Microbiology Flashcards
6-year-old immigrant from Eastern Europe having difficulty breathing. Has fever, not eating or drinking. Neck swelling, palatal paralysis, and gray pharyngeal exudate. No vaccination history.
• Diphtheria (caused by Corynebacterium diphtheriae).
• Acute infection of the naso-oropharynx transmitted via respiratory droplets.
• Pseudomembranous pharyngitis (gray pharyngeal exudate)
• Sx. Sore throat, fever, LAD, upper airway dyspnea, odynophagia.
•Diphtheria toxin has tropism for neural/cardiac tissue –> can cause CNS/cardiac sequelae.
• Diphtheria infection associated with 5-10% mortality rate, esp in young patients or those with myocarditis.
• Cardiomyopathy is the most common cause of death.
• Tx. Diphtheria antitoxin (passive immunization)- inactivates all circulating toxin but ineffective against toxin that has already gained access to cardiac or neural cells.
• Rapid administration of antitoxin essential –> transfer of pre-existing neutralizing antibodies.
• Penicillin or erythromycin kills bacteria, halting release of new exotoxin into bloodstream and preventing transmission.
• TDaP vaccine (active immunization)- provides lasting immunity against future infection.
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Diphtheria exotoxin
AB toxin that ADP-ribosylates and deactivates elongation factor-2, inhibiting protein synthesis. Tropism for neural and cardiac tissue.
Most common causes of viral meningitis
•Enteroviruses (eg, coxsackievirus, echovirus, poliovirus) –> cause 90% of aseptic meningitis cases
• Arboviruses
•HSV type 2
•Mumps virus, but unlikely in fully immunized child. •Meningitis caused by mumps virus accompanied by parotitis in 50% of cases.
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Most common causes of bacterial meningitis
Adults: Streptococcus pneumoniae, Neisseria meningitidis
Neonates: Group B streptococcus (S. agalactiae), gram-negative bacilli
CSF profile of viral (aseptic) meningitis
• Sx. Fever, headache, vomiting, stiff neck, typically less severe sx than bacterial meningitis. No focal neurologic signs, seizures, AMS.
• CSF WBC count: less than 500, lymphocytic predominance
• CSF Glucose: normal or slightly reduced
• CSF Protein: usually less than 150 mg/dL
•CSF Gram stain/culture: No organisms identified.
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CSF profile of bacterial meningitis
• CSF WBC count: greater than 1000, neutrophilic predominance
• CSF Glucose: less than 45 mg/dL
• CSF Protein: greater than 250 mg/dL
•CSF Gram stain/culture: often positive for specific organism
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Bronchiolitis
•Lower respiratory tract infection most commonly caused by respiratory syncytial virus (RSV) and typically in infants less than 2 years old.
•Presents with low-grade fever, cough, tachypnea, and increased work of breathing (retractions and nasal flaring).
• Apnea in high-risk patients (less than 2 months old or premature).
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Disseminated mycobacterial disease in infancy or early childhood
•AR deficiencies of IFN-γ receptor (or other elements in IFN-γ signaling pathway) lead to impaired IFN-γ-mediated immunity.
•Can cause disseminated mycobacterial disease in infancy or childhood, including disseminated infection by the BCG vaccine strain if administered.
• Once identified, patients require lifelong treatment with continuous antimycobacterial agents.
• Host defense against mycobacterial infections depends on interactions btw macrophages and T cells through the IFN-γ and IL-12 signaling pathway.
• IFN-γsecreted by TH1 cells or NK cells is key to elimination of these infections.
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IFN-gamma signaling pathway
• Møs infected by mycobacteria produce IL-12, which stimulates TH1 cells and NK cells to produce IFN-γ.
• IFN-γ binds to its receptor on the Mø, leading to dimerization of receptor and activation of intracellular JAK1 and 2.
• STAT1 activation by JAK1 and JAK2 leads to nuclear translocation of STAT1 and transcription of IFN-γ-regulated genes that promote intracellular killing.
• IFN-γ also enhances viral and parasitic resistance by increasing MHC expression and intrinsic defense factors.
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C3 deficiency
Predisposes to recurrent infections with encapsulated organisms.
C5-C9 deficiency
Predisposes to recurrent infections with Neisseria meningitidis or N gonorrhoeae. C5-C9 = membrane attack complex (MAC).
Isotype switching
• Isotype switching to IgE induced by IL-4
• Isotype switching to IgA induced by IL-5
•Occurs in naive B lymphocytes on initial exposure to antigen.
• Primarily induced by CD40 interaction with CD40L on T-helper cells, which then secrete IL-4 and IL-5.
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HBV infection
•Worldwide, countries with high rates of HBV infection have more than 85% of all hepatocellular carcinoma (HCC) cases.
•Korea, Taiwan, Mozambique, and China have the highest annual rates of HCC.
• Individuals who develop HCC in those countries usually have chronic HBV infection acquired through vertical transmission at childbirth.
• In US, HCC normally arises after age 60, while in these countries with high rates of HBV infection, HCC commonly presents in adults 20-40 years old.
• Universal vaccination of children against HBV infection would likely cause a steep decline in worldwide incidence of HCC.
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HBV phases of infection
- Proliferative phase- entire virion and related antigens of the episomal HBV DNA are present. HBsAg and HBcAg are expressed with MHC Class I molecules on hepatocyte cell surface, activating cytotoxic CD8+ T lymphocytes, which respond by destroying infected hepatocytes.
- Integrative phase- HBV DNA is incorporated into the host genome of those hepatocytes that survived the immune response. Infectivity ceases and liver damage tapers off when the antiviral antibodies appear and viral replication stops. However, risk of HCC remains elevated due to HBV DNA integration into host genome.
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Features of systemic mycoses
• Cause pneumonia and can disseminate
• Dimorphic fungi: cold=mold, heat=yeast
• Exception: coccidioidomycosis is a spherule (not yeast) in tissue.
• Tx fluconazole/itraconazole for local infection.
• Tx amphotericin B for systemic infection.
• Systemic mycoses can form granulomas (like TB) but cannot spread person-to-person (unlike TB).
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Histoplasmosis
•Pneumonia-like sx caused by infection with Histoplasma capsulatum
• Location: Mississippi and Ohio River valleys
• Macrophages filled with Histoplasma (organisms smaller than an RBC).
• Histo “hides” within macrophages.
•Associated with bird (eg, starlings) or bat droppings and cave exploring
• Tx fluconazole/itraconazole for local infection
• Tx amphotericin B for systemic infection
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Blastomycosis
• Pneumonia-like sx caused by infection with Blastomyces dermatitidis
• Location: Eastern US and Central America
•Inflammatory lung disease and can disseminate to skin and bone, causing granulomatous nodules.
• Broad-base budding (same size as an RBC).
• Blasto buds broadly.
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Coccidioidomycosis
• Pneumonia-like sx caused by infection with Coccidioides immitis or Coccidioides posadasii
•Location: Southwest US, California
• Pneumonia and meningitis, can disseminate to skin and bone
•Case rate increases after earthquakes, b/c spores in the dust are thrown into the air and inhaled by people, forming spherules in the lungs.
• Spherule filled with endospores (much larger than RBC)
•”San Joaquin Valley Fever”
•”Desert bumps” = erythema nodosum
•”Desert rheumatism” = arthralgias associated with dissemination.
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Paracoccidioidomycosis
•Caused by Paracoccidioides brasiliensis
• Location: Latin America
•Budding yeast with “captain’s wheel” formation (much larger than RBC)
•PARAcoccidio PARAsails with the Captain’s Wheel all the way to Latin America.
•Tx with fluconazole/itraconazole (local), Amphotericin B (systemic)
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Aerobes
• Nagging Pests Must Breathe • Nocardia • Pseudomonas aeruginosa • MycoBacterium tuberculosis • Reactivation TB ---> predilection for lung apices ******************************
India ink stain
• Cryptococcus neoformans
• Mucicarmine can also be used to stain thick polysaccharide capsule red
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Exotoxin
• Present in both gram + and gram - bacteria
• Gene for exotoxin on plasmid or bacteriophage
• Polypeptide secreted from cell
• Fatal dose on order of 1 µg
• Induces high-titer antibodies called “antitoxins”
• Toxoids used as vaccines
• Ex. tetanus toxin, botulinum toxin, diphtheria toxin
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Capsule
• Organized polysaccharide layer that protects against phagocytosis
• Bacillus anthracis is only bacteria to have poly-D-glutamate capsule instead of polysaccharide
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Charcoal-yeast extract agar buffered with cysteine and iron
• Legionella pneumophila
• Think: “Legionnaire (soldier) with SILVER helmet sitting at a campfire (CHARCOAL) with his IRON dagger - he is no sissy! (CYSTEINE)”
• Silver stain to see legionella, doesn’t gram stain
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Eosin-methylene blue (EMB) agar
• E. coli colonies grow with green metallic sheen
• Other lactose fermenters grow as purple/black colonies
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Ecthyma gangrenosum
Rapidly progressive necrotic cutaneous lesion caused by Pseudomonas, typically seen in immunocompromised patients.
Obligate intracellular pathogens
• “Stay inside when it’s Really CHilly COld!”
• Rickettsia
• Chlamydia
• Coxiella
• These pathogens rely on host ATP to replicate/survive and thus are obligate intracellular pathogens.
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Facultative intracellular pathogens
• Some Nasty Bugs May Live FacultativeLY • Salmonella • Neisseria • Brucella • Mycobacterium • Listeria • Francisella • Legionella • Yersinia pestis ******************************
Ziehl-Neelsen stain
• Aka carbol fuchsin stain
• Stains acid-fast bacteria: Mycobacteria (stains mycolic acid in cell wall), Nocardia (weakly), protozoa (eg, cryptosporidium oocysts)
• Cheaper alternative with greater sensitivity but decreased specificity: auramine-rhodamine
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Hemolytic Uremic Syndrome
• E coli 0157: H7
• Triad of anemia (MAHA), thrombocytopenia (platelet consumption), and acute renal failure (decreased RBF) due to platelet microthrombi on damaged endothelium.
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EHEC
• Enterohemorrhagic E. coli
• Most common serotype in the US is E coli 0157:H7
• Undercooked meat/raw leafy vegetables
• Shiga-like toxin causes HUS
• Dysentery (toxin alone causes necrosis and inflammation)
• Doesn’t ferment sorbitol, differentiating EHEC from other E. coli
• HUS, Hamburgers, Hemorrhagic diarrhea
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Sabouraud agar
• Grows fungi
• “Sab’s a fun guy!”
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MacConkey agar
• MacConKEE'S agar • Klebsiella • E coli • Enterobacter • Serratia (grows weakly/slowly) • Lactose-fermenting enterics (eg, E. coli) grow on this agar • Contains a pH indicator • Fermentation of lactose creates acidic metabolites causing colonies to turn pink ******************************
Spores
• Keratin-like coat over bacterium
• Some bacteria can form spores at the end of the stationary phase when nutrients are limited.
• Only Gram + bacteria.
• Spores highly resistant to dehydration, heat, and chemicals, no metabolic activity
• Dipicolinic acid, peptidoglycan, DNA
• Must autoclave to potentially kill spores by steaming at 121 celsius for 15 mins.
• Bacillus anthracis - Anthrax
• Bacillus cereus - food poisoning
• Clostridium botulinum - botulism
• Clostridium difficile - pseudomembranous colitis
• Clostridium perfringens - gas gangrene
• Clostridium tetani - tetanus
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Anaerobes
• Anaerobes "Can't Breathe Fresh Air" • Clostridium spp. • Bacteroides fragilis • Fusobacterium • Actinomyces • Foul smelling, difficult to culture, produce gas (CO2, H2) in tissue, normal flora in GI tract • Susceptible to oxidative damage • AminO2glycosides ineffective against anaerobes b/c they require O2 to enter the bacterial cell wall. ******************************
Organisms seen best with silver stain
• Fungi (eg, coccidioides, Pneumocystis jiroveccii)
• Legionella pneumophila
• Helicobacter pylori
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Gram-negative coccobacilli
• Haemophilus influenzae: requires X and V factors, pleomorphic
• Legionella pneumophila: charcoal/yeast agar with Fe and cysteine, silver stain
• Bordetella pertussis: Bordet-Gengou agar, pertussis toxin, tracheal cytotoxin, anti-FHA vaccine
• Coxiella burnetii: Q fever, spores inhaled from cattle/sheep amniotic fluid, culture-negative endocarditis
• Brucella: aerobic, zoonotic, unpasteurized dairy
• Francisella tularensis: requires cysteine, ticks/rabbits/deer flies
• Pasteurella multocida: oxidase +, catalase +, cellulitis/osteomyelitis, animal/cat/dog bite
• Bartonella henselae: cat scratch disease
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Gram-negative diplococci
• Neisseria meningitidis: aerobic, maltose and glucose utilizer
• Neisseria gonorrhoeae: aerobic, glucose utilizer only
• Moraxella catarrhalis: aerobic, oxidase +
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Gram-negative curved bacilli
• Campylobacter jejuni: microaerophilic, oxidase +, catalase +, urease –, grows in 42 C, assoc. with Guillain–Barré syndrome
• Helicobacter pylori: microaerophilic, oxidase +, catalase +, urease +, silver stain
• Vibrio cholerae: oxidase +, glucose +, grows in alkaline media, non-lactose fermenting
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Gram-negative bacilli
• Bacteroides fragilis: strict anaerobe
• Klebsiella pneumoniae: fast lactose fermenter
• Escherichia coli: fast lactose fermenter, indole +
• Enterobacter spp: fast lactose fermenters
• Citrobacter: slow lactose fermenters
• Serratia: slow lactose fermenters
• Pseudomonas aeruginosa: non-lactose fermenting, oxidase +
• Salmonella typhi, enteritidis: motile, non-lactose fermenting, oxidase –, H2S producing on TSI agar
• Proteus mirabilis: non-lactose fermenting, oxidase –, H2S producing on TSI agar, urease +
• Shigella dysenteriae: non-motile, non-lactose fermenting, oxidase –, non-H2S producing on TSI agar
• Yersinia pestis: non-lactose fermenting, oxidase –, non-H2S producing on TSI agar, bipolar staining
• Yersinia enterocolitica: non-lactose fermenting, oxidase –, non-H2S producing on TSI agar, motile at 25 C, not at 37 C
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Haemophilus influenzae
• Small gram-negative coccobacillus
• Aerosol transmission, human-to-human
• Cultured on chocolate agar with factors V (NAD+) and X (hematin) for growth –> can also be grown with S aureus, which provides factor V through RBC hemolysis.
• Nontypeable (unencapsulated) strains are the most common cause of mucosal infections (otitis media, conjunctivitis, bronchitis) since Hib vaccine
• Produces IgA protease, protecting organism from secretory IgA
• HaEMOPhilus causes:
• Epiglottitis (“thumbprint sign” on X-ray)
• Meningitis
• Otitis media
• Pneumonia
• Hib vaccine: type B capsular polysaccharide and PRP (polyribosylribitol phosphate) conjugated to diphtheria toxoid: given to 2-18 months old
• Dx: +Quellung reaction, immunofluorescence, or growth on chocolate agar with factor X and V.
• Tx: amoxicillin/clavulanate for mucosal infections, ceftriaxone for meningitis, rifampin prophylaxis for close contacts
• Hib causes meningitis most commonly in infants after maternal Ab protection has declined (6 months) and before they have developed their own Abs.
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Bordetella pertussis
• Gram-negative aerobic coccobacillus
• Virulence factors: pertussis toxin (disables Gi by ADP-ribosylating it, leading to uninhibited AC and increased cAMP, which causes lymphocytosis and impairs phagocytosis to permit its own survival) and tracheal cytotoxin (kills ciliated cells impairing mucous clearance)
• Whooping cough = child coughs on expiration and whoops on inspiration, mechanism unknown, spreads bacteria
• May be mistaken as viral infection due to lymphocytic infiltrate resulting from immune response
• Filamentous hemagglutinin (FHA) = adherence to ciliate epithelium of respiratory tract
• Tdap and DTaP vaccines (2, 4, 6, 18 months) generate Anti-FHA antibodies
• 3 stages of whooping cough:
• Catarrhal stage (1-2 weeks): flulike sx, highly contagious
• Paroxysmal stage (3rd week-2 months): intermittent bouts of many coughs on a single expiration followed by a whooping inspiration
• Recovery stage (2-3 months): coughing subsides
• Tx. erythromycin only useful before paroxysmal stage aka if already whooping, supportive care
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Legionella pneumophila
• Gram-negative coccobacillus, gram stains poorly, best seen with silver stain.
• Grows on charcoal yeast extract medium with cysteine and iron
• Detected by urine antigen
• No person-to-person transmission
• Aerosol transmission from contaminated environmental water source (eg, air conditioning systems, hot water tanks), adheres to respiratory epithelium via pili, phagocytosed by alveolar macrophages
• Legionnaires’ disease: severe atypical PNA, CXR reveals nodular infiltrates (micro-abscesses in lungs), fever, GI sx (diarrhea), CNS sx, hyponatremia on labs, common in smokers and patients with chronic lung disease
• Pontiac fever: mild flu-like illness lasting 2-5 days
• CAP in elderly smokers
• Tx. erythromycin, azithromycin (macrolide)
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Coxiella burnetii
• Small gram-negative coccobacillus
• Obligate intracellular pathogen
• Q fever, presents as pneumonia, no rash
• Most common cause of culture-negative endocarditis
• Spores inhaled as aerosols from cattle/sheep amniotic fluid
• Coxiella genus morphologically similar to Rickettsia but with differences
• No arthropod vector
• Endospores highly resistant to high temperature, osmotic pressure, UV light and can survive outside
• Tx. Doxycycline
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Francisella tularensis
• Gram-negative coccobacillus, pleomorphic!
• Requires cysteine for growth
• Tularemia- site-specific infection: ulceroglandular tularemia (ulcer with black base), oculoglandular (conjunctival infection), pulmonary tularemia (inhalation), typhoidal tularemia (GI ingestion).
• Transmission from rabbits to humans by tick bite/infected animal, bacteria phagocytosed, localize to RES, cause caveating granulomas (conjunctiva, lungs, GI tract), regional LAD and long-lasting fever.
• Papule develops into ulcer with black base, erythematous tender surrounding, axillary LNs on same side enlarged
• Vector = ticks
• Source: deer flies, rabbits (eg, rabbit farm)
• Dx. Skin test (delayed-type hypersensitivity response), serology
• Tx. streptomycin, live-attenuated vaccine for high-risk individuals
• F. tularensis and BCG (for TB) are the only live-attenuated vaccines for bacteria.
• Most cases occur in Arkansas, Oklahoma, Missouri
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Pasteurella multocida
• Gram-negative coccobacilli with “bipolar staining”, oxidase +, catalase +
• Cellulitis or osteomyelitis (sharp cat’s teeth can directly implant into bone) following cat/dog bite with local LAD
• Inhabits oral cavity of animals, enters human skin via bite, elicits inflammatory response at inoculation site and spreads locally.
• May progress to septicemia
• Transmission: animal bite
• Source: cats, dogs
• Dx, Gram stain
• Tx. penicillin G, clean and drain wound, suturing wound could worsen infection by creating closed anaerobic environment
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Brucella spp.
• Gram-negative aerobic coccobacillus, facultative intracellular
• Brucellosis- undulant fever, fatigue, spinal tenderness, anorexia, enlarged LNs
• Undulating fever- fever rises during the day and peaks after dinner, declines at night, lasts for months
• Phagocytosed in macrophages –> caseating granulomas and abscess formation
• Unpasteurized dairy (eg, imported goat cheese)
• Brucellergin skin test (delayed-type hypersensitivity response) indicates current or previous exposure
• Tx. doxycycline + gentamicin
• Osteomyelitis is most common complication
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Bartonella henselae
• Gram-negative coccobacillus best seen with silver impregnation stains
• Varying clinical presentations of “cat scratch disease”: regional lymphadenopathy and FUO in immunocompetent patients
• Cats are natural reservoir–> inoculate humans with bite/saliva/scratch causing primary cutaneous lesion–> regional LAD from local skin infection
• Disseminated infection in HIV+ patients: ocular infection (Parinaud’s oculoglandular syndrome, granulomatous conjunctivitis, periauricular LAD, optic neuritis), bacillary angiomatosis (bxp of skin lesions show granulomatous inflammation with clusters of bacilli), CNS infection (encephalitis, transverse myelitis, cerebellar ataxia), myalgias, arthralgias, osteomyelitis, necrotizing granulomas causing HSM or peliosis hepatis (blood-filled cavities throughout liver)
• Dx based on serology, blood cx, PCR or bxp of lesion showing granulomatous inflammation with bacilli
• Doxycycline or Azithromycin
• Cat fleas implicated in transmission between cat, and flea feces implicated in transmission to humans
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Quellung reaction
Biochemical reaction in which antibodies bind to bacterial capsule of Streptococcus pneumoniae, Klebsiella pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, and Salmonella. Antibody reaction allows these species to be visualized under a microscope. If reaction is positive, capsule becomes opaque and appears to enlarge.
HACEK organisms
• Gram-negative bacilli of normal oral flora that can infect heart valves • Most common gram-negative causes of endocarditis in non-IV drug users •Haemophilus species • Actinobacillus actinomycetemcomitans • Cardiobacterium hominis • Eikenella corrodens • Kingella ******************************
Neisseria meningitidis
• Gram-negative diplococci within PMNs
• Meningococcemia = fever with petechial hemorrhages and gangrene of toes
• IgA protease allows N. meningitidis to cross mucosa into bloodstream via phagocytic vacuoles–> meningococcemia –> endotoxin release leads to vascular necrosis and hemorrhage in skin –> petechial rash
• Pathogens may have tropism for meninges–> meningitis
• Waterhouse-Friederichsen syndrome = fulminant meningococcemia with vascular necrosis and hemorrhage in adrenal glands causing adrenal insufficiency, fever, DIC, and shock –> multiorgan failure
• LP reveals increased PMNs, increased protein, decreased glucose and gram-negative intracellular diplococci
• Dx. selectively grows on Thayer-Martin media, metabolizes maltose AND glucose (MeninGitidis vs. N. gonorrhoeae)
• Tx. Ceftriaxone or penicillin G, rifampin for close contacts as prophylaxis, vaccine with capsular polysaccharides
• Most common causes of meningitis from 6-60 years old: N. meningitidis, Enterovirus, S. pneumoniae.
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Neisseria gonorrhoeae
• Gram-negative diplococci within PMNs
• Local gonorrhea = may be asymptomatic, urethritis/dysuria (in men), cervicitis (in women), or ophthalmia neonatorum (risk for blindness)
• Systemic gonorrhea = septic arthritis, organisms can invade submucosa and enter bloodstream, collecting in synovial fluid
• In women, cervicitis may progress to uterus, fallopian tubes, and ovaries, causing pelvic inflammatory disease and increased risk for ectopic pregnancies
• Complications: PID, ectopic pregnancy, sterility, Fitz-Hugh-Curtis syndrome (bacterial infection from fallopian tubes may spill into the peritoneal cavity causing infection of the liver capsule)
• Virulence factors: specialized pili (allows attachment to mucosal cells of urethra/vagina, antigenic variation to evade host defense, prevent phagocytosis), IgA protease, endotoxin
• Dx. selectively grows on Thayer-Martin media, metabolizes glucose but not maltose (vs. N. meningitidis)
• Tx. ceftriaxone (+ doxycycline (or azithromycin) for probable concurrent Chlamydia coinfection)
• Prophylactic erythromycin eye drops for all neonates to prevent blindness
• Antigenic variation of pili makes vaccine development difficult and prevents immunity, allowing for recurrent gonorrhea infections.
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Neisseria gonorrhoeae vs. Neisseria meningitidis
• Both gram-negative diplococci, oxidase +
• Gonococci ferment Glucose only
• MeninGococci ferment Maltose and Glucose
• Gonococci have no capsule
• Meningococci have a polysaccharide capsule
• Gonococci have no vaccine due to antigenic variation of pilus proteins
• Meningococci have a vaccine against polysaccharide capsule
• Gonococci are sexually or perinatally transmitted
• Meningococci are transmitted via respiratory/oral secretions and are more common in close quarters (eg, army bases, college dorms)
• Gonorrhea is treated with ceftriaxone (+doxycycline, erythromycin eye ointment in neonates to prevent conjunctivitis and blindness
• Meningococcemia is tx with ceftriaxone, prophylaxis with rifampin, ciprofloxacin, or ceftriaxone given to close contacts of infected patients.
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Moraxella catarrhalis
• Gram-negative diplococci
• Otitis media, sinusitis, pneumonia
• Normally colonizes nasopharynx–> spreads to contiguous mucosal surfaces and releases endotoxin, stimulating an inflammatory response
• Virulence factors: specialized pili (antigenic variation to evade immunity), endotoxin
• Dx. hydrolyzes tributyrin, produces DNAse, reduces nitrite/nitrate, dose not utilize sucrose/glucose/maltose/lactose
• Tx. amoxicillin-clavulanate (95% produce beta-lactamase), 2nd or 3rd gen cephalosporins, TMP-SMX
• Second most common cause of bacterial PNA in patients with COPD behind nontypeable H. influenzae
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Gardnerella vaginalis
•Pleomorphic gram variable rod
• Causes bacterial vaginosis (BV) - gray vaginal discharge with fishy odor, nonpainful, not sexually transmitted, overgrowth of anaerobic bacteria in vagina
• Dx. “clue cells” on wet mount (vaginal epithelial cells covered with Gardnerella), amine whiff test (10% KOH) –> fishy odor
• Tx. metronidazole or clindamycin
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Campylobacter jejuni
• Gram-negative curved S-shaped rod with polar flagellum (motile), oxidase +, urease –
• Presents clinically with bloody or secretory diarrhea
• Carried by poultry/cattle –> transmitted by fecal-oral route or unpasteurized milk –> colonizes terminal ileum/colon and often invades –> may release enterotoxin and cytotoxin
• Grows best at 42 C, microaerophilic (lower oxygen than atmospheric)
• Tx. erythromycin, ciprofloxacin
• Many cases of Guillain-Barré syndrome (GBS) thought to be complications of Campy infections
• Can also cause reactive arthritis
• Rotavirus, ETEC, and C. jejuni are most common causes of diarrhea world-wide
• Major cause of bloody diarrhea in children
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Helicobacter pylori
• Gram-negative spiral-shaped bacilli with polar flagellum (motile), oxidase +, urease +, catalase + (triple positive)
• May present as acute gastritis or chronic antrum gastritis, pangastritis, or peptic ulcers
• Organism colonizes gastric antrum but does not invade–> produce ammonia (via urease) to protect from acidic environment –> host inflammatory response leads to mucosal damage and loss of mucus-secreting cells –> acute gastritis
•If gastritis limited to antrum –> somatostatin secretion by D cells in antrum decreases, causing acid hypersecretion and risk of duodenal ulcers
• If pangastritis –> acid hyposecretion –> chronic infection and inflammation –> risk of gastric ulcers and gastric carcinoma
• Chronic H. pylori gastritis is associated with gastric adenocarcinoma and MALT lymphoma
• Dx. urease + breath test (C14-labeled urea breath test, urea ingested and labeled CO2 exhaled if urease bacteria present), or fecal antigen, IgG titer in serum, biopsy showing gram-negative rods
• Tx. Amoxicillin + Clarithromycin + PPI (Antibiotics Cure Pylori)
• Tx. If allergic to penicillin: PPI + BMT (bismuth, metronidazole, tetracycline)
• 100% of duodenal ulcers vs. 70% of gastric ulcers are associated with H. pylori infection
• Ulcers associated with infection have “punched-out” appearance and smooth borders, while ulcers associated with malignancies have heaped borders.
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Vibrio cholerae
• Gram-negative, flagellated, comma-shaped rod, single flagella
• Oxidase +, grows in alkaline media, lactose non-fermenter, glucose fermenter
•Water, food, shellfish –> very sensitive to stomach acid –> large inoculum is required (ID50), but much lower inoculum required in people on chronic PPIs or H2 blockers with less acidic stomach pH –> produces mucinase to digest mucous coat on intestinal cells –> attaches to proximal small intestine with little competition from other bacteria
• Endemic to developing countries
• Cholera toxin (carried on bacteriophage): ribosylates Gs –> permanent Gs activation –> increased AC activity –> increased cAMP –> crypt cells secrete more Cl- into bowel lumen, villous cells absorb less Na+ –> osmotic H2O efflux –> “rice-water” diarrhea and severe dehydration
• Flat yellow colonies on TCBS agar
• Tx. oral rehydration solution (glucose + Na) or IV fluids to prevent hypovolemic shock/death, tetracycline
• ORS capitalizes on Na-glucose cotransporters in small intestine
• Blood group O patients are more vulnerable!
• Vibrio parahaemolyticus = similar but associated with raw seafood consumption (Japan), grows in 8% NaCl and more invasive
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Bacteroides fragilis
• Gram-negative obligate anaerobic rod
• Large capsule gives colonies mucoid appearance
• Only gram-negative rod without typical endotoxin (inactive LPS); Listeria monocytogenes is only gram+ with endotoxin
• Presents clinically with peritonitis or GI/pelvic abscesses (below the diaphragm)
• Normal GI flora (make vitamin K) –> ruptured intestinal mucosa (trauma, surgery, perforation) –> spills into peritoneum with GI facultative anaerobes –> catalase and SOD allow pathogen to survive in oxygen environment until all O2 used up and organism thrives –> purulent abscess formation
• Tx. drain abscess + repair lesions + metronidazole/clindamycin
• May cause pelvic abscesses 2/2 septic abortions or IUDs
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Klebsiella pneumoniae
• Gram-negative rod, fast lactose fermenter
• Presents as pneumonia or nosocomial UTI
• Aspiration of intestinal flora in elderly, unconscious, or alcoholics –> pneumonia (most frequently right upper lobe) –> large antiphagocytic capsule causes mucoid colonies –> stimulates inflammation, necrosis, forms cavity –> bloody “currant jelly” sputum
• Klebsiella causes UTIs when all competing bacteria are killed (eg, hospital-administered antibiotics) and when urinary tract is blocked by catheter or stone
• Tx. third-generation cephalosporin, very drug-resistant
• 4 A’s of KlebsiellA: Aspiration PNA, Abscess in lungs/liver, Alcoholics, diAbetes
• Similar nosocomial infections are caused by the lactose fermenters: Klebsiella, Serratia marcescens, Enterobacter
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EIEC
• Gram-negative rod, fast lactose fermenter
• Enteroinvasive E. coli
• Invasive –> adhere to colonic epithelium –> invade mucosa causing necrosis and inflammation
• Dysentery aka bloody diarrhea
• Similar presentation to Shigella –> bloody diarrhea with leukocytes in stool
• Tx. rehydration
******
EPEC/EAEC
• Gram-negative rod, fast lactose fermenter
• Enteropathogenic E. coli, Enteroaggregative E. coli
• No toxin produced
• Adhere to ileal epithelium but do not invade –> induce structural changes in mucosa –> flatten intestinal villi (effacement) causing malabsorption and diarrhea
• EPEC = “infants diarrhea” in newborn nurseries
• EAEC = diarrhea in children
• Think E”P”EC in “P”pediatrics!
• Tx. rehydration
******
ETEC
• Gram-negative rod, fast lactose fermenter
• Enterotoxigenic E. coli
• E”T”EC = Traveler’s diarrhea, produces enTeroToxins
• Watery diarrhea (like Vibrio cholerae), no invasion/inflammation
• Adhere to jejunum/ileum but do not invade
• Produce heat-labile toxin (LT) and heat-stable toxin (ST) enterotoxins, which both contribute to watery diarrhea
• LT = similar to cholera toxin: ADP ribosylates Gs –> activates AC –> increased cAMP –> crypt cells secrete more Cl-, villous cells absorb less Na+ –> osmotic loss of water to lumen –> watery diarrhea
• ST = similar to Yersinia enterocolitica toxin: activates guanylate cyclase –> increased cGMP –> decreased cotransport of NaCl into cells –> water remains in lumen of gut –> watery diarrhea
• Tx. rehydration
******
EHEC
• Gram-negative rod, fast lactose fermenter
• Enterohemorrhagic E. coli
• Adhere to colonic epithelium but do not invade –> secrete cytotoxic Shiga-like toxins 1 and 2 –> inflammation, bleeding –> hemorrhagic colitis –> SLTs and endotoxin may enter bloodstream, spreading to kidneys and causing damage aka HUS = fever, hemolytic anemia, thrombocytopenia, acute renal failure
• SLT (verotoxin): inactivates 60S ribosome subunit –> blocks protein synthesis –> cell death –> hemorrhagic colitis
• SLT = Shiga-like toxin
• Tx. rehydration
******
What are the different types of Enterovirulent Escherichia coli (EEC)?
• Gram-negative rod, fast lactose fermenter, green metallic sheen on EMB agar, light purple on MacConkey agar, serology (O and H antigens)
• EnteroInvasive E. coli (EIEC) invades intestinal wall to produce severe bloody diarrhea
• EnteroHemorrhagic E. coli (EHEC): E. coli 0157:H7 causes bloody diarrhea and HUS
• EnteroToxigenic E. coli (ETEC) produces toxins that act on the intestinal lining, and is the most common cause of traveler’s diarrhea.
• EnteroPathogenic E. coli (EPEC) causes diarrhea outbreaks in newborn nurseries.
•Enteroaggregative E. coli (EAEC) causes acute and chronic (long-lasting) diarrhea in children.
• Tx. rehydration
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Escherichia coli
• Gram-negative rod, fast lactose fermenter
• May present as enteritis (watery/bloody diarrhea depending on strain), UTI, pneumonia, neonatal meningitis, septic shock (endotoxin release), HUS
• Normal flora of humans –> virulent strains transmitted via fecal-oral route –> use pili to adhere
• Virulence factors: K antigen = capsule, O antigen = component of LPS in outer membrane, H antigen = flagella, pili mediate attachment to specific sites, endotoxin (lipid A component of LPS) causes septic shock
• UTIs caused by pathogen adhering to urethra (urethritis) –> may ascend to bladder (cystitis) –> or kidneys (pyelonephritis)
• E. coli toxins: ST and LT in ETEC, SLT in EHEC
• Dx. green metallic sheen on EMB agar, light purple colonies on MacConkey agar, serology (O and H antigens)
• Tx. rehydration for diarrhea, TMP-SMX or penicillin for UTIs, third-generation cephalosporin for meningitis/sepsis
• E. coli is the most common cause of UTI and gram-negative sepsis
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Most common causes of neonatal meningitis and neonatal pneumonia
• Neonatal meningitis: Group B Streptococcus, E. coli, Listeria
• Neonatal pneumonia: Group B streptococcus, E. coli
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Salmonella spp. (not S. typhi)
• Eg, Salmonella enteritidis
•Gram-negative flagellated (motile) rod, non-lactose fermenter, oxidase –, H2S-producing
• Human and animal reservoir (poultry, eggs, pets, turtles)
• Hematogenous spread
• Virulence factors: endotoxin, H antigen (flagella)
•High infectious dose (ID50, inoculum) required
• Immune response = PMNs
• Gastroenteritis/diarrhea usually caused by non-typhoidal Salmonella
• Tx. aggressive rehydration, antibiotics not indicated as prolong the duration of fecal excretion (carrier state)
• Tx. only for patients with risk of invasive disease or neonates
• Turtles or uncooked chicken are common sources of Salmonella gastroenteritis
• No vaccine
******
Salmonella typhi
• Gram-negative flagellated (motile) rod, non-lactose fermenter, oxidase –, H2S-producing
• Asx carriers, vs. typhoid fever vs. osteomyelitis in patients with SCD (functionally asplenic)
• Human reservoir only –> fecal-oral transmission –> penetrate colonic mucosa (hematogenous spread) –> capsular Vi polysaccharide allows survival in phagocytes of Peyer’s patches –> spread via phagocytes to gallbladder, liver, spleen –> release endotoxin –> typhoid fever –> may progress to carrier state
• Carrier state: stored in gallbladder (esp gallstones) –> may reenter bowel to spread via feces–> may present with S. typhi-induced necrotizing cholecystitis
• Virulence factors: endotoxin, Vi capsule, H antigen (flagella)
•High infectious dose (large inoculum) required to overcome gastric acid defense
• Immune response = monocytes
• Constipation followed by diarrhea
• Tx. abx prolong duration of fecal excretion and increase chance of relapse
• Ciprofloxacin/ampicillin may be used for carriers or cholecystectomy may be necessary
• Oral vaccines are killed or live attenuated, IM vaccine (Vi capsular polysaccharide)
• Typhoid fever = rose spots on abdomen, constipation, GI pain, fever, followed by diarrhea
• Tx with ceftriaxone/fluoroquinolone for resistant strains
******
Shigella spp
• Gram-negative non-lactose fermenter, oxidase –, does not produce H2S, no flagella, non-motile
• Four F’s for transmission: Fingers, Flies, Food, Feces
• Human reservoir only –> fecal-oral –> endocytosed by colonic epithelium –> escapes vesicles –> replicate intracellularly and spread cell-to-cell (no hematogenous spread) –> mucosal ulcers and bleeding –> damage prevents fluid reabsorption –> bloody diarrhea
• Virulence factors: endotoxin, Shiga toxin (inactivates 60S ribosomes, further damage to mucosa), invasion is the key to pathogenesis (little toxin-mediated effects)
• O antigen: polysaccharide in outer membrane used to classify Shigella genus into 4 groups
• Low infectious dose (small inoculum) required, resistant to gastric acid, hypochlorhydric patients not at increased risk
• Immune response = PMNs
• Bloody diarrhea (dysentery)
•Tx. antibiotics shorten duration of fecal excretion, rehydration for moderate cases, fluoroquinolones for severe cases
• No vaccine
• Order of decreasing virulence for Shigella spp: Shigella dysenteriae, S. flexneri, S. boydii, S. sonnei (least amount of toxin produced)
• Shiga toxin (like SLTs produced by EHEC) can cause HUS
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Yersinia enterocolitica
• Gram-negative rod, non-lactose fermenter, oxidase –, does not produce H2S, motile at 25 C not at 37 C
• Transmitted from pet feces, contaminated milk, pork
• Acute diarrhea (enterocolitis) or mesenteric adenitis
• Raw milk or fecal-oral route –> terminal ileum –> heat-stable enterotoxin –> diarrhea –> invades and spreads to colon –> ulceration and bleeding –> bacteria carried to mesenteric LNs by lymphatics –> replicates in LNs –> swelling of mesenteric LNs (adenitis)
• Pseudo-appendicitis - RLQ abdominal pain 2/2 mesenteric adenitis or terminal ileitis
• Rarely causes septicemia, usually self-limiting
• Most common complication is arthritis
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Pseudomonas aeruginosa
• Gram-negative rod, non-lactose fermenter, oxidase +
• Aerobic, flagellated (motile), produces pyocyanin pigment (blue-green colonies), grape-like odor
• Associated with moisture (eg, respiratory equipment, visitor’s flowers, endoscopes)
• Endotoxin (shock), pyocyanin (generates ROS)
• Exotoxin A: ADP ribosylates host EF2 –> paralyzes host cell protein machinery (similar to diphtheria toxin)
• Phospholipase C: cleaves phosphates from phospholipids –> damages host cell membrane –> phosphates feed microorganism
• Elastase: cleaves elastin, collagen, complement components, Igs –> dissemination
• Inhabits many environments: soil, water, colon
• CP: chronic pneumonia (CF patients); UTI (hospital patients); burn wound infection (ecthyma gangrenosum), septicemia; endocarditis (IVDUs); osteomyelitis (DM, IVDUs); malignant external otitis (DM); hot tub folliculitis; other ifxns in hosts with weakened immunity
• Mucoid polysaccharide capsule creates biofilms
• AERuginosa = AERobic
• Tx. CAMP FIRE
• Carbapenems (imipenem, monopenem), Aminoglycosides (gentamicin), Monobactams (Aztreonam), Polymyxins (colistin), Fluoroquinolones, thIRd generation cephalosporins (ceftazidime, cefepime), Extended-spectrum penicillins (piperacillin, ticaricillin)
• Tx. anti-pseudomonal penicillin + aminoglycoside (eg, piperacillin + gentamicin) or fluoroquinolones
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PSEUDOMONAS
• Pneumonia (CF pts), pyocyanin (ROS), phospholipase C
• Sepsis (due to endotoxin)
• Ecthyma gangrenosum, Exotoxin A, Endotoxin
• UTIs (hospital patients)
• Diabetes/IVDU (endocarditis)
• Osteomyelitis (eg, puncture wounds)- DM/IVDU
• Mucoid polysaccharide capsule, Motile
• Otitis externa (swimmer’s ear or malignant OE in DM), Oxidase +
• Nosocomial infections, Non-lactose fermenter
• Aerobic, exotoxin A
• Skin –> hot tub folliculitis
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Proteus mirabilis
•Gram-negative rod, non-lactose fermenter, oxidase –, urease +, many flagella, very motile, “swarming” growth
• Normal GI flora –> enter through urethra –> urease splits urea to form ammonium hydroxide, increasing urinary pH –> precipitation of ammonium magnesium phosphate stones –> struvite calculi –> stones backlog urine causing damage to kidney and serving as sites of persistent infection
• O antigen used in Weil-Felix reaction used to diagnose Rickettsia –> Proteus antigens cross-react with patient’s serum antibodies against Rickettsia
• Large radiopaque stones (struvite stones) in urinary tract
• Alkaline urine (high pH)
• Tx. TMP-SMX, ampicillin
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Yersinia pestis
• Gram-negative rod, lactose non-fermenter, bipolar staining (looks like a safety-pin)
• Bubonic plague, fleas are the vector, rodents and prairie dogs are the reservoir
• Causes fever, dark black skin patches, enlarged, painful LNs in groin
• Endotoxin causes DIC –> cutaneous hemorrhagic necrosis causing black color (“Black Death”)
• Regional lymphadenitis = buboes, often in groin
• Capsular F-1 antigen prevents phagocytosis, generates antibody response
• Streptomycin, tetracycline
• Vaccine: killed and attenuated vaccines available, generate antibodies against F1 antigen
******
Anaplasma spp.
• Ixodes tick is vector (mice and deer)
• Granulocytes with morulae in cytoplasm ("MEGA berry")
• Monocytes = Erlichiosis
• Granulocytes = Anaplasmosis
• Tx. doxycycline
******************************Ehrlichia chafteensis
• Lone Star tick is vector
• Monocytes with morulae in cytoplasm, mulberry-like inclusions, ("MEGA berry")
• Monocytes = Erlichiosis
• Granulocytes = Anaplasmosis
• Tx. doxycycline
******************************Gram-positive bacilli
• Bacillus cereus: spore-forming, aerobic, motile
• Bacillus anthracis: spore-forming, aerobic, non-motile
• Clostridium tetani: spore-forming, obligate anaerobe, motile
• Clostridium botulinum: spore-forming, obligate anaerobe, motile
• Clostridium difficile: spore-forming, obligate anaerobe, motile
• Clostridium perfringens: spore-forming, obligate anaerobe, non-motile
• Listeria monocytogenes: non-spore forming, motile
• Corynebacterium diphtheriae: non-spore forming, non-motile
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Gram-positive branching filaments
• Actinomyces: anaerobic, not acid-fast
• Nocardia: aerobic, weakly acid-fast
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Gram-positive cocci (all aerobic)
• Staphylococcus aureus: catalase +, coagulase +, β-hemolytic
• Staphylococcus epidermidis: catalase +, coagulase –, novobiocin sensitive
• Staphylococcus saprophyticus: catalase +, coagulase –, novobiocin resistant
• Streptococcus pyogenes (Group A): catalase –, β-hemolytic, bacitracin sensitive
• Streptococcus agalactiae (Group B): catalase –, β-hemolytic, bacitracin resistant
• Streptococcus pneumoniae: catalase –, α-hemolytic, optochin sensitive, bile soluble, encapsulated
• Streptococcus mutans/mitis (Viridans streptococci): catalase –, α-hemolytic, optochin resistant, bile soluble, not encapsulated
• Enterococcus faecium/faecalis: catalase –, γ-hemolytic, grows in 40% bile, grows in 6.5% NaCl
• Streptococcus bovis (Group D streptococcus): catalase –, γ-hemolytic, grows in 40% bile, does not grow in 6.5% NaCl
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Bacillus cereus
• Gram-positive, spore-forming rod, aerobic, motile
• Causes food poisoning - “reheated rice syndrome”
• Bacteria contaminate uncooked food (eg, rice) –> during high-temperature cooking form protective spores –> when food rewarmed later results in spore germination and enterotoxin secretion
• Toxin type determines syndrome
• Heat-stable enterotoxin (like Staph enterotoxin) –> emetic syndrome –> N/V within 1-5 hours of ingesting reheated rice/pasta, caused by preformed toxin cereulide
• Heat-labile enterotoxin (like ETEC LT) –> increased cAMP concentration causes reabsorption of NaCl in gut lumen –> diarrheal syndrome –> watery, non-bloody diarrhea within 8-20 hours of ingestion
• Tx. rehydration, avoid reheating rice, etc.
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Bacillus anthracis
• Gram-positive rod in chains, spore-forming, aerobic, non-motile, only medically-relevant bacterium with polypeptide capsule (poly-D-glutamate)
• Endospore- spores destroyed by boiling but survive for years in dry earth or goat skin
• Anthrax toxin: protective antigen (PA) and edema factor (EF) or lethal factor (LF)
• PA binds cell membranes and mediates endocytic entry of EF or LF
• EF increases AC activity, leading to increased cAMP, causing edema and inhibition of PMNs
• LF causes cell death
• Spores from goat/cow products enter via cutaneous abrasion –> germinate and multiply –> secrete anthrax toxin –> tissue hemorrhage/necrosis/edema –> cutaneous anthrax –> painless papule/pustule surrounded by vesicles –> painless, necrotic ulcer with black eschar
•Spores ingested –> germinate and multiply in intestines/oropharynx causing lesions in throat and dysentery 2/2 anthrax toxin (GI anthrax)
• Spores inhaled –> germinate and multiply in respiratory tract –> enter bloodstream with anthrax toxin secreted systemically –> fever, dyspnea, cough –> 100% mortality
• Pulmonary anthrax (woolsorter’s disease)–> inhalation of spores leads to flu-like symptoms, rapidly progresses to fever, pulmonary hemorrhage, mediastinitis and shock
• Tx. Parenteral penicillin G
• Px. anti-PA vaccine
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Clostridium tetani
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Spores survive in soil/feces for years –> enter through skin injury –> bacteria germinate and release tetanospasmin –> tetanospasmin travels retrogradely on axons of peripheral motor neurons and through bloodstream –> spinal cord –> tetanus progresses from head to trunk to extremities (determined by length of neurons) –> masseter muscle most sensitive (lockjaw)
• Tetanospasmin = exotoxin protease that cleaves SNAREs –> blocks vesicular release of inhibitory GABA and glycine from Renshaw cell interneurons of spinal cord–> motor neurons hyperexcited –> spastic paralysis and tetanus (sustained muscle contraction) –> trismus (lockjaw), risus sardonicus (raised eyebrows, open grin)
• Prophylaxis: DTaP vaccine administered at 2, 4, 6, 18 months, with 10 year boosters, tetanus toxoid
• Tx. antitoxin (human anti-tetanospasmin Ig), wound debridement, +/- DTaP vaccine booster, diazepam (GABA agonist) to tx muscle spasms, penicillin/metronidazole
• “Looks sort of odd, spore-forming rod, anaerobic, makes you so sick, it overrides gangliosides, your jaw is locked, GABA is blocked!”
******
Clostridium botulinum
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Botulinum toxin = heat-labile exotoxin protease that cleaves SNAREs at the NMJ, inhibiting vesicular release of ACh at the NMJ–> Botulism (descending flaccid paralysis)
• Adult botulism –> food poisoning caused by preformed toxin ingestion –> heat-labile toxin released in anaerobic environment (eg, canned foods) –> ingestion contaminated food –> neurotoxin enters vascular system and spreads to peripheral cholinergic nerve terminals w/i 12-36 hours –> blocks ACh release at CNs (diplopia, dysarthria, dysphagia), NMJs (symmetric descending paralysis spreading from head to extremities), postganglionic parasympathetic nerve endings (dizziness, dry throat, ptosis)
• Infant botulism –> preformed spores often ingested with contaminated honey –> spores germinate in large intestine, release toxin –> toxin slowly absorbed over days, blocking ACh release –> constipation, floppy baby syndrome (descending flaccid paralysis) –> good prognosis with supportive care
•No fever, bacteria do not invade
•Dx. check for toxin in uneaten food or mouse test: inject patient serum into mouse and check for paralysis/death
• Tx. antitoxin + respiratory support
• Watch out for swollen food cans! Bacteria generate gas.
• Local botox (BOtulinum TOXin) injection used to tx focal dystonia, achalasia, strabismus, muscle spasms, wrinkles
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Clostridium difficile
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Associated with PPI use and antibiotic use (clindamycin, ampicillin)
• Normal GI flora –> abx tx disrupts normal flora, but C. diff survives by forming spores –> spores germinate after tx and grow rapidly due to fewer competing microorganisms –> secrete two toxins
• Toxin A = enterotoxin = binds to brush border of gut, altering fluid secretion –> watery diarrhea
• Toxin B = cytotoxin = cytoskeletal disruption via actin depolymerization, cytotoxic to epithelial cells –> pseudomembrane formation
• Toxin release causes diarrhea and pseudomembranous colitis –> pseudomembranes are yellow-white plaques
• Dx. detection of toxin B in stool sample by PCR
• Tx. metronidazole or oral vancomycin (not absorbed), withdraw causative agent (often clindamycin)
• Tx for recurrence: fidaxomicin or fecal transplant
• Inflammation by toxin A can sometimes cause hypoalbuminemia
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Clostridium perfringens
• Gram-positive rod, spore-forming, obligate anaerobe, non-motile
• Cellulitis, gas gangrene (myonecrosis with crepitus), food poisoning
• Cellulitis: spores in soil –> bacteria infect anaerobic environment of necrotic skin wound –> release collagenase, hyaluronidase –> slow, painless infection and gas production –> forms collections of gas under skin that crackle when touched (crepitus)
• Gas gangrene: spores in soil –> introduced via deep muscle laceration (military wounds, auto accidents, crude abortions) –> growth in anaerobic environment –> release α-toxin (lecithinase-phospholipase) myonecrosis and hemolysis, degradative enzymes cause subQ gas bubbles (crepitus) –>gangrenous muscles –> black fluid exudate –> shock
• Tx. surgical debridement, hyperbaric oxygen to kill anaerobic bacteria, penicillin, clindamycin (effective only in local, weak infections)
• Food poisoning: spores in meat/poultry can survive in undercooked food and germinate –> when ingested cause food poisoning by releasing heat-labile enterotoxin in GI tract –> enterotoxin inhibits glucose transport and damages epithelium –> diarrhea, gastric pain, nausea (no fever)
******
Listeria monocytogenes
• Gram-positive rod, non-spore forming, motile, facultative intracellular bacillus, catalase +
• Only gram+ with endotoxin
• Ingestion of unpasteurized dairy or cold deli meats –> mild self-limiting gastroenteritis in healthy individuals, sepsis/meningitis in immunocompromised patients or neonates
• Patients deficient in cell-mediated immunity (pregnant women, neonates, AIDS) have ineffective phagocytosis –> Listeria invades phagocytes of GI mucosa and grows intracellularly –> spreads through blood –> tropism for neural tissue (meningitis)
• Transplacental (amnionitis, spontaneous abortion) or transvaginal transmission at birth possible (granulomatosis infantiseptica, neonatal meningitis)
• Forms “rocket tails” via actin polymerization to allow intracellular movement and cell-to-cell spread avoiding antibody opsonization –> “tumbling” motility in cultures
• Tx. ampicillin +/- gentamicin in infants, immunocompromised, and elderly patients for empiric tx of meningitis, TMP-SMX
• Listeria and β-hemolytic streptococci look similar on blood agar plates but Listeria is catalase +
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Corynebacterium diphtheriae
• Gram-positive rod, non-spore forming, non-motile, aerobic
• “Chinese letters” appearance on culture
• Black colonies on cystine-tellurite agar
• Enters nasopharynx via respiratory droplets –> creates gray fibrinous exudate composed of bacteria, WBCs, necrotic mucosa –> may obstruct airway –> secretes diphtheria toxin
•Diphtheria toxin = potent exotoxin encoded by β-prophage, inhibits protein synthesis in all cells via ADP-ribosylation of EF-2–> myocarditis, cranial and peripheral nerve palsies
• Sx. sore throat, difficulty breathing/swallowing, large gray mucous film on oropharynx (pseudomembranous pharyngitis), LAD, myocarditis, arrhythmias, polyneuritis
• Dx. Gram + rods with metachromic (blue + red) granules, Elek test + for toxin
• Tx. antitoxin, penicillin or erythromycin, DTaP booster
• Do not scrape pseudomembrane –> toxin spread
• Preventable with DTaP vaccine: diphtheria toxoid
• ADP-ribosylation (of EF2)
• β-prophage (encodes exotoxin)
• Corynebacterium
• Diphtheriae
• Elongation
• Factor 2 (+ Elek) (inhibits protein synthesis)
• Granules (metachromic)
******
Actinomyces israelii
• Gram-positive anaerobic branching filaments, yellow “sulfur” granules, not acid-fast
• Found in normal oral, reproductive, and GI flora –> trauma/surgery disrupts mucosal barrier –> local infection –> yellow sulfur granules develop surrounded by PMNs –> forms pus-filled abscess –> slow expansion to contiguous tissue without respect to tissue planes –> sinus tracts through skin, muscle, bone, organs
• Causes facial abscesses that drain yellow fluid through sinus tracts
•Can cause abscesses in mouth, lungs, GI tract, GU tract
• Forms yellow-orange “sulfur” granules–> eosinophilic proteinaceous coating over filamentous actinomycetes, no actual sulfur present
• Can cause PID with IUDs
• Tx with penicillin G, surgical abscess drainage
• Tx is a SNAP: Sulfonamides Nocardia: Actinomyces Penicillin
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Nocardia asteroides, N. brasiliensis
• Gram-positive weakly acid-fast aerobic branching filaments
• Found in soil –> inhaled –> phagocytosed –> mycelia acid cell wall allows for intracellular survival and proliferation –> caseous granulomas in lungs –> may spread via blood to adjacent tissues –> abscesses in kidneys, brain
• Intracellular survival –> caseous granulomas
• Pulmonary infections in immunocompromised patients, mimics TB but PPD negative and beaded filamentous growth
• Cutaneous infections after trauma in immunocompetent patients
• Tx with TMP-SMX, surgical abscess drainage
• Tx is a SNAP: Sulfonamides Nocardia: Actinomyces Penicillin
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Staphylococcus aureus
•Gram-positive β-hemolytic cocci in clusters, aerobic, catalase +, coagulase +
• Protein A binds Fc-IgG –> inhibits complement activation and phagocytosis
• Coagulase –> forms fibrin coat around organism
• Hemolysins, leukocidins –> destroy RBCs, WBCs
• Hyaluronidase –> breaks down connective tissue
• Staphylokinase –> lyses formed clots
• Lipase –> breaks down fat
• Colonizes the nares
• Skin infections: impetigo, cellulitis, folliculitis, furuncles, carbuncles
• Organ abscesses, PNA after influenza (with cavitations)
• Systemic infxns: acute endocarditis, meningitis, septic arthritis, osteomyelitis (leading cause in children/adults)
• MRSA - altered PBPs, methicillin/nafcillin resistant, tx with vancomycin
• Tricuspid valve endocarditis frequently affects IV drug users
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Staphylococcus aureus toxin-mediated diseases
• Toxic Shock Syndrome –> tampon/nasal packing/surgery introduce bacteria –> TSST-1 released and diffuses systemically –> TSST-1 is super antigen that promotes excess cytokine (TNF, IL-1) release –> acute fever, vomiting, rash, desquamation on palms and soles, hypotensive shock, end organ failure due to hypoperfusion
• Scalded Skin Syndrome –> skin wound/ cutting umbilicus in neonates promotes local epidermal infection–> exfoliative toxins (ET-A, ET-B) released systemically –> epidermis separates and skin sloughs off –> fluid loss and potential secondary infection –> 50% mortality rate
• Ritter’s syndrome –> most severe form of SSS in neonates –> S. aureus colonizes umbilicus and releases ET-A, B systemically
• Rapid-onset food poisoning –> bacteria release heat-stable enterotoxins (SE-A) in food –> non-bloody diarrhea and emesis when ingested–> self-limited, 8-24 hour nausea, vomiting, diarrhea, abdominal pain
• Dx. detection of toxin production by in vitro culture, BCx negative b/c organism doesn’t invade bloodstream
• Tx. remove foreign bodies, drain abscesses, penicillinase-resistant penicillins
• Abx not curative, kill bacteria but do not remove already-released exotoxin
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Staphylococcus epidermidis
• Gram-positive cocci in clusters, aerobic, catalase +, coagulase –, novobiocin sensitive, urease +
• Normal skin flora –> often contaminates BCx
• Adhesin polysaccharide promotes adherence to inserted indwelling medical devices (prosthetic heart valves, hip joints, Foley catheters) and IV lines with adherent biofilms
• Indwelling device inoculates bacteria to internal site, causing inflammation at site of device
• Endocarditis with a prosthetic heart valve: S. epidermis within 60 days of valve replacement, Viridans streptococci after 60 days of valve replacement
• Tx. vancomycin (most strains resistant to penicillins and cephalosporins), removal of foreign device
• Neutropenic patients most susceptible –> bacteremia
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Staphylococcus saprophyticus
• Gram-positive cocci in clusters, aerobic, catalase +, coagulase –, novobiocin resistant, urease +
• Normal flora of female genital tract and perineum
• 2nd most common cause of uncomplicated UTI in young women (most common is E. coli)
• Most common causes of cystitis among sexually active young women also: 1. E. coli, 2. S saprophyticus
• Bacteria enter urinary tract by sexual activity, may spread to bladder
• Tx. TMP-SMX
******
Streptococcus pyogenes aka Group A Beta-Hemolytic Strep (GABHS)
• Gram-positive β-hemolytic cocci in chains, catalase –, aerobic, bacitracin sensitive, ASO+, pyrrolidonyl arylamidase (PYR) +
• Pyogenic: pharyngitis, impetigo, erysipelas, cellulitis
• Toxigenic: scarlet fever, toxic shock-like syndrome, necrotizing fasciitis
• Normal flora of skin/oropharynx
• Pharyngitis –> human-to-human via droplets –> adhere to epithelium via pili –> sore throat, enlarged cervical LNs due to inflammation –> either spontaneous recovery, bacterial spread (bacteremia, meningitis, otitis), toxin release (scarlet fever, TSS), or anti-streptococcal antibody immunologic reactions (PSGN, rheumatic fever)
• Skin infections–> trauma inoculates skin –> pustular lesions with honeycomb-like crusts (impetigo) –> deeper infection causes erysipelas/cellulitis –> may cause anti-streptococcal Ab reactions (PSGN, not rheumatic fever)
• Virulence factors: streptokinase (converts plasminogen to plasmin causing fibrinolysis), M protein (resists phagocytosis), hyaluronidase (breaks down connective tissue), DNase digests DNA
• Dx. Throat/skin culture, anti-streptolysin O antibody titer detects recent infection with S. pyogenes
• Tx. penicillin G
• While “strep throat” (GABHS pharyngitis) is usually self-limited, tx mandatory to prevent complications
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Streptococcus pyogenes toxin-mediated diseases
• Scarlet fever: S. pyogenes pharyngitis –> systemic release of pyrogenic exotoxins A, B, C –> fever, “sandpaper” rash (begins on trunk and spreads outward, spares soles/palms), strawberry tongue within first 2 days, desquamation of palms and soles after rash subsides
• Toxic shock syndrome: S. pyogenes skin infection (eg, cellulitis) –> systemic release of pyrogenic exotoxin A (superantigen) –> polyclonal activation of T cells –> acute fever, shock, multiorgan failure
• Necrotizing fasciitis: trauma/surgery inoculates bacteria in fascia investing muscles –> release of exotoxin B (protease) –> rapid necrosis along fascial planes, no damage to muscles
• Streptolysin O and Streptomycin S: destroy RBCs, WBCs
• Tx. penicillin G, clindamycin added in TSS to prevent toxin production, surgical debridement in necrotizing fasciitis
******
Scarlet fever
• GABHS (S. pyogenes) pharyngitis + blanching, sandpaper body rash, strawberry tongue, and circumoral pallor
• Erythrogenic toxin
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Jones criteria for diagnosis of acute rheumatic fever
• 2 major criteria or one major + two minor criteria and evidence of prior infection:
• JONES major criteria
• Joints - migratory polyarthritis
• O - carditis (endocarditis, myocarditis, or pericarditis)
• Nodules - subcutaneous nodules
• Erythema marginatum rash
• Sydenham’s chorea
• Minor criteria: fever, arthralgia, elevated ESR/CRP, prolonged PR interval, ASO +
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5 most common pediatric diseases with rash
- Measles (measles virus)
- Rubella (rubella virus)
- Scarlet fever (S. pyogenes infection)
- Roseola (HHV-6)
- Erythema infectiosum (parvovirus B19)
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Streptococcus pyogenes immune-mediated disease
• Post-streptococcal glomerulonephritis (PSGN): S. pyogenes skin infection/pharyngitis –> anti-streptococcal antibodies generated –> immune complexes form –> deposit on glomerular BM –> glomerular inflammation –> 2-3 weeks after infection, develop hematuria, hypertension, periorbital edema –> complete recovery likely
• C3 complement levels low, BUN and Cr bump, RBC casts in urine, EM would reveal sub epithelial humps “lumpy-bumpy” in glomerulus
• Rheumatic fever: S. pyogenes pharyngitis left untreated –> autoimmune cross-reaction of anti-streptococcal antibodies with antigen of joints and heart tissue –> 2 weeks after pharyngitis develop inflammatory response at various tissues (eg, mitral valve) –> permanent endocardial damage may present years later as murmur (mitral regurgitation)
• Tx. penicillin prophylaxis to patients with hx of rheumatic fever to prevent further valve damage
• M protein = antiphagocytic protein in cell wall
• Antibodies to M protein enhance host defense against S. pyogenes and confer immunity but give rise to rheumatic fever
•Valves damaged by rheumatic fever susceptible to colonization by enterococci or Viridans streptococci endocarditis
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Streptococcus agalactiae (Group B β-hemolytic streptococci)
• Gram-positive β-hemolytic cocci in chains, catalase –, aerobic, bacitracin resistant, PYR–, Hippurate test +, produces CAMP factor
• Group B is for Babies
• Colonizes maternal vagina –> causes neonatal pneumonia (respiratory distress, lethargy, hypotension), neonatal meningitis (seizures, irritability), and neonatal sepsis, especially after labor complications
• Most common cause of meningitis in newborns
• Tx. penicillin G
• Screen pregnant women at 35-37 weeks gestation –> if + culture –> intrapartum ampicillin prophylaxis to prevent vertical transmission to neonate
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Streptococcus pneumoniae aka “pneumococcus”
• Gram-positive α-hemolytic lancet-shaped diplococci, catalase –, optochin sensitive, bile soluble, encapsulated
• Capsule = antiphagocytic, Quellung +, antigens for Pneumovax
• IgA proteases
• Colonizes nasopharynx epithelium esp if clearance hindered by viral infection/allergy/smoking
• Most common cause of: meningitis, otitis media (in children), community-acquired pneumonia (lobar pneumonia), sinusitis
• May also cause osteomyelitis, septic arthritis, endocarditis
• Tx. penicillin or cephalosporins, vancomycin for meningitis
• Associated with rusty sputum
• Sepsis in patients with SCD or splenectomy –> give Pneumovax
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Streptococcus mutans, S. mitis, S. sanguinis (Viridans group streptococci)
• Gram-positive α-hemolytic cocci, catalase –, optochin resistant, bile soluble, not encapsulated
• Normal oropharynx flora that cause dental caries (S. mutans, S. mitis) and subacute bacterial endocarditis on damaged heart valves (S. sanguinis)
• Optochin resistant unlike S. pneumo
• S. sanguinis makes dextrans that bind to fibrin-platelet aggregates on heart valves
• Physical exam: low-grade fever, general malaise, Janeway lesions (non-painful), Osler’s nodes, Roth’s spots (retina), splinter hemorrhages
• Osler’s nodes- painful, from immune complex vasculitis
• S. intermedium may cause brain/abdominal abscesses, normally inhabits GI tract –> microaerophilic, thrive in low-oxygen brain/liver –> Bcx positive for S. intermedius often indicate presence of abscesses
• Tx. penicillin G
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Enterococcus faecium, E. faecalis
•Gram-positive γ-hemolytic cocci, catalase –, grows in 40% bile, grows in 6.5% NaCl, PYR +, hardier than non-enterococcal group D
• Capsule prevents bile salt degradation
• Some strains may be α-hemolytic
• Normal flora of intestines, biliary tract, GU tract —> overgrows locally when normal flora suppressed by cephalosporins or when mucosal/epithelial barrier disrupted (subacute endocarditis in IVDUs, infection following biliary/hepatic/GI surgery or procedures) –> UTIs, biliary tract infections, subacute bacterial endocarditis
• Tx. ampicillin or vancomycin + aminoglycosides (synergistic)
• Tx for Vancomycin-Resistant Enterococcus (VRE). linezolid, daptomycin
• 2nd most common cause of nosocomial infections in the US due to high resistance: all strains resistant to cephalosporins, penicillin G, some strains also resistant to vancomycin (VRE)
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Streptococcus bovis (Group D streptococcus)
•Gram-positive γ-hemolytic cocci, catalase –, grows in 40% bile, does not grow in 6.5% NaCl
• Capsule prevents bile salt degradation
• Bovis in the Blood = Cancer in the Colon
• Colonizes gut –> penetrates epithelium via lesions in the colon (eg, CRC or IBD) –> enters lymphatics and bloodstream –> localizes to aortic valve, adhering to platelet-fibrin aggregates –> endocarditis
• S. gallolyticus (S. bovis biotype I) can cause bacteremia and subacute bacterial endocarditis associated with colorectal cancer
• Tx. penicillin
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Most common causes of pneumonia in adults and elderly, and most common causes of meningitis in elderly
• Adults (40-65): S. pneumoniae, H. influenzae, Legionella
• Elderly (>65): S. pneumoniae, Gram – rods, H. influenzae
• Meningitis in 60+: S. pneumoniae, Gram – rods, Listeria
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Streptolysin O
• Streptococcus pyogenes
• Lyses cell membranes
• Protein that degrades all cell membranes, lyses RBCs, contributes to β-hemolysis
• Host antibodies against toxin (anti-streptolysin O antibodies) used to diagnose rheumatic fever
• Do not confuse these antibodies with the immune complexes of post-streptococcal GN
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Exotoxin A (Streptococcus pyogenes)
• Streptococcus pyogenes
• Superantigen –> binds to MHC class II and TCR outside of the Ag-binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α
• Release of cytokines causes Toxic Shock Syndrome –> fever, rash, shock
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M protein
• Expressed by Streptococcus pyogenes (GABHS)
• Helps prevent phagocytosis
• Shares similar epitopes to human cellular proteins (molecular mimicry)
• Possibly underlies autoimmune response seen in acute rheumatic fever
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Protein A
•Expressed by Staphylococcus aureus
• Virulence factor that binds Fc region of IgG
• Prevents opsonization and phagocytosis
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IgA protease
• Secreted by many bacteria (S. pneumoniae, H. influenzae, Neisseria meningitidis)
• Enzyme that cleaves IgA immunoglobulins to colonize respiratory mucosa
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Endotoxin (gram negative bacteria)
• Endotoxin not secreted –> released upon cell lysis or bleb detachment from membrane, lipid A = toxic component of LPS
• Part of bacterial chromosome, poorly antigenic so no vaccine
• Edema (C3a activation)
• Nitric oxide (hypotension)
• DIC (TF activation)
• Outer cell membrane (of most gram – bacteria)
• TNF-α –> fever and hypotension
• O-antigen + core polysaccharide + lipid A = LPS
• eXtremely heat stable
• IL-1 and IL-6 –> fever
• Neutrophil chemotaxis (C5a activation)
• Shock/Sepsis by gram – rods
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3 main effects of endotoxin (lipid A)
- Macrophage activation (TLR4) –> IL-1, IL-6 (fever), TNF-α (fever and hypotension), nitric oxide (hypotension)
- Complement activation –> C3a (histamine release –> edema and hypotension), C5a (neutrophil chemotaxis)
- Tissue factor activation (coagulation cascade –> DIC)
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Botulinum toxin
• Clostridium botulinum
• Inhibits vesicular release of stimulatory NT –> Ach
• Protease that cleaves SNAREs, a set of proteins required for NT release from vesicles
• Exotoxin prevents release of acetylcholine at NMJ –> symmetric descending flaccid paralysis
• Also prevents ACh release at CNs (diplopia, dysarthria, dysphagia) and postganglionic parasympathetic nerve endings (dizziness, dry throat, ptosis)
• Don’t feed babies honey as may have botulinum spores!
• AB toxin: B binds cell surface receptor, A cleaves SNAREs
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Tetanospasmin
•Clostridium tetani
• Inhibits vesicular release of inhibitory NTs –> glycine and GABA
• Protease that cleaves SNAREs (synaptobrevin), a set of proteins required for NT release via vesicles into synapse
• Exotoxin prevents release of GABA and glycine from interneuron Renshaw cells in the spinal cord
• Causes spastic paralysis, maintained muscle contraction (tetanus), risus sardonicus, trismus (lockjaw)
• AB toxin: B binds cell surface receptor, A cleaves SNAREs
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Alpha toxin
• Clostridium perfringens
• Lyses cell membranes
• Phospholipase (lecithinase) that degrades tissue and cell membranes –> degradation of phospholipids –> myonecrosis (“gas gangrene”) and hemolysis (“double zone” of hemolysis on blood agar)
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Toxic Shock Syndrome Toxin (TSST-1)
• Staphylococcus aureus
• Superantigen –> binds MHC class II and TCR outside of Ag binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α
• Release of cytokines causes Toxic Shock Syndrome –> fever, rash, shock
• TSST-1 causes TSS
• exfoliative toxin causes Scalded Skin Syndrome
• enterotoxin causes S. aureus food poisoning
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Shiga toxin (ST)
• Shigella spp.
• Inhibits protein synthesis
• Inactivates 60s ribosome unit by removing adenine from rRNA (ADP ribosyltransferase)
• Inhibition of protein synthesis causes GI mucosal damage, however, not main mechanism of disease –> Shigella invades host cells, causing ulcers and bleeding –> bloody diarrhea
• ST also enhances cytokine release, causing HUS if gets into systemic circulation–> ST damages vascular endothelial cells in glomeruli –> platelet microthrombi –> microangiopathic hemolytic anemia and renal failure
• AB toxin: B binds cell surface receptor, A ADP-ribosylates 60S ribosomal subunit
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Shiga-like toxin (SLT)
• Enterohemorrhagic E coli (EHEC), prototypically EHEC serotype 0157:H7 causes HUS
• Inhibits protein synthesis
• Inactivates 60s ribosome unit by removing adenine from rRNA (ADP ribosyltransferase)
• Inhibition of protein synthesis causes GI mucosal damage
• SLT also enhances cytokine release, causing HUS if gets into systemic circulation–> damages vascular endothelial cells in glomeruli –> platelet microthrombi –> microangiopathic hemolytic anemia and renal failure
• Unlike Shigella spp, EHEC doesn’t invade host cells –> SLT is main mechanism of damage
• AB toxin: B binds cell surface receptor, A ADP-ribosylates 60S ribosomal subunit
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Diphtheria toxin
• Corynebacterium diphtheriae
• Inhibits protein synthesis
• Inactivates elongation factor 2 (EF-2), which is necessary for protein synthesis with ribosomes
• Inhibition of protein synthesis causes pseudomembrane to form in throat –> gray plaque of necrosis and PMNs
• Severe LAD due to pharyngitis in diphtheria –> bull neck
• AB toxin: B binds cell surface receptor, A ADP-ribosylates EF-2
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Exotoxin A (P. aeruginosa)
• Pseudomonas aeruginosa
• Inhibits protein synthesis
• Inactivates elongation factor 2 (EF-2), which is necessary for protein synthesis with ribosomes –> host cell death
• AB toxin: B binds cell surface receptor, A ADP-ribosylates EF-2
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Heat-labile toxin (LT)
• Enterotoxigenic E. coli (ETEC)
• Increases fluid secretion
• LT over activates adenylate cyclase, which increases cAMP production –> increased Cl- secretion into gut lumen with osmotic H20 efflux –> watery diarrhea
• AB toxin: B binds cell surface receptor on gut epithelium, A overactivates AC.
• “Labile in the Air (Adenylate cyclase activation), Stable on the Ground (Guanylate cyclase activation)”
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Heat-stable toxin (ST)
• Enterotoxigenic E. coli (ETEC)
• Increases fluid secretion
• ST over activates guanylate cyclase, which increases cGMP production –> decreases resorption of NaCl and H2O –> watery diarrhea
• AB toxin: B binds cell surface receptor on gut epithelium, A overactivates GC.
• “Labile in the Air (Adenylate cyclase activation), Stable on the Ground (Guanylate cyclase activation)”
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Cholera toxin
• Vibrio cholerae
• Increases fluid secretion
• Cholera toxin permanently activates Gs –> constitutively active adenylate cyclase increases cAMP production –> increased Cl- secretion into gut lumen with osmotic H20 efflux –> voluminous “rice-water” diarrhea
• AB toxin: B binds cell surface receptor on gut epithelium, A permanently activates Gs.
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Edema toxin
• Bacillus anthracis
• Edema factor = component of anthrax toxin
•Increases fluid secretion
• Anthrax toxin: protective antigen (PA) + either edema factor (EF) or lethal factor (LF)
• PA binds cell membranes and mediates endocytic entry of EF or LF
• EF mimics adenylate cyclase, leading to increased cAMP, causing edema –> likely responsible for characteristic edematous borders of black eschar in cutaneous anthrax
• LF causes cell death –> dermal necrosis
• AB toxin: B binds cell surface receptor, A either EF or LF
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Pertussis toxin
• Bordetella pertussis (whooping cough)
• Inhibits phagocytosis
• ADP-ribosylates/disables Gi –> overactivates adenylate cyclase –> increased cAMP –> impaired phagocytosis to permit survival of microbe
• AB toxin: B binds cell surface receptor, A disables Gi
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Type III secretion system
• Needle-like protein appendage that facilitates direct delivery of toxins from certain gram-negative bacteria to the host
• “Injectisome”
• Pseudomonas, Salmonella, Shigella, E. coli
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Rash that affects palms and soles
• “You drive CARS using your palms and soles”
• Coxsackievirus A (hand, foot and mouth disease)
• Rocky Mountain Spotted Fever
• Secondary syphilis
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Pigment-producing bacteria
• Actinomyces israelii - “Israel has yellow sand.” –> yellow “sulfur” granules composed of filaments of bacteria with proteinaceous covering
• Staphylococcus aureus - “Aureus is latin for gold.” –> golden yellow pigment
• Pseudomonas aeruginosa - “Aerugula is green.” –> pyocyanin is a blue-green pigment
• Serratia marcescens - “Red maraschino cherry” –> reddish-orange pigment
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In vivo biofilm-producing bacteria
•Staph epidermidis - catheter/prosthetic device infections
• Viridans streptococci - dental plaque, subacute infective endocarditis
• Pseudomonas aeruginosa - respiratory-tree colonization in CF patients, contact lens associated keratitis
• Nontypeable (unencapsulated) H. influenzae - otitis media
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Spore-forming bacteria
• Some bacteria can form spores at the end of their stationary phase, when nutrients are limited
• Highly resistant to heat and chemicals
• Dipicolinic acid in core
• Must autoclave at 121 C to kill spores
• Bacillus anthracis, Bacillus cereus
• Clostridium botulinum, C. tetani, C. difficile, C. perfringens
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Organisms that don’t Gram stain well
• These Microbes May Lack Real Color
• Treponema pallidum (syphilis), Leptospira - spirochetes are too thin to be visualized well
• Mycobacteria - cell wall has high lipid content, require special stain
• Mycoplasma, Ureaplasma - no cell wall to stain
• Legionella - primarily intracellular organism
• Rickettsia - intracellular, use Giemsa stain
• Chlamydia - intracellular, lacks classic peptidoglycan due to decreased muramic acid, use Giemsa stain
• Others: Bartonella, Ehrlichia, Anaplasma
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Giemsa stain
• Certain Bugs Really Try my Patience • Chlamydia • Borrelia • Rickettsia • Trypanosomes (eg, Trypanosoma brucei "sleeping sickness", Trypanosoma cruzi "Chagas disease") - protozoa • Plasmodium falciparum, etc. - protozoa ******************************
Bacterial toxins encoded in a lysogenic phage
• ABCD'S • A - GABHS (S. pyogenes) erythrogenic toxin • B - Botulinum toxin in C. botulinum • C - Cholera toxin in V. cholerae •D - Diphtheria toxin in C. diphtheriae • S - Shiga toxin in Shigella spp. ******************************
What is a lysogenic phage?
• Lysogenic phage = prophage (genetic material) of a virus that can infect bacteria (bacteriophage) during a lysogenic cycle, causing survival advantage to both the bacterium and the bacteriophage within.
• Bacteriophages are viruses that infect and replicate within a bacteria.
• Lysogeny is characterized by integration (excision event) of bacteriophage nucleic acid into host bacterium’s genome or formation of a circular replicon in the bacterium’s cytoplasm.
• During the lysogenic cycle, the bacterium continues to live and reproduce normally, transmitting the prophage (genetic material) to daughter cells at each subsequent cell division.
• Non-virulent bacteria can transform into highly virulent pathogens through lysogenic conversion with the virulence factors carried on the lysogenic prophage. (eg, Vibrio cholerae, Shigella, etc.)
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Encapsulated bacteria
• Plz SHINE my SKiS
• Pseudomonas aeruginosa
• Streptococcus pneumoniae*
• Haemophilus
• Influenzae type B *
• Neisseria meningitidis *
• Escherichia coli
my
• Salmonella
• Klebsiella pneumoniae
i
• Streptococcus - group B
• Give these vaccines to asplenic patients *
• Vaccine = capsular polysaccharide + protein conjugate
• Vaccines containing a polysaccharide capsule antigen are conjugated to a carrier protein to enhance immunogenicity by promoting T-cell activation and class switching.
• Polysaccharide antigen alone cannot be presented to T-cells.
• Eg, Pneumococcal conjugate vaccine (PCV) vs. pneumococcal polysaccharide vaccine (PPSV)
• HiB and meningococcal vaccines are both conjugated
• Capsules are an antiphagocytic virulence factor, they must be opsonized and removed by the spleen (RES), thus asplenic patients are at greater risk for infection with these encapsulated pathogens.
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Urease + organisms
• Pee CHUNKSS • Proteus mirabilis • Cryptococcus •Helicobacter pylori •Ureaplasma • Nocardia • Klebsiella pneumoniae •Staphylococcus epidermidis •Staphylococcus saprophyticus • Urease hydrolyzes urea to release ammonia and CO2 --> thus increasing the pH •UTIs with urease + organisms (eg, Proteus) potentiate struvite stones (ammonium magnesium phosphate) ******************************
Catalase + organisms
• Cats Need PLACESS to Belch Hairballs • Need - Nocardia •P - Pseudomonas • L - Listeria • A - Aspergillus • C - Candida • E - E. coli • S - Staphylococci • S - Serratia • Belch - Burkholderia cepacia • Hairballs - Helicobacter pylori • Catalase degrades H2O2 into H2O and O2 before in can be converted into microbicidal products by PMNs by the enzyme myeloperoxidase (MPO). Patients with Chronic Granulomatous Disease (NADPH oxidase deficiency) have recurrent infections with catalase + organisms. ******************************
Acid-Fast Bacilli
•Similar to gram-positive bacteria
• Differ in that cell wall has high amounts of mycolic acid (lipid), which makes cell wall hydrophobic and hard to stain
• Gram stain poorly
• Once stained with carbol fuschin they retain the stain and do not decolorize with acid-alcohol washes
• Ziehl-Neelson stain
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Mycobacterium tuberculosis
• Acid-fast bacilli, non-motile, obligate aerobes
• Interferon-gamma release assay (IGRA) has fewer false positives from the BCF vaccination than PPD.
•PPD + if current infection or past exposure. PPD – if no infection (eg, sarcoidosis).
• Primary TB = Ghon complex = calcified hilar LAD + Ghon focus (cavitary lesion usually in the mid/lower lobes)
• >90% of primary TB heals by fibrosis and calcification, will be tuberculin +
•Less than 10% of patients with primary TB will go on to have progressive primary tuberculosis (if AIDS or malnutrition), which causes progressive lung disease and bacteremia –> miliary tuberculosis spreads to LNs, meninges, vertebrae (Pott disease), throughout lungs, liver, spleen, adrenal glands, and joints and long bones.
•Secondary (reactivation) TB = caseating granuloma with central necrosis and Langerhans giant cells characteristic of secondary tuberculosis–> fibrocaseous cavitary lesion in the upper lobes –> may progress to localized destructive disease or to bacteremia and miliary TB.
• Cord factor = creates “serpentine cord” appearance in virulent M. tuberculosis strains –> inhibits macrophage maturation and induces TNF-α release. Sulfatides (surface glycolipids) inhibit phagolysosomal fusion.
• TB symptoms include fever, night sweats, weight loss, cough (either nonproductive or productive), hemoptysis
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Mycobacterium leprae
• Causes leprosy (Hansen disease): 2 forms
• AFB that prefers cool temperatures
• Infects skin and superficial nerves in “glove and stocking” distribution loss of sensation
• Cannot be grown in vitro
• Armadillos are the US reservoir
• 1. Lepromatous disease - presents diffusely over skin with leonine facies, communicable, can be lethal; characterized by low cell-mediated immunity with humoral Th2 response
• 2. Tuberculoid disease - limited to a few hypoesthetic, hairless skin plaques; characterized by high cell-mediated immunity with Th1 immune response
• Tx. Dapsone and rifampin for tuberculoid leprosy, add clofazimine for lepromatous form
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Mycobacterium avium-intracellulare (MAI) aka Mycobacterium avium complex (MAC)
• Causes disseminated non-TB disease in patients with AIDS
• Often resistant to multiple drugs
• Prophylaxis with azithromycin when CD4+ count is below 50 cells/mm3
• Tx. macrolide (azithromycin/clarithromycin) + ethambutol + rifampin
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Mycobacterium marinum
Hand infection in aquarium handlers
Mycobacterium scrofulaceum
Cervical lymphadenitis in children
Bacterial transformation
• Ability to take up naked DNA (from cell lysis) from the environment - this is also known as “competence”
• Tranformation is a feature of many bacteria, especially S. pneumoniae, H. influenzae type B, and Neisseria.
• Adding deoxyribonuclease to the environment will degrade the naked DNA in the medium and no transformation will be seen.
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Bacterial conjugation
• F+ x F-
• F+ plasmid contains the genes required for a sex pilus and conjugation. Bacteria without this pilus are F-.
•Sex pilus on F+ bacterium contacts F- bacterium and a single strand of plasmid DNA is transferred across the conjugal “mating” bridge.
• There is NO transfer of chromosomal DNA.
• vs. Hfr x F-
• The F+ plasmid can also become incorporated into the bacterial chromosome DNA via high-frequency recombination, creating an Hfr cell
• Replication of the incorporated plasmid DNA includes some flanking chromosomal DNA, so that conjugation will now transfer pieces of plasmid and chromosomal genes to the F- bacterium.
•F- bacterium DNA and donor DNA will recombine, creating an F- recombinant bacterium (with no F plasmid, and no sex pilus).
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Bacterial transposition
• Occurs when a segment of DNA (transposon) can “jump” (via excision and reintegration) from one location to another, i.e., can transfer genes from a plasmid to a chromosome and vice versa.
• When excision occurs, some flanking chromosomal DNA may be included, which can be incorporated into a plasmid and transferred to another bacterium via conjugation
• eg, vanA gene from vancomycin-resistant Enterococcus to Staphylococcus aureus.
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Generalized bacterial transduction
• Can be thought of as an accidental “packaging” event.
• A lytic phage infects the donor bacterium, leading to cleavage of bacterial DNA and replication of phage DNA.
• Occasionally during phage assembly, pieces of bacterial chromosomal DNA are packaged in phage capsids (no viral DNA included)
• Donor cell lyses, releasing phage particles containing donor bacterial DNA.
•Phage capsid containing bacterial DNA then “infects” a recipient bacterium, transferring donor bacterial chromosomal DNA that can be incorporated into genome of recipient bacterial cell, which becomes a recombinant cell.
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Specialized bacterial transduction
• Can be thought of as an “excision” event.
• Lysogenic phage infects a bacterium and incorporates viral DNA into bacterial chromosome.
• This bacterium can replicate normally, passing on bacterial chromosome with viral DNA to daughter cells.
• When phage DNA is eventually excised, during a lytic cycle, flanking bacterial genes may be excised with it.
•DNA is packaged into a phage capsid, which can infect another bacterium.
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Spirochetes
• Spiral-shaped bacteria with axial filaments
• BLT
•Borrelia burgdorferi is Big
• Leptospira interrogans
• Treponema pallidum
• Only Borrelia can be visualized using aniline dyes (Wright/Giemsa stain) in light microscopy due to its big size
• Treponema is visualized by dark-field microscopy or direct fluorescent antibody (DFA) microscopy
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Jarisch-Herxheimer reaction
Flu-like syndrome (fever, chills, headache, myalgias) after antibiotics are started due to killed bacteria (usually spirochetes) releasing toxins.
Leptospira interrogans
• Spirochete found in water contaminated with animal urine
• Leptospirosis = flu-like symptoms, myalgias (classically calves), jaundice, photophobia with conjunctival suffusion (erythema without exudate)
• Leptospirosis is prevalent among surfers and in the tropics (eg, Hawaii)
• Weil disease = icterohemorrhagic leptospirosis = severe form of leptospirosis with jaundice and azotemia from liver and kidney dysfunction, fever, hemorrhage, and anemia.
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Borrelia burgdorferi
• Spirochete transmitted by Ixodes deer tick, causes Lyme disease (common in northeastern US)
• Natural reservoir is the mouse –> mice important to tick life cycle
• Ixodes deer tick is also a vector for Anaplasma and the protozoa Babesia
• “Key LYME pie to the FACE!”
• Facial nerve palsy (typically bilateral)
• Arthritis
• Cardiac block
• Erythema migrans
• Stage 1 - early localized: erythema migrans, flu-like sx
• Stage 2 - early disseminated: secondary lesions, carditis, AV block, facial nerve (Bell) palsy, migratory myalgias/transient arthritis
• Stage 3 - late disseminated: encephalopathies, chronic arthritis
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Treponema pallidum
• Primary syphilis: localized disease presenting with painless chancre.
• VDRL + in 80% of patients.
• Use dark-field microscopy to visualize treponemes in fluid from chancre if possible.
• Secondary syphilis: systemic/disseminated disease with constitutional sx, maculopapular rash (including palms and soles), condylomata lata (smooth, moist, painless, wart-like white lesions on genitals), lymphadenopathy, and patchy hair loss.
• Confirm dx with dark-field microscopy if possible.
• Serologic testing: VDRL/RPR (nonspecific), confirm diagnosis with specific test (eg, FTA-ABS)
• Latent syphilis (+serology without sx) may follow.
• Tertiary syphilis characterized by:
• Gummas = chronic granulomas that destroy tissue
• Aortitis = vasa vasorpum destruction leads to aortic aneurysm
• Argyll Robertson pupil = constricts with accommodation but not reactive to light; also called “prostitute’s pupil” since it accommodates but does not react
• Stroke without hypertension
• Neurosyphilis (tabes dorsalis, “general paresis”) = broad-based ataxia, + Romberg, Charcot joint
• Test CSF with VDRL, FTA-ABS, and PCR for neurosyphilis
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Congenital syphilis
• Caused by placental transmission of Treponema palladium infection, typically during first trimester • Test and treat mother early in pregnancy to prevent congenital syphilis •Presents with facial abnormalities: • Rhagades (linear scars at angle of mouth) • Snuffles (nasal discharge) • Saddle nose • Notched Hutchinson teeth • Mulberry molars • Short maxilla • Saber shins • CN VIII damage (deafness) ******************************
VDRL false positives
•VDRL test detects nonspecific antibodies that react with beef cardiolipin.
• Inexpensive, widely available test for syphilis, quantitative, sensitive but not specific.
• False-positive VDRLs:
• Viral infection (EBV, hepatitis)
• Drugs
• Rheumatic fever
• Lupus (anti-cardiolipin abs) and leprosy
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Rickettsia rickettsii
• Rocky Mountain Spotted Fever (RMSF)
• Classic triad: headache, fever, and rash (vasculitis)
• Vector = Dermacentor (dog tick)
• Disease occurs primarily in South Atlantic states, especially North Carolina
• Rash starts at the wrists and ankles and spreads to the trunk, palms, and soles
•Remember: Rickettsii (RMSF) on the wRists, Typhi on the Trunk
• Tx. doxycycline
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Rickettsia typhi
• Endemic typhus
• Vector = fleas
• Rash starts centrally and spreads out, sparing palms and soles
•Remember: Rickettsii (RMSF) on the wRists, Typhi on the Trunk
• Tx. doxycycline
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Rickettsia prowazekii
• Epidemic typhus
• Vector = human body louse, human-to-human spread
• Rash starts centrally and spreads out, sparing palms and soles
•Remember: Rickettsii (RMSF) on the wRists, Typhi on the Trunk
• Tx. doxycycline
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Chlamydiae spp.
• Chlamydiae cannot make own ATP and are therefore obligate intracellular organisms –> cause mucosal infections
• Chlamys = cloak aka “cloaked by cell”
• 2 forms: elementary body vs. reticulate body
• Elementary body (small, dense) is “Enfectious” and Enters cell via Endocytosis –> once inside transforms into reticulate body
• Reticulate body Replicates in cell via fission–> Reorganizes into elementary bodies
• Chlamydia trachomatis: cause reactive arthritis (Reiter syndrome), follicular conjunctivitis, nongonococcal urethritis, and PID.
• Chlamydophila pneumoniae and Chlamydophila psittaci cause atypical pneumonia, transmitted by aerosol
• Chlamydophila psittaci has an avian reservoir (PARROTS), and causes atypical Pneumonia (“psittacosis”)
• Dx. cytoplasmic inclusions seen on Giemsa or fluorescent antibody-stained smear
• Tx. azithromycin (favored b/c one-time treatment) or doxycycline
• Chlamydial cell wall lacks classic peptidoglycan (reduced muramic acid), rending beta-lactams less effective.
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Chlamydia trachomatis serotypes
• Types A, B, C = Africa, Blindness, Chronic infection –> serotypes A, B, C cause blindness due to follicular conjunctivitis
• Types D-K = everything else; urethritis, PID, ectopic pregnancy, neonatal pneumonia (staccato cough) with eosinophilia, neonatal conjunctivitis (infected mother–> neonatal disease acquired during passage through infected birth canal). Tx. azithromycin or doxycycline
• Types L1, L2, L3 = Lymphogranuloma venerum –> small, painless ulcers on genitals cause swollen painful inguinal LNs that ulcerate (buboes). Tx. doxycycline
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Mycoplasma pneumoniae
• Pleomorphic bacteria with no cell wall. Not visualized on Gram stain. Bacterial membrane contains sterols for stability.
• Classic cause of atypical “walking” pneumonia –> more common in patients less than 30 years old
• Frequent outbreaks in military recruits and prisons.
• Insidious onset, headache, nonproductive cough, patchy or diffuse interstitial infiltrate
• X-ray looks worse than patient
• High titer of cold agglutinins (IgM), which can agglutinate or lyse RBCs
• Grown on Eaton agar
• Tx. macrolides, doxycycline, or fluoroquinolone
• Penicillins ineffective as no cell wall
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Periodic acid-Schiff (PAS) stain
• Stains glycogen, mucopolysaccharides
• Used to diagnosed Whipple disease (Tropheryma whipplei)
• PaS the sugar
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Eaton agar
Used to grow Mycoplasma pneumoniae, requires cholesterol
Löwenstein-Jensen agar
Used to grow Mycobacterium tuberculosis
Tellurite agar (aka Hoyle’s agar)
Selective for Corynebacterium diphtheriae. Used with Löffler’s medium for enrichment. Corynebacterium reduces tellurite to tellurium causing brown colonies or black halo around colonies.
Regan-Low medium
Used to grow Bordetella pertussis. Charcoal, blood and antibiotic medium.
Bordet-Gengou agar
Classically used to grow Bordetella pertussis. Agar plate contains blood, potato extract (nitrogen, vitamins), glycerol (carbon source), and antibiotics. Mostly replaced by Regan-Lowe medium.
Chocolate agar
Chocolate blood agar (CBA) - contains lysed RBCs, factors V (NAD+) and X (hematin) to grow H. influenzae. Bacitracin selects for Haemophilus influenzae.
Thayer-Martin agar
Variant of chocolate blood agar selective for Neisseria. “Very Typically Cultures Neisseria” –> Vancomycin (kills most Gram+), Trimethoprim (inhibits gram -, esp Proteus), Colistin (most gram - killed, except Neisseria), Nystatin (kills most fungi).
Cutaneous mycoses
• Tinea = clinical name given to cutaneous fungal infections by dermatophytes
• Dermatophytes include Microsporum, Trichophyton, Epidermophyton
• Branching septate hyphae visible on KOH preparation with blue fungal stain
• Tinea capitis = occurs on head/scalp; associated with lymphadenopathy, alopecia, scaling.
• Tinea corporis = occurs on torso; characterized by erythematous scaling rings (“ringworm”) and central clearing.
• Tinea cruris = occurs in inguinal area; “jock itch”, often does not show central clearing seen in tinea corporis.
• Tinea pedis = 3 varieties: interdigital is most common, moccasin distribution, vesicular type.
• Tinea unguium = onchomycosis; occurs on nails.
• Tx. selenium sulfide, topical (clotrimazole, miconazole) and/or oral (terbinafine, griseofulvin) anti fungal medications
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Tinea versicolor aka Pityriasis versicolor
• Caused by Malassezia spp. (Pityrosporum spp.)
• Yeast-like fungus - NOT a dermatophyte despite being called tinea
• Degradation of lipids produces acids that damage melanocytes and cause hypo pigmented and/or pink patches
• Can occur any time of the year, but more common in summer (hot, humid weather)
• “Spaghetti and meatballs” appearance on microscopy
• Tx. selenium sulfide, topical (clotrimazole, miconazole) and/or oral (terbinafine, griseofulvin) antifungal medications
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Candida albicans
• Opportunistic fungal infection
• Dimorphic fungus –> forms pseudohyphae and budding yeasts at 20ºC, germ tubes at 37ºC
• Causes systemic or superficial fungal infections
• Oral and esophageal thrush in immunocompromised patients (neonates, pts on steroids, diabetics, AIDS)
• Vulvovaginitis (diabetics, use of antibiotics)
• Diaper rash
• Endocarditis in IVDUs
• Disseminated candidiasis (to any organ)
• Chronic mucocutaneous candidiasis
• Tx. topical azole (clotrimazole, miconazole) for vulvovaginitis
• Tx. Nystatin, fluconazole, or caspofungin for oral/esophageal candidiasis
• Tx. Fluconazole, caspofungin, or amphotericin B for systemic candidiasis
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Aspergillus fumigatus
• Opportunistic fungal infection
• Septate hyphae that branch at 45ºC
• Produces conidia in radiating chains at end of conidiophore
• Causes invasive aspergillosis, especially in immunocompromised hosts and those with chronic granulomatous disease
• Can cause aspergillomas in pre-existing lung cavities, especially after TB infection
• Produce carcinogenic Aflatoxins = associated with hepatocellular carcinoma
• Allergic bronchopulmonary aspergillosis (ABPA): hypersensitivity response associated with asthma and cystic fibrosis; may cause bronchiectasis and eosinophilia.
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Cryptococcus neoformans
• Opportunistic fungal infection
• Heavily encapsulated yeast. Not dimorphic.
• 5-10µm with narrow budding
• Found in soil and pigeons droppings
• Acquired through inhalation with hematogenous dissemination to meninges
• Culture on Sabouraud agar
• Highlighted with India ink (clear halo) and mucicarmine (red inner capsule)
• Latex agglutination test detects polysaccharide capsule and is more specific
• Cryptococcosis, cryptococcal meningitis, cryptococcal encephalitis (“soap bubble” lesions in brain) primarily in immunocompromised
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Mucor and Rhizopus spp.
• Opportunistic fungal infection
• Irregular, broad, nonseptate hyphae branching at wide angles
• Mucormycosis = disease mostly in ketoacidotic diabetic and/or neutropenic patients (eg, leukemia)
• Fungi proliferate in blood vessel walls, penetrate cribriform plate, and enter brain
• Rhinocerebral, frontal lobe abscess
• Cavernous sinus thrombosis
• Headache, facial pain, black necrotic eschar on face, may have cranial nerve involvement
• Tx. surgical debridement, amphotericin B
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Pneumocystis jirovecii
• Pneumocystis pneumonia (PCP) = diffuse interstitial pneumonia caused by inhalation of Pneumocystis jirovecii
• Yeast-like fungus (originally classified as a protozoan)
• Most PCP infections asymptomatic
• Immunosuppressed individuals predisposed to PCP
• Diffuse, bilateral ground-glass opacities on CXR/CT scan
• Dx by lung biopsy or bronchioalveolar lavage
•Disc-shaped yeast seen on methenamine silver stain of lung tissue
• Tx/prophylaxis: TMP-SMX, pentamidine, dapsone (prophylaxis only), atovaquone
• Start prophylaxis when CD4+ count drops to less than 200 cells/mm3 in HIV patients
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Sporothrix schenckii
• Dimorphic, cigar-shaped budding yeast that grows in branching hyphae with rosettes of conidia
• Lives on vegetation, eg, roses
• Spores traumatically introduced into skin, typically by a thorn (“rose gardener’s” disease) –> sporotrichosis
•Local pustule or ulcer with nodules along draining lymphatics (ascending lymphangitis)
• Disseminated disease possible in immunocompromised host
• Tx. itraconazole or potassium iodide
• Plant a rose in the POTassium iodide.”
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Giardia lamblia
• Protozoan causing GI infection - Giardiasis
• Bloating, flatulence, foul-smelling, fatty diarrhea
• Often seen in campers/hikers
• Transmitted by cysts in water
• Dx. multinucleated trophozoites or cysts in stool
• Tx. metronidazole
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Entamoeba histolytica
• Protozoan causing GI infection - Amebiasis
• Bloody diarrhea (dysentery), liver abscess (“anchovy paste” exudate), RUQ pain
• Histology of intestinal amebiasis shows flask-shaped ulcer–> base in submucosa with small opening in mucosa
• Transmitted by cysts in water
• Dx. Serology and/or trophozoites (with engulfed RBCs in the cytoplasm) or cysts with up to 4 nuclei in stool
• Tx. Metronidazole; iodoquinol for asymptomatic cyst passers
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Cryptosporidium
•Protozoan causing GI infection –> cryptosporidiosis
• Severe diarrhea in AIDS
• Mild disease (watery diarrhea) in immunocompetent hosts
• Transmitted by oocysts in water
• Dx. Oocysts on acid-fast stain
• Tx. prevention (by filtering city water supplies); nitazoxanide in immunocompetent hosts
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Toxoplasma gondii
• Protozoan causing CNS infection –> toxoplasmosis
• Congenital toxoplasmosis = classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications.
• Toxoplasmosis asymptomatic in majority of adults –> some may have latent infection with tissue cysts (bradyzoites)
• Reactivation in AIDS/immunocompromised patients –> brain abscess seen as ring-enhancing lesions on MRI
• Transmission via cysts in poorly cooked meat (most common) or oocysts in infected cat feces –> toxoplasmosis crosses placenta (pregnant women should avoid cat litter)
• Dx. Serology (test blood for antibodies, or amniotic fluid for DNA), tachyzoite on biopsy
• Tx. sulfadiazine + pyrimethamine
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Naegleria fowleri
• Protozoan causing CNS infection
• Rapidly fatal meningoencephalitis
• Transmission by swimming in freshwater lakes –> enters CNS via cribriform plate
• Dx. Amoebas in CSF
• Tx. Amphotericin B effective for a few survivors
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Trypanosoma brucei
• Protozoan causing CNS infection
• African sleeping sickness - enlarged lymph nodes, recurring fever (due to antigenic variation), somnolence, coma
• Two subspecies: Trypanosoma brucei rhodesiense, gambiense
• Transmission by Tsetse fly –> painful bite!
• Trypomastigote in blood smear
• SURamin for blood-borne disease or MELarsoprol for CNS penetration
• It SURe is nice to go to sleep”; MELatonin helps with sleep
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Malaria
• Plasmodium vivax, P. ovale, P. falciparum, P. malariae
• Malaria presents as fever, headache, anemia, splenomegaly
• P vivax/ovale - 48-hr cycle (tertian; includes fever on first day and third day, thus fevers are actually 48 hrs apart); dormant forms (hypnozoite) in liver
• P falciparum - severe; irregular fever patterns; parasitized RBCs occlude capillaries in brain (cerebral malaria), kidneys, lungs
• P malariae - 72-hr cycle (quartan)
• Transmission via Anopheles mosquito
• Dx. Blood smear: trophozoite ring form within RBC, schizont containing merozoites; red granules throughout RBC cytoplasm (Schüffner stippling) seen with P vivax/ovale
• Tx. Chloroquine (for sensitive species)- blocks Plasmodium heme polymerase
• Tx if resistant. Mefloquine or atovaquone/proguanil
• Tx if life-threatening. IV quinidine or artesunate (test for G6PD deficiency)
• Tx for P vivax/P ovale. Add primaquine for hypnozoites (test for G6PD deficiency)
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Babesia
• Babesia is a protozoan that causes hematological infection
• Babesiosis presents as fever and hemolytic anemia
• Predominantly in the northeastern US
• Asplenia increases risk of severe disease
• Ixodes tick = vector
• Dx. blood smear: ring form or “Maltese cross” form
• Dx. PCR
• Tx. Atovaquone + azithromycin
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Trypanosoma cruzi
• Chagas disease
• Dilated cardiomyopathy with apical atrophy, megacolon, megaesophagus (achalasia)
• Predominantly in South America
• Unilateral periorbital swelling (Romaña sign) characteristic of acute stage
• Transmitted by Reduviid bug (“kissing bug”) feces –> deposited in a painless bite (like a kiss)
• Dx. Trypomastigote in blood smear
• Tx. Benznidazole or nifurtimox
• CRUZing in my BENZ with a FUR coat on??
• aka BENZnidazole or niFURtimox tx T. CRUZi
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Leishmania donovani
• Visceral leishmaniasis (kala-azar) = spiking fevers, HSM, pancytopenia
• Cutaneous leishmaniasis = skin ulcers
• Transmitted by sandfly
• Dx. Macrophages containing amastigotes
• Tx. Amphotericin B, sodium stibogluconate
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Trichomonas vaginalis
• Trichomonas vaginitis = foul-smelling, greenish discharge; itching and burning
• Do not confuse with Gardnerella vaginalis, a gram-variable bacterium associated with bacterial vaginosis
• Transmission is sexual –> cannot exist outside human body b/c cannot form cysts
•Dx. trophozoites (motile) on wet mount –> strawberry cervix
• Tx. Metronidazole for patient and partner (prophylaxis)
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Nematode routes of infection
• INGESTED: “You’ll get sick if you EATT these!!!”
• Enterobius, Ascaris, Toxocara, Trichinella
• CUTANEOUS: “These get into your feet from the SANd!”
• Strongyloides, Ancylostoma, Necator
• BITES from vectors: “Lay LOW to avoid getting bitten.”
• Loa loa, Onchocerca volvulus, Wuchereria bancrofti
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Immune response to helminths
• Eosinophils act by type I and type II hypersensitivity reactions in responding to helminths.
• Type I - neutralization of histamine and leukotrienes
• Type II - eosinophils attach to surface of helminths via IgE and release cytotoxins (eg, major basic protein) contained in their granules
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Ascaris lumbricoides (giant roundworm)
• Nematode, transmitted by ingestion (fecal-oral route), causes intestinal infection
• Most common helminthic infection
• Found in tropical climates/ Southern USA
• Ascariasis - can either cause pneumonia, asymptomatic, or abdominal pain –> may cause intestinal occlusion at the ileocecal valve with worm ball (mass)
• Eggs hatch in the small intestine –> hematogenous spread to the lungs
• Dx. Eggs with “rough surface” in stool
• Labs reveal eosinophilia
• Tx. Pyrantel pamoate, mebendazole, albendazole
• Tx. with BENDazoles b/c worms are BENDY!
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Enterobius vermicularis (pinworm)
• Nematode, transmitted by ingestion (fecal-oral route), causes intestinal infection
• Most common helminthic infection in the USA
• Primarily infects children
• Presents with perianal pruritus
• Eggs hatch in duodenum, mature in ileum/colon, mate in colon –> at night females migrate out of the rectum to lay eggs in the perianal area, causing sx
• Dx. via “scotch tape test” by seeing eggs
• Tx. Mebendazole, albendazole, pyrantel pamoate
• Tx. with BENDazoles b/c worms are BENDY!
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Trichuris trichiura (whipworm)
• Nematode, transmitted by ingestion (fecal-oral route), causes intestinal infection
• Similar to lifestyle enterobius but no perianal pruritus
• Tx. Mebendazole, albendazole, pyrantel pamoate
• Tx. with BENDazoles b/c worms are BENDY!
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Taenia saginata (beef tapeworm)
• Cestode (tapeworm), transmitted by ingestion (fecal-oral route), causes intestinal infection
• Platyhelminth (flatworm)
• Presents as asymptomatic or abdominal pain, malnutrition
• Larvae present in cow muscle –> ingested in poorly cooked beef–> adults attach scolex to wall of intestine –> proglottids (autonomous segments) containing eggs pass in feces
• No hooks on scolex!
• Dx. eggs and proglottids in stool
• Tx. niclosamide + cathartic OR praziquantel
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Taenia solium (pork tapeworm)
• Cestode (tapeworm), transmitted by ingestion (fecal-oral route), causes intestinal infection OR tissue infection (cysticercosis, neurocysticercosis)
• Platyhelminth (flatworm)
• Larvae are present in cysticerci in pig muscle –> ingested in poorly cooked pork –> scolex (with hooks!) attaches to intestinal wall –> proglottids containing eggs pass in feces
• Dx. eggs and proglottids in stool
• Tx. niclosamide + cathartic OR praziquantel
• Neurocysticercosis - neurologic defects (seizures, headaches)
• Humans ingest eggs from infected feces –> eggs hatch into oncospheres in small intestine –> oncospheres penetrate intestinal wall and travel to other tissues –> form cysticerci containing larvae in brain, skeletal muscle, and eyes
• Cysts grow slowly, causing neurological defects (seizures, focal sx) or blindness over time –> when cysts die after several years –> increased inflammation causes worsened symptoms
• Dx. calcified cysticerci in muscles/brain on x-ray or CT scan, eosinophilia
• Larvae can be detected swimming in vitreous humor of eyes
• Tx. Albendazole + steroids to reduce inflammation from dying cysts, praziquantel
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Diphyllobothrium latum (fish tapeworm)
• Cestode (tapeworm), transmitted by ingestion of poorly-cooked fish (fecal-oral route), causes intestinal infection
• Platyhelminth (flatworm)
• Ingestion of larvae from raw freshwater fish
•Tapeworm competes for B12 in intestine –> leads to vitamin B12 deficiency due to malabsorption –> megaloblastic anemia
•Does not pass Schilling test (radiolabeled B12)
• Tx. Praziquantel
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Trichinella spiralis
• Nematode, transmitted by ingestion (fecal-oral route), causes intestinal infection and tissue infection
• Most common parasitic cause of myocarditis
• Trichinosis = fever, vomiting, nausea (gastroenteritis), periorbital edema, myalgias
• Reservoir in pigs –> encysted larvae ingested from uncooked pork –> adult organisms in small intestine mate and lay eggs –> larvae penetrate intestinal wall into blood –> hematogenous spread to skeletal muscle (often extraocular muscles, masseters, tongue, diaphragm) causing myalgias
• Larvae form fibrous cysts that may calcify and last for years
• If many larvae are ingested –> severe infection –> larvae migrate to heart and brain causing myocarditis and encephalitis
• Dx. eosinophilia, increased IgE levels, increased muscle enzymes (CK), biopsy of striated muscle showing cysts
• Tx. mebendazole/thiabendazole, steroids for severe myositis/myocarditis
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Toxocara canis
• Nematode, transmitted by ingestion (fecal-oral route), causes tissue infection
• Visceral larva migrans - nematodes migrate to blood through intestinal wall causing inflammation and damage
• Organs frequently affected include heart (myocarditis) liver, and CNS (seizures, coma)
• Dx. eosinophilia, increased IgE levels
• Tx. mebendazole/thiabendazole
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Echinococcus granulosus (dog tapeworm)
• Platyhelminth (flatworm), Cestode (tapeworm), transmitted by ingestion (fecal-oral route), causes echinococcosis aka Hydatid cyst disease
• Scolex with hooks and only 3 proglottids!
• Ingestion of eggs in dog feces –> eggs hatch in small intestine –> larvae penetrate intestinal wall –> travel to and infect other tissue –> form hydatid cysts in liver, lung, or brain
• Hydatid cysts grow and divide, causing organ displacement and dysfunction, esp. in the liver
• Enlarged cyst may rupture, releasing antigenic cyst contents (anaphylaxis) and larvae into blood stream
• Dx. x-ray/CT, serology
• Presence of daughter cysts within hydatid cyst is pathognomonic
• Tx. Albendazole, surgery to remove hydatid cyst
• Hydatid cysts in liver cause anaphylaxis if antigens released (hydatid cyst injected with ethanol or hypertonic saline to kill daughter cysts before removal incase rupture occurs during surgery)
• Common in sheepherders –> get it from their sheep dogs (feces) of dogs that eat raw sheep meat (sheep are intermediate hosts)
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Strongyloides stercoralis (threadworm)
• Nematode, transmitted by contact (fecal-cutaneous), causes intestinal infection
• ASSOCIATED with HTLV-1 infection
• Strongyloidiasis may present as asymptomatic, pneumonia, gastroenteritis, or peritonitis autoinfection in immunodeficient patients
• Fecal-cutaneous transmission–> infectious (filariform) larvae in soil penetrate skin on feet causing local pruritus –> enter bloodstream –> spread hematogenously to lungs –> enter alveoli and ascend the trachea –> PNA –> pass through pharynx into small intestine –> mature into adults and mate –> females lay eggs in mucosa –> eggs hatch, causing epigastric pain (mimics PUD), diarrhea, vomiting –> larvae exit feces and contaminate soil
• In immunocompromised –> larvae may penetrate intestinal wall and enter the bloodstream to spread to lungs and repeat the infectious cycle (autoinfection) or may tunnel through intestinal wall to cause peritonitis
• Dx. detect larvae (NOT eggs) in stool, eosinophilia, “string test” for duodenal pathogens –> swallow long string to pull out larvae
• Tx. Ivermectin, thiabendazole
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Necator americanus (hookworm)
• Nematode, transmitted by contact (fecal-cutaneous), causes intestinal infection + anemia
• Fecal-cutaneous transmission similar to Strongyloides stercoralis –> larvae penetrate skin on foot
• Once larvae mature into adults in the small intestine –> attached to mucosa via cutting plates or teeth, causing gastroenteritis
• Secrete anticoagulant and suck blood from the host –> iron-deficiency anemia
• In small intestine lumen –> adults mate and eggs are passed in feces
• Dx. Detect eggs (NOT larvae) in stool, eosinophilia
• Tx. Mebendazole or pyrantel pamoate, iron and folic acid for anemia
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Ancylostoma duodenale (hookworm)
• Nematode, transmitted by contact (fecal-cutaneous), causes intestinal infection + anemia
• Fecal-cutaneous transmission similar to Strongyloides stercoralis –> larvae penetrate skin on foot
• Once larvae mature into adults in the small intestine –> attached to mucosa via cutting plates or teeth, causing gastroenteritis
• Secrete anticoagulant and suck blood from the host –> iron-deficiency anemia
• In small intestine lumen –> adults mate and eggs are passed in feces
• Dx. Detect eggs (NOT larvae) in stool, eosinophilia
• Tx. Mebendazole or pyrantel pamoate, iron and folic acid for anemia
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Ancylostoma braziliense (cat and dog hookworm)
• Nematode, transmitted by contact (fecal-cutaneous), causes cutaneous larva migrans
• Cutaneous larva migrant = pruritic, serpiginous rash from walking barefoot on contaminated beach
• Larvae cannot invade bloodstream in humans –> larvae travel subcutaneously
• Tx. Albendazole, thiabendazole
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Schistosoma spp. (Blood fluke)
• Platyhelminth (flatworm), Trematode (flukes), transmitted by contact (fecal-cutaneous route), causes schistosomiasis and Katayama fever
• Schistosomal eggs are highly immunoreactive, but adults coat themselves with host antigens, surviving in venous plexuses for years
• Acute disease: pruritus at site of infection, Katayama fever, chills, lymphadenopathy
• Chronic disease: periportal fibrosis, intestinal polyps, bladder inflammation, hematuria, risk for bladder carcinoma
• Larvae (cercariae) are released by snails into fresh water –> penetrate human flesh and enter bloodstream –> locate to portal vein, where larvae mature –> adult pairs migrate against portal flow to various venous plexuses
• Schistosoma mansoni and Schistosoma japonicum travel to intestinal venous plexus –> mate and release eggs –> cause acute inflammation (Katayama fever) –> eggs exit through intestinal lumen to feces –> some eggs carried to portal circulation –> cause chronic inflammation and periportal fibrosis –> portal hypertension, HSM, esophageal varices
•Some eggs lodge in the intestinal wall causing chronic inflammation and polyps
• Schistosoma haematobium travels from portal flow to bladder venous plexus –> mate and release eggs –> acute inflammatory response (Katayama fever) –> eggs exit into bladder lumen and lodge in the bladder wall –> chronic inflammation causes painless hematuria and increases risk for squamous cell carcinoma of the bladder
• Dx. Detect eggs in feces/urine, eosinophilia
• Dx. S mansoni = egg with lateral spine, S haematobium = egg with terminal spine
• Tx. Praziquantel
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Onchocerca volvulus
• Nematode, Filariae, transmitted by bite (vector), causes tissue infection
• Onchocerciasis aka River blindness = skin nodules, thick hyperpigmented pruritic rash, loss of elastic fibers, blindness –> (black flies, black skin nodules, “black” sight)
• Vector = Female blackfly (found near rivers)
• Blackfly bite release larvae into skin –> larvae move through subcutaneous tissue –> mature into adults –> fibrosis around adults creates subcutaneous nodules –> adults mate and release microfilariae into the subcutaneous tissue –> microfilariae move subcutaneously throughout body causing inflammation and a thickened pruritic rash –> if microfilariae reach eye, cause inflammation and blindness
• Microfilariae can be ingested by mosquitos to form larvae
• Dx. skin biopsy detects microfilariae
• Tx. Ivermectin (IVERmectin for rIVER blindness)
• Ivermectin only active against microfilariae –> surgical removal of nodules required
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Wuchereria bancrofti
• Nematode, transmitted by bite (vector), causes tissue infection
• Elephantiasis/ Filariasis = fever, lymphadenopathy, edema and scaly skin of the legs and genitalia
• Transmitted by female mosquito –> bite releases larvae into blood –> carried to LNs of genitals and lower extremities –> mature into adults over 9 months to 1 year –> mate and release larvae (microfilariae) into blood at night –> adult worms trigger fever/inflammation and LN swelling –> with repeated infections fibrosis around the dead adult worms in LNs causes obstruction of lymphatic drainage of the legs and genitalia –> edema in legs/scrotum
• Tx. Diethylcarbamazine - only effective against microfilariae
• Larval forms have nocturnal schedule and emerge into the blood at night –> draw blood at night to detect microfilariae
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Loa loa
• Nematode, transmitted by bite (vector), causes tissue infection
• Causes swelling in skin and worms in conjunctiva
• Transmitted by deer fly, horse fly, mango fly
• Tx. Diethylcarbamazine
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Clonorchis sinensis
• Trematode, transmitted by ingestion of undercooked fish (fecal-oral route), causes biliary tract infection
• Biliary tract inflammation leads to pigmented gallstones
• Associated with cholangiocarcinoma
• Tx. Praziquantel
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Vitamin B12 deficiency. Which parasite is this?
Diphyllobothrium latum
Portal hypertension. Which parasite is this?
Schistosoma mansoni, Schistosoma japonicum
Perianal pruritus. Which parasite is this?
Enterobius vermicularis
Myalgias, periorbital edema. Which parasite is this?
Trichinella spiralis
Microcytic anemia. Which parasite is this?
Ancylostoma, Necator
Liver (hydatid) cysts. Which parasite is this?
Echinococcus granulosus
Hematuria, squamous cell bladder cancer. Which parasite is this?
Schistosoma haematobium
Brain cysts, seizures. Which parasite is this?
Taenia solium aka neurocysticercosis
Biliary tract disease, cholangiocarcinoma. Which parasite is this?
Clonorchis sinensis
Sarcoptes scabiei
• Ectoparasite
• Scabies = mites burrow into stratum corneum of skin and cause pruritic serpiginous burrows in webspaces of hands and feet.
• Common in children, crowded populations (jails, nursing homes)
• Transmission through fomites
• Tx. permethrin cream, washing/drying all clothing/bedding, treat close contacts.
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Pediculus humanus, Phthirus pubis
• Ectoparasites
• Lice = blood-sucking insects that prefer to live on clothing
• Cause intense pruritus, pink macule and papules commonly in intertriginous regions
• Lice can transmit Rickettsia prowazekii (typhus), Borrelia recurrentis (relapsing fever), Bartonella quintana (trench fever)
• Tx. pyrethroids, malathion, or ivermectin lotion, and nit combing
• Children with head lice can be treated at home without interrupting school
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Viral replication
• DNA viruses all replicate in the nucleus, except poxvirus
• RNA viruses all replicate in the cytoplasm, except influenza virus and retroviruses
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DNA viral genomes
• All DNA viruses have dsDNA viral genomes, except Parvoviridae (parvovirus)
• All are linear except: papillomavirus, polyomavirus, and hepadnaviruses, which are circular
• All are dsDNA, except “part-of-a-virus” (parvovirus) is ssDNA –> Parvus = small.
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Nonenveloped viruses
• Naked (nonenveloped) viruses include: •Papillomavirus (HPV) • Adenovirus • Parvovirus (B19) • Polyomavirus (JC virus) • Calicivirus (eg, norovirus) • Picornavirus (eg, rhinovirus, poliovirus) • Reovirus (eg, rotavirus) • Hepevirus (eg, Hep E virus) • "Give PAPP smears and CPR to a naked hippie (hepevirus)!" haha. • DNA viruses = PAPP, RNA = CPR and hepevirus ******************************
Enveloped virus
• Virion with a phospholipid-containing particle surface.
• Most enveloped viruses acquire lipid bilayer envelopes by budding through the PLASMA membrane of host cell when they exit from cell.
• However, the herpesviruses (CMV, VZV, HSV) bud through and acquire the lipid bilayer envelope from host cell NUCLEAR membrane.
• Envelope renders virus susceptible to anything capable of destroying lipids eg, bile acids
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How do HCV, mumps virus, and CMV obtain their envelope?
- HCV, an enveloped flavivirus, obtains its envelope by budding through plasma membrane of host cell
- Mumps virus, an enveloped paramyxovirus, obtains its envelope by budding through plasma membrane of host cell.
- CMV, an enveloped herpesvirus, obtains its envelope by budding through the nuclear membrane of the host cell!
* ***********
RNA viral genomes
• All RNA viruses are ssRNA, except Reovirus (eg, rotavirus)
•I.e., All are ssRNA, except “repeato-virus” (reovirus) is dsRNA –> RNA is repeated
• Positive-sense ssRNA viruses: “I went to a RETRO TOGA party, where I drank FLAVored CORONA and ate HIPPIE CALIfornia PICkles.”
• Retrovirus (eg, HIV, HTLV)
• Togavirus (eg, Rubella)
• Flavivirus (eg, HCV)
• Coronavirus (eg, SARS, common cold)
• Hepevirus (eg, HEV)
• Calicivirus (eg, norovirus)
• Picornavirus (eg, rhinovirus)
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Viral recombination
Exchange of genes btw 2 chromosomes by crossing over within regions of significant base sequence homology
Viral reassortment
• When viruses with segmented genomes (eg, influenza virus) exchange genetic material with each other.
• Eg, 2009 novel H1N1 influenza A pandemic emerged via a complex viral reassortment of genes from human, swine, and avian viruses.
• Has potential to cause antigenic shift.
• Changes in genomic composition that occur when host cells are coinfected with 2 segmented viruses that exchange whole genome segments –> any genomic change in the first generation progeny will be present in subsequent progeny
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Viral complementation
• When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein, the nonmutated virus “complements” the mutated one by making a functional protein that serves both viruses
• eg, hepatitis D virus requires presence of replicating HBV to supply HBsAg, the envelop protein for HDV
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Viral phenotypic mixing
• Occurs with simultaneous infection of a cell with 2 viruses
• Genome of virus A can be partially or completely coated (forming pseudovirion) with surface proteins of virus B
• Type B protein coat determines the tropism (infectivity) of the hybrid virus
• However, the progeny of this infection with the pseudovirion will have a type A coat that is encoded by type A genetic material
• Acquisition of new viral surface protein is often all that is necessary for virus to infect new type of host cell.
• Phenotypic mixing occurs when a host cell is connected with 2 viral strains and progeny visions contain unchanged parental genome from one strain and nucleocapsid (or envelope) proteins from the other strain
• B/c no change in underlying viral genomes (no genetic exchange) subsequent progeny will revert to having only nucleocapsid proteins of the parental genome
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Live attenuated viral vaccines
• Smallpox vaccine
• Yellow fever vaccine
• Rotavirus vaccine
• Chickenpox (VZV) vaccine
• Polio vaccine (Sabin)
• MMR vaccine (measles, mumps, rubella)
• Influenza vaccine (intranasal)
• Live attenuated vaccines induce humoral (B-cell) and cell-mediated (T-cell) immunity but have reverted to virulence on rare occasion.
• Dangerous to give live vaccines to immunocompromised patients –> close contacts may be vaccinated with live vaccines (except live polio or influenza)
• MMR is the only live attenuated vaccine that CAN be given to HIV+ patients who do not show signs of immunodeficiency.
• No booster needed for live attenuated vaccines.
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Killed viral vaccines
• "RIP Always" (killed virus) • Rabies vaccine • Influenza vaccine (IM) • Polio vaccine (SalK = Killed) • hepatitis A vaccine (HAV) • Killed/inactivated vaccines induce only humoral (B-cell) immunity (create plasma cells that secrete antigens) but are stable. ******************************
Subunit viral vaccines
• HBV = antigen is HBsAg
• HPV = types 6, 11, 16, 18
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Viral interference
Occurs when one virus inhibits replication and/or release of a second virus infecting the same host cell.
Naked viral genome infectivity
• Purified nucleic acids of most dsDNA (except poxvirus and HBV) and + strand ssRNA (equivalent to mRNA) viruses are infectious
• Naked nucleic acids of – strand ssRNA and dsRNA viruses are not infectious on their own and require polymerases encoded in the complete vision.
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Characteristics of DNA viruses
• HHAPPPPy viruses!
• Hepadnavirus (HBV), Herpesviruses, Adenovirus, Poxvirus, Parvovirus, Papillomavirus, Polyomavirus
• dsDNA, except: parvovirus (part-of-a-virus) is ssDNA
• Linear genomes, except: papillomavirus, polyomavirus (circular, supercoiled) and hepadnaviruses (circular, incomplete)
• Icosahedral capsid, except: poxvirus (complex)
• Replicate in the nucleus, except: poxvirus (carries own DNA-dependent RNA polymerase)
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Hepadnavirus
• Enveloped, circular, partially dsDNA virus; icosahedral capsid
• Hepatitis B virus (HBV)
• Causes acute or chronic hepatitis
• Not a retrovirus but has a reverse transcriptase, not infectious without reverse transcriptase
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Herpes simplex virus-1 (HSV-1)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: respiratory secretions, saliva
• Presents as gingivostomatitis, keratoconjunctivitis, herpes labialis, herpetic whitlow on finger, temporal lobe encephalitis
• Most common cause of sporadic encephalitis, can present as altered mental status, seizures, and/or aphasia
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Herpes simplex virus-2 (HSV-2)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: sexual contact, perinatal
• Herpes genitalis, neonatal herpes (passing through infected mother’s vaginal canal)
• Virus remains latent in sacral ganglia
• Viral meningitis more common with HSV-2 than HSV-1
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Varicella-Zoster virus (VZV, HHV-3)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: respiratory secretions
• Varicella-zoster = chickenpox, shingles
• May cause encephalitis or pneumonia
• Most common complication of shingles is post-herpetic neuralgia
• Virus remains latent in dorsal root or trigeminal ganglia –> can reactivate as shingles
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Epstein-Barr virus (EBV, HHV-4)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: respiratory secretions, saliva
• EBV aka “kissing disease” (common in teens/young adults)
• Mononucleosis - fever, HSM, pharyngitis, LAD (especially posterior cervical nodes
• Avoid contact sports until resolution due to risk of splenic rupture
• Associated with lymphoma (eg, endemic Burkitt lymphoma) and nasopharyngeal carcinoma
• EBV infects B cells through CD21 receptor
• Labs reveal atypical lymphocytes on blood smear –> these are not infected B cells but reactive cytotoxic T cells.
• Positive Monospot test = heterophile antibodies detected by agglutination of sheep or horse RBCs
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Cytomegalovirus (CMV, HHV-5)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: congenital, sexual contact, saliva, urine, transplant
• CMV infects cells through integrin receptor (heparan sulfate)
• Mononucleosis with negative Monospot test in immunocompetent patients
• Infection in immunocompromised patients, especially pneumonia in transplant patients
• AIDS retinitis (“sightomegalovirus”): hemorrhage, cotton-wool exudates, vision loss.
• Congenital CMV
• Infected cells have characteristic “owl eye” inclusions
• Virus remains latent in mononuclear cells and may reactivate in immunocompromised hosts
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Human herpesvirus 6 and 7 (HHV-6, HHV-7)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: saliva
• HHV-6 = Roseola infantum (exanthem subitum): high fevers for several days that can cause seizures, followed by diffuse macular rash
• HHV-7 = less common cause of roseola
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Human herpesvirus 8 (HHV-8)
• Enveloped, linear, dsDNA virus; icosahedral capsid
• Herpesviruses acquire lipid bilayer envelope by budding through host cell NUCLEAR membrane after replication and assembly.
•Route of transmission: sexual contact
• Kaposi sarcoma = neoplasm of endothelial cells
• Seen in HIV/AIDS and transplant patients
• Dark/violaceous plaques or nodules representing vascular proliferations
• Can also affect GI tract and lungs
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Adenovirus
• Nonenveloped, linear, dsDNA virus; icosahedral capsid
• Causes febrile pharyngitis, sore throat
• Acute hemorrhagic cystitis
• Pneumonia
• Conjunctivitis - “pink eye”
• Remember “PAPP” for unenveloped DNA viruses
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Poxvirus
• Enveloped, linear, dsDNA virus; NO icosahedral capsid, complex capsid
• Largest DNA virus
• Smallpox eradicated world wide by use of live-attenuated vaccine
• Cowpox = milkmaid blisters
• Molluscum contagiosum = flesh-colored papules with central umbilication
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Parvovirus
• Nonenveloped, linear, ssDNA virus; icosahedral capsid
• Smallest DNA virus
• Parvovirus B19 - causes aplastic crises in patients with sickle cell disease or asplenia due to HS
• Parvovirus B19 in children = erythema infectiosum or fifth disease –> “slapped cheek” rash
• RBC destruction in fetus leads to hydrops fetalis and death, in adults leads to pure RBC aplasia and rheumatoid arthritis-like sx
• Remember “PAPP” for unenveloped DNA viruses
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Papillomavirus
• Nonenveloped, circular supercoiled, dsDNA virus; icosahedral capsid
• Human Papillomavirus (HPV)
• Serotypes 1, 2, 6, 11 –> genital warts, aka “low risk” serotypes
• Serotypes 16, 18, 31, 32 –> CIN and cervical cancer, aka “high risk” serotypes
• Remember “PAPP” for unenveloped DNA viruses
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Polyomavirus
• Nonenveloped, circular supercoiled, dsDNA virus; icosahedral capsid
• JC virus = progressive multifocal leukoencephalopathy (PML) in HIV patients
• BK virus = transplant patients, commonly targets kidneys
• JC = Junky Cerebrum vs. BK = Bad Kidneys
• Remember “PAPP” for unenveloped DNA viruses
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HSV identification
• Viral culture for skin/genitalia
• CSF PCR for herpes encephalitis
• Tzanck test - a smear of an opened skin vesicle to detect multinucleated giant cells commonly seen in HSV-1, HSV-2, and VZV infection
• Intranuclear inclusions also seen with HSV-1, HSV-2, VZV
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Receptors used by: CMV, EBV, HIV, rabies (rhabdovirus), rhinovirus (picornavirus)
• CMV - integrins (heparan sulfate) • EBV - CD21 on B-cells • HIV - CD4, CXCR4, CCR5 on CD4+ T-cells • Rabies - Nicotinic AChR • Rhinovirus - ICAM-1 (cellular adhesion molecules on endothelium) ******************************
Negative-stranded viruses
• Must transcribe – strand to + sense RNA to use host cell machinery for protein synthesis
• Virion brings its own RNA-dependent RNA polymerase
• RNA viruses that are – stranded:
• Always Bring Polymerase Or Fail Replication
• Arenaviruses
• Bunyaviruses
• Paramyxoviruses
• Orthomyxoviruses
• Filoviruses
• Rhabdoviruses
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Segmented virus
• Segmented viruses are all RNA viruses • Think "BOAR" • Bunyaviruses • Orthomyxoviruses (influenza) • Arenaviruses • Reoviruses ******************************
Reoviruses
• Nonenveloped, linear, segmented, dsRNA; icosahedral double capsid
• 10-12 segments of dsRNA
• Coltivirus = COLorado TIck fever (arbovirus)
• Rotavirus = #1 caused of fatal diarrhea in children
• Rotavirus is the most important global cause of infantile gastroenteritis and a major cause of acute diarrhea in the US during winter, especially in daycare centers and kindergartens.
• CDC recommends routine vaccination of all infants
• Villous destruction with atrophy –> decreased absorption of Na+ and loss of K+
• Remember “CPR Hippie” for unenveloped DNA viruses
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Picornaviruses
• Nonenveloped, linear, + ssRNA; icosahedral capsid
• RNA is translated into 1 large polypeptide that is cleaved by proteases into functional viral proteins
• Pico = small RNA virus
• All are enteroviruses (fecal-oral spread) except rhinovirus
• “PERCH”
• Poliovirus - aseptic meningitis, Salk/Sabin polio vaccines (IPV/OPV)
• Echovirus - aseptic meningitis
• Rhinovirus - “common cold”, uses ICAM-1 as viral receptor, greater than 100 serologic subtypes, acid labile (destroyed by stomach acid) and does not infect the GI tract as the other picornaviruses do.
• Coxsackievirus - aseptic meningitis, herpangina (mouth blisters and fever), HFM disease, myocarditis, pericarditis
• Hepatits A virus (HAV) - acute viral hepatitis
• Remember “CPR Hippie” for unenveloped DNA viruses
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Caliciviruses
• Nonenveloped, linear, + ssRNA; icosahedral capsid
• Norovirus - viral gastroenteritis
• Remember “CPR Hippie” for unenveloped DNA viruses
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Hepevirus
• Nonenveloped, linear, + ssRNA; icosahedral capsid
• HEPEvirus = Hep E virus –> hepatitis
• Remember “CPR Hippie” for unenveloped DNA viruses
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Flaviviruses
• Enveloped, linear, + ssRNA; icosahedral capsid
• Flavi = yellow aka jaundice
• Hepatitis C virus (HCV)
• Yellow fever (arbovirus) –> Vector is Aedes mosquitoes. Monkey or human reservoir. Sx. High fever, black vomitus, and jaundice. Liver biopsy may reveal Councilman bodies (eosinophilic apoptotic globules).
• Dengue fever (arbovirus)
• St. Louis encephalitis (arbovirus)
• West Nile virus (arbovirus)
• Arbovirus = ARthropod BOrne virus (mosquitos, ticks)
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Togaviruses
• Enveloped, linear, + ssRNA; icosahedral capsid
• Rubella
• Eastern equine encephalitis (arbovirus)
• Western equine encephalitis (arbovirus)
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Retroviruses
• Enveloped, linear, + ssRNA (2 copies) • HTLV has icosahedral capsid • HIV has complex conical capsid • Reverse transcriptase • HTLV –> T-cell leukemia • HIV –> AIDS ******************************
Coronaviruses
• Enveloped, linear, + ssRNA; helical capsid • "Common cold" cause • SARS • MERS ******************************
Orthomyxoviruses
• Enveloped, linear, segmented (8) – ssRNA; helical capsid
• Influenza virus
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Paramyxoviruses
• Enveloped, linear, – ssRNA; helical capsid
• PaRaMyxovirus
• Parainfluenza –> croup
• RSV –> bronchiolitis in neonates (Rx = Ribavirin)
• Measles, Mumps
• MMR vaccine = against 2 paramyxoviruses and 1 togavirus
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Rhabdoviruses
• Enveloped, linear, – ssRNA; helical capsid
• Rabies virus= bullet-shaped virus
• Negri bodies (cytoplasmic inclusions) commonly found in Purkinje cells of cerebellum and in hippocampal neurons
• Rabies has long incubation period of weeks to months before sx onset
• Postexposure prophylaxis is wound cleaning plus immunization with killed vaccine and rabies immunoglobulin
• Example of passive-active immunity
• Rabies virus travels to CNS by migrating in a retrograde fashion up nerve axons after binding to nicotinic ACh receptors
• Progression of disease: fever and malaise –> agitation, photophobia, hydrophobia, hypersalivation –> paralysis, coma –> death
• Infection more commonly from bat, raccoon, skunk bites than from dog bites in the US
• Aerosol transmission from bat caves is also possible
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Filoviruses
• Enveloped, linear, – ssRNA virus with helical capsid
• Ebola/Marburg hemorrhagic fever –> often fatal!
•Ebola virus is a filovirus that targets endothelial cells, phagocytes, and hepatocytes
• Following incubation period of up to 21 days, presents with abrupt onset of flu-like sx, diarrhea/vomiting, high fever, myalgia
• Can progress to DIC, diffuse hemorrhage, and shock
• Dx with RT-PCR within 48hr of sx onset
• Transmission of ebola virus requires direct contact with bodily fluids, fomites (including dead bodies), infected bats or primates (apes/monkeys) –> high incidence of nosocomial infection
• Tx. Supportive care. No definitive tx.
• Strict isolation of infected individuals and barrier practices for health care workers are key to preventing transmission.
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Arenaviruses
• Enveloped, circular, + or – ssRNA; helical capsid
• 2 segments circular ssRNA
• Lymphocytic choriomeningitis virus (LCMV)
• Lassa fever encephalitis (spread by rodents)
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Bunyaviruses
• Enveloped, circular, – ssRNA; helical capsid
• 3 segments circular ssRNA
• California encephalitis (arbovirus)
• Sandfly fever (arbovirus)
• Rift Valley fever (arbovirus)
•Crimean-Congo hemorrhagic fever (arbovirus)
• Hantavirus - hemorrhagic fever, pneumonia
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Delta virus
• Enveloped, circular, – ssRNA
• Uncertain capsid
• HDV is a “defective” virus that requires presence of HBV to replicate –> uses complementation
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Influenza viruses
• Orthomyxovirus
• Enveloped, negative-sense ssRNA viruses with 8-segment linear genome and helical capsid
• Contain hemagglutinin antigen (promotes viral entry) and neuraminidase antigen (promotes progeny virion release)
• Patients at risk for fatal bacterial superinfection with Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae due to destruction of mucociliary clearance mechanisms
• Reformulated vaccine (flu shot) contains viral strains most likely to appear during the flu season, due to virus’ rapid genetic change
• Killed viral vaccine most frequently used
• Live attenuated vaccine contains temperature-sensitive mutant that replicates in the nose but not in the lung –> administered intranasally.
• Genetic/antigenic shift: causes pandemics –> reassortment of viral genome segments, such as when segments of human influenza A virus reassort with swine flu A virus
• Genetic/antigenic drift: causes epidemics –> minor (antigenic drift) changes based on random mutation in hemagglutinin or neuraminidase genes.
• “Sudden Shift is more deadly than graDual Drift.”
• Epidemic occurs when a disease affects more people than usual for a locality or spreads to areas not usually associated with the disease. A pandemic is an epidemic of world-wide proportions, i.e. one that affects a much larger geographic region.
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Rubella virus
• Togavirus
• Enveloped, linear + ssRNA virus with icosahedral capsid
• Rubella once known as German (3-day) measles
• Fever, postauricular LAD, other LAD, arthralgias, and a fine confluent rash that starts on the face and spreads centrifugally to involve the trunk and extremities
• Causes mild disease in children but serious congenital disease (ToRCHeS infection) –> Congenital Rubella Syndrome (CRS) if pregnant woman unvaccinated and contracts rubella while pregnant
• Congenital rubella findings include “blueberry muffin” rash due to dermal extramedullary hematopoiesis, as well as heart disease, microcephaly, glaucoma, cataracts, deafness
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Paramyxoviruses
• Enveloped, linear – ssRNA virus with helical capsid
• Parainfluenza (croup, seal-like barking cough), RSV, Measles, Mumps
• Paramyxoviruses cause disease in children
• RSV causes bronchiolitis or pneumonia in infants
• All contain surface F (fusion) protein –> causes respiratory epithelial cells to fuse and form multinucleated cells (syncytia)
• Palivizumab (monoclonal antibody against F protein) prevents pneumonia caused by RSV infection in premature infants
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Croup
• Acute laryngotracheobronchitis
• Caused by parainfluenza virus (paramyxovirus) –> enveloped, linear – ssRNA virus with helical capsid
• “Seal-like” barking cough with inspiratory stridor
• Narrowing of upper trachea and subglottis leads to characteristic steep sign on x-ray
• Severe croup can result in pulsus paradoxus due to upper airway obstruction
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Measles (rubeola) virus
• Enveloped, linear – ssRNA paramyxovirus with helical capsid
• 3 C’s of measles: Cough, Coryza, Conjunctivitis
• Usually presents with prodromal fever, cough, coryza (discharge from nose, eyes, etc.), and conjunctivitis –> eventually Koplik spots (bright red spots with blue-white center on buccal mucosa) –> followed 1-2 days later by a maculopapular rash that starts at head/neck and spreads downward.
• Koplik spots are a prodromic viral exanthem manifesting 2-3 days before measles rash itself.
• Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in background of paracortical (paracortex is where T-cells are in LNs) hyperplasia.
• SSPE (subacute sclerosing panencephalitis) occurring years later, encephalitis (1:2000), and giant cell pneumonia (rarely, in immunosuppressed) are possible sequelae
• Tx. Vitamin A supplementation can reduce morbidity and mortality from measles, particularly in malnourished children
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Mumps virus
• Enveloped, linear – ssRNA paramyxovirus with helical capsid
• Uncommon due to effectiveness of MMR vaccine
• Sx. Parotitis, Orchitis, aseptic Meningitis, and Pancreatitis
• “Mumps makes your parotid glands and testes as big as POM-Poms.”
• Mumps orchitis can cause sterility, especially if infected after puberty
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HBV
• DNA hepadnavirus –> enveloped, circular, partial/incomplete dsDNA virus with an icosahedral capsid
• Hepatitis sx: episodes of fever, jaundice, increased levels of ALT and AST
• Transmission is parenteral (Blood), sexual (Baby-making), perinatal (Birthing)
• Incubation period is long (months)
• Initially like serum sickness (fever, arthralgias, rash) –> may eventually progress to carcinoma (HCC)
• Most adults have full resolution, minority have chronic infection
• Liver bxp shows granular eosinophilic “ground glass” appearance –> cytotoxic T cells mediate damage
• Carrier state is common
• HBV DNA polymerase has DNA- and RNA-dependent activities –> upon entry into host cell nucleus, polymerase completes partial dsDNA –> host RNA polymerase transcribes mRNA from viral DNA to make viral proteins –> DNA polymerase reverse transcribes viral RNA to DNA to become genome of progeny virus
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HAV
• RNA picornavirus –> nonenveloped, linear, + ssRNA with icosahedral capsid
• Transmission is fecal-oral (shellfish, travelers, day care)
• Incubation period is short (weeks)
• Clinical course typically Asymptomatic, sometimes Acute hepatitis
• Good prognosis, no risk for HCC
• Liver bxp shows hepatocyte swelling, monocyte infiltration, Councilman bodies (eosinophilic apoptotic globules).
• No carrier state
• Hepatitis sx: episodes of fever, jaundice, increased levels of ALT and AST
• Naked viruses (HAV and HEV) lack an envelope and are not destroyed by the gut –> the “vowels” hit your “bowels”
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HCV
• RNA flavivirus –> enveloped, linear, + ssRNA with icosahedral capsid
• Transmission primarily blood (IVDU, post-transfusion)
• Long incubation period
• May progress to Cirrhosis or Carcinoma (risk for HCC)
• Majority develop stable chronic Hepatitis C
• Liver bxp shows lymphoid aggregates with focal areas of macrovesicular steatosis
• Carrier state common
• Hepatitis sx: episodes of fever, jaundice, increased levels of ALT and AST
• HCV lacks 3’-5’ exonuclease activity –> variation in antigenic structures of HCV envelope proteins –> host antibody production lags behind production of new mutant strains of HCV
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HDV
• RNA deltavirus –> enveloped, circular, -ssRNA
• Transmission parenteral, sexual, or perinatal (same as HBV)
• Superinfection (HDV after HBV) has a short incubation period
• Coinfection (HDV with HBV) has a long incubation period
• Clinical course similar to HBV
• Superinfection has a worse prognosis
• HCC risk
• Liver biopsy similar to HBV –> granular eosinophilic “ground glass” appearance –> cytotoxic T cells mediate damage
• Defective virus, Depends on HBV
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HEV
• RNA hepevirus
• Transmission is fecal-oral (especially waterborne)
• Incubation period short
• Fulminant hepatitis in Expectant (pregnant) women
•High mortality in pregnant women
•No HCC risk
•Liver biopsy shows patchy necrosis
• Enteric, Epidemic, no carrier state
• Hepatitis sx: episodes of fever, jaundice, increased levels of ALT and AST
• Naked viruses (HAV and HEV) lack an envelope and are not destroyed by the gut –> the “vowels” hit your “bowels”
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Hepatitis A serologic markers
•Anti-HAV (IgM) – IgM antibody to HAV; best test to detect acute hepatitis A.
• Anti-HAV (IgG) – IgG antibody indicates prior HAV infection and/or prior vaccination; protects against reinfection.
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Hepatitis B serologic markers
• HBsAg – Antigen found on surface of HBV; indicates hepatitis B infection. –> can be detected during incubation period
• HBeAg – Secreted by infected hepatocyte into circulation. Not part of mature HBV virion. Indicates active viral replication and therefore high transmissibility. –> can be detected during incubation period
• HBcAg –Antigen associated with core of HBV.
• Anti-HBc IgM – IgM antibody to HBcAg indicates acute/recent infection. IgM anti-HBc may be the sole positive marker of infection during “window” period.
•Window period = btw acute infection and chronic infection or recovery
•Anti-HBc IgG – IgG antibody to HBcAg indicates prior exposure or chronic infection.
• Anti-HBs –Antibody to HBsAg; indicates immunity to hepatits B, either by recovery or immunization.
• Anti-HBe – Antibody to HBeAg; indicates low transmissibility. May also be present during window period.
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What serologic markers would someone with acute HBV have?
HBsAg, HBeAg, IgM anti-HBc, increased ALT
What serologic markers would someone with acute HBV during the incubation period have?
HBsAg
What serologic markers would someone with HBV during early convalescence (aka window period) have?
IgM anti-HBc +/- anti-HBe
What serologic markers would someone with chronic HBV have?
HBsAg, HBeAg (if high infectivity), IgG anti-HBc
What serologic markers would someone with a past HBV infection who is now immune have?
Anti-HBs IgG, Anti-HBe, and Anti-HBc IgG
What serologic markers would someone who has been vaccinated against HBV have?
Anti-HBs IgG
HIV
•Retrovirus: enveloped, linear, + ssRNA (2 copies) in a complex conical capsid
• HIV binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection) or CXCR4 receptors on CD4+ T-cells (late infection)
•Homozygous CCR5 mutation = immunity
•Heterozygous CCR5 mutation = slower course
• Diploid genome (2 molecules of RNA)
• 3 structural genes: env, gag, pol
•env codes for gp120 and gp41, which are formed from cleavage of gp160 to form envelope glycoproteins
• Envelope proteins are acquired through budding from the host cell plasma membrane
• gp120 is a docking glycoprotein that allows for attachment to host CD4+ T-cells
• p41 is a transmembrane glycoprotein that allows for fusion and entry
• gag codes for p24 (capsid protein) and p17 (matrix protein)
• pol codes for reverse transcriptase, aspartate protease, and integrase
•Reverse transcriptase synthesizes dsDNA from genomic RNA –> dsDNA integrates into host genome
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HIV diagnosis
- Presumptive diagnosis made with ELISA (sensitive, high false + rate, low threshold) –> rule out test
- Positive results with ELISA test confirmed with Western blot assay (specific, low false + rate, high threshold) –> rule in test
- Viral load tests determine amount of viral RNA in plasma
- High viral load associated with poor prognosis
- Viral load used to monitor effect of drug therapy
- AIDS = less than 200 CD4+ cells/mm3 (normal: 500-1500)
- HIV+ with AIDS-defining condition or CD4+ percentage
Time course of untreated HIV infection
• Four stages of untreated HIV infection:
• 1. Flu-like (acute)
•2. Feeling fine (latent)
• 3. Falling count (CD4)
• 4. Final crisis –> opportunistic infections
• During acute phase, wide dissemination of virus, seeding of lymphoid organs
• During latent phase, virus replicates in lymph nodes
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CD4+ count less than 500 in HIV+ patients
• Candida albicans –> oral thrush –> white plaque that scrapes off easily, pseudohyphae on microscopy
• EBV –> oral hairy leukoplakia –> unscrapable white plaque on lateral tongue
• Bartonella henselae –>bacillary angiomatosis –> bxp with neutrophilic inflammation
• HHV-8 –> Kaposi sarcoma –> bxp with lymphocytic inflammation
• Cryptosporidium (protozoan) –> chronic, watery diarrhea –> acid-fast stain reveals oocysts in stool sample
• HPV –> squamous cell carcinoma of anus (MSM) or cervix
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CD4+ count less than 200 in HIV+ patients
• HIV dementia
• JC virus reactivation –> progressive multifocal leukoencephalopathy –> non enhancing areas of demyelination on MRI
• Pneumocystis jirovecii pneumonia –> “ground-glass” opacities on CXR
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CD4+ count less than 100 in HIV+ patients
• Aspergillus fumigatus –> hemoptysis, pleuritic pain –> cavitation or infiltrates on CXR
• Cryptococcus neoformans –> meningitis –> encapsulated yeast on India ink stain or capsular antigen +
• Candida albicans esophagitis –> white plaques on endoscopy, yeast and pseudohyphae on bxp
• CMV –> retinitis, esophagitis, colitis, pneumonitis, encephalitis –> linear ulcers on endoscopy, cotton-wool spots on fundoscopy, bxp reveals cells with intranuclear (owl eyes) inclusion bodies
• EBV –> B-cell lymphoma (eg, non-Hodgkin lymphoma, CNS lymphoma) –> CNS lymphoma appears as solitary ring-enhancing lesion (vs. Toxoplasma)
• Histoplasma capsulatum –> fever, weight loss, fatigue, cough, dyspnea, nausea, vomiting, diarrhea –> oval yeast cells within macrophages
• Mycobacterium avium-intracellulare (MAI) –> nonspecific systemic sx (fever, night sweats, weight loss) or focal lymphadenitis
• Toxoplasma gondii –> brain abscesses appear as multiple ring-enhancing lesions on MRI
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Prion diseases
• Creutzfeldt-Jakob disease (CJD) = rapidly progressive dementia, typically sporadic (some familial forms exist)
• Bovine spongiform encephalopathy (BSE) = “mad cow disease”
• Kuru = acquired prion disease noted in tribal populations practicing human cannibalism
• Prion diseases caused by conversion of normal (predominantly alpha-helical) protein termed prion protein (PrPc) to a beta-pleated form (PrPsc), which is transmitted via CNS-related tissue (iatrogenic CJD) or food contaminated by BSE-infected animal products (variant CJD)
• PrPsc resists protease degradation and facilitates conversion of more PrPc to PrPsc
• Prion disease resistant to standard sterilizing procedures including autoclaving
• Accumulation of PrPsc results in spongiform encephalopathy and dementia, ataxia, and death
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