2019

Microbiologia

Microbiologia

An integrated and conceptual approach to Special Microbiology and Chemotherapy Editor: Azhar Hussain, Muhammad Hamid Qayyum Microbiologia i Microbiologia ii

First Edition

Author: Azhar Hussain Baloch BSc, MBBS (3rd Year) Ameer Ud Din Medical College, PGMI, Lahore

Co-Author: Muhammad Hamid Qayyum MBBS (4th Year) Ameer Ud Din Medical College, PGMI, Lahore Microbiologia iii

This book is dedicated to Hazrat Muhammad (SAW), Hazrat Imam-e-Hussain Ibn-e-Ali (R.A), Our Parents and Our Teachers.

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How to Use This Book- 1. Sit to learn something new! 2. Just have a glance through an organism for just 1 minute. 3. Watch a Sketchy Micro Video. 4. Just give a read and try to save it as pictorial memory along with clinical correlation, Boom!

The Salient Features of the Book: The shortest and most comprehensive book ever written in Microbiology and Chemotherapy Professional exams and USMLE oriented content Point to point description of Special Features, Reservoir, Transmission, Pathogenesis, Diseases, Lab Diagnosis, Drug of Choice and Prevention of a particular organism. Key distinguishing and diagnosing points of various organisms spotted. Chemotherapy in just 4 pages. 7 days treatment for Special Microbiology and Chemotherapy for any Competitive Exams. Important MCQs, SEQs and VIVA Points Fruitful for MBBS, BDS, DPT, Optometry and other allied sciences. Microbiologia v

Preface to the First Edition

The need for having a simple but comprehensive book with basic principles of microbiology which can satisfy all the needs of our examination system as well as competitive exams i.e. USMLE, AMC, PACES etc, has been felt since long. A sincere attempt has been made with the idea of fulfilling the requirements of present-day curriculum as well as competitive exams i.e SEQs,MCQs, VIVA Questions and OSPE. The script of the book is formatted in such a way that it will be suitable not only for medical students, but also for dental students and the students of allied health subjects like Physiotherapy, Occupational Therapy, Pharmacy, Nursing, Speech, Hearing and Language, etc. An attempt is made to describe the microbiology system vise and related clinical aspects with each system for the 3rd year students. Most of the figures are given in schematic form to enable students to understand and reproduce the facts. The sections of special features, pathogenesis, diseases, diagnosis and treatment for each microbe will help the students preparing for examinations. You can simply refer it as “MICROMA” for microbiology like Pathoma. However, it will be ideal for the students to read each section thoroughly before referring to the questions. We will be very happy to receive opinions, comments and valuable suggestions from all our senior colleagues, fellow teachers and students so that, every aspect of the book can be reviewed in succeeding editions.

Azhar Hussain Baloch [email protected] MBBS (3rd Year) Ameer Ud Din Medical College, PGMI, Lahore Muhammad Hamid Qayyum MBBS (4th Year) Ameer Ud Din Medical College, PGMI, Lahore

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Table of Contents

I. Special Bacteriology ...... 01 1. Quick Reference Chart ...... 01 2. Gram Positive Algorithm ...... 02 3. Gram Negative Algorithm ...... 03 4. Gram Positive Cocci ...... 04 5. Gram Positive Rods ...... 07 6. Gram Negative Cocci ...... 13 7. Gram Negative Rods ...... 15 8. Gram negative rods associated with Animal/Human bites ...... 24 9. Spirochetes ...... 25 10. Obligate Intracellular Organisms ...... 26 11. Bacterial Genetics ...... 28 II. Antimicrobials ...... 30 1. Antimicrobials Algorithm ...... 30 2. Cell Wall Synthesis Inhibitors ...... 31 3. Protein Synthesis Inhibitors ...... 33 4. Nucleic Acid Synthesis Inhibitors ...... 35 5. Antimycobacterial Drugs ...... 36 III. Fungi ...... 37 1. Systemic Mycoses ...... 37 2. Opportunistic Mycoses ...... 39 3. Superficial Infections ...... 41 4. Cutaneous Infections ...... 41 5. Subcutaneous Infections ...... 41 IV. Antifungals ...... 42 V. Parasites ...... 43 1. Protozoa ...... 43 2. Trematodes ...... 49 3. Cestodes (tapeworms) ...... 49 4. Nematodes (roundworms) ...... 51 VI. Antimalarials ...... 53 VII. Antiprotozoals ...... 53 VIII. Virology ...... 54 1. DNA Viruses ...... 54 2. +ssRNA Viruses ...... 56 3. -ssRNA Viruses ...... 58 IX. Antivirals ...... 60

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Microbiologia 1

Special Bacteriology Quick Reference Chart Encapsulated Catalase  Oxidase  Urease  Obligate Aerobes Culture media Strep (pneumo & GBS) Pseudomonas Campylobacter Proteus Nocardia Haemophilus Chocolate agar (factors V & Klebsiella Listeria Pseudomonas Ureaplasma Pseudomonas Neisseria X) Thayer Martin (VPN*) Haemophilus Aspergillus Vibrio Nocardia M. tuberculosis Bordetella Bordet-Gengou Pseudomonas Candida Helicobacter Cryptococcus Bacillus anthracis C. diphtheriae Tellurite, Loffler’s Neisseria E.coli Legionella Helicobacter Obligate Anaerobes M. tuberculosis media Lowenstein- Cryptococcus Staph aureus Neisseria Epidermidis Mycoplasma pneumo Jensen Eaton’s agar Clostridium E. Coli Serratia Saprophyticus Legionella Buffered Charcoal Yeast Bacteroides Salmonella (Enterobacteriae Klebsiella Fungi Extract Sabouraud’s agar Actinomyces are negative) Some Killers Have Pretty PLACESS for Ox Can Pull Very PUNCHES Kill Aerobes—Nagging Pests Special stains Nice Capsules (Even your Cat Heavy Loads Must Breath Giemsa Chlamydia, Borrelia, Rickettsia, Trypanosomes, Salmonella) Nonstop Plasmodium Anaerobes—Can’t Breathe India ink Cryptococcus neoformans Air Acid Fast Mycobacterium, Nocardia (partial) *VPN= Vancomycin (kills gram positive), Polymyxin (kills gram neg except Neisseria), Nystatin (kills fungi)

Toxin comparisons ADP ribosylation of eEF<2 Inactivate 60s ribosome subunit ADP ribosylation of Gs (cAMP) Act as adenylate cyclase C. diptheriae EHEC ETEC (heat labile toxin) B. pertussis (adenylate cyclase toxin) Pseudomonas Shigella Vibrio Cholera B. anthracis (edema factor)

Microbiologia 2 Microbiologia 3 Microbiologia 4

Gram  stains violet

Gram Positive Cocci Staphylococcus (facultative anaerobes)  Cocci in clusters (grapes) , non motile and do not form spores  Catalase  Streptococcus  Cocci in chains  Catalase negative  Facultative anaerobes S. aureus (Coagulase ) Features Pathogenesis Diseases Treatment  Small yellow/golden  Protein A— inhibits opsonization Skin— (pathogenicity= exfoliatins/coagulase) DOC colonies on blood agar (binds Fc component of IgG and  ImpetigoErythematous papules to bullae (blisters w/ clear fluid)  Nafcillin due to pigment prevents phagocytosis)  Scalded Skin SyndromeDiffuse epidermal peeling (destroys  Oxacillin ―staphyloxanthin‖  Polysaccharide capsule keratinocyte attachments in stratum granulosum)  -hemolytic  TSST<1— (Toxic shock syndrome  Abscess/mastitisSubcutaneous tenderness, redness, swelling,central MRSA  Ferments mannitol on toxin-1) superantigen binds MHC II necrosis,usually drain to outside(furuncles,boils etc)  Vancomycin mannitol salt agar  Coagulase— converts fibrinogen to  Surgical infections( MCC)Fever w/ cellulitis fibrin clot (can hide out in blood clots)  Folliculitis most common cause VRSA Reservoir   hemolysis)  Toxic shock syndrome Fever, hypotension, scarlantiniform rash nasal mucosa and (particularly palms and soles, innumerable small red papules diffusely  Linezolid  Exfoliatin—protease skin distributed), multiorgan failure that cleaves desmoglein Transmission  Infective endocarditis (acute)  2nd MCC overall and MCC in IVDA) Fever, Gastroenteritis is self ‗epidermolytic (scalded  Hands, sneezing malaise, leukocytosis, heart murmur (tricuspid regurg) limiting skin syndrome/bullous  Surgical wounds  Pneumonia Salmon colored sputum, rapid onset, high rate of necrosis, impetigo)  Food: custard, potato salad, high fatality: **MC postantibiotic  Causes biofilms to grow on plastic devices placed within the body (IV DOC  Novobiocin Sensitive treatment largely ineffective, and catheters and medical prostheses)  Vancomycin +  Infections are always implants must be removed)  Most common cause of cerebrospinal fluid shunt infections aminoglycoside hospital acquired  Infective endocarditis MCC of patient with prosthetic valves *Must remove or replace Normal flora of skin infected implant Microbiologia 5 S. saprophyticus (Coagulase )  Usually non hemolytic  Adhesins (lactosamine structure)  Honeymoon cystitis UTI’s in newly sexually active females when DOC  Novobiocin Resistant facilitate adherence to urothelium bacteria is displaced from the normal flora into the urethra  Trimethoprim- (within 24 hrs) sulfamethoxazole (TMP< Normal flora of female genital  2nd most common cause of UTI in sexually active females (#1 E.Coli) SMX) tract  Quinolones

S. pyogenes (Group A) Features Pathogenesis Diseases Treatment   Pharyngitis Abrupt onset of sore throat, fever, malaise, headache,  Rapid Strep test (ELISA- classification antiphagocytic most imp. tonsillar abscesses, tender anterior cervical lymph nodes based)  PYR  Virulence factor (M12 strains  Scarlet fever Pharyngitis followed by:  ASO titer >200 is (pyrrolidonyl assoc. w/ acute o Blanching ―sandpaper rash‖(spares palms and soles, however significant for RF arylamidase) glomerulonephritis desquamation of palms and soles is common) Anti DNase B titer  Bacitracin Sensitive  C carbohydrate (basis of o Strawberry tongue, nausea/vomiting indicator for acute lancefield classification) o Circumoral pallor (paleness around mouth) glomerulonephritis Reservoir  Streptolysin O— immunogenic o Fever and rash mediated by exotoxins DOC  Human throat and skin (creates antibodies, allows it to be  Impetigo Pyogenic skin infection (honey crusted lesions)  Beta lactam drugs assayed= ASO titer)  Necrotizing fasciitis rapid, amputation, high mortality  (Macrolides for allergy) Transmission  Streptolysin S—not immunogenic Non-suppurative sequelae to infection: Consider prophylactic  Direct contact  DNase  Rheumatic fever (Type 2 hypersensitivity) Antibodies to heart tissue 2 antibiotics for 5 years post  Respiratory droplets weeks post-pharyngitis (fever, joint inflammation, carditis, erythema acute RF Spreading Factors marginatum, chorea) Jones criteria for RF  Streptokinase—breaks fibrin clot  Acute glomerulonephritis (M12 serotype) (Type 3 hypersensitivity) Joints  Streptococcal DNAse—liquefies pus Post skin infection; immune complexes bound to glomeruli (HT, ♥(carditis)  Hyaluronidase—hydrolyzes ground pulmonary edema, smoky urine) Nodules (subcutaneous) substance of connective tissue

 Exotoxins A

Microbiologia 6 S. pneumoniae Features Pathogenesis Diseases Treatment  Lancet shaped dipplococci  Polysaccharide Capsule—major MCC Adult Meningitis Peptidoglycan and teichoic acids are highly DOC   Optochin Sensitive Septicemia MCC death in Sickle cell children  Meningitis: ceftriaxone  Lysed by bile  IgA protease— colonizing factor  Otitis media/sinusitis: aids in attachment to respiratory MCC Otitis media and sinusitis in children amoxicillin + Reservoir mucosa by cleaving immunoglobulins (can lead to cerebellar/temporal lobe abcesses) clavulanate (erythro Upper respiratory tract (also in: Neisseria, Haemophilus) 1. Strep Pneumo for allergy) 2. H. Influenza Transmission  Pneumolysin O—damages respiratory 3. Moraxella catarrhalis Vaccine Respiratory droplets epithelium and inhibits respiratory  Pediatric—Conjugated burst/ classical complement fixation MCC Typical pneumonia shaking chills, high fever, lobar consolidation, to diptheria toxoid w/ blood tinged ―rusty sputum‖ (due to pneumolysin O) 13 MC invasive  Techoic acid Leading cause of sepsis in aslenic patients serotypes  Adult (>65 years)— Predisposing Factors—Antecedent MOPS= Meningitis, Otitis media, Pneumonia, Sinusitis Polysaccharide vaccine influenza/measles infection, COPD, CHF, w/ 23 MC serotypes Alcoholism, Asplenia,sickle cell Diagnosis (for elderly, AIDs, anemia,nephrosis  Quellung  reaction (swelling of capsule) asplenics, sickle cell)  Lattex particle agglutination (tests for capsular antigen)

Viridans Streptococci (S. Sanguis, S. mutans)  

Transmission= endogenous

Microbiologia 7 Gram Positive Rods Sporelymphadenopathy  Gram stain, serology, PCR  Polypeptide capsule antiphagocytic glutamate  Wool Sorter‘s disease (Pulmonary) Life threatening pneumonia: cough, DOC  Potential biowarfare agent Anthrax toxin fever, malaise, facial edema, cyanosis, shock with mediastinal hemorrhagic  Ciprofloxacin or  Protective antigen— (immunogen) lymphadenitis ,Mediastinal widening is imp. Diagnostic criterion Doxycycline Reservoir mediates entry of LF/EF into cells  Animals, skin, soil  Lethal factor—cleaves  Gastrointestinal anthrax rare, edema + blockage of GI tract, Toxoid vaccine given to phosphokinase (activator of MAPK bloody diarrhea/vomiting, high mortality high risk occupations Transmission pathway controlling cell growth) thus  Contact w/ infected animals reduce cell growth Population at risk: postal workers, farmers, veterinarians or inhalation of spores  Edema factor—adenylate cyclase  Not spread from person to (calmodulin activated like pertussis person adenylate cyclase) B. cereus Reservoir= nature  Emetic toxin—preformed, fast (fried  Gastroenteritis nonbloody, Diagnosis Transmission rice 1-6 hrs)  Emetic type (fried rice) similar to s. aureus.  Clinical  Reheated Fried rice from  Diarrheal toxin—prod in vivo  Diarrheal type (meats/sauces) similar to LT of ETEC. Chinese (meats/sauces 18 hrs) cAMP= Tx= self limiting buffet, meats/sauce watery diarrhea

Clostridium (Anaerobic) C. tetani  Produces Tetanus toxin  Tetanospasmin—tetanus toxin  Tetanus Risus sardonicus (sardonic grin), Opisthotonus (hyperextension  TIG (tetanus produced by germination of spores in of back), Lock jaw/tingling (first sign), extreme muscle spasms immunoglobulin) to Reservoir= soil the tissues neutralize toxin plus Tetanus prone wound metronidazole or Transmission  Toxin carried intra-axonally to CNS  Blunt, burn, frostbite, w/ contaminants 1 cm deep and > 6 hrs old penicillin  Puncture wounds/trauma binds to ganglioside receptors  Vaccine (if >5yrs since last booster) + TIG (if vacc history unknown)  Contaminated w/ soil Blocks release of inhibitory NT  Spasmolytic drugs  Requires low tissue O2 glycine/GABA at spinal synapses Not tetanus prone wound (diazepam); debride; Neonatal tetanus excitatory neurons unopposed=  Linear, 1 cm deep, no contaminants, < 6 hrs old  delay closure .contaminated umbilicus or extreme muscle spasms  Vaccine if > 10 years since booster (or history unknown) circumcision wound Microbiologia 8 C. botulinum Features Pathogenesis Diseases Treatment  Produces Botulinum Toxin  Spores survive in soil and dust; Forms of Botulism  Respiratory support in germinate in moist, warm, nutritious,  Adult—Preformed toxin ingested (alkaline vegetables—canned green all cases Reservoir= soil/dust but nonacidic and anaerobic beans, smoked fish); 1-2 day onset weakness, dizziness, blurred vision,  Antitoxin for adults, conditions flaccid paralysis, nausea, diarrhea, vomiting hyperimmune human Transmission serum for infants  Food (canned vegetables,  Botulinum toxin (lysogenic phage  Infant—Spores ingested (honey, dust), toxin produced in gut; constipation,  Antibiotics may worsen smoked fish, honey for encoded)—polypeptide neurotoxin ―floppy baby‖ flaccid paralysis, diplopia, poor feeding, crying or prolong symptoms infants) (A B types MC), heat labile  Traumatic implantation  Wound—Traumatic implantation of spores (IVDA) in vivo production of Prevention  MOA—Absorbed by gut blood to toxin; weakness, dizziness, flaccid paralysis (no GI symptoms)  Proper canning/heating peripheral nerve synapses Blocks  Descending paralysis occurs in contrast to ascending paralysis that of vegetables release of ACh at neuromuscular occurs in GBS(Campylobactor jejuni)  No honey first year junction flaccid paralysis Note: the flaccid paralysis is reversible C. perfringens  Nonmotile  Spores germinate in anaerobic Gas gangrene (myonecrosis) mediated by alpha toxin Gangrene:  ―Stormy fermentation‖ in conditions in tissue  Contamination of wound w/ soil or feces  Debridement milk media  Alpha toxin (phospholipase C)—  Acute/increasing pain at site  delayed closure  Double zone of hemolysis (produced by vegetative cells) a  Tense tissue (edema, gas= crepitation) and exudate  Clindamycin+ penicillin lecithinase which disrupts membranes,  Fever, tachycardia  hyperbaric chamber Reservoir= soil, colon cells, etc  massive hemolysis, tissue  Rapid, high mortality  Prevent w/ extensive destruction (gamma toxin)  Other imp. Causes include MRSA and streptococcus pyogenase debridement+ penicillin Transmission Traumatic implantation  Nagler Reaction—(egg yolk agar) Food poisoning Food poisoning Food (Reheated meat dishes) identifies alpha toxin using antitoxin  Reheated meat dishes;  Self-limiting on one side  Organism grows to high numbers (8-24hrs incubation)  Enterotoxin—produced in gut,  Enterotoxin produced in gut disrupts ion transport; heat labile  Self-limiting noninflammatory watery diarrhea  12 other toxins damage tissues C. difficile Reservoir= colon/GI tract  Toxin A—enterotoxin damaging Antibiotic associated diarrhea, colitis, or pseudomembranous colitis (yellow DOC mucosa leading to fluid increase; plaques on colon; necrosis, exudates, fibrin, leukocytes)  Metronidazole Transmission granulocyte attractant  Clindamycin  Oral Vancomycin (if no  Endogenous  Cephalosporins other drug available)  Long term broad spectrum  Toxin B—cytotoxin: actin  Amoxicillin, Ampicillin  Discontinue antiobiotic antibiotic therapy depolymerization and loss of  Toxic megacolon can occur and surgical resection of bowel is necessary in therapy cytoskeleton integrity such cases  Visualized by sigmoidoscopy Isolate symptomatic nursing home patients; Caution in over-prescribing broad spectrum antibiotics (consider limited autoclave bed pans spectrum first)

Check for C. diff toxin in stool Microbiologia 9 NonCorynebacterium diphtheria  Aerobic, nonmotile  Diptheria toxin (A-B component) Diptheria DOC:  Gray black colonies of club< lysogenic phage encoded—inhibits  Sore throat w/ dirty gray pseudomembrane (bleeds easily)  Erythromycin and shaped rods in V/L shapes protein synthesis by adding ADP-  Bull neck (extremely swollen—potential respiratory obstruction) antitoxin (Chinese letter formation) ribose to eEF-2 (similar to  Recurrent laryngeal nerve palsy, lower limb polyneuritis  Tellurite medium pseudomonas)  Myocarditis, cardiac dysfunction (most likely cause of death) Endocarditis  Granules (volutin) on  Shick

Transmission  Bacteria/phage via respiratory droplets

Microbiologia 10 Actinomyces israelii Features Pathogenesis Diseases Treatment  Anaerobic  Invasive growth in tissues with Actinomycosis  Gram  branching bacilli  Branching rods compromised oxygen supply  Non-painful but very invasive (penetrating all tissues) w/ sulfur granules =  Tissue swelling draining abscesses (sinus tracts) w/ sulfur granules in diagnostic Reservoir= normal flora exudate (hard yellow microcolonies; for diagnosis)  Gingival crevices  Cervicofacial (lumpy jaw) dental trauma or poor hygiene DOC  Female genital tract  CNS solitary brain abscess (Nocardia produces multiple foci)  Ampicillin or penicillin  Thoracic (aspiration w/ spread), Pelvic (from thoraci or IUDs), Abdominal G, plus surgical drainage Transmission= endogenous (surgery or bowel trauma) Nocardia (N. asteroides, N. brasiliensis)  Aerobic  Predisposition in immune Cavitary bronchopulmonary nocardiosis (N. asteroides) Diagnosis—sputum or  Branching rods compromised (transplant patient)  Cough, fever, dyspnea, localized or diffuse pneumonia w/ cavitation pus culture  Partially acid fast (some and cancer  May spread hematogenously to brain (abscesses< multiple foci) blue and some red on stain) Cutaneous/Subcutaneous Nocardiosis (N. brasiliensis) DOC  Traumatic implantation Cellulitis w/ swelling—draining subcutaneous  TMPstaining of sputum (zeihl-nelson or kenyon version) Auramine staining can be used for rapid diagnosis 2.culture of specimen on Lowenstein –Jensen agar (for 8 weeks) or liquid BECTAC medium Containing radioactive metabolites (for 2 weeks) Liquid medium is preferred because of rapid detection and more reliability.M.Tuberculosis produces niacin and catalase +ve in contrast to other mycobacteria M. Tuberculosis does not grow on blood agar 3.NAAT tests detects DNA and RNA of organisms 4.Gene expert confirmatory method 5.LUCIFERASE assay for detecting drug resistant organisms For latent infections 1.Interferon –Y release assay 2.PPD skin test M. leprae Features Pathogenesis Diseases Treatment  Acid fast rods (seen in  Obligate intracellular parasite Leprosy (Hansen‘s disease) Diagnosis punch biopsy)  Cooler parts of body Tuberculoid (Paucibacillary) Lepromatous (Multibacillary)  Punch biopsy or nasal  Obligate intracellular  Replicates intracellularly in skin Strong CMI (TH1) Weak CMI (TH2) scrapings acid fast parasites (cannot be histiocytes, endothelial cells , schwann Lepromin test  Lepromin test   Cannot be cultured cultured in vitro) cells of the nerves Low number of organisms High number (foam cells filled) DOC  Optimal growth at less than  Involves two processes: Damage due to CMI killing infected Damage due to large number of body temp  Dapsone + rifampin  1. Direct contact with bacterium cells intracellular organisms  Phenolase   2. Cell mediated immune attack  Granulomas nerve damage/  Overgrowth in cells nerve (clofazimine added for enlargement damage lepromatous) Reservoir  Sensation loss burns/trauma  Sensation loss burns/trauma  Mucosa, skin, nerves (Dapsone for close family Symptoms Symptoms  Armadillos in contacts—can cause  Fewer lesions; macular  Numerous lesions; nodular Texas/Louisiana hemolysis in G6PD  Nerve enlargement  deficiency)  Paresthesia Transmission  Destruction of nasal septum (saddle nose)  Nasal discharge from  Leonine (lion

Mycobacterium other than tuberculosis (MOTTs)  Atypical mycobacteria commonly found in southeastern U.S.  Noncontagious, found in surface waters, soil, cigarettes Organism Transmission Disease/Presentation Diagnosis Treatment M. aviumBlood culture— grows at 41°C) ethambutol, & rifampin Lung involvement resembles TB (fever, chills, etc) Prophylaxis for AIDS Reservoir- aerosolized Seen in AIDS, cancer, chronic lung disease patients at <50 CD4 with water, dust, soil, cigarettes Azithromycin or Clarithromycin Microbiologia 12 M. kansasii Resembles pulmonary tuberculosis Photochromogen (pigment Rifampin, ethambutol, Seen in AIDS, organ transplants, silicosis, hairy cell when exposed to light) isoniazid, & pyridoxine for leukemia, chronic bronchitis, COPD 12 months M. scrofulaceum Contaminated water sources Painless solitary cervical lymph node in children Scotochromogen (pigment Surgery (scrofula) with overlying bluish-purple color when exposed to dark) (Scrofula in adult most likely secondary TB) M. marinum Abrasion to extremity in Soft tissue infection ―fish tank granuloma‖ seen in Photochromogen Clarithromycin + non-chlorinated water tropical fish enthusiasts (purple papule) ethambutol Microbiologia 13 Gram  stain pink Gram Negative Cocci

Neisseria  Kidney-bean shaped diplococci w/ flattened sides  Oxidase  (test turns black)  Glucose  fermentation  Capsule= Lipooligosaccharide (as compared to Lipopolysaccharide in other bacteria) N. meningitidis ( maltose fermentation) Features Pathogenesis Diseases Treatment  Large capsule latex  Oropharyngeal colonization; spreads to Meningitis and meningococcemia (MCC children/young adults) DOC children/adults particle agglutination meninges via bloodstream  Abrupt onset of fever, chills, malaise  Ceftriaxone  Chocolate agar growth  Polysaccharide capsule— (B  Prostration (stretched in prone position; weakness)  Cefotaxime (with 5% CO2) strain MC but not immunogenic=  Stiff neck (nuchal rigidity), vomiting, photosensitivity  Prophylaxis of close  Ferments maltose no vaccine)  Generalized petechial rash (including palms and soles) in later stages (NOT contacts rifampin (or  IgA1 protease— allows colonization a good sign) ciprofloxacin) Reservoir in oropharynx DOC neonates  Nasopharynx (5-10%  Endotoxin (LOS)— causes fever, Fulminant cases ecchymoses, DIC, shock, coma, death (Waterhouse<  Cefotaxime, ampicillin carriers) septic shock, overproduction of outer Friedrichsen syndrome—rapid hemorrhage into adrenal glands adrenal membrane insufficiency) Vaccine Transmission  Pili— help colonize and invade  Capsular polysaccharide  Respiratory droplets  C5Gonorrhea Complications DOC  Thayer Martin medium attachment to Males urethritis, proctitis, septic Epididymitis, prostatitis, urethral  Ceftriaxone (test for (chocolate agar w/ VPN mucosal surfaces; inhibit phagocytosis; arthritis (knee MC) strictures Chlamydia , syphilis) antibiotics to prevent antigenic variation Females  endocervicitis, Fallopian tube scarring normal flora growth) Outer membrane proteins— Pelvic inflammatory disease, (infertility, ectopic pregnancy), Prevention  PCR  OMP I (for serotyping) septic arthritis (knee MC) Fitz

Moraxella catarrhalis (close relative of Neisseria) Reservoir= Normal flora  Endotoxin may play role in disease  Otitis media (3rd MCC) DOC  Upper respiratory tract  Sinusitis (3rd MCC)  Amoxicillin + Clavulanate Transmission  Bronchitis and bronchopneumonia in elderly w/ COPD  Respiratory droplets Microbiologia 15 Gram Negative Rods AEROBIC (Pseudomonas, Legionella, Francisella, Bordetella, Brucella) Pseudomonas aeruginosa (Obligate aerobe) Features Pathogenesis Diseases Treatment  Oxidase   Glycocalyx capsule/slime layer—  Healthy Hot tub folliculitis, otitis externa (swimmer‘s ear— Diagnosis  Motile, Non-lactose allows formation of pulmonary malignant Otitis Externa in diabetics), GI (loose stools), corneal infections  Gram stain and culture fermenter on microcolonies; antiphagocytic (trauma, prolonged contact wear)  Oxidase  MacConkey/EMB  Endotoxin (LPS)—causes  Motile, Non-  Fluorescein and inflammation in tissues and shock in  Diffuse bronchopneumonia in Neutropenic, burn patients [recurrent in lactose Pyocyanin septicemia Cystic Fibrosis—(slime-producing strains, biofilm)] fermenter on (blue-green pigment on TSA  Exotoxin A—ADP ribosylation of eEF- MacConkey/E agar) 2; inhibits protein synthesis (similar to  Most common cause of ventilator associated pneumonia MB  Grapeecthyma gangrenosum in neutropenic patients Pyocyanin Reservoir (Elastases+ Proteases) (black, necrotic center w/ erythematous margins) (blue-green pigment on  Ubiquitous in water TSA agar) Are histotoxic and facilitate invasion  Cellulitis w/ blue green pus in Burn patients (GI tract colonization, skin,  Grape 55 yrs w/ high alcohol  High mortality without treatment immunocompromised) intake Reservoir  Immunosuppressed patients  Pontiac Fever Prevention—routine  WATER (rivers, streams, air< Young person w/ pneumonitis decontamination of air conditioners, produce Can go untreated conditioner cooling tanks misters) Transmission Diagnosis DFA (direct fluorescent antibody) on biopsy, by silver stain Microbiologia 16

 Inspired aerosolized H2O Antigen can also be detected in urine  NOT PERSON TO PERSON!! Francisella tularensis (requires cysteine) Reservoir= animals  Facultative intracellular pathogen— Tularemia DOC  Rabbits, deer, rodents localizes in reticuloendothelial cells  Ulceroglandular form Tick bite or traumatic implantation while  Streptomycin (granulomatous response—type IV skinning rabbits (ulcer with black base, fever, regional lymph node  Doxycycline Transmission hypersensitivity) enlargement and necrosis)  Tick bite (dermacentor)  Pneumonial form inhalation of aerosol from skinning rabbits Vaccine  Skinning rabbits (implant or Highest in Arkansas, Missouri  Typhoidal form ingestion of infected meat or contaminated water  Live, attenuated for high inspiring aerosol) Potential biowarfare agent as aerosol risk (vets, forest ranger,  Undercooked meat *Rabbit hunter from Arkansas* hunter) Brucella (B. abortus, B. melitensis, B. suis) (requires cysteine) Features Pathogenesis Diseases Treatment Reservoir= livestock  Facultative intracellular pathogen— Brucellosis (undulant fever) DOC  Cattle (abortus) localizes in reticuloendothelial cells  Acute septicemias, fever 100< 104°F (often in evening)  Rifampin + Doxycycline  Goats/sheep (melitensis) (granulomatous response with central  Profuse sweating, influenza like, (6 wks)  Pigs (suis) necrosis)  Arthralgias, anorexia, myalgia, back pain  Endotoxin  Hepatomegaly (children: cotrimoxazole Transmission instead of doxy)  Unpasteurized dairy Potential biowarfare agent Undulant form is milder (often result of incomplete products—goat milk Prevention (recent travel to Mexico— treatment)  Vaccinate cattle and high Cali and Texas highest # risk humans (vets, cases) Chronic form (more than one year w/ disease) slaughterhouse workers,  Direct contact with animal  Usually B. melitensis in older veterinarians military) (slaughterhouse)  Cyclic bouts of depression, confusion, profuse sweating  Pasteurize milk  Most common complication is osteomyelitis Bordetella pertussis (cysteine NOT required)  Encapsulated Attachment (to nasopharyngeal ciliated Pertussis (Whooping cough) Supportive care,  Bordet

Microbiologia 17 with transfer of signals from cell  Immunity wanes 5-7 surface to intracellular mediator Diagnosis years system= cAMP  Regan

 Tracheal cytotoxin—kills ciliated cells; interferes with cilliary action

 Endotoxin (LPS)

Microbiologia 18

FACULTATIVE ANAEROBIC (rest of gram  except Bacteroides) Curved/S shaped Rods with Flagella  Oxidase  (test turns black) Campylobacter jejuni Features Pathogenesis Diseases Treatment  Curved rods with polar  Low infectious dose (as few as 500) Gastroenteritis  Supportive via fluid and flagella (―gulls’ wings‖)  Acid resistant  MCC infectious diarrhea in US electrolyte replacement  Grows well at 42C on  Invades/destroys mucosa of colon  10 or more stools/day, may be frankly bloody  Generally self

Vibrio Cholerae (V. parahaemolyticus, V. vulnificus)  Curved rod w/ polar flagella  High infectious dose >107 (sensitive Cholera (O1;O139 strains)  Fluid and electroyte  Growth on alkaline media to stomach acid)  Rice water diarrhea (specks of mucous) replacement (IV) Thiosulfate citrate bile salt  Tremendous fluid loss (20L per day!)  Doxycycline or sucrose (TCBS)  Motility, mucinase, and toxin (ddx—ETEC is oxidase negative) ciprofloxacin shorten  ―Shooting star motility‖ coregulated pili (TCP) aid in V. parahaemolyticus V. Vulnificus disease and reduce  O1 biotypes—El Tor (MC) attachment to small intestinal Consumption of undercooked/ raw Swimming in brackish water, carriage and Cholerae (classic) mucosa seafood shucking oysters Microbiologia 19  O139 is more recent Gastroenteritis watery diarrhea Cellulitis rapidly spreading; Prevention=  Oxidase  (test turns  Cholera enterotoxin (choleragen)— with cramping and abdominal pain difficult to treat, may require Proper sanitation black) similar to E. coli LT ADP Cause of 25% food poisoning in amputation Reservoir= colon and ribosylation of Gs alpha activating Japan (3 day diarrhea) *Fisherman cuts themselves Tetracyclines or third invertebrates (shellfish adenylate cyclase cAMP efflux of shucking oysters* generation cephalosporins contaminated by water) Cl- and H2O (ions leave cells, water (consumption could cause GE for V. vulnificus cellulitis follows) similar to V. parahaemolyticus) Transmission= fecal- Self-limiting (Doxy if severe) DOC: Tetracyclines oral (hurricane, flood) Lysogenic phage encoded Microbiologia 20

Enterobacteriae Family Lactose fermenters turn pink on MacConkey Agar (vs. colorless)  Catalase , Oxidase  Lactose fermenters  Facultative anaerobic Citrobacter Non motile Motile  Ferment glucose Enterobacter (non-H2S producers) (H2S producers)  Reduce nitrates to nitrites (UTIs—nitrites in urine) E. coli Proteus Lactose Fermenters Klebsiella Salmonella

Escherichia coli Colonies with iridescent Disease Pathogenesis Clinical Clues Treatment green sheen on EMB UTI (MCC) Endogenous fecal flora contaminate; ascend Females> Males TMP-SMX Pink colonies on Motility, adherance to uroepithelium—pili (pyelonephritis associated), X- Fluoroquinolones Mcconkey agar adhesins, -hemolytic (many) Distinguishing features Neonatal septicemia/ Maternal fecal flora contaminate during parturition Blood culture Ceftriaxone from other lactose meningitis (2nd MCC) Capsule—K1 serotype CSF culture fermenter are: Endotoxin (LPS) causes shock, inflammation at BBB 1.Motile Septicemia (MCC gram neg Indwelling IV lines, cytotoxic drugs (damage intestinal mucosa; allow escape) Blood culture Fluoroquinolones 2.Decarboxylates lysine sepsis) Endotoxin (LPS, Lipid A)— Fever, hypertension 3.Produce indole from ETEC (Traveler’s LT- heat labile Stimulates adenylate cyclase (ADP ribosylation of Gs— Noninflammatory Rehydration tryptophan diarrhea) similar to Cholera toxin) Bioassay, DNA probe (TMP-SMX may 4.Use acetate only as a ST< heat stable toxin Stimulates guanylate cyclase—capsule impedes shorten symptoms) source of carbon phagocytosis; colonizing factor adhesins (CFAs) bind to intestine mucosa Reservoir (jejunum and ileum) Colon, may colonize 2nd MCC infantile diarrhea (1st is rotavirus) Noninflammatory; Fluoroquinolones vagina or urethra EPEC (Pediatric Adherance to M cells rearrangment of actin; effacement of brush border Babies in developing Crops where human diarrhea) microvilli world fecal fertilizer is used Inflammatory diarrhea similar to shigella (watery bloody) Blood, pus, fever, Fluoroquinolones EHEC strains: bovine EIEC (Invasive diarrhea) Formation of actin jet trails; invades large bowel abdominal pain feces Transmission EHEC (Hamburger, bloody O157:H7 strain most common; hamburger meat, petting zoos No fever or PMNs, NO antibiotics Endogenous diarrhea) Inflammatory, noninvasive bloody diarrhea Blood in stool, may  risk of HUS Fecal-oral Verotoxin—Shigella-like toxins 1 and 2,  protein synthesis by binding 60S progress to HUS in (releases more Maternal fecal flora ribosomal subunit (similar to shigella) also cause hemolytic uremic children (anemia, toxin) EHEC: raw beef, syndrome(hemolytic anemia, thrombocytopenia, acute renal thrombocytopenia, acute renal failure) milk, apple juice from failure) occurs when shiga toxin enters bloodstream fallen apples Does not ferment sorbitol or contain glucuronidase Others: EAEC (developing world—biofilm; EAST toxin); DAEC (infants to 5yrs—elongation of microvilli w/ bacteria in cell membrane) Klebsiella pneumoniea Features Pathogenesis Diseases Treatment  Large polysaccharide capsule  Capsule—impedes Pneumonia (lobar) Diagnosis—sputum culture  Mucoid, lactose fermenting phagocytosis  Seen in older males, chronic lung disease, alcoholism, diabetes or clean catch urine sample on MacConkey agar  Endotoxin (LPS)—causes  Frequent abscesses make treatment difficult; high fatality  ―Viscuous colonies‖ fever, inflammation and  Sputum thick and blood (currant jelly) NOT foul smelling DOC rd Reservoir= colon/Upper shock (septicemia) UTIs (3rd MC) Catheter related (nosocomial) from fecal contamination  3 gen cephalosporins respiratory tract Transmission= Septicemia Immunocompromised; bowel defects, IV line invasion  Fluoroquinolones endogenous (2nd MCC gram neg sepsis) Many resistant strains Microbiologia 21 Nonisolation from stool during illness and culture on selective Prevent w/ proper  Flies cytotoxic, enterotoxic) A-B component media sanitation  Food toxin is internalized in human cells;  Feces inhibits protein synthesis by clipping 60s ribosomal subunit Yersinia pestis  Bipolar staining  Coagulase (most important)—clots Bubonic plague Diagnosis:  Facultative intracellular stomach content of flea and makes  Flea bites infected animal and then later uninfected human  No cultures—they are parasite them hungry  Rapidly increasing fever hazardous  Coagulase   Endotoxin and exotoxin  Regional buboes (swollen lymph nodes)  Serodiagnosis or direct   Envelope antigen (F<1)—inhibits  Conjunctivitis immunofluorescence Reservoir phagocytosis  Leads to septicemia and death if untreated (DIC—turns black)  ―Safety pin‖ staining  US desert southwest  V and W antigen (bipolar staining)  Rodents, prairie dogs  Type III secretion system Pneumonic plague (potential biological warfare) DOC suppresses  Highly contagious!  Aminoglycosides Transmission cytokine production and resists  Arises from septic pulmonary emboli in bubonic plague or inhalation of  Wild rodent flea bite phagocytic killing organisms from infected individual Prevention (regurgitates stomach  Killed vaccine (military) contents into humans) Yersinia enterocolitica Features Pathogenesis Diseases Treatment  Motile at 25C (not 37)  Enterotoxin, endotoxin Enterocolitis Diagnosis  Cold growth  Multiplies in the cold  Very young—febrile diarrhea (blood and pus)  Stool culture, 25C, cold Reservoir= zoonotic  Adolescents—mimics appendicitis!!! (also y. pseudotuberculosis) enrichment  Adults—enterocolitis with postinfective sequelae like reactive arthritis Transmission  Supportive care  Unpasteurized milk, pork, Blood transfusion associated infections  Fluoroquinolones for pet feces immunocompromised  Northern climates Microbiologia 22 Motile (H2S producers) Proteus (P. mirabilis, P. vulgaris) Features Pathogenesis Diseases Treatment  ―Swarming motility‖ on  Peritrichous flagella motility (may  Urinary tract infections (4th MCC) DOC blood agar aid entry into bladder)  Kidney stones staghorn renal calculi (Ammonium magnesium  Fluoroquinolones  Urease  Production  Urease—raises uring pH to cause phosphate)  TMP-SMX  Weil Felix Reaction-Its kidney stones (staghorn renal  Septicemia  Remove stones antigen cross reacts with calculi) rickettsiael antibodies.  Endotoxin—fever and shock when Diagnosis—culture of blood or urine for lactose negative organisms with Prevention septicemia occurs swarming motility;  urine pH Remove urinary cath Reservoir  Colon and environment (water and soil) Transmission= Endogenous Salmonella enterica (subsp. typhi)  Highly motile with the Ingested organism ileocecal infection Typhoid fever DOC Virulent capsule M cells  mesenteric lymph nodes  Constipation first symptom (due to ileocecal infection)  Ceftriaxone  Sensitive to acid blood  At 1 week 80%  blood cultures, 25% rose spot rash on trunk  Fluoroquinolones  Facultative intracellular  Liver and spleen infected  bacteria in blood (septicemia/fever) parasite Survives intracellularly and replicates in  Biliary system infected organisms enter intestinal tract in bile macrophages; resists macrophage killing  Fever, headache, abdominal pain Prevention= Reservoir due to:  Alternating constipation and diarrhea  Humans only  Decrease fusion of lysosomes with sanitation 3 Vaccines Transmission phagosomes Complications if untreated  Parenteral  Fecal-oral (infection sets up  Defensins (proteins) allow it to  Necrosis of Peyer patches perforation (local endotoxin) polysaccharide capsular in gall bladder) withstand oxygen dependent and  Thrombophlebitis, cholecystitis, pneumonia, abscess, etc.  Attenuated oral   Stomach acid or independent killing (strain 21 Ty21a) impairment of mononuclear  Vi capsular antigen—withstands Diagnosis— organisms isolated from blood, bone marrow, urine, tissue  Parenteral heat killed cells (sickle cell anemia with Complement-mediated killing from the rose spots (no longer used in US) osteomyelitis- children) Blood culture in first two weeks of illness  predisposes to infection Bone marrow and stool culture maybe  Salmonella enterica (subsp. enteritidis, typhimurium, choleraesuis, paratyphi, dublin)  Serotyped with O, H, and Vi  High infectious dose— (>105) Enterocolitis/gastroenteritis Gastroenteritis antigens—detected by Sensitive to stomach acid  2nd MC bacterial cause (1st Campylobacter)  Self-limiting, agglutination: Widal test  Lowered stomach acidity (PPi’s,  6-48 hr incubation nausea, vomiting; loose stools (occasionally bloody),  NO ANTIBIOTICS (may antacids) increases risk fever, abdominal pain, myalgia, headache prolong fecal Reservoir  Endotoxin in cell wall Septicemia excretion)  Enteric tracts of humans and  Invades mucosa in ileocecal region,  Choleraesuis, paratyphi, Dublin domestic animals (chickens invasive to lamina propria  Rare, only very young or elderly; 10% complicated w/ endocarditis Invasive disease & turtles) inflammation  PG cAMP= loose  Ampicillin diarrhea; shallow ulceration Osteomyelitis  Ceftriaxone Transmission  Salmonella is MCC causual agent in sickle cell disease  Fluoroquinolones  Raw chicken, eggs MOA= inflammation (NO toxins)  TMP-SMX  Reptile pets (snakes, turtles) Diagnosis: culture on Hektoen agar (green agar that turns black) Microbiologia 23 Haemophilus  Pleomorphic rod (considered coccobacillus)  Requires growth factors X (hematin) and V (NAD) for growth on blood agar  Satellite phenomenon (with S. aureus on blood agar) o Pinpoint colonies (S. aureus secretes NAD and lysed blood releases hematin)  Chocolate agar (provides both X and V factor) Haemophilus influenzae Features Pathogenesis Diseases Treatment  Encapsulated  Polysaccharide capsule (most Meningitis DOC  95% of invasive disease important)—type b capsule is  Epidemic in unvaccinated children ages 3 months (after maternal antibody  Ceftriaxone caused by capsular type b polyribitol phosphate wanes) to 2 years (before immune response is adequate)  Cefotaxime  Attachment pili  Before 1990. MCC meningitis in 1-5 yr old Rifampin= prophylaxis Reservoir  IgA protease—colonizing factor  Human nasopharynx Epiglottitis Unvaccinated toddlers—catcher‘s stance w/ drooling (dog Vaccine  Latex particle agglutination screen sniffing position—drop heads to catch breath due to swelling of epiglottis)  Conjugate capsular Transmission for capsular antigen in CSF polysaccharide protein  Resiratory droplets Nontypable strains vaccine coupled to  Shared toys Otitis media/sinusitis 2nd MCC cause (also presents w/ conjunctivitis) protein carrier (diptheria toxoid) *Unvaccinated child* Bronchitis exacerbations of acute bronchitis in smokers w/  Prevents type b COPD Pneumonia smoking history; rare in vaccinated children  TChancroid DOC  Human genitals  PAINFUL genital ulcer (syphilis is painless)  Azithromycin and/or  Often associated with unilateral swollen lymph node (can rupture releasing Ceftriaxone Transmission pus)  Ciprofloxacin  Sexual and direct contact Painful chancroid= ―you do cry with ducreyi‖ Gardnerella vaginalis  Gram4.5, Vaginal saline smear clue cells (vaginal epithelial cells that  Vagina contain tiny plemorphic gram negative bacilli within the cytoplasm)  pH associated with reduction of Whiff test: add KOH to sample ―fishy‖ amine odor Transmission= endogenous vaginal Lactobacillus  Flora gets disturbed (stress, Other discharges menses, antibiotics, pH)  Gonorrhea cloudy yellow green, purulent  Chlamydia clear, white  Trichomonas frothy green w/ foul odor (strawberry cervix)  Candida cottage cheese (only one with decreased pH) Microbiologia 24 Gram negative rods associated with Animal/Human bites

Pasteurella multocida Features Pathogenesis Diseases Treatment Reservoir  Endotoxin Cellulitis with lymphadenitis DOC  Animal mouth; especially  Capsule  Wound infections, rapidly spreading (could spread to bone)  Amoxicillin + cats and dogs  Spreads rapidly within skin  Frequently polymicrobial infections Diagnosis— Clavulanate (treatment  Requires cysteine and prophylaxis) rarely cultured (prophylaxis is common) Transmission Resistant to macrolides  Animal bite: particularly Oher cysteine requiring bacteria: Francisella, Brucella, Legionella from cats (Francis and Bruce play with Legos in the Pasture) Additional organisms Eikenella Corrodens ―Corrodes‖ agar; bleach like odor Human bites or fist fight injuries Cellulitis 3rd gen cephalosporins Fluoroquinolones Capnocytophaga Filamentous rods Dog bite wounds Cellulitis (overwhelming sepsis in asplenic pts) 3rd gen cephalosporins canimorsus Fluoroquinolones Bartonella henselae Immunocompromised (AIDS) Cats/dog bits/ scratches ―cat scratch fever‖ Azithromycin Bacillary Angiomatosis (AIDS) raised purple/black splotches Doxycycline Bartonella quintana Spread by lice Trench fever (5 day fever with bone pain) HACEK group infections Haemophilus aphrophilus Actinobacillus  All part of normal flora  5-10% of infective endocarditis (subacute) 3rd gen cephalosporins actinomycetemcomitans  MCC gram negative endocarditis in non

OBLIGATE ANAEROBIC Bacteroides fragilis Features Pathogenesis Diseases Treatment  ONLY gram negative  Modified LPS (missing heptose Septicemia (used to be MCC before prophylaxis during surgery) DOC obligate anaerobe and 2- Keto-3 deoxyoctonate)= Peritonitis (mixed infection)  Metronidazole  Black colonies reduced endotoxin activity Abdominal abscess foul smelling  Clindamycin  Modified LPS with reduced Postpartum endometritis foul smelling discharge with tender uterus Abscess should be activity  Capsule is antiphagocytic Aspiration pneumonia with abscess and foul smelling sputum think surgically drained anaerobic Reservoir= normal flora  Enzymes: Antibiotic resistance  Human colon Diagnosis common (7-10% Transmission= endogenous  Hyaluronidase, collagenase, Anaerobes identified by biochemical tests and gas clindamycin resistant)  Bowel defects (cytotoxic phospholipase chromatography Other anaerobes: Prevotella, Fusobacterium, drug use) Peptostreptococcus Prophylactic antibiotics for  Surgery or trauma GI surgery Microbiologia 25 Spirochetes Treponema pallidum (Thin spiral with axial filaments) Features Pathogenesis Diseases Treatment  Endoflagella- allow  NOT intracellular Syphilis: Stages DOC movement  Endarteritis (vasa vasorum Primary  PainLESS chancre on glans/vulva Dark field  IM Penicillin G  Poor gram stain (but destruction, aortic aneurysm)  Clean, indurated edge; contagious Benzathine gram neg envelope)  Strong tendancy to chronicity  Heals 3-6 weeks (long acting— for 1  Obligate pathogen; Diagnosis Secondary  Serology non & 2) cannot culture  Dark field microscopy palms and soles (infectious) specific and  IV Penicillin G (for  Serology (2 types)  Patchy alopecia (beard) congenital & late) Reservoir= Humans 1. Nontreponemal (screening)—  positive  Doxycycline  Genital tract Ab binds to cardiolipin membrane lesions—highly infectious) Transmissi  Cheap source of Ab usually Tertiary  3-15 years after after secondary; not infectious Jarisch

 Ab binds to spirochetes  Still birth, keratitis, rash, fever, pneumonitis, revert to negative rigors, leucopenia)  More specific, positive earlier, within 3 months of False positive VRDL remain  for life hepatosplenomegaly, metaphyseal dystrophy birth if unaffected Benzathine penicillin Viruses  FTALyme disease (#1 tick borne disease in U.S.) MC in northeast— spring DOC  Doxycycline Reservoir bloodstream to involve heart, 1: Early localized Target rash (aka bull’s eye, annular lesion, red w/ central  White footed mice joints, and CNS (Days—Weeks) clearing) Fatigue, fever, headache  Ceftriaxone (2)  Arthritis caused by immune  White tailed deer Hematogenous spread Bilateral Bell‘s Palsy, muscle and  Amoxicillin (for complexes Transmission children<8 and

 ticks (Ixodes lesions, cardiac (AV block/myocarditis) pregnant women) Diagnosis also carry Babesia, 3: Late persistent  Encephalitis, meningitis, extreme fatigue, conjunctivitis  Serodiagnosis (ELISA) Prevention—DEET; Ehrlichia)  Arthritis (MC in knees; immune complex-mediated)  I. scapularis  Western blot now test of avoid tick bites

 I. pacificus choice Borrelia recurrentis recurrent fevers (from variable surface antigens) also tick vector Leptospira interrogans (Very thin with tight terminal hooks on both ends)  Aerobic Leptospirosis (swamp fever, mud fever, swineherd’s disease) DOC  Zoonotic (dogs, rats, livestock)  Influenza like disease, high spiking temperatures, muscle aches (thighs/lower back)  Penicillin G Transmission  Severe if not treated (Weil‘s disease—hepatitis, jaundice, renal failure, organ hemorrhage,  Doxycycline  Contact with animal urine in the water mental status changes, photophobia)  Penetrates mucous membranes/ small breaks in skin Diagnosis Prevention: animal  Jetskiers in Hawaii, Sewer workers  Serodiagnosis (agglutination test), Culture (blood, CSF, urine), vaccination, rat control  Darkfield NOT recommended Microbiologia 26 Unusual Bacteria Obligate Intracellular Organisms (Chlamydia, Rickettsia, Anaplasma)  Do not make sufficient ATP (must utilize host cell) Chlamydia trachomatis (C. pneumoniae, C. psittaci) Features Pathogenesis Diseases Treatment  NOT seen on gram stain;  Infects non ciliated columnar or Sexually Transmitted Disease (Serotypes D-K) Diagnosis: (peptidoglycan lacks cuboidal epithelial cells of mucosal  MC bacterial STD in US (Overall: HPV, herpes)  DNA probes (US) muramic acid) surfaces granulomatous response,  Non gonococcal urethritis, cervicitis, PID, inclusion conjunctivitis  Cytoplasmic inclusions  Does not produce any ATP inflammation, damage  Inclusion conjunctivitis/pneumonia in neonates (staccato cough) (reticulate bodies) on Complications Sterility, Reiter’s syndrome, Fitz Hugh Curtis Giemsa Reservoir  Elementary body (infective form) Lymphogranuloma venereum (Serotypes L1,2,3) DOC  Human genital tract; inactive, extracellular  Prevalent in Africa, Asia, South America  Doxycycline eyes  Tertiary: rectal strictures, fistulas, ulcers, swollen LN genital  Azithromycin  Transmission  Reticulate body (replicating form) elephantiasis Erythromycin (mothers at  Sexual contact, birth active, intracellular Trachoma (Serotypes A-C) birth; drops for neonatal  Trachoma by hand to eye  Leading cause of preventable infectious blindness conjunctivitis) contact and flies  Follicular conjunctivitis  inturned eyelashes corneal scarring C. pneumoniae  Intracellular growth; infects smooth Walking pneumonia (2nd MCC)—(Atypical pneumonia) DOC TWAR strain— Person to muscle endothelial cells; coronary  Single lobe, bronchitis, scant sputum, dry cough/hoarseness  Doxycycline person by respiratory route artery (atherosclerosis)  Diagnosis= serology (complement fixation)  Macrolides C. psittaci  Intracellular growth Psittacosis (ornithosis)—(Atypical pneumonia) DOC Inhaled dried feces dust of  No glycogen in inclusion bodies Very contagious; cough initially absent  Doxycycline birds, parrots, turkeys (US) Hepatitis; CNS and GI symptoms may be present Rickettsia ricketsii  Aerobic, Gram  bacilli  Invade endothelial cells lining Rocky Mountain Spotted Fever Diagnosis (too small to stain) capillaries vasculitis in many organs  Prevalent on East Coast (North Carolina area); 2-12 day incubation  Clinical, start doxy before Reservoir= zoonotic (brain, liver, skin, lungs, kidney, and GI  Headache, fever (102F), malaise, myalgias, toxicity, vomiting lab confirmation  Dogs, rabbits, rodents tract)  Maculopapularpetechial rash on ankles/wrists (w/ swelling) spread  4X  titer is diagnostic Transmission  WeilQ fever—interstitial pneumonia with NO rash; Weil-Felix Negative (Most infectious bacteria- urine, placenta of slaughterhouses) Pneumona+hepatitis= strongly suggestive infectious dose 1 organism) R. prowazekii Human louse humans (war, prisons) Epidemic Typhusabrupt fever, headache, rash (no palms/soles), delirium R. typhi Rats Fleas humans Endemic Typhusfever, headache, rash Orientia tsutsugamushi Rodents Mites humans Scrub Typhus fever, headache, rash, muscle pain, cough hemorrhaging Anaplasma (formerly Ehrlichia; A. chaffeensis, A. phagocytophila)  Gram  bacilli Infects WBCs— Anaplasmosis DOC Reservoir= ticks/deer Monocytic (chaffeensis)  Similar to RMSF but without rash  Doxycycline Transmission= ticks Granulocytic (phagocytophilum)  Leukopenia, low platelets, morulae (mulberryMycoplasmas  Missing peptidoglycan—No cell wall (not seen on gram stain)  Requires cholesterol (plus nucleic acids) for in vitro culture fried egg appearance (not seen in M. pneumoniae)

Mycoplasma pneumoniae Features Pathogenesis Diseases Treatment  Smallest extracellular  Surface parasite (not invasive) Walking pneumonia (MCC) (patients do not feel very sick) DOC bacteria  P1 Protein—attaches to  MC atypical pneumonia in young adults  Erythromycin (and  Sterols/cholesterol in respiratory epithelium  Dry hacking cough; pharyngitis, fever, otitis media other macrolides) membrane (but does not  Inhibits ciliary action  Also common in children and teens  Tetracyclines synthesize cholesterol)  Produces hydrogen peroxide,  Can cause Steven- Johson Syndrome, Raynaude’s  Eaton‘s agar superoxide radicals, cytolytic Phenomenon, cardiac arrhythmias and Guillian-Barre Syndrome Cephalosporins or enzymes (damage respiratory Diagnosis penicillins do NOT Reservoir epithelium necrosis, bad hacking  Primarily clinical; PCR/nucleic acid probes work(no cell wall!!!)  Human respiratory tract cough)  ELISA and immunoflueorescence sensitive and specific Transmission  Functions as superantigen—elicits  Mulberry shaped colonies on sterol containing media, 10 days  Respiratory droplets production of IL<1, IL<6, and TNF<  Positive cold agglutinins (IgM autoantibody to red cells) test is  Close contact: military (overwhelming immune response; non-specific and only positive in 65% of cases (however this plus a recruits, college dorms inflammation) clinical presentation has been an effective diagnostic tool)

Ureaplasma urealyticum  Urease   Becomes normal flora of sexually active  Urethritis (yellow mucoid discharge) DOC adults  Prostatitis  Erythromycin  Seen in child= sexual abuse  Renal calculi  Tetracycline

Microbiologia 28 Bacterial Genetics

Three different types of DNA found in a bacterial cell 1. Bacterial chromosomal DNA—one large circular DNA molecule (often multiple copies) organized into loops around a protein center contain essential genes 2. Plasmid DNA—extrachromosomal genetic elements (circular DNA) for nonessential genes (fertility genes, antibiotic resistance, and exotoxins) 3. Bacteriophage DNA—stable pieces of bacteriophage DNA inserted into the bacterial chromosome can enhance virulence (lysogenic conversion)

Rearrangement of DNA within a bacterium (can help stabilize) Homologous Recombination Site

Mechanisms of DNA exchange Transformation Conjugation Transduction  Uptake of naked DNA Gene transfer from one bacteria to another with direct cell

crosses bacterial DNA can be carried along into F< becomes the next generation of viruses F+ Only certain genes because phages but no new genes integrate at certain sites using repressors

Microbiologia 29 Hfr cell F– cell  Only genes closest to oriT are transferred  Must be stabilized by homologous recombination  No ―sex change‖ (tra is last and doesn’t transfer)

Bacteria that undergo natural transformation:  H. influenzae  S. pneumoniae  Bacillus and Neisseria

Microbiologia 30

Microbiologia 31 Cell Wall Synthesis Inhibitors

MOA Bacteriocidal— D-ala D-ala analogs that bind and inactivate transpeptidase (PBP) Prevent cross-linkage of peptidoglycan chains (loss of cell rigidity cell death) Work best at period of maximal growth (log phase)

Resistance 1. Penicillinases (beta-lactamases) break lactam ring structure produced in periplasm of gram-negatives 2. Structural change in PBPs (MRSA) 3. Change in porin structure (Pseudomonas)

Penicillins Cephalosporins Narrow Spectrum Neurosyphillis, Strep viridans, pneumo (Penicillin G) First generation First—surgical prophylaxis (gram positive + Proteus, E.coli, (penicillinase susceptible) Strep pharyngitis (Penicillin V)  Cephalexin (oral) Kebsiella)  Cefazolin (IM or IV)  Penicillin G (IM or IV) Safe in pregnancy Second— increased gram negative coverage including some anaerobes (Cefuroxime only one to enter CNS)  Penicillin V (oral) Second generation

 Cefoxitin Narrow Spectrum Mostly staphylococci (not MRSA) Third—gram positive/negative cocci, & many gram negative  Cefotetan (penicillinase resistant) rods (all enter CNS except cefoperazone) All penicillins are renally excreted except for oxacillin and  Cefaclor  Ceftriaxone (DOC Neisseria, strep pneumo meningitis,  Methicillin nafcillin (excreted in bile)  Cefamandole Salmonella, Haemophilus)  Cefotaxime (strep pneumo meningitis)  Naficillin  Cefuroxime Methicillin can cause interstitial nephritis  Cefoperazone & Ceftazidime (pseudomonas)  Oxacillin Third generation  Ceftriaxone & Cefoperazone eliminated in bile Broad Spectrum Mostly treat ear nose and throat infections  Cefotaxime (penicillinase susceptible)  Streptococcus, H. influenza Fourth—wider spectrum, resistant to most beta-lactamases,  Ceftriaxone (IM)  Listeria (ampicillin+gentamycin) and enters the CNS  Ceftazidime  Ampicillin (IV)  Borrelia, H. pylori, ear infections (amoxicillin)  Cefoperazone  Amoxicillin Bacteria NOT COVERED by cephalosporins are LAME  Cefixime  Listeria Extended Spectrum Increased activity against gram-negative rods including  Atypicals (Chlamydia, Mycoplasma) (penicillinase susceptible) pseudomonas Fourth generation  MRSA  Ticarcillin Carbenicillin concentrates in urinary tract (for UTIs)  Cefepime (IV)  Enterococci  Piperacillin Do not give ticarcillin to cardiac/hypertensive pts  Azlocillin Cefotetan and Cefoperazone have disulfiram-like effects B

Vancomycin Monobactams MOA: binds at D

 Amikacin  Nephrotoxicity (especially with cephalosporins)  Clarithromycin  Erythro drops: neonatal conjunctivitis (chlamydia/gonorrhea)  Ototoxicity (epecially with loop diuretics)  Erythromycin  Neuromuscular blockade (don’t give to myasthenia gravis or  Roxithromycin A/E— p450 inhibitors (especially erythromycin), prolongs QT with succinylcholine)  Telithromycin interval, GI distress from stimulation of motilin receptors  Contraindicated in pregnancy Resistance: Transferase enzymes inactivate the drug by Resistance: production of methyltransferases that alter drug acetylation, phosphorylation or adenylation binding sites, or active transport out of cells

Bacteriostatic—blocks attachment of aminoacyl

 Tetracycline  Minocycline: concentrates in saliva/tears (meningitis carrier) Linezolid Treatment of VRSA, VRE, and drug-resistant pneumococci  Doxycycline  Demeclocycline can be used in SIADH

 Tigecycline: used in complicated resistant skin infections  Minocycline A/E—bone marrow suppression, thrombocytopenia; inhibits MAO A/E  Demeclocycline increasing risk of serotonin syndrome Microbiologia 34  Tigecycline  GI distress, photosensitivity Bacteriostatic—blocks the attachment of aminoacyl tRNA to  Children—discoloration of teeth & bone growth inhibition Streptogramins acceptor site; stimulate dissociation from ternary complex  Contraindicated in pregnancy  Decreased absorption when taken with milk/antacids Treatment- parenterally in severe infections caused by VRSA and  Quinupristin VRE, as well as other drug resistant gram+ cocci  Dalfopristin Resistance: Decreased uptake into cells or increased efflux out of the cell by plasmid-encoded transport pumps A/E—nausea, diarrhea, myalgias, arthralgias, hepatotoxicity Microbiologia 35 Nucleic Acid Synthesis Inhibitors Inhibitors of Folic Acid Synthesis Direct inhibitors of Nucleic Acid Synthesis Bacteriostatic—antimetabolites that competitively inhibit dihydropteroate synthase (structural analogs of PABA) Bactericidal—Inhibit topoisomerase II (DNA gyrase) and Treatment: topoisomerase IV (responsible for separation of daughter cells Sulfonamides during cell division)  Sulfasalazine—prodrug used in ulcerative colitis, Crohn’s and

rheumatoid arthritis (inhibits PGs and LTs)  Sulfamethoxazole  Sulfacetamide—eyedrops for conjunctivitis Treatment  Sulfadoxine  Silver Sulfadiazine—1% cream for burns  TMP-SMX resistant UTIs  Sulfasalazine Fluoroquinolones  STDs/PID caused by chlamydia, gonorrhea  Sulfacetamide A/E  Skin, soft tissue, and bone infections (gram negative)  Sulfadiazine  Hypersensitivity reactions (Stevens Johnson), Phototoxicity  Ciprofloxacin  Diarrhea (Shigella, Salmonella, E. coli, Campylobacter) rd  Drug resistant pneumococci (levofloxacin)  Mafenide  Kernicterus in neonates ( protein binding; avoid in 3 trimester)  Levofloxacin

 Hemolysis in G6PD deficiency  Norfloxacin Iron/Calcium limit absorption (forms a chelate)—do not take Bacteriostatic—antimetabolites that inhibit dihydrofolate  Moxifloxacin with antacids reductase Eliminated by kidney filtration/secretion Trimethoprim Treatment Synergy with sulfonamides (resistance) A/E  Trimpethoprim-sulfamethoxazole (TMP-SMX) DOC Nocardia, UTIs Tendonitis, tendon rupture (inhibits elastin incorporation) Pyrimethamine (S. sapro, E.coli, Proteus), P.jiroveci Phototoxicity, rashes, prolongs QT interval  Sulfadoxine+Pyrimethamine—DOC Toxoplasma, resistant malaria  CNS effects (insomnia, dizziness, headache, anxiety)—due to inhibition of GABA binding; glutamate overdrive A/E Contraindicated in pregnancy/children  Megaloblastic anemia, leukopenia, granulocytopenia CANNOT be used for anaerobes  Reversed by giving folinic acid

Microbiologia 36 Antimycobacterial Drugs

Drug Use MOA and Resistance Side Effects

Isoniazid Tuberculosis Prodrug requiring conversion by catalase inhibits Hepatitis (age/dose dependant) mycolic acid synthesis Standard= Peripheral Neuritis & sideroblastic anemia (must supplement with vitamin B6) Resistance: deletions in katG gene (encodes catalase) SLE in slow acetylators 2 months: Isoniazid, Rifampin, Ethambutol, Rifampin Pyrazinamide Inhibits DNA-dependent RNA polymerase (nucleic Hepatitis 4 months: Isonizid + acid synthesis inhibitors) Inducer of p450 (OC failure) Rifampin Body secretions turn orange (metabolites in urine, sclera)

Ethambutol Inhibits synthesis of arbingalactan (cell-wall Dose-dependent retrobulbar neuritis Prophylaxis— Isoniazid component) Decreased red

Pyrazinamide Decreased pH in the tubercle cavity Hepatitis, phototoxicity Hyperuricemia (competes with uric acid secretion)

Streptomycin Protein synthesis inhibition Nephrotoxicity, Ototoxicity Vestibular dysfunction

Dapsone Leprosy Related to sulfonamides: inhibits DHT synthase Hemolytic anemia in G6PD deficiency, Lepra reaction (Jarish Herxheimer)

Clofazimine Lepra reaction from Binds to DNA and inhibits template function Dye with a half life of 70 days; can cause reddish black skin Dapsone Produces cytotoxic free radicals that kill bacteria Microbiologia 37

Fungi Randall Systemic Mycoses  Dimorphic fungi [mold in cold (25°C), yeast in the beast (37°C)]  Most commonly present with pneumonia-like symptoms  No person to person transmission  Best diagnosis= biopsy; (also sputum culture on Sabouraud)

Histoplasma capsulatum Microscope Features Epidemiology Diseases Treatment Environmental form Ohio and Mississippi Fungus flu (pneumonia) DOC Hyphae with River Valleys  Asymptomatic or acute (self-resolving)  Itraconazole microconidia and tuberculate Found in soil or dust  Hepatosplenomegaly may be present  Amphotericin B macroconidia enriched with bird/bat  Lesions tend to calcify as they heal (severe or feces  Increased relapse with T-cell immunosuppression pregnant) Tissue form Spelunking,  Disseminated in AIDS (mucocutaneous lesions) Small, oval

Environmental form  Same as Histoplasma but Blastomycoses DOC  Hyphae with small pear-shaped extending north to great  Acute and chronic pulmonary disease (pneumonia)  Itraconazole conidia lakes, Ohio, Canada; and  Less likely to self-resolve than Histoplasma/Coccidiodes  Amphotericin B Southeast to Carolinas)  Lesions do NOT calcify as they heal (severe or Tissue form  Soil or rotting wood  Disseminated disease in immunocompromised (mostly pregnant)  Broad

Broad-based budding yeast

Coccidiodes immitis

Environmental form  Southwest US (Arizona, Valley Fever DOC  Hyphae breaking up into barrel New Mexico, southern Cal—  Asymptomatic to self resolving pneumonia  Fluconazole shaped arthroconidia San Joaquin Valley)  Erythema nodosum (Desert bumps) and arthritis are good  Amphotericin B prognostic signs (severe or Tissue form  Arthroconidia inhaled from  Lesions tend to calcify as they heal pregnant)  Spherules with endospores desert sand spherules w/  Dissemination in immunocompromised, AIDS, and 3rd endospores in tissue trimester of pregnancy (meningitis, mucocutaneous) Spherules with endospores Microbiologia 38 Paracoccidiodes brasiliensis

Environmental form  Latin America Paracoccidioidomycosis DOC  Hyphae of variant forms  Soil fungus  Inhalation mild pneumonia (can resemble TB)  Ketoconazole  Mucous membrane ulceration of the mouth and nose with  Amphotericin B Tissue form spreading through the lymphatic system (severe or  Multiple-budding yeast with pregnant) captain‘s wheel formation

Captain’s wheel budding Microbiologia 39 Opportunistic Mycoses Yeast Candida albicans Microscope Features Epidemiology Diseases Treatment  Oval yeast with single bud in  Part of the normal flora of  Oral/esophageal thrush (neonates, AIDS, steroids, antibiotic DOC mucous membranes skin, mucous membranes overuse)—white patches easily scraped off  Miconazole;  Germ tubes in serum and GI tract  Yeast vaginitis (pH; diabetic women, antibiotic overuse) Clotrimazole  Forms pseudohyphae and true  Immunocompromised  Endocarditis (IVDA)  Nystatin hyphae when invading tissues patients, IVDA, overuse of  Cutaneous infections (obesity, infants—diaper rash)  Fluconazole, antibiotics Amphotericin B (disseminated) Nystatin—swish and swallow for oral thrush (topical for diaper Yeast GermTube P-hyphae rash or vaginitis) Cryptococcus neoformans  Urease   Soil enriched with pigeon Meningitis DOC  Monomorphic encapsulated droppings  Dominant meningitis in AIDS patients (begins in lungs;  Amphotericin B yeast  Hodgkin/ AIDS patients pneumonia-like symptoms soap bubble lesion in brain) w/ flucytosine  Mucicarmine stains capsule red  Pidgeon breeders Detect capsular antigen in CSF—latex agglutination (min 10 weeks) India ink mount budding yeasts with ―capsular halos‖ (misses then fluconazole India ink—capsular halos 50%—only rules in) Pneumocystis jirovecii  Obligate extracellular parasite  Yeast inhaled Diffuse interstitial pneumonia in AIDS (CD4<200) DOC  Silver stained cysts in  AIDS patients,  Fever, cough, SOB, non productive sputum  TMP

 Monomorphic filamentous  Compost pits, moldy  Allergic bronchopulmonary aspergillosis (asthma, CF— DOC fungus (only exists as mold) marijuana growing in mucus plugs but not penetrating tissue) Type I HS;  Itraconazole  Dichotomously branching  Asthmatics, Cystic Fibrosis Eosinophilia, perihilar nodules, eventual bronchiectasis  Amphotericin B  Radiating chains of conidia patients  Fungus ball—free in preformed lung cavities (surgical  Septate hyphae forming V< removal to reduce coughing) ―colonizing aspergillus‖ DOC Invasive shaped acute 45angles *Some species produce  Invasive aspergillosis aspergillosis= aflatoxins associated with Severe neutropenia, CGD, CF (burn victims—cellulitis) Voriconazole ± Hepatocellular Carcinoma Invades tissues causing infarcts/hemorrhage; Caspofungin 45 septate Conidiophore Nasal colonization pneumonia or meningitis Microbiologia 40 Mucor, Rhizopus, Absidia—(Zygomycophyta)

 Sporangiospores  Soil—sporangiospores Rhinocerebral infection  Debride  Nonseptate hyphae with broad inhaled  Facial pain/headache, paranasal swelling, black necrotic necrotic tissue 90 angles  Ketoacidotic diabetic eschar on face, hemorrhagic exudates from nose/eyes, mental (black pus) patients and leukemic lethargy  Immediately patients at risk  Can progress rapidly from sinuses (sphenoid to cavernous) start into brain tissue (frontal lobe abscesses) Amphotericin B Nonseptate, broad angle Biopsy KOH of tissue—broad nonseptate hyphae at 90 angles Microbiologia 41 Superficial Infections Malassezia furfur Microscope Features Epidemiology Diseases Treatment

 Spaghetti and meatballs  Moist, warm climates, Pityriasis (Tinea versicolor) DOC appearance on KOH mount of sweating  Superficial infection of keratinized cells  Topical skin cells (yeast clusters & short  Normal skin flora (lipophilic  Hypo< or hyperpigmented spots on the chest/back (blotchy selenium curved septate hyphae) yeast) suntan) sulfide  Coppery fluorescence under Wood lamp (UV) Premature infants on lipid supplements fungemia

Spaghetti/meatballs on KOH

Cutaneous Infections Dermatophytes (Microsporum, Trichopyton, Epidermophyton)

 Monomorphic filamentous fungi  Infect only skin, hair and/or Tineas (ringworms)—itching MC symptom DOC (mold form) nails—pruritic lesion w/ Tinea capitis (scalp)  Miconazole;  Mycosporum fluoresces a bright central clearing itch)  Oral imidazoles scrapings show arthroconidia  Skin, hair, & nails -pedis (athlete’s foot) or griseofulvin and hyphae Epidermophyton -unguium (nails) w/infected hair  Skin & nails Highly inflammatory = generally from animals Microsporum Little inflammation= generally from humans Keep areas dry

Subcutaneous Infections Sporothrix schenckii

Environmental form  Found on plant material Sporotrichosis (rose gardener disease) DOC  Hyphae with rosettes and (plum tree, rose thorns,  Subcutaneous or lymphocutaneous lesions  Itraconazole sleeves of conidia wire/sphagnum moss)  Potassium iodide Tissue form  Rose gardeners, alcoholics in milk (not for  Cigar

Pulmonary sporotrichosis (acute or chronic) Hyphae with rosettes  Homeless urban alcoholics (alcoholic rose garden-sleeper disease) Microbiologia 42 Antifungals Drug Mechanism Clinical Use Toxicity Amphotericin B Binds ergosterol; forms membrane Serious systemic mycoses (disseminated)  Fever, chills, malaise, hypotension during IV pores that allow leakage of  Histoplasma infusion (alleviated by NSAIDs) electrolytes  Blastomyces  Nephrotoxicity, arrhythmias, anemia, IV ―Polyene antifungal‖  Coccidiodes phlebitis, hypermagnesemia, hypokalemia  Candida  Cryptococcal meningitis (with or without flucytosine)  Hydration and liposomal amp B reduce nephrotoxicity Administered via slow IV infusion (½ life > 2 weeks)  Flucytosine allows for synergism so not as Poorly penetrates CNS; safe in pregnancy much amp B needs to be used Nystatin Same as amphotericin B Candida infections Too toxic for systemic use (only use topical  Diaper rash or vaginal candidiasis (topical) form)  ―Swish and swallow‖ for oral thrush (not absorbed in GI tract)

 Posaconizole—for Mucor (Amp B more common treatment) Flucytosine Needs to be converted into active 5-  Used in systemic fungal infections (esp. Cryptococcal meningitis in  Bone marrow suppression FU by cytosine deaminase combo with amphotericin B)  GI symptoms Inhibits thymidine synthase=  Synergism reduces side effects of ampB (less ampB used); helps thymidine, DNA and RNA penetrate CNS biosynthesis  Resistance emerges rapidly if used alone Caspofungin Inhibits cell wall synthesis by  Invasive aspergillosis (in combo with voriconazole)  GI upset Micafungin inhibiting synthesis of -glucan  Candida  Flushing (histamine release) ―fungal cell wall polysaccharide‖ Terbinafine Inhibits squalene epoxidase Dermatophytoses (especially onychomycosis—finger/toenail)  GI distress, rash, headache Accumulates in stratum corneum  Abnormal LFTs, visual disturbances Griseofulvin Interferes with microtubule Oral treatment of superficial infections  Teratogenic, carcinogenic, confusion, function; disrupts mitosis (mitotic Inhibits growth of dermatophytes (tinea, ringworm) headaches spindle). Deposits in keratin-  P450 inducer (warfarin metabolism) containing tissues (stratum Disulfuram

Parasites Randall PROTOZOA— GI infections

Entamoeba histolytica (amebae) Findings Form/Transmission Diagnosis Disease Treatment

 Cysts—water, fresh fruits  ―Ova parasite stool study‖ Amebiasis DOC and vegetables (Trophozoites or cysts in stool)  Dysentery (bloody diarrhea)  Metronidazole  Fecal-oral transmission  Serology—Nuclei have sharp  Inverted flask shaped lesions in large intestine (for trophozoites)  History of travel central karyosome and fine  Lesions can extend to liver, lungs, brain, heart  Followed by iodoquinol chromatin ―spokes‖  Liver abscess: ―anchovy paste‖ exudate with RUQ (for cyst form) pain

Trophozoite Cyst

Giardia lamblia (flagellate)

 Cysts—fecal (human, beaver,  ―Ova parasite stool study‖ Giardiasis DOC muskrat) (Trophozoites or cysts in stool)  Ventral sucking disk attaches to lining of duodenal  Metronidazole  Oral transmission—  Fecal antigen test wall inflammation decreases absorption at villi ―Campers—water from a  ―Falling leaf motility‖  Fatty, foul

Cryptosporidium parvum (apicomplexa)

 Cysts—undercooked meat,  Acid fast oocysts in stool Cryptosporidiosis  No treatment is 100% water  Biopsy shows dots (cysts) in  Transient watery diarrhea in healthy effective  Not killed by chlorination intestinal glands  Severe diarrhea in AIDS (immunocompromised)  Prevent with filtration  Intracellular multiplication in (Chlorination does NOT Acid fast oocysts in stool brush border work)  Nitrazoxanide for AIDS

Others (cause diarrhea in AIDS) (apicomplexa) Isospora belli  Ingestion of oocysts  Acid fast elliptical oocysts in Transient diarrhea in AIDS (mimics giardiasis)  TMP-SMX  Fecal-oral stool Cyclospora cayetanesis  Oocysts in water  Acid

Microbiologia 44 PROTOZOA—Sexually transmitted

Trichomonas vaginalis (flagellate) Findings Form/Transmission Diagnosis Diseases Treatment

 One form= trophozoites  Motile trophozoites in Trichomoniasis DOC  Sexually transmitted methylene blue wet mount  Often asymptomatic  Metronidazole  Corkscrew motility  Foul smelling, Frothy green vaginal discharge (increased vaginal pH)

Motile trophozoites Microbiologia 45 PROTOZOA—Hematologic infections

Babesia (apicomplexa) Findings Form/Transmission Diagnosis Disease Treatment

 Ixodes tick  Giemsa stain Babesiosis DOC  Co

Ring, maltese cross tetrad

Plasmodium (P. vivax/ovale, P. malariae, P. falciparum) (apicomplexa)

Two hosts 1. Anopheles mosquito  Sexual phase (sporogony) 2. Vertebrates (humans)  Asexual phase in liver/RBCs (schizogony)

Symptoms Chills, fever

Species Blood smear/ features Disease Liver stages Treatment

P. vivax  Enlarged host cells Benign tertian Relapse due to persistant hypnozoites Chloroquine then  Ameboid trophozoites  48 hour fever spikes (dormant form in liver) primaquine rd  Shüffner’s dots (every 3 day) Ameboid trophozoite

P. ovale  Similar to vivax Benign tertian Relapse due to persistant hypnozoites Chloroquine then  RBCs more oval, jagged  48 hour fever spikes (dormant form in liver) primaquine  Shüffner’s dots (every 3rd day)

Oval trophozoite Microbiologia 46

P. malariae  Bar and band forms Quartan No persistant form Chloroquine  Rosette schizonts  72 hour fever spikes Recrudescence (symptoms reoccur) due (every 4th day) to low level remaining in RBCs  Recrudescence Rosette schizont

P. falciparum  Multiple ring forms Malignant tertian (most serious) No persistant form Chloroquine resistance a  Crescent

Multi-ring Gamete Microbiologia 47 PROTOZOA— CNS infections

Toxoplasma gondii (apicomplexa) Findings Form/Transmission Diagnosis Disease Treatment

 Cat is essential  Serology  Healthy heterophile neg mononucleosis (flu-like illness with DOC definitive host  High IgM or rising IgM lymphadenopathy/fever)  Primethamine +  Raw pork MCC (acute infection)  Pregnant heterophile neg mononucleosis, can cross placenta sulfadiazine (+ folinic  Contact with cat feces  Crescentric (early: congenital infections— chorioretinitis, hydrocephalus, acid)  Most common protozoal tachyzoites and intracerebral calcifications; late: blindness in teens)  Prophylaxis at CD4<100 infection in US necrosis  AIDS MCC focal CNS disease (ring

Naegleria fowleri (free-living amoebae)

 Swimming in warm  Motile trophozoites in Primary amebic meningoencephalitis (PAM)  Amphotericin B (rarely fresh water CSF  Severe prefrontal headache, altered sense of smell, nausea, high successful)  Enters cribiform plate fever; often fatal Trophozoites in CSF

Acanthamoeba (free-living amoebae)

 Contaminated contact  Star

Star-shaped cysts CSF

PROTOZOA— Hemoflagellates Trypanosoma Species Transmission Diagnosis Disease Treatment T. cruzi  Reduviid bug (kissing  Trypomastigote in Chagas disease  Nifurtimox bug, cone bug)—painless blood films  Swelling around eye (Romaña sign), dilated cardiomyopathy,  Benznidazole bite megacolon, megaesophagus  Brazil, South America

T. brucei  Tsetse fly (painful bite)  Trypomastigote in African Sleeping Sickness  Suramin (acute) (gambiense, rhodesiense) blood films, CSF  Enlarged lymph nodes, recurring fever (due to antigenic  Melarsoprol variation), somnolence, coma (chronic/CNS involvement)

Microbiologia 48 Leishmania L. donovani  Sandfly bite  Amastigotes in Visceral Leishmaniasis (most severe) Visceral (Phlebotomus) macrophages in bone Hepatosplenomegaly, spiking fever, weight loss, fatigue, anemia,  Lipsomal Amp B  Middle East, India, South marrow, liver, spleen mucosal ulcers America, North Africa Cutaneous  Sodium Stibogluconate Amastigotes Promastigotes in macrophage L. braziliensis  Amastigotes in Mucocutaneous Leishmaniasis macrophages in Extensive disfigurement of nasal septum, lips, and palate Leishmania cutaneous lesions Cutaneous Leishmaniasis (About 15 different species) Oriental sore (local; open ulcerative lesion) Microbiologia 49

Trematodes (flukes, flatworms)—Snails are 1st intermediate hosts Ingestion Organism Acquisition Disease progression Ova Treatment Clonarchis sinensis  Raw fish  Biliary tract inflammation pigmented gallstones (chinese liver fluke)  Southeast Asia  Assoc. with cholangiocarcinoma (MCC eastern world)  Raw crab meat, crayfish  Mimics pulmonary TB Paragonimus westermani Operculated  Lung inflammation & 2° bacterial infection; hemoptysis (lung fluke) Eggs Praziquantel Fasciola hepatica  Aquatic plants  Fever, nightsweats, malaise (sheep liver fluke) (watercress) Fasciolopsis buski  Aquatic plants  Diarrhea and abdominal pain (giant intestinal fluke) (water chestnuts) Skin penetration

Schistosoma mansoni  Contact with water; Intestinal schistosomiasis (TH2 mediated) Schistosoma japonicum (Asia)  Skin penetration by cercariae  Skin penetration (itching) mature in veins of mesentery (motile larva form)  Eggs cause granulomas in liver (portal hypertension) Praziquantel Schistosoma  Contact with water Vesicular schistosomiasis  Skin penetration by cercariae  Enter skin (itching) mature in bladder veins (hematuria) haematobium  Egypt and Africa  Chronic infection high association with squamous cell carcinoma of the bladder

Non

Human: No ova

Cestodes (tapeworms) Ingestion Organism Acquisition IH DH Disease progression Diagnosis Treatment Taenia saginata Rare beef Cattle Humans Intestinal tapeworm (sm intestine) Proglottids or (beef tapeworm) (containing cysticerci)  Asymptomatic or vague abdominal pains eggs in feces Raw pork Swine Humans Intestinal tapeworm (same symptoms as saginata) Proglottids or (containing cysticerci) eggs in feces Praziquantel Taenia solium Water, vegetation Cysticercosis Biopsy (surgery for (pork tapeworm) (contaminated with eggs) Humans —  Larvae develop in brain (brain cysts) ―swiss cheese brain‖ eye, heart, lung adult onset epilepsy, seizures some T. solium  ―Immigrant with new onset seizures‖ cysts) Microbiologia 50 Diphyllobothrium Raw pickled fish Crustacean Humans Intestinal tapeworm Proglottids or (with sparganum/larvae)  fish  Competes for B12 in intestine (megaloblastic anemia) eggs in feces latum Drinking pond water Sparganosis Biopsy (fish tapeworm) (contaminated by copepods Humans —  Larvae penetrate/encyst intestinal wall carrying larvae) Echinococcus Ingestion of eggs from Humans; Herding Hyatid cyst disease Imaging; Surgery; granulosus dog feces Sheep dog  Liver cysts with brood capsules (and/or lung cysts) serology albendazole Larvae develop in Intermediate hosts (IH)… Adult tapeworms develop in Definitive hosts (DH)… Cysticerci= encysted larvae found in Intermediate host Microbiologia 51

Nematodes (roundworms) [treatment usually –bendazoles (remember bendy worms)]

Ingestion—Eggs (larvae ingestion for Trichinella) Mnemonic—EAT Species Acquisition Disease Diagnosis Treatment

Enterobius vermicularis  Eggs ingested Pinworms in large intestine  Scotch tape test (sticky Mebendazole; (MC helminth in U.S.)  Also person to person  Perianal itching swab of perianal area) (treat entire  Child scratches and gets eggs under nails  Ova have flattened side family) with larva inside

Ascaris lumbricoides  Eggs ingested Ascariasis  Bile stained, knobby eggs Mebendazole; (MC helminth worldwide)  Egglarva migrate through lung (cough)  Adult roundworms up to a Surgery for  Mature in sm intestine (may obstruct) foot long migrations Trichinella spiralis  Wild game meat Trichinosis  Muscle biopsy (cysts with larvae) Mebendazole  Raw bacon  Larvae encyst in muscle myalgia  Eosinophilia (Type I HS) (Severe: add  Encysted larvae  Fever, splinter hemorrhages, periorbital steroids) consumed edema Toxocara canis (cati)  Eggs ingested Visceral larva migrans  Clinical findings and serology Mebendazole; (Dog & Cat Ascarids)  Handling puppies  Larva wander aimlessly until they die Self-limiting  Eating dirt in yard  Cause inflammation

Trichuris trichiura  Eggs ingested Whipworm in cecum  Barrel

Skin penetration—Larvae Mnemonic—SANd Strongyloides stercoralis  Skin penetrated by Threadworm strongyloidiasis  Larvae in stool Ivermectin filariform larva  Early—pneumonitis, abdominal pain, diarrhea  Serology Thiabendazole  Autoinfection unless  Late—malabsorption, ulcers, bloody stool treated Ancylostoma braziliense  Skin penetrated by Cutaneuous larva migrans  Presumptive diagnosis Thiabendazole; filariform larva  Intense skin itching  Larva cannot mature in humans Topical Ancylostoma caninum corticosteroids (Dog & Cat hookworms)

Necator americanus  Bare feet Hookworm  Fecal larvae- up to 13mm Mebendazole (New World hookworm) penetrated by  Bloodsucking intestine wall  Ova- oval, transparent, 2<8 (+ iron therapy) filariform larva microcytic anemia cell stage  Lung migration pneumonitis  Occult blood possible Filarial Nematodes Wucheria bancrofti  Female mosquito  Elephantiasis—Blockage of lymphatic Microfilariae in blood; Eosinophilia; IgE- Surgery, Brugia malayi, Brugia timori vessels (takes a year for symptoms) mediated degranulation of mast cells DEC+ivermectin

Loa Loa  Chrysops (Deer fly,  Pruritis, calabar swellings (local swelling  Micropfilariae in blood; Surgery; (African Eye worm) horsefly, mangofly) where worm travels; subcutaneous) Eosinophilia DEC, ivermectin  Worm in conjunctiva Microbiologia 52 Onchocerca volvulus  Female blackfly  River blindness  Skin snips from calabar swellings Surgery;  Itchy leopard rash (black skin nodules) DEC, ivermectin

Dracunculus medinensis  Drinking water with  Creeping eruptions, ulcerations, inflammation  Increased IgE Metronidazole; (Guinea worm, fiery serpent) infected copepods  Worm eruption from skin Slow worm removal w/stick

DEC= Diethylcarbamazine Microbiologia 53 Ectoparasites Pediculosis capitis (head lice)  Head to head contact; prevalent in school children  Permethrin 1% cream, Pyrethrin, Malathion, Lindane Pediculosis pubis (crabs)  Sexual contact (must also check for STDs) Scarcoptes scabiei (scabies)  Burrows under skin (intense itching); interdigital webbing, feet, hands, trunk, elbows  Permethrin 1% cream, Ivermectin, Lindane Antimalarials Drug Mechanism Clinical Use Toxicity/Contraindications Chloroquine Erythrocytic shizotocide—Accumulates P. vivax/ovale use chloroquine + primaquine  Retinal damage in food vacuole of parasite and prevents P. falciparum/malariae use chloroquine alone  Itching (contraindicated in psoriasis) conversion of heme to hemozoin Resistance= mutated transporter  Depression (heme accumulates= death) Drugs: Quinine + pyri/sulf > Mefloquine > Artemisinins Primaquine Tissue schizontocide For Plasmodium vivax/ovale (dormant in liver)  Hemolysis in G6PD deficiency (Used with chloroquine) Works against hypnozoites to prevent relapse  Contraindicated in pregnancy Chloroquine resistant cases Quinine First line for chloroquine resistant P. falciparum  Cinchonism (vertigo, tinnitus, flushing)  Blackwater fever (hemolysis in G6PD deficiency) Pyrimethamine< Sulfadoxine Used in combo with quinine for chloroquine resistant P. falciparum  Hypersensitivity reaction Mefloquine Second line for resistance; prophylaxis in high risk areas  Syncope, cardiac conduction defect, pneumonitis Only take orally (20 day half life)  Contraindicated in psychosis, seizures Artemisinins (Artsunate, Arthemether) Multi-drug resistance (obtained from Chinese herb)  Generally well tolerated

Antiprotozoals Trematodes/Cestodes Drug Clinical Use Toxicity Drug Mechanism Metronidazole Accumulation of toxic metabolites (free radicals)  Praziquantel  Increases calcium efflux which damage DNA with alcohol  DOC: Giardia, Entamoeba, Trichomonas,  GI distress Nematodes (GET GAP on the Metro) Drug Mechanism  Hypersensitivity reaction with THF/ DNA synthesis)  Megaloblastic anemia Mebendazole  Decrease glucose uptake & microtubular Albendazole  structure  Prophylaxis at CD4<100 for AIDS Pyrantel Palmoate  Spastic paralysis of worms Trypanosomiasis PARASITE HINTS Benznidazole Produce T.cruzi-sensitive free radicals  Rash  DOC: Chagas disease (T. cruzi) Findings Organism  Adrenal damage Cholangiocarcinoma Clonarchis sinensis Early (hemolytic) stages  Uticarial rash Hemoptysis Paragonimus westermani Melarsopral African sleeping sickness (T. brucei)  Similar to arsenic posioning Portal hypertension Schistosoma mansoni Late (CNS) stages Text Hematuria, bladder cancer Schistosoma haematobium Backup (T. cruzi, T. brucei)  GI & Neurological Brain cysts, seizures Taenia solium Leishmaniasis B12 deficiency Diphyllobothrium latum Liver cysts Echinococcus granulosus Sodium Leishmaniasis (IV administration)  Phlebotoxic Perianal itching Enterobius  Pancreatitis Microcytic anemia Necator, Ancylostoma

Microbiologia 54

DNA Viruses

―Her Po He Pa Par Ade‖ General rules (exceptions)  Icosahedral (Pox= complex)  dsDNA (Hepadna= partial; Parvo= ssDNA)  DNA replicates in nucleus (Pox= cytoplasm)

Enveloped Herpes Pox Hepadna  Large dsDNA (linear)  Large dsDNA (linear)  Partial  Envelope derived from nuclear membrane  Replicates in cytoplasm dsDNA  Virus assembly in nucleus (others assemble in cytoplasm)  Box shape, complex; (circular)  Establishes latency NOT icosahedral Smallpox (Variola) Hepatitis B ➀HSV<1 [Latent in trigeminal ganglia] ➃EBV [Latent in Bwhitlow (dentists- vesicles on finger) ➄CMV [Latent in mononuclear cells] of development) HBsAg= currently infected HBsAb= provides immunity ➁HSV<2 [Latent in sacral nerve ganglia]  MCC in utero infection U.S. (blueberry muffin  Guarnieri bodies (intracytoplasmic)

 Human mucosa sexual contact baby- thrombocytic purpura, MR, jaundice, pneumonitis, periventricular calcifications) Molluscum contagiosum HBcAg=  acute & chronic  Painful genital vesicles, (encephalitis is mild) HBcAb= IgM (acute) IgG  Heterophile neg mononucleosis  Neonatal herpes (at birth; encephalitis)  Young adult—wrestling, swim team (chronic); could be  during  AIDS= retinitis + ulcerations of GI tract  Direct contact (sexual) or fomites window phase ➂VZV [Latent in dorsal root ganglia]  Owl‘s eye inclusion bodies  Replicates in dermis; Single/multiple benign  Human mucosa respiratory (also touch) ➅HHV<6 [Transmitted by saliva] umbilicated wartChickenpox (fever, pharyngitis, asynchronous increased transmissibility  Roseola (infants— 3 day fever, seizures; lacy  Molluscum bodies in central caseous material rash-macules, vesicles, scabs not same stage) (eosinophilic cytoplasmic inclusion bodies) HBeAb= low risk of body rash when fever breaks)  Shingles (Stress reactivation of latent transmissibility infection in 5th or 6th decade of life; pain & ➇HHV<8 [AIDS patients] vesicles restricted to 1 dermatome (unilateral) Dane particle= infectious HBV  Kaposi sarcoma (VEGF expression causes Tzanck smear—intranuclear Cowdry type A (All 3) purple splotches)

Microbiologia 55 Naked

Papova (papilloma/polyoma) Parvo Adeno  dsDNA (circular)  ssDNA (linear)  dsDNA (linear)  infects erythroid  Penton fibers toxic to cells progenitor cells  Virus is lytic in permissive cells Human Papilloma Virus (HPV) Polyomaviridae B19 (Erythrovirus) Pneumonia (children, military recruits, college)  Direct contact, fomites (AIDS/transplant patients)  Child— erythema infectiosum, fifth’s Pharyngoconjunctivitis (swimming pool; pink eye)  Genital warts (serotypes 6 & 11) BK virus (Bad Kidney) (flu ―slapped cheek‖ facial rash) Epidemic keratoconjunctivitis (shipyard dust)  CIN, Cervical cancer (16, 18, 31, 33, 35) JC virus (Junky  Adults—rash, stiff/swollen hands Acute hemorrhagic cystitis (young boys; hematuria)  E6 inhibits p53 Cerebrum: progressive  Fetus—hydrops fetalis, abortion Gastroenteritis (daycare; nonbloody diarrhea)  E7 inhibits Rb multifocal  Sickle cell—aplastic crisis leukoencephalopathy) Microbiologia 56 + ssRNA Viruses

―Pi Ca To Fla Co‖ General rules (exceptions)  Icosahedral (Corona= helical)  Linear, Non-segmented  DNA replicates in cytoplasm; No virion-associated polymerase

Naked Enveloped

Picorna Calici Toga Flavi Corona  Fecal-oral (Rhino= resp)  Helical

Polio Norwalk virus Rubella (German measles) Hepatitis C 2nd MCC common cold  Virus targets anterior horn motor neurons (norovirus) 3 day measles  Asymmetric paralysis (no sensory loss)  Fecal-oral, contaminated Truncal rash (Discrete, red Arboviruses (mosquito spread) SARS (Severe acute maculopapular rash begins on  Progressive muscle atrophy (iron lung) food/water respiratory syndrome) face, progresses to torso); Hemorrhagic  Cruise ships  Vaccines [Live Sabin; Killed Salk (U.S.)] posterior auricular -Aedes mosquito (monkey host) Bird/civet cat reservoir  Lose appetite watery lymphadenopathy Atypical pneumonia Echovirus  Dengue (breakbone fever; diarrhea Congenital rubella syndrome  MCC acute fever in young rash, muscle/joint pain; Fever > 100.4  Children and adults (crosses placenta/ breast milk— reinfection can cause  MCC aseptic meningitis (death= liver Flu-like, dry cough, (infants= rotavirus) cataracts, PDA, deafness, MR) hemorrhagic shock) failure/myocarditis; summer months) progressive hypoxia highest risk first 20 weeks  Yellow Fever (black vomit Coxsackie A gestation History of travel to with jaundice; damage to China or Toronto  Hand foot and mouth (A16; vesicular) Live, attenuated vaccine (MMR) liver, kidney, heart, GI) Patchy distribution of  Herpangina (blisters) Hepevirus Non-hemorrhagic focal interstitial Coxsackie B Alphaviruses (arboviruses) infiltrates Hepatitis E -Culex mosquito (bird host)  Bornhom disease (devil’s grip) Mosquito spread -Encephalitis  High mortality rate in  Aseptic meningitis, severe in newborns pregnancy East/West/Venezuelan  St. Louis Encephalitis equine encephalitis  Myocarditis (MCC heart transplant)  West Nile (can lead to muscle Rhinovirus weakness and flaccid paralysis—damage to  Acid-labile; Receptor= ICAM-1 anterior horn motor neurons)  MCC common cold; >100 serotypes Hepatitis A (Heparnavirus) Microbiologia 57

Retroviridae (+ssRNA; enveloped; contain reverse transcriptase) Viruses HIV genes/functions HIV associated conditions HIV labs/prophylaxis HTLV (Human T-cell Leukemia Virus)—Oncovirus group Gag genes Early symptomatic period Screening—ELISA  Adult TListeriosis Viral load—RT-PCR Reverse transcriptase HIV (Human Immunodeficiency Virus)—Lentivirus group  PID, Cervical dysplasia, Peripheral neuropathy Newborns—PCR Integrase (DNA integration to host AIDS associated conditions Early marker—p24 antigen  Diploid genome (2 copies of ssRNA) DNA)  Recurrent pneumonia (MCC death) P. jiroveci Progression—CD4:CD8 ratio  Sexual contact, blood (needles), vertical transmission Protease (cleaves viral  Candidiasis of esophagus/upper airway,  Homosexual males, IVDA, sexually active adults polyprotein)  Infects macrophages and T-cells; progresses to AIDS Env genes Coccidioidomycosis, Cryptococcosis, Histoplasmosis P. jiroveci < 200 CD4 gp120 (binds CD4 &  Malignancies—Cervical carcinoma, Kaposi sarcoma, Toxoplasma < 100 Progression followed by declining CD4 count coreceptors CCR5:macrophages; Burkitt’s lymphoma (immunoblastic or primary CNS) Histoplasma < 100 -Early flu-like, generalized lymphadenopathy CXCR4: T-cells)  CMV, HSV, PML (JC virus), wasting due to TNF- M. avium <50 -Later progresses to AIDS-defining conditions gp41 (fusion to host cell)  Cryptosporidiosis, toxoplasmosis (brain lesions) CMV <50 -Homozygous CCR5 mutation= immune Regulatory genes  TB (>200 CD4), M. avium (<200), salmonella Cryptococcus < 50 -Heterozygous CCR5 mutation= slow course  LTR (integration), Tat (transcription) Rev (transport), Nef (Virulence; when defective= won’t progress to AIDS) Microbiologia 58 — ssRNA Viruses General rules (exceptions)  ALL enveloped & helical  Linear (Bunya/Arena/Delta= circular)  ALL contain RNA

NON

Paramyxo Orthomyxo (8 segments)  Surface F protein (Fusion protein creates multinucleated giant cells)  HA & NA glycoproteins (used to serotype)  HA (hemagglutinin) glycoprotein (Measles); HN glycoprotein (Mumps) Measles Influenza  3 C’s Cough, Coryza, Conjunctivitis Headache, malaise, fever, chills, myalgias, anorexia  Koplik spots (blue/white spots with red base on buccal mucosa—white grains of sand in mouth) Bronchiolitis, croup, otitis media, vomiting (younger children)  Descending maculopapular rash (action of CTL on infected cells) ears down; presents last At risk for fatal bacterial superinfection (S. Aureus pneumonia MC; rapid 2-3 days)  Sequelae Subacute sclerosing panencephalitis (Progressive CNS degeneration to death); Can lead to Reye syndrome (aspirin) or Guillain-Barre (also c. jejuni) Giant cell pneumonia (immunocompromised, rare; Warthin-Finkeldey cells) Influenza A (birds, pigs, humans); Influenza B (humans only)  Live attenuated vaccine (MMR—Measles, Mumps, Rubella) HA (hemagglutinin- promotes viral entry); Mumps NA (neuraminidase- promotes progeny virion release)  Parotitis, Orchitis, Meningoencephalitis, Pancreatitis (Parotids & testes as big as POM-Poms)  Antigenic drift—(A and B) epidemics; mutations in HA and/or NA  Orchitis can cause sterility in males  Antigenic shift—(A only) pandemics; recombination/reassortment Respiratory syncytial virus (RSV) Treatment  Major cause of bronchiolitis in young (infants); pneumonia (Tx: Palivizumab; Ribavirin) Amantadine/rimantadine inhibit viral coating Parainfluenza Zanamivir/oseltamivir inhibit neuraminidase (prevent viral maturation and release)  Infants—Croup (seal-like barking cough); ―steeple sign‖ narrowing Vaccines: Killed (2 strains A, 1 strain B); Live attenuated (intranasal for children< 5yrs)  Children/Adults—subglottal swelling, barking cough

Rhabdo Bunya (3 segments—one ambisense)  Bullet-shaped Pseudocircular Rabies California Encephalitis  Rabid animal bite/contact U.S. (raccoons, bats, foxes, skunks); Worldwide (dogs) La Crosse Encephalitis  Virus binds to peripheral nerves (nicotinic ACh receptor)  Mosquito transmission (Minnesota area) Viral encephalitis  Travels via retrograde anxoplasmic transport to DRG & spinal cord (then rapid to brain) Hantavirus  Flu-like Hydrophobia, seizures, disorientation, hallucination coma, death  Rat excrement/urine Pulmonary syndrome  Intracytoplasmic Negri bodies (eosinophilic inclusions) Cough, mylagia, pulmonary edema, hypotension; 50% fatal  Post exposure prophylaxis= Rabies Ig, 5 doses killed vaccine (day of, 3, 7, 14, 28) Southwest U.S. (like coccidiodes & Y. pestis) Vesicular stomatitis (Flu-like in humans—handling livestock with foot & mouth disease) Microbiologia 59

Filo Arena (2 segments—one ambisense)  Circular Ebola virus (Bleeding from eyes; contact with blood transmission; high mortality) Lymphocytic Choriomeningitis (South America—mouse excrement) Marburg virus (Fatal Hemorrhagic fever) Lassa Fever Virus (Africa—spread by mice; hemorrhagic fever) Delta Reo (10-12 segments)  Circular  ONLY double stranded RNA virus (not + or –); naked, icosahedral Hepatitis D Rotavirus  Defected virus— requires Hepatitis B to ―coat‖ Hep D for infection  MCC diarrhea in infants—―Right Out The Anus‖ (day cares, kindergartens in winter months)  Worse prognosis and chronic state more likely with superinfection (HBV carrier Villous destruction with atrophy (decreased absorption of Na+ and loss of K+) exposed to HDV) than with co

Drug Mechanism Uses Side effects

Antiherpetics

Acyclovir Inhibits Viral DNA polymerase by acting as a chain HSV<1, HSV<2, VZV Crystalluria (must stay hydrated) terminator (must be first phosphorylated by viral thymidine kinase Reduces viral shedding; decreases acute Neurotoxicity (agitation, confusion, seizures) & bioactivated by other kinases) neuritis but no effect on postherpetic Valacyclovir (prodrug) shingles Famciclovir Resistance= TK mutation/absence or change in DNA pol Famciclovir DOC VZV Ganciclovir Mechanism and resistance similar to acyclovir CMV (2nd line for HSV-1, HSV-2, VZV) Hematotoxicity (leukopenia, thrombocytopenia) In CMV requires phosphotransferase for phosphorylation Prophylaxis and treatment of CMV retinitis Mucositis (swallowing problems, GERD) Valganciclovir (prodrug) inhibits DNA polymerase in AIDS & transplant patients Crystalluria Foscarnet Inhibits DNA/RNA polymerases & HIV reverse transcriptase Same as ganciclovir Nephrotoxicity, acute tubular necrosis, Does not require phosphorylation Acyclovir resistant HSV<1/2 electrolyte imbalance (avoid pentamidine IV) Cidofovir Acyclic nucleoside phosphonate that selectively inhibits DNA CMV retinitis (AIDS)—Intravenous Nephrotoxicity polymerase; does not require phosphorylation Resistant HSV Fomivirsen Antisense oligonucleotide- Binds mRNA; inhibits protein synth CMV retinitis (AIDS)—Intravitreal injection

HIV Therapy

Nucleoside RTi Competitive inhibition of reverse transcriptase preventing HAART therapy  Myelosuppression (Zidovudine greatest) Zidovudine (AZT) the formation of dsDNA (interupts elongation and impairs Prevents vertical transmission  Peripheral Neuropathy (Didanosine, complementary DNA synthesis) Stavudine (D4T) Used in pregnancy- 2nd and 3rd trimester Zalcitabine, Stavudine, Zidovudine) Didanosine (DDI) Triphosphate is active form and requires phosphorylation by Prophylaxis following needlestick injury  Pancreatitis (Didanosine) Lamivudine (3TC) host enzymes (Zidovudine+ Lamivudine 1 month) Zalcitabine (DDC) Lamivudine active in Hep B Lamivudine—Least toxic, some neutropenia Non

Integrase inhibitor Prevents integration of viral genome in host cell DNA (impairs Added when resistance to HAART Possible hypercholesterolemia; no other Raltegravir mRNA transcription) metabolic syndrome effects Fusion Inhibitors Enfuvirtide Binds gp41 to inhibit fusion of HIV-1 onto CD4 T-cells (Added in when other drugs fail) Injection site reaction Enfuvirtide Maraviroc (entry inhibitor) Blocks CCR5, preventing gp120 association and subsequent viral entry Maraviroc Other Antivirals Amantidine Blocks attachment, penetration, & inhibits uncoating of Influenza prophylaxis Nervousness, insomnia, seizures in OD Rimantidine Influenza A May  duration of flu symptoms 1-2 days Atropine-like peripheral effects Parkinson’s rescue drug; Chronic Hep C Livedo reticularis (purplish networking on skin)

Zanamivir (intranasal) Inhibit influenza neuraminidase, prevents release and Influenza prophylaxis Oseltamivir maturation of progeny virus (Influenza A and B) May  duration of flu symptoms 2-3 days Ribavirin Monophosphorylated form inhibits IMP dehydrogenase; RSV, Hantavirus, Lassa Fever, adjunct to Hematotoxic, upper airway irritation triphosphate inhibits RNA polymerase and end-capping alpha-interferons for Hep C Teratogenic Interferon- Activates host ribonuclease which degrades viral mRNA HepB (+Lamivudine); HepC (+Ribavirin) Palivizimab Monoclonal antibody—Blocks RSV protein F RSV (when Ribavirin cannot be used) Microbiologia 62

Microbiologia 63

Microbiologia 64