Microbiology, Immunology, Mycology, Virology, Bacteriology And Parasitology

MICROBIOLOGY, IMMUNOLOGY, MYCOLOGY, VIROLOGY, BACTERIOLOGY AND PARASITOLOGY ------------------------------------------------------------------------

I. MICROBIOLOGY  study of microorganisms which are large and diverse group of microscopic organisms that can occur as either single cell or in cluster arrangement including viruses which are microscopic but acellular I. CELLULAR STRUCTURES  Eukaryotes – presence of true nucleus; nucleus enclosed by nuclear membrane o Fungi – multicellular  Yeast – unicellular fungi; filamentas; saprophytic; process a cell wall (chitin) o Animals  Endoparasites – helminthes  Ectoparasites – insects, arachnids o Protozoans – considered as endoparasites; unicellular; free living o Plants (e.g. algae) – multicellular; photosynthetic (cellulose); possess a cell wall o EUKARYOTIC CELL STRUCTURE  Plasma Membrane – phospholipid bilayer  Cytoplasm – composed of fluid and organelles  Organelles  Golgi Apparatus – packaging center; post-translational modification; removes unnecessary peptides  Mitochondria – “powerhouse of the cell”; oxidative phosphorylation; 1% of DNA  Endoplasmic Reticulum o Rough ER – ribosomal attachment o Smooth ER – lipid attachment  Ribosomes – site of protein synthesis; primary ribosomal subunit (RSU); (80S  40S;  60S)  Nucleus – composed of genetic materials; biochemical processes: DNA Replication (synthesis); Transcription (synthesis of RNA – mRNA, tRNA, rRNA)  Prokaryotes – pathogenic + non-pathogenic; absence of true nucleus + organelles; with ribosomes, Golgi bodies, endoplasmic reticulum; relatively small in size (diameter: <1µm) o Eubacteria – simple bacteria; pathogenic; cell wall – 1o component: peptidoglycan (aka murein/mucopeptide) o Arachaebacteria – non-pathogenic; no cell wall; lives in extreme environmental conditions  Thermophiles – (>85oC); lives in high temperature environments PAGE 1 OF 18

 Halophiles – live in high salt concentration environments  Basophiles – live in high pressure environment  Methanogens – live in high methane concentration environment o PROKARYOTIC CELL STRUCTURE  Plasma Membrane – phospholipid bilayer  Cytoplasm  Inclusion Bodies – storage of energy; (ex. glycogen granules; sulfur granules; polyhydroxybutyric acid granules; magnetosomes; metachromatic granules)  Nucleoid – composed of genetic material  TRANSFER OF DNA o Conjugation – transfer of genetic material using plasmids o Transduction – bacteriophage – mediated transfer of genetic material o Transformation – direct transfer of genetic material from donor to recipient cell  Specialized Structures GRAM POSITIVE Peptidoglycan (7-8 layers) – crystal violet Plasma Membrane Teichoic Acid (cell wall; plasma membrane)

GRAM NEGATIVE Outer membrane Peptidoglycan (1-2 layers) Periplasmic space Plasma Membrane

 Endospores o Genus: Bacillus – aerobe; Clostridium – anaerobe o Dormant Stage: depleted with required nutrients sporulation active cell (vegetative)

SPORES germination

o heat resistant; desiccation resistant (Ca2+ dipicolinate  heat resistant spore) o Spore staining: malachite green; VR green o Microscopy: Bacillus – non-swollen spore; Clostridium - swollen spore  Plasmids – extrachromasomal genetic material (ex. R factor/ R plasmid – antimicrobial resistance)  Teichoic Acid –primary surface antigen gram positive; functions: (1) provides negative charged surface for gram positive; (2) surface antigen of gram positive organisms  stimulates antibody production  Outer Membrane – exclusively found in gram negative organisms; composed of: lipopolysaccharides (LPS) & lipid A © MANOR REVIEW CENTER NOTES (K.L)

 Periplasmic Space – gram negative only; contains hydrolytic enymes (ex. beta lactamases)  Cell Wall – rigid structure that protects organism against difference in osmotic pressure o 1O component – peptidoglycan o interlinking of peptidoglycan layer: Nacetylmuramic acid (N-AM); N-acetylglucosamide (N-AG)

α Monotrichous – single polar flagella at 1 end

α Peritrichous – flagella all over the cell

o Pili – small rigid structure  Function: special type of movement or locomotion; twitching motion  Forms: α Ordinary Pili/Fimbriae  Function: bacterial attachment α Sex Pili  Function: bacterial conjugation o Axial Fillament – (ex. spirochetes  Leptospira enterogans; Treponema palidum; Borrelia burgdorferi; Borelia recurrentis)  Function: spiral locomotion

PENICILLIN BINDING PROTEINS (PBP) NAG N-AM

 Glycocalyx – polysaccharide materials found outside cell wall o Capsule – firmly attached to cell, does exclude particle  Function: contribute to bacterial virulence  escape phagocytosis  General Rule: α ALL cocci are non-encapsulated except: streptococci α ALL bacilli are non-encapsulated except: Bacillus, Haemophilus, Klebsiella o Slime Layer – loosely attached to cell, does not exclude particle  Function: contribute to bacterial attachment to mucosal membrane  Cell Appendages o Flagella – (ex. Vibrionaceae)  Function: locomotion/movement  Highly Antigenic: H-antigen  Primary Protein: flagellin  Forms: α Lophotrichous – tuft of flagella at 1 end

α Amphitrichous – single polar flagella at both ends

II. OPTICAL METHODS/STAINING METHODS  Optical Methods o Light Microscope  Bright Field Light Microscope – difference in contrast black and white the specimen and surrounding medium; killed and stained specimen  Magnification: 1000x  Ocular Lens: 10x  Objective Lens: 100x  Phase Contrast Light Microscope – provides magnification of living cells which are unstained  Dark Field Light Microscope – lighting system is just able to reach sides of specimen; (ex. Treponema pallidum)  Fluorescent Microscope – substances or specimen that fluoresces – able to short wavelengths of light and emits long wavelength of light; used in clinical diagnostic microbiology; (ex. Auramin O – used for staining M. tuberculosis)  Differential Interference Contrast Microscope – polarizer; provides 3D structure of spores, vacuoles and granules o Electron Microscope  Transmission Electron Microscope – uses electron beam coming from an electron gun focused by an electron condenser into a thin specimen  Scanning Electron Microscope – provides 3D structure of microscopic surfaces of microorganism

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© MANOR REVIEW CENTER NOTES (K.L)

 Staining Methods o Gram Staining

carbol fuschin heat ethanol methylene blue

FUNCTION primary stain mordant decolorizer counterstain

CONVALESCENCE PERIOD

o Acid-Fast Staining – Ziehl-Neelsen Staining; hot method and cold method

DECLINE PERIOD

GRAM blue violet blue violet colorless pink red

ACME PERIOD

GRAM + blue violet blue violet blue violet blue vioet

PRODROMAL PERIOD

FUNCTION primary stain mordant decolorizer counterstain

INCUBATION PERIOD

crystal violet iodine ethanol saffranin

 Stages of Infectious Disease – imbalance of 3 agents of disease

TIME

o Negative Staining – cell/specimen appears colorless; primary stain: nigrosin o Flagella Staining – stain: unstable colloidal suspension of tannic acid which forms a precipitate o Capsule Staining – stain: (1) hot solution of crystal violet then rinsing with copper sulfate; (2) india ink – use for Cryptococcus neoformans (pigeon fluconazole) o Nucleoid Staining – stain: Feulgen stain – sensitive for DNA o Spore Staining – stain: malachite green; carbol fucshin III. GROWTH, CULTIVATION, AND REPRODUCTION  Primary Method of Reproduction – bacteria: binary fission (asexual reproduction)  Stages of Microbial Growth

a. Incubation Period – pre-pathogenesis period; absence of signs and symptoms; varies on characteristic of organism; (ex. Rabies  the nearer the site of the bite to the brain, the shorter the incubation period) b. Prodromal Period – presence of prodromes or mild signs and symptoms (non-pathognomonic) of infection; (ex. measles  3Cs: cough, corysa, conjunctivitis) c. ACME Period – period of illness; presence of major signs and symptoms (pathognomonic); (ex. measles  rashes, Koplik spots) d. Decline Period – signs and symptoms subsides e. Convalescence Period – body is restored to its healthy condition  Epidemiologic Triangle

LAG PHASE LOG PHASE STATIONARY PHASE DEATH PHASE

TIME

o Lag Phase – phase of adjustment; synthesis of important macromolecules/nutrients; susceptible to effects of antimicrobials o Log Phase – exponential growth rate; rapid increase in number of microorganisms at a constant maximum rate; accumulation of toxic waste o Stationary Phase – phase of equilibrium; cell division = cell death o Death Phase – cell death > cell division

 Koch’s Postulates o Causative Agent – suspected microorganism must be present in all stages of disease o Environment/Pure Culture Media – suspected microorganism must be grown in pure culture media o Healthy Host – suspected microorganism when inoculated or introduced to a healthy host, must cause same disease o Disease Host – suspected microorganism when isolated from disease host, must be same organism  Occurrence of Disease o Endemic Disease – presence of clinical cases all year round; January to December; (ex. schistosomiasis – Samar, Leyte; malaria – Palawan, Mindoro; filariasis – Bicol)

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© MANOR REVIEW CENTER NOTES (K.L)

o Epidemic Disease – outbreak; sudden increase in number of clinical case at a certain place and time period o Sporadic Disease – scattered or isolated number of clinical cases at a certain place or time period o Pandemic Disease – affects more than one continent; highest level: level 6; (ex. 2009 – influenza AH1N1; 2014 – Ebola virus = level 4)  Culture Media TYPE OF CULTURE MEDIA Simple Media – used for nonfastidious microorganisms Enriched Media – used for fastidious microorganisms; contains special nutrients, vitamins, minerals needed for development Differential Media – subclassifies large group of microorganisms into categories; presence of visible reaction

Selective Media – allows growth of one group of microorganism and inhibits other groups

Anaerobic Media

o Enterobacteriaceae  Rapid Lactose Fermenters (EKE) – E. coli; Klebsiella; Enterobacter  Slow Lactose Fermenters (SCAPE Edward Haf) – Serratia; Citrobacter; Arizona; Providencia; Erwinia; Edwardsiella; Hafnia  Non-Lactose Fermenters (SPPS) – Shigella; Proteus; Pseudonomas; Salmonella o Hemolytic Reaction  α-Hemolytic Reaction – partial hemolysis  green (ex. Streptococcus pneumoniae; Viridans streptococci; Streptococcus mutans)  β-Hemolytic Reaction – complete hemolysis  colorless; further subclassified into Lancefield Classification (A-G)  Group A – Streptococcus pyogenes  Group B – Streptococcus agalactiae  Gamma-Hemolytic Reaction – no visible reaction

CULTURE MEDIA 1. Nutrient Agar 2. Nutrient Broth

1. Milk Agar  high protein nutrition 2. Chocolate Agar  sheep’s blood (1%); high hemoglobin nutrition

1. Eosin Methylene Blue (EMB) & MacConkey Agar (MCA) – subclassify group of enterobacteriaceae into lactose and non-lactose fermenters VR EMB MCA

LF metallic green pink

NLF colorless colorless

2. Blood Agar Plate (BAP) – both enriched and differential media; identification of streptococci based on hemolytic reactions 3. Mannitol Salt Agar (MSA) – subclassifies group of staphylococci - s. aureus  golden yellow - s. epidermidis  porcelain white - s. saprophyticus  no visible reaction 1. EMB & TCA – both differential and selective media 2. Saboraud Dextrose Agar (SDA) – selective only for fungal growth; provides an acidic pH (pH = 5.6) 3. Colistin-Nalidixic Acid (CNA) – selective only for gram positive organisms 4. Theyer-Martin – selective for gramnegative diplococcic, Neisseriae; modified chocolate agar 5. Lowenstein-Jenssen Media – very selective only for Mycobacterium tuberculosis; very expensive  extrapulmonary TB 6. Thiosulfate Citrate Bile Sucrose (TCBS) – selective only for Vibrionaceae 7. Leoffler’s Serum Media & Tellurite Media – selective only for Corynebacterium diphtheriae 8. Skirrow’s Agar & Campy BAP – selective only for Campylobacter jejuni 9. Bordet-Gengou Agar – selective only for Bordetella pertussis 1. Candle Jar Method 2. Thioglycollate Agar 3. GasPak®

IV. CONTROL OF MICROORGANISMS  Chemotherapy – Paul Ehrlich  (1) atineoplastics; (2) antimicrobials  Antibiotics – compounds sourced from microorganisms that can inhibit growth of other microorganisms o Classifications a. Based on their Source – (ex. bacteria, fungi)

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ANTIBIOTIC Bacitracin Polymyxin Penicillin Griseofulvin Gentamicin Streptomycin Vancomycin Chloramphenicol Clindamycin Nystatin Amphotericin B Erythromycin Cycloserine

SOURCE Bacillus subtilis Bacillus polymyxa Penicillum notatum Penicillum griseofulvum MIcromonospora purpurea Streptomyces griseus Streptomyces orientalis Streptomyces venezuelae Streptomyces lincolnensis Streptomyces noursei Streptomyces nodosus Streptomyces erythreus Streptomyces orchidaceus

b. Based on Spectrum of Activity  Narrow Spectrum – (ex. Aztreonam)  Broad Spectrum – (ex. Carbopenems; Tetracylines) c. Based on Antimicrobial Activity  Bacteriostatic Agents – inhibits growth and reproduction of microorganisms; general rule  ALL protein synthesis inhibitors and antimetabolites are bacteriostatic except aminoglycosides  Bactericidal Agents – kills pathogens; general rule  ALL cell wall synthesis inhibitors are bactericidal d. Based on Mechanism of Action MECHANISM OF ACTION Inhibitor of Cell Wall Synthesis

ANTIBIOTICS  Beta Lactams – Penicillins; Cephalosporins; Carbapenems; Monobactams  Glycopeptides – Vancomycin; Teicoplanin; Telavancin  Cycloserine  Polypeptide

© MANOR REVIEW CENTER NOTES (K.L)

Inhibitor of Protein Synthesis

Inhibitor of Nucleic Synthesis Antitubercular Agents

Antimetabolites Miscellaneous Agents

Acid

 30s Inhibitors – Tetracyclines; Aminoglycosides  50s Inhibitors – Macrolides; Chloramphenicol; Lincosamides; Oxazolidinones; Streptogramins  Rifamycins  Quinolones/Fluoroquinolones  First Line Agents (RIPE) – Rifampicin; Isoniazid; Pyrazinamide; Ethambutol  Second Line Agent – Aminoglycosides; Fluoroquinolones; Ethonamides; p-aminosalycilic acid  Sulfonamides  Pyrimethamine/Trimethoprim  Nitroimidazole  Mupirocin  Polymyxin  Urinary Antiseptics – Nitrofurantoin; Methenamine

A. Inhibitors of Cell Wall Synthesis  Beta Lactam o MOA: inhibits cell wall synthesis by binding to penicillinbinding proteins (PBP) o Clinical Use:  effective for gram positive and gram negative  ineffective for: (1) wall-less microorganisms (ex. mycoplasma) (2) microorganisms with atypical cell wall component (ex. mycobacterium) (3) intracellular parasites (ex. legionella; brucella; chlamydia; rickettsia) (4) resistant microorganisms (ex. MRSA; MRSE) o Adverse Effects: allergic reaction; anaphylactic reaction; cross-sensitivity reaction  PENs & CEPHs; JarischHerxheimer Reaction – idiosyncratic reaction 1.) Penicillins a. Natural Penicillins  Pen G – benzyl penicillin; poor oral bioavailability; parenteral (IV/IM)  Pen V – phenoxymethyl penicillin; good oral bioavailability; oral b. Isoxazolyl Penicillins – antistaphylococcal penicillins; resistant to action of beta lactamases; prototype: methicillin – withdrawn due to nephrotoxicity; (ex. cloxacillin; oxacillin; dicloxacillin; nafcillin) c. Extended Spectrum Penicillins – increases gram negative coverage; increases gram negative membrane penetration  Aminopenicillins – (ex. amoxicillin; ampicillin; bacampicillin)  Carboxypenicillins – has activity for Pseudomonas infection – (ex. carbenicillin; ticarcillin)  Ureidopenicillins – (ex. piperacillin; azlocillin; mezlocillin)

2.) Cephalosporins 1st

RANGE OF EFFECTIVENESS G+ G+++ +

2nd

++

++

3rd

+

+++

4th 5th

+++

++

NOMENCLATURE ALL starts with CEPH except Cefazolin, Cefadroxil ALL starts with CEPH; nothing ends in –ONE or –IME except Cefuroxime, Lovacarbef ALL starts with CEF; ALL ends with –ONE or –IME except Cefdinir, Ceftibulen, Cefditoren, Moxalactam Cefepime, Cefipirome Ceftaroline fosamil

COMMONLY USED CEPHALOSPORINS:  Cefazolin – only 1st generation ceph in parenteral form; clinical use  surgical prophylaxis  Cefuroxime – extensively used for treatment of community-acquired pneumonia  Cephamycins – 2nd generation cephs with activity for anaerobic infection (Cefoxitin, Cefotetan, Cefmetazole)  Ceftaroline Fosamil – only ceph active against MRSA and MRSE  Ceftriaxone & Cefotaxime – used for treatment of meningitis (except: Listeria monocytogens)  Cefexime – used for treatment of gonococcal or nongonoccocal urethritis and cervicitis  Cefoperazone & Ceftazidime – has activity for Pseudomonas infection 3.) Carbapenems – widest spectrum among beta-lactam antibiotics  Imipenem + Cilastatin  dihydropeptidase enzyme inhibitor  Meropenem  Ertapenem 4.) Monobactam – (ex. Aztreonam) – only effective for aerobic and gram negative organisms  Glycopeptides o Vancomycin  MOA: inhibits cell wall synthesis by binding to terminal peptide D-ala-D-ala terminus of nascent peptide chain  Clinical Use: formerly DOC for Pseudomembranous colitis; DOC for treatment infection caused by MRSA and MRSE  Adverse Effect: Red Man Syndrome – form of phlebitis or allergic reaction; management: prophylaxis  Ndiphenhydramine (via slow IV infusion) o Teicoplanin – same MOA, same spectrum; IV and IM o Telavancin  Chemical Structure: semisynthetic lipoglycopeptide derived from Vancomycin  MOA: same with Vancomycin; alters membrane potential and membrane permeability o Dalbavacin  Chemical Structure: semisynthetic lipoglycopeptide derived from Teicoplanin

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© MANOR REVIEW CENTER NOTES (K.L)

 Cycloserine o MOA: inhibits cell wall synthesis by inhibiting activity of: (1) alanine racemase, (2) D-ala-D-alanyl ligase o Clinical Use: 2nd line of agent for Mycobacterium tuberculosis resistant to the first line agents  Polypeptide (ex. Bacitracin) – poor oral bioavailability  topical o Chemical Structure: mixed cyclic polypeptide B. INHIBITORS OF PROTEIN SYNTHESIS  Inhibitors of 30s Ribosomal Subunit 1.) Tetracyclines – (ex. Tetracyclines; Doxycycline; Minocycline; Demedocyline) o widest/broadest spectrum among antibiotics (gram positive, gram negative, wall less organisms, intracellular parasites; spirochetes, plasmodium) o Chemical Structure: naphthacene ring o MOA: inhibition of binding of aminoocyl tRNA to mRNA  prevents peptide elongation o Adverse Effects: (contraindicated in patients < 8 yrs old)  Permanent yellow staining of teeth  Hypoplasia of teeth  Use of expired tetracyclines  Fanconi-like Syndrome  Ototoxicity  Minocycline  Phototoxicity  Demeclocycline 2.) Aminoglycosides o Source: Micromonaspora (-micins); Streptomyces (mycins) o MOA: inhibit protein synthesis: (1) prevention of formation of initiation complex, (2) misreading of mRNA complex, (3) formation of nonfunctional polysomes o Pharmacodynamic Properties: concentration dependent killing; postantibiotic effect; synergistic effect o Adverse Effects:  Ototoxicity – Kanamycin; Amikacin; Neomycin  Vestibulotoxicity – Streptomycin; Gentamicin  Nephrotoxicity – Neomycin; Gentamicin; Tobramycin  Inhibitors of 50s Ribosomal Subunit 1.) Macrolides o Chemical Structure: large lactone ring o MOA: blocks peptide exit tunnel  dissociation of peptidyl tRNA from ribosome o Erythromycin  Clinical Use: alternative for patients allergic to Blactam antibiotics  Adverse Effect: abdominal discomfort; stimulates motillin receptors (increases peristalsis); jaundice – associated with use of erythromycin estolate salt o Clarithromycin – least associated with adverse effects  Chemical Structure: methylated erythromycin

 Clinical Use: treatment for infection caused by staphylococci and streptococci; treatment for peptic ulcer disease caused by H. plyori o Azitrhromycin  Pharmacokinetics: (1) excellent distribution to body tissues; (2) longer t ½  Dosing: once a day for 3-5 days  Adverse Effect: arrhythmia 2.) Chloramphenicol o MOA: inhibition of peptidyl transferase; (RLE: peptide elongation) o Adverse Events: nitro group  aplastic anemia – low RBC, WBC, platelets  Grey Baby Syndrome – lacking for enzyme for glucoronidation o Toxic Dose: > 50mg/kg/day o Clinical Use: alternative for treatment of typhoid fever (enteric fever) 3.) Lincosamides – MOA: same as macrolides o Lincomycin  Chemical Structure: sulfur containing antibiotic o Clindamycin – DOC for anaerobic infections above diaphragm; alternative treatment for toxoplasmosis (+ pyrimethamine); treatment of skin and soft tissue infection caused by staphylococci and streptococci 4.) Oxazolidinones – (ex. Linezolid – treatment of VRSA, VRSE) o MOA: inhibits 23s subunit of the 50s subunit 5.) Streptogramins o Ratio: 70 (A) : 30 (B)  Streptogramin A – Dalfopristin  Streptogramin B – Quinupristin o Clinical Use: treatment of VRSA, VRSE C. INHIBITORS OF NUCLEIC ACID SYNTHESIS  Rifamycin – (ex. Rifampicin; Rifabutin) o MOA: Inhibition of RNA polymerase (RLE: transcription) o Clinical Use: treatment of pulmonary and extrapulmonary tuberculosis; treatment of cutaneous tuberculosis (leprosy) o Adverse Effect: Red-orange discoloration of body fluids (ex. sweat, urine, saliva)  Quinolones/ Fluoroquinolones o MOA: inhibitor of:  Topoisomerase II (DNA Gyrase) – relaxation of supercoiled DNA  Topoisomerase IV – separates DNA strand o Addition of fluorine:  Increase gram negative coverage  Improved penetration to gram negative membrane

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© MANOR REVIEW CENTER NOTES (K.L)

First Generation Second Generation

Third Generation

Fourth Generation

 Nalidixic acid and Cinaxacin  Moderate gram (-) activity  Limited use for uncomplicated UTI  Ciprofloxacin, Ofloxacin, Norfloxacin, Eroxacin, Lomefloxacin  Improved gram (-) activity  Has activity for gram (+) and atypical microorganisms  Levofloxacin, Sparfloxacin, Gemifloxacin, Gatifloxacin, Moxifloxacin  Retained gram (-) activity  Improved activity for gram (+) and atypical microorganisms  Trovafloxacin  Retained activity for gram (-), gram (+), and atypical microorganisms  Has activity for anaerobic microorganisms

o COMMONLY USED FLUOROQUINOLONES  Ciprofloxacin – used as treatment and prophylaxis for anthrax  Respiratory Fluoroquinolones – used for treatment of lower respiratory tract infections and upper respiratory tract infection; (Levofloxacin; Gatifloxacin; Gemifloxacin; Moxifloxacin)  Ciprofloxacin and Levofloxacin – treatment of uncomplicated UTI  Adverse Effects: bone/cartilage toxicity; (ex. tendinitis; phototoxicity) D. ANTITUBERCULAR AGENTS  First Line Agents – (HRZE or RIPE) o Isoniazid  Chemical Structure: isonicotinic hydrazine  MOA: inhibits mycolic acid synthesis  Pharmacokinetics: acetylation  Enzyme: N-acetyltransferase; fast acetylators  rapid development of resistance  Management: ethambutol  Adverse Effects: peripheral neuritis  management: Vit B6 (Pyridoxine) o Rifampicin o Pyrazinamide – short term therapy; Adverse Effect: hepatotoxicity o Ethambutol  MOA: inhibits arabinosyl transferase  ↓arabinoglucan  Adverse Effects: red-green visual disturbance (optic neuritis)  Second Line Agents o Aminoglycosides – Streptomycin IM o Fluoroquinolones – Levofloxacin or Moxifloxacin o Ethionamides o Cycloserine o p-Aminosalicylic Acid

E. ANTIMETABOLITES SULFONAMIDES

PABA

X PYRIMETHAMINE/TRIMETHOPRIM

X

dihydropteroate synthetase

Dihydrofolate dihydrofolate reductase

X

X

Tetrahydrofolate

Purine Bases

Nucleic Acid Synthesis

 Sulfonamides o Chemical Structure: PABA-like o MOA: inhibition of dihydropteroate synthetase o Adverse Effects:  Steven-Johnson Sydrome Counterindicated: G6PD Deficient G6PD↓ NADPH↓ oxidized glutathione –(glutathione reductase)-> reduced glutathione (master antioxidant)  Jaundice  Pyrimethamine/Trimethoprim o MOA: inhibition of enzyme dihydrofolate reductase o Adverse Effects: megaloblastic anemia  management: leucovorin  Combinations: o Sulfamethoxazole + Trimethoprim (Co-Trimoxazole) – DOC for Pneumocystis jiroveci pneumonia o Sulfadiazine + Pyrimethamine (Daraprim®) – DOC for toxoplasmosis o Sulfadoxime + Pyrimethamine (Fansidar®) – treatment of malaria F. MISCALLANEOUS AGENTS  Nitroimidazoles – (ex. Metronidazole; Tinidazole) o Clinical Use: DOC for trichomoniasis, amobiasis, giardiasis (TAG); DOC for anaerobic infection below diaphragm; DOC for Pseudomembranous colitis o Adverse Effect: metallic aftertaste + etOH  disulferam-like effect  Mupirocin – pseudomonic acid; topical o MOA: inhibits staphylococcal isoleucyl tRNA synthetase o Clinical Use: treatment of skin infection caused by staphylococcus (Impetigo)  Polymyxin – (ex. Polymixin B; Polymixin E – Colistin); topical o MOA: acts like cationic detergents  disruption of cell membrane G. URINARY ANTISEPTICS  Nitrofurantoin – active at an acidic pH; for uncomplicated UTI  Methanamine – prodrug  formaldehyde (urinary antiseptic); active at an acidic pH; for uncomplicated UTI

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© MANOR REVIEW CENTER NOTES (K.L)

H. DRUG-DRUG RELATIONSHIPS  Addition (1+1 = 2) – bacteriocidal + bacteriocidal; except: penicillins + aminoglycosides  Synergistic (1+1 = 3) – bacteriostatic + bacteriostatic  Antagonism (1+1 = 0) – bacteriocidal + bacteriostatic  Potentiation (1+0 = 2) – penicillins + β lactamase inhibitors; (ex. amoxicillin + clavulanic acid; ampicillin + sulbactam; piperacillin + tazobactam; imipenem + cilastatin)

II. IMMUNOLOGY  physiological process in which body (self) recognizes itself from foreign (non-self)  Types of Immunity: NON-SPECIFIC (INNATE)  does not require antigen recognition  not antigen specific  response is immediate  does not result to antibody production  does not result to immunologic memory

SPECIFIC (ADAPTIVE)  requires antigen recognition  antigen specific  lagtime before response  result to antibody production  results to immunologic memory

I. CELLS INVOLVED IN IMMUNITY  Granulocytes (BEN) o Basophils – for histamine release; present during acute allergic reaction; found in peripheral circulation  Mast Cells – for histamine release; found near organs/tissues o Eosinophils – present during type I HS reaction and helminthic infestation o Neutrophils – for phagocytosis; present in bacterial infection and acute inflammation  Agranulocytes o Monocytes + Macrophages  Monocytes – young macrophages; no phagocytic

effect o Macrophages – for phagocytosis and antigen presentation; (>2 weeks) – present during chronic inflammation  Lymphocytes – mature/activated in lymphoid organs o B Lymphocytes/B Cells – for antigen presentation; matures into 2 types of cells: (1) Plasma Cells – antibody production; (2) – Memory Cells – immunologic memory  Example: Vaccination:  Measles – 1 strain; 9 months  Dengue Virus – 1, 2 (memory cells), 3, 4 o T Lymphocytes/T Cells  Helper T Cells – aka CD4 + cells; attacked by HIV; stimulates B cells and cytotoxic T cells  Cytotoxic T Cells – aka CD8 + cells; for directly attacks; viruses and tumor/cancer cells HELPER T CELLS

B CELLS PLASMA CELLS

MEMORY CELLS

 Natural Killer Cells (NK cells) – Antibody Dependent Cellular Cytotoxicity (ADCC); indirectly attacks viruses and tumor/cancer cells III. NON-SPECIFIC IMMUNITY – Innate Immunity  Inflammation o 5 Cardinal Steps:  Rubor – redness  Calor – heat  Tumor – swelling/edema  Dolor - pain  Functio Laesa – loss of function  Chemotaxis – movement of neutrophils to site of infection o Margination o Diapedesis  Phagocytosis  Complement System o Primary Goal – to create membrane attack complex (C5b, C6, C7, C8, C9) o MAC:  Classical Pathway  Alternative Pathway  Mannose-Binding Lectin

Bacteria

N

IV. SPECIFIC IMMUNITY – Adaptive Immunity  Branches: o Humoral Immunity – B-cells o Cellular-Mediated Immunity – T-cells  Lymphoid Organs o Primary Lymphoid Organs – site of maturity; (ex. bone marrow; thymus) o Secondary Lymphoid Organs – site of activation; (ex. tonsils; lymph nodes; spleen; Peyer’s Patches)  Immunoglobulins

CYTOTOXIC T CELL

CT

CT

CT

MAC

CT

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o Immunoglobulin A – aka secretory immunoglobulin; found in body secretions/fluids (saliva; sweat; tears; colostrum) o Immunoglobulin E – responsible for type I hypersensitivity (allergy) © MANOR REVIEW CENTER NOTES (K.L)

o Immunoglobulin M – largest immunoglobulin (macroglobulin); first to respond during infection o Immunoglobulin G – most dominant immunoglobulin; crosses placental barrier o Immunoglobulin D – has no known function; found in B cell receptor  Hypersensitivity Reaction o Antibody Mediated Hypersensitivity Reaction – Type I, II, III  Type I Hypersensitivity Reaction – aka Intermediate Hypersensitivity Reaction; (ex. allergy; atropy; anaphylaxis); mediated by IgE  Type II Hypersensitivity Reaction – aka Cytotoxic Hypersensitivity Reaction; (ex. blood transfusion reaction – ABO incompatibility, Rh incompatibility; erythroblastosis fetalis; grave’s disease)  Type III Hypersensitivity Reaction – aka Antigen-Antibody Complex Formation; mediated by IgG; (ex. rheumatic heart disease; acute glomerulonephritis; arthus reaction; vasculitis; serum sickness; SLE) o Cellular Mediated Hypersensitivity  Type IV Hypersensitivity Reaction – aka Delayed Hypersensitivity Reaction; (ex. tuberculin skin test/PDD; contact dermatitis)

 Mycoses o Hypersensitivity Reaction o Mycotoxicosis – ingestion of preformed fungal toxin; (ex. Aflatoxin – stale peanuts acted upon Aspergillus, carcinogen  hepatocellular carcinoma; Ergotoxin – wheat acted upon by Claviceps purpurea) o Mycetisma – ingestion of a poisonous fungi; (ex. Amanita phalloides) o Fungal Infections  Superficial Mycoses

III. MYCOLOGY  Forms o Molds – multicellular; filamentous; lives at room temperature (20-25oC) o Yeasts – unicellular; non-filamentous; lives at body temperature (37oC)  Characteristics – multicellular and filamentous (except yeasts); saphrophytic; parasitic/pathogenic; plant-like  Morphology o Hyphae – filamentous; microtubular structures found in molds o Septum – cross-walled structures; found inside a hyphae o Conidia & Spores – primary method of asexual reproduction  Phyla PHYLA Phylum Glomerulomycota, Order Mucorales – formerly known as Phylum Zygomycota Phylum Ascomycota – largest phylum; aka “sac” fungi Phylum Basidiomycota – aka “club” fungi

SEXUAL REPRODUCTION zygospores

ascospores

basidiospores

ASEXUAL REPRODUCTION sprorangium/spores

MYCOSES Black Piedra – aka Tinea nodosa White Piedra

Piedraia hortae

Pityriasis – aka Tinea vesicolor Tinea Nigra

Malasssezia furfur

I. MEDICAL MYCOLOGY  study of fungal diseases (mycoses) and associated treatment PAGE 9 OF 18

Exophiala werneckii

TINEA Tinea Pedis

PART OF BODY feet

Tinea Cruris – jock itch

groin area

Tinea Unguium – onchomycosis

nail/hands

Tinea Corporis

trunk/body

Tinea Barbae Tinea Capitis

beard area scalp area

DERMATOPHYTES T. rubrum; E. mentagrophytes; E. Acossum T. rubrum; E. mentagrophytes; E. Acossum T. rubrum; E. mentagrophytes; E. Acossum T. rubrum; E. flocossum E. mentagophytes E. mentagophytes; M. canis

 Subcutaneous Mycoses – introduced into SQ/hypodermis area via a skin incision/trauma MYCOSES

CAUSATIVE AGENT

Chromoblastomycosis

Phialophora verrucosa; Fonsaccrea pedrosoi; Fonsacaea compacta; Rhinocladiella aquaspersa; Chladophialophora carrionii Pseudallescheria boydii; Modurella mycetomatis; Modurella grisea; Exophiala jeanselmei; Acremonium falciforme

Sporotrichosis – aka Occupational Disease of Gardeners; MOT: rose thorns; tree barks; and soil Phaeohyphomycosis

conidia/spores

Trichosporon beigelii

CLINICAL MANIFESTATIONS Black nodules found on hairshaft Beige nodules found on hairshaft Hypo/hyperpigmented serpentine skin lesions Brown to black lesions found on palms and soles

 Cutaneous Mycoses  Causative Agent: Dermatophytes o Epidermophyton – affects skin and nails o Microsporon – affects skin and hair o Trichophyton – affects skin, nails, and hair  Clinical Manifestation: Tinea/Ringworms

Mycetoma – aka Madura Foot; associated with barefoot individuals

conidia

CAUSATIVE AGENT

CLINICAL MANIFESTATIONS wartylike/verracous skin lesions found along draining of lymphatics suppuration; abcess formation; granuloma formation nodules found along draining of lymphatics

Phialophora richardsiae; Wangiella dermatitidis; Bipolaris spicifira; Exophiala jeanselmei; Alternaria (sp. of molds); curvuloria; Exorhilum rostratum

solitary encapsulated cyst found on skin

© MANOR REVIEW CENTER NOTES (K.L)

 Systemic/Endemic Mycoses  Causative Agent: Thermally Dimorphic Fungi  Mode of Transmission: respiratory (initial site of lungs)  Mode of Treatment: o Mild to Moderate – Itoconazole (DOC) o Moderate to Severe – Amphotericin B (DOC) MYCOSES

Coccidiomycosis – First Outbreak: San Joaquin Valley, California Histoplasmosis – Spelunker’s Disease; MOT: inhalation of spores from bat droppings South American Blastomycosis North American Blastomycosis

CAUSATIVE AGENT

CLINICAL MANIFESTATION

Coccidioides immitis; Coccidioides posadasii Histoplasma capsulatum

Valley Fever/Desert Rheumatism

TISSUE FORM/ MICROSCOPIC FORM spherules containing endospores

mimics signs and symptoms of PTB (cough hemolysis)

oral yeasts inside macrophages

Paracoccidioides brasiliensis Blastomyces dermatitidis

painful mouth and pharyngeal ulcers pulmonary/lung infiltrates lesions or ulcerations found on genitalia, bones and CNS-brain

large, multiple budding yeast thick walled yeast with broad based single bud

 Opportunistic Mycoses MYCOSES Candidiasis

Cryptococcosis –MOT: spores inhaled from pigeon droppings; Capsule Staining: india ink Pneumocystis Jiroveci Pneumonia

Aspergillosis

Mycomycosis

CAUSATIVE AGENT Candida albicans – formation of germ tube; C. glabrata; C. tropicalis; C. krusei; C. lusetanei

Cryptococcus neoformans

Pneumocystis jiroveci – Humans (former protozoan) Aspergillus fumigatus; Aspergillus flavus Zygomucor

CLINICAL MANIFESTATION cutaneous/mucosal – oral thrush, diaper rash, vaginosis, intertriginous infections, onychomycosis; systemic – associated with prosthetic devices; chronic mucocutaneous – associated with immunocompromised state and endocrinopathies (ex. diabetes mellitus) cryptococcus meningitis

TREATMENT Nystatin (DOC); Ketoconazole

Standard Treatment – Amphotericin B+ Flucytosine; Alternative Fluconazole Meningitis – Fluconazole (DOC); Systemic: Amphotericin B + Flucytosine

pneumonia

Cotrimoxazole (DOC)

bronchopulmonary aspergillus; invasive aspergillosis; aspergilloma – fungal ball rhinocerebellar infection

Variconazole (DOC)

Posaconazole (DOC)

III. ANTIFUNGAL  Superficial Mycoses – oral; topical o Griseofulvin – fungistatic  no known MOA; PROPOSED MOA: protects early formed skin against dermatophytic infection  Pharmacokinetics: ↑absorption: high lipid/fatty meal  Clinical Use: treatment of skin infection caused by dermatophytes o Terbenafine – fungicidal  MOA: inhibition of squalene epoxidase  ↑↑↑ squalene epoxide o Nystatin – topical; poorly absorbed  Chemical Structure: polyene antifungal  MOA: inhibition of ergosterol synthesis  Clinical Use: effective for skin infection caused by yeasts o Azoles  MOA: inhibition of fungal CYP450  Chemical Structures:  Imidazoles – less selective in inhibiting human CYP450; (ex. Ketoconazole; Topical Azoles – Clotrimazole, Ticonazole, Miconazole)  Triazoles – more selective in inhibiting fungal CYP450; (ex. Fluconazole; Voriconazole; Itraconazole; Posaconazole)  Adverse Effects: antiadrogenic effects (Males: gynecomastia; Females: galactorrhea); enzyme inhibition o Topical Agents  Salicylic Acid – APAP solution  Salicylic Acid + Benzoic Acid – Whitfield’s ointment  Selenium Sulfide – Selsun Blue Shampoo  Potassium Iodide Solution – DOC for sporotrichosis  Less Serious Mycoses o Ketoconazole – 1st azole available for clinical use o Fluconazole – (1) excellent penetration into BBB; (2) good water solubility; least associated with adverse effects o Itraconazole – 2nd line treatment for systemic/endemic mycoses  Life Threatening Mycoses o Amphotericin B – grandfather of antifungals; + flucytosine = synergistic effect  MOA: binds to ergosterol in fungal membrane and create holes (cytoplasmic leakage)  Clinical Use: initially use to decease fungal burden  Adverse Effects: nephrotoxicity – acute renal failure with wasting K+ and Mg2+ o Flucytosine  Chemical Structure: pyrimidine analogue  Prodrug  5-fluorouracil (antifungal)  MOA: (1) taken up cytosine permease; (2) converted to 6fluorouracil; (3) 5-fluorouracil is converted to: fluorodoxyuridine monophosphate (FDUMP), fluorouridine triphosphate (FUTP)

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© MANOR REVIEW CENTER NOTES (K.L)

 Clinical Use: treatment for systemic yeast infection; + amphotericin B o Echinocandins  MOA: inhibition of β-1,3-D-glucan synthesis  Examples: caspofungin; anidulafungin; micafungin o Voriconazole o Posaconazole – broadest spectrum among azoles; zygomucor, aspergillus, candida (ZAC)

 Prion Diseases  Bovine Spongiform Encephalopathy – Mad Cow’s Disease

 Scrapie – prion disease in sheeps  Kuru – association with human cannibalism; tribe in Papua New Guinea  Creutzfeld-Jakob Disease – associated with use of human growth hormone from corpse

IV. VIROLOGY  Characteristics – obligate intracellular parasites; acellular (nucleic acids + proteins); does not replicate (replication happens inside cell)  Morphology o Nucleic Acid Core – either DNA or RNA o Viral Capsid – protein part; for protection and basis for viral symmetry o Viral Envelope – enveloped virus – more vulnerable to effects of surfactants; naked virus  Viral Symmetry o Cubic/Icosahedral – spherical  General Rule: (1) all DNA viruses except POXVIRIDAE; (2) all RNA (+) sense viruses except FLAVIVIRIDAE, CORONAVIRIDAE, RETROVIRIDAE o Helical  General Rule: all RNA (-) sense viruses except AENAVIRIDAE o Complex – neither cube nor helical; Poxviridae, Flaviviridae, Aenaviridae, Coronaviridae, Retroviridae (PoFACoR)  Viral Genome o Double Stranded (DS)  General Rule: all DNA viruses except PARVOVIRIDAE o Single Stranded (SS)  General Rule: all RNA viruses except REOVIRIDAE o Segmented Viruses – Bunyaviridae, Arenaviridae, Reoviridae, Orthomyxoviridae (BARO)  Viral Life Cycle o Lysogenic Stage – no signs and symptoms (avirulent stage); synthesis and packaging of virions (mature viral particles) o Lytic Stage – presence of signs and symptoms; release of virions  Steps in Viral Infection – ASPERSP 1. Attachment of virus to host cell 2. Penetration of virus into host cell 3. Expression of viral genome 4. Replication of virus 5. Synthesis of virions 6. Packaging and release of virions  Unconventional Virus o Viroid – single stranded; smallest pathogen that can infect plants o Prions – only composed of proteins; heat resistant; desiccation resistant

II. GENERAL PROPERTIES OF DNA & RNA VIRUSES DNA VIRUSES  Double Stranded  Icosahedral  Nucleus (replication) NAKED DNA  Adenoviridae  Parvoviridae  Papilloviridae  Polyomaviridae RNA VIRUSES  Single Stranded  Enveloped  Cytoplasm  Spherical – Helical

EXCEPTION:  Parvoviridae (ss)  Poxviridae  Poxviridae (cytoplasm) ENVELOPED DNA  Hepadnaviridae  Poxviridae  Herpesviridae EXCEPTION:  Reoviridae (ds)  Picornaviridae; Reoviridae; Caliciviridae (PRC)  Retroviridae; Orthomyxoviridae; Influenza (nucleus)  Rabies Virus (helical-bullet shape)

III. DNA VIRUSES  Adenoviridae o Sites of Infection: conjunctiva; pharynx; small intestine; urinary bladder o Clinical Manifestation: pink conjunctivitis (sore eyes); pharyngitis (sore throat); gastroenteritis; hemorrhagic cystis  Parvoviridae – simplest DNA virus (single stranded); Parvovirus B19 (humans); red blood cell (tropism) o Clinical Manifestation:  Erythema Infectiosum – aka “5th disease”; slapped cheek appearance (children); severe arthralgia (adults)  Glove and Socking Syndrome – rashes found on hands and lower extremeties  Transient Aplastic Anemia  Pure Red Cell Aplasia  Hydrops Fetalis  Papillomaviridae – human papilloma virus

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HPV STRAINS 1 2 3 7 6, 11 16, 18

DISEASES Plantar Warts Common Skin Warts Cutaneous Warts Butcher’s Hand Warts Anogengenital Warts, Laryngeal Carcinoma Cervical Carcinoma

o Prevention:  Papanicolau Smear (Pap Smear) – early detection; start at age 21 years old

© MANOR REVIEW CENTER NOTES (K.L)

 Vaccination  Gardasil (Quadrivalent) – HPV 6, 11, 16, 18  Cervarix (Bivalent) – HPV 16, 18  Polymaviridae – BK virus; JC virus; Ki and Wu virus; Merkett cell virus; SVAD virus  Poxviridae – brick shape virus o Orthopox  Monkey Pox – 1o member; clinical manifestation: cervical and inguinal lymphadenopathy  Small Pox – variola; eradicated (last case was 1978 – Somalia); clinical manifestation: skin lesions (starts at head/facial area; skin lesions are of same stages)  Vaccinia – 1o component of small pox vaccine; model virus in terms of structure and replication  Cow Pox – ancestor of vaccinia; rodents (host); clinical manifestation: hemorrhagic/red-based skin lesions o Parapox  ORF Virus – found in sheeps; clinical manifestation: benign pustular dermatitis; aka occupational disease among sheep handlers o Mollusca Pox  Mollusca Contagiosum Virus – clinical manifestation: small, pink warty-like skin lesions found at back, buttocks, and genitalia o Yatapox – Yaba Pox; Tana Pox  Herpesviridae – latency period – asymptomatic; cytopathic effects – formation of “giant” cells FAMILY Alpha Herpes

STRAIN 1

2 3

COMMON NAME Herpes Simplex Virus 1 – non-sexually transmitted Herpes Simplex Virus 2 – sexually tranmitted Varicella-Zoster Virus Varicella (chicken pox); Zoster (shingles)  reactivation of varicella

CLINICAL MANIFESTATIONS gingivastomatitis; cold sores; fever blisters; hepatic encephalitis genital herpes; neonatal sepsis; hepatic meningitis skin lesions (starts at trunk); skin lesions are of different stages (most are vesicular) skin lesions are dermatomal (dermatomes); more painful

90-95%  asymptomatic 5-10%  symptomatic: stillbirth; intrauterine; growth retardation; blindness; deafness; mental retardation 6 Human Herpes Virus 6 roseola – aka infanten subitum; 6th disease 7 Human Herpes Virus 7 Gamma 4 Epstein-Barr Virus (EBV) infectious mononucleosis Herpes (IM) – aka kissing disease, monospot test (diagnosis); burkitt’s lymphoma; hodgkin’s and nonhodgkin’s lymphoma; gastric carcinoma 8 Human Herpes Virus 8 kaposi sarcoma *Organisms that can cross placenta: toxoplasma gondii; rubella; cytomegalovirus; herpes/HIV/Hepa B; syphilis (TrOCHeS – Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, Herpes Simplex) Beta Herpes

5

Cytomegalovirus (CMV) – most common congenital infection*

 Hepadnaviridae – Hepatitis B

IV. RNA VIRUSES  RNA (+) SENSE – immediately translated into proteins; (PiCoTCaFlaRe2) o Picornaviridae – smallest RNA virus  Enterovirus a. Polio Virus  Clinical Manifestation: paralytic poliomyelitis  Prevention: vaccination  Sabin – live attenuated virus; oral (OPV)  Salk – killed virus; IM (IPV) b. Rhino Virus – most common cause of common colds c. Coxsakie Virus  Coxsackie A – herpangian (vesicular pharyngitis); hand-foot-mouth disease; hemorrhagic conjunctivitis  Coxsackie B – pleurodynia; pericardis; myocarditis  Aphtho Virus – foot and mouth disease  Kobu Virus  Cardio Virus  Hepato Virus – Hepatitis A o Coronaviridae – solar/petal shape; clinical manifestations: SARS; MERS; gastroenteritis; common colds o Togaviridae – arbovirus (arthropod borne)  Alpha Virus – Chinkungunya Virus – crippling arthritis  Rubi Virus – Rubella (german measles) – clinical manifestations: 3-day maculopapular rash; congenital defects: cataract formation (blindness), deafness, valvular defects; forchheimer spots – petechiae seen at soft palate o Calciviridae  Callci Virus/Norwalk Virus – Norwalk Ohio Elementary School (first outbreak); clinical manifestations: viral gastroenteritis o Flaviviridae – arbovirus  Dengue Virus  Vector: aedes aegypti; aedes albopictus  Clinical Manifestations: dengue hemorrhagic fever  3 Clinical Phases: (1) Febrile Phase – occurs below D2 – D7 of illness (2) Critical Phase – occurs at D5 – D6 of illness; signs and symptoms include: plasma leakage; bleeding; severe organ involvement; can last for 24 – 48 hours (3) Convalescence Period – recovery phase

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© MANOR REVIEW CENTER NOTES (K.L)

 Classification: o Probable Dengue – recent travel/residency in a place with dengue epidemic; fever + 2 of the following: nausea/vomiting, rashes, muscle aches/joint pains, mucosal bleeding, positive tourniquet test – > 20 petechiae/sq. inch, CBCPC – leukopenia o Dengue with Warning Signs – abdominal pain; persistent vomiting; mucosal bleeding; clinical sign of plasma leakage (low BP); lethargy/restlessness; liver enlagement (> 2 cm); laboratory confirmation (↓platelets; ↑hematocrit) o Severe Dengue – severe hemorrhage/bleeding; severe plasma leakage; severe organ involvement (liver + kidneys)  Yellow Fever Virus  Japanese Encephalitis Virus – most common cause of viral encephalitis in Asia; vector: culex mosquito  St. Louis Encephalitis Virus  Zika Virus  West Nile Fever Virus  Hepacivirus – Hepatitis C o Retroviridae – presence of reverse transcriptase (RNA  DNA); promote effect of oncogenes  Human T Lymphocyte Virus (HTLV) – clinical manifestations: leukemia  Human Immunodeficiency Virus (HIV) – tropism: helper T cells; strains: (1) HIV 1 – Philippines; (2) HIV 2 – Africa o Reoviridae – double stranded  Coltivirus – vector: dermacentor andersoni (tick); clinical manifestations: Colorado tick fever/mountain fever  Rotavirus – most common cause of diarrheal illness in infants  Orbivirus  RNA (-) SENSE – (ParFABOR) o Paramyxoviridae  Respiro Virus a. Para Influenza Virus – aka laryngotracheobronchiolitis (LTB); signs and symptoms: barking cough  Viral Group: 1, 2, 3  Mild URTI: 4  Rubula Virus a. Mumps Virus  Host: humans  MOT: respiratory droplets  Clinical Manifestations: infectious parotitis  Complication: orchitis – inflammation of prostate glands  Mobili Virus a. Measles – Rubeola  Host: humans  MOT: respiratory droplets  Prodromes: 3 C’s – cough, coryza, conjunctivitis

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 Clinical Manifestations: morbilliform rashes all over body; Koplik spots; opposite lower molar  Complications: otitis media – most common; pneumonia – most fatal; sub sclerosing panencephalitis (SSPE) – chronic complication  Prevention: MMR vaccine – given at 9 months  Pneumovirus – Respiratory Syncytial Virus (RSV) – clinical manifestations: acute bronchiolitis (< 1 year old) Filoviridae – thread-like virus o Ebola Virus  MOT: direct contact to body fluids (ex. blood)  5 Strains: a. Zaire & Sudan – most virulent; 2014 West Africa Outbreak b. Tail Forest c. Bundibugyo d. Reston – found in Philippines and China; sourced from Philippine Macaque Monkey; does not cause disease in humans; disease in swines/pigs  Clinical Manifestations: severe bleeding in all outlets of body o Marburg Virus – came from African Green Monkey Arenaviridae o Lassa Virus – house rat o Tacaribe Complex – South American Hemorrhagic Fever  Junin Virus – Argentine Hemorrhagic Fever  Machupo Virus – Bolivian Hemorrhagic Fever  Guanarito Virus – Venezuelan Hemorrhagic Fever  Sambia Virus – Brazilian Hemorrhagic Fever  Lymphocytic Choriomeningits (LCM) – house mouse Bunyaviridae – arbovirus o Encephalitis – arbovirus; phlebo virus; la crosse virus o Hemorrhagic Fever – Harta Virus; Dobrava Virus; Sin Nombre Virus; Puumala Virus Orthomyxoviridae – influenza virus o Influenza A – most antigenically unstable  genetic rearrangement; cause of major epidemics; antigens: Haemaggglutinin (H); Neuraminidase (N) o Influenza B – may cause epidemics o Influenza C – most antigenically stable; does not cause epidemics Rhabdoviridae o Rabies Virus – helical-bullet shape  Incubation Period: 1 – 3 months (usual)  Clinical Manifestations: rabies encephalitis – 100% fatal  General Rule: a. Observation Period: 10 days b. All suspected rabid animals should be sacrificed for autopsy c. Check for negri bodies for confirmation in autopsy  Levels of Exposure a. Casual Contact – wash area with soap and water; do not give vaccine; do not give rabies immune globulin (RIG) © MANOR REVIEW CENTER NOTES (K.L)

b. Minor Scratches/Abrasions – wash area with soap and water; give vaccine; do not admin RIG c. Transdermal Wound – wash area with soap and water; administer vaccine and RIG V. ANTIVIRALS  Treatment for Respiratory Viral Infection o Neuraminidase Inhibitors – (ex. Oseltamivir; Zanamivir); for influenza A, B o Inhibitors of Viral Uncoating – (ex. Amantadine; Rimantadine); for influenza A o Ribavirin – DOC for treatment of respiratory syncytial virus infection (RSV) in children; combine with interferon alpha for treatment for Hepatitis C  Treatment for Hepatic Viral Infection – Interferon Alpha; Lamivudine – hepatitis B, HIV; Adefovir; Entecavir; Telbivudine  Treatment for Herpetic Viral Infection – Acyclovir; Cidofovir; Ganciclovir – herpes resistant to Acyclovir; Foscarnet; Fumivirsen; Penaclovir; Famciclovir; Trifluridine  Treatment for Retroviral Infections o Mode of Treatment  2 NRTI’s + 1 NNRTI’s  Lamivudine + Tenofovir + Efavirenz  Lamivudine + Zidovudine + Efavirenz o Nucleoside Reverse Transcriptase Inhibitors (NRTI’s) – end in –ine; (DAZZLE ST)  Didanosine; Abacavir; Zidovudine; Zalcitabine; Lamivudine; Emtricitabine; Stavudine; Tenofovir o Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s) – (NEED)  Nevirapine; Efavirenz; Etravirine; Delaviridine o Protease Inhibitors – end in –vir; (Trip sa SRI LANFA)  Tripranavir; Saquinavir; Ritonavir; Indinavir; Lopenavir; Ampenavir; Nelfinavir; Fosamprenavir; Alazanivir o Entry Inhibitors – Enfaviritide; Maraviroc o Integrase Inhibitors – Raltegravir

V. BACTERIOLOGY I. GRAM POSITIVE  Staphylococci o Staphylococcus aureus – acute infevtive endocarditis; catalase (+); coagulase (+); most abundant: anterior nares;  Clinical  Manifestations: abcess formation – stye, furuncle, carbuncle; food poisoning – toxic producer (enterotoxin), projective vomiting; toxic shock syndrome – sepsis, toxic shock syndrome  TTST-1 (toxin responsible), associated with child-bearing age women that uses tampons; acute infective endocarditis; osteomyelitis  Treatment: penicillins o Staphylococcus epidermis - most common microorganism on skin; most contaminant of laboratory samples; PAGE 14 OF 18

associated with infections of implants, prosthetic devices; catalase (+); coagulase (-) o Staphylococcus saprophyticus – most common cause of UTI in sexually active women  Streptococci o Streptococcus pneumonia – lancet shaped; capsulated  Quellung reaction  Clinical Manifestations: bacterial pneumonia  adults  Treatments: penicillins (amoxicillin); cephalosporins (cefuroxime) o Streptococcus mutans – α-hemolysis; clinical manifestations: dental carries sucrose -(fermentation)-> lactic acid -> destroys enamel -> dental cones o Viridans – α-hemolytic; causing subacute infective endocarditis; treatment: pen G (DOC) o Streptococcus pyogenes – only group A, β-hemolytic  Clinical Manifestations: most common cause of bacterial pharyngitis, sore throat/strep throat  Complications: peritonsilar abcess formation; functional otitis media; scarlet fever (2nd disease); rheumatic heart disease; acute glomerulonephritis  Treatments: penicillins (amoxicillin) o Streptococcus agalactiae – group B, β-hemolytic; clinical manifestations: neonatal sepsis meningitis; normal flora in vagina  Non-Spore Forming Aerobic Bacilli o Corynebacterium diptheriae – Chinese letter appearance in microscope  metachromatic granules (Babes-Ernest Bodies); clinical manifestations: diphtheria – formation of necrotic membrane, found in tonsil area, bull-neck appearance; Dacron Swab; DOC  macrolides (Erythromycin, Azithromycin); prevention: Diptheria vaccine, Pentavax  (1) D; (2) P (3) T; (4) Hep B; (5) Hib (Haemophilus Influenzae Type B) o Listeria monocytogenes – clinical manifestations: meningitis, granulomatosis infantiseptica; treatment: penicillin (ampicillin)  Spore Forming Bacteria o Bacillus (Aerobes)  Bacillus cereus  Clinical Manifestations: food poisoning  Types: o Emetic Type – associated with contaminated fried rice o Diarrheal Type – associated with saucy/meaty food  Bacillus anthracis – discovered by Robert Cobb; anthrax  Forms: o Cutaneous Anthrax – most common form; necrotic tissue, black eschar o Pulmonary Anthrax – Woolsorter’s Disease; zoonotic disease; most fatal form of anthrax; © MANOR REVIEW CENTER NOTES (K.L)

widening of mediastinum (compartment of thoracic cavity), death due to inability to breathe o Gastrointestinal Anthrax – rarest form; treatment: antibiotic (ciprofloxacin) o Clostridium (Anaerobes)  Clostridium botulinum – botolinum toxin (botox)  MOT: inhibition of 1o excitatory transfer neuron (acetylcholine)  Clinical Manifestations: flaccid paralysis; floppy baby syndrome – associated with ingestion of contaminated honey  Treatment: give antitoxin  Clostridium tetani – tennis-racket shape; tetanospasmin (toxin)  MOT: inhibition of GABA and glycine = ↑Ach  Clinical Manifestations: spastic paralysis  trismus (lock jaw), sardonic smile, dysphagia/dyspnea, muscle stiffness, opisthotonus  Treatment: antibiotic (metronidazole) – DOC  Prevention: tetanus toxoid; antitetanus serum  Clostridium perfringens – alpha toxin (toxin); clinical manifestations: gas gangrene  Clostridium difficile – clinical manifestations: pseudomembranous colitis; treatment: metronidazole (DOC) II. ACID-FAST  Mycobacterium – 1o component  mycolic acid (waxy) o Mycobacterium leprae  Clinical Manifestations: leprosy; Hansen’s disease; cutaneous tuberculosis  Forms: Description

TUBERCULOUS small number of microorganisms

Skin Lesion

erythematous; flat skin lesions

Lepromin Test

positive

LEPROMATOUS depressed cutaneous sensation; large number of microorganisms; Treatment: dapsone (DOC); rifampicin; clofazimine nodular skin lesions found in well-ventilated parts of body (ex. nose) negative

o Mycobacterium tuberculosis  Clinical Manifestations: pulmonary TB; extrapulmonary TB  Diagnosis:  Clinical Diagnosis – based on signs and symptoms  cough (> 2 weeks); unexplainable weight loss; low grade fever; night sweats; chest pain/back pain; hemoptysis  Laboratory Diagnosis o Direct Sputum Smear Microscopy (DSSM) – gold standard; submit 2 samples (consecutive days); positive result = at least 1 sample has acid-fast bacillus o Chest X-Ray (PAIL)

o PPD Skin Test/Tuberculin Skin Test – used to determine TB exposure; reading: after 48-72 hours  positive result = > 15 mm  Culture: Lowenstein-Jenssen Media – used to determine extrapulmonary TB  Prevention: TB-DOTS o 5 Pillars: (1) tool for diagnosis; (2) adequate drug supply; (3) treatment partner; (4) LGU support; (5) proper reading and monitoring o Follow Up: 2nd, 5th, 6th month of treatment o Failure of Treatment: non-compliance for more than 2 months III. GRAM NEGATIVE  Spirochetes o Treponema pallidum – MOT: sexual contact, child birth; incubation period: 3 weeks; clinical manifestations: syphilis, congenital syphilis  Syphilis  Stages: o Primary – appearance of hard chancre (painless genital lesion/ulcer); inflammation of groin area; resolves after 1 week o Secondary – latency period: asymptomatic; reactivation: rashes all over body o Tertiary – multiorgan involvement; gumma formation  Congenital Syphilis – ToRCHes; transmitted during 2nd trimester of pregnancy  STI Work Up: - Venereal Disease Research Laboratory (VDRL); Rapid Plasma Reagin (RPR); HIV test; Hepatitis B Surface antigen (HBsAg)  Clinical Manifestations: still birth; intrauterine growth restriction (IUGR); congenital defects (saddle nose; hutchinson teeth; mulberry molars; scaphoid scapula; saber skin)  Diagnosis: Serological Methods o Non-Treponemal – screening: Veneral Disease Research Lab Method (VDRL); Rapid Plasma Reagin (RPR) o Treponemal – confirmation: Treponema Pallidum Hemagglutination Assay (TPHA); Fluorescenth Treponemal Antibody Absorption (FTA-Abs)  Treatment: penicillin (DOC) o Leptospira interoggans – MOT: direct contact with leptospire infected urine; clinical manifestation: leptospirosis  Classifications:  Suspected Leptospirosis  Anicteric Leptospirosis – mild  Icteric Leptospirosis – severe; aka Weil’s Disease; triad: jaundice, hemorrhage, proteinuria

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 Treatment: doxycycline (DOC  prophylaxis and mild); pen G (severe) o Borrelia  Borrelia burgodoferi – vector: tick; clinical manifestations: Lyme Disease – bull’s eye appearance (tick bite)  Borrelia recurrentis – clinical manifestations: relapsing fever  Forms: o Epidemic – body louse (vector); humans (host) o Endemic – ticks (vector); rodents (host) Neisseriae o Neisseriae gonorrhea – gram (-); intracellular; diplococcic  MOT: sexual contact (1o); child birth  Risk of Infection:  Men – 20%; asymptomatic  Women – 50%; symptomatic  Clinical Manifestations: Pelvic Inflammatory Disease (PID); opthalmia neonatorum – blindness: < 24 hours; STI – urethritis, epidydimitis, cervicitis  Treatment: ceftriaxone; cefixime; azithromycin o Neisseria meningitides – gram (+); diplococci; coffee bean/kidney shape; clinical manifestations: meningitis; meningococcemia – fulminant stage (purpura fulminans – large ecchymoses  bullae) Bordetella Pertussis – strict aerobe o Selective Media: Bordet-Gengou Media; colony: mercury drop colony o Clinical Manifestations: pertussis – whooping cough  Stages: (1) paroxysmal; (2) catarrhal – infectious; toxin production o Treatment: macrolides (ex. azithromycin) o Prevention: DPT vaccine Haemophilus o Haemophilus infuenzae  Humans: Type B (Hib)  Clinical Manifestations: pneumonia (infants); meningitis; sepsis; osteomyelitis  Prevention: H influenza b conjugate vaccine  Treatment: vaccination  Complete – penicillin (pen G)  Incomplete – penicillin (ampicillin) o Haemophilus ducreyi – appears like a school of red fish; MOT: sexual contact; clinical manifestations: soft chancre/chancroid – painful genital ulcer/lesion; treatment: ceftriaxone (DOC), cefixime Chlamydia o Chlamydiae  Chlamydia trachomatis  MOT: sexual contact (1o); child birth  Risks of Infection: men  symptomatic; women  asymptomatic  Clinical Manifestations: pelvic inflammatory disease; ophthalmia neonatorum; blindness: > 72 hours;

trachoma; lymphogranuloma vencreum (LGV); STI: urethritis, cervicitis, precititis, epidydimitis  Treatment: tetracycline (ex. doxycycline) o Chalmydophila  Chlamydia psittaci – clinical manifestations: psittacosis  Chlamydia pneumoniae  Mycoplasma and Ureaplasma o Mycoplasma pneumoniae – wall-less; pleomorphic  1o component – sterols  Staining Method: Diene’s Staining; colony: fried egg colony  Clinical Manifestations: walking pneumonia  Treatment: tetracycline (DOC) o Ureaplama urealyticum – clinical manifestation: nongonococcal urethritis in men  Enterobacteriaceae o Shigella  Causative Agent: shigella dysenteriae; s. flexneri; s. sonnei; s. boydii  MOT: fecal-oral (associated with improper hand washing)  Clinical Manifestation: bloody dysentery – scanty stool with blood and mucus  Treatment: ampicillin (DOC) o Salmonella typhii  MOT: ingestion of contaminated poultry products (ex. chicken; eggs)  Clinical Manifestations: bacterial gastroenteritis ot salmonellosis; typhoid fever – enteric fever  rose spots – samon colored; blanching maculopapular rashes  Treatment: empirical therapy – ceftriaxone; azithromycin; severe typhoid fever – ciprofloxacin (1st line) o Escherichia coli – most common cause of UTI  Strains:  ETEC – enterotoxigenic; associated with Traveller’s Diarrhea  EPEC – enteropathogenic; associated with infantile diarrhea in 3rd world countries  EIEC – enteroinvasive; associated with shigella-like diarrhea  EAEC – enteroaggregative; associated with diarrhea in immunocompromised individuals  EHEC – enterohemorrhagic; aka O157:H7 strain; hemolytic uremic syndrome (HUS)  Pseudomonas aeruginosa – obligate aerobe; oxidase (+) o Clinical Manifestations: wound infection/burn wound infection (pigment: pyocyanin, pyoverdin; odor: grapelike/sweet-taco-corn like); sepsis – skin lesion: ecthyma gangeonosum; pneumonia  atypical o Treatment: penicillin (ex. carbenicillin; ticarcillin; piperacillin); cephs (ex. ceftazidine; cefoperazone)

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 Campylobacter and Helicobacter o Campylobacter jejuni – j-shape/gull-wing shape; MOT: fecal-oral; clinical manifestation: bloody diarrhea; treatment: macrolides (ex. azithromycin) o Helicobacter pylori – urease (+)  Clinical Manifestations: gastric carcinoma; peptic ulcer disease (gastric – 70%, nocturnal pain; duodenal – 90%, pain is relieved by food  obese patients)  Diagnosis: endoscopy – gold standard; urea breathe test – urea –(urease)-> ammonia  Treatment:  Monotherapy  Double Therapy  Triple Therapy – PPI + 2 ABX (clarithromycin; amoxicillin; metronidazole)  Quadriple Therapy – PPI + 2 ABX + surface coating agent (sucralfate; rebamipide)  Vibrionaceae o Vibrio cholerae  MOT: fecal-oral  Clinical Manifestations: cholera – osmotic type diarrhea  rice watery stool  Diagnosis: selective media  TCBS – colony: yellow colony  Treatment: fluoroquinolones (ex. ciprofloxacin) o Vibrio parahemolyticus – MOT: ingestion of raw shell fish; clinical manifestations: cholera-like diarrhea; TCBS: green colony o Vibrio vulnificus – clinical manifestations: mild URTI, wound infection; TCBS: blue-green colony

VI. PARASITOLOGY

Amebiasis

Fresh Water Amoeba

Acanthamoeba castellani

I. PROTOZOAN – unicellular; free-living  Phyla: o Sarcomastigophora  Sarcodina > Pseudopods  Mastigophola > Flagella o Cillophora – cilia; (ex. Balantidium coli – spherical shape ulcer) o Apicomplexa o Microspora

CLINICAL MANIFESTATION amebic dysentery; amebic liver abcess

TREATMENT

dysuria; burning sensation during urination; severe vaginal pruritis; yellow-green/yellow curdy vaginal discharge with fishy odor cervical lymphadenopathy; retinitis

Metronidazole (DOC)

Metronidazole (DOC); Tinidazole; Iodoquinol Primary amebic meningoencepalopathy (PAM) Granulomatous amebic encephalopathy (GAE) traveller’s diarrhea; Metronidazole gay bowel syndrome (DOC) abdominal pain; foul –smelling diarrhea; malabsorption of adek (steatorrhea) abdominal pain; Co-Trimoxazole nausea and vomiting; (DOC) diarrhea

Giardiasis

Giardia lamblia

fecal-oral

Cyclosporidiasis

Cylcospora cayetanensis

Trichomoniasis

Trichomonas vaginalis

ingestion of cystcontaminated fruits and vegetables sexual contact

Toxoplasmosis

Toxoplamsa gondii

Malaria

Vector: anopheles mosquito (female) Causative Agent: Plasmodium spp.  Plasmodium falciparum – 50%; most virulent; malignant tertian malaria  Plasmodium vivax – 40%; benign tertian malaria  Plasmodium malaria – 10%; quartan malaria  Plasmodium ovale – rarest form; benign tertian malaria Life Cycle: sporozoites  merozoites (liver) ↔ trophozoites (erythrocytes)  gametocytes Treatment:  chloroquine + Fansidar® (sulfadoxine + pyrimethamine) – DOC as first line agent for P. falciparum  non-resistant and severe  arthemeter + lumenfantrine – DOC as second line treatment for plasmodium resistant to first line  quinine + doxycycline – DOC as third line agent for SEVERE malaria  primaquine – radical cure; DOC to prevent transmission and relapse  chloroquine – DOC for erythrocytic stage of malaria; DOC for P. vivax Vector: sand fly Causative Agent: Leishmania spp.  Leishmania tropica, L. Mexicana – cutaneous leishmaniasis  Leishmania brasiliensis – mucocutaneous leishmaniasis (espundia)  Leishmania donovani, L. chagasi – visceral leishmaniasis (Kala-azar) Treatment: Stibogluconate Trypanosiomasis Trypanosoma tse-tse fly West African Non-Nervous: brucei Suramin, gambiense Pentamidine Trypanosoma East African Nervous: brucei Melarsprol rhodesiens Typanosoma kissing bug Chaga’s disease Nifurtimox; cruzi Benznidazole

Leishmaniasis

African Trypanosomiasis

 Branches  protozoology & helminthology

CAUSATIVE MOT AGENT Entamoeba fecal-oral histolytica Entamoeba dispar Naegleria fowleri

American Trypanosomiasis

inhalation of cyst from cat’s feces; ingestion of raw pork

Sulfadiazine + Pyrimethamine (DOC); Clindamycin (Alternative)

II. HELMINTHOLOGY  Platyhelminthes – flatworms; trematodes (flukes); cestodes (tapeworm)  Roundworms – nematodes I. NEMATODES Ascariasis – aka giant intestinal roundworm Strongloidiasis – aka thread worm Hookworm

Trichinellosis

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CAUSATIVE AGENT Ascaris lumbricoides Stronglyoides stercoralis Necator americanus (New World); Ancylostoma duodenale (Old World) Trichinella spiralis

MOT

CLINICAL MANIFESTATION

ingestion of eggs

TREATMENT Albendazole; Mebendazole

direct penetration into skin of larvae direct penetration of larvae into skin

massive autoinfection

Ivermectin

iron deficiency anemia

Albendazole; Mebendasone

ingestion of eggs encysted in raw pork

muscle aches

Albendazole; Mebendazole

© MANOR REVIEW CENTER NOTES (K.L)

Whip Worm Enterobiasis

Onchocerca Volvus Filiriasis

Trichuris trichiuria Enterobius vermicularis (Human Pinworm) Onchocerca Volvus Wuchereria bancrofti; Brugia malayi

ingestion of eggs

rectal prolapse

ingestion of eggs

severe nocturnal perianal itching

black fly (vector)

river blindness

mosquito bites

elephantiasis; tropical eosinophilia

Albendazole; Mebendazole Pyrantel pamoate; Albendazole; Diagnosis: scotch tape swab test Ivermectin Diethylcarbamazine

II. TREMATODES  Schisotomiasis o Causative Agent: Schistosoma japonicum; S. mansoni (liver); S. haematobium (urinary bladder) o MOT: direct penetration of cercariae into skin o Clinical Manifestations: swimmer’s itch; katayama fever; liver cirrhosis; portal HTN  ascites o Treatment: praziquantel III. CESTODES Taenia solium Taenia saginata Diphyllobothrium latum Hymenolepis nana

COMMON NAME pork tapeworm beef tapeworm fish tapeworm dwarf tapeworm

MOT Ingestion of raw pork Ingestion of raw beef ingestions of eggs  raw fish ingestion of eggs

CLINICAL MANIFESTATION neurocystecercosis GI disturbances Vitamin deficiency

B12

TREATMENT Niclosamide; Praziquantel Praziquantel Praziquantel Praziquantel

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