diagnosis of pulmonary tuberculosis. 2 pulmonary tuberculosis
TRANSCRIPT
Diagnosis of pulmonary tuberculosis
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PULMONARY TUBERCULOSIS
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 infectionhilar nodes enlargment
bronchus, alveolar, pleural involvment
=Primary TB
Hematogenous dissemination: pulmonary miliaryand 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…)
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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
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.
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-Séquella (inactive or not :TPM- / M+)
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Infiltrat Cavities Milliary
TB pneumonia TB adenopathies VIH- Péricarditis TBAFB+ +
AFB +AFB+/-
AFB - AFB -
AFB -
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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 withZiehl %
positive culture
1 66 93
2 76 97
3 84 99
4 85 100
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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
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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.
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❏ 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®)
4 Sample automaticallyfiltered and washed
5 Ultrasonic lysisof filter-capturedorganisms torelease DNA7
6 DNA moleculesmixed with dryPCR reagents7
7 Seminested real-timeAmplificationand detectionin integrated reaction tube
1 Sputum liquefactionand inactivation with2:1 sample reagent
2 Transfer of2 ml materialinto test cartridge
3 Cartridge inserted intoMTB-RIF test platform(end of hands-on work)
8 Printabletest result
Résults in less than 2 hours
X pert MTB/RIF Test
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❏ 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
Some questions
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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
• 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 .
Q1. What is the role of the chest x-ray in the national TB program
(2)
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Disagreement between clinician and radiologist about the analysis of the chest radiography
Evaluation Percentage of disagreement
Detection of a cavity 28%Pulmonary abnormality 34%Adenopathy 60%Pulmonary calcification 42%Deterioration between 2 chest x-rays
30%
Deciding whether an abnormality is TB or not TB
45%
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
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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)…
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• 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).
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B. Extra-pulmonary tuberculosis (EPTB)
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)
Aids epidemy: gradual increase of percentage of EPTB
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
Main forms of EPTBSerous
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 Differential diagnosis
Certitude criteria
Pleural TB.
Clinical and radiological signs.
Pleural effusion:- serofibrinous-Protein > 30g or ratioor 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.
Diagnosis procedure (2)
Type of
EPTB
Presumption criteria Differential 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
Diagnosis procedure (3)Type of EPTB
Presumption criteria Differential diagnosis
Certitude criteria
TB meningitis
Clinical contextCerero-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)
Diagnosis procedure (4)Type of EPTB
Presumption criteria Differential diagnosis
Certitude criteria
TB peritonitis
Abdominal pain, fever, weight loss, sub-occlusive syndromeAscitis without portal hypertension or cirrhosisUltrasound: mesenteric adenopathiesFluid: -lemon yellow color -leucocyte count: 150 to 4000/mm3 (lymphocitic) -protein>30 g/l-serum/ascite gradiant albumine <1.1
-peritoneal carcinomatosis-Pancreatic ascite-non-TB poly microbial infection(beginning)
Laparoscopy and biopsy
specimen for anapath
Examination and culture:
(Multiple whitish nodules on visceral and
parietal peritoneum)
Diagnosis procedure (5)Type of EPTB
Presumption criteria Differential diagnosis
Certitude criteria
Spinal TB(=TB of the vertebra)
-Local pain +++indolent on the beginning>>delay in diagnosis>>>neurologicSequela-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,HistoplasmosisInfection.Bone metastasis.
Biopsy: culture and anapath exam. of the infected bone:But rarely possible in DC, except if soft tissue abcess
Diagnosis procedure (5)Type of EPTB
Presumption criteria Differential diagnosis
Certitude criteria
Genito-urinary
Tuberculosis
Dysury, steril pyuri, hematuryCombination 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, mensesEndometrial biopsyLaparoscopic biopsy
examples of EPTB…
Multi-visceral TB in case of miliary
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Affected Vertebrae in Spinal Tuberculosis
Cervical
Thoracic
Lumbar
Sacral
Chen WJ, et al. Acta Orthop Scand 1995;66:137-42
Affected Vertebrae in Spinal Tuberculosis
Cervical
Thoracic
Lumbar
Sacral
Chen WJ, et al. Acta Orthop Scand 1995;66:137-42
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Pott’s disease
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Lyse costaleLyse costale© OFCP
Abcès TB du psoas GAbcès TB du psoas G© OFCP Psoas abcess
Rib lysis
Pott’s disease
TB arthritis with important destruction of the joint
UIV
Adénites TBcervicales et axillaires Gchez un patient cambodgien SIDA
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Pulmonary and skin tuberculosis(1)
After treatment
After treatment
* Courtesy of Dr Fabrice Simon
Courtesy of Dr Guy Aurégan