Categories
Prions
- abnormal form of host proteins, PrP
- cause transmissible spongiform
encephalopathies
o kuru (cannibalism)
o Crutzfeldt-Jacob dz (CJD)
o bovine spongiform encephalopathy (BSE)
o variant CJD
- PrP found in neurons
- PrP undergoes conformational change that
makes it resistant to proteases
- parasitic worms
- adult worms produce eggs or larvae that are
passed in stool
- some dz caused by inflammatory rxn to
eggs/larvae (schistosomiasis)
arenaviruses (Lassa, Machupo)
o infections via GI tract occur when local
defenses are weakened or the organisms
Category B
develop strategies to overcome these
Brucellosis (Brucella sp.)
defenses
Epsilon toxin (Clostridium perfringens)
- Respiratory tract
Food safety threats
o large number or organisms are inhaled
Ectoparasites
Salmonella
daily often in dust or aerosol particles
- insects/arachnoids that attach to and live on or
E. coli O157:H7
o distance they travel is inversely
in skin
Shigella
proportional to their size
- insects: lice, bedugs, fleas
Glanders (Burkholderia mallei)
o microorganisms that invade the normal
- arachnoids: mites ticks, spiders
Melioidosis (Burkholderia pseudomallei)
healthy respiratory tract have developed
Psittacosis (Chlamydia psittaci)
specific mechanisms to:
Special techniques for Dx of infectious agents
Q fever (Coxiella burnetti
 overcome mucociliary defenses
Viruses
Gram stain
most bacteria
Ricin toxin from Ricinus communis (castor beans)
 avoid destruction by alveolar
- obligate intracellular parasites
Acid-fast stain mycobacteria, nocardiae
Staphylococcal enterotoxin B
macrophages
- depend on host’s metabolic machinery for
Silver stain
fungi, legionella, pneumocystitis Typhus fever (Rickettsia prowazekii)
- Urogenital tract
replication
PAS
fungi, amebae
Viral encephalitis (alphaviruses)
o almost always invaded from the exterior
- nucleic acid genome + protein coat (capsid)
Mucicarmine
cryptococci
Venezuelan equine encephalitis
via the urethra
- smallpox & rabies form cytoplasmic inclusions Giemsa
campylobacteria, leishmaniae,
eastern equine encephalitis
o regular flushing of urine serves as defense
malaria, parasites
western equine encephalitis
o lactobacilli in vagina protect by creating
Bacteria
Antibody
all classes
Water safety threats
low pH from catabolism of glycogen
- Chlamydia & Rickettsia = obligate intracellular Culture
all classes
Vibrio cholera
o chlamydia replicate in epithelial cells
DNA
all classes
Cryptosporidium parvum
Spread & dissemination
o rickettsia replicate in endothelial cells
- proliferate locally at the site of infection
- Chlamydia trachomatis = MC cause of female
- organisms are usually best visualized at
Category C
- penetrate the epithelial barrier
sterility & blindness
advancing edge of a lesion rather than at its
Emerging infectious dz threats
- spread to distant sites via lymphatics, blood,
- Mycoplasma & Ureaplasma are unique among
center
Nipah virus
nerves
extracellular pathogens bc lack cell wall
Hantavirus
- major manifestations may appear at sites
Agents of bioterrorism
different from the point of entry
Fungi
Category A
Transmission & dissemination of microbes
- placental-fetal route
- eukaryotes w/ thick chitin-containing cell wall - pose highest risk
Routes of entry
- ergosterol cell membrane
- readily disseminated or transmitted
- microbes can enter by inhalation, ingestion,
Release of microbes from the body
- grow as yeast or hyphae (septate or aseptate) - high mortality
sexual transmission, insect/animal bites, or
- person-to-person transmission
- produce sexual or asexual spores (conidia)
- major public health impact
injection
o respiratory (M. tuberculosis)
- dermatophytes are confined to superficial
- can cause public panic & social disruption
- Skin
o fecal-oral (viruses, helminths, etc.)
layers of human skin (“tinea”)
o the dense keratinized outer layer is
o sexual
- AIDS pts often infected by P. jiroveci
Category B
natural barrier to infection
 viruses – HPV, HSV, HBV, HIV
- moderately easy to disseminate
o low pH & presence of fatty acids inhibit
 bacteria – T. pallidum, N.
Protozoa
- moderate morbidity, low mortality
growth of microorganisms
gonorrhoeae, C. trachomatis,
- single-celled eukaryotes
- require specific Dx
o most organisms enter through breaks in
 fungi – Candida
- can replicate intracellularly in variety of cells
- require dz surveillance
skin
 protozoa – Trichomonas
o Plasmodium – RBCs
- GI tract
 arthropods
o Leishmania – macrophages
Category C
o most GI pathogens are transmitted by food
o blood (needle sharing, cuts)
- or extracellularly in UG system, intestine, blood - emerging pathogens
or drink contaminated w/ fecal material
- zoonotic transmission
- intestinal protozoans have 2 forms:
o normal defenses:
o direct contact
o motile trophozoites that attach to
Potential agents of bioterrorism
 acidic gastric secretion
o consumption of animal products
intestinal epithelial wall (can invade)
Category A
 layer of viscous mucous
o indirectly through vector
o immobile cysts that are resistant to
Anthrax (Bacillus anthracis)
 lytic pancreatic enzymes and bile
stomach acids (infectious form)
Botulism (Clostridium botulinum toxin)
detergents
STIs
- blood borne protozoa are transmitted by insect Plague (Yersinia pestis)
 defensins (mucosal antimicrobial
- infections w/ one STI-associated organism
vectors
Smallpox (Variola major virus)
peptides)
increases risk for additional STIs
- intestinal protozoa are ingested as cysts
Tularemia (Francisella tularensis)
 normal flora
- microbes that cause STIs can be spread from a
Viral hemorrhagic fevers
 secreted IgA antibodies from MALT
pregnant woman to the fetus and cause severe
Helminths
filoviruses (Ebola, Marburg)
damage to the fetus
How microorganisms cause disease
o large diversity of serotypes (Rhinoviruses,
Mechanisms of viral injury
S. pneumoniae)
- directly damage cells by entering them &
- some microbes have devised methods for
replicating at the host’s expense
evading innate immune defenses (escaping
- tropism = predilection for viruses to infect
killing by phagocytic cells and complement)
certain cells
- viruses can produce molecules that inhibit
- major determinant of tropism is presence of
innate immunity
viral receptors on host cells
- some microbes produce factors that decrease
- direct cytopathic effects
recognition of infected cells by CD4+ helper T
- antiviral immune responses (CTL)
cells and CD8+ cytotoxic T cells
- transformation of infected cells (to tumor cells)
Spectrum of inflammatory responses to infection
Mechanisms of bacterial injury
Suppurative (purulent) inflammation
- damage to host tissues depends on ability to:
- rxn to acute tissue damage
o adhere to host cells (adhesins, pili)
- increased vascular permeability & leukocytic
o invade cells and tissue
infiltration (predom. neutrophils)
o deliver toxins
- neutrophils attracted to chemoattractants
- virulence genes encode these properties; coded
from the pyogenic bacteria
on pathogenicity islands
- mostly extracellular gram pos. cocci and gram
- plasmids & bacteriophages can spread btwn
neg rods.
bacteria; can convert nonvirulent  virulent
- quorum sensing – many bacteria coordinately Mononuclear & granulomatous inflammation
regulate gene expression
- diffuse, predominantly mononuclear
o S. aureus coordinately regulates by
interstitial infiltrates
secreting autoinducer peptides
- usually from viruses, intracellular bacteria, or
- communities of bacteria can form biofilms
intracellular parasites
o form viscous layer of extracellular
- granulomatous inflammation
polysaccharides that adhere to host tissues
o form of mononuclear inflammation
or devices
o evoked by infectious agents that resist
o resistant to antimicrobial drugs & immune
eradication & capable of stimulating
mechanisms
strong T cell-mediated immunity
- endotoxin (LPS)
o accumulation of activated macrophages,
o O antigen is used diagnostically to
“epitheloid” cells; may fuse to form giant
serotype different strains of bacteria
cells
o LPS binds to CD14 on host cells which then
binds to TLR4  cellular response
Cytopathic-cytoproliferative rxn
- exotoxins
- usually produced by viruses
o enzymes
- cell necrosis or cellular proliferation usually
o toxins that alter intracellular signaling or
with sparse inflammatory cells
regulatory pathways (has an active
- viruses may make aggregates (inclusion
subunit and binding subunit)
bodies)
o neurotoxins
- may cause epithelial cells to proliferate
o superantigens
- may contribute to development of malignant
neoplasms
Immune evasion by microbes
- replication in sites inaccessible to host immune Tissue necrosis
system
- C. perfringens & others that secrete toxins
- antigenic variation
- can cause rapid/severe necrosis (gangrenous
o high mutation rate (HIV, influenza)
necrosis)
o genetic reassortment (Influenza,
- tissue damage = dominant feature
rotavirus)
- few inflammatory cells present
o genetic rearrangement (B. burdorferi, N.
gonorrhoeae, Trypanosoma, Plasmodium) Chronic inflammation & scarring
- can lead to complete healing or extensive
scarring
- Dx can be made by viral culture of throat
secretions or stool, or serology
VIRAL INFECTIONS
West Nile virus
- arbovirus of flavivirus group
- mosquitos  birds
- in the CNS, infects neurons
- usually asymptomatic
- 20% mild short-lived febrile illness assoc. w/
HA and myalgia
- maculopapular rash in half of cases
- complications (meningitis, encephalitis,
meningoencephalitis) in 1/150 clinically
apparent cases
- immunosuppressed and elderly at greatest risk
for severe dz
Acute (transient) infections
Measles
- rubeola; ssRNA virus; paramyxovirus family
- only one serotype
- respiratory droplets
- important cause of death in malnourished
children
- croup, pneumonia, diarrhea w/ protein-losing
enteropathy, keratitis w/scarring & blindness,
encephalitis, hemorrhagic rashes (“black
measles”)
- SSPE rare but serious complication
- morphology:
o blotchy red brown macular papular rash
o Koplik spots (ulcerated mucosal lesions in
oral cavity near opening of Stensen ducts)
o Warthin-Finkeldey cells (multinucleate
giant cells w/ eosinophilic inclusions)
Mumps
- paramyxovirus
- enter URT as respiratory droplets  spread to
draining lymph nodes  replicate in
lymphocytes  spread thru blood to salivary &
other glands
- classically presents w/ salivary gland pain &
swelling
- aseptic meningitis = MC extra-salivary gland
complication
- parotitis – mostly B/L; glands enlarged, doughy
consistency, moist, glistening, reddish brown
on cross-sec
- orchitis – testicular swelling; may compromise
blood supply  scarring & atrophy  sterility
- pancreatitis – parenchymal & fat necrosis;
neutrophil-rich inflammation
- encephalitis – perivenous demyelination &
perivascular mononuclear cuffing
Poliovirus
- enterovirus; unencapsulated RNA virus
- 3 major strains
- infects the oropharynx  swallowed 
multiplies in intestinal mucosa & lymph nodes
- fecal-oral route
- most infections = asymptomatic
- spinal or bulbar poliomyelitis – virus invades
CNS & replicates in motor neurons of spinal
cord or brainstem
Viral hemorrhagic fevers
- systemic infections
- caused by enveloped RNA viruses
- 4 families:
o arenaviruses
o filoviruses
o bunyaviruses
o flaviviruses
- all depend on animal or insect host for survival
& transmission
- potential biologic weapons
Chronic (latent) infections (Herpesvirus)
- Herpesviruses
o large encapsulated virus
o dsDNA genome
o acute infection followed by latent
infection
HSV-1
- major cause of fatal sporadic encephalitis in US
- major cause of infectious corneal blindness
- 2 types of corneal lesions:
o herpes epithelial keratitis – virus-induced
cytolysis of superficial epithelium
o herpes stromal keratitis – infiltrates of
mononuclear cells around keratinocytes
& endothelial cells  neovascularization,
scarring, opacification of cornea 
blindness
- gingivostomatitis (usually in children)
HSV-2
- genital herpes
- neonatal herpes (usually fulminant)
- Kaposi varicelliform eruption – generalized
vesiculating involvement of skin
- eczema herpeticum – confluent pustular, or
hemorrhagic blisters
- herpes esophagitis – complicated by
bacterial/fungal superinfection
- herpes bronchopneumonia through intubation
- herpes hepatitis may cause liver failure
- morphology:
o Cowdry type A inclusions –large pink to
purple intranuclear inclusions
o inclusion-bearing multinucleated
syncytia
- MC opportunistic viral pathogen in AIDS
Transforming infections
Epstein-Barr virus
- causes infectious mono
- assoc. w/ development of neoplasms
(lymphomas, nasopharyngeal carcinomas,
Burkitt lymhoma)
- begins in nasopharyngeal & oropharyngeal
lymphoid tissues (tonsils)  infection of B
cells
- occurs mostly in adolescents/young adults in
Varicella-zoster virus
upper socioeconomic classes in developed
- transmitted by aerosols, disseminates
nations
hematogenously
- clinical:
- chickenpox (acute)
o fever
o 2 weeks after respiratory infection
o generalized lymphadenopathy
o crops of lesions
o splenomegaly (soft & fleshy; vulnerable to
o dew drop on rose petal  vesicle 
rupture)
crusted lesion
o sore throat
- shingles (reactivation of latent infection)
- morphology:
o MC latent in trigeminal ganglia (very
o peripheral blood = absolute lymphocytosis
painful)
w/ atypical lymphocytes
o virus infects keratinocytes and cause
o expansion of paracortical areas activated
vesicular lesions
by T cells
o intense pruritus, burning, sharp pain
- diagnosis depends on
o Ramsey hunt syndrome – facial paralysis
o lymphocytosis with atypical lymphocytes
from involvement of geniculate nucleus
o pos. heterophile antibody rxn (monospot)
o dermatomal pattern
o specific antibodies for EBV antigens (viral
capsid antigen, early antigens, EBV nuclear
Cytomegalovirus
antigen)
- latently infects monocytes & their bone
- Duncan disease – X linked lymphoproliferation
marrow progenitors, can be reactivated when
syndrome causes pts to fail to respond to EBV
cellular immunity is depressed
infection  chronic infection,
- transmission – transplacental, neonatal, saliva,
agammaglobulinemia, B-cell lymphoma
sex, fecal-oral, iatrogenic
- morphologic:
BACTERIAL INFECTIONS
o CMV infected cells and nucleus 
Gram-positive
gigantic
S. aureus
o intranuclear basophilic inclusions
- pyogenic gram pos. cocci
surrounded by clear halo (owl eyes)
- form clusters like grapes
- clinical:
- cause multiple types of skin lesions:
o mostly asymptomatic
o boils/furuncle
o MC = mono-like syndrome
o carbuncle
o devastating systemic infection in
o impetigo
neonates & immunocompromised
- hidradentis – chronic suppurative infection of
o common cause of congenital hearing loss
apocrine glands mostly in axilla
o disseminated infection  pneumonitis & - scalded skin syndrome (Ritter dz) – mostly in
colitis
children; sunburn-like rash over entire body 
o congenital infections  erythroblastosis
fragile bullae; desquamation of epidermis at
fetalis, IUGR, microcephaly, mental
granulosa layer
retardation
- also cause abscess, sepsis, osteomyelitis,
o perinatal infections  acquire maternal
pneumonia, endocarditis, food poisoning, TSS
antibodies (usually asymptomatic)
- S. epidermidis cause opportunistic infections in
catheterized pts, prosthetic heart valves, drug
addicts
- S. saprophyticus cause UTI in young women
- many virulence factors:
o protein A (binds Fc portion of Igs)
o clumping factor (receptor for fibrinogen)
o exotoxins
- superantigens cause TSS & food poisoning
- MRSA growing problem
Streptococcal & enterococcal
- gram pos. cocci
- grow in pairs or chains
- cause myriad of suppurative infections of skin,
oropharynx, lungs, heart valves
- S. pyogenes (group A)
o pharyngitis  GN or scarlet fever
o scarlet fever – exotoxin causes fever/rash,
usually in kids
o erysipelas –MC in middle aged in warm
climates; caused by exotoxin; butterfly
distribution on face; sharp demarcated
serpiginous border
o others – impetigo, necrotizing fasciitis,
rheumatic heart dz, TSS
o protein M prevents phagocytosis
- S. agalactiae (group B)
o neonatal sepsis
o chorioamnionitis
- S. pneumoniae
o α-hemolytic; pneumolysin
o lobar pneumonia
o meningitis
- S. mutans
o dental caries
- S. viridans
o endocarditis
- Enterococci
o endocarditis
o UTI
- S. pyogenes, S. agalactiae, S. pneumoniae,
enterococci have capsules
Listeriosis
- gram pos. facultative intracellular bacillus
- food-borne infections (dairy, chicken, hot dogs)
- pregnant, neonates (neonatal sepsis), elderly,
immunosuppressed susceptible
- can cause disseminated dz or meningitis
- surface protein internalin on L. monocytogene
bind E-cadherin on host epithelial cells 
internalization
- infants born with sepsis have papular red rash
all over extremities
Anthrax
- large spore forming gram pos. rod
- spores ground into powder = biologic weapon
- cutaneous – 95%; painless, pruritic papule 
vesicle  rupture black eschar (painless
ulcer)
- inhalation – hemorrhagic mediastinitis;
meningitis frequent
- GI – uncommon; undercooked meat
- exposure to animals or animal products (hides
& wool)
- large boxcar shaped gram pos. extracellular
bacteria in chains
Nocardia
- similar to molds (branching filaments)
- aerobic gram pos. found in soil
- opportunistic infections in
immunocompromised
- irregular staining  beaded appearance
- N. asteroides
o causes respiratory infections; small #
involves CNS
o most pts infected have defect in T cell
mediated immunity (prolonged steroid
use, HIV, DM)
- N. brasiliensis infects skin
Gram-negative
Neisseria
- gram neg. diplococcic, coffee bean appearance
- grow on chocolate agar
Diphtheria
- antigenic variation allows escape from immune
- Corynebacterium diphtheria
response
- slender gram pos. rod w/ clubbed ends
- pili proteins  initial adherence to epithelial
- person to person; aerosol
cells; altered by genetic recombo
- cause skin lesions in infected wounds
- OPA proteins  increase binding to epithelial
- formation of tough pharyngeal membrane from
cells & promote entry into cells
exudates (dirty gray to black)
- N. meningitides
- produces toxin that blocks host cell protein
o have multiple serotypes  allows
synthesis  damage to heart, nerves, and other
infection from new serotype
organs (fatty changes)
o cause meningitis (esp in kids <2)
o common colonizer of oropharynx
o complement important in immune
response (those who are deficient in
complement activation are susceptible)
o inhibits opsonization thru capsule
- N. gonorrhoeae
o STD, 2nd after chlamydia
o urethritis in men
o often asymptomatic in women  PID 
infertility & ectopic pregnancy
o neonatal infection causes blindness
Whooping cough (B. pertussis)
- gram neg. coccobacillus
- highly contagious
- violent paroxysms of coughing followed by
inspiratory “whoop”
- vaccine effective but due to antigenic
divergence, incidence has increased in US since
80s
- colonizes brush border of bronchial epithelium
& invades macrophages
- toxin paralyzes cilia  impairs pulmonary
defense
- laryngotracheobronchitis – severe case of
bronchial mucosal erosion, hyperemia, copious
mucopurulent exudate
- striking peripheral lymphocytosis
- no pneumonia unless superinfected
Pseudomonas (P. aeruginosa)
- opportunistic gram neg. bacillus
- infects in CF, severe burns, neutropenia
- common cause of HAI
- can be very resistant to antibiotics
- have pili, adherence proteins, endotoxin,
exotoxin A, exoenzyme S, phospholipase C, and
iron-containing compounds (toxic)
- in pts with CF, secretes alginate to form biofilm
- necrotizing pneumonia – distributed through
terminal airways in fleur-de-lis pattern w/
striking pale necrotic centers + red
hemorrhagic peripheral areas
- vasculitis – masses of organisms cloud tissues
w/ bluish haze; concentrate in walls of BVs
where there is coagulative necrosis
- ecthyma gangrenosum – well demarcated
necrotic & hemorrhagic oval lesions seen in
skin burns
- DIC = frequent complication of bacteremia
Plague aka black death (Y. pestis)
- gram neg. intracellular bacterium
- fleas  rodents  humans
- Yop virulon – complex of genes that kill host
phagocytes; codes type III secretion system
- proliferate in lymphoid tissue & cause lymph
node enlargement (buboes), pneumonia, or
sepsis w/ striking neutrophilia
- bubonic plague – infected fleabite usually on
legs, marked by small pustule or ulcer
- pneumonic plague – severe, confluent,
hemorrhagic & necrotizing bronchopneumonia
w/ fibrinous pleuritis
- septicemic plague – lymph nodes throughout
body and organs rich in mononuclear
phagocytes develop foci of necrosis
- macrophages are primary cells infected
- hallmark of MAC in HIV = abundant acid-fast
bacilli within macrophages
Primary TB
- involves lymph nodes, liver, spleen or remain
- mostly asymptomatic; some have flulike illness
localized to lungs
- starts out in lungs; infects alveolar macrophage - yellow pigmentation to organs secondary to
- proliferates in phagosome for up to 3 weeks
large number or organisms inside swollen
- Ghon focus = as sensitization develops, 1 cm
macrophages
area of gray-white inflammation w/
consolidation emerges; center of focus 
Leprosy or Hansen’s disease (M. leprae)
caseous necrosis
- slowly progressive infection
- Gohn complex = lung lesion + nodal
- acid-fast obligate intracellular
involvement
- can be propagated in armadillo
- Ranke complex = Ghon complex  fibrosis &
- affects skin & peripheral nerves
calcification
- can cause disabling deformities
Chancroid (H. ducreyi)
- spread through aerosols  taken up by
- soft chancre
Secondary TB
alveolar macrophages  hematogenous
- painful genital ulcer
- arises in previously sensitized host
dissemination  replicates in cool tissues
- tender erythematous papule on external
- commonly many years after initial infection
(skin & extremities)
genitalia  irregular ulcer (may be multiple)
- apex of upper lobes of 1 or both lungs
- T-helper cell response determines tuberculoid
- base of ulcer covered by shaggy, yellow-gray
- malaise, anorexia, fever, hemoptysis, pleuritic
vs. lepromatous leprosy
exudate
pain
- inguinal lymph nodes become enlarged and
- initial lesion is a small focus of consolidation
Tuberculoid leprosy
tender
w/in apical pleura
- strong TH1 response
- common in low socioeconomic in tropics
- lesion undergoes progressive fibrous
- localized, flat, red skin lesions; enlarge to
- MC cause of genital ulcers in Africa & SE Asia
encapsulation leaving fibrocalcific scars
irregular shapes w/ indurated, elevated,
- active lesions = coalescent tubercles w/ central
hyperpigmented margins w/ depressed pale
Granuloma inguinale
caseation
centers (central healing)
- Klebsiella granulomatis
- “paucibacillary” = bacilli never found at lesions
- encapsulated coccobacillus
Miliary pulmonary disease
- asymmetric involvement of large peripheral
- chronic inflammatory dz
- occurs when organisms draining through
nerves
- STI
lymphatics enter venous blood and circulate
- small nerves can be destroyed by
- tropics; endemic in rural tropics
back to lung
granulomatous inflammation
- extensive scarring & lymph obstruction
- small foci of consolidations scatter throughout - nerve degeneration lead to:
(elephantiasis) of external genitalia
lung (like millet seeds)
o skin anesthesias
- raised papular lesion on genitalia  enlarges, - may expand and fuse  consolidation of large
o skin & muscle atrophy
borders become raised and indurated
regions or whole lobe
o chronic skin ulcers
- regional lymph nodes spared
o contractures, paralyses, autoamputation
- pseudoepitheliomatous hyperplasia – marked Systemic military TB
- facial nerve involvement can cause:
epithelial hyperplasia at borders of ulcer mimic - bacteria disseminate hematogenously
o paralysis of eyelids
carcinoma
- liver, bone marrow, spleen, adrenals,
o keratitis/corneal ulceration
- organisms seen in Giemsa stained smears of
meninges, kidneys, fallopian tubes, epididymis - granulomas + absence of bacteria = strong T
exudate as minute encapsulated coccobacilli
- Pott disease = vertebrae affected
cell immunity
(Donovan bodies) in macrophages
Lymphadenitis
Lepromatos leprosy (“LEthal”)
Mycobacteria
- MC presentation of extrapulmonary TB
- more severe form due to weak TH1 response;
Tuberculosis
- usually occur in cervical region (“scrofula”)
some TH2 involvement
- flourishes in poverty, crowding, chronic
- skin thickening
debilitating illness
- cooler areas of body severely affected (skin,
- HIV pts susceptible to rapid progression
MAC
peripheral nerves, anterior eye chamber, upper
o usually have multifocal dz, systemic
- M. avium-intracellulare Complex
airways, testes, hands, feet)
symptoms
- common in soil, water, dust, domestic animals - macular, papular, nodular lesions form on face,
- airborne; person to person
- occur in AIDS or low CD4+ count
ears, wrist, elbows, knees; lesions coalesce to
- infection leads to delayed hypersensitivity that - fever, night sweats, weight loss
form leonine facies
can be detected by tuberculin test
- multibacillary = lesions contain large
aggregates of lipid-laden macrophages (lepra
cells) filled w/ masses (globi) of acid-fast
bacilli
- peripheral nerves (esp. ulnar & peroneal)
where they approach skin surface are
symmetrically invaded by mycobacteria w/
minimal inflammation
- testes usually extensively involved  sterility
- benign syphilis – gummas in various sites
(nodular lesions from delayed
hypersensitivity)
Congenital
- happens during primary or secondary syphilis
- infantile or tardive
- bullous rash & sloughing
- osteochondritis & periostitis commonly affect
nose & lower legs
Spirochetes
- saddle nose deformity
Syphilis (Treponema pallidum)
- saber shin
- silver stain, dark-field, immunofluorescence
- liver severely affected; lymphoplasmacytic
- can’t culture; too small for gram stain
infiltrate
- sexual or congenital
- lungs may have diffuse interstitial fibrosis
- Jarisch-Herxheimer rxn = after antibiotic tx, pts - tardive congenital syphilis triad:
w/ high bacterial load can get massive release
o interstitial keratitis
of endotoxins  cytokine storm (high fever,
o Hutchison teeth
rigors, hypotesion, leukopenia
o eighth nerve deafness
- pathogenesis: proliferative endarteritis occurs
in all stages of syphilis (immune response)
Relapsing fever
- serologic testing:
- insect-transmitted disease
o nontreponemal
- epidemic relapsing fever – caused by body
 VDRL – for cardiolipin (present in
louse-transmitted Borrelia recurrentis
host and T. pallidum)
- endemic relapsing fever – transmitted from
 RPR – rapid plasma reagin
small animals  humans from Ornithodorus
 both used to see if Tx is working
soft-bodied ticks
 false + not uncommon; certain acute - shaking chills, fever, headache, fatigue 
infections, collagen vascular dz,
- DIC & multiorgan failure
drug addiction, pregnancy,
lepromatous leprosy
Lyme disease
o antitreponemal
- Borrelia burgdorferi
 fluorescent antibody that react w/ - transmitted from rodents  people by Ixodes
T. pallidum
deer ticks
 remain + indefinitely (even after Tx) - Northeastern states and some parts of Midwest
- stage 1
Primary syphilis
o spirochetes multiply & spread in dermis at
- chancre on penis or vulva
site of tick bite (redness w/ pale center)
- chancre contain organisms
o erythema chronicum migrans
o fever, lymphadenopathy
Secondary syphilis
- stage 2
- systemic; 2-10 wks after primary due to
o early disseminated stage
proliferation in skin & mucocutaneous tissues
o hematogenous spread throughout body
- mucocutaneous lesions on palm, soles, mouth
o secondary skin lesions
- may be maculopapular, scaly, or pustular
o lymphadenopathy
- may have condylomata lata on moist skin
o migratory joint & muscle pain
- condylomata lata contain Treponema
o cardiac arrhythmias
o meningitis
Tertiary syphilis
- stage 3
- can occur after latent period of 5+ years
o late disseminated stage (2-3 yrs after bite)
- occurs in 1/3 untreated pts
o chronic arthritis
- cardiovascular syphilis – MC (80%); aortitis
o severe damage to large joints
- neurosyphilis – tabes dorsalis,
o polyneuropathy and encephalitis
meningovascular dz, general paresis
- pathogenesis:
o immune response + inflammation
o B. burdorferi escape antibody response
through antigenic variation
- Morphology:
o early Lyme arthritis resembles early RA
o arteritis produces onion-skin lesions
Anaerobic
Abscesses
- usually mixed anaerobic & facultative aerobic
bacteria
- usually caused by commensal bacterial
- morphology:
o abscess caused by anaerobes contain
discolored, foul-smelling pus that’s
poorly walled off
Head & neck
- gram neg: Prevotella, Porphyromonas
- gram pos: S. aureus, S. pyogenes
Lemierre syndrome
- caused by Fusobacterium necrophorum (oral
commensal)
- infection of lateral pharyngeal space & septic
jugular vein thrombosis
Abdominal
- gram neg: Bacteriodes fragilis, E. coli
- gram pos: Peptostreptococcus, Clostridium
Genital
- Bartholin cyst abscess: Prevotella
- Tubo-ovarian abscess: E. coli, S. agalactiae
Clostridium
- spores; found in soil
- don’t grow in presence of O2
- virulence = toxins
- C. tetani = tetanus, neurotoxin
- C. botulinum = neurotoxin, canned foods
- C. dificile = overgrowth in intestine after
antibiotic use, pseudomembranous colitis
- C. perfringens, C. septicum, et al
o cellulitis, myonecrosis of trauma &
surgical wounds
o uterine myonecrosis (illegal abortion)
o mild food poisoning
o small bowel infection w/ ischemia or
neutropenia
o if spread hematogenously, widespread
formation of gas bubbles
- clostridial cellulitis
o originates in wounds
o foul odor, thin discolored exudate
o quick & wide tissue destruction
- clostridial gas gangrene
o life-threatening
o marked edema & enzymatic necrosis of
involved muscle cells 1-3 days after
injury
o large bullous vesicles
o inflamed muscles become soft, blueblack, friable, semifluid
Obligate intracellular
Chlamydia (C. trachomatis)
- MC bacterial STD in the world
- serotypes define type of infection
o D-K: UG infection & inclusion
conjunctivitis
o L1-L3: lymphogranuloma venereum
o A, B, C: ocular infection of children
(trachoma)
- 2 forms in unique lifestyle:
o elementary body (EB) = infectious form;
sporelike structure
o reticulate body = metabolically active
form; replicates
- frequently asymptomatic in women
- urethritis = mucopurulent discharge w/
neutrophils
- lymphogranuloma venereum = chronic
ulcerative dz; starts as small papule in/by
genital mucosa; chlamydial inclusions
- can also cause epididymitis, prostatitis, PID,
pharyngitis, conjunctivitis, perihepatic
inflammation, proctitis
Rickettsia
- vector-borne (lice, chiggers, ticks)
- mostly affect vascular endothelial cells
Typhus fever (body lice)
- mild = rash & small hermorrhages
- severe = skin necrosis, gangrene of fingers,
nose, earlobes, scrotum, penis, & vulva
- small vessel lesions, focal areas of hemorrhage
& inflammation in various organs and tissues
Scrub typhus (chiggers/mites)
- milder form of typhus fever
- rash transitory or not evident
Rocky Mountain spotted fever RMSF (dog ticks)
- hemorrhagic rash over entire body, including
palms and soles
- noncardiogenic pulmonary edema  adult
respiratory distress syndrome = major cause
death in RMSF
Erlichiosis (ticks)
- infect neutrophils or macrophages
- leukocyte inclusions shaped like mulberries
made of masses of bacteria (morulae)
- abrupt onset of fever, headache, and malaise
FUNGAL INFECTIONS
- eukaryotes w/ cell walls
- mold = multicellular filaments
- yeast = single cells or chains of cells
- mycoses (fungal infections) can be:
o superficial & cutaneous
o subcutaneous
o endemic (serious systemic in healthy)
o opportunistic (life-threatening in
immunosuppressed)
Candidiasis
- usually benign commensal
- C. albicans MC cause of fungal infections
- diabetics & burn pts susceptible
- virulence factors:
o phenotype switching
o adhesins  adhere to cells
o enzymes  tissue invasion
o secrete adenosine
o grow as biofilms
- can appear as blastoconidia (yeastlike) or as
pseudohyphae
- thrush – MC form of superficial infection; seen
in newborn, oral steroids, broad-spectrum
antibiotics
- esophagitis – commonly seen in AIDS; painful
swallowing & retrosternal chest pain
- vaginitis – curdlike discharge; seen in diabetic,
pregnant, OC pills
- cutaneous –
o onychomycosis (nail proper)
o paronychia (nail fold)
o hair follicle (folliculitis)
o armpit, webs of fingers/toes (intertrigo)
o penile skin (balanitis)
o diaper rash
- invasive – blood borne dissemination
o renal or hepatic abscess
o myocardial abscess
o endocarditis (MC fungal endocarditis; IV
drug users or prosthetic valves)
o brain microabscess, meningitis
o endophthalmitis
Cryptococcosis (C. neoformans)
- Yeast; thick gelatinous capsule; no hyphae;
intense red-staining w/ PAS or mucicarmine
- opportunistic infection in AIDs, leukemia,
lymphoma, SLE, sarcoidosis, transplant (high
dose steroids)
- soil, bird droppings  inhaled
- makes laccase  melanin pigment
- lung is primary site of infection
- meningoencephalitis
o gelatinous masses grow in meninges or
expand to Virchow-Robin spaces
o produce soap bubble lesions
Aspergillosis (A. fumigatus)
- Mold; air-borne conidia; fruiting bodies w/
septate filaments branching at acute angles
- allergies in healthy (allergic
bronchopulmonary aspergillosis)
- tendency to invade BVs
- makes aflatoxin on peanuts
Colonizing aspergillosis (aspergilloma)
- growth in pulmonary cavities
- form brown “fungal balls”
- recurrent hemoptysis
-
o merozoites (asexual, haploid)
o trophozoites (1st stage in RBC) 
o schizonts (2nd stage in RBC; multiple
chromatin that become merozoites; some
form gametocytes)
latent hypnozoites made by P. vivax and ovale
leading cause of death in <5 yrs in sub-Saharan
host resistance:
o inherited alterations in RBCs
o repeated or prolonged exposure
P. falciparum causes severe malaria:
o can infect RBC of any age
o clumping of RBCs to each other (rosette)
& endothelial cells of BVs (sequestration)
through PfEMP1 knobs on surface of
RBCs
o high lvls of parasitemia, severe anemia,
cerebral symptoms, renal failure,
pulmonary edema, death
o malignant cerebral malaria = BVs in brain
are plugged w/ parasitized RBCs; ring
hemorrhages around BVs and Dürck
granulomas
o high lvls of cytokines
Babesiosis
- deer ticks, white footed mice are reservoirs
- fever & hemolytic anemia
- erythrocytes form maltese cross forms
Invasive aspergillosis
- occur in immunosuppressed
- primary lesions in lung with widespread
Leishmaniasis
hematogenous dissemination to heart valves & - chronic inflammatory dz of skin, mucous
brain
membranes, or viscera
- target lesions
- obligate intracellular, kinetoplast-containing
protozoan parasites
Zygomycosis (Mucormycosis)
- endemic in Middle East, South Asia, Africa,
- nonseptate, irregularly wide fungal hyphae w/
Latin America
frequent right angle branching
- sandflies (promistagote), macrophages
- bread mold fungi
(amistagote)
- transmitted by airborne asexual spores
- different species in Old and New world
- cause no harm in immunocompetent
- visceral
- neutropenia, steroids, DM, iron overload,
o hepatosplenomegaly, pancytopenia,
burns, trauma predispose
fever, weight loss
- rhinocerebral mucormycosis
o hyperpigmentation of skin in S. Asian
o MC in diabetics
ancestry (kala-azar or “black fever”)
o fungus spread from nasal sinus  orbit
o fibrotic liver & glomerulonephritis in
later stages
PARASITIC INFECTIONS
- cutaneous
o papule becomes ulcer w/ heaped up
Protozoa
border
Malaria (Plasmodium)
- mucocutaenous (espundia)
- spread by anopheles mosquito
o only in New World
- life cycle:
o ulcerating or nonulcerating leisons in
o sporozoite (infectious form) 
nasopharyngeal areas, disfiguring
- diffuse cuteaneous
o rare form
o single nodule spreads to entire body
African Trypanosomiasis (Trypanosoma
brucei)
- kinetoplastic parasite; proliferates as
extracellular forms in blood
- intermittent fevers, lymphadenopathy,
splenomegaly, progressive brain dysfunction
(sleeping sickness), cachexia, death
- transmitted by tsetse flies
- initial spike of fever kills most organisms;
antigenic variation of variant surface
glycoprotein (VSG) allow some to escape
immune response & cause waves of fever
before they finally invade the CNS
- large, red, rubbery chancre at site of bite
- parasites breach BBB  demyelinating
panencephalitis (Mott cells frequently present)
Chagas (Trypanosoma cruzi)
- “kissing bugs”
- common in S. America (Brazil)
- acute myocarditis (4-chamber cardiac dilation)
- chronic cardiomyopathy (cardiac & digestive
tract damage)
Metazoa
Strongyloidiasis (Strongyloides stercoralis)
- larvae in soil
- penetrate skin  blood  lung  trachea 
swallow  GI
- can reinvade colon and reinitiate infection
- immunocompromised can have high worm
burden due to severe autoinfections
Tapeworms (cestodes)
- caused by undercooked meats or fish
Taenia solium
- causes cysticercosis
- eating undercooked pork w/ cysticerci (larval
cyst)  development of adult tapeworm; mild
abdominal symptoms
- eating eggs in feces contaminated food/water
 larvae hatch and penetrate gut wall 
hematogenous dissemination  encyst many
organs (brain, muscles, skin, heart)
- cysts evoke little host rxn until they degenerate
Echinococcus granulosus
- causes hydatid dz
- ingestion of eggs shed by dogs or foxes
- eggs hatch in duodenum and invade liver,
lungs, bones
- 2/3 of cysts are found in liver; 5-15% in lung
- form fine, sandlike sediment within hydatid
fluid (hydatid sand)
Trichinosis (Trichinella spiralis)
- nematode parasite
- pork
- penetrate skeletal muscle (rich blood supply)
- cause fever, myalgias, marked eosinophilia,
periorbital edema
- parasites die  calcify  leave behind scars
Schistosomiasis
- freshwater snails
- cirrhosis MC cause of mortality
- mild infections  pinhead-size granulomas
scattered in gut & liver; liver is darkened
- severe infections  pseudopolyps form in
colon; liver fibrosis (pipestem fibrosis); portal
HTN
- cystitis  mucosal erosions, hematuria, sandy
appearance from calcified granulomas,
increased risk of squamous cell carcinoma of
bladder
Lymphatic filariasis
- transmitted by mosquitoes
- elephantiasis
- tropical pulmonary eosinophilia (MeyersKouvenarr bodies)
Onchocerciasis
- transmitted by black flies; river blindness
- subQ nodule
- microfiliariae are released by females and
accumulate in skin and eye chambers
o accumulation in anterior chamber =
iridocyclitis & glaucoma
o involvement of choroid & retina =
atrophy & loss of vision
- chronic itchy dermatitis w/ focal darkening or
loss of pigment & scaling (lizard or elephant
skin)
- punctate keratitis (inflammation around
degenerating microfilaria)