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