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57 Cards in this Set
- Front
- Back
“Emerging” Infectious Diseases:
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“Emerging” Infectious Diseases aren't really emerging. Instead, they are re-emerging.
- Microorganisms do not change much - Human behavior changes a lot - Almost everything that we talk about in path has been made worse because of some kind of human behavior |
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PARALYTIC POLIO: Poor Sanitation
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PARALYTIC POLIO: Poor Sanitation
Poor Sanitation (U.S. in 1800) Children do get infected so they get childhood diarrhea, gastro-enteritis, and they become immune. Paralysis is rare in childhood. Why? because children don't have the receptors for polio virus on the anterior horn of their SC, therefore no paralysis. |
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Cause of Polio?
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Enterovirus
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PARALYTIC POLIO: Good Sanitation
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PARALYTIC POLIO: Good Sanitation
Good Sanitation (U.S. in 1900) Children are not infected and do not become immune, so... young adults are infected. Young adults do have the receptors for Polio virus on anterior horn cells so paralysis occurs. |
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When do you NOT see polio?
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You don't see polio:
1. with poor sanitation 2. If there's good sanitation and good immunization |
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Legionnaire’s Disease
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Legionella is present in fresh water ponds, plumbing systems and aerosols
Sporadic cases occur American Legion convention with many elderly attendees with chronic lung disease - they all got exposed to Legionella through the air conditioning. New tools developed to identify Legionella- DFA, urine antigen test and DNA probes With new tests, we found that there was a lot of Legionnaire's disease in hospitals. But we could rid of it. How? Hyper-chlorination of water in hospitals |
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What is this?
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Legionella DFA (direct fluorescent antibody)
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Toxic Shock Syndrome
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Toxic Shock Syndrome
Staphylococcus aureus with TSST-1 toxin 1980s- Use of hyperabsorbent tampons (RELY brand) caused an epidemic of cases - of left in too long, this was a great environment for the staph aureus to grow and release its toxin. Toxic shock still seen sporadically caused by both staphylococci and streptococci |
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Clinical presentation of Toxic Shock Syndrome:
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Clinical presentation of Toxic Shock Syndrome:
1. Hypotension 2. Rash - because of sepsis with staph arureus 3. Skin falling off palms and a lot of the body |
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Lyme Disease
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Lyme Disease
Caused by a spirochete Borrelia burgdorferi- rash, arthritis, (meningitis and myocarditis) Cause: deer tick bite that live on the white-tail deer Cause in Cali: rat tick and woodrat reservoir in California that live in the palm trees more deer-more ticks-more people wildlife protection-housing development |
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Human Papillomavirus
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Human Papillomavirus
Causes condyloma, dysplasia and cervical carcinoma (we see a lot of carcinoma in-situ, but not a lot on invasive cervical cancer because it can take around 10 years to actually become invasive.) There is a more sexually active population The incidence (and prevalence) of CIS is increasing in the U.S. (but mortality is decreasing) We are also seeing more head and neck tumors cause the HPV because of spread from the mouth and throat. |
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What types of HPV cause cervical CA?
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HPV DNA Types 16 and 18
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HPV DNA Types 16 and 18: How do they cause cervical CA
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HPV Infection produces proteins E6 and E7
p53 protein, RB and p21 protein are inactivated Apoptosis does not occur and the infected cells are not killed Dysplasia and cervical cancer may result |
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What is the pathogenesis of HPV?
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The virus eventually integrates in the human chromosome, it takes over the human cell machinery, shuts down p53 and the brakes on the retinoblastoma gene (RB), so the cells proliferate and become immortal. If they're there long enough, they'll go through mild dysplasia, moderate dysplasia, marked dysplasia, carcinoma in-situ, and then invasive CA. But since it takes so long do this to happen, we can catch it.
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What is this?
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Cervical Carcinoma In-Situ
The Number of cases of CIS increases annually, but the number of cases of invasive cervical CA goes DOWN annually |
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Tuberculosis
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Tuberculosis
Mycobacterium tuberculosis In the U.S. the people at risk are: homeless, elderly in nursing homes, prisoners and AIDS patients If people are poor, malnourished, and have CROWDED living conditions, tuberculosis will flourish. This is a communicable disease that is spread from person to person. As long as people are crowded, malnourished, and don't have good access to medical care, TB will thrive. |
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How is TB spread?
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What is this?
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TB in the upper lobe- caseous granulomas
This is reactivation TB. When TB reactivates, it does so in the apex of the lung, and it's a much more aggressive disease. |
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T or F: In TB, mycobacterium does the damage to our lungs.
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FALSE:
In TB, it's not the bacteria that does the damage, it's US. Our cell-mediated response to the organism does the damage. Therefore, there's more damage in reactivation TB because we already have memory T-cells. There's more necrosis and more cavitation in reactivation TB, compared to primary TB. |
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Hantavirus
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Hantavirus
A hemorragic fever virus. 4 corners area (SW USA) - Utah, Arizona, Colorado, and New Mexico flu-like illness to hemorrhagic fever with sudden death (carried by deer mice) excess rain leads to bumper (extra) crop of pinon nuts. Mice and humans collected the nuts. The mice urinated on the nuts and the people ate these nuts. This caused an outbreak. deer mice eat nuts and population increases Navajos harvest pinon nuts for food and decoration |
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What are the two out-breaks of infectious disease that are constant (not seasonal)?
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MRSA and C. difficile
MRSA: 1. Wide use of beta-lactams - we select for resistant organisms 2. Poor hand-washing- more patients per nurse/doctor (everyone is busy and don't wash their hands as much) Clostridium difficile 1. Use of Clindamycin 2. Use of proton pump inhibitors 3. Use of quinolones (gattifloxacin, moxifloxacin) - there's a strain of quinolone resistant C. difficile that's very prevalent now. |
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Koch’s Postulates
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Koch’s Postulates
Microrganism is found in lesions of the disease Organism is isolated on solid media cultures Organisms from culture causes lesions in experimental animals Organisms can be recovered on solid media cultures from lesions in the animals This is how you prove that something causes infection. BUT, we found that several organisms don't grow on solid media. |
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Problems with Koch’s Postulates
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Problems with Koch’s Postulates
Viruses, Rickettsiae, Chlamydia etc. do not grow on solid media DNA Probes and Amplified DNA Probes are more sensitive and more specific than culture (on solid media or tissue culture) Therefore, the “Gold Standard” is often NOT culture, it's MOLECULAR standards. 2 positive molecular test give a true positive. |
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Categories of Infectious Agents
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Categories of Infectious Agents
Prions- kuru, C-J Disease, mad cow disease Viruses Bacteriophage/Plasmid Bacteria Chlamidiae/Rickettsiae/Mycoplasma Fungi Parasites (protozoa, worms, ectoparasites) |
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What makes a disease infectious?
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In order for a disease to become infectious, it has to penetrate some epithelial surface.
It then may go via nerves or may be taken up by phagocytes into the lymphatics or blood stream, and then it's spread to organs. |
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Release and Transmission of Infectious Agents
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Release and Transmission of Infectious Agents:
1. Contact- wound, body fluids or mucosal surfaces (as in STDs) 2. Cough with aerosol as in TB 3. Insect vectors as in malaria and lyme disease 4. Diseases spread from person to person are said to be contagious or COMMUNICABLE 5. Diseases acquired in the hospital are NOSOCOMIAL. In general, 72 hours after admission, if you get a new infection, it can be considered nosocomial. |
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How Do Microorganisms Cause Disease?
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How Do Microorganisms Cause Disease?
1. Direct contact with cell death (streptococcus produces cellulase - enzymes that destroy tissue) 2. Release of toxins that enter the blood and kill target tissue (C. diphtheriae - the psuedomembrane in the airway produces an exotoxin that travels to the myocardium, and you get myocarditis.) 3. The host response, such as abscess (staphylococci) or granuloma (TB), that destroys host tissue |
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Viral Surface Protein Receptors
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Viral Surface Protein Receptors
There are attachment points: EBV- CD21 (aka CR2) receptor on B-cells and perhaps macrophages, In the peripheral blood smear there are atypical lymphocytes in the blood are mainly CD8+ (T-cells) Rabies- acetylcholine receptor on neurons Rhinovirus- ICAM-1 on mucosal cells HIV- CD4 , CXCR4 or CCR-5 |
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Why is HIV so deadly?
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HIV Kills CD4 (Helper) T- Lymphocytes
Only 1/100,000 CD4 lymphocytes are infected Infected cells induce non-infected cells to commit suicide by APOPTOSIS and other mechanisms |
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What is the general pathogenesis of viruses?
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Viruses enter the cell and take over the cell machinery.
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What is the general pathogenesis of viruses?
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Viruses enter into the host cell and take over that cells machinery.
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Bacterial Injury
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Bacterial Injury
A lot of bacterial have Virulence genes, but some do not. (TB doesn't have any virulence genes, strep does.) Salmonella and E. coli have similar virulence genes but E. coli lacks genes for attachment and invasion. This means that E. coli lacks the ability to become a serious disease. This is a good thing because E. coli is the most common gram negative bacteria. Helicobacter pylori (gastric ulcers) and Corynebacterium diphtheria strains that do NOT produce toxins are not pathogenic. they are not pathogenic unless that have the gene to make the toxin. In Corynebacterium, this gene is found in a phage.) |
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Bacterial Adhesins
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Bacterial Adhesins:
Lipoteichoic acids on G+, Streptococci bind tightly to blood cells and oral epithelial cells Pili on G- rods and cocci- proteins at the tips of the pili bind sugars type I- mannose (UTI) type P- galactose (pyelonephritis) type S- sialic acid (meningitis) |
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Bacterial Targets
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Bacterial Targets
Unlike viruses that invade many cell types, bacteria primarily infect epithelial cells (Shigella, E. coli), macrophages (TB) or both (Salmonella, Listeria) Don't have to know below: Macrophages- receptors for Ab or C’ Epithelial Cells- many bacteria bind to integrins such as CR3 (complement iC3b) |
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Bacterial Toxins
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Bacterial Toxins
Endotoxin Exotoxin Enterotoxin - affects the gut |
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Diphtheria Exotoxin
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Diphtheria Exotoxin:
There are 2 parts to the toxin. 1. Fragment B (COOH)- attachment 2. Fragment A (NH2)- enzymatically active Connected by a S-S bridge |
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What is the pathogenesis for the Diptheria toxin?
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The Diptheria toxin attaches to cell receptors on myocytes of the myocardium. Then the toxin in split so you get the enzyme activity.
This is an exotoxin. The organism grows in the upper airway, and it releases the toxin that has its affect on the myocardial cells. |
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Immune Evasion
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Immune Evasion
1. Inaccessibility- C. difficile in the intestinal lumen there are few protective organisms in the intstine- they hide from the immune system 2. Block phagocytosis- S. pneumoniae’s mucopolysaccharide capsule - presents phagocytosis 3. Antigenic Variation- influenza virus and rhinovisus - ex. H1N1 - this virus is a dramatic departure from the influenza viruses that have been seen over the past 50-60 years - it is very different so most of us have luttel immunity to it. Most of the time, the antigenic variation is very minimal so even though we aren't totally immune, we do have some partial protection with immunity. But with H1N1, many young people have NO immunity. 4. Immunosuppression- HIV and EBV - as they infect, they suppress the immune system |
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What are the mechanisms in which organism hide from the immune system?
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Mechanisms in which organism hide from the immune system
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Diagnosing Infectious Diseases
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Diagnosing Infectious Diseases
1. Special Stains 2. Laboratory Culture 3. Nucleic acid probes (DNA probes) 4. Amplified nucleic acid probes 5. Clinical History 6. Blood - serologic testing to look for the presence of Abs |
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Special Stains for Microorganisms
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Special Stains for Microorganisms
1. Gram Stain- G+ and G- bacteria; Candida, not good for anything else 2. Giemsa Stain- bacteria, fungi (all), viral inclusions, parasites - this will miss acid fast bacteria such as TB 3. Silver Stain (GMS)- fungi and a few bacteria (Modified)-Acid-Fast Stain- mycobacteria and Nocardia |
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GRAM STAIN
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GRAM STAIN
Any fluid or tissue Screen for or identify bacteria 30 minute turnaround GPC, GPR, GNC, GNR and yeast Poor sensitivity for filamentous fungi, mycobacteria, parasites and viral inclusions |
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Giemsa Stain or Diff-Quick (rapid Giemsa) Stain
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Giemsa Stain or Diff-Quick (rapid Giemsa) Stain (very close to being equivalent)
Any tissue or fluid Works best on smears Bacteria, fungi, parasites, viral inclusions Rapid preparation (1 minute) |
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MICROWAVE GMS (Silver) STAIN
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MICROWAVE GMS (Silver) STAIN
Any tissue or fluid- 30 minutes All fungi including Pneumocystis Histoplasma, Cryptococcus, Mucor, Aspergillus Most sensitive stain for fungi Poor for bacteria and mycobacteria O.K. for Nocardia and Actinomyces |
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ACID-FAST STAINS(Kinyoun, Ziel-Neelsen, etc.)
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ACID-FAST STAINS(Kinyoun, Ziel-Neelsen, etc.)
If you think you have TB or Nocardia, use this. Carbolfucsin or fluorescent(more sensitive) “modified” AFB for Nocardia- weak acid wash Mycobacteria, Nocardia, Rhodococcus, Cryptosporidium Sputum must be decontaminated and concentrated for high sensitivity |
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What is this?
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Acid-fast Stain of M. tuberculosis demonstrating “cording”
95% of the time when you see cording, it's M. tuberculosis. |
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SPECIAL SILVER STAINS
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SPECIAL SILVER STAINS
1. Warthin Starry, Dieterle 2. Treponema pallidum 3. Legionella 4. Bartonella |
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DIRECT FLUORESCENT ANTIBODY STAIN
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DIRECT FLUORESCENT ANTIBODY STAIN
1. Sputum or respiratory washings 2. Legionella, Bordetella persussis Herpes virus and others 3. Currently, we are identifying Influenza A by DFA and most are H1N1 (by PCR) |
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Laboratory Culture
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Laboratory Culture
1. Solid Media- wounds, throat, urine, sputum 2. Broth- blood and sterile body fluids 3. Tissue Culture- virus, Chlamydia (rare) These are used less and less are more molecular testing is done. |
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DNA Probes
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DNA Probes:
1. Gonorrhea and Chlamydia from urogenital specimens 2. ID of bacterial, fungal and mycobacterial growth in broth and on solid media 3. Candida, Gardnerella and Trichomonas from vaginal discharges The most common type of DNA probe is against rRNA. |
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Amplified DNA Probes
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Amplified DNA ProbesPCR, LCR, TMA, SDA
GC and Chlamydia- urogenital swabs or urines M. tuberculosis in respiratory specimens You take a small part of the organism, you amplify it, and test for it. This increases the sensitivity. |
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Transcription Mediated Amplification (TMA)
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Transcription Mediated Amplification (TMA)
The test used for amplified TB testing. If a patient has a positive acid fast smear on a sputum, you submit that to a lab and do this test. This test uses reverse transcriptase and polymerase. |
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MRSA -
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MRSA:
The problem with methicillin resistant Staph. aureus is that they have a mutation, and the penicillin binding proteins are different, so antibiotics like methicillin and oxacillin and all of the beta-lactams don't work because the target have been modified. The gene responsible is the mecR1 gene. |
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Real-time PCR
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Real-time PCR
Results in 1-2 hours Methicillin-resistant Staphylococcus aureus (MRSA) and Group-B streptococcus/ S. agalactiae (GBS) are FDA-approved tests - these can be identified very quickly. Other tests are ASRs (analyte specific reagents) that must be validated in your own laboratory; NO ready-to-use kits The reason this real-time PCR works is that you read it before it completes. This is why its so quick. |
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Inflammatory Response to Infectious Diseases
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Inflammatory Response to Infectious Diseases
Host Dependent- eg. Greatly reduced in AIDS - In pts. with AIDS or who are very immune compromised, there may be no immune response at all so a biopsy will not show classic granulomas. PMNs- pyogenic response to many bacteria: staphylococci, streptococci, GNRs Granulomatous- tuberculosis, histoplasmosis (fungi) Lymphocytes - virus Therefore: Bacteria- usually neutrophils (PMNs); liquefactive necrosis; abscess Fungi- usually macrophages/lymphocytes; granulomas Virus- usually lymphocytes; may show cytopathic effect (CPE) Immune Deficient Host- there may be absence of the normal inflammatory response and high numbers of microorganisms (eg. M. avium in AIDS) Cytopathic- viral inclusions in Herpes and CMV or dysplastic changes in HPV Necrosis- Clostridium perfringens in gas gangrene |
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What's going on in primary TB during granuloma formation?
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Always remember INF- gamma
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TB Locations in Lung
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Primary TB - mid lung fields
Re-Activation TB - apex of lung |