Lecture 15 Myobacteria Flashcards
What is the sole genus of Mycobacteriaceae?
Mycobacterium.
“Myco”- fungus or wax
-May refer to the waxy compound s in cell wall or branching/cording behaviors of some members
Where are mycobacterium found in the environment?
Often found in water, soil, foodstuffs. Many are opportunistic pathogens in humans.
What are two obligate parasites?
- mycobacterium tuberculosis (common)
- Mycobacterium Leprae (Rarer)
What is important for determinant of disease presence and severity of diseases caused by mycobacterium?
Host susceptibility.
What are some disease caused by nontuberculous mycobacterium?
- pulmonary disease similar to TB
- Lymphadenitis
- skin and soft tissue disease
- disseminated disease.
What are some distinguishing characteristics of mycobactrium cell wall/membrane?
- acid fastness: Neither gram negative or positive.
- 60 % of the cell wall is made with mycolic acid (waxy) and LAM
- resistant to drying
- retains stain to well, cannot be destained.
What is acid fast staining?
Also known as Ziehl-Neelsen or kinyou stain)
- Stain with carbol fuchsin
- Decolorize with acid-alcohol
- Counterstain with methylene blue.
Other than being acid fast, what are some other distinguishing characteristics of mycobacterium?
- Slow growing (fastidious)
- Pigments (cartenoids)
- Aerobic
- Generally nonmotile
- Host genetics play important role in susceptibility and manifestations.
What makes mycobacterium difficult to study/Dx?
Difficult to culture in vitro. difficult to manipulate genetically.
What makes mycobacterium difficult to treat?
-slow-growing nature, causing it to be less likely to respond to abx, resistance can be easily developed. Tend to use multiple abx together when treating to make sure resistance is not developed.
Which mycobacterium can move intracellularly?
M. Marinum.
Who discover mycobacterium tuberculosis?
Robert Koch
Is tuberculosis presently a problem?
- Infects 1/3 of all people worldwide.
- Responsible for untold death and illness over history.
- 3 million TB deaths per year worldwide
What were some Forensic evidence of M Tuberculosis?
Fossils dating back beyond 500K years ago show TB infecting Homo Erectus. Found in Neolithic humans 4K years ago. Identified in the spines of mummified Egyptians.
What are some historical accounts of M tuberculosis?
- Hippocrates describes and pthisis consumption.
- Aristotle believed it to be contagious.
- Ibn Sina believed it to be rom a microorganism.
- accelerated in Europe’s industrial revolution.
What areas in the world are hit hard with TB?
-Asia, Africa.
Countries of poverty.
What disease correlates with TB around the world?
-HIV/AIDS is prevalent where TB is because the best defense against TB are T cells. HIV/AIDS infected individual are more susceptible.
What sx occurs in in primary infection?
- often clinically dormant, inactive
- immunocompromised individuals can get disseminated disease
- in normal hosts usually latent.
What sx occurs in secondary infection?
- Nigh sweats, fever, weight loss
- cough (tranmission)
- can infect spinal column and meninges.
- clinical impact attributed to host response.
How si Tb transmitted?
- Nearly always thought to be through inhalation of infectious particles (drop nuclei)
- produced by infected person via coughing, talking, sneezing
- need prolonged exposure
- penetrate alveoli and infects
What is the pathogenesis of primary infection?
- ingested by macrophage
- replication in macrophage, destroying them
- blood-borne inflammatory cells migrate to infection, ingest and process (granuloma)
- immunity can take weeks to develop, immune response is main defense.
What is usually the outcome of primary in immunocompetent hosts?
- Once hypersensitivity/ cellular immunity develop, infection is usually controlled.
- latent, cannot be reinfected. Reactivation can occur later.
What is the outcome of primary infection in immunocompromised hosts?
– Can get progressive, often disseminated disease
What factor affect manifestations of primary infection?
-often progressive in infants and elderly.
What is the pathogenesis of secondary TB?
- can occur 2 years- 7 decades later
- Usually in apices of lungs
- HIV is common reason
- necrosis of granuloma, cavitation
- very infectious at this point
What are key factors of immunity and host response to TB?
- cellular immunity, this is why so long for response, B cells do not help
- Macrophages have multiple Mtb receptors, but MTb can resist
- CD4+ T cells critical for activating immune system
- hypersensitivity will develop 3-8 weeks (increase killing and granulomas)
What are ways to dx TB?
- microscopy
- culture
- PCR (increasingly used)
- Skin test (PPD), old school
- IFN-y release test
What is the gold standard to dx TB?
Culture (often 3-6 weeks)
What is a more common method of identifying TB?
- INF-y test (quantiferon gold)
- not as impacted by vaccine as PPD.
- Blood test
How is TB treated?
-must use 3 or more agents to make sure resistance does not develop
Includes:
-INH (isoniazid), pyrazinamide, ethambutol (cell wall)
-Rifampin (polymerase)
-Amino glycosides (ribosome)
-Fluoroquinolones (gyrase)
How is TB prevented?
BCG vaccine:
- Attenuated version of M. Bovis
- Used in a lot of the world except US
- Variable efficacy against TB
- Give false-positive skin (PPD) test, not IFN-y release
What is Hansen’s disease?
-Leprosy
What are some social implications of Leprosy?
-stigmatized due to the fact that religion caused people to believe it is due to sin.
What is astounding about the cases of Leprosy?
We have a lot of defenses against it, but not doing a good job of control.
What is historical about Leprosy?
-first bacterium identified to cause disease in humans.
What are some hosts for leprosy?
- humans, primates
- armadillos in Americas
- Eurasion red squirrel
What is the natural history of Leprosy?
-long incubation (2-10 years)
-Several types of manifestations:
– Tuberculoid or paucibacillary (low skin organism burden)
– Lepromatous or multibacillary (high skin organism burden)
-many intermediate forms
What is the method of transmission of Leprosy?
- maybe via aerosol
- exposure to animals
- Epi is difficult because of long incubation time
- Though that long-term close exposure
- Genetic predisposition (minority of Population)
What is the pathogenesis of Leprosy?
- Tropism of nerve cells
- taken up by macrophages, via receptor
How is Leprosy dx?
- complicated cause cannot cultivate in vitro
- culture and hypersensitivity not used
- usually by clinical suspicion, Exams
What is the treatment for leprosy?
Mutli-drug therapy:
– Dapsone (DHFR inhibitor)
– Rifampin (RNA synthesis inhibitor)
– Clofazimine (DNA replication inhibitor)
Highly effective, usually dissipates in 3 days
What does M bovis cause?
TB
What does M kansasii and M avium cause?
Intracellulare: TB like resp disease
What does M scrofulaceum cause?
-Lymphadenitis
What does M fortuitum, marinum, and ulcerans cause?
Skin and soft tissue infections
What doe M abscessus spp, M Chelonae cause?
Opportunistic pulmonary infections
