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MICROBIOLOGY
Prepared by: Dr. D. Boyd, DDS
Oral & Maxillofacial Pathologist
Associate Professor
Reference: Kaplan Review Notes
INTRODUCTION
• NORMAL MICROBIAL FLORA
• Properties:
– Population of microbes that usually reside in
the body.
– Resident flora: fixed population that will
repopulate if disturbed, e.g S mutans (caries)
– Transient flora: from environs & reside in
body without invasion, & prevent infection
by more pathogenic organisms (bacterial
interference)
Distribution of Normal
Microbial Flora
• Location
• Skin
Major Organism
Propionibacteria acnes,
Staph epidermis & aureus, diptheroids
• Oral cavity
viridians Streptococcus,
Prevotella melaninogenicus,
Actinomyces, Peptostreptococcus,
other anaerobes
• Nasopharynx:oral microbes, Staph pneumonia,
Hemophilus, Nisseria meningitis
• Vagina Childbearing age: Lactobacillus,
yeast, Streptococcus
Microbial Virulence Factors
• Gene products required for establishment in
the host.
• Gene products located on chromosomes, or
plasmid or transposons
(mobile genetic material)
• Primary pathogens  virulence factors
disease.
• Opportunistic pathogens (environ or normal
flora)  disease ONLY if host is
immunocompromized
Categories of Virulence Factors
1. Enzyme production
Hyaluronidase breaks down Hyaluronic acid
digestion of tissue
Protease digests protein  spread of infection
Coagulase allows coagulation of fibrinogen  clot
Collagenase breaks down collagen (connective
tissue)
Categories of Virulence Factors
• 2. Toxins
• Exotoxins
– heat-labile proteins with specific enzymatic
activities
– Produced by both Gram positive & negative
microbes
– Released extracellularly
– Often sole cause of disease
Categories of Virulence Factors
• Exotoxins:
– Domains with discrete biologic functions 
maximal
toxicity
– A - B toxins
• B subunit bind to host tissue
Glycoproteins
• A subunit enzymatically attack
susceptable
Categories of Virulence Factors
– Endotoxins
• Heat-stable lipopolysaccharide molecule
• Located on outer membrane of
Gram negative microbes
• When released by cell lysis  Lipid A
portion  septic shock (fever, acidosis,
hypotension, complement consumption,
and
disseminated
intravascular
coagulation DIC)
Categories of Virulence Factors
• 3.
–
–
–
Surface components
Protect organism from immune response
Polysaccharide capsule of H influenzae
Acidic polysaccharide capsule of
Streptococcus pneumoniae
– Adhesins  attach microb to cell of host
– Filamentous appendages (fimbriae, pili) 
attach microb to cell of host
– Flagella  motility
Classification & Identification
of Bacteria
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General properties
Prokaryotic = single –cell organism
70 S ribrosomes
Naked, single, circular chromosome of double
stranded DNA the replicates bi-directionally)
• No true nucleus (no nuclear membrane)
• No membrane bound organelles
• Cell wall is rigid, peptidoglycan layer  Gram
positive or negative, Acid fast (resist acid decoloration e.g Mycobacteria)
Classification & Identification
of Bacteria
• Mycoplasma + Ureaplasm
– Only bacteria that do NOT have cell walls
• Chlamydia’s cell wall lack muramic acid
• Both resistant to beta-lactam antibiotic
(penicillin + cephalosporins)
• Prokaryotic flagella do NOT have:
– 9 + 2 microtubles arangement
– microtubules
Classification of Bacteria
• Biomedical characteristics
– Bordetella pertussis grows only on BordetGengou agar)
– E. coli ferment only Lactose sugar
– M. tuberculosis produces Naicin
• Serologic reactivity with specific Antibodies in
diagnostic immunoassays
• Bacteriophage typing used in tracing source of
epidemics
• Animal pathogenicity & Antibiotic sensitivity
Bacterial Structure
• 1. CELL ENVELOPE
• Gram positive smooth surface with 3 layers
– Cytoplasmic membrane = smooth surface
– Thick layer of:
• Peptidogylcan
• Lipoteichoic acids
• Polysaccharides
• Teichoic acid (sometimes
– Outer capsule (sometimes)
Bacterial Structure
• Gram negative (complex cell envelope)
– Cytoplasmic membrane (inner membrane)
– Periplasmic space (containing peptidoglycan
– Outer membrane
• Tri-layered anchored to cell membrane by
lipoprotein
• Endotoxin (LPS, somatic O antigen, core
polysaccharide)
• Protein porin channels
– Capsule (sometimes)
Bacterial Structure
2. PLASMA (cell) MEMBRANE
Function as osmotic barrier
60 – 70% protein
30 – 40% lipid (fat)
Carbohydrate (small amounts)
Bacterial electron transport chain (cytoplasmic
membrane)
Membrane polyribosome-DNA
Mesosomes = convoluted structures of cell
membrane important in cell division)
Bacterial Structure
• 3. CYTOPLASMIC STRUCTURES
• 1. Nucleoid region = circular chromosome of
double-stranded DNA
• Lack introns, histones, nuclear membrane
• 2. Ribosomes
– 70% RNA (ribonucleic acid), 30% protein
– 70S ribosome attached to messenger RNA 
proteins
– 70 S complex  subunits 50S + 20S
Bacterial Structure
• 3. Polyamines located in Ribosomes
• Prevent dissociation of the 70S ribosome
• 4. Cytoplasmic granules store:
• Glycogen
• Lipid (poly-bete-hydroxybutyrate)
• Phosphate (volutin granules)
Bacterial Structure
• Spores (endospores):
• Bacillus & Clostridium species
• Promote survival
• Resit heat + drying
• Highly dehydrated + refractile
• Convert to vegetative state via
germination when environ favorable
• Bacillus species used to check Autoclave used in
Sterilizing instruments
Bacterial Growth
• Depends on
– Available nutrients
– External environs e.g Temperature
– Growth rate of specific species
• Lag phase = period of no growth, adapting
• Exponential phase
– Steady state of growth,
– Continues until nutrients are depleted or
toxic wastes products accumulate
– Antibiotics maximally effective
Bacterial Growth
• Stationary phase occurs when nutrients are
exhausted or toxins accumulate (cell loss = cell
formation)
• Phase of decline occur when death rate
increases due to cell starvation or sensitivity to
toxins
Survival in Oxygen
• Used to classify bacteria
• All bacteria produce Superoxide ion (O2-) in
the presence of Oxygen.
• Superoxide dismutase + O2-  Hydrogen
peroxide (H2O2)
• Catalase or Peroxidase + H2O2 H2O + O2
• Obligate Anaerobes lack these enzymes
therefore Oxygen is toxic to them.
(Clostridium & Bacteroides)
• Facultative organisms grow with or without
oxygen.
Energy Production
• Requires a source of Carbon
• Fastidious bacteria lost their
machinery and need many
requirements.
metabolic
additional
• Siderophores = Iron (Fe3+) chelating
compound essential for bacterial growth.
Mechanisms of Energy
Production
• 1. Fermentation
• Anaerobic degradation of glucose to
obtain ATP
• Less efficient than respiration
• Used by most Obligate Anaerobes & all
Streptococcus species
Mechanisms of Energy
Production
• 2. Respiration
– Completely oxidizes Organic fuels
– Requires an Electron Transport Chain to
drive the synthesis of ATP
– Produces 20 times as much ATP
– Requires terminal electron acceptor (TEA)
• Oxygen, nitrate, fumarate
• Obligate Aerobes
– Uses respiration only
– Must use O2 as TEA (M. tuberculosis)
Sporulation
• Spore
• Dormant structure capable of surviving
long period of unfavorable environs.
• Capable of re-establishing the vegetative state.
• Resistant to radiation, drying, disinfectants.
• Thermal resistance due to high content of
Calcium & Dipicolinic acid in the core.
Sporulation
• Bacillus & Clostridium species.
• Inhibition of sporulation related to Guanosine
Tri-phosphate (GTP) pool.
• Carbon & Nitrogen important
• Germination & Outgrowth occur when
environs & nutrition (glucose, nucleic acid,
amino acids) allow.
Genetic Transfer
• Movement of genetic material into Host
• 1. Transformation
– Uptake & Integration of naked DNA
– Once inside the cell homologous recombination with chromosome of the
recipient must occur
– Induced in the Lab with Salt & Heat shock,
which force cells to take up plasmids
carrying genes of interest.
– Streptococcus, Haemophilius, Neisseria
gonorrhea, Helicobacter pylori (stomach ulcers)
Genetic Transfer
• 2. Transduction
– Phage-mediated transfer of bacterial DNA
• Generalized:
– bacterial DNA mistakenly packaged into
empty phage head
– Recombination occur
Genetic Transfer
• Transduction (cont)
• Specialized:
– Lysogenic phage integrated into bacterial
chromosome excises itself
– Accidentially takes up chromosomal DNA
– Phage replicates  bacterial gene picked up
replicates
– Genes carried into cells that the progeny virus
infected
– Occurs most often
Genetic Transfer
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3. Conjugation (bacterial sex)
Direct transfer of bacterial DNA
Requires cell to cell contact
Most important mechanism for widespread
transfer of genetic information between
bacteria.
• Plasmid mediated. (Extrachromosomal piece of
circular DNA that can replicate itself)
– Carries genes that encode resistance to antibiotics +
virulence factors
– Narrow-host-range, broad-host-range plasmids
Genetic Transfer
• 3. Conjugation (continued)
• Narrow-host-range exist in single species
• Broad-host-range transfer between different
genera
• Conjugated plasmid code for genes involved in
transfer between cells
• Non-conjugated plasmids require help of
conjugated plasmid
Genetic Transfer
• 4. Insertion Sequences are small pieces of DNA
that code for the enzyme Transposase which
allow pieces to jump into & out of DNA
• Transposons consist of:
– Two insertion sequences flanking an
antibiotic resistance genes
– Frequently associated with mutiple drug
resistance plasmids
Dental Clinic Microbiology
• Sterilization
– Most commonly used
– Bacteria + Fungi + Viruses + Spores killed
• Disinfection
– Killing of pathogenic organisms + most
microbes in general.
– Will NOT kill spores
– Disinfected instruments are NOT sterile but
safe to use
Classification of Instruments
• Critical Instruments
– Pierce mucous membrane or enter sterile
tissues
– Scalpel blades, Periodontal scalers,
Endodontic files, Handpieces
– Must be Sterilized or Disposable
• Semi-critical Instruments
– Touch mucous membrane
– Mouth mirrors, Explorers, Xray instruments
Sterilization Methods
• Autoclave (Steam) dull or corrode sharp edges
– 121 degrees F for 20 – 30 minutes, 15psi
• Dry Heat (Driclave) – maintain sharp edges
– 160 degrees F for 1 – 2 hours
• Ethylene oxide (Chemiclave) 8 – 12 hours
– Used for heat-sensitive instruments
• “Cold Sterilization (misnomer)
– Uses long-term disinfectants
– Spores are NOT killed unless placed in
Glutaraldehyde 12 – 15 hours
Sterilization Methods
• All instruments must be clean & free of debris
• Failure to Strelize due to:
– Autoclave over packed
– Time insufficient (wrapped instrument need
more time)
– Autoclave cycle interrupted (power cut)
– Tissue (protein) left on instruments
Material Method & Action
• Material/Method
• Steam Heat &
Disinfectants
Alcohol & Phenols
• Glutaraldehyde
& Ethylene oxide
• Detergent
• Chlorohexidine
• Peroxides & Hg & I
• Soap
Action
Protein denaturation
Protein denaturation
Alkylation protein / DNA
Membrane disruption
Membrane disruption
Oxidize Sulfhydryl bond
Emulsifcation of Fat
Disinfectant Guidelines
• Must be Environmental Protection Agency
(EPA) approve
• Must kill “benchmark” organism
Mycobacterium tuberculosis
• Must have Dental Association seal of approval
for use on dental instruments
• Disinfectants used on materials & surfaces
• Antiseptics used on live tissue
• Hepatitis A & Mycobacterium hard to kill on
surfaces
Sterilization Monitors
• Sterilizers should be checked weekly
• Process Indicator(Does NOT show sterilization)
– Shows that sufficient Temperature was
reached for a specific period of time.
– Color change strip or section on autoclave
bag.
• Biological Monitors (Legal requirement)
– Spore strips of Bacillus sp loaded with
instruments & cultured after autoclaving.
– “Control strip” used to show viability of
spores.
Universal Precautions
• All patients are assumed to be infectious.
• Equal Disinfectant/Sterilization/Cleaning
procedures for all patients
• Preparation of Rooms Instruments & Materials
depend on Procedure NOT Patient.
• Hand Washing:
– Single most effective measure for infection
control
– Arrival & leaving work, before & between
patients, before & after going to restroom
Procedures Included in
Universal Precautions
• Sterilization of MOST instruments.
• Disinfection of semi-critical instruments +
“Touch and Splash” surfaces.
• Barrier methods (Gloves, Masks, Face Shields,
Plastic Chair Covers, Light Handle Covers)
• Disposable instruments (Saliva Ejectors,
Prophy angles, etc)
HISTORY OF UNIVERSAL
PRECAUTIONS
• 1970s: Hepatitis B “clusters”traced to dental
offices
• 1980s: HID disease refocused dental profession
• Much easier to contract HBV than HIV
• Approximate conversion rate after needle stick:
– HBV 30%
– HCV 3%
– HIV 0.3%
VACCINATION
• Hepatitis B vaccination MUST be offered Free
to all Dental Health Care Workers
• Three injections (0 month, 1 month, 6 months)
• Cannot contract disease from vaccination, not
made from human blood products.
• Recombivax:
– Made HBsAg
– Produced by Yeast
Gram Positive Cocci
Staphlococcus & Streptococcus
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STAPHLOCOCCUS
Genus Characteristics & Classification
Gram positive
Divide in perpendicular plane  Clusters
Relatively resistant to Heat & Drying
Metabolically
– Facultative organism
– Possess Superoxide dismutaese & Calalase
Staphylococcus (cont)
• Clinically:
• S. aureus only is pathogenic
– +ve Coagulase Test identifies S. aureus
• S. epidermidis most numerous on the Skin
– Coagulase test negative
• Also S. Saprophyticus
– Urinary tract infection in sexually
active women
– Treatment: Penicillin
Staphylococcus aureus
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Common infectious agent in humans
NOT part of normal flora
Transient in Nasopharynx, Skin, Vagina (30%)
Host defense = PMNs
NO protective immunity  repeated infection
Virulence factors include:
– Protein A Binding protein Coagulase
– DNAse
Staphylokinase Lipase
– Hyaluronidase
Exotoxins (hemolysis)
Staphylococcus aureus (cont)
• Conditions Commonly Caused by S. aureus
• Direct Infection of Skin:
– Folliculitis Furuncle Carbuncle Abscess
– Cellulitis
Wound infection
• Systemic Infection:
– Osteomyelitis
– Lung abscess
Endocarditis
pneumonia
• Toxic-mediated disease:
– Food poisoning
Scalded skin syndrome
– Bullous impetigo Toxic shock syndrome
Staphylococcus aureus (cont)
Treatment:
• Penicillinase-resistant penicillin:
– Amoxicillin, Methicillin, Nafcillin
• Cephalosporin (first generation)
• Vancomycin (methicillin-resistant S. aureus)
– VRSA have been discovered
Staphylococcus epidermidis
Common nosocomial pathogen (Hospital based)
Associated with:
IVs
Catheters
Prosthetic devices
Major virulence factor:
Exopolysacharidebiofilm (slime)
Difficult for Immune system to detect
Treatment = Vancomycin
Streptococcus
Know Very Well
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Genus Characteristics
Gram positive cocci, grow in Chains
Metabolically:
Aerotolerant Anaerobes (facutative anaerobes)
Energy from fermentation only (lack
cytochromes)  Lactic acid
• Lack Catalase (cytochrome-containing enzyme
degrades Hydrogen peroxide  oxygen + HOH
• Medically most important Streptococcus are
auxotrophs (require vitamin, amino acids for
growth, not free living in the environs)
Streptococcus (cont)
• Classification
• Based on reaction in Blood agar
• Alpha Hemolytic
– RBCs intact, partial breakdown of heme
green (viridans) pigment
• Beta Hemolytic
– RBCs completely lysed
– Group A clinically most important
• Gamma Hemolytic: no effect on RBCs
Alpha Hemolytic Steptococcus
S. pneumoniae & Viridans
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STREPTOCOCCUS PNEUMONIAE
Grow in short chains
Inhibited by Optochin or Bile
Transmission via aerosol droplets from person
to person
• 20 – 40% of normal people colonized in Nose
• Clinical Manifestations:
– Most common cause of bacterial pneumonia
– Otitis media
Sinusitis
Bronchitis
– Bacteremia Meningitis (#1 cause in elderly)
STREPTOCOCCUS PNEUMONIAE (cont)
• Risk Factors for infection with S. pneumoniae
– Poverty
Debilitated state of Health
– Absence of Spleen
Sickle cell anemia
– Hodgkin’s disease
Multiple myeloma
– AIDS
• Most important virulence factor =
carbohydrate capsule
STREPTOCOCCUS PNEUMONIAE (cont)
• Prevention
• Vaccination with its polysaccharide antigen
(Pneumovax)
– Should be given to:
• Elderly, Splenectomy, smokers,
alcoholics, children
• Treatment
– Penicillin (resistant forms)
– Vancomycin
Erythromycin
Viridans Streptococcus
(non-beta-hemolytic Streptococcus)
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Found in oral flora, non-hemolytic Strep
S. mutans- tooth surface
S. mitis
S. sanguis - tongue
S. salivarius
• Facultative anerobes. Gram positive
Streptococccus mutans
• Chief etiologic agent for caries
• Characteristics:
– Aciduric
– Attaches to pellicle [glucan (dextrans)] 
Plaque  caries + Periodontal disease
– Produces Glucosyltransferase  Glucans
– Preferred substrate Sucrose (Energy +
Glucans)
– pH in Plaque < 5  demineralize Teeth
Caries (cont)
• Other Aciduric Bacteria:
– Lactobacillus species:
• Colonize late carious lesions
• Acid produced eliminate other bacteria +
dissolve Enamel
Caries (cont)
• Effects of Fluoride on S. mutans & Caries:
– Makes enamel more resitant to acid
– Changes Hydroxyapatite to Fluorapatite by
substituting F- for –OH ion
– Shifts Remineralization – Demineralization
equilibrium towards Remineralization
– Toxic to bacteria, interferes with
Glucosyltransferase
– In high concentration (topical gel) will kill bacteria
– 1 part per million (1mg/L)
– Absorbed into developing teeth
Viridans Streptococcus &
Subacute Bacterial Endocarditis
• Caused due to bactermia with lodgement on
artifical or defective Heart valves
• Occur when:
– Susceptible conditions:
• Replacement valves
• Previous history of Endocarditis
• Mitral valve prolapse with regugitation
• Rhematic heart disease
Viridans Streptococcus &
Subacute Bacterial Endocarditis
• Occur when: (cont)
– Colonization by bacteria  valve damage
– Procedure involving bleeding (extractions,
scaling, periodontal probing, endodontics)
• Antibiotic Premedication: Patients with Heart
Murmurs:
– Amoxicillin (First choice)
– If allergic to penicillin:
• Clindamycin
Azithromycin
• Clarithromycin Cephalexin Cephadroxil
Beta Hemolytic Steptococcus
• Subdivide into groups A – D, F & G
• Based on antibodies to heat-labile, acid-stable
Carbohydrate in cell wall
• Antigen called C carbohydrate or Lancefield
antigen
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GROUP A STREPTOCOCCUS (GAS)
STREPTOCOCCUS PYOGENES
Most important
Growth inhibited by antibiotic Bacitracin
Beta Hemolytic Steptococcus
• Clinical Manifestations:
• Suppurative(pus) complications of pharyngitis:
– Otitis media
Peritonsillar cellulitis
– Erysipelas (skin) Scarlet Fever
– Meningitis
Pneumonia
– Peritonsillar & Retropharygeal abscess
– Pyoderma (impetigo)
– Bacteremia
Perianal abscess
– Lymphangitis
Emphyema
– Meningitis
Pneumonia
GROUP A STREPTOCOCCUS
STREPTOCOCCUS PYOGENES (cont)
• Clinical Manifestations (cont)
• Non-suppurative
• Occur weeks after initial Skin infection
– Glomerulonephritis
• Edema, Hypertension, Hematuria)
– Rheumatic fever: (Post Pharngeal infection)
• Fever, Endocarditis, Polyarthritis
• 7 – 28 days after Pharyngitis)
GROUP A STREPTOCOCCUS
STREPTOCOCCUS PYOGENES (cont)
• Transmission & Epidemiology
• Obligate parasite in humans
• Spread from person to person via air droplets
or direct contact with Skin or Fomites
• Pharyngitis most common in Winter & Spring
• Highest incidence in Adolescents
• Contaminated Milk & Eggs causes for foodborne epidemics
• Impetigo-like Skin infection mostly in summer
due to Insect Bites.
• Virulence Factor: most important is M protein
Group B Streptococcus
(Streptococcus agalactiae)
• Part of normal flora of Vagina + GIT (25%)
• Resistant to Bacitracin
• Virulence factor = antiphagocytic
polysaccharide capsule
• Infants more susceptible, aspirate organism
during passage thru Birth Canal, lack passive
resistance from maternal IgG antibodies
• Clinical Manifestations: pneumonia, sepsis,
meningitis
• Treatment: penicillinase-resistant penicillin
Group B Streptococcus
(Enterococcus)
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Previously group D Streptococcus
Enterococcus faecalis and E. Faecium
Part of normal Fecal flora
Cause infection when spread to Urinary Tract
in Hospital Patients  Abscess
• Cause 10% Subacute Endocarditis
• Inhibited by Penicillin
• Vancomycin-resistant Enterococci (VRE)
Gram Positive Bacilli
• Listeria – NO Spores
• Corneybacterium - NO Spores
• Bacillius – Spores
• Clostridium - Spores
Listeriia monocytogenes
• Small Gram positive coccobacillus. No spores
• Microscopically resemble non-pathogenic
Corynebacterium genus, part of normal Skin
flora
• Transmission:
– Facultative intracellular pathogen
– Infects phagocytic cells
– Prduces listeriolysis O  beta-hemolysin
– Contaminated Meat or unpasteurized Milk
Listeriia monocytogenes (cont)
• Risk Factors
– Neonates (transmission across placenta or
during delivery
– Pregnancy (Bacteremia)
– Alcoholics (Meningitis)
– Immunosuppression: (AIDS, Steroids,
Chemotherapy, Transplants)  Meningitis
Cornybacterium diphtheriae
• Non-motile
Club-shaped
No Spores
• Diphtheria toxin (encoded by lysogenic phage)
• Clinical Manifestations:
– Upper Respiratory tract infection
– Tonsillar gray pseudo-membrane
– Compromised airway
– Diphtheria toxin especially toxic to Heart
• Treatment: anti-toxin & Erythromycin ASAP
• Prevention: Vaccine (diphtheria toxoid) during
1st year. Boosters every 10 years
Bacillius anthracis
• Spores persists in Soil for many years
• Encoded on Plasma is Anti-phagocytic capsule
composed of D-glutamate
• 3 Virulence Factors (Anthrax toxin)
– Protective antigen (PA)
– Lethal factor
– Edema factor
• Anthrax toxin = combination of all three
• Transmission via Skin cuts or Inhalation
Bacillius anthracis (cont)
• Clinical Manifestations
• Cutaneous antrax:
– 95% of all infections
– Papules  Ulcers with necrotic centers
– Regional Lymphadenopathy
– Edema major complication  death 20%
• Systemic anthrax
– Acquired thru Inhalation or GIT 
Lymphadenopathy  death
• Treatment: penicillin
Killer vaccine
Bacillus cereus
• Two Enterotoxins
• Grows on Food, especially Cereal Grain (rice)
• Clinical Manifestations: Food Poisoning
– Short incubation ( 1- 6 hours – emetic type)
 severe nausea & vomiting
– Long incubation (10 – 24 hours – diarrheal
type)  abdominal cramps + diarrhea
• Treatment & Prevention:
– Fluids. Vancomycin if indicated.
Clostridium
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Large obligate anaerobe
Spore forming
Found in Soil or human GIT
4 major pathologic species
– C. perfringens
C. tetani
– C. diffcilie
C. botulinum
• Destructive Enzymes + Toxins
– Collagenase
Protease
– Hyaluronidase
Lecithinase
Clostridium perfringens
• Fast growing Non-motile
Soil & GIT
• Alpha toxin (Lecithinase)  Lysis of RBC &
other cells
• Transmission thru disrupted:
– Skin GIT Other Epithelial tissues
– Due to Trauma
Surgery (septic abortion)
– Spores found in Soil
Clostridium perfringens (cont)
• Clinical Manifestations
• Gas gangrene (myonecrosis)
– Life threatening (muscle & CT necrosis)
– Gas is end product of Fermentation 
crepitation
– 80% of cases of Gas gangrene.
• Food Poisoning
• Third most common cause of bacterial foodborne epidemics (1st S. aureus, 2nd Salmonella)
• Abdominal pain & diarrhea for 24 hrs. No Rx
Clostridium perfringens (cont)
• Clinical Manifestations (cont)
• Skin & Soft tissue infections localized
• Suppurative infection usually polymicrobial
• Intra-abdominal infection  Bowel perforation
+ emphysematous cholecystitis
• Pelvic infection  Tubo-ovarian abscess +
Shock
• Treatment: Surgical Debribment + Penicillin
Clostridium difficile
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Normal bowel flora(small percentage of adults)
2 Heat-labile toxins:
Enterotoxin (exotoxin A) Cytotoxin (exotoxin B
Clinical Manifestations:
Cause 25% of antibiotic-associated diarrhea
Cause 95% of pseudomembranous colitis
– Associated with Clindamycin & Ampicillin
– Nausea
Vomiting Abdominal pain
Voluminous green diarrhea
• Treatment: Vancomycin or Metronidazole
Clostridium tetani
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Spores abundant in the Soil
Spores inoculated into wounds
50% of case no history of a wound
Produces tetanospasim a plasmid encoded
neurotoxin that blocks the normal inhibition of
Spinal motor neurons  spastic paralysis 
Death
• Tetanospasim prevents release of the inhibitory
neurotransmitter glycine & gamma-amino
butyric acid  spastic paralysis.
Clostridium tetani (cont)
• Four Clinical Manifestations:
• Local infection  local muscle contraction
• Cephalic infection can follow chronic Otitis
media.
• Generalized Tetanus infection (60% mortality)
– Pain
“Lock-jaw”
Death
– Opisthotonos (head & heels bent backwards
& body bowed forward)
• Neonatal tetanus: infection of umbilical stump
& major cause of infant mortality in developing
countries.
Clostridium tetani (cont)
• Treatment:
– Surgical Debridement of wound
– Human Tetanus anti-toxin
– Respiratory support
– Muscle relaxants (curare-like drugs)
– Metronidazole
• Prevention:
– Immunization with Tetanus toxoid
– Booster shots every 10 years
– No natural immunity
Clostridium botulinum
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Ubiquitous in Soil
Produces powerful heat-labile neurotoxin
Ingested in improperly canned food
Toxin blocks release of Acetylcholine from
neurons in the peripheral nervous system 
Flaccid paralysis
Clinical Manifestations:
Dilated un-reactive pupils (bulbar paralysis)
Descending paralysis starting with Cranial Ns
Progressive respiratory weakness
Dry mucous membranes (mouth)
Clostridium botulinum (cont)
• Clinical Manifestations (cont)
• Infant botulism (floppy baby syndrome)
– Failure to thrive
– Progressive muscular weakness
– Poor motor development
– Infants should not be fed Honey
– Unexpalined Hypotension
No Fever
• Treatment:
– Human anti-toxin
– Respiratory support
Gram Negative Cocci
•
•
•
•
NEISSERIA
Non-motile
Non-spore-forming
Gram negative cocci
Arranged in pairs (diplococci) with flattened
adjacent sides facing each other (“coffee beans)
• Fastidious organisms
• Very susceptible to Heat Cold
Drying
Neiseeria meningitis
• Key virulence factors:
– Anti-phagocytic capsule
– Endotoxin
– IgA protease
• Transmission:
• via Respiratory droplets
• Carriage rate in adult Nasopharynx is 10-30%
• Most carriers are asymptomatic
• Greatest risk in those with late complement (C6
– C8) deficiencies
Neisseria meningitis (cont)
• Clinical Manifestations:
• Meningitis usually sudden & fulminant onset
• Waterhouse-Friderichsen syndrome:
(coagulopathy, Hypotension, Adrenal cortex
necrosis, sepsis, death)
• Diagnosis:
• Identifying Gram negative cocci in Spinal fluid
• Demonstrate production of oxidase & maltose
fermentation.
• Treatment: Penicillin G.
– Carriers & Close contacts Rifampin
Neisseria gonorrhoeae
• Produce beta-lactamase
• Transmission:
– Venereal contact
Fomites
– Increased incidence in:
• Sexually active young adults (15-30 y o)
• Non whites
Low socio-economic class
• Urban settings
Neisseria gonorrhoeae (cont)
• Clinical Manifestations:
• Primarily uro-genital tract
• Men:
– Acute urethritis & yellow purulent discharge
– 90% will be symptomatic
– Common complications:
• Urethral stricture
Epididymitis
• Prostatitis
Proctitis (homosexuals)
Neisseria gonorrhoeae (cont)
• Women:
– Asymtomatic in 20 – 80% of cases
– Inability to observe discharge
– Complications;
• Pelvic inflammatory disease (15 – 20%)
• Generalized Peritonitis
• Infertility
Neisseria gonorrhoeae (cont)
• Disseminated disease observed as:
– Meningitis
Arthritis
– Subacute bacterial endocarditis
• Ophthalmic neonatorum:
– Maternal transmission during birth
– Ophthalmic Tetracycline, Erythromycin,
Silver nitrate for prevention
• Pharyngitis:
– Oral manifestation of gonorrhea
– More common with oral sex
Neisseria gonorrhoeae (cont)
• Diagnosis;
• Men : Gram negative diplococci in Urethral
discharge
• Women: Culture + Biochemical Tests
Treatment & Prevention:
• No longer susceptible to penicillin
• Ceftriaxone
• plus Doxycycline (anti-chlamydial drug)
• Safe sex decrease incidence of gonorrhea
Gram Negative Bacilli
Enterobacteriaceae
•
•
•
•
•
•
•
•
•
Gram negative
Non-spore forming
Facultative
Motile
Many are normal GI flora (symbiotic relation)
Synthesize Vitamin K
Deconjugate Bile & Sex hormones 
recirculated in the Liver
Prevent colonization by primary pathogens
Escherichia
Citrobacteria
Klebsiella
Enterobacteria Serratai
Proteus
Klebsiella not motile
Enterobacteriaceae
• Mostly lack virulence factors
• Act as Opportunistic pathogens when break thru
normal anatomical barriers or in cases of
Immunosuppression
• Most common cause for Intra-abdominal sepsis + UTI
• Those with Virulence Factors:
– Shigella sp
Salmonella sp
– Yersinia sp (not in GIT)
– Escherichia col
Shigella + Salmonella only pathologic in Humans
Enterobacteriaceae
•
•
•
•
•
•
Physiology:
Facultative
Ferment or Respire
Easily destroyed by Heat + Disinfectants
Sensitive to Drying or Desiccation
Survive best in High Moister environ
Respiratory + Anesthesia equipment common
causes for Nosocomial infections
• Ice machines + Water supply  Epidemics
Enterobacteriaceae
• Pathogenicity:
• Due to Endotoxin (LPS)  Fluid into GIT 
Diarrhea
• Toxicity due to Lipid A portion of LPS
• LPS may cause Endotoxic Shock
– Blood pools in Microcirculation 
Hypotension
– Vital organs reduced Blood  decreased
perfusion  Acidosis + Ischemia + Hypoxia
– Disseminated Intravascular Congestion
Shigella
Obligate human pathogen
Not motile
S. Dysenteria
S. flexneri S. sonnei S. boydi
• Transmission by fecal-oral route
– Not killed in stomach, < 100  disease
•
•
•
•
Pathogenesis
Colon site of disease  destroys GI lining
Virulence factors (Adhesin, Toxins, Invasins)
Endotoxin  increased local inflammation
Shigella
• Clinical Manifestations: (Shigellosis)
• Bacillary dysentery:
– Abdominal cramps
– Diarrhea (Blood + PMNs + Mucus)
– Carrier state 1 – 4 weeks after disease
• Treatment
• Hydration
Electrolyte replacement
• Fluoroquinolones
• Prevention thru personal hygiene, proper
garbage disposal & water purification.
Enterotoxigenic Escherichia coli
(E. coli)
• Pathogenicity (virulence factors)
• K 1 capsular antigen (inhibits phagocytosis) 
neonatal meningitis + urinary tract infection
• Hemolysin  Kidney infection
• Clinical Manifestations:
• Major cause of infant death (persistent watery
diarrhea)
• Most common cause of “Traveler’s diarrhea”
• Acquired via fecally contaminated water
• Most common cause of Urinary Tract
Infections.
Treatment = Bactrin
Salmonella
LPS  inhibit Complement-mediated
killing
• Non-Typhoidal Salmonella infection
– Inflammatoey Diarrhea & Fever
– Acquired thru Eggs + Chicken + Food +
HOH
– Large inoculum (> 1 million cells) needed
– More severe under age 10
• Cause Osteomyelitis in Sickle Cell Anemia
patients
• Motile
Salmonella (cont)
•
•
•
•
•
•
•
•
Typhoidal Salmonella infection
Caused by S. typhi (only Human Colon)
Thyphoid (Enteric) Fever
Progressive
Subacute Fibrile-wasting
Common in developing countries
Worst in young children
Transmission:
Large inoculum in Fecally contaminated Food
or Water
• Ulcers & perforation of GIT
Typhoid Fever (cont)
• Clinical Manifestations (3 phases)
• First week: fever, lethargy, constipation, pain
• Second week bacteremia occur
– High fever : Low Pulse Abdominal pain
– “Rose” spots Skin Diarrhea
• Third week:
Exhaustion
Less fever
• Complicatons:
– Relapse (20%)
Bleeding Abscess
• Treatment: Chloroamphenicol (1st choice)
Cephalosporins
Common Opportunistic
Enterobacteriaceae
• Klebsiella sp
• Non-motile
Lactose fermenting Rods
• Laboratory: colonies appear large + mucoid
due to large Capsule
• Klebsiella pneumonia = major pathogen
• Clinical Manifectation:
• Severe Lobar pneumonia (Aspiration, Abscess)
– Sputum “currant jelly”
– Alcoholics
Diabetics
COPD
Common Opportunistic
Enterobacteriaceae
• Proteus sp
• Highly Motile
Cause UTI
• Produce Urease  increase pH  Struvite
(stones)  obstruct UT  hiding place
• Citrobacter  Pyelonephritis
• Enetrobacter  Pneumonia
• Serratia  Pneumonia + UTI
Gram Negative Bacilli: Additional Enteric
Pathogens
Vibrio chlolerae (Cholera)
• Gram negative bacillus
“Comma” shape
• Fresh & Salt Water, Cold blooded animals.
• Pathogenecity
– Pili  adherence to GIT (small intestine)
– Non-invasive infection, clinical effets due to
enterotoxin (choleragen)
• Transmission: fecal-oral (food/water)
• Clinical: severe watery (“rice water”) diarrhea
(20 liters/day). Loss of Na, Cl, K, Bicarbonate)
• Treatment: Hydration & Doxycycline
Gram Negative Bacilli: Additional Enteric
Pathogens
•
•
•
•
Campylobacter
Small
Curved
Gram negative Rods
Reservoirs = Domestic animals
C. jejuni:
– Transmission via Fecal-Oral (Food/HOH)
– Clinical Manifestations: (Enterocolitis)
• Bloody diarrhea
Fever Malaise
• Painful Abdominal cramps
• C. fetus:Bacteremia + Metastatic Infections(IC)
Gram Negative Bacilli: Additional Enteric
Pathogens
Helicobacteria pylori
•
•
•
•
•
Spiral shaped
motile Rod
Produces urase  Alkaline environ
Reservoir possibly Humans only
Older patients + Families
Lives in close proximity to Gastric Epithelial
cells
• High association with Antral gastritis &
Duodenal ulcers (90%)
• Treatment: Bismuth salts, Tetracycline,
Amoxicillin, Metronidazole
Gram Negative Bacilli: Additional Enteric
Pathogens
Pseudomonas
•
•
•
•
Gram negstive Rod
In Soil + HOH
Component of Bowl flora
Human very resistant
• P. aeruginosa
– Important Nosocomal infection in
immunocompromised + chronically ill
Gram Negative Bacilli: Additional Enteric
Pathogens
Pseudomonas
• P. Aeruginosa (cont):
– Groups at Risk:
• Radiation treated patients
• Burn patients
• Patients with Metastatic + Metabolic
diseases
• Prolonged Immunosupression (Steroids)
+ Antibiotics
• Prior instrumentation + manipulation
• Cystic fibrosis
Gram Negative Bacilli: Additional Enteric
Pathogens
Pseudomona
• P. Aeruginosa (cont):
– Clinical Manifestations:
• Wound + Burn infetions
• Ecthyma gangrenosum
– Skin lesions with vascular invasion
• Ear infections:
– Otitis externa – swimmers (mild)
– Malignant Otitis externa – Diabetics
Gram Negative Bacilli: Additional Enteric
Pathogens
Pseudomona
• P. Aeruginosa (cont):
– Clinical Manifestations: (cont)
• Pulmonary infections
– Cystic fibrosis + Immunocompromised
• Corneal infections –Contact Lens wearers
• UTI
– Treatment: Antipseudomonal penicillin:
Gentamicin, Ticaricillin, Piperacillin
– Aminoglycosides (Tobramycin)
RESPIRATORY PATHOGENS
•
•
•
•
•
HEMOPHILUS
Small pleomorphic coccobacillus
Many species are normal flora of Nasopharynx
Hemophilus influenza type b (major pathogen)
Clinical Manifestations:
– Meningitis (30 mo – 6yo) Otitis media
– Acute epiglossitis: rapid onset,
compromised airway
• Treatment: Cefotaxime
Amoxicillin
• Prevention: vaccine for H. influenza type b.
RESPIRATORY PATHOGENS
• H. ducreyi
– Associated with Chancroid:
• Venereal disease
• Painful Non-indurated ragged ulcer
• Genitalia + Perianal
• Presence of beta-Lactamase in both H.
influenza and H. ducreyi result in high
resistance to treatment with Penicillin
Respiratory Pathogens (cont)
•
•
•
•
BORDETELLA PERTUSSIS
Small Gram negative fastidious coccobacillus
Strict Aerobe
Cause of Whooping cough
• Virulence factor:
• Attach to host via pili
• Toxins:
– Pertussis toxin
Adenylate cyclase toxin
– Tracheal cytotoxin
Lipopolysaccharide
Bordetella pertussis (cont)
•
•
•
•
•
•
Clinical Manifestations of Whooping Cough
Highly communicable via respiratory route
Humans only known reservoir
Incubation period = 7 – 10 days 3 Stages:
Catarrhal or prodromal: mild URT infection
Paroxysmal cough followed by “whoop” on
inspiration
• Convalescence: decline in “whoop” over mos.
• Treatment & Prevention: Erythromycin
(catarrhal stage) & Immunization (DPT)
Respiratory Pathogens (cont)
•
•
•
•
•
•
LEGIONELLA PNEUMOHILIA
Gram negative
Facultative Aerobe
Intracellular parasite
Widely distributed in aquatic environments
Requires Fe & Cystine to grow
Uses Complement receptor to infect
Macrophages
• Transmission: (Aerosol)
• Air conditioning units
Humidifiers
• Respiratory devices, Shower head, Whirlpools
LEGIONELLA PNEUMOHILIA (cont)
• Clinical Manifestations:
• Can be asymptomatic
• Pontiac fever: mild, febrile illness without
pneumonia
• Legionnaires’ disease: severe often fatal
pneumonia
• Treatment: Erythromycin
ANAEROBES
• Obligate anaerobes require a reducing agent
(substance able to donate electrons, reducing a
2nd substance & itself being oxidized {combined
with Oxygen or lose an electron})
• Obligate anaerobes cannot survive in Oxygen
since they cannot detoxify the Superoxide ion.
• Include: Gram positive & negative, cocci &
bacilli
– “coil-shaped” Spirochetes
Obligate Anaerobes (cont)
• Greatest natural defense is tissues with high
oxidation-reduction potential  no growth.
• Normal inhabitants of:
– Oral cavity
Vagina
GIT
• Can cause opportunistic infections in tissues
adjacent to their normal habitat due to tissue
injury or vascular compromise.
Obligate Anaerobes (cont)
• Pathology
• Primarily purulent abscess formation
• Culture most often reveal polymicrobal
infection with multiple facultative & anaerobic
species.
• Treatment:
– Surgical drainage
– Clindamycin
– Chloroamphenicol
Penicillin G
Metronidazole
Cefoxitin
Anaerobic Gram Negative
Bacilli
•
•
•
•
•
•
BACTEROIDES:Primary organism of Colon
Bacteroides fragilis:
Most frequent cause of anaerobic infection
Gram negative
No Spore Non-motile
Inhabits GIT & Genital tract
4 virulence factors:
– Polysaccharide capsule(antiphagocytic + chemotactic)
– Endotoxin
– Superoxide dismutase  survive in Oxygen
– Beta-lactamase  resistance to Penicillin
Bacteroides fragilis (cont)
• Clinical Manifestations:
• Intra-abdominal infections:
– Appendicitis
Abscesses
– Peritonitis
• Treatment:
– Metronidazole
Clindamycin
– Chloroamphenacol
– Incision & Drainage (I & D)
Prevotella (Bacteroides)
melaninogenicus
•
•
•
•
Small coccobacillus
Primarily found in Oropharynx
Black pigmented colonies grown on Blood agar
Virulence factors:
– Anti-phagocytic capsule
Collagenase
• Important agent in Oral & Lung infections
• Associated with Chronic Periodontal Disease
(periodontitis)
Fusobacterium nucleatum
• Pleomorphic Gram negative Rod (tapered end)
• Normally inhabit:
– Mouth
GIT
Female Genital Tract
• Possess potent Endotoxin
• Most common isolate in Oral & Lung infections
• With Spirochetes  Acute Necrotizing
Ulcerative Gingivitis (ANUG)
• F.necrophorum (Liver abscess)
• Treatment: Penicillin, Cephalosporins,
Clindamycin
ANAEROBIC GRAM POSTIVE
BACILLI
• Spore Forming:
– Clostidium sp – see Gram positive bacillus
section
• Non-spore Forming:
– Propionibacteria
• Skin  infect Shunts + Prosthetic devices
• Skin  Acne
– Actinomyces – to come later
ANAEROBIC COCCI
• ANAEROBIC GRAM POSITIVE COCCI
• Peptosteptococci:
– Found in Mixed infections
• Skin
Oral
URT
• Female Genital tract
– Treatment:
• Penicillin
• Clindamycin
Cephalosporins
Metronidazole
ANAEROBIC COCCI
• ANAEROBIC GRAM NEGATIVE COCCI
• Veillonella sp
– Resemble Neissera sp
– Normal Flora of:
• Mouth
Nasopharynx
Vagina
– Rarely cause infection
– Can be confused with Neissera on Gram
Stain
PERIODONTAL PATHOGENS
•
•
•
•
•
Part of Normal flora of Sulcus (not teeth)
Mostly Gram Negative (LPS)
Mostly Anaerobic
Mostly Capnophilic (loves Carbon Dioxide)
Examples:
– Prevotella melaninogenicus
– Porphyromonas gingivalis
– Spirochetes Borrelia
Fusobacteria
– Campylobacter rectus
Eichenella corrdens
PERIODONTAL PATHOGENS
• Examples:
– Actinobacillus actinomycetemcomitans (A. a)
– Veillonella
• Periodontal disease (PDD)  Collagen
Attachment loss + Bone destruction
• Juvenile Periodontitis:
– Mainly associated with A.a
– Very little Plaque clinically
– Young patients (Blacks)
Very aggressive
– Hyper-responsive Immune state
MYCOBACTERIA &
ACTINOMYCETES
• MYCOBACTERIA
– Acid-fast Bacilli
– High Lipid Content in Cell Wall
– Cause Tuberculosis & Leprosy
• ACTINOMYCETES
– Gram Positive with Branching growth
pattern
– Abundant in Soil
Mycobacterium tuberculosis
• Obligate anaerobe Acid-fast bacillus (AFB)
• Cell wall contains Mycolic acid, Lipoproteins &
Glycolipoproteins essential for Tuberculin
activity and confers the ability to induce Type
1V Hypersensitivity Reactions.
• Slow growing 20 – 60 day to see colonies
• Antigenicity:
Purified-protein derivative
(PPD) antigenic material for Skin Testing.
Mycobacterium tuberculosis
(cont)
• Pathogenicity
– Cord factor: (Virulence)
• Serpentine grouping pattern
• Inhibits PMN migration
• Elicit Granuloma formation
• Attacks Mitochondrial membranes
– Sulfatides protect against attack from hosts
Lysosome hydrolytic enzymes
Mycobacterium tuberculosis
(cont)
•
•
•
•
Epidemiology:
Only found in Humans
More common in lower socio-economic groups
Rapid rise due to HIV/AIDS + Immigration
• Transmission:
• Primarily air droplet inhalation
• Most infectious are those with untreated
cavitary lung TB  actively expel bacilli.
• Risk of infection greater than risk of disease.
Mycobacterium tuberculosis
(cont)
• Pathogenesis:
• 1st : Delayed-type Hypersensitivity (T-cell),
3-4wks after infection 
positive Tuberculin reaction.
• Acquired cellular immunity with resistance or
protection from re-infection.
Mycobacterium tuberculosis
(cont)
• Primary infection:
• Exudative type:
– Organism inhaled spreads to:
• Macrophages
LNs
Blood
– Signs of infection minimal
– Immune competent host limit organism to
Lung.
• Productive type:
– Granuloma tubercles & calcified lesion
(Ghon complexes) form.
– PPD test positive
Mycobacterium tuberculosis
(cont)
• Secondary infection (re-activated):
• Usually localized in apex of Lung (high Oxygen
tension)
• Granuloma with caseation necrosis & fibrosis
• Results from quiescent focus or new infection
insipte of immunity.
• Clinical manifestations:
• Fatigue
Weight loss
• Weakness
Fever
Anorexia
Night sweats
Mycobacterium tuberculosis
(cont)
• Clinical Manifestations (cont)
• Pulmonary TB (80%)
– Hemoptysis (cough + blood)
– pneumonitis
• Miliary (disseminated) TB
– Mostly:
• Bone & joints Brain
Kidney
• Peritonium
Lymph nodes
Mycobacterium tuberculosis
(cont)
• Diagnosis of TB:
• Abnormal Chest X-ray
• Acid-fast bacteria in Sputum, culture M.
tuberculosis
• Skin Testing:
• PPD-S injected into Skin, read at 48-72 hrs
• Diameter of Induration (> 10 mm = positive)
• False Negative if injection too deep into skin
• False positive due to previous immunization
• Positive PPD test does NOT = active disease
Mycobacterium tuberculosis
(cont)
• Treatment:
• Period of 6 - 9 months
• Combination of at least 3 anti-tuberculosis
drugs
• If HIV-positive treat for 9 – 12 months
• Multiple-Drug-Resistant TB (MDRTB)
– Do Sensitivity Testing
• Isoniazid
• Ethambutol
Rifampin
Pyrazinamide
Mycobacterium tuberculosis (cont)
• Prevention:
• INH (Isonicotine hydrazine) prophylaxis if:
– Contact with patient with active disease
– Recently converted PPD-positive person
–
• BCG (Bacille Calmette-Guerin):
– Used to establish cell-mediated immunity
– PPD negative persons
– Positive PPD skin test.
Mycobacterum bovis
• TB in cattle
Present in Soil
Positive PPD
• In humans with Ingestion of unpasteurized
contaminated milk, or Inhalation (dairy
farmers)
• Clinical Manifestations:
• Pulmonary disease:
– Elderly with Bronchitis + Emphysema
– M. kanasasii,
M. avium-intracellulare,
– M. forttuitum-chelone
Mycobacterum bovis
•
•
•
•
Clinical Manifestations: (cont)
Lymphadenitis: M. scrofulaceum, Children
Cervical & Mesenteric Lymphadenopathy
Cutaneous leasion: M. marinum
– Open wound (“swimming pool” granuloma
• Disseminated disease: HIVD
– M. kansasii M. avium-intracellulare
• Dissemination to Bones & Joints will give
positive PPD Skin test
• BCG vaccine from live attenuated M. bovis
Mycobacterium leprae
•
•
•
•
•
•
Cannot grow in vitro on any culture media
Acid fast
Delayed-type Hypersensitivity
Leprosy (Hansen’s disease):
Endemic (Africa, South & SE Asia, S. America)
Transmission:
Contact with Nasal secretions or Ulcer
exudates of infected cases.
• Lesions involve cooler parts of body (Skin of
Nasopharynx, Cartilage, Eyes,
Testicles & Larynx)
• Incubation = 5 – 7 years
Mycobacterium leprae (cont)
• Disease Forms:
• Tuberculoid Leprosy:
– Indolent (causing little pain, slow growing)
– Non- progressive
– Mature granulomas in Skin
• Lepromatous Leprosy:
• Progressive & Invasive
• Foamy Histiocytes, no Eiptheliod or Giant cells
• Schwann cell (neural) infected  nerve damage
• Skin lesions are invasive & nodular
Mycobacterium leprae (cont)
• Immunity:
• Mediated by CD4 T-helper cells
• Low infectivity rate
•
•
•
•
Treatment:
3 – 5 years
Dapsone + Rifampin
Close contacts should also be treated
ACTINOMYCETES
• Filamentous shape & causes Actinomycosis
• Actinomyces, Nocardia, Steptomyces
• Actinomyces israelii & A. naeslundii
• Anaerobic
Gram positive bacilli
• Part of normal oral flora
• Pathogenic only after trauma (surgery)
Actionmycetes israelii (cont)
• Clinical Manifestations:
• Cervicofacial actinomycosis:
• Mandibular infection following dental caries
(50%)  Pulpitis Extractions
• Pyogenic abscess  swelling, pain, erythema
• “Yellow” sulfur granules expelled from fistula
– Mycelial filaments surrouned by Eosinophils
• Osteomyelitis may occur post Extractions
Actionmycetes israelii (cont)
• Thoracic Actinomycosis:
– Extension of Cericofacial infection (20%)
• Abdominal Actinomycosis
– Traumatic perforation of GIT mucosa
– Ruptured Appendix
Ulcers
• Pelvic Actionmycosis
– Women using Intrauterine devices
• Traetment: Penicillin or Ampicillin for several
weeks + surgical drainage
Nocardia asteroides
•
•
•
•
•
Soil + Aquatic Environs
Aerobic Gram positive
Filamentous AFB
Clinical Manifestations (Nocardosis)
50% have underlying disease e.g. Diabetes
Opportunistic infection with Hematologic
malignancies e.g. Leukemia
• Begins as Chronic Lobar Pneumonia
• CNS Most Common site for Metastatic
infection  Abscess formation
• Treatment: Sulphonmides + Surgical drainage
Rickettsiacae & Chlamydia
•
•
•
•
RICKETTSIACEAE
Genera:
Rickettsiia, Bartonella, Coxiella, Ehrlichia
Obligate intracellular parasites in Endothelial
cells.
• Small pleomorphic Gram negative coocobacilli
• Transmitted by Arthropods (except Bartonella,
Cociella burnetti)
• Treated with Tetracycline (Doxycycline)
Rickettsial Diseases
•
•
•
•
•
•
Rocky Mountain Spotted Fever (RMSF)
Caused by Rickettsia rickettsi (90% of cases )
Epidemiology: S Central & Eastern USA
Transmission: Ticks (reservoir =rodents, dogs)
Clinical Manifestations:
After 1 – 3 day incubation  malaise, frontal
headache & fever
• Skin  maculo-papular rash on palms & soles
within 2 –4 days of unset of symptoms 
spreads centripetally on Trunk
Rickettsial Diseases (cont)
•
•
•
•
•
•
•
•
•
Epidemic Typhus (louse-bourne typhus)
Caused by Ricketsia prowazkii
Transmission by human body Louse
Clinical Manifestations:
Similar to RMSF but not as severe
NO rash on sole or palms
Brill-Zinzzer disease: recurrent form
Endemic (Murine) Typhus: R. typhi
Cycled by Rats & its Ectoparasites (Fleas) thru
Rickettsial Diseases (cont)
• Q Fever Coxiella burnetii No Rash
No Arthropod vevtor
• Transmission:
– Inhaling infected Dust
– Handling infected Hides or Tissue
– Drinking contaminated Milk
• Reservoirs: Ticks, wild animal, Sheep, Cows,
Goats
• Clinical Manifestations: Fever Chills Headache
– Malaise, Myalgia, mild Pneumonia
CHLAMYDIAE
•
•
•
•
•
•
Obligate intra-cellular parasite. Humans only
Infects Birds + Mammals
Possess gram negative envelope (LPS)
EB (Elementary Body) infectious form
Reticular Body (RB) non-infectious form
Infected cells develop oval vacuolar inclusions
containing Glycogen (stain with Iodine)
• Chlamydia trachomatis
• Transmitted by:
– Fomites
Sexually
Perinatally
Chlamydia trachomatis (cont)
• Treatment: Erythromycin Tetracycline
• Prevention: safe sexual practices
• Clinical Manifestations:
• Ocular trachoma  blindness (developing
countries)
Chlamydia trachomatis (cont)
• Sexually Transmitted Diseases:
• Number one cause of STD
• In Men:
– non-gonococcal Urethritis
– Epididymitis
– Prostatitis
– Proctitis
Chlamydia trachomatis (cont)
• Sexually Transmitted Diseases (cont)
• In Women:
– Cervicitis
Urethritis Salpingitis PID
• Lymphogranuloma venereum
• Venereal disease
• More common in Black Males
• Primary lesion painless, vesicular on Penis,
Anus or Rectum
• Then becomes painful, suppurative & spread
into Inguinal & Femoral LNs
CHLAMYDIAE (cont)
• C, psittaci
• Transmission: Inhalation of infected Bird
Droppings  Pneumonia
• C. pneumonia
• Human-only pathogen believed to be
transmitted by Inhalation
• Clinical Manifestations:
– Pharyngitis
Bronchitis
– Mild Atypical Pneumonia
SPIROCHETES
• Motile
Helical
Coiled
• Divide by Transverse Fission (splitting along
the short axis)
• Contain axial fibril (flagella) , outer sheath,
protoplasmic cylinder (cell wall & membrane)
and cytoplasm.
• Three Genera:
– Treponema (syphilis, yaws, pinta, bejel)
– Borrelia (Lyme disease, Relapsing Fever
– Leptosipra (leptospirosis)
SPIROCHETES
• Treponema pallidum
• Most important species
• Highly motile
• Does not grow on artificial media therefore
can not be grown in the Lab
• Agent of Syphilis
Syphilis (cont)
• Transmission:
• Sexually
• Blood Transfusion
Across Placenta
• Risk groups:
– People with multiple sex partners
– Infants born to infected mothers
Syphilis (cont)
•
•
•
•
•
Clinical Manifestations:
Primary syphilis:
Arise within 2 – 10 weeks of exposure
Organism spread to LNs & Blood
Chancre forms at site of innoculation:
– Firm
Painless
Reddish
– Raised border
Center ulcerated
– Heals within 3 – 6 weeks without scarring
– Contains numerous spirochetes (highly
infectious)
Syphilis (cont)
• Secondary syphilis:
• Occur 1 – 3 months after primary syphilis
• Symptoms:
– Skin rash
Fever
Sore Throat
– Headache
– Generalized lymphadenopathy especially
Epitrochlear region (inner condyle of
Humerus).
– Mucous patch on mucous membrane Orally
& Genital. Highly infectious.
Syphilis (cont)
•
•
•
•
•
Latent syphilis:
30 – 40% of cases.
Mucocutaneous relapses
Lesions remain infectious
Tertiary syphilis: (30% of untreated cases)
Benign tertiary syphilis
– Gumma in Skin (not infectious)
• Cardiovascular syphilis  aneurysms
• Neurosyphilis  Tabes dorsalis (wide-bases
gait with long “slapping” motion of Legs
– Argyll-Robertson pupils(fail to react to light)
Syphilis (cont)
•
•
•
•
•
Congenital syphilis:
Transplacental transmission  fetus
Mother has Primary or Secondary syphilis
25% mortality if left untreated
Manifestations in Newborn:
– Hepatosplenomegaly
Hemolytic anemia
– Pneumonia
Skin lesion
– “Snuffles” (obstructed nasal breathing)
Syphilis (cont)
• Congenital syphilis (cont)
• Hutchinson’s Triad:
– Teeth:
• “barrel (screw-driver)” shaped Incisors
• “peg-shaped” Lateral Incisors
• “mulberry” Molars
– Eye: interstitial keratitis
– Nerve: Eight Nerve Deafness
– Nose: ”Saddle nose” deformity
Syphilis (cont)
• Serology Diagnosis:
• Darkfield Microscopy
• VDRL (Venereal Disease Experimental
Laboratory)
• RPR (Rapid Plasma Reagin)
• VDRL & RPR uses cardiolipin as a antigen as
Complement Fixation (CF)or Flocculation
Tests.
• FTA (Fluorescent Treponemal Antibody) Test
• Treatment: Penicillin
• Prevention: Safe sex
Other Treponemal Disease
• Yaws (T. pertenue)
• In the Tropics Direct contact Mainly Children
• Lesion = painless, erythematous (Arm or Leg)
• Pinta (T. carateum)
• Person to person
Sexually Transmited
• Bejel (T. pallidum)
• Poor hygiene Transmission by direct contact
• Skin lesions highly infectious
BORRELIA
•
•
•
•
Transmitted by Arthropods
Coarse, irregular Coils, very flexable, motile
Lyme Disease
Caused by Borrelia burgdorferi
– Reside in Tick vectors (Ixodes) that feed on
infected Deer or Mice reservoirs
• First described in Lyme, Connecticut (USA)
• Now thru out USA, Europe, Australia
BORRELIA
• Lyme Disease (cont)
• Clinical Manifestations:
• Erthymatous Chronicum Migrans
– Red macule  annular erythema with cental
clearing (“bull-eye’) at site of Tick bite
• Rash within 10 days, fades within 3 – 6 weeks
• Infection still active  Fever, Headache,
Malaise, Myalgia, Adenopathy, Meningeal
irritation.
BORRELIA
• Lyme Disease (cont)
• Clinical Manifestations:
• Untreated  Neurologic + Cardiac disease
• Neurolgic Symptoms:
– Severe Headache Meningitis
– Cranial nerve palsies
– Painful peripheral neuropathies
BORRELIA
• Lyme Disease (cont)
• Clinical Manifestations:
• Cardiac Symptoms:
– Cardiac Arrhythmias (resolve after several
weeks)
– Myocarditis
Pericarditis
• Diagnosis: Clinical Hx Tick bite Serology
• Relapsing Fever: Borrelia recurrentis
– Transmitted by Human Body Louse
MYCOPLASMA & UREAPLASMA
• Smallest free-living organisms
• Prokaryoitic cells looking like Gram negative
bacteria
• Ability to Hydrolyze Urea
• Clinically Important:
– Mycoplasma pneumoniae
– Mycoplasma hominis
– Ureaplasma urealyticum
MYCPLASMATACEAE
•
•
•
•
•
•
•
•
Characteristics & Physiology:
Filamentous
Pleomorphic
Facultative
Uses Fermentation for Energy
Require Sterols for growth, because cell
membranes contain Cholesterol
Lack cell wall, therefore resistant to
beta-lactam antibiotics (Penicillin)
Mycoplasma pneumoniae
Found word wide
Transmitted by Aerosol Droplets
Mycoplasma pneumoniae
• Clinical Manifestations:
• Most common cause for Pneumonia in Young
Adults (“walking pneumonia”)
– Non-productive Cough
– Low-grade Fever
Insidious Headache
– Non-purulent Otitis media in 20% of cases
– Bullus myringitis in 20% of cases
• Treatment: Macrolides (Erythromycin,
Azithromycin), Tetracycline, Fluoroquinolones
• Diagnosis using cold agglutinins (IgM)
Mycoplasma hominis
• Sexually transmitted
• Major cause of postpartum women
• Clinical Manifestations:
• Postabortal & Postpartum Fever + Bactaremia
• Pelvic Inflammatory Disease (PID)
Ureaplasma urealyticum
• Sexually transmitted
• Produces Urea
• Minor cause for non-gonococcal Urethritis
VIROLOGY
• Smallest agents of infection (20 – 300 nm dia)
• RNA or DNA surrounded by protective protein
shell (capsid).
• Shell surrounded by an envelope containing
lipid & protein.
• Multiplication occur intracellularly.
• Can become latent & integrate their Genome
into host cell and transmitted to each daughter
cell
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology:
• Terminology:
– Viron: complete virus particla
– Capsid:
• Protein shell encloses / protects Nucleic
Acid Genome (DNA or RNA)
• Protein units = Capsomeres
• Control host range & cell tropism
• Adsorb to cell surface
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology:
• Terminology: (cont)
– Nucleocapsid: Protein Shell + Nucleic Acid
– Peplomeres: Protein Spikes on Envelope
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology: (cont)
• Nucleocapsid:
– Helical Nucleocapsid:
• Extended Nucleic Acid cavity, surrounded
by Helical arranged Proteins
• Outer Lipid Envelope
• Orthomyxoviruses
Paramyxoviruses
• Rhabdoviruses
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology: (cont)
• Nucleocapsid:
– Icosahedral Nucleocapsid
• Condensed Nucleic Acid forming a
Cuboidal shape (Hexagonal)
• Enveloped or Naked
• Parvoviruses
Adenoviruses
• Herpesviruses
Picornaviruses
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology: (cont)
• Envelope:
– Lipid structures
– Derived from Nuclear or Plasma cell
Membrane acquired during viral maturation
when the Nucleocapsid buds thru the Host’s
membrane
– Not rigid, appear heterogeneous
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology:
• Envelope: (cont)
– Viral Glycoproteins Peplomeres:
• Viral Attachment Proteins (VAP)
• In Outer Envelope
• Important role in Antigenic structure +
Host Immune response
• Mediate viral Binding + Entry in Host cell
• Antibodies to gp120 GP of HIV used to tell
course of disease & viral load
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology: (cont)
• Viral Classification
– Based on Nucleic Acid composition
• Single or double-strand DNA or RNA
• Positive-sense RNA (+RNA) serve as
mRNA
• Negative-sense RNA need a RNA
polymerase
to
synthesize
a
complementary positive strand to serve as
mRNA
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology: (cont)
• Viral Proteins:
– Important in initial contact with Host cell
– Dictate which cell is infected
– Hemagglutinins: Vaccine Antigens
– Enzymes:
• Neuraminidase:
– Release viral particles from cells 
continue infection
VIRAL CLASSIFICATION &
IDENTIFICATION
• Morphology:
– Enzymes: (cont)
• RNA polymerase
– Needed for viral Replication of
Negative-sense RNA viruses
– Carried into cell as part of Viron
• Reverse Transcriptase: (Retroviruses)
– Transcribe Single-stranded RNA into
Double-stranded DNA 
Integrated into Host by Intergrase
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication
• Depend on Host cell to provide synthetic
mechanism & metabolic machinery
• Replication Cycle:
• Lyse Host cell or form stable interaction so
Host cell can survive
– 1. Adsorption (attachment):
• Viral Surface Protein (Capsomere or
Peplomere) + Host cell Receptor
• Host & Tissue specific
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 2. Penetration & Uncoating:
• Helped by Receptor-Specific Endocytosis
• Virus loses it Coat or Envelope 
separate Capsid & Envelope from
Nucleic Acid
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 3. Synthetic Stage:
• mRNA transcribed from Viral Nucleic
Acid by Host cell
• Minus-strand RNA virus, Double-strand
DNA & DNA viruses initiate Nucleic Acid
synthesis  mRNA
• Positive-strand RNA viruses initiate
Protein synthesis
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 4. Production of Viral Proteins:
• With Positive-sense RNA (polio virus),
viral RNA (mRNA) read directly by Host
cell Ribosome & Enzymes for RNA
synthesis produced
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 4. Production of Viral Protein
• With RNA viruses, viral genome (-RNA,
double-strand RNA or DNA) synthesize
mRNA using RNA-dependent RNA
polymerase (Transcriptase) found in
Viron & encoded by viral genome.
• Others by Transcription of viral DNA to
synthesize mRNA  protein synthesis
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 4. Production of Viral Protein (cont)
• Some Proteins = structural units
(Capsomeres, Peplomeres)
• Others = Enzymes needed for DNA
synthesis (DNA polymerase)
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 5. Replication of Viral Genome (Nucleic Acid)
• Plus-stranded RNA viruses immediately
synthesize proteins without Nucleic Acid
Replication of Transcription.
• RNA synthesis occur when enough RNA
polymerase are formed, using host cell
machinery
• Minus-strand copy made from parental
strand RNA  Template  Replication
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 5. Replication of Viral Genome (Nucleic Acid)
• Minus-strand & Double-strand RNA
viruses first synthesis mRNA for the
translation into viral proteins
• Minus-strand act as negative Template
for synthesis of mRNA
• Viral genome carry RNA-dependent RNA
polymerase needed to synthesize mRNA
from minus-strand.
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 5. Replication of Viral Genome (Nucleic Acid)
• Double-strand
viruses
(Retrovirus)
synthesize a Positive Strand from
Negative Strand of parent which act as
both mRNA & replicative intermediate to
make Negative-sense RNA
• Retroviruses use Negative Strand of DNA
intermediate to make Positive-sense RNA
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 5. Replication of Viral Genome (Nucleic Acid)
• Double Strand DNA virus replicate by
using each Strand as a Template for
synthesis of complimentary DNA copy.
VIRAL CLASSIFICATION &
IDENTIFICATION
• Replication Cycle: (cont)
– 5. Replication of Viral Genome (Nucleic Acid)
• Hepatits B virus have a viral RNAdependent DNA polymerase (reverse
transcriptase) that uses viral mRNA as a
template to synthesize missing portion of
viral genome, which duplicate using Host
DNA polymerase
• Single-strand DNA virus (Parvovirus)
synthesize Double-strand intermediate as
VIRAL CLASSIFICATION &
IDENTIFICATION
• Viral Assembly:
– Occur at towards end synthetic period
– Viral Genomes & Capsid Polypeptides
assembly  Infectious viral offspring
• Release: (Final Stage)
• Enveloped virus released by Budding process
• Nucleocapsid bud thru viral membrane
patches, gaining viral specific Glycoproteins.
• Poxvirus & Naked Capsid viruses breakout
rapidly  cell disintegration
SUMMARY OF VIRAL GROWTH
CYCLE
•
•
•
•
•
•
•
•
Attachment of virus to cell
Penetration of cell
Uncoating of viral genome
Transcription of genome into mRNA
Translation into proteins
Replication of viral genome
Assembly of particles into new virus
Release of virus
SUMMARY
• All RNA viruses have Single-stranded RNA
EXCEPT Reovirus
• All RNA viruses have an Envelope EXCEPT
Reovirus, Calicivirus, Picornavirus
• All DNA viruses have a Double-stranded DNA
EXCEPT Parvovirus (ss); Hepadnavirus has ss
in its DNA.
• All DNA viruses have Icosahedral Nucleocapsid
EXCEPT Poxvirus
SUMMARY
• All viruses with Helically Symetrical
Nucleocapsid are RNA viruses
• Positive-sense RNA viruses are mRNA, so can
directly encode proteins needed for replication.
• Other viruses require enzymes (RNAdependent
or
DNA-dependent
RNA
polymerase), to produce mRNA for replication
• NOTE: Non-enveloped viruses are resistant to
Disinfectants
SUMMARY
• All DNA viruses replicate in the Nucleus
EXCEPT Poxvirus
• All RNA viruses replicate in the Cytoplasm
EXCEPT Influenza virus & Retroviruses
DNA Viruses (HHAPPP)
•
•
•
•
•
ADENOVIRUSES:
Double stranded DNA
Naked icosahedral nucleocapsid
Transmission:
Person to person via respiratory & ocular
secretions
• Infects mucous membranes & LNs
• Humans only known Host
ADENOVIRUSES (cont)
• Clinical Manifestations:
• Acute Respiratory Disease:
– Tonsils
Adenoids
LNs
– Most infections acute & self-limiting
– Influenza-like illness in late Fall & Winter
– Pharyngitis, fever, cough, malaise
– Conjunctivitis “pink-eye”
– Diarrhea & Gastroenteritis
– Treatment: Supportive (fluids etc)
Vaccine with live non-attenuated virus
PAPOVAVIRUSES
• Papiloma
Polyoma Vacuolating viruses
• Double stranded circular DNA
• Naked icoahedral nucleocapsid
• HUMAN PAPILLOMAVIRUS: (HPV)
• World wide distribution
• Cause Skin “warts” (Papilloma) &
Genital “warts (Condyloma Acuminata)
• Lesions pedunculated
• Most common cause of viral STD
Papillomavirus (cont)
• Transmission via contact with “warts”
• Associated with:
– Laryngeal papillomas
– Oral, Laryngeal, Penile & Cervical Cancer
•
•
•
•
Treatment:
Electrocautery
Cryocautery
Excision
Chemicals
Recurrence common (auto-inoculation)
HERPESVIRUSES
•
•
•
•
•
•
•
Double stranded DNA
Enveloped icosahedral nucleocapsid
Latent infection with recurdescence of disease
HERPES SIMPLEX VIRUS, TYPE 1 & 2
Cause Oral & Genital vesicular lesions
Epithelial cell are infected & destroyed
Upon resolution of acute illness, virus migrates
to ganglions where they reside, later to migrate
down neuron to re-infect Epithelial cell giving
rise to new lesion.
HERPES SIMPLEX VIRUS, TYPE 1 & 2
(cont)
• Humans are only known host
• Transmission: direct contact with vesicular
lesions (infectious) or secretions
• HSV 1:
• Clinical Manifestations: (“fever blisters”)
• Usually acquired early in life (< 5 y o)
• Oral lesions on all mucosal surfaces
• Pain, Fever, Lymphadenopathy (Primary
Herpetic Gingivostomatitis)
• Intraoral Recurrent lesions on Keratinized,
bound down mucosa (Hard Palate + Gingiva)
HERPES SIMPLEX VIRUS, TYPE 1 & 2
(cont)
•
•
•
•
•
•
HSV-2
Transmission: sexual contact
Clinical Manifestations;
Genital vesicular lesion + neurologic disease
Pain
Vesicular lesion  superficial ulcers  heal
with “yellow” crusting
• Recurrent infection at site of primary infection
• Activation of latent virus by stress, menses,
fever, sunlight, trauma, immune suppression
HERPES SIMPLEX VIRUS, TYPE 1 & 2
(cont)
•
•
•
•
•
•
•
•
Diagnosis:
Identification of clinical lesion
Tissue culture
Tzanck Cytologic smear show multinucleated
giant cell with margination of chromatin
Immunofluorescent stains show intranuclear
inclusion bodies
Treatment:
Primary Herpetic Gingivostomatitis:supportive
Acyclovir for severe disease or
immunosuppression
Herpesviruses (cont)
•
•
•
•
•
•
VARICELLA-ZOSTER VIRUS (VZV)
Chicken-pox & Shingles (Herpes-Zoster)
CHICKENPOX (VARICELLA)
Clinical Manifestations: (2 weeks incubation)
Mild self-limiting illness
Fever, macular then papular eruption on Skin
& mucous membranes (oral)
• Papules are pruritic  vesicular
• Highly contagious  epidemics
• Transmission: Respiratory secretions
Herpesviruses (cont)
•
•
•
•
•
VARICELLA-ZOSTER VIRUS (VZV)
SHINGLES
Recurrent infect of VZV in adults
VZV latent in sensory ganglia of spinal nerves
Activated by:
– Trauma
Neoplasm
Drugs
– Imunosuppression
• Clinical Manifestations:
• Severe dermatomal pain with vesicular lesions
• Treatment: Acyclovir, VZIG, attenuated Vaccine
Herpesviruses (cont)
• EPSTEIN- BARR VIRUS (EBV)
• Agent for Infectious mononucleosis (IM)
• Virus replicates in Epithelial cells 
infect B-lymphocytes
• Transmission: Saliva & Respiratory secretions
• Associated with:
– Burkitt’s lymphoma
Nasophayngeal Ca
– Hairy leukoplakia (lesion on lateral Tongue
seen with diagnosis of AIDS)
Herpesviruses (cont)
•
•
•
•
EPSTEIN- BARR VIRUS (EBV) [cont]
Clinical Manifestations: Last for 2 – 4 weeks
Fatigue Tender Lymphadenopathy Fever
Headache
Splenomegaly (rupture0
Pharyngitis
• Histology show Warthin-Finkeldey cells +
Atypical Lymphocytes with “foamy cytoplasm
(Downey cells) on Cytology
• Diagnosis: Heterophile Ab (90%) Paul-BunnelTest
(Monospot Test)
• Treatment: Supportive. Acyclovir severe disease
Herpesviruses (cont)
• CYTOMEGALOVIRUS (CMV)
•
•
•
•
Mononucleosis-like illness (subclinical)
Life-long latent infection
Incubation period = 4 – 8 weeks
Reactivation in immunosuppressed patients
[cancer, transplant (esp. Kidney), AIDS]
• CMV Retinitis in AIDS patients
• Congenital disease transplacentally 
Cytomegalic Inclusion Disease
• Treatment: Ganciclovir in severe disease
Herpesviruses (cont)
• Human Herpesvirus-6 (HHV-6)
• Lymphotrophic etiologic agent for Pediatric
“sixth disease” or Roseola infection
(exanthem subitum)
– Erythematous pruritic rask on Skin, last
several weeks
• Human Herpesvirus-8 (HHV-8)
• Associated with Kaposi Sarcoma
– Associated with AIDS
POXVIRUS
•
•
•
•
•
•
•
•
•
Largest of all viruses
Linear double stranded DNA with envelope
Replicate in cytoplasm of infected cell
Ovoid to brick-like in shape
VARIOLA VIRUS (smallpox virus)
Transmission: direct contact.
Humans only.
MOLLUSCUM CONTAGIOSUM)
“wart-like” Skin lesions (face, trunk, limbs)
COWPOX: contact with cow udders.
Fingers & Hands. Self limiting.
OTHER DNA VIRUSES
• HEPADNAVIRUSES:
– Include Hepatitis B virus (HBV)
•
•
•
•
PARVOVIRUSES:
Single-standed DNA virus
Serotype B19 only Human pathogen
Cause Erythema infectiosum (“fifth disease”)
in Children  “slapped cheek” rash
CONDITION WITH
ERYTHEMATOUS RASH
• Measles
• Rubella
• Scarlet fever
• Roseeola
• Exanthem subitum (HHV-6)
RNA Viruses
•
•
•
•
PICORNAVIRUSES
Small single stranded RNA
Naked nucleocapsid
Positive sense (can serve as mRNA)  replicate
in cytoplasm of infected cell.
• Divided into:
• Enteroviruses (polioviruses, coxsackie,
echovirus, enterovirus)
• Acid resistant
• Rhinoviruses (“common cold”)
RNA Viruses
•
•
•
•
•
•
PICORNAVIRUSES
ENTEROVIRUSES:
Poliovirus:
Bind to receptor in the GIT & Neurons
Only Primates. Majority of disease subclinical
Transmission: Person-person via contaminated
water (virus excreted in feces)
• Pathogenesis:
• Virus ingested  replicates in oropharynx &
GIT  drain to LNs  viremia  CNS
destruction (motor neuron in Spinal cord)
RNA Viruses (cont)
•
•
•
•
•
•
•
•
•
PICORNAVIRUSES
ENTEROVIRUSES:
Poliovirus (cont)
Clinical manifestations: Flaccid paralysis.
Prevention:
Live attenuated virus vaccine(oral: OPV, Sabin
Killed virus vaccine (IPV, Salk vaccine)
Both vaccines induce serum Ab  immunity
Oral vaccine  GIT immunity & sIgA
synthesis
RNA Viruses (cont)
•
•
•
•
•
PICORNAVIRUSES
ENTEROVIRUSES:
Echovirus(Enteric Cytopathic Human Orphan)
All infect the GIT
Transmission:
– Ingestion or Inhalation  Throat  GIT
• Epidemiology: incidence increased in Summer
• Clinical Manifestations:
• Fever
Rash
Enteritis
“common cold”
Hemorrhagic conjunctivitis
Meningitis
RNA Viruses (cont)
•
•
•
•
•
•
•
•
PICORNAVIRUSES
ENTEROVIRUSES:
Coxsackieviruses:
Coxsackievirus A  Herpangina & HandFoot-Mouth Disease
Clinical: Headache Sore throat Stiff Neck
Dysphasia Fever Anorexia Abdominal pain
Transmission: (contact with Horses)
Nasopharyngeal secretions
Oro-fecal
Epidemiology: epidemics in Summer & Fall
RNA Viruses (cont)
•
•
•
•
PICORNAVIRUSES
ENTEROVIRUSES:
Coxsackieviruses:
Coxsackie B
– Myocarditis
– Pleurodynia
Pericarditis
• Enterovirus 72: Etiologic agent for Hepatitis A
RNA Viruses (cont)
•
•
•
•
•
•
•
•
PICORNAVIRUSES
RHINOVIRUSES (causes “common cold”)
Transmission & Epidemiology
Over 100 Serotypes
Infect only Humans (Nose & Throat)
Incubation period = 2 – 4 days
Clinical Manifestations (up to a week)
URT irritation Headache Nasal discharge
Cough Malaise
Chills
Myalgia
• Treatment & Prevention: Supportive.
RNA Viruses (cont)
• ORTHOMYXOVIRUS (Influenza virus A, B, C)
• Medium size , negative sense, single stranded,
segmented RNA + enveloped nucleocapsid.
• Transmission: Inhalation
• Clinical Manifestations:
• Influenza C: Incubation period = 1 – 4 days
– symptoms of “common cold”
• Influenza A & B
(B  Reye syndrome)
• Fever
Chills
Myalgia Sore throat
Headache Nasal congestion
Dry cough
• Rx: Amantadine, Rimantadine ( Type A)
RNA Viruses (cont)
•
•
•
•
•
PARAMYXOVIRUSES
Negative sense with Envelope Nucleocapsid
Genetically stable
Initial infection via URT (respiratory)
Common cause of URT infection in Children
– PARAINFLUENZA VIRUSES:
• Transmission: Aerosol Droplets
• Etiologic agent for Croup (barking cough)
• Laryngo-tracheobronchitis
RNA Viruses (cont)
• PARAMYXOVIRUSES
– MEASLES VIRUS (RUBEOLA)
– Highly infectious childhood infection
– Fever & Maculopapular exanthem (skin
rash)
– Virus multiples in the Oropharynx  LNs
– Infection  permanent immunity
– Transmission: Respiratory secretions
RNA Viruses (cont)
• Clinical Manifestation of Measles:
• Koplick spots:
– “bluish-white” specks on a”red” base found
on Buccal mucosa
• Abrupt onset of Anorexia (loss of appetite)
• Nausea Fever
Malaise
Cough
• Coryza (profuse nasal discharge)
• Conjunctivitis
• Maculo-papular erythematous rash, lasting 5
days, starts on the Face  Trunk
RNA Viruses (cont)
•
•
•
•
•
•
Complications of Measles:
Encephalitis (inflammation of the Brain)
Pneumonia (immunodeficiency)
Otitis media (middle Ear infection)
Subacute Sclerosing Panencephalitis (fatal)
Possible association with Multiple sclerosis
(demyelination of nerves with numbness &
weakness of the extremites)
• Treatment & Prevention:
• Live attenuated vaccine at 15 months (MMP)
• Serum Globulin (most donors have Antibodies)
RNA Viruses (cont)
• PARAMYXOVIRUSES
– MUMPS VIRUS
– Causes an acute contagious, nonsuppurative
Parotitis(unlateral or bilateral)
– Orchitis (Testicular inflammation) possible
complication
– Prevention:
– Immunization with live attenuated virus
(part of Measles-Mumps-Rubella (MMR)
vaccine)
RNA Viruses (cont)
• PARAMYXOVIRUSES
– RESPIRATORY SYNCYTIAL VIRUS
(RSV)
– Main cause of Lower URT infection in
Infants
– Transmission: Aerooal Droplets, Fomites
– Clinical Manifestation:
• “common cold-like” symptoms
• Severe Lower URT infection (Infants)
RNA Viruses (cont)
• TOGAVIRUSES
• Disease range from Febrile Encephalitis 
severe Bleeding
• Positive single-stranded RNA + Enveloped
Nuceocapsid
– ALPHAVIRUS
• Include Encephalitis viruses
• Transmission: Insects (Zoonotic agents)
RNA Viruses (cont)
• TOGAVIRUSES
– ALPHAVIRUS
• Eastern Equine Encephalitis (EEC) virus
– Abrupt Headache & Fever
– Nuchal rigidity
• Western Equine Encephalitis virus
– Less severe disease
– Mostly Childran
RNA Viruses (cont)
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TOGAVIRUSES
RUBIVIRUS (rubella)
Cause German measles (3 day measles)
Only Togavirus not transmitted by arthropod
Disease of shorter duration & less severe
Infection starts in URT  throughout Body
due to viremia
• Morbilliform rash (like measles) occur 2 – 3
weeks post infection
RNA Viruses (cont)
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Rubella (German measles )(cont)
Congenital rubella
Virus transmitted across the Placenta
Serious consequence if it occurs in 1st Trimester
Complications:
– Mental retardation
Blindness
– Heart abnormalities
Motor dysfunction
– Encephalitis
• Prevention: live attenuated virus vaccine
(MMR)
RNA Viruses (cont)
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FLAVIVIRUSES (arthropod-borne)
Yellow Fever:
Mosquito borne
Incubation period = 3 – 6 days
Clinical Manifestations:
Acute onset Fever
Proteinuria
Jaundice (yellow skin/sclera of eye)
Vomiting (vomitus black)
Hemorrhage
Prevention: attenuated vaccine
RNA Viruses (cont)
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FLAVIVIRUSES (cont)
Dengue Fever (mosquito borne illness)
Clinical Manifestations:
Fever
Rash
Arthralgia
Lympadenopathy
Hemorrhage
• Death (10%)
• Occur primarily in the Tropics
RNA Viruses (cont)
• RABDOVIRUSES
• Rabies virus (causes Rabies)
• “bullet-shaped” Enveloped, single stranded,
Negative sense RNA virus, with Nucleocapsid
with Glycoprotein spikes.
• Replicates within Host cell cytoplasm
• Transmission: Bite from dog, skunk, bats, fox.
• Pathogenesis:
• Break in Skin  Muscle & CT (incubation
period 2 – 16 weeks)  along Nerves 
CNS (Basal Ganglia) & Salivary Gld
RNA Viruses (cont)
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Rabies (cont)
Negri bodies in Neurons of the Hippocampus
Clinical Manifestations: (4 phase)
Prodrome symptoms:
– Paresthesia at site of wound
– Irritability (mood & temperament change)
– Flu-like illness
• Pharyngeal spasm  drooling (hydrophobia)
• Seizures & coma  Death
RNA Viruses (cont)
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Rabies (cont)
Diagnosis:
Direct Immunofluorescenc assay for virus
Immunofluorescenc assay for Nergi bodies in
Nerve tissue (Ammon’ horn)
• Treatment & Prevention:
• Vaccine: Human & Pets with inactive virus
from infected Human diploid cells
• Human rabies immunoglobulin(HRIG)
immediately in case probable infection. Very
painful.
RNA Viruses (cont)
• RETROVIRUSES
• Diploid, positive sense, single-stranded RNA
• Viral-encoded reverse transcriptase which
produces double-stranded DNA from RNA
• Viral genome encodes 3 groups of proteins:
– Pol (reverse transcriptase + integrase)
– Env (type-specific envelope protein)
– Gag (type-specific viral core protein
• Include Human T-cell leukemia viruses (HTLV
1 & 11) & HIV (Lentivirus)
RNA Viruses (cont)
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RETROVIRUSES (cont)
ONCOVIRUSES (promote cell growth)
Human T-Lymphotrophic Virus 1 (HTLV 1)
Infects CD4 (helper) T-cells  Acute T-cell
Lymphocytic Leukemia (ATLL)
• Human T-Lymphotrophic Virus 11 (HTLV 11)
• Causes Hairy cell leukemia
RNA Viruses (cont)
• RETROVIRUSES (cont)
• HUMAN IMMUNODEFICIENCY VIRUS
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Cause Acquired Immunodeficiency Syndrome
AIDS initially recognized in 1981
HIV isolated in 1983
Infects helper T-cells by attachment to cell
surface protein (CD4) & Macrophages.
• Patient prone to opportunistic infections (when
CD4 count drops below 200), malignancies &
Wasting syndrome
HEPATITIS VIRUSES
• HEPATITIS A VIRUS (HAV)
• Picornavirus
RNA virus
• Transmission:
– Fecal-orally. Incubation period = 15-40 days
– Epidemic
Endemic (institutional)
– Childhood disease mild, adult severe
• No chronic hepatitis or carrier state
• Diagnosis: presence of anti-hepatitis A IgM
• Treatment: Killed virus vaccine (food-handlers
& day care workers) & gamma Globulin
HEPATITIS VIRUSES (cont)
• HEPATITIS B VIRUS (HBV)
• Enveloped double stranded DNA virus
• Viral Antigens:
– Surface antigen (HBsAg) found in virion
• Indicates active viremia (infectivity)
– Core antigen (HBcAg) found in capsid
– E antigen (HBeAg) found in capsomere
HEPATITIS VIRUSES (cont)
HBV (cont)
• Antibodies to HBV:
– Ab to HBsAg
• Protective
• Detected after virus disappears from
serum
– Ab to HBcAg
• Detected after appearance of HBsAg
• Confirm infection when HBsAg & Ab to
HBsAg is absent (window phase)
HEPATITIS VIRUSES (cont)
• Antibodies to HBV (cont)
– Ab to HBeAg associated with low risk of
infectivity
• Transmission:
– Parenteral (not by mouth) & Sexual contact
HEPATITIS VIRUSES (cont)
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Clinical Manifestations of HBV Infection:
Anorexia
Nausea
Vomiting
Headache
Fever
Dark Urine
Abdominal pain
Jaundice
Arthralgia
Arthritis
Nephritis
Dermatitis (Skin)
10 – 15% develop:
– chronic hepatitis (cirrhosis & hepatocellular
carcinoma)
– Carrier state (infectious)
HEPATITIS VIRUSES (cont)
• Liver function tests for HBV:
• Elevated Transaminase Hyperbilirubinemia
• Elevated Alkaline phosphatase
• Prevention of HBV:
• Recombinant HBsAg (Health Care Workers)
• Children 3 doses: 1st at birth, 2nd at 2 –4 mos,
3rd at 6 – 18 mos
HEPATITIS VIRUSES (cont)
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HEPATITIS C VIRUS (HCV)
Positive sense, single stranded RNA virus
Classified as a Flavivirus
Associated with post-transfusion hepatitis
HEPATITIS D (delta agent)
RNA virus, replicate only in cells infected with
HBV.
• HEPATITIS E VIRUS
• Single stranded RNA. Disease similar to HAV.
Severe in pregnancy.
Spread oro-fecally.
MYCOLOGY
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Eukaryotic organisms (True Nucleus)
Cell Wall ( Glucose + Mannose polymers (chitin)
Cell membrane (Ergosterol)
Yeast: Round or oval, reproduce by budding
Mold:
– Tubular structures called Hyphae
– Grow by branching & extensions (mycelia)
• Reproduction: sexual or asexual (mitosis)
• Immunity: T-cell is protective in fungal disease
Eosinophils also found in tissue
DERMATOPHYTOSIS
(Cutaneous Mycosis)
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Stratum corneum infections: (Ringworm)
Tinea corporis  body
Tinea cruris  groin (jock itch)
Tinea pedis  feet (athlete’s foot)
Tinea manuum  hands
Tinea capitis  head
Tinea barbae  beard
Tinea unguium  nails
Diagnosis: Skin scrapings (KOH & UV light)
Treatment: Miconazole or Clotrimazole
SUBCUTANEOUS MYCOSES
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SPOROTRICHOSIS:
Etiology: Sporothrix schenckii (fungus)
World wide in soil, plants, plant debris
Classically associated with rose thorns
(rose gardener’s disease)
• Clinical Manifestations:
• Limited to Skin
• Regional lymphadenopathy
SYSTEMIC MYCOSES
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Deep invasion into organs
HISTOPLASMOSIS (Darling’s disease)
Etiology: Histoplasma capsulatum
Transmission via Bird & Bat droppings
Histology: Yeasts found in Macrophages
• Clinical Manifestations;
• Acute pulmonary histoplasmosis (5-21 days
after exposure.) Headache & Fever.
• Treatment: None, self-limiting
SYSTEMIC MYCOSES (cont)
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COCCIDIOIDOMYCOSIS
Etiology: Coccidioides immitis (fungus)
Deserts of SW United States & N. Mexico
Transmission via inhalation due to fresh
diggings, dust storms)
Clinical Manifestations:
Acute pneumonia sub-clinical in 60% of cases
40% develop influenza-like symptoms 7-28
days post exposure
Fever
Malaise
Dry cough Eosinophilia
Erythematous rash.
Rx Amphotericin B
SYSTEMIC MYCOSES (cont)
• BLASTOMYCOSIS
• Etiology: Blastomyces dermatidis (fungus)
• Transmission via inhalation of spores
associated with dust.
• Clinical Manifestations:
• Acute blastomycosis pneumonia
– Asymptomatic or Severe  Death
– “influenza-like” symptoms:
• Fever
Chills
Productive cough
• Pleuritic chest pain
OPPORTUNISTIC MYCOSES
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Causes disease in immunocompromised.
Sometimes found in Normal Flora (oral & skin)
CANDIDA
Pseudohyphae or Chlamydospores
Etiology: Candida albicans
Found on or in:
– Mucocutaneous surfaces
Soil
– Hospitals
Some foods
OPPORTUNISTIC MYCOSES
(cont)
• CANDIDA (cont)
• Clinical Manifestations:
• Oropharyngeal candidiasis (Thrush)
– “white plaques” on Tongue & Buccal
mucosa
– Cytology shows pseudo-hyphae (PAS stain)
– Treatment: Nystatin
Ketoconazole
»
Mycelex troches (no sugar)
OPPORTUNISTIC MYCOSES
(cont)
• CANDIDA (cont)
• Clinical Manifestations (cont)
• Vaginal candidiasis
– Diabetics
Antibiotic therapy
– Pregnancy  Neonatal “Thrush”
– Thick yellow-white discharge
– Intense pruritis
• Treatment: Nystatin suppositories
OPPORTUNISTIC MYCOSES
(cont)
• CANDIDA (cont)
• Clinical Manifestations (cont)
• Invasive candidiasis associated with:
– Diabetes
– Damaged mucosal surfaces (catheters)
– Immunosuppression (AIDS, Chemotherapy
(leukemia, lymphoma), long term Steroids &
Antibiotics)
• Treatment: Systemic Ketoconazole
OPPORTUNISTIC MYCOSES
(cont)
• CRYPTOCOCCOSIS
• Etiology: Cryptococcus neoformans (yeast)
• Found in:
– Pigeon droppings,
Soil
Fruits
Milk
Wood products
• Immunosuppression predisposes to disease
• Clinical Manifestations:
– Pulmonary
Meningitis
• Treatment: Amphotericin B
OPPORTUNISTIC MYCOSES
(cont)
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ASPERGILLOSIS
Etiology: Aspergillus fumigatus
Found in naturally in Soil, spores in the Air
Clinical Manifestations:
Allergic bronchopulmonary aspergillosis
– Hypersensitivity reaction (IgE mediated) 
bronchospasm
– Wheezing
Fever
Eosinophilia
• Treatment: Steroid for symptoms
OPPORTUNISTIC MYCOSES
(cont)
• ZYGOMYCOSIS (Mucormycosis)
• Etiology: genera Rhizopus & Mucor
(nonseptate hyphae)
• Molds found in decaying vegetation
• Persons predisposes:
– Diabetics
Immunosuppression
– Malnutrition
• Clinical Manifestations:
– Rhinocerebral (Erode thru Nose, Palate,
Sinus, Orbit  Brain
– Pulmonary due to inhalation of spores
OPPORTUNISTIC MYCOSES
(cont)
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PNEUMOCYSTIS CARINII
Fungus based on rRNA homology
Clinical manifestation:
Interstitial Pneumonia in Immunosuppressed
 Death
• Treatment:
• Trimethoprim-sulfamethoxazole (TMP-SMX)
• Pentamidine
SUMMARY
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IN VIVO FORMS OF FUNGI:
Coccidioides – spherules
Histoplasma – intracellular yeast
Blastomyces – broad-base buds
Cryptococcus – large capsule
Candida – pseudohyphae
Aspergillus – branching septate hyphae
Mucor / rhizopus – broad non-sptate hyphae
PROTOZOA
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Unicellular eukaryotic organisms
Usually reproduce asexually in Human host
GIT & MUCOCUTANEOUS PROTOZOA
GIARDIASIS
Etiology: Giardia lamblia
Transmission: Feces in Water or Food
Clinical Manifestations:
– Diarrhea
Abdominal cramps
– Bloating
Flatulence
Malaise
– Weight loss
Steatorrhea
PROTOZOA (cont)
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AMEBIASIS
Etiology: Entamoeba histolytica
Transmission: fecal-oral route (poor sanitation)
Clinical Manifestations: (Colon of Humans)
– Diarrhea
Abdominal cramps
Nausea
– Vomiting
Flatulence
– Dysentery
• Severe abdominal pain
Dehydration
• Bloody stool
Liver abscess
PROTOZOA (cont)
• TRICHOMONAS VAGINITIS
• Etiology: Trichomonas vaginalis
• Clinical Manifestations:
– Dysurea
Pruritis
– Copious “yellow-frothy” discharge
– Symptoms worse with alkaline vaginal PH
– Dyspareunia
– Men: Prostatitis
Urethritis
BLOOD & TISSUE
PROTOZOA
• MALARIA
• Etiology: Plasmodium falciparum
(intracellular parasite)
– Sexual phase occur in Anopheles mosquito
– Asexual phase occur in Humans
• Clinical Manifestations
– Periodic Fever & Chills (lasts up to 1 hour)
– Diaphoresis (profuse perspiration)
– Nausea
Vomiting Malaise
• Treatment: Chloroquine
BLOOD & TISSUE
PROTOZOA (cont)
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LEISMANIASIS
Etiology: Leishmania species
Transmission: bite from Sandfly.
Pathogenesis:
parasite
Reticuloendothelial
cells
&
Phagolysosomes.
invades
reside
in
• Clinical Manifestations:
– Skin Mucocutaneous Visceral
• Treatment: Pentostam
Glucantime
BLOOD & TISSUE
PROTOZOA (cont)
• AFRICAN SLEEPING SICKNESS
• Etiology: Trypanosoma brucei
• Transmission: bite fro infected Tsetse Fly 
CNS involvement  Death
• Clinical Manifestations:
– Chancre at site of inoculation
– Parasitemia in 2 – 3 weeks  LNs
– Fever Rash Headache Mental changes
– CNS involvement: Anorexia, Lassitude,
Fatique, Wasting, Stupor, Coma, Death
– Treatment: Suramin Melarsoprol (CNS)
BLOOD & TISSUE
PROTOZOA (cont)
• TOXOPLASMOSIS
• Etiology: Toxoplasma gondii
• Transmission: via secondary hosts
– Sexual cycle in GIT of Cats  oocyst
(encapsulate zygote)  Feces
– Infested oocytes invade GIT of intermediate
host  disseminate in blood  pseudocysts
in tissue.
– Tissue ingested by human in raw or
undercooked meat.
BLOOD & TISSUE
PROTOZOA (cont)
• TOXOPLASMOSIS (cont)
• Clinical manifestations:
• Primary infection with mild mononucleosis-like
illness
• Immunodeficiency: meningoencephalitis 
seizures
• Congenital infection:
– Chorioretinitis
Hydrocephaly
– Diffuse Intracranial Calcifications
– Anemia
Seizures
• Treatment: Pyrimethamine
Sulfadiazine