INFECTIOUS DISEASES

Still an important cause of death
among elderly & immunocompromised
patients
BIOTERRORISM AGENTS
Category A

Highest risk

Readily disseminated

Highly mortality

Eg: anthrax, botulism, smallpox.
plaque
Category B

Moderately easy to disseminate

Moderately morbidity

Low mortality

Foodborne or waterborne

Eg: brucelliosis, epsilon toxin,
glandera, etc.
Category C

Can be engineered for mass
dissemination

Potential high morbidity & high
mortality

Emerging infectious disease threats

Eg: nipah virus, hantavirus
TABLE 8-4 -- Potential Agents of
Bioterrorism
Category A Diseases/Agents

Anthrax (Bacillus anthracis)

Botulism (Clostridium botulinum toxin)

Plague (Yersinia pestis)

Smallpox (Variola major virus)

Tularemia (Francisella tularensis)

Viral hemorrhagic fevers (filoviruses [e.g.,
Ebola, Marburg] and arenaviruses [e.g.,
Lassa, Machupo])
Category B Diseases/Agents

Brucellosis (Brucella sp.)

Epsilon toxin of Clostridium perfringens

Food safety threats (e.g., Salmonella sp.,
Escherichia coli O157:H7, Shigella)

Glanders (Burkholderia mallei)

Melioidosis (Burkholderia pseudomallei)

Psittacosis (Chlamydia psittaci)

Q fever (Coxiella burnetti)

Ricin toxin from Ricinus communis (castor
beans)

Staphylococcal enterotoxin B
Prepared by: EGBII w/ AFB; 09-17-11


Typhus fever (Rickettsia prowazekii)
Viral encephalitis (alphaviruses [e.g.,
Venezuelan equine encephalitis, eastern
equine encephalitis, western equine
encephalitis])

Water safety threats (e.g., Vibrio
cholerae, Cryptosporidium parvum)
Category C Diseases/Agents

Emerging infectious disease threats such
as Nipah virus and Hantavirus
TABLE 8-1 -- Classes of Human
Pathogens and Their Lifestyles
Taxonomic
Site of
Propagation
Prions
Intracellular
Viruses
Obligate
intracellular
Obligate
intracellular
Extracellular
Bacteria
Fungi
Facultative
intracellular
Extracellular
Protozoa
Facultative
intracellular
Extracellular
Helminths
Facultative
intracellular
Obligate
intracellular
Extracellular
Intracellular
Disease/
causative
agents
CreutzfeldJacob disease
Poliomyelitis
Chlamydia
Streptococcus
pneumonia
Mycobacterium
tuberculosis
Candida
albicans
Histoplasma
capsulatum
Trypanosoma
gambiense
Trypanosoma
cruzi
Leishmania
donovani
Wuchereria
bancrofti
Trichinella
spiralis
CATEGORIES OF INFECTIOUS AGENTS

Prion

Viruses

Bacteria
o
Chlamydiae
o
Ricketssiae
o
Mycoplasma

Fungus

Protozoa


Helminths
Ectoparasites
PRION

With prion protein (PrP)

Normally found in neurons

(+) disease in conformational changes
 protease resistance

Spongiform encephalitis
o
Kuru (human cannibalism)
o
Creutzfeld Jacob Disease
(corneal transplant)
o
Bovine Spongiform
Encephalopathy (mad cow
disease)
o
Variant CJD
VIRUSES

Obligate intracellular parasite

20-300 nm

Nucleic acid genome surrounded by
CAPSID

Classified according to:
o
Nucleic acid genome
o
Shape & capsid
o
(+)/(-) of lipid envelope
o
Mode of replication
o
Tropism
o
Type of pathology

(+) inclusion bodies
o
CMV
o
Herpesvirus
o
Smallpox & Rabies

Transient, latent infection, tumor
production
BACTERIA

Prokaryotes – have cell membrane but
lack membrane-bound nuclei &
organelles

Cell wall with peptidoglycan
o
Thick (gram positive)
o
Thin (gram negative)

Classified according to
o
Gram staining
o
Shape
o
Need for oxygen

Some with flagella or pilli

Colonize body parts of normal people

Synthesize their own DNA, RNA, &
proteins but depend on hosts for
favorable growth conditions
Obligate Intracellular Bacteria
Chlamydia
Rickettsia
Cannot synthesize
ATP
Replicate inside
membrane-bound
vacuoles in
epithelial cells
C.trachomatis –
most common cause
of female sterility &
blindness
Depend on host cell
for ATP
Replicate inside
membrane-bound
vacuoles in
endothelial cells 
hemorrhagic
vasculitis
Transmitted by
arthropod vectors
Causes:
-Q fever
-RMSF
Mycoplasma

Extracellular bacteria; lacks cell wall

Tiniest free living org.like ureaplasma

Person to person

Atypical pneumonia
UREAPLASMA

Sexually transmitted

Nongonococcal urethritis
FUNGUS

Eukaryote

Chitin (+) cell wall

Ergosterol – cell membrane

Yeast cells or hyphae

Some dimorphic
o
Hyphae @ room temp
o
Yeast @ body temp

(+) sexual spores or asexual spores
(conidia)

Superficial (nails, hairs, skin,
dermatophytes, tinea)

Subcutaneous (tropical mycosis)

Deep (coccidiodes)

Opportunistic fungi (Candida,
Aspergillus, Mucor, Cryptococcus

Pneumocystis jiroveci in AIDS patients
PROTOZOA

Single cell eukaryotes

Can replicate intracellularly or
extracellularly
o
o
o
o
o
o
o
Trichomonas vaginalis
Entamoeba histolytica
Giardia lambia
Plasmodium
Trypanosoma
Leishmania
Toxoplasma gondii
TABLE 8-3 -- Some Recently
Recognized Infectious Agents and
Manifestations

ADAPTIVE – mediated by T & B
lymphos

o
Blood & blood products (drug
abusers, needle sticks)
Animals to humans
TRANSMISSION & DISSEMINATION OF MICROBES
1.
2.
3.
4.
5.
6.
HELMINTHS

Highly differentiated

Multicellular

Complex life cycle
o
Sexual – definitive host
o
Asexual – intermediate
host/vector

Disease is due to reaction to eggs or
larvae

Disease is proportionate to number of
organism
Routes of entry of microbes
Spread & dissemination of microbes
Release of microbes from the body
Sexually transmitted infections
Healthcare-associated infections
Host Defenses against infections
1. Routes of entry of microbes





Inhalation
Ingestion
Sexual transmission
Insect or animal bites
Injection
2. Spread & dissemination of
microbes
ECTOPARASITE

Insects or arachnids

Direct effect or as vector

Itching & excoriation

Transmitted disease


SPECIAL TECHNIQUES FOR
DIAGNOSING INFECTIOUS AGENTS

Initially, spreads LOCALLY (Cholera,
dermatophytes) or INVADE & SPREAD
thru blood (malaria), LYMPHATICS
(staphylococcus), or NERVES (rabies)
Placental fetal route (rubella &
syhphilis), birth canal (gonococcal),
milk (CMV, HBV)
Major manifestations at distant sites
(airway)
o
Chickenpox & Measles
3. Release of microbes from the
body
TRANSMISSION &
DISSEMINATION OF MICROBES




Prepared by: EGBII w/ AFB; 09-17-11
o
Need to infect before transmission
Factors: infecting organism & host,
virulaent factor
Host barriers:
o
Prevent microbe’s entry
o
Innate or adaptive
INNATE – physical barriers, phagocytic
cells, NK cells, plasma proteins





Skin shedding
Coughing
Sneezing
Urine or feces
Insect vectors
TRANSMISSION OF MICROBES FROM
PERSON TO PERSON

Respiratory – virus & bacteria
(*important)

Fecal-Oral – water borne viruses

Sexual – STDs, HBV, HIV, HSV, HPV

Others
o
Skin penetration (hook worm)
4. Sexually transmitted
infections



Infection w/ one STI increases the risk
with another STD
Can be spread from pregnant mother
to the fetus  severe damage to
fetus/child
INITIAL SITE: urethra, vagina, cervix,
rectum, oral, pharynx
TABLE 8-5 -- Classification of Important Sexually
Transmitted Diseases
5. Healthcare-associated
infections




“nosocomial” infections  hospital
acquired (usually after 5 days of
admission)
Transmitted through blood
transfusions, organ transplant, invasive
procedures
Most common, hands of healthcare
providers (wash hands after every
patient)
Hygiene & hand washing greatly reduce
transmission of MRSA & VRE
6. Host Defenses against
infections
HOST DEFENSES AGAINST INFECTION:
SKIN

Keratin layer - *good factor

Low pH (5.5)

Fatty acids

Microbes penetrate INTACT skin or thru
breaks
o
Schistosoma – can enter intact
the skin
HOST DEFENSES AGAINST INFECTION:
GIT

Acidic gastric

Secretions

Mucus layer

Pancreatic enzymes

Bile

Defensins

Normal flora

IgA

Host defenses weakened by:
o
Low gastric acidity
o
Antibiotics
o
Disturbance in peristalsis
o
Obstruction

Enterotoxins, exotoxins invasion &
mucosal damage, systemic infection
Prepared by: EGBII w/ AFB; 09-17-11
HOST DEFENSES AGAINST INFECTION:
RESPIRATORY TRACT

Mucociliary defense

Alveolar macrophages

Damage to mucocilliary defense by:
o
Smoking
o
Cystic fibrosis
o
Aspiration
o
Intubation
BACTERIAL VIRULENCE

Virulence genes in pathogenicity
islands
o
*encode proteins for their
ability to adhere, invade, or
deliver toxins

PLASMIDS or BACTERIOPHAGES –
virulence factors

PLASMIDS or TRANSPOSONS –
antibiotic resistance

QUORUM SENSING – expression of
virulence Fs related to concentration
(more bacteria = increase virulence)

Secretion of autoinducer peptides –
toxin production

BIOFILMS – viscous layer of
extracellular polysaccharides that
adhere to host tissue or devices 
adherence, immune evasion,
inc.antibiotic resistane
o
Ex: Pseudomonas aeruginosa
*There are some bacteria that
avoid phagocytosis
(eg.pneumococcus TB)
HOST DEFENSES AGAINST INFECTION:
GENITOURINARY TRACT

Urination

Low vaginal pH (glycogen lactobacilli)

Anatomy

Obstruction

Antibiotics (vaginal infection) – w/c
destroyed by lactic bacilli
o
*Female – more prone to
infection
HOW MICROORGANISMS
CAUSE DISEASE
Mechanisms of Injury
1. Enter host cells & directly cause
disease
2. Release of toxins/ enzymes (during cell
lysis)
3. Host cellular response
MECHANISMS OF VIRAL INJURY

Directly damage host cells by entering
& replicating inside host cells

Direct cytopathic effects, antiviral
immune responses, & transformation of
infected cells

Has factors for tissue tropism, d/t:
o
Host cell receptor – for the
virus
o
Cellular transcription Fs
o
Anatomic barriers (ex.polio)
o
Local temp.,pH & host
defenses
MECHANISMS OF BACTERIAL INJURY

Bacterial virulence

Bacterial adherence to host cells

Virulence of intracellular bacteria

Bacterial toxins

Injurious effect of host immunity
BACTERIAL ADHERENCE

ADHESINS – adhere to host cells or
ECM fibrillae (eg. S. pyogenes)
o
S. pyogenes adheres to host
tissues by protein F and
teichoic acid projecting from
the bacterial cell wall

PILI/ FIMBRIAE are filamentous
proteins on the surface of bacteria
o
Eg. E. coli, N. gonorrhoeae
VIRULENCE OF INTRACELLULAR
BACTERIA

Infect epithelial cell, macrophage, or
both

Escape immune response or facilitate
spread

Gain entry thru immune response
o
Eg.coating with Abs or C3b
(opsonization)  phagocytosis

When inside the cell – inhibit host
protein synthesis, replicate rapidly, &
lyse host cell
o
*phagolysosome – kills most
bacteria
o
MTB – prevent fusion of
phagosome &lysosome
BACTERIAL TOXINS

EDOTOXINS – component of bacterial
cell
o
Eg.LPS (in gm (-) bacteria
o
Induce cytokines & chemokines
o
Plays a role in Septic shock,
DIC, ARDS – d/t excessive
cytokines

EXOTOXINS – secreted by bacterium
o
Enzyme (proteases,
hyaluronidases, coagulases,
fibrinolysins)
o
Toxins that alter INTRAcellular
signals or regular pathways (AB toxins)
o
Neurotoxins
(C.botilinum/tetani) - paralysis
o
Superantigens – stimulate very
large amounts of T
lymphocytes  cytokines 
capillary leak & shock

Superantigens made
by S. aureus and S.
pyogenes cause toxic
shock syndrome (TSS)
INJURIOUS EFFECTS OF HOST IMMUNITY

Tuberculosis – type IV hypersensitivity

HBV & HBC – immune reponse

Rheumatic Fever – cross reaction

Post.Strep GN – type III
hypersensitivity
o
Can develop infection –
S.pyogenes
*Chronic inflammation – provides fertile
ground for the development of cancer
IMMUNE EVASION BY
MICROBES
Microorganisms have developed many means
to resist and evade the immune system.
Mechanisms:


(1) Growth in niches that remains
inaccessible/ hidden to host immune
response. Eg.intestinal lumen,
gallbladder
(2) Variation or shedding antigens
Prepared by: EGBII w/ AFB; 09-17-11


(3) Resistance to innate immune
defenses – capsule, host proteins,
protease  can destroy host body
(4) Impairment of effective T-cell
antimicrobial responses by specific or
nonspecific immunosuppression
*after viral infection = decrease immune
response
INFECTIONS IN
IMMUNOSUPPRESSED HOSTS





Inherited or acquired defects in
immunity  partial  susceptible to
specific types of infection
X-linked agammaglobulinemia – severe
bacterial infections
o
S.pneumoniae
o
H.influenzae
o
S.aureus
T-cell defects – intracellular pathogens
Complement protein deficiency –
susceptible to
o
S.pneumonia
o
H.influenzae
o
N.meningitides
AIDS (destroys CD4 T-helper cells),
leukemia – opportunistic infections
o
Pneumocystis jirovecii –
common opportunistic
5 PATTERNS of INFLAMMATORY RESPONSE

Suppurative inflammation –
pyogenic bacteria
o
d/t digestion of normal
structures

Mononuclear & Granulomatous
inflammation – caused by:
o
Virus, intracellular bacteria, or
intracellular parasites
o
*EXCEPT acute viral infection –
by macrophage

Cytopathic-Cytoproliferative
inflammation
o
Usually, by a virus

Tissue necrosis – without or few
inflammatory cells but NO inflammation
o
C.perfringes, E.histolytica

Chronic inflammation & Scarring –
by HBV (cirrhosis)
VIRAL INFECTIONS
Transient infections
.Measles
.Mumps
.Poliovirus
.West Nile Virus
.Viral H’gic virus
Chronic LATENT
infections
.HSV
.VZV
.CMV
Transforming
infections
.EBV
.HPV
Chronic
PRODUCTIVE
infections
.Hepa B
TRANSIENT INFECTIONS
1. Measles (Rubeola)





Single standed RNA
Paramyxovirus family
Only 1 strain
Cell surface receptors:
o
CD46 – all nucleated cells
o
Signaling lymphocytic
activation molecule (SLAM) –
cells of immune systems

a molecule involved in
T-cell activation
MOT: respiratory droplets
Characteristics/ Morphology:

WARTHIN-FINKELDEY CELLS
o
Multinucleated giant cells
w/eosinophilic nuclear &
cytoplasmic inclusion bodies
o
Seen in lymphoid organs with
follicular hyperplasia

REDDISH BROWN RASH
o
Dilated vessels, edema,
mononuclear perivascular
infiltrates

KOPLIK SPOT (pathognomonic)
o
Mucosal ulcerated lesions
o
Marked by: Necrosis,
neutrophils, neovascularization
o
Appear during 4th day of fever;
usually in 2nd molar
Complications of measles

Croup, pneumonia

Diarrhea

Keratitis (blindness), encephalitis
(Subacute sclerosing
panencephalitis)

Hemorrhagic measles (“black
measles”)
Prepared by: EGBII w/ AFB; 09-17-11
2. Mumps
4. West Nile Virus






Paramyxovirus
2 types of surface glycoproteins
o
Hemagglutinin (w/c enter the
cell) & neuramidase (w/c exit
the cell) activities
o
Cell fusion & cytolytic activities
Inhalation of respiratory droplets 
regional LN  replicate in lymphocytes
 blood  tropisms: salivary glands &
other tissues  desquamation of
involved cells, edema, & inflammation
 swelling (both side of parotid) & pain
Other sites: CNS, testis, ovary,
pancreas





Arthropod-borne virus
Flavivirus (includes Dengue & Yellow
fever)
Mosquitoes to bird to mammals
Humans – accidental host
Transmitted by blood transfusion,
transplanted organs, breast milk, &
transplacental route
Usually asymptomatic, 20% mild febrile
illness
DANGEROUS complicationsL
o
Meningitis
o
Encephalitis
o
Meningoencephalitis
Morphology

Salivary gland pain & swelling
o
70% bilateral
o
Mononuclear cells compress
acini
o
PMN & debris – lumen
(parotitis)

Aseptic meningitis 0 most common
extrasalivary complication (10%)

Mumps orchitis – scar & atrophy –
causing sterility

Pancreatic parenchyman & fat necrosis,
pmn-rich

Mumps encephalitis – monos
5. Viral Hemorrhagic Fever
3. Polivirus










Spherical, unencapsulated RNA
Enterovirus
w/ 3 major stains, all included in
vaccine
it uses human CD155 to gain entry into
cells
Fecal-oral route
Infects oropharynx  secreted into
saliva  swallowed  multiplies in
intestinal mucosa & LN  transient
viremia & fever  1/100 invades CNS
 replicates in SPINAL motor neurons
or BRAIN STEM (bulbar)  POLIO







Enveloped RNAs of arena virus:
o
Filoviruses
o
Bunyaviruses
o
Flaviviruses
Depend on animal or insect host for
survival and transmission
Transmitted on contact with infected
hosts or insect vectors, humans NOT
the natural reservoir
Some can spread from person to
person: Lassa, Ebola, Marburg
Mild to acute disease to life-threatening
disease with sudden hemodynamic
deterioration & shock
NO cure or vaccines
Potential biologic weapons
Pathogenesis NOT well-understood
Manifestations:
o
d/t thrombocytopenia or
severe platelet (as low as 500)
or endothelial dysfunction 
increased vascular
permeability
Activates innate immune response
*there are 4 serotypes of dengue
CHRONIC LATENT INFECTIONS
1. Herpes Simplex virus









Includes: HSV 1 & HSV 2
Differ serologically
Genetically similar
Acute & laten
Replicate – skin & mucus membrane
Vesicular lesions
Spread thru sensory neurons
Latency associated transcripts
Repeated reactivations

HSV-1 – associated with CORNEAL
blindness, FATAL sporadic
encephalopathy
Neonates & immunocompromissed,
disseminated HSV infection
Large, pink to purple intranuclear
inclusions (Cowdry tupe A)
o
Also with halo


Manifestations

Fever, blisters, cold sores (bilateral)

Gingivostomatitis (HSV-1)

Genital herpes (HSV 2>1)

2 types of corneal lesions:
o
Epithelial keratitis - virusinduced cytolysis of the
superficial epithelium
o
stromal keratitis - is
characterized by infiltrates of
mononuclear cells

KAPOSI varicelliform eruption

eczema herpeticum is characterized
by confluent, pustular, or hemorrhagic
blisters

esophagitis - superinfection with
bacteria or fungi

bronchopneumonia – d/t intubation
o
NOT a typical manifestation

Herpes hepatitis
2. Varicella Zoster Virus







Chicken pox & shingles
Mild in children
Infects mucous membrane, skin, &
neurons
LATENT infections – sensory ganglia
Transmitted thru AEROSOLA
Spread hematogenously
Spread vesicular lesions
o
Centrifugal = trunk to
extremities
Chickenpox
.2wks after
respiratory infection
.Rash (macule in
torso to head &
extremities)
.Vesicles rupture,
crusts, heal
Shingles
.Chickenpox
Latent 
REACTIVATION
*Dorsal root ganglia
SHINGLES

Vesicular lesions, intense itching,
burning or sharp pain (radiculoneuritis)

Facial paralysis (geniculate nucleus)
o
RAMSAY HUNT SYND

Other VZV associated diseases:
o
Intestinal Pneumonia
o
Encephalitis
o
Tranverse Myelitis
o
Necrotizing Visceral lesions
3. Cytomegalovirus






Beta group herpesvirus
Major envelop CHON binds with
epidermal growth factor receptor
Latent with WBCs
Asymptomatic or mononucleosis like
infection in healthy people
Gigantism of cell & nucleus
Inclusion body surrounded by HAL
(OWL’s eye)
Mode of transmission

Transplacental (congenital)

Thru vaginal/ cervical secretions
(neonatal) or milk (perinatal)

Thru saliva – preschool

Venereal – after 15 years – ONLY in
U.S.
Prepared by: EGBII w/ AFB; 09-17-11


Iatrogenic/ blood transfusion – any age
Respiratory secretions & fecal-oral
o
Intranuclear & cytoplasmic
basophilic inclusions
o
Seropositive for life – already
with antibody
High Risks

Solid organ transplant patients
allogenic BM transplant patients AIDS
patient (most common opportunistic
organism)


Manifestations of CMV: disseminated

Pneumonitis, Colitis, Retinitis
lymphocytic inflammation, apoptotic
hepatocytes resulting from CTLmediated killing, and progressive
destruction of the liver parenchyma.
Long-term viral replication and
recurrent immune-mediated liver injury
can lead to cirrhosis of the liver and
an increased risk for hepatocellular
carcinoma.
CTL response is dormant, resulting in
the establishment of a “carrier” state,
without progressive liver dam
GRAM POSITIVE BACTERIAL DISEASES
1. Staphycoccal infections
2. Streptococcal & Enterococcal
infections
3. Diptheria
4. Listeriosis
5. Anthrax
6. Nocardia
1. Staphylococcus



TRANSFORMING INFECTIONS

Diagnosis:

Morphology

Culture

Antibody

Antigens

PCR (DNA)
1. Epstein-Barr Virus




CHRONIC PRODUCTIVE
INFECTION
1. Hepatitis B Virus







Serum hepatitis
Hepadnavirus
DNA virus
Spread: percutaneously, perinatally,
sexually
Cell injury secondary to reponse to
infected liver cells
Envade immune defenses by inhibiting
INF-B & down regulating viral gene
expression
o
Infected hepatocytes
destroyed by CTL
o
Replicating virus is eliminated
o
Infection is cleared
If the rate of infection of hepatocytes
outpaces the ability of CTLs to
eliminate infected cells, a chronic
infection is established. This may
happen in about 5% of adults and up
to 90% of children infected
perinatally. In this setting the liver
develops a chronic hepatitis, with
Causes infectious mononucleosis (IM)
Associated with lymphomas (Burkitt) &
nasopharyngeal carcinomas
IM occurs in late adolescents & young
adults
Close contact (*saliva) “kissing virus”
EBV spread

The major alterations involve the
blood, lymph nodes, spleen, liver, CNS,
and, occasionally, other organs

Viral ingestion  in normal person, it
resolves in 4-6 weeks

In immunosuppressed  EBV targeted
nasopharynx & oropharynx  causing
B-cell neoplasms
IM diagnosis depends on:

90% lymphocytosis with atypical
lymphocytes in PBS

Positive heteophile antibody reaction

Specific EBV antigens (viral capsid
antigen, early antigen, EB nuclear
antigen)
2. Human Papilloma virus






Non-enveloped DNA virus
Papovavirus family
>100 types
Warts, benign tumors, squamous cell
CA (cervix)
Initially infect basal cells of epithelium
Koilocytosis (perinuclear vacuolization)


Gram (+) cocci
Grapelike clusters
Skin lesions, TSS, respiratory
infections, heart lesions, osteomyelitis,
food poisoning
S. epidermis, S. saprophyticus, S.
aureus
Toxins
o
Hemolytic toxins
o
Exfoliative toxins (bullous
impetigo)
o
Superantigens (TSS & food
poisoning)
Pyogenic inflammation
Morphology

Furuncle or boil

Carbuncle

Hidradenitis suppurativa - infection of
apocrine glands, most often in the
axilla

Paronychia (nailbeds)

Felons (fingertips)

Staphylococcal scalded skin syndrome
or ritter disease - infections of the
nasopharynx or skin in children
2. Streptococcus






Facultative or obligate anaerobe
Gram (+) cocci in pairs or chains
S.pyogenes: pharyngitis, scarlet fever,
erysipelas, impetigo, RF, TSS, GN
S. agalactiae: neonatal sepsis,
meningitis, chorioamnionitis
S. Pneumoniae: community acquired
pneumoniae
S. mutans: dental caries
o
3. Diphtheria







Corynebacterium diptheriae
Gm (+) rod
MOT: person to person, aerosol or skin
shedding
Tough pharyngeal membrane
Toxin mediated damage to tissues
Phage encoded A-B toxin blocks CHON
synthesis
Immunization – protection against
lethal effect of toxin
4. Anthrax






Bacillus antharcis
Spore former
Gm (+) rod
Box-car shaped
Spore – potent biological weapon
Major anthrax syndromes:
o
Cutaneous
o
Inhalational
o
Gastrointestinal
CUTANEOUS Anthrax

95%

Painless pruritic papule  vesicle
(2days)  rupture  black eschar

Bacteremia, rare
INHALATIONAL Anthrax

Inhaled  growth in LN  spore
germinates  toxin release 
hemorrhagic
GASTROINTESTINAL Anthrax

Uncommon

Eating undercooked meat

Nausea, abdominal pain, vomiting

Severe bloody diarrhea

Mortality – 50%
5. Listeria







Gm (+) bacillus
Intracellular
Motile, facultative
Food borne
Exudative pattern of inflammation
INTERNALIS – leucine rich proteins on
surface bind E-cadherins
Protection mediated by IFN-y
Prepared by: EGBII w/ AFB; 09-17-11
Activates macrophages

6. Nocardia









Aerobic
Gram (+)
(+) terminal spores
“beaded”
Branching
N. asteroids – respiratory infection
N. brasiliensis – skin infection
Patients with defective T-cell mediated
immunity
Suppurative lesion with liquefaction,
granulation & fibrosis
Gram Negative Bacterial infections
1. Neisserial infections
2. Whooping cough
3. Pseudomonas infection
4. Plaque
5. Chancroid (Soft chancre)
6. Granuloma Inguinale
1. Neisserial infections




Gm (-) diplococcic
Coffee bean shaped
Grow best in enriched media (lysed in
sheeps’s blood agar, “chocolate” agar)
N.meningitides & N.gonorrhea –
clinically significant
N.meningitides

13 serotypes

Bacterial meningitis in 5-19 years old

Colonize oropharynx  invade
respiratory epithelium  circulation 
capsule reduces opsonization &
destruction by complement

Spread by respiratory route

Tx: antibiotics

10% death
N.gonorrhea

Causes of STD:
o
1st – C.trachomatis
o
2nd – N.gonorrhea

Urethritis in men

Asymptomatic in women  PID 
sterility or ectopic pregnancy

Disseminated infection in those lacking
complement proteins (MAC)  septic
arthritis + hemorrhagic papules &
pustules
Neonatal gonorrhea  blindness
(conjunctivitis), rarely, sepsis
o
Tx: silver nitrate or antibiotics
Pathogenesis

Use antigenic variation to escape
immune response:
o
Pili proteins are altered by
genetic recombination
o
Has three or four genes for
OPA proteins

OPA-ability to change
their antigen; They
increase binding of
Neisseria organisms to
epithelial cells and
promote entry of
bacteria into cells

Has multiple serotypes  disease with
new strain

Adhere to pili+CD46) & invade (OPA
proteins) non ciliated epithelial cells at
site of entry (nasopharynx, urethra, or
cervix)
2. Whooping cough











Bordatella pertussis
Gm (-) coccobacillus
Acute, highly communicable
Paroxysms of violent coughing followed
by “whoop”
Vaccine available but high rate due to
antigenic divergence & waning
immunity
Dx: PCR, culture (less sensitive)
Pathogenesis:
o
Colonizes brush border of
bronchial epithelium & invades
macrophages
Bortedella virulence gene (bvg) –
regulates transcription of adhesins &
toxins
Hemaglutinin adhesins binds with
CHON on surface of cells
EXOTOXINS – paralyze cilia
Cause: LARYNGOTRACHEOBRONCHITIS
o
Bronchial mucosal erosions

o
Hyperemia
o
Copious mucopurulent exudate
Peripheral lymphocytosis (90%)
o
Hypercellularity & enlargement
of mucosal lymph follicales &
peribronchial LN
3. Pseudomonas infection




P.aeruginosa
o
Common cause of hospital
acquired
Opportunistic, aerobic, gm (-) bacillus
o
a frequent, deadly pathogen of
people with cystic fibrosis,
severe burns, or neutropenia
 d/t sepsis
Resistant to antibiotics
Hospital acquired infection, corneal
keratitis (contact lenses), endocarditis
& osteomyelitis (IV abuses), otitis
media (swimmers/diabetics)
Virulence factors

PILI & adherence proteins  binds to
epithelial cells & lung mucin

ENDOTOXIN – symptoms & signs of gm
(-) sepsis

ALGINATE – slimy biofilm, protects
bacteria from antibody, complement,
phagocytes, antibiotics

EXOTOXIN – inhibits protein synthesis

PHOSPHOLIPASE C – lyze rbc &
degrades pulmonary surfactant

ELASTASE – degrades IgG & ECM

Iron containing compounds – toxic to
E.C.  causing vasculitis
Manifestations

Necrotizing pneumonia – terminal
airways in a fleur-de-lis pattern

Gram (-) vasculitis + thrombosis +
hemorrhage – highly suggestive

Bronchial obstruction in CF +
P.aeruginosa  bronchiectasis &
pulmonary fibrosis

Skin burns  Ecthyma gangrenosum

Bacteremia  DIC
4. Plague
5. Chancroid (Soft Chancre)









Yersinia pestis, gm (-) facultative
intracellular bacterium
Transmitted from rodents to humans
by fleabites or human to humans by
aerosols
Causes invasive, frequently fatal
infection (black death)
Y.enterocolitica &
Y.pseudotuberculosis:
o
Cause fecal-oral transmitted
ileiteis & mesenteric
lymphadenitis
Proliferative within lymphoid cells
Yop virulon genes  proteins
assemble into type 3 secretion system
 binds & injects bacterial toxins
(Yops) to host cells  kill host
phagocytes & block phagocytosis &
production of cytokines
Histologic features

Massive proliferation of organism

Appearance of protein rich &
polysaccharide rich effusion

Necrosis of tissues & blood vessels with
hemorrhage & thrombosis

Neutrophilic infiltrates
Manifestations

BUBONIC PLAQUE – fleabite on legs
with pustule or ulceration  draining
LN enlarges become soft, pulpy &
plum-colored (buboes)  may infarct
or rupture thru skin

PNEUMONIC PLAQUE – severe,
confluent, hemorrhagic & necrotizing
bronchopneumonia with fibrinous
pleuritis

SEPTICEMIC PLAQUE – LN & REC all
throughout the body develop foci of
necrosis + neutrophilia

FULMINANT BACTEREMIAS – DIC with
hemorrhages & thrombosis




Chancroid

Irregular ulcer:
o
neutrophil debris and fibrin
o
granulation tissue with
necrosis & thrombosed vessels
o
dense lymphoplasmatic
infiltrates

Gram or silver stain – coccobacilli
MYCOBACTERIA
1.
2.




Tuberculosis
Mycobacterium aviumintracellulare complex
3. Leprosy
Slender, aerobic rods that grow in
straight or branching chain
Waxy cell wall composed of mycolic
acid
Acid fast
Weakly gram (+)
6. Granuloma Inguinale
(Donovanosis)






Klebsiella granulomatosis (formerly
Calymmatobacterium donovani)
minute, encapsulated, coccobacillus
Sexually transmitted
Untreated  entensive scarring asst’d
with lymphatic obst’n & lymphadema
(elephantiasis) of external genetalia
Dx: microscopy of smears or ulcer
biopsy
Raised papule  ulceration 
granulation tissue  disfiguring scars
pseudoepitheliomatous hyperplasia
neutrophils and monos in ulcer base
Donovan bodies (bacteria in
macrophage on Giemsa stain/silver
stain smears of exudates)
1.






Tuberculosis






M. tuberculosis, M. bovis
Infection thru airborne droplets
Organism may be dormant for years
within macrophages
Reactivation occurs with depressed
immune status
Delayed hypersensitivity to antigen
Tuberculin (mantoux) test






Prepared by: EGBII w/ AFB; 09-17-11
Versus Syphilis (Hard chancre)
Hemophilus ducreyi, coccobacilli
Acute, sexually transmitted, ulcerative
infection
4-7 days after inoculation  tender,
erythematous papule
Males – lesion in penis; females –
vagina and periurethral area
Erodes  irregular ulcer 
enlargement of regional lymph nodes
(buboes)  erodes overlying skin 
chronic, draining ulcers
Must be cultured in special conditions;
PCR






NOT specific!
(+) means there is exposure or
immunization received
induration that peaks in 48 to 72
hours
Macrophages - 1° cells infected
Replicate w/ phagosomes
Bacteremia
NRAMP1 gene – gen. of anti-microbial
oxygen radicals
TH1 response in 3 wks makes
macrophages bactericidal
Other roles of TH1:

INF-y – for competence of
macrophages

iNOS – for oxidative destruction
formation of granulomas and
caseous necrosis
Non-specific signs:

early dse: malaise, anorexia, wt. loss
low grade fever, night sweats

hemoptysis, pleuritic pain

AFB. culture, PCR
2.










1° TB – ghon (parenchyma)
occurs in prev. unexposed (usually in
children), unsensitized person
usually w/ latent dse
some progressive
pneumonia like,hillar adenopathy,
pleural effusion
Ghon complex:
o
parenchymal lung lesion
o
nodal involvement
Ranke complex:
o
radiologically detectable
o
calcification
2° TB @ apex
seen in prev. sensitized host
shortly after primary or reactivation or
exogenous reinfection
@ apex of upper lobes
cavitation is common
initial lesion may heal
progressive pulmonary TB in elderly &
immunocompromised
Miliary pulmonary dse
o
organism drain through
lymphatics into ducts or thru
the pulmonary artery
microscopic/visible (2mm)
Systemic military TB
o
liver,BM,spleen,adrenals,menig
es,kidneys,FT,epididymis
isolated-organ TB (mostly systemic,
EXCEPT this!)
o
TB meningitis, renal
TB,adrenals,osteomylelitis,salpi
ngitis,scrofula,GIT TB
* FIGURE 8-28 The natural history and spectrum of
tuberculosis. (at the back)
MYCOBACTERIUM AVIUM –
INTRACELLULARE COMPLEX






MAC
Uncommon except in AIDS & low
levels of CD4 lymphocytes (<60
cell/mm3)
widely dessiminated
lungs
mononuclear system
granuloma, lymphocyte, & tissue
destruction rare
LEPROSY





Hansen dse
M. leprae
Aerosols
Grow in cool tissues of skin (32-34C)
acid fast, obligate intracellular
organisms
o
tuberculoid
o
lepromatous
o
intermediate
Tuberculoid Type

dry, scaly skin w/o sensation

TH1 (IL-2,IFN-y)

hyperpigmented margins w/
depressed centers – seen in
patients with intact immune sys.

granulomatous, no bacilli or very
few anesthesia
Lepromatous Type

more severe from, anergic type –
severe form of leprosy*

symmetric skin thickening &
nodules

defective TH1 response or dominant
TH2 response

lepra cells w/ numerous acid fast
bacilli - *a macrophage

leonine facies

hypoesthetic or anesthetic
Prepared by: EGBII w/ AFB; 09-17-11
OBLIGATE INTRACELLULAR
BACTERIA
 Chlamydia
SPIROCHETES
1.
2.
3.
Syphilis
Relapsing fever
Lyme Disease
Syphilis (3 stages)

1° stage
o
3 wks after contact
single,firm,nontender,raise
d,red lesion (chancre)
o
numerous spirochetes
o
heals in 3 – 6 wks

2° stage
o
2-10 wks after primary
skin & tissues
maculopapular,scaly, or
pustular
o
condylomata lata
o
lymphadenipahty, mild
fever, malaise, weight loss

Tertiary stage
o
rare
o
after a latent period of 5
yrs
o
CVS, neurosyphilis,benign
tertiary Sy
o
gummas – white gray
rubbery lesions
Congenital Syphilis

crosses the placenta during 1° and
2° early (infantile), late (tardive)
homework: “take note of the
differences”
Serologic Tests for Syphilis



Serology - mainstay
PCR
Nontreponemal tests - measure
antibody to cardiolipin, a phospholipid present in
both host tissues and T. pallidum

 RPR,VDRL measure Ab to cardiolipin
Treponemal tests
 FTA-Abs, MHATP
o
o
o

gram (-)
STD
urethritis, lymphogranuloma
venereum
Ricketssia
o
o
gram (-)
typhus fever, rocky mountain
spotted fever, scrub typhus
SUMMARY OF BACTERIAL INFECTIONS
ANAEROBIC BACTERIA
1.
2.
Abscesses caused by anaerobes
Clostridial infections
Abscess


mixed anaerobic and facultative
bacteria
foul smelling, pus filled
Clostridium Infections





Gram (+), anaerobes, spore former
C.perfringes – gas gangrene
C.tetani – tetanus
C.deficilli – pseudomembranous
colitis
C.botolinium 0 botulism
FUNGAL INFECTIONS
1.
2.
3.
4.
Candidiasis
Cryptococcosis
Aspergillosis
Zygomycosis (Mucormycosis)
1. Candidiasis






superficial infections
esophagitis
vaginitis
cutaneous
chronic mucocutaneous
invasive
PARASITIC INFECTIONS
2 general categories:
1. Protozoa

Malaria, Babesiosis, Leishmaniasis,
African typanosomiasis, Chagas
dse.
2. Metazoa

Strongyloidiasis, Tapeworms,
Trichinosis, Schistosomiasis,
Filariasis, Onchoceriasis
*read about MALARIA!
2. Cryptococcosis




Life Cycle and Pathogenesis.
Encapsulated yeast
Meningoencephalitis
Opportunistic infection in AIDS,
leukemic lymphoma patients
In soil, bird droppings
Plasmodium vivax, P. ovale, and P. malariae
cause low levels of parasitemia, mild anemia,
and, in rare instances, splenic rupture and
nephrotic syndrome. P. falciparum causes high
levels of parasitemia, severe anemia, cerebral
symptoms, renal failure, pulmonary edema,
and death. The life cycles of the Plasmodium
species are similar, although P. falciparum
differs in ways that contribute to its greater
virulence.
3. Aspergillosis





Mold
brewer’s lung in healthy people
sinusitis, pneumonia,fungermia in
immunocompromised individuals
neutropenia,corticosteroids
aspergilloma, invasive aspergillosis
The infectious stage of malaria, the
sporozoite, is found in the salivary glands of
female mosquitoes. When the mosquito takes
a blood meal, sporozoites are released into
the human's blood and within minutes attach
to and invade liver cells by binding to the
hepatocyte receptor for the serum proteins
thrombospondin and properdin[112] ( Fig. 8-49
). Within liver cells, malaria parasites multiply
rapidly, releasing as many as 30,000
merozoites (asexual, haploid forms) when
each infected hepatocyte ruptures. P. vivax
and P. ovale form latent hypnozoites in
hepatocytes, which cause relapses of malaria
long after initial infection.
4. Zygomycosis







Prepared by: EGBII w/ AFB; 09-17-11
mucomycosis
bread mold fungi
no harm to immunocompetent
infect immunosuppressed
individuals
neutropenia, corticosteroid,
diabetes, breakdown of cutaneous
barriers
nonseptate, irreg. wide hyphae
rhinocerebral mucormycosis, lung
involvement
Plasmodium falciparum, which causes severe
malaria, and the three other malaria parasites
that infect humans (P. vivax, P. ovale, and P.
malariae) are transmitted by female
Anopheles mosquitoes that are widely
distributed throughout Africa, Asia, and Latin
America. Nearly all of the approximately 1500
new cases of malaria each year in the United
States occur in travelers or immigrants,
although rare cases transmitted by Anopheles
mosquitoes or blood transfusion do occur.
Worldwide public health efforts to control
malaria in the 1950s through 1980s failed,
leaving mosquitoes resistant to DDT and
malathion and Plasmodium resistant to
chloroquine and pyrimethamine.
Malaria, caused by the intracellular parasite
Plasmodium, is a worldwide infection that
affects 500 million and kills more than 1
million people each year. According to the
World Health Organization, 90% of deaths
from malaria occur in sub-Saharan Africa,
where malaria is the leading cause of death in
children younger than 5 years old.
Once released from the liver, Plasmodium
merozoites bind by a parasite lectin-like
molecule to sialic acid residues on glycophorin
molecules on the surface of red cells. Within
the red cells the parasites grow in a
membrane-bound digestive vacuole,
hydrolyzing hemoglobin through secreted
enzymes. The trophozoite is the first stage of
the parasite in the red cell and is defined by
the presence of a single chromatin mass. The
next stage, the schizont, has multiple
chromatin masses, each of which develops
into a merozoite. On lysis of the red cell, the
new merozoites infect additional red cells.
Although most malaria parasites within the
red cells develop into merozoites, some
parasites develop into sexual forms called
gametocytes that infect the mosquito when it
takes its blood meal.
Plasmodium falciparum causes more severe
disease than the other Plasmodium species
do. Several features of P. falciparum account
for its greater pathogenicity:
•
•
•
P. falciparum is able to infect red
blood cells of any age, leading to high
parasite burdens and profound
anemia. The other species infect only
young or old red cells, which are a
smaller fraction of the red cell pool.
P. falciparum causes infected red cells
to clump together (rosette) and to
stick to endothelial cells lining small
blood vessels (sequestration), which
blocks blood flow. Several proteins,
including P. falciparum erythrocyte
membrane protein 1 (PfEMP1), form
knobs on the surface of red cells ( Fig.
8-49 ).[113] PfEMP1 binds to ligands on
endothelial cells, including CD36,
thrombospondin, VCAM-1, ICAM-1,
and E-selectin. Ischemia due to poor
perfusion causes the manifestations of
cerebral malaria, which is the main
cause of death due to malaria in
children.
P. falciparum stimulates production of
high levels of cytokines, including
TNF, IFN-γ, and IL-1. GPI-linked
proteins, including merozoite surface
antigens, are released from infected
red cells and induce cytokine
production by host cells by a
mechanism that is not yet understood.
These cytokines suppress production
of red blood cells, increase fever,
Prepared by: EGBII w/ AFB; 09-17-11
stimulate nitric oxide production
(leading to tissue damage), and
induce expression of endothelial
receptors for PfEMP1 (increasing
sequestration).
Host Resistance to Plasmodium.
There are two general mechanisms of host
resistance to Plasmodium. First, inherited
alterations in red cells make people resistant
to Plasmodium. Second, repeated or
prolonged exposure to Plasmodium species
stimulates an immune response that reduces
the severity of the illness caused by malaria.
Several common mutations in hemoglobin
genes confer resistance to malaria. People
who are heterozygous for the sickle cell trait
(HbS) become infected with P. falciparum, but
they are less likely to die from infection. The
HbS trait causes the parasites to grow poorly
or die because of the low oxygen
concentrations. The geographic distribution of
the HbS trait is similar to that of P.
falciparum, suggesting evolutionary selection
of the HbS trait in people by the parasite.
HbC, another common hemoglobin mutation,
also protects against severe malaria by
reducing parasite proliferation. People can
also be resistant to malaria due to the
absence of proteins to which the parasites
bind. P. vivax enters red cells by binding to
the Duffy blood group antigen. Many Africans,
including most Gambians, are not susceptible
to infection by P. vivax because they do not
have the Duffy antigen.
Individuals living where Plasmodium is
endemic often gain partial immune-mediated
resistance to malaria, evidenced by reduced
illness despite infection. Antibodies and T
lymphocytes specific for Plasmodium reduce
disease manifestations, although the parasite
has developed strategies to evade the host
immune response. P. falciparum uses
antigenic variation to escape from antibody
responses to PfEMP1. Each haploid P.
falciparum genome has about 50 var genes,
each encoding a variant of PfEMP1. The
mechanism of var regulation is not known, but
at least 2% of the parasites switch PfEMP1
genes each generation. CTLs may also be
important in resistance to P. falciparum.
Despite enormous efforts, there has been little
progress in developing a vaccine for malaria.
Morphology. Plasmodium falciparum
infection initially causes congestion and
enlargement of the spleen, which may
eventually exceed 1000 gm in weight.
Parasites are present within red cells, which is
the basis of the diagnostic test, and there is
increased phagocytic activity of the
macrophages in the spleen. In chronic malaria
infection, the spleen becomes increasingly
fibrotic and brittle, with a thick capsule and
fibrous trabeculae. The parenchyma is gray or
black because of phagocytic cells containing
granular, brown-black, faintly birefringent
hemozoin pigment. In addition, macrophages
with engulfed parasites, red blood cells, and
debris are numerous.
With progression of malaria, the liver becomes
progressively enlarged and pigmented.
Kupffer cells are heavily laden with malarial
pigment, parasites, and cellular debris, while
some pigment is also present in the
parenchymal cells. Pigmented phagocytic cells
may be found dispersed throughout the bone
marrow, lymph nodes, subcutaneous tissues,
and lungs. The kidneys are often enlarged and
congested with a dusting of pigment in the
glomeruli and hemoglobin casts in the tubules.
In malignant cerebral malaria caused by P.
falciparum, brain vessels are plugged with
parasitized red cells ( Fig. 8-50 ). Around the
vessels there are ring hemorrhages that are
probably related to local hypoxia incident to
the vascular stasis and small focal
inflammatory reactions (called malarial or
Dürck granulomas). With more severe
hypoxia, there is degeneration of neurons,
focal ischemic softening, and occasionally
scant inflammatory infiltrates in the meninges.
Nonspecific focal hypoxic lesions in the heart
may be induced by the progressive anemia
and circulatory stasis in chronically infected
people. In some, the myocardium shows focal
interstitial infiltrates. Finally, in the
nonimmune patient, pulmonary edema or
shock with DIC may cause death, sometimes
in the absence of other characteristic lesions.
Prepared by: EGBII w/ AFB; 09-17-11