Transcript Fall MSII CLIs

Fall exam 1 MSII CLIs
Bacteria and Viruses
Salmonella
Type: Gram (-) rods, motile enterobacteria, flagellate; lactose non-fermenters
-S. enterica- gastroenteritis
-S. typhimurium- osteomyelitis (in pts with sickle cell)
-S. typhi and S. paratyphi- typhoid fever (human specific)
Encounter: fecal-oral route; requires large inocula so transmission is typically through contaminated
food/water
-S. enterica- transmitted by, chicken meat, eggs, and diary
-S. typhi –typically on human carrier
Entry: Oral; often in summer; acid sensitive; require large inocula; thrive in distal ileum and colon
Spread & Multiplication: invade intestinal cells by bacterial-mediated endocytosis (using the type III
secretion system) and enter the lamina propria. Typhi: Multiplies in macrophages.
Damage:
-gastroenteritis: inflammatory mediators; neutrophils
-typhoid fever: little inflammation and dissemination of bacteria from the intestine; uses
antiphagocytic capsule (Vi antigen) to evade inflammatory response; daily fevers for 4-8 weeks
(untreated); invasion of gallbladder, kidneys, peyer patches and much more severe secondary gut
invasion.
-does not cause sustained bacteremia
Diagnosis: culture. In typhoid, can be aspirated from bone marrow when blood and urine are negative
for culture.
Tx and prevention: fluoroquinolones, resistance is starting to appear. Cooking food to completion can
help prevent infection.
Shigella
Type: Gram(-) rods; nonmotile, intracellular bacteria; lactose-negative; facultative anaerobes
-S. dysenteriae (most serious illness; developing nations)
-S. flexneri
-S. boydii
-S. sonnei (mildest form; industrialized nations)
Encounter: fecal-oral route; highly contagious= mostly person-to-person
Entry: Oral; acid resistant; thrive in colon. Invade M-cells first to gain access to basal side of
enterocytes.
Spread & Multiplication: invade intestinal cells and enter the lamina propria; spreads directly
from cell to neighboring cell (using Shigella Type III secretion effectors to manipulate the
cells actin)
Damage: Shiga toxin-kills intestinal epithelial cells by stopping protein synthesis
-dysentery (bloody stools)
-direct infection of cells and activation of intense cytokine response + ulceration of gut
wall blood and pus-containing stools
-tenesmus- painful bowel movements (blood and pus present in stools)
-bacteremia uncommon
Diagnosis: culture and agglutination reactions with antisera to group antigens
Tx and prevention: oral fluids. Antibiotics can be used to shorten length of illness; resistance is
growing. Mostly Fluoroquinolones, but some beta-lactam and cephalosporins work too.
Cryptosporidium
• Type: apicomplexan
• Encounter: zoonotic
• Entry: ingestion of cysts; fecal-oral, usually in food or water (water
sources and swimming pools)
• Spread: confined to digestive tract; do not invade mucosa or
disseminate
• Multiplication: intracellular; multiply at the apical end of epithelial
cells and are released back to the luminal surface
• Damage: infect the small intestines; cause noninflammatory, watery
diarrhea that can last for days or weeks
• AIDS pts: may have intractable cholera-like diarrhea
• Diagnosis: finding parasite in feces or fecal immunoassays
• Tx: highly resistant to most antiparasitic drugs
• Prevention: isolate raw foods and potable water from fecal
contamination
Hepatitis A
Type: Hepatovirus (picornavirus), single-stranded RNA (+),
replicates in cytoplasm, non-enveloped, icosahedral
Encounter: fecal-oral route
Entry: oral; tropism for liver cells
Spread & replication: produce only transient infection followed
by resolution
Damage: Liver cells; fever, abd pain, nausea, vomiting. In more
severe cases, Jaundice… in more severe cases, mental dysfxn
Diagnosis: testing for specific viral proteins, specific antibodies
against those proteins, or viral RNA
Tx and prevention: vaccine available
Hepatitis E (similar to HepA)
Type: Hepatovirus (orthohepevirus), single-stranded RNA (+),
replicates in cytoplasm, non-enveloped, icosahedral
Encounter: fecal-oral route
Entry: oral; tropism for liver cells
Spread & replication: produce only transient infection followed
by resolution
Damage: More severe than HepA infections (esp. pregnant
women, maybe life-threatening). Liver cells; fever, abd pain,
nausea, vomiting. In more severe cases, Jaundice… in more
severe cases, mental dysfxn
Diagnosis: testing for specific viral proteins, specific antibodies
against those proteins, or viral RNA
Tx and prevention: vaccine UNAVAILABLE
Hepatitis B
Type: Hepadnavirus, partly double-stranded circular DNA, replicates in
Nucleus by reverse transcription, enveloped
Encounter: blood borne or sexually transmitted. Perinatal exposure.
Entry: tropism for liver cells
Spread & replication: can produce lifelong persistent infection with
ongoing replication in the liver and viremia
Damage: liver cells; fever, abd pain, nausea, vomiting. In more severe
cases, Jaundice… in more severe cases, mental dysfxn. Chronic cases
lead to cirrhosis and increased risk of HCC. 5% of cases become
chronic, but exposure in childhood highly increases tendency to
become chronic.
Diagnosis: testing for specific viral proteins, specific antibodies against
those proteins, or viral RNA
Tx and prevention: vaccine! avoiding hi-risk behavior; blood bank
screening; adefovir, lamivudine, and tenofovir
Hepatitis C
Type: Flaviviridae family, enveloped, single-stranded, (+) sense
RNA
Encounter: blood borne or sexually transmitted
Entry: tropism for liver cells
Spread & replication: can produce lifelong persistent infection
with ongoing replication in the liver and viremia
Damage: liver cells; fever, abd pain, nausea, vomiting. In more
severe cases, Jaundice… in more severe cases, mental dysfxn.
Chronic cases lead to cirrhosis and increased risk of HCC. 80%
of cases become chronic.
Diagnosis: testing for specific viral proteins, specific antibodies
against those proteins, or viral RNA
Tx and prevention: avoiding hi-risk behavior; blood bank
screening. Tx with interferon-alpha and ribavirin
Hepatitis D
Type: subviral agent; single stranded circular RNA
Encounter: blood borne or sexually transmitted
Entry: tropism for liver cells; requires HBV coinfection
Spread& replication: can produce lifelong persistent infection
with ongoing replication in the liver and viremia
Damage: fever, abd pain, nausea, vomiting. In more severe
cases, Jaundice… in more severe cases, mental dysfxn.
Increases risk of fulminant hepatitis with HBV
Diagnosis: antibodies against HDAg
Tx and prevention: no specific tx. Tx Hep B infection
Streptococci (Group A)
pyogenes
• Type: Gram (+) cocci; grow in chains or pairs. Ferment carbon sources to produce lactic acid. Betahemolytic
• Encounter: human reservoir; person-to-person transmission
• Entry: strict human pathogens; colonize nasopharynx and skin
• Multiplication: extracellular, on mucous membranes, in skin, or in deeper tissue
• Spread:
• Head: Meningitis, sinusitis, otitis, pharyngitis, tonsilitis, adenitis
• Skin: impetigo, erysipelas, cellulitis, scarlet fever
• Systemic: Acute rheumatic fever, Toxic shock syndrome, Acute post-strep glomerulonephritis,
pneumonia
• Extremities: Myositis, necrotizing fascitis, puerperal fever, septic artritis, osteomyelitis
• Damage: virulence factors
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Tissue damage: Proteases, hyaluronidase, DNases, Streptokinase,
Blood Cell lysis: streptolysins S and O
M-protein-adhesion, anti-opsonization
Hyaluronic acid capsule-anti-phagocytic
Toxins: Strepococal pyrogenic exotoxins (SPE) A, B and C
• Diagnosis: culture or rapid immunoassays
• Tx: penicillin
• Prevention: no vaccine; tx prevents locally invasive infection, rheumatic fever, and transmission to
other hosts
Yersinia
Type: Gram (-) rod-shaped coccobacillus, facultative anaerobes
-Y. pestis
-Y. enterocolitica
Encounter: animal products (enterocolitica); infected fleas or aerosol (pestis)
Entry: oral or inhaled (pestis for pneumonic plague)
Spread: Mammals are reserviors for this microbe. Pestis is transmitted to humans
via fleas Enterocolitica is ingested.
Multiplication:
Damage: symptoms are age-related for Y. enterocolitica
-Y. pestis- cause of pneumonic and bubonic plagues
-Y. enterocolitica- terminal ileum, invades Peyer’s patches; causes fever, watery,
sometimes bloody diarrhea, RLQ abd pain. Systemic-type symptoms (in adults)erythema nodosum, uveitis, arthritis, mesenteric adenitis Can be confused with
appendicitis
Diagnosis: culture
Tx and prevention: can resolve untreated. Can be treated with
trimethoprim/sulfamethoxazole if symptoms become systemic
Herpes Simplex virus
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Pathogen:
• Alphaherpesvirus
• DsDNA virus
• HSV Type I and II and Varicella- Zoster crius (VZV)
Encounter:
• Almost all individuals become infected with HSV type I
• Most infections are asymptomatic
Entry:
• HSV Acquired by direct contact. VSV is usually acquired from infectious aerosols
Replication & spread:
• Establish latent infections following primary infection allowing virus to persist for life of the infected
host; can reactivate
Damage:
• Cause oral and genital herpes and occasionally encephalitis
• HSV I – primarily oral
• HSV II – primarily genital
• VZV – causes chicken pox and shingles
Diagnosis:
• Clinical presentation and virus deteciton in lesion samples, virus isolation in cell culture, or PCR
Treatment:
• Antivirals such as acyclovir. However, doesn’t prevent future recurrence
• Vaccine to prevent VZV
Candida spp.
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Pathogen:
• Round or oval yeasts that reproduce by forming buds or blastoconidia
• Potential to form hyphae in vivo
• C. albicans (most infections), C. glabrata (resistant to some antifungal agents), C. parapsilosis (central venous catheter associated
infections)
Encounter:
• Normally colonize GI tract (mouth to rectum), vagina, and skin
• Most infections endogenous
• Immunosuppressed (especially neutropenic and ICU patients.)
• Risk factors: broad-spectrum antibiotics, renal failure requiring dialysis, central venous catheters, parenteral nutrition
Entry:
• Disruption of normal flora will cause opportunistic infection
• Decreased T- cell immunity allows proliferation
• Neutropenia and central venous catheters
Spread and multiplication:
• Main host defense in T-cell mediated immunity (protects against mucosal surfaces)
• Neutrophils protect from spread through mucosa and subsequent dissemination
Damage:
• Mucosal candidiasis – adherent white plaques on oropharyngeal and vaginal mucosa (thrush); non-painful
• Proliferation in warm moist areas (intertriginous candidiasis and diaper rash)
• Underlying tissues are not damaged
• Candidemia is dissemination which can cause microabscesses in many organs, meningitis, chorioretinitis and vitritis, hepatosplenic
abscesses, and vertebral osteomyelitis. Endocarditis on prosthetic valves.
Diagnosis:
• Scrapings of lesion show budding yeast and pseudohyphae
• Blood culture for disseminated candidiasis with blood agar or Sabouraud agar (selective for fungi).
• C. albicans can be differentiated by development of germ tubes when exposed to calf serum
Treatment and prevention:
• Local antifungal topical creams/powders
• Invasive/disseminated infection can be treated with systemic fungal agent fluconazole or amphotericin B
Mycobacterium
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Pathogen: Mycobacterium tuberculosis
• Is a slow-growing, obligate aerobe
• Facultative intracellular
• The acid-fast staining characteristic of Mycobacteria spp. Results from the mycolic acid linked to the cell wall.
• Non-Gram stainable
• Thin rods
Encounter:
• This agent infects one-third of the world’s population, but only 10% of those infected develop clinical disease
Entry:
• The bacterium is usually acquired by inhaling aerosolized droplet nuclei.
Spread and multiplication:
• M. tuberculosis can cause illness that begins soon after initial infection (primary disease) or can remain latent for years before
reactivating and causing illness (endogenous reactivation).
• Chronic inflammation caused by bacterial persistence in macrophages, release of cytokines, adjuvant effect.
Damage:
• Infection may elicit a cellular immune response that controls infection, with only sequelae being a positive tuberculin skin test. Or
infection may elicit a host immune response responsible for the pathologic features of the disease. Active tuberculosis (TB) most
often causes pulmonary disease associated with fever, weight loss, and drenching night sweats . Pott’s disease = vertebral body
infection
Diagnosis:
• TB is usually diagnosed by microscopy and culture of sputum (can take 2 weeks or longer to grow)
Treatment and prevention:
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TB is treated with combination antimicrobial therapy
Pathogen: Mycobacterium leprae – Hansen’s disease
• Is a slow-growing, acid-fast bacillus that is causative agent of leprosy
• Armadillos and humans with leprosy are sources
• Causes illness that ranges between two polar forms: tuberculoid (strong immune response with few organisms) and lepromatous
(minimal immune response with immense numbers of organisms)
Pathogen: M. avium-intracellular
• Encounter: soil, water
• Typically infect AIDs patients.
Helicobacter
• Pathogen: Gram negative , helical shaped microbe with high degree genetic diversity
• Encounter:
• Infects half of the world, acquired in childhood. Fecal-oral or oral-oral routes.
• Entry:
• Able to survive in highly acidic environment of the stomach. Produces urease that buffers the
acid by producing ammonium (NH4+) from urea.
• Spread and multiplication:
• Colonizes the mucus layer and epithelial surface of the stomach.
• It evades host immunity via vacuolating toxin (VacA) that suppresses T-Cell responses
• Damage:
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VacA – causes cell death of the gastric epithelium
CagA- disrupts tight junctions between cells
Gastritis- via low levels of inflammation
Chronic infection-10% chance of developing gastric/duodenal ulcers, atrophic gastritis, and
gastric adenocarcinoma, or gastric MALT lymphoma
• Diagnosis:
• Rapid urease test, histology and microbial culture on endoscopic biopsy.
• H.Pylori specific serology and stool antigens by immunoassay- stool antigen is highly accurate.
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Triple therapy- two antibiotics with a proton pump inhibitor.
Pneumocytis
• Pathogen: Pneumocytis jiroveci (formerly Pneumocytis Carnii
aka PCP)
• Encounter:
• Opportunistic Infection -Incompetent host(HIV)- CD4 count <200
• Diagnosis: Need to use silver stain
• Treatment and prevention:
• Trimethoprim-Sulfamethoxazole(TMP-SMX) with steroids for acute
illness. May give TMP-SMX as a prophylaxis also.
Toxoplasmosis
• Pathogen: Toxoplasmosis Gondii
• Encounter:
• Cats (intestine) are definitive hosts; all other animal (sheep, pigs, cattle) s develop dormant
toxoplasmic cysts in their muscles and viscera
• Entry:
• Ingesting oocytes from cat feces or muscle cysts in undercooked meat (beef or lamb)
• Spread and multiplication:
• Enters by active invasion of the cell. Creates parasitophorous vesicle which becomes invisible
to the lysosomes
• Damage: Mono-like primary infection, chorioretinitis, congenital infection, or mass lesions
in the brain (in persons with AIDSS)
• Diagnosis:
• Competent host- elevated toxoplasmosis antibody titer especially IgM
• Incompetent Host (ie HIV)- unable to mount immunological response. Must look for ringenhancing lesions in Brain MRI.
• Congenital – Usually chorioretinitis is the first and only symptoms. May have asymptomatic or
have various learning disabilities.
• Treatment and prevention
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Competent Host- Self limited, no treatment
Incompetent host- pyrimethamine plus either sulfadiazine or clindamycin
Congenital- screen all pregnant women. Difficult to treat once in utero. Greatest chances of
congenital diseases if they seroconvert in the 1st trimester. Little effect to the fetus if they convert
in the 3rd trimester.