mycobacteriae Flashcards
mycobacteriae: histology
acid fast bacilli stained with Ziehl Neelsen stain or auramine fluorescent dye
mycobacteriae: character
strict aerobes
mycobacterium waxy cell wall:
peptidoglycan layer has different chemical basis for cross linking to the lipoprotein layer
outer envelope contains a variety of complex lipids (mycolic acids)
consequences: provides resistance to drying, cell wall components possess pronounced adjuvant activity (promotes immunologic responsiveness)
mycobacteriae: culture
slow growing
name the mycobacterium tuberculosis complex (MTC) species
m. tuberculosis, m. africanum, m. canetti, m. microti
mycobacterium tuberculosis complex (MTC): transmission
respiratory route; very small infective droplet nuclei
only need 1-5 bacilli to impact terminal alveolus to cause infection
mycobacterium tuberculosis complex (MTC): virulence factors
cord factor: inhibits acidification of phagolysosome, allowing survival and multiplication of afb within macrophages
mycobacterium tuberculosis complex (MTC): pathogenesis
primary tb: occurs in lungs, often asymptomatic and non-infective
post primary tb: can occur in lung or any other organ, usually infective
miliary tb: due to progressive primary or post-primary tb
describe pathogenesis of primary tb:
stage 1: phagocytosis of afb by macrophages, survival and multiplication of afb in macrophages
stage 2: blood monocytes attracted to the site of infection and differentiate into macrophages, but still remain unable to kill afb -> forms Ghon focus - small foci of inflammation with a few mtc surrounded by dense granuloma in lung; primary complex - Ghon focus + enlarged regional lymph nodes
stage 3: few weeks later; influx of antigen-specific t cells that secrete interferon-gamma which enhances microbicidal ability of macrophages, afb killed
stage 4: final stage of infection, may lead to 1 of the 3 outcomes;
- complete cure and resolution
- dormancy; latent tb that may result in post primary tb
- active disease if immune cells fail to control multiplication of afb (progressive primary tb into miliary tb)
describe pathogenesis of post-primary tb:
due to the reinfection or reactivation of latent tb
forms large exuberant granulomata often with central caseous necrosis (in lungs, necrotic tissue coughed up leaves behind cavities)
if immune cells fail to control multiplication of afb, progressive post-primary tb -> miliary tb
describe pathogenesis of miliary tb:
involves haematogenous dissemination of afb, affecting multiple organs
multiple granuloma visible in organs macroscopically as small white nodules
mycobacterium tuberculosis complex (MTC): clinical presentations
tuberculosis
systemic symptoms: fever, weight loss, night sweat
pulmonary symptoms: chronic cough, hemoptysis, dyspnea, pleuritic chest pain, pleural effusion
cns symptoms: tb meningitis, commonly affects base of brain causing cranial nerve palsies
lymph node involvement: mediastinal and hilar lymph node enlargement, cervical lymphadenitis
gastrointestinal symptoms: enlargement of peyer’s patches
bone and joint tb: tb of spine (pott’s disease), can cause vertebral collapse
miliary tb: multiple granuloma seeded to multiple organs around the body
mycobacterium tuberculosis complex (MTC): diagnosis
haematology: full blood count (non specific white cell count is usually normal or near upper limit of normal)
biochemical tests:
- body fluids analysis of adenosine deaminase of pleural and peritoneal fluids
- csf analysis: characteristically low glucose levels in tb meningitis, raised protein and lymphocyte counts
- urine analysis: sterile pyuria
imaging: chest x-ray for pulmonary tb, ct/mri of brain for cns tb - base of brain leptomeningeal enhancement, ct/mri of spine for spine tb
culture: slow but good
- specimens: use early morning sputums, nasogastric aspirate for children who cannot expectorate sputum, first pass urine, csf, lymph node, bone, pleural biopsies
- culture medium: solid based or broth based, incubation at 35-37degc for up to 8 weeks
microscopy:
acid fast bacilli with ziehl neelsen stain, auramine fluorescent dye; caseating granulomas in histological sections
molecular methods: naat with pcr or isothermal amplification methods
latent tb: usually done in context of known exposure to case of pulmonary tb
- mantoux testing
- ifn gamma release assays
mycobacterium tuberculosis complex (MTC): treatment and management
anti-tuberculosis drugs:
- first line: isoniazid, rifampicin, streptomycin, pyrazinamide, ethamutol
- second line: cycloserine, aminoglycosides, quinolones (oflaxacin), p-aminosalicylic acid, ethionamide, prothionamide, thiacetazone
- *note: multidrug resistant tb are resisant to isoniazide and rifampicin
- *note: extensively drug resistant tb = mdr + resistant to 2nd line drugs
standard therapy: always use combination of drugs in treatment of active disease to avoid emergence of drug resistance
- 2 months of daily rifampicin + isoniazid + pyrazinamide followed by 4 months of daily rifampicin + isoniazid
- prophylactic pyridoxine supplement to prevent peripheral neuropathy due to isoniazid
- ^ 6 month isoniazid is given for treating latent tb infection
monitoring of treatment progress:
- weight gain, resolution of symptoms by 2nd week of treatment, no longer infective and can return to work
- sputum conversion from positive to negative culture, expected in 2-3months (if not, suspect non compliance or drug resistance)
- improvement of chest xray lesions though fibrous scars may remain
failure of treatment or emergence of resistance: use second line drugs, longer duration, refer to specialist in tb management
test for hiv
mycobacterium leprae: character
obligate intracellular pathogens, grow very slowly (1 replication per fortnight)
mycobacterium leprae: transmission
close and prolonged contact through the respiratory route
