Lec9 tuberculosis Flashcards
What are koch’s 4 postulates?
- bacteria must be present in every case of disease
- bacteria must be isolated from host with disease and grown in pure culture
- specific disease must be reproduced when pure culture of bacteria is inoculated into healthy host
- bacteria must be recoverable from experimentally infected host
What are the microbiological properties of TB?
- lipid rich cell wall so resistant to traditional stains and antibiotics
- contains mycolic acid in cell wall
- cell wall is hydrophobic so get clumping of bacteria
- slow incubation time
What is mycolic acid?
major component of cell wall of TB
What is shape of mycobacteria? gram? acid fast or non acid fast? other notable characteristics?
- non-motile non-spore forming aerobic
- rods [bacilli]
- gram null or weakly +
- acid fast
- cell wall contains lots of mycolic acids
What is acid fast staining?
- first stain with carbolfuschin
- then put on acid acohol solution, if does not decolorize with acid alcohol solution then it is an acid fast organism
- all myobacteria are acid fast
What is rate of growth of class I myobacteria? does it produce yellow pigment? how frequently is it pathogenic? what are two representative organisms?
- rate of growth: slow
- produces yellow pigment
- usually pathogenic
- representative:
- — M. kansasii
- — M. marinum
What is rate of growth of class 2 myobacteria? does it produce yellow pigment? how frequently is it pathogenic? what is one representative organism?
- rate of growth: slow
- produces yellow pigment
- sometimes pathogenic
- representative:
- — M. scrofulaceum
What is rate of growth of class 3 myobacteria? does it produce yellow pigment? how frequently is it pathogenic? what is one representative organism?
- rate of growth: slow
- does not produce yellow pigment
- usually pathogenic
- representative:
- — M. avlum complex
What is rate of growth of class 4 myobacteria? does it produce yellow pigment? how frequently is it pathogenic? what are two representative organisms?
- rate of growth: fast
- does produce yellow pigment
- sometimes pathogenic
- representatives:
- — M. abscessus
- — M chelonae
What is rate of growth of non-runyon class myobacteria? does it produce yellow pigment? how frequently is it pathogenic? what is one representative organism?
- rate of growth: slow
- does not produce yellow pigment
- always pathogenic
- representative:
- — M. tuberculosis
What are m tuberculosis virulence factors?
- does not have toxins or capsules [traditional virulence factors]
- major virulence factor = intracellular survival
What is mech of tuberculosis intracellular survival?
- makes antibody and complement ineffective
- inhibits phagosome-lysosome fusion after phagocytosis
- interferes with toxic ROS produced in phagocytosis
After transmission how much time until positive skin conversion test?
6-8 weeks
How is TB transmitted?
- airbone
- can remain suspended in air for several hours
- close contacts, cough, sneezing
- droplet of TB enter alveoli and ingested by alveolar macrophages
What happens in primary infection of TB?
- at first very minimal host immune response
- get intracellular replication that destroys alveolar macrophages
- spread via lymphatic channels and via blood stream
How is latent TB infection [LTBI] established from primary?
- cell-mediate immune response
- immunologic basis for skin testing
- macrophages presenting TB antigen attract T lymphocytes
- immune response kills most of bacilli leading to formation of granuloma
- MTB persists within inactivated macrophages inside granuloma
How is granuloma formed?
- aggregation of macrophages, lymphocytes, fibroblasts
- due to low pH and anoxic environment of caseating center TB does not replicate but is able to survive
What is ghon’s complex?
- calcified subpleural [surface] granulomas in mid lung and in hilar lymph node
Are there any symptoms in latent TB?
No
Are patients with latent TB contagious?
No
How can you diagnose latent TB?
- PPD
- interferon gamma release assay [IGRA]
What are IRGAs [interferon gamma release assays]?
- quantiferon-TB and TB-spot
- they are Elisa tests to detect release of interferon gamma from patients after incubation with 2 synthetic peptides that are specific to TB
What is PPD?
- antigenic components [tuberculins] are extracted from culture filtrate by protein precipitation
- if you have TB, will get delayed hypersensitivity rxn to intradermal tuberculin 6-8 wks after infection
What are the downsides of PPD testing?
- required proper intradermal administration
- need to return 48-72 hrs later
- false positive from BCG vaccination and non TB myobacteria
- false negatives in patients who are immunocompromised
What is the clinical approach to latent TB?
- get chest radiograph
- take 3 consecutive sputum AFB samples to look for evidence of active disease or of prior healed TB
- give isoniazid for 9 months if no evidence of active disease
What are the risk factors for TB exposure and infection?
- prison
- health care workers
- homeless, medically underserved, low income
- recent immigration
What makes you at risk for developing TB once exposed?
- HIV infection
- diabetes
- organ transplant
- treatment wtih IF inhibitor
- recent TB infection
- illicit drug use
- history of inadequately treated TB
What are 4 disease that TNF [tumor necrosis factor] inhibitors usually treat?
- crohns
- ulcerative colitis
- rheumatoid arthritis
- psoriasis
What are 3 examples of TNF inhibitors?
- infliximab
- etanercept
- adalimumab
What is possible complicated of TNF inhibitors?
- they can cause reactivation of latent TB infection
What happens in development of active TB?
- TB bacilli multiplying extracellular in environment and overcome immune system
- large TB load necroses wall of bronchi, lead to cavity formation, spread to other parts of lung
What are symptoms of acute TB?
- cough
- hemoptysis
- nigh sweats
- anorexia
- weight loss
- weakness
- dyspnea
What is cavitary vs miliary pulmonary TB?
cavitary: TB has destroyed part of lung, get big hole in the lung = enlarged air space, usually occurs in reactivation
miliary: has spread via lymph nodes all over lung, get lots of tiny little nodules
What are principles of TB treatment?
- provide effective treatment for shortest duration possible
- give 3-4 drugs with probable susceptibility to minimize risk for resistance
- never add single drug to failing regiment
- direct observed therapy
What is standard TB treatment strategy?
- 2 months of 4 drug regiment RIPE
- – Rifampin [RIF]
- – Isoniazid [INH]
- – Pyrazinamide [PZA]
- – Ethambutol [EMB]
- maintenance with RIF [rifampin] and INH [isoniazid] for 4 months
What is mech of rifampin action? bacteriostatic or bactericidal?
- inhibits DNA-dependent RNA polymerase
- bactericidal
What are adverse rxns of rifampin?
- hepatotoxicity [most important]
- thrombocytopenia
- orange-red colored urine
What are pharmacokinetic properties of rifampin – can it be absorbed orally? where is it excrete?
- well absorbed orally
- excreted in feces
Why does rifampin have a lot of other drug interactions?
because it induces hepatic cytochrome p450 enzymes so affects other drugs’ metabolism
What is mech of action of isoniazid [INH]? bacteriostatic or bactericidal?
- prodrug
- inhibits mycolic acid synthesis [by inhibition mycolase synthetase]
- bactericidal
Is isoniazid absorbed orally?
yes well abosrbed orally
What are adverse effects of INH [isoniazid]?
- hepatotoxicity [most common]
- peripheral neuritis
What is mech of action of PZA [pyrazinamide]? bacteriostatic or bactericidal?
- mech largely unknown
- bacteriostatic
Can PZA be given orally? how is it metabolized?
- yes — well absorbed via oral administration
- metabolized in liver by PZA deaminase
- metabolites then excreted by kidneys
What are adverse effects of PZA?
- arthralgias aka joint pain [most common]
- hepatotoxicity
- hyperuricemia
What is mech of action of Ethambutol? bactericidal or bacteriostatic?
- inhibits cell wall polysaccaride syntehsis [inhibits arabinosyl transferase]
- bacteriostatic
What are adverse effects of ethambutol?
- optic neuritis [most common]
- decreased red-green color discrimination
- peripheral neuropathy
Is ethambutol absorbed orally? how is it eliminated?
- absorbed well orally but impaired by food/antacid
- excreted unchanged in urine
What is MDR?
- multi drug resistant TB
- resistant to isoniazid and rifampin
What is XDR?
- extensively drug resistnat TB
- resistant to isoniazid and rifampin
- also resistant to fluorquinolones and at least one other 2nd line agent
What is bedaquiline? action? concerns?
- new approved TB drug
- inhibits mycobacterial ATPase
- concern becuase of liver inflammation and QT prolongation
How do you prevent TB?
- bacillus calmette guerin [BCG] vaccine
- N95 respirator masks
- negative pressure isolation rooms
