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

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Presentation on theme: "MICROBIOLOGY Prepared by: Dr. D. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor Reference: Kaplan Review Notes."— Presentation transcript:

1 MICROBIOLOGY Prepared by: Dr. D. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor Reference: Kaplan Review Notes

2 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)

3 Distribution of Normal Microbial Flora LocationMajor Organism SkinPropionibacteria acnes, Staph epidermis & aureus, diptheroids Oral cavityviridians Streptococcus, Prevotella melaninogenicus, Actinomyces, Peptostreptococcus, other anaerobes Nasopharynx:oral microbes, Staph pneumonia, Hemophilus, Nisseria meningitis VaginaChildbearing age: Lactobacillus, yeast, Streptococcus

4 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

5 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 )

6 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

7 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

8 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)

9 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

10 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)

11 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

12 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

13 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)

14 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)

15 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)

16 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

17 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)

18 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

19 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

20 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

21 Survival in Oxygen Used to classify bacteria All bacteria produce Superoxide ion (O 2 - ) in the presence of Oxygen. Superoxide dismutase + O 2 -  Hydrogen peroxide (H 2 O 2 ) Catalase or Peroxidase + H 2 O 2  H 2 O + O 2 Obligate Anaerobes lack these enzymes therefore Oxygen is toxic to them. (Clostridium & Bacteroides) Facultative organisms grow with or without oxygen.

22 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.

23 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

24 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 O 2 as TEA (M. tuberculosis)

25 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.

26 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.

27 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)

28 Genetic Transfer 2. Transduction –Phage-mediated transfer of bacterial DNA Generalized: –bacterial DNA mistakenly packaged into empty phage head –Recombination occur

29 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

30 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

31 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

32 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

33 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

34 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

35 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

36 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

37 Material Method & Action Material/MethodAction Steam Heat &Protein denaturation Disinfectants Alcohol & PhenolsProtein denaturation GlutaraldehydeAlkylation protein / DNA & Ethylene oxide DetergentMembrane disruption ChlorohexidineMembrane disruption Peroxides & Hg & IOxidize Sulfhydryl bond SoapEmulsifcation of Fat

38 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

39 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.

40 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

41 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)

42 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: –HBV30% –HCV3% –HIV0.3%

43 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

44 Gram Positive Cocci Staphlococcus & Streptococcus STAPHLOCOCCUS Genus Characteristics & Classification Gram positive Divide in perpendicular plane  Clusters Relatively resistant to Heat & Drying Metabolically –Facultative organism –Possess Superoxide dismutaese & Calalase

45 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

46 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 ABinding proteinCoagulase –DNAseStaphylokinaseLipase –HyaluronidaseExotoxins (hemolysis)

47 Staphylococcus aureus (cont) Conditions Commonly Caused by S. aureus Direct Infection of Skin: –FolliculitisFuruncleCarbuncleAbscess –CellulitisWound infection Systemic Infection: –OsteomyelitisEndocarditis –Lung abscesspneumonia Toxic-mediated disease: –Food poisoningScalded skin syndrome –Bullous impetigoToxic shock syndrome

48 Staphylococcus aureus (cont) Treatment: Penicillinase-resistant penicillin: –Amoxicillin, Methicillin, Nafcillin Cephalosporin (first generation) Vancomycin (methicillin-resistant S. aureus) –VRSA have been discovered

49 Staphylococcus epidermidis Common nosocomial pathogen (Hospital based) Associated with: IVsCathetersProsthetic devices Major virulence factor: Exopolysacharidebiofilm (slime) Difficult for Immune system to detect Treatment = Vancomycin

50 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)

51 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

52 Alpha Hemolytic Steptococcus S. 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 mediaSinusitisBronchitis –BacteremiaMeningitis (#1 cause in elderly)

53 STREPTOCOCCUS PNEUMONIAE (cont) Risk Factors for infection with S. pneumoniae –PovertyDebilitated state of Health –Absence of SpleenSickle cell anemia –Hodgkin’s diseaseMultiple myeloma –AIDS Most important virulence factor = carbohydrate capsule

54 STREPTOCOCCUS PNEUMONIAE (cont) Prevention Vaccination with its polysaccharide antigen (Pneumovax) –Should be given to: Elderly, Splenectomy, smokers, alcoholics, children Treatment –Penicillin (resistant forms) –VancomycinErythromycin

55 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

56 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

57 Caries (cont) Other Aciduric Bacteria: –Lactobacillus species: Colonize late carious lesions Acid produced eliminate other bacteria + dissolve Enamel

58 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

59 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

60 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: ClindamycinAzithromycin ClarithromycinCephalexin Cephadroxil

61 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

62 Beta Hemolytic Steptococcus Clinical Manifestations: Suppurative(pus) complications of pharyngitis: –Otitis mediaPeritonsillar cellulitis –Erysipelas (skin)Scarlet Fever –MeningitisPneumonia –Peritonsillar & Retropharygeal abscess –Pyoderma (impetigo) –BacteremiaPerianal abscess –Lymphangitis Emphyema –MeningitisPneumonia

63 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)

64 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 food- borne epidemics Impetigo-like Skin infection mostly in summer due to Insect Bites. Virulence Factor: most important is M protein

65 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

66 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)

67 Gram Positive Bacilli Listeria – NO Spores Corneybacterium - NO Spores Bacillius – Spores Clostridium - Spores

68 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

69 Listeriia monocytogenes (cont) Risk Factors –Neonates (transmission across placenta or during delivery –Pregnancy (Bacteremia) –Alcoholics (Meningitis) –Immunosuppression: (AIDS, Steroids, Chemotherapy, Transplants)  Meningitis

70 Cornybacterium diphtheriae Non-motileClub-shapedNo 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 1 st year. Boosters every 10 years

71 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

72 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: penicillinKiller vaccine

73 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.

74 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 –CollagenaseProtease –HyaluronidaseLecithinase

75 Clostridium perfringens Fast growing Non-motileSoil & GIT Alpha toxin (Lecithinase)  Lysis of RBC & other cells Transmission thru disrupted: –SkinGITOther Epithelial tissues –Due to TraumaSurgery (septic abortion) –Spores found in Soil

76 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 (1 st S. aureus, 2 nd Salmonella) Abdominal pain & diarrhea for 24 hrs. No Rx

77 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

78 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 –NauseaVomitingAbdominal pain Voluminous green diarrhea Treatment: Vancomycin or Metronidazole

79 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.

80 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.

81 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

82 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)

83 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

84 Gram Negative Cocci NEISSERIA Non-motileNon-spore-forming Gram negativecocci Arranged in pairs (diplococci) with flattened adjacent sides facing each other (“coffee beans) Fastidious organisms Very susceptible to HeatColdDrying

85 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

86 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

87 Neisseria gonorrhoeae Produce beta-lactamase Transmission: –Venereal contactFomites –Increased incidence in: Sexually active young adults (15-30 y o) Non whitesLow socio-economic class Urban settings

88 Neisseria gonorrhoeae (cont) Clinical Manifestations: Primarily uro-genital tract Men: –Acute urethritis & yellow purulent discharge –90% will be symptomatic –Common complications: Urethral strictureEpididymitis ProstatitisProctitis (homosexuals)

89 Neisseria gonorrhoeae (cont) Women: –Asymtomatic in 20 – 80% of cases –Inability to observe discharge –Complications; Pelvic inflammatory disease (15 – 20%) Generalized Peritonitis Infertility

90 Neisseria gonorrhoeae (cont) Disseminated disease observed as: –MeningitisArthritis –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

91 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

92 Gram Negative Bacilli Enterobacteriaceae Gram negativeNon-spore forming FacultativeMotile Many are normal GI flora (symbiotic relation) Synthesize Vitamin K Deconjugate Bile & Sex hormones  recirculated in the Liver Prevent colonization by primary pathogens EscherichiaCitrobacteriaKlebsiella EnterobacteriaSerrataiProteus Klebsiella not motile

93 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 spSalmonella sp –Yersinia sp (not in GIT) –Escherichia col Shigella + Salmonella only pathologic in Humans

94 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

95 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

96 Shigella Obligate human pathogenNot motile S. DysenteriaS. flexneriS. sonneiS. 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

97 Shigella Clinical Manifestations: (Shigellosis) Bacillary dysentery: –Abdominal cramps –Diarrhea (Blood + PMNs + Mucus) –Carrier state 1 – 4 weeks after disease Treatment HydrationElectrolyte replacement Fluoroquinolones Prevention thru personal hygiene, proper garbage disposal & water purification.

98 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

99 Salmonella MotileLPS  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

100 Salmonella (cont) Typhoidal Salmonella infection Caused by S. typhi (only Human Colon) Thyphoid (Enteric) Fever ProgressiveSubacuteFibrile-wasting Common in developing countries Worst in young children Transmission: Large inoculum in Fecally contaminated Food or Water Ulcers & perforation of GIT

101 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: ExhaustionLess fever Complicatons: –Relapse (20%)BleedingAbscess Treatment: Chloroamphenicol (1 st choice) Cephalosporins

102 Common Opportunistic Enterobacteriaceae Klebsiella sp Non-motileLactose 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” –AlcoholicsDiabeticsCOPD

103 Common Opportunistic Enterobacteriaceae Proteus sp Highly MotileCause UTI Produce Urease  increase pH  Struvite (stones)  obstruct UT  hiding place Citrobacter  Pyelonephritis Enetrobacter  Pneumonia Serratia  Pneumonia + UTI

104 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

105 Gram Negative Bacilli: Additional Enteric Pathogens Campylobacter Small CurvedGram negative Rods Reservoirs = Domestic animals C. jejuni: –Transmission via Fecal-Oral (Food/HOH) –Clinical Manifestations: (Enterocolitis) Bloody diarrheaFeverMalaise Painful Abdominal cramps C. fetus:Bacteremia + Metastatic Infections(IC)

106 Gram Negative Bacilli: Additional Enteric Pathogens Helicobacteria pylori Spiral shapedmotile 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

107 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

108 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

109 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

110 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)

111 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.

112 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

113 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 toxinAdenylate cyclase toxin –Tracheal cytotoxinLipopolysaccharide

114 Bordetella pertussis (cont) Clinical Manifestations of Whooping Cough Highly communicable via respiratory route Humans only known reservoir Incubation period = 7 – 10 days3 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)

115 Respiratory Pathogens (cont) LEGIONELLA PNEUMOHILIA Gram negativeFacultative Aerobe Intracellular parasite Widely distributed in aquatic environments Requires Fe & Cystine to grow Uses Complement receptor to infect Macrophages Transmission: (Aerosol) Air conditioning unitsHumidifiers Respiratory devices, Shower head, Whirlpools

116 LEGIONELLA PNEUMOHILIA (cont) Clinical Manifestations: Can be asymptomatic Pontiac fever: mild, febrile illness without pneumonia Legionnaires’ disease: severe often fatal pneumonia Treatment: Erythromycin

117 ANAEROBES Obligate anaerobes require a reducing agent (substance able to donate electrons, reducing a 2 nd 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

118 Obligate Anaerobes (cont) Greatest natural defense is tissues with high oxidation-reduction potential  no growth. Normal inhabitants of: –Oral cavityVaginaGIT Can cause opportunistic infections in tissues adjacent to their normal habitat due to tissue injury or vascular compromise.

119 Obligate Anaerobes (cont) Pathology Primarily purulent abscess formation Culture most often reveal polymicrobal infection with multiple facultative & anaerobic species. Treatment: –Surgical drainagePenicillin G –ClindamycinMetronidazole –ChloroamphenicolCefoxitin

120 Anaerobic Gram Negative Bacilli BACTEROIDES:Primary organism of Colon Bacteroides fragilis: Most frequent cause of anaerobic infection Gram negativeNo 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

121 Bacteroides fragilis (cont) Clinical Manifestations: Intra-abdominal infections: –AppendicitisAbscesses –Peritonitis Treatment: –MetronidazoleClindamycin –Chloroamphenacol –Incision & Drainage (I & D)

122 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)

123 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

124 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

125 ANAEROBIC COCCI ANAEROBIC GRAM POSITIVE COCCI Peptosteptococci: –Found in Mixed infections SkinOralURT Female Genital tract –Treatment: PenicillinCephalosporins Clindamycin Metronidazole

126 ANAEROBIC COCCI ANAEROBIC GRAM NEGATIVE COCCI Veillonella sp –Resemble Neissera sp –Normal Flora of: MouthNasopharynxVagina –Rarely cause infection –Can be confused with Neissera on Gram Stain

127 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 –SpirochetesBorreliaFusobacteria –Campylobacter rectusEichenella corrdens

128 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

129 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

130 Mycobacterium tuberculosis Obligate anaerobeAcid-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.

131 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

132 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.

133 Mycobacterium tuberculosis (cont) Pathogenesis: 1 st : Delayed-type Hypersensitivity (T-cell), 3-4wks after infection  positive Tuberculin reaction. Acquired cellular immunity with resistance or protection from re-infection.

134 Mycobacterium tuberculosis (cont) Primary infection: Exudative type: –Organism inhaled spreads to: Macrophages LNsBlood –Signs of infection minimal –Immune competent host limit organism to Lung. Productive type: –Granuloma tubercles & calcified lesion (Ghon complexes) form. –PPD test positive

135 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 lossAnorexia WeaknessFeverNight sweats Mycobacterium tuberculosis (cont)

136 Clinical Manifestations (cont) Pulmonary TB (80%) –Hemoptysis (cough + blood) –pneumonitis Miliary (disseminated) TB –Mostly: Bone & jointsBrainKidney PeritoniumLymph nodes

137 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 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

138 Mycobacterium tuberculosis (cont) Treatment: Period of 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 IsoniazidRifampin EthambutolPyrazinamide

139 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.

140 Mycobacterum bovis TB in cattlePresent in SoilPositive 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

141 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. kansasiiM. avium-intracellulare Dissemination to Bones & Joints will give positive PPD Skin test BCG vaccine from live attenuated M. bovis

142 Mycobacterium leprae Cannot grow in vitro on any culture media Acid fastDelayed-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

143 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

144 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

145 ACTINOMYCETES Filamentous shape & causes Actinomycosis Actinomyces, Nocardia, Steptomyces Actinomyces israelii & A. naeslundii AnaerobicGram positive bacilli Part of normal oral flora Pathogenic only after trauma (surgery)

146 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

147 Actionmycetes israelii (cont) Thoracic Actinomycosis: –Extension of Cericofacial infection (20%) Abdominal Actinomycosis –Traumatic perforation of GIT mucosa –Ruptured AppendixUlcers Pelvic Actionmycosis –Women using Intrauterine devices Traetment: Penicillin or Ampicillin for several weeks + surgical drainage

148 Nocardia asteroides Soil + Aquatic Environs AerobicGram positiveFilamentous 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

149 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)

150 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

151 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 Feces

152 Rickettsial Diseases (cont) Q Fever Coxiella burnetiiNo 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

153 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: –FomitesSexuallyPerinatally

154 Chlamydia trachomatis (cont) Treatment: ErythromycinTetracycline Prevention: safe sexual practices Clinical Manifestations: Ocular trachoma  blindness (developing countries)

155 Chlamydia trachomatis (cont) Sexually Transmitted Diseases: Number one cause of STD In Men: –non-gonococcal Urethritis –Epididymitis –Prostatitis –Proctitis

156 Chlamydia trachomatis (cont) Sexually Transmitted Diseases (cont) In Women: –CervicitisUrethritisSalpingitisPID 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

157 CHLAMYDIAE (cont) C, psittaci Transmission: Inhalation of infected Bird Droppings  Pneumonia C. pneumonia Human-only pathogen believed to be transmitted by Inhalation Clinical Manifestations: –PharyngitisBronchitis –Mild Atypical Pneumonia

158 SPIROCHETES MotileHelical 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)

159 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

160 Syphilis (cont) Transmission: SexuallyAcross Placenta Blood Transfusion Risk groups: –People with multiple sex partners –Infants born to infected mothers

161 Syphilis (cont) Clinical Manifestations: Primary syphilis: Arise within 2 – 10 weeks of exposure Organism spread to LNs & Blood Chancre forms at site of innoculation: –FirmPainlessReddish –Raised borderCenter ulcerated –Heals within 3 – 6 weeks without scarring –Contains numerous spirochetes (highly infectious)

162 Syphilis (cont) Secondary syphilis: Occur 1 – 3 months after primary syphilis Symptoms: –Skin rashFeverSore Throat –Headache –Generalized lymphadenopathy especially Epitrochlear region (inner condyle of Humerus). –Mucous patch on mucous membrane Orally & Genital. Highly infectious.

163 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)

164 Syphilis (cont) Congenital syphilis: Transplacental transmission  fetus Mother has Primary or Secondary syphilis 25% mortality if left untreated Manifestations in Newborn: –HepatosplenomegalyHemolytic anemia –PneumoniaSkin lesion –“Snuffles” (obstructed nasal breathing)

165 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

166 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

167 Other Treponemal Disease Yaws (T. pertenue) In the TropicsDirect contact Mainly Children Lesion = painless, erythematous (Arm or Leg) Pinta (T. carateum) Person to personSexually Transmited Bejel (T. pallidum) Poor hygieneTransmission by direct contact Skin lesions highly infectious

168 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

169 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.

170 BORRELIA Lyme Disease (cont) Clinical Manifestations: Untreated  Neurologic + Cardiac disease Neurolgic Symptoms: –Severe HeadacheMeningitis –Cranial nerve palsies –Painful peripheral neuropathies

171 BORRELIA Lyme Disease (cont) Clinical Manifestations: Cardiac Symptoms: –Cardiac Arrhythmias (resolve after several weeks) –MyocarditisPericarditis Diagnosis: ClinicalHx Tick bite Serology Relapsing Fever: Borrelia recurrentis –Transmitted by Human Body Louse

172 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

173 MYCPLASMATACEAE Characteristics & Physiology: FilamentousPleomorphic FacultativeUses 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

174 Mycoplasma pneumoniae Clinical Manifestations: Most common cause for Pneumonia in Young Adults (“walking pneumonia”) –Non-productive Cough –Low-grade FeverInsidious 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)

175 Mycoplasma hominis Sexually transmitted Major cause of postpartum women Clinical Manifestations: Postabortal & Postpartum Fever + Bactaremia Pelvic Inflammatory Disease (PID)

176 Ureaplasma urealyticum Sexually transmitted Produces Urea Minor cause for non-gonococcal Urethritis

177 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

178 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

179 VIRAL CLASSIFICATION & IDENTIFICATION Morphology: Terminology: (cont) –Nucleocapsid: Protein Shell + Nucleic Acid –Peplomeres: Protein Spikes on Envelope

180 VIRAL CLASSIFICATION & IDENTIFICATION Morphology: (cont) Nucleocapsid: –Helical Nucleocapsid: Extended Nucleic Acid cavity, surrounded by Helical arranged Proteins Outer Lipid Envelope Orthomyxoviruses Paramyxoviruses Rhabdoviruses

181 VIRAL CLASSIFICATION & IDENTIFICATION Morphology: (cont) Nucleocapsid: –Icosahedral Nucleocapsid Condensed Nucleic Acid forming a Cuboidal shape (Hexagonal) Enveloped or Naked Parvoviruses Adenoviruses HerpesvirusesPicornaviruses

182 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

183 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

184 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

185 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

186 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

187 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

188 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

189 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

190 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

191 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

192 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)

193 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

194 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.

195 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

196 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.

197 VIRAL CLASSIFICATION & IDENTIFICATION Replication Cycle: (cont) –5. Replication of Viral Genome (Nucleic Acid) 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

198 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

199 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

200 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

201 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

202 SUMMARY All DNA viruses replicate in the Nucleus EXCEPT Poxvirus All RNA viruses replicate in the Cytoplasm EXCEPT Influenza virus & Retroviruses

203 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

204 ADENOVIRUSES (cont) Clinical Manifestations: Acute Respiratory Disease: –TonsilsAdenoidsLNs –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

205 PAPOVAVIRUSES Papiloma PolyomaVacuolating 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

206 Papillomavirus (cont) Transmission via contact with “warts” Associated with: –Laryngeal papillomas –Oral, Laryngeal, Penile & Cervical Cancer Treatment: ElectrocauteryCryocautery ExcisionChemicals Recurrence common (auto-inoculation)

207 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.

208 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)

209 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

210 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

211 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

212 Herpesviruses (cont) VARICELLA-ZOSTER VIRUS (VZV) SHINGLES Recurrent infect of VZV in adults VZV latent in sensory ganglia of spinal nerves Activated by: –TraumaNeoplasmDrugs –Imunosuppression Clinical Manifestations: Severe dermatomal pain with vesicular lesions Treatment: Acyclovir, VZIG, attenuated Vaccine

213 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 lymphomaNasophayngeal Ca –Hairy leukoplakia (lesion on lateral Tongue seen with diagnosis of AIDS)

214 Herpesviruses (cont) EPSTEIN- BARR VIRUS (EBV) [cont] Clinical Manifestations: Last for 2 – 4 weeks FatigueTender LymphadenopathyFever HeadacheSplenomegaly (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

215 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

216 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

217 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.

218 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

219 CONDITION WITH ERYTHEMATOUS RASH Measles Rubella Scarlet fever Roseeola Exanthem subitum (HHV-6)

220 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”)

221 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)

222 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

223 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: FeverRash Enteritis “common cold” Hemorrhagic conjunctivitisMeningitis

224 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 secretionsOro-fecal Epidemiology: epidemics in Summer & Fall

225 RNA Viruses (cont) PICORNAVIRUSES ENTEROVIRUSES: Coxsackieviruses: Coxsackie B –MyocarditisPericarditis –Pleurodynia Enterovirus 72: Etiologic agent for Hepatitis A

226 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 irritationHeadacheNasal discharge CoughMalaiseChillsMyalgia Treatment & Prevention: Supportive.

227 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) FeverChills Myalgia Sore throat Headache Nasal congestion Dry cough Rx: Amantadine, Rimantadine ( Type A)

228 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

229 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

230 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) NauseaFeverMalaiseCough Coryza (profuse nasal discharge) Conjunctivitis Maculo-papular erythematous rash, lasting 5 days, starts on the Face  Trunk

231 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)

232 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)

233 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)

234 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)

235 RNA Viruses (cont) TOGAVIRUSES –ALPHAVIRUS Eastern Equine Encephalitis (EEC) virus –Abrupt Headache & Fever –Nuchal rigidity Western Equine Encephalitis virus –Less severe disease –Mostly Childran

236 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

237 RNA Viruses (cont) Rubella (German measles )(cont) Congenital rubella Virus transmitted across the Placenta Serious consequence if it occurs in 1 st Trimester Complications: –Mental retardationBlindness –Heart abnormalitiesMotor dysfunction –Encephalitis Prevention: live attenuated virus vaccine (MMR)

238 RNA Viruses (cont) FLAVIVIRUSES (arthropod-borne) Yellow Fever: Mosquito borne Incubation period = 3 – 6 days Clinical Manifestations: Acute onset FeverProteinuria Jaundice (yellow skin/sclera of eye) Vomiting(vomitus black)Hemorrhage Prevention: attenuated vaccine

239 RNA Viruses (cont) FLAVIVIRUSES (cont) Dengue Fever (mosquito borne illness) Clinical Manifestations: Fever RashArthralgia Lympadenopathy Hemorrhage Death (10%) Occur primarily in the Tropics

240 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

241 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

242 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.

243 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)

244 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

245 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

246 HEPATITIS VIRUSES HEPATITIS A VIRUS (HAV) Picornavirus RNA virus Transmission: –Fecal-orally.Incubation period = days –EpidemicEndemic (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

247 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

248 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)

249 HEPATITIS VIRUSES (cont) Antibodies to HBV (cont) –Ab to HBeAg associated with low risk of infectivity Transmission: –Parenteral (not by mouth) & Sexual contact

250 HEPATITIS VIRUSES (cont) Clinical Manifestations of HBV Infection: AnorexiaNauseaVomiting HeadacheFeverDark Urine Abdominal painJaundice Arthralgia ArthritisNephritis Dermatitis (Skin) 10 – 15% develop: – chronic hepatitis (cirrhosis & hepatocellular carcinoma) –Carrier state (infectious)

251 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: 1 st at birth, 2 nd at 2 –4 mos, 3 rd at 6 – 18 mos

252 HEPATITIS VIRUSES (cont) 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.

253 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

254 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

255 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

256 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

257 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 MalaiseDry coughEosinophilia Erythematous rash. Rx Amphotericin B

258 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: FeverChillsProductive cough Pleuritic chest pain

259 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 surfacesSoil –HospitalsSome foods

260 OPPORTUNISTIC MYCOSES (cont) CANDIDA (cont) Clinical Manifestations: Oropharyngeal candidiasis (Thrush) –“white plaques” on Tongue & Buccal mucosa –Cytology shows pseudo-hyphae (PAS stain) –Treatment: NystatinKetoconazole » Mycelex troches (no sugar)

261 OPPORTUNISTIC MYCOSES (cont) CANDIDA (cont) Clinical Manifestations (cont) Vaginal candidiasis –DiabeticsAntibiotic therapy –Pregnancy  Neonatal “Thrush” –Thick yellow-white discharge –Intense pruritis Treatment: Nystatin suppositories

262 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

263 OPPORTUNISTIC MYCOSES (cont) CRYPTOCOCCOSIS Etiology: Cryptococcus neoformans (yeast) Found in: –Pigeon droppings, Soil Fruits Milk Wood products Immunosuppression predisposes to disease Clinical Manifestations: –PulmonaryMeningitis Treatment: Amphotericin B

264 OPPORTUNISTIC MYCOSES (cont) ASPERGILLOSIS Etiology: Aspergillus fumigatus Found in naturally in Soil, spores in the Air Clinical Manifestations: Allergic bronchopulmonary aspergillosis –Hypersensitivity reaction (IgE mediated)  bronchospasm –WheezingFeverEosinophilia Treatment: Steroid for symptoms

265 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

266 OPPORTUNISTIC MYCOSES (cont) PNEUMOCYSTIS CARINII Fungus based on rRNA homology Clinical manifestation: Interstitial Pneumonia in Immunosuppressed  Death Treatment: Trimethoprim-sulfamethoxazole (TMP-SMX) Pentamidine

267 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

268 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: –DiarrheaAbdominal cramps –BloatingFlatulenceMalaise –Weight loss Steatorrhea

269 PROTOZOA (cont) AMEBIASIS Etiology: Entamoeba histolytica Transmission: fecal-oral route (poor sanitation) Clinical Manifestations: (Colon of Humans) –DiarrheaAbdominal crampsNausea –VomitingFlatulence –Dysentery Severe abdominal painDehydration Bloody stool Liver abscess

270 PROTOZOA (cont) TRICHOMONAS VAGINITIS Etiology: Trichomonas vaginalis Clinical Manifestations: –DysureaPruritis –Copious “yellow-frothy” discharge –Symptoms worse with alkaline vaginal PH –Dyspareunia –Men:ProstatitisUrethritis

271 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) –NauseaVomitingMalaise Treatment: Chloroquine

272 BLOOD & TISSUE PROTOZOA (cont) LEISMANIASIS Etiology: Leishmania species Transmission: bite from Sandfly. Pathogenesis: parasite invades Reticuloendothelial cells & reside in Phagolysosomes. Clinical Manifestations: –SkinMucocutaneousVisceral Treatment: PentostamGlucantime

273 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 –FeverRashHeadacheMental changes –CNS involvement: Anorexia, Lassitude, Fatique, Wasting, Stupor, Coma, Death –Treatment: Suramin Melarsoprol (CNS)

274 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.

275 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 –AnemiaSeizures Treatment: PyrimethamineSulfadiazine


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