A disease caused by Mycobacterium tubeculosis (and occasionally M. bovis and M. africanum). M. tuberculosis is an obligate aerobe bacilli. Transmission via respiratory droplets.
Describe the epidemiology of tuberculosis
Estimated 1/3 of world is infected with tuberculosis Commoner in developing countries: childhood onset MDR-TB is widespread in parts of Asia, Eastern Europe, and Africa. HIV co-infection is a growing problem due to the risk of MDR- and XDR-TB, and high mortality. 1/4 of TB cases are co-infected with HIV.
Name 5 risk factors for tuberculosis
Contact with high-risk groups: -Originated from high-incidence country (>40/100,000) -Frequent travel to high-incidence areas Immune deficiency: -Corticosteroids or immunosuppressant therapy: TB screened prior to starting biological agents due to potential reactivation -Chemotherapy drugs Co-morbidities: -HIV*: 1/4 of TB cases are co-infected -Nutritional deficiency -DM, CKD, malnutrition Lifestyle: -Drugs/alcohol misuse -Homelessness/hostels/overcrowding Genetic susceptibility
Define Ghon focus, and describe its formation
Ghon focus: The initial focus of tuberculosis disease Initial infection: MTb is inhaled into the lung and engulfed by alveolar macrophages. It is protected from phagocytosis and proliferates and releases cytokines. This results in a inflammtory infiltrate of the lungs and hilar lymph nodes. Macrophages present the antigen to T lymphocytes, causing a delayed hypersensitivity reaction and formation of a caseating granuloma. As the caseating granuloma heals and calcifies, it may contain bacteria, and become the initial focus of disease, termed the 'Ghon focus'.
Define primary TB
Active disease (symptomatic with abnormal CXR) upon initial infection with MTb, featuring a subpleural focus of inflammation, and granulomatous infection of hilar lymph nodes. Occurs in 5% upon initial infection of MTb. 95% develop latent TB.
Define latent TB
Initial infection with MTb results in containment and cell-mediated immune memory. Latent TB is asymptomatic and produces a normal CXR.
Describe the pathogenesis of TB cases
5% develop active primary TB upon initial infection Majority of TB cases: reactivation of latent TB (95% of initial infection)
Name 3 factors implicated in the reactivation of latent TB
HIV co-infection* Ageing Immunsuppressant therapy: -Corticosteroids, chemotherapy, Anti-TNF Co-morbidities: -DM, CKD, Malnutrition
Differentiate features of latent and active TB
Latent: asymptomatic + normal CXR -Bacilli present in Ghon focus -Sputum and culture -ve -Tuberculin skin test usually +ve -CXR normal: may have small calcified Ghon focus -Asymptomatic -Not infectious to others Active: symptomatic + abnormal CXR -Bacilli in tissues or secretions -Sputum and culture commonly +ve in pulmonary TB, MTb can be cultured from infected tissue -Tuberculin skin test usually +ve -CXR: consolidation, cavitation, pleural effusion -Symptoms: night sweats, fever, weight loss, cough -Infectious if sputum +ve
How can tuberculosis manifest?
Pulmonary TB Lymph node TB Extrapulmonary (rare): regions of high endemicity -GI TB: most commonly in ileocaecal area -TB arthritis (1%) -TB osteomyelitis and Potts disease -Miliary TB -CNS TB -Gentiourinary TB -Pericardial TB: acute constrictive pericarditis -Skin TB: lupus vulgaris
Describe the symptoms of pulmonary TB
Productive cough +/- haemoptysis Weight loss Fever Nocturnal drenching sweats Laryngeal involvement: hoarse voice, severe cough Pleural involvement: pleuritic pain
What CXR findings may be present in pulmonary TB
Patchy consolidation: usually in upper zones Cavitation +/- fibrosis and/or calcification (late) Lymphadenopathy: wide mediastinum, enlarged hilar Pleural effusion
How does lymph node TB present?
Extrathoracic nodes more common than intrathoracic or mediastinal nodes. Commonly, firm, non-tender enlargement of a cervical or supraclavicular node. Cold abscesses and sinuses can form May become necrotic/liquefy: overlying skin indurates
Describe the presentation of Gastrointestinal TB
Most commonly in ileocaecal area Abdominal pain, anaemia Fever, weight loss, night sweats Obstruction, RIF pain, palpable mass 1/3 present acutely with obstruction or generalised peritonitis.
Describe the presentation of TB of bone and spine
Tuberculosis arthritis (1%): affects spine (50%), hip or knee (30%). Fever, night sweats, weight loss. Pott's disease (TB spondylitis): Back pain, lower limb weakness, kyphosis. Fever, night sweats, weight loss.
Define and describe miliary TB
Widespread haematogenous spread of TB. Systemic upset, majority include pulmonary symptoms. Multiple nodules throughout CXR
Describe the presentation of TB meningitidis
Slow onset Vague headache Lethargy Anorexia Vomiting Focal signs: e.g. diplopia Seizures
Describe the presentation of pericardial TB
Acute constrictive pericarditis Pericardial pain: Like pleurisy: Sharp, worse on inspiration Like angina: Central chest pain, radiating to shoulder Specific: Relieved by sitting forward Fever Dyspnoea: if pericardial effusion or cardiac tamponade
Describe the presentation of genitourinary TB
Flank pain Dysuria Frequency
How is latent tuberculosis diagnosed?
Mantoux testing for latent TB: offered to all recent arrivals from high-incidence countries Quantiferon gold
How is active tuberculosis diagnosed?
FBC, U&Es, LFTs* HIV test Vitamin D test Acid-fast staining within 24hr: Auramine-rhodamine or Ziehl-Neelsen stain. TB culture*: can take 6-8 weeks due to slow growth -Pulmonary TB: 3 respiratory samples CXR CT: pulmonary TB suspected but atypical presentation Rapid Nucleic acid amplification (NAA): if HIV co-infection, rapid information, large contact-tracing
What is the medical management of active tuberculosis (without CNS involvement)?
Active TB (without CNS): 2 months: Rifampicin, isoniazid (+ Vit B6), pyrazinamide, and ethambutol, then Further 4 months: Rifampicin, and isoniazid (+ Vit B6) Dose is weight-dependent
Outline the medical management of active tuberculosis with CNS involvement
CNS involvement: Further 10 month rather than 4 months of rifampicin and isoniazid (+ Vit B6), and Prednisolone or dexamethasone Dose of RIPE is weight-dependent
Whilst awaiting tuberculosis cultures, when should treatment be started?
No need to start anti-tubercular treatment unless very unwell, in which case start prior to culture results.
Outline the management principles of tuberculosis
Infection control*: -Low-risk: Isolation in single room -High-risk: Negative pressure room, rapid NAA testing -Visitors wear masks when entering room -Patient must wear mask when leaving room Notify TB nurse specialists: -Support patient -Contact tracing If pneumonia cannot be excluded, begin pneumonia treatment as per CURB-65 score. Directly observed therapy for: -Non-adherence -High-risk individuals -MDR-TB
Define multidrug-resistant TB
Tuberculosis resistant to both rifampicin and isoniazid
Define extensively drug-resistant TB
Tuberculosis resistant to both rifampicin and isoniazid (MDR-TB), with additional resistance to quinolones and injectable-second line agents.
Name 3 side-effects of rifampicin
Hepatitis: monitor baseline LFTs* Rash Febrile reaction Orange secretions CYP450 inducer
Name 3 side-effects of isoniazid
Hepatitis: monitor baseline LFTs* Rash Peripheral neuropathy: prophylactic Vit B6 Drug-induced lupus: lacks renal or CNS involvement Psychosis
Name 3 side-effects of pyrazinamide
Hepatitis: monitor baseline LFTs* Rash Vomiting Arthralgia