sketchy micro compilation Annya Suman
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Staph Aureus – “Golden Staff of Moses”
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Bundle of grapes. Grown on blood agar – yellow appearance. Gram positive (take up crystal violet stain in their thick cell walls). Catalase positive. Coagulase positive (converts fibrinogen to fibrin). Beta hemolytic. Plate on mannitol salt agar – can ferment and turn agar yellow. Protein A – main virulence factor, component of cell wall and binds Fc portion of Ig and prevents opsonization. Colonizes anterior nares.
1. Causes pneumonia – patchy infiltrates on xray, icosahedron shaped lamps (capsules) post-viral bacterial pneumonia. 2. Most common cause of septic arthritis, cellulitis, impetigo, carbuncles, pharuncles, abscesses. 3. Rapid onset of acute bacterial endocarditis in IV drug users – right sided heart valves (tricuspid valve). 4. Most common cause of osteomyelitis. Toxin mediated diseases • Scalded Skin Syndrome – exfoliatin toxin – a protease • Toxic Shock Syndrome – superantigen toxic shock syndrome toxin (TSST)– non specific binding (MHC II and TCR), cytokine storm – TAMPON. • Staph food poisoning – rapid onset, preformed toxin. More associated with vomitting than diarrhea – found in meats and custards and mayonnaise. MRSA - resistance by altering PBP – use vancomycin. If methicillin sensitive than use appropriate penicllin – nafcillin.
Staph Epidermidis & Saprophyticus “Beauty and the Plumber”
Epidermidis • infects artificial joints and catheters. • MCC of endocarditis affecting artificially implanted heart valves. Makes copious amounts of biofilms (a mess of polysaccharides, helps it stick to surfaces and acts as coating that protects it from antibiotics and immune cells) therefore resistant to many antibiotics. • Treat with vancomycin van. Contaminates blood cultures. NOVOBIOCIN SENSITIVE. Saprophyticus • NOVOBIOCIN RESISTANT. Common cause of UTIs in sexually active females. BOTH ARE CATALASE POSITIVE Gram Positive BOTH ARE UREASE POSITIVE COAGULASE NEGATIVE
Strep Pyogenes – Group A Strep “The Pie Genies’ Bakery”
Strep: Grow on a single axis and form long chains/pairs - GRAM POSITIVE, BACITRACIN SENSITIVE Strep Pyogenes • Encapsulated – Hyaluronic acid capsule therefore not immunogenic. Beta hemolytic. • Clinical Features 1. Impetigo – honey crusted (also in staph aureus) 2. Pharyngitis – strep throat 3. Cellulitis & eriseplas pyogenic infections.
*Eriseplas (very superficial cellulitis infection – erythema of the skin - with well demarcated borders)
Streptococcal pyrogenic exotoxin (Spe) 1. Scarlet fever (strawberry tongue, pharyngitis, diffuse rash that spares the face) – SpeA, C 2. Toxic shock like syndrome (TSLS) mediated by a superantigen – SpeA, C 3. Necrotizing fasciitis – protease – Spe B
Secondary Infections: 1. Rheumatic Fever (AFTER PHARYNGITIS) -
M protein antiphagocytic by interfering with opsonization, very antigenic & elicits strong humoral response, molecular mimicry (attacks myosin) mitral heart valves JONES – joints (polyarthritis), valvular damage pericarditis, subcutaneous nodules (extensor surfaces of arms, elbows, knees), erythema marginatum, Syndenham’s chorea
2. Glomerulonephritis (AFTER PHARYNGITIS OR IMPETIGO) -
Type III hypersensitivity reaction, antigen antibody complexes, facial edema Colacolored urine, facial puffiness/facial edema 2 weeks from onset of strep infection Penicillin
Rx – early Rx of strep throat can prevent rheumatic fever but will not stop glomerulonephritis. VIRULENCE FACTORS 1. Streptolysin O lyse RBCs and be B hemolytic (ASO Ab (tongs) – titers are good for Dx RF/Glomerulonephritis) 2. Streptokinase (phosphate cupcakes) converts plasminogen to plasmin which lyses clots 3. Dnase depolymerize DNA
Strep Agalactiae – Group B “Galactic Baby”
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Serious infections in new borns Hippurate positive hydrolyzes sodium hippurate Polysaccharide capsule CAMP test positive (DISTINGUISHING) increasing zone of hemolysis with staph aureus. B hemolytic. Bacitracin resistant Meningitis in neonates - #1 cause Causes neonatal sepsis Causes pneumonia. CAMP test “arrowhead” zone of hemolysis Passes through vaginal canal of mother 35 weeks get vagina swabbed. Give mom intrapartum penicillin if colonized
Strep Pneumoniae & Viridans “The Alpha Knight Tournament”
Both species are alpha hemolytic. hue.
partial hemolysis in which surrounding zone of hemolysis has a green
Strep Pneumoniae • Polysaccharide capsule – major virulence • Optochin sensitive • Lancet-shaped diplococci • Bile soluble • #1 reason for community acquired pneumonia lobar pneumonia with “rust-colored” sputum • MOPS – meningitis, otitis media, pneumonia, sinusitis – MOST COMMON CAUSE OF ALL THESE THINGS • IgA protease reduces host defenses • Sickle cell disease (Asplenia) particularly susceptible • Macrolide or 3rd generation cephalosporin like ceftriaxone • PREVENTION: Adult vaccine 23 valent polysaccharide (T cell independent response - IgM response), Children vaccine is 7 valent polysaccharide with a conjugated protein(IgG response) Strep Viridans • No capsule • Optochin resistant • Bile resistant • Strep mutans & strep sanguinis causes dental caries foul teeth on donkey • If strep sanguinis gets in the blood subacute endocarditis in damaged valves (mitral valves) • Adheres to platelets (plate armor), dextrans that sticks to platelets (deck of cards)
Enterococcus “Protest at the Caucus”
• Entero – intestinal tract, coccus • Gram +ve cocci Faecalis – cali(fornia) more common Faecium – stop the fees! (super bug, more dangerous). • Both grow in mediums of 6.5% NaCl. • Resisting being hit by the billy club BILE RESISTANT boots. 3 main infections (DO U <3 trees?) 1. UTI’s 2. Endocarditis 3. Biliary tree infections
bile resistant
E. faecium is a nosocomial infection resistant to every drug including vancomycin. Vancomycin Resistant Enterococcus (VRE) Instead treat with LINEzolid/tigecycline
B. Anthracis & B. cereus “King Anthra’s Axe”
B. Anthrax: can be stained in blood - boxcar shaped gram +ve • Dead black charred center of circle with surrounding red hot flames black eschar (a.k.a. black necrotic cutaneous lesion with a surrounding erythematous ring) • Large gram +ve rods in chains. • {{Malachite green stain for spores because they cant take up regular stain. On culture medium they form ground glass colonies. Spores not formed in humans – only bacteria. In clinical specimen you will not find spore. }} • Armor – encapsulated (unique – made up of protein (poly D glutamate) all the other ones are made of polysaccharides.) • Obligate aerobe • Forms spores (walnuts)– hibernates without any metabolic activity and highly resistant to temperature and chemicals and can survive in any environment for a long time. Bacillus and clostridius species are the only spore species. TOXINS 1. Lethal factor (lf) (most important virulence factor)**** - Exotoxin acts as a protease and cleaves MAP kinase (signal transduction protein that controls cell growth). LF involved in tissue necrosis. Black escar.
2. Edema factor (ef) -
Adenylate cyclase & ↑ cAMP intracellularly ↑ causes fluid to go into extracellular space and causes edema. Inhibits host defenses and inhibits phagocytosis.
3. Protective antigen (Pag gene) -
bind to the cell surface & forms the channel to allow entry of 2 other toxins.
Pulmonary Anthrax - sheep’s wool. Wool sorter’s disease. Starts off with non specific pulmonary symptoms like a dry cough. Important to catch so that it doesn’t go to mediastinal lymph nodes and lead to hemorrhagic mediastinitis. Pulmonary hemorrhage. 100% mortality rate when developed. Widened mediastinum on x-ray. DOC: Fluoroquinolones and secondary is doxycycline or ciprofloxacin. Acellular vaccine adsorbed (AVA) – preparation of protective antigen (PA) B. Cereus
Clostridium tetani “Rhesus Research Revolution”
Gram +ve Obligate anaerobe Spore forming Transmission: Spores found in soil and rusty nails C/F: - spastic paralysis leading to rigidity - Rhesus sardonicus – evil smile – locked jaw symptoms - Opisthotonus – exaagerated arched back Toxin mediated disease 1.Tetanus toxin travels retrograde from motor neurons to periphery. 2.Tetanus toxin acts as a protease cleaving SNARE protein. 3.Cleavage of SNARE inhibits release of GABA and Glycine. 4.GABA and Glycine release from Renshaw cells is inhibited Tetanus vaccine – toxoid vaccine (toxin conjugated to the protein)
Clostridium botulinum “Robotulism”
Gram +ve, transmitted by improper canning of food (travel of spores), spore forming, Obligate anaerobe Flaccid paralysis – descending paralysis. Early symptoms include ptosis and diplopia. Preformed toxin absorbed into gut travels to PNS via blood. ONLY affects PNS. Cannot cross BBB. Toxin targets nerves that release acetylcholine. Ach neurons are excitatory. Toxin is a protease that cleaves SNARE proteins. (prevents fusion of vesicles to presynaptic nerve terminals) In adults normal flora outcompetes spores and kills them – not in babies. “Floppy baby syndrome” –infantile botulism transmitted through ingestion of honey. Spores found in honey. ADULTS BABIES
preformed toxin causes botulism Spores in honey cause botulism
C. Difficile “Field Trip to the Chocolate Factory”
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Spore formers (walnut symbol) Nosocomial diarrhea (spores easily transferred from patient to patient) Antibiotics wipe out normal flora which cannot fight C. difficile anymore Clindamycin is conducive to C. diff infection (causing it + improper hand washing leads to transmission) Exotoxin A (apples) - Targets brush border enzymes of intestine and causes inflammation, cell death and watery diarrhea Exotoxin B (black liquorice) - Disrupts cytoskeleton integrity by depolymerizing actin which leads to enterocyte death and necrosis. It also leads to a yellowish gray exudate which forms a pseudomembrane that covers the colonic mucosa pseudomembranous colitis Diagnosis: Assay to detect toxin in stool Gas masks: obligate anaerobe (all clostridium species) Treatment: 1. Oral vancomycin delivery to lumen 2. Metronidazole
Clostridium Perfringens “Private Ringen’s Motorcycle Accident”
• Infection associated with motorcycle accidents & deep penetrating wounds from military combat. • A lot of flesh exposed to dirt and soil spore forming. Spores found in soil. • Obligate anaerobe. 2 diseases: 1. Soft tissue infection – In the disease process gas is produced under the infected tissue crepitus or crackling sound on palpation. Clostridal myonecrosis: gas gangrene – ALPHA TOXIN: myonecrosis involves alpha toxin, or lecithinase (cleaves lecithin which is a phospholipase and causes damage to cell membrane by damaging the lipoproteins)– can cause red cell hemolysis. Double zone of hemolysis. Treatment of choice is IV penicillin G 2. Late, slow onset watery diarrhea – caused by spore ingestion; spores have to germinate in gut. Transient and doesn’t require antibiotic treatment
Cornyebacterium diphtheriae “Corazon de la Corrida”
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Gram +ve Club shaped, metachromatic granules, V or Y formation (zigzag lines).
Exotoxin AB subunit A subunit – active subunit B subunit – binding subunit • • •
ADP ribosylation of EF2 to inhibit protein synthesis. Leads to formation of pseudomembranes (cell death - gray cotton candy (similar to C.diff). “Bull’s neck” – due to lymphadenopathy transmitted by respiratory droplets, therefore colonizes the oropharynx and spread to larynx and trachea and cause airway obstruction. If it gets into blood stream: – Cardiotoxic effects -
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Myocarditis//Arrhythmia//Heart block
Local paralysis that generally begin in post. oropharynx (myelinated axon deficit) & lead to other CN deficits
Plated on tellurite medium and Loeffler’s medium. To differentiate between toxic and non-toxic diphtheriae: Elek’s test – in vitro assay on filter paper that has antitoxin on it. If toxin binds to it there is a reaction. Patients are often immigrants therefore may not be vaccinated. Toxoid vaccine (inactivated exotoxin bound to protein and often given with tetanus and acellular pertussis vaccine)– powerful IgG response
Listeria monocytogenes “Santa’s List”
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Gram +ve bacillus Most associated in pregnant women. B hemolytic – narrow zone of hemolysis when plated. Motile. Facultative intracellular. Actin rockets intracellularly. Rapidly polymerizes actin against the bacterial wall so it is propelled along in the opposide direction and jump cell to cell. When outside cell uses flagella. Tumbling motility extracellularly. Catalase positive. Survives and multiplies in near freezing temperatures. Contaminates unpasteurized milk and soft cheeses. Common in pregnancy – may lead to early termination or disease in newborn. Third most common cause of meningitis after Group B Strep and E.Coli. Causes meningitis in adults over 60. Standard empirical treatment is vancomycin, ceftraxine for gram positives but in elderly you give ampicillin to cover listeria. Therefore treatment for Listeria is ampicillin
Actinomyces “Israeli Soldier”
• Gram +ve, filamentous, branching rods. • Obligate anaerobe. • Normal flora in oral cavity. Recent dental work in question system. Infection associated with jaw trauma. Cervicofacial actinomyces has a fairly slow course and begins with a non tender lump on the jaw, this will eventually form an abscess formation of sinus tracts which drain the pus that contains characteristic yellow sulfur granules. • Treat with Penicillin G. • White molar tooth colonies
Nocardia “No Card Game for Old Men”
• Gram +ve, filamentous branching rod. • Obligate aerobe (air bellow), found in soil. Does not form spores. • Weakly stains acid fast because of mycolic acids carbol fuscin stain • Catalase positive. Patients with CGD have increased risk of infection with catalase positive organisms. Urease positive. • Primarily infects immunocompromised patients (HIV, transplant patients, or glucocorticoid ones). Infection more in men. 1.Pulmonary - Pneumonia like symptoms with lung abscess formation - Associated with cavitary lesions in lungs - Can disseminate from lungs to brain 2. CNS - Brain abscess formation 3. Cutaneous- pyogenic response with indurated lesions and inflammatory reaction Sulfonamides are the treatment.
Neisseria species overview “MAC the private eye”
Gram –ve diplococci, oxidase positive, chocolate agar, VPN agar (Thayer Martin agar) (enriched with vancomycin, polymyxin and nystatin). Also w/ trimethoprim + colistin “MAC” C5-C9 complement deficiency, unable to form MAC complex, leading to increased infections. MAJOR VIRULENCE FACTORS: 1. Pili – frequent genetic rearrangement, display antigenic variation, prevents lasting immune response. 2. IgA protease – cleaves IgA at hinge region
Neisseria meningitidis “A shocking death on campus”
College kid presenting with meningitidis. Ferments MALTOSE and GLUCOSE. Colonizes nasopharynx first (q-tip). Transmitted by respiratory secretions/droplets. Polysaccharide capsule – important virulence factor as it inhibits phagocytosis. Vaccine contains polysaccharide capsule. Type B capsule not included in vaccine. Most infections are caused by type B strain. Sickle cell and asplenic patients at higher risk of infection. LOS envelope proteins cause inflammatory response. Neisseria produces so much of it that it starts blebbing off. Inflammation leads to leaky capillaries leads to hypovolemia peripheral vasoconstriction goes to a maximum in order to maintain pressure leading to adrenal insufficiency (waterhouse-friderichsen syndrome, characterized by hemorrhage of adrenals) Petechial rash thrombocytopenia Capillary leakage can lead to shock. Rx: third generation cephalosporin ceftriaxone Give close contacts a prophylaxis rifampin
Neisseria gonorrhoea “The Violinist’s Last Clap”
STI Gram –ve diplococci, facultative intracellular in PMNs (invades PMNs). NOT ENCAPSULATED. For male: - Urethritis prostitis, orchitis For women: - PID can lead to infertility or ectopic pregnancies - Characteristic white purulent discharge (can occur in both men and women) thicker than chlamydia. - Can spread into the peritoneum – fitz hugh kurtis syndrome. Can lead to adhesions to capsule of liver and these thin long adhesions are referred to as violin string adhesions. - Can cause polyarthiritis and affects the knee asymmetrically. - Doesn’t gram strain because infection is intracellular.
Congenital infection untreated gonococcal infection in mother can be paused onto baby and can present as purulent conjunctivitis that can occur in first 5 days of life. Early onset Chlamydia also causes neonatal conjunctivitis is usually delayed ( a week after birth ) Rx: ceftriaxone + chlamydia treatment for co-infection (macrolide or doxycycline)
Enterobacter, Serratia & Klebsiella “Enterodactyl, Triserratiatops and the Kleb-Tailed Dinosaur”
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Nosocomial infections. Pneumonia + UTI most common clinical infection by these bacterias. Multi-drug resistance. Carbapenem to treat these. All ferment lactose. (+ E.coli) Pink on MacConkey agar
Enterobacter Motile Serratia Motile Produces red pigment when cultured Klebsiella Alcoholics, Abcesses, Aspiration Polysaccharide capsule Currant jelly sputum Immotile In chest x-ray may look like TB but infact its Klebsiella Urease positive
Salmonella “The Salmon Dinner”
Salmonella is motile. H2S positive (all enterobacter bacteria that are motile are also H2S positive) – grows black colonies on Hektoen Agar. Capsule. Acid labile – means they get easily degraded in the stomach and therefore you need a high dose to cause an infection. Omepraxozole or any other substance that raises stomach pH will make you more susceptible to salmonella. Facultative intracellular in macrophages. Salmonella typhi Salmonella typhi in the gall bladder of chronic carriers Typhoid Mary Rose-colored macules that patients with enteric fever get on their abdomen #1 cause of osteomyelitis in patients with sickle cell disease Associated with constipation but can cause diarrhea and when it does it resembles “pea soup” diarrhea. Treated with a fluoroquinolone (i.e. Cipro) Live attenuated vaccine Salmonella enteritidis By eating chicken Causes inflammatory diarrhea Virulence factor: (same for shigella and yersinia pesistis) type 3 secretion system – protein that detects eukaryotic cells and secretes a protein that helps with infectivity
Shigella “She-Gorilla’s Circus”
Gram –ve enteric that causes gastroenteritis that specifically leads to bloody diarrhea.
Shigella sonnei – more common in US Green colonies on hektoin agar (differentiate from salmonella, makes black colonies) Immotile Acid stable (few organisms needed for infection) From intestinal lumen to intestinal mucosa: specifically in Peyer’s patches (M cells). Shigella induces M cells to phagocytose them and then escape from the phagolysosome before they’re degraded. Once in cytoplasm use host cells actin cytoskeleton to create a tail it uses to propel itself from one cell to another. (similar to actin rockets in listeria) Facultative intracellular Bloody diarrhea due to inflammatory response Shigella dysenteriae In kids, hemolytic uric syndrom (HUS) pts under 10 years of age, present with signs of acute renal failure a week later Once shigella invades it produces a shiga toxin, which induces endothelial damage in glomerulus of kidney through the blood and activates platelet aggregation leading to drop in platelet count. Red blood hemolysis (schistocytes) Binds to 60s subunit of ribosomes and inhibits translation Type 3 secretion system to release inflammatory cytokines (same as salmonella)
E.Coli “E.cola’s Soda Fountain”
Ferment lactose (milk) pink on MacConkey agar. Encapsulated (glass capsule) (cake)K antigen (for serotyping) Grows on EMB agar metallic green sheen Catalase positive (cat) Frimbriae important because cause UTIs. #1 cause (ribbons in hair) Leading cause of gram –ve sepsis (LPS endotoxin – virulence factor for all gram negatives) Neonatal meningitis only if it has the K antigen. EHEC By eating undercooked hamburgers (meat) Bloody diarrhea (blood ketchup/stool) Only one that doesn’t ferment sorbitol (sorbitol free) Inhibits ribosomes at 60s subunit (shiga-like toxin) Can cause HUS: damages endothelial cells of capillaries in glomerulus. Damaged lining becomes thrombogenic platelet aggregation and decrease in platet count and lyse RBCs as they pass through the capillaries O157:H7 serotype is associated with outbreaks ETEC traveler’s diarrhea Transmitted via water Watery diarrhea Recent travel to mexico: Heat labile toxin: increases cAMP (eL Agua): similar to cholera toxin Heat stable toxin: increases cGMP (San Gabriel)
Yersinia “Yersin’s Pets”
Cause of the black plague. Gram –ve organism. Bipolar staining (also in pasteurella), described as looking like a safety pin. Encapsulated. Yersinia enterocolitica - transmitted through puppy feces - Toddlers commonly infected by y.enterocolitica - Can be transmitted through contaminated milk products (like listeria - Resistant to cold temperatures (like listeria) - Causes diarrhea: invasive: blood in stool - Can cause systemic effects: fever, leukocytosis, abscesses - Specifically in abdomen can lead to necrotic small bowel, intestinal perfortion, paralytic ileus - Can mimic appendicitis - Can also be transmitted by other infected toddlers Yersinia pestis - Black plague – bubonic plague - Rodents or prairie dogs are the main reservoir - Transmitted by flea bites - Characteristic buboes form on skin - Once in blood cause abscesses in organs, DIC (by endotoxin) and cutaneous hemorrhage. DIC is caused by endotoxin and can lead to necrosis of digits. - Virulence factors: exotoxins & yersinia associated outer proteins (YAOPs) cause macrophage and neutrophil dysfunction by inhibiting phagocytosis and cytokine production. YAOPs secreted via type III secretion system. - Treatment: aminoglycosides such as streptomycin in combination with tetracycline - Killed vaccine (not routinely used)
Campylobacter jejuni “Camping Guy and the Bears”
• 3 gram –ve rods of enteric tract. • Guillan Barre Syndrome • Thermophilic – fire. Grows at 42 degrees celsius. Intrinsically linked to heat. • Poultry reservoir. Fecal oral route of transmission. • Bloody diarrhea. • Curved gram negative rod (comma shaped) • Oxidase positive. • Bacteremia – invasive • Reactive knee slap – reactive arthiritis (writer’s syndrome) can’t see, can’t pee, can’t climb a tree • Guillan Barré: occurs after being infected by some bacterial or viral infections campy being the most common. • Autoimmune response causes demyelination of peripheral nerves causing ascending paralysis (starts from lower extremities and ascends). Nodes of ranvier. • OPPOSITE OF BOTULISM (DESCENDING PARALYSIS)
Vibrio Cholera “Colonel Cholera’s Base cAMP”
VIBRIO CHOLERA • Curved gram negative rod • Endemic to developing countries. • Colonel – comma shaped • Perfuse watery diarrhea – stool has consistency of rice water. • Transmitted fecal orally via poor sanitation that leads to contamination of food and water sources with human feces. • River – intestinal lumen . River banks – mucosal of intestinal wall. PATHOGENESIS: • Raft – one vibrio bacteria: gram –ve. • Attached to dock by rope – cholera does NOT invade mucosa but uses fimbriae for attachment to attach to ganglioside receptors in the gut wall • Increases cAMP. Constitutively activates Gs pathway secretion of water into lumen watery diarrhea • Rx: oral rehydration therapy with electrolytes. • BASE cAMP – BASIC environment: grows on alkaline media. Has tough time surviving in acidic environment of stomach and is therefore acid labile. • Oxidase positive. Vibrio Parahemolyticus+ other one: Contaminate seafood, especially oysters.
Helicobacter Pylori `The Helicopter Pilot`
• Curved gram –ve rod. Helico – helical shape. Pylori – found in pylorus near antrum of the stomach. • Propellers – motile – flagella whipping around.
• UREASE POSITIVE. ****** Urease splits urea into NH3 & CO2 which helps reduce acidity of stomach & helps H.pylori invade • Urea breath test = swallow urea labeled with radioactive carbon which then splits into CO2 and ammonia. This CO2 with radioactive carbon is exhaled and detected in breath. If you’re INFECTED it will be positive. • Biopsy during endoscopy &then directly check for urease with rapid test • Oxidase positive. • Duodenal ulcers. (bullet holes) Mechanism unknown – but chronic infection increases acid production by reducing somatostatin or increasing gastrin. • If not treated can get gastric adenocarcinoma (crab). Can also get lymphoma of MALT aka maltoma (pile of tissues). If treat H.pylori infection, maltoma will go away. • Treatment: triple therapy proton pump inhibitor (counter acid production), amoxicillin + macrolide (clarithromycin keep clear sign) • Stains with silver stain
Pseudomonas Aeruginosa “The Suitors of Pseudo Mona”
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Gram –ve rod (tub), nosocomial infection Thrives in aquatic environments causes hot tub folliculitis (water in tub) Oxidase positive Catalase positive Puts CGD patients at risk Produces blue-green pigment when plated: pyocyanin, pyoveridin Produces fruity-grape like odor. Obligate aerobe Nosocomial pneumonia (nurse) and respiratory failure in cystic fibrosis patients. Osteomyelitis 1. IV drug users 2. Diabetics Glass capsule ENCAPSULATED Infection associated with burn infections Nosocomial UTIs.
SKIN LESIONS 1. Pruritic papular pustule folliculitis underchlorinated hot tubs 2. Ecthyma gangrenosum – black necrotic lesions on skin
hot tub folliculitis
Otitis EXTERNA Exotoxin A – Toxin inactivates EF-2 by ribosylation (same as diphtheria toxin) protein synthesis & cell death.
inhibition of
Rx: Anti-pseudomonal penicillins: piperacillin + tazobactam Aminoglycosides (combination with B lactams) and fluoroquinolones (especially useful in UTIs)
Proteus mirabilis “The God of the Public Restroom”
• Gram –ve • Demonstrates swarming motility when plated (tentacles) • May form staghorn calculi (helmet) • Urease positive (NH3 spray bottle) • Alkaline environment can cause struvite stone formation (kidney stone formation) cause pain and kidney damage but also act as a nidus for proteus to cause recurrent infections • May cause UTI • Fishy odor • Treat with sulfonamides
Bordetella pertussis “Board and Care”
Highly contagious. Spreads by respiratory droplets. Its able to infect people by attaching to the respiratory epithelium using pili. And once attached rather than invading it releases toxins that cause the systemic effects. This pillus is called: Filamentous Hemagglutinin – fimbrae, pili. Antibodies against it help in protecting against it. Culture: Bordet-Gengou agar (contains potato), Regan-Lowe medium (contains charcoal, blood, and antibiotic) Pertussis toxin Ribosylates Gi thus disabling it (toxin acts by ribosylation and inhibits Gi) + disabling chemoking receptors for lymphocytes, making them unable to enter lymphoid tissue. So they get stuck in the blood stream causing massive lymphocytosis (popcorn kernels) Increase cAMP Adenylate cyclase toxin (acts directly) Acts like the anthracis EF toxin Tracheal toxin (tractor in midline) Part of peptidoglycan wall Damages ciliated cells in respiratory epithelium Clinical findings Catarrhal phase (1/2 weeks): Initially presents with non-specific symptoms, conjunctival infection and lacrimation Paroxysmal phase (2 weeks, 2 months): whooping cough – 100 day cough Convalescent phase (3 months): gradual reduction of symptoms Rx: Macrolides but not good for symptoms so treat early Killed Vaccine – no longer available in US Acellular Vaccine – purified antigens of bacteria (DTaP vaccine)
Haemophilus influenzae “Phyllis’s Chocolate Covered Cherries”
Gram negative bacteria Coccobacillary shape (candy dispenser) • Requires chocolate agar – factor V (nicotinamide) added to chocolate agar; factor x (hematin) added to chocolate agar • Aerosol transmission • Causes 1. pneumonia, 2. cherry red epiglottitis (inflamed epiglottis, inspiratory stridor, drooling), 3. otitis media, 4. meningitis – only in capsular form of bacteria: type B • Increased risk of infection in sickle cell or asplenic patients (b/c spleen is required to remove capsulated organisms) • Vaccine for type B capsule – consists of polysaccharide of haemophilus capsule conjugated to diptheria toxoid increasing immunogenicity of capsular polysaccharide so body can produce a strong IgG response. • Vaccinate children between 2 and 18 months • Use a B-lactam antibiotic: ceftriaxone for meningitis or systemic disease. Rifampin prophylaxis in close contacts.
Legionella “The S.S. Cysteine Joins the Legion”
Gram –ve but needs a silver stain to be visualized. Grown on buffered charcoal yeast extract – growth requires iron & cysteine. 1. Legionnaire’s disease More common in smokers Atypical pneumonia Patchy infiltrate with consolidation of one lobe in x-ray Hyponatremia (if sodium level is less than 130) May present with headache and confusion Diarrhea High fever • Lab test: urine antigen test 2. Pontiac fever Self limited fever and malaise Rx: Macrolides, and fluoroquinolones Oxidase positive
Bartonella henselae “Bart the Leopard”
• Gram –ve. Warthin Starry stain – silver stain. • Cat scratch fever transmitted by cat scratches occurs in immunocompetent patients • Axillary lymphadenitis • Bacillary angiomatosis (only infects immunocompromised patients) also transmitted by cat scratches develop raised red vascular lesions all over their skin [[SIMILAR TO KAPOSI SARCOMA]] • Treatment: – doxycycline treatment for bacillary angiomatosis – macrolides (for both diseases)
Brucella “Bruce Farms”
• Gram negative. • Reservoir: farm animals – cows, pigs, goats. • Cow – brucella abortis • Patient will have direct contact like veterinarian, slaughter house worker, rancher. • OR • Indirect contact like ingestion of unpasteurized dairy products. • Facultative intracellular Organism. Ability to survive in macrophages makes it especially apt to travel to multiple organs throughout the reticulo-endothelial system (can enlarge spleen, liver, lymph node). Can lead to host cell lysis and spread systemically. • • • •
Symptoms: Non-specific – fever, chills, anorexia. UNDULANT FEVER Osteomyelitis in chronic brucella infection Tx: Doxycycline. Rifampin commonly used as adjunctive therapy (for primary treatment)
Francisella tularensis “Francis the Rabbit”
• Rabbits are main reservoir. • Transmitted by dermacentor tick. • Transmission can be aerolized – bioterrorism. • Red for gram negative – radishes are coccobacilli • Facultative intracellular organism. Recovery from infection depends on CMI. • Painful ulcer at site of infection. • Granulomas with caseating necrosis in reticuloendothelial organs (i.e. lymph nodes). • Regional lymphadenopathy. • Rx: streptomycin – an aminoglycoside
Pasteurella multocida “Louis Pasteur’s Lab”
• Transmitted by dog or cat bites. • Soft tissue infection – cellulitis may occur within first 24 hours of infection. Can develop into a necrotizing fasciitis OR travel to bone and cause osteomyelitis. • Catalase positive. • Oxidase positive. • Swan neck flask – capsule is important virulence factor. • Grows well on 5% sheep’s blood agar. • Bipolar staining (like yersinia) – safety pin staining. • Rx: Empiric treatment is penicillin + a B-lactamase inhibitor to help prevent resistance . Good combo = amoxicillin + clavulonic acid
Mycobacterium tuberculosis “Shootout at the TB Corral”
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Acid fast takes up carbol fuscin stain because of high concentration of mycolic acids – take up the dye. Grown on Lowenstein-Jensen medium (slow to grow) Obligate aerobe Human to human through respiratory droplets Resides and proliferates in macrophages. Cord factor. Sulfatides – lysosomes and phagosomes don’t coalesce. (MAJOR VIRULENCE FACTOR)
• Paths of Progression after Primary Infection: 1. Healed latent infection • Ghon Complex = Hilar lymphadenopathy + peripheral granulomatous lesion in middle or lower lung lobe • Necrotic macrophages • Fibrosis • PPD positive – Type IV hypersensitivity reaction, BCG vaccine can cause a false positive PPD 2. Systemic infection (miliary TB) • Bacteremia – multi organ failures: can be lethal 3. Reactivation TB • Neutralized TNFa uncontained infection • Reactivation affects the UPPER lung lobes • Cough, night sweats, hemoptysis • Skeletal disease : Potts disease • CNS involvement: meningitis or tuberculoma Tx: RIPE : rifampin, isoniazid, pyrazinamide, ethambutol Prophylaxis for people with latent TB: rifampin, isoniazid (for 9 months)
Mycobacterium leprae “The Good, the Bad and the Lion Faced”
• • • •
•
Thrives in cool temperatures, explaining predilection for extremities. Mycolic acids – acid fast stain (carbol fuschin stain) Armadillo reservoir – leprosy also known as Hansen’s disease Tuberculoid leprosy Tuberculin response Th1 response with CMI Able to contain bacteria within macrophages Symptoms include well demarcated hairless lesions on skin Positive lepromin skin test demonstrates good cell mediated response (PPD) Tx: Dapsone, Rifampin, clofazimine (2-5 years) Lepromatous leprosy Th2 mediated humoral response Bacteria unable to be contained by macrophages Humoral response Human to human transmission symmetric glove and stocking neuropathy Poorly demarcated raised lesions on extensor surfaces of extremities Facial deformity described as “leonine facies”
Tx: multi drug therapy
Borrelia “The Bows and Arrows of Borrelia”
• • • • •
Spirochetes. Borrelia burgdorferi – lyme disease. Northeastern United States (new hampshire, connecticut) Ixodes Scapularis tick borne disease (tick bite) transmission LIFE CYCLE OF TICK: Larvae feasts on white footed mice (main reservoir), adult form feasts on white tailed deer (obligatory host). Tick is the vector.
• • • • • -
Wright stain and Giemsa stain lime green, stages of lyme disease 3 stages of borrelia with different symtpoms Stage 1 (rash + fever & chills) Erythema chronica migrans (bull’s eye rash – not painful or pruritic) Flu-like symptoms Stage 2 Heart block caused by myocarditis Bilateral facial nerve palsy (Bell’s palsy) Stage 3 Arthiritis of large joints (knee) + other joint and symptoms can move from joint to joint – migratory polyarthritis Encephalopathy, CNS effects – cognitive slowing
-
Rx: ideally start in stage 1 – doxycycline, later presentations
ceftriaxone
Leptospirosis “The Surfer’s Oasis”
Leptospira interrogans • Endemic in tropical regions. Spirochete, question mark shaped. • Commonly found in animals like rodents and dogs and excreted in their urine and transmitted to human when they swim in their water. • Leptospira found in water contaminated with animal urine. • Flu-like symptoms (fever), conjunctival suffusion. In its more severe form it’s called “weil’s disease” • Travels through blood stream and affects many different organs (hematogenous spread) – renal dysfunction and jaundice from liver damage. 1.Kidney: if patient presents with fever and high creatinine levels and azotemia kidney dysfunction 2.Liver dysfunction causes jaundice.
Treponema pallidum “Pallidum Observatory”
• • • • • • •
Transmission: sexually transmitted Spirochete Darkfield microscopy needed for direct visualization VDRL is screening test – non specific RPR also screening tool. Can be many false positives: mono, RF, sle, Lep, drg FTA-ABS is a specific test to confirm positive a screening result.
Primary Painless, genital chancre Secondary Systemic disease Maculopapular rash occurs on palms and soles weeks to months after infection Condyloma latum Spirochetes can be visualized within condyloma latum via darkfield microscopy Tertiary Formation of gummas – soft growths with firm necrotic center Aneurysm of ascending aorta, with “tree-barking” appearance Destroys vasa vasorum that supplies aorta with blood Tabes Dorsalis: damage to posterior column of spinal cord Argyll Robertson pupil: reacts to accomodation but NO REACTION TO LIGHT CONGENITAL SYPHILLIS Saber shins, an anterior bowing of tibia Saddle nose Hutchinson’s teeth & mulberry molars Congenital deafness Rx: penicllin for all stages, tetracycline but better to desensitize them and use penicllin. Jarisch-Herxheimer reaction may occur hours after treatment, dying spirochetes release LPS leading to cytokine release (fevers and chills)
Chlamydia “The Pirates of Chlam Island”
• • • • • •
Obligate intracellular. Poor gram staining. Lack of muramic acid in cell wall. Life cycle: 1st stage: Elementary bodies – infectious form 2nd stage: Reticular bodies – active form that can multiply
• • • • • • •
Inclusion bodies visible within cells under microscope. May be visualized with Giemsa stain. Commonly diagnosed by NAAT (nucleic-acid amplification test) Reactive arthiritis Reiter’s syndrome – Uveitis, Urethritis, arthritis (can’t see, can’t pee, can’t climb a tree) Chlamydophila pneumoniae causes atypical pneumonia (walking pneumonia but in adults and elderly) Chlamydophila psittaci also causes pneumonia – transmitted by bird droppings
• • • •
Trichomatis A-C: blindness Leading cause of blindness in the world Transmitted by hand to eye contact, or fomites
• • • • •
D-K: STI Watery discharge if left untreated, may lead to pelvic inflammatory disease (PID) newborns born to infected mothers can develop conjunctivitis and pneumonia (gonorrhea conjunctivitis will occur earlier) staccato cough
• •
L1-L3: LGV Lymphogranuloma venereum characterized by tender inguinal lymphadenopathy
• •
Rx: Macrolides (because no cell wall) , oral macrolides effective against trachoma Tetracycline like doxycycline
•
Coinfection with gonorrhea – always add ceftriaxone to treatment
Coxiella “Curly Q the Ram”
• • • • • •
Gram negative. No rash. Q fever. Obligate intracellular organism Contained in spore like structures in animal feces Transmitted to humans via aerosol transmission from farm animals to farmers or veterinarian exposed to placental secretion. • No antibiotics needed – goes away on its own. • Vets can receive an acellular vaccine for preventive measures. • Pneumonia, headache, fever. • May cause hepatitis.
Garnerella vaginalis “The Fish Garden”
• Cause of bacterial vaginosis. • Gram variable rod (stain as gram negative or gram positive) • Normal vaginal flora contains lactobacilli, but if there is increase in anerobic overgrowth, decreases lactobacilli and increases garnerella vaginalis. Bacterial overgrowth that disrupts the normal flora. • Grayish-white discharge w/ a pH > 4.5. • 10% KOH whiff test. • Clue cells = epithelial cells coated with bacteria.
• Rx: Metronidazole (same as clostridium difficile)
Mycoplasma pneumoniae
• • • • • •
Affects young adults and military personnels plated on Eaton agar lyses RBC’s IgM binds to RBCs cold agglutinin x-rays (sky) is much worse than clinical symptoms they can walk (walking pneumonia) • Treat with macrolides no cell wall
Rickettsia overview “Rickettsia Tennis”
• • • • • •
Obligate intracellular. Poor gram staining. Unable to produce CoA, gets it from eukaryotic cells. NAD+ also important for bacterial growth and replication. Coccobacillary shape, weakly gram negative. Weil Felix test – agglutination test used to diagnose, tests for cross-reactivity between rickettsia and proteus vulgaris. • Headache and fever in early Rickettsial infection. • Vasculitis. Rash may be associated with vasculitis. • Rx: doxycycline +other tetracyclines
Rickettsia prowazekii “Pro Boot Camp”
• Obligate intracellular, poor gram staining. • Require CoA + NAD+ for growth. • Doxycycline treatment. • • • • •
Rash starts at trunk, and spreads outwards towards extremities. Rash spares hands, feet, and head. At risk? Affects military camp recruits and prisoners of war Arthropod bacteria spread by louse. Louse feeds on blood usually defecates on feeding sites and the scratching usually deposits the feces into blood. • The Outbreak illness is called epidemic typhus (widespread rampant outbreak) • Causes myalgia, arthralgia, pneumonia, encephalitis, with dizziness and confusion. • Can cause coma in a patient
Rickettsia rickettsii “Rickett’s Rock Climbing Competition”
• • • •
Rocky Mountain Spotted Fever. Obligate intracellular, poor gram staining. Giemsa staining. NAD+ and CoA necessary for growth and replication = provided by host. • Doxycycline treatment. • UNIQUE: – Transmission: direct contact with dermacentor tick. – Rash not immediate – has incubation period between 2-14 days – Rash begins at extremities, spreads centrally from extremities.
• Headache, sweating, sore and muscle pains (myalgias), fever
HSV1 and HSV2 “Hermes, the God of Herpes”
• • •
Herpes is a DNA virus (blue cool tones) and Herpes Simplex Virus is part of the larger Herpes virus family. Enveloped. Replicates in the nucleus and double stranded and linear. Dry cow hyde – intranuclear inclusion bodies eosinophilic (Cowdry bodies), same as VZV and CMV vs. poxviruses which has similar inclusion bodies except they are in the cytoplasm.
• Transmission: 1. Vertically transmitted (TORCH) 2. sex 3. saliva. • • • • • • • • • • •
HSV-1 Confined to upper half of body. Gingivostomatitis is first sign of HSV-1 Herpes labialis, or “cold sores” Keratoconjunctivitis Serpiginious corneal ulcers on Fluorescein slit lamp exam HSV-1 causes temporal lobe encephalitis, include usual fever headache altered mental status, personality changes #1 cause of sporadic encephalitis in USA. HSV1 latent in trigeminal ganglia. Herpes rash has “dew drops on rose petal” appearance Herpetic whitlow, more common in dentists (in HSV1 and 2) Erythema multiforme may appear 1-2 weeks after infection.
• • • • • •
HSV-2 Sexual or obstetric – herpes genitalis. Painful and vesicular. Painful inguinal lymphadenopathy associated with HSV-2. HSV-2 lies dormant in the sacral ganglia. HSV-2 may cause aseptic meningitis in adolescents and adults.
• •
PCR – choice of diagnosis. Tzank smear showing multinucleated giant cells, characteristic of herpes infections.
•
Rx: Acyclovir or Valcyclovir to prevent breakouts.
EBV “Ye Olde Epstein Bar”
• • • • • • • • • • • •
Double stranded DNA – blue dominated colour scheme. Causes infectious mononucleosis. “Kissing disease” passed through saliva when you share a drink or a kiss. Primarily transmitted through saliva. Fever; Tender lymphadenopathy. T cell important for cellular immunity. Reactive cytotoxic CD8+ T cells (Downey, or atypical lymphocytes), seen on blood smear. Splenomegaly due to T-cell proliferation + maybe hepatomegaly. EBV remains latent in B cells. EBV envelope glycoprotein binds CD21 to infect B cells. Pharyngitis and tonsillar exudates. If mistakenly given amoxicillin or ampicillin (confused with strep pharyngitis), can develop maculopapular rash.
Risk factors for some cancers (crab): 1. B cell lymphoma 1. Hodgkin’s lymphoma – Reed Sternberg cells that look like “owl’s eyes” 2. Non-hodgkin’s lymphoma – Endemic or African Burkitt’s lymphoma – large jaw lesion and swelling
2. Nasopharyngeal carcinoma associated with Asian EBV patients • - Oral hairy leukoplakia in HIV patients, non-cancerous lesion Diagnosis: • Monospot test – rapid diagnosis, heterophile Abs, clump sheep or horse blood cells Rx: Supportive therapy, and avoid contact sports due to risk of splenic rupture
CMV “Cyto ‘Mega-Lo’ Virus”
• • •
DNA virus. Herpes virus family. Remains latent in WBCs – monocytes, macrophages, lymphocytes (B and T cells). Reactivation by immunosuppression.
Transmission: • Blood, Saliva, TORCHES infection (Taxoplasmosis, Rubella, CMV, HIV, Herpes, Syphillis, VZV and Parvo) •
Congential CMV #1 cause of congenital viral infection - Blueburry muffin rash: thrombocytopenia - Jaundice and hepatosplenomegaly - Sensorineural deafness #1 cause of hearing loss in children, and mental retardation - Intracranial calcifications – ventriculomegaly, periventricular calcifications (SAME AS TAXOPLASMOSIS), intraventricular calcifications - Seizures
80-90% asymptomatic Pregnant woman – 2nd trimester with highest risk of CMV transfer. Hydrops fetalis (heart failure and severe fluid accumulation) Organ transplant patients at risk for developing CMV pneumonia. To detect CMV in transplant patients you can conduct a buffy coat culture (contains WBCs and platelets) and you can incubate these cells with fluorescent anti-CMV antibodies and detec the presence of the virus. AIDS patients – CD4 count < 50, CMV retinitis Linear ulcerations in esophagus (singular, deep, linear) CMV colitis with ulcerated walls. Owl’s eye inclusion bodies. Rx: Ganciclovir, Phoscarnet when resistant to ganciclovir due to mutations in the UL97 gene. Diagnosis: Monospot test is negative
VZV “Varicella ‘Zeus’-ter Virus”
• • • • •
Herpes virus family - Enveloped virus Chicken pox – childhood xanthem (widespread rash), associated with fever and headache Transmission: via respiratory droplets or ruptured vesicles themselves. “Dew drop on a rose” or a vesicular lesion with surrounding erythema. - Lesions in different stages of healing. Tzank smear shows multinucleated giant cells.
•
Adult presentation with chicken pox: pneumonia and encephalitis especially in immunocompromised
• •
Live attenuated vaccine for children. Acyclovir treatment for children ages 12+, adults, and immunocompromised.
• • • • • •
Remains latent in DRG: Reactivation with stress, aging, or immunocompromised state. Herpes zoster, or shingles, is reactivated form. Herpes zoster, or shingles has “dew drop on a rose” appearance with dermatomal distribution. Extremely painful rash. Postherpetic neuralgia – pain after rash subsides. Affects thoracic dermotome but can affect trigeminal nerve, especially in immunocompromised host. Herpes Zoster Opthalmicus – vision loss possible if V1 affected. Zoster vaccine – live attenuated vaccine, recommended for adults over 60. HIV patients with CD4 count > 200 may be given shingles vaccine. Famciclovir , Valacyclovir treatment for shingles.
• • • • •
Congenital infections – vertical transmission (TORCH) If pregnant woman becomes infected with VZV in first two trimesters, the child can develop congenital varicella syndrome – limb hypoplasia, cutaneous dermatomal scarring, blindness.
• •
Affects babies, children, adults, elderly. Two major diseases: – –
Chickenpox Herpes zoster (shingles)
HHV-6: Roseola “A Roseola by any other name would smell as sweet”
• Double stranded DNA virus. (Herpes virus family) • Sixth disease (fifths disease). Ro6ola (Roseola) • HHV-6 infects CD4+ cells and has the ability to cause immunosuppression. • Clinical symptoms: – Xanthum subitem – high fever lasts 3-4 days (over 104 degrees F). Fever so high can cause febrile seizures and then lacy body rash occurs that spares the face.
• Affects children ages 6 months to 2 years, and is usually self-limiting. • Rx: supportive with cooling fluids
HHV-8: Kaposi Sarcoma “Ring around a Ka-posi”
• • • • • • •
HHV-8 causes Kaposi Sarcoma – double stranded DNA. AIDS and immunosuppressed associated with Kaposi sarcoma. Causes violacious lesions on nose, extremities and mucous membranes. Causes proliferation of vasculature – dysregulation of VEG-F. Lesions can be found within the GI tract. Kaposi’s lesions most commonly occur on the hard palate. Infection of B cells can cause Primary Effusion Lymphoma (B-cell lymphoma).
• Elderly Russian men who have typically lower extremity lesions and adults in Africa with classical presentation of palatal lesions. Therefore higher incidence in Russian men and African populations. • Differential diagnosis: Bartonella henselae, bacillary angiotomatosis (neutrophilic infiltrate). Kaposi’s accompanied with lymphocytic infiltrate. • Rx: Anti-retroviral therapy if patient is HIV positive and hasn’t started yet. • IMPORTANT FEATURES MUST REMEMBER: - Can be confused with bartonella hensleae - Causes angiogenesis via dysregulation of VEG-F - Infects B-cells, can cause Primary Effusion Lymphoma
Papillomavirus “Pilloma Bugs”
• • • •
Double stranded DNA, naked virus. HPV1-4 (children in the background) verrucan vulgaris = cutaneous common wart Children get it, so do adults Not a genital strain, r equires physical contact
HPV6, 11 • Laryngeal papillomatosis = recurrent respiratory papillomatosis • Acquired during vaginal birth • Not considered a sexually transmitted disease • Anogenital warts: condyloma acuminata HPV 16, 18 • Anogenital cancers – squamous cell carcinoma (31, 33) • Post-coital bleeding – think cervical cancer HPV Vaccine – covers HPV 6, 11, 16, 18 (not 31, 33) • Guardasil , inactivated subunit vaccine – recommended for women and men 9-26 years of age Most common STD. Nearly all sexually active individuals will get HPV at some point. Virus disrupts regulation of cell cycle, tumor suppressor proteins: p53 and Rb inhibit progression from G1 to S phase. HPV encodes E6 (fork with shrimp) , E7 (straw in Root Beer (RB), with fork) which promotes proteolysis of p53 and Rb respectively increasing likelihood of cancer. Pap Smear: screening for cervical cancer takes cells from transition zone, koilocytes. AIDS-defining illnesses: invasive cervical/anal/penile cancers
Adenovirus “A Den-O Lions”
• •
DNA virus – cold, dark shades of blue but back part of cave is red. Why? Because adenovirus isolated in adenoids. #1 cause of tonsilitis (cave is an oropharynx) Adeno is a naked virus (statue of David)
Transmission: 1. Respiratory droplets (dripping stalactites) 2. Fecal-oral (poop) Commonly affects: 1. Children 2. Military barracks 3. Swimmers at public pools Causes 1. Tonsilitis 2. Hemorrhagic cystitis (pee from David’s crotch) 3. Viral conjunctivitis pink eye Live Attenuated Vaccine
only indicated for military recruits
Poxvirus “Pox in a Box”
• • • • •
DNA virus blue tones Comes with everything it needs inside of it. Pox viruses make their own envelopes instead of taking it from their host Only DNA virus that completely replicates inside the cytoplasm Pox virus has a special DNA dependent RNA polymerase (RNA polymerase that reads DNA) • Pox forms intra-cytoplasmic inclusion bodies •
Guarnieri bodies, or inclusion bodies, are sites of viral replication in the cytoplasm
• Dumbbell shaped core • Largest known DNA virus 1. Smallpox (variola) causes raised blisters on the skin and mucosal surfaces. Lesions are of the same age (vs. chickenpox – varicella has a mixture of blisters, lesions, etc.) 2. Cowpox: transmitted by infected cow udders 3. Molluscum Contagiosum (snail mail)– flesh-colored, dome-shaped, umbilicated skin lesions (affects children: found everywhere except palms and soles, most commonly found on the trunk, axilla, antecubital fossa and popliteal fossa). – When involving adults, diffuse molluscum contagiosum infection suggests an HIV infection (old man with cane). Otherwise, in a healthy adult it will be a single umbilicated lesion contracted through sexual transmission.
Missing in SM: Parvovirus FA: B19 virus – aplastic crises in sickle cell disease, “slapped cheeks” rash in children (erythema infectiosum, or fifth disease) RBC destruction in fetus leads to hydrops fetalis and death, in adults leads to pure RBC aplasia and rheumatoid arthritis – like symptoms Not enveloped. SS and linear (smallest DNA virus)
Missing in SM: Hepadnavirus Enveloped. Partially DS and circular. HBV: • Acute or chronic hepatitis • Not a retrovirus but has reverse transcriptase
Missing in SM: Polyomavirus • Not enveloped. • DS and circular • JC virus – progressive multifocal leukoencephalopathy (PML) in HIV AIDS defining illness (CD4 count <200) • BK virus – transplant patients, commonly targets kidney • JC: Junky Cerebrum • BK: Bad Kidney
Orthomyxovirus “Night Shift at the Orthodontist’s”
• • • • •
RNA negatives (moon with cloud) all single stranded EXCEPT Reovirus Need to be transcribed into a positive strand so must bring along their own RNA polymerases ALL RNA viruses replicate in the cytoplasm EXCEPT orthomyxovirus (replicates in nucleus) Enveloped Influenza virus (strains A, B, C) – replicates inside the nucleus – 8 virus segments (4 segmented BOAR: – Antigenic drift: point mutations in viral genome, ∆vin neuroaminidase/hemagglutinin molecules. (doKtor drift) endemics – Antigenic shift – antigenic segments of RNA are shared between species. H’s and N’s can combine and form new viruses – reassortment. Responsible for Pandemics [[Antigenic variation (different coloured curtains]] – Influenza A – endemics and pandemics // Influenza B – endemics only – Virulence Factors: • Hemagluttinin (HA) – glycoprotein on surface of influenza viruses binds to sialic acid on membranes of cells in the URT or RBC’s. causes RBCs to clump together. • HA antigens: H1, H2, H3, etc. Determines cell tropism. • HA molecules binds to sialic acid and is then endocytosed. M2 protein - create correct pH for viral encoding. • Neuraminidase (NA) – cleaves sialic acid to release newly formed virions from host cell (nurse assistant) – Treatment: • Amantadine/Rimantadine inhibit M2 (influenza B lacks this). Amantadine is also used to treat parkinson’s • Oseltamivir/Anamivir: NA inhibitors prevent release of virion. Giving after 72 hours- not effective b/c virions will already be released • Live attenuated nasal spray and killed injectable vaccine. Killed vaccine comes in two forms: – Trivalent vaccine – 2A strains and 1 B strains – Quadrivalent vaccine – 2A strains and 2B strains – Transmission: Respiratory droplet during flu season (December to February) – Complication of influenza: pneumonia (S.aureus, S.pneumo) – Aspirin is contraindicated in children with viral illnesses Reyes syndrome & uncouples oxidative phosphorylation (disrupt proton gradient along the ETC): hepatic mitochondria extensive damage – Associated with Guillan Barre syndrome (ascending paralysis, high protein with low WBC counts )
Paramyxovirus “Paranormal Mixer”
• Single stranded, -ve sense RNA viruses Replicates in the cytoplasm Enveloped • Respiratory droplet transmission • MMR: live attenuated vaccine (live puppet show), contraindicated in pregnancy Measles (Rubeola) • Symptoms: 4 “C”’s: Cough, Coryza, Conjunctivitis, Koplik spots (blue and white spots), high grade fever lasts for 4 days –
• •
maculopapular rash (face and moves downwards) – confluent rash
Complications: Pneumonia, SSPE (subacute sclerosing pan encephalitis) patient had hx of measles/never vaccinated (emigration), then 5-15 years later gets myoclonus, ataxia, coma/death. anti-measle antibodies in CSF. No effective treatment. Virulence Factors: 1. Hemagluttinin; 2. Fusion protein –
•
4 days after Koplik spots
multinucleated giant cells (warthin-finkeldey cells nuclear bodies
lymphoid tissue); cytoplasmic & intranuclear eosinophilic/red
Treatment –
Vitamin A reduces measles morbidity and mortality
Mumps • Parotitis, orchitis (inflammation of epididymis – unilateral testicular atrophy and infertility), meningitis (neck brace) • Virulence Factors: 1. Hemagluttinin; 2. Fusion protein; 3. Neuraminidase RSV • Infants less than 6 months of age • Virus infects cells by attaching to respiratory endothelium through the G protein • Bronchiolitis, pneumonia (#1 cause in infants), rhinitis, pharyngitis • Virulence Factors: 1. Fusion proteins • Treat with Ribavirin, palivizumab Parainfluenza virus • Seal bark cough • Virulence factors: 1. Fusion protein; 2. NA and 3. HA • X-ray “steeple sign” • Laryngotrachiobronchitis = croup • Inspiratory stridor
Rhabdovirus “Rabid Wrecking Yard”
• Single stranded, negative sense RNA virus enveloped bullet shaped on EM helical capsid • #1 carrier of rabies in U.S. Bats • Foxes, skunks, and other rodents are also common carriers • Binds to nicotinic acetylcholine receptors Initially infects neurons at the post-synaptic motor endplate • Pathogenesis – Retrograde movement of the virus along peripheral nerves – Replicates in the motor neurons – Travels to dorsal root ganglia
• Fever, rabies encephalitis • Diagnosis: clinical, eosinophilic Negri bodies in the hippocampus cytoplasm, hippocampal pyramidal cells, purkinje cells • Antidote given prior to onset of symptoms – passive immunization with human rabies immunoglobulin (post-exposure prophylaxis) + killed vaccine for active immunization
Filovirus “Soccer Field’o virus!”
• Negative-sense virus RNA (orange) with helical capsid enveloped Ebola, Marburg • Fever, petechial rash • Hemorrhagic fever, end-organ failure • Death occurs due to hypovolemic, hemorrhagic shock • Bats may by the viral reservoir • Possibly transmitted via primates FA: Ebola – targets endothelial cells, phagocytes, hepatocytes. - Abrupt onset of flu-like symptoms, D/V, high fever, myalgia - Can progress to DIC, diffuse hemorrhage, shock - High mortality rate, no treatment - Supportive care - Transmission requires direct contact with bodily fluids or fomites (including dead bodies); high incidence of nosocomial infections
Bunyavirus “Paul Bunyavirus”
• Single stranded, RNA negatives envelope (gains from host golgi) • 3 circular segments Arboviruses 1. Rift valley fever 2. California encephalitis • Shaking = seizures, encephalitis • Transmitted by the Aedes mosquito Hantavirus • Reservoir: deer mouse • Transmitted via rodent urine/feces • Pulmonary edema, pulmonary capillary leak, prerenal azotemia – capillary leak, hemorrhagic fever, pneumonia
Arenavirus “Welcome to the Arenavirus”
• Single stranded, negative sense RNA virus cytoplasm enveloped • Encode positively and negatively – ambisense (sword in both hands) • Helical shaped nucelocapsid (spiral bands up columns) • Segmented virus – 2 segments • Grainy appearance on EM • Rodent transmission LCV lymphocytic choriomeningitis virus – Meningoencephalitis – Fever
• Inactivated by heat, low pH, irradiation Lassa Fever encephalitis – spread by rodents
Reovirus “A Race on the Rio”
• RNA, double stranded (no sun or moon – both positive and negative sense), replicates in cytoplasm • Non-enveloped, naked virus • Segmented (BOAR) 11 segments Rotavirus • Fecal oral route • Toxin (NSP4 – increases chloride permeability) mediated secretory watery diarrhea • More common in the wintertime • Children are at risk for rotavirus infections • #1 cause of severe diarrhea in young children • Treatment: oral rehydration • Prophylaxis: live attenuated virus vaccine – must be given before 3 months of age – Vaccine side effect: intussusception = telescoping of the bowel
Colorado Tick Virus (Coltivirus) • Fever, vomiting, myalgia NO RASH
Picornaviruses Overview “The Peak-orna Animal Nursery”
• Positive sense, naked virus • Transmitted fecal oral route (exception: rhinovirus transmitted respiratory droplets) • Uses host RNA polymerase – (+) sense mechanism of replication • Polyprotein product cleaved into smaller subunits • Replicate in cytoplasm Hepatitis A (exhibit A) • hepatosplenomegaly Enteroviruses (exhibit B = birds) • Polioviruses • Coxsackie A and B • Echovirus • #1 cause of aseptic meningitis (children most affected) • CSF glucose is normal, no organisms, elevated protein Rhinoviruses (exhibit C = common cold) • Upper respiratory infection
Poliovirus “The Flamingo Breeding Pool”
• RNA virus, +ve sense, picornavirus, naked virus • Fecal oral route, acid stable • Replication occurs in Peyer’s patches (submucosa of gut) • Affects the anterior horn of the spinal cord • Causes asymmetrical paralysis, myalgias and decreased DTR, respiratory insufficiency • Aseptic meningitis • Prevention: – Salk vaccine – inactivated, killed vaccine • Bypasses GI tract so only forms IgA NO IgG
– Sabin vaccine – live, attenuated vaccine given orally • Can get shed in feces and cause paralysis in another person
Coxsackie “Coxsackie Cockatoos”
Picornavirus, Positive-sense RNA virus Naked virus (statue of david) Infection common in summer months, causes aseptic meningitis A/B cages – two flavours of coxsackie virus Coxsackie A • hand, foot and mouth disease > red vesicular rash Coxsackie B • Causes dilated cardiomyopathy • Devil’s grip – Bornholm’s disease/pleurodynia (extreme sharp pain in lower chest and is often unilateral and makes it difficult to breathe) Treatment: supportive
Rhinovirus “Rhino Petting Zoo”
• Picornavirus but has some exceptions • Naked virus • Transmission: respiratory /through fomites (grubby hands) • Acid labile so cannot go through the GI tract • Rhinovirus enters host cells by attaching to ICAM-1 • Grows best in cooler temperatures – around 33 degrees Celsius (in upper respiratory tract) – causes URI • Rhinovirus has many different serotypes :. No treatment
Hepatitis A “Hungry Hungry Hep A Hippos”
• RNA virus, +ve sense, Naked virus • Acid Stable, fecal oral transmission • How to inactivate Hepatitis A – – – –
• • • •
Chlorinated water Bleached water UV irradiated water OR Boiled water
Contaminated water is a common source in DEVELOPING countries Contaminated shellfish are a common source in DEVELOPED countries Commonly seen in travelers to endemic areas Symptoms (one month duration, self-limiting, no carrier/chronic state) – Jaundice (especially in adults) – Anicteric hepatitis in young children and infants – Smokers with Hep A develop aversion to smoking
• Inactivated vaccine give to patients in high risk situations (MSM who enjoy oysters and travelling)
Calicivirus “Cali Sea Cruise”
• Positive sense, RNA virus, single stranded • Naked virus • Produces one long polyprotein that is cleaved by viral proteases into smaller viral constituents (tickets) • Calicivirus replicates in the cytoplasm • Most common clinical calicivirus: norwalk virus (dolphin) • Outbreaks common in day care centers and schools, cruise ship passengers • Consumption of shellfish is associated with Norovirus • Causes viral gastroenteritis explosive watery diarrhea
Flavivirus “Flavor Packed Flavi!”
• RNA virus, positive sense • Enveloped virus • Non-segmented Hepatitis C (a member of the flaviviruses) Dengue Fever (break bone fever, Type 2) • Mosquitos = Aedes Egyptei • Thrombocytopenia • Hemorrhagic fever • Dengue fever can lead to renal failure • Treatment: supportive, hydration Yellow Fever • Jaundice, backache, bloody diarrhea, bloody vomiting • Live attenuated vaccine for travelers West Nile virus • Birds are the reservoir • Coulex mosquitoes are the vector • Encephalitis – major complication • Meningitis • Flaccid paralysis • Seizures • Coma
Togavirus “Toga-toga-togavirus!”
• RNA virus, positive sense replicate in cytoplasm • Enveloped • Long polyprotein precursor, cleaved by proteases Arbovirus • Arthropod borne virus (arthropod vector) • Western/Eastern/Venezuelan-Equine encephalitis • No treatment, therefore must protect with clothing, sprays, netting Rubella (german measles) • Childhood exanthem • Immigrant • Causes postauricular and occipital lymphadenopathy • Maculopapular rash – begins on face and moves downward • Transmitted via respiratory droplets • TORCHeS infection (Toxoplasma gondii, Rubella, CMV, HIV, HSV, and Syphilis – varicella zoster, parvovirus) • Congenital Rubella: Classic Triad: 1. 2. 3. 4. 5.
• •
Congenital cataracts Sensory-neural deafness PDA Blueberry muffin rash (additional) Jaundice (additional)
Rubella in Adults: arthritis, lymphadenopathy, fever MMR vaccine, live attenuated – elicits humoral and cell mediated immunity • •
Do not give to pregnant women/immunocompromised HIV positive patients should receive vaccine only with CD4 count above 200
Coronavirus “Kingdom of SARS”
• • • • • •
Positive single standed RNA virus Corona = crown Encapsulated virus Helical shaped A cause of the common cold SARS, MERS - Acute bronchitis, can lead to acute respiratory distress syndrome – Dx: w/ antibodies to SARS or confirm w/ PCR – Negative finding clinically if no antibodies over 28 days – Rx: broad spectrum antibiotics, ribavirin, corticosteroids (efficacy variable)
• Replicates in cytoplasm
HIV “One Cane to Rule them All”
• • • •
HIV, immunocompromised, RNA positive virus, Enveloped Retrovirus, single stranded positive RNA virus turns into DNA w/ reverse transcriptase Diploid RNA positive virus (2 molecules of RNA stranded RNA in each virion) 3 very important genes – – –
• • •
Env = gp41 and 120. serve to form a viral envelope. Makes glycoprotein 160 then cleaved to 41 and 120. Gp41 is transmembrane protein. Gp 120 is outer glycoprotein. Gag = p24, which is the capsule for RNA strands Pol = reverse transcriptase
Transmission: sexual contact, vertical transmission (TORCHES), blood (IV drug use or needle sticks) HIV initially infects macrophages, helper T cells Progression of the disease: – – – –
Prodrome consists of flu or mono-like symptoms, lymphadenopathy, fever, CD4+ cells are infected Latent for up to 10 years (sleeping squire) Steep decline in CD4+ cells. AIDS diagnosed when CD4+ cells < 200 HIV can cause diffuse large B cell lymphoma (archers + crab)
Gains entry via CCR5 receptor in early stages OR gains entry via CXCR4 receptor in late stages Screening test: ELISA test for antibodies (multiple screening tests done up to 6 months after exposure) Diagnosis: Positive ELISA must be confirmed with a Western Blot. Neonate: test with HIV RNA and HIV DNA nucleic acid amplification tests. Looks for virus itself and not antibodies Treatment: HAART: Combination therapy is always better than monotherapy Reverse transcriptase inhibitors: • NRTIs are the backbone of antiretroviral therapy (nucleotide analog) •
Zidovudine for pregnant patients
• NNRTIs (doesn’t incorporate itself into the chain) Protease inhibitor CCR5 Inhibitor – Maraviroc Many HIV strains so must do genotype testing to figure out what combination of therapy is best for them. Everyone should get treatment CD4 count under 350, pregnant women, and those with high viral road must get treatment.
Histoplasmosis “The Historian’s Cave”
All fungi: Cause profound disease in immunocompromised First group: Systemic fungi. Spread to other parts besides lung Associated w/ bird or bat droppings or somebody who has been in a cave or been in a chicken coop (like a farmer) Endemic to Midwestern and central U.S.; along the Mississipi and Ohio river valley Transmission through respiratory tract Histology: Macrophages w/ intracellular oval bodies (stain w/ KOH prep) Serum rapid antigen test Urine rapid antigen test (stalactite + MO puddle) Histoplasma much smaller than a RBC. Many fit inside a MO. Dimorphic form of fungus depends on the temperature of its surroundings MOLD IN THE COLD, YEAST IN THE HEAT (37°C) Asymptomatic/subclinical however can cause granuloma formation causing pneumonia. Granulomas can calcify leading to chronic pulmonary complications looks a lot like TB w/ cavitary lesions in upper lobes and calcified nodes with fibrotic scarring Erythema Nodosum on legs (Bull) Dissemination disease in immunocompromised hepatosplenomegaly Fungus targets reticuloendothelial system which is prevalent in liver and speen Treatment: • Local or mild infections are treated with “-conazoles” • Systemic or disseminated infections are treated with amphotericin
Blastomycosis dermatidis “The Blast of the Cannons”
Southern & Eastern U.S.: The Great Lakes & Ohio River Valley Dimorphic Fungus (butterfly) Transmission: Inhalation of aerosolized spores Broad Based Budding Same size as a RBC Chest X-Ray has patchy alveolar infiltrate (haziness), lesions or cavities in lungs Pneumonia can be acute or chronic: local lung infection but can spread to other organs in immunocompromised Dissemination of blasto from the lungs is likely to occur in skin and bones bone involvement: osteomyelitis KOH stain Urine antigen test (yellow river) Treatment: Azoles for local infections (Itraconazole) Disseminated infections: Amphotericin B
Coccidioides “Presidio San Joaquin”
Distribution: Southwestern United States (California – San Joaquin Valley) Route of transmission: Inhalation of spores in dust (Earthquakes are a risk factor for spread of infection) Dimorphic Fungi MOLD IN THE COLD, SPHERULE OF ENDOSPORES IN YEAST Bigger than RBC Healthy Person Asymptomatic but can present as acute pneumonia: fever, cough and arthralgia Radiographic images may show either nothing or cavitites and/or nodules. Erythema nodosum on shins (indicates robust immune response – so healthy people) Immunocompromised Skin and lungs are common sites of infection May disseminate to the bone + cause meningitis KOH stain/culture Serology for antibody titers. IgM against cocci is a recent infection TREATMENT Local infection: conazoles Systemic infection: Amphotericin B
Dermatophytes “Tinea Tin Man”
Dermatophytes are the fungus itself that colonize the skin. Tinea is the disease they cause. 3 types of dermatophytes and multiple types of tinea BUT all tinea have same pathology but change name depending on location. 1. Trichophyton 2. Epidermophyton 3. Microsporum Tinea – ringworm (rings of rust) • Tinea capitis on the head and the scalp • Tinea corporis is on the body • Tinea cruris is on the groin • Tinea pedis is on the feet (athletes foot –swimmers, wrestlers) Animals are a common source of dermatophytes. Tinea lesions are pruritic. Hyphae can be seen with KOH prep of skin scrapings Woods lamp can be used to diagnose Microsporum. Onychomycosis: dermatophyte infection of the nails TREATMENT Azoles are used to treat Tinea infections Oral medication for onychomycosis – Terbinafine (turban) For any severe tinea infections and onychomycosis that won’t go away you can treat with oral griseofulvin (likes to deposit in keratin containing tissues like skin and nails, has a lot of GI side effects and is not well tolerated)
Sporothrix Schenckii “Shanked by a Rose”
Sporothrix is found in rose thorns, tree bark, and other plants. Dimorphic fungus Branching hyphae grown at 25 degrees Celsius. Causes “rose gardener’s disease” Cigar shaped yeast under a microscope Infection spread in an ascending pattern along the path of draining lymphatics (network of vines, red bulbs = red bumps that appear on skin) Culture is the gold standard. Can also do biopsy where you will see granulomas consisting of histiocytes, multinucleated giant cells, and cigar shapped budding yeast. Treatment: Itraconazole – for lymphocutaneous sporotrichosis Saturated solution of potassium iodide (no longer a standard of care)
Candida Albicans “Candid Canadians”
Causes both cutaneous and fungal infections - MCC of opportunistic mycoses. Patient who is neutropenic, has HIV/AIDS, or is a diabetic you should have Candida on the differentials. Dimorphic BUT mold in the heat and yeast in the cold (pseudohyphae, budding yeast at 20° & germ tubes @37°) Catalase +ve (people with CGD are susceptible to catalase +ve infection) Candida causes diaper rash in a characteristic distribution due to the heat and humidity within a baby’s diaper Oral candidiasis: - Immunocompromised patients - People using oral steroids - Oral steroid use must be followed by oral rinsing to avoid development of oral candidiasis - Easily scraped off the oral mucosa. This feature directly contrasts to leukoplakia, which may present in a similar manner. - KOH is used to prep oral scrapings when attempting to diagnose oral candidiasis - Candidal esophagitis is an AIDS defining illness (CD4 count < 100) Vulvovaginitis candidiasis: - Diabetes predisposes to candidal infections - Prescription pills and birth control pills can predispose women to getting candida - Antibiotics kill bacteria including vaginal microflora allowing it to flourish. Candida does not change vaginal pH (3.8-4.2pH) and flourishes below 4pH (contrast with Gardenerella – 4.5 and up) Candidal endocarditis commonly seen in drug users. Candida commonly found growing in certain types of heroin, which when injected can seed in tricuspid heart valves Treatment • Conazoles for less severe infection • Amphotericin for more severe disseminated infections + Capsofungin for resistant Candida • Oral/Esophageal candidiasis – Nystatin (liquid, swish+swallow OR swish+spit)
Aspergillus fumigatus “Asparagus Farm”
Catalase positive Peanuts associated with aflatoxins produced by Aspergillus flavus • Aflatoxins associated w/ development of hepatocellular carcinoma Acute angle branching (Acute Septate) Forms conidiophores with fruiting bodies transmitted via inhalation 3 types of infection 1. Allergic Bronchopulmonary Aspergillosis (ABPA) Wheezing, fever, migratory pulmonary infiltrate (Type I HS – :. Increased IgE), also assoc. with CF patients 2. Aspergillosis causing Aspergillomas Associated with TB cavities Fungus balls within cavities are gravity dependent 3. Angioinvasive Aspergillosis Affects immunocompromised patients (patients with neutropenia with leukemia/lymphoma) Invades blood vessels and disseminates through the body (fever, cough, hemoptysis) -
Kidney failure, endocarditis, ring enhancing brain lesions Spread to paranasal sinuses may cause necrosis around the nose
Treatment Voriconazole for less serious infections (-conazoles) Must be surgically debrided in addition to medical treatment. For Angioinvasive disease use Amphotericin B
Cryptococcus Neoformans “Crypt for Cryptococcus”
Cryptococci are heavily encapsulated. Capsule is made up of repeating polysaccharide capsular antigens. Found in soil and pigeon droppings. Transmission: inhalation Urease positive Opportunistic infection – symptoms in immunocompromised (HIV patients) Symptoms: 1. Fever 2. Pneumonia (pulmonary symptoms-cough, dyspnea, and other serious lung infections) 3. Meningitis - spread to CSF Diagnostic tests: 1. Bronchopulmonary washings can be used to diagnose Cryptococcal infection. Tissue samples can be stained with mucicarmine (red) or methanamine silver stains 2. Lumbar puncture, CSF stained with India ink – stain background dark while organism remains transparent (5-10 micrometres of yeast with wide capsular “halos”) 3. Latex-agglutination test: detects repeating polysaccharide capsular antigens and causes agglutination 4. Gross pathology seen in cryptococcal meningitis: “Soap bubble” lesions in gray matter of brain Treatment for cryptococcal meningitis: • Joint therapy with amphotericin B + Flucytosine • Maintenance therapy: Fluconazole
Mucormycosis “Mu Car Auto Shop”
2 Fungi: Mucor + Rhizopus [Rides’R’Us] Immunocompromised and diabetic patients are highly susceptible to infection (leukemia and neutropenia) Rhizopus = bread mold [baguette] Transmitted through spore inhalation. After being inhaled, fungi like to proliferate in blood vessel wall [red jumper cables] (especially where there is excess glucose + ketones Diabetic Ketoacidosis (DKA) – most common predisposing factor to infection) Morphology: hyphae is non-septate with wide angle branching (90 degrees) After invading blood vessels, the fungi penetrates the cribiform plate. Proliferation of fungi eventually leads to necrosis of surrounding tissue (rhinocerebral mucormycosis). Dead tissue needs to be removed via surgical debridement. Also need medical therapy Amphotericin B
Pneumocystis jiroveci “PCP Ping Pong”
Transmission: respiratory AIDS (symptomatic) + healthy individuals (asymptomatic) CD4 count < 200 (when susceptible, begin prophylaxis here) PCP causes diffuse interstitial pneumonia (cough, dyspnea, fever) that may take on a ground glass appearance on Xray (can also look like crushed ping pong balls) Diagnosis: bronchoalveolar lavage (BAL) BAL sample is stained with methamine silver to identify PCP that will look like disc shaped yeast (ovoid) Prophylaxis & Treatment Bactram (trimethaprim + sulfamethoxazole) Pentamidine can be used in individuals allergic to sulfa drugs
Giardia “Jungle Ride”
Associated with hikers and campers [backpack] that drink unfiltered or unpurified water from rivers or streams. This water is contaminated with animal/human feces that contain cysts [bubbles] of Giardia. Fecal-oral transmission [poop + brown water]. Foul smelling diarrhea Causes steatorrhea, or “fatty diarrhea” Cyst form differentiates into trophozoite form (flagellated with ventral sucking discs) [shields on boat] Trophozoites attach but don’t invade intertinal wall. Diagnostic: Trophozoites in stool Stool O&P is diagnostic test Elisa stool antigen test Treatment: Metronidazole
Entamoeba Histolytica “Entering the Historical Dig”
Cyst form – infectious when ingested from contaminated water. Associated with men who have sex with men. Found to be related to anal oral transmission. When cyst form resides in GI tract it differentiates into trophozoites which invades colon and can spread via portal circulation to liver. Right lobe of liver is most common involved site of amoebic liver abscess. RUQ pain + enlarged/tender livers. Pus/Abscess having the consistency of anchovy paste. Intestinal amebiasis: ulcerations in colon (flask shaped ulcers) invasive :. Bloody diarrhea Diagnostic: Stool O&P Under microscope: trophozoites that contain endocytosed RBCs ELISA antigen test on stool/serum Perform serology to detect entamoeba antibodies Intestinal biopsy may show flask-shaped lesions Treatment: Metronidazole treatment Paramycin – luminal agent to eliminate cysts Iodoquinol – luminal agent to eliminate cysts
Cryptosporidium “Tales from the Crypt”
AIDS patient – causes severe unrelenting diarrhea; In immunocompetent – mild watery diarrhea Unicellular, partially acid-fast organisms. Complete entire life cycle in a single animal and :. create infectious cysts passed through stool. Those at risk are people who swim in dirty waters, campers, and people who work with animals. Cysts composed of 4 motile sporozoites. Sporozoites attach to intestinal wall, cause diarrhea and small intestine damage. (however can cause colitis as well) Filtration can remove oocysts from infected water Treatment: Nitazoxanide Spiramycin treatment (macrolide) – not FDA approved in the US Supportive treatment – fluid status and electrolyte balance
Toxoplasma Gondii “OH HI, IZ MAKIN SUM TOXO”
Important to pregnant and immunocompromised. Intracellular parasitic protozoan that can infect any warm blooded animal. 30% of the world’s population carries toxoplasma. Transmission: 1. Cysts in raw uncooked meat 2. In contact with oocysts shed in animal (cat) feces 3. Transplacental transmission (ToRCHeS infection)
In immunocompromised patients it causes brain abscesses showing ring enhancing lesions on CT or MRI. Encephalitis. Brain biopsy to differentiate from CNS lymphoma. Clinical Symptoms: In healthy people it’s asymptomatic or causes flu symptoms Congenital Toxoplasmosis: • Intracranial calcifications, • Hydrocephalus, seizures • Chorioretinitis • Deafness Diagnosis by serology or biopsy where you are looking for intramuscular cysts. Even if serology is positive doesn’t mean the infection is active. Treatment: Sulfadiazine + Pyrimethamine Prophylaxis for HIV patients when CD4 count < 100 and IgG is positive for toxo: TMP-SMX
Trypanosoma Brucei Gambience/Rhodesiense “Prince Bruce to the Rescue”
Sleeping sickness Coma Tsetse fly vector [fly in tea] Endemic to western and southeastern Africa (Gambiense, Rhodesiense) After biting parasite moves from blood to lymph nodes Cervical lymphadenopathy, Axillary lymphadenopathy Recurrent fevers (undulating) Trypomastigotes seen on blood smear Variable surface glycoprotein coats, undergoing constant antigenic variation Motile with flagella Treatment: Melarsoprol – CNS infection Suramin – peripheral blood infection * Side effect profile that is very highly toxic
Naegleria fowleri “Naegleria Falls”
Associated with freshwater. Ameoba. Trophozoite enters CNS via cribiform plate primary amoebic meningoencephalitis (nuchal rigidity, fevers, altered mental status) Rapidly fatal disease with poor prognosis Affects patients involved in water-sports. Has been associated with nasal irrigation systems and contact lens solutions Diagnosis by lumbar puncture Treatment: Amphotericin for primary amebic meningoencephalitis
Trypanosoma Cruzi “Cruzin’ through Che’s Gas”
Parasitic protozoan located in South America or Central America. Chagas disease. Transmitted by Reduviid, or “Kissing bug” “Kissing Bug” bites around victim’s mouth, and deposits feces which can later be introduced by scratching area. Clinical Symptoms: Megacolon – acute abdomen/constipation Dilated cardiomyopathy Mega-esophagus * Unilateral periorbital swelling (Romana sign) characteristic of acute stage (from FA) Diagnosed by blood smear in active infection Serology and clinical symptoms in chronic infection Trypanosomes may be seen within cardiac myocytes on heart biopsy. Burrows into endocardium Treatment: Nifurtimox treatment OR Benznidazole No known effective treatment for chronic Chagas
Babesia “The Vampire Babes”
For 25% to 50 % of patients symptoms are subclinical or mild. Severe cases can cause malaria like symptoms/death. Vampire babes: blood-related symptoms (hemoglobinuria, hemolytic anemia, resulting jaundice) Americas, north-east. 25% of people in rhode island are seropositive for babesia. Tick-borne illness. Ixodes tick is a deer tick. Clinical symptoms: Sweat: fever Irregularly cycling fevers Higher risk of severe disease in sickle cell disease. Asplenic patients are more at risk to be symptomatic. Healthy people are scarcely symptomatic Diagnosis: thick blood smear. Maltese cross appearance in RBCs (tetrad of trophozoites. Differentiate from malaria) Treatment: Atovaquone: Ato-vampire queen Axithromycin: Macrolide
Plasmodium Species “The Queens and Warlords of Plasmodium”
Malaria – fever, headache, anemia, splenomegaly. Dx – blood stain and Giemsa stain to see parasites in RBCs Plasmodium malariae • Quartan fever cycle (72 hours) Plasmodium vivax and ovale • Hypnotist: produce dormant hypnozoites in hepatocytes • Tertian fever cycle (48 hours) Plasmodium falciparum • most severe malarial illness Irregular fever pattern • Neurologic symptoms parasitized RBC’s occlude capillaries in brain (Cerebral malaria) • Parasitized RBC’s occlude vessels to kidneys & lungs • Banana shaped in peripheral blood smear Treatment Chloroquine blocks plasomdium heme polymerase - Chloroquine S species are rare because of anti malarial resistance. - Chloroquine R only in Caribbean, central america west of panama canal Primaquine destroy hypnozoites hiding out in liver. Check for G6PD deficiency in patients otherwise will cause anemia. (P.vivax & ovale) Mefloquine for travelers to chloroquine resistant areas Atovaquone + Proguanil for travelers to chloroquine resistant areas In order to treat severe infections by P. falciparum you can use Artemisins Sickle cell disease is protective against P. falciparum Use IV artesunate for severe malaria infections. IV quinidine – used against resistant species (SE: cinchonism, including tinnitus)
Life Cycle of Virus 1. Anopheles mosquitoes carry sporozoites in saliva 2. Sporozoites mature to trophozoites in liver 3. Shizont divides into merozoites which burst from hepatocyte and infect RBCs Lifecycle continues in RBC: Trophozoite shizont merozoites infect RBCs Ring form of immature schizont shape in it Merozoites can also form gametocyte
Blood smear: trophozoite ring form within RBC, shizont containing merozoites; red granules (Schuffner stippling) throughout RBC cytoplasm seen with P. vivax/ovale
Leishmania Donovani “Desert Mainia”
Leishmania Braziliensis • Host = vertebrates (humans) • Cutaneous leishmaniasis disfiguring ulcers • Sandfly vector • Diagnosis: Amastigote is intracellular form, seen within macrophages (requires aspirates from marrow, spleen, skin lesions Leishmania Donovani • Visceral leishmaniasis • Black fever, or kala-azar • Bone marrow affected causing pancytopenia • Affects liver, spleen (hepatosplenomegaly), bone marrow • Donovani strain mediterranean, middle east, Africa Treatment: Stibugluconate for cutaneous leishmaniasis Amphotericin B for visceral leishmaniasis
Trichomoniasis Vaginalis “Tricks for Money”
Cervicitis capillary dilation, punctate hemorrhage (strawberry cervix) Vaginitis: • Burning • Itching • Malodorous yellow green discharge Diagnosis: wet mount (use for gardnerella, candida) motile trophozoites Vaginal fluid pH is generally 4.5 or above with infection STI treatment For both partners Metronidazole
Intestinal Nematodes “Super Worms!”
Enterobius vermicularis (pinworm) Female pin worms lay eggs at the anus; Fecal oral route; Typically affects children Scotch tape test shows eggs under the microscope Treatment: Pyrantel pamoate & Albendazole America Dude: Ancyclostoma duodenale and Necator americanus Two types of hookworms found in rural southern U.S. Hookwarm larvae penetrate skin of soles of feet Blood stream lungs GI tract Blood suckers iron deficiency anemia Diagnosis: eggs in stool & high eosinophil count Treatment: pyrantel pamoate & albendazole Ascaris lumbricoides Transmitted by eating eggs in contaminated food or water Once they hatch in the small intestine the larva migrate through the gut wall blood stream lungs. Once there they go through the capillaries into the alveoli and ascend into bronchus and are then swallowed back down again and mature into adults in small intestine. (Blood stream lungs GI tract) No red boots doesn’t enter through the feet Signs of malnutrition or respiratory symptoms; Major complication: intestinal obstruction (ileocecal valve) Diagnosis: eggs in stool, high eosinophil count Treatment: Albendazole (work by causing MT dysfx and :. eventually makes these worms immobile, but it you immobilize too many then you can induce obstruction. Don’t give to pregnant women either give PAM) Strongyloides stercoralis: Strong Guy Larvae penetrate skin of soles of feet Blood stream lungs GI tract Autoinfection: Strongyloides larvae hatch from eggs laid in intestinal wall, repenetrate wall, enter blood stream In immunocompromised, hyperinfection and dissemination of the worms Diagnosis: Larvae in stool, eosinophilia Treatment: Albendazole & Ivermectin Trichinella spiralis Periorbital edema + Vomiting + Fever Severe myalgias (Why? After ingestion of cysts from undercooked meat, larvae blood stream, travel to striated muscle. Larvae form cysts w/I striated muscle. Muscle inflammation) Diagnosis: eosinophilia Treatment: Albendazole
Tissue Nematode “Screamatodes III: Return of the Flesh Eaters”
Dracunculus medinensis - Transmitted by drinking contaminated water with copepods (crustaceans found in sea and fresh water) containing larvae - Adult females emerge from painful ulcer in skin - Diagnosis: peripheral eosinophilia - Treatment: slowly extract worm with a stick & Metronidazole Onchocerca volvulus - Black flies found around rivers in africa, central and south america - Black fly bites human host & deposits larvae in skin which penetrate skin and mature into adults. Adults produce microfilariae which migrate throughout the body. Microfilariae in eye causes blindness - Hyper and hypo-pigmented spots occur with onchodermatitis - 2nd most common cause of infectious blindness after trichoma - Diagnosis: eosinophilia, microfilariae seen in skin biopsy under microscope - Treatment: Ivermectin
Wuchereria bancrofti -elephantiasis: long standing lymphedema -Cough from microfilariae in lungs (HS reaction) -Transmitted by mosquitos -Diagnosis: organsisms seen on thick blood smear, eosinophilia -Treatment: diethylcarbamazine Toxocara canis -Transmitted from contamination of food with dog or cat feces -When parasitic larvae get in human they never mature. Visceral larva migrans. If gets to eye causes ocular larva migrans leading to blindness -Diagnosis: eosinophilia -Treatment: Albendazole Loa Loa (African eye worm) -As it migrates through subcutanous tissue of its host, it causes transient angioedema -Local subcutaneous swellings -Adult worms can migrate across conjunctiva -Diagonsis: microfilariae seen on blood smear, eosinophilia -L. loa transmitted by deer flies -Treatment: Diethylcarbamazine & Albendazole
Cestodes = Tapeworms “Cestode County Carnival”
Taenia genus – tents • T. Saginata (cattle) • T. Solium (Pig): Hooks on proglottid heads of T. solium seen on O&P • Neurocysticercosis looks like swiss cheese on Head CTs (suspect if pt. is immigrant/farmer and has symptoms of seizures/hydrocephalus) • Taenia eggs transmitted by water contaminated with animal feces • Seizures • Treatment: praziquantel + Albendazole for neurocysticercosis Diphyllobothrium latum – fish tapeworm • Resides in small intestine and causes diarrhea • B12/Cobalamin deficiency – megaloblastic deficiency • Is the longest tapeworm • Diagnosis: Proglottid segments seen on stool O&P • Treatment: Praziquantel & Niclosamide Echinococcus granulosus • Dogs are definitive host, sheep are intermediate host for E. granulosus • E. granulosus transmitted by dog feces • Eggshell calcifications in cyst on liver CT hydatid cyst in liver • When cysts rupture anaphylactic reaction and acute abdomen • Diagnosis: eosinophilia
Trematodes “San Franschisto Ocean Park”
Schistosoma mansoni - Swimmers at risk of infection: swimmer’s itch - Snails are intermediate host -
Schistosomas
-
Mature in liver and then migrate to other parts of body: -
Mansoni: mesenteric veins -
-
Large lateral spine, portal HTN
Japonicum: mesenteric veins -
-
migrate against portal flow to reach venous destination
Small spine, portal HTN, jaundice
Haematobium -
Veins of the bladder, large terminal spine, hematuria, bladder cancer
- Treatment: Praziquantel Clonorchis sinensis (Chinese liver fluke) - Snails are intermediate host - Biliary fibrosis, cholangiocarcinoma, pigmented gallstones - Operculated eggs on O&P - Treatment: Praziquantel Paragonimus westermani - chronic cough with bloody sputum - Snail is intermediate host - Transmitted through consumption of raw or undercooked crab meat with larvae - Diagnosis: operculated eggs on O&P - Treatment: Praziquantel
