Sketchy Micro

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 antibodiesprevents 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  Part of normal skin flora; contaminates blood cultures

 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

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 Dark brown urine  Facial swelling and edema  Two weeks after onset of strep infection  Early treatment will NOT prevent Treat-penicillin Virulence  Steptolysin O- lyse red blood cells  Body makes antibodies against (ASO)  Streptokinase-plasmogenin to plasmin-can lyse clots  DNases-depolymerizes DNA Bacitracin sensitive 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  Protease to cleave IgA

Asplenia susceptible Macrolide suscept and cephtriaxone suscept Vaccine  Adults-polysaccharide-IgM response  Children-polysaccharide conjugated to proteinIgG 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 o o o

Anthra’s Axe: Bacillus anthracis and Bacillus cereus Black eschar (cutaneous) Gram positive rods in chains Encapsulated-Made of protein! (not polysaccharides); PolyD glutamic acid o Obligate aerobe o Able to form spores o Anthracis  LF and EF toxins both needed for symptoms

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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 hemorrhagehigh 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 Cause red blood cell hemolysis

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o Double zone of hemolysis on blood agarunique 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 Gram positive

Bacillus (base) Catalase positive Can survive and multiply in near freezing temperatures 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 o o o o

   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  CNS

 Brain abscess formation Cutaneous  Indurated lesions and inflammatory reaction; fever produced o Treatment-sulfonamides 

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Series: Neisseria species Gram negative diplococcic Oxidase positive 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 infectionbecause 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 syndromecharacterized by hemorrhage of adrenals-shock o Mortality 15% o Treatment- Ceftriaxone o Prophylaxis of close contacts- Rifampin

   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 through puppy feces

 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-Yopsmacrophage 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 foodoysters  

   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 tissueMALT 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 Osteomyelitis-IV drug users and diabetics

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 pelvispain and impt for reinfection (due to alkaline environment) o Urease positive-impt to form struvite stone formationammonia 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 40C –not specific

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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 lymphnodesaxillary 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 organsenlargement 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)  Can be aerosolized-watch for biowarfare

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 shapesCord factor  Protect bacteria  Granuloma formation through increasing cytokines (TNF alpha)  Allows bacteria to stay alive inside the granuloma with activated macrophages o Sulfatides-prevent lysosome phagosome fusion

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 coldemineralization 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

Thrives in cold temperatures-predication for extremities Acid fast-mycolic acids-waxy chains- Carol fuchsin Reservoir-armadillo Hansen’s disease 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 o o o o o

   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 Leptospirosis ;“Weils disease” Endemic in tropical regions Spirochete or question mark shaped 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 o o o o

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"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 "treebarking" 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

● ● ● ●

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. ( 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 blueishwhite 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 antiMeasles 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).   Parainfluenza virus CROUP

 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.   Marburg virus & Ebola 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).   HSV-1:

 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

 Causes infectious mononucleosis (mono).  Mono AKA “The Kissing Disease” is primarily transmitted via saliva (sharing drinks or kissing).  Sx include fever, tender posterior cervical lymphadenopathy and generalized lymphadenopathy, pharyngitis, and tonsillar exudates  Reactive CD8 T cells (Downey or atypical cells) are seen on a blood smear. These atypical lymphocytes are large with an oval or indented nucleus. Atypical lymphocytes can also be NK cells.  In response to infection T cells proliferate, resulting in splenomegaly and hepatomegaly (less common).  When the virus infects a new host, it targets B cells. To infect B cells, the EBV envelope glycoprotein binds to CD21 (receptor for C3d).  EBV infection can remain latent in B cells.  Mono also causes pharyngitis and copious tonsillar exudates.  Distinguish between strep pharyngitis and mono: strep pharyngitis is seen more in children; mono is asymptomatic at a young age.  Patients with Mono, who are treated with Amoxicillin or Ampicillin for strep pharyngitis, develop a maculopapular rash. This rash is an adverse affect (not an allergic reaction). It can also be associated with other antibiotics.  EBV is a risk factor for cancer:  In patients with weakened immune systems, EBV infection is associated with increased risk of B cell lymphoma.  Hodgkin’s Lymphoma: Reed Sternberg cell’s that look like owl’s eyes. EBV is seen in some subtypes, commonly the mixed cellular subtypes (70% of cases).  Non-Hodgkin’s Lymphoma: Burkitt Lymphoma is associated with EBV. Endemic or African Burkitt Lymphoma is associated with a large jaw lesion and swelling. In Non-Endemic or Sporadic Burkitt Lymphoma, the lesion develops in the ileocecum and peritoneum (t 8:14).  Nasopharyngeal Carcinoma: often seen in people with Asian ancestry.   Oral Hairy Leukoplakia: most commonly seen in patient with HIV. This is not a precancerous lesion (unlike other cancers associated with EBV) and does not develop in to SCC. Lesions are present on lateral portions of the tongue (similar to Candida but can NOT be scraped off tongue).  In acute infection, EBV activates B cells to secrete heterophile anti-sheep RBC antibodies. Presence of antibodies is used to make

diagnosis of Mono as they agglutinate sheep/horse RBCs. This is called the MonoSpot test (rapid detection).  Tx includes supportive treatment. Patients must avoid contact sports due to risk of splenic rupture. Splenomegaly occurs in 5060% infected with Mono. Cytomegalovirus (Cyto “Mega-Lo” Virus)  Herpesvirus family. dsDNA (replicates in nucleus). Enveloped  CMV remains latent in mononuclear cells (WBCs with a single nucleus – lymphocytes, monocytes, & macrophages).  Reactivation occurs with immunosuppression.  Transmitted via blood, sexual contact, breast milk, saliva, & urine.  CMV is a TORCHES infection (toxoplasmosis, rubella, CMV, HIV, Herpes, Syphilis, VZV and Parvovirus)  Congenital CMV is the #1 cause of fetal viral infection.  Congenital Blueberry muffin rash occurs because CMV causes thrombocytopenia (petechial rash). The same rash as in Congenital Rubella.  Congenital CMV also causes hepatosplenomegaly and jaundice.  Also causes sensorineural hearing loss and brain structural abnormalities (intracranial calcifications and ventriculomegaly). calcifications occur around the ventricles (periventricular calcifications) or in the brain parenchyma. Changes in brain structures lead to mental retardation and seizures.  Congenital CMV is more likely to be asymptomatic (80-90%).  15% of children later develop sensorineural hearing loss (mostly unilateral). Must screen at birth and once older.  2nd trimester infections are associated with greatest risk of transmission to fetus.  Hydrops fetalis: heart failure leading to severe edema with fluid accumulation in multiple compartments. Often leads to spontaneous abortion.   CMV is #1 cause of mental retardation from congenital virus infection.   CMV is #1 cause of sensorineural hearing loss.  CMV is associated with immunosuppression (transplant patients & AIDS pateints).  Transplant patients are at risk for CMV pneumonia.  To detect CMV in transplant patients, perform buffy coat culture. Buffy coat is part of blood containing white cells and platelets. Incubate with Fluorescein anti-CMV antibodies to detect virus.

 AIDS patients are at risk for CMV infections, especially when CD4 counts are below 50.  Most common manifestation is CMV retinitis (full thickness retinal necrosis, sometimes called “Pizza Pie” Retinopathy). Sx include flashing lights, blind spots, and vision loss. Typically occurs unilaterally (can be bilateral if no treatment).  CMV esophagitis and colitis also occur in AIDS patients. CMV esophagitis is usually single, deep and linear. Herpes esophagitis is multiple and shallow. CMV colitis has ulcers in colon walls.  CMV infects cells, causing Owl’s eye inclusions (not specific for CMV).  Tx: Ganciclovir (1st line) or Foscarnet (used when virus is resistant to Ganciclovir due to UL97 gene mutations.  Immunocompetent can be infected with CMV  causes CMV mononucleosis (same sx as EBV mononucleosis (pharyngitis, tender posterior lymph), but has a negative MonoSpot test). Varicella Zoster Virus (Varicella “Zeus”-ter Virus)  Herpesvirus family. Linear dsDNA. Enveloped.   Chicken Pox  Childhood exanthem associated with VZV is Chicken Pox, which is associated with fever and headache. Rash is classically described as “dew drop on a rose” or vesicular with an erythematous base. Lesions occur in different stages (blisters, healing scabs, etc). Smallpox has similar rash, but lesions are all at the same stage.  Virus transmission occurs via respiratory droplets or ruptured vesicles.  Diagnose using Tzank smear (shows multinucleate cells).  Adults with chicken pox have higher likelihood of developing pneumonia (major cause of morbidity and mortality) and encephalitis. These complications can occur in both children and adults. Immunocompromised adults are more likely to develop pneumonia and encephalitis.  There is a live attenuated VZV vaccine or children.  Tx with Acyclovir (typically used in children >12, adults and immunocompromised).  Chicken pox remains latent in Dorsal Root Ganglion.   Herpes Zoster (Shingles)  Reactivated virus is referred to as Herpes Zoster virus or Shingles.

 Reactivation occurs in older individuals, typically with stress or immunocompromise.  Shingles has “dew drops on a rose” with a dermatome distribution (rash travels down nerve until reaching the skin). Typically involves the lumbar/thoracic regions and rarely crosses the midline.  Disseminated VZV  rash will cross redline. This is a red flag that a person is immunocompromised.  Rash is very a painful. There is also postherpetic neuralgia (pain in dermatome after rash subsides).  Herpes Zoster Ophthalmicus: reaction affects trigeminal (V1) nerve and can cause vision loss. This is more likely to occur in immunocompromised patients.  Zoster vaccine is a live-attenuated virus for adults older than 60 (Can be given to HIV patients if CD4 count is over 200).  Tx includes Acyclovir or Famiciclovir or Valcyclovir.  VZV is a TORCHES infection. Women infected during first two trimesters can have Congenital Varicella Syndrome (limb hypoplasia, cutaneous dermatomal scarring, & blindness). HHV-6 Roseola (A Roseola By Any Other Name Would Smell As Sweet)  Herpesvirus family. dsDNA. Enveloped. Causes Roseola (AKA 6th disease).  HHV-6 infects CD4 cells and can cause immunosuppression (by killing CD4 cells).  Roseola (exathem subitem) occurs primarily in children ages 6 months-2 years. Characterized by 3-4 days of high fever followed by diffuse maculopapular rash (lacy appearance sparing face).  Fever can be 104F and can cause febrile seizures.  Fever lasts 4 days, then rash appears.  There is no FDA approved treatment for Roseola. Tx is supportive with fluids and cooling measures. HHV-8 Kaposi’s Sarcoma (Ring Around A Ka-posi)  Herpesvirus family. dsDNA. Enveloped.  Infection most commonly occurs with immunosuppression and AIDS.  Characterized by erythematous, violacious lesions on nose, extremities, and mucous membranes. May be present as plaque, patch, macule, or nodule. Lesions arise from primitive vasculature

      



forming mesenchymal cells (high vascularity due to angiogenesis causes violacious color). Virus causes proliferation of vasculature by dysregulation of VEGF, resulting in angiogenesis. Lesions can also form on mucosal surfaces, including the GI tract. Most common location of plaques is the hard palate (arched ceiling of mouth) HHV-8 can also infect B cells, causing a B-Cell lymphoma (Primary Effusion Lymphoma). Transmission via sexual contact, including kissing (especially in men who have sex with men). High suspicion of infection in AIDS/immunocompromised, elderly Russian men (lower extremity lesions), and Africans (adults have palatal lesions; can be fatal in children). Kaposi’s is commonly confused with Bacillary Angiomatosis (Bartonella henselae). Differentiate via microscopy. Kaposi Sarcoma has a lymphocytic infiltrate (viral etiology) and Bacillary Angiomatosis has a neutrophillic infiltrate (bacterial etiology). Tx includes anti-retroviral therapy in HIV positive patients (should cause lesions to shrink).

Polyomavirus (Et Tu, BK?)  Circular dsDNA genome. Naked virus. Includes JC virus and BK virus.  JC Virus (John Cunningham Virus)  Causes progressive multifocal leukoencephalopathy (PML).  PML is a demyelinating disease that kills myelin producing oligodendrocytes. Occurs throughout CNS (multifocal) and is progressive (50% die within months).  Imaging shows non-enhancing multifocal brain lesions in white matter.  Leukoencephalopathy is a demyelinating disorder (similar to MS).  Over half of the population has JC virus, but it is asymptomatic in persons with normal immune system.  In HIV patients with a CD4 ALT  Viral hepatitis  ALT > AST (Subsequent fall of ALT after prodromal phase).  ALT is normal in neonatal hepatitis.  HBV titer levels (We are all one species)  S = HepB Surface antigen (HBsAg)  first marker of infection; indicates active infection (acute or chronic).

 E = HepB E antigen (HBeAg)  highly correlates to infectivity; high levels indicate that a person is infectious. This is also time frame that person has symptoms.  C = HepB Core antibody (Anti-HBc)  positive during window period (patient has begun producing antibodies to antigens and sometimes neither are detected, which gives false reassurance that person is not infected). HepB Core antibodies will be positive during window period and indicate infection.  E = HepB E antibody (Anti-HBe)  indicates low infectivity.  S = HepB Surface antibody (Anti-HBs)  indicates recovery. Person no longer has and infection (acute or chronic). This is value check for person immunized. Only this value is positive in vaccinated persons.  Distinguish immunized persons from previously infected person using Anti-HBc and Anti-HBe. Immunized people are negative for both. Recovered will be positive for at least Anti-HBc antibodies.  HBV is a risk factor for liver cirrhosis and hepatocellular carcinoma.   Hepatitis D  HDV cannot cause disease without HBV. Hepatitis D is an enveloped (-)sense RNA virus with a circular genome.  HDV requires HepB Surface antigen (HBsAg) to cause infection.  Co-infection: both HepB and HepD are transmitted simultaneously.  Superinfection: HepD is transmitted ontop of existing HepB infection. Associated with worse outcomes.  Most acute infections clear without treatment.  Pregnant women and people with chronic infections should receive treatment. Treatment does not eradicate disease, only reduces damage by preventing replication. Tx includes antivirals (Lamivudine) and nucleoside reverse transcriptase inhibitors (NRTIs) and IFN-  These drugs (except IFN-can be given to pregnant women prior to delivery.  If mother is HepB positive, baby must be treated with immunoglobulin and HepB vaccine (passive and active immunization).

FUNGI Chapter 1: Systemic Mycoses

Histoplasma capsulata (The Historian’s Cave)  Systemic fungi can spread to other organ systems (typically originate in the lung). Systemic fungi have specific geographic distributions.  Histoplasma capsulata causes histoplasmosis.  Histoplasma is most commonly associated with bird or bat droppings. It typically presents in people who were inside a cave, spelunkers, or farmers inside chicken coups.  Histoplasma is endemic in the Midwest and Central US along the Mississippi and Ohio River Valleys.  Transmission occurs via the respiratory systems. Spores in bird or bat droppings are inhaled and travel to the lungs, where they are ingested by macrophages.  Diagnosis of Histoplasma:  Macrophages from tissue samples or respiratory prep are stained with a KOH prep. Visualization of macrophages filled with small, intracellular oval bodies suggests Histoplasma. Histoplasma is much smaller than a RBC and numerous Histoplasma can be seen within a single RBC (macrophages are only slightly larger than RBCs). A single macrophage can contain 10 to 100 Histoplasma.  Histoplasma can also be cultured, but this is time intensive.  Rapid Histoplasma serum or urine antigen test is also used.  Histoplasma is dimorphic, which means that the form of the fungus is dependent upon the temperature of its surroundings (this feature is shared among all of the systemic fungi).  Mold in the cold and yeast in the heat.  In the soil (cold), the fungus is in the mold form.  In the body (heat or 37C), the fungus is in the yeast form.  Systemic fungi are generally asymptomatic or subclinical in most people. They can cause granuloma formation in some people, which results in pneumonia with cough. The granulomas of the lungs will eventually calcify, which leads to pulmonary issues. Chronic Histoplasma can mimic TB with cavitary lesions in the upper lobes and calcified nodules with fibrotic scarring. Hilar Calcifications  Histoplasma can also cause erythema nodosum, which are painful red nodules that are usually found on the shins.  Systemic fungi are especially associated with the immunocompromised. Immunocompromised persons can have disseminated Histoplasma. Dissemination to the liver and spleen results in hepatosplenomegaly with gross calcifications.

 Fungus disseminates to the liver and spleen because the fungus targets the reticuloendothelial system, which has abundant macrophages.  Dissemination can also produce some skin and neurological findings.  Systemic fungi can cause local infections or can progress to systemic infections. Treatment is dependent on the status of the infection.  Local infections and mild infections should be treated with – conazole drugs, such as Fluconazole or Ketoconazole.  Systemic infections should be treated with Amphotericin B (much stronger). Amphotericin is associated with numerous side effects and should be reserved for disseminated infections. Blastomycosis dermatitidis (The Blast of the Cannons)  Blastomycosis dermatitidis causes blastomycosis.  Blastomycosis is endemic to the Great Lakes and Ohio River Valley (Southern and Eastern US). The distribution of Blastomycosis has some overlap with Histoplasma.  Blastomycosis is a dimorphic fungus that changes forms depending on the temperature (mold in the cold, yeast in the heat).  Fungus lives in the dirt and has potential to become aerosolized. Spores are inhaled and are converted to the yeast form as it colonizes the lungs.  Blastomycosis replicates via broad based budding.  Blastomycosis is very large and appears roughly the same size as a RBC.  Blastomycosis causes the lungs to have a patchy alveolar infiltrate (haziness) on CXR. Lesions or cavities may also be present on imaging.  This pneumonia can be acute or chronic and it is considered a local lung infection. The infection can spread to other organs, especially in the immunocompromised. The majority of infections are subclinical or asymptomatic.  Systemic infection typically only occurs in the immunocompromised.  Dissemination of Blastomycosis is most likely to occur in the skin and bones.  Chronic Blastomycosis infection with bone involvement can cause osteomyelitis.  Diagnosis can be achieved via KOH prep or culture.  KOH prep will show round yeast with a single broad based bud.  Blastomycosis can also be detected using a urine antigen test.

 Treatment  Local infections are treated with –conazoles, such as Itraconazole.  Systemic or disseminated infections are treated with Amphotericin B. Coccidioides immitis (Presidio San Joaquin)  Coccidioidomycosis is endemic to the Southwestern US.  Transmission occurs via inhalation of a single arthroconidium (spore). Spores normally reside within dust and transmission is greatly increased when large amounts of dust are dispersed into the air (dust storms and earthquakes are risk factors for spread of infection).  Frequent dust storms in San Joaquin Valley of California cause high incidence of Coccidioidomycoses  San Joaquin Valley Fever is another name for Coccidioidomycosis.  Coccidioides is a dimorphic fungus that changes forms depending on the temperature.  In the cold, the fungus is in the mold form.  In the body, the fungus exists as spherules of endospores. Spherules rupture and release endospores, which spread throughout the lungs and possibly throughout the body.  Cocci spherules are larger than a RBC (Cocci > Blasto = RBC > Histo).  Coccidioidomycosis is asymptomatic or subclinical. In some it can present as a self-limited acute pneumonia with fevers, sweats, and arthralgias (lasts a couple weeks).  Radiographic imaging can be unremarkable in the majority of patients, but others may show cavities or nodules (or both).  Coccidioidomycosis can also cause erythema nodosum, which is an inflammatory condition that leads to the formation of red, extremely tender nodules that are usually located over the shins.  Erythema nodosum is present in both Histoplasmosis and Coccidioidomycosis, but it is more commonly present in Coccidioidomycosis.  Erythema nodosum symbolizes a robust immune response and is typically only seen in healthy individuals.  In immunocompromised persons, the infection can disseminate.  Skin and lungs are common sites of infection in the immunocompromised.  Coccidioidomycosis may also disseminate to the bone in immunocompromised persons.

 The fungus can also disseminate into the meninges, which results in a fungal meningitis (associated with headache and stiff neck).  Definitive diagnosis is achieved via a KOH stain or a culture.  Serology for antibody titers can be used for diagnosis (serology can be used for all systemic mycoses). IgM for Coccidioidomycosis would indicate recent infection.  Treatment is dependent on the status of the infection.  Local lung infections should be treated with –azole drugs, such as Ketoconzaole.  Systemic infections should be treated with Amphotericin B. Paracoccidioides brasiliensis (Piratas del Sur)  Paracoccidioidomycosis is distributed in Brazil and other parts of South America. It is sometimes referred to as the Brazilian Blastomycosis.  Geographic distribution = South America  Paracocci in yeast form has a distinct form, which consists of multiple buds that radiate out from a central vacuole. This pattern is described as looking like a “Captain’s Wheel” with round and bulb shaped handles.  Paracocci is a dimorphic fungus. (Mold in the cold [environment], yeast in the heat [body]).  Paracocci yeast are very large; they are larger than a RBC (Paracocci and Cocci are roughly the same size). Paracoccidioidomycosis is transmitted via respiratory droplets. After inhalation, the fungus disseminates and causes lymphadenopathy (cervical, axillary, and inguinal). As the disease progresses, it moves downwards to affect the lungs and upper respiratory system. In the lungs, the disease cause granuloma formation.  Mucosal ulcers can develop in the upper respiratory tract, especially in the mouth. The ulcers are often in the gum in the mouth with ragged borders and small spots of hemorrhage.  Mucocutaneous lesions and cervical lymphadenopathy are the most important defining clinical features of the fungus.  Treatment includes Itraconazole (mild infections) or Amphotericin (severe infections). Chapter 2: Cutaneous Mycoses Malassezia furfur (Malassezia’s Italian Restaurant)

 Fungus that causes the disease Pityriasis versicolor.  “Spaghetti and meatball” appearance on KOH prep of skin scrapings. KOH prep can be used for diagnosis.  Malassezia is part of the normal skin flora and generally thrives in hot and humid conditions. Heat and humidity will cause fungus to convert to its disease form.  Malassezia causes Pityriasis versicolor (hyperpigmented or hypopigmented patches) in healthy patients. Patches are typically located on the back and chest, especially in persons who spend a lot of time in the sun.  Patches form due to lipid degradation, which produces acid that damages melanocytes (results in pigmentation problems).  Malassezia furfur is lipophilic (requires olive oil for growth).  Malassezia furfur is a cutaneous mycoses that generally remains confined to the skin. It remains in the stratum corneum (most superficial layer).  In healthy persons, Malassezia furfur causes dermatologic problems. In immunocompromised persons, it can cause devastating systemic effects.  Malassezia fungemia can be seen in neonates receiving TPN (total parenteral nutrition). Neonates in the NICU will often receive a lipid infusion with TPN via catheters. Malassezia is lipophilic and the catheter provides access to the bloodstream. Fungus will grow in the lipid transfusions, enter the body, and cause sepsis and thrombocytopenia.  Malassezia can also cause problems in adults receiving lipid transfusions, but symptoms are generally less severe.  Treatment of cutaneous mycoses includes topical selenium sulfide (Selsun Blue), which promotes the shedding of the stratum corneum (location where fungus resides). Dermatophytes (Tinea Tin Man)  Dermatophytes are a fungus that colonizes the skin and causes Tinea (rash).  There are three types of Dermatophytes and multiple types of Tinea (all types of Tinea have the same general pathology, but are named differently based on the affected loation).  Types of Dermatophytes include: Trichophyton, Epidermophyton, and Microsporum.  Dermatophytes (literally means “skin plants”) live on the skin.  Tinea is commonly referred to as Ringworm.   Tinea capitis: located on head and scalp.

  Tinea corporis: located on the body.   Tinea cruris: located in the groin (jock itch)   Tinea pedis: located on the feet (athlete’s foot).  Tinea lesions are pruritic (itchy).  Athletes are typically at risk for Tinea infections, especially swimmers (walk barefoot in locker rooms) and wrestlers (contact with sweaty mats and other wrestlers).  Animals and pets can also be a source of transmission.  Diagnosis is typically via history and physical, but can be confirmed by visualizing hyphae on KOH prep of skin scrapings. Woods lamp can be used to diagnose Microsporum (only).  Treatment includes topical –azoles (Clotrimazole).  Dermatophytes can also infect the nails, which is referred to as Onychomycosis.  Treatment includes the Terbinafine (oral antifungal).  For more severe Tinea infection or resilient Onychomycosis, oral Griseofulvin can be used (deposits in keratin containing tissues such as skin and nails). Griseofulvin has many GI side effects and is poorly tolerated. Sporothrix schenckii (Shanked by a Rose)  Sporothrix causes the subcutaneous infection known as Sporotrichosis. It is classically contracted by cuts from a rose bush (Rose Gardener’s disease).  Sporothrix is found on roses, tree bark, bushes, and plants.  Sporothrix is a dimorphic fungus. Branching hyphae (mold) are seen in cultures grown at 25C.  Buds or cigar-shaped yeast are seen under a microscope.  Sporothrix is most commonly introduced into the skin by physical trauma (e.g., thorn of rose bush). This can result in formation of a local pustule or ulcer at the site of the trauma. Further nodules can then develop in an ascending pattern along the path of draining lymphatics. The cutaneous infection will track up the lymphatics in an ascending fashion.  Culture is the gold standard to confirm the diagnosis of Sporotrichosis. Biopsy can also be performed and will show granulomas (consisting of histiocytes), multinucleated giant cells, and cigar-shaped budding yeast.  Treat lymphocutaneous sporotrichosis with Itraconazole (drug of choice). Former treatment was a saturated solution of potassium iodide (rarely used, but was previously the standard of care until the 90s).

Chapter 3: Opportunistic Fungal Infections Candida albicans (Candid Canadians)  Candida causes cutaneous and systemic fungal infections. It is the most common cause of opportunistic mycoses (especially in patients with HIV/AIDS, diabetes, and neutropenia).  Candida is dimorphic, but it forms pseudohyphae and budding yeast at 20C. Germ tubes (true hyphae or mold) are formed at 37C. REVERSED  Cold environment  yeast  Warm environment  mold  Candida is catalase positive. Catalase is important because people with Chronic Granulomatous Disease are susceptible to infection with catalase-positive organisms.  Candida is part of the normal flora of the GI tract, including the oral cavity (present in 40% of population). It does not usually cause problems in immunocompetent hosts. Candida will commonly contaminate sputum cultures.  Candida can cause clinically significant problems in different populations.  Candida causes diaper rash in a characteristic distribution due to the heat and humidity within a baby’s diaper.  Oral candidiasis is generally seen in the immunocompromised or those using steroids (especially in persons using steroid inhalers). The white patches that form in the mouth can be scraped off (in contrast to precancerous leukoplakia, which cannot be scraped off easily).  KOH is used to prep oral scrapings to diagnose oral candidiasis.  Candidal esophagitis occurs when the infection extends into the esophagus. It is most common in persons with AIDS and Candidal esophagitis is an AIDS defining illness.  Candidal esophagitis occurs at a CD4 count < 100.  Candidal vulvovaginitis (vaginal candidiasis) most commonly occurs in females on antibiotics or birth control and female diabetics.  Antibiotics kill the vaginal microflora, which allows Candida to flourish. Candida does not change the vaginal pH (unlike Gardnerella). Normal vaginal pH is acidic (3.8-4.2). Candida infections do not occur at higher pH.  Candida is an important cause of endocarditis. Candidal endocarditis is commonly seen in drug users because Candida often grows in certain types of heroin. When injected IV, it can

seed heart valves (most often the Tricuspid valve because this valve is encountered first).  Treatment  Trear with –conazoles for minor infections.  Amphotericin severe or disseminated infection (most often occur in immunocompromised persons).  Capsofungin may be used for disseminated infections that are resistant to Amphotericin.  Nystatin is used for oral or esophageal candidiasis. Nystatin is a liquid that is either taken via swoosh and spit/swallow depending on the location of the infection. Aspergillus fumigatus (Asparagus Farm)  Aspergillus is catalase-positive.  Peanuts are associated with aflatoxins, which is a toxin produced by Aspergillus flavus. These aflatoxins are also associated with grain crops (wheat).  Aflatoxin is extremely carcinogenic, especially in the development of hepatocellular carcinoma.  Morphology can be used to distinguish Aspergillus vs. Mucor.  Aspergillus  hyphae form acute angles that are usually less than 45 degrees. Hyphae contain septations. (ASpergillus = Acute Septate)  Aspergillus forms conidiophores with fruiting bodies. Conidiophores sit at the top of the stalk, where they are released into the air and later inhaled by humans.  Aspergillus causes 3 main infections:  Allergic Bronchopulmonary Aspergillosis (ABPA)  Type I Hypersensitivity Reaction that causes wheezing, fever, and migratory pulmonary infiltrates. ABPA is also associated with asthma and CF. Blood tests will show increased IgE.  Aspergillomas (fungus balls)  solid balls of fungus within the lungs. Persons that are susceptible to this type of infection are those with preexisting cavitary lesions (TB or Klebsiella). Fungus balls within the cavities are gravity dependent (in an upright CXR, fungus balls are at the bottom of the cavity).  Angioinvasive Aspergillosis  typically affects immunocompromised persons (patients with neutropenia due to leukemia or lymphoma). Angioinvasive aspergillosis invades blood vessels and disseminates quickly (acute angle hyphae with septae can be seen invading vessels and surrounding tissues on light microscopy). It also causes fever, cough, and hemoptysis. Due to its ability to disseminate, many organs are affected, including

kidneys (renal failure), heart (endocarditis), brain (ring enhancing lesions), paranasal sinuses (necrosis around the nose).  Treatment  A –conazole is used for less serious infections, more specifically – Voriconazole should be used for Aspergillus infections.  Aspergillomas need to be surgically debrided.  Angioinvasive Aspergillosis should be treated with Amphotericin. Cryptococcus neoformans (Crypt for Cryptococcus)  Cryptococci are heavily encapsulated. Capsule is made of repeating polysaccharide capsular antigens.  Capsule is a virulence factor and makes the Cryptococci antiphagocytic.  Capsule can be used for diagnosis.  Cryptococci are found in soil and pigeon droppings. Cryptococci enters the body via inhalation and it settles in the lungs as the primary focus and can disseminate elsewhere.  Cryptococci are urease positive.  Cryptococcus is an opportunistic infection that most commonly occurs in immunocompromised persons, especially those with HIV, malignancy, or those on high dose steroid therapies.   Pulmonary symptoms  Infection settles in the lungs and can remain asymptomatic. It can also cause cough, dyspnea, and other serious lung infections. Diagnosis at this stage is unlikely and Cryptococci will likely progress to more worrying symptoms.  Cryptococci can spread to the CSF and cause meningitis. #1 cause of fungal meningitis. Cryptococcal meningitis requires a long treatment course at best, but can also lead to permanent neurological deficits and mortality.  Cryptococci can also cause fever and pneumonia.  Diagnosis  Cryptococci can be cultured on Sabouraud’s agar, but culture requires weeks.  Bronchopulmonary washings of lung tissue can be stained with Mucicarmine (red) or Methanamine silver stains.  Diagnosis of Cryptococcal meningitis requires a lumbar puncture and the CSF is stained with India Ink. India Ink stains the background dark while the organism remains transparent (negative staining technique). 5-10 um yeast with wide capsular halos are seen on India Ink stains. Test is not very sensitive.

 Latex agglutination test is more sensitive. It detects the repeating capsular polysaccharide and causes agglutination.  After invading the CSF, Cryptococci causes distinct gross pathology that can be seen on imaging. This pathology is known as “soap bubble” lesions, which are found in the gray matter of the brain.  Treatment of Cryptococcal meningitis is laborious.  Consists of joint therapy with Amphotericin B and Flucytosine, followed by maintenance therapy with Fluconazole. Mucormycosis (Mu Car Autoshop)  Mucormycosis is caused primarily by 2 fungi (Mucor & Rhizopus).  Typically opportunistic infections that occur in immunocompromised persons (especially patients with leukemia and neutropenia). Diabetics are also at increased risk.  Rhizopus is essentially a bread mold.  Transmission occurs via inhalation. After inhalation, the fungi proliferate in the vessel walls, especially where there is excess glucose and ketones. DKA is the most common predisposing factor to infection with this fungus.  Mucor has non-septated hyphae with wide angle branching (90 degrees).  Fungus proliferates in blood vessels. After invading blood vessels, the fungus will penetrate the cribiform plate (contains holes that allow passage of CN I) of the skull and enter the brain. After penetrating the brain, the fungus continues to proliferate in blood vessels and causes tissue necrosis. This can lead to rhinocerebral mucormycoses and frontal cortex abscesses.  Necrotic tissue presents as a black eschar on the face and nasal cavity. This typically has a poor prognosis as the fungi has likely spread deep into the recesses of the brain, causing neurological deficits and death.  Treatment  Dead tissue should be removed via surgical debridement.  Amphotericin B should also be used. Pneumocystis jiroveci (PCP Ping Pong)  Pneumocystis jiroveci causes Pneumocystis pneumonia. The infection is transmitted via respiratory transmission.  Symptoms are evident in immunocompromised persons (especially AIDS). It can also infect healthy individuals, but these persons are typically asymptomatic.

 PCP is an AIDS defining illness and is associated with a CD4 count < 200 (value when people become susceptible to PCP and when prophylaxis should be started).  PCP is a diffuse interstitial pneumonia that causes a nonproductive cough, dyspnea, and fever. CXR typically shows a ground glass appearance with diffuse & wispy infiltrate in both lungs. Ground glass appearance can also look like crushed ping pong balls. Consolidation is not seen on CXR.  Diagnosis is confirmed using bronchoalveolar lavage (BAL), which is a bronchoscopy procedure that obtains lung samples using fluid rinses. Lung biopsy can also be used, but it is more invasive. The tissue sample must be stained with Methamine silver to identify the fungus, which appears as disc-shaped yeast. The yeast are ovoid.  Prophylaxis should be initiated in HIV positive patients with a CD4 count < 200.  Bactrim (TMP-SMX) is the drug of choice for PCP prophylaxis.  Pentamadine should be used in patients with sulfa allergies.  Bactrim or Pentamadine can be used for prophylaxis and treatment.

Parasites Chapter 1: Protozoa of the Intestinal Tract Giardia lamblia (Giardia Jungle Ride)  Giardia is a common parasite that is often associated with hikers, campers, or travelers who visit an area endemic to Giardia and drink unfiltered water from a stream or river. The water is contaminated by animal or human feces that contain cysts of Giardia (fecal-oral transmission).  Disease is most often associated with campers who do not purify water before drinking it.  Giardia causes bloating, flatulence, and foul-smelling diarrhea. Giardia also causes steatorrhea (fatty diarrhea).  The stools become fatty due to fat malabsorption. The exact mechanism of fat malabsorption is unknown. It is proposed that Giardia stimulates excessive mucus production that impairs the absorptive capacity of the intestine.  Infected people who do not receive treatment can have significant weight loss and health problems due to malabsorption (deficiency of Vitamins DEAK = fat soluble vitamins).

 After ingestion of the cyst form, it differentiates into the trophozoite form. The trophozoite form has a distinct shape (flagellated with ventral sucking discs).  Trophozoites attach to the intestinal wall, but do not invade (does NOT cause bloody diarrhea).  Trophozoites can be passed into the stool. Stool O&P is used for diagnosis (trophozoites in stool is diagnostic). Diagnosis can also be made using the ELISA stool antigen.  Some trophozoites in the intestine will turn back into the cyst form, which is also detected on stool O&P and can infect other people.  Giardiasis is treated with Metronidazole.

Entamoeba histolytica (Entering the Historical Drug)  Entamoeba histolytica is a parasite that causes amebiasis with bloody diarrhea.  Entamoeba histolytica has two main life cycle stages.  The cyst form is infective when it is ingested (usually from contaminated drinking water). Infection is also associated with men who have sex with men due to anal-oral transmission.  While the cyst resides in the GI tract, it differentiates into trophozoites. Trophozoites invade the colon and can spread via the portal circulation to the liver.  Right lobe of the liver is the most common site involved amoebic liver abscesses. 70-80% of the lesions are solitary, but there can also be multiple lesions.  Patients with amoebic liver abscesses complain of RUQ pain and may have enlarged, tender livers. Pus inside the liver abscesses is classically described as having the consistency of anchovy paste.  Entamoeba histolytica also causes intestinal amebiasis. Intestinal amebiasis causes flask-shaped ulcers along the colon. The presence of colonic ulcers indicates that Entamoeba is invasive and can cause bloody diarrhea (dysentery).  Diagnosis  Stool O&P for cysts or trophozoites. Entamoeba can be diagnosed under the microscope by the presence of trophozoites that contain endocytosed RBCs.  ELISA antigen test can be performed on stool and serum.  Serology can be used to detect Entamoeba antibodies.  Colonoscopy can be used to biopsy for flask-shaped lesions.

 Treatment  Metronidazole  Alternative drugs work by eliminating cysts while they are in the lumen of the intestine. These drugs are referred to as luminal agents.  Parmycin or Iodoquinol  Use Iodoquinol in combination with Metronidazole.  Medical treatment is important and surgical intervention can NOT be performed on a liver with Entamoeba abscesses (unlike Echinococcus liver mass, which can be treated surgically). Cryptosporidium (Tales from the Crypt)  Cryptosporidium is a parasite that causes diarrhea in immunocompromised patients.  In AIDS patients, Cryptosporidium causes severe and unrelenting diarrhea. It is the organism most commonly identified in HIV patients with diarrhea.  In immunocompetent persons, it causes mild watery diarrhea.  Cryptosporidia are unicellular, partially acid-fast organisms. They complete their entire live cycle within a single animal and in the process they create oocysts that are released in the feces, which can then be transmitted fecal-orally.  At risk population includes those who swim in dirty water, campers, and people that work with animals.  Cryptosporidium stains acid-fast.  Cryptosporidium looks like Amethyst crystals floating in water on acid-fast staining.  Infectious cysts are passed through watery stool. Each cyst is composed of 4 motile sporozoites that are released after ingestion. Sporozoites then attach to the intestinal wall, causing diarrhea and damage to the small intestine.  Cryptosporidium is usually associated with the small intestine, but it can occasionally colitis.  Treatment  Nitazoxanide (anti-protozoal that can be used exclusively in immunocompetent hosts).  Filtration can remove oocysts from infected water. Cryptosporidium is highly resistant to chlorination, so filtration must be used for protection.  Spiramycin (macrolide antibiotic). This drug is not FDA approved in the US.

 Supportive treatment with special attention to fluid status and electrolyte balance. Chapter 2: Protozoa of the CNS Toxoplasma Gondii (Oh Hi, Iz Makin Sum Toxo)  Toxoplasma gondii is an intracellular parasitic protozoan that can infect almost any warm blooded animal. It is estimated that approximately 30% of the world’s population carries Toxoplasma (few symptoms in the immunocompetent).  Pregnant women and immunocompromised persons are populations at risk for Toxoplasma infection.  Transmission:  Consumption of raw or undercooked meat that contains Toxoplasma tissue cysts.  Ingestion of water or vegetable contaminated with oocytes shed in the feces of infected animals. It is commonly transmitted via cat feces.  Transmitted via through the placenta from mother to fetus in utero if the mother is first exposed to Toxoplasma during pregnancy (TORCHES infection). Pregnant women should not change cat litter boxes during pregnancy d/t transplacental transmission.  In immunocompromised patients (especially HIV patients), Toxoplasma causes brain abscesses that are seen as multiple ring enhancing lesions on MRI/CT. Toxoplasma encephalitis can cause a single brain lesion, but this is more typical of alternative diagnoses (CNS lymphoma).  Toxoplasma can be differentiated from CNS lymphoma via brain biopsy.  In healthy individuals, Toxoplasmosis can cause flu-like symptoms but it is generally asymptomatic.  Congenital Toxoplasmosis has a classic triad consisting of chorioretinitis, hydrocephalus, and intracranial calcifications.  It can also present with seizures or congenital deafness.  HIV patients with low CD4 counts can also develop chorioretinitis.  Diagnosis is made via serology or biopsy (presence of intramuscular cysts)  Even if serology is positive, it does not indicate active infection (large proportion of the population has been exposed to Toxoplasmosis).  Treatment includes Sulfadiazine and Pyrimethamine.

 HIV patients with a CD4 count < 100 and serology positive for IgG antiboides against Toxoplasma should receive prophylaxis with TMP-SMX. Trypanosoma brucei (Prince Bruce to the Rescue)  Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are both members of the larger Trypanosoma brucei family. These are both parasites that cause African sleeping sickness.  Transmission occurs via painful bite of the Tsetse fly (vector).  Trypanosoma brucei are endemic to Western (Gambiense) and Eastern (Rhodesiense) Africa.  After bites by the Tsetse fly, the parasites move from the blood to the lymph nodes (cervical and axillary lymphadenopathy). It also causes recurrent fevers.  Symptoms indicate where parasites dwell – blood (fever), lymph nodes (lymphadenopathy), and CNS (sleeping sickness)  Trypomastigotes are seen on blood smear. Trypomastigotes can also be found in lymph nodes or cerebrospinal fluid.  Parasite has variable surface glycoproteins, which undergo constant antigenic variation. This allows the parasite to evade the host immune system and enables chronic infection (recurrent fevers).  Parasites are motile with a single flagella.  Treatment  Melarsoprol is used to treat CNS infections.  Suramin is used to treat peripheral blood infections.  Trypanosoma brucei is one of the few parasites that penetrate the CNS. The few treatments that exist have toxic side effect profiles. Naegleria fowleri (Naegleria Falls)  Naegleria fowleri is an amoeba found in freshwater lakes that can cause meningoencephalitis.  Trophozoite enters the CNS via the cribiform plate.  Naegleria fowleri causes meningoencephalitis (inflammation of brain and meninges), which presents as nuchal rigidity, fevers, and AMS (altered mental status).  When Naegleri is responsible for these symptoms, the disease is termed Primary Amoebic Meningoencephalitis. The disease is rapidly fatal with a poor prognosis.  Most often presents in persons who swim in freshwater lakes, waterski/watersports, backpack, or spend time in hot springs.

 Nasal irrigation systems and contact lens solutions have also been identified as a source of Naegleria infections (Naegleria can contaminate water supplies and stagnant water is a perfect environment for the organism to thrive).  Diagnosis is made via lumbar puncture with amoebas seen in the CSF.  Treatment for Primary Amoebic Meningoencephalitis is Amphotericin. Chapter 3: Protozoa of the Blood Trypanosoma cruzi (Cruzin’ Through the Che’s Gas)  Trypanosoma cruzi is a parasitic protozoan located primarily in South America, but it can also be found in Central America.  Trypanosoma cruzi causes Chagas disease.  Trypanosoma cruzi tunnels into tissue and feeds on blood and lymph of the victim.  It is transmitted when the vector (reduviid bug) bites the victim and deposits infected feces into the open wound. Infiltration is further promoted with scratching of the area.  Kissing (reduviid) bug bites (painless) around the mouth and deposits feces (T. cruzi is located in the feces), which can later be introduced by scratching the area. Bites often occur at night.  Illness can be devastating and fatal. Acutely the infection may be asymptomatic or there can be localized inflammation around the bite site. 10-20 years after inoculation, the symptoms of Chagas disease may appear.  Symptoms of Chagas disease:  Megacolon  enlarged colon that can present as severe constipation with a large bolus of poop (seen of XRAY) or it can present as acute abdomen due to a perforated colon.  Dilated cardiomyopathy  cause of fatality in many patients with Chagas disease.  Mega-esophagus  esophagus is dilated.  Trypanosoma cruzi is diagnosed via blood smear, which is used to visualize motile Trypanosomes during active infection.  In chronic Chagas, diagnosis is made via serology and clinical symptoms.  Trypanosomes can also be found in cardiac myocytes on heart biopsy (not frequently performed). Trypanosome enters the bloodstream and then burrows into the endocardium.  Treatment  Acute treatment includes Nifurtimox.

 There is no known effective treatment for chronic Chagas disease. Babesia (The Vampire Babes)  Babesia is a parasitic protozoan that causes Babesiosis.  For 25-50% of patients, infection with Babesia is subclinical or mild. Severe cases can cause malaria-like symptoms and death. Infection can present in several different ways, but mainly involves the blood and causes blood-related symptoms (hemolytic anemia, hemoglobinuria, and resulting jaundice).  Babesia is carried by the Ixodes tick (deer tick) and is spread to humans and farm animals through the tick’s saliva (longer attachment of the tick  increased likelihood of transmission of Babesia).  Ixodes tick is the vector for other parasites, such a Borrelia burgdoferi (Lyme disease). Coinfection is common.  Babesia is most common in the Northeastern US. In these areas, Borrelia is more commonly transmitted than Babesia.  Hemolytic anemia with RBC lysis can result in jaundice.  Babesiosis also causes fever with irregular fever cycles.  There is a higher risk of severe disease in patients with sickle cell disease. Asplenic patients are more likely to be symptomatic with Babesiosis and have higher risk of severe disease. Patients with SCD have asplenia due to autosplenectomy.  Diagnosis of Babesiosis is made using a blood smear. Infected RBCs have a Maltese cross appearance. The cross is formed by a tetrad of trophozoites. The Maltese cross is useful in the diagnosis of Babesiosis and in differentiating Babesia infection from Malaria.  Treatment includes Atovaquone and Azithromycin.  Many healthy people with Babesiosis are scarcely symptomatic and can spontaneously recover. Plasmodium species (The Queens and Warlords of Plasmodium)  Plasmodium malariae, Plasmodium vivax, Plasmodium ovale, and Plasmodium falciparum  Plasmodium causes the mosquito-born (female Anopheles) illness malaria (characterized by fever, headache, anemia, and splenomegaly).  Malaria is diagnosed using a blood smear with a Giemsa stain to visualize parasites within RBCs using light microscopy.  There are four Plasmodium species that cause malaria. Each species has a unique fever pattern.

 Plasmodium malariae  quartan fever cycle (fever occurs on day 1 and occurs again 72 hours later on day 4).  Plasmodium vivax & Plasmodium ovale  these two species are similar. They produce dormant forms in the liver called hypnozoites (dormant hypnozoites hide in hepatocytes). These species follow a tertian fever cycle (fever occurs on day 1 and occurs again 48 hours later on day 3).  Plasmodium falciparum  species that causes the most severe malarial illness. Irregular fever patterns. Patients may present with neurological symptoms as parasitized RBCs occlude the capillaries in the brain (cerebral malaria). Parasitized RBCs can also occlude vessels to the kidneys and lungs. P. falciparum appears banana shaped in a peripheral blood smear.  Antimalarial drugs end in –quine.  Chloroquine blocks plasmodium heme polymerase. It is not effective against vivax and ovale due to the dormant hypnozoites in the liver.  Chloroquine-sensitive species are rare due to anti-malarial resistance. Chloroquine-sensitive areas include the Caribbean, Central America (west of Panama Canal), and some countries in the Middle East.  Primaquine can destroy hypnozoites hiding in the liver.  Must check for G6PD deficiency before administering this drug due to the risk of severe hemolytic anemia.  Mefloquine is a stronger antimalarial drug that is used to treat Chloroquine-resistant Plasmodium. It can also be used as a prophylactic drug to prevent Malaria in travelers to the Chloroquine-resistant countries.  Atovaquone and Proguanil can be used to for prophylaxis in travelers to Chloroquine-resistant countries. It can also be used to treat malaria.  Artemisins (Artesunate and Artemether) should be used to treat severe infections with Plasmodium falciparum. These infections can also be treated with Atovaquone-Proguanil.  Use IV Artesunate for severe infections.  Use IV Quinidine for resistant species and severe infections. Cinchonism (headaches and tinnitus) are side effects.  Sickle cell disease is protective against P. falciparum malaria.  Malaria is transmitted via the Anopheles mosquito, which carries the sporozoites in their saliva. Mosquito will bite a human host and sporozoites travel to the liver, where they mature into trophozoites. This is followed by schizonts, leading to the rupture of the hepatocyte and the release of merozoites, which infect RBCs. Once inside the RBC, the life cycle continues again to a trophozoite

form, followed by a schizont. Schizonts rupture the RBCs, which release merozoites that will infect additional RBCs. After the merozoite infects the RBC, it can also form gametocytes (sexual form of Plasmodium). The cycle is continued when a mosquito bites an infected person and takes up RBCs containing gametocytes.  Immature schizont has a ring form in the RBC. Leishmaniasis (Desert Mainia)  Leishmania donovani and Leishmania baziliensis   Leishmania baziliensis  Leishmania baziliensis causes cutaneous or mucocutaneous Leishmaniasis.  Host for the parasite is vertebrates, especially humans. Sandfly is the vector.  In cutaneous Leishmaniasis, the parasite consumes the flesh of its victims, causing disfiguring ulcers.  The Sandfly is the vector and it carries the promastigote (infectious form of parasite). In the host, the parasite becomes the amastigote form, which is the intracellular form (typically within macrophages).  Diagnosis requires aspirates from marrow, spleen, lymph nodes, or skin lesions. Aspirates are spread on a slide and visualized using light microscopy. Amastigotes are seen within macrophages (multiple amastigotes per macrophage).   Leishmania donovani  Leishmania donovani causes visceral Leishmaniasis.  Donovani strain exists mainly in the Mediterranean, Middle East, and Africa.  Black hyperpigmented spots on the skin represent one sign of visceral Leishmaniasis. This is also known as Black fever or kala-azar.  Infection of the bone marrow can cause pancytopenia.  Visceral Leishmaniasis can affects almost every organ, but it most commonly affects the liver, spleen, and bone marrow. This is characterized by a pattern of symptoms including hepatosplenomegaly, pancytopenia, and fever.  Treatment  Stibugluconate is used for treatment of cutaneous Leishmaniasis.  Amphotericin B is used for treatment of visceral Leishmaniasis. Chapter 4: Protozoa of Other Tissue

Trichomonas vaginalis (Tricks for Money)  Trichomonas vaginalis causes vaginitis and cervicitis.  Cervicitis can cause severe inflammation and a speculum will reveal a red cervix (d/t capillary dilation) and areas of punctate hemorrhage. Therefore, the cervicitis is referred to as a “strawberry” cervix.  Vaginitis causes burning, itching, and a malodorous yellowgreen vaginal discharge.  Trichomonas can be diagnosed readily with a wet mount. Wet mount will show motile trophozoites.  Gardnerella  clue cells on wet mount.  Candida  pseudohyphae with budding yeast on wet mount.  Trichomonas generally remains in vaginal fluid with a pH greater than 4.5 (similar to Gardnerella). Candida causes infection at normal vaginal pH (4.5 or less).  Trichomonas is considered a sexually transmitted infection and both partners should be treated. Men typically do not show symptoms.  Treatment incudes Metronidazole. Must treat both partners. Chapter 5: Helminths – Nematodes Intestinal Nematodes (Super Worms!)  Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Ascaris lumbricoides, Strongyloides stercoralis, and Trichinella spiralis.   Enterobius vermicularis (pinworm)  In Enterobius infection, the female worms migrate to the anus at nighttime to lay their eggs.  Pinworms are transmitted via the fecal-oral route. Typically, the worms are very itchy (infected individuals will scratch anus and eventually put fingers in mouth). This process results in repeated infections. Disease typically affects children.  Diagnose Pinworm infection by placing a piece of Scotch tape over the anus in the morning. The eggs deposited at the anus over the night will stick to the tape under the microscope.  Treatment includes Pyrantel pamoate (PAM) or Albendazole (all intestinal nematodes can be treated with bendazoles).   Ancylostoma duodenale and Necator Americanus  Two types of hookworm found in the rural southern US.  Host infection occurs when the larvae penetrate the soles of the feet (walking barefoot). Once the larvae enter the

bloodstream, they travel to the lungs where they ascend the bronchial tree. Eventually they are coughed up and swallowed. The larvae mature into adults in the small intestine.  Hookworms attach to gut wall and feed from capillaries of the intestinal villi. Patients can develop severe iron deficiency anemia (microcytic and hypochromic).  Diagnosis is made by the presence of eggs in stool. There will also be a high eosinophil count (WBCs with pink granules and bilobed nucleus).  Treatment includes Pyrantel pamoate (PAM) or Albendazole.  Prevention includes wearing shoes.   Ascaris lumbricoides (giant roundworm)  Transmitted by eating eggs in contaminated food or water. Once the eggs hatch in the small intestine, the larva migrates through the gut wall into the bloodstream and eventually travels to the lungs. Once in the lungs, the larva travel through the capillaries into the alveoli before ascending into the bronchus, where they are eventually swallowed. The larvae mature into adults in the small intestine. Adults multiply and eggs are passed into the feces, which restarts the cycle of infection.  Life cycle can cause large build up of worms.  Some people are asymptomatic. Others show signs of malnutrition or respiratory symptoms (as more worms travel into bronchus).  Of the worms that travel into the lungs, Ascaris lumbricoides is the most likely to cause respiratory symptoms.  Major complication of infection is intestinal obstruction (most often occurs at the ileocecal valve).  Diagnosis is made by the presence of eggs in the feces. Patients also have high eosinophil counts.  Treatment  Albendazole (causes microtubule dysfunction which immobilizes the worms. Immobilization of large numbers of worms can induce obstruction). Cannot be used in pregnant women.  Pregnant women should be treated with Pyrantel pamoate.   Strongyloides stercoralis  Larvae penetrate the skin of the soles of the feet. Once in the blood stream, it travels to the lungs where it climbs the bronchial tree and is swallowed. The larvae mature in the GI tract.  Strongyloides can further propagate by auto-infecting its host. It lays its eggs into the intestinal wall. The larvae hatch, repenetrate the intestinal wall and enter the blood stream to travel to the lungs.

 In immunocompromised patients, the inflammation from continual wall penetration can lead to hyper-infection and dissemination of the worms.  Eggs are laid into the intestinal wall and are NOT passed into the stool. Only larvae that have hatched from the eggs are found in the stool. Larvae in the stool and eosinophilia can be used for diagnosis.  Treatment includes Albendazole and Ivermectin   Trichinella spiralis  Intestinal nematode found in undercooked meat, such as pork or bear.  Infection with Trichinella causes a wide range of symptoms, including fever, vomiting, and periorbital edema.  Trichinosis also causes severe myalgias (muscle aches).  After ingestion of the cysts, the cysts develop into larvae that enter the bloodstream and form cysts within the striated muscle cells. Cysts will damage muscles and cause inflammation, which leads to myalgias.  Eosinophilia is also seen.  Treatment includes Albendazole. Tissue Nematodes (Screamatodes III: Return of the Flesh Eaters)  Dracunculus medinensis, Onchocerca volvulus, Wuchereria bancrofti, Toxocara canis, and Loa loa   Dracunculus medinensis  Infection occurs by drinking contaminated water, which contains copepods (crustaceans in the sea and freshwater) containing larvae. Copepods are intermediate hosts because they contain the parasitic larvae that penetrate the stomach and intestinal wall after the copepods die. The larvae mature in the abdominal cavity and females migrate to surface of the skin (usually on lower extremities) and produce a painful skin ulcer.  Adult females will emerge from the skin ulcer.  Treat the disease by extracting the worm with a small stick (match stick) by coaxing the worm out and slowly twisting the stick (over a period of days). Process can be sped up by treating with Metronidazole.  Dracunculus can cause peripheral eosinophilia.   Onchocerca volvulus  Black flies are often found around rivers in Africa, Central America, and South America.

 Black fly bites human host and deposits larvae in the skin. The larvae penetrate into the skin and mature into adults. The adults produce microfilariae, which migrate throughout the body.  Physical signs of infection include scatter pruritic papules, which can later become hyperpigmented. Hypo-pigmented spots can also occur (usually on the skin of older patients.  Hyper- and hypo-pigmented spots with onchodermatitis.  Microfilariae can also float into the eyeball and cause blindness  disease is also called River Blindness.  #2 most common cause of infectious blindness (#1 cause is Trichoma [chlamydia]).  Onchocerca can also cause eosinophilia.  Diagnosis is made by visualizing microfilariae from a skin biopsy using light microscopy.  Treatment includes Ivermectin.   Wuchereria bancrofti  Wuchereria bancrofti is a parasite that causes elephantiasis.  Elephantiasis is a complication of long standing lower extremity lymphedema, which makes the legs and other body parts look like those of an elephant. The parasite enters the lymphatics and causes inflammation and disruption of the lymphatic system.  The parasite causes lymphadenopathy.  Wuchereria bancrofti infection leads to microfilariae that travel to the lungs, which causes a hypersensitivity reaction, which leads to coughing.  Wuchereria bancrofti is transmitted by mosquitoes (intermediate host). Mosquito bites deposit larvae on the skin. The larvae will penetrate the skin and enter the lymphatics, where they produce microfilariae.  Diagnosis is made using a thick blood smear to see the organisms.  Wuchereria bancrofti also causes eosinophilia.  Treatment includes Diethylcarbamazine (DEC).   Toxocara canis  Transmitted by ingestion of contaminated food with dog, cat, or wolf feces.  When the parasitic larvae of Toxocara enter the body, they never mature out of the larva stage and will continue to circulate in the body for years (disease is also called Visceral Larva Migrans).  If the larva reaches the eye, the disease is called Ocular Larva Migrans (can cause blindness).

 Toxocara can also cause eosinophilia.  Treatment includes Albendazole.   Loa loa  Loa loa worm migrates through the subcutaneous tissue of host and causes transient angioedema.  Localized subcutaneous swellings are referred to as Calabar swellings.  Adult worm can migrate to the eye and can be seen crawling beneath the conjunctiva, causing transient inflammation and edema. The worm can be seen crawling across the eye and the disease is also known as African Eyeworm.  Diagnosis can also be made using a blood smear.  Loa loa is transmitted by Deer flies.  Loa loa also causes eosinophilia.  Treatment includes Diethylcarbamazine (DEC) and Albendazole. Chapter 6: Helminths – Trematodes & Cestodes Cestodes (Cestode County Carnival)  Taenia solium, Taenia saginata, Diphyllobothrium latum, and Echinococcus granulosus  Cestode = tapeworm   Taenia genus (Taenia solium and Taenia saginata)  Transmission occurs via consumption of cysts or larvae in undercooked meat, which leads to Taeniasis.  Intermediate host for T. saginata is cattle. T. saginata lacks hooks.  Intermediate host for T. solium is pigs. Hooks of proglottid heads of T. solium can be seen on stool O&P.  Taeniasis is usually asymptomatic, but may cause GI problems or malabsorption.   Neurocysticercosis  Occurs after ingestion of Taenia eggs that are floating around in water contaminated by animal feces.  Eating the eggs causes the parasite to go to the brain, where it forms cystic brain lesions. Brain lesions have the potential to cause seizures or hydrocephalus.  Neurocysticercosis has a “Swiss cheese” appearance on head CT.  Suspect Neurocysticercosis if the patient is an immigrant or farmer and has symptoms of seizures or hydrocephalus.

 Treatment includes Praziquantel. Persons with Neurocysticercosis require additional treatment with Albendazole.   Diphyllobothrium latum (fish tapeworm)  Transmitted by eating uncooked or undercooked fish.  Fish tapeworm resides in the small intestine and causes diarrhea.  It is also associated with B12 deficiency, which leads to megaloblastic anemia.  Fish tapeworm is the largest tapeworm and it can grow up to 10 meters long.  Diagnosis is made by visualization of proglottid segments (break off) on stool O&P.  Treatment includes Praziquantel or Niclosamide.   Echinococcus granulosus (sheep tapeworm)  Dogs are the definitive hosts. Sheep are intermediate hosts.  Humans are incidental hosts that accidentally ingest the eggs from dog feces that contaminates food or water.  Sheep tapeworm causes Hydatid cysts (liver abnormality), which appear similar to slow growing tumors on imaging. Egg shell calcifications are seen within a cyst-like mass in the liver on CT.  Rupture of Hydatid cysts can cause anaphylactic shock or acute abdomen. Surgeons inject the cysts with ethanol or hypertonic saline to kill the cells before attempting to remove the cysts.  Rupture of cysts in the lungs can result in hooks in the sputum.  Echinococcus infection also causes eosinophilia. Trematodes (San Franschisto Ocean Park)  Schistosoma mansoni, Schistosoma japonicum, Schistosoma haematobium, Clonorchis sinensis, and Paragonimus westermani  Trematodes are a group of worms that as a whole are termed the “flukes.”   Schistosoma  Schistosoma causes Schistosomiasis.  Shistosoma have free living cercariae that penetrate the skin (usually in an aquatic environment) and enter the bloodstream.  Swimmers are at risk of infection.  After gaining access to the bloodstream, they are then carried to the liver and mature into adults. Adults will lay eggs in humans. Humans poop and pee while swimming in water

sources. Snails are exposed to the excrement and become intermediate hosts.  Mature adults will migrate from the liver to other parts of the body. Location depends on type of Schistosoma. Schistosoma migrate against the portal flow to reach their venous destination.  All 3 types of Schistosoma cause a swimmer’s itch where the larvae penetrate the skin.   S. mansoni & S. japonicum  Schistosoma mansoni and Schistosoma japonicum like to reside primarily in mesenteric veins.  S. mansoni has eggs with a large lateral spine (spine comes off side of body).  S. japonicum has eggs with small or absent spine.   Eggs can be seen on a stool O&P.  Chronically, S. mansoni & S. japonicum will cause portal hypertension, which can lead to GI hemorrhage, abdominal pain, and eventually cirrhosis and liver failure with jaundice.   S. haematobium  Resides in the veins of the bladder and typically causes bladder-related symptoms.  Shape of haematobium eggs have a large terminal spine (at end of the oval) that can be seen on stool O&P.  Migrate against portal vein flow.  Primarily causes hematuria, but it is also associated with bladder cancer.  To prevent progression to bladder cancer, treatment should be initiated promptly.  Treatment for all 3 types of Schistosoma (and all Trematodes) is Praziquantel.   Clonorchis sinensis (Chines liver fluke).  Snails are an intermediate host. Worms are transmitted from snails to fish. Humans eat uncooked fish and cyst/larvae will mature inside humans before residing in the biliary system.  Eventually causes biliary tract fibrosis, pigmented gallstones (black), and even progress to cholangiocarcinoma.  The egg of the Clonorchis trematode has a distinct appearance. Operculated eggs (have Yamaka hat) are seen on stool O&P.  Treatment includes Praziquantel.   Paragonimus westermani (lung fluke)  Lung fluke that can cause chronic cough with bloody sputum.  Snail is the intermediate host. Fluke is transmitted via the consumption of raw or undercooked crab meat that carry the

encysted larvae. After ingestion, the larvae mature into adults and travel to the lung.  Diagnosis of Paragonimus is made by observing operculated eggs on stool O&P.  Treatment includes Praziquantel.