MICROBIOLOGY Prepared by: Dr. D. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor...

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 Major Organism• Skin 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 productionHyaluronidase 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)

• 2. Toxins• Exotoxins

– heat-labile proteins with specific enzymatic activities

– Produced by both Gram positive & negative microbes

– Released extracellularly– Often sole cause of disease

• Exotoxins:– Domains with discrete biologic functions

maximal toxicity

– A - B toxins• B subunit bind to host tissue

Glycoproteins• A subunit enzymatically attack

susceptable

– 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)

• 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

• 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 de-coloration 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 Bordet-

Gengou 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) MEMBRANEFunction as osmotic barrier60 – 70% protein30 – 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 metabolic machinery and need many additional requirements.

• 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 re-combination

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

• 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 Action • Steam Heat & Protein denaturation

DisinfectantsAlcohol & Phenols Protein denaturation

• Glutaraldehyde Alkylation protein / DNA & Ethylene oxide

• Detergent Membrane disruption• Chlorohexidine Membrane disruption• Peroxides & Hg & I Oxidize Sulfhydryl bond• Soap 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 CocciStaphlococcus & Streptococcus

• 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

• 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 Endocarditis– Lung abscess 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

• 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 SteptococcusS. pneumoniae & Viridans

• 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)

• 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

• 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 STREPTOCOCCUSSTREPTOCOCCUS 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 STREPTOCOCCUSSTREPTOCOCCUS 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 food-

borne 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)

• 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

• 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 food-borne

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

• 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

• 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

• 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 strictureEpididymitis• Prostatitis Proctitis (homosexuals)

• Women:– Asymtomatic in 20 – 80% of cases– Inability to observe discharge– Complications;

• Pelvic inflammatory disease (15 – 20%)• Generalized Peritonitis• Infertility

• 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

• 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 BacilliEnterobacteriaceae

• 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

• Motile 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

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 SkinDiarrhea

• 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

• 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)

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

Pseudomonas• Gram negstive Rod

• In Soil + HOH

• Component of Bowl flora

• Human very resistant

• P. aeruginosa

– Important Nosocomal infection in immunocompromised + chronically

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

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

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 Penicillin G– Clindamycin Metronidazole– Chloroamphenicol 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 Cephalosporins• Clindamycin 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

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

• 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.

• Pathogenesis:• 1st : Delayed-type Hypersensitivity (T-cell),

3-4wks after infection positive Tuberculin

reaction.

• Acquired cellular immunity with resistance or protection from re-

infection.

• 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

• 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 Anorexia• Weakness Fever Night sweats

• Clinical Manifestations (cont)• Pulmonary TB (80%)

– Hemoptysis (cough + blood)– pneumonitis

• Miliary (disseminated) TB– Mostly:

• Bone & joints Brain Kidney• Peritonium Lymph nodes

• 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

• 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 Rifampin• EthambutolPyrazinamide

• 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

• 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 Feces

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)

• Sexually Transmitted Diseases:• Number one cause of STD• In Men:

– non-gonococcal Urethritis– Epididymitis– Prostatitis– Proctitis

• 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 Across Placenta• Blood Transfusion

• 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

• 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

• Morphology:• Terminology: (cont)

– Nucleocapsid: Protein Shell + Nucleic Acid

– Peplomeres: Protein Spikes on Envelope

• Morphology: (cont)• Nucleocapsid:

– Helical Nucleocapsid:• Extended Nucleic Acid cavity, surrounded

by Helical arranged Proteins

• Outer Lipid Envelope• Orthomyxoviruses Paramyxoviruses• Rhabdoviruses

• Morphology: (cont)• Nucleocapsid:

– Icosahedral Nucleocapsid• Condensed Nucleic Acid forming a

Cuboidal shape (Hexagonal)• Enveloped or Naked • Parvoviruses Adenoviruses • Herpesviruses Picornaviruses

• 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

• 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

• 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

• 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

• 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

• 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

• Replication Cycle: (cont)– 2. Penetration & Uncoating:

• Helped by Receptor-Specific Endocytosis

• Virus loses it Coat or Envelope separate Capsid & Envelope from

Nucleic Acid

• 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

• 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

• 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

• Replication Cycle: (cont)– 4. Production of Viral Protein (cont)

• Some Proteins = structural units (Capsomeres,

Peplomeres)

• Others = Enzymes needed for DNA synthesis (DNA polymerase)

• 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

• 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.

• 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

• Double Strand DNA virus replicate by using each Strand as a Template for synthesis of complimentary DNA copy.

• Hepatits B virus have a viral RNA-dependent 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 template

• 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 (RNA-dependent 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)

• 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

• 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

• 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

• 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)

• 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

• 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

• 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 & Hand-

Foot-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 Pericarditis– Pleurodynia

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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

• 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

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)

• Antibodies to HBV (cont)– Ab to HBeAg associated with low risk of

infectivity

• Transmission:– Parenteral (not by mouth) & Sexual contact

• 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)

• 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 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

• 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)

• 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

• 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

• 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)

• 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

• 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)

• CANDIDA (cont)• Clinical Manifestations (cont)

• Vaginal candidiasis– Diabetics Antibiotic therapy– Pregnancy Neonatal “Thrush”– Thick yellow-white discharge– Intense pruritis

• Treatment: Nystatin suppositories

• 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

• 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

• 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

• 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

• PNEUMOCYSTIS CARINII • Fungus based on rRNA homology• Clinical manifestation:• Interstitial Pneumonia in Immunosuppressed

• Treatment:• Trimethoprim-sulfamethoxazole (TMP-SMX)• Pentamidine

SUMMARY

• 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

• 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)

• 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)

• LEISMANIASIS• Etiology: Leishmania species • Transmission: bite from Sandfly.• Pathogenesis: parasite invades Reticuloendothelial

cells & reside in Phagolysosomes.

• Clinical Manifestations:– Skin Mucocutaneous Visceral

• Treatment: Pentostam Glucantime

• 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)

• 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.

• 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

MICROBIOLOGY Prepared by: Dr. D. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor...

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