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Mycobacteria possess a lipid-rich cell wall that retains some dyes,
resisting decolourization with acid (hence they are known as
acid-fast). There are more than 50 species; although most are
environmental organisms that rarely cause human infection.
Epidemiology and pathogenesis
Tuberculosis is spread from person to person by the airborne
route. In childhood, the lung is the first site of infection and most
infections resolve with local scarring (the primary complex). In
about 5% the infection is not controlled and it spreads from the
primary focus throughout the body (miliary spread). This may
resolve spontaneously or develop into other localized infections
(e.g. meningitis, osteomyelitis). Disease may emerge if immunity
wanes or in later life (10% lifetime risk). Immunity depends on
effective T-cell function so if compromised, individuals are more
likely to develop symptomatic disease.
Mycobacterium tuberculosis is ingested by macrophages but
escapes from the phagolysosome to multiply in the cytoplasm. The
intense immune response causes local tissue destruction (cavitation
in the lung) and cytokine-mediated systemic effects (fever and
weight loss). Many antigens have been identified as possible virulence
determinants, including lipoarabinomannan (stimulates
cytokines) and superoxide dismutase (promotes intramacrophage
Mycobacterium tuberculosis may affect every organ of the body
mimicking both inflammatory and malignant diseases.
- Pulmonary: chronic cough, haemoptysis, fever and weight loss,
or recurrent bacterial pneumonia. If untreated, it follows a chronic,
- Meningitis: fever and deteriorating level of consciousness.
- Renal: signs of local infection, fever and weight loss, complicated
by ureteric fibrosis and hydronephrosis.
- Bone: the lumbosacral spine is a common site of infection. Complicated
by vertebral collapse and nerve compression. Pus may
spread under the psoas sheath to appear in the groin (psoas
- Joints: infects large joints causing destructive arthritis.
- Abdominal: mesenteric lymphadenopathy and chronic peritonitis
may present as fever, weight loss, ascites and intestinal
- Miliary disease: may occur without evidence of active lung
A wide range of specimens can be examined, using a variety of
Treatment and prevention
- Direct staining with Ziehl-Neelsen's method or auramine.
- Culture on lipid-rich (egg-containing) medium with malachite
green (L�wenstein-Jensen or L-J medium) to suppress other
- Automated growth detection, which can speed isolation.
- Susceptibility is usually tested in automated systems (e.g. Mycobacterial
Growth Indicator Test [MGIT]).
- Nucleic acid amplification tests (NAATs) that include detection
of drug resistance mutations allow rapid identification of patients
with multidrug resistance TB (MDRTB) so they can be isolated
and appropriately treated.
- Typing by identification of the number of copies of 23 repetitive
- Immunity is determined by measuring the ?-interferon response
to specific antigens (Interferon Gamma Release Assay [IGRA]).
The standard regimen for pulmonary infection is rifampicin and
isoniazid for 6 months, with ethambutol and pyrazinamide for the
first 2 months. Regimens for other sites are similar, taking into
account drug penetration (e.g. into CSF). There is a rising trend
of MDRTB. Features that predispose a patient to this include:
- previous incomplete treatment;
- being a known contact of an MDR patient;
- residence in a country where MDRTB is common;
- failure to respond to an adequate regimen.
Treatment of MDRTB is complex, requiring a combination of
second-line agents, such as aminoglycosides, fluoroquinolones,
ethionamide or cycloserine, guided by susceptibility tests.
Vaccination with attenuated bacille Calmette-Gu�rin (BCG)
strain may protect against miliary spread, but trials in some
countries have shown no benefit. Patients at high risk of developing
tuberculosis may be given prophylaxis with isoniazid and
Mycobacterium leprae attacks peripheral nerves, causing anaesthesia.
Digital destruction and deformity follow, leaving the patient
severely disabled. The end result of infection depends on the individual
immune response, forming a spectrum from 'tuberculoid'
dominated by a Th1 response, through 'borderline', to 'lepromatous'
dominated by a Th2 response. Patients with tuberculoid
disease have a stronger immune response, more localized disease
and fewer bacteria. With lepromatous disease there is poor cellmediated
immunity (CMI) and generalized disease (leonine facies,
depigmentation and anaesthesia).
Diagnosis is by Ziehl-Neelsen's stain of a split-skin smear
and histological examination of a skin biopsy. Treatment with
rifampicin, dapsone and clofazimine rapidly renders the patient
non-infectious, but cannot alter nerve damage and deformity,
which must be managed by remedial surgery.
Mycobacterium marinum and Mycobacterium ulcerans
Mycobacterium marinum causes a chronic granulomatous infection
of the skin and is acquired from rivers, poorly maintained
swimming pools or fish tanks. It is characterized by encrusted
pustular lesions. M. ulcerans infection is associated with farming
in Africa and Australia. The lower limb is usually affected with a
papular lesion, which ulcerates and may destroy underlying tissue