Week 9: TB and Leprosy Flashcards
Causative agent of leprosy
Mycobacterium leprae
Only motile subspecies of the Mycobacterium genus
M. marinum - causes skin lesions in amphibians and humans
Characteristics of Mycobacterium
Acid-fast Non-motile Aerobic Don't form endospores Outer membrane but no capsules
Which stain is used to identify M. tuberculosis?
Zheil Neelson (acid-fast) stain
In a Zheil Neelson stain, the property of acid-fastness is based on the presence of a) _____ in the b) _____ of mycobacteria. The primary stain c) _____ binds to cell wall d) _____. The intense decolourisation with e) _____ f) does/does not release the primary stain from the cell wall and the mycobacteria g) loses/retains the h) _____ colour of fuchsin.
a) mycolic acids
b) cell wall
c) fuchsin
d) mycolic acids
e) strong acid or alcohol
f) does not
g) retains
h) red
Attributes of Mycobacterial PG and their biological significance
- DAP-DAP and DAP-Ala peptide cross-linkage provide increased rigidity to the PG to help survive stressful conditions
- N-Glycoylmuramic acid and NAM could tighten the PG sacculus by providing more opportunities for hydrogen bonding and increase resistance to β-lactams and lysozyme
- Amidated L-Glu and DAP May play a role in the regulation of cross-linking and could increase resistance to hydrolysis by specific endopeptidases, as seen with the
amidation of PG sugar residues increasing resistance to muramidase - D-Glutamate or L-alanine modified with glycine
True or false: AFB bacilli found in respiratory specimens of patients from countries with high TB prevalence are almost always TB bacilli.
True
a) Leprosy is a chronic infection with which species?
b) Describe immunological appearance of the specie causing Lepracy.
c) Describe the various forms of lepracy
d) Lepracy pathogenesis (entry route, risk factors, clinical manifestations and pathogenesis)
a) Mycobacterium leprae
b) Acid-fast bacilli, 8um rod in groups
c) Tuberculoid (mildest) and lepramatous (most severe)
d) Most probable entry route is via the skin (main site of infection), as well as respiratory tract.
Risk factors include poor hygiene, diet and immune status. M. leprae are phagocytosed by macrophages in the skin and may be contained or killed (tuberculoid) or ineffective response (lepromatous).
Clinical manifestations result mostly from the immune response to bacillus. If immune response develops into a strong cell-mediated response, patient will manifest tuberculoid leprosy, leading to formation of granulomas under the skin containing cytokine-producing macrophages. Very few AFB found in scrapings. The lepromatous form of leprasy is associated with a humoral response leading to foamy macrophages, large numbers of bacteria and widespread disease. Demyelination and loss of axonal conductance associated with M. leprae may ischaemic injury due to release of inflammatory cytokines or activity of cytotoxic T cells, leading to apoptosis of the cells around the neuron.
e) 1-3 granulomatous skin lesions
Clinical presentation of tuberculoid leprasy
1-3 granulomatous lesions and very few M. leprae found in macrophages
Clinical abnormalities limited to a few peripheral nerves (sensory nerve damage causing numbness)
Increased the frequency of damage to extremities
Clinical presentation of lepromatous leprasy
- Multiple lesions
- Large number of AFB in tissue, mostly in macrophages
- Marked thickening and folding of the skin
- Results from failure of Th1 cell activation, necessary to eradicate mycobacteria. Th1 cell-mediated response is suppressed due to reciprocal inhibition (IL-4; IL-10).
- Internal organs, bones, joints and marrow are affected
Diagnosis of leprasy
Based on a clinical diagnosis
One or more hyperpigmented, anaesthetic skin patches
One or more thickened peripheral nerves
Positive skin smear to look for AFB
Treatment of leprasy
Dapsone - first drug against leprasy
MDT now available: rifampicin, clofazimine, and dapsone
Properties and characteristics of M. tuberculosis
- Highly aerobic and requires high levels of oxygen
- Acid fast bacillus
- Can be grown on artificial media
- Highly contagious
- Most people overcome infection without symptoms
Tuberculosis pathogenesis
Small bacilli penetrate alveoli in droplet nuclei (< 5 μm) and are phagocytosed by alveolar macrophages but avoid being killed and subsequently replicate within the macrophage. Infected macrophages attract more macrophages through chemokines, resulting in local inflammation, and the accumulation of inflammatory cells called a tubercle. A caseous centre forms within a tubercle composed of necrotic cells and multiplying bacteria, forming a tuberculous cavity. Eventual deposition of fibrotic tissue around the tubercle contains the mycobacteria. Breakdown of the tubercle may result in the rupture of the bronchiole wall and the dissemination of mycobacteria.
In susceptible individuals, both healing and progressing lesions may coexist, and disease takes a chronic, cyclic course. In severe cases, primary lesions are never brought
under control, and grow larger, coalesce, and liquefy, forming a large cavity in the lung.
Clinical presentation of tuberculosis
Different forms exist: pulmonary TB, joint and bone TB, meningitis (most common in infants), skin TB, lymph nodes (scrofula).
Many symptoms due to overproduction of TNF, such as fever, night sweats, severe weightloss,
One of the chief symptoms is cough with increasing mucous and blood (haemoptysis) due to breakdown of granulomas in the lungs.
