Microbiology
Pathogens
An immunocompromised patient originally from Nigeria, complaining of a persistent cough and haemoptysis, is sent to ED by his GP with suspected tuberculosis. Which of the following is most important in acquired immunity to Mycobacterium tuberculosis:
Answer:
Primary tuberculosis infection begins with inhalation of tubercle bacilli. Alveolar macrophages initially ingest the bacilli and often destroy them. Mycobacteria which escape the initial intracellular destruction will multiply, and this will lead to disruption of the macrophage. When this happens, blood monocytes and other inflammatory cells are attracted to the lung. These monocytes will differentiate into macrophages which again readily ingest but do not destroy the mycobacteria. Two to three weeks after infection, T-cell immunity develops, with antigen-specific T lymphocytes that arrive, proliferate within the early lesions or tubercles, and then activate macrophages to kill the intracellular mycobacteria. Central solid necrosis in these primary lesions inhibits extracellular growth of mycobacteria. As a result, infection may become stationary or dormant.Mycobacterium Tuberculosis
Microbiology / Pathogens / Tuberculosis
Last Updated: 21st April 2019
Tuberculosis (TB) is caused by Mycobacterium tuberculosis, spread via the airborne route and characterised by chronic granulomatous inflammation. The lung is the usual primary site of infection, and most infections resolve with local scarring.
| Microorganism | Mycobacterium Tuberculosis |
|---|---|
| Gram stain | Weakly Gram positive, or does not stain (strictly classified as neither) |
| Shape | Rod |
| Oxygen requirements | Aerobic |
| Additional features | Acid fast organism (Ziehl-Neelsen stain) |
| Transmission | Airborne route |
| Disease | Tuberculosis |
Risk Factors
Risk factors for developing active TB include:
- Children < 5 years old
- HIV/AIDs
- Malignancy
- Renal failure
- Diabetes mellitus
- Immunosuppressants
- Social risk factors e.g. homelessness, institutions, overcrowding, prisons
- Alcohol or drug misuse
Pathogenesis
Mycobacterium tuberculosis bacilli are ingested by alveolar macrophages but have the ability to escape the phagolysosome to survive and multiply in the cytoplasm of the macrophage. Some bacilli are carried in phagocytic cells to the hilar lymph nodes where additional foci of infection develop. The initial focus of infection in the lungs together with the enlarged hilar lymph nodes forms the primary complex. The intense immune response this generates causes local tissue destruction and granuloma formation resulting in lung cavitation and cytokine-mediated systemic effects e.g. fever, weight loss.
In about 5 - 10% of patients, the infection is not controlled (progressive primary TB) and it may give rise to progressive local lesions with symptoms specific to the site involved, such as the central nervous system, peripheral lymph nodes, bones and joints, pericardium and genitourinary system, or it may disseminate throughout the body via haematogenous spread (miliary TB).
Latent TB occurs when the Mycobacterium bacteria remain dormant, and is asymptomatic and noninfectious. Latent TB infection may be detected by using the tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). It is estimated that about one third of the world's population has latent TB infection.
There is a 10% lifetime risk of reactivation of latent TB, particularly if immunity is impaired, resulting in post-primary TB. Reactivation usually occurs in the apex of the lungs and can spread locally or to distant sites.
Immunity against TB is dependent on effective T-cell function, so if compromised such as in HIV infection, individuals are more likely to develop symptomatic infection, reactivation of latent disease, and extrapulmonary TB.
Clinical Disease
Clinical features of active TB (progressive primary or post-primary) include:
- Pulmonary features
- Persistent cough
- Breathlessness
- Haemoptysis
- Pleuritic chest pain
- Systemic features
- Fever
- Weight loss
- Night sweats
- Anorexia
- Malaise
- Clubbing
- Lymphadenopathy (typically painless rubbery lymph node swelling, often affecting the cervical or supraclavicular lymph node chains)
- Bone/joint involvement: Bone or joint pains, back pain (Pott's disease), joint swelling, paravertebral/psoas abscess, kyphosis, paraplegia
- Gastrointestinal involvement: Abdominal or pelvic pain, anorexia and weight loss, irregular bowel habit, bowel obstruction, fistula or perforation
- Genitourinary/renal involvement: dysuria, frequency, haematuria, flank pain, sterile pyuria, prostatitis, epididymo-orchitis, endometritis, salpingitis
- CNS involvement: Headache, fever, vomiting, irritability, confusion, altered consciousness, cranial nerve palsies, seizures
- Skin involvement: Erythema nodosum, lupus vulgaris
- Pericardium involvement: Breathlessness, chest pain, ankle swelling, cardiac tamponade
- Miliary disease may occur without evidence of active pulmonary disease
Investigations
- Three sputum samples for AFB smear (Ziehl-Neelsen stain), culture and sensitivities
- CXR typically shows upper lobe involvement with cavitation, consolidation, fibrosis and calcification in chronic disease in addition to hilar/paratracheal lymphadenopathy and pleural effusion
- Bronchoalveolar lavage is an option if sputum is absent/negative
- Consider system-specific investigations for suspected extrapulmonary TB e.g. urine sample, pleural fluid, ascitic fluid, CSF
Management
- TB is a notifiable disease
- Antibiotic drug treatment (6 months) - the standard unsupervised six month treatment regimen may be used during pregnancy and breastfeeding (but streptomycin should not be used in pregnancy); renal and hepatic function should be monitored during treatment
- Initial Phase (2 months)
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
- Continuation Phase (4 months)
- Isoniazid
- Rifampicin
- Initial Phase (2 months)
- Infection control
- Risk assessment for HIV infection
- Specialist coordination of care – people at risk of poor adherence to treatment may have directly observed therapy (DOT)
- Contact tracing and consideration of TB prophylaxis for susceptible close contacts (with isoniazid, rifampicin or both)
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
