Diagnosis of pulmonary tuberculosis Slide 2 2 PULMONARY
TUBERCULOSIS Slide 3 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 Slide 4 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) Slide 5 5 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 Slide 6
Main bacteriological techniques (1) Microsopic examination of
sputum for research of acid fast bacillus by Ziehl coloration or
auramine TPM+ 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 Slide 7 But TPM- are numerous
pauci-bacillar cases : < 5000 bacilli per ml in sputum:-Nodular
tuberculosis (non-excavated) pauci-bacillar cases : < 5000
bacilli per ml in sputum:-Nodular tuberculosis (non-excavated)
-miliary -miliary - tubercular adenopathy - tubercular adenopathy -
extra-pulmonary cases (EPT) - extra-pulmonary cases (EPT) Too weak
patients who cannot produce sufficient sputum for bacterial
analysis or are not cooperating (salivary sputum) Too weak patients
who cannot produce sufficient sputum for bacterial analysis or are
not cooperating (salivary sputum) Treatment has begun before
screeningTreatment has begun before screening Technical error in
the research of AFB.Technical error in the research of AFB. Slide 8
But radiological aspects of TB are numerous and not always specific
In cases of TPM- the physician must decid of TB treatment on
clinical and radiological datas Differential diagnosis are
numerous, especially in case of Coinfection with HIV Nodules : TPM-
Infiltrates: TPM-/+ Cavities: TPM+ Pneumoniae: generally TPM+
Miliary: TPM- Pleural effusion: TPM- Adenopathies: TPM- Squella
(inactive or not :TPM- / M+) Slide 9 Infiltrat Cavities Milliary TB
pneumoniaTB adenopathies VIH-Pricarditis TB AFB+ + AFB + AFB+/- AFB
- Slide 10 10 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 16693 27697 38499 485100 Slide 11 11
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
Slide 12 12 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. Slide 13 13 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) Slide 14 4 Sample automatically
filtered and washed 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 1 Sputum liquefaction and inactivation with 2:1
sample reagent 2 Transfer of 2 ml material into test cartridge 3
Cartridge inserted into MTB-RIF test platform (end of hands-on
work) 8 Printable test result Rsults in less than 2 hours X pert
MTB/RIF Test Slide 15 15 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
Slide 16 Some questions Slide 17 17 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) The chest
x-ray is not recommended Developing countries: The chest x-ray is
not recommended in first intention (recommandations of OMS and
UICTMR) TB treatment without chest x-ray 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 Slide 18 The radiography cannot make, as microscopy, a
definite diagnosis of TB, because radiological aspects of TB are
varied and often non-specific.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. 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 analysisThe 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. >>> TPM-
diagnosis is often made in excess, with a useless treatment and
failure to spot or diagnose another pathology. Q1. What is the role
of the chest x- ray in the national TB program (2) Slide 19 19
Disagreement between clinician and radiologist about the analysis
of the chest radiography Evaluation Percentage of disagreement
Detection of a cavity 28% Pulmonary abnormality 34% Adenopathy60%
Pulmonary calcification 42% Deterioration between 2 chest x-rays
30% Deciding whether an abnormality is TB or not TB 45% Slide 20 3
distinct situations: The chest x-ray strongly suggests TB.The chest
x-ray strongly suggests TB. The chest x-ray does not remotely
suggest TBThe chest x-ray does not remotely suggest TB The chest
x-ray could suggest TB, but differential diagnoses are certainly
possible.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 Whatever the situation, it is always
important to confront patient history, clinical signs, bacteriology
and radiology Slide 21 21 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) Slide 22 22 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 extra- pulmonary cases (EPTB). Slide 23 23 B. Extra-pulmonary
tuberculosis (EPTB) Slide 24 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 BUTin developing countries, these
techniques are not always available Slide 25 INTRODUCTION(2) Aids
epidemy: gradual increase of percentage of EPTB If a
bacteriological or anapath sample doesnt exist, the diagnosis is
made with the association of clinical, biological, radiological
arguments and sometimes with the analysis of the evolution under TB
treatment Slide 26 Main forms of EPTB Serous membrane TB
Pericarditis pleuritis Peritonitis Adenopathies Miliary Genital and
urinary Bones Neuro meningeal Hepatic and intestinal multivisceral
Slide 27 Diagnosis procedure (1) Type of EPTB Presumption
criteriaDifferential diagnosis Certitude criteria Pleural TB.
Clinical and radiological signs. Pleural effusion: - serofibrinous
-Protein > 30g or ratio or fluid.prot / serum prot.> 0.5
-lymphocytes 80 to 100% - Neoplasic effusion -Non-TB infectious
disease -Others Positive culture of liquid. Positive culture and
anapath. of biopsy specimen. Slide 28 Diagnosis procedure (2) Type
of EPTB Presumption criteriaDifferential diagnosis Certitude
criteria Node TB Clinical signs indicative localisation (cervical,
mediastinal...) Cancer, lymphoma, Non-TB infectious disease
Puncture and biopsy: AFB+ at microscopic examination. Positive
culture and anapath Slide 29 Diagnosis procedure (3) Type of EPTB
Presumption criteriaDifferential diagnosis Certitude criteria TB
meningitis Clinical context Cerero-spinal fluid: -clear fluid -CSF
cell count: lymphocytosis 30 to 500/mm3 -CSF protein: >100mg /dl
-CSF glucose: < 0.5 glycemy -Fungal (cryptococcus) - Bacterial
(beginning of infection or pre-treated) -Neoplasic -viral meningo-
encephalitis (herpes simplex) AFB+ in CSF (infrequent) India ink
Culture + (but late result) Slide 30 Diagnosis procedure (4) Type
of EPTB Presumption criteriaDifferential diagnosis Certitude
criteria TB peritonitis Abdominal pain, fever, weight loss, sub-
occlusive 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 Diagnosis procedure (5) Type of
EPTB Presumption criteriaDifferential diagnosis Certitude criteria
Spinal TB (=TB of the vertebra) -Local pain +++indolent on the
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)
Staphyloccocus brucellosis, Histoplasmosis Infection. Bone
metastasis. Biopsy: culture and anapath exam. of the infected bone:
But rarely possible in DC, except if soft tissue abcess Slide 32
Diagnosis procedure (5) Type of EPTB Presumption
criteriaDifferential diagnosis Certitude criteria Genito- urinary
Tuberculosis Dysury, steril pyuri, hematury Combination of upper
and lower tract involvment female: pelvic chronic pain, sterility,
salpingitis ectopic pregnancy Male: epydidymitis and
orchi-epidydimitis Non-TB genital and urinary infection AFB+ or
culture+ in urine, menses Endometrial biopsy Laparoscopic biopsy
Slide 33 examples of EPTB examples of EPTB Slide 34 Slide 35
Multi-visceral TB in case of miliary Slide 36 Slide 37 Potts
disease Psoas abcess Rib lysis Slide 38 Potts disease Slide 39
Slide 40 Slide 41 Slide 42 Slide 43 TB arthritis with important
destruction of the joint Slide 44 Slide 45 Slide 46 Slide 47 Slide
48 Slide 49 UIV Slide 50 Slide 51 Slide 52 Slide 53 Adnites TB
cervicales et axillaires G chez un patient cambodgien SIDA Slide 54
Pulmonary and skin tuberculosis(1) Slide 55 Slide 56 Slide 57 After
treatment Slide 58 Slide 59 * Courtesy of Dr Fabrice Simon Courtesy
of Dr Guy Aurgan Slide 60 Slide 61 Slide 62
