Notes:
Golden Staff of Moses: Staph aureus o Gram positive cocci
o Catalase positive o Coagulase positive
o Beta hemolytic- Gold on blood agar o Look like a bundle of grapes
o Plate on mannitol salt agar-turn agar yellow because it can ferment mannitol
o Protein A-part of cell wall can bind Fc portion of antibodies-prevents compliment, opsinization, and phagocytosis
o Colonizes nasopharynx o Symptoms
Pneumonia-patchy infiltrates on x ray Usually a post viral infection pneumonia Septic arthritis
Abscesses-impetigo, cellulitis, etc Rapid onset-Endocarditis
Worry IV drug user-usually right side tricuspid valve
Osteomyelitis-most common cause o Toxin mediated disease
Scalded skin syndrome-skin peals off due to exfoliation toxin
Toxic Shock Syndrome-TSST-superantigen-cytokine storm and shock
Staph food poisoning-rapid onset from preformed toxins-vomiting-meats and cream based foods o MRSA-alters PBPs
Treatment-Vancomycin or naficillin (Naf for staph)
Beauty and the Plumber: Staph epidermidis and Staph saprophyticus o Gram positive o Catalase positive o Urease positive o Coagulase negative o Epidermidis
Infects prostetics, indwelling catheters, endocarditis in artificial heart valves (super important)
Biofilms-makes a lot of polysaccharides-resistant to many antibiotics
Treatment-Vancomycin; surgical treatment of prosthetics may be needed
Novobiocin sensitive o Saprophyticus
Novobiocin resistant
UTI-sexually active females
Pie Genies’ Bakery: Streptococcus pyrogenes o Gram positive; long chains or pairs
o Beta hemolytic o Encapsulated
Hyaluronic acid-in our tissue as well-not immunogenic
o Impetigo-honey crusted skin o Pharyngitis
o Cellulitis and erysipelas
o Toxin diseases-strep pyrogenic exotoxin-SPE
Scarlet fever-reddening and swelling of tongue (strawberry tongue); pharyngitis; Widespread rash that spares the face(Spe A and C)
Toxic shock like syndrome-TSLS-mediated by a superantigen (Spe A and C)
Necrotizing fasciitis-surgical treatment (SpeB) o Complications of Strep
Rheumatic fever
ONLY AFTER PHAR Type II hypersensitivity
M protein-highly antigenic and virulence factor; interferes with opsinization (anti-phagocytic) and strong humoral response (molecular mimicry to myosin)
Mitral valve-most commonly damaged-stenosis JONES
o Joints-polyarthritis
o Heart problems-myo and para carditis and murmurs
o Subcutaneous nodules
o Erythema marginatum-rash with thick red boarders
o Sydenham’s chorea-rapid movements face and hands
Early treatment will prevent
PSGN
AFTER PHAR OR CUTANEOUS
Type III hypersensitivity (post step stipper) Glomerular damage
Dark brown urine
Facial swelling and edema
Two weeks after onset of strep infection Early treatment will NOT prevent
o Treat-penicillin o Virulence
Steptolysin O- lyse red blood cells
Body makes antibodies against (ASO)
Streptokinase-plasmogenin to plasmin-can lyse clots DNases-depolymerizes DNA
o Bacitracin sensitive
o Antistreptolysin O titer-done for diagnosis
Galactic Baby: Strep Agalactiae (Group B)
o Very serious infections in newborns-get it from mother going through vaginal canal; at 35wks pregnant women should be swabbed-give mom intrapartum penicillin o Hippo-positive hippurate test
o Polysaccharide capsule
o CAMP test positive-distinguishes it from all the other streps; Increasing zone of hemolysis when plated with Staph aureus o Beta hemolytic o Bacitracin resistance o Meningitis in neonates o Sepsis in neonates o Pneumonia
Alpha Knight Tournament: Streptococcus pneumoniae and Streptococcus viridans
o Alpha hemolytis-partial, green o Pneumoniae
Encapsulated; polysaccharide capsule Optochin sensitive
Lancet shaped diplococcic Bile soluble
CAP; lower respiratory, rust colored sputum MOPS Meningitis Otitis media Pneumonia Sinusitis
Asplenia susceptible
Macrolide suscept and cephtriaxone suscept Vaccine
Adults-polysaccharide-IgM response
Children-polysaccharide conjugated to protein-IgG response o Viridans No capsule Optochin resistant Bile resistant
Strep mutans cause dental carries
Mitral valve-subacute endocarditis with previously damaged heart valves-Adheres to platelet’s with dextrans
Protest at the Caucus: Enterococcus o Intestinal tract
o Gram positive cocci o Faecalis
More common o Faecium
Less common but more serious Bile resistant
Nosocomial infection-lots of resistance
VRE-Vancomycin resistant
Treat with linezolid or tigecycline (or daptomycin)
o
Can grow in 6.5% NaCl o Do u heart trees?
UTI
Endocarditis
Biliary tree infections
King Anthra’s Axe: Bacillus anthracis and Bacillus cereus o Black eschar (cutaneous)
o Gram positive rods in chains o
Encapsulated-Made of protein! (not polysaccharides); PolyD glutamic acid
o Obligate aerobe o Able to form spores o Anthracis
EF-Edema factor-adenyline cyclase increasing cAMP
LF-Lethal factor-exotoxin acting as protease cleaves MAP kinase-responsible for tissue necrosis
Wool sorter’s disease Pulmonary anthrax
o Dry cough and can move to mediastinal lymphnodes and pulmonary hemorrhage-high mortality
o Widened mediastinum
Treatment: Fluroquinones and doxycycline (tetracycline)
o Cereus
Food poisoning; after reheating rice mainly vomiting
Rhesus Research Revolution: Clostridium tetani o Gram positive
o Obligate anaerobes o Spore forming
o Found in soil; often puncture wounds with barbed wire and rusty nails
o Rhesus sardonicus- Lock Jaw syndrome- “evil grin” o Opisthotonus-exaggerated arching of back
o Tetanus toxin-travels retrograde through the motoneurons to the spinal cord; acts as a protease cleaving snare, inhibiting GABA and Glycine (inhibitory) release from Renshaw cells in spinal cord interneurons
o Toxoid vaccine- inactivated toxin on protein
Robotulism: Clostridium botulinum o Gram positive
o Adults- Improper canning of foods; preformed toxin o Spore forming
o Obligate anaerobe
o Flaccid paralysis-absence of muscle contraction; starts superiorly and moves inferiorly
Early symptoms- ptosis and diplopia Descending paralysis
o
Only affects the peripheral nerves o
Cleaves the SNARE protein of Ach neurons
o Babies-effect the same “floppy baby syndrome”; good anerobic intestinal space because hey don’t have natural
flora yet; Infantile botulism transmitted through ingestion of honey-ingestion of spores
Field Trip to the Chocolate Factory: Clostridium difficile o Spore forming
o Nosocomial diarrhea-need to wash with soap and water; antibiotic takers are at more risk since they don’t have normal flora
o Clindomycin linked to more C. diff o Obligate anerobe o Gram positive o Virulence factors Exotoxin A A for Apple
o Target brush border villi o Causes diarrhea
Exotoxin B
B for black licorice
o Depolymerization of actin filaments->enterocyte death and necrosis o Pseudomembrane
formation->pseudomembraneous colitis o Diagnose
Assay to detect toxin in stool
Look because they may be colonized anyway with a non toxin strain
Endoscope to look for pseudomembraneous o Treatment-Oral vancomycin and IV metronidazole
Private Ringen’s Motorcycle Accident: Clostridium perfringens
o Gram positive
o Motorcycle accidents and deep puncture wounds from military combat
o Spore former-found in dirt and soil o Obligate anerobe
o Disease
Gas gangrene
Clostridial myonecrosis
Crackling sound upon palpation
Alpha toxin-lecithinase; damage to cell membranes by cleaving phospholipids
o Double zone of hemolysis on blood agar-unique from other ones in that it is an anerobe!
Treatment: Penicillin G
Food poisoning
Late onset-need to inject a lot of the spores, toxin formed in the gut
Watery diarrhea
Transient-doesn’t require antibiotic treatment
Corazon de la Corrida: Corynebacterium diphtheriae o Gram positive rod
o Club shaped, metachromatic granules, V or Y formation o Virulence
Exotoxin
Inhibits elongation factor 2 (EF-2) to inhibit protein synthesis
Ribosylation of EF-2
Leads to cell death and pseudomembrane formation in oropharynx-gray
o Respiratory droplet transmission-can cause airway obstruction or lymphatonopathy
Bull’s neck-due to lymphadenopathy o Systemic
Cardio-myocaditis, arrhythmia, heart block— potentially lethal effect
Local paralysis-starting in the oropharynx due to the toxin killing myelinated neurons
o Diagnosis
Culturing-Tellurite agar and Loeffler’s medium Elek’s Tests-in vitro assay with antitoxin to see if it
has toxin
o Vaccine-in developed countries-inactivated exotoxin attached to protein leading to IgG response
o Treatment-administering antitoxin; passive immunization
Santa’s List: Listeria monocytogenes o Beta hemolytic
o Modal and facultative intracellular which can polymerize actin to move around inside the cell and even jump cell to cell “actin rockets” (body temp)
o
outside cell used flagella “tumbling motility” extracellularly (cold)
o Bacillus (base) o Catalase positive
o Can survive and multiply in near freezing temperatures o Can contaminate food items even in fridge-unpasturized
milk, soft cheeses
o Pregnant women at risk-may lead to early termination or disease in newborn
o Newborns- Meningitis
o Elderly- Meningitis- empiric treatment for meningitis vancomycin and ceftriaxone-LISTERIA treatment with ampicillin
Israeli Soldier: Actinomyces israelii o Gram positive filamentous rod o Obligate anaerobe!!!!
o Normal flora of the oral cavity o Recent dental work
o Associated with jaw trauma
o Cervio facial actinomyces infection
Begins with a nontender lump on jaw Form abscess
Sinus tracts form and drain infection through skin Thick yellow puss-sulfur granules
o Treatment-Penicillin G and surgical drainage may be necessary
No Card Game for Old Men: Nocardia species o Gram positive filamentous rod
o Obligate aerobe!!!!! o
Found in soil-does NOT form spores o Weakly stains acid fast-mycolic acids o Catalase positive
People with Chronic Granulomatis disease have an increase risk of infection with catalase positive organisms
o Urease positive o Diagnosis
Effects immunocompromised-impaired cell mediated immunity; HIV, transplant, glucocorticoids
Effects men more than women Pulmonary
Pneumonia with lung abscess formation; cavitary lesions of the lungs
Brain abscess formation Cutaneous
Indurated lesions and inflammatory reaction; fever produced
o Treatment-sulfonamides
Noir Series: Neisseria species o Gram negative diplococcic o
Oxidase positive
o Culture-VPN agar (Thayer Martin) and Chocolate agar not blood agar
o C5-C9 deficiency unable to form MAC complex-increased Neisseria infections
o Virulence factors
Pilis-allows for attachment to mucosal surfaces and frequent genetic rearrangement for antigenic
variation-makes it difficult for our immune system to target and prevents lasting immune response
IgA protease-facilitates survival along mucosal surfaces; cleaves at hinge point
A Shocking Death on Campus: Neisseria meningitidis o Respiratory droplets; college aged kid
o Ferments maltose and glucose (gonorrhea does not do maltose)
o Colonizes the nasopharynx first
o Polysaccharide capsule-inhibits phagocytosis
o Vaccine contains a polysaccharide capsule-Type B capsule not included in vaccine
Most infections in US then due to Type B strain o Sickle cell and asplenic pt at higher risk of
infection-because it is encapsulated
o LOS envelope proteins cause inflammatory response Increased permeability of capillaries-can lead to
hypovolemia and shock
Petechial rash-thrombocytopenia
Peripheral vasoconstriction due to hypovolemia- infart of adrenals
Waterhouse- Friderichsen
syndrome-characterized by hemorrhage of adrenals-shock o Mortality 15%
o Treatment- Ceftriaxone
Violinist’s Last Clap: Neisseria gonorrhoeae o STI
o Facultative intracellular in PMNs o
Not encapsulated
o White purulent discharge-thicker o Urethritis-can travel up the tract prosititis
o Pelvic inflammatory disease-can cause scarring leading to infertility or ectopic pregnancy
Can spread into peritoneum-Fitz Hugh Curtis Syndrome
Adhesions on capsule of liver- Violin Sting Adhesions o Can cause polyarthritic-asymmetric, usually knee
Purulent synovial fluid that won’t Gram stain because intracellular
o Congenital
Purulent conjunctivitis-Early onset
o Treatment- Ceftriaxone and assume coinfection so treat for chlamydia as well with macrolide or doxacycline
Enterodactyl, Triserratiatops and the Kleb-Tailed
Dinosaur: Enterobacter cioacae, Serratia marcescens, Klebsiella pneumoniae
o Gram negative o
Nosocomial infections-pneumonia and UTI-multidrug resistance
o Treatment-think Carbopenem
o Ferment lactose-Pink colonies on MacConkey agar-Serratia may show negative because slower
o Enterobacter cioacae Motile
o Serratia marcescens Motile
Produces red pigment; can see in shower o Klebsiella pneumoniae Capsule- polysaccharide Three As Alcoholics Abscesses Aspiration
Cough up currant jelly sputum
Immotile
Urease Positive
Abscesses may make you think Tb-watch and don’t confuse them by chest x-ray
Salmon Dinner: Salmonella typhi, Salmonella enteritidis o Motile
o H2S positive-grows black colonies on Hektoen Agar o Encapsulated
o Acid labile-easily degraded in stomach-need many organisms to infected; increasing pH can increase risk of infection
o Facultative intracellular; particularly within macrophages o
Salmonella typhi
Gall bladder of chronic carriers
Typhoid Mary-asymptomatic carrier that passed it to a number of people she cooked for
Rose spots macules on abdomen-25% of time Osteomyelitis in Sickle Cell disease
Associated with “pea soup” diarrhea and constipation Treatment-Fluoroquinolone (Cipro) Vaccine-live attenuated o Salmonella enteritidis Chicken reservoir Inflammatory diarrhea
Type III secretion system-detects eukaryotic cells and increases infectivity
She-Gorilla’s Circus: Shigella sonnei, Shigella lysenteriae o Gram negative enteric leading to BLOODY diarrhea
o Green colonies Hektoen agar o Immotile
o Acid stable-need fewer organisms to cause infection o M cells in Peyer’s patches-normally test antigens- Shigella
gets phagocytosed but escapes immune degradation; uses actin cytoskeleton to propel from one cell to another
o Facultative intracellular
o Damages tissue and causes cytokine release-inflammatory diarrhea-bloody
o Children-Shigella-HUS (Hemolytic-uremic syndrome) can happen-Acute renal failure (glomerular damage); drop in platelet count; red blood cell hemolysis
o Shiga toxin
Binds 60s portion of ribosomes o Type III secretion system
E. cola’s Soda Fountain: Escherichia coli,
Enterohemorrhagic E. coli (EHEC), Enterotoxigenic E. coli (ETEC)
o Gram negative
o Lactose fermentation; pink on MacConkey agar o
Encapsulated
K antigen in capsule-useful for serotyping o Green on EMB agar
o
Catalase positive
o Fimbriae or pili-UTI-number one cause of UTI
o Leading cause of Gram negative Sepsis-LPS endotoxin in outer cell membrane
o Neonatal meningitis-only if it has the K antigen o
EHEC
Undercooked meat Bloody diarrhea
ONLY E.coli that does NOT ferment sorbitol Shiga like toxin
60s subunit of ribosomes targeted
Children-HUS-damages endothelial cells in glomerulus; platelet aggregation and decrease in platelet count; hemolysis of red blood cells O157:H7 antigen associated with outbreaks
o
ETEC
Traveler’s diarrhea Transmitted via water
Classic history of someone with ETEC is recent travel to Mexico
Toxins
Heat labile
o Increases cAMP-very similar to cholera toxin Heat stable o Increases cGMP Watery diarrhea
Yersin’s Pets: Yersinia enterocolitica, Yersinia pestis o Gram negative
Bipolar staining, sometimes described as looking like a safety pin
Encapsulated o
Yersinia enterocolitica
Transmitted though milk products Resistant to cold temperatures Commonly effects toddlers
Diarrhea-invasive resulting in blood
Fever, leukocytosis, abscess; causes GI problems Can mimic appendicitis symptoms
o
Yersinia pestis Plague
Reservoir-rodents or now prairie dogs Fleas spread it to humans
Buboes-swollen tender lymph nodes
Systemic-Abscesses and DIC in cutaneous hemorrhage from endotoxin
Exotoxins
Yersinia associated outer
proteins-Yops-macrophage and neutrophil disruption by inhibiting phagocytosis and cytokine production
Type III secretion system
Treatment-aminoglycosides (Streptomycin) along with tetracycline
Vaccine-Killed vaccine
Camping Guy and the Bears: Campylobacter jejuni o Thermophilic-42C (loves heat)
o Reservoir intestinal tract of other animals-Poultry o Bloody diarrhea
o Curved gram negative rod o Oxidase positive
o Invasive o
Reactive arthritis-Reiter’s syndrome
o Complication-Guillain-Barre Syndrome-autoimmune response causing demyelination of peripheral nerves; ascending paralysis; lower extremities and works up
Colonel Cholera’s Base cAMP: Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus
o Endemic to developing countries o Gram negative
o Comma shaped o
Vibrio cholerae
Perfuse watery diarrhea Consistency of rice water
Fecal-oral route-poor sanitation-contaminated food and water sources
Fimbraie attachment-doesn’t penetrate mucosa Releases cholera toxin
Binds and consituateively activates adenylate cyclase part of GS pathway
Increases cAMP
Treatment-oral rehydration therapy with electrolytes Alkaline media-Acid labile (likes BASIC, need
many to infect) Oxidase Positive o
Vibrio parahaemolyticus and vulnificus
Can contaminate sea food especially sea food-oysters
Helicopter Pilot: Helicobacter pylori o Helical, comma shaped Gram neg ROD o Near our pylorus in our stomach
o Motile
o Urease positive-most important reduces acidity of environment
Urea breath test
Biopsy during endoscopy o Curved gram negative rod o Oxidase positive
o
Ulcers-duodenal
o Without treatment-increased risk of gastric adenocarcinoma
Lymphoma of mucosal associated lymphoid tissue-MALT
o Treatment- Proton pump inhibitor, amoxicillin, clarithromycin (macrolide)
Suitors of Pseudo Mona: Pseudomonas o Gram negative rod
o Encapsulated
o Thrives in aquatic environments o Oxidase positive
o Catalase positive-CGD pt at risk
o Blue green pigment when plated-pyocyanin and pyoverdin o Fruity grape like odor
o Obligate aerobe-helps distinguish
o Nosocomial pneuomonia-Gram negative very common o Cystic Fibrosis-pulmonary infection; common cause of
respiratory failure
o
Burn patients-often fatal and unresponsive to antibiotics o Nosocomial UTIs
o Skin lesions-
1-Pruritic pustular folliculitis Hot tub folliculitis
2-Ecthyma gangrenosum-black necrotic lesions on skin
o
Otitis externa
Swimmer’s ear o Exotoxin A
Ribosylation of elongation factor 2 to inactivate (like DIP)
o Treatment-Piperacillin/tazobactam
Less common treatment-aminoglycosides (in combo with B lactam) and fluoroquinilones (UTI)
God of the Public Restroom: Proteus mirabilis o Gram negative facultative anaerobe
o Swarming motility when plated
o Staghorn calculi-shape of kidney stones in renal pelvis-pain and impt for reinfection (due to alkaline
environment)
o Urease positive-impt to form struvite stone formation-ammonia magnesium and phosphate
o Cause UTI o Fishy odor
o Treatment-sulfonamides
Board with Care: Bordatella pertussis o Causes whooping cough
o
Highly contagious; respiratory droplets
o Attaches with pilis-Filamentous hemagglutinin o Toxins
Pertussis toxin
Ribosylates Gi disabling it-disabled inhibitory G protein—leading to increase in cAMP
Disables chemokine receptors for lymphocytes so they can’t enter lymph tissue
o Lymphocytosis
Adenylate cyclase toxin
Increases cAMP similar to EF toxin
Tracheal toxin
Peptidoglycan wall, damages ciliated cells in respiratory epithelium
o Clinical
Early-not specific symptoms
Paroxysmal stage-whooping cough Convalescent stage-can last for months o Treatment-macrolides (early)
o Vaccine-acellular vaccine-purified antigens (DTaP)
Phyllis’s Chocolate Covered Cherries: Haemophilus influenzae
o Gram negative
o Coccobacillary shape
o Chocolate agar-need Factor 5 (nicotinamide; NAD) and 10 (hematin)
o
Aerosol transmission
o Epiglottitis-children- inflammation, inflamastrider, drooling; cherry red epiglottis
o
Otitis media
o Meningitis-only when capsular form type B strain
o Sepsis and septic arthritis in asplenic and sickle cell o Vaccination-against the type B only; strong IgG response;
2-18 months; polysaccharide conjugated to diphtheria toxin
o Treatment-beta lactam-ceftriaxone for meningitis and systemic; rifampin for prophylaxis for meningitis and close friends
S.S. Cysteine Joins the Legion: Legionella
o Atypical-use silver stain to visualize; technically Gram negative
o Grow on buffered charcoal yeast extract with cysteine and iron
o Oxidase positive o Diseases
Legonaires’ disease
Very severe and potentially fatal More common in smokers
Pneumonia-X-ray shows patchy infiltrate with consolidation of one lobe-variable
Hyponatremia-less sodium <130 Neurologic symptoms-headache and
confusion Diarrhea
Lab-Culture sputum takes a while; Rapid urine antigen test used for rapid diagnosis
Treatment-macrolides, fluoroquinolones
Pontiac fever
Fever and malaise; usually self limiting
Bart the Leopard: Bartenella henselae
o Gram negative, but need to use Warthin-Starry stain (silver) to visualize
o Disease
Cat Scratch disease
Transmitted through cat scratches Fever
Cause painful enlargement of lymphnodes-axillary lymphadenitis
Immunocompetent patients
Usually self limiting but if it gets bad you can give macrolides (azithromycin)
Bacillary angiomatosis
Immunocompromized patients often HIV Transmitted by cat scratches
Fevers, chills, headaches
Raised red vascular lesions-do biopsy Treatment-Doxycycline, macrolides
Bruce Farms: Brucella
o Zoononitic; farm animals (direct or indirect contact) o Gram negative
o Facultative intracellular
Ability to survive in macrophages
Can spread to reticuloendothelial organs-enlargement of spleen, liver, and lymphnodes o Fever, chills, anorexia
Undulant fever
o Osteomyelitis-often in chronic
o Treatment-tetracycline (doxycycline) and rifampin (adjunctive therapy)
Francis the Rabit: Francisella tularensis o Zoononitic-Rabbits main reservoir
Direct or indirect through tick contact (dermacentor tick)
o Gram negative coccobacilli o
Facultative intracellular organism
Impt because it means recovery depends on cell mediated immunity
Facilitate movement from one side of body to the other
o Painful ulcer at site of infection
o Goes into macrophages and travels through the lymph system to reticuloendothelial organs and causes
granulomas with caseating necrosis
Lymph swelling; regional lymphatenopathy; can spread
o Treatment: Aminoglycosides (Streptomycin)
Louis Pasteur’s Lab: Pasteurella multocida
o Found in respiratory tract of small mammals; dog and cat bites
o Cellulitis may occur in first 24 hours
Possibility to develop into necrotitis or osteomyelitis Lymphadenopathy or systemic only if compromised o
Catalase positive o Oxidase positive
o Encapsulated-virulence factor o Grows well on 5% Sheep blood agar o Bipolar staining-“safety pin”
o Treatment-penicillin and can use a b lactamase inhibitor
Shootout at the TB Corral: Mycobacterium tuberculosis o Acid fast- Carbol fuchsin stain
Mycolic acid cell wall; thick
o Lowenstein Jensen medium-Starch, egg, etc Very slow growth
o Obligate aerobe
o Human transmission via respiratory droplets
Resides and proliferates inside of macrophages o Glycolipids in cell wall-clumping into serpentine
shapes-Cord factor
Protect bacteria
Granuloma formation through increasing cytokines (TNF alpha)
Allows bacteria to stay alive inside the granuloma with activated macrophages
o PPD skin test-will be come positive due to type IV hypersensitivity; if you have gotten vaccine (BCG), primary, latent, or active TB infections
o Progression Primary
Lungs-lower or middle lobes
Lesion becomes fibrotic and calcifies as well as nearby lymphnodes (Hilar lymphadenopathy )
o Ghon complex- Hilar lymphadenopathy and peripheral granulomatous lesion in middle or lower lung lobe
o Caseating granulomas-fibrosis and scaring
o Can be seen on X-ray
Symptoms-fever and more in children; most resolve with fibrosis and latent
Progression after primary can be
Healed latent infection
Systemic infection (military TB)
o Commonly infecting bone, lymphatics, liver-very acute
o Variable presentation-potentially lethal Reactivation TB
o Only in 5-10%
o Immunosuppression-though down regulation of TNF alpha release
Neutralized TNF alpha leads to uncontained infection
o Primarily effects upper lobes
o Symptoms-Cough, night sweats, and hemophtysis (bloody cough)
o
Cachexia-wasting, due to TNF alpha o Pott’s disease-TB in spinal
col-demineralization of bone-usually multiple vertebra-soft tissue swelling
o CNS involvement-meningitis or
tuberculoma (cavitary lesion in brain) o Treatment-Combo
RIPE-Rifampin, Isoniazid, Pyrazinamide, Ethambutol Prophylaxis-Rifampin and Isoniazid (9 months)
The Good, the Bad, and the Lion Faced: Mycobacterium Leprae
o Thrives in cold temperatures-predication for extremities o Acid fast-mycolic acids-waxy chains- Carol fuchsin
o Reservoir-armadillo o Hansen’s disease o Diseases
Tuberculoid Presentation
Th1-cell mediated immunity
Contain bacteria within macrophages
Well demarcated hairless lesions on skin Lepromin skin test-antigen injection and look
for response
Lepromatous response
Th2-humoral response
Weak Th1 response-can’t be contained within macrophages
Classic lepracy
Human to human transmission Symptoms
o Neuropathy symmetric with glove and stocking pattern
o Raised lesions demarcated –extensor surfaces-see large amount of bacteria in biopsy
o Facial deformity-Leonine facies o Treatment-Combo
Tuberculoid-Rifampin, Dapsone
Lepromatous- Clofazimine , Rifampin, Dapsone
Bows and Arrows of Borrelia: Borrelia burgdorferi o Lyme disease
o Northeastern US o Spirochete o
Tick born disease-Ixodes Scapularis
Reservoir-mouse and deer is obligatory host Humans dead end host
o Don’t Gram stain-can be visualized with Wright and Giemsa stains
o Symptoms Three Stages
1- Rash, bulls eye rash, not painful; flu like illness (fever and chills)
2- Heart block by myoendocarditis, bilateral facial nerve palsy (bilateral Bell’s palsy)
3- arthritis of large joints, migratory polyarthritis; CNS-encephalopathy
o Treatment-Doxycycline (early) and Ceftriaxone (for later and more severe)
Surfer’s Oasis: Leptospira interrogans o Leptospirosis ;“Weils disease”
o Endemic in tropical regions
o Spirochete or question mark shaped
o Animals-excreted in urine and transmitted via water (mainly swimming)
o Symptoms
Early- Flu like symptoms (fever), Conjuntival suffusion (diffuse reddening without pus)
Travels through blood stream-hematogenous spread
Renal dysfunction
Liver dysfunction-Jaundice
"Palladium Observatory” Treponema Pallidum o ● Spirochete: May be described as spiral shaped. o Primary
● FTA-ABS is specific test to confirm a positive screening result.
● Darkfield microscopy needed for direct visualization. ● Possible false positive antigens.
● Primary syphilis characterized by painless genital chancre.
o Secondary: Systemic disease.
● May see condyloma latum on mucous membranes. ● Maculopapular rash occurs on palms and soles weeks to months after infection.
● Spirochetes can be visualized within condyloma latum via dark-field microscopy.
o
Tertiary
● Tertiary aneurysm of ascending aorta with "tree-barking" appearance.
● Destroys vasa vasorum that supplies aorta with blood.
● Tertiary: Argyll Roberson pupils, reacts to accommodation but no reaction to light.
● Tertiary: Damage to posterior column of spinal cord. ● Formation of gummas: Soft growths with firm necrotic center.
● Congenital saddle nose.
● Congenital saber sings and anterior bowing of tibia. ● Congenital deafness.
● Congenital: Hutchinson's teeth and Mulberry molars. ● Treatment: Penicillin for all stages.
● Jarisch-Herxheimer reaction characterized by fever and chills.
● Jarisch-Herxheimer reaction may occur hours after treatment.
"Pirates of Chlam Island": Chlamydia
o Gram-Indeterminate Bacteria
● Chlamydia divided into three groups. Trachomatis also divided into three groups.
---General:
● Obligate intracellular organisms. ● Poor gram staining.
o Life Cycle
● 1st lifestyle stage: Elementary body, infectious form, outside of organism and needs to enter.
●
2nd stage: Reticular body active form that can divide and replicate.
●
Final stage: Release back out of cell into elementary body. ● Inclusion bodies visible with cells under microscope.
● Cell walls lack muramic acid.
● Commonly diagnosed by NAAT (Nucleic-acid amplification test). ● May be visualized with Giemsa stain.
● Commonly coinfected with gonorrhea.
worldwide. It's transmitted by hand to eye contact or fomites. ---Trachomatis:
● A-C blindness leading cause of blindness.
● D-K STI if left untreated, may lead to pelvic inflammatory disease (PID).
STI characterized by watery discharge.
STI Newborns born to infected mothers can develop conjunctivitis and pneumonia.
● L1-L3 LGV Lymphogranuloma venereum characterized by tender inguinal lymphadenopathy.
●Reactive arthritis (Reiter's syndrome): urethritis, arthritis and uveitis.
---C pneumoniae:
● Chlamydophila pneumoniae causes atypical pneumonia. ---C psittaci:
● Pneumonia associated with bird droppings. ----Treatment:
● Add Ceftriaxone to treatment for gonorrhea coinfection.
● May use macrolides for treatment, oral macrolides effective against trachomas.
● Doxycycline is effective treatment.
-"Curly Q the Ram" Coxiella burnetii
● Gram negative. ● Q-fever.
● Headache. ● Fever.
● May cause hepatitis. OBLIGATE INTRACELLULAR
● Transmitted to humans via aerosol transmission, farm animals are major reservoir.
● Contained in spore like structures in animal feces. ● No rash caused.
-"Fish Garden" - Gardnerella vaginalis
Gram-Indeterminate Bacteria ● Gram variable staining. ● Metronidazole for treatment.
● Infection occurs when pH over 4.5.
● Grayish-white malodorous "fishy" discharge.
● Bacterial overgrowth that disrupts normal flora is method of infection.
● KOH whiff test.
● Clue cell = Epithelial cells coated with bacteria visible under microscope.
-"Walking on Thin Ice" Mycoplasma pneumoniae
Gram-Indeterminate Bacteria
● X-Ray shows reticulonodular or "patchy" infiltrate, appears much worse than patients seem clinically.
● No cell wall, can't appear on gram stain. ● Commonly occurs in young adults. (<30)
● Common in military recruits living in close quarters. ● Macrolide for treatment because there's no cell wall. ● Eaton's agar.
● Cell membrane contains cholesterol. ● Walking pneumonia.
● IgM cold agglutinins cause agglutination of red blood cells.
- "Rickettsia Tennis"
Gram-Indeterminate Bacteria
● Obligate intracellular organism
● Weil-Felix agglutination test for Rickettsial infections.
● Unable to produce NAD+, important for bacterial growth and reproduction.
● Unable to produce CoA, gets it from eukaryotic cells. ● Vasculitis.
-rash may be associated with vasculitis
● Headache and fever early Rickettsial infection. ● Poor gram staining.
-Coccobacilli -Weakly G(-)
● Doxycycline for treatment.
-"Pro Boot Camp" Rickettsia prowazekii Gram-Indeterminate Bacteria
● Obligate intracellular organism.
● Spread by louse, defecates near bite spread to blood by scratching. ● Affects military camp recruits and prisoners of war.
● Illness is called epidemic typhus.
● Rash starts at trunk, and spreads outward towards extremities. -Spares Hands/Feet
● Require CoA and NAD+ for growth. ● Causes pneumonia.
● Encephalitis with and confusion. Can cause coma if very serious. ● Doxycycline treatment.
-"Rickett's Rock Climbing Competition"Rickettsia rickettsii Gram-Indeterminate Bacteria
● Obligate intracellular organism.
● Rash spreads centrally from extremities.
-INCLUDES hands/feet
● Symptoms include headache, fever and myalgias. ● Poor gram staining.
● Transmitted by direct bite of Dermacentor ticks . ● CoA and NAD+ necessary for growth, provided by host.
VIRUSES
Chapter 1: RNA Viruses – Positive
Sense
Picornaviridae Overview (The Peak-orna Animal Nursery) (+)sense ssRNA genome. Naked viruses. Replicate in
cytoplasm.
Transmitted primarily via fecal-oral route (virus shed in feces and is introduced via hands to the mouth. Exception is the Rhinovirus (transmitted via respiratory system).
(+)sense ssRNA has same structure as mRNA and can be directly translated into protein. Uses cellular RNA polymerase for replication. Viral RNA is translated into a long viral polyprotein (inactive) and is cleaved by viral proteases into active products.
All (+)sense RNA viruses replicate in the cytoplasm. 3 main subgroups of the Picornavirus family:
Hepatitis A causes hepatosplenomegaly.
Enterovirus includes Poliovirus, Coxsackie A and B, and
Echovirus. Enteroviruses are #1 cause of aseptic (nonbacterial) meningitis. Children are particularly susceptible to meningitis cause by Enteroviruses. Viral meningitis CSF findings include normal glucose, no bacterial organisms (aseptic), elevated protein levels.
Rhinovirus primary cause of the common cold. Transmitted via respiratory system (unlike other Picornaviridae, which are fecal-oral transmission).
(Pico) Polio Virus (The Flamingo Breeding Pool)
Causes Polio, which has largely been eradicated (except in portions of Africa & Asia).
Transmitted via the fecal-oral route (acid-stable).
Virus enters via the GI tract and begins to replicate in lymphoid tissue (tonsils and Peyer’s patches). Replication takes
approximately 2-3 weeks. Virus then spreads to anterior horn of LMNs (lower motor neurons).
Causes an asymmetric paralysis (usually concentrated in the lower legs), myalgias, and decreased DTRs. Paralysis ascends and can cause respiratory insufficiency (d/t paralysis of
diaphragm).
Also causes aseptic meningitis (Enteroviruses are #1 cause of aseptic meningitis).
There is no treatment for Polio. Vaccination:
Salk vaccine
Inactivated (killed) vaccine given parenterally.
Bypasses GI tract via injection and only forms IgG
antibodies. It does not stimulate formation of IgA antibodies (mucosal immunity).
Method used in the US.
Sabin
Live attenuated vaccine given orally. Creates both IgG and IgA antibodies.
Can be shed in feces or live virus convert to another form, which causes vaccine associated paralysis.
(Pico) Coxsackie A & B (Coxsackie Cockatoos) (+)sense ssRNA genome. Naked virus. Enterovirus.
Coxsackie A
Associated with hand, foot and mouth disease. Causes a red vesicular rash on the hands and feet (Syphilis & Rickettsia ricketsii also cause rash on hands & feet).
Causes aseptic meningitis (viral meningitis with no bacteria on gram stain).
Infections occur most often in summer months.
Coxsackie B
Causes dilated cardiomyopathy.
Devil’s Grip (Bornholm’s disease & pleurodynia) characterized by extreme sharp pain in the lower chest that is often unilateral and makes it difficult to breath.
(Pico) Rhinovirus (Rhino Petting Zoo) (+)sense ssRNA genome. Naked virus. Most common cause of the common cold.
Transmitted via inhalation. Rhinovirus is acid-labile and cannot survive GI tract (no fecal-oral transmission). It can also be
transmitted on fomites (hands/surfaces). Enters the host cell by attaching to ICAM-1.
Grows best in 33C (cooler temperature). Air is cooler in the upper respiratory tract due to air flow. Rhinovirus only affects the upper respiratory tract.
Rhinovirus has many serotypes (113 different serotypes), which makes it difficult to vaccinate against all serotypes.
There is no treatment or vaccine.
Hepatitis A (Hungry Hungry Hep A Hippos) (+)sense ssRNA genome. Naked virus.
Acid-stable can be transmitted via fecal-oral route.
Hep A can be shed in feces and contaminate water supplies. Developed countries have water purification systems to clean
water. Inactivation of Hep A requires chlorination, bleach, UV irradiation, or heat to 85C for over 1 minute.
Direct transmission via contaminated water is rare.
Indirect transmission can occur via shellfish (esp. uncooked) from contaminated water sources. Common source in
developed countries.
In developing countries, contaminated water is a common source of transmission of Hep A d/t poor water sanitation systems.
Hep A is common among travelers who travel to endemic areas (esp. in southern hemisphere).
Clinical symptoms:
Can be clinically silient or subclinical and can be anicteric (without jaundice).
Also causes acute hepatitis (fever, hepatomegaly, and jaundice). Jaundice is especially common in adults, but in
children acute viral hepatitis causes anicteric hepatitis. Smokers who develop Hep A will also develop an eversion to smoking tobacco products.
Symptoms typically last 1 month. Disease is also self-limiting.
Inactivated vaccine. High risk patients (living in endemic regions, chronic liver failure, and men who have sex with men) should especially be vaccinated.
Calcivirus (Cali Sea Cruise)
(+)sense ssRNA genome. Naked virus.
Produces one long polyprotein that is cleaved by viral protease into smaller, active constituents.
Replicates in the cytoplasm (like all (+)sense ssRNA viruses). Norovirus (Norwalk virus)
Outbreaks typically occur in areas with many people confined to limited space.
Commonly seen on cruises (responsible for 90% of diarrheal outbreaks on cruises).
Also associated with young children, day care facilities, and schools.
Can also be transmitted via consumption of shellfish, oysters, and raw foods. Situations where people touch food can transmit virus (buffet meals).
Causes viral gastroenteritis (diarrheal illness) that has an explosive, watery diarrhea.
Flavivirus Group (Flavor Packed Flavi)
(+)sense ssRNA genome. Enveloped virus. Genome is non-segmented.
Includes several viruses (including Hep C).
Dengue Fever
Transmitted via mosquitoes (aedes egyptei).
There are 4 types of Dengue fever (Type 2 is most important). Infects the bone marrow (Dengue fever is also called break-bone
fever). Platelet production is decreased, producing thrombocytopenia and increased risk of bleeding.
Causes hemorrhagic fever, renal failure, and eventually leads to septic shock and death.
Tx is supportive (hydration).
Yellow Fever
Transmitted via mosquitoes (aedes egyptei).
Causes jaundice and back ache. It can also cause bloody diarrhea and bloody vomiting.
Live attenuated vaccine.
Birds are the reservoir. Transmitted via mosquitoes (culex mosquito).
Causes encephalitis (major complication). Can also cause myelitis (leads to flaccid paralysis) and meningitis. Infection can eventually lead to seizures and coma. Definitive diagnosis via PCR and serology of CSF.
Tx is supportive.
Hepatitis C is also a Flavivirus. (Flavi) Hepatitis C (The Hep Sea)
(+)sense ssRNA genome. Enveloped virus. Member of the Flavivirus.
Most common mode of transmission is exposure to infected blood.
Prior to 1990 transmission via blood transfusions (formerly a major problem).
IV drug users and needle sticks.
Also transmitted via placenta, breast feeding, and sex. Difficult to develop a vaccine because Hep C envelop proteins
develop antigenic variability. Viral RNA polymerase lacks
proofreading exonucleases activity in 3’ 5’ direction, which results in frequent mutations.
Hep C causes inflammation of the liver.
Acute stage: inflammation leads to jaundice, RUQ pain, enlarged liver, and elevated liver enzymes.
60-80% of Hep C infections progress to chronic infection (unlike Hep B).
Lymphocytes infiltrate the portal tract and chronic inflammation/infection cause hepatocyte death. Liver can
become fibrotic and cirrhotic; liver can also become malignant (hepatocellular carcinoma).
In acute infection: Hep C RNA is found in serum during first 6 months; ALT will rise and fall within 6 months; anti-HCV will rise after 2 months (lag due to antigenic variation. Anti-HCV antibodies can be present in acute and chronic infection due to antigenic
variation (antibodies are ineffective and there is no protection against recurrent infection).
In chronic infection: Hep C RNA persists in serum after 6 months; liver biopsy with lymphocytes in portal tract.
Hep C is associated with cryoglobulins (serum proteins containing immunoglobulins [mostly IgM] that precipitate out in cooler
Tx: Ribavirin + IFN-alpha. Newer drugs include protease inhibitors & polymerase inhibitors.
Viral genotype testing must be performed to determine drug combinations for treatment.
Common cause of liver transplants. Togavirus Group (Toga-Toga Togavirus) (+)sense ssRNA genome. Enveloped virus. There are 2 types of Togavirus:
Arbovirus (Arthropod born virus) Mosquito vector
Multiple different types of Arbovirus Western Equine
Encephalitis, Eastern Equine Encephalitis; Venezuelan Equine Encephalitis (found in US & Venezuela; named after geographic location).
Encephalitis presents with headache, fever, AMS, and focal neurological deficit.
No treatment. Use netting, clothing, and repellant to protect from mosquitoes.
Rubella (German Measles) Childhood exanthem.
Causes tender postauricular and occipital lymphadenopathy.
Distinct maculopapular rash that begins on the face and spreads downward.
Prodrome includes mild fever, lymphadenopathy, and fatigue. Rash of rubella moves faster than Measles and does not coalesce. Rash is present for 3 days.
Transmitted via respiratory droplets.
Congenital Rubella
TORCHES infection. Crosses placenta and affect child in utero.
Constellation of symptoms: mental retardation, microcephaly, deafness, blindness, cataracts, jaundice, PDA, pulmonic stenosis, purpuric blueberry muffin rash, & radiolucent bone lesions.
Main triad: congenital cataracts, sensorineural deafness, and PDA.
Adult Rubella
Causes lymphadenopathy, fever, arthralgia, and arthritis. No treatment.
Live attenuated vaccine (MMR) that induces both humoral and cell mediated immunity. Do NOT give to pregnant women or immunocompromised persons (CD4 <200).
Rubella is associated with immigrants.
Togaviruses produce a polyprotein precursor that is produced by viral and host proteases.
Coronavirus (Kingdom of SARS)
(+)sense ssRNA genome. Enveloped virus. Helical capsid.
Causes SARS and common cold.
Different strains cause SARS and MERS (Middle East Respiratory Syndrome)
Causes acute bronchitis, which can lead to respiratory distress syndrome.
Diagnose with test for antibodies to SARS and confirm with PCR. Tx: broad spectrum antibiotics, ribavirin, and corticosteroids. Retrovirus – HIV/AIDS (One Cane to Rule Them All)
(+)sense ssRNA genome. Enveloped virus.
Diploid RNA positive virus (2 (+) RNA molecules in each virion) HIV leads to AIDS, which is the quintessential state of being
immunocompromised.
HIV is retrovirus. (+) RNA is converted to a DNA intermediate via reverse transcriptase. DNA can incorporate into host
chromosomes and replicate forever.
Replication uses env, gag, and pol genes.
gag produces a protein (p24), which serves as a capsule for RNA strands. Capsule is cone shaped.
env producs glycoproteins 41 and 120, which are proteins that form the envelop. (env produces glycoprotein 160, which is
cleaved into glyproteins 41 & 120).
Gp41 = transmembrane protein of envelope.
Gp120 = outer glycoprotein that contact host receptors. pol produces reverse transcriptase.
Transmission: sexual contact, vertical transmission, blood (IV drug use & needle stick).
HIV is a TORCHES infection.
Primary infection (prodrome) is characterized by flu or mono-like symptoms with cervical lymphadenopathy and fever. Primary
infection can last for several weeks.
Virus can enter a latent period (lasting up to 10 years), where it is replicating in lymph nodes.
AIDS CD4 count less than 200. AIDS can also be diagnosed in patients with CD4 > 200 if an AIDS defining illness is present. AIDS can cause B cell lymphoma (most often a diffuse large B
cell lymphoma).
HIV fuses with host cell via host cell receptors (CCR5 and CXCR4 coreceptor), entry, uncoating, reverse transcription, and integration into host genome.
CCR5 entry during early stage. CXCR4 entry during late stage. Diagnosis:
Screening test via ELISA detects antibodies. If tested too early there can be a false negative (antibodies not produced yet). Multiple screening test should be performed up to 6 months after exposure.
Confirm positive ELISA with Western Blot. Measure viral load and CD4 count via PCR.
Vertical transmission (HIV + mother infant) ELISA & Western blot will be positive if performed on infant because mother’s
antibodies cross placenta
Neonates must be tested with HIV RNA/DNA nucleic acid amplification tests (looks for virus itself).
Treatment:
HAART = Highly Active Antiretroviral Therapy.
Combination therapy > monotherapy (because HIV is prone to resistance d/t mutations).
Nucleotide Reverse Transcriptase Inhibitors (NRTIs) pose as nucleotide, incorporate in DNA via RT, halts prolongation. Zidovudine use during pregnancy and postpartum
(reduce transmission to baby). Mothers take at 14 weeks gestation until 6 weeks postpartum.
Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTIs) do NOT incorporate into chain, but still inhibits RT.
Protease Inhibitors inhibit cleavage of proteins necessary for viral replication.
Maraviroc CCR5 inhibitor, which prevents viral entry into host cells.
Genotype testing should be performed to determine optimal drug combination.
Everyone with HIV should receive treatment (prevent high viral load and low CD4 count).
Chapter 2: RNA Viruses – Negative
Sense
Orthomyxovirus (Night Shift at the Orthodontist’s)
(-)sense ssRNA genome. Segmented virus (8 segments). Enveloped virus.
Must be transcribed into a (+) RNA strand for translation (must bring RNA dependent RNA polymerase).
Orthomyxovirus is the only RNA virus that replicates in the nucleus.
Orthomyxovirus causes influenza. There are 3 influenza strains (A, B, & C).
Orthomyxovirus has a segmented genome (8 segments), which allows for antigenic shift. (biggie)
Antigenic drift = point mutations in viral genome lead to changes in HA or NA. Associated with epidemics (disease
outbreaks limited to certain areas). Causes seasonal flu & problems with yearly vaccination.
Antigenic shift = antigenic segments of RNA are shared between different species. H & N can combine to form new virus that is a mixture of surface antigens (reassortment). Associated with pandemics (disease outbreaks that are over multiple continents or worldwide). Most recently swine flu (H1N1) in 2009.
Influenza A causes epidemics and pandemics (drift and shift). Influenza B causes endemic outbreaks (drift). (smaller)
Hemagluttinin (HA): glycoprotein on the surface of influenza virus that binds to sialic acid (found on membranes of cells in upper
respiratory tract and RBCs). Causes RBCs to clump together. There are many HA antigens, but H1, H2, & H3 are seen in
influenza viruses that infect humans. Determines cell tropism (cells that can be infected with virus). Anti-HA antibodies protect from re-infection with same strain in future.
HA molecule binds to sailic acid on cell membrane and the virus is endocytosed. pH must be correct for uncoating to occur.
M2 protein (proton channel) maintains pH for viral uncoating. Amantadine and Rimantadine inhibit M2 protein (no longer
recommended for treatment). Previously only used for Influenza A treatment (Influenza B LACKS M2 protein). Amantadine is used to treat Parkinson’s disease (increases Dopamine).
Virus replicates in the nucleus and viruses then bind to host cell via sailic acid. Neuraminidase (NA) cleaves sialic acid to release newly formed virion from cell.
Oseltamivir/Anamivir (Tamiflu) inhibits NA, which prevents release of newly formed virion from the host cell. Must be given early in the course (prior to 72 hours) when virions have NOT been released.
Transmitted via respiratory droplets. Flu season in US is
December-February. Vaccination occurs in October (allows building of immune response prior to viral exposure).
Two vaccines available:
Live attenuated nasal spray Killed intramuscular
Trivalent vaccine (2 A strains & 1 B strain)
Quadrivalent vaccine (2 A strains & 2 B strains) Children can be vaccinated after age 6 months.
Pneumonia is a common complication of influenza (commonly S. aureus, but also S. pneumo).
Aspirin CANNOT be given to children with flu due to increased risk for developing Reye’s syndrome (life-threatening complication involving fatty liver, liver failure, encephalitis, fever, rash, and vomiting).
Aspirin causes uncoupling of oxidative phosphorylation (disrupts proton gradient along ETC). In Reyes syndrome, this occurs in hepatic mitochondria (extensive damage can be seen microscopically).
AVOID Aspirin in children and teenagers with recent/current viral infection.
Influenza virus is also associated with Guillan Barre Syndrome
(ascending paralysis). CSF has high protein with low WBC counts (albuminocytologic dissociation).
Paramyxovirus (Paranormal Mixer)
(-)sense ssRNA genome. Enveloped virus. Replicates in cytoplasm.
Spread via respiratory droplets.
MMR vaccine is a live attenuated vaccine that should not be used in pregnant women.
Measles (Rubeola)
Four Cs (prodromal or early phase): cough, conjunctivitis, coryza (runny/stuffy nose), and Koplik spots (small blueish-white spots on a red background found on buccal mucosa near 2nd molars). Also causes high fever lasting around 4 days.
Maculopapular rash develops 1-2 days after appearance of Koplik spots. Rash starts near back of ears, spreads to face/neck, and travels downward. Rash is itchy. Measles is more likely to form a confluent rash (unlike Rubella).
Major complications:
Viral or bacterial pneumonia.
Subacute sclerosing encephalitis (SSPE) = inflammation and sclerosing of brain caused by persistent Measles infection. Classically presents as person with history of childhood
Measles or an unvaccinated immigrant. 5-10 years later person develops personality changes, seizures,
myoclonus, ataxia, coma, or death. Diagnosis with anti-Measles antibodies in the CSF. No treatment.
Virulence factors of Paramyxovirus family: any combination of Hemagluttinin, NA, fusion proteins.
Measles virus virulence factors HA and fusion protein Fusion protein causes formation of syncytia or
multinucleate giant cells (warthin finkeldey cells). Typically found in lymphoid tissue. Also have characteristic cytoplasmic and intranuclear eosinophilic inclusion bodies (pathognomonic for measles).
Vitamin A reduces Measles morbidity and mortality.
Mumps
Replicates in the salivary glands (parotid glands). Can also be found in the testes and causes orchitis
(inflammation of the epididymis). Inflammation is typically
unilateral, but can be bilateral. Results in testicular atrophy and impaired fertility. Sterility is rare (more common in men with bilateral orchitis).
Mumps can also replicate in CNS and cause meningitis. Mumps virulence factors HA, fusion protein, and NA.
Respiratory Syncytial Virus (RSV)
Found in infants less than 6 months of age.
Virus infects cells by attaching to G protein in respiratory epithelium.
Causes bronchiolitis, rhinitis, pneumonia, and pharyngitis.
#1 cause of pneumonia and bronchiolitis in infants. Infiltrates on CXR.
RSV virulence factors fusion protein
Tx: Ribavirin (in adults, but NOT children/pregnant women).
Palivizumab is MAb against fusion protein; used to prevent RSV in children who are high risk (esp. premature infants).
Cause croup (characterized by seal bark cough and inspiratory stridor).
Croup = laryngotracheobronchitis
Parainfluenza virulence factors HA, NA, and fusion protein. CXR shows steeple sign (narrowing of sub-glottic region). Mainly effects children, but adults will have a severe cold. Rhabdovirus (Rabid Wrecking Yard)
(-)sense ssRNA genome. Enveloped virus. Capsid is bullet shaped. Helical capsid.
Zoonotic virus that is carried by animals and transmitted to
humans. Bats are most common carrier in the US (dogs are carriers in developing countries). Other US carries include squirrels, foxes, skunks, and raccoons.
Rhabdovirus has a glycoprotein that binds to nicotinic ACh receptors in the post-synaptic membrane of the NMJ.
Incubation period can be weeks to months (depends on distance of site of inoculation to CNS) before symptoms appear. Virus travels in a retrograde direction via peripheral nerves at a rate of 1-3 mm per day. Causes tingling and muscle spasms as it travels along nerves. Once it reaches salivary glands, it causes increased saliva production and spasms of muscles in throat/larynx (results in
dysphagia & foaming of mouth). Virus continues to travel along and eventually leads to high fever, encephalitis, neuronal death, and is invariably fatal.
Virus replicates in motor neurons.
Virus travels to dorsal root ganglion before spreading to brain. Diagnosis is typically clinical with a positive history of exposure.
Confirm on autopsy/biopsy via presence of Negri bodies in
neurons (eosinophilic cytoplasmic inclusions in soma of Purkinje cells in cerebellum or Pyramidal cells of hippocampus ).
Very few survivors of rabies.
Antidote must be administered prior to onset of symptoms and immediately after exposure.
Tx is passive immunization with human rabies
immunoglobulin and active immunization with the killed vaccine. Give treatment even if uncertain if patient bitten (but was still
exposed).
Filovirus (Soccer Field’o Virus)
(-)sense ssRNA genome. Helical capsid. Enveloped virus.
Causes fever and petechial rash beginning days to weeks after infection.
Symptoms progress to hemorrhagic fever and end-organ failure. Many cases are fatal. Death occurs due to severe blood loss,
leading to hypovolemic shock.
Virus originated from direct contact from animal infected with virus, such as monkeys or fruit bats (potential reservoir). People in contact with monkeys or bats in endemic areas (Africa) are prone to infection.
In the US, healthcare workers are most likely to get infection. Virus can spread easily via contact with bodily fluids, especially
after death of patient (caution contact with patient and body disposal).
Bunyavirus (Paul Bunyavirus)
(-)sense ssRNA genome. Segmented genome (3 circular
segments). Enveloped virus (obtained from Golgi of host cells). Most viruses in the Bunyavirus family are arboiruses, which have a mosquito vector (except Hantavirus – spread via contact with rodents or rodent excrement).
Hantavirus
Reservoir is the deer mouse (robovirus = rodent born). Transmitted via rodent urine and feces.
Causes pulmonary edema (via capillary leak) and pre-renal azotemia (low volume that occurs due to capillary leak and fluid
loss)
Can also cause hemorrhagic fever
Rift Valley Fever & California Encephalitis
Both are Arboviruses that are spread by the Aedes mosquito Causes neurologic problems (seizures and encephalitis),
myalgias, and fever.
Arenavirus (Welcome to the Arenavirus)
(-)sense ssRNA genome. Segmented genome (2 segments). Enveloped virus. Helical capsid.
Ambisense = has capacity to encode both negative and positive sense RNA.
On EM, virus has a characteristic “sandy” appearance with a granular capsid.
Associated with rodent transmitted diseases in humans. Virus infects rodents, which transmit virus to humans.
Lymphocytic Choriomeningitis Virus (LCV)
Leads to febrile, aseptic meningoencephalitis with fever. Virus is inactivated by heating, low pH, irradiation, and
detergents.
Reovirus (A Race on the Rio)
dsRNA genome. Naked virus. Segmented (11). Replicates in the cytoplasm.
Rotovirus
Transmitted via fecal-oral route.
Causes toxin-mediated secretory diarrhea. It can be fairly explosive and watery (similar to Norovirus).
NSP4 is the toxin responsible for diarrhea. It is a viral enterotoxin that increases viral permeability. (Increase chloride permeability)
Seasonal virus (outbreaks classically occur in winter months). Children are at high risk (classically infants and children at
daycare).
#1 cause of severe diarrhea in infants and children. Tx includes supportive care and oral rehydration.
Live attenuated ORAL vaccine (now part of standard vaccination schedule).
First dose should be given before age 3 months (due to
decreased efficacy and increased risk of side effects; vaccine also thought to increase risk intussusception d/t
stimulation/enlargement of Peyer’s patches).
Colorado Tick Virus
Causes fever, vomiting, and myalgias. NO RASH.
Occurs in Rocky Mountain states (similar to RMF, but no rash).
Chapter 3: DNA Viruses
HSV 1 & 2 (Hermes, the God of Herpes)
Herpesvirus family. Linear dsDNA. Enveloped. Replicates in the nucleus.
Cowdry bodies: host cells with large eosinophilic intranuclear inclusion bodies (appear similar to targets).
HSV transmission: sex; saliva; vertical transmission (TORCH infection).
Usually confined to upper half of the body.
Commonly thought of as cold sores, but initial infection causes gingivostomatitis (more aggressive & painful; occurs more often in infants; causes widespread inflammation of gums that
eventually become cold sores)
Cold sores (herpes labialis) are the most common infection of mouth
Causes kertoconjunctivitis with serpiginous corneal ulcers on fluorescein slit lamp exam.
HSV-1 causes temporal lobe encephalitis (hemorrhage and necrosis of the inferior and medial temporal lobes. Sx include bizarre behavior, olfactory hallucinations, personality changes, confusion, fever, headache, seizure, AMS. #1 Cause of sporadic encephalitis in the US.
Remains latent in the trigeminal ganglion & reactivated with stress or when immunocompromised.
Herpes rash has “dew drops on a rose petal” appearance due to the presence of clear vesicles on a erythematous base.
Herpetic whitlow: caused by HSV-1 and HSV-2; presents with rash on finger; more common in dentists. It can also be
transmitted via genital-hand contact (HSV-2).
Erythema multiforme: HSN reaction that causes small target lesions usually on the backs of hands/feet before moving centrally. Rash appears 1-2 weeks after infection. More common in HSV-1. Most commonly associated with HSV, but also
associated with other viruses, bacteria, and drugs.
HSV-2:
Usually confined to the genitals. Transmitted via sex and obstetrics.
Herpes genitalis: painful inguinal lymphadenopathy with clusters of vesicles with a red base.
Herpes lesions are painful and vesicular. HSV-2 lies dormant in the sacral ganglia.
HSV-2 causes aseptic meningitis in adolescents and adults. PCR is test of choice for diagnosis. Prior to PCR, the ulcer base was
scraped and used for a Tzank smear (should see multinucleate giant cells).
Tx with Acyclovir or Valcyclovir to prevent breakouts (HSV is not curable).
Epstein-Barr Virus (Ye Olde Epsetein Bar) Herpesvirus family. dsDNA. Enveloped