Gram positive: look blue with the crystal violet stain.

Gram negative: look red from the crystal violet stain and instead absorb the safranin
from the counter stain.
Cell layers from the gram or + organisms
o Have multiple layers each.
o Both have a peptidoglycan layer that is the cell wall.
o Gram positive
2 layers.
Inner cytoplasmic membrane.
Outer peptidoglycan layer is thick with extensive AA cross-linking.
Have an outer cell wall with complex cross-linked proteoglycan, teichoic
acid, polysaccharides, and other proteins.
Low lipid content.
NO endotoxin.
NO periplasmic space.
NO porin channel.
Vulnerable to lysozyme and penicillin attack.
o Gram negative
3 layers.
Inner cytoplasmic membrane
Thin peptidoglycan layer with minimal AA cross linking.
Outer membrane with LPS.
High lipid content.
Have endotoxin - LPS
LPS layers (out to in)
o O-specific side chain (made up of oligiosaccharides) that
are useful for ags for the immune system to respond to.
o Water soluble core polysaccharide.
o lipid A that is toxic to humans as the gram negative
endotoxin. It is released as our immune system lysis the
cells and allows it to be released into the system.
Periplasmic space.
Porin proteins.
Resistant to lysozyme and penicillin attack.
Clinical relevance of the difference between gram +/-
o Gram + cell membranes have the ability to allow low molecular weight
substances through like dyes and antibiotics, while the gram does not, making
them more resistant.
4 main shapes of bacteria
o Cocci: spherical
o Bacilli: rods
Short rods are coccobacilli
o Spiral forms: comma shaped, S-shaped, or spiral shaped
 o Pleomorphic: lacking a distinct shape (like jello).
7 classic gram + bugs in humans
o Cocci
Form strips of cocci.
Streptococcus.
Enterococcus
Form clusters of cocci.
Staphylococcus.
o Rods
Produce spores
Bacillus
Clostridium
No spores
Corynebacterium
Listeria
Gram
o Diplococcic (only cocci for g-)
Neisseria
Moraxella
o Spirochetes (only g- spiral shaped)
Treponema
Sorrelia
Leptospira
o The rest are rods or pleomorphic
Exceptions to g+/-
o Mycobacteria
Weakly g+, stain better with acid fast.
o Spirochetes
Have a g- cell wall, too small to be seen on light microscope, better with
dark field.
Have few exposed membrane proteins and hidden internal periplasmic
flagella.
o Mycoplasma
No cell wall, only cell membrane so are neither g+/-
Pro vs eukaryotes
o Bac DNA is circular and can send out small circles called plasmids.
o Ribosomes
Pro
70S with 50S and 30S subunits.
Eu
80S
O2 spectrum for microbes
o Obligate aerobes
 Use all of the same O2 energy gaining mechanisms that humans use.
Possess catalase, peroxidase, superoxide dismutase.
o Facultative anaerobes
Prefer to use O2 like humans, but can also go to fermentation if need be
to continue to live
Possess catalase and SOD.
o Microaerophilic
Use only fermentation and can only survive a little O2 with the help of
only SOD.
o Obligate anaerobes
Have no defense against O2.
Have to take special precautions to collect and grow these bugs.
Catalase
o Allows for H2O2 to be broken down to water and O2.
G+ obligate aerobes
o Bacillus cereus
G+ facultative anaerobes
o Staph
o Bacillus antracis
o Cornyebacterium
o Listeria
G+ microaerophilic
o Enterococcus
o Strep
Some are facultative
G+ obligate anaerobes
o Clostridium
G- obligate aerobes
o Neisseria
o Pseudomonas
o Bordetella
o Legionella
o Brucella
G- facultative anaerobes
o Most other G- rods
G- microaerophilic
o Spirochetes
Treponema
Borrelia
Leptospira
o Campylobacter
G- obligate anaerobes
o Bacteroides
 Acid-fast obligate aerobes
o Mycobacterium
Mycoplasma O2 use system
o Facultative anaerobes
Virulence
o The ability to be pathogenic.
Flagella
o Long protein to help the bug move around.
o For either g+/-.
o Attaches to the basal body that inserts in all the cell walls that are available for
that organism.
Bugs with a single polar flagellum
o Vibrio cholera
Bugs with peritrichous flagella
o Have flagella all around the organism.
o E. coli and proteus mirabilis.
Bugs with periplasmic flagella
o Have a flagella hidden in the periplasmic space.
o Spirochetes.
Pilli
o AKA: fimbriae
o Straight filaments to make the bug look like a porcupine.
o Much shorter, do not move.
o Can help with cellular adherence to be called adhesions.
Neisseria gonorrhea and pilli
o Has pilli that allow it to adhere and infect buccal and cervical cells to cause
gonorrhea.
Bugs that need pilli just to hold on to the host
o E. coli and campylobacter jejuni to cause diarrhea in the gut.
o Bordetella pertussis to bind to ciliated respiratory epithelium to cause whooping
cough.
Capsules
o Protective walls that are made up of carbs to protect them from phagocytosis.
Composition of bacillus anthracis capsule
o Made up of AAs
India ink stain
o Stain is not taken up into the capsule and there appears to be a transparent halo
around the bug.
o Mainly used to identify Cryptococcus.
Quellung rxn
o Opsonization is used to bind abs to the capsule and that causes the capsule to
swell with water and this can be viewed on the microscope.
Opsonization
 o The ab binds to the capsule and the fc portion sticks out so that the
Mf/neutrophil can come by and better eat it.
Endospores
o Metabolically dormant forms of bugs that are resistant to heat, boiling, cold,
drying, and chemical agents.
o Consist of:
Cell membrane
Thick peptidoglycan mesh
Cell membrane
Wall of keratin-like protein
Outer layer called exosporium
o Bugs that make spores
Bacillis (aerobic)
Clostridium (anaerobic)
Biofilms
o Extracellular polysaccharide network that is like capsule.
o Provides a scaffolding for the bug to grow that protects it from antibiotics and
the immune system.
o Like a big bunker.
Bug that uses biofilms to cause prbs on prosthetics like IV catheters
o Staph. Epidermis
Facultative intracellular bugs
o Listen sally yer friend bruce must leave now.
o Listeria monocytogenes
o Salmonella typhi
o Yersinia
o Francisella tularensis
o Brucella
o Mycobacterium
o Legionella
o Nocardia
Exotoxins
o Proteins released by gram bac.
o Can cause lots of prbs.
Neurotoxins
o Exotoxins that act on the nerves or motor end plates to cause paralysis.
o Ex: tetanus and botulinum toxins.
Enterotoxins
o Act on the GI to cause diarrhea by Inhibiting NaCl reabsorbtion.
o Can cause infectious diarrhea or food poisoning.
Infectious diarrhea
o Will continue until the bug or host dies.
o Ex: e. coli, campylobacter jejuni, vibrio cholera, and shigella dysenteriae.
 Food poisioning
o From enterotoxins that are released into the food before it was eaten.
o Causes vomiting and diarrhea that lasts for less than 24 hours.
Pyrogenic exotoxins
o Stimulate the release of cytokines that can cause rash, fever, and toxic shock
syndrome.
o Ex: Staph aureus and Strep pyogenes.
Tissue invasive exotoxins
o Allows the bug to tunnel and destroy as it invades.
o Can destroy DNA, collagen, fibrin, NAD, RBC, and WBC.
Endotoxins
o Only present in gram bac.
o Normal part of the cell membrane that is only released in small amounts with
shedding or in large amounts with lysis of lots of cells.
o Endotoxin is synonymous with lipid A.
Septic shock
o Bacteria enter the blood and may pose no prbs or symptoms (bacteremia).
o If the bac causes a systemic response, then it can lead to sepsis.
o Septic shock occurs when there is a bad drop in blood pressure that leads to
hypoperfusion of the organs due to the host response to release endogenous
mediators of sepsis.
o Most common cause of death in the ICU.
Endogenous mediators of sepsis
o TNF, IL-1, NO
o Defends the host from the bugs at first, but then causes too much bad stuff to
happen and cuases too much vasodilation, hypotension, and organ dysfunction.
Treating septic shock
o 40% of pts with this die.
o Need to find what bug it is, so take cultures and then hit as many different bugs
as fast as possible.
o Support with SNS agonists and ventilation if needed and wait for culture to come
back.
Septic shock on vascular system
o Vasodilation leading to decreased BP and organ hypoperfusion.
Septic shock on the heart
o Myocardial repression leading to decreased CO, BP, and organ hypoperfusion.
Septic shock on kidneys
o Acute renal failure leading to decreased urine output, volume overload, and
accumulation of toxins.
Septic shock on lungs
o Adult RDS leading to hypoxia.
Septic shock on liver
o Hepatic failure leading to accumulation of toxins and hepatic encephalopathy.
 Septic shock on the brain
o Encephalopathy leading to alteration in mental status.
Coagulation system
o DIC leading to clotting and bleeding.
Bac genetics
o DS DNA that is in a single loop, haploid.
o Replicate with binary fission.
o Have sex through transformation, transduction, conjugation, and transposons.
Transformation
o A lysed bac will release its DNA fragments for them to be taken up by another
competent and related enough bac.
o The fragments will then be inserted into the hosts DNA sequence.
o This way, a helpful trait can be passed onto another bac.
Transduction
o A bacteriophage (Bf) takes the RNA/DNA and inserts it into the host bac.
o The Bf will attach with its feet to certain receptors on the bac (adsorption).
o The Bf will then use penetration to insert a tube into the bac and release the
DNA/RNA.
o In virulent Bfs: the DNA then takes over the RNA polymerase to code for more
proteins to make more Bfs until the cell is full and it lyses.
o In temperate Bfs. The DNA joins in with the host DNA and waits to be activated
where it does the other cycle.
The Bf also makes a repressor protein to block another Bf from attacking.
Generalized transduction
o When a Bf comes into the bac, it will eventually destroy the original bacs DNA.
o A little piece of this can survive and insert into the Bfs DNA.
o This DNA will then get packaged into a Bf and sent off to another bac.
o This increase the change that a new function can be gained in the other bac from
the new genetic material.
o This works well since there is a capsid protecting it during the transfer process.
Specialized transduction
o Happens with temperate Bfs where they insert into the hosts DNA to become a
prophage and make the bac lysogenic.
o Eventually the prophage is activated and it wants to leave the host, but there is
an error in the splicing and part of the host DNA is taken with the Bf to be placed
in the capsule.
E coli or cornyebacterium diphtheria and specialized transduction
o Occurs when the lambda Bf comes by and spices out part of the E coli genome to
take either the biotin (BIO) or galactose (GAL) gene to another bac.
o Cornyebacterium diphtheria is able to get its exotoxin gene this way.
o This is called lysogenic conversion.
Conjugation
o Main way to transfer DNA and can happen between unrelated bac.
 o Needs an F plasmid to send over the info.
o F(+) donor send info over to F(-) bac to turn that bac into F(+).
o One strand of the DNA is passed by a sex pilus that is long and narrow to the
other bac where duplication happens in both at the same time while still being
connected.
Transposons
o Mobile genetic elements that can be transmitted via any of the other mechs, but
do NOT need genetic homology to insert into the host.
o Very fast way to transfer info like antb resistance.
Strep vs staph
o Both are cocci.
o Strep lines up like a strip.
o Staph lines up in a group and is catalase positive, like a staff picture with a cat.
Classification of streptococci on blood agar
o Beta-hemolytic: complete lysis of blood and a pale area around the colony.
o Alpha-hemolytic: incomplete lysis that leads to green area around the colony.
o Gamma-hemolytic: no lysis around the colony.
Lancefield ags
o Carb chain (C carb) found on Strep bugs.
o Only 5 human pathogens and use A, B, or D.
o The remaining 2 dont have the ags and are called by their name:
Strep pneumoniae and Viridians group of strep.
Group A beta hemolytic
o Called strep pyogenes.
o Virulence factors
Lancefield group A.
M protein
Allows the cell to avoid complement and phagocytosis, but the
host can coat it with abs and get past those defenses.
Streptolysin O
O2 labile, inactivated by O2.
Allows the bug to lyse RBC and WBC, can order an ASO titer to see
if the body has high circulating levels.
Streptolysin S
O2 stable.
Allows the bug to lyse RBC and WBC, not antigenic.
Pyrogenic exotoxin (erythrogenic toxin)
The strains that have it can cause scarlet fever.
Can also be a super-ag that makes T cells pump out cytokines and
place the pt into septic shock.
o Strep throat, scarlet fever, rheumatic fever, and post strep glomerulonephritis.
o 4 dzs from strep pyogenes that cause prbs from local invasion or exotoxin
release.
 Strep pharyngitis
Strep skin infections
Scarlet fever
Strep toxic shock syndrome
o 2 dzs from strep pyogenes that cause prbs from delayed ab mediated dz
Rheumatic fever
Glomerulonephritis
o Strep pharyngitis
Classic red swollen tonsils/pharynx with purulent exudate on the tonsils,
fever, and swollen lymph nodes.
Lasts about 5 days.
Should swab with a rapid ag detection test (RADT) and/or culture to
confirm.
o Skin infections
Range from folliculitis (infection of hair follicle), pyoderma, erysipelas,
cellulitis (deep infection of skin cells that is red and swollen/hot to
touch), impetigo (Honey colored, vesicular, blistered, eruption, most
common in kids that becomes crusty and flaky, esp aroun the mouth).
Commonly caused by staph.
Erysipelas
Infection of dermis only.
Raised, bright red rash with sharp border that advances from the
site of infection.
Rarely caused by staph.
Pyoderma
Pustule that forms on face or extremity, breaks down after 4-6
days to make a thick crust.
Heals slowly to make a depigmented area.
Necrotizing fasciitis
Flesh-eating strep.
Enters the skin at the site of injury and rapidly moves along the
facial layer.
Within a day the pt develops swelling, heat, and redness.
Another day and the skin changes from red to purple to blue and
form large blisters (bullae).
The skin will eventually die.
Myositis may also occur.
May need to remove the fascia.
May present as fourniers gangrene:
o Involves the male genital and perineum area.
o Scarlet fever
Due to pyrogenic toxin.
 Scarlet red-rash that begins on the trunk and neck and spreads to
extremities, does not involve the face.
o Strep toxic shock syndrome
From pyrogenic toxin.
Presents like toxic shock from staph.
o Rheumatic fever
Usually occurs to kids 5-15.
Happens after pharyngitis, but not after a skin infection.
Fever
Myocarditis (from ab reactivity) that can lead to arrhythmias or heart
failure.
Years later, esp from recurring infections, rheumatic valvular
heart dz can occur with the mitral (most common) or aortic
valves.
Joint swelling (arthritis), esp acute migratory polyarthritis as the pain will
arise in rdm joints throughout the day.
Chorea (uncontrolled dance movements of the extremities that begins 2-
3 weeks after pharyngitis).
Subcutaneous nodules.
Rash with a red margin that spreads out from the center (erythema
marginatum).
o Acute post strep glomerulonephritis
Only caused by a few nephritogenic strains of strep and appears a week
after a sore throat or skin infection.
The ab complexes are deposited in the glomerular membrane and cause
damage.
Will present with puffy face, tea-colored urine, hypervolemia, and high
BP.
Good prognosis in kids.
What are the 3 bugs that cause meningitis in the first 3 months of life?
o Listeria monocytogenes
o E coli
o Group B strep
What are the bugs that cause meningitis after the maternal abs go away and before the
new ones are made?
o Neisseria meningitides
o Haemophilus influenzae
Group B strep
o Also called strep agalactiae.
o Think group B for baby.
o 25% of women have this normally in their vagina and can transfer to baby on
delivery.
o Presents with meningitis, pneumonia, and sepsis.
 o Neonates dont present with a stiff neck, look for fever, vomiting, poor feeding,
and irritability.
o In pregnant moms: bacteremia and sepsis that can lead to stillbirth or
spontaneous abortion.
o In other people: causes pneumonia or sepsis in people with other med prbs like
diabetes, malignancy, renal/liver prbs, and stroke in the elderly.
Viridans grp strep
o Alpha hemolytic.
o Commonly found as commensal in the GI, nasopharynx, and gingiva.
o Can cause 3 main types of infections: dental infections, endocarditis, and
abcesses.
o Dental infections
Some bugs like S. mutans can bind to teeth and ferment sugar to make
acid.
o Endocarditis
Dental work can allow the bug to enter the blood and attach onto a valve
that was previously injured by rheumatic fever, prolapse, or congenital
defect.
Attaches on with dextran.
Subacute bacterial endocarditis (SBE): low grade fevers, fatigue, anemia,
and heart murmers.
Different from acute infective endocarditis due to staph.
o Think green foliage that drops on to the heart valves with a root canal.
o Anginosus species group
Strep intermedius.
Microaerophilic and hide in organs.
Immediately look for occult abscesses with CAT scan.
Group D strep
o Enterococci and non-enterococci.
o Alpha or gamma hemolytic.
o Enterococcus
Grow in bile and NaCl.
Found in the bowel normally.
Nosocomial infections that cause UTI, biliary tract infections, bacteremia,
and SBE.
Refer to ID specialist if a multi-drug resistance bug is found.
o Non-enterococci
Strep bovis.
Grows in bile, NOT NaCl.
Thrives in GI tract.
Found in 50% of pts with colon cancer.
Strep pneumoniae
o Major cause of bac pneumonia and meningitis in adults, most common cause of
community acquired pneumonia and meningitis.
 o No lancefield ags.
o Alpha hemolytic.
o Major virulence factor is the polysaccharide capsule.
o Found with quellung rxn when mixed with anti-serum and methylene blue as the
capsule will swell.
o Optochin sensitivity
Allows to differentiate from strep viridens by placing optochin on the
agar.
Strep pneumoniae will be inhibited, strep viridens will not.
o Presents:
Suddenly
Shaking chills (rigors)
High fever
Chest pain with respirations
SOB
Alveoli of one or more lobes will fill with pus, bac, and exudate to make a
consolidation.
Pt will cough up a yellow-green sputum.
Nuchal rigidity if it is meningitis.
o Give vaccine to:
Elderly pts, immunocompromised, or asplenic.
o More and more antb resistance is occurring.
What are the 3 main causes of otitis media in kids?
o Strep pneumoniae, haemophilus influenza, and Moraxella catarrhalis.
Strep vs. staph
o Staph looks like a cluster of grapes on g stain and is catalase +.
o Strep looks like a line in a row on g stain and catalase -.
3 pathogenic species of staph
o staph aureus
o staph epidermidis
o staph saprophyticus
Staph colonized vs infected
o Lots of people can be colonized without showing symptoms and act as a carrier
Staph aureus
o Beta hemolytic.
o Looks gold on blood agar.
o Coagulase +.
o Has a microcapsule that has lots of virulence factors sticking out of it.
o Proteins that disable our immune system
Protein A: protects the bug from phagocytosis or opsonization by binding
to the Fc portion of abs.
Coagulase: leads to fibrin formation around the bug.
Hemolysins: kill RBCs, WBCs, neutrophils, Mfs, and platelets.
Leukocidins: kill WBCs. MRSA makes PVL that makes abcessess.
 Penicillinase: secreted form of beta lactamase that inactivates
penicillin.
Novel penicillin binding protein (transpeptidase): Protein needed to make
the cell wall that is inactivated by penicillin.
o Tissue tunneling protiens
Hyaluronidase (spreading factor): breaks down proteoglycans in
connective tissue.
Staphlokinase: lyses formed fibrin clots.
Lipase: degreades fats and oils that accumulate on the surface of the
body.
Helps to colonize the sebaceous glands.
Protease: kills tissue proteins.
o Assault proteins
Exfoliatin: exotoxin that cuases the skin to shed off (scalded skin synd).
Enterotoxins: heat stable toxins that cause food poisoning.
Toxic shock syndrome toxin (TSST-1): super ag that binds to the MHC II to
activate Mfs and cause massive T cell activation.
o Dzs caused by exotoxin release
Gastroenteritis
TSS
Scalded skin synd
o Dzs caused by direct organ invasion
Pneumonia
Meningitis
Osteomyelitis
Acute bacterial endocarditis (ABE)
Septic arthritis
Skin infections
Bacteremia/sepsis
UTI
o Gastroenteritis
Toxin release in the food causes food poisoning: increased peristalsis,
vomiting, diarrhea, abdominal pain, and sometimes fever.
Lasts 12-24 hours.
o TSS
Commonly caused by women that leave their tampons in too long, but
can happen to any adult.
Esp in surgical wounds, cutaneous and subQ infections, or infections
following childbirth or abortion.
Presents as:
Sudden
o Fever.
o Nausea.
o Vomiting.
 o Diarrhea
Few days
o Erythematous rash
o Desquamation of the palms and soles (skin peeling off)
o Maybe septic shock.
o Scalded skin synd
Typically happens to infants after umbilical cord is cut or kids with a skin
infection.
Comes from exfoliative toxin A or B.
Cleaves off the middle epidermis and leaves red moist skin underneath
that heals quickly.
o Pneumonia
Rare cause of pneumonia, but can be nosocomial.
Typically is superimposed on another lower respiratory infection to cause
necrotizing pneumonia that makes holes and causes empyema (pus in
pleural space).
o Meningitis, cerebritis, and brain abscess
Present with high fever, stiff neck, headache, obtundation, coma, and
focal neurological signs.
o Osteomyelitis
Typically occurs in boys under 12.
Infection of the bone that spreads hematogenously and presents as
fever, shakes, and redness over the tissue above the bone.
o ABE
Presents suddenly with a high fever, chills, myalgias.
Vegetations grow quickly and can embolize to the lungs (right heart) or to
the brain (left heart).
Can be exacerbated by IV drug users that targets the tricuspid valve.
o Septic arthritis
Closed infection of the joint that is marked by yellowish fluid with lots of
neutrophils.
Found in kids and adults over the age of 50.
Can lose the joint if not treated quickly.
o What are most minor skin infections caused by?
Strep pyogenes or staph aureus.
They are almost impossible to differentiate.
o Impetigo
Contagious infection that occurs on the face, esp around the mouth.
Small vesicles lead to pustules to crust over, become honey colored, wet
and flakey.
o Cellulitis
Deeper infection of the skin that looks red, hot, shiny, and swollen.
o Local abscesses
Collection of pus.
 o Furuncles
Abscess of a hair follicle that penetrates deep into the subQ.
o Carbuncles
Many furuncles that combine under the skin to make painful lesions.
o Wound infections
Need to be reopened and left to heal as secondary intention.
o Blood and catheter infections
Can go from the skin and colonize on central venous catheters that can
lead to bacteremia, sepsis, TSS, or endocarditis.
o MRSA
Multi-drug resistant.
Typically occurs from the selective pressure of antb therapy in the
hospital.
Works by encoding a new penicillin binding protein 2A that is able to take
over building of the cell wall once the original protein is blocked by
penicillin.
o Community acquired MRSA (CA-MRSA)
Found out in the community, esp with outbreaks of sport teams.
Staph aureus is commonly found in the nasopharynx and skin folds.
There is a propensity to develop skin or soft tissue infections from the
bug and contacts are common places that act as a carrier.
Commonly carries panton-valantine leucocidin (PVL) toxin to create
abscesses.
Staph epidermidis
o Coagulase .
o Found normally on the skin, but can infect someone when they are foley
catherterized or have an IV line.
o Can also cause infections of prosthetic valves, joints, and dialysis catheters.
o Will form biofilms on the things inserted into the body.
Staph saprophyticus
o Coagulase -.
o Is the second most common case of UTI in women who are sexually active.
o Community acquired.
2 g+ spore forming bacilli
o Bacillus
Aerobic
o Clostridium
Anaerobic
2 pathogenic species of g+ aerobic spore forming rods
o bacillus cereus and bacillus anthracis
Bacillus anthracis
o Spread occurs from animals or animal products like feces or goat drums.
o Contains a unique capsule that is composed of protein (poly-D-glutamic acid)
that comes from pOX2, only bac to have this.
 o Forms a spore that is very resistant to heat, drying, UV, disinfectants and can
survive in the soil for years dormant.
o Makes toxins once it comes in contact with the lungs, intestines, or skin wound.
o Virulence agents pXO1 and pXO2 are only activated in the conditions of being
within the host.
o The spores are taken up by the host Mfs and then they begin to germinate.
o Skin: causes a localized tissue necrosis that is a painless black lesion with a rim of
edema.
Malignant pustule cuz it can go to the blood and cause death w/o antb.
Sometimes severe skin edema and shock can occur too.
Most common route of entry.
o Pulmonary inhalation: wool sorters dz. Spores are taken up by alveolar Mfs and
transported to the mediastinal and hilar LNs where they germinate.
Mediastinal hemorrhage that results in mediastinal widening around the
heart.
Pleural effusion can also occur.
o GI: commonly causes death and is rare.
Can come from ingestion of the spores, typically from tainted meat.
The bug activates and causes there to be necrotic lesion and release of
the exotoxin.
o Exotoxin
Comes from the plasmid pXO1 that encodes 3 protiens.
Edema factor (EF): Decreases cAMP, impairs neutrophils, and
causes severe edema.
Protective ag (PA): Promotes entry of EF into phagocytic cells.
Lethal factor (LF): inactivates protein kinase to stimulate Mfs to release
TNF and IL-1 that lead to death.
Bacillus cereus
o Different from anthracis: motile, non-encapsulated, resistant to penicillin.
o Causes food poisoning when it delivers its spores to food that is later ingested
and can survive the cooking. Must be killed with high temps or by refrigeration.
Bacillary dysentery.
o Enterotoxins
Heat labile toxin: similar to LT from E coli and the cholera toxin.
Nausea, abdominal pain, and diarrhea lasting 12-24 hours.
Heat stable toxin: similar to the food poisoning from staph aureus, short
intubation period.
Nausea, vomiting, and little diarrhea
o Remember antb will not help in this case.
Clostridium
o G+ anaerobic spore forming rods.
o Causes botulism, tetanus, gas gangrene, and pseudomembranous colitis.
o Pt will die from rapid secretion of exotoxins and enzymes unless they receive
quick medical care.
 Clostridium botulinum
o Produces a lethal neurotoxin that quickly causes food poisoning by blocking the
release of ach from the ANS and motor end plate to cause flaccid paralysis.
o Adult botulism
Associated with home canned veggies or eating smoked fish.
Can be killed if the food is raised to the appropriate temp first, but the
toxin cant be once its made.
Pts present with:
B/l cranial n. palsies, diplopia, and dysphagia.
Followed by progressive muscle weakness, respiratory distress,
and death.
o Infant botulism
Often times is due to the baby eating honey that still have some spores
present.
Once the spores reach the GI, they can activate and colonize to start
producing spores.
Present with :
Constipation for 2-3 days, then difficulty swallowing and muscle
flaccidity.
Will need supportive care until the toxin is neutralized.
Clostridium tetani
o Spores are typically found in dirt and animal feces.
o Once a puncture wound is inflicted by something, maybe even a rusty nail, then
the spores will activate in the necrotic tissue that is now anaerobic.
o Releases its exotoxin: tetanospasmin that causes tetany of the muscles.
o Presents as lock jaw called trismus and grinning expression called risus
sardonicus from the spasm of the facial muscles.
o Immunization of tetany
Given with diphtheria and pertussis in a DPT shot at 2, 4, 6, and 18
months and at 4-6 yo.
A booster of just the tetanus is then given every 10 years.
Clostridium perfringens
o AKA: gas gangrene.
o Spores are found in the soil and like to live in necrotic anaerobic spaces that
have been caused by trauma from thing like war.
o Cellulitis/wound infection
The bug grows and infects the necrotic tissue and secretes exotoxins to
destroy the surrounding tissue.
Presents with a moist, spongy, crackling consistency.
o Clostridial myonecrosis
The trauma went into the muscle and the bug was able to infect the area.
Secretes exotoxins into the surrounding muscle to destroy it.
 These anaerobic bacteria digest the carbs in the area and release gas
within the muscles and the surrounding tissue.
A thin black fluid comes out of the skin.
Fatal unless treated very early.
o Diarrheal illness
Can germinate in foods like poultry, meats, and gravy.
Leads to toxin in the gut and subsequent watery diarrhea.
A rare form can lead to hemorrhagic necrosis of the jejunum, but it is
very uncommon in the US.
Clostridium difficile
o Pseudomembranous enterocolitis.
o Normal gut flora but can be allowed to take over when too many of the other
bugs have been killed off with antbs.
o Once it grows large enough, it will begin to produce exotoxins.
Toxin A: diarrhea.
Toxin B: cytotoxic to colonic cells.
o Presents with severe diarrhea, abdominal cramping, and fever.
G+ non-spore forming rods
o Corynebacterium diphtheriae and listeria monocytogenes.
o Affect pediatric pts.
Corynebacterium diphtheriae
o Responsible for diphtheria.
o Attaches onto the nasopharynx and develops into a dark thick patch of exudate
that releases exotoxins that target the heart and neurons, messing with their
protein synthesis.
o Kid presents with sore throat and fever.
o Culture on potassium tellurite agar and Loefflers coagulated blood serum.
o Treatment:
Antitoxin, antb, DPT vaccine.
o Bug must first get the toxin gene from a Bf before it can make the exotoxin.
o Exotoxin has 2 subunits
B subunit binds to target cells and allows A to enter and block protein
synthesis by blocking elongation factor.
o Diptheroids
Other coryneform bacteria.
They have similar morphological features with the coryenform bac like
being little rods.
Use the genera of Corynebacterium, brevibacterium, microbacterium,
and arcanobacterium.
Normally found in the soil, water, skin, and mucous membranes.
Typically they are simply contaminants in the culture from the lab
sample, but can also be community derived or nosocomial.
Rhodococcus equi
 o G+ aerobic nonmotile bacillary bac (rod like that can grow long, curved, clubbed,
and short branching filaments).
o Typically grows in manure and soil and infects animals.
o Infects humans if they are immunocompromised like from having HIV or organ
transplant.
o Forms infiltrates, single or multiple nodules that caviate and pleural effusions.
Upper lobe lung nodules and cavities that form air-fluid levels are
characteristic.
o May stain partially acid-fast.
o TB rarely forms the air-fluid levels though.
Listeria monocytogenes
o Facultative anaerobic non-spore forming G+ rod.
o Lab may think it is a diptheroid until they grow the culture in a cold
environment.
o Listeriolysin O: major virulence factor that allows it to avoid phagolysosomes.
o Think of the list to know why its bad: pregnant women, neonates, meningitis in
the elderly, and immunocompromised.
o Pregnant women
Infection occurs in the 3rd trimester when cell mediated immunity
decreases.
Typically presents as bacteremia and sepsis from eating soft cheeses, cold
cuts, and coleslaw. Thus, they are told not to eat those. Although it can
also come from milk or butter in some cases.
The fetus can either die or will come out premature with an active
infection.
o Fetus and neonate
Is acquired in utero or gets the infection when delivered vaginally in a
asymptomatic mom.
The vaginal mode of delivery presents with neonatal meningitis about 2
weeks after delivery and accounts for 20% of all neonatal cases of
meningitis.
o Elderly and immunocompromised
Listeria is the second most common cause of meningitis after
pneumococcus in pts over 50.
Listeria is the most common cause of meningitis in pts with lymphoma,
on corticosteroids, or organ transplant.
Listeria commonly causes meningitis in pts with AIDS.
o Overall, mainly affects pts with cell mediated immune prbs
Listeria is a facultative intracellular bug that can resist phagocytosis and
live in the phagocytes.
A competent immune system can activate the phagocytes to try harder
and kill the bug.
 What are the 3 bac that cause meningitis when baby comes out of vaginal canal in the
first 3 months and when the maternal abs are gone, but the baby doesnt have them
yet?
o First 3 months: Listeria monocytogenes, E coli, Group B strep.
o Later: niesseria meningitides and H. influenzae.
Only pathogenic g- cocci
o Neisseria meningitides and Neisseria gonorrheae.
o Hang out in pairs and are called diplococci, kidney bean shaped that sit face to
face with each other.
Neisseria meningitides
o AKA: meningococcus.
o Can cause meningococcemia.
o Virulence factors:
Capsule: polysaccharide capsule that make it phagocytic resistant unless
there are abs for it.
Endotoxin: LPS can be released in blebs and cause blood vessel damage
(hemorrhage) and sepsis.
Can be seen on the skin as petechiae and can also damage the
adrenals.
IgA1 protease: only found in pathogenic forms of Neisseria.
Cleaves the IgA ab in half.
Can steal Fe from humans in a passive mech.
Pili: allow for attachment to the nasopharyngeal airway and undergo ag
rearrangement.
o Carrier state
About 5% of the population are carriers and have developed natural
immunization against the bug.
The bug just lives on the nasopharynx as normal flora.
o High risk groups
Infants 6 months to 2 years.
Moms abs only protect them for 6 months.
Army recruits.
Lots of young men are placed close together in conditions that
reduces their immune systems.
The result is that the carriers will easily be able to spread the dz.
College freshman.
From living in dormitories.
o Meningococcal dz
Rarely does the bug leave its happy home in the nasopharynx and enter
the blood stream, but it can cause meningococcemia with the
characteristic petechial rash.
Also presents with spiking fevers, chills, arthralgia, and muscle
pains.
 Look very ill.
Fulminant meningococcemia (waterhouse-friderichsen synd)
Shock: B/l hemorrhage into the adrenal glands occurs leading to
adrenal insufficiency, abrupt hypotension, tachycardia, enlarging
skin petechial skin lesions, DIC, coma, and death.
Meningitis
Most common form of meningococcal dz.
Typically occurs in infants less than 1 yr old.
Infants display nonspecific findings of infection like fever,
vomiting, irritability, and/or lethargy.
There may be bulging anterior fontanelle in infants and there may
be nuchal rigidity in slightly older infants.
Petechial skin rash is characteristic and occurs when
meningococcemia occurs with meningitis.
Caused mostly by n. meningitides now that there is a vaccine for
H. influenza.
Grows best on chocolate agar (blood agar that has been heated to look
brown) and given antbs to eliminate the competition in an atmosphere of
CO2.
Neisseria gonorrhoeae
o AKA: gonococcus.
o 2nd most common STD.
o Developing more and more antb resistance.
o Virulence factors
Pili: adhere to the host to infect and to prevent phagocytosis.
Undergoes recombination frequently so that it can evade the
immune system and vaccines.
Outer membrane porins: PorA and PorB help to invade into epithelial
cells.
Opa proteins: another class of outer membrane proteins that promote
the adherence and invasion into epithelial cells.
o Taken up into the ovarian tube where it uses LPS with the other factors to get
into the subepithelial space through endocytosis to cause systemic infection.
o Gonococcal dz in men
Urethritis, painful urination, purulent urethral discharge.
Can be complicated with epididymitis, prostatitis, and urethral strictures.
Can still transmit if there are no symptoms.
MSM: rectal gonococcal infection that leads to anal pruritus (itchy
bumps), tenesmus (need to poop a lot), and/or rectal bleeding and
purulent discharge.
o Gonococcal dz in women
Can also present with painful urination and discharge, but it is less
common.
 Most are asymptomatic.
If they are symptomatic, typically present with lower abdominal pain,
pain with sex, and purulent vaginal discharge.
Can infect the cervix and can become reddened and friable with purulent
exudate.
Can progress to pelvic inflammatory dz (PID)
Endometritis, salpingitis, and/or oophoritis (infection of the
ovaries).
Presents with fever, lower abdominal pain, abnormal menstrual
bleeding, and cervical motion tenderness (when touched).
50% of pts have this after menstruation where it is better able to
move up the genital tract.
An IUD makes it more likely for the dz to progress to PID.
Complications of PID
Sterility: risk increases with each infection from scarring of the
ovarian tubes.
Ectopic pregnancy: increased with previous salpingitis from
scarring that may impede the travel of the egg down the tube.
Abscesses in the ovarian tubes, ovaries, or peritoneum.
Peritonitis: Bac can travel from the ovarian tubes to infect the
peritoneum.
Peri-hepatitis (Fitx-High-Curtis synd): infection of the capsule
around the liver that presents with RUQ pain and tenderness that
may follow PID.
o Gonococcal dz in men and women
Gonococcal bacteremia: can rarely get in the blood stream.
Causes fever, joint pains, skin lesions on the extremities,
pericarditis, endocarditis, and meningitis.
Septic arthritis: infection of 1-2 joints.
Most common septic arthritis in the young, sexually active
individuals.
Confirmed by finding g- diplococci in WBCs that are taken out of
the joint.
o Gonococcal dz in infants
Transmitted from pregnant mom to baby during delivery.
Results in ophthalmia neonatorum: infection of the eye that destroys the
cornea and causes blindness.
Can also happen in adults with the exchange of fluids.
Moraxella (branhamella) catarrhalis
o Causes otitis media and upper respiratory infection in pts with
COPD/emphysema or in the elderly.
What 3 bac are the main causes of otitis media?
o Strep pneumonia, H influenza, and Moraxella catarrhalis.
 What are the 5 bac that typically cause endocarditis?
o HACKE group
o Haemophilus
o Actinobacillus
o Cardiobacterium
o Kingella
o Eikenella
Enterics
o G- bacteria that are normal bacterial flora.
o Enterobacteriaceae, vibrionaceae, pseudomonadaceae, bacteroidaceae.
Biochemical classification of the enterics
o Ability to ferment lactose
E coli and most of the other enterobacteriaceae are able to.
Salmonella, shigella, and pseudomonas aeruginosa are not able to.
o Ability to split urea, liquefy gelatin, decarboxylate certain AAs, and produce H2S.
Growth media of the enterics
o EMB agar (eosine methylene blue):
Methylene blue inhibits g+ bacteria, leaving colonies of lactose
fermenters to become deep purple to black.
E coli takes on a metallic green sheen.
o MacConkey agar: bile salts in the medium inhibit g+ bac, leaving lactose
fermenters to develop a pink-purple coloration.
Fecal contamination of water
o By looking for the presence of E coli in the water, you are able to check to see if
there is poop in the water.
o Presumptive test:
Add the water to a nutrient broth like agar that has lactose in the mix.
The vial has 2 test tubes and a dye that allows you to check if acid and gas
are produced.
A positive test is that something grew in there that can ferment the
lactose, but were not sure if its from the E coli yet.
o Confirmed test
Streak 2 EMB plates with the water and grow one at 45.5 for the E coli
(most others cant grow at this temp) and another at 37.
E coli should have a metallic green look.
Compare the colonies.
o Completed test
Place the colony of the metallic green in another test tube to see if it is
positive.
Antigenic classification of enterics
o O ag: the outer most part of the LPS, differs depending on the bug.
o K ag: this is the capsule ((Kapsule)) that covers the O ag.
o H ag: the ag that makes up the flagella of motile bac.
 Shigella does not have one.
Salmonella does have one.
Pathogenesis of the enterics
o Typically produce 2 types of dz:
Diarrhea w/or w/o systemic invasion.
Various other infections including UTI, pneumonia, bacteremia, and
sepsis esp in debilitated hospitalized pts.
o Diarrhea:
No cell invasion:
The bug just binds to the GI wall and releases enterotoxins that
causes watery diarrhea w/o other systemic symptoms like fever.
There can be some GI cell death.
Ex: E coli and vibrio cholera.
Invasion of the epithelial cells.
The bac have virulence factors that allow them to penetrate the
cells and digest everything around them.
The immune system comes in to fight and some of it gets placed
into the stool.
There is also cell death that places RBCs in the stool too.
Can present with fever.
Ex: enteroinvasive E coli, shigella, and salmonella enteritidis.
Invasion of LNs and blood stream
Abdominal pain, diarrhea containing WBCs and RBCs.
Systemic symptoms like fever, headache, and WBC count
elevation.
Can progress to mesenteric LN enlargement, bacteremia, and
sepsis.
Ex: salmonella typhi, yersina enterocolitica, and campylobacter
jejuni.
o Various other infections
The enterics are normally very happy living with us, but in hospitals and
nursing homes, they can develop antb resistance and rise against the
masters.
The bugs that cause this sometimes called nosocomial g-s.
Ex: E coli, klebsiella pneumoniae, proteus mirabilis, Enterobacter,
serratia, and pseudomonas aeruginosa.
Family enterobacteriaceae
o E coli
Normally does not cause any prbs, but from the enteric orgy in the GI
they can get the genetic info needed to make virulence factors.
Virulence factors
Mucosal interaction:
o Mucosal adherence with pili (colonization factor).
 o Ability to invade intestinal epithelial cells.
Exotoxin production
o Heat labile and heat stabile toxin (LT and ST).
o Shiga-like toxin.
Endotoxin
o LPS.
Iron binding siderophore
o Obtains Fe from human transferrin or lactoferrin.
Dzs from E coli with virulence factors
Diarrhea, UTI, neonatal meningitis, G- sepsis (esp in debilitated
hospital pts).
E coli diarrhea
Can affect infants or adults worldwide.
Often kills infants from dehydration as they have not developed
an immunity.
Can also affect travelers and their diarrhea is called Montezumas
revenge.
o Enterotoxigenic E coli (ETEC)
Causes travelers diarrhea.
Binds to GI with pili.
Releases exotoxins LT (like cholera) and ST to inhibit the resorption of
NaCla and stimulate the secretion of Cl and HCO3 into the lumen.
This causes very watery diarrhea where the stool looks like rice water
diarrhea.
o Enterohemorrhagic E coli
Have pili to hold onto the GI.
Releases Shiga-like toxin (verotoxin) to inhibit the 60S ribosome that
ultimately kills the GI epithelium.
Results in a very bloody stool and abdominal cramps termed hemorrhagic
colitis.
o Hemolytic uremic synd
Presents with anemia, thrombocytopenia, and renal failure that leads to
uremia.
Due to infection with E Coli 0157:H7.
Related to eating bad hamburger from fast food restaurants.
o Enteroinvasive E Coli (EIEC)
Has a plasmid that allows the E coli to invade the epithelial cells and
produce a little bit of shigella like toxin.
The result is fever, WBC infiltrate in the diarrhea, and blood in the
diarrhea too.
o Remember that E coli can make diarrhea that looks like cholera or shigella
depending on what plasmid it contains.
o E coli UTI
 If the E coli has the pili plasmid, then it can travel up the urethra and
cause cystitis or pyelonephritis.
Most commonly happens in women and catheterized pts.
Presents with dyuria (painful urination), frequent urination, and always
feeling like a full bladder.
Look for a colony count of over 100,000 in the urine.
o E coli meningitis
Common cause of neonatal meningitis, esp during the first month of life.
Remember that group B strep is the most common cause.
o E coli sepsis
Most common cause of g- sepsis due to LPS, especially in debilitated
hospital pts.
o E coli pneumonia
Common cause of hospital derived pneumonia.
Klebsiella pneumoniae
o K for killer.
o O ag and K ag.
o Causes pneumonia is debilitated pts (hospital and alcoholics) that will commonly
lead to sepsis.
o Can also cause UTIs in pts with foley catheters.
o Violent pneumonia that kills lung tissue and sends up a thick sputum coughed up
that looks like red current jelly from the capsule surrounding the O ag.
Proteus mirabilis
o Is very motile and will spread all over the plate when streaked.
o Has cross reactivity with Rickettsia so that it can be mixed with the serum of a pt
to see if they have rickettsia.
o Is a common cause of UTIs, esp nosocomial, urine will be alkaline from the
organism being able to split urea and release NH3 into the urine.
Enterobacter
o Very motil g- rod that is flora in the GI.
o Sometimes nosocomial in the hospital.
Enterobacter serratia
o Known for its production of a bright red pigment.
o Can cause UTIs, wound infections, or pneumonia.
Shigella
o 4 species of shigella
dysenteriae, flexneri, boydii, and sonnei.
o All are non-motile, does not ferment lactose, or split urea.
Remember that E coli ferments lactose and salmonella can split urea.
o Humans are the only hosts.
o Infections happen from the fecal-oral route and occur in young kids and the
elderly (esp in nursing homes) it is always a pathogen.
o Acts like a EIEC so that it invades GI cells and releases shiga toxin.
 o Because of the invasion, it causes there to be a fever, there is also abdominal
pain, and diarrhea.
o Will find RBCs and WBCs in the diarrhea.
o Upon scope, you will find ulcers and the pt will not be able to absorb water and
electrolytes through those damaged section of the GI.
Salmonella
o Non-lactose fermenter, motile, and splits urea.
o Contains the Vi ag that is like the K ag to surround the O ag.
This capsule makes it more common for asplenic pts to have this
infection and make it difficult to clear.
o Sickle cell pts are more likely to get salmonella osteomyelitis (bone infection).
o 1 main species: salmonella cholerasuis that has 3 subgroups.
Salmonella typhi
Salmonella cholera-suis
Salmonella enteritidis
o They all live in the GI tract of animals and are zoonotic except for salmonella
typhi which only lives in humans.
o Always a pathogen.
Causes 4 dz states:
Typhoid fever
Carrier state
Sepsis
gastroenteritis
Typhoid fever
o Salmonella typhi is facultative intracellular parasite.
o After invading the GI epithelium, it goes to regional LNs and then to the organ
systems and live inside the monocytes.
o Presents 1-3 weeks after exposure as:
Fever, headache, and RLQ abdominal pain that looks like appendicitis,
rose spots on light skinned people.
As inflammation of the organs increases, there may be splenomegaly.
Carrier state for salmonella
o Some people can asymptomatically carry salmonella in their gallbladders and
spread it in their feces.
o Some need to have their gallbladders removed to clear their infection.
Sepsis and salmonella
o Salmonella choleraesuis can get into the blood and swim to infect the lungs,
brain, and bone.
Diarrhea (gastroenteritis) and salmonella
o Most common type of salmonella infection.
o Presents as nausea, abdominal pain, and watery diarrhea (sometimes with
mucous or blood).
o Fever happens in 50% of pts.
 o Antbs dont work with this infection.
Yersina enterocolitica
o Motile g- rod that causes gastroenteritis.
o Not an enteric.
o Transferred by the fecal-oral route which is different from being transferred by a
flea bite as is in yersina petis.
o Comes from contaminated local milk or fecal contaminated water.
o Presents as:
Fever, diarrhea, and abdominal pain in the RLQ (like appendicitis).
There will be ulceration in the terminal ilium.
o Pathogenesis:
Invasion: Is able too invade the GI wall and go to the regional LNs and the
blood stream leading to mesenteric LN swelling and sepsis.
Enterotoxin: able to produce a toxin that is similar to the heat stable
toxin in E coli that causes diarrhea.
Vibrio cholera
o Curved g- rod with a single polar flagellum.
o Mainly affects travelers and kids in endemic areas.
o Fecal-oral route.
o The bug attaches itself to the GI wall and releases the cholera toxin choleragen,
which is like a worse version of ETEC.
o Leads to severe dehydration that can lead to death.
Presents as diminished, sunken eyes, and poor skin turgor.
o Choleragen
Results in continual activation of cAMP that leads to the loss of
resorption of NaCl and the active secretion of NaCl.
There is then a massive amount of water and electrolyte loss from
everything getting pulled out of the system osmotically.
Vibrio parahaemolyticus
o Leading cause of diarrhea in japan as it comes from eating uncooked seafood.
Campylobacter jejuni
o Camps out in the jejunum to cause diarrhea.
o Looks like V cholera in that it is a g- curved rod with a single polar flagellum.
o Zoonotic dz that lives in the jejunum of animals and can come from
unpasteurized milk.
o Can come from fecally contaminated water.
o Presents as fever and headache, followed half day later of abdominal cramps
and a bloody loose diarrhea.
o Invades the small intestine and spreads systemically like Salmonella typhi and Y
enterocolitica.
o Also produces a toxin similar to LT.
What are the 3 most common causes (bugs) of diarrhea in the world?
o Campylobacter jejuni, ETEC, and rotavirus.
 H pylori
o Most common cause of duodenal ulcers and chronic gastritis with aspirin being
the second leading cause.
o Can be cultured from gastric biopsy where it localizes to the superficial lining
cells.
o Growth is inhibited by bismuth salts like from pepto-bismol.
Family bacteroidaceae
o Obligate anaerobic G- rods that comprise 99% of the flora in the GI tract.
o Also found in the mouth and vagina.
o Bacterioides fragilis
Does NOT have lipid A in the cell membrane, one of the few g- that does
not have it.
Low virulence, but it goes nuts when there is a perforation of the gut that
allows it to enter the peritoneum and form abscesses that can lead to a
systemic infection.
Abscesses also happen in pts with a septic abortion, pelvic inflammatory
dz (tubo-ovarian abscess, or pts that have an IUD.
Rarely involved in pneumonias.
o Bacteroides melaniogenicus
Produces a black pigment on blood agar.
Lives in the mouth, vagina, and intestine.
Involved in necrotizing anaerobic pneumonias caused by aspiration of
lots of sputum from the mouth during a drunken state or seizure.
Can also cause periodontal dz.
o Fusobacterium
Just like Bacteroides melaniogenicus, but it can also cause abdominal and
pelvic abscesses and otitis media
Anaerobic g+ cocci
o Peptostreptococcus (chain of cocci) and peptococcus (cluster of cocci).
o Normal flora in the mouth, vagina, and intestine.
o They are found in abscesses and aspiration pneumonias.
Strep viridians
o G+ microaerophilic and frequently found in abscesses since they hate O2.
o Ex: Strep anginosus and strep milleri.
What are the 4 most common ways to get a nosocomial infection?
o 4 Ws
o Wind (ventilator), wire (IV), Water (foley catheter), and wounds.
What are the 4 most common multi-drug resistant g- bac that attack debilitated hospital
pts?
o Pseudomonas, acinetobacter, stenotrophomonas, and burkholderia.
Pseudomonas aeruginosa
o G- rod, non-lactose fermenter, obligate anaerobe.
o Is only able to infect sick people, like in the hospital.
o Once inside a weakend pt it is able to proliferate.
o Produces a green florescent pigment: pyoverdin and Produces a blue pigment:
pyocyanin that give wounds and agar a green-blue color that smells like grapes
(sweet/sour).
o Produces exotoxin A that stops protein synthesis like diphtheria.
o Contains a capsule that antiphagocytic and help to adhere to target cells.
o Pneumonia
CF pts: this bug causes chronic pneumonia that will progressively destroy
their lungs.
Immunocompromised pts: cancer and ICU pts are very susceptible to this
bug for pneumonia.
o Osteomyelitis
Happens in relation to wounds.
Diabetic pts: this bug can infect the diabetic abscesses that leads to bone
infection.
IV drug users: increased risk of osteomyelitis in the vertebrae or clavicle.
Children: can happen with any wound, but commonly when they step on
a nail with sweaty tennis shoes on, as pseudomonas aeruginosa loves the
warm wet environment.
o Burn-wound infections
Easily makes a home in the burn wounds that can lead to fatal sepsis.
o Sepsis
Easily creates a sepsis environment that comes from wounds, winds, or
water.
Has a high mortality rate.
o UTIs, Pyelonephritis
Happens to debilitated pts that have a foley catheter in.
o Endocarditis
P aeruginosa and staph aureus are frequent causes of right heart valve
endocarditis in IV drug users.
o Malignant external otitis
Pseudomonas external ear canal infection burrows into the mastoid
bone, esp in elderly and diabetic pts.
o Corneal infections
Happens in contact wearers.
o Mnemonic
BE PSEUDO
Burns
Endocarditis
Pneumonia
Sepsis
External malignant otitis media
UTI
Diabetic osteomyelitis
 Burkholderia cepacia
o Related to pseudomonas.
o Oxidase positive, aerobic g- baclillus.
o Able to grow in water, soil, plants, and animals.
o Very antb resistant.
o People with CF are most likely to be affected and present with:
Asymptomatic carriers, bronchiectasis, or a rapidly progressive
pneumonia with bacteremia
Acinetobacter
o Aerobic g-.
o Found in the soil and water and is able to survive in the environment (like a
hospital) for a long time.
o Most common type is acinetobacter baumannii.
o Very similar to pseudomonas and can looks like Neisseria to the lab techs.
Why are haemophilus, bordetella, and legionella grouped together?
o They all are transmitted in through the respiratory system
Haemophilus influenza
o Obligate human parasite.
o Blood loving: blood contains hematin for the bugs cytochrome system and NAD
for the metabolic activity.
o Jumps onto the the infection that influenza has created.
o Virulence factors:
Capsule b is the esp bad subtype that can help cause meningitis,
epiglottitis, and septic arthritis.
o People with COPD get frequently get nontypeable H. influenza (does not have a
capsule and is thus less pathogenic) that causes wheezing, SOB, and cough that
all exacerbate COPD.
o Kids are most likely to get the dz between the age of 6 months and 3 years since
the maternal abs are gone (less if not breast feeding) and it takes 3-5 years to
develop the abs.
Haemophilus influenza type b
o Meningitis
Until vaccine was created, it was the main cause of meningitis in kids 6
months to 3 yo.
Inhaled, invades local LNs/blood, and penetrates into the meninges.
Kids this young typically dont display the stiff neck sign and will instead
display non-specific sgns like fever, vomiting, and altered mental status.
Mortality is low, but even with treatment, it is likely to causes mental
retardation, deafness, seizures, or language delay.
Tx with antbs can lead to a massive immune rxn from the released LPS
lipid A that will cause damage to neurons, can be limited by giving steroid
15-20 min before the antbs.
o Acute epiglottitis
Can cause rapid swelling of the epiglottis that has a cherry red base to it.
 Examination can cause complete closure of the epiglottis that can only be
overcome with a tracheotomy.
Following a sore throat and fever the child will develop stridor and
drooling
o Septic arthritis
Most common cause of septic arthritis in infants.
Presents as a single painful swollen joint, decreased mobility, and fever.
The synovial fluid will have pleomorphic g- rods.
o Sepsis
Kids 6 m to 3 yo will present with fever, lethargy, loss of appetite, and no
signs of localized infection in places like the epiglottis, middle ear, or
meningitis.
Most likely enter the blood stream from the respiratory tract.
Kids w/o a spleen or have sickle cell dz are most likely to be affected.
o Vaccination
The b capsule itself is not terribly effective, but combining it with
diphtheria or Neisseria makes it much more potent in developing abs.
Given at 2, 4, 6, and 15 months.
Haemphilus ducreyi
o Responsible for the STD chancroid.
o Present with a painful genital ulcer, unilateral inguinal LN that become painful
and swollen in half of pts. The LNs can become matted and rupture releasing
pus.
o DDx:
Syphilis (treponema pallidum): can also cause an ulcer, but it will be
painless and the associated adenopathy is bilateral, painless, and there
will be no pus.
Herpes (herpes simplex virus I and II): herpetic lesions start as vesicles,
but they can break open and look like chancroids and they are painful.
Herpes is associated with myalgias and fevers though and chancroids are
not associated with any systemic symptoms.
Lymphogranuloma venereum (LGV) (chlamydia trachomatis): In LGV the
mutted supprative nodes are painless that develop more slowly than the
chancroids and the ulcers in LGV go away before the LNs enlarge while
the LNs are enlarged at the same time as the chancroids are there.
Gardnerella vaginalis
o Causes bacterial vaginitis in women that have another anaerobic vaginal
infection.
o Presents with burning, pruritis (itching), of the labia, dysuria, and lots of fishy
discharge coming out of the vagina.
o Need to differentitate it from candida and trichomonas by examining a slide to
look for clue cells.
o Clue cells: vaginal epithelial cells that contain tiny pleomorphic bacilli within the
cytoplasm.
 Bordetalla pertussis
o Pertussis means violent cough.
o G- rod.
o Attaches to the ciliated epithelial cells of the trachea and bronchi to cause
whooping cough.
o Will not grow on cotton, so is collected with a calcium alginate swab while the pt
coughs.
Then grow it on Bordet-Gengou medium.
o He boards the hosts respiratory system with 4 main weapons:
Pertussis toxin:
B subunit that binds to target cell receptors to unlock the cell so
that the A subunit is able to activate the G proteins to Activate the
cell.
cAMP is released to cause histamine sensitization, increase in
insulin synthesis, and promotion of lymphocyte production and
inhibition of phagocytosis.
Extracytoplasmic adenylate cyclase:
Throws the andenylate cyclase granades at the neutrophils,
lymphocytes, and monocytes.
This causes them to increase cAMP levels that impairs them from
creating chemotaxis, H2O2, and superoxide.
Filamentous hemagglutinin (FHA)
B pertussis just hangs out on the outside of the cells like a fucking
commando and doesnt need to breach.
To help him hold on is FHA which is a pili rod extending from its
surface.
Tracheal cytotoxin
This toxin destroys the ciliated epithelial cells that makes it harder
to clear bacteria, mucus, and inflammatory exudate.
This ultimately makes the violent cough.
o Whopping cough
Will happen in kids between ages 1-5 that are not vaccinated and in
adults that have had a decreasing vaccine immunity.
Very contagious and transmitted via respiratory secretions on the hands
or through the air.
There is a week-long incubation period and 3 main stages of the dz:
Catarrhal stage: lasts 1-2 weeks and is similar to an URI, low fever,
runny nose, sneezing, and mild cough. Most infectious during this
time.
Paroxysmal stage:
o Fever goes away and a non-productive cough develops
that happens in bursts throughout the day, with nothing
between.
 o There will be a deep rapid inhalation at the end through
the narrowed glottis that causes a whoop sound.
o Pt can be hypoxemic, cyanotic, bulging tounge/eyes/neck
veins.
o Vomiting often occurs after the attack.
o The stage lasts for about a month and some pts need to be
hospitalized esp infants younger than 6 months and other
young kids.
o Partially immunized kids and adults may not present with
the whoop and is the cause of chronic coughs 20-30% of
the time.
o There is an increased number of lymphocytes and only a
little increase in neutrophils that makes it look like a viral
infection, most likely from the pertussis toxin.
Convalescent stage
o The attacks are less frequent over the course of the month
and the pt is no longer contagious.
Legionella pneumophila
o Legionnaries pneumonia, cuz of the outbreak in philly
o Contaminated water is inhaled from something like an AC, whirlpools, shower
heads, and veggie spray systems in the store.
o Is not transferred from person to person.
o Settles in the lower respiratory tract as a facultative intracellular parasite and
eaten by Mfs where it hangs out (like TB).
o This is how legionella lives in the wild too, inhabits things like amoebas where it
can be protected in times of hardship.
o Can also survive in a low metabolic state in a biofilm where it can be released
into the water if messed with.
o Causes dzs:
Pontiac fever:
Looks like influenza where it strikes rapidly and then leaves in
about a week.
Presents with headache, muscle aches, fatigue, fever, and chills.
Legionnaires dz:
Pts develop very high fevers and a severe pneumonia
o Legionella pneumophila is a common cause of community acquired pneumonia
that accounts for 2% of all cases of pneumonia, but its hard to tell since it is only
correctly identified in 3% of cases.
o Look for these things to tell it apart from pneumococcal pneumonia:
Pulse-temp dissociation (high fever, low pulse), severe headache,
confusion, cough, myalgia, and sometimes rhabdomyolysis with
increased levels of CPK and myoglobinemia in the serum, hyponatremia,
hypophosphatemia, elevated liver enzymes.
 Diarrhea and abdominal pain can also occur that precede the rest of the
symptoms and can make it look like influenza.
Yersina, francisella, Brucella, and pasteurella
o All share the following characteristics, yersina is a bitch and only does the first 2
though.
o All g- rods that are bacilli.
o All are zoonotic dzs.
o Very virulent and can enter anywhere on the body, which is typically the skin,
but can also be inhaled.
Many times it is from an insect/animal bite or simply direct contact.
o They are eaten by Mfs and are facultative intracellular bac so they can hang out
until they are delivered to the LNs and then they can setup shop.
o From the LNs they are free to move to bloodstream and other organs like the
liver, spleen, and lungs.
o Like other facultative bugs, immunity is cell mediated and thus there is a DTH rxn
that occurs when doing an intradermal skin test. 1-2 days after injection of the
ag, there is swelling and induration at the site of injection.
Yersina pestis
o G- with bipolar staining (ends of the rod takes up more staining than the center).
o Causes the bubonic plague and now just hangs out in the prairies of the
southwest.
o Rides around on rodents and uses fleas to send itself over to humans.
o Virulence factors:
Fraction 1 (F1): capsule ag that resists phagocytosis
V and W ags: protein and lipoprotein, respectively, that have ukn
function.
o Commonly affects people that are hiking/camping in AZ or NM.
o Presents as:
The pt is bit by the flea and within the week they have moved on to the
regional LNs, usually the inguinal LNs.
The LNs swell, become red, hot, and painful (buboes).
Fever and headache develops.
The bacilli move into the blood and head over to the liver, lungs, and
other organs.
Hemorrhages develop under the skin that cause black discoloration (black
death).
Kills 75% of untreated people, so treat quickly if the risk factors are there.
Francisella tularensis
o Tularemia.
o Very closely resembles the bubonic plague.
o Very virulent and can invade any spot of contact that results in more than 1 dz
presentation.
Only 10 individual bugs can cause dz, thus most labs will not culture it.
 Must make diagnosis from skin test, titers for abs against the dz, or just
the clinical picture.
o Ulceroglandular tularemia
Initial contact comes from the bite of a tick or deerfly, or with a wild
rabbit (or lots of others).
A well-defined black hole in the skin develops with the local LNs
becoming swollen, red, and painful with pus draining sometimes.
Bac can spread to the blood and other organs.
Similar to the black plague, but there is typically no ulcer in tularemia and
does not kill nearly as often.
o Pneumonic tularemia
Aerosilization of the bac from the rabbit while cleaning it or
hematogeneous spread from a skin ulcer to the lungs can lead to
pneumonia.
Brucella
o Species name depends on what they infect
Brucella melitensis (goats)
Brucella abortus (abortions in cows)
Brucella suis (pigs)
Brucella canis (dogs)
o Passed on from infected animal meat, aborted placenta, or ingestion of infected
milk products.
o Not common in the US, but more common than bubonic plague and tularemia in
the rest of the world.
o Most likely infected person will work as a meat packer, works with live animals,
or consumes beef/milk/animal products from around the world.
o Penetrates the skin, conjunctiva, lungs, or GI tract to get into the Mfs as
facultative intracellular.
o Presents as:
Fever, chills, sweats, loss of appetite, backache, headache, and
sometimes lymphadenopathy.
Fever peaks in the evening and returns to normal in the day (undulant
fever).
Can last from months to years, rarely fatal.
Does not have a buboes (swollen LN in groin or armpit) or skin ulcer.
Pasteurella multocida
o G- zoonotic organism.
o NOT facultative intracellular.
o Found in cats and can infect birds and other mammals.
o Most common exposure is from a dog/cat bite/scratch.
o Invades local joints or bones.
Chlamydia and rickettsia
o Obligate intracellular parasites that must steal the hosts ATP.
o Both have ATP/ADP translocator.
 o Rickettsia can make ATP with oxphos, but chlamydia cannot.
o They differ from viruses in that they have both DNA and RNA and they make
their own protiens.
Chlamydia
o Very small, g-, though has no peptidoglycan layer and has no muramic acid.
o Likes to live in columnar epithelium that lines the mucous membranes to cause
things like conjunctivitis, cervicitis, and pneumonia.
o Life cycle
Elementary body (EB)
Metabolically inert, dense, round, small, and infectious.
Has an extensive disulfide bond outer layer to protect itself.
Fired from the host cell like a cannon ball.
Initial body (IB) (reticulate body)
The EB undergoes endocytosis and remains in the vesicle, the EB
triples in size and undergoes binary fusion while inhibiting
phagolysosome digestion to make the initial body.
The IB will make more IBs while stealing the hosts ATP and will
even make more EBs to fire at other cells.
o Chlamydia trachomatis
Infects the eyes, genitals, and lungs.
o Chlamydia psittaci and chlamydia pneumoniae
Generally infects the respiratory system.
o Trachoma
Chlamydia trachomatis is the cause.
The leading cause of preventable blindness.
Happens to people living in poverty and is transferred by hand to hand
contact or eye secretions from sharing towels/clothing.
Happens most commonly in US Indians with kids being the main carriers.
Blindness occurs slowly over 10-15 years.
Scar traction pulls and folds the eyelid inward so that the eyelashes rub
against the conjunctiva and cornea leading to scarring, secondary
infections, and blindness.
o Inclusion conjunctivitis
Chlamydia trachomatis is the most common STI in the US.
Can get into the eye of infant as its being born or in an adult that has a
genital infection.
Presents as:
Yellow discharge and swelling of the eyelids 5-14 days after birth.
Diagnosis is made from intracytoplasmic inclusion bodies in cells that
came from the palprebral conjunctival surface.
o Infant pneumonia
Passage through an infected birth canal can also lead to infant
pneumonia.
 Presents 4-11 weeks after birth where the infant develops URI symptoms,
followed by rapid breathing. Cough, and respiratory distress.
o Urethritis
Infection of the urethra that is contracted sexually.
Urethritis not caused by N. gonorrhoeae is called non-gonococcal
urethritis (NGU).
NGU is most commonly caused by Chlamydia trachomatis and
ureaplasma urealyticum and is the most common STD.
Most pts with NGU are asymptomatic.
Pts with symptoms present as:
Dysuria, thin to thick mucoid urethral discharge.
o Cervicitis and pelvic inflammatory dz (PID)
Cervix is commonly infected by Chlamydia trachomatis or N. gonorrhoeae
to appear red, swollen, and have a yellow mucopurulent endocervical
discharge.
Infection can go up to involve the ovarian tubes and the ovaries.
This is called PID.
Presents as:
Abnormal vaginal discharge, uterine bleeding, dyspareunia,
nausea, vomiting, and fever.
The most common symptom is lower abdominal pain from
inflammation of the cervix, uterus, tubes, and ovaries being
painful.
PID walk and chandelier sign.
Often leads to ovarian tube scarring that can lead to infertility.
Can cause asymptomatic or mild PID that can lead to infertility w/o the
woman knowing.
o Epididymitis
Happens in men with urethritis.
Presents as unilateral scrotal swelling, tenderness, and pain that is
associated with fever.
o Reiters synd
Inflammatory arthritis of the large joints that commonly occurs in young
men between 20-40.
May also occur with uveitis, conjunctivitis, or urethritis.
Other bugs may also be present.
o Fitz-hugh-Curtis synd
Infection of the liver capsule that happens with N. gonorrhoeae or
Chlamydia trachomatis.
o Lymphogranuloma venereum
Caused by Chlamydia trachomatis serotypes L1-L3.
Starts w/a painless papule (bump) or ulceration on the genitals that heals
spontaneously. The bac then moves to the regional LNs during the next
couple months and become tender and could open up to produce pus.
 o Chlamydia psittaci
Causes atypical pneumonia called psittacosis.
Carried on birds and poultry that typically infects those working with
parrots, vets, poultry workers, and others.
Occurs 1-3 weeks after exposure.
Atypical pneumonia vs pneumonia
o Atypical is caused by things like viruses and chlamydophila pneumoniae.
o Pneumonia is typically caused by strep pneumonia.
o Supposed to appear as less sick, dry cough, fever, and less defined radiological
infiltrates.
o This is pretty much BS.
Rickettsia
o Small g-, non-motile, coccobacillary bacterium.
o Ricky requires an arthropod vector except for Q fever.
Ricky rides a louse in epidemic typhus and a flea in endemic typhus.
o Replicates in the cytoplasm instead of the endosome like Chlamydia.
o Ricky likes to live endothelial cells that line the blood vessels while Chlamydia
likes the columnar epithelial cells.
o Mostly Ricky causes rashes, high fevers, and bad headaches.
o Some Rickys coincidentally share ag characteristics with some strains of proteus
vulgaris bac (OX-2, OX-9, OX-K).
Weil-Felix rxn uses the cross-reacting proteus vulgaris ags to look for
Rickey and differentiate between the different types
Rickettsia rickettsii
o Rocky Mountain spotted fever.
o Found mostly in the southeastern tick belt.
o Transmitted by a tick after being on for about 6-10 hours and symptoms show up
within a week.
o Presents as:
Fever, conjunctival redness, severe headache, and a rash that begins on
the palms/soles and eventually reaches the trunk.
o Bugs proliferate in the endothelial linings of small blood vessels and capillaries
that cause thrombi and hemorrhage that cause inflammation and damage that
leads to the symptoms.
Rickettsia akari
o Causes Rickettsialpox.
o Transmitted by mites that live on household mice.
o Begins as papule where the bite happened that turns into a blister, days later a
fever and headache develop with more vesicles appearing on the body.
Rickettsia prowazekii
o Causes an epidemic form of typhus that is transmitted via a louse (lice).
o Comes from flying squirrels to the lice.
o Provides immunity, if infected, from Rickettsia typhi.
o Presents as:
 2 week incubation period, small pink macules appear on the upper trunk
and then spread to the rest of the body except for the palms and soles.
Pt can become delirious and stuporous and there is an increased risk of
blood vessel clotting and gangrene of the hand/feet.
o Will typically resolve in 3 weeks, but can be fatal esp in the elderly.
o Brill-Zinsser dz
The bug can go latent and then come back at a later time to provide
milder symptoms like no skin rash from the presence of IgG abs.
This is how you can tell if it came back by looking at a titer for greater
levels of IgG abs instead of IgM abs.
Rickettsia typhi
o Causes endemic or murine typhus.
o Transmitted by a flea.
o Provides immunity, if infected, from Rickettsia prowazekii.
o Presents as:
10 day incubation period. Fever, headache, and maculopapular rash
which all looks like Rickettsia prowazekii, but its not as severe.
Rickettsia tsutsugamushi
o Causes scrub typhus or Tsutsugamushi fever.
o Transferred by chiggers of mites that live on rodents and the soil.
o Presents as:
High fever, headache, and a scab at the original bit site.
Later a maculopapular rash will develop
Rickettsia parkeri
o Presents as fever, headaches, eschars, and regional lymphadenopathy.
Rickettsia africae
o Responsible for the African tick-bite fever (ATBF).
o Often causes fever in travelers to sub-saharan Africa.
Bartonella Quintana fever
o Causes trench fever.
o Transmitted by lice.
o NOT an obligate intracellular organism like Rickettsia is.
o Presents as:
High fevers, rash, headache, severe back and leg pains.
Pt recovers and then relapses 5 days later.
Can relapse many times, always with 5 days between, and is rarely fatal.
Bartonella henselae
o Occurs after a cat bite/scratch.
o Presents as:
Low fever, regional LN enlargement, and general malaise for a few
months w/o complications.
Bartonella henselae and Bartonella Quintana in AIDS pts
 o Can cause bacteremia, endocarditis, and a synd called bacillary angiomatosis,
which involves the proliferation of small blood vessels in the skin and organs.
Coxiella burnetii
o Causes Q fever.
o Similar to other Rickettsia, but it is an endospore former.
o The endospore:
Resistance to heat and drying that can contaminate milk and needs to be
heated to greater than 60 degrees.
Extracellular existence is allowed this way, but still needs to be
intracellular to use the hosts ATP and do its thing.
Non-arthropod transmission: normally coxiella burnetii lives in cows and
ticks, but they can leave their spores in tick feces on cow hides and in
dried cow placentas. These can be breathed in a lead to Q fever and a
pneumonia that is similar pneumonia that is caused by mycoplasma
pneumonia.
o Presents as:
Most infections are asymptomatic.
Abrupt onset fever and soaking sweats 2-3 weeks after infection with
pneumonia.
Can also cause granulomatous hepatitis and culture negative
endocarditis.
This is the only Rickettsia-type dz in which there is no rash.
Human Ehrlichiosis
o Tick borne dz that is similar to Rocky Mountain spotted fever w/o a rash.
o Caused by:
Ehrlichia chaffeensis (human monocytic ehrlichiosis), anaplasma
phagocytophilum (human granulocytic anaplasmosis), or rarely by
ehrlichia ewingii.
Spirochetes
o G-
o Look like corkscrews that spin uniquely due to axial filaments.
o Very slender and tightly coiled.
o Replicate by transverse fission.
o Have a structure like all other g- bac with an inner cytoplasmic membrane and a
thin peptidoglycan layer surrounded by LPS outer layer.
o 2 things different:
Surrounded by an additional phospholipid-rich outer membrane with few
exposed proteins to stealth them from the immune system.
Axial flagella come out of the ends of the bug, but they hang out in the
periplasmic space to make the bug spin to move around.
o Too small to be seen w/light microscope.
Need to use darkfield, silver stains, and serologic tests.
o 3 genera: Treponema, borrelia, leptospira.
Stages of syphilis (general)
 o Primary stage: painless chancre (ulcer)
o Secondary stage: rash on palms and soles, condyloma latum,
CNS/eyes/bones/kidneys/joints can be involved.
o Latent syphilis: 25% can relapse and enter second stage again.
o Tertiary stage: gummas of skin and bone, aortic aneurysm, neurosyphilis.
Treponema
o Dont have any toxins or things to destroy tissue with, just use our immune
system against us to cause inflammatory cell infiltrates, proliferative vascular
changes, and granuloma formation.
Treponema pallidum
o Causes syphilis.
o Most cases come from MSM are associated with HIV co-infection and high-risk
sexual behavior.
o STI
o Enters the body by penetrating through intact mucous membranes or through
epithelial abrasions especially if there is an ulcer present and bare skin touches
it.
o If untreated, there will be a progression through 3 stages with a latent period
between the 2nd and 3rd.
Primary syphilis
o Primary lesion of syphilis is painless chancre (firm ulcerated lesion with a
punched out base and rolled edges) that happens at the site of entry 3-6 weeks
later.
o The chancre is very infectious and lasts for 4-6 weeks before it heals without a
scar.
o There is also regional non-tender LN swelling.
Secondary syphilis
o After about 6 weeks after the primary chancre heals, or sometimes at the same
time, systemic symptoms will present.
o Bac multiply and spread throughout the body resulting in widespread rash,
generalized lymphadenopathy, weight loss, fever, and involvement of many
organs.
The rash entails a small flat red rash that is all over the body, esp on the
palms, soles, and oral cavity.
The rash can also popular (bumpy) and pustule.
o Condyloma latum appears: painless wartlike lesions that occur in warm wet
places like the vulva or scrotum and very contagious since they bug is having a
party in there.
o Skin infection around hair leads to hair loss like bald patches or loss of eyebrows.
o Typically resolves after about 6 weeks.
Latent syphilis
o The secondary symptoms have gone away, but 25% of pts will have 1 or more
relapses.
 o After 4 years, they will no longer be contagious except pregnant women to their
fetus.
Tertiary syphilis
o About 1/3 of pts from the latent phase will enter the tertiary phase over the
course of 6-40 years.
o There is slow inflammatory dz to organ tissue, small blood vessels, and nerve
cells.
o Grouped into 3 general categories:
Gummatous syphilis, CV syphilis, and neurosyphils.
Gummatous syphilis
o Occurs 3-10 years after the primary infection in 15% of untreated pts.
o Localized granulomatous lesions that will necrose and become fibrotic.
o Happen to the skin (painless sharp borders) and bone (deep gnawing pain) that
can be cleared with antb.
CV syphilis
o Occurs at least 10 years after the primary infection.
o Characteristically an aneurysm forms in the ascending aorta or aortic arch.
o Due to chronic inflammation of the small aa. that supply the first part of the
aorta (vasa vasorum) leading to necrosis and splitting of the arterial walls.
o The dissection can lead to the coronary aa. to involve them too.
o Can NOT be fixed with antb.
Neurosyphils
o Occurs in about 8% of untreated cases.
o Asymptomatic neurosyphils
Pt looks normal, but SCF shows + for syphilis.
o Subacute meningitis
Pt has a fever, headache, and stiff neck.
CSF has high lymphocyte, high protein, low glucose, + for syphilis,
increased opening pressure (for each time, not just this case).
Normal bac infections will cause acute meningitis with a high neutrophil
count, high protein, and low glucose.
Exceptions that also have high lymphocyte counts: treponema
pallidum and TB.
o Meningovascular syphilis
Spirochetes attack blood vessels in the brain (circle of willis) and
meninges that results in cerebrovascular occlusion and infarction of the
nerve tissue with a large variety of neuro prbs.
o Tabes dorsalis
Affects the posterior column and dorsal roots of the spinal column.
Causes prbs in vibration and proprioceptive senses leading to ataxia (post
column) and loss of reflexes and pain and temp (dorsal root and ganglia)
o General paresis (of the insane)
Progressive mental deterioration that leads to psychiatric symptoms.
o Argyll-robertson pupil
 Can be present in tabes dorsalis and general paresis.
Midbrain lesion.
Pupil constricts during accommodation, but not react to light.
Rule of 6s for tertiary syphilis
o 6 axial filaments.
o 6 week incubation.
o 6 weeks for ulcer to heal.
o 6 weeks after the ulcer heals, seconday syphilis develops.
o 6 weeks for secondary syphilis to resolve.
o 66% of latent pts will not progress.
o 6 years, at least, to develop tertiary syphilis.
Congenital syphilis
o Treponema palladium is able to pass into the placenta from an infected mom.
o Commonly causes abortion, still birth, or neonatal death.
o Will only infect the fetus after 4 months gestation, important to treat mom
before this.
o Those that live will develop early or late congenital syphilis.
o Early congenital syphilis
Occurs within 2 years and presents like severe secondary syphilis.
Systemic rash, condyloma latum, involvement of the nasal muscous
membranes that leads to a runny nose called the snuffles.
LNs, liver, and spleen enlarge.
Osteitis (bone infection)
o Late congenital syphilis
Similar to adult tertiary syphilis except that CV involvement is rare.
Neurosyphilis is common, esp with deafness.
Bone and teeth are commonly involved.
Hutchinsons teeth: upper central incisiors are widely spaced with
a central notch in each tooth.
Mulberry molars: molars have too many cusps.
Saddle nose: periosteum inflammation leads to loss of cartilage of
the nose and palate that leads to a sunken appearance.
Saber shins: periosteal bone inflammation leads to bowing of the
tibias.
Corneal inflammation can occur.
Diagnostic tests for syphilis
o Looking for the spirochetes only works during the active phases of the infection,
so serological screening methods are important for other times.
o Nonspecific treponemal tests
Can quantify the amount of abs a pt has to cardiolipin and lecithin, both
of these are released with cellular damage from treponema.
2 most common tests are the Venereal dz research lab (VDRL) and rapid
plasma reagin (RPR) test.
 1% of pts will also have a false positive for this test, esp those who are
pregnant, acute febrile illness like mono or viral hepatitis, use IV drugs, or
after immunization.
Must be confirmed with a specific treponemal test.
o Specific treponemal tests
Looks for specific tests against treponema.
Indirect immunofluorescent treponemal antibody-absorption (FTA-ABS)
test.
First mix the pts serum with a normal treponemal flora strain to
remove the normal abs and then take the serum and place it on a
slide with dead pathogenic treponema to see if there is ab
binding.
There can be false positives with other spirochetal bugs like yaws, pinta,
leptospirosis, and lyme dz.
PCR detection can also work.
Jarisch-Herxheimer phenomenon
o Most pts with a spirochete infection will worsen right after antb therapy.
o The lysed bug release a pyrogen as a final fuck you that induces fever, chills,
headache, myalgia, and malaise.
o Self-limiting.
Treponema pallidum subspecies
o Endemicum, pertenue, carateum.
o All 3 cause skin ulcers, gummas in the bone and skin, except for carateum which
only causes skin discoloration and not gummas.
o Genetically and morphologically identical to treponema pallidum but dont cause
the sexually transmitted dz syphilis.
o Primary stage: skin ulcer or papule at the site of infection.
o Secondary stage: widespread skin lesions.
o Tertiary stage: gummas of the skin and bone, NO involvement of the CV or CNS.
o Will give a positive VDRL and FTA-ABS.
Treponema pallidum subspecies endemicum
o Causes endemic syphilis.
o Found in the middle east and Africa and is casued by sharing drinking and eating
utensils.
o Skin lesions typically occur in the oral mucosa, similar to the condyloma lata of
secondary syphilis.
o Gummas of the skin and bone may occur later.
Treponema pallidum subspecies pertenue
o Caues yaws.
o Occurs in the tropics from person to person with ulcers.
o Papule occurs at the site first and grows into a wart-like mother-yaw over a
few months.
o Secondary lesions appear on exposed parts of the body.
 o Tertiary lesions appear years later as gummas on the skin and long bones that
will commonly seriously affect the face from the bugs (gangosa) destroying the
skin, cartilarge, and bone.
Treponema pallidum subspecies carateum
o Causes pinta.
o Purely a skin dz limited to rural latin America.
o Think of a Hispanic saying por favor, no pinta la cara.
o Infection comes from direct contact that leads to a papule at the site that slowly
expands.
o The lesions then expand to be red tha turn blue in the sun.
o Within a year, they will leave the skin depigmented as white spots.
Borrelia
o Corkscrew shaped Borrelia are larger than the treponema and can be viewed
with the light microscope with gimsa or wright stains
Borrelia burgdorferi
o Causes lyme dz.
o Seen mainly in the northeast, Midwest, and northeastern U.S.
o Most common tick-borne illness in the U.S.
o Tick must be attached for more than 24 hours to transfer the dz.
o The tick picks it up from mice or deer that then transfer it to humans.
o Resembles syphilis, but not an STI.
Lyme dz
o Early localized stage
Begins about 10 days after the initial infection and lasts for about 4
weeks.
Consists of a skin lesion erythema chronicum migrans (ECM) that is Red,
over Time, it Moves.
Flat round rash that is red in the beginning, but as time goes on it
will get bigger and the edge will still be red, but the center will go
back to normal, turn blue, or even necrose.
Think of lime juice spreading over the skin.
Also presents as general flu like symptoms and regional
lymphadenopathy.
o Early disseminated stage
There is dissemination of the bugs to the skin, heart, nervous system, and
joints.
Skin: ECM that has spread, but become smaller.
Nervous: brain, cranial nerves (esp Bells palsy), and/or motor/sensory
nerves.
CV: Commonly is AV nodal block, less commonly is left ventricular
dysfunction. Most symptoms resolve in a matter of weeks, esp with antb.
Joints: 6 months later arthritis can occur in large joints like the knee
where it becomes hot swollen, and painful.
 o Late stage
About 10% of pts will develop arthritis that lasts for a year or more that
involves 1-2 peripheral joints like the knee.
Many pts have the all B-cell ags: HLA-DRB180401, HLA-
DRB1*0101, and others.
Lyme dz can lead to chronic neuro damage like encephalopathy
characterized by memory impairment, irritability, and somnolence.
o Diagnoses
If there is ECM, the leading edge of the rash can be biopsied.
This bug is difficult to culture, so testing for abs is typically better with
ELISA and western blot.
Borrelia recurrentis
o Causes relapsing fever.
o Transmitted via the tick for 17 species and via the louse for 1.
o Feeds on sleeping campers in the western US, esp in rodent cabins.
o Presents as:
After infection the bac disseminates into the blood that results in a high
fever (drenching sweats), chills, headaches, and myalgia.
Rash and meningeal involvement may follow.
Symptoms resolve in 3-6 days and remain afebrile for about 8 days and
then relapse to develop the features again for another 3-6 days.
Relapses will continue with them getting shorter and milder as time goes
on.
o Why is there relapse?
Borrelia recurrentis is able to constantly rearrange its ags so that the
immune system cant find it anymore with the abs.
o Diagnosis
Only culture during the febrile periods.
Look for the spirochete between RBCs.
Darkfield is also helpful.
Leptospria
o Long, thin, aerobic spirochetes.
o 2 different species, but the only one we care about is leptospira interrogans.
o Found globally in the urine of dogs, rats, livestock, and wild animals.
o Can be transmitted via contact with the urine abraded skin or mucous
membranes come into contact with the urine.
o Typically happens while swimming, esp through swallowed water.
o Common sport that imposes a risk is adventure racing in remote places.
Leptospira interrogans
o Phase 1 (leptospiremic phase):
Bac invade the blood and cause abrupt high spiking temperature,
headache, severe myalgia (thighs and low back).
The conjunctiva are red and the pt experiences photophobia.
After 1 week there is a short afebrile period and the syptoms come back.
 Think of a leprochan being integrated for his wealth and is being forced
to watch noxious things while sitting in a very uncomfortable chair.
o Phase 2 (immune phase):
Happens with the presence of IgM abs.
There can be meningitis with an elevated CSF white cell count.
o Weils dz:
Classically comes from the serogroup icterohaemorrhagiae.
Presents as:
Infectious jaundice that involves renal failure, hepatitis with
jaundice, mental status changes, and hemorrhage in many organs.
o Diagnosis
Culture during the first febrile phase from blood/CSF, then can culture
from the urine on the second phase.
Must treat before cultures come back though.
Mycobacterium
o Rods that have lipid-laden cell walls that makes them acid-fast staining (like
nocardia).
They will stain red.
o 3 main groups
TB: tuberculosis
Mycobacterium leprae: leprosy
Nontuberculosus mycobacteria: group of lots of different species that is
way more prevalent than the other 2 combined.
Mycobacterium TB
o 10 million cases of TB globally with 2 million deaths.
o 1/3 of all AIDS pts also have TB.
o Obligate aerobe so it commonly infects the lungs.
o Grows very slowly.
o Mycosides: Virulence factors
Mycolic acid: large fatty acid.
Mycoside: mycolic acid bound to a carb to make a glycolipid
Card factor: 2 mycolic acids and a disaccharide come together to make a
virulence factor that inhibits neutrophil migration and damages mito.
Causes release of TNF.
Sulfatides: mycosides that look like cord factor with sulfates attached to
the disaccharide.
Inhibits phagosome from fusing with the lysosome.
May lead to the intracellular nature of TB during the early
infection.
Wax D
Complicated mycoside that helps to bind abs to assist the immune
system to kill the microbe.
o Pathogenesis
 Facultative intracellular growth:
First exposure typically comes in through the lungs where the
body has never seen it before.
There is infiltration of neutrophils and Mfs and the TB is resistant
to phagocytosis so they can live and multiply in the Mfs.
They use the Mfs to travel around the body and set up camp in
lots of places.
The intracellular living doesnt last long cuz cell mediated
immunity comes by and evicts them.
Cell mediated immunity:
Some of the Mfs are able to digest the TB and presnt the ag to T
cells.
This allows the T cells to hunt the TB, which results in the
response also killing lung tissue.
The necrosed lung tissue looks like granular cheese and is called
caseous necrosis.
This soft caseous center is surrounded by Mfs, multinucleated
giant cells, fibroblasts, and collagen deposits that frequently
calcifies.
The TB are kept at bay inside the granuloma, but can become
active again if there is repression in the host immune system.
o PPD skin test
Purified protein derivative can be injected just under the skin to see if
someone has been exposed to TB before.
A positive result will be a red and hard induration that appears 48 hours
later due to DTH.
Positive result sizes are:
>5mm in persons that have HIV or are immunosuppressed.
>10mm in persons with common risk factors for exposure to TB
like being from somewhere that is endemic, working in
healthcare, prior incarceration, having diabetes or renal failure.
>15mm for all others.
Positive test means that they have been exposed, not that they have a
current infection.
False positive test:
Some people have had the bacillus calmette Guerin (BCG) vaccine
that will give a false result.
False negative test:
Do not react, even though they have been infected before since
they are currently anergic from malnutrition, steroid use, or
having AIDS.
o Transmitted from an infected person that has pulmonary tuberculosis to another
person.
 The drops will typically go to the middle or lower lobes to casue a small
pneumonitis that looks like any other bac pneumonia with neutrophils
and edema.
Here the Mfs allow them to proliferate inside them and take the TB all
over the body.
o Asymptomatic primary infection
Cell defenses finally get their shit together and wall off the TB in the
caseous granuloma that heal with fibrosis, calcification, and scar tissue.
These are very small tubercles and cannot be seen on CXR, but sometime
LN enlargement or calcification can be seen.
Ghon focus
A calcified tubercle in the middle or lower lung areas
Ghon/ranke complex
Ghon focus accompanied by a perihilar LN calcified granuloma.
o Symptomatic primary infection
Overall less frequent than asymptomatic primary infection.
If it does occur, it will happen in a kid, elderly person, or
immunocompromised (esp HIV).
CXR will commonly show enlargement of the mediastinal or hilar LNs and
maybe middle/lower lung infiltrates.
Most people will still be able to wall off the TB in encapsulated calcified
granulomas without help.
Primary progressive dz:
Sometimes the infection will not be contained and the person will
be overtly ill with worsening pulmonary and or disseminated dz.
Can lead to lung necrosis forming holes in the lungs or cavities.
These cavities can become fluid filled and visualized on CXR or CT
scans.
o Secondary or reactivation TB
Most adult cases work through this manner.
Through some mech that is most likely from being immunocompromised.
HIV infected pts have a 10% / yr of having this happen, whereas a normal
person only has a 10% chance in a lifetime.
o Systems affected by TB
Pulmonary TB
Most common site of reactivation of the TB.
Typically infects in the lower lobes but then reactivate to the
upper lobes because of the highest partial pressure of O2 from
less blood flow.
Presents as:
o Chronic low grade fever, night sweats, weight loss, and a
productive cough that may have blood in it.
 o Slowly erosive due to the immune system trying to block
the TB.
Pleural and pericardial infection
Infection in these spaces results in infected fluid collection around
the organ.
LN infection (scrofula)
Most common extrapulmonary manifestation of TB.
The cervical LNs are typically involved, they become swollen, mat
together, and drain.
Kidney
Pts will have WBC/RBC in the urine but no bac that are seen in
culture cuz they take weeks to grow in acid-fast.
This is called sterile pyuria.
Skeletal
Potts dz: usually involves the thoracic and lumbar spine
destroying the intervertebral discs and adjacent vertebral bodies.
Joints
There is usually chronic arthritis of 1 joint.
CNS
TB causes there to be subacute meningitis and forms granulomas
in the brain.
Military TB
Typically only happens in the young and elderly.
Tiny millet seed sized granulomas are all over the body and organs
like the lungs, kidneys, and liver
o Always think of TB when looking at a pt that has a chronic dz where there is
weight loss, low grade fever, and symptoms related to the organ infected.
It commonly looks like cancer.
o Diagnosis of TB
PPD skin test, negative in up to 1/3 of pts with active TB.
CXR: may find isolated granuloma, ghon focus/complex, old scarring in an
upper lobe, or active TB pneumonia.
Sputum acid-fast stain and culture: indicates an active infection when +.
Rapid molecular detection of MTB: used on the sputum, uses PCR, gold
standard, but expensive.
o TB rule of fives
Droplet nuclei are 5um and contain 5 TB bacilli.
Pts with TB have a 5% reactivation risk in the first 2 years and then a 5%
lifetime risk.
Pts with a high-five HIV will have a 5+5% risk of reactivation each year.
Mycobacterium leprae
o Causes leprosy (Hansens dz).
 o Acid fast rod that is impossible to grow on artificial media, needs to be grown on
some poor animal.
o Most cases are in: India, Brazil, Burma, Indonesia, Madagascar, and Nepal.
o There are over 100 cases in the US each year.
o No one knows why or how someone gets infected, even with trying to infect
human volunteers.
o Clinical manifestation of leprosy depend on:
Bac grow better on cooler surfaces closer to the skin.
Severity is dependent on the hosts cell mediated immune response since
it is also a facultative intracellular bacterium.
o Affects the skin of all areas except those that are warm like the armpits, groin,
and perineum.
o Lepromatous leprosy (LL)
Severest form of leprosy since the body cannot form a response against
the bac which is most likely mediated by Treg cells.
The bacilli are found over the entire body, esp on the skin, nerves, eyes,
and testes.
The skin lesions all over the body are bumpy and thick with the face skin
becoming so thick that the person looks like a lion (leonine facies).
Nasal cartilage can be destroyed to create a saddlenose deformity and
the testicle can be damaged leading to infertility.
Anterior segment of the eyes can be involved leading to blindness.
Peripheral nerves become thickened and there is loss of sensation
leading to glove and stocking distribution that leads to more more
trauma and secondary infections, ultimately there will be contraction and
resorption of the fingers and toes.
o Tuberculoid leprosy (TL)
Pts can still mount a T cell response against the bac so the skin damage is
milder and more contained.
There are only 1-2 lesions that are well-defined, hypopigmented,
elevated blotches.
The area within the rash is typically hairless with diminiehed or absent
sensation and enlarged nerves near the skin can typically be palpated.
Most common nerves affected are the ulnar, greater auricular,
posterior tibial, and peroneal.
The bacilli are hard to find in the lesions or blood.
Pts often spontaneously recover.
o Lepromin skin test
Similar to the PPD for TB.
Used mostly to place the pt on the spectrum than to diagnose.
Tuberculoid Borderline Lepromatous
# of skin lesions Single Several Many
Hair growth on skin Absent Slightly decreased Not affected
lesions
Sensation in the Completely lost Moderately lost Not affected (except
lesions of the for glove/stocking
extremities neuropathy)
Acid-fast bacilli in None Several Innumerable
skin scrapings
Lepromin skin test Very strong No rxn No rxn

Nontuberculous mycobacteria (NTM)

o Huge group of organisms.
o Healthy people rarely contract the dz.
o Incidence is increasing though.
o Can cause things from asymptomatic bac colonization to chronic disabling
pneumonia.
o Mycobacterium avium-complex (MAC) dz
Common opportunistic dz that affects pts with AIDS.
Presents as unexplained fevers, weight loss, diarrhea, and general
malaise with an elevation of alkaline phosphatase on their routine labs.
Diagnosis is confirmed with growth on blood cultures.
Most common cause of NTM lung dz:
Presents as:
1) upper lung cavitary dz, esp in male smokers.
2) lower and middle lung involvement with bronchiectasis and
nodular infiltrates in middle-aged non-smoking women.
o NTM can also cause:
Pulmonary dz, lymphadenitis, skin lesion, bone and joint infections.
Mycoplasmataceae
o Smallest free-living organisms capable of self-replication.
o They only have a cell wall that contains a lot of steroids.
o They can easily change their shape into lots of things are not classified as a bacilli
or cocci.
Mycoplasma pneumoniae
o Causes a mild and self-limited pneumonia.
o The most common pneumonia in teens and young adults.
o Transmission happens via the respiratory route and attaches on using the P1
protein.
o Incubates for 2-3 weeks and then pts will present with a gradual onset fever,
sore throat, malaise, and a persistent dry hacking cough that is referred to as a
walking pneumonia since they dont feel very sick.
o CXR shows a streaky infiltrate that looks more like a viral (atypical) pneumonia.
o Up to 7% of pts can develop severe skin rxn that has erythematous vesicles and
bullae over the mucocutaneous junctions of the mouth, eyes, and skin.
o Diagnosis
 Cold agglutinins: Pts will develop an ab that binds to the I ag of the RBC
and will cause RBCs to agglutinize (clump) when the temp goes down to 4
degrees.
the abs develop during week 1-2, peak at 3 weeks, and then
slowly decline over the next few months.
Complement fixation test: mix the pts serum with glycolipd ags prepared
from mycoplasma.
4X rise in ab titer is diagnostic of a recent infection.
Sputum culture: can be grown on media that has lots of cholesterol and
nucleic acids (purines and pyrimidines).
In 2-3 weeks, both M pneumoniae and U. urealyticum will have a
dome shaped appearance.
M. pneumoniae will not have a halo and will look like a mulberry.
Mycoplasma DNA probe: use PCR.
Ureaplasma urealyticum (T-strain mycoplasma)
o Loves swimming in urine and and produces urease to break down urea.
o Still a mycoplasma since it make Tiny culture colonies.
o Part of the normal flora in 60% of healthy actively sexual females.
o Can infect the lower urinary tract to cause urethritis to cause dysuria and
sometimes a yellow mucoid discharge.

Viruses
Are energy-less, must use the host cells energy and machinery.
o They have a capsid that surrounds their DNA or RNA, but not both.
o They do not have any organelles, but they may have structural proteins and
enzymes within their capsid.
Genetic structure of viruses
o Can be single stranded, double stranded, linear, looped, in separate segments, or
one continuous strand.
o Can encode a little or a lot of info.
RNA viruses
o + stranded
Just like an mRNA so that it is prepped and ready to be translated by host
ribosomes.
 o stranded
Must first be translated to a + strand RNA using an enzyme that the virus
carries called RNA-dependent RNA polymerase (RDRP).
2 special RNA viruses
o Retroviruses, like HIV, can incorporate into the host genome.
They use reverse transcriptase to get into the host genome.
o Reovirdae, like retrovirus, is unique by having a double stranded RNA genome.
DNA viruses
o Must first be translated into RNA to do anything.
o Most viruses have both a + and Strand.
The strand is read, while the + strand is ignored.
Exception: parvoviruses only have a single stranded DNA genome.
Capsids
o Icosahedral symmetry capsids
1 or more polypeptide chains that are organized into a globular protein
subunit, this is a capsomer and the building block of the capsid.
These are then built into a triangle and 20 triangles are placed together
to form the capsid.
Can contain RNA or DNA.
o Helical symmetry capsid
Protein capsomers are always bound to RNA and then coiled into a helical
nucleoprotein capsid, most of which arrange into a spherical shape
except for the rhabdoviruses (like rabies) that have a bullet-shaped
capsid.
o Envelope
Viruses take a piece of host membrane with them as they leave that are
studded with glycoproteins.
Viruses that dont have this are called naked.
DNA virus family
o HHAPPy
o Herpes
o Hepadna
o Adeno
o Papova
o Parvo
o Pox
General characteristics of DNA viruses
o Most are double stranded, icosahedral symmetry, and replicate in the nucleus.
o Exceptions:
Parvoviridae only has one strand of DNA (one PAR hole in golf), very
simple.
Poxviridae is very complex and codes for hundreds of proteins, does not
have icosahedral symmetry and instead looks like a box (POX in a box).
o 3 DNA viruses have envelopes
 Herpes, Hepadna, Pox.
o 3 DNA viruses are naked
Woman must be naked for a PAP smear.
PApova, Adeno, Parvo.
General characteristics of RNA viruses
o Most are SS (half +/-), enveloped, helical capsid symmetry, and replicate in the
cytoplasm.
+ stranded:
The CALCIfied old emperor PICORNA is wearing his Crown and
TOGA and eating FLAVorful grapes from a RETRO bowl.
Calici, Picl, Corona, Toga, Flavi, and Retroviridae.
- stranded:
Old Petes RABid dog FILO fights paul BUNYon in the ARENA.
Orthomyxo, Paramyxo, Rhabdo, Filo, Bunya, and Arenaviridae.
o Exceptions:
Reoviridae are DS.
3 are nonenveloped: Picrona, Calici, and Reoviridae (no need to mail
anything to the PCR)
5 have icosahedral symmetry: Reo, Picorna, Toga, Flavi, Calici, Rhabdo
(has helical symmetry, but is shaped like a bullet).
2 undergo replication in the nucleus: retro and orthomyxo.
4 steps of viral reproduction
o Adsorption and penetration
o Uncoating the virus
o Synthesis and assembly of the viral proteins while inhibiting the hosts protein
synthesis and assembly.
o Release of virons from the host cell (either by lysis or budding).
Adsorption and penetration
o The viral particle binds to the host cell membrane, typically at a receptor.
o The virus is completely internalized by endocytosis or fusion of the viral envelope
with the host cell membrane.
Uncoating
o The nucleic acid (DNA or RNA) is released from the capsid into the nucleus or
cytoplasm.
Replication of RNA viruses
o Typically do all of their work in the cytoplasm.
o + strand are like mRNA in that they are ready for translation as soon as they are
in the cell.
The + strand then makes the RDRP so that there are strands for
replication.
o strand RNA viruses carry a RDRP with them when they infect a cell so that their
genetic info can be turned into + strand and translated into proteins.
Replication of retroviruses
 o They are single strand + RNA viruses, but do not undergo immediate translation
once they invade the cell.
o They carry a preformed RNA dependent DNA polymerase (RDDP) that they use
to convert their RNA into DNA so they can be inserted into the host DNA which is
then converted into mRNA.
DNA virus replication
o DNA viruses are typically more complex and transcription is divided into
immediate early, early, and late transcription.
o Immediate early and early transcription
The initially transcribed mRNA encodes enzymes and protein needed for
DNA replication and for further transcription of late mRNA.
o Late transcription
The mRNA is usually transcribed after viral DNA replication has begun
and is transcribed from progeny DNA.
The capsid proteins are made in this stage.
DNA v assembly and release
o The structural proteins and genome (RNA or DNA) assemble into the intact viron
and released.
o Naked virons can be released via exocytosis or lyse the cell.
o Enveloped virons leave via the golgi, nuclear membrane, or cell membrane.
Taking a piece of the membrane as a coat.
Host cell outcome after the v has its way with it.
o Death: the machinery is taken over by the v and may leave the cell to die, alone
and sad.
o Transformation: the v can leave some oncogenes so that the cell can grow and
proliferate.
o Latent infection: the v just hangs out and sleeps until the beast awakes.
o Chronic slow infection: it take the v many years before it can cause illness.
Orthomyxoviridae
o All are influenza viruses.
o About 20% of the global population is infected with the flu each year.
o Every year there are epidemics in communites where up to 40% of the
population can be infected.
o Pandemics are typically due to the new type A influenza v and are more severe
since we dont yet have an immunity.
o The flu presents as:
High fever, chills (maybe shaking chills), headaches, malaise, and
myalgias.
Also URI viral symptoms: dry cough, sore throat, and rhinorrhea (runny,
clogged nose).
o Influ can cause primary pneumonia esp with the pandemic outbreaks or weaken
the immune system to allow for a secondary bac pneumonia to occur from
something like staph aureus, haemophilus influenzae, or strep pneumoniae.
 o When an epidemic hits a community the kids are the first ones to be hit with an
abrupt illness after a 1-2 day incubation period and miss school and maybe even
diagnosed with pneumonia or otitis media.
o The adults are the next to be infected with missed work and secondary
pneumonia.
o The elderly and immunocompromised are the last to be hit and are the most
likely to be killed.
Structure and pathogenesis of orthomyxoviridae
o Spherical vrions.
o Have 8 segments of stranded RNA connected with nucleocapsid protein (NP)
that forms a helical symmetry capsid.
o Contains an outer membrane that is studded with long glycoprotein spikes,
hemagglutinin activity (HA) and neuraminidase activity (NA) that are anchored
intracellularly with M protein.
Abs can be directed to either of these to stop their virulence.
o Hemagglutinin
Will bind to host sialic cell membrane receptors that are found on RBCs
and on the respiratory tract epithelium.
Allows the v to fuse with the membrane to penetrate into the cell.
o Neuraminidase
Neuraminic acid is an important component of mucin and mucin is an
important part of the upper respiratory defense system.
NA cleaves the mucin so that the sialic acid spots are exposed and the v
can bind.
NA is also important for the v to leave the cell after replication cuz the v
binds to the sialic acid on the way out and needs the NA to cleave the
receptor for it to detach.
Influenza serology and epidemiology
o Type A can infect humans, mammals (like pigs) and birds. Types B and C only
infect humans.
They are separated by changes in their HA and NA.
o Ag drift: there is a small variation that occurs in the v overtime that it allows it to
slightly evade our immune system and cause a milder dz.
o Ag shift: happens when the type A infects an animal and infects another cell that
is already infected with another strain, they can exchange RNA products and
come out with entirely new HA and/or NA.
o The strains are identified by their ags H#N#.
Reyes syndrome
o If a kid is given asprin for a fever while they have the flu or chicken pox, then
they can get a severe brain and liver dz.
o Always give acetaminophen to kids that have a fever.
Diagnostic tests for influ
o Virus isolation: culture of the virus to perform genetic and ag analysis.
 o Detection of viral protiens: new one hour tests can be done to help choose
antiviral agent.
o Detection of RNA using reverse transcriptase and PCR (RT-PCR), most sensitive.
o Serological diagnosis: 4X increase in specific ab levels over 2 weeks.
Flu vaccine
o Guesswork is done to decide what the main strain will be in the next flu season.
o 3 are chosen and then grown, inactivated, purified, and used as vaccines that are
given to elderly, immunocompromised pts, and the healthcare workers.
o Live-attenuated vaccine can be given to healthy people 5-49 yo that is called cold
adapted influ vaccine trivalent (CAIV-T).
Bird flu pandemics
o So far the H5N1 has had limited infections, but they kill 50% of the pts that are
infected.
o It takes really heavy/close human to human contact and most comes from bird
to human transmission from people working with poultry, fighting cocks, or
playing with ducks.
Clinical manifestations of H5N1
o Incubation period of 2-4 days (up to 8).
o Pts develop a high fever, headache, myalgias, diarrhea, abdominal pain,
vomiting, sore throat, rhinorrhea, cough, SOB, and sputum production.
o Almost all pts progress to develop pneumonia with diffuse patchy infiltrate on
CXR and then go on to form consolidation with air-bronchiograms in more than 1
lung zones.
o Typically does not have a secondary bac infection.
o Eventually progresses to acute RDS (non-cardiogenic pulmonary edema) that is
defined as low blood O2 levels, infiltrates in multiple parts of the lung and no
evidence of heart failure.
o 50% of pts die, with 90% being kids, this is one of the few infections that is worse
in kids.
Diagnosis of H5N1
o Viral culture or RT-PCR from nasal-pharyngeal washings or feces.
o Serology tests for H5 ag or 4X increase in H5 abs.
Paramyxovirdae
o Very similar structure to orthomyxoviridae except that the strand is continuous
and not segmented, HA and NA are on the same protein spike, have a fusion (F)
protein that causes neighboring cells to fuse into giant multinucleated cells.
These syncytial cells are similar to those made by herpesviridae and
retroviridae infections.
o 5 species that are pathogenic to humans:
Pareinfluenza virus, respiratory syncytial virus, metapneumovirus,
mumps virus, and measles virus.
o General picture for all:
All absorb and replicate in the upper respiratory tract.
Most infections occur in kids.
 There is viremia so that the v is disseminated to the other sites in the
body.
Parainfluenza virus
o Presents as URI in adults with rhinitis, pharyngitis, and sinus congestion to
bronchitis and flu-like symptoms. Kids, elderly, and the immunocompromised
can also develop LRI like pneumonia.
o Croup: laryngealtracheobronchitis that happens in kids to cause airway
narrowing, stridor, and a seal barking cough.
Respiratory syncytial virus (RSV)
o Contains the F protein to make syncytial cells and lacks both HA and NA.
o RSV is the most common cause of pneumonia in kids, esp in ones that are
younger than 6 months.
o Very contagious with outbreaks in winter and spring.
o Recurrent infections are milder and more limited to the UR tract.
Metapneumovirus
o Second most common cause of LRI in kids, esp those that are 1yo.
o Most kids present with bronchiolitis (50%), croup (20%), and pneumonia (10%).
o Adults can present with symptoms too, that range from URI to LRI, but are more
mild and less common. More have URI infections.
o Diagnosis is made by RT-PCR from respiratory secretions and nasopharyngeal
swabs.
Mumps virus
o Replicates in the URT and regional LNs and spreads via the blood to other
organs, esp in the parotid gland.
o After exposure 3 weeks prior, the parotid gland swells and the testis typically
joins the party too with about 25% of males who have reached puberty
developing orchitis.
Orchitis results in swelling of the testicle and stretch the capsule to cause
intense pain and rarely cause infertility.
o Rarely progresses to meningitis and encephalitis with meningitis being more
common and less severe.
o There is only one antigenic type and is covered by a vaccine.
Measles virus
o Due to the vaccine, US cases very rare, but it causes 1 million deaths globally.
o Very contagious and spreads through direct contact and air nasopharyngeal
secretions.
o V multiplies in the respiratory mucous membranes.
o There is a 2 week incubation period before there is a development of a rash.
o Prodrome
During the incubation period, before the rash, there is conjunctivitis,
swelling of the eyelids, photophobia, high fevers up to 105, hacking
cough, rhinitis, and malaise.
Lasts for 3-4 days.
o Kopliks spots
 1-2 days before the rash, pt develops small red lesions with blue-white
centers in the mouth (like a cop licking a red-blue-while lollipop).
Lasts for 1-2 days
o Rash
Red, flat or maculopapular and spreads from the forehead to the face,
neck, torso and feet by the third day.
The rash will become thicker and then disappear in the same pattern and
be gone in 6 days
o Complications
Can go to many other organs to cause pneumonia, eye damage,
myocarditis, and encephalitis (the rarest, but 10% of pts who develop this
will die).
During pregnancy, can cause abortion and premature delivery resulting in
death 20% of the time. Does not cause there to fetal defects.
Subacute sclerosing panencephalitis (SSPE): slow form of encephalitis
that is caused by measles v. Takes years, but the child or adolescent can
have progressive CNS dz, mental deterioration, and incoordination.
The vaccine is preventative.
Hepatitis viridae
o Viral infections that go after hepatocytes.
o 5 RNA viruses
HAV
HCV
HDV
HEV
HGV
o 1 DNA virus
HBV
o HAV and HEV are both transmitted via the fecal-oral route, while all the others
are transmitted via blood to blood. A and E are on either sides of all of them and
are transmitted from one end of the body to the other end.
Acute viral hepatitis
o Caused by all of the hepatitis v subtypes.
o Have a variable incubation period depending on type.
o Presents as: growth of the virus results in systemic symptoms like the flu with
fatigue, low grade fever, myalgias, joint aches, cough, rhinitis, and pharyngitis.
1-2 weeks later the pt can develop jaundice as the level of bilirubin
increases due to decreased liver function.
In addition to decreased liver function, the liver cells also release
enzymes that can be measured in the serum like AST, ALT, gumma-
glutamyl transpeptidase (GGT), and alkaline phosphatase.
About 2 weeks into the illness the pt will have jaundice, painful
hepatomegaly, and greatly increased liver enzyme levels.
Chronic viral hepatitis
 o More difficult to diagnose since the pt is often asymptomatic with only a tender
enlarged liver that and mildly elevated liver enzyme levels.
Pattern of liver enzyme elevation
o Viral hepatitis:
ALT and AST are greatly elevated.
GGT, alkaline phosphatase, and bilirubin are mildly elevated and rise
more as the dz progresses.
o Cholelithiasis
GGT, alkaline phosphatase, and bilirubin are greatly elevated.
ALT and AST are mildly elevated.
HAV
o Naked icosahedral capsid with + ssRNA.
o In the picornaviridae family.
o Transmitted fecal-orally.
o 40% of americans in urban areas have been infected at some point due ot
contact with someone who doesnt wash their hands.
o There is about a 1 month (15-40 day) incubation period before the pt develops
acute hepatitis (HAV for Acute, no chronic).
o Most commonly affects kids w/o jaundice and mild to no symptoms.
o Can affect some adults and can lead to severe symptoms/death in a very small
%.
o Serology
HAV is antigenic and the host will produce IgM and IgG (later) abs against
it.
Abs will remain around forever and only show that the person was
affected at some point.
HBV
o Lives in all body fluids in pts that have the dz.
o Transmitted via blood-blood (parenteral) and is very contagious from sex, needle
contact
o Big virus with an enveloped icosahedral capsid and a circular ds DNA genome.
o Intact virus is called the dane particle.
o Electron microscopy will show longer filamentous structures that are pieces of
the envelope and capsid called the hepatitis B surface ag (HBsAg).
The immune system will make abs against this ag and their presence
indicates that the pt in immune against HBV.
o Also contains the hepatitis B core ags (hepAg), but abs against these are not
protective.
o During infection, there is a soluable core ag released (HBeAg) and acts as a
marker against the dz in a highly infectious state.
90% of pregnant moms with this ag in their serum will pass HBV on to
their child as compared to only 10% w/o the ag.
o HBV pathogenesis
Acute hepatitis.
 Fulminant hepatitis: severe acute hepatitis with destruction of the liver.
Chronic hepatitis:
Asymptomatic carrier: the carrier never makes HBsAg and can
spread it around.
Chronic-persistent hepatitis: pt has a low grade smoldering
hepatitis.
Chronic active hepatitis: acute hepatitis that lasts longer than 6-12
months.
Co-infection with hepatitis delta virus
Liver injury occurs from the cell mediated immune system attacking
infected liver cell and making abs that deposit in the joints, skin, and
kidney leading to inflammation.
In pts with a compromised immune system like malnutrition, AIDS, and
chronic illness are more likely to be a carrier since the immune system
doesnt attack and clear the virus.
o HBV complications
Primary hepatocellular carcinoma: pts that are carriers of HBV are 200X
more likely to develop the cancer.
Infection can also lead to permanent liver scarring and loss of hepatocyte
(cirrhosis).
o Testing for HBV
HBsAg: presence of this means that there is a live virus and infection
(acute or chronic or carrier) will go away once there is AbsAg abs.
HBcAg abs
IgM: new infection
IgG: old infection
HBeAg: means that there is high infectivity, while abs to this means that
there is low infectivity.
Hepatitis delta virus (HDV)
o Transmits parenterally and needs the help of HBV to infect someone as it needs
to steal the HBsAg coat as HDVs envelope.
Abs against HBsAg are protective against both HBV and HDV.
o Acts to take a pt that has chronic HBV or is an asymptomatic carrier and makes
them have acute hepatitis that results in a severe infection that has a greater
chance of fulminant infection, cirrhosis, and mortality (5-15%).
o The pt can no longer make HBsAg and will remain chronically infected to both.
o There is no way to test for it since IgM/IgG only stays in the serum for a short
period.
o Only Tx is to take care of the HBV before the pt gets HDV.
HCV
o Leading causes of chronic hepatitis and liver transplants in the US.
o 1.5% of americans are seropositive for HCV.
 o 85% of pts that have acute hepatitis will go on to have chronic hepatitis as
compared with 10% in HBV.
o Transmission:
Icosahedral flavivirus.
3 genotypes with type 1 being the most common in the US.
Transmitted parenterally, with IV drug use being the most common.
o Presents as:
Incubation period is 6-12 weeks.
Acute infection is typically asymptomatic, but a small % will develop
acute hepatitis (fever, jaundice, nausea, myalgia, fatigue, and RUQ pain).
85% of pts will continue onto chronic hepatitis with 20% of those
developing cirrhosis.
o Diagnosis:
Looking for the HCV abs after 6-8 weeks after exposure.
Can measure using recombinant immunoblot assay (RIBA) or by
measuring the HCV viral RNA.
o Treatment:
Can be treated and cured since it is an RNA virus that hangs out in the
cytoplasm instead of incorporating into the hosts DNA like HBV.
HEV (non-A hepatitis)
o Very similar to HAV and is transmitted via the fecal-oral route as well, esp during
monsoon season.
o Endemic to Asia, India, Africa, and Central America.
HGV
o RNA flavivirus family that.
o Transmitted via the parenteral and transfusion routes.
o Not shown to cause liver dz.
Retroviridae, HIV, and AIDS
o 3 main concepts for these viruses.
Retro: Contains the RDDP reverse transcriptase that converts the RNA it
carries into DNA that has sticky ends and is able to incorporate into the
host genome.
Grow: can cause cancer in cells they infect by bringing oncogenes with
them.
Blow: some are cytotoxic to the cells they infect are able to blow them
up, like is the case in HIV to CD4 T cells.
Oncogenes
o Src: rous sarcoma virus oncogene encodes a transmembrane protein that also
phosphorylates tyrosine at 10X the normal rate leading to lots of cell activation.
o Retroviridae oncogenes: most of the retroviridae viruses cause either leukemia
or sarcoma in their vertebrate hosts. They are sometimes called leukemia
sarcoma viruses.
Can bring in an oncogene directly (acute) or activating a host proto-
oncogene (nonacute).
 Acute transforming viruses
o The retroviridae that have direct oncogenes, they can insert them into the host
genome with the enzyme integrase.
o This is the case with the rous sarcoma virus that carries the src gene around with
it to enter into the host genome and the host makes it into a protein and shit
goes down from there.
o Most viruses are defective acute transforming viruses since they cant hold the
long sequence needed for an oncogene. Rous sarcoma is the only known one
that can bring it with it.
They also dont have enough space to carry around all of things needed
to be virulent, so they need another virus to co-infect with.
Nonacute transforming viruses
o Have enough room to carry around the code to be virulent.
o Infect the cell and insert code that screws up the host cell to convert a proto-
oncogene into an oncogene.
HTLV-I: human T cell leukemia virus
o Causes a paralytic dz that occurs in the tropical islands (Japan, Caribbean, parts
of S. America, and Africa) called tropical spastic paraparesis.
o Can also induce leukemia after latently infected cells are around for decades.
HIV structure
o Spherical enveloped viron with a central cylindrical nucleocapsid.
o Viron core: 2 identical ssRNA pieces (dimer) with associated nucleocapsid (NC)
proteins. There are also 3 essential retroviral enzymes protease, reverse
transcriptase, and integrase.
o Surrounding the RNA dimer: the capsid shell, which has icosahedral symmetry
made up of capsid proteins (CA), with the main one being p24.
P24 can be measured early on in the serum to find early detection of HIV.
o The rest of the virus has the same components of the influenza virus.
o Also has surface proteins gp 120 and gp 41.
HIV genome variation
o The difficulty in creating a vaccine against HIV is that its able to change critical
proteins very easily.
o The gp120 changes its sequence in sets of 3 to keep the reading frame the same,
but screw up the immune system.
o The reverse transcriptase gene is also able to change its sequence a lot so that it
can avoid the reverse transcriptase inhibitor drugs that are thrown at it.
o HIV is divided into groups depending on its GAG and ENV protien mutations.
Group M accounts for more than 99% of the worlds infections with the
M subgroup. The B subtype is the most common in north America and
Europe.
HIV transmission
o Spread via the parenteral route like HBV.
 In the US, MSM is the main method of transmission followed by
heterosexual intercourse, and then IV drug use.
HIV is found in seminal and vaginal secretions and the viral particles are
able to enter tiny ulcerations in the vagina, urethral, rectal, or penile
tissue.
Women are 20X more likely to get HIV with vaginal intercourse than men
because the fluids stay in them for longer.
Other STI also increase the risk of contracting HIV, like Treponema
pallidum, herpes simplex virus, chlamydia trachomatis, and Neisseria
gonorrhoeae as they create mucosal erosions and increase the amount of
the HIV in the secretions.
o Spread via blood transfusions
Can be transmitted by whole blood, concentrated RBC, platelets, WBCs,
concentrated clotting factors, and plasma.
Gamma-globulin is not associated with transmission.
Blood donations are examined by ELISA to look for HIV-1/2 via the
protein p24.
o IV drug use and needle sharing
Heavily impacts urban areas
o Transplacental
Happens to about 30% of infants born to HIV + moms and can happen
during gestation, delivery, and perinatally.
o Healthcare workers
Very unlikely to contract the dz after an accidental needle stick, but those
chances increase if the pt has a high viral load, there was visible blood on
the needle, the needle was in an artery or vein.
Almost no chance of getting the dz just by touching the pt unless there is
fluid contact.
o The dz is not spread by kissing, sharing food, mosquitos, urine, sweat, tears, or
saliva.
HIV cell infection
o HIV uses its gp 120 glycoprotein to bind to the CD4 receptor that is mostly found
on helper T cells, but also on Mfs.
o To get across the cell membrane, the co-receptor CCR5 or CXCR4 is needed.
o Once the viral RNA is in the cell, it is reverse transcribed into DNA in the
cytoplasm and it goes to the nucleus to insert into the T cell DNA.
Here the viral DNA can lie dormant or activate and create more viral
particles.
Some infections like TB, PCP, CMV, herpes, mycoplasma, or
immunizations will activate the T cell and thus activate the viral DNA.
o Once replicated, the virus will bud through the host membrane to steal some of
it on its way out.
HIV pathogenesis
 o Once infected, the pt can remain in the latent period for a variable amount of
time with an average of 8 years.
o Once activated, the pt will live for about 2 years unless they receive adequate
antiviral therapy.
o Acute viral illness
Looks like mono after about 1 month after infection to include symptoms
like fever, malaise, lymphadenopathy, and pharyngitis.
Happens to 80% of those infected.
There are high levels of HIV in the blood (viremia) but the immune
system eventually brings this down so that the virus just spread in the
LNs and the peripheral blood.
o Clinical latency
Pt can remain in the latent period for a variable amount of time with an
average of 8 years.
There are no symptoms of AIDS, but there can be massive generalized
lymphadenopathy.
The virus is continually replicating and destroying T helper cells.
By the end of the latent period, the pt is more likely to get bacterial and
skin infections.
o AIDS
Now the pt is really fucked.
Develops for a period of 2 years and is diagnosed by have a CD4 count of
less than 200, a serologic test confirming HIV, and/or having an AIDS
opportunistic infection like candida esophagitis, pneumocytosis carinii
pneumonia, kaposis sarcoma, or many others.
Clinical course of HIV infection
o Normal CD4 T cell count is about 1000, but decreases by about 60/y.
o Having a T cell count of 200-400 (happens after about 7y) constitutes symptoms
like weight loss, fever, night sweats, and adenopathy.
o Infections like severe athletes foot, oral thrush (candida albicans), herpes zoster
become more common.
o TB becomes more common once T cell count goes below 400.
o Once the count goes below 200, the immune system really begins to fail and
leads to killing infections like pneumocytosis carinii pneumonia, Cryptococcus
neoformans, and toxoplasma gondii.
o Once the count is below 50, the immune system is almost nonexistent and can
allow mycobacterium acium-intracellulare and CMV to come in.
HIV viral load
o The HIV viral load can be examined with PCR or branched chain DNA assay.
o The viral load helps to predict the risk of opportunistic infection, progression to
AIDS, and risk of death.
o Although, CD4 counts are still the best predictor for determining what infections
a person is likely to get.
 o The viral load is the rate at which the train is going towards a cliff, but the CD4
count is where the train actually is.
T cell death
o Multinucleated giant cells: T cells can fuse together under the direction of the
HIV which may help them spread and avoid the blood/abs.
o The T cells are frantically telling the B cells that the body needs abs, and so there
is hypergammaglobinemia that creates auto-abs and immune-complex
formation.
Eventually w/o T helper cells, B cells cannot be activated to make abs to
new ags which particularly hurts infants that have not been exposed to
lots of different ags.
o Mfs and monocytes: HIV is able to infect and divide in these cells, but doesnt kill
them.
This means that Mfs/monocytes serve as reservoirs that are protected
from the immune system.
These cells can then move across the blood-brain barrier to lead to brain
dz.
AIDS
o Direct viral dz leads to widespread body symptoms (night sweats, fevers,
enlarged LNs, and severe weight loss) and neurological damage (generalized
encephalopathy from the AIDS dementia complex that leads to progressive
mental decline).
There can also be meningeal infection (aseptic meningitis).
There can also be infections of the spinal cord resulting in myelopathy
and peripheral neuropathy.
o Cancers:
There is a high incidence of B cell lymphoma that commonly presents as a
brain mass. Half of B cell lymphomas have EBV DNA inside of them.
Kaposis sarcoma: most cases occur in homosexual men (96%) and there
may be a co-factor HHV-8 involved too.
Presents as red-purple plaques or nodules all over the body skin.
Can remain limited with only some skin involvement or can
progress and go after the LNs, Lungs, and GI tract too
Non-Hodgkins lymphoma: there is more than 100X risk in AIDS pts.
Hodgkins lymphoma: 10X risk.
Cervical cancer from HPV co-infection and anal intraepithelial neoplasia
in homosexual males.
o Opportunistic infections
Strep pneumoniae and other encapsulated bac are more likely to cause
infection.
TB: there is a greater chance of reactivation.
Mycobacterium acium-intracellulare (MAI)
Can cause a smoldering wasting dz that is characterized by fever,
night sweats, weight loss, diarrhea, and elevated liver enzymes.
 Common cause of fever of unk origin (FUO)
o Fungal infections
Candida albicans: common in AIDS pts and causes oral thrush and
esophagitis.
Crytococcus neoformans: causes meningitis in pts with less than 100 CD4
T cells.
Pts with AIDS do not show all of the signs that a healthy pt would
with meningitis and they may only show fever w/o stiff neck,
headache, or Kurnig/Brudinskis.
Histoplasma capsulatum and coccidiodes immitis: cause disseminated dz
in AIDS pts leading to infected meninges, lungs, skin, and other areas.
Pneumocystis jiroveci pneumonia (PCP): this is the most common
opportunistic infection in the US.
In AIDS pts, w/o prophylactic tx, there is a 15% each year that
they will be infected when their CD4 count is less than 200.
AIDS pts will present with cough and hypoxa.
CXR will show interstitial infiltrates or be normal.
Rarely causes pneumothorax.
o Viral infections
Herpes zoster: painful vesicles develop in the dermatome distribution or
can be disseminated and not reside in a dermatome.
EBV: can cause oral hairy leukoplakia (OHL) when CD4 counts are less
than 400 and is characterized by white hair-like projections that are
coming off the side of the tongue.
Is different from candidia in that it cannot be brushed off with a
tongue blade.
Herpes simplex: results in severe genital and oral outbreaks.
CMV: Can cause esophagitis (pain with swallowing) and diarrhea, but the
most important thing to watch for is chorioretinits resulting in blindness.
Important to look at the eyes in AIDS pts as it could mean that
there are retinal lesions from CMV or masses from toxiplasmosis
or lymphoma.
o Protozoal infections
Toxoplasma gondii: will cause a brain mass in 15% of AIDS pts that can
present as seizures, weakness, and aphasia.
Cryptosporidium, microsporidia, and isospora belli: will cause chronic
diarrhea.
Diagnosis of HIV and AIDS
o HIV viral ags are in the bloodstream within weeks.
Can be tested with PCR for the viral ags.
o 3-6 weeks after infection there will be abs.
ELIZA can be used to test for this, but these rapid tests need to be
confirmed with western blot as they can give false positives
 Herpesvirdae
o Can develop into a latent state.
o The sub-family of alpha have a cytolplsmic effect on cells to make the cells
become multinucleated giant syncytial cells with intranuclear inclusion bodies.
o Controlled by the cell mediated immune response.
o The virus is able to remain latent by hanging out in the sensory ganglion until
they are activated by stress like menstruation, anxiety, sunlight, fever, or
weakening of the cell mediated immune response.
o The main cytopathic viruses are the alpha subgroup which includes the HSV-1,
HSV-2, and varicella-zoster.
o The beta subgroup (CMV) and the gamma subgroup (EBV) have less cytopathic
effects.
o Pts that are immunocompromised are more likely to suffer from severe
herpesviridae infections like disseminated HSV or multi-dermatomal zoster.
o CMV is a frequent infection in AIDS pts.
Herpes simplex virus 1 & 2 (HSV-1/2)
o By age 50, 90% will have abs to HSV 1 and 20% will have abs to HSV 2, people in
lower SES will have even more.
o Gingivostomatitis: swollen gums with painful vesicles in the mucous membranes
and where the entry occured.
Can be accompanied with fever and other systemic symptoms.
Typically resolves in about 2 weeks.
o Genital herpes: fever, headache, vaginal and urethral discharge, enlarged LNs,
followed by painful blisters and painful or painless ulcers.
Cannot tell the difference between 1 and 2 by looking at the vesicles.
o Herpetic keratitis: the most common cause of infectious corneal blindness in the
US.
o Neonatal herpes: infection transferred via transplacental can lead to congenital
defects or intrauterine death.
Can also be transferred to neonate during delivery if there is an active
genital infection at the same time.
o Herpetic whitlow: HSV infection of the finger where it becomes swollen, hot,
bright red, and painful.
o Disseminated herpes: in immunocompromised pts, the HSV infection can lead to
mucocutaneous infections, the liver, lungs, and GI.
o Encephalitis: HSV-1 is the most common cause of viral encephalitis in the US.
Infection of the brain cells results in cell death and swelling that leads to
sudden onset of fever and focal neurological deficits.
One of the few treatable causes of viral encephalitis.
o Reactivation: about 25% of pts reactivate a previous infection while in a stressed
state.
Bugs that can affect pregnant mom
o ToRCHeS
Toxoplasmosis
 Rubella
CMV
Herpes/HIV
Syphilis
Varicella zoster virus (VZV)
o In kids the v is varicella and then becomes latent to reappear later as herpes
zoster to affect a person in a time of stress or immunocompromised, typically an
elderly person.
Varicella
o Causes chicken pox.
o Very contagious and typically happens in epidemics to kids in the winter and
spring.
o 90% of people have been exposed, typically during childhood.
o Infects the respiratory tract and replicates for 2 weeks, followed by viremia.
o Presents as:
Fever, malaise, headache and a characteristic rash that begins on the face
and trunk and then spreads to the entire body including mucous
membranes like mouth and vagina.
Skin vesicles that form are called dew on a rose petal which means that
there is a fluid filled vesicle on top of a red base.
The fluid becomes cloudy, ruptures, and then scabs over.
Multiple vesicles can occur together to form a crop.
There will be vesicles in different stages so that some may be
making a crop while others are scabbing over.
All should have scabbed in a week.
Difference between chicken pox and smallpox lesions
o Chicken pox
Small lesions.
Lesions are not umbilicated.
Lesions at different stages of development.
Lesions more common on trunk.
Centripetal spread (center seeking).
o Small pox
Deep hard lesions.
Lesions are umbilicated (central depression).
Lesions are all at the same level of development.
Lesions are more common at the extremities and face.
Centrifugal spread (center fleeing).
Zoster (shingles)
o Upon reactivation, there will be vesicle development along a dermatome pattern
(unilateral) that are a burning pain.
o Can infect other kids and adults that have never been exposed to the VZV virus
before.
 Cytomegalovirus (CMV)
o Cells undergo cytomegaly (swollen cells).
o Just like with other herpesviridae v, the cells become multinucleated giant cells
with intranuclear inclusion bodies.
o Asymptomatic infection: about 80% of adults have abs against CMV and most
infections are asymptomatic.
o Congenital dz: CMV is one of the TORCHES bugs.
Most common viral cause of mental retardation and can also cause
microcephaly, deafness, seizures, and other birth defects.
Typically happens when the mom is in a latent state and the pregnancy
reactivates the v and there is transplacental transmission.
o CMV mononucleosis: causes mono in young adults.
Pts will have monospot negative mono like in EBV.
o CMV can reactive in the immunocompromised pt to cause retinitis (blindness),
pneumonia, disseminated infection, and even death.
In AIDS pts: when the CD4 count drops below 50-100 cells there will be
viremia, retinitis (leading to blindness), and colitis (leading to diarrhea).
In bone marrow transplant pts that were CMV abs + before or got bone
marrow transplant from someone that was CMV abs +, they can develop
severe pneumonia that often leads to death.
They can also get viremia and colitis, but not retinitis.
o Diagnosis of CMV
There is higher yield of CMV if the buffy coat layer, which contains that
WBCs, is cultured since CMV infects WBCs.
CMV ag: the ag can be found in the blood using an ab only when the v is
actively replicating.
PCR: CMV DNA can be found only when the virus is actively replicating.
Epstein-Barr virus (EBV)
o Causes mononucleosis.
o Involved in Burkitts lymphoma and nasopharyngeal cancers.
o Transformation and malignant potential.
EBV virus binds to the Cd3 receptor on B cells that allows it to be
internalized and infect the cell.
Causes the cell to proliferate way too much.
Remains latent in some of the cells, but can also lyse out of some of the
cells.
Eventually, the cells and virus disappears with the mono, which is
thought to be mediated by the cell immune response.
In immunocompromised pts, EBV can reactivate and cause continual
growth of the B cell line.
o Mononucleosis
Happens to people in lower SES earlier in life and has a milder course.
In teens of higher SES, the dz happens later and often comes from kissing.
Presents as:
 Fever, shills, sweats, headaches, and a very painful pharyngitis.
Most pts will have lymphadenopathy from the proliferating B cells
and splenomegaly.
Blood work will show atypical lymphocytes on blood smear that
are large activated T cells.
Blood also has heterophile ab that is an ab against EBV that reacts
and agglutinates with sheep RBCs to give a + monospot test that is
useful for differentiating from CMV and quickly diagnosing EBV
mono.
HHV 8
o Herpes virus that appears to cause Kaposis sarcoma.
Poxiveridae
o Structurally complex: looks like a brick (pox in a box), has 2 envelopes, the DNA
codes for hundreds of proteins and shaped like a dumbbell.
o Replicates in the cytoplasm unlike the rest of the DNA viruses.
smallpox
o Has been eradicated from the earth, but vaccinations stopped in 1972.
o Could be used as a bioterror weapon:
Very contagious and spreads from person to person in large droplets that
move from one person to another (3-6 ft) that land on the mucous
membrane and infect them.
Rarely the particle can move in an aerosolized form that are generated by
cough and hang out in the air for long periods.
There is no treatment, 30% of pts die and leave pocked scars on those
that survive.
There may be hidden stockpiles around the world.
May possibly be confused with chicken pox.
o Molluscum contagiosum
Smallpox virus causes small 1-2mm white bumps that have a central
dimple.
Similar to warts with benign hyperproliferation of epithelial cells.
Mostly likely to happen to AIDS pts.
Papovaviridae
o 3 members of the PA-PO-VA family:
PA: papilloma v causes human warts and cervical cancer.
PO: polyomavirus
BK and JC virus.
VA: simian vacuolating v does not infect humans.
o Think O
O for circular dsDNA (naked icosahedral capsid).
O for round warts.
O for round cervix.
Papilloma virus
 o Warts: Do not occur to everyone with the virus.
The v goes after squamous epithelium and different strains go for
different locations like genital warts, laryngeal warts, common warts.
Warts are benign hyperproliferations of keratinized squamous epithelium
that will generally resolve in 1-2 years.
o Cervical cancer: the PAP smear looks for the PAPilloma virus.
Cervical dysplasia and carcinom is associated with sexual activity and
types 16 and 18 of HPV (70 % of cervical cancer).
The vaccine helps to prevent HPV in 98% of pts that are immunized.
Polyomavirus
o Infect globally at an early age.
o BK polyomavirus
Causes mild to no symptoms in kids.
Mostly causes prbs to immunocompromised kids with the main prbs
being nephritis and ureteral stenosis in renal transplant pts and
hemorrhagic cystitis in bone marrow transplant recipients.
o JC polyomavirus
Causes opportunistic infections that lead to progressive multifocal
leukoencephalopathy (PML).
Leads to CNS white matter damage leading to memory loss, poor speech,
and incoordination.
Adenoviridae
o Causes a den of sick kids.
o Causes URI leading to rhinitis, conjunctivitis, sore throat, and cough in kids and is
the cause of 10% of childhood respiratory infections.
o Can sometimes lead to pneumonia.
o All adults have serological evidence that they were infected at some point.
o There are also enteric adenoviruses that lead to the second leading viral cause of
endemic diarrheal illness in infants and kids globally.
The 5 most common respiratory illness in children
o RSV, metapneumovirus, parainfluenza, rhinovirus, and adenovirus.
Rest of the RNA viruses
o Paroviridae
Think of PAR 1.
The smallest icosahedral virus that has only one strand of DNA.
Causes the childhood dz of erythema infectiosum (fifth dz) that is
characterized by fever and a slapped face rash on the cheeks.
o Arboviruses
ARthropod BOrne viruses.
RNA v that include the togaviride, flavivirdae, and bunyaviridae.
Exceptions: rubivirus (rubella) and Hantavirus (Hantavirus pulmonary
syndrome) are not borne by arthropods.
o Picornaviridae
Enteroviruses.
 Spread fecal-orally.
Poliovirus, coxsackie A and B, and echovirus.
o Common cold viruses
Rhinoviruses (picornaviridae family)
Coronaviridae
Includes SARS
o Viruses that cause diarrhea
Rotovirus and caliciviridae (Norwalk virus)
o Rabies
Rhabdoviridae.
o Hemorrhagic fever and bioterror weapons
Deadly filoviridae (ebola), Marburg viruses, arenaviridae (lassa fever
virus).
Arboviruses
o Bunyaviridae, togaviridae, and flaviviridae.
o Transmitted by blood-sucking arthropods that cause fever and encephalitis.
o The logger paul bunyon wears a toga and has a great flavor that brings all the
mosquitos and arthropods to the yard while he chops down a arbol that has
given him a bad headache (encephalitis).
Togaviridae
o Alpha viruses
Mosquito borne and cause encephalitis (fever, brain inflammation,
headache, and focal neurological deficits).
o Rubiviruses
Causes rubella.
Alpha viruses
o 3 main ones all infect horses, birds, and humans while using mosquitos as a
vector.
o WEE: western equine encephalitis (western US and Canada).
o EEE: eastern equine encephalitis (Eastern US).
o VEE: Venezuelan equine encephalitis (Southern US, central and south America)
o Chikungunya virus is a mosquito borne alpha virus that does NOT typically cause
encephalitis.
Found in tropical Africa and Asia where it is transmitted via Aedes
mosquitos.
Presents as: fever, rash, and joint pain/swelling.
The fever and rash only stay for a few days, but he joint prbs last for
much longer.
Rubiviruses
o Only infects humans and so is a togavirus and not an arbovirus.
o Causes rubella (german measles, 3 day measles).
o Mild febrile condition that presents as mild fever, lymphadenopathy, and flu-like
symptoms.
 o Also presents with a maculopapular rash that goes from the forehead to the face
to the torso to the extremities, rash only lasts 3 days.
o Young women can develop a self-limiting arthritis.
o The biggest problem is if the infection goes across the placenta (typically 1st
trimester to cause bad congenital defects.
There is chromosomal breakage and inhibition of mitosis.
Heart: patent ductus, interventricular defects, pulmonary artery stenosis.
Eyes: cataracts and chorioretinitis.
CNS: mental retardation, microcephaly, and deafness.
Flaviviridae
o Spread by mosquitos.
o St louis encephalitis
Second leading cause of epidemic viral encephalitis that is named for the
endemic region.
10-100s of cases each y, with up to 3000 in epidemic y.
o Yellow fever
Pts develop hepatitis with jaundice, fever, headache, back ache, nausea,
and vomiting after a week incubation period.
Spraying for mosquitos stops most cases, but still a prb in Africa where
90% of cases now happen.
o Dengue fever (break-bone fever)
Mosquito borne illness that is typically found in the tropics, but can
happen anywhere in the world except for Europe and antartica.
Sever painful backache, muscle and joint pain, fever and severe
headache.
4 main serotypes and you can get reinfected by another one that can lead
to Dengue hemorrhagic fever to cause hemorrhage and shock esp in kids
(10% death).
Worst serotype is type 2.
Serotype 2 takes you down in round 2.
o West nile virus
Carried by mosquitos and can infect birds, horses, humans, or other
animals.
Can also be transmitted via blood transfusions, organ transplants,
placenta, lab, and maybe breast milk.
Clinical manifestations
Most commonly asymptomatic.
West Nile fever: headache and occasional maculopapular rash.
o Typically lasts a week, but can continue for months as
fatigue, weakness, and difficulty concentrating.
Neuroinvasive dz: aseptic meningitis, encephalitis with decreased
level of consciousness, dramatic motor paresis or paralysis.
 o Typically presents a polio-like affecting the anterior horn
of the spinal cord or like Guillian-Barre syndrome with
demyelination.
Elderly and immunocompromised are the most likely to get the
worst symptoms and fare poorly.
Kids typically fare quite well.
Diagnosis
Culture or RNA amplification from PCR.
o By the time there is clinical presentation, the ags are
usually gone and there is already abs.
IgG and IgM against WNV in the serum.
o The best method, but IgM can last for over a y and needs
to be confirmed with IgG.
o There can also be some cross reactivity with the other
flaviviridae v.
CSF IgM against WNV.
4X increase serum ab titers.
Bunyaviridae
o Also cause dz characterized by fever and encephalitis like CA encephalitis and rift
valley fever.
Hantavirus pulmonary syndrome
o First appeared in the 4 corners area.
o Presents like the flu, high fevers, muscle aches, myalgia, cough nausea, vomiting,
tachycardia, and tachypnea that leads to respiratory failure, and often leads to
death even in healthy adults.
Pulmonary is the main cause of death and most pts will need ventilator
therapy.
40% of pts die.
o In Asia and Europe, it is associated with hemorrhagic fever and renal failure.
o 4 main types in the US that each have their own vector
Sin Nombre virus is most common with deer and mouse vectors.
o Blood work shows high WBC, high RBC, and low platelets.
o Diagnosis:
Confirmed with IgG and IgM to Sir Nombre v.
Picornaviridae
o 4 genera that matter most to humans:
Enterovirus, rhinovirus, hepatovirus, and parechovirus.
o Enteroviruses 5 subgroups
Poliovirus
Coxsackie A v
Coxsackie B v
Echovirus
New enteroviruses (including Rhinoviruses)
 Poliovirus
o Pretty much only found in parts of India and Pakistan
o Can infect tonsils, payers patches and the motor neurons.
o Transmitted fecal-oral.
o Can also be transmitted orally when there is infection of the tonsils.
o Mild illness:
Mild febrile or asymptomatic illness that occurs in kids, especially in
developing nations where sanitation is poor.
o Aseptic meningitis:
Fever and meningismus can develop as the meninges are infected.
Recovery is complete in a week.
o Paralytic poliomyelitis
Likelihood of neuro prbs increases the older you get.
The mild febrile illness occurs, goes away and then comes back 5-10 days
later with meningitis.
This leads to infection and destruction of pre and post synaptic motor
neurons in the anterior horn of the spinal cord so there is both CNS
motor neuron damage and peripheral motor neuron damage.
There can be asymmetric paralysis, paraplegia, quadriplegia, or even
respiratory muscle failure (worse in pts over 15).
There will be painful muscle spasms that ultimately ends with atrophy
and loss of reflexes.
o Vaccines
Inactivated polio vaccine (Salk)
Injected subQ to produce IgG abs and is the primary vaccine used.
Oral polio vaccine (Sabin)
Attenuated polio virus that is no longer virulent to the CNS, but
can still proliferate in the GI.
Positives:
o Oral.
o Makes both IgG and IgA.
o Can spread to others so they are also immune.
Negatives:
o Can pick up virulence and cause paralytic polio in those
with the vaccine or those who get it secondarily.
o Although this is very rare, the vaccine is not used anymore.
Coxsackie A and B, echoviruses, and new enteroviruses
o All enteroviruses in the picornaviridae family.
o All have multiple serotypes and all can cause asymptomatic or mild afebrile
infections, Cold-like symptoms, Rashes, and Aseptic meningitis.
Enteroviruses are the most common cause of non-bacterial (aseptic)
meningitis in the US.
Coxsackie A
 o In mice: paralysis and death with extensive muscle necrosis.
o In humans:
Herpangina: mild self-limiting illness characterized by fever, sore throat,
and small red vesicles on the back of the throat.
Hand, foot, and mouth syndrome: a common acute illness in kids with
fever, oral vesicles, and small tender lesions on the hands, feet, and butt.
Coxsackie B
o In mice: less severe infection, but still causes damage to the heart, brain, liver,
pancreas, and skeletal mm.
o In humans:
Pleurodynia: fever, headache, lower thoracic pain on breathing (pleuritic
pain).
Myocarditis/pericarditis: infection and inflammation of the heart and
pericardial sack that can lead to self-limited chest pain, arrhythmias,
cardiomyopathy, and heart failure.
Many v can cause this, but Cox B is the most common with
causing over 50%.
Enterovirus D68
o More likely to affect kids with asthma.
o Kids develop a severe respiratory illness.
o May be associated with polio-like illness too.
2 viruses that cause the common cold
rhinovirus and coronavirus.
Spread from hand to hand contract with mucous membrane secretions
SARS (severe acute respiratory synd) virus
Identified to be coronavirus (SARS CoV).
Maybe came from palm civets or raccoon dogs.
Primarily transmitted by direct/indirect contact of mucous membrane (eyes, nose,
mouth).
Not easily spread, but there can be super spreaders.
Presents as:
2-10 day incubation time.
Fevers, myalgia, chills, and later dry cough, chest pain (pleurisy), and
dyspnea. Few pts presented with a sore throat.
CXR or CT showing alveolar consolidation that could progress to acute
respiratory distress synd (ARDS).
20-30% were in ICU and most needed ventilator support.
Symptoms are very similar and need to use PCR or serum abs to determine if they
had the virus.
Viruses that cause diarrhea
Obtained via the fecal oral route.
Typically prey on infants and kids with a 1-2 day incubation period and resolve in 4-7
days.
 4 groups are involved: caliciviruses (Norwalk and norovirus), rotaviruses,
adenoviruses, and astroviruses.
Calicivirdae
Mostly goes after young children and infants.
The gastroenteritis is indistinguishable from that of rotovirus with diarrhea,
vomiting, and fever.
Norwalk virus
Can occur in adults, but mostly affects kids.
Norovirus
Major thing causing outbreaks on cruise ships or anytime lots of people are
placed into a cramped place.
Rotovirus
Part of the reovirus family (Respiratory enteric orphan).
Major cause of acute infectious diarrhea and infant mortality globally.
The vaccine (Rotoshield) was taken away due to being associated with
intussusception.
New ones are RotaTeq (human-bovine reassortment) and Rotarix (live
attenuated).
Astroviruses
Periodic outbreaks of diarrhea in kids and the elderly.
Treatment for the diarrhea viruses is supportive in that IV fluids and electrolytes are
given.
Oral rehydration therapy is esp important in developing nations where it is
hard to get IV fluids.
The rabies virus is the only one that causes dz in humans.
Rhabdoviridae family.
Can infect any warm blooded animal to cause encephalitis, making them aggressive,
fearless, and disoriented.
When bitten, the v replicates at the site of injury for a few days and then travels up
the nerves to get to the brain to inflict fatal encephalitis.
In the brain, the v causes there to be neuropathic changes and pathognomonic
collections of virons in the cytoplasm called Negri bodies.
The incubation period after the bite can last from a week to years, but death comes
in 1-2 weeks once symptoms start.
Presents as:
Prodrome: pts first develops things like fever, headache, sore throat, fatigue,
nausea, and painfully sensitive nerves around the wound site that can even
lead to locally fasciculating muscles.
Acute encephalitis: hyperactivity and agitation lead to confusion,
meningismus, and seizures.
Classic brainstem encephalitis: cranial nerve dysfunction that leads to very
painful contractions of the pharyngeal muscles that leads to not wanting to
swallow (hydrophobia) and foaming at the mouth from over collection of
saliva.
 Death: ultimately comes from central respiratory center dysfunction. Rabies
has the highest death rate of any infection, there have only been a couple of
reported cases of recovery and they still have some CNS issues.
What should someone do if they are bit by an animal that may have rabies?
Wash the area with enough soap and water to wash away that curse word
you said when you were six.
If the animal has rabies, or it is not known, then the pt should be given rabies
immune globulin, followed by 5 injections of the killed rabies vaccine while
the virus is still in the incubation period.
Similar protocol for treating a pt exposed to tetanus.
Filoviridae
Ebola and Marburg virus
Both cause hemorrhagic fever.
Can come from monkeys or humans.
Endemic mostly in sub-Saharan Africa.
Both have been weaponized.
Ebola virus
Presents as:
Initially: abrupt onset of fever, chills, malaise, nausea, vomiting, diarrhea, and
abdominal pain in the first few days.
Rash can develop by day 5-7.
About 20% of pts develop hemorrhage of the GI tract that leads to a poor
prognosis.
Other symptoms can includes confusion, seizures, chest pain, and
conjunctivitis
Pts that survive will typically begin to get better by the second week of
illness.
Diagnosis: PCR for viral RNA, usually able to be found by the 3rd day of symptoms.
Transmission is typically given to the caregivers for the outbreak, most of which
were from direct contact with bodily fluids like blood, vomitus, urine, stool of
semen.
Arenaviridae
Includes the Lassa fever v and the 4 south American hemorrhagic fever viruses
(Argentine: junin virus; Bolivian: Machupo v; Venezuelan: Guanarito v; and Brazilian:
Sabia v).
Slower onset, but similar symptoms once the dz is fully going as the filoviridae
viruses.
Means of transmission: direct contact and droplet spread, maybe even airborne.
Much more easily treatable though.
Rift valley fever (Family bunyaviridae) and yellow fever v (family filoviridae)
Both cause hemorrhagic fever.
Suspected of being weaponized.
NOT transmissible from person-to-person.
Rift valley fever is treatable.
 Yellow fever is NOT treatable.

Fungi
Fungi
Eukaryotic cells that lack chlorophyll and require an aerobic environment.
Infections are more common now that immunocompromised pts are becoming
more common.
Yeast: unicellular growth of fungi that are spherical to ellipsoidal in shape.
Reproduce by budding.
Pseudophyphae: the yeast bud, but do not separate, so they form long chains
of cells.
Reproduce at a slower rate than bacteria.
Hyphae: threadlike, branching, cylindrical tubules composed of fungal cells attached
end to end.
Grow by extending in length from the tips of the tubules.
Molds (mycelia): multicellular colonies composed of clumps of intertwined
branching hyphae.
Reproduce by making spores and are rarely seen in skin scrapings.
Dimorphic fungi: fungi that can grow as either a yeast or a mold depending on
environmental conditions/temperatures.
Saprophytes: fungi that live in and utilize organic matter (soil, rotten vegetation) as
an energy source.
Fungal morphology
Cell membrane
Bilayered cell membrane is the innermost layer.
Contains sterols, with ergosterol as the essential one.
Cell wall
Just outside the cell membrane.
Composed mostly of carbs with some protein.
Greatly activates the human immune system.
Capsule
Surrounds the cell wall.
Polysaccharide.
Seen by using india ink stain.
Superficial fungal infections
Pretty much only symptom is skin color change.
 Diagnose with KOH on skin scrapings to look for hyphae and spherical yeast, like
spaghetti for malassezia.
Pityriasis versicolor (tinea versicolor).
Caused by malassezia furfur.
Chronic superficial fungal infection that leads to hypo or hyperpigmented
skin patches.
The patches dont change color with sunlight.
Tinea nigra
Caused by exophilia werneckii.
Superficial fungal infection that leads to dark brown or black painless patches
on the soles of the hands and feet.
Cutaneous fungal infections of the skin, hair, and nails.
Dermatophytoses
Live in the dead horny layer of the skin, hair, and nails.
Secrete an enzyme called keratinase to digest keratin which removes the
main structural protein of skin, hair, and nails.
3 most common ex:
Microsporum, Trichophyton, epidermophyton.
Tinea corporis
Ring worm.
The fungi invade and then spread to make a red, raised border.
The outside edge is active inflammation surrounding a healing center.
Tinea cruris
Jock itch.
Pts develop itchy red patches on the groin and scrotum.
Tinea pedis
Athletes foot.
Fungus that requires warmth and moisture, so only happens in those
wearing shoes.
Begins between the toes and causes there to be cracking and peeling
of the skin.
Tinea capitis
Primarily affects the scalp of children.
Presents as red scaly lesion with loss of hair that progresses in an
expanding ring.
Tinea unguium (onychomycosis)
The nails are thickened, discolored, and brittle.
Diagnosis
Take skin scrapings, digest the keratin with KOH and look for the
presence of branched hyphae.
Directly examine the hair or nails with woods light (UV 365nm).
Some species of microsporum will fluoresce a brilliant green
Candida albicans
Oral thrush: mouth infection.
 Diaper rash: groin infection.
Candida vagina: vaginal infection.
SubQ fungal infections
Typically gain entrance to the body by skin trauma.
Stay localized to the local subQ or travel along lymphatics to local nodes.
Normally found in the soil and are low virulence.
Sporothrix schenckii
Dimorphic fungi that is found in soil and on plants like splinters and rose
thorns.
Gardners are the most likely to get the dz.
Causes sporotrichosis:
SubQ nodule appears gradually, becomes necrotic and ulcerates.
The first ulcer heals, but then other ones show up along the lymphatic
tract.
Culture at 37 to find yeast, while culture at 25 shows branching
hyphae (dipmorphism).
Phialophora and cladosporium
SubQ infection caused by copper-colored soil saprophytes.
Found on rotting wood and infects humans with a puncture wound.
Causes chromoblastomycosis.
There is an initial small violet, wartlike lesion that develops and will
be joined by others like it over the next months to years.
Clusters of them look like cauliflower.
Diagnosis
Skin scrapings and KOH show copper-colored sclerotic bodies.
Systemic fungal infections
3 fungi that cause dz in humans:
Histoplasma capsulatum, blastomyces dermatitidis, and coccidioides immitis.
Dimorphic:
At 25 on sabourauds agar, they grow as mycelial forms with spores.
Useful to release spores from the soil.
At 37 on blood agar, they grow as yeast.
Useful to colonize the lungs that the spores are breathed into.
Geography:
Histoplasma capsulatum and blastomyces dermatitidis are found in the areas
that drain into the Mississippi river.
A rocket HITS and BLASTS a hole into the Mississippi river.
Coccidioides immitis is found in the SW US and northern mexico.
The second most common infection an AIDS pt gets living in Arizona.
Mechanism of dz:
Has many similarities to TB.
Inhaled as spores from the soil, vegetations, or bird droppings, never person
to person.
Once inhaled, like TB, it is disseminated throughout the blood.
 Most infections are killed at this point due to cell mediated immunity.
3 clinical presentations
Majority of cases are asymptomatic or are mild respiratory cases that no one
cares about.
Pneumonia: mild pneumonia can develop with fever, cough, and CXR
infiltrates.
Like in TB, granulomas with calcifications can develop after the
resolution of the pneumonia.
A small number of people can develop a severe pneumonia that may
progress to a chronic cavitary pneumonia that is marked by weight
loss, night sweats, and low grade fevers (like TB pneumonia).
Disseminated: in immunocompromised pts the fungus can cause meningitis,
bone lytic granulomas, skin granulomas (that break down into ulcers), and
other organ lesions.
Diagnosis:
Antigenic preperations called coccidiodin and histoplasmin can be checked in
the same way PPD is in the skin to check for previous exposure, but most
people have been exposed before and will not be very helpful.
Biopsy of the affected tissue (lung, skin, etc), culture on Sabourauds or blood
agar, and examination with silver stain.
Can also use serologic tests like complement fixation and latex agglutination.
Can also use urine Histoplasma atg test.
Histoplasma capsulatum
Nonencapsulated, wtf.
Found in bird and bat droppings.
Pneumonia can occur when cave exploring or cleaning chicken coops.
Blastomyces dermatitides
Fungi are found in soil and rotten wood.
Rarest systemic fungal infection, but the worst to get.
Presents as chronic disseminated dz with weight loss, night sweats, lung
involvement, and skin ulcers.
Coccidioides immitis
Commonly causes mild pneumonia in normal people in the SW US, esp
common in AIDS pts.
Crytococcus neoformans and Cryptococcus gattii
Causes cryptococcosis.
Mostly endemic to Papua New Guinea and northern Australia, but there have
been some cases in the Pacific Northwest US.
Encapsulated yeast that is NOT dimorphic.
Begins when inhaled into the lung and primarily presents as
meningoencephalitis.
Found primarily in pigeon droppings.
75% of cases happen to AIDS pts and 10% of all AIDS pts will develop this.
Presents as:
 Headache, nausea, confusion, staggering gait, and/or cranial n.
deficits.
Mild fever and meningismus.
Fatal unless treated due to cerebral edema leading to brainstem
compression.
Can also cause pneumonia, skin ulcers, and bone lesions less
commonly.
Diagnosis
CSF india ink stain shows yeast cells with surrounding halo (the
capsule), but only works half the time.
Better test is to look for the cryptococcal atgs and confirm with
culture.
Candidia albicans
Causes candida albicans.
Very common leads to 3 cutaneous infections, and in the
immunocompromised pt, can lead to invasive systemic dz.
Oral thrush: creamy white exudate with a reddish base cover the mucous
membrane of the mouth.
Vaginitis: vaginal itching and thick copious secretions.
Inflamed vaginal mucosa with patches of white clumps (cottage
cheese) on the vaginal wall.
Diaper rash: warm moist areas in diapers or under skin folds can become red
and mascerated.
In immunocompromised pts:
Esophagitis: extension of thrush into the esophagus that causes a
substernal burning sensation upon swallowing.
Disseminated: can go to any organ, but the retina is important to look
at, look for fluffy candidal patches.
Diagnosis:
Normal flora that can be found in most places/secretions of the body,
but never normal in the blood.
Cultures are the gold standard.
Use KOH on skin scrapings or biopsies of tissue.
Blood test for beta-D-glucan (from fungal cell wall).
T2Candida assay: looks for amplified DNA using magnetic resonance
technology and PCR assay
Aspergillus fumigatus
Allergic bronchopulomonary aspergillosis (ABPA)
Spores are very common in the air and some people develop asthma
when they breathe in the spores.
Presents as a type I hypersensitivity rxn with bronchospasm, increase
in IgE and blood eosinophilia.
Can also have DTH with lung infiltrates.
aspergilloma
 Infection of preformed lung cavities that were made by TB or cancers.
Can grow to the size of a golf ball and needs to be surgically removed.
Invasive pneumonias can develop in immunocompromised pts, it can lead to
bloody sputum from blood vessel invasion of the aspergillus hyphae.
Invasive aspergillosis
Typically happens to pts who are neutropenic from chemo, high doses
of steroids for GVH dz, or AIDS pts that have a count less than 50.
Presents as a slowly progressive, often asymptomatic, low grade
fevers, mild pneumonia, and multiple nodular infiltrates on the chest
CT scan.
Very high mortality rate.
Aspergillus as a carcinogen
Commonly infects moldy nuts, grains, and rice.
Produces a mycotoxin (damaging to liver and leads to liver cancer)
called aflatoxin.
Mucormycosis (zygomycosis)
Opportunistic infection caused be several molds in the order Mucorales of
the phylum Zygomycota.
Pathogens are found in the generas of rhizopus, rhizomucor, and mucor.
Molds are found everywhere, but typically only people who develop acidosis
like diabetics, immunocompromised, burn pts, or people taking the iron
chelator deferoxamine become infected.
Rhinocerebral and pulmonary involvement is the most common as the molds
go after the sinuses, cranial bones, and blood vessels.
The fungi-like bacteria
Actinomycetes
Actinomyces and Nocardia.
They are really bacteria, but they look like fungi (theyre really ACTually NO
fun)
Grow in the form of myeclia.
Water and soil saprophytes.
Gram + rods.
Actinomyces israelii
G+, beaded, filamentous, anaerobic.
Grows as normal flora in the mouth and GI tract.
Causes abscesses after trauma to the mouth or GI tract mucous membranes.
Named according to where it makes an abscess.
Cervicofacial actinomycosis, abdominal actinomycosis,
thoracic actinomycosis.
The pus draining from the abscesses forms yellow granules called sulfur
granules that are really just collections of actinomyces and cellular debris.
Nocardia asteroides
Weakly g+, partially acid-fast, beaded branching thin filaments.
Not normal flora.
 Often thought to be TB cuz of acid-fast and similar dz process.
Nocardia is inhaled into the lung where it creates cavitations and abscesses.
Erosion into the pleural space, dissemination in blood/brain to cause
abscesses in the brain or other organs.
Immunocompromised pts or those taking steroids are most at risk.

Parasites
Protoza
Free-living, single celled, eukaryotic cells with a cell membrane and organelles (1-2
nuclei).
Have both an outer layer (ectoplasm) and an inner layer (endoplasm).
Ingest food through the cytosome.
Reproduce asexually by fission or sexually by fusion, exchange of DNA, and then
fission.
Can change depending on the environmental conditions like make a protective coat
and shrink into a round armored form called a cyst. Once it reaches a host, it
converts back into the active form called a trophozoite.
Intestinal protozoa
5 intestinal protozoa that cause diarrhea:
Entamoeba histolytica, giardia lamblia, cyclospora cayetanensis, cryptosporidium,
isospora belli.
Entamoeba histolytica
Classic amoeba that uses pseudopodia to pull itself along and surround food
particles.
Most people are asymptomatic and the amoebas live in peace inside us.
Transferred via the fecal-oral route.
MSM are common carriers.
Life cycle:
The motile feeding form of the amoeba is the trophozoite that eats the
intestinal wall, bacteria, protozoa, and RBCs.
Can convert into a precyst form with 2 nuclei that matures into a
tetranucleoid cyst as it travels down and out of the colon.
The precyst contains aggregates of ribosomes called chromatid
bodies and food vacuoles that are extruded as it shrinks to the
mature cyst.
The mature cyst is what infects others.
Presents as:
 10% of the time the trophozoites are able to invade the intesintal mucosa
and cause erosions resulting in abdominal pain, loose stools, and flecks of
blood/mucous in the stool.
May progress to become severe with bloody voluminous diarrhea.
Can penetrate the portal system to cause liver abscesses and move into
diaphragm and lung to do the same, these pulmonary abscesses often lead to
death.
Diagnosis:
Look at the stool for trophozoites or cysts, only the presence of trophozoties
with internalized RBCs indicates active dz.
Best option is to use ag detection tests on the stool or serum as this will also
allow to differentiate from the non-pathogenic bug E dispar.
Use CAT scan to look for liver abscesses
Giardia lamblia
2 forms, like a cyst and a kite shaped trophozoite with a flagellum.
5% of people are asymptomatic carriers.
Outbreaks occur with sewage contaminated drinking water or when people drink
unfiltered mountain stream water.
Presents as:
Ingested as a cyst where it then converts to a trophozoite and adheres to the
small intestine wall.
It coats the wall to inhibit fat absorption to give the pt really smelly nasty fat
poops. They will also have greasy, frothy diarrhea with gassy distention and
cramps.
They do not invade the intestinal wall and there is NO blood in the stool.
Diagnosis:
Examination of stool for cysts or trophozoties,
Immunoassay to detect Giardia lamblia ags in aqueous extracts of stool
samples.
Cryptosporidium
Found everywhere.
25% of Americans show previous evidence of having the infection.
Outbreaks occur from contaminated water treatment centers and infants in day care
centers.
Sporadic cases can sometimes happen to travelers.
Presents as:
Ingested as a round oocyst that contains 4 motile sporozoites that goes
inside the GI epithelial cells.
Causes diarrhea and abdominal pain that are self-limiting in healthy pts.
In immunocompromised pts, there is severe, protracted diarrhea that can
lead to 3-17 liters of stool a day being released
Isospora and cyclospora
Cause severe diarrhea in immunocompromised pts.
Transmitted via the fecal-oral route.
 Cyclospora is associated with contaminated raspberries.
Both are diagnosed by acid-fast on stool microscopy, but can also do fluorescent
microscopy.
Trichomonas vaginalis
Sexually transmitted.
Hangs out in the female vagina and the male urethra.
The trophozoite is flagellated.
Presents as:
Females present as itching (pruritis), burning on urination, and lots of vaginal
secretions.
There will be a thin, watery, frothy, malodorous discharge from the vagina.
Males are asymptomatic, but need to be treated with the female since the
body does not create immunity to this bug and the male will reinfect the
female.
Diagnosis
Microscopic examination of the vaginal discharge to find a very motile
parasite.
May also find it in the urine.
The free living meningitis causing amoebas
Naegleria fowleri, acanthamoeba, and balmuthia mandrillaris.
Live in fresh water and moist soil.
Often causes infection when people swim in lakes or contaminated swimming pools.
Rarely infects pts, but often fatal when they do.
Naegleria fowleri
95% of pts die in a week.
Present as:
Will indicate they were swimming a week earlier.
Fever, headache, nausea, vomiting, and stiff neck like bacterial meningitis.
CSF will show high protein, low glucose and high neutrophil count, just like a
bac infection.
The g stain and culture will show no bac and microscopic examination may
show motile amoeba.
Acanthamoeba
Causes chronic, granulomatous, brain infection in immunocompromised patients like
those with AIDS.
Over a period of weeks, pts will develop headache, fever, seizures, and focal
neurological signs.
Examination of the CSF and brain tissue will show acanthamoeba in cyst and
trophozoite stages.
Can also infect the cornea (keratitis) in healthy pts if their contact lenses are not
cleaned well enough.
Balamuthia mandrillaris
Has a similar presentation as acanthamoeba, but it infects immunocompromised
and healthy pts.
 Can produce chronic granulomatous skin lesions either with or w/o amoebic
encephalitis.
Most infections are asymptomatic, but those that present are likely to be fatal.
Toxoplasma gondii
Humans can ingest the spores that are found in undercooked meat (like pork) or
food contaminated with cat feces.
Dz occurs by reactivation of latent infection in an immunocompromised pt.
Fever, LN/spleen/liver enlargement, pneumonia, and/or infection of the
brain and meninges.
Toxoplasma encephalitis is the most common CNS infection in AIDS pts.
The brain infection can involve a growing mass like a tumor with symptoms
of headache and focal neurological signs (seizures, gait instabilities,
weakness, or sensory losses)
Chorioretinitis that looks like yellow-white fluffy patches that stand out from
the surrounding red retina.
Transplacental infection in pregnant women.
Can occur in pregnant women that have never been exposed to toxoplasma
gondii before.
The mom will get generalized LN enlargement.
Congenital toxoplasmosis can cause lots of prbs like chorioretinitis, blindness,
seizures, mental retardation, microcephaly, encephalitis, and other defects.
Causes severe prbs or stillbirth if it happens early in the pregnancy.
Even pts that look normal at birth can have reactivation in the 2 nd or 3rd
decade of life that commonly leads to chorioretinitis.
Diagnosis
CAT scan will show contrast enhancing mass.
Retinal examination will show retinal inflammation.
Serology: Ab titers will indicate if there has been previous exposure.
Pneumocystis carinii (P. jiroveci)
Flying saucer appearing fungus.
Infects the young at an early age and sits around in a latent state that 85% of kids
have been exposed with mild symptoms by the age of 4.
Happy to hang out and chill unless there is immunocompromise, in which case it will
cause severe interstitial pneumonia called pneumocystis carinii pneumonia (PCP).
Most common opportunistic infection in AIDS pts.
15% each year w/o prophylactic tx in pts w/less than 200 T cells.
Presents as:
Fever, SOB, nonproductive cough, and death if not treated.
Diagnosis
Silver or immunofluorescent staining cultures obtained by (in increasing
yield):
Induce sputum sample by spraying saline into the bronchioles and collecting
coughed material.
 Bronchoalveolar lavage: insert a camera and wash out the deep bronchial
tree with saline.
Biopsy the lung by bronchoscopy.
Malaria
Caused by 5 different protozoa:
Plasmodium falciparum, plasmodium vivax, plasmodium ovale, plasmodium
malariae, and plasmodium knowlesi.
Transmitted by the mosquito.
The human is infected, the organisms grow in the liver and then spread to the RBCs
where they reproduce until the RBCs burst.
All of the RBCs will burst at the same time releasing factors to induce fever
periodically.
P. vivax and P. ovale burst loose every 48 hours to cause fevers and chills
followed by sweats. Called a tertian malaria.
P. malariae bursts every 72 hours causing there to be fever, chills and then
sweats every 3 days. Called quartan malaria.
P. falciparum (the most common and deadly) bursts RBCs irregularly every
36-48 hours and has less defined periods of mild fevers and can be
continuous.
Plasmodium life cycle
Plasmodia undergo sexual division in the anopheles mosquito and asexual
division in the liver and RBCs.
Sporozoties leave the salivary gland of the mosquito and enter the
bloodstream to go to the liver to begin the pro-erythrocytic cycle.
In the liver cell they round up into a ball to become a trophozoite where it
makes thousands of new nuclei.
This schizont then makes cytoplasmic membranes around each nucleus to
crate lots of merozoites which causes the liver cell to burst open.
Some of these that are released can reinfect other liver cells in the exo-
erythrocytic cycle, while the rest will infect RBCs in the erythrocytic cycle.
In the RBC, the merozoite will round up to form a trophozoite that looks like
a diamond ring.
Nuclear division will happen again to cause the formation of a shizont and
ultimate release of lots of merozoites and lysis of the RBC to cause the fever.
This cycle will continue for 2-3 more days and also produce female and male
gametes to be taken up by a mosquito again.
Which malaria bugs can remain dormant in the liver?
P. vivax and P. ovale can make hypnozoites that grow years after the original
infection to cause relapsing malaria.
What are the 2 malaria bugs that cause severe clinical manifestations?
P. falciparum (brain and kidney)
P. Knowlesi
Sexual plasmodia cycle in the mosquito
 The gametes are sucked into the mosquito where DNA is exchanged to make
an oocyst.
The oocyst then divides into many sporozoites that can enter the salivary
gland to start all over again.
Malaria
6 hour episodes of periodic fever.
Can lead to anemia and sticky RBCs that get clogged in post-capillary venules
of the kidney, lung, and the brain that lead to hemorrhages and blocked
perfusion esp by P. falciparum.
Renal failure, lung edema, and coma can all lead to death.
Most deaths occur in kids younger than 5 yo in sub-Saharan Africa from
cerebral malaria that leads to seizures, impaired consciousness, and coma
(20% death rate even with tx).
There is also heptosplenomegaly from the body trying to clean up the mess
from the lysed RBCs.
Malaria resistance
P. vivax resistance is due to lack of RBC ags Duffy a and b since P. vivax uses
those for binding.
Sickle cell trait helps to protect against P. falciparum.
Diagnosis
Examination of blood smears on oil-immersion magnification can reveal
trophozoites and schizonts inside the RBCs.
There are also rapid ag tests that can be used, but are very expensive.
Babesiosis
Transmitted by a tick, causes invasion and lysis of RBCs that causes fever.
Different from malaria:
There are more than 100 species to cause the dz in mostly animals.
Spread by ticks.
They do not affect the liver cells.
Babesia microti
Reservoir is the mouse, spread by ticks.
Found in northeastern costal US
Sporozoites come out of the tick and invade the RBCs to differentiate into pear or
ring-shaped trophozoites.
The trophozoites then bud and divide into 4 merozoites that stick together to form
an X shaped tetrad (maltese cross).
RBC infection leads to mild anemia that is often asymptomatic.
Asplenic pts are unable to clear the bug and have a very similar presentation as that
of someone with P. falciparum.
Leishmaniasis
Zoonotic blood-borne flagellate that is carried by rodents, dogs, and foxes.
Transmitted by the sandfly.
Commonly found in south and central America, Africa, and the middle east.
 Upon transmission, the mastigote invades Mfs and transforms into the nonmotile
amastigote which then multiplies in the Mf in the LNs, spleen, liver, and bone
marrow.
Dz presentation ranges from a single skin ulcer to a very severe infection that
involves the spleen and liver depending on genetics of the pt, like leprosy.
Cutaneous leishmaniasis
An ulcer will appear where the sandfly transmitted the leishmania into the
skin called the oriental sore that takes a year to heal leaving a depigmented
pale scar.
Diagnosis is made from skin scrapings of the ulcer base or by taking dead
leishmania and placing it under the skin like PPD.
Diffuse cutaneous leishmaniasis
Occurs in Venezuela and Ethiopia.
Chronic form of cutaneous leishmaniasis that happens in pts with deficient
cell mediated immune systems.
A nodular skin lesion arises, but does not ulcerate.
Eventually there will be lots of the lesions occur all over the body with an
increased collection of them near the nose.
Can last up to 20 y.
The leishmania skin test is negative since there is no T cell response for DTH.
Mucocutaneous leishmaniasis
There is a dermal ulcer that appears at the bite location, but quickly heals.
Then there will be multiple ulcers in the mucous membranes of the mouth
and nose that will lead to the erosion of the nasal septum, soft palate, and
lips over the course of 20-40 y unless treated.
Death by secondary bac infection can also occur.
Diagnosis is made by skin scrapings.
Visceral leishmaniasis (kala-azar)
Caused by L. donovani or L. chagasi.
Most commonly infects young malnourished kids.
Will be infected and then months later complain of abdominal discomfort
and distention.
This comes from hepatomegaly and massive splenomegaly due to the
bug invading the Mfs of the liver and spleen.
They will present with low fevers, anorexia, and weight loss.
There can be a severe drop in WBC and RBC counts that leads to death in
90% of cases if untreated.
Diagnosis
Liver and spleen biopsies.
High leishmanial IgG levels.
Leishmanin skin test is negative during the active dz since the cell
mediated response is deficient.
African sleeping sickness
Caused by trypanosoma rhodesiense and trypanosoma gambiense.
 Transmitted via the tsetse fly.
Releases trypomastigotes via the bloodstream to the LNs and the CNS.
Presents as:
Hard, red, painful skin ulcer that heals in 2 weeks.
The bug will spread and cause fever, headache, dizziness, and LN swelling
that lasts a week.
The fever comes back after a few weeks, only to go away again continuing
the cycle for a few months.
Eventually the CNS symptoms present as daytime drowsiness, behavioral
changes, difficulty in walking, slurred speech, and finally coma and death.
West African sleeping sickness
Caused by trypanosoma brucei gambiense.
Noted for slowly progressing fevers, wasting, and late neurological
symptoms.
East African sleeping sickness
Caused by trypanosoma brucei rhodesiense.
Like the west version, but more severe with death occurring in weeks to
months.
What causes the intermittent fevers in African sleeping sickness?
The trypanosoma express a single variable surface glycoprotein (VSG) that
repeats.
The bug can make lots of different types of VSGs though and every time the
body makes abs against one type, the bug makes progeny with a different
VSG.
So the fever comes every time there is immune recognition and lots of the
bugs are killed.
Diagnosis
Should always be performed using microscopy of the peripheral blood, LNs,
or CSF.
Chagas dz
Caused by trypanosoma cruzi (the American trypanosome).
Found from the southern US all the way down to mexico, central and south America.
Lives in rodents, opossums, and armadillos.
Vector is the reduviid bug (kissing bug).
The reduviid bug comes and eats on the human where it also shits and leaves T.
cruzi trypomastigote as a gift.
The trypomastigote then loses its undulating membrane and flagellum and rounds
up to form the amastigote which quickly multiplies.
The bug then invade the local skin, Mfs, LNs, and distant organs.
Acute chagas dz
Where the parasite entered, a hardened red area develops called a chagoma.
This is followed by systemic spread with fever, malaise, and swollen LNs.
 The heart becomes inflamed and is tachy with electrocardial changes and the
CNS involvement can lead to severe meningoencephalitis (typically young
pts).
Typically resolves in a month where pts then enter the intermediate phase
where there are no symptoms, but there are persistent low levels of the
parasite in the blood and abs against T. cruzi.
Most pts will remain in this state for life.
Chronic chagass dz
Some pts will go on from the intermediate phase to the chronic stage years
to decades later.
Heart: arrhythmias are the earliest manifestation (heart block and ventricular
tachycardia) that eventually leads into dilated cardiomyopathy (increase in
heart size and heart failure).
Megadisease of the esophagus and colon: a big dilated, poorly functioning
esophagus develops with symptoms of difficulty and pain in swallowing with
regurgitation of food. The dilated megacolon leads to constipation and
abdominal pain where the pt goes weeks without a poop.
Diagnosis
Acute chagas dz:
Direct examination of blood for the trypomastigotes.
Xenodiagnosis: 40 lab grown reduviid bugs are placed on the skin to
feed on the pt for a month and then their abdominal contents are
examined.
Chronic chagas dz:
Classic clinical findings (cardiac and megadisease) with serological
evidence of past infection.
Balantidium coli
Largest protozoans found in the intestine.
Cysts come from pig feces that mature into ciliated trophozoites and then dig into
the intestinal wall where they eat the other bugs already down there.
Most pts are asymptomatic, but some can develop diarrhea.
Diagnosis is made by looking for the ciliated trophozoites or cysts in the stool.

Helminths
Intestinal nematodes
All mature into adults in the GI.
 Acquired by the ingestion of eggs:
Ascaris lumbricoides, trichuris trichiura (whipworm), and enterobius
vermicularis (pinworm).
Acquired when the larvae penetrate the skin:
Necator americanus (hookworm) and strongyloides stercoralis.
Acquired when eating encysted larvae while eating meat:
Trichinella spiralis (esp from pork)
Ascaris lumbricoides
Endemic in the tropical and mountainous areas of the southern US.
Comes from eating the eggs which mature into larvae that go through the intestinal
wall into the blood and then to the lungs.
In the alveloli they grow so they can be coughed up and swallowed.
They become adults in the intestines and produce 200K eggs each day.
Presents as:
Can be mild or asymptomatic, but heavy infections can lead to abdominal
cramping.
Severe infections can leads to adult worm invasion into the bile ducts, gall
bladder, appendix, and liver.
Kids with lots of worms can suffer from malnutrition from competition or a
block in the intestine.
When they invade the lung, the pt may develop a cough, CXR pulmonary
infiltrate, and a high eosinophil count in the blood and sputum.
Diagnosis
Look for the eggs in feces or larvae in the sputum.
There may be an increased # of eosinophils on peripheral blood smear.
Necator americanus (hookworm)
Lives in soil to eat bac and vegetation as a larval form for a week, it then turns into a
filariform larva that can penetrate the skin between the toes after a week.
It goes straight for the lungs to grow and be swallowed so it can attach onto the
intestine with its mouth, drink blood, and copulate to release fertilized eggs in the
stool.
Presents as:
Diarrhea, abdominal pain, and weight loss.
May cause iron loss anemia from sucking blood.
There will be an intense itching from where it entered between the toes.
When they invade the lung, the pt may develop a cough, CXR pulmonary
infiltrate, and a high eosinophil count in the blood and sputum.
Diagnosis
Identify the eggs in a fresh fecal sample.
Strongyloides stercoralis
Lives in the soil and penetrates the skin and travels to the lung to grow and be
swallowed.
They mature and lay eggs in the GI, but the eggs do not leave with the stool, instead
they hatch to make filariform larvae.
 The filariform larvae can invade the intestinal cells and go back to the lungs to
continue the process, they can go out with the stool to infect someone else, or they
can turn into male/females, have sex, make eggs, develop into filariform larvae and
infect another person.
Presents as:
Vomiting, abdominal bloating, diarrhea, anemia, and weight loss.
Causes a pruritic rash at the site of entry.
Cough or wheezing and eosinophila.
Dangerous if given steroids like prednisone
Lowers their immune system and allows the filariform larvae to invade the
lungs, GI, and other organs leading to ARDS, pneumonia, and multi-organ
failure.
Make sure to check COPD and asthma pts stool and eosinophil count before
steroids.
Diagnosis
Made by identifying the larvae in feces, not the eggs.
Enterotest: long nylon string is swallowed and then brought back up later to
look for the presence of larvae.
Sputum can be examined for larvae.
Can also do an ELIZA to look for abs.
Trichnella spiralis
Comes from eating the encysted larvae present in the muscle of pork.
The cysts develop into larvae and mature into mating adults where the males leave
with the feces, the females penetrate into the intestinal mucosa to produce lots
more larvae where they can enter the blood, skeletal muscle, and organs.
In the skeletal muscle, they become encysted where they can last for decades.
Presents as:
Most pts are asymptomatic with the initial infection.
Some pts will develop diarrhea, pain, and fever as the larvae mature and go
through the GI wall.
About a week after the invasion, the larvae enter the skeletal muscle where
they produce fevers and muscle aches.
In rare severe cases, they worms can invade the heart and brain tissue to
possibly kill the pt.
Diagnosis
Made with serologic tests or muscle biopsy that reveal the encysted larvae.
There will be increased amount of eosinophils.
There may also be increased amounts of muscle enzymes like CPK.
Trichuris trichiura (whipworm)
Simple slow life cycle that begin and ends in the gut without going to the blood or
lungs.
Eggs hatch in the GI and hang out in the cecum and ascending colon where the adult
will produce lots of eggs for a y.
 There is no autoinfection since the eggs must incubate in moist soil for 3-6 weeks
before they are infective.
Presents as:
Pts may have abdominal pain and diarrhea.
Diagnosis
Look for the eggs in the stool.
The eggs look like footballs with bumps on each end.
Enterobius vermicularis (pinworm)
Simple slow life cycle that begin and ends in the gut without going to the blood or
lungs.
Eggs hatch in the GI and hang out in the cecum and ascending colon.
At night the female comes out and lays eggs in the perianal area that causes severe
itching in that area.
The individual will then infect others after itching the spot (hand to mouth).
Presents as:
A very itchy and annoying perianus.
Diagnosis:
There is no eosinophila since there is no invasion.
Use scotch tape to pick up the eggs in the perianal region.
Onchocerca volvulus
Found in Africa and central and south America.
Transmitted by the black fly.
The microfilariae are transmitted and they mature into adults in fibrous nodules in
the skin and subQ.
The adults make more microfilariae that migrate through the dermis and connective
tissue.
Presents as:
Pruritic skin rash with darkened pigmentation.
Skin may thicken with popular lesions (intraepithelial granulomas) that can
make the skin look dry, scaly, and thick.
Microfilariae can also go to the eye where it causes blindness.
This can often happen in rivers and there are endemic areas where
most inhabitants are blind.
Diagnosis:
Look for microfilariae in skin biopsies or adult worms in a nodule.
Can also look for the microfilariae in the cornea with a slit-lamp examination.
What are the 2 bugs that can cause elephantiasis?
Wuchereria bancrofti and brugia malayi
Wuchereria bancrofti and brugia malayi
Wuchereria is endemic to the pacific islands and Africa.
Brugia is endemic to the Malay Peninsula and Southeast Asia.
Transmitted by a mosquito.
The microfilariae mature into adults in the lymph vessels and LNs of the lower
extremity and genitals.
 The adults then mate and make more microfilariae that enter blood vessels.
Presents as:
Small infections can end with just enlarged LNs.
Multiple infections can lead to acute febrile episodes with headache and
swollen inguinal LNs.
Sometimes after enough infections, fibrous tissue will form around the dead
microfilariae and clog up the lymph system casusing there to be massive
swelling and edema that is covered with thick scaly skin.
Diagnosis:
Look for the microfilariae in blood that is drawn at night since there are very
few microfilariae that circulate during the day (nocturnal periodicity)
Can also be made by looking for abs on immunofluorescence.
Dracunculus medinensis (guinea worm)
Primarily only found in Africa (Sudan and Ghana).
The larvae live inside of copepods and when these tiny crustaceans are ingested
from drinking freshwater, the larvae are able to penetrate the intestine and move
deep into the subQ tissue where the adults develop and mate.
The male dies, but the female continues to grow up to 100cm.
The female then migrates to the surface to poke out the uterus from the skin to
release lots of motile larvae when contact with water is made.
Presents as:
Allergic symptoms including nausea, vomiting, hives, and SOB during the
larval release.
Can use a stick that is slowly turned each day to remove it.
Cutaneous larval migrans
AKA: creeping eruption.
Happens in the SE US.
Larvae of dog/cat hookworm (ancylostoma brazilense) enter the skin and move to
under the epidermis.
Necator americanus and strongyloides stercoralis can produce similar eruptions.
Presents as:
They then move a few cm that results in an allergic response: red, raised,
itching rash that moves with the migrating larvae.
Diagnosis:
Biopsy of the advancing edge of the rash.
Platyhelminthes (flatworms)
They do not have a digestive tract.
Trematodes (flukes)
Include the schistosomes.
Mate within the human, but not in the GI.
Have intermediate hosts in freshwater snails.
Cestodes (tapeworms)
Live and mate in the human GI.
Hermaphrodites so they can reproduce on their own.
Schistosoma (blood flukes)
Second most common infection in the tropics after malaria.
Found in freshwater, penetrate exposed skin, and invade intrahepatic portion of the
portal venous system where they mate and lay eggs around the intestines or
bladder.
The adult worms can live an produce eggs for years by using molecular mimicry to
trick the immune system.
The eggs must reach freshwater to hatch though and thus they cannot multiply in
humans.
The eggs must hatch and the larvae must find a freshwater snail where they can
then become infectious to humans.
Schistosomiasis
3 major dz processes that happen in order.
Dermatitis as the cercariae penetrate the swimmers skin.
Presents with intensely itchy skin and rash.
Katayama fever as the grown adults begin to lay eggs.
Happens 4-8 weeks after the infection and rash occur.
Symptoms include fever, headache, weight loss, hives, and cough that
persist for 3 weeks that can lead to LN, liver, and spleen enlargement
with eosinophilia.
Chronic fibrosis of organs and blood vessels from chronic inflammation
around deposited eggs.
Many of the eggs do not reach the feces and are instead taken by the
blood to the liver, spleen, and brain.
The immune system then locks them away inside granulomas, but
there is also inflammation and ulcer formation.
The eggs in the wall of the venous system leads to fibrosis and
blockage of the portal system and portal HTN.
Can lead to hematuria, chronic abdominal pain, and diarrhea, CNS
injury, or pulmonary HTN.
Diagnosis
Eggs in the stool or urine and serology for abs.
Increased eosinophil counts, esp during katayama fever.
Cestodes (tapeworms)
Tapeworms are flatworms that live in the intestine of the host.
They have no GI system and must take already digested stuff from the host GI.
It is long and segmented with many box segments called proglottids.
The mature proglottids have both of the sex organs.
Gravis proglottids have fertilized eggs.
Scolex: most anterior segement of the tapeworm that has suckers and sometimes
hooks.
Taenia solium (pork tapeworm)
Comes from infected pork with larvae.
Attaches onto the GI epithelium and releases eggs into the feces.
 Can reach a length of 2-8m.
A farmer then poops in a pig field for them to eat.
The eggs also turn into larvae that go through the intestine into the muscle tissue
where they turn into cysticercus (round fluid filled bladder with the larval form
inside) and ready for that farmer to eat rare.
Presents as:
Typically pts have minimal symptoms.
Diagnosis:
Look for eggs or proglottids in the fecal sample.
Cysticercosis.
Happens when humans play the role of the pig and ingest the eggs instead of
the larvae.
The eggs hatch in the gut and then move around the body to encyst in tissues
forming cysticerci, esp in the brain and skeletal tissue.
Diagnosis:
Biopsy of affected tissue (brain or muscle) that reveals calcified
cysticerci.
There are also some serological tests that can be done.
Neurocysticercosis
Cysticerci in the brain causes seizures, obstructive hydrocephalus, or focal
neurological deficits.
After 5-10 y they begin to die and leak their contents out and the resulting
immune rxn casues more seizures, meningitis, hydrocephalus, and focal
deficits.
Most common cause of seizures where it is endemic, like mexico, central and
south America, Philippines and SE Asia.
Taenia saginata (beef tapeworm)
Same life cycle as taenia saginata except that there is no dz manifestation if the eggs
are ingested.
Can reach a length of over 10m.
Presents as:
Pts are typically asymptomatic, but they can dvelop malnutrition and weight
loss.
Diagnosis:
Look for gravid proglottids or eggs in the feces.
Diphyllobothrium latum (fish tapeworm)
Comes from ingesting larvae in freshwater fish.
Can grow to 45m in length.
Uses both a crustacean and then a fish as intermediate hosts.
Presents as:
Mostly asymptomatic with few abdominal symptoms.
Can cause vit B12 deficiency anemia.
Diagnosis:
Look for the eggs in the feces.
Hymenolepis nana (dwarf tapeworm)
Smallest tapeworm that infects humans and has the simplest life cycle.
NO intermediate hosts.
The pt grows the tapeworm from an egg that makes more eggs to give to other
humans.
Presents as:
Abdominal discomfort and occasional nausea with vomiting.
Diagnosis:
Look for eggs in the feces.
Echinococcus granulosus and multilocularis
Causes hydatid dz, an extra-intestinal tapeworm infection.
Dogs and sheep keep the life cycle going, ends in humans.
Humans eat the eggs that turn into larvae that penetrate the GI wall.
The larvae then disseminate through the body (lungs, kidney brain), but they
concentrate mostly in the liver.
Each larvae forms a single fluid filled cyst (hydatid) where they continue to bud
inside the cyst until it is 5-10 cm in size.
The expansion leads to compression of the organ (live and brain).
Humans are also very allergic to the fluid in the cysts and the rxn can be fatal if the
cyst burts.
Echinococcus cysts grow larger and spread only if they rupture.
Multilocularis cysts grow out laterally and can look like a slowly growing tumor.
Only 10% of hydatids cause symptoms.
Diagnosis:
Use a CAT scan and biopsy.

Prions
Transmissible spongiform encephalopathies (TSE)
Creates spongiform pathological changes that lead to brain damage.
Very rare.
Inheritable and infectious.
Long incubation time (months to years).
Gradual increase in severity that leads to death.
No immune response.
Non-inflammatory.
Neuropathological findings may include:
Macroscopically looks normal.
Microscopic spongiform changes:
 Small apparently empty vacuoles of varying sizes within neural tissue.
Neuronal loss with amyloid plaques.
Related dzs
Creutzfeldt-Jacob dz (CJD), kuru (shivering), Gerstmann-Straussler-Scheinker
dz (GSS), and fatal familial insomnia.
Prions
Mostly or entirely made up of the PrP protein with little to no nucleic acid.
Located on chromosome 20.
Can fold into 2 different isoforms: PrP-c or PrP-sc.
PrP-c has some function and is always being made, while PrP-sc is involved
with the dz.
3 different ways to get the dz
Inherited: mutations in the gene that lead to spontaneous conversion to PrP-
sc. Autosomal dominant.
Infectious: exogenous PrP-sc converts the host PrP folding pattern to that of
PrP-sc.
Sporadic: spontaneous conversion of the PrP to the sc form or a rare de novo
mutation in the PrP gene.
Can be caused by feeding infected brain products of sheep to cows and then the
cows are eaten leading to variant CJD (vCJD).
All vCJD cases had a homozygous mutation in met129.
The kuru epidemic was most likely caused by ritualistic cannibalism.
Iatrogenic cases of CJD (iCJD) have been linked to contaminated surgical
instruments, dural and cornel grafts, and admin of cadaveric pituitary hormones.
Presents as:
Rapidly progressive dementia.
Psychiatric symptoms.
Cerebellar symptoms (ataxia).
Involuntary movements (myoclonic jerks and choreoathetosis).
Fatal.
Kuru
Infectious that take months before death.
Presents as atxia, myoclonus followed by dementia.
sCJD, fCJD, and iCJD
Can be infected (iatrogenic), inherited, or unknown source.
Takes 1-few y to die.
Presents as dementia, myoclonus, and followed by ataxia.
vCJD
Infectious dz that takes month to a few years to die.
Presents as psychiatric changes, ataxia, and dementia.
FFI
Inherited dz that takes a y to kill you.
Presents with sleep disturbances followed by dementia.
GSS
 Inherited dz that takes a few y to kill you.
Ataxia followed by dementia.
Diagnosis
Best option is histopathologic examination and immunostaining for PrP-sc of
brain tissue.
CSF is normal except with mildly elevated protein levels.
Tau protein is useful marker for vCJD.
14-3-3 protein is a useful marker for sCJD (sporadic CJD).
MRI can show the hockey stick sign (dorsomedial thalamic
hypersensitivity) and pulvinar sign in vCJD.
Serial EEG: esp useful for sCJD.
There is an abnormal wave pattern (periodic sharp and slow
wave complexes, PSWC).
Found in 2/3 of sCJD, but none of vCJD.
Tonsil biopsy looking for PrP-sc is useful as an early diagnostic tool for
vCJD.