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leading cause of death in early 1900s
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tuberculosis
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Mycobacterium tuberculosis
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gram pos bacillus, acid fast(mycolic acids=waxy), slow growing, obligate aerobe;
facultative intracellular parasite of macrophages;
extremely conserved genome and low mutation rate w/ long coevolutionary relationship with humans- obligate human pathogens, not in enviro
facultative intracellular parasite of macrophages;
extremely conserved genome and low mutation rate w/ long coevolutionary relationship with humans- obligate human pathogens, not in enviro
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where is TB endemic?
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Southeast Asia, Brazil, Subsaharan Africa; bc HIV most common here; HIV pandemic caused resurgence in TB but decreasing since 2000
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M. tuberculosis virulence factors
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atypical! No true endo/exotoxins-- damage is done by host's own immune system.
Intracellular survival in macrophages via iron scavenging, sulfolipids in cell wall prevent phagosome-lysosome fusion=esccape into cytoplasm;
granuloma formation=live inside structure and hide out=prolonged survival;
lipid rich cell wall- waxy mycolic acids=resist phagocytosis and cord factor=glycolipid that causes bacterium to grow in serpentine cords=inhibits leukocyte migration;
lipoarabinomannan(LAM) sim to endotoxin, inhibits macrophage activation and digestion within phagocyte
Intracellular survival in macrophages via iron scavenging, sulfolipids in cell wall prevent phagosome-lysosome fusion=esccape into cytoplasm;
granuloma formation=live inside structure and hide out=prolonged survival;
lipid rich cell wall- waxy mycolic acids=resist phagocytosis and cord factor=glycolipid that causes bacterium to grow in serpentine cords=inhibits leukocyte migration;
lipoarabinomannan(LAM) sim to endotoxin, inhibits macrophage activation and digestion within phagocyte
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acid fast cell wall
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Neither Gm + or -
Contains mycolic acid (waxy lipid; makes it the most resistant type of bacteria)
impedes entry of chemicals=slow growth, enhances resistance to toxins, glycolipids can stem an inflammatory response
Contains mycolic acid (waxy lipid; makes it the most resistant type of bacteria)
impedes entry of chemicals=slow growth, enhances resistance to toxins, glycolipids can stem an inflammatory response
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Transmission of M. tuberculosis
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highly transmissible: source case-->aerosolization-->airborne survival-->exposure and inhalation--> depending on susceptibility to infection bacteria enter respiratory tract to infect lung alveoli
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Stages of M. tuberculosis infection (pathogenesis)
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1) alveolar macrophages recognize, engulf & attempt to destroy bacilli
2)bac grow on log scale within macrophages, unable to stop bac growth
3)infected areas transform into granuloma(wall of lymphocytes) -->chest pain. Granuloma forms solid caseous center where bac can survive for years, most don't exhibit disease progression (latent state)
4)caseous center liquifies and fills lungs with free-floating bac=pulmonary TB. Bac can go to organs via lymphatic system or bloodstream=extrapulmonary TB
2)bac grow on log scale within macrophages, unable to stop bac growth
3)infected areas transform into granuloma(wall of lymphocytes) -->chest pain. Granuloma forms solid caseous center where bac can survive for years, most don't exhibit disease progression (latent state)
4)caseous center liquifies and fills lungs with free-floating bac=pulmonary TB. Bac can go to organs via lymphatic system or bloodstream=extrapulmonary TB
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symptoms of TB
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start at lungs--> <10% systematic spread, takes long time.
chest pain, dry cough, structural abnormalities, productive cough, fever, weight loss, weakness, night sweats, poor appetite, cough with increasing mucus, coughing up blood-->extrapulmonary in meninges, lymph nodes, bone and joint sites, genitourinary tract
chest pain, dry cough, structural abnormalities, productive cough, fever, weight loss, weakness, night sweats, poor appetite, cough with increasing mucus, coughing up blood-->extrapulmonary in meninges, lymph nodes, bone and joint sites, genitourinary tract
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TB dynamic spectrum: infection to active pulmonary disease
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infection eliminated via innate(no T cell memory) or acquired response;
latent TB capable of active or eliminated infection;
Subclinical (asymptomatic) and active (symptomatic, higher bacterial load, infectious) TB capable of transmission
latent TB capable of active or eliminated infection;
Subclinical (asymptomatic) and active (symptomatic, higher bacterial load, infectious) TB capable of transmission
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Isoniazid and rifampin resistance in TB granulomas
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Resistance via mutations—> resistant bacteria grow within host which can spread resistant bac to others;
Didn't finish antibiotics=resistant bac are selected for and can spread in community
Didn't finish antibiotics=resistant bac are selected for and can spread in community
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Types of TB resistance
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Drug resistant TB=resistant to 1/4 antibiotics ex)INH resistance;
MDR TB= resistant to 2/4 antibiotics;
XDR TB= also resistant to 1+/3 of 2nd line antibiotics, bad side effects, huge concern.
MDR TB= resistant to 2/4 antibiotics;
XDR TB= also resistant to 1+/3 of 2nd line antibiotics, bad side effects, huge concern.
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Covid effect on TB
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Slight increase in cases