoses are certainly
possible.
Whatever the situation, it is always
important to confront patient history,
clinical signs, bacteriology and
radiology
Q2. What is the role of the
tuberculin skin test ?
A tuberculin skin test is sometimes useful
for the diagnosis of TB (contact with
contagious patient)
 The interpretation of a test result is often
very difficult:
-False positive : BCG vaccination, technical error in
injection or in the induration measurement, other
mycobacterial infection
-False negative : technical error in injection or in the
induration measurement, viral infection,
immunodepression, anergic time (+/- 40 days)…
21
• Q3. Who should be
considered a “case” of TB?
• 1 smear (+) examination for TB should be
recorded as smear positive (TPM+).
• All other cases should be recorded as
smear negative (TPM-) or as extrapulmonary cases (EPTB).
22
B. Extra-pulmonary
tuberculosis (EPTB)
23
INTRODUCTION
The diagnosis of EPTB is difficult and
sometimes requires sophisticated means:
• Surgical biopsies and anapath.
examination
• Bacterial samples obtained by puncture
with culture if possible
BUT…in developing countries, these
techniques are not always available
INTRODUCTION(2)
If a bacteriological or anapath sample
doesn’t exist, the diagnosis is made
with the association of clinical,
biological, radiological arguments and
sometimes with the analysis of the
evolution under TB treatment
Aids epidemy: gradual increase of
percentage of EPTB
Main forms of EPTB
Serous
membrane TB
Pericarditis
pleuritis
Peritonitis
Adenopathies
Miliary
Genital and
urinary
Bones
Neuro
meningeal
Hepatic and
intestinal
multivisceral
Diagnosis procedure (1)
Type of
EPTB
Presumption criteria
Pleural Clinical and radiological
TB.
signs.
Differential
diagnosis
Certitude
criteria
- Neoplasic
effusion
-Non-TB
infectious
disease
Positive
culture of
liquid.
Positive
culture and
anapath. of
biopsy
specimen.
Pleural effusion:
- serofibrinous
-Protein > 30g or ratio
or fluid.prot / serum prot.> 0.5 -Others…
-lymphocytes 80 to 100%
Diagnosis procedure (2)
Type
of
EPTB
Node
TB
Presumption criteria
Clinical signs
indicative localisation
(cervical, mediastinal...)
Differential
diagnosis
Cancer,
lymphoma,
Non-TB
infectious
disease
…
Certitude
criteria
Puncture and
biopsy:
AFB+ at
microscopic
examination.
Positive
culture and
anapath
Diagnosis procedure (3)
Type of
EPTB
TB
meningitis
Presumption criteria
Clinical context
Cerero-spinal fluid:
-clear fluid
-CSF cell count:
lymphocytosis 30 to
500/mm3
-CSF protein:
>100mg /dl
-CSF glucose:
< 0.5 glycemy
Differential
diagnosis
-Fungal
(cryptococcus)
- Bacterial
(beginning of
infection or
pre-treated)
-Neoplasic
-viral
meningoencephalitis
(herpes
simplex)
Certitude
criteria
AFB+ in CSF
(infrequent)
India ink –
Culture +
(but late
result)
Diagnosis procedure (4)
Type of
EPTB
TB
peritonitis
Presumption criteria
Abdominal pain, fever,
weight loss, subocclusive syndrome
Ascitis without portal
hypertension or cirrhosis
Ultrasound: mesenteric
adenopathies
Fluid:
-lemon yellow color
-leucocyte count: 150 to
4000/mm3 (lymphocitic)
-protein>30 g/l
-serum/ascite gradiant
albumine <1.1
Differential
diagnosis
Certitude
criteria
-peritoneal
Laparoscopy
carcinomato
and biopsy
sis
specimen for
anapath
-Pancreatic
ascite
Examination
and culture:
-non-TB poly
microbial
infection
(Multiple whitish
(beginning)
nodules on
visceral and
parietal
peritoneum)
Diagnosis procedure (5)
Type of
EPTB
Presumption criteria
Spinal TB -Local pain
(=TB of the +++indolent on the
vertebra) beginning>>delay in
diagnosis>>>neurologic
Sequela
-Sometimes local abcess
(cold abcess)
-++Radiological findings
(but not specific):
osteolytic lesion with or
without disc involvment,
on 1 or many levels
(chest x-ray normal in > 50% of
cases)
Differential
diagnosis
Certitude
criteria
Biopsy:
Staphyloccocus culture and
brucellosis,
anapath
Histoplasmosis exam. of the
infected bone:
Infection.
But rarely
Bone
possible in
metastasis.
DC, except if
soft tissue
abcess
Diagnosis procedure (5)
Type of
EPTB
Presumption criteria
GenitoDysury, steril pyuri,
urinary
hematury
Tuberculosis Combination of upper
and lower tract
involvment
female: pelvic chronic
pain, sterility, salpingitis
ectopic pregnancy
Male: epydidymitis and
orchi-epidydimitis
Differential
diagnosis
Certitude
criteria
Non-TB genital
and urinary
infection
AFB+ or
culture+ in
urine, menses
Endometrial
biopsy
Laparoscopic
biopsy
examples of EPTB…
Multi-visceral TB in case of miliary
© OFCP
© OFCP
Cervical
Affected Vertebrae in Spinal Tuberculosis
Cervical
Thoracic
Thoracic
Lumbar
Lumbar
Sacral
Sacral
Chen WJ, Chen
et al.WJ,Acta
Orthop
1995;66:137-42
et al. Acta
OrthopScand
Scand 1995;66:137-42
© OFCP
Pott’s disease
© OFCP
© OFCP
© OFCP
Rib costale
lysis
Lyse
Psoas
Abcès
TB abcess
du psoas G
Pott’s disease
TB arthritis with important destruction
of the joint
UIV
© OFCP
Adénites TB
cervicales et
axillaires G
chez un patient
cambodgien SIDA
Pulmonary and skin tuberculosis(1)
After treatment
After treatment
* Courtesy of Dr Fabrice Simon
Courtesy of Dr Guy Aurégan