diagnosis of pulmonary tuberculosis. 2 pulmonary tuberculosis

Diagnosis of pulmonary tuberculosis

2

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+)

© OFCP © OFCP

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

© OFCP

© OFCP

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

© OFCP

Pott’s disease

© OFCP

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

© OFCP

Pulmonary and skin tuberculosis(1)

After treatment

After treatment

* Courtesy of Dr Fabrice Simon

Courtesy of Dr Guy Aurégan