I. Bacteriology
Outline of General Bacteriology
1. Morphology and ultrastructure (overview)
a. Shapes (cocci, bacilli, fusiform, spiral, curved; concept
of pleomophism)
b. Reproduction (binary fission)
c. General cytology (structure and function)
cell wall, plasma membrane, nucleoid, ribosomes, mesosome, inclusions,
appendages (flagella, pili, fimbriae), capsule/glycocalyx
d. Gram stain
e. Gram positive envelope (structure and functions)
peptidoglycan, teichoic acids, lipoteichoic acids, plasma membrane
f. Gram negative envelope
outer membrane (lipopolysaccharide, OM proteins), peptidoglycan,
lipoprotein, periplasmic space, plasma membrane
2. Taxonomy (overview)
a. Kingdom & Divisions (Genus & species example)
b. Basis for classification and identification
visible features, nutrition, endproducts, surface molecules
c. Molecular techniques for identification
nucleic acid homology, PCR, genetic probes
3. Envelope structures, synthesis, and functions
a. Peptidoglycan (PG)
(1) Basic structure (repeating units of ?-1,4 linked N-acetyl-D-glucosamine
and N-acetyl-D-mruamic acid tetra- or pentapeptide; O-acetylated MurNAc
resists lysozyme)
(2) Cross-link options
(3) Synthesis (soluble precursors, carrier [bactoprenol-P],
transglycosylation, transpeptidation, dephospholylation of carrier;
sites of antibiotic actions)
(4) Proinflammatory effects of PG
b. Capsule & glycocalyx
(1) Properties, structure, and composition (examples)
(2) Function in virulence
(3) Assembly (bactoprenol carrier)
c. Pili and fimbreae (somatic versus sex; structure, function,
role in virulence [adherence])
d. Motility and chemotaxis
(1) The flagellum (Basic arrangements [monotrichous, peritrichous],
Structure [differences between Gram positive and negative arrangements;
L, P, S, and M rings, switch and Mot proteins])
(2) Chemotaxis (molecular mechanisms of directed movement; methylation
and phosphorylation reactions)
(3) Axial filament (structure and function)
e. Plasma membrane
(1) Structure and function
(2) Transport (passive, primary and secondary active, group
translocation, periplasmic carriers)
(3) Electron transport and generation of ATP (proton motive
force)
(4) Secretory mechanisms (Types I, II, and III; roles in virulence)
f. Gram Positive envelope
(1) PG (many layers, extensive cross-linking)
(2) Teichoic acids (structure, function, role in virulence)
(3) Teichuronic acids (structure and function)
(4) Lipoteichoic acids (structure, function, role in virulence)
g. Acid fast envelopes
(1) The acid-fast stain
(2) Components and their biological activity
(mycolic acids, cord factor, trehalose mycolates and sulfolipids,
arabinogalactan, arabinomannan, and wax D)
h. Gram negative envelope
(1) PG (few layers, little cross-linking
(2) Outer membrane (structure, function)
(a) lipoprotein (structure, function)
(b) OM proteins (functions, roles in virulence)
(c) Lipopolysaccharide (O-Ag, Core, Lipid A)
Biologic activities of Lipid A (endotoxin): LPS
binding protein/CD14 interactions, effects on phagocytes and endothelial
cells (Sepsis syndrome), LPS assembly (bactoprenol carrier)
4. Endospores
a. Structural and functional aspects of endospores (core, cortex,
coats, dipicolinic acid)
b. Sporulation (induction [quorum sensing], forespore, release)
c. Germination (induction, initiation, outgrowth)
5. Growth and Metabolism
a. General (nutrient requirements, temperature and pH optimum)
b. Carbohydrate metabolism
(1) Aerobic (EMB)
(2) Fermentative (endproducts resulting from alcoholic, homolactic,
mixed acid, butyric, propionic fermentative pathways)
c. Respiration
Anaerobic versus aerobic; TCA (heterotrophic CO2 fixation, reductive
TCA cycle); glyoxylate shunt
d. Nitrogen and sulfur assimilation
(assimilatory reductases)
6. Bacterial genetics, gene transfer, and antibiotic resistance
a. General characteristics of the bacterial chromosome
b. DNA Replication
mechanisms and proteins involved (DnaA, DnaB, DnaC, SSB, Primase
[DnaG], PolI, PolIII, ligase, gyrase)
c. Endonucleases (function and use in cloning)
d. Antibiotic resistance mechanisms (modifying enzymes, target
mutations, uptake mutations, efflux pumps)
e. Mechanisms of gene transfer
(1) Transformation
competence, competence pheromones, quorum sensing, gene
activation, DNA uptake and incorporation
(2) Conjugation
F plasmids, Hfr and transfer of chromosomal genes, F’
plasmids, R factors, roll of transposons
(3) Transduction
mechanisms of generalized and specialized
7. Protein synthesis and regulation of gene expression
a. Review transcription and translation
polycistronic messages, initiation, elongation, termination
b. Transcriptional regulation
operons, regulator proteins and effectors and where they bind
mRNA, catabolite-sensitive operons (Lac operon)
8. Antibiotics
a. General principles
(1) Desired properties
(broad range, bactericidal versus bacteriostatic, good
distribution, selective toxicity)
(2) Measurement of antimicrobial activity
(Diffusion [Etest, Bauer-Kirby], macrodilution, microdilution,
determination of MIC and MBC)
(3) Antimicrobial combinations
(synergism, antagonism, indifference, indications for
combined therapy)
(4) Appropriate prophylactic use of antibiotics
(contacts, preexisting condition, surgery, immunocompromised)
b. Antibiotics that affect cell wall synthesis
(1) Beta-lactam antibiotics (mechanisms of action [inhibit transpeptidation
and activate autolytic enzymes], examples of uses, combinations
with beta-lactamase inhibitors [clavulanic acid, sulbactam,
tazobactam], resistance mechanisms)
(a) Penicillins (natural [Pen G & V], penicillinase-resistant
[methicillin, nafcillin, cloxacillin, oxacillin],
amino-penicillins [ampicillin, amoxacillin],
anti-pseudomonas [azlocillin, ticarcillin], extended spectrum
[mezlocillin, pipercillin])
(b) Cephalosporins (relationship between generations and
activity) (1st generation [cephalexin, cefazolin,
cephalothin; for non-life threatening infections,
surgical prophylaxis], 2nd generation [cefaclor, cefuroxime,
cefoxitin; increased activity against Gram negatives, more resistant to
beta-lactamases], 3rd generation [ceftriaxone, cephotaxime, cefoperazone;
broad spectrum, good CNS penetration], 4th generation [cefepime,
cefirome; broadest spectrum of activity]
(c) Aztreonam (a monobactam; resistant to beta-lactamases;
effective against most Gram negatives)
(d) Imipenem and meropenem (carbapenems; resistant to
most beta- lactamases; used for Gram negative and
positive infections)
(2) Bacitracin (mechanism of action [blocks dephosphorylation
of carier] and uses)
(3) Vancomycin (mechanism of action [blocks transglycosylation]
and uses [for resistant staph])
(4) Other
(a) Cycloserine (uses and mechanism of action [D-alanine
analog])
(b) Isoniazid (uses and mechanism of action [inhibits
mycolic acid synthesis])
(c) Ethambutol (uses and mechanism of action [inhibits
arabinogalactan synthesis])
(d) Ethionamide (uses and mechcanism of action [inhibits
mycolic acid synthesis)
c. Antibiotics that affect membrane integrity
(1) Polymyxins (uses and mechanism of action [disrupts plasma
membrane])
d. Antibiotics that affect nucleic acid and protein synthesis
(1) Antimetabolites
(a) Sulfonamides (examples [sulfisoxazole, sulfmethoxazole,
dapsone], uses, and mechanism of action [inhibit PABA incorporation into
dihydropteroic acid])
(b) Trimethoprim (uses and mechanism of action [inhibits
dihydrofolate reductase])
(2) Inhibitors of DNA synthesis
(a) Quinolones (examples [ciprofloxacin, norfloxacin,
ofloxacin, levofloxacin, moxifloxicin, gatifloxicin], mechanism of action
[inhibit DNA gyrase], and uses)
(b) Rifamycins (rifampin and rifabutin) (mechanism of
action [inhibit RNA polymerase] and uses)
(c) Metronidazole (mechanism of action [damages DNA, not
an inhibitor of synthesis] and uses)
(3) Inhibitors of protein synthesis
(a) Aminoglycosides (examples [streptomycin, neomycin,
gentamicin, tobramycin, amikacin], mechanism of action [binds 30S, blocks
initiation], and uses)
(b) Tetracyclines (examples [tetracycline, doxycycline,
minocycline], mechanism of action [binds 30S, stops elongation], and uses)
(c) Chloramphenicol (mechanism of action [binds 50S, inhibits
peptide bond formation] and uses)
(d) Macrolides (examples [erythromycin, azithromycin,
clarithromycin], mechanism of action [bind 50S, blocks translocation and/or
inhibits peptide bond formation], and uses)
(e) Lincosamides (clinadamycin)(mechanism of action [binds
50S, inhibits peptide bond formation] and uses)
(f) New agents:
i. quinupristin+dalfopristin=Synercid (FDA
approved to treat vancomycin-resistant E. faecium; also effective against
vano-resistant staph)
ii. oxazolidinones (linezolid; FDA approved to treat
MRSA and vancomycin-resistant E. faecium)
9. Sterilization and disinfection
a. Define the following: antiseptic, disinfectant (high
and low levels), germicide,sporicide, bacteriocide, fungicide, virucide,
pasteurization
b. Describe the following: dry and moist heat sterilization,
radiation sterilization, sterilization by filtration
c. Describe common methods of disinfection and what microbes
survive the following agents: alcohols, halogens, aldehydes, phenols, gases,
cationic detergents
d. Describe the following antiseptics and their limitations:
iodine compounds, alcohol, chlorhexidine, hexachlorphene
10. Normal flora
a. Microbe/host interactions (commensalism, symbiosis, parasitism;
residents, transients, carrier state; effects of the normal flora on the
host)
b. Skin (major inhabitants: S. epidermidis, Micrococcus sp.,
Corynebacterium sp., P. acnes; minor: Yeasts, S. aureus, Lactobacillus
sp.)
c. Nose and Nasopharynx (major inhabitants: S. epidermidis, Corynebacterium
sp.; minor: S. aureus, Haemophilus sp., Streptococcus sp., Branhamella
sp.)
d. Mouth (major inhabitants: S. mitis, S. sanguis, S. salivarius, S.
mutans (plaque and caries); other: S. epidermidis, Peptostreptococcus
sp., Lactobacillus sp., Treponema sp., Actinomyces sp., Bacteroides
sp., Fusobacterium sp., Veillonella sp.)
e. Oropharynx (like mouth plus Corynebacterium sp.)
f. Stomach (H. pylori)
g. Small intestine
Jejunum (Corynebacterium sp., Lactobacillus sp., Enterococcus
sp.)
Ileum (distal) (Candida albicans, Enterobacteriaceae,
Gram negative anaerobes)
h. Large intestine (major inhabitants [strict anaerobes]: Bacteroides
sp., Fusobacterium sp., Eubacterium sp., Peptostreptococcus
sp., Bifidobacterium sp.; minor: Enterococcus sp., Staphylococcus
sp., Enterobacteriaceae, C. albicans)
i. Genitourinary tract
Kidneys, bladder, urethra (sterile except for distal urethra
[flora like skin])
Vagina and Uterine cervix (Lactobacillus sp., Bacteriodes
sp., Corynebacterium sp., S. epidermidis, Enterococcus
sp., [C. albicans, T. vaginalis in carriers])
11. Introduction to the pathogens
a. Definition of a pathogen (strict versus opportunistic; intracellular
versus extracellular; definition of virulence and virulence
factors)
b. Events associated with infection
(1) Routes of transmission (secretions, stool, skin, blood,
zoonotic)
(2) Adherence, entry, and dissemination
(3) Incubation, exotoxins and pathologic change (inflammation,
necrosis)
(4) Subclinical infection and carrier state
c. Epidemiology
(1) Define and identify agents, their habitats, reservoirs,
modes of transmission, and define methods of management
(treatment and prevention)
(2) Surveillance (disease prevalence and incidence)
(3) Terms that define disease patterns (outbreak, epidemic,
pandemic, endemic)
(4) Terms that define disease severity (mortality and fatality
rates, attack or infection rates)
The Pathogenic Bacteria (62 major agents)
Staphylococcus aureus
Characteristics:
Gram pos. cocci, facultative anaerobe, tolerates high salt, grows in
clusters, coagulase pos., catalase pos., ferments mannitol, human reservoir
(carriers)
Virulence factors:
biofilm, quorum sensing, ?-toxin, enterotoxins, pyrogenic exotoxins
(TSST-1), exfoliatins, facultative intracellular parasite, proinflammatory
cell wall (induces IL1, TNF), beta-lactamases, adhesion mol (fibrinogen,
collagen, & fibronectin-binding proteins), Protein A, transmission
by direct contact
Infections:
folliculitis, furuncle, carbuncle, cellulitis, impetigo, scalded skin
syndrome, septicemia, endocarditis, pneumonia, osteomyelitis, septic arthritis,
purulent meningitis, food poisoning, toxic shock
Control:
hand washing, mupirocin, macrolide, beta-lactam (w/ or w/o aminoglycoside),
vancomycin
S. epidermidis
Characteristics:
Gram pos. cocci, facultative anaerobe, tolerates high salt, grows in
clusters, coagulase neg., catalase pos., human reservoirs
irulence factors:
biofilm, quorum sensing, proinflammatory products (induces IL1, TNF),
beta-lactamases, transmission by direct contact
Infections:
neonatal bacteremia, prosthetic devise infection, surgical infections,
infections associated with peritoneal dialysis, urinary tract infection
Control:
hand washing, beta-lactams, vancomycin+rifampin
S. saprophyticus
Characteristics:
Gram pos. cocci, facultative anaerobe, tolerates high salt, grows in
clusters, coagulase neg., catalase pos., human reservoir
Virulence factors:
adherence to UT epithelial cells, transmission by direct contact
Infections:
community-acquired UTI
Control:
sulf-trimeth, quinolone, amox+clavulanic
Streptococcus pyogenes
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in chains, catalase neg.,
Group A carb, beta-hemolytic, human reservoirs
Virulence factors:
M-proteins, proinflammatory wall, capsule, Streptolysin O & S,
Streptococcal pyrogenic exotoxins, facultative intracellular pathogen(?);
transmission by aerosols, food, water and direct contact
Infections:
pharyngitis, scarlet fever, toxic shock-like syndrome, impetigo, cellulitis,
erysipela, necrotizing fasciitis, puerperal sepsis, rheumatic fever,
postinfectious glomerulonephritis
Control: penicillin, macrolide
S. agalactiae
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in chains, catalase neg.,
Group B carb, weakly beta-hemolytic; human reservoir
Virulence factors:
proinflammatory wall, capsule, C5a peptidase, intracellular growth;
transmitted by direct contact, person to person
Infections:
neonatal infections (early and late onset), adult infections (septicemia,
meningitis, RT, UT)
Control:
hand washing, hospital control policies, penicillin, vancomycin, ampicillin+aminoglycoside
S. bovis
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in chains, catalase neg.,
Group D carb; animal reservoir
Virulence factors:
proinflammatory wall?; endogenous source (GIT) or transmitted by contaminated
food or water
Infections:
endocarditis, bacteremia (assoc. with GI malignancy)
Control:
penicillin
Enterococcus faecalis and faecium
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in chains, catalase neg.,
Group D carb, hydrolyze esculin, tolerates high salt and bile
Virulence factors:
proinflammatory wall, adhesins, cytolysin (bacteriocin), antibiotic
resistance, endogenous (GIT & vagina) or nosocomial source; transmitted
by direct contact or person to person
Infections:
catheter-associated UTI, septicemia, endocarditis
Control:
hand washing, vancomycin, quinupristin/dalfopristin, linezolid (minocycline
+ chloramphenicol)
Viridans Strep: S. mutans, mitis, sanguis, and others
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in chains, catalase neg.,
inhabit oral cavity & tooth surfaces
Virulence factors:
proinflammatory wall, adhesins ?; endogenous source of infection
Infections:
dental caries, endocarditis
Control:
penicillin
S. pneumoniae
Characteristics:
Gram pos. cocci, facultative anaerobe, grows in pairs, catalase neg,
human reservoir, optochin sensitive
Virulence factors:
transmitted by aerosols or endogenous; capsule, proinflammatory wall,
adhesins (capsule, choline-binding protein, neuraminidase), Pneumococcal
surface protein A & C, autolysin, pneomolysin O, antibiotic resistance
Infections: pneumonia, otitis media, meningitis, sinusitis
Control:Vaccines (adult & child); CAP: macrolide, quinolone, ceftriaxone,
cefotaxime; OM, sinusitis: amox+clav; Meningitis: vanco+3rd gen ceph
Listeria monocytogenes
Characteristics:
Gram pos. rod, facultative anaerobe, catalase pos, oxidase neg, facultative
psychrophile, hydrolyzes esculin, zoonotic, widespread in nature, many
foods contaminated
Virulence factors:
facultative intracellular pathogen (Th1 needed), lysteriolysin, internalin,
actin tails, Act A; transmitted by ingestion, transplacental (in utero),
vaginal
Infections:
pregnancy (septicemia, infection of fetus), neonatal (early and late
onset), adults (meningitis and septicemia most important)
Control:
avoid processed meats; sulf-trimeth prophylaxis; ampicillin+aminoglycoside
Corynebacterium diphtheriae
Characteristics:
Gram pos. club-shaped rods, aerobe, arabinogalactan & mycolic acids
in wall (related to Mycobacteria), black colonies on tellurite agar, human
reservoir
Virulence factors:
aerosol spread, toxin, (other species may produce toxin)
Infections:
related to toxin (myocarditis, neuritis); cutaneous and pharyngeal
Control:
vaccine (DPT); anti-toxin + penicillin, macrolide, or tetracycline
Mycobacterium tuberculosis
Characteristics:
gram pos rod, slow grower, aerobe, human reservoir, lipids in wall
(cord factor, etc.), acid fast, produces niacin
Virulence factors:
facultative intracellular pathogen (Th1 needed), proinflammatory wall,
aerosol spread (prolonged contact), PPD+
Infections:
pneumonia (hypersensitive reaction to bugs); disseminated disease (bone
marrow, nodes, CNS, etc)
Control:
vaccine (limited use in USA); rifampin, isoniazid, pyrazinamide
NOTE: M. bovis causes similar disease. It doesn’t produce niacin and
many animals serve as reservoirs. Transmission by consumption.
Other mycobacteria:
M. kansasii, M. marinum, M. scrofulaceum, M. ulcerans, M. fortuitum,
M. avium, intracellulare
many reservoirs (soil, water, etc); localized to disseminated infections
(M. avium, intracellulare cause disseminated disease in AIDS); treatments
depend on bug
M. leprae
Characteristics:
gram pos rod, intracellular parasite, no growth on lab media, human
and armadillo reservoir, lipids in wall (cord factor, etc.), acid fast
Virulence factors:
intracellular pathogen (Th1 needed but also mediates tissue damage),
proinflammatory wall, phenolic glycolipid capsule, phenolase, transmission
by nasal secretions (?), lepromin+
Infections:
Hansen’s disease: chronic disease of skin, peripheral nerves, &
URT; tuberculoid (paucibacillary), borderline, lepromatous (multibacillary)
Control: multibacillary: rifampin+clofazimine+dapsone; paucibacillary:
rifampin+dapsone
Bacillus anthracis
Characteristics:
gram pos rod, fac. anaerobe, catalase pos, non-motile, endospores,
soil microbe
Virulence factors:
zoonosis; capsule; toxin (PA-EF, PA-LF)
Infections:
toxin & route of entry: intestinal, inhalation, cutaneous anthrax
Control:
vaccine (limited use in USA); penicillin, doxycyline, quinolone
B. cereus
Characteristics:
gram pos rod, fac. anaerobe, catalase pos, motile, endospores, soil
microbe
Virulence factors:
heat labile & stable enterotoxins, cereolysin ?
Infections:
emetic and diarrheal diseases (food-borne); other: bacteremia, pneumonia,
ophthalmitis, osteomyelitis
Control:
proper food storage; serious infections with vancomycin
other Bacillus sp.:
B. subtilis (emetic gastroenteritis, septicemia), B. licheniformis
(diarrheal gastroenteritis)
Clostridium perfringens
Characteristics:
gram pos rod, anaerobe (aerotolerant), non-motile, endospores, soil
and gut microbe, 5 strains based on exotoxin profile (A-E)
Virulence factors:
toxins: alpha (most important) and beta toxin (enteritis necroticans),
enterotoxin (super Ag, heat-labile)
Infections:
traumatic entry of endospores or ischemic tissue; septicemia, intra-abdominal,
biliary tract, genital, pleuropumonary, cellulitis, fasciitis, myonecrosis,
gastroenteritis
Control:
debridement + penicillin or clindamycin
other histotoxic clostridia:
C. septicum (myonecrosis, neutropenic colitis); C. novyi,
C. sordellii, C. histolyticum (myonecrosis);
C. difficile (see below)
C. difficile
Characteristics:
gram pos rod, anaerobe, motile, endospores, soil microbe?, human reservoir?
Virulence factors:
survival in hospitals, adhesins, enterotoxin (toxin A), cytotoxin (toxin
B)
Infections:
self-limited diarrhea, pseudomembranous enterocolitis
Control:
vancomycin, metronidazole
C. tetani
Characteristics:
gram pos rod, anaerobe (very oxygen sensitive), motile, endospores,
soil microbe
Virulence factors:
traumatic entry of endospores; tetanolysin (hemolysin), tetanospasmin
(neurotoxin)
Infections:
tetanus (spastic paralysis): generalized, localized, cephalic, neonatal
Control:
vaccine (Td); wound management, TIG, Td
C. botulinum
Characteristics:
gram pos rod, anaerobe, motile, endospores (very resistant), soil microbe
Virulence factors:
neurotoxins; group I (proteolytic, toxins A, B, or F), group II (nonproteolytic,
toxins B, E, or F)
Infections:
food, wound, infant botulism
Control:
anti-toxin (A, B, E), penicillin, metronidazole
Non-spore forming anaerobes
Gram positive cocci: Peptostreptococcus, Streptococcus (predisposing
conditions; proinflammatory cell walls; infections: brain abscess, pulmonary
infection, intra-abdominal infection, female pelvic infections, skin and
soft tissue infections; control: penicillin, clindamycin, imipenem)
Gram negative rods: Bacteroides fragilis group (~60% of intra-abdominal
infections and ~70% of anaerobic bacteremias), Prevotella, Porphromonas,
Fusobacterium (virulence factors: varies with genus, includes capsule,
adhesins, endotoxin, enzymes; infections: brain, oral, URT, dental, sinuses,
LRT, female genital tract infections; control: drain, debride, metronidazole,
clindamycin, chloramphenicol, imipenem)
Gram positive rods: Propionibacterium acnes (associated with
acne)
Moraxella catarrhalis
Characteristics:
gram neg diplococcus, aerobe, oxidase pos, catalase pos, grows on most
media (not fastidious), human reservoir (5-50% colonization)
Virulence factors:
LOS (no somatic O-polysacch), adhesins (pili and OM proteins), aerosol
transmission
Infections:
otitis media, sinusitis, bronchitis, pneumonia
Control:
cefaclor, marcrolides, quinolones, trimeth-sulfameth
Neisseria meningitidis
Characteristics:
gram neg diplococcus, fastidious (needs extra CO2), oxidase pos, no
growth at room temp, don’t survive on environ surfaces, human reservoir
(3-15% carriers), most cases late winter- early spring, group-specific
capsule (B, C, and Y most common)
Virulence factors:
aerosol transmission, LOS (blebs, no somatic O-polysacch), capsule,
adhesins (OM proteins & pili), sol PG, IgA peptidase
Infections:
septicemia, meningitis, Waterhouse-Friderichsen syndrome
Control:
Vaccine; penicillin, chloramphenicol, ceftriaxone
Neisseria gonorrhoeae
Characteristics:
gram neg diplococcus, fastidious (needs extra CO2), oxidase pos, no
growth at room temp, don’t survive on environ surfaces, human reservoir
Virulence factors:
sexual transmission (neonatal infection in utero or during birth),
LOS (blebs, no somatic O-polysacch), adhesins (OM proteins &
pili [pili antiphagocytic]), sol PG, beta-lactamase, IgA peptidase
Infections:
urethritis (men), cervicitis (women), PID, Disseminated gonococcal
infection (arthritis w/ or w/o skin lesions), gonococcal opthalmia
Control:
ceftriaxone or cefixime or quinolone + doxycycline or azithromycin
Haemophilus influenzae
Characteristics:
gram neg coccobacilli, facultative anaerobe, catalase pos, require
hematin (X-factor) & NAD or NADP (V-factor) for growth, capsule (a-f),
human reservoir (carriage rates <4% for b, ~80% for unencapsulated strains)
Virulence factors:
aerosol transmission, LOS, capsule, OM proteins (adherence, invasion,
intracellular growth), sol PG, IgA peptidase
Infections:
pharyngitis, sinusitis, pneumonia, bronchitis, otitis media, conjunctivitis,
epiglottitis, septicemia, meningitis
Control: Vaccine; cefuroxime, ceftriaxone, amox for non-life-threatening
Other Haemophilus sp.: non-typeable H. influenzae (otitis media, pneumonia, sinusitis, neonatal & postpartum sepsis; macrolide, trimeth-sulfmeth, quinolone); H. influenzae biotype aegypticus (conjunctivitis that may disseminate); H. aphrophilus (endocarditis); H. ducreyi (STD=chancroid)
Pasteurella multocida
Characteristics:
gram neg coccobacilli, facultative anaerobe, catalase pos, oxidase
pos, capsule, mouth of domestic animals (cats)
Virulence factors:
transmission by bite, LPS, capsule
Infections:
cellulitis, septicemia
Control:
penicillin, ampicillin, tetracycline
Bordetella pertussis (and B. parapertussis)
Characteristics:
gram neg coccobacilli, aerobe, capsule, pili, human reservoir
Virulence factors:
aerosol transmission, LPS, capsule, sol PG, pertussis toxin, invasive
adenylate cyclase, adhesins (pertactin, filamentous hemagglutinin, pili,
pertussis toxin)
Infections:
pertussis in children, persistent cough in adults
Control:
Vaccine; macrolide
Francisella tularensis
Characteristics:
gram neg pleomorphic, aerobe, catalase pos, oxidase neg, requires cysteine
for growth, capsule, many animal reservoirs
Virulence factors:
transmission by ticks, biting flies, direct, ingestion, or inhalation;
LPS, capsule, facultative intracellular pathogen, very infectious
Infections:
ulceroglandular, glandular, oculoglandular, pharyngeal, typhoidal,
pneumonic
Control:
avoid infected animals; streptomycin or gentamicin
Brucella melitensis (biovars melitensis, abortus, suis, and canis)
Characteristics:
gram neg coccobacilli, aerobe, catalase pos, oxidase pos, urease pos,
animal reservoir
Virulence factors:
transmission by direct contact or ingestion, LPS, facultative intracellular
pathogen
Infections:
septicemia, granulomas or abscesses in reticuloendothelial tissue (nodes,
bone marrow, spleen, liver)
Control:
doxycycline + rifampin
Yersinia pestis
Characteristics:
gram neg coccobacilli, facultative anaerobe, bipolar staining, capsule,
animal reservoir
Virulence factors:
transmission by flea bite (or aerosols), LPS, capsule (fraction 1 Ag);OM,
membrane, and secreted proteins (type III secretion, adherence [yadA gene
product], invasion & intracellular growth [V & W Ags, yop gene
products, lcr gene products])
Infections:
bubonic, pneumonic, septicemic plague
Control:
streptomycin, gentamycin, tetracycline
Y. pseudotuberculosis
Characteristics:
gram neg coccobacilli, facultative anaerobe, facultative psychrophile,
urease pos, animal reservoir
Virulence factors:
transmission by ingestion, LPS; OM, membrane, and secreted proteins
(type III secretion, adherence [yadA gene product], invasion & intracellular
growth [V & W Ags, yop gene products, lcr gene products])
Infections:
mesinteric adenitis
Control:
avoid contaminated food and water; doxycycline, ceftriaxone, trimeth-sulfmeth
Y. enterocolitica
Characteristics:
gram neg coccobacilli, facultative anaerobe, facultative psychrophile,
urease pos, animal reservoir
Virulence factors:
transmission by ingestion, LPS; OM, membrane, and secreted proteins
(type III secretion, adherence [yadA gene product], invasion & intracellular
growth [V & W Ags, yop gene products, lcr gene products])
Infections:
mesinteric adenitis, gastroenteritis
Control:
avoid contaminated food and water; doxycycline, ceftriaxone, trimeth-sulfmeth
Rickettsia rickettsii
Characteristics:
gram neg coccobacilli, intracellular pathogen, animal reservoir, tick
progeny infected
Virulence factors:
transmission by tick (wood or dog), LPS, strict intracellular pathogen,
phospholipase, actin tails mediate cell to cell spread
Infections:
RMSF (vasculitis, rash)
Control:
avoid tick contact; tetracyclines (preferred), chloramphenicol
Other Rickettsia sp: R. akari (rickettsiapox; zoonotic in mice; mite transmission; rash); R. prowazekii (louse-borne or sporadic typhus; human louse transmission; rash); R. typhi (murine or endemic typhus; zoonotic in rodents; flea transmission; rash).
Ehrlichia chaffeensis
Characteristics:
gram neg?, intracellular pathogen, animal reservoir, life cycle similar
to Chlamydia (elementary bodies, initial bodies, morula [reticulate bodies])
Virulence factors:
transmission by tick (Lone Star tick), strict intracellular pathogen
(monocytes)
Infections:
human monocytic ehrlichiosis
Control:
avoid tick contact; tetracyclines
E. phagocytophila group (phagocytophila & equi)
Characteristics:
gram neg?, intracellular pathogen, animal reservoir, life cycle similar
to Chlamydia (elementary bodies, initial bodies, morula [reticulate bodies])
Virulence factors:
transmission by tick (Ioxodes), strict intracellular pathogen (myeloid
precursors)
Infections:
human granulocytic ehrlichiosis
Control:
avoid tick contact; tetracyclines, chloramphenical
Coxiella burnetii
Characteristics:
gram neg bacilli, intracellular pathogen, animal reservoir, endospores
Virulence factors:
transmission by tick to animals, to humans by inhalation or ingestion;
strict intracellular pathogen
Infections:
Q-fever (febrile disease or atypical pneumonia), chronic (endocarditis,
hepatitis, CNS infections)
Control:
tetracyclines
Chlamydia trachomatis
Characteristics:
gram neg, intracellular pathogen, human reservoir, life cycle (elementary
bodies, reticulate bodies)
Virulence factors:
transmission (elementary bodies) route depends on syndrome; strict
intracellular pathogen
Infections:
trachoma (seros A, B, Ba, C; transmitted by direct contact or flies;
keratitis), inclusion conjunctivitis (seros B, Ba, D-K; direct contact),
urethritis (seros B, Ba, D-K; STD; PID, epididymitis, prostatitis),
lymphogranuloma venereum (seros L1-3; STD)
Control:
tetracyclines, macrolides
C. psittaci (Chlamydophila)
Characteristics:
gram neg, intracellular pathogen, bird reservoir, life cycle (elementary
bodies, reticulate bodies)
Virulence factors:
transmission (elementary bodies) by bite or inhalation; strict intracellular
pathogen
Infections:
atypical pneumonia
Control:
tetracyclines
C. pneumoniae (Chlamydophila)
Characteristics:
gram neg, intracellular pathogen, human reservoir, life cycle (elementary
bodies, reticulate bodies)
Virulence factors:
transmission (elementary bodies) by aerosols; strict intracellular
pathogen
Infections:
pneumonia, bronchitis, sinusitis, pharyngitis, atherosclerosis
Control:
tetracyclines, macrolides
Ureaplasma urealyticum (Ureaplasma & Mycoplasma require exogenous
sterols for their membrane)
Characteristics:
no PG, pleomorphic, extracellular pathogen, human reservoir, urease
pos., prefers anaerobic growth
Virulence factors:
transmission by direct contact ?
Infections: urethritis, PID, perinatal & postpartum sepsis
Control:
tetracyclines, macrolides
Mycoplasma hominis
Characteristics:
no PG, pleomorphic, extracellular pathogen, human reservoir, prefers
aerobic growth
Virulence factors:
transmission by direct contact ?
Infections:
urethritis, cervicitis, PID, perinatal sepsis, neonatal conjunctivitis,
postpartum sepsis
Control:
tetracyclines, macrolides
M. genitalium
Characteristics:
no PG, pleomorphic, extracellular pathogen, human reservoir, prefers
anaerobic growth
Virulence factors:
transmission by direct contact ?
Infections:
urethritis
Control:
tetracyclines, macrolides
M. pneumoniae
Characteristics:
no PG, pleomorphic, extracellular pathogen, human reservoir, aerobe
Virulence factors:
transmission by aerosols, adheres to cilitated epithelial cells (kills
them with cytotoxic membrane?), induces cytokines (IL-1, 6 & TNF) and
inflammatory infiltrate
Infections:
pneumonia, tracheobronchitis, pharyngitis, hemorrhagic bullous myringitis
Control:
tetracyclines, macrolides
Klebsiella pneumoniae spp pneumoniae
Characteristics:
gram neg rod, facultative anaerobe, catalase pos, oxidase neg, capsule,
non-motile, animal reservoir
Virulence factors:
transmission by aerosols, LPS, capsule
Infections:
lobar pneumonia, UTI, septicemia, meningitis
Control:
3rd gen ceph + aminoglycoside
(other species: K. oxytoca, pneumoniae spp ozaenae, pneumoniae spp
rhinoscleromatis)
Proteus mirabilis
Characteristics:
gram neg rod, facultative anaerobe, motile, urease pos, H2S produced,
animal reservoir
Virulence factors:
transmission by direct contact, LPS, motility, urease
Infections: UTI, stones (in compromised: pneumonia, septicemia) (other
species: P. vulgaris)
Control:
3rd gen ceph + aminoglycoside for life-threatening infections; quinolone,
ampicillin or amoxicillin for other
Enterobacteria causing nosocomial UTI, septicemia, or other infection : Enterobacter, Hafnia, Serratia, Citrobacter, Providencia, Morganella, Erwinieae, Edwardsiella
Escherichia coli
Characteristics:
gram neg rod, facultative anaerobe, lactose fermented, oxidase negative,
animal resevoir
Virulence factors:
adhesins, type III secretion, quorum sensing, cytotoxins, LPS, enterotoxins,
etc (see individual syndromes below), source endogenous or exogenous; transmitted
by contaminated food or water, direct contact, fecal-oral
non-GIT Infections & control:
UTI (specific adhesins, cytotoxin, LPS; trimeth-sulfmeth, quinolone,
azithromycin), pneumonia (LPS; 3rd gen ceph + aminoglycoside), sepsis (LPS;
3rd gen ceph + aminoglycoside), meningitis (neonatal; LPS, K-1 strains;
3rd gen ceph + aminoglycoside)
GIT infections:
EPEC (bundle-forming pili, type III secretion, intimin-mediated attachment;
loss of microvilli in sm intestine/absorption inhibited; infant diarrhea)
ETEC (adhere to sm intestine via pili, secrete heat labile (LT) and/or
heat stable (ST) enterotoxins; fluid & electrolyte loss; traveler’s
diarrhea)
EIEC (attaches and invades lg intestine; absorption inhibited; inflammatory
diarrhea that is watery to bloody; adult infection)
EHEC (adheres to lg intestine via pili; secrete Shiga-like toxins I
& II; absorption inhibited; watery diarrhea; O157:H7 & SLT-II causes
hemolytic uremic syndrome)
EAggEC (adheres via bundle-forming pili; noninflammatory diarrhea by
unknown mechanism)
Control:
avoid contaminated food and water, symptomatic, trimeth-sulfmeth, quinolone,
azithromycin
Shigella sonnei
Characteristics:
gram neg rod, facultative anaerobe, nonmotile, no lactose fermentation,
human reservoir
Virulence factors:
transmission by direct contact, person to person, food or water; adherence,
LPS, type III secretion, intracellular growth, Shiga toxin, actin tails
mediate cell to cell spread
Infections:
inflammatory diarrhea that is watery or classic dysentery
Control:
avoid contaminated food/water; quinolone, trimeth-sulfmeth
(other species: S. dysenteriae, flexneri, boydii)
Salmonella enterica (proposed new species name)
(serotypes choleraesuis, paratyphi, typhi, enteritidis, typhimurium,
newport, heidelberg)
Characteristics:
gram neg rod, facultative anaerobe, motile, no lactose fermentation,
H2S production, human (typhi and paratyphi) and animal reservoirs (chickens,
etc. for the rest)
Virulence factors:
transmission by direct contact, person to person, food or water; adherence,
LPS, type III secretion, intracellular growth, enterotoxin, actin rearrangement
Infections:
typhoid fever (S. typhi & paratyphi); inflammatory diarrhea that
is watery and mucoid; septicemia
Control:
vaccine for typhoid fever; avoid contaminated food/water; quinolone
for GIT, ceftriaxone or choramphenicol for septicemia
Vibrio cholerae
Characteristics:
curved gram neg rod, facultative anaerobe, motile, oxidase positive,
only O1 and O137 are associated with cholera; aquatic environment the natural
reservoir
Virulence factors:
transmission by food or water; pili, cholera toxin
Infections:
noninflammatory watery diarrhea
Control:
avoid contaminated food/water; tetracyclines, rehydration
V. parahaemolyticus
Characteristics:
curved gram neg rod, halophilic, facultative anaerobe, motile, oxidase
positive; salt water environment the natural reservoir
Virulence factors:
transmission by food or water; pili, enterotoxin, cytotoxin
Infections:
noninflammatory watery diarrhea to inflammatory dysentery
Control:
avoid raw or undercooked seafood; tetracyclines
V. vulnificus
Characteristics:
curved gram neg rod, halophilic, facultative anaerobe, motile, oxidase
positive; salt water environment the natural reservoir
Virulence factors:
transmission by food or water; pili, proteases, cytotoxin
Infections:
wound infections (rapidly progressive cellulitis), invasive gastroenteritis,
septicemia
Control:
avoid raw or undercooked seafood; tetracyclines, aminoglycosides
Aeromonas hydrophila (and A. caviae, veronii biovar sobria)
Characteristics:
gram neg rod, facultative anaerobe, motile, oxidase positive; aquatic
environment the natural reservoir
Virulence factors:
transmission by trauma, food or water; LPS, enterotoxin, hemolysin?
Infections:
gastroenteritis (noninflammatory to inflammatory), wound infection
(cellulitis, osteomyelitis), sepsis
Control:
avoid raw or undercooked food; tetracyclines, aminoglycosides, trimeth-sulfmeth
also from aquatic envrioments: Plesiomonas shigelloides (inflammatory diarrhea; quinolone, trimeth-sulfmeth)
Pseudomonas aeruginosa
Characteristics:
gram neg rod, mostly aerobic, motile, oxidase & catalase pos, non-fermenter,
wide temp range, nutritionally versatile, fluorescein pigment (pyocyanin);
many environmental reservoirs (including hospitals)
Virulence factors:
transmission by direct contact, food, water; LPS, pili, capsule or
biofilm, proteases, cytotoxin, hemolysin, exotoxin A, exoenzyme (exotoxin)
S, quorum sensing, antibiotic resistance
Infections:
mostly opportunistic and nosocomial; endocarditis, respiratory tract
infections, pneumonia in cystic fibrosis, septicemia, meningitis, otitis,
keratitis, bone and joint infections, UTI, skin (burn infections), generalized
folliculitis
Control:
aminoglycoside + anti-Pseudomonas beta-lactam
Related opportunistic bacteria: Burkholderia cepacia (RT infections in cystic fibrosis, catheter-associated UTI & septicemia; trimeth-sulfmeth), Stenotrophomonas maltophilia (nosocomial septicemia, meningitis, UTI, wound infections; trimeth-sulfmeth)
Legionella pneumophila
Characteristics:
gram neg rod, aerobe, catalase pos, oxidase neg, hydrolyzes hippurate,
motile, fastidious; aquatic environment the natural reservoir (parasitizes
amoebas and cilliated protozoans)
Virulence factors:
transmission by aerosols (point-source); LPS (OM blebs), type II, III,
IV secretion, intracellular growth (internalized by coiling phagocytosis),
pili, Th1 response needed
Infections:
Pontiac fever (high attack rate, self limiting febrile disease), Legionnaires’
disease (low attack rate, predisposing condition, bronchopneumonia with
dry cough that becomes productive; GIT, CNS, and kidneys may be involved)
Control:
macrolide, quinolones
Campylobacter fetus (ssp fetus & venerealis)
Characteristics:
gram neg spiral rod, microaerophilic, motile (at 37C), oxidase &
catalase positive, grows at 25C & 42C; zoonotic; many animal reservoirs
Virulence factors:
transmission by direct contact or food or water; LPS, capsule
Infections:
infections in immunocompromised; septicemia following gastroenteritis
Control:
avoid undercooked food and contaminated water; tetracyclines, macrolides,
quinolones
C. jejuni (ssp jejuni)
Characteristics:
gram neg spiral rod, microaerophilic, motile (at 37C), oxidase &
catalase positive, grows at 42C but not at 25C; many animal reservoirs
(especially food animals)
Virulence factors:
transmission by contaminated food or water; LPS, invasive, enterotoxin?,
cytotoxin?
Infections:
the leading cause of bacterial food-borne gastroenteritis (inflammatory);
disseminated disease in immunocompromised; Guillain-Barre syndrome
Control:
avoid undercooked food and contaminated water; tetracyclines, macrolides,
quinolones
Helicobacter pylori
Characteristics:
gram neg spiral rod, microaerophilic, motile (at 37C), urease, oxidase
& catalase positive; many animal reservoirs
Virulence factors:
route of transmission fecal/oral or direct contact; LPS, urease, acid-inhibitory
protein, motility, mucinase, cytotoxin, adhesins (hemagglutinin, sialic
acid-binding protein, Lewis blood group adhesin)
Infections: chronic gastritis leading to ulcerations; predisposes to
carcinoma
Control:
improve sanitation; macrolide or tetracycline + metronidazole + bismuth
subsalicylate
Treponema pallidum (ssp pallidum)
Characteristics:
gram neg spirochete, microaerophilic, motile, no growth on lab media,
cardiolipin in OM; human reservoir
Virulence factors:
sexual transmission; LPS, highly invasive, intracellular growth ??
Infections:
Syphilis (primary, secondary, latent, tertiary, congenital)
Control:
condoms, sexual behavior; penicillin
Borrelia
B. recurrentis (lice vector, humans only host), B. hermsii
and others (tick vector, rodents and small mammal are natural hosts)
Characteristics:
gram neg spirochete, motile, microaerophilic, difficult to culture
Virulence factors:
LPS, changes antigenic structure, highly invasive, intracellular growth??
Infections:
Relapsing fever
Control:
avoid vectors; tetracyclines, macrolides, chloramphenicol
B. burgdorferi
(2 other species in Europe and Japan)
Characteristics:
gram neg spirochete, motile, microaerophilic, can be cultured; tick
vector, mice, deer, birds are reservoirs
Virulence factors:
LPS, adhesins, invasive ??
Infections:
Lyme disease (early localized [erythema chronicum migrans], early disseminated
[secondary skin lesions, facial nerve palsy, meningitis, carditis], late
disease [arthritis])
Control:
avoid vectors; vaccine off the market; doxycycline, ceftriaxone
Leptospira interrogans
Characteristics:
gram neg spirochete, motile, aerobe, can be cultured; many animals
are reservoirs
Virulence factors:
transmitted by direct contact with contaminated water, etc; LPS, invasive,
intracellular growth??
Infections:
anicteric leptospirosis, icteric leptospirosis (Weil’s disease)
Control:
avoid vectors; penicillin, tetracyclines, macrolides
Miscellaneous Bacteria
Bartonella henselae (gram neg rod; cat scratch disease; bacillary angiomatosis in immunocompromised; rifampin, quinolones, azithromycin)
Actinomyces israelli (gram pos filaments that fragment; anaerobes to facultative anaerobes; “sulfur granules” common; pyogenic abscesses connected by sinus tracts; cervicofacial, thoracic, abdominal, and genital infections; penicillin, tetracyclines, macrolides)
Norcardia asteroides (gram pos filaments that fragment; strict
aerobes; no sulfur granules; RT infection that disseminates to CNS in immunocompromised;
trimeth-sulfmeth, tetracyclines)
II. Virology
Outline of General Virology
1) Morphology and structure of viruses
a) Nucleic Acid serving as genome -(DNA or RNA; double-stranded or
single-stranded; positive strand RNA, or negative strand RNA)
b) Nucleocapsid
i) Composition (capsid proteins, enzymes and nucleic acid genome)
ii) Function of individual components (e.g., capsid proteins- protection
of nucleic acids; nucleic acid genome- replication and transcription)
iii) Types (helical vs icosahedral)
c) Envelope or Membrane
i) Composition and origin - (trilaminar phospholipid membrane derived
from host cell)
ii) Viral proteins associated with envelope
(1) Matrix proteins
(2) Glycoproteins
(a) Composition - (viral protein moiety, cellular carbohydrate moiety)
(b) Functions - (enzymatic, serves in attachment of virus to cells,
major antigen that gives rise to neutralizing antibodies)
d) Types of Viruses
i) Naked viruses
ii) Enveloped viruses
2) Classification of viruses
a) Epidemiological scheme- based on transmission of viruses (respiratory
vs enteric vs arthopod-borne)
b) Biochemical scheme- based on the structure and composition of viruses
3) Life Cycle of Viruses
a) Attachment (basis of specificity)
b) Penetration (receptor-mediated endocytosis and membrane fusion)
c) Uncoating (location and mechanism)
d) Replication (location of viral protein and of viral nucleic acid
biosynthesis)
e) Assembly (location)
f) Release (cell lysis vs budding)
4) Types of viral infections (abortive vs acute vs persistent vs latent)
5) Replication of viral genomes
a) DNA-containing viral genomes (most replicate within nucleus, synthesize
early and late mRNAs, and encode a DNA-dependent DNA polymerase, but not
a DNA-dependent RNA polymerase). Notable exceptions are indicated below.
i) Papovaviruses - does not encode a viral DNA-dependent DNA polymerase
ii) Parvoviruses - does not encode a viral DNA-dependent DNA polymerase;
no temporal control of translation of viral proteins
iii) Poxviruses - core contains a DNA-dependent RNA polymerase, replicates
within core and in cytoplasm
iv) Adenoviruses - no exceptions
v) Herpesviruses - encodes a thymidine kinase, three classes of RNA
transcripts - alpha, beta and gamma transcripts.
vi) Hepadnaviruses - replicates in cytoplasm, contains a reverse transcriptase,
DNA genome is replicated via a RNA intermediate, DNA replication occurs
within cores, no temporal control of translation of viral proteins.
b) RNA-containing viral genomes (all encode a RNA-dependent polymerase;
most replicate in cytoplasm and synthesize transcripts at the same time).
Exceptions and other features are listed below.
i) Double-stranded RNA viruses - early and late transcripts, replication
of genome occurs within cores using positive-strand RNA as template.
ii) Positive-stranded viruses - genome is synthesized using negative
strand viral RNA as a template; translation results in polyproteins which
are cleaved to form RNA polymerases and viral proteases. Togaviruses synthesize
early and late RNA transcripts.
iii) Negative-stranded viruses - nucleocapsid contains a RNA-dependent
RNA polymerase which synthesizes a positive strand RNA for translation
and as a template for synthesis of genome. Orthomyxoviral genomes replicate
in nucleus using cellular RNA as primer and virions assemble in cytoplasm
iv) Retroviruses - nucleocapsid contains a RNA-dependent DNA polymerase
and an integrase. The virion RNA is a template for the synthesis of a DNA
copy. The viral double-stranded DNA integrates into the host's chromosome.
Transcription of the integrated viral DNA results in viral RNA that serves
as progeny genomes and is used for translation. Viral polyproteins are
cleaved by viral proteases to form virion proteins including the RNA-dependent
DNA polymerase and integrase.
6) Anti-viral agents
a) Interferon
i) Types and characteristics (alpha, beta, and gamma interferons)
ii) Properties of alpha- and beta-interferon
(1) Encoded by cellular gene
(2) Transcription occurs upon viral infection, associated with viral
nucleic acid replication
(3) Binds to specific receptor proteins on cell membrane, accounting
for species specificity
(4) Induction of interferon-inducible proteins by signal transduction
and phosphorylation of cellular transcription factors
(5) Activation and functioning of the interferon inducible enzymes
requires viral double-stranded RNA and ATP
(6) Functions of interferon-inducible 2'-5' adenylate synthetase and
of the interferon inducible protein kinase
b) Antiviral agents affecting nucleic acid synthesis
i) Nucleoside analogs
(1) Inhibits viral polymerase activity by causing chain termination
(a) Acyclovir (derivatives of acyclovir include valacyclovir, penciclovir,
famciclovir)
(i) Specifically phosphorylated by herpesvirus thymidine kinase.
(ii) Preferentially inhibits herpesviral DNA-dependent DNA polymerase
(b) Ganciclovir, Cidofvir
(i) Used in treatment of cytomegaloviral retinitis in AIDS patients.
Specific inhibition of viral DDDP
(ii) Phosphorylated by CMV protein kinase
(c) Adenine arabinoside
(i) No preferential phosphorlyation by herpes viral thymidine kinase
(ii) Preferentially inhibits herpesviral DDDP
(iii) Rapidly inactivated by adenosine deaminase to an inactive metabolite
(d) Azidothymidine (AZT)
(i) Phosphorylated by cellular enzymes
(ii) Inhibits HIV reverse transcriptase preferentially as compared
to cellular DNA polymerase
(iii) Other nucleoside analogs that inhibit HIV reverse transcriptase:
lamivudine, didanosine, stavudine, zalcitabine, abacavir
(2) Causes errors in replication and transcription
(a) Ribavirin - inhibits respiratory synctial virus; also inhibits
nucleoside biosynthesis and formation of the mRNA 5' guanosine cap
(b) Trifluorothymidine (TFT) - thymidine analog, phosphorylated by
cellular enzymes, topical administration.
(c) Iododeoxyuridine - same as TFT
ii) Non-nucleoside analogs
(1) Foscarnet - Binds to the pyrophosphate binding site of the herpesvirus
DNA polymerase and inhibits the viral DNA polymerase activity. Does not
require phosphorylation to be active. Treatment of CMV retinitis in AIDS
patients.
(2) Nevirapine, and delavirdine - noncompetitively inhibits HIV-1 reverse
transciptase by binding to the enzyme. Does not require phosphorylation
to be active.
c) Antiviral agents inhibiting uncoating - amantadine and rimantadine
(specifically inhibits uncoating of influenza A viruses
d) Antiviral agents affecting enzymatic functions of viral proteins
i) Protease Inhibitors (saquinavir, indinavir, ritinavir, ritonavir,
amprenavir) - Binds to active site of the HIV protease inhibiting the cleavage
of HIV polyproteins.
ii) Neuraminidase Inhibitors (zanamivir, oseltamivir) - competitive
inhibitor of sialic acid binding, prevents the functioning of neuraminidase
and the formation of infectious progeny virions.
Pathogenic Viruses (43 major agents)
Adenovirus (family Adenoviridae, genus Mastadenovirus)
Characteristics:
naked icosahedral capsid (hexon, hexon-associated proteins, fiber [attachment,
hemagglutination] penton base [cytotoxic], core proteins [no enzymes]),
genome dsDNA
Replication:
in nucleus; may be asymmetric; pre-early, early, and late transcripts;
release by cell lysis
Pathogenesis:
lytic or latent infections; transmission by aerosols, direct contact,
fecal/oral; inhibits assembly of MHC I proteins, blocks TNF and IFN signals
Infections:
acute febrile pharyngitis, atypical pneumonia, pertussis-like syndrome,
pharyngoconjunctival fever, epidemic keratoconjunctivitis, acute hemorrhagic
cystitis, gastroenteritis
Control/prevention:
none
Human Herpes Virus -1 & -2 (family Herpesviridae, genus Simplexvirus)
Characteristics:
enveloped [from nucleus] icosahedral capsid (envelope proteins [B,
D, E, C, H], no core enzymes), genome dsDNA
Replication:
in nucleus; immediate early (? proteins), early (? proteins), and late
(? proteins) transcripts; release by budding and cell lysis
Pathogenesis:
lytic and latent infections; transmission by saliva, sex, and vesicle
fluid; giant cells, syncytia, and intranuclear inclusions occur
Infections:
gingivostomatitis, pharyngotonsillitis, vulvovaginitis, skin infections
(whitlow, gladiatorum), genital herpes, meningitis, encephalitis, neonatal
infection, infection in the immunocompromised, recurrent infections
Control/prevention:
acyclovir, famciclovir, valacyclovir; topical preparations
Human Herpes Virus -3 (family Herpesviridae, genus Varicellovirus;
Varicella-zoster virus)
Characteristics:
similar to HHV-1 & -2 except envelope proteins gpI-V
Replication:
similar to HHV-1 & -2
Pathogenesis:
lytic and latent infections; transmission by aerosols (RT droplets)
and vesicle fluid; giant cells, syncytia, and intranuclear inclusions occur;
infects reticuloendothelial tissue then mucous membranes and skin following
viremia
Infections:
chickenpox (varicella), shingles (zoster)
Control/prevention:
vaccine, VZIG; acyclovir for varicella, famciclovir or valacyclovir
for zoster
Human Herpes Virus -4 (family Herpesviridae, genus Lymphocryptovirus;
Epstein Barr Virus)
Characteristics:
similar to HHV-1 & -2 except has a matrix protein surrounding capsid
(pp65 Ag)
Replication:
similar to HHV-1 & -2
Pathogenesis:
cellular receptor is CD21 (CR2); productive, transforming and latent
infections; transmission by intimate contact (saliva); IL-10-like protein
inhibits Th1 response; B cell activation and proliferation (heterophile
Abs), 2 phases of lymphocytosis (B cells and Downey cells)
Infections:
mononucleosis (complications), chronic HHV-4 infection, neoplastic
diseases
Control/prevention:
none
Human Herpes Virus -5 (family Herpesviridae, genus Cytomegalovirus)
Characteristics:
similar to HHV-1 & -2; the largest virus infecting humans
Replication:
similar to HHV-1 & -2; large nuclear inclusions occur (“Owl’s eye”
inclusion bodies); grows only in human cells
Pathogenesis:
inhibits MHC I expression; productive and latent infections; congenital,
perinatal, oral, sexual, blood, and transplants route of transmission
Infections:
congenital infection (cytomegalic inclusion disease), perinatal inection,
mononucleosis, hepatitis, infection in immunocompromised (pneumonia, chorioretinitis,
colitis/esophaitis, CNS
Control/prevention:
cytogam, ganciclovir, foscarnet, cidovir
Human Herpes Virus -6 (& 7) (family Herpesviridae, genus
Roseolovirus)
Characteristics:
similar to HHV-1 & -2
Replication:
similar to HHV-1 & -2
Pathogenesis:
transmitted by saliva; productive and latent infections; infects mononuclear
cells
Infections:
Roseola (6th disease) in children; adult infection (lymphadenopathy,
hepatitis, mono-like syndrome); in immunocompromised (pneumonitis, encephalitis,
hepatitis); HHV-7 may cause second cases of Roseola
Control/prevention:
foscarnet for serious infections
Human Herpes Virus -8 (family Herpesviridae, genus Rhadinovirus)
Characteristics:
?
Replication:
?
Pathogenesis/Infections:
Kaposi’s sarcoma
Control/prevention:
none ?
Smallpox (Family Poxviridae, genus Orthopoxvirus, species Variola
virus)
Characteristics:
complex envelope and symmetry; genome is linear dsDNA; core contains
DNA-dependent-RNA pol
Replication:
synthetically self-contained; replicates and assembles in cytoplasm;
release by cell lysis
Pathogenesis:
humans only reservoir; transmission by aerosols or direct contact;
replicates in reticuloendothelial tissue then disseminates to skin and
mucous membranes
Infections:
variola major and minor
Control/prevention:
no treatment; vaccine (Vaccinia virus) not available to public
Molluscum contagiosum virus (Family Poxviridae, genus Molluscipoxvirus)
Characteristics:
similar to other Poxviridae
Replication:
similar to other Poxviridae
Pathogenesis:
transmitted by direct contact; self-limiting wart-like cutaneous lesions
occur
Infections:
Molluscum contagiosum
Control/prevention:
no treatment
Human Parvovirus (B19) (Family Parvoviridae, genus Erythrovirus)
Characteristics:
smallest DNA virus; non-enveloped, icosahedral symmetry; ssDNA genome
Replication:
in nucleus
Pathogenesis:
aerosol or transplacental routes of infection; infects stem cells (e.g.
erythroid precursors); requires mitotically active cells; humans only reservoir
Infections:
Erythema infectiosum (5th disease) in children; mild disease in adults
(polyarthritis)
Control/prevention:
none
Human Papillomavirus (Family Papillomaviridae, genus Papillomavirus)
Characteristics:
non-enveloped, icosahedral symmetry; circular dsDNA genome; no enzymatic
activity
Replication:
in nucleus utilizing host enzymes
Pathogenesis:
the most common viral STD; transmission by direct contact (lesions
or inanimate objects); long incubation; latent and productive infections
occur; infection induces epithelial hyperplasia (inhibits apoptosis)
Infections:
Papillomas: cutaneous, head and neck, anogenital; cervical cancer
Control/prevention:
chemicals, surgery, IFN? for genital infection
Polyomavirus (family Polyomaviridae; JC and BK viruses)
Characteristics:
similar to the Papilloma viruses
Replication:
similar to Papilloma viruses except prefer to replicate in the respiratory
and urinary tracts (JC and BK)
and CNS (JC)
Pathogenesis:
aerosol transmission (?); multiply in respiratory tract then kidney
after viremia; latent infection in kidney
Infections:
JC: progressive multifocal leukoencephalopathy; BK & JC: UTI in
immunosuppressed
Control/prevention:
none
Enterovirus (family Picornaviridae; Coxsackie A & B, Echovirus,
[new] Enterovirus, Poliovirus)
Characteristics:
positive polarity ssRNA genome; non-enveloped icosahedral symmetry;
capsid proteins (VP1-4) mediate adherence
Replication:
in cytoplasm; one large protein processed to structural proteins, polymerase,
and protease; release by cell lysis
Pathogenesis:
transmitted by fecal oral, direct contact, or aerosols; initial replication
in GIT; humans only reservoir; resistant to low pH, salt, detergents; final
target tissue varies with virus (e.g. skin, heart, CNS)
Infections:
Poliovirus (Poliomyelitis), Coxsackie A (acute febrile disease, meningitis,
encephalitis, cold w/ fever, febrile rashes, pericarditis, hemorrhagic
conjunctivitis), Coxsackie B (acute febrile disease, meningitis, encephalitis,
cold w/ fever, myocarditis, pericarditis, pleurodynia, transplacental infection),
Echovirus (acute febrile disease, meningitis, encephalitis, cold w/ fever,
febrile rashes, diarrhea w/ fever, transplacental infection), new Enterovirus
(hemorrhagic conjunctivitis)
Control/prevention:
no treatment; vaccine for Poliovirus (IPV)
Rhinovirus (family Picornaviridae)
Characteristics:
like genus Enterovirus
Replication:
like genus Enterovirus
Pathogenesis:
most cases in early fall & late spring; transmitted by direct contact
(hand to hand, object to hand) or aerosols; replication in URT; humans
only reservoir; ICAM-1 host cell receptor
Infections:
cold, lower RT infection, exacerbation of chronic lung and bronchial
diseases (e.g. asthma)
Control/prevention:
no treatment or vaccine
Influenzavirus (family Orthomyxovirus; species Influenza A, B,
C)
Characteristics:
helical symmetry, enveloped, A and B have 8 negative polarity ssRNA,
C has 7 segments; NA (N) and HA (H) envelope proteins (antigenic drifts
and shifts); polymerase (PA, PB1, PB2); matrix protein (M1); membrane protein
(M2); nucleocapsid (NP); nonstructural proteins (NS1, NS2)
Replication:
replicates in nucleus, assembles in cytoplasm; viral RNA-dependent
RNA Pol synthesizes pos pol RNA for translation and templates for genome
replication
Pathogenesis:
birds and other animals reservoirs for Inf A; B and C reservoir humans;
aerosol transmission; NS1 inhibits host translation; replication in RT
induces desquamation; cytokines and T cells responses contribute to pathogenesis
Infections:
influenza (complications: influenza pneumonia, bacterial pneumonia,
myositis, meningitis, Reye syndrome), common cold
Control/prevention:
vaccine; amantadine, rimantadine, zanamivir, oseltamivir
Parainfluenza (Human Parainfluenza viruses, HPIV 1, 2, 3, 4A,
4B) (family Paramyxoviridae, genus Respirovirus (HPIV 1 & 3), genus
Rubulavirus (HPIV 2 & 4A, B)
Characteristics:
enveloped, helical symmetry, 1 segment neg polarity RNA for genome;
NP, nucleoprotein (capsid); P & L proteins (polymerases); M, matrix
(assembly); F, fusion protein (promotes syncytia); HN, hemagglutinin/neuraminidase
(attachment)
Replication:
replicates and assembles in cytoplasm; polymerases synthesize pos pol
RNA for translation and template for genome synthesis
Pathogenesis:
transmitted by aerosols or direct contact; humans only reservoir; replicates
in mucosal epithelium of URT; immunity short-lived so re-infections common;
Th1 response contributes to path; HPIV-1 and 2 peaks in fall and winter;
HPIV-3 all year with peak in spring; HPIV-4 all year
Infections:
HPIV-1-3: croup, pneumonia, bronchiolitis/bronchitis; HPIV-1-4: cold,
otitis media, conjunctivitis
control/prevention:
upper airway support
Mumps virus (family Paramyxoviridae, genus Rubulavirus)
Characteristics:
like Parainfluenza
Replication:
like Parainfluenza
Pathogenesis:
transmitted by aerosols; humans only reservoir; replicates in mucosal
epithelium of URT yielding viremia; infects parotids and submandibular
glands; also may infect pancreas, testes, ovaries, peripheral nerves, eye,
inner ear, and CNS; virus occurs in oral secretions and urine
Infections:
mumps (parotitis); complications (orchitis, oophoritis, meningitis,
encephalitis)
Control/prevention:
vaccine
Measles virus (Rubeola) (family Paramyxoviridae, genus Morbillivirus)
Characteristics:
like Parainfluenza excepts has H protein for attachment rather than
HN
Replication:
like Parainfluenza
Pathogenesis:
transmitted by aerosols; humans only reservoir; replicates in URT,
then reticuloendothelial tissue yielding viremia; infects conjunctivae,
UT, CNS, RT; infection of endothelial cells results in vasculitis; virus
occurs in RT secretions, urine
Infections:
measles; complications (encephalitis, pneumonia, subacute sclerosing
panencephalitis)
Control/prevention:
vaccine
Respiratory Syncytial virus (family Paramyxoviridae, genus Pneumovirus)
Characteristics:
like Parainfluenza
Replication:
like Parainfluenza except has G protein for attachment rather then
HN
Pathogenesis:
transmitted by aerosols and direct contact (hands); humans only reservoir;
replicates in mucosal epithelium of URT then spreads to LRT; incomplete
immunity from infection; pathologic change associated with syncytia and
inflammation-mediated necrosis
Infections:
infants and young children: bronchiolitis, bronchiolitis, pneumonia,
tracheobronchitis, croup, otitis media; older children and adults: cold,
pharyngitis, tracheobronchitis, pneumonia
Control/prevention:
Ribavirin, RSV Ig
Coronavirus (family Coronaviridae, genus Coronavirus)
Characteristics:
enveloped, helical nucleocapsid symmetry; 1 segment pos pol RNA genome;
E2 protein (attachment), E1 protein (matrix for assembly), E3 protein (hemagglutinin
on some strains), L protein (RNA-dependent-RNA polymerase (synthesizes
neg pol template RNA; early protein during replication), N protein (nucleocapsid)
Replication:
replication and assembly in cytoplasm; neg pol template strand made
from which 6 mRNAs and progeny genomes are made; bud into ER for assembly;
released through golgi
Pathogenesis:
peak late winter through early spring; transmitted by aerosols, hand
to hand, object to hand; infects mostly URT epithelial cells; inflammation
and cytokines contribute to pathogenesis
Infections:
cold (with pharyngitis), pneumonia, gastroenteritis
Control/prevention:
none
Rabies Virus (family Rhabdoviridae, genus Lyssavirus)
Characteristics:
enveloped, helical nucleocapsid symmetry; 1 segment neg pol RNA genome;
G protein (attachment), M protein (matrix for assembly), L an NS proteins
(RNA-dependent-RNA polymerase (synthesizes pos pol template RNA; found
in core), N protein (nucleocapsid)
Replication:
replication and assembly in cytoplasm; pos pol template strand made
from which progeny genomes are made; 5 mRNAs made from neg pol strand
Pathogenesis:
zoonotic disease; transmission by bite or scratch or aerosols; virus
travels by retrograde axonal transport to CNS then via afferent neurons
to eye, skin, salivary glands
Infections:
Rabies encephalitis
Control/prevention:
vaccine
Marburg and Ebola viruses (family Filoviridae, genera Marburg-like
viruses and Ebola-like viruses)
Characteristics:
enveloped, helical nucleocapsid symmetry; 1 segment neg pol RNA genome;
filamentous and pleomorphic
Replication:
similar to Rabies; genome codes for 7 proteins
Pathogenesis:
reservoirs and routes of spread uncertain; probably spread by direct
contact or vectors; massive tissue necrosis and hemorrhage; cytokines contribute
to pathogenesis
Infections:
hemorrhagic fever
Control/prevention:
hyperimmune serum (?)
Rubella Virus (family Togaviridae, genus Rubivirus)
Characteristics:
enveloped (from cytoplasm), icosahedral symmetry, 1 segment pos pol
RNA genome; transmembrane envelope protein (E1, 2, & 3 subunits) anchored
to capsid (C protein)
Replication:
2/3 of genome translated into early proteins (protease, RNA-dep-RNA
pol); neg pol strand made for genome template and 26S transcript; 26S translated
into precursor protein that is cleaved by protease into structural proteins
(E, C)
Pathogenesis:
aerosol transmission; humans only reservoir; infects URT, then 1st
viremia, infection of reticuloendothelial tissue then second viremia (fetal
infection possible) and immune complex-mediated vascultis (rash)
Infections:
Rubella (German measles), congenital rubella
Control/prevention:
vaccine
Alphaviruses (Eastern Equine, Western Equine, Venezuelan Equine
Encephalitis viruses; family Toagaviridae, genus Alphavirus)
Characteristics:
like Rubella
Replication:
like Rubella
Pathogenesis:
transmitted by mosquito; birds (WEE & EEE), rodents reservoirs
(VEE)(possibly also amphibians and reptiles for all); infection of reticuloendothelial
tissue then viremia and CNS infection; inflammatory neuronal necrosis
Infections:
encephalitis
Control/prevention:
control vector; vaccine for EEE & WEE
St. Louis Encephalitis virus (family Flaviviridae, genus Flavivirus
)
Characteristics:
similar to Togaviridae except envelope derived from intracytoplasmic
membranes
Replication:
similar to Togaviridae except all of genome translated into one protein
that is processed into structural and non-structural proteins (protease,
RNA-dep-RNA-pol)
Pathogenesis:
transmitted by mosquito; bird reservoir; infects reticuloendothelial
tissue, then viremia and dissemination to CNS
Infections:
fever & headache, meningitis, encephalitis
Control/prevention:
control vector
Dengue fever virus (family Flaviviridae , genus Flavivirus )
Characteristics:
like SLE
Replication:
like SLE
Pathogenesis:
transmitted by mosquito and vertically to neonate; primate and mosquito
reservoir; infects reticuloendothelial tissue, then viremia (virus circulates
in blood cells) with dissemination to many tissues; inflammatory
cytokines associated with pathogenesis and symptoms
Infections:
self-limited disease, Dengue hemorrhagic fever, Dengue shock syndrome
Control/prevention:
control vector
Yellow fever virus (family Flaviviridae , genus Flavivirus )
Characteristics:
like SLE
Replication:
like SLE
Pathogenesis:
transmitted by mosquito; primate reservoir; pathogenesis similar
to Dengue except hepatitis and circulatory failure more prominent
Infections:
self-limited disease, hemorrhagic form
Control/prevention:
vaccine, control vector
Japanese encephalitis virus (family Flaviviridae , genus Flavivirus
)
Characteristics:
like SLE
Replication:
like SLE
Pathogenesis:
transmitted by mosquito; pigs and aquatic birds main reservoir
Infections:
subclinical, encephalitis
Control/prevention:
vaccine, control vector
West Nile fever virus (family Flaviviridae , genus Flavivirus
)
Characteristics:
like SLE
Replication:
like SLE
Pathogenesis:
transmitted by mosquito; crows and aquatic birds main reservoir
Infections:
subclinical, mild febrile disease, meningitis, encephalitis
Control/prevention:
control vector
Bunyavirus (family Bunyaviridae, major strains: California encephalitis
virus, La Crosse encephalitis virus, Jamestown Canyon encephalitis virus)
Characteristics:
envelope with 2 types of glycoproteins (G1 & G2); genome composed
of 3 neg pol RNA strands (large [L], medium [M], small [S]); L codes for
RNS-dep-RNA pol (found in nucleocapsid), M codes for envelope glycoproteins
and a nonstructural protein, S codes for nucleocapsid and a nonstructural
protein
Replication:
replication in cytoplasm; bud into golgi and released by exocytosis
or cell lysis
Pathogenesis:
transmitted by mosquito; mosquitos, squirrels, chipmunks major reservoirs
Infections:
subclinical, mild febrile disease, meningitis, encephalitis
Control/prevention:
control vector
Hantavirus (family Bunyaviridae, major strains: Hantaan virus,
Muerto Canyon virus, others)
Characteristics:
like Bunyavirus
Replication:
like Bunyavirus
Pathogenesis:
mice major reservoir (strains are species-specific); transmitted by
mouse saliva, urine, feces
Infections:
fever with renal syndrome, pulmonary syndrome
Control/prevention:
control reservoir
Rotavirus (serogroups A-E) (family Reoviridae, genus Rotavirus)
Characteristics:
2 capsid layers and inner core; outer capsid composed of VP4 (host
attachment), VP7 (structural); inner capsid composed of VP6 (structural);
core contains complete transcription system (polymerase [VP1-3]); genome
composed of 11 segments of dsRNA
Replication:
VP4 and 7 hydrolyzed; transcription occurs in inner core, translation
in cytoplasm; genome replicated in progeny cores using pos pol RNA template;
buds into ER, release by cell lysis
Pathogenesis:
estimated 4 million cases/yr; fecal/oral or human to human transmission
(virus survives in environment); humans probably only reservoir; peak age
6mo-2yr but all ages infected; infects villus cells in sm intestine preventing
absorption
Infections:
gastroenteritis (fever, vomiting, watery diarrhea)
Control/prevention:
prevent transmission; rehydration
Colorado tick fever virus (family Reoviridae, genus Coltivirus)
Characteristics:
like Rotavirus but outer capsid not as organized; genome 12 dsRNS segments
Replication:
like Rotavirus
Pathogenesis:
transmitted by wood ticks; small mammals are reservoirs; infects erythroid
precursors
Infections:
Colorado tick fever (relapsing fever, headache, myalgia)
Control/prevention:
control vector and reservoirs
Norwalk virus (5 serogroups) (family Caliciviridae, genus Norwalk-like
viruses)
Characteristics:
non-enveloped, icosahedral symmetry; genome pos pol RNA
Replication:
replicates and assembles in cytoplasm
Pathogenesis:
transmitted by fecal/oral, aerosol, common source, human to human;
many animal reservoirs; estimated 20 million cases per year; infects epithelial
cells in jejunum and prevents absorption; peaks in fall and winter; all
ages infected
Infections:
gastroenteritis (vomiting and diarrhea)
Control/prevention:
control transmission
Human Astrovirus (8 serogroups) (family Astroviridae, genus Astrovirus)
Characteristics:
like Norwalk virus (?)
Replication:
like Norwalk virus (?)
Pathogenesis:
fecal/oral transmission; peak in winter; mostly infects children under
3yr but all can be infected; estimated 4 million cases per yr
Infections:
gastroenteritis (nausea and diarrhea)
Control/prevention:
block transmission
Hepatitis A virus (~ 20 strains) (family Picornaviridae, genus
Hepatovirus)
Characteristics:
like Enterovirus but more resistant
Replication:
like Enterovirus but infects hepatocytes
Pathogenesis:
fecal/oral and common-source transmission; humans only significant
reservoir; incubation 2-6 wks; portal inflammation and periportal necrosis
(mediated by virus and CMI); no carriers or chronic disease
Infections:
Hepatitis (acute)
Control/prevention:
block transmission; passive or active immunizations; single vaccine
for both HAV and HBV now on market (Twinrix)
Hepatitis B virus (family Hepadnaviridae, genus Orthohepadnavirus)
Characteristics:
enveloped; circular ssDNA and dsDNA genome; Major antigens: HBsAg (envelope
protein), HBcAg (core/capsid protein), HBeAg (truncated core protein);
core has DNA-dep-RNA pol that also has RNA-dep-DNA pol activity
Replication:
replicates in hepatocytes; dsDNA synthesis completed in core, DNA to
nucleus; following transcription and translation, RNA pregenome enclosed
in progeny core; RNA pregenome serves as template for synthesis of neg
pol DNA strand, then partial synthesis of pos DNA strand; buds into golgi
and released by exocytosis
Pathogenesis:
blood, sex, direct contact, transplacental, during birth transmission;
portal and periportal necrosis (mediated by virus and inflammatory infiltrate)
that may lead to fibrosis and cirrhosis; estimated that 1 million are carriers;
humans most significant reservoir; incubation 4 - 26 wks (avg 8 wks)
Infections:
Hepatitis (subclinical; acute, self-limited; chronic persistent; chronic
active; cirrhosis; hepatocellular carcinoma)
Control/prevention:
block transmission; passive or active immunizations; single vaccine
for HAV and HBV (Twinrix); ? IFN for chronic infection
Hepatitis D virus (genus Deltavirus)
Characteristics:
satellite virus that co-infects with HBV; enveloped; circular ssRNA
genome; HDVAg is core protein; requires HBsAg for replication
Replication:
replication in hepatocytes completed only in presence of HBV
Pathogenesis:
exacerbation of HBV infection
Infections:
coinfection with HBV yielding fulminant hepatitis with death or recovery
with immunity; superinfection of HBV carriers yielding fulminant
hepatitis with death, acute hepatitis with recovery, or chronic HBV/HDV
hepatitis with cirrhosis
Control/prevention:
block transmission; ? IFN for chronic infection
Hepatitis C virus (family Flaviviridae, genus Hepacivirus)
Characteristics:
enveloped; pos pol RNA genome; E1 and E2 envelope proteins; genome
codes for 2 proteases and a RNA-dep-RNA-pol
Replication:
similar to other Flaviviruses (?); genome encodes for a polyprotein
that is cotranslationally processed into at least 10 proteins (4 structural
and 6 nonstructural proteins); may replicate in cells other than hepatocytes;
multiple genetic variants recovered from single individual
Pathogenesis:
transmitted predominantly by blood (transfusions, iv drug use); high
percentage (~80%) of infections become chronic; incubation 2-26 wks (avg
6-12 wks)
Infections:
Hepatitis (acute with resolution, chronic that is stable or results
in cirrhosis [stable, progressive, or carcinoma])
Control/prevention:
block transmission; chronic treated with ? IFN or ? IFN + ribavirin
(Rebetron)
Hepatitis E virus (family ?)
Characteristics:
non-enveloped; pos pol RNA genome
Replication:
?
Pathogenesis:
pathogenesis and transmission like HAV; incubation 4-8 wks; infects
a number of mammals but humans probably main reservoir for human strain-associated
infection
Infections:
Hepatitis (acute)
Control/prevention:
block transmission
Other Hepatitis viruses
Hepatitis F virus (unknown family affiliation)
Hepatitis G virus (family Flaviviridae, genus Hepacivirus)
Human immunodeficiency virus 1 & 2 (family Retroviridae,
genus Lentivirus)
Characteristics:
enveloped (envelope proteins: gp 120, gp 41 and host proteins); nucleocapsid
composed of outer matrix (Gag protein p17) and inner core (Gag proteins
p24 and p6); inner core contains genome (2 identical strands of pos pol
RNA), integrase, reverse transcriptase, protease, and regulator proteins
Replication:
attaches via CD4 and chemokine receptor; envelope fuses, core enters
cytoplasm, reverse transcriptase synthesizes DNA that integrates into host
DNA; transcripts and progeny genomes synthesized; assembly and buds through
plasma membrane; core maturation occurs after release
Pathogenesis:
chronic infection that induces profound immunosuppression resulting
in life-threatening secondary infections; lymphopenia, reduced T-cell activity,
and reduced macrophage activity; incubation 1-6 wks before onset of acute
retroviral syndrome; routes of transmission like HBV; humans only significant
reservoir
Infections:
AIDS CDC classification: acute (acute retroviral syndrome), chronic
(asymptomatic with persistent generalized lymphadenopathy), final crisis
(secondary infections, neurologic disease, secondary neoplastic disease,
unexplained constitutional diseases)
Control/prevention:
block transmission; nucleoside RT inhibitors (zidovudine, didanosine,
zalcitabine, stavudine, lamivudine, abacavir, combivir (zid+lam);
non-nucleoside RT inhibitors (only for HIV-1)(nevirapine, delavirdine,
efavirenz); protease inhibitors (saguinavir, ritonavir, indinavir, nelfinavir,
amprenavir)
Human T-cell lymphotrophic virus 1 & 2 (family Retroviridae,
genus Deltaretrovirus)
Characteristics:
enveloped (contains gp 46 and gp 21 proteins); capsid and matrix protiens
(p15, 24, and 19 gag proteins); 2 identical pos pol RNA segment genome;
core contains reverse transcriptase
Replication:
similar to HIV except genome encodes a variety of transregulatory proteins
associated with transformation and oncogenesis
Pathogenesis:
HTLV-1 transforms T cells; transmitted by blood, sex, and transplacentally
Infections:
adult T-cell leukemia (HTLV-1)
Control/prevention:
block transmission; cytotoxic chemotherapy
Miscellaneous Viruses
prions (Kuru, Crueutzfeldt-Jakob, new-variant Crueutzfeldt-Jakob)
Lymphocytic Choriomeningitis virus
Lassa virus
III. Mycology
Outline of General Mycology
1. Morphology & Structure
a. Yeasts (single cells that reproduce by budding)
(1) Pseudohyphae (Yeasts like Candida albicans
can, under special conditions, form elongated cells that stick together
and look like hyphae.)
b. Molds (grow as filaments or hyphae [septate or non-septate]
and reproduce with specialized structures that bear the conidia or produce
conidia within the filament.)
(1) Dimorphism is an important trait in many pathogenic
fungi. It means that at one temperature (usually 25C), the fungus grows
as a mold, and at another temperature (usually 37C) the fungus grows as
a yeast.
c. Cell wall composition (Usually composed of a mixture
of chitin, glucan, and mannan. Yeasts usually only have chitin at the bud
scar. The cell wall is a potent immunogen, however the role of Abs
in protection is limited.)
d. Plasma membrane (Fungal plasma membranes contain the
sterols ergosterol & zymosterol. Ergosterol
and enzymes that synthesize it are the major targets of antifungal drugs.)
2. Asexual Reproduction
Examples of conidia and conidiophore structures
3. Simplified Classification
Kingdom Fungi
Division Amastigomycota
Subdivision Zygomycotina
Class Zygomycetes
Order Mucorales
Genus Rhizopus, Mucor
Subdivision Ascomycotina
Class Ascomycetes
Order Endomycetales
Genus Saccharomyces
Subdivision Deuteromycotina
Class Deuteromycetes
Order Cryptococcales
Genus Cryptococcus, Candida
Order Moniliales
Genus Trichophyton, Microsporum,
Epidermophyton, Sporothrix, Coccidioides, Blastomyces, Penicillium, Aspergillis,
Histoplasma
4. Physiology
(heterotrophic; utilize a variety of carbohydrates [specific
for the species]
some are strict aerobes, some facultative anaerobes)
5. Pathogenesis
a. Portals of entry (skin, inhalation, GIT, UT, normal
flora)
b. Virulence determinants (predisposing condition [reduced
CMI, underlying disease]; filament vs. yeasts; components immunosuppress
and/or evade immune system; extracellular enzymes; induction of proinflammatory
cytokines; tissue trophism and adherence; allergic reactions)
c. Disease Classification
(1) superficial (Pityriasis versicolor, Tinea nigra)
(2) cutaneous (Dermatophytosis)
(3) subcutaneous (Sporotrichosis)
(4) systemic
(a) primary (Coccidioidomycosis, Histoplasmosis,
Blastomycosis, Cryptococcosis)
(b) opportunistic (Candidiasis, Aspergillosis,
Mucormycosis)
6. Lab Diagnosis
a. Microscopy (cotton blue, KOH, methenamine silver stain,
periodic acid-Schiff stain)
b. Culture (slide culture, birdseed agar for Cryptococcus,
dermatophyte test medium, Sabouraud dextrose agar, biochemical tests)
c. Serology
(1) Cryptococcus neoformans (EIA for capsular Ag
in serum and CSF,
latex agglutination for Ag, tube agglutination
for low Ag conc.)
(2) Coccidioides immitis (latex agglutination for
Ab, immunodiffusion for Ab, complement fixation [CF] for Ab to
mycelial Ag)
(3) Histoplasma capsulatum (latex agglutination
for Ab,immunodiffusion for Ab, CF for Ab to mycelial and yeast Ag)
(4) Sporothrix schenckii (latex agglutination for
Ab)
(5) Candida albicans (immunodiffusion for Ab, EIA
for Abs to cytoplasmic Ag)
(6) Blastomyces dermatitidis (immunodiffusion for
Ab, CF for Ab)
(7) Aspergillus (immunodiffusion for Ab, CF for
Ab)
7. Antifungal drugs
a. Polyenes (Nystatin, Amphotericin B [AmB]; bind
ergosterol and cause an increase in membrane permeability; nystatin used
topically for oral and vaginal candidiasis; AmB used topically and systemically
[colloidal complex in desoxycholate or as a lipid complex]; AmB drug of
choice for most disseminated fungal infections)
b. Azoles (Miconazole, Ketoconazole, Clotrimazole, Itraconazole,
Fluconazole; inhibit cytochrome P-450 and thus block ergosterol synthesis
that results in increased membrane permeability; miconazole used
topically for superficial infections; ketoconazole & clotrimazole used
topically for superficial infections; itraconazole & fluconazole used
to treat certain systemic infections [non-life threatening candidiasis,
cryptococcosis, histoplasmosis, blastomycosis])
c. Flucytosine (inhibits DNA synthesis; used systemically
in combination with AmB)
d. Griseofulvin (disrupts microtubules; used for dermatophyte
infections)
e. Terbinafine (inhibits squalene epoxidase and thus ergosterol
synthesis; used for dermatophyte infections)
f. Caspofungin (an echinocandin; inhibits glucan synthesis;
used to treat aspergillosis)
Pathogenic Fungi (20 major agents)
The Dermatophytes & agents causing superficial infections
anthropophilic, zoophilic, & geophilic varieties
routes of transmission: usually indirect by contact with free spores
or spore-laden hair or skin scales
pathogenesis: spores adhere to keratinized tissue, germinate, secrete
keratinases, and invade and grow; hair infection may be endothrix or ectothrix
pattern; extent of inflammation varies; Th1 response needed to control
Dermatophytoses (listed by infection)
Infection:
Tinea pedis (foot and toes)
Etiology:
Trichophyton mentagrophytes var interdigitale, T. rubrum, less frequently
Epidermophyton floccosum
Control:
topical, itraconazole, terbinafine, fluconazole
Infection:
Tinea manus (hands)
Etiology:
T. rubrum
Control:
as for T. pedis
Infection:
Onychomycosis (Tinea unguium) (nails)
Etiology:
T. rubrum, T. mentagrophytes var. interdigitale, E. floccosum
Control:
terbinafine, fluconazole, griseofulvin
Infection:
Tinea corporis and Tinea faciei (skin and face, respectively)
Etiology:
Microsporum audouinii, M. canis var canis, M. gypseum, T. rubrum, T.
verrucosum
Control:
topical, terbinafine, fluconazole, itraconazole
Infection:
Tinea barbae (beard)
Etiology:
T. verrucosum, T. mentagrophytes var. mentagrophytes
Control:
topical, terbinafine, fluconazole, itraconazole
Infection:
Tinea cruris (groin)
Etiology:
T. rubrum, E. floccosum
Control:
topical, terbinafine, fluconazole, itraconazole
Infection:
Tinea capitis (scalp)
Etiology:
T. tonsurans (most common in this country), M. canis var canis, M.
audouinii, T. verrucosum
Control:
griseofulvin, terbinafine, itraconazole
Superficial infections
Infection:
Tinea nigra (epidermis, usually hands)
Etiology:
Exophiala werneckii
Control:
topical, ketoconazole, itraconazole
Infection:
Tinea versicolor (skin, trunk common)
Etiology:
Malassezia furfur
Control:
topical selenium sulfide, ketoconazole, fluconazole, itraconazole
Fungi Causing Subcutaneous and Systemic infections
Sporothrix schenckii (Sporotrichosis)
Characteristics:
ubiquitous (especially soil and vegetation) dimorphic fungus; at ambient
temps grows as branching septate hyphae with single or clusters of microconidia;
at 37C grows as elongated yeasts
Pathogenesis:
traumatic inoculation of skin with conidia or hyphae; inflammation,
induration at site; asending lymphangitis may occur; pulmonary infection
initiated by inhaling conidia
Infections:
lymphocutaneous sporotrichosis, pulmonary sporotrichosis, osteoarticular
sporotrichosis, disseminated in AIDS
Control:
cutaneous with itraconazole or fluconazole, disseminated with amphotericin
B
Coccidioides immitis (Coccidioidomycosis)
Characteristics:
found in desert soil (endemic in southern Texas, New Mexico, Arizona,
and California); at ambient temps grows as branching, septate, hyphae that
forms arthrospores; at 37C forms spherules containing endospores
Pathogenesis:
~60% of the infections are asymptomatic; infection initiated by inhalation
of arthrospores; pulmonary symptoms generally mild and are associated with
inflammatory reaction to spherules; may form cavity or nodular granuloma;
may disseminate to skin, bone and joints, and CNS
Infections:
primary pulmonary coccidioidomycosis, disseminated coccidioidomycosis,
primary cutaneous coccidioidomycosis
Control:
fluconazole, itraconazole, amphotericin B
Histoplasma capsulatum (var capsulatum and var duboisii) (Histoplasmosis)
Characteristics:
grows in rich, acidic soil enriched by bird and bat feces (endemic
in the Ohio-Mississippi valleys); at ambient temps grows as branching,
septate hyphae that form microconidia and tuberculate macroconidia; at
37C grows as small, oval yeasts
Pathogenesis:
~90% of cases asymptomatic or mild influenza-like; inhale microconidia,
ingested by macrophages, undergoes dimorphic transition; disseminates to
reticuloendothelial tissue; a facultative intracellular parasite (in macrophages)
Infections:
acute primary pulmonary histoplasmosis, chronic (cavitary) pulmonary
histoplasmosis, progressive disseminated histoplasmosis (acute and chronic),
cutaneous histoplasmosis (African histoplasmosis caused by H. capsulatum
var duboisii)
Control:
itraconazole, amphotericin B
Blastomyces dermatitidis (Blastomycosis)
Characteristics:
epidemiology similar to H. capsulatum except endemic area larger; grows
in rich soil contaminated with bird feces or decaying vegetation; at ambient
temps grows as branching, septate hyphae that produce microconidia; at
37C grows as a thick-walled yeast with large-pore buds
Pathogenesis:
~50% of infections are asymptomatic; inhale microconidia, dimorphic
transition, WI-1 cell wall protein mediates adherence to host cells; yeast
cell wall may be antiphagocytic; tissue damage mediated by inflammatory
infiltrate; lesions may become granulomatous
Infections:
primary pulmonary blastomycosis (course may invole complete recovery
or become progressive with or without dissemination), chronic pulmonary
blastomycosis, disseminated blastomycosis, cutaneous blastomycosis
Control:
itraconazole, amphotericin B
Cryptococcus neoformans (var neoformans and var gattii) (Cryptococcosis)
Characteristics:
var neoformans has worldwide distribution, found in areas contaminated
with dried bird feces, infects the immunocompromised; var gattii restricted
to regions with eucalyptus trees, infects the immunocompetent; grows as
a yeast at all temps; prominent polysaccharide capsule; deposits melanin
in cell wall when grown on catecols
Pathogenesis:
capsule is antiphagocytic and immunosuppressive; melanin protects from
oxidative damage; small-capsule yeasts inhaled, primary infection established
in lung, disseminates to CNS
Infections:
pulmonary cryptococcosis (acute and chronic), disseminated cryptococcosis
(skin, CNS)
Control:
fluconazole, amphotericin B
Candida albicans (C. tropicalis, parapsilosis, glabrata)
(Candidiasis)
Characteristics (C. alb):
grows as yeasts at all temps; at 37C in the presence of inducers forms
germ tubes and eventually hyphae (dimorphic transition); on special media
forms pseudohyphae and chlamydospores; C. albicans causes ~70% of the candidiasis
cases; normal inhabitant of the GIT
Pathogenesis (C. alb):
usually requires predisposing condition to cause infection; attachment
followed by release of proteases and tissue invasion associated with acute
infection; chronic infection often involves formation of granulomas
Infections (C. alb):
oral and vaginal candidiasis, intertriginous candidiasis, paronychia,
onychia, generalized cutaneous, chronic mucocutaneous, esophagitis, gastrointestinal
candidiasis, bronchopulmonary candidiasis, UTI, fungemia, endocarditis,
hepatosplenic candidiasis
Control (C. alb):
topical (nystatin, miconazole), itraconazole, fluconazole, amphotericin
B
Aspergillus sp. (A. fumigatus) (Aspergillosis)
Characteristics:
A. fumigatus causes ~90% of the infections; common soil fungus, worldwide
distribution; thin septate hyphae that typically branch at 45 degree angles;
asexual cycle involves formation of conidia on complex conidiophore
Pathogenesis:
inhale conidia, germinate, hyphae adhere to extracellular matrix proteins,
secrete enzymes and toxic secondary metabolites, hyphae invade tissue or
grow in cavities; Th1 response induced; immunocompromised at greatest risk
Infections:
allergic bronchopulmonary aspergillosis, aspergilloma (fungus ball),
invasive sinusitis, invasive pulmonary aspergillosis, disseminated aspergillosis
Control:
amphotericin B, itraconazole, caspofungin
Mucormycosis (Rhizopus, Absidia, Mucor, Rhizomucor)
Characteristics:
ubiquitous soil fungi; grow as irregularly shaped, non-septate hyphae
with right-angle branches; sporangiospores contained in sporangia
Pathogenesis:
infections limited to the immunocompromised, diabetics, and trauma;
inhale spores, germinate, invade tissue and blood; results in tissue necrosis,
thrombosis
Infections:
rhinocerebral mucomycosis (most in poorly managed diabetics), pulmonary
mucormycosis (neutropenia), cutaneous mucomycosis (trauma)
Control:
amphotericin B
Pneumocystis carinii (Pneumocystosis)
Characteristics:
complex sexual cycle, simple asexual cycle involving yeast-like trophic
form
Pathogenesis:
transmitted by aerosols; trophozoite or sporozoite infectious form
inhaled, adheres to type I epithelial cells, proliferates, and induces
inflammatory exudate resulting in hypoxemia; immunosuppression required
for infection
Infections:
pneumonia (disseminates to reticuloendothelial tissue in advance AIDS
patients)
Control:
trimethoprim+sulfamethoxazole
IV. Parasitology
Outline of General Parasitology
1. Morphology, physiology, and reproduction
a. Protozoa (size 2-100 µm, cytoplasm often
composed of inner endoplasm [nutrition] and outer ectoplasm[organelles
of locomotion])
(1) Rhizopods (amebas; reproduce by binary fission)
(2) Ciliates (reproduce by binary fission)
(3) Flagellates (reproduce by binary fission)
(4) Sporozoans (reproduce sexually [sporogony] and
asexually [shizogony])
(5) Physiology (most fac. anaerobes; heterotrophic;
engulf food by pinocytosis or phagocytosis; some have specific site for
ingestion [the peristome or cytostome]; many can form resistant cysts)
b. Helminths (elongated, bilaterally symmetric, length
varies from <1mm to >1m; body wall covered with cuticle; anterior
end may possess suckers, hooks, teeth, etc. for attachment; all have
differentiated organs [primitive nervous and excretory systems and
well developed reproductive systems
(1) Roundworms (nematodes; have cylindrical bodies,
tubular alimentary track, and the sexes are separate)
(2) Tapeworms (cestodes; have flattened bodies;
the anterior end [scolex] has suckers and or hooklets for attachment;
reproductive segments are called proglottids and each contains both male
and female gonads; no digestive tract)
(3) Flukes (trematodes; flat with branching alimentary
tracts; particulate wastes are regurgitated through the mouth; have two
suckers for attachment; most are hermaphroditic [except S.mansoni])
(4) Physiology (ingest or absorb body fluids, etc.;
usually anaerobic respiration)
2. Immunity (all aspects of the immune system important; eosinophils
directed at worms; IgE made to many; acquired resistance often absent or
incomplete; effector mechanisms usually directed at surface antigens of
the parasite)
3. Diagnosis (direct examination of specimens [microscopy],
serology [ELISA, IF, CF], molecular probes)
4. Major chemotherapeutic agents
a. Heavy Metals (arsenicals and antimonial agents)
b. Antimalarial Quinolines
(1) Chloroquine phosphate
(2) Primaquine phosphate
(3) Quinine
(4) Mefloquine
c. Folate Antagonists
(1) Trimethoprim
(2) Pyrimethamine
d. Nitroimidazoles
(1) Metronidazole
e. Benzimidazoles
(1) Thiabendazole
(2) Mebendazole
(3) Albendazole
f. Avermectins
(1) Ivermectin
g. Praziquantel
Pathogenic Parasites (19 major agents)
Plasmodium (P. vivax, P. ovale, P. malariae, P. falciparum)
Characteristics/life cycle:
sporogeny in mosquito (gametocytes, ookinete, oocyst, sporozoites),
schizogony in human (sporozoite, merozoite [liver & RBC], trophozoite,
schizont, gametocyte
Pathogenesis:
transmitted by female Anopheles; symptoms associated with RBC rupture
and proinflammatory cytokines; anemia associated with depression of marrow
function; RBCs sequestered in spleen
Infections:
malaria: P. vivax most prevalent worldwide, invades immature RBC, may
cause chronic infection; P. falciparum invades any RBC, associated with
microvascular disease as a result of mature trophozoite-infected RBC adhering
to microvascular endothelium
Control:
chloroquine, mefloquine, primaquine
Toxoplasma gondii
Characteristics/life cycle:
schizogony and sporogeny in cat GIT (trophozoites, merozoites, gametocytes),
oocyst released in feces that mature to contain sporozoites; oocyst ingested
by intermediate host (humans), intracellular schizogony occurs yielding
tachyzoites that encyst; cyst produces sporozoites and bradyzoites that
are passed in feces and infect definitive host
Pathogenesis:
transmitted by fecal-oral route or from ingesting undercooked infected
meat; various sizes cysts occur in tissue with varying degrees of inflammation
Infections:
acute and chronic toxoplasmosis, congenital toxoplasmosis, toxoplasmosis
in the immunocompromised
Control:
pyrimethamine + sulfadiazine
Cryptosporidia parvum
Characteristics/life cycle:
acid fast oocysts containing 4 sporozoites ingested, sporozoites released
and attach to microvilli in GIT; become schizonts that release merozoites
that become gametes that mate and become oocyst that is released in the
feces
Pathogenesis:
many animals serve as reservoirs; transmitted by fecal/oral and person
to person; oocyst resistant to chlorination
Infections:
Cryptosporidiosis (noninflammatory, watery diarrhea); may be prolonged
in immunocompromised
Control:
none; avoid contaminated water
Cyclospora cayetanensis
Characteristics/life cycle:
like C. parvum but oocyts contain 2 sporocysts that each contain 2
sporozoites
Pathogenesis:
like C. parvum ?
Infections:
like C. parvum
Control:
like C. parvum
Entamoeba histolytica
Characteristics/life cycle:
trophozoite with ameboid morphology; forms cyst with chromatoidal body
Pathogenesis:
transmitted by anal sex, fecal/oral, fomites; ingest cyst, gastric
acid induces release of trophozoites, adhere to epithelial cells in colon
via galactose-specific lectin, release pore-forming protein, invade, and
multiply; kill epithelial cells resulting in a loss of fluid uptake and
inflammatory diarrhea
Infections:
amebiasis (inflammatory diarrhea), may be asymptomatic (carriers),
may disseminate in immunocompromised
Control:
metronidazole + diloxanide
Trichomonas vaginalis
Characteristics/life cycle:
flagellate morphology (flagella, axostyle, undulating membrane); exists
only as trophozoite that divides by binary fission
Pathogenesis:
transmitted by sexual contact; infects urethra, vagina, prostate; serious
infections involve necrosis and inflammation; men mostly asymtomatic and
the predominant reservoirs
Infections:
women: asymptomatic, vaginitis; men: asymtomatic, urethritis, prostatitis
Control:
safe sex; metronidazole
Giardia lamblia
Characteristics/life cycle:
flagellate morphology (flagella, sucker [adhesive disk], 2 nuclei);
trophozoite and cysts occur; trophozoites multiply by longitudinal binary
fission
Pathogenesis:
transmitted by fecal/oral or contaminated food or water; ingest cyst,
trophozoites released and attach to epithelial cells in duodenum; attachment
induces inflammation, tissue damage, and reduce absorption
Infections:
acute or chronic noninflammatory diarrhea; may be asymptomatic
Control:
avoidance; metronidazole, quinacrine
Leishmania (L. tropica, L. mexicana, L. braziliensis)
Characteristics/life cycle:
hemoflaellate morphology; free-living promastigote, intracellular amastigote
Pathogenesis:
numerous animal reservoirs; transmitted by the bite of female sandfly;
promastigote invades reticuloendothelial tissue and becomes the intracellular
amastigote; replicates and invades other tissue, resulting in inflammation
and necrosis
Infections:
cutaneous, mucocutaneous, and disseminated leishmaniasis
Control:
stibogluconate, amphotericin B
Trypanosoma cruzi
Characteristics/life cycle:
hemoflagellate morphology; epimastigote in insect gut, trypomastigote
free-living in host, amastigote intracellular
Pathogenesis:
numerous animal reservoirs; transmitted by feces of reduviid (kissing)
bug; trypomastigote invades tissue, becomes intracellular amastigote that
replicates and lyses cell; trypomastigote released into blood; tissue inflammation
and necrosis
Infections:
American trypanosomiasis (Chagas’ disease)
Control:
nifurtimox
Enterobius vermicularis (Pinworm)
Characteristics/life cycle:
nematode morphology (cylindrical body, tubular alimentary tract, separate
sexes)
Pathogenesis:
humans only reservoir; hand to mouth or fecal/oral transmission; ingest
eggs, hatch, larvae penetrate mucosa of large intestine, mature into different
sexes, mate, female lays eggs in perianal area; eggs induce allergic reaction
Infections:
Pinworm disease (Enterobiasis)
Control:
pyrantel pamoate, mebendazole
Trichuris trichuria (Whipworm)
Characteristics/life cycle:
nematode morphology (cylindrical body, tubular alimentary tract, separate
sexes)
Pathogenesis:
humans only reservoir; fecal/oral transmission; ingest embyonated egg,
larvae penetrate mucosa of large intestine, sexes mature, mate, female
releases eggs in feces; larvae develop in moist, dark environment; whip
penetrates and damages mucosa; symptoms related to worm burden
Infections:
Whipworm disease (Tricuriasis)
Control:
mebendazole
Ascaris lumbricoides
Characteristics/life cycle:
nematode morphology; worms may reach 1 m in length
Pathogenesis:
humans main reservoir; fecal/oral, hand to mouth transmission; ingest
embyonated egg, larvae penetrate duodenal wall, enter blood then lung,
grow in alveoli, coughed up and swallowed, mature in small intestine, mate,
female produces eggs that are passed in feces; larvae in fertilized eggs
mature in moist dark environments; symptoms related to worm burden
Infections:
Ascariasis
Control:
mebendazole, pyrantel pamoate
Necator americanus (Ancylostoma duodenale) (Hookworm)
Characteristics/life cycle:
nematode morphology; 2 larval morphologies (rhabditiform [free-living],
filariform [infective])
Pathogenesis:
transmitted by contact with contaminated soil; filariform larvae penetrate
skin, enter blood, then lungs, coughed up, swallowed, attach to mucosa
of small intestine, induces inflammation and necrosis; mate, eggs pass
in feces, mature in soil, rhabditiforn larvae released, free-lining, develop
into infective filariform larvae
Infections:
Hookworm disease (hypersensitive pneumonitis, GIT symptoms)
Control:
mebendazole, pyrentel pamoate
Strongyloides stercoralis
Characteristics/life cycle:
like Necator
Pathogenesis:
transmitted by contact with contaminated soil; filariform larvae penetrate
skin, enter blood, then lungs, coughed up, swallowed, mate in small intestine,
males ejected, female burrow into mucosa and produce eggs; hatch liberating
rhabditiform larvae, some pass in feces, some develop into filariform and
continue the infection; pathogenesis dependent on worm burden
Infections:
Strongyloidiasis (acute [hypersensitive pneumonitis, GIT asyptomatic
to inflammatory diarrhea], hyperinfection syndrome in immunocompromised)
Control:
thiabendazole, mebendazole
Toxocara canis (T. cati)
Characteristics/life cycle:
eggs of non-human ascarid hatch in GIT and undergo limited development
Pathogenesis:
ascarids migrate into skin and other tissue; symptoms and pathogenesis
related to migration
Infections:
Toxocariasis
Control:
thiabendazole
Trichinella spiralis
Characteristics/life cycle:
nematode morphology
Pathogenesis:
many reservoirs; transmitted by eating undercooked meat; ingest cyst,
larvae released, develop in intestinal mucosa of small intestine (intracellular
parasites), mature, mate, females produce larvae that enter the blood,
then muscle where the coil and encyst; pathogenesis depends on worm burden;
myositis and vasculitis occur
Infections:
Trichinosis (symptoms depend on worm burden and location of cysts)
Control:
mebendazole stops development of new larvae
Taenia (T. saginata, T. solium)
Characteristics/life cycle:
cestode morphology and life cycle (proglottids, scolex, resistant cuticle);
life cycle below
Pathogenesis:
pig ingests embryophores, cattle ingest gravid proglottids and embyonated
eggs, larvae liberated in intestine, enter blood then muscle; humans eat
undercooked meat containing cysticerci, scolex attaches to mucosa of small
intestine, worms mature, eggs and gravid proglottids released in feces;
dead end when human ingests T. solium embryophore (Cysticercosis)
Infections:
tapeworm disease (GIT symptoms depend on worm burden); Cysticercosis
when T. solium embryophore is ingested
Control:
avoid undercooked meat; niclosamide, praziquantel
Diphyllobothrium latum (freshwater fish tapeworm)
Characteristics/life cycle:
cestode morphology; crustaceans and fish intermediate hosts; prevalent
in cool lake water
Pathogenesis:
humans ingest undercooked fish infected with sparganum larvae, attach
to mucosa of small intestine, mature, eggs in feces, eggs released into
freshwater develop into coracidium that infects crustaceans
Infections:
Fish tapeworm disease (GIT symptoms depend on worm burden)
Control:
niclosamide
Schistosoma mansoni (blood fluke)
Characteristics/life cycle:
trematode morphology; unlike most trematodes sexes are separate; eggs
have characteristic lateral spine; adults are obligate intravascular parasites;
aquatic snail intermediate host
Pathogenesis:
cercaria penetrate skin, enter blood, develop in portal circulation
(inferior mesenteric vein near lower colon), coat themselves with host
proteins, mate, eggs produced; eggs pass into GIT and bladder and released
in feces and urine
Infections:
Schistosomiasis (blood fluke infection; hypersensitive skin reaction
at sites of skin penetration; hepatic and GIT symptoms depend on worm and
egg burden)
Control:
praziquantel
Ectoparasites and Vectors
Sarcotes scabiei (itch mite; scabies in humans, mange in animals)
Pediculus humanus (body or head louse)
Phthirus pubis (crab louse)
Xenopsylla cheopis (rodent flea; vector of plague and murine typhus)
Cimex hemipterus (bed bugs)
Ornithodoros sp. (soft tick; transmits relapsing fever)
Dermacentor andersoni (transmits tularemia, RMSF, Q fever, Colorado
tick fever)
Ixodes sp. (transmits Lyme disease)
Anopheles sp. (transmits malaria)