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481 Cards in this Set
- Front
- Back
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Which fungus causes 75% of candidiasis?
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Candida albicans
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How many species of Candida are there?
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More than 160
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How many Candida species cause infection?
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At least 13
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Which Candida species most commonly cause infection?
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Candida albicans (75%),
Candida krusei, Candida parapsilosis, Candida tropicalis |
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Is Candida albicans dimorphic?
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No, the culture and tissue forms are not fundamentally different
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Candida albicans histo
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Oval yeast
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Candida albicans in tissue
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oval yeast with pseudohyphae and true hyphae
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Which fungus forms germ tubes and under what conditions?
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Candida albicans at 37 Celcius in protein solution
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Is Candida albicans a primary or opportunistic pathogen?
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Opportunistic
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Candida albicans virulence factors
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pseudohyphae
ability to adhere to epithelial surfaces proteases, phospholipases, lipases |
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Host defenses against Candida albicans
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Normal T cell function
normal flora |
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Where is Candida albicans usually found in the body?
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normal flora of GI and vagina
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What fungus is part of normal flora?
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Candida albicans in GI and vagina
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Dzs caused by Candida albicans
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thrush,
vulvovaginitis, esophagitis, invasive candidiasis (esp. severe in neutropenics) |
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Candida albicans dx
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culture and/or visualization (no Ab or Ag testing)
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What are dermatophytes and where do they infect?
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monomorphic mycelial fungi that infect only epidermis and its appendages (hair and nails)
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Dzs caused by dermatophytes
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ringworm of the scalp and body
jock itch athlete's foot paronchyia of the nails |
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How many genera of dermatophytes are there, what are they and where do they infect?
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3:
Microsporum (hair and skin), Trichophyton (hair, skin and nails), Epidermophyton (skin) |
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What holds dermatophyte in check?
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saturated fatty acids in mammalian sebum
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What can dermatophytes do with keratin?
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degrade and utilize it
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Dermatophytosis dx
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microscopic demonstration of mycelia in scrapings of skin lesion on standard fungal media
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Is Cryptococcus neoformans a primary or opportunistic pathogen
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Primary
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Is Cryptococcus monomorphic or dimorphic?
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Monomorphic
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Crypto histo
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round yeast
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Crypto histo when grown in sexual state
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mold
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How many species of Crypto?
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38
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How many species of Crypto are pathogenic?
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1: Crypto neoformans
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Cryptococcus neoformans virulence factors
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CAPSULE!
urease positive phenol oxidase can grow at 37-39 Celsius produces mannitol |
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Which Crypto virulence factor contributes to brain edema in fungal meningitis?
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mannitol
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What is phenol oxidase?
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Crypto virulence factor
converts phenolic compounds (catecholamines: dopamine, epi) to melanin, which accumulate in cell wall and protect vs. immune system |
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2 Crypto variants
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Crypto neoformans neoformans: pigeons worldwide
Crypto neoforman gatti: eucalyptus trees in SoCal and Australia |
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How is Crypto acquired?
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via inhalation
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Dzs caused by Crypto neoformans
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Pneumonia
Fungal meningitis |
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Which fungus can cause a meningitis that presents like hydrocephalus (N/V, CN defects)?
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Crypto neoformans
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Crypto host defenses
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T cell mediated immunity
NK cells Macrophages |
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Crypto dx
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visualization (India ink of CSF), culture or latex agglutination test for Ag
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What color is Crypto on Nigerseed agar?
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black (melanin produced by phenol oxidase)
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Are fungi prokaryotes or eukaryotes?
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Eukaryotes
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Eukaryotic features of fungi
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80s ribosomes
membrane bound organelles sterols in PM nucleus with multiple linear chromosomes |
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Structure of fungi cell wall
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Chitin, glucan and polysaccharide protein complexes
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What is chitin?
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linear polysaccharide composed of N-acetyl-D-glucosamine
(also exoskeleton of crustaceans) |
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What is glucan?
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polymer of polymers of D-glucose
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What is the most common polysaccharide in fungi's polysaccharide protein complexes?
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Mannan, a polymer of D-mannose
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What functions do fungi's polysaccharide-protein complexes serve?
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Cement and immunodeterminant groups of cell wall antigens
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How do fungi acquire nutrients?
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heterotrophs, produce extracellular enzymes that break down organic material and absorb it
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Are there any obligate anaerobic fungi?
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No, there are facultative and obligate aerobic fungi, though
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Are fungi motile?
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No
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What is dimorphism?
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Existence in two different forms, for example, fungi that grow as a yeast in humans but a mold in lab
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What is a thallus?
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A visible colony of fungus
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What is a hypha?
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the principal element of mold, a tubular structure that grows by elongation into an intertwining mycelia, and may be divided into cells by septa.
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Which form of mycelia bears conidiophores?
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Aerial mycelia
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What are pseudohyphae?
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Elongated yeasts that resemble hyphae, but show constriction (not true septa) at the cell wall junctions. present in Candida albicans
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Are monomorphic molds usually primary or opportunistic pathogens?
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Opportunistic
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What are the two major groups of monomorphic molds?
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Aspergillus
Mucor and Rhizopus (Zygomycetes) |
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What makes Zygomycetes unique?
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only fungi with non-septate mycelia,
asexual spores contained within sporangia borne on sporangiophores |
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What types of people do Zygomycetes cause dz in?
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Uncontrolled diabetics and leukemics
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Are dimorphic molds usually primary or opportunistic pathogens?
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Primary
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How can you grow dimorphic fungi in the yeast form in lab?
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Grow on rich medium incubated at 37-40 celsius.
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What are imperfect fungi
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Fungi that we haven't figured out the reproductive cycle yet
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How are fungi classified?
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By morphology and reproductive structures formed during the asexual stage.
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Do fungi reproduce sexually?
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Yes
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How do yeasts reproduce?
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Budding, which leaves scars from the new cells breaking away from each other.
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How do molds reproduce?
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Spores, produced either asexually or sexually
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What are sporangiospores and which species exhibit them?
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spores that are contained in sporangia (sac-like structures), Mucor and Rhizopus
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What are arthroconidia and which species exhibit them?
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spores that develop directly in a hyphal segment and become barrel-shaped and double walled. Coccidioides
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What are macroconidia and which species exhibit them?
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Spores that are large, double-walled and multicellular, and develop within the hyphae or at the ends of hyphae. Histoplasma and dermatophytes
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What is the most common fungus in the air?
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Aspergillus
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What features do the 4 most common primary pathogenic fungi share?
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dimorphic, soil organisms, require a T-cell mediated immune response for self-limited infection
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What are the 4 most common primary pathogenic fungi?
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Histoplasma capsulatum
Blastomyces dermatitidis Coccidioides immitis Sporothrix schenckii |
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what type of conidia does Coccidioides produce?
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Arthroconidia
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Which fungi produces spherules with endospores?
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Coccidioides immitis
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Where is Coccidioides immitus found?
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growing as a mold in the soil of the Southwestern US desert and Northern Mexico
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How is Coccidioides acquired?
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inhalation of airborne arthroconidia, transformation into a spherules of endospores inside lung
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Can PMNs and macrophages kill Coccidioides spherules?
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No, spherules can survive inside them
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Dzs caused by Coccidioides immitis
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Subclinical pneumonia
Disseminated dz (meningitis, bone, skin, other organs) Meningitis (by itself) |
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Is a high titer of Coccidioides immitis Abs a good or bad sign?
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Poor prognostic sign, sign of disseminated severe infection
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What factors predispose to disseminated Coccidioides immitus dz?
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Race (black, filipino)
pregnancy immunocompromised (drug therapy, lymphoid malignancy, AIDS) |
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Coccidioides immitis dx
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culture spherules from tissue (or ID in tissue)
positive Ab titer hypersensitivity test (can be positive from prior dz, or negative due to anergy) |
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Does Coccidioides have conidiophores?
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No, it has arthrospores within the mycelia
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Histoplasma capsulatum conidia
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Microconidia and tuberculate macroconidia (pathognomic)
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Where is Histoplasma capsulatum found?
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Soil contaminated with birds and bat feces, Ohio and Mississippi River Valley
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How is Histoplasma acquired?
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inhalation of microconidia
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Can phagocytes kill Histoplasma?
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No, Histoplasma can survive inside phagocytes
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What is the most prevalent endemic mycosis in the US?
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Histoplasmosis
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Dzs caused by Histoplasma capsulatum
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Acute pulmonary infections
Severe disseminated infections (most frequent to mucosa and GI tract) Most cases are asx or self-limited |
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Factors predisposing to disseminated Histoplasma infection
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age (infancy), immunosuppression, AIDS patients
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Dx of Histoplasma capsulatum
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culture/visualization, though conversion to yeast form may be req'd
rapid urine or serum Ag test skin test sometimes, high Ab titer |
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Is a high Histoplasma Ab titer a good or a bad sign?
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Rarely, Ab titer can be used to dx it, but generally not a prognostic sign at all.
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Blastomyces dermatitidis conidia
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oval, pear-shaped conidia on short conidiophores
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Histoplasma budding in tissue
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narrow neck budding
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Blastomyces budding in tissue
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broad neck budding
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Dz caused by Blastomyces
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disseminated dz (skin, bones/joints, GU)
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Dx of Blastomyces
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visualization of yeast in tissue/culture
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Where is Blastomyces found?
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Central US (Great Lakes to Arkansas)- often hunters and woodsmen infected
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How is Blastomyces acquired?
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inhalation, though pneumonia is rare
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Sporothrix schenckii conidia
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triangular pigmented macrospores, in flower-like groups on short conidiophores
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Yeast shape of Sporothrix
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cigar shaped
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Where is Sporothrix schenckii found?
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soil enriched with vegetable matter, rose gardens, xmas tree farms
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How is Sporothrix acquired?
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Inoculation into the skin (different from the other primary pathogenic fungi!)
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Dz caused by Sporothrix
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"Alcoholic rose gardener's dz"
Ulcerated, erythematous nodule on skin with pus subcutaneous nodules from spread up lymphatics disseminated infection (RARE- only in severely immunocompromised) |
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Factors predisposing to Sporothrix infection
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malnutrition, alcoholism, and immunosuppression,
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Dx of Sporothrix
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culture
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What are the 3 medically important species of Aspergillus?
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Aspergillus fumigatus (main pathogen)
A. flavus A. niger |
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How can you differentiate the 3 Aspergillus species on slants of agar?
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Fumigatus looks like cracked ice, flavus is fluffy (with visible mushrooms), niger grows black
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Describe the hyphae of Aspergillus fumigatus
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narrow septated hyphae with branches at ACUTE angles.
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Aspergillus fumigatus conidia
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conidia come off top half of conidiophore.
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Aspergillus fumigatus histo
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gray-green mature colonies
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How is Aspergillus acquired?
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inhalation (small spores reach the alveoli)
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Dzs caused by Aspergillus fumigatus
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invasive pulmonary infections
sinus infections allergic pulmonary syndromes (esp. in asthmatics) pulmonary aspergilloma (fungus ball) if pre-existing pulmonary cavity |
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Factors predisposing to Aspergillus fumigatus infection
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neutropenia
steroids (inhibit macrophage killing) chronic granulomatous dz (WBCs have defect oxidative bursts) |
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Host defense against Aspergillus fumigatus
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PMN req'd to kill hyphae
Macrophages req'd to phagocytose and destroy spores |
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Dx of Aspergillus fumigatus
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culture/visualization in infected tissue
serum assay for galactomannan (carb found in Aspergillus) usually presumptive based on x-ray and fever in immunocompromised host on ABX |
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galactomannan
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complex carbohydrate found in Aspergillus but not in all fungi
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What are the zygomycetes?
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mucor and rhizopus oryzae
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Zygomycetes conidia
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sporangia borne on sporangiophores
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Dist. Rhizopus from Mucor
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Rhizopus has roots, Mucor does not
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How are the Zygomycetes acquired?
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Inhalation
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Dzs caused by Zygomycetes
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rhinocerebral infarction in DKA patients
dz in other predisposed (immunocompromised) populations |
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Factors predisposing to Zygomycetes infection
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Neutropenia
Diabetics (esp. in DKA) AIDS, organ transplantation.... |
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Why are diabetics predisposed to infection with Zygomycetes?
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Zygomycetes produce a siderophore that scavenges for iron, which diabetics have in abundance due to impaired transferrin binding
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What are the consequences of Zygomycetes sinus infection?
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Rapid death (can spread sinus to sinus, to palate, turbinates, orbit and brain)
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Sx of Zygomycetes sinus infection
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acute sinusitis, fever, nasal stuffiness, purulent nasal discharge, HA, sinus pain
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Sx of Zygomycetes infection spread
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tissue necrosis of the palate, destruction of the turbinates, perinasal swelling, erythema and cyanosis of facial skin, black eschar in nasal mucose or palate
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Are mycobacteria motile?
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No
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Are Mycobacteria anaerobic, aerobic, or facultative?
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Obligate Aerobic
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How long does it take to grow visible Mycobacteria colonies?
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3 weeks (they are slow growers)
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Instead of N-acetylmuramic acid, what does mycobacterium have it its cell wall?
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N-glycolylmuramic acid
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Are mycobacteria catalase positive?
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Yes, except M. kansasii and INH resistant strains
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Do mycobacterium tuberculosis have a capsule?
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No, it is unencapsulated
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Mycobacterium tuberculosis histo (acid fast stain)
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Slim rods with Irregular beading due to vacuoles and polyphosphate granules (cord factor lets it grow in serpentine cords)
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What are optimal conditions for mycobacterium tuberculosis growth?
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37 degrees Celsius, 5-10% CO2, pH 6-7.6
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Why is there confusion about the obligate aerobe status of Mycobacterium tuberculosis?
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Because it has enzymes capable of anaerobic metabolism, that are not used in vivo.
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How does Mycobacterium tuberculosis obtain iron?
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Exochelin (takes iron from ferritin), and mycobacitin (in cell envelope, grabs iron solubilized by Exochelin)
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Can mycobacterium tuberculosis grow on regular media?
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No, it requires Lowenstein Jensen media (mint ice cream green colored)
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Can Mycobacterium tuberculosis be detected by nucleic acid hybridization probes?
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Yes
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What is the doubling time of Mycobacterium tuberculosis?
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18 hours
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Tests to distinguish Mycobacterium tuberculosis from other mycobacteria
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Niacin test (non-drug-resistant strains of M. tuberculosis produce lots of niacin)
Catalase test (M tuberculosis has a heat sensitive catalase, except some INH resistant strains) Nitrate test (M. tuberculosis and M. bovis can reduce nitrate) |
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What is the Gen Probe MTD test?
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Nucleic acid identification test for Mycobacterium tuberculosis
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Is M. tuberculosis resistant to drying and most disinfectants?
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Yes
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Is M. tuberculosis resistant to formaldehyde and glutaraldehyde?
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No
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What is most of Mycobacterium's genome devoted to?
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lipid synthesis and metabolism
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Is M. tuberculosis resistant to highly polar inorganic acids and alkaline solvents?
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Yes
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Is M. tuberculosis resistant to UV and heat?
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No. 2 hours in sun kills, it, 20-30 hours if in sputum.
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Where does M. tuberculosis replicate?
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Intraphagosomally!
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Which bacteria kills guinea pigs?
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M. tuberculosis
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Which virulence factor is implicated in Mycobacteria's guinea pig killing?
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catalase (b/c catalase negative strains are less virulent in guinea pigs)
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What makes up M.tuberculosis' cell wall?
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asymmetric lipid bilayer of mycolic acids covalently bound to arabinogalactans with shorter chain glycerolphospholipids, and an inner layer of PDG
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How do you get PPD (purified protein derivative) from OT (old tuberculin)?
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Run OT through an ammonium sulfate fractionation
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M. tuberculosis virulence factors
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cord factor (trehalose 6, 6 dimycolate)
catalase, peroxidase, lipoarabinomannan sulfatides |
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What is the function of lipoarabinomannan in M. tuberculosis cell walls?
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resist host cell oxidative response, induce cytokine production, prevent apoptosis
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What virulence factors of M. tuberculosis contribute to granuloma formation?
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mycolic acid glycolipids, cord factor, waxes D
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How much of the world is infected with TB?
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1/3
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What is the typical source of infection of TB-infected people?
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Cavitary lung dz from another person
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What is the risk of TB infection proportional to?
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the intensity of exposure
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Does TB infection always lead to dz?
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No, it usually does not, unless in infants or immunocompromised people.
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Are TB cases in the US currently declining or rising?
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Declining since 1992
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Is Mycobacterium tuberculosis a zoonotic pathogen?
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No, exclusively human.
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Is Mycobacterium bovis a zoonotic pathogen?
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Yes, it is acquired from ingesting meat or milk, and causes a dz in humans indistinguishable from TB
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What is a tubercle?
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A nodular, granulomatous structure with macrophages at the center, and monocytes, alveolar macrophages, lymphocytes, etc. around it
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Does TB spread through the blood?
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First, just in the peripheral lung, but then yes, the bloodstream and lymph nodes can both disseminate infection
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Where does TB spread besides the lung?
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Liver, spleen, kidney, bone, brain, meninges and other parts of the lung
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Which immune cells are involved in immunity to TB?
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alpha-beta CD4, CD8, gamma delta, and NK T cells
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cytokines released in TB granuloma formation
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IFN gamma, IL-1, IL-12, TNF-alpha (generally TH1)
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What type of a hypersensitivity response is a positive PPD?
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Delayed type hypersensitivity
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What happens to TB hosts that can't launch a TH1 granulomatous response?
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They develop milary TB
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What % of TB granulomas reactivate the dz later?
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less than 10%
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What are Ghon complexes?
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Calcified granulomas and draining lymph nodes (remnants of primary TB infection)
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Does the necrosis from TB involve the bronchial wall?
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Yes, and this can discharge bacilli and necrotic material into the airway
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Risk factors for active TB after primary infection:
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infants/young children and elderly
HIV-infected persons IV drug users and Prison inmates Homeless Foreign born ppl from TB-endemic areas Native Americans, Blacks, Latinos Pregnancy Post-measles Alcoholism End stage renal dz, DM, immunosuppressed |
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Where does TB reactivation occur in the lung?
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Areas of high O2 tension and low lymphatic drainage (apices)
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What is the Mantoux method?
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Intradermal injection
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What is considered a positive PPD?
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>10mm in ppl with normal immune systems
>5mm in HIV ppl |
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If a person has been infected with a NTM, will they get a positive PPD?
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Yes (ex. BCG)
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Risk factors for TST (tuberculin skin test) anergy (false negative)
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HIV with T cell count<200
acute viral infections (measles) ppl with active miliary or disseminated TB (so place some other tests to check for general anergy) |
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TB dx
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Culture (GOLD STANDARD)
Ziehl-Neelson stain showing acid fast bacilli Nucleic acid assays |
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Tx of Latent TB Infection (LTBI)
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INH over 6-9 months, 4-9 months of Rifampin
beware: increased risk of hepatitis in patients over 35 yo |
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What is BCG?
|
Bacillus of Calmette and Guerin, a low virulence M. bovis strain with variable evidencial support
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Tx TB
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INH, Rifampin, Ethambutol, Pyrazinamide for 8 weeks,
INH, Rifampin for 16 weeks more "4 for 2 and 2 for 4" |
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How effective is TB tx?
|
Cures 95% of infections
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How is TB resistance acquired?
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Mutations, not plasmids
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Which mutations are responsible for INH resistance?
|
25% mutation in catalase
75% mutation in enoyl-acyl carrier protein reductase (involved in mycolic acid synthesis) |
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Are NTM exclusively human pathogens, like M. TB?
|
No, they are environmental
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Which bacteria cannot be cultured?
|
Mycobacterium leprosae
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Where can Mycobacterium leprosae be grown?
|
armadillos or mouse footpads
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What is optimal temp for Mycobacterium leprosae?
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lower than core body temp, grows best by surviving in macrophages and Schwann cells in skin and superficial nerves
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Where does Mycobacterium leprosae grow best in the infected body?
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In macrophages and Schwann cells in skin and superficial nerves
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What cell wall component is specific to Mycobacterium leprosae?
|
PGL-1, M. leprae-specific phenolic glycolipid
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What cell wall component do Mycobacterium leprosae and tuberculosis share?
|
LAM (lipoarabinomannan)
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What's Hansen's dz?
|
Leprosy
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Incubation period for leprosy
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5-7 years
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How is M. leprosae transmitted?
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Household contact, maybe mosquito or bed bug bite
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What % of ppl infected with M.leprosae develop the dz?
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10%
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States with highest M. leprosae rates
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CA, TX, NY, HI (immigrants from endemic areas)
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Endemic leprosy areas
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India, China, Brazil, Nigeria
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Tuberculoid leprosy aka
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Paucibacillary dz (since few of the bacilli are found in skin cultures)
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Treatment for leprosy
|
Dapsone, Rifampin with or without clofazimine
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Role of IFN-gamma in lepromatous granulomas
|
secreted by CD4 cells to stimulate macrophages to contain M. leprae growth
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Role of IL-2 in lepromatous granulomas
|
secreted by CD4 cells to recruit more CD4 cells
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Are CD8 cells present in a lepromatous granuloma?
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Yes, on the periphery
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Tuberculoid leprosy sx
|
anesthetic skin plaques, asymmetric peripheral nerve trunk involvement
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Which form of leprosy has a poor cell-mediated response?
|
Lepromatous
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What is the role of CD8 cells in lepromatous leprosy?
|
secrete cytokines that ENHANCE bacterial growth and inhibit CD4 function and expansion
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Which form of leprosy produces well-formed granulomas?
|
Tuberculoid
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What is the role of IL-4 in lepromatous leprosy infection?
|
secreted by CD8 cells, suppresses CD4 cell proliferation and function
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Lepromatous leprosy sx
|
symmetric skin nodules, plaques, leonine (lion-like) facies, loss of eyelashes and body hair, loss of digits secondary to trauma, and testicular dysfcn (infertility)
|
|
|
Which dz causes leonine facies?
|
Lepromatous leprosy
|
|
|
Where is Mycobacterium ulcerans endemic?
|
wetlands of tropical and subtropical Africa, Western Pacific, Asia and South America
|
|
|
How is Mycobacterium ulcerans transmitted?
|
Unknown
|
|
|
What is the 3rd most common mycobacterial infection in immunocompromised ppl?
|
Buruli ulcer (m. ulcerans)
|
|
|
What causes Buruli ulcer?
|
M. ulcerans
|
|
|
How long does it take a Buruli ulcer to develop?
|
1-2 months
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|
name the organism:single, small, painless, subq nodule on a limb expands to 15cm ulcerated nodule over months, with whole limb edema
|
M. ulcerans
|
|
|
What is a Buruli ulcer?
|
single, small, painless, subq nodule on a limb expands to 15cm ulcerated nodule over months, with whole limb edema
|
|
|
Does a Buruli ulcer yield inflammatory infiltrate/pus?
|
No!
|
|
|
Tx for Buruli ulcer
|
No antibiotics, wide surgical debridement (stop before greater disfiguring/deformity!)
|
|
|
Which mycobacteria species are not in the Runyon grouping?
|
M. leprae and M. ulcerans
|
|
|
How are NTM transmitted?
|
They are not, there's no human to human spread, people pick them up from the environment
|
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|
What settings do NTM infections occur in?
|
trauma/surgical disruption, immunosuppression, or other underlying lung disorder
|
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|
NTM Gram Stain
|
acid fast
|
|
|
Are NTM's genomes small or large?
|
Large
|
|
|
Are NTMs resistant to INH?
|
Yes, all of them.
|
|
|
NTM dx
|
acid fast staining, followed by culture (except M. leprosae) and/or 16s rRNA probes
|
|
|
Which MHC class displays NTM Ags
|
MHC Class II (After macrophage ingestion)
|
|
|
What cytokine do activated macrophages secrete to interact with T cells in a NTM infection?
|
IL-12
|
|
|
Which cytokine, released by T helper cells in the context of NTM infection, actually works AGAINST host response?
|
IL-6
|
|
|
The Runyon Classification System applies to...
|
NTM (Non Tuberculosis Mycobacterium)
|
|
|
Photochromogens are in which Runyon Class?
|
Runyon class 1
|
|
|
Scotochromogens are in which Runyon class?
|
Runyon class 2
|
|
|
Nonchromogens are in which Runyon class?
|
Runyon class 3
|
|
|
Rapid growers are in which Runyon class?
|
Runyon class 4
|
|
|
When do photochromogens produce pigment and what color?
|
Produce yellow-orange pigment when exposed to light
|
|
|
When do scotochromagens produce pigment and what color?
|
Produce yellow-orange pigment whether in light or dark
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|
|
When do nonchromogens produce pigment and what color?
|
Never, N/A
|
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|
What Runyon class is M. kansasii in?
|
Runyon 1: Photochromogens
|
|
|
What Runyon class is M. marinum in?
|
Runyon 1: Photochromogens
|
|
|
What Runyon class is M. scrofulaceum in?
|
Runyon 2: Scotochromogens
|
|
|
What Runyon class is M. avium intracellulare in?
|
Runyon class 3: Nonchromogens
|
|
|
What Runyon class is M. chelonae in?
|
Runyon class 4: rapid growers
|
|
|
What Runyon class is M. fortuitum in?
|
Runyon class 4: rapid growers
|
|
|
Are males and females equally infected by M. kansasii lung dz?
|
No, males more than females
|
|
|
Dz caused by M. kansasii
|
lung dz resembling TB
|
|
|
M. kansasii tx
|
Rifampin, Ethambutol, INH
|
|
|
Which NTM is NOT resistant to INH?
|
M. kansasii
|
|
|
M. kansasii histo
|
long, banded, beaded, "barber pole" yellow bacillus (pigment from beta carotene crystals)
|
|
|
Does M. kansasii reduce nitrate?
|
Yes, just like M. TB
|
|
|
Which NTM is antigenically similar to M. TB?
|
M. kansasii
|
|
|
Where are M. kansasii infections found?
|
Midwestern US, Louisiana, Florida and Texas, though possible anywhere
|
|
|
Is M. kansasii catalase positive?
|
Some strains, yes, some nonpathogenic strains are not.
|
|
|
Dz caused by M. marinum
|
"swimming pool granulomas"
"fish fancier's finger" abscesses at sites of abrasion |
|
|
Are M. marinum infections self-limited?
|
No, they don't heal well and last for weeks to months, responding slowly to treatment
|
|
|
Does M. marinum grow better at high or low temperatures?
|
Low, this is why it grows on sites of abrasion
|
|
|
Does M. marinum inhabit fresh or salt water?
|
Both
|
|
|
Is M. marinum zoonotic?
|
Yes, it infects many marine organisms
|
|
|
M. marinum tx
|
No standard treatment
1-4 months of rifampin, ethambutol, doxycycline, trimethoprim-sulfamethoxazole surgically debride deep hand wounds |
|
|
Dz caused by M. scrofulaceum
|
scrofula (granulomatous cervical adenitis, usually in children)
|
|
|
How does M. scrofulaceum enter the body?
|
Through the oropharynx and draining lymph nodes
|
|
|
M. avium intracellulare (MAC) complex histo
|
pleomorphic acid fast rods
|
|
|
Dzs caused by MAC
|
TB-like lung dz (in white, middle-aged smokers with COPD or bronchiectasis),
Lung infiltrates (in ppl with bronchiectasis from old TB or CF), Persistent cough and interstitial changes in right middle lobe or lingula (in non-smoking women over 50) |
|
|
MAC dx
|
sputum for AFB smear and culture
|
|
|
What is the most common cause of cervical lymphadenitis in children?
|
Scrofula
|
|
|
What is the most common NTM seen in HIV/immunosuppressed people? (presents as intermittent/persistent fever, fatigue, malaise, anorexia and weight loss, potentially anemia, diarrhea, ab pain, cough)
|
MAC
|
|
|
Is MAC a zoonotic organism?
|
No, it lives in soil and water and the environment
|
|
|
What mechanisms does MAC have against macrophages?
|
MAC can impair the superoxide anion production within the macrophage, AND inhibits phagolysosomal fusion
|
|
|
Which is easier to cure: TB or MAC?
|
TB. MAC patients typically need to be treated for prolonged periods.
|
|
|
How do you serotype MAC?
|
Sugars (there are 30 types, only a few are pathogenic)
|
|
|
How is M. avium different from M. intracellulare
|
M. avium is the name for MAC infecting immunocompromised people, whereas M. intracellulare infects normal healthy hosts
|
|
|
How can you distinguish between M. avium and M. intracellulare?
|
16S rRNA probes, though this is rarely done
|
|
|
MAC tx
|
Prophyllaxis when T cell <50: Azithromycin 1200mg q week or clarithromycin qday.
Treat active dz: Clarithromycin or Azithromcyinm, ethambutol, maybe Rifabutin |
|
|
How long does it take NTM rapid growers to make colonies?
|
5 days
|
|
|
When do M. chelonae and M. fortuitum infect?
|
post surgery, though rare cases happened post injury with contamination
|
|
|
What are M. chelonae and M. fortuitum resistant to?
|
Almost everything
|
|
|
What are M. chelonae and M. fortiutum sensitive to?
|
Clarithromycin, Amikacin, Sulfonamides and Imipenem are the best bets
|
|
|
Dz caused by M. chelonae and M. fortuitum
|
Infections of soft tissue, lung, bone, CNS, eye (keratitis, rarely)
|
|
|
Legionella histo
|
Gram negative, difficult to stain
|
|
|
Legionella metab
|
facultative intracellular (though can be cultured on agar)
|
|
|
How many species of Legionella?
|
40
|
|
|
Most important species of legionella
|
L. pneumophil (15 serotypes) most impt.
L. micdadei 2nd most impt. |
|
|
Will Legionella grow on conventional agar?
|
No
|
|
|
What kind of agar does Legionella require?
|
Buffered (pH 6.9) Charcoal Yeast Extract Agar (contains iron and cysteine)
|
|
|
What factors does Legionella require for growth?
|
Iron and cysteine
|
|
|
Is Legionella catalase positive or negative
|
Positive
|
|
|
Is Legionella gelatinase positive or negative?
|
Positive
|
|
|
Does Legionella have a beta-lactamase?
|
Yes
|
|
|
Is Legionella susceptible to beta lactams?
|
No, it has a beta-lactamase
|
|
|
Is Legionella motile or nonmotile?
|
Motile
|
|
|
What is found in large numbers when Legionella is put through gas-liquid chromatography?
|
branched-chain fatty acids
|
|
|
Where does Legionella pneumophila multiply?
|
Intracellularly in alveolar macrophages and monocytes
|
|
|
What is coiling phagocytosis?
|
Legionella pneumophile's uptake by alveolar macrophages and monocytes.
legionella's C3 attaches to phagocyte's complement receptors, and coils the membrane in with it, arranging the receptors. |
|
|
How are the cell membrane receptors rearranged upon coiling phagocytosis?
|
concentrates complement receptors in the phagosome, excludes MHC class I (marker of PM), MHC class II and transferring receptors (markers of endosome) and CD64, LAMP 1 and 2 (markers of the lysosomes).
|
|
|
What are markers of the PM that are excluded from the phagosome by Legionella in coiling phagocytosis?
|
MHC Class I
|
|
|
What are markers of the endosome that are relocated to the PM by Legionella in coiling phagocytosis?
|
MHC Class II and transferrin receptors
|
|
|
What are markers of the lysosomes that are relocated to the PM by Legionella in coiling phagocytosis?
|
CD63, LAMP1 and 2
|
|
|
What cell membrane components are concentrated in the phagosome during coiling phagocytosis?
|
complement receptors
|
|
|
Do Legionella-filled vesicles undergo acidification and phagolysosomal fusion?
|
No, this is inhibited
|
|
|
What cell structures gather around a legionella-filled phagosome?
|
ribosomes, smooth vesicles and mitochondria
|
|
|
What forms the channel through inner and outer bacterial membrane in legionella infection?
|
icm/dot gene products
|
|
|
What is the doubling time of Legionella?
|
2 hours
|
|
|
How many times does Legionella replicate intracellularly?
|
As many times as possible until the host cell is destroyed.
|
|
|
What is the primary host defense against Legionella infection?
|
Cell mediated immunity
|
|
|
How do lymphocytes participate in host response to Legionella infection?
|
Lymphocytes become sensitive to Legionella and secrete cytokines that activate macrophages
|
|
|
How do macrophages participate in host response to Legionella infection?
|
Macrophages are activated by cytokines from lymphocytes, downregulate the complement receptor to limit the uptake of Legionella, and IFN-gamma activates monocytes to limit iron availability by down-regulating transferrin receptors, iron uptake and intracellular ferritin concentrations
|
|
|
How do PMNs participate in host response to Legionella infection?
|
release apolactoferrin (when endocytosed by monocytes, helps limit iron available to Legionella)
|
|
|
How do humoral immunity/Abs participate in host response to Legionella infection?
|
They are not effective, Legionella resists killing by Ab and complement. Ab actually works against the host by promoting uptake of L. pneumophil by macrophages
|
|
|
Can Legionella be killed by Ab and complement?
|
No, Abs actually help L. pneumophila uptake by macrophages
|
|
|
Where are legionella infections found (geographically)?
|
Worldwide
|
|
|
What is the most likely time of year to get a Legionella infection?
|
Summer (air conditioners!)
|
|
|
Risk factors for legionella infection
|
Age>30,
men>women immunocompromised cigarette smoking alcohol abuse |
|
|
Are most Legionella infections fatal or nonfatal?
|
Most are mild.
|
|
|
How is Legionella transmitted?
|
Inhaled from mist, no person-to-person or fomite spread
|
|
|
Sources of legionella
|
air-conditioning equipment
respiratory therapy devises shower heads whirlpools mist generators |
|
|
Is Legionella zoonotic?
|
yes, unicellular aquatic organisms are thought to be its reservoir.
|
|
|
Is asx Legionella infection associated with a high or low Ab titer?
|
High Ab titer
|
|
|
Dzs caused by Legionella
|
Asx infection (high Ab titer)
Legionnaire's Dz Pontiac fever |
|
|
What is the incubation period of Legionnaire's dz?
|
2-10 days
|
|
|
What is the incubation period of Pontiac fever?
|
1-2 days
|
|
|
Stages of Legionnaire's dz
|
incubation 2-10 days
Stage 1: mild flu-like illness Stage 2: mod. severe pneumonia Stage 3: multilobar pneumonia (often severe and fatal- 5-30%) |
|
|
What is the mortality rate from severe Stage 3 legionnaire's dz?
|
5-30%
|
|
|
Sx of Pontiac fever
|
mild fever
|
|
|
Dx Legionella (gold standard! and others)
|
culture Legionella from sputum, pleural fluid and blood.
Also available: fluorescent staining or gene probe of sputum/tissue, ELISA for Ag in urine, retrospective serology |
|
|
Tx Legionella
|
community acquired: erythromycin or long-acting macrolides
Immunocomp or hospitalized: Azithromycin or fluoroquinolone |
|
|
Does L. pneumophila make protective Abs?
|
It has been demonstrated in guinea pig vaccines.
|
|
|
Characteristics differentiating atypical pneumonia
|
insidious onset
lower fevers less localized consolidation on CXR |
|
|
Most common organisms causing Atypical pneumonia
|
Mycoplasma pneumoniae
Chlamydia pneumoniae Legionella pneumophile |
|
|
What ABX do atypical pnuemonias respond to?
|
Doxycycline
Erythromycin |
|
|
Most common organisms causing typical pneumonia
|
Strep pneumo
Haemophilus influenza Klebsiella pneumoniae |
|
|
Which intracellular pathogens live in the phagolysosome?
|
Coxiella brunetti
Leishmania |
|
|
Which intracellular pathogens live in the cytosol?
|
Rickettsia
Shigella Listeria monocytogenes |
|
|
Which intracellular pathogens live in phagosome (and prevent phagolysosomal fusion)?
|
Mycobacterium tuberculosis
Ehrlichia Chlamydia Legionella Toxoplasma gondii |
|
|
Which intracellular pathogen adheres to endothelial cells and is engulfed, but can be grown on special media?
|
Bartonella
|
|
|
Rickettsia, Coxiella, Ehrilichia and Bartonella histo
|
Gram negative but requires Giminez/Giemsa/Macchiavello stain,
|
|
|
What is the vector of Family Rickettsiaceae?
|
arthropod
|
|
|
Arthropod characteristics
|
articulated exoskeleton, insects (6 legs) and arachnids (8 legs)
|
|
|
mechanical vector borne transmission
|
a vector transmits pathogen from 1 host to another, but is not essential in the life cycle of the pathogen
|
|
|
biological vector borne transmission
|
vector is essential to life cycle of the pathogen it carries (pathogen develops or multiplies in the body of the vector)
|
|
|
Transovarian transmission
|
infection of all progeny via their infected mother
|
|
|
Transtadial transmission
|
infection throughout different life stages (even when metamorphically different!)
|
|
|
What time of year are arthropod borne diseases more prominent?
|
Summer (lots of bugs, lots of people outside)
|
|
|
Why is an arthropod reservoir an advantage for an intracellular pathogen like Rickettsia?
|
Rickettsia shows transovarian transmission and arthropods have very large numbers of progeny
|
|
|
Typhus group of genus Rickettsia consists of
|
R. prowazekii
R. typhi |
|
|
Spotted fever group of genus Rickettsia consists of
|
R. rickettsii
|
|
|
How are the typhus group and spotted fever group of genus Rickettsia differentiated?
|
Serologically by LPS reactivity on IFA
|
|
|
What genus was Orientia tsutsugamushi a former member of?
|
genus Rickettsia
|
|
|
How does Rickettsia species disseminate?
|
Disseminate via bloodstream, parasitize endothelial cells
|
|
|
Dzs caused by endothelial cell damage by Rickettsia
|
Vasculitis,
Obstruction, Capillary leaks, Thrombosis, Rash (incl. palms and soles), Organ damage, Shock |
|
|
Clinical triad of Rickettsia/Rocky Mountain Spotted Fever
|
fever
HA rash |
|
|
If you suspect a Rickettsial infection, should you confirm the diagnosis?
|
Treat first, then serologically confirm dx. untreated has high mortality rate!
|
|
|
Rickettsia tx
|
Tetracyclines,
long acting macrolides, fluoroquinolones (anything that can reach a therapeutic intracellular concentration) |
|
|
How do Rickettsia and Orientia adhere to endothelial cells?
|
adhere to XOL receptors via a slime layer
|
|
|
How do Rickettsia and Orientia escape from the phagosome?
|
Phospholipase
|
|
|
How do Rickettsia and Orientia get out of the cell in order to infect the next one?
|
They subvert actin and propel themselves to the end of the cell, protrude and infect the next cell. OR they lyse the cell, releasing Rickettsia to be taken up by other cells
|
|
|
What components of host defense act against Rickettsia?
|
Humoral and cell-mediated (activated macrophages kill Ab-coated extracellular Rickettsia)
|
|
|
What is the agent of epidemic typhis?
|
Rickettsia prowazekii
|
|
|
What is the agent of endemic (murine) typhus?
|
Rickettsia typhi
|
|
|
What make provoke an epidemic of typhus?
|
War, famine
|
|
|
How is R. prowazekii transmitted?
|
person to person VIA body louse vector
|
|
|
What are reservoirs of R. prowazekii?
|
humans
flying squirrels |
|
|
Is the body louse (pediculus humanus) a reservoir of R. prowazekii?
|
No, it dies of the infection, so humans and flying squirrels are the reservoirs and body louse is the vector
|
|
|
Overall mortality of epidemic typhus (untreated)
|
40%
|
|
|
Dzs caused by R. prowazekii
|
epidemic typhus
Brill-Zinsser dz |
|
|
What is Brill-Zinsser dz?
|
a mild illness caused by reactivation of dormant R. prowazekii
|
|
|
Where in the US is endemic (murine) typhus seen?
|
California/Texas border regions, Hawaii
|
|
|
What are the most important vectors for Rickettsia typhi in the US?
|
Rats, opossums and rat fleas
|
|
|
What are vectors of Rickettsia typhi in the US?
|
Cats, rat fleas
|
|
|
Mortality of endemic (murine) typhus untreated
|
2%
|
|
|
What causes Rocky Mountain Spotted Fever?
|
Rickettsia rickettsii
|
|
|
What are the vectors of Rickettsia rickettsii?
|
ticks of Dermacentor species
|
|
|
Which US states have highest rates of Rocky Mountain Spotted fever?
|
Oklahoma and North Carolina
|
|
|
What are the reservoirs of Rocky Mountain Spotted Fever?
|
ticks (transovarian and transtadial passage), various mammals
|
|
|
What time of year are Rickettsia rickettsii infections most likely?
|
Summer
|
|
|
What is SIRS?
|
Systemic Inflammatory Response Syndrome: a widespread inflammatory response to a variety of severe clinical insults.
|
|
|
SIRS consists of 2+ of:
|
1. Temperature >38 or <36
2. Heart rate >90 bpm 3. Respiratory rate >20 breaths/min, or PaCO2 <32mmHg 4. WBC>12,000 cells/mm3, <4000cells/mm3 or >10% immature/bands |
|
|
Sepsis
|
systemic response to infection (SIRS plus evidence of infection)
|
|
|
Severe sepsis
|
sepsis plus organ dysfunction,
hypoperfusion, or hypotension |
|
|
Clinical manifestations of hypoperfusion
|
lactic acidosis,
oliguria, acute alteration in mental status, etc. |
|
|
A septic patient requires inotropic or vasopressor support, despite adequate fluid resuscitation. Are they considered to be in septic shock?
|
Yes
|
|
|
septic shock
|
sepsis with hypoTN despite adequate fluid resuscitation, combined with perfusion abnormalities (lactic acidosis, oliguria, acute alteration in mental status, etc.).
|
|
|
hypotension
|
systolic BP<90mmHg, or a reduction of >40mmHg from baseline (in the absence of other causes for the fall in BP)
|
|
|
multiple organ failure
|
presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention
|
|
|
Sx of septic shock (in addition to SIRS and signs of infection)
|
Feeling of impending doom,
Organ damage (liver, kidney, lung, heart, gut) DIC- disseminated intravascular coagulation, Activation of neuroendocrine axis, Cytokine induction (IL-1, 6, 10, 12, TNF and others) |
|
|
Which cytokines are induced in septic shock?
|
IL-1, 6, 10, 12, TNF and others
|
|
|
What % of patients with septic shock have bacteremia?
|
50%
|
|
|
What % of septic shock patients with +blood cultures grow gram negative rods?
|
35%
|
|
|
What % of septic shock patients with +blood cultures grow gram positive organisms?
|
35%
|
|
|
What % of septic shock patients with +blood cultures grow a mixed infection?
|
19%
|
|
|
What % of septic shock patients with +blood cultures grow fungi?
|
13%
|
|
|
Can the site of infection help you predict clinical outcome in septic shock patients?
|
Yes
|
|
|
Is the source of septic shock infection usually endogenous or exogenous?
|
Endogenous
|
|
|
Most common sites of infection leading to septic shock
|
lungs
abdomen urinary tract |
|
|
Is the incidence of sepsis increasing or decreasing?
|
Increasing
|
|
|
What factors contribute to the increasing incidence of sepsis?
|
Aggressive oncological therapy,
widespread corticosteroid and immunosuppressant use, antimicrobial resistance, increased use of invasive devices, longer lives of the predisposed (elderly, diabetics, cancer patients) |
|
|
Why is it difficult to do a good sepsis study (to identify a good treatment)?
|
patients are heterogeneous,
multiple triggers, therapies may be trigger-specific, multiple cytokines involved, blocking one has little effect. |
|
|
Therapies for septic shock that have been tried and failed include:
|
Anti-inflamm. meds,
anti-endotoxin therapy (monoclonal Abs to lipid A), anticytokine therapy (IL-1inhibitors, TNF inhibitors), iNOS inhibitors |
|
|
mainstay of septic shock therapy
|
appropriate antibiotic therapy,
good quality ICU care, careful attention to fluids and pressors |
|
|
Early in sepsis, which is dominant, pro-inflammatory or anti-inflammatory?
|
Pro-inflammatory is dominant
|
|
|
Late in sepsis, which is dominant, pro-inflammatory or anti-inflammatory?
|
Anti-inflammatory becomes dominant
|
|
|
What about the anti-inflammatory dominant state post-sepsis predisposes patients to opportunistic infections?
|
Immune cells apoptosis
|
|
|
Early in sepsis, which is dominant, coagulation or fibrinolysis?
|
Coagulation is dominant
|
|
|
The initial pro-inflammatory response to sepsis includes what cytokines?
|
TNF, IFN-gamma, IL-1, IL-6, IL-12
|
|
|
In early sepsis, how are coagulation proteins activated?
|
by TF expression on macrophages and endothelial cells
|
|
|
In early sepsis, how is fibrinolysis inactivated?
|
By loss of activated protein C and thrombomodulin from endothelial cells
|
|
|
What causes the relaxation of arteriolar SM in early sepsis?
|
iNOS transcriptional activation
|
|
|
Is complement involved in sepsis?
|
Yes, it is activated in early sepsis
|
|
|
What anti-inflammatory cytokines/inhibitors are released by the body in response to a pro-inflammatory septic response?
|
IL-10, soluble TNF receptors, IL-1 receptor type 1, IL-1 receptor antagonist
|
|
|
What is the mortality rate from septic shock?
|
30-50%
|
|
|
In septic shock, which organs may be affected and how?
|
Lungs: ARDS
Kidneys: Acute tubular necrosis Liver: hepatitis Heart: decrease contractility Brain: confusion |
|
|
What are PAMPs?
|
Pathogen Associated Molecular Patterns
|
|
|
What bacterial products set off the systemic cascade that results in septic shock?
|
LPS/endotoxin
PDG Bacterial lipoproteins Mycobacterium tuberculosis lipoproteins and lipoarabinomannan Flagellin Heat shock proteins |
|
|
What is the most common and most potent bacterial potentiator of sepsis?
|
LPS
|
|
|
What does TLR-2 interact with?
|
PDG
bacterial lipoproteins lipoteichoic acid fungal glycan |
|
|
What does TLR-4 interact with?
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LPS, heat shock proteins
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What does TLR-5 interact with?
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flagellin
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Which cells respond in sepsis?
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Macrophages, PMNs, Endothelial cells and Epithelial cells
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How many macrophage genes are transcriptionally activated by microbial products?
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over 100 genes
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What mediators do macrophages secrete in response to sepsis?
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IL-1, 6, 8, 10, 12, GMCSF, TNF, reactive O2 intermediates, PAF, LTs
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What macrophage cell membrane components are upregulated in sepsis?
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MHC, ICAM, VCAM, Tissue Factor
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Besides genes, mediators and cell membrane components, what else is upregulated in macrophages in sepsis?
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Upreg of the respiratory burst through the induction of inducible nitric oxide synthetase (iNOS)
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What is required for an endothelial cell response to sepsis?
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Soluble CD14
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What causes endothelial cells to upregulate integrins in sepsis?
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Inflammation, IL-1 and TNF
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Which integrins do endothelial cells upregulate in sepsis?
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ICAM, VCAM and ELAM
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Which cytokines/mediators do endothelial cells produce in sepsis?
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IL-1, 6, 8, TNF, endothelin, PGs
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What relation do endothelial cells have with muscular response to sepsis?
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iNOS is upregulated in endothelial cells, producing NO that diffuses to arteriolar SM causing relaxation and low SVR (systemic vascular resistance)
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What happens to tight junctions between endothelial cells in sepsis?
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Tight junctions loosen
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Which cells apoptose in sepsis?
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Immune cells (leaving patient predisposed to opportunistic infections), and endothelial cells (which can lead to irreversible organ damage)
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What is upregulated in epithelial cells in sepsis?
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VCAM, ICAM, IL-1, IL-6, TNF
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Which cytokines engage in a positive feedback loop in epithelial cells during sepsis?
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IL-1 and TNF
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Which types of epithelial cells respond to LPS?
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Bladder and respiratory epithelial cells
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Which set of signal transducing receptors is highly conserved between species (i.e. between fruit flies and humans)?
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TLRs
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How does TLR-4 binding to LPS lead to transcriptional activation of genes?
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TLR4 complexes with CD14 and MD2 (extracellular molecule associated with TLR4), and when it binds LPS, it phosphorylates specific transmembrane tyrosines that activate intracellular signaling cascades leading to transcriptional activation
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Which immune cell receptors or plasma proteins bind LPS?
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TLR4, CD14, and LBP (LPS binding protein)
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What is LBP
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LPS binding protein, 60kD acute phase plasma protein that tightly binds LPS and enhances cell responses by catalzying CD14's binding to LPS
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In sepsis, are levels of LBP increased or decreased?
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Usually LBP = 5 microg/mL
In sepsis, LBP>100 microg/mL |
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What is CD14?
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CD14 is a 55kD glycoprotein, present in cell surface (GPI-anchored in macrophages and neutrophils, no TM domain) and plasma (as sCD14), that binds many things and serves as a pattern recognition receptor.
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What can CD14 bind?
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LPS, PDG, heat shock proteins among other things
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Is LBP produced by immune cells?
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No (I think), it is found in the plasma.
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Does CD14 transmit an intracellular signal?
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No, it is a pattern recognition receptor that allows immediate response to invasion by bringing bacterial Ags to the membrane of macrophages and neutrophils.
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What causes scrub typhus?
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Orientia tsutsugamushi
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Dz caused by Orientia tsutsugamushi
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scrub typhus
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Where is Orientia tsutsugamushi found?
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Asia Pacific rim
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What is Orientia tsutsugamushi's vector?
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Chiggers- larval stage of trombiculid mites
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What is Orientia tsutsugamushi's reservoirs?
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Chiggers- larval stage of trombiculid mites (transovarial passage)
Rodents |
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Which drugs have Orientia tsutsugamushi shown resistance to?
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Doxycycline and chloramphenicol
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Dz caused by Coxiella brunetti
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Q fever (query fever)
Acute: pneumonia, sometimes with pericarditis a/o myocarditis or HA aseptic meningitis a/o encephalitis Chronic: endocarditis and hepatitis |
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How does Coxiella brunetti survive adverse environmental conditions?
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obligate intracellular parasite with a "spore-like" body that resists drying and other environmental conditions
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How is Coxiella acquired?
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inhalation, or ticks
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What are reservoirs of Coxiella?
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sheep and cattle
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Where in the body does Coxiella concentrate?
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Placenta
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Where does Coxiella replicate?
|
within the phagolysosome (where it lives)
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Ehrlichia histo
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obligate intracellular Gram negative bacteria
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Do Ehrlichia have LPS?
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No
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What differentiates Ehrlichia from Rickettsia?
|
Ehrlichia can make ATP
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Ehrlichiosis resembles what other dz?
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Rocky Mt Spotted Fever (RMSF), except most patients don't get the rash
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What is the mortality rate for Ehrlichiosis?
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1-3%
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Ehrlichiosis tx
|
doxycycline, before you've even confirmed the diagnosis
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What type of illness does not require laboratory confirmation before treatment is indicated?
|
Rickettsial dz
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Ehrlichiosis sx
|
undifferentiated fever with potential complications such as
meningoencephalitis, ARDS, toxic shock-like illness |
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Types of Ehrlichiosis
|
HME - human monocytic ehrlichiosis
HGE/HGA - human granulocytic ehrlichiosis/anaplasmosis |
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What causes HME?
|
Ehrlichia chaffeensis infects monocytes, causes leukopenia
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Where does HME occur?
|
Rural southeastern and south central regions of the country
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What is HME's reservoir?
|
white tailed deer
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What is HME's vector?
|
lone star tick ("Amblyomma americanum")
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What causes HGE/HGA?
|
Anaplasma phagocytophilum infects granulocytes, causes leukopenia
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What is HGE/HGA's vector?
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ticks of the Ixodes species
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What is HGE/HGA's reservoir?
|
small mammals such as mice (Peromyscus leucopus)
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What types of patients get fulminant dz from Ehrlichia?
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immunocompromised, elderly, those lacking spleens (asplenic)
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Dzs caused by Bartonella
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B. henselae - cat scratch dz
B. henselae and B. quintana- bacillary angiomatosis in AIDS patients B. quintana- trench fever B. bacilliformis - Carrion's dz |
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How is Bartonella henselae acquired?
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scratch of a young cat
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What is the vector of Bartonella henselae?
|
Fleas between cats, cats to humans
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What type of cells does Bartonella henselae invade?
|
Endothelial cells
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Sx of cat scratch dz
|
low grade fever
malaise painful, tender lymph node |
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|
Best stain for visualizing Bartonella
|
silver stain
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What culture conditions does Bartonella require?
|
specific media and 5% CO2. slow growth
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What species of Bartonella cause bacillary angiomatosis in AIDS patients?
|
B. henselae and B. quintana
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What is the mechanism of Bacillary Angiomatosis?
|
Bartonella spreads to angioblasts, causes angioproliferation and hemangioma-like lesions in the liver and spleen or skin and bone (different species affect different organs)
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When did B. quintana "trench fever" epidemics occur?
|
WWI
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Who does B. quintana affect currently?
|
Homeless individuals, esp. chronic alcoholics
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What is B. quintana's vector?
|
Human body louse
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What is the vector of B. bacilliformis (Carrion's dz)?
|
sandflies of the Phelobotomus genus
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Where is B. bacilliformis endemic?
|
Andean regions of Peru, Colombia and Ecuador
|
|
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what is the course of Carrion's dz?
|
Biphasic-
acute septicemic phase (Oroya fever) and chronic verruga peruana phase |
|
|
Sx of Oroya fever
|
fever, HA, anorexia, malaise.
lasting several days to a few weeks. acute septicemic phase of Carrion's dz |
|
|
Sx of verruga peruana
|
eruptive hemangioma-like skin nodules.
chronic phase of Carrion's dz |
