Hannah Leaver hyl1g10@soton.ac.uk Tuberculosis Hannah Leaver hyl1g10@soton.ac.uk

Definition “a multisystem disease with countless presentations and manifestations. It is the most common cause of infectious disease- related mortality worldwide”

Aetiology Modifiable RFs: Alcoholism Silicosis Malnutrition and low body weight Smoking IV drug abuse Immunosuppressed – HIV, Head and Neck Cancer, Diabetes Mellitus Immunosuppressive therapy – TNFα antagonists, steroids Non-Modifiable RFs: Age < 5 years Elderly Geographical - ↑ in tropical regions Family history

Pathophysiology Healing scar Primary infection Primary complex Ghon focus Regional lymphadenopathy Primary complex Activation of cell-mediated immunity Healing scar Persistence of viable bacteria (latent) Progressive disease Miliary TB Post primary TB Death New infection

Resolution Infection 1° TB Latent (90%) 2° infection

Primary Infection Childhood exposure in endemic areas Elderly in western regions Immune response limits damage to a localised mid-zone area of the lung (Ghon focus) Hilar involvement Develops within 4 weeks Calcification on chest XR.

Post Primary Pulmonary TB Often due to reactivation/ reinfection Signs and Symptoms: Persistent cough Haemoptysis – occurs only in 1/3 Pleurisy Tiredness, chronic ill health Weight loss Fever Night sweats Investigations: Sputum Ziehl-Neelsen stain of AFB Sputum culture (Takes up to 8 weeks) XR   Complications Severe haemoptysis Exudative Pleural effusion Cavitation TB empyema

Pleural Effusions Transudate Exudate Cause ↑ hydrostatic pressure, ↓ colloid osmotic pressure e.g. HF Inflammation e.g. Pneumonia, Lung cancer, TB Appearance Clear Cloudy Protein (g/L) <30 >30 Fluid protein: Serum protein ratio <0.5 >0.5 LDH (IU/L) <200 >200 Fluid LDH : Serum LDH ratio <0.6 >0.6 Other Often bilateral (larger on R side) Unilateral

Chest X-rays Consolidation in the left upper lobe. Two densely calcified granulomas are also present on the left, one near the hilum and the second in the left lower lobe. No convincing lymph node enlargement. 

Multifocal patchy opacities in the right upper lobe with thickening Upward shift of the minor fissure

Patchy opacities in the posterior segment of the upper right lobe, consistent with post- primary tuberculosis

Diffuse bilateral, largely upper lobe, consolidation and pulmonary infiltrates.   Suggestion of small area of cavitation at the left lung apex.

Extrapulmonary TB Pleural TB Cough, pleuritic pain, unilateral effusions   Lymph node TB Cervical lymph nodes Unilateral, painless, increased size and matted TB Meningitis Headache, fever, mental state changes (coma), neck stiffness, CN palsies Bone/Joint TB Potts disease of spine – back pain or stiffness Monoarticular arthritis – hips and knees GU TB Flank pain, dysuria, ↑f Men – painful scrotum, prostatitis, epididymitis Women – mimics PID   GI TB Ulcers of mouth and anus Dysphagia Abdominal pain Malabsorption Change in bowel habits

Appearance Cells (/μL) Protein (g/L) Glucose (mmol/L) NORMAL Gin clear 0.4 Lymphocytes 0.15-0.4 2.7 – 4.4 BACTERIAL MENINGTIS Cloudy/ purulent 1000 – 5000 Polymorphs 0.8 – 4.0 0 - 2.2 TB MENINGITIS Clear/ slightly turbid. “Spider web” 50 – 5000 Polymorphs/ lymphocytes mixed 0.6 – 6.0 0 – 2.2 VIRAL MENINGITIS Clear/ slight haze 10 – 2000 Normal * Polymorph = polymorphonuclear leukocyte or granulocyte

Miliary TB SYSTEMIC DISSEMINATION 2 clinical syndromes occur, with malaise, weight loss and weakness Young/HIV infected – rapid onset, high fever, very unwell Elderly – insidious onset, chronic course and slow decline in health without fever Diagnosis – Miliary pattern on CXR ( multiple, small nodules) and organisms may be found in sputum, bone marrow, liver and GU tract

Investigations Pulmonary TB Extrapulmonary Mantoux test Ziehl-Neelsen stain Sputum culture Extrapulmonary Histology – granulomata/ AFB XR (Potts) CSF TB meningitis – lymphocytes, ↑protein, ↓glucose Mantoux test Measures delayed hypersensitivity reaction to intradermal purified protein derivative +ve = previous exposure or previous BCG vaccine

Management Conservative Isolate Contact trace Inform local authority – TB is a notifiable disease Medical  Short form chemo Rifampin Isoniazid Pyrazinamide Ethambutol All taken for 2 months. -Rifampin/Isoniazid taken for a further 4months. -If meninges involved, Rifampin/Isoniazid for 10 months + corticosteroid S/Es - hepatotoxicity

Differentials EXTENSIVE!! - Such a non specific disease

Prognosis Poor prognostic markers include Immunocompromised older age history of previous treatment