MICROBIOLOGY and PARASITOLOGYMedical Board Exam Review

for August 2007

Nenacia Ranali Nirena R. Palma, MD

BACTERIOLOGY

Basic Bacterial Structure

• Appendages– flagella and pili

• cell envelope– capsule, cell wall and plasma

membrane

• cytoplasmic region– genome (DNA), ribosomes

and inclusions

Appendages• Flagella

– filamentous protein structures for motility

• Pili ~ Fimbriae– short, hair-like structures – usually involved in adherence

(attachment) – resist attack by phagocytic

white blood cells – F or sex pilus, mediates the

transfer of DNA

Cell Wall

• Gives rigid support• protects from osmotic lysis• Peptidoglycan– polymer of disaccharides cross-linked by short

chains of amino acids (peptides)– Murein (N-acetylmuramic acid)

Cell Wall

• Gram positive– Thicker

– Teichoic acid – an antigenic determinant

– No endotoxin, except Listeria monocytogenes

• Gram negative– periplasmic space

(contains enzymes, eg beta-lactamases)

– Outer membrane w/ lipopolysaccharide

– Endotoxin = Lipid A

– High lipid content

Plasma/Cytoplasmic Membrane

• site of oxidative phosphorylation and photophosphorylation

• permeability barrier • consist of saturated or monounsaturated fatty

acids (rarely polyunsaturated fatty acids) and do not normally contain sterols

Capsule/Glycocalyx

• Composed of polysaccharide, except Bacillus anthracis (D-glutamate)

• Mediates adherence to surfaces• Protects against phagocytosis

Cytoplasmic Constituents

• Chromosome – typically one large circular molecule of DNA

• Plasmids – extra-chromosomal; genes for antibiotic resistance, enzymes and toxins

• Ribosomes – for protein synthesis

ExotoxinExotoxin EndotoxinEndotoxinSourceSource Gram (+) and gram Gram (+) and gram

(-) bacteria (-) bacteria Cell wall of gram (-) Cell wall of gram (-) bacteria & Listeriabacteria & Listeria

Secreted from Secreted from cellcell

YesYes NoNo

Location of Location of genesgenes

Plasmid or Plasmid or bacteriophagebacteriophage

Bacterial chromosomeBacterial chromosome

toxicitytoxicity highhigh LowLow

vaccinesvaccines toxoidstoxoids No toxoids formed, no No toxoids formed, no vaccines availablevaccines available

Heat stabilityHeat stability Destroyed at 60 CDestroyed at 60 C Stable at 100 C for 1 Stable at 100 C for 1 hourhour

antigenicityantigenicity Induces antitoxinsInduces antitoxins Poorly antigenicPoorly antigenic

Typical Typical diseasesdiseases

Tetanus, botulism, Tetanus, botulism, diphtheriadiphtheria

Meningococcemia, Meningococcemia, sepsis by gram (-) sepsis by gram (-) rodsrods

Gram Stain

• Crystal Violet (the Primary Stain)

• Iodine Solution (the Mordant)

• Decolorizer (ethanol) • Safranin (the

Counterstain) • Water

Gram Positive Cocci

• Staphylococcus– Clusters

• Streptococcus– Chains

• Micrococcus– tetrad

Gram Positive Bacilli

• Bacillus and Clostridium– Produces spores

• Listeria and Corynebacterium

Gram negative Cocci

• Neisseria– diplococci

• Acinetobacter– Coccobacilli– Often gram variable

Gram negative Bacilli

• Enterobacteriaciae– Thin rods

• Hemophilus– Coccobacilli

• Vibrio and Campylobacter– curved

Gram (+) Cocci

Catalase (+)

Staphylococcus

Catalase (-)

Streptococcus

Coagulase (+)

S. aureus

Coagulase (-)

Novobiocin sensitive

S. epidermidis

Novobiocin resistant

S. saprophyticus

α-hemolysis

(green)

S. Pneumo

Optochin sensitive, bile soluble, (+) capsule

Viridans strep.

S. mutans

β-hemolysis

(clear)

Group A

S. pyogenes

Bacitracin sensitive

Group B

S. Agalactiae

Bacitracin resistant

No hemolysis

Enterococcus

E. fecalis

Pepto-

streptococcus

Gram negative

Coccoid

H. influenza

Bordetella pertussis

Pasteurella

Brucella

BacilliCocci

Neisseria

Maltose

fermenter

N. meningitidis

Maltose

Non-fermenter

N. gonorrhea

Lactose fermenter

Fast

Klebsiella

E. Coli

Enterobacter

Slow

Citrobacter

Serratia

Lactose non-fermenter

Oxidase (+)

Pseudomonas

Oxidase (-)

Shigella

Salmonella

Proteus

Genetic Exchange in Bacteria

• Conjugation– cell-to-cell contact as DNA crosses a sex pilus from

donor to recipient

• Transduction– a virus transfers the genes between mating

bacteria

• Transformation– DNA is acquired directly from the environment,

having been released from another cell

Oxygen Requirement• Obligate Aerobes

• Facultative anaerobes– Aerobic but can grow in the absence of oxygen

• Microaerophilic (aerotolerant anaerobes)– Can tolerate low amounts of oxygen

• Obligate anaerobes

Obligate Obligate aerobesaerobes

FacultativFacultative e anaerobeanaerobess

Micro-Micro-aerophilicaerophilic

Obligate Obligate anaerobesanaerobes

Gram (+)Gram (+) NocardiaNocardia

Bacillus cereusBacillus cereusStaph.Staph.

B. B. anthracisanthracis

Corynebac.Corynebac.

ListeriaListeria

ActinomycActinomyceses

StreptococcuStreptococcuss

ClostridiumClostridium

Gram (-)Gram (-) NeisseriaNeisseria

PseudomonasPseudomonas

BordetellaBordetella

LegionellaLegionella

BrucellaBrucella

all other all other gram gram negativesnegatives

SpirochetesSpirochetes

TreponemaTreponema

BorreliaBorrelia

LeptospiraLeptospira

CampylobactCampylobacterer

BacteroidesBacteroides

Acid fastAcid fast MycobacteriumMycobacterium

NocardiaNocardia

No cell No cell wallwall

MycoplasmMycoplasmaa

Koch’s Postulate• The bacteria must be present in every case of the

disease.

• The bacteria must be isolated from the host with the disease and grown in pure culture.

• The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.

• The bacteria must be recoverable from the experimentally infected host.

Staphylococcus aureus• nonmotile, nonsporeforming facultative anaerobe• fermentation of glucose produces mainly lactic acid• ferments mannitol (distinguishes from S.

epidermidis) • catalase positive • coagulase positive• golden yellow colony on agar

Staphylococcus aureus• Protein A – protect from opsonization and

phagocytosis• Coagulase – clumping factor• Hemolysins• Leukocidins• Hyaluronidase – spreading factor• Staphylokinase• Exfoliatin – scalded skin• Enterotoxins• TSST-1 – superantigen; binds to MHC class II

Staphylococcus aureus• Pneumonia –

cavitations, empyema and effusions

• Endocarditis – acute

• Food poisoning – due to a preformed toxin, onset 1-8 hours

• TSS – tampon use

Staphylococcus aureus

• Treatment– Methicillin– Nafcillin– Dicloxacillin– For MRSA – give Vancomycin

• No vaccine

• Staphylococcus epidermidis–Normal flora of skin– Foley catheters and IV lines–Blood culture contaminant– Infection of prosthetic devices

• Staphylococcus saprophyticus–Urinary tract infections in sexually active

women

Streptococcus pyogenes (GABHS)

• nonmotile, nonsporeforming• capsule composed of hyaluronic acid• exhibit beta (clear) hemolysis on blood agar

Streptococcus pyogenes (GABHS)

• M protein – protection from phagocytosis but susceptible to antibodies

• Streptolysin O - oxygen-labile leukocidin, antigenic

• Streptolysin S – oxygen stable• Pyrogenic/erythrogenic toxin - superantigen• Streptokinase - fibrin lysis

Streptococcus pyogenes (GABHS)• Scarlet fever –

strawberry tongue• Pharyngitis• Rheumatic fever –

sequela of pharyngitis• Glomerulonephritis –

sequela of pharyngitis and skin infections

• Tx: penicillin, erythromycin

• S. agalactiae (Group B)– Beta hemolytic– Neonatal meningitis, pneumonia and sepsis (B for baby)

• Group D Streptococci– Enterococci (E. faecalis, E. faecium)– Non-enterococci (S. bovis, S. equinus)– Urinary and biliary tract infections, SBE– S. bovis associated with colon cancer

Viridans streptococci

• S. salivarius, S. sanguis, S. mitis, S. intermedius, S. mutans

• alpha hemolytic (green)• Optochin resistant• Dental caries (S. mutans)• Subacute bacterial endorcarditis (S. sanguis)

Streptococcus Pneumoniae

• lancet-shaped diplococci

• Alpha-hemolytic, optochin sensitive

• Capsule (Quellung reaction)

Streptococcus Pneumoniae

• Adults: pneumonia and meningitis• Children: otits media

• Pneumonia – lobar with consolidation• Increasing resistance to penicillins, erythromycin, co-

trimoxazole, chloramphenicol

• Pneumococcal vaccine – advised for elderly and asplenic patients

Clostridium perfringens

• Alpha toxin – lecithinase• Spores resistant to cooking

• Gas gangrene/myonecrosis• Food poisoning - abdominal cramps and

diarrhea 8-16 hours after eating contaminated meat or poultry

Clostridium difficile

• Antibiotic associated diarrhea (pseudomembranous colitis)

• Toxin A - causes fluid accumulation in the bowel

• Toxin B - an extremely lethal (cytopathic) toxin • Tx: Metronidazole or vancomycin

Clostridium tetani• Found in soil• terminal spores within a swollen sporangium –

“drumstick appearance”

• Tetanus toxin/tetanospasmin – blocks release of inhibitory glycine neurotransmitter from Renshaw cells in spinal cord

Clostridium tetani

• severe painful spasms and rigidity of the voluntary muscles

• "lockjaw" - spasms of the masseter muscle

• rigidity and violent spasms of the trunk and limb muscles

• Spasms of the pharyngeal muscles - difficulty in swallowing

• Death - interference with the mechanics of respiration

Clostridium tetani

• Vaccines– Immune globulin – preformed Ig– Toxoid – formaldehyde treated toxin

• Penicillin, ventilatory support, muscle relaxant

Clostridium botulinum

• Flaccid paralysis• Floppy babies• Botulinum toxin– Neurotoxin– Toxin ingested in food absorbed in duodenum

and jejunum bloodstream peripheral neuromuscular synapses

– Blocks release of acetylcholine

• Canned foods; ingestion of honey (infants)

Bacillus cereus

• Motile, non-encapsulated• "short-incubation" or emetic form– nausea and vomiting and abdominal cramps– incubation period of 1 to 6 hours– resembles Staphylococcus aureus food poisoning– caused by a preformed heat-stable enterotoxin – Associated with fried rice and eating in Chinese

restaurants

Bacillus cereus

• "long-incubation" or diarrheal form– abdominal cramps and diarrhea with an incubation period

of 8 to 16 hours– Diarrhea may be a small volume or profuse and watery– resembles more food poisoning caused by Clostridium

perfringens– heat-labile enterotoxin - activates intestinal adenylate

cyclase and causes intestinal fluid secretion– meat or vegetable-containing foods after cooking

Bacillus anthracis

• large cells with square ends and centrally-located ellipsoid spores

• Non-motile • Spores on animal products (skin, hide)• Poly-D-glutamate capsule

Bacillus anthracis• Factor I - edema factor (EF); inherent adenylate

cyclase• Factor II - protective antigen (PA), induces protective

antitoxic antibodies; binding (B) domain• Factor III - lethal factor (LF)

• PA+LF combine to produce lethal activity EF+PA produce edema EF+LF is inactive PA+LF+EF produces edema and necrosis and is lethal

Bacillus anthracis• Cutaneous anthrax– via injured skin or mucous membranes – Vesicular papules covered by black eschar

• Inhalation anthrax (woolsorters' disease)– inhalation of spore-containing dust where animal

hair or hides are being handled– begins abruptly with high fever and chest pain– progresses rapidly to a systemic hemorrhagic

pathology and is often fatal

Bacillus anthracis• Gastrointestinal anthrax– Rare– Very high mortality rate

• Tx: Penicillin, tetracyclines and fluoroquinolones effective if administered before the onset of lymphatic spread or septicemia, estimated to be about 24 hours

• Vaccine: protective antigen (three subcutaneous injections given two weeks apart followed by three additional subcutaneous injections given at 6, 12, and 18 months)

Listeria monocytogenes

• Peritrichous flagella are produced at room temperature but not at 37° C

• may be coccoid, so they can be mistaken for streptococci; longer cells may resemble corynebacteria

• Tumbling motility

Listeria monocytogenes

• listeriolysin O • LPS• ability to multiply at low temperatures -

associated with ingestion of milk, meat or vegetable products that have been held at refrigeration temperatures for a long period of time

• Neonatal meningitis and sepsis, abortion, premature delivery

• Tx: ampicillin, no vaccine

Corynebacterium diphtheriae

• Loeffler’s bacillus• aerobic, nonmotile • irregular shaped, club-shaped or V-shaped

arrangements (resembles Chinese letters)• Metachromatic granules

Corynebacterium diphtheriae• Culture: potassium tellurite agar, Loeffler’s

coagulated blood serum• Beta prophage – encodes exotoxin (inhibits

protein synthesis via ADP ribosylation of elongation factor 2 (EF2)

• Pharyngitis with grayish pseudomembrane• Hematogenous spread to affect heart and

neural cells (myocarditis and laryngeal nerve palsy)

Corynebacterium diphtheriae

• Tx: penicillin or erythromycin

• Vaccine: trivalent toxoid (diphtheria, pertussis, tetanus)

Neisseria gonorrhea• Kidney bean shaped• Gram (-) intracellular diplococci• Fimbriae• No capsule• IgA protease, LPS• Culture: Thayer-Martin chocolate agar– V – Vancomycin– C – Colistin (polymixin)– N - Nystatin

Neisseria gonorrhea• Males: urethritis (discharge); painful urination• Females: dyspareunia due to cervicitis; PID,

sterility, ectopic pregnancy, tubo-ovarian abscess, perihepatitis (Fitz-Hugh-Curtis syndrome)

• Neonates: ophthalmia neonatorum• Most common cause of septic arthritis in

sexually active

Neisseria gonorrhea

• Treatment: – Ceftriaxone; Ciprofloxacin or spectinomycin if

allergic to cephalosporins– Plus Doxycycline or azithromycin for Chlamydia– Erythromycin eyedrops – prophylaxis for

ophthalmia neonatorum

• No immunity

Neisseria meningitidis• Meningococcus• Encapsulated, maltose fermenter• Strict human parasite (in nasopharynx)• Respiratory transmission

• IgA protease• Serotypes A, B and C associated with

meningitis (usually type B)

Neisseria meningitidis

• Meningitis – fever, HA, stiff neck, photophobia• Meningococcemia – fever, arthralgias, myalgias,

petechial rash• Waterhouse-Friedrichsen – fulminant; fever, purpura,

DIC, adrenal insufficiency (bilateral adrenal hemorrhage), shock, death

Neisseria meningitidis

• Treatment:– Penicillin or ceftriaxone– Rifampicin for prophylaxis of close contacts

• Vaccine– Against capsular antigens

Enterobacteriaciae• E. coli, Salmonella, Shigella, Klebsiella,

Enterobacter, Serratia, Proteus• Ferments glucose• Oxidase negative• Antigens:– O – somatic (polysaccharide of endotoxin)– H – flagellar– K – capsular

• Lactose fermenters: Klebsiella, E. coli, Enterobactor and Citrobacter

E. coli• 2nd most common cause of neonatal

meningitis• UTI, diarrhea, gram (-) sepsis

• LT (heat labile toxin) – cAMP; similar to cholera toxin

• ST (heat stable) – cGMP

E. coli• Enterotoxigenic (ETEC)– Do not invade– diarrhea in infants and travelers – diarrhea without fever

• Enterohemorrhagic (EHEC)– Serotype O157:H7– moderately invasive – pediatric diarrhea, copious bloody discharge (hemorrhagic

colitis)– hemolytic uremic syndrome (HUS)– inadequately cooked hamburger meat

E. coli• Enteroinvasive (EIEC)– invasive (penetrate and multiply within epithelial

cells)– does not produce shiga toxin– dysentery-like diarrhea (mucous, blood), severe

inflammation, fever – similar to Shigella

• Enteropathogenic (EPEC)– non fimbrial adhesin (intimin)

moderately invasive– usually infantile diarrhea; some inflammation, no

fever;

E. coli

• Index organism for fecal contamination of water (coliforms)

• Treatment– Cephalosporins– Aminoglycosides– Trimethoprim-Sulfamethoxazole– Fluoroquinolones

Salmonella• Non-lactose fermenter, motile, produces H2S

• Vi antigen• Contamination of food and water with animal

feces, except S. typhi (carried only by humans)• 105 organisms – infective dose

Salmonella• Never part of normal flora, always pathogenic• Typhoid fever – fever, rose spots, RLQ pain• Carrier state – in gallbladder• Sepsis – S.cholerasuis, osteomyelitis (in

asplenic patients and those with sickle cell disease)

• Gastoroenteritis – S. enteritidis; watery diarrhea, may contain mucus and trace blood

Salmonella

• Can survive intracellularly in monocytes

• Treatment:– Ciprofloxacin or ceftriaxone for typhoid fever– Fluid and electrolyte replacement in S. enteritidis

as antibiotics may prolong the course of bacterial shedding

Shigella

• 101 organisms – infective dose• Non-motile, no H2S production• No animal reservoir, transmitted via food,

fingers, feces and flies• Never part of normal flora• Shiga toxin – verotoxin; inactivates 60s

ribosomal unit

Shigella

• S.boydii• S.dysenteriae type I - deadly epidemics; HUS• S.flexneri - "group B“; Reiter's syndrome

(urethritis, conjunctivitis, arthritis) • S.sonnei - "Group D" Shigella, accounts for

over two-thirds of the shigellosis

Shigella• Bloody diarrhea, fever, and stomach cramps

starting a day or two after exposure• Usually resolves in 5 to 7 days

• Treament– ampicillin, trimethoprim/sulfamethoxazole,

nalidixic acid, ciprofloxacin– Avoid loperamide or diphenoxylate which

prolong excretion of the organism

Klebsiella pneumoniae

• Usually nosocomial, UTI in px with foley catheters, pneumonia in debilitated px

• 2nd most common cause of sepsis in hospitals (next to E. coli)

• Cavitary pneumonia with red “currant jelly” sputum

• Serratia – bright red pigment

Proteus mirabilis

• Very motile, “swarming” colony on blood agar• Urea-splitting• Cross-reacts with rickettsia• Common cause of UTI and nosocomial

infections

Vibrio cholera• Comma-shaped, single flagella

• Toxin – via ADP ribosylation that permananently activates adenylyl cyclase

• rapidly fatal illnesses - healthy person may become hypotensive within an hour of the onset of symptoms and may die within 2-3 hours if no treatment is provided; first liquid stool to shock in 4-12 hours, with death following in 18 hours to several days

Vibrio cholera

• “rice-water stools”• Treatment:– Immediate fluid and electrolyte replacement– Tetracyclines may shorten the duration of

diarrhea and reduce fluid loss

• V. parahemolyticus– Uncooked seafood– Leading cause of diarrhea in Japan

Campylobacter jejuni

• Comma or S-shaped• Zoonotic (reservoir in wild animals and

poultry)• Fecal-oral transmission or by drinking

unpasteurized milk• Bloody diarrhea

Helicobacter pylori

• Most common cause of duodenal ulcers and chronic gastritis

• Urease (+) – protects from stomach acid• Risk for gastric CA• Treatment:– Combination bismuth, metronidazole, ampicillin

and/or tetracycline– Combination metronidazole, omeprazole and

clarithromycin

Pseudomonas aeruginosa

• Aerobic• single, polar flagellum• Ubiquitous in soil and water• Colony types– rough colony– smooth fried-egg appearance which is large,, with

flat edges and an elevated appearance– mucoid - respiratory and urinary tract secretions,

attributed to the production of alginate slime

Pseudomonas aeruginosa

• Pigments (pyoverdin and pyocyanin)

• Opportunistic pathogen• Wound and burn infections, pneumonia,

sepsis, external otitis (swimmer’s ear), UTI, drug or diabetic osteomyelitis, hot tub folliculitis

Pseudomonas aeruginosa

• Endotoxin (fever, shock)• Exotoxin A (inactivates EF2)

• Treatment– Aminiglycoside plus extended-spectrum penicillin

(piperacillin, ticarcillin)

Bacteroides fragilis• Anaerobic• No lipopolysaccharide• Encapsulated• Predominant flora of colon• Exits colon via break in mucosa in chronic

disease, PID or trauma• Peritoneal abscesses• Tx: metronidazole, clindamycin,

chloramphenicol, drain surgically

Hemophilus influenza

• Coccobacillus• Polysaccharide capsule• Culture:– Chocolate agar with Factor X (hemin) and Factor V

(NAD) present in blood

Hemophilus influenza• Type B

– Leading cause of meningitis in children (6 mos to 1 yr)

– Bacteremia– epiglottitis (obstructive

laryngitis)

• Non-typable– osteomyelitis, and joint

infections– otitis media and sinusitis in

children– pneumonia in infants,

children and adults.

Hemophilus influenza• Treatment – Meningitis: ampicillin for strains of the bacterium

that do not make ß-lactamase, and a third-generation cephalosporin or chloramphenicol for strains that do

– Sinusitis, otitis media and respiratory infections: Amoxicillin with clavulanic acid

– Penicillin-resistant meningitis: Chloramphenicol– Sinusitis or respiratory infection caused by

nontypable H. influenzae: Tetracyclines and sulfa drugs

Hemophilus influenza

• Vaccine– Hib conjugate vaccines - children 15 - 59 months

old should receive a single dose of conjugate vaccine; Children 60 months of age or older and adults normally do not need to be immunized

• Rifampicin prophylaxis in close contacts

Legionella pneumophila

• Identified using silver stain (poor gram stain properties)

• Aerosol transmission from water source habitat

• No person-to-person transmission• Culture: charcoal yeast extract with iron and

cysteine• Atypical pneumonia with high fever and

unproductive cough• Tx: erythromycin

Bordetella pertussis• Gram-negative aerobic coccobacillus that

appears singly or in pairs

• Pertussis toxin – increase in cAMP• Filamentous hemagglutinin – attachment to

ciliated epithelial cells; does not invade• Tracheal cytotoxin – damages ciliated cells• Culture: Bordet-Gengou agar

Bordetella pertussis• Catarrhal stage– Lasts 1-2 weeks, most contagious

• Paroxysmal stage– 2-10 weeks– Lymphocytosis; bursts of non-productive cough

(whoop)– Antibiotics ineffective at this stage

• Convalescent stage

• Tx: erythromycin, if given before the paroxysmal stage

Zoonotic Bacteria• Yersinia pestis– Bipolar staining– flea bite; rodents and prairie dogs– Bubonic plague – swollen regional lymph nodes– “black death”– Tx: Streptomycin, gentamycin, doxycycline

• Brucella– Unpasteurized dairy products– Undulant fever– melitensis (goat/sheep), abortus (cattle), suis

(pigs)

Zoonotic Bacteria• Francisella tularensis– Tick bite; rabbits and squirrels– Tularemia – ulceroglandular lesions (hole in skin,

black base, swollen LN, draining pus)– Tx: gentamycin or streptomycin

• Pasteurella multocida– Animal bite; cats and dogs– Rapid onset cellulitis at bite site– Tx: penicillin

Spirochetes• Borrelia burgdorferi– Bite of Ixodes tick that live on deer and mice

– Lyme disease • Stage I – erythema chronicum migrans (“bull’s

eye” red rash with central clearing

Lyme Disease

• Stage 2 – disseminated stage– Neurologic and cardiac manifestations

• Stage 3 – persistent infection– Autoimmune migratory polyarthritis

• Treatment: Tetracycline

Borrelia recurrentis

• Transmitted via body louse (Pediculus humanus)

• Relapsing fever – antigenic variation– Fever every 8 days– Chills, drenching sweat, headaches, muscle aches

• Culture: during febrile periods only• Treatment: doxycycline or erythromycin

Treponema pallidum• Primary syphilis – painless chancre• Secondary syphilis – disseminated disease,

maculopapular rash on palms and soles, condyloma lata

• Tertiary syphilis – gummas, aortitis, neurosyphilis, Argyll Robertson pupil (accommodates but unreactive to light)

• Congenital syphilis – saber shin, saddle nose, deafness

Treponema pallidum• Non-specific tests: VDRL, RPR• Specific tests: FTA-ABS, MHA-TP• Jarisch Herxheimer reaction – acute

worsening of symptoms after initiation of antibiotics

• Tx: Penicillin G, Erythromycin, Doxycycline

• T. pertenue– Yaws (skin infection, not an STD but VDRL

positive)

Leptospira• Tight coil with hooks on one or both ends (“ice

tongs” appearance)• Direct contact with infected urine or animal

tissue (intact mucous membrane, abraded skin)

• Leptospiremic phase– Spiking temperature, headache, myalgias, red

conjunctiva, photophobia• Immune phase– IgM antibodies; meningismus (neck pain)– urine

Leptospira• Culture: – blood and CSF during the 1st week– Urine during 2nd week to months later

• Weil’s disease (icteric leptospirosis)– Renal failure, hepatitis, mental status changes and

hemorrhage in many organs

• Tx: Penicillin G, Doxycycline

Mycobacterium tuberculosis• Infects only humans• Acid fast (Ziehl-Nielsen stain)• Obligate aerobe• Facultative intracellular parasite• Slow generation time• Culture: Lowenstein-Jensen medium (egg-

based)

Mycobacterium tuberculosis• Virulence factors– Mycolic acid– Cord factor – inhibits neutrophil migration and

damages mitochondria; present only in virulent strains

– Sulfatides – inhibit phagosome from fusing with lysosome

– Wax D – activates protective cellular immune system

Mycobacterium tuberculosis• Primary infection– Middle and lower lung zones– Ghon focus – calcified tubercle in middle or lower

lung zone– Ghon or Ranke complex – focus plus perihilar

lymph node calcified granulomas• Secondary or Reactivation– Pulmonary – apical areas of lungs– Lymph node (scrofula), kidney, spine (Pott’s

disease), joints, CNS– Miliary

Mycobacterium leprae• Hansen’s bacillus• Favors cool areas• not grown in vitro (only in footpads of mice,

armadillos and monkeys)• Transferred through respiratory secretions; less

likely, skin lesions• Lepromatous – most severe form; defective T8 (T

suppressor cells); leonine facies, saddlenose deformity

• Tuberculoid – greater auricular, ulnar, posterior tibial and peroneal nerves usually affected

Mycobacterium lepraeTuberculoidTuberculoid BorderlineBorderline LepromatouLepromatou

ss

Number of Number of skin lesionsskin lesions

singlesingle severalseveral ManyMany

Hair growth Hair growth on skin on skin lesionlesion

absentabsent Slightly Slightly decreaseddecreased

Not Not affectedaffected

Sensation Sensation in lesions of in lesions of the the extremitiesextremities

Completely Completely lostlost

Moderately Moderately lostlost

Not Not affected*affected*

Acid fast Acid fast bacilli in bacilli in scrapingsscrapings

nonenone severalseveral InnumerablInnumerablee

Lepromin Lepromin skin testskin test

Strongly Strongly positivepositive

No reactionNo reaction No reactionNo reaction

Mycobacterium leprae

• Treatment– Long-term oral dapsone (toxicity: hemolysis and

methemoglobinemia)– Alternative: rifampin and combination of

clofazimine and dapsone

Chlamydia• Obligate intracellular parasite• Elementary bodies– Extracellular form– Infectious form, non-replicating, non-

metabolically active

• Reticulate bodies– Intracellular form– Replicating, metabolically active, non-infectious

Chlamydia trachomatis

• Types A, B, C – trachoma• Types D-K – urethritis/PID, ectopic pregnancy,

neonatal pneumonia, inclusion conjunctivitis (ophthalmia neonatorum – inclusion bodies stain with iodine or giemsa)

• Types L1 L2 L3 – lymphogranuloma venereum (positive Frei test)

• Tx: Doxycycline (for adults only), erythromycin (infants and pregnant), azithromycin

Mycoplasma pneumonia• No cell wall• Eaton’s Agent• Cholesterol in cell membrane• Cold agglutinins – agglutination of RBC’s at 4

C, due to cross-reactivity• Dome-shaped colonies with “fried egg”

appearance• Walking pneumonia (fever, with dry non-

productive hacking cough)• Tx: Erythromycin, Tetracycline

MYCOLOGY

Fungi• Eukaryotic with rigid cell wall• chemoheterotrophs (require organic compounds for

both carbon and energy sources)• Obtain nutrients by absorption• obtain nutrients as saprophytes (live off of decaying

matter) or as parasites (live off of living matter)

• Yeast - unicellular fungi which usually appear as oval cells

• Molds - multinucleated, filamentous fungi composed of hyphae

Superficial Mycoses• Malassezia furfur– Tinea/pityriasis versicolor – hypo/hyperpigmented

patches– “spaghetti and meatballs”– Tx: selenium sulfide shampoos; imidazoles

• Exophiala werneckii– Tinea nigra– Black lesions on palms and soles– Tx: topical salicylic acid

Cutaneous Mycoses• Dermatophytes– Microsporum (Wood’s light), Trichophyton,

Epidermophyton floccosum• Branched hyphae• Affects skin, hair and nails– Tinea corporis, cruris, capitis, pedis, unguium,

barbae• Pruritic lesions with central clearing

resembling a ring• Tx: topical imidazoles; oral griseofulvin for

hair and nail involvement

Subcutaneous Mycoses• Sporothrix schenckii– Rose gardener’s disease– Dimorphic fungus that grows on vegetation– Cigar-shaped budding yeast– Local pustule or ulcer with ascending lymphangitis– Tx: Amphotericin B or potassium iodide

• Phialophora and Cladosporium– Chromoblastomycosis – cauliflower warts– Copper-colored sclerotic bodies

Systemic Mycoses

• Dimorphic– Mycelial forms with spores at 25 C on Saboraud’s

agar, yeast at 37 C on blood agar or tissue, except Coccidioides (spherule in tissue)

• Transmitted by spore inhalation• Tx: Amphotericin B, itraconazole

Coccidioides immitis

• San Joaquin valley or desert (“desert bumps,” “valley fever”)

• Mild lung infection• Dissemination: bone

granulomas or meningitis

• Erythema nodosum in 10%

Histoplasma capsulatum

• Bird/bat droppings• Tiny yeasts within

macrophages• Mild pneumonia,

disseminated in immunocompromised

• Mississippi and Ohio river valleys

Blastomyces dermatitidis

• Big, broad-based budding• Almost always symptomatic• From the soil or rotten wood• Rarest systemic mycoses

• Paracoccidioides brasiliensis• “Captain’s wheel” appearance

Opportunistic Mycoses• Candida albicans– oval yeast with

pseudohyphae– Oral thrush in

immunocompromised– Vulvovaginitis– Chronic mucocutaneous

candidiasis– TX: clotrimazole for skin

infections; imidazole supppositories for vaginitis; nystatin for oral thrush; Amphotericin B for sytemic

Cryptococcus neoformans

• Heavily encapsulated yeast• India ink stain• Soil, pigeon droppings• Culture: Saboraud’s agar• Meningitis• Tx: Amphotericin B x 6 months, Flucytosine

Aspergillus fumigatus• Allergic bronchopulmonary aspergillosis –

type I hypersensitivity reaction• Invasive necrotizing pneumonia in AIDS, with

aspergilloma (fungus ball)• not dimorphic• Mold with hyphae that branch at 45 deg.

Angle (V-shaped)

• A. flavus – produces aflatoxin in cereals and nuts (carcinogenic to the liver)

Mucor and Rhizopus

• Mold only – with irregular non-septate hyphae

• Rhinocerebral mucormycosis – assoc. with diabetes

• Proliferate in walls of blood vessels causing infarction of distal tissue

Pneumocystis carinii

• Diffuse interstitial pneumonia

• Yeast• Usually seen in AIDS

patients• Methenamine silver

stain• Tx: co-trimoxazole,

pentamidine, dapsone

Fungi-like bacteria

• Actinomyces israelii– Has sulfur granules– Causes eroding abscesses

• Nocardia asteroides– Acid fast– Lung abscess and cavitations

VIROLOGY

DNA viruses• HHAPPPy (Hepadna, Herpes, Adeno, Pox,

Parvo, Papova)• Double-stranded except Parvo• Linear except Papova (circular, supercoiled)

and Hepadna (circular, incomplete)• Icosahedral except Pox (complex)• Replicate in the nucleus except Pox• Naked: PAP (Parvo, Adeno, Papova)• Enveloped: HPH (Hepadna, Pox, Herpes)

Parvoviridae

• Smallest DNA virus• B19– Fifth disease (erythema infectiosum)– Slapped-cheek appearance– Transient aplastic anemia crisis– Hydrops fetalis– Transmitted via respiratory droplets

Papovaviridae

• Human Papilloma virus– Common warts (types 1 2 4 7)– Genital warts (6 11 16 18)– Cervical cancer (16 18)– Through direct contact

• BK Polyomavirus – nephritis/urethritis• JC Polyomavirus – progressive multifocal

leukoencephalopathy; inhalation of infectious aerosols

Adenoviridae

• Respiratory diseases (3 7 14 21)• Epidemic keratoconjunctivitis “pink eye” (8 11

19 37)• Acute hemorrhagic cystitis (11 21)• Gastroenteritis (40 41)• Hepatitis (1 2 3 5)• Transmitted via respiratory droplets, fecal

matter, hands, fomites

Herpesviridae• HSV 1 – oral lesions; keratoconjunctivitis• HSV 2 – genital lesions– Tzanck smear – multinucleated giant cells with

Cowdry type A inclusion bodies

• Varicella zoster (Human herpesvirus 3)– “dewdrop on a rose petal”– Respiratory droplets or direct contact with

ruptured vesicles– Shingles – single dermatome

Herpesviridae• Epstein Barr virus (HHV 4)– Infectious mononucleosis (kissing disease) – fever,

sore throat, enlarged lymph nodes and spleen– Burkitt’s lymphoma– (+) heterophile antibody– Downey cells – atypical lymphocytes

• Cytomegalovirus (HHV 5)– In milk, saliva, urine and tears– Congenital defects; immunocompromised,

transplant recipients– Owl’s eye inclusion body

Herpesviridae• HHV 6 (Human B-lymphotrophic virus)– Exanthem subitum, roseola infantum, fourth

disease – high fever for 3 to 5 days followed by rash as the fever subsides

– Saliva

• HHV 8 – Sexually transmitted esp. in homosexual men– Kaposi’s sarcoma

Poxviridae

• Largest virus• No animal reservoirs• Variola – smallpox; Guarneri’s inclusion bodies• Vaccinia – cowpox; milkmaid’s blisters• Molluscum contagiosum – small white bumps

with a central dimple, genital region

Hepadnaviridae

• Hepatitis B virus– Acute or chronic hepatitis– Has reverse transcriptase

HBs HBs AgAg

Anti-Anti-HBsAgHBsAg

HBe HBe AgAg

Anti-Anti-HBeAHBeA

gg

Anti-Anti-HBcAgHBcAg

Acute Acute HBVHBV

++ -- ++ -- IgMIgM

Chronic Chronic HBV, high HBV, high infectivityinfectivity

++ -- ++ -- IgGIgG

Chronic Chronic HBV, low HBV, low infectivityinfectivity

++ -- -- ++ IgGIgG

RecoveryRecovery -- ++ -- ++ IgGIgG

ImmunizeImmunizedd

-- ++ -- -- --

RNA viruses• Single stranded except Reoviridae• Replicate in the cytoplasm except

orthomyxoviruses and retroviruses• Enveloped except Calicivirus, Picornavirus,

Reovirus• Helical capsid symmetry except Reo, Picorna,

Toga, Flavi, Calici which have icosahedral symmetry

• Toga, Corona, Retro, Picorna, Calici, Reo, Orthomyxo, Parmyxo, Rhabdo, Bunya, Arena, Filo

Picornaviridae• Smallest RNA virus• Poliovirus – affects anterior horn cells of

spinal cord• Coxsackie A – herpangina; hand foot and

mouth disease• Coxsackie B – aseptic meningitis; pleurodynia,

myocarditis• Echovirus – aseptic meningitis• Rhinovirus – common cold• Hepatitis A virus – acute viral hepatitis

Caliciviridae

• Cup-shaped• Norwalk virus – epidemic viral gastroenteritis

(summer diarrhea)• Hepatitis E virus – endemic hepatitis

Reoviridae

• Rotavirus – leading cause of fatal diarrhea in children

• Colorado tick fever - encephalitis

Togaviridae• Rubella– German measles – 3 day measles– Congenital rubella syndrome – cataracts,

deafness, heart defects, microcephaly

• Alphavirus– Eastern and Western equine encephalitis

• Chikungunya – myositis and arthritis• Onyong-nyong – fever, rash, arthralgia

Flaviviridae

• Dengue – “break bone fever”• Yellow fever• Hepatitis C virus• St. Louis encephalitis• West Nile virus

Arenavirus

• Lymphocytic choriomeningitis virus– Hamsters, animals in rodent breeding facilities

• Lassa fever virus – West Africa

Coronaviridae• 2nd most common cause of common cold• SARS

Retroviridae• Reverse transcriptase• HTLV – adult T-cell leukemia• HIV

– ELISA – screening, highly sensitive, RULE OUT– Western blot – confirmatory, highly specific, RULE

IN

Orthomyxoviridae

• Influenza virus– Hemagglutinin (HA)– Neuraminidase (NA)– Antigenic drift – minor changes; epidemics– Antigenic shift – major reassortment; pandemics– Amantadine and Rimantadine (Influenza A)– Zanamivir, Oseltamivir (Ifluenza A and B)

Paramyxoviridae• Parainfluenza virus – laryngotracheobronchitis

(croup)• Respiratory syncytial virus – most common

cause of pneumonia in infants less than 6 months of age

• Mumps – parotitis• Measles – rubeola– SSPE

Rhabdoviridae

• Zoonotic – all warm-blooded animals; saliva of infected animal

• Bullet-shaped• Negri bodies – collection of virions in the

cytoplasm• Hydrophobia – most characteristic symptom

of the neurologic phase

PARASITOLOGY

Protozoa• Entamoeba hystolytica– Bloody diarrhea, liver abscess; most are

asymptomatic– Trophozoite: single nucleus with ingested RBC– Cyst: 4 small nuclei– Transmission: cyst in water

• Giardia lamblia– “old man’s face,” pear-shaped trophozoite– Bloating, flatulence, foul-smelling diarrhea– Cyst in water

Protozoa• Cryptosporidium– Severe diarrhea in AIDS– Fecal-oral transmission of oocyst

• Trichomonas vaginalis– Foul-smelling green vaginal discharge– Sexually transmitted– Trophozoite: undulating membrane, jerky

movement

Protozoa• Toxoplasma gondii– Brain abscess in HIV– Birth defects– Transmitted via cysts in meat or cat feces– Tx: sulfadiazine + pyrimethamine

• Naegleria– Rapidly fatal meningoencephalitis– Swimming in freshwater lakes (enter via

cribriform plate)

Plasmodia• Vector: Anopheles mosquito• P. falciparum – most severe; cerebral malaria,

almost constant fever• P. malariae – Quartan malaria (every 72

hours)• P. vivax and ovale – Tertian malaria (every 48

hours)

Malaria

• Treatment– Chloroquine– Mefloquine – falciparum resistant to chloroquine– Primaquine – prevent relapse of vivax and ovale– Prophylaxis: mefloquine/chloroquine

Protozoa

• Trypanosoma cruzi– Chaga’s disease – dilated cardiomyopathy,

megacolon, megaesophagus– Reduviid bug “kissing bug”– Tx: Nifurtimox

• T. gambiense/rhodesiense– African sleeping sickness– Tse-tse fly– Tx: suramin for blood-borne disease; melarsoprol

for CNS penetration

Protozoa• Leishmania donovani– Kala-azar – visceral leishmaniasis– Fever, anorexia, weight loss, bone marrow

involvement, splenomegaly– Sandfly– Tx: sodium stibogluconate

• L. tropica (cutaneous, Old World)• L. mexicana (cutaneous, Americas)• L. braziliensis (mucocutaneous, Central/South

America)

Cestodes• Taenia solium (pork tapeworm)– Undercooked pork– Cysticercosis – mass lesions in brain caused by

larva– Tx: Niclosamide, Praziquantel

• Taenia saginata (beef)– No cysticercosis

• Diphyllobothrium latum (fish)– Megaloblastic anemia (B12 deficiency)

Cestodes

• Echinococcus granulosus (dog)– Unilocular hydatid cyst disease – in liver– Anaphylaxis– Humans are dead end hosts

• Hymenolepsis nana (dwarf)– No intermediate host– Eggs directly infectious to humans

Trematodes• Schistosoma– Snails are intermediate hosts– Cercaria – infective stage; skin penetration

(swimmer’s itch)– Fever, chills, diarrhea, lymphadenopathy– S. hematobium (bladder), mansoni (large

intestine), japonicum (small intestine)

• Clonorchis sinensis– Oriental liver fluke– Eating undercooked fish

Trematodes

• Paragonimus westermani– Lung fluke– Chronic cough with bloody sputum– Eating undercooked crab

Intestinal Nematodes• Enterobius vermicularis– Pinworm– Perianal itching– Scotch tape swab

• Trichuris trichiura– Whipworm– Soil-transmitted

• Ascaris lumbricoides– Giant roundworm– Larval migration to lung

Intestinal Nematodes• Ancylostoma/Necator– Hookworm– Microcytic anemia, Skin penetration by larva

• Strongyloides stercoralis– Pneumonitis, eosinophilia– Larvae in stool used for diagnosis– Tx: Ivermectin

• Trichinella spiralis– Eating raw pork with encysted larva– Larva develop in striated muscle– Inflammation of muscle, periorbital edema

Tissue Nematodes• Wuchereria bancrofti– Filariasis – blockage of lymphatics (elephantiasis)– Female Anopheles mosquito– Diethylcarbamazine against microfilariae

• Onchocerca volvulus– River blindness– Female blackflies– Tx Ivermectin

• Loa loa– Deerfly; swelling in skin– TX DEC

Tissue Nematodes

• Dracunculus medinensis– Guinea fire worm disease– Worm protrudes from skin– Ingestion of tiny crustaceans (copepods) in

drinking water

• Toxocara canis– Visceral larva migrans – Blindness due to retinal involvement– Dog: definitive host– Humans: dead end hosts

THANK YOU!