Post on 23-Aug-2020
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Clinical and radiographic manifestations of drug resistant Tuberculosis
Dr Sarabjit Chadha
The Union
Pathogenesis of TB
• Once inhaled, bacteria travel to lung alveoli –Eliminated by the macrophages
–Establish infection
• 2–12 wks after infection – immune response limits activity; granuloma
– infection is detectable
• Some bacteria survive and remain dormant –but viable for years (latent TB infection, or LTBI)
Latent TB infection
• People with LTBI are
–Asymptomatic
–not infectious
• LTBI is diagnosed with
–Mantoux (TST or PPD)
–IGRAs
TB pathogenesis
• Bacilli exposure
• Inhalation of bacilli
– Entry into the alveoli
– Contact alveolar macrophages
• Local inflammatory response
– Activation of CD4, CD8 and other immune cells
– Granuloma
• Primary TB: local dissemination
– Regional adenopathy: lymphangitis
– Ghon’s Nodule
TB infection to TB disease
• 5% -10% of people with untreated latent infection during lifetime – Mostly within the first two years after infection
• Certain conditions increase the risk : – HIV infection: 10% each year
– Diabetes Mellitus
– Children under 4 years of age and elderly
– Immunocompromised states
Primary TB disease
• Usually in adults this condition is resolved by the immune system
– Scar on the chest X ray
• In children or immune compromised evolving to active primary disease
Ghon’s Nodule
lymphangitis
Ability of the immune system to keep the bacilli imprisoned (inside of the granuloma)
• Depends on the immune system
• Genetic factors
• Age:
– not too old and mature enough immune system
• Nutrition:
– lack of vitamins, protein deficiency
• Tobacco smoking and others
• DM
• HIV infection
Liquefaction of
granuloma and
creation of the
cave
AFB +++
Post primary Tuberculosis
• Reactivation
– Bacilli escape from the granuloma
– Granuloma becomes a cavity
• Bronchial dissemination
– Classical TB presentation: multiple cavities and bronchogenic seeding
• Hematogenous dissemination (atypical TB)
– Miliary TB, pleural effusion
– Extrapulmonary TB: hepatitis, meningeal,
– Disseminated TB
Diagnosis of patients presenting with cough and other chest symptoms
• Chief complaints and symptoms
• History
– Co-morbidity (HIV, Diabetes Mellitus, Cancer, etc.)
– Tuberculosis treatment
– Contact of TB and/or MDR-TB
– Social-economic, traveling, immigration
• Signs
• Chest radiograph manifestations
Frequency of symptoms in consecutive patients presenting to chest clinics in Sudan
El-Sony A.I., et al Int J Tuberc Lung Dis 2003;7:550-555
Frequency of symptoms in consecutive patients presenting to chest clinics in Sudan
El-Sony A.I., et al Int J Tuberc Lung Dis 2003;7:550-555
Clinical characteristics of patients with multidrug-resistant tuberculosis in Russia
Balabanova Y, Eur J Clin Microbiol Infect Dis 2005; 24:136-139
Symptoms of TB
• General symptoms
– Unintentional weight loss
– Fatigue
– Fever
– Night sweats
– Loss of appetite
• Specific symptoms
– Pulmonary TB • Cough (usually with
expectoration)
• Haemoptysis
• Chest pain
Symptoms of TB
• Extra-pulmonary TB
– Lymhnodes
– Pleural
– Peritoneal
– Musculoskeletal
– CNS
– Genital
– Abdominal
Are symptoms and signs different in DR-TB?
Symptom/sign Drug sensitive TB Drug resistant TB
Cough 82% 79%
Fatigue 81% 80%
Weight loss 72% 56%
Fever 42% 39%
Chest pain 17.4% 10%
Night sweats 17% 8.8%
Hemoptysis 10% 18%
Clinical features in HIV-TB
• Depend on the severity of immunodepression
• Less severe immunodeficiency (CD4 count is high)
– Typical symptoms
• Severe immunodeficiency (CD4 count is low)
– Non-specific or atypical
– Extra-pulmonary TB is more common
– TST negative
• Screening rule
• Cough (any duration)
• Fever
• Night sweats
• Weight loss
• Sensitivity 79% (58-90%); Specificity 50% (29-70%)
• Add CXR - Sensitivity – 90.6%; Specificity- 38.9%
• NPV – 98%;
• Absence of these symptoms – NO TB
• Cough (81%), Fever (50%), dyspnea (30%), night sweats and chest pain were the most common symptoms and proportionate to severity on CXR and sputum
• With therapy fever, sweats and dyspnoea resolved faster than cough and chest pain
• Cases who relapsed were more likely to have cough (75% vs 12%), fever (31% vs 5%), and chest pain (25% vs 7.6%)
• Cough was the most common symptom after therapy (sequelae)
• Symptom resolution did not differ between relapse and non relapse
• Microbiological success and failure mirrored the resolution and recurrence of symptoms
Clinical signs of TB
• May be normal in mild–moderate disease
• Chest: rales, rhonchi; absent breath sounds and dullness
to percussion if pleural fluid is present
• Extrapulmonary (site specific): adenopathy, skin lesions,
bone tenderness, neck stiffness, etc.
The physical examination is nonspecific, but it is helpful
to identify extrapulmonary sites of involvement
There is no difference in signs and symptoms in
DR-TB compared to DS-TB
Radiological manifestations of TB
Extensive
Bilateral
Lesions
Pulmonary
MDR-TB
Radiological manifestations of TB
Cavitary
MDR-TB
R.L.L.
Miliary TB
Miliary TB
Radiological features in TB
• Radiology is a sensitive but non-specific test
• No lesions are specific for TB
• Inter and intra-observer variation
Tokyo study
• Study conducted by Research Institute of TB, Tokyo
• Radiographs of 50 persons taken with known health status read by 192 physicians
• Based on the reading recommend further tests
The Union study on CXR classification
• Sample of 1100 CXR films were selected from mass radiographic survey in Norway
– Included patients with TB, non-TB lung disease and no abnormality
• 90 physicians (radiologists and chest physicians) across 9 countries and 10 WHO staff read the CXRs
• Smear positive TB patients
– 5% reported to have normal CXR
– 17% as having some abnormality- non TB
– 24% not requiring any clinical action
Under-reading and over-reading of radiographs
Toman K, 1979
Can radiology help you diagnose DR-TB?
See the X-rays and decide which is XDR, MDR and DS TB?
XDR TB MDR TB DS TB
Radiological features in DR-TB
Radiological features in TB HIV
• Non severe immune depression
– Similar signs to HIV neg
• Severe immune depression
– Typical lesions of primary TB
– Frequent lymphatic signs
– Haematogenic dissemination
– Normal chest x ray
– Extrapulmonary lesions
CXR Pattern: Early vs. Advanced HIV
Early HIV
(CD4 >200)
Advanced HIV
(CD4 <200)
Pattern “Typical”
(Reactivation)
“Atypical”
(Primary)
Infiltrate Upper lobes
Lower lobes,
multiple sites, or
miliary
Cavitation Common Uncommon
Adenopathy Uncommon Common
Effusion Uncommon More common
ISTC Training Modules 2008
Variations in X-rays appearence and smear correlate which CD4 decline in a
significant continuous trend.
23% sm- in CD4 <50 vs 1% in CD4>500
21% X-rays normal in CD4<50 vs 2% in CD4>500
Higher levels of CD4 are associated with higher likelihood of
cavities in the X-rays
CT Scan , MRI
Other Imaging Techniques
in Diagnosis of MDR TB
Active Pulmonary TB (macronodules)
Active Pulmonary TB (bronchogenous dissemination in form of central lobule nodules)
Active Pulmonary TB(“tree in bud” and cavitation)
DS TB MDR TB XDR TB
CXR
Nodules 89% 83% 100%
Large nodules 69% 34% 36%
GGO 64% 19% 33%
Cavities 6% 17% 20%
CT Scan
Nodules 93% 98% 87%
Large nodules 50% 71% 86%
GGO 25% 17% 7%
Cavities 36% 69% 43%
• Cavities more common in MDR-TB than DS-TB
• No difference in nodules, consolidation,
bronchiectasis, calcification, effusion,
lymphadenopathy
Add hardly anything to X-ray
In General, NOT Advisable
CT Scan , MRI
Other Imaging Techniques
in Diagnosis of MDR TB
• No improvement clinically or radiologically
during the treatment are not specific for
diagnosis of MDR/XDR-TB
• Other Diseases frequently associated with TB
(Bronchiectasis, Respiratory Infections, etc)
could justify this lack of Improvement
• This lack of improvement needs further
evaluation
• Never diagnose MDR TB based on clinical or
radiological criteria
Clinical and X-ray limitations in diagnosis of
MDR
Thank You