EXOTOXIC MODELCORYNEBACTERIUM DIPHTERIAE

Received its name from the hide-like pseudomembrane that forms on the tonsils, palate, or pharynx Even though the exotoxin can cause fatty degeneration of heart muscle and nervous system, young children

often die because their Airway is occluded. Exotoxins

o Secreted proteins from microorganismso Take form of A-B toxin where B interacts with a cell receptor as a ligand. A is then released,

internalized and causes damage to the cell.

I. GENUS CORYNEBACTERIUMA. CHARACTERISTICS

Club Shape Rods Gram Positive Non-spore forming Non-acid fast Aerobic or Facultative anaerobic Catalase Positive Non-motile

B. CHEMOTAXONOMICALLY Cell walls contain:

Meso-diaminopimelic acid Arabino-galactan polymer Short chain mycolic acids

C. CORYNEBACTERIUM SPP. World Wide

D. CLOSELY RELATED GENERA Rhodococcus, Nocardia, Mycobacterium

II. CORYNEBACTERIUM DIPHTERIAEA. PATHOGEN

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Occurs naturally only in humans but we can infect farm animals Produces Characteristic METACHROMATIC Granules that Stain Bluish Purple with

Methylene blue. Grows with Snapping division which results in Angular and Palisade arrangements that

look like Chinese Letters.

B. CYCLE OF INFECTION1. Respiratory tract diphtheria is most common in temperate climate2. Cutaneous diphtheria are seen in tropical areas

a. Spread by Touch and Fomitesb. Transmitted to cows by infected milker’s fingersc. Unpasteurized milk can then transmit the infection

C. PATHOGENESIS1. Classic AB exotoxic disease

a. B domain binds to cell receptor and forms membrane channel for A b. A binds to Elongation Factor 2 (EF-2) and causes it to be ADP

rebosylated and made inactive. Thus, the cell can no longer make proteins.

2. Toxin Productiona. Low iron stimulates toxin production

3. Biological Toxin Effectsa. Local pharyngeal membrane formationb. Heart, nerves, and kidney are most sensitive

D. CLINICAL MANIFESTATIONS1. Pharyngitis2. Bullneck due to neck swelling which leads to difficult air passage3. No lymphadenopathy4. Open mouth and look for membrane, which is 1-3mm thick and is curling away from

the tonsils, palate, uvula, or pharynx. 5. Foul breath associated with necrosis and the greenish or blackened membrane are

hallmarks****

E. DIAGNOSIS1. Elick Test and Schick Test

F. TREATMENT1. Erythromycin or penicillin2. Maintenance of open airway

G. PREVENTION1. DPT in children2. Td in adults (booster every 10 years)

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ENDOTOXIC MODELNEISSERIA MENINGITIDIS

ENDOTOXINSo Integral parts of microbial cell wall and are normally released only when the cell dieso Characteristic of Gram Negative Bacteria

I. NEISSERIA MENINGITIDIS

A. CELLULAR MORPHOLOGYo Small Gram Negative Diplococcuso Bean Shaped o Non-motile

B. PHYSIOLOGYo Aerobic or facultativeo Oxidase Positiveo Grow on Chocolate Agaro Sensitive to drying

C. ANTIGENIC CHARACTERISTICSo Capsular Polysaccharideo Surface antigens include proteins for iron uptake from transferrin

D. VIRULENCE FACTORSo Pili – Attach to cells of mucous membrane of pharynx or nasopharynxo Capsule – Anti-phagocytico Endotoxin – Causes shock and necrosiso IgA protease

E. CYCLE OF INFECTIONo Enters through Upper Respiratory Tracto Invade and enter bloodstream to infect skin, eyes, joints, lungs, and meninges.

F. DISEASESo Causes mild to acute pharyngitiso Skin affected with Petechial Rash** along the nuchal rigidity are early signs of meningitis. o Spinal fluid is turbid. o Sequellae: Nerve Deafness Skin Damage CNS Damage Death without treatment

G. LABORATORY IDENTIFICATIONo Thayer Martin Agar (Chocolate agar plus vancomycin)

H. MORBIDITY AND MORTALITYo Highest disease rate among children o Mortality is less than 10% with early diagnosis and treatment

I. TREATMENTo Before Lab diagnosis treat with Cephalosporin or Ampicillino After lab diagnosis teat with Penicillin

J. RELATED ORGANISMSo Neisseria gonorrhoea, Moraxella, and Branhamella

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PYOGENIC MODELSTAPYLOCOCCUS AUREUS

I. CHARACTERISTICS OF STAPHYLOCOCCI

A. CELLULAR MORPHOLOGYo Gram Positive Coccio Grape like clusters

B. PHYSIOLOGYo Non motileo Facultative anaerobeso Produce Catalase to breakdown hydrogen peroxide

C. ECOLOGICAL NICHEo Normal flora of humans (Anterior nares, perineum, axillae)

D. GENETIC ASPECTSo Antibiotic resistance is plasmid or transposon mediated.

II. INFECTIOUS CYCLE Mode of Transmission: Direct contact and Fomites No vaccine to prevent disease.

III. PATHOGENIC CHARACTERISTIC Primary or opportunistic pathogens that can infect any organ or tissue Excrete Coagulase*** Toxic Shock Syndrome by Toxin-1 Epidermolytic (exofoliative) toxin (scalded skin)

IV. STAPHYLOCOCCAL DISEASES1. Cause >80% of Suppurative diseases and are major cause of Nosocomial Infections***2. Toxic Shock Syndrome

i. Associated with tampon use. S. aureus grows in vagina, producing exotoxins which cause symptoms of Fever, Hypotension, Diarrhea, Conjunctivitis, myalagia, and rash with desquamation.

3. Stapylococcal Food Poisoningi. Short term, Self limiting, Violent vomiting for 24-48 hours

4. Staphylococcus epidermidis infectionsi. Colonization of prostheses. Slimy capsule enhances adherence to tissue

V. TREATMENT Drain abscesses, remove foreign bodies (prostheses) Penicillin or Erythromycin

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CAPSULAR MODELSTREPTOCOCCUS PNEUMONIAE

Most have Polysaccharide Capsule Cause Non-Invasive (Otitis media) and Invasive Infections (pneumonia, meningitis, sepsis)

I. CAPSULAR FUNCTION Adhesins and invasions are essential during the contact of bacteria with their target cells and for invasion. When the bacteria enter the circulation, capsules are required to counteract complement and phagocytic

activity.

II. BIOLOGICAL PROPERTIESA. CELLULAR MORPHOLOGY

o Gram Positive Lancet-shaped Diplococcio Non-motileo Non-spore forming

B. VIRULENT STRAINS PRODUCE A POLYSACCHARIDE CAPSULEo Encapsulated strains produce smooth colonies on agar

C. PHYSIOLOGYo Facultative anaerobeso Require Cholineo Catalase Negative**o Alpha Hemolysis on Sheep Blood Agar

III. VIRULENCE FACTORSA. COLONIZATION AND MIGRATION FACTORSB. TISSUE DESTRUCTIONC. PHAGOCYTIC SURVIVAL

IV. INFECTIOUS CYCLE Reservoir: Human Nasopharynx Enter through respiratory tract Causes Lobar Pneumonia, Meningitis, Bacteremia, and Otitis

V. CLINICAL PRESENTATION Accumulation of edema fluid (X-ray) Sudden onset with Fever, Chills, and Sharp Pleural Pain and Rusty colored sputum due to Alveolar

exudates containing erythrocytes***

VI. TREATMENT Penicillin G or erythromycin

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OTHER STREPTOCOCCI

I. CLASSIFICATION OF THE STREPTOCOCCI C carbohydrate (Lancefield group serological designation) Hemolytic Characteristics

II. BETA HEMOLYTIC STREPTOCOCCI Produce soluble hemolysins detectable on blood agar

A. GROUP A: STREPTOCOCCUS PYOGENESo Bacitracin sensitiveo Large zones of hemolysis

B. GROUP B: STREPTOCOCCUS AGALACTIAEo Normal flora of human pharynx, GI and female genital tracto Small zones of hemolysiso Positive CAMP test

C. GROUP C AND Go Found in pharynxo Cause sinusitis, bacteremia, endocarditis

III. NON-BETA HEMOLYTIC STREPTOCOCCI Alpha (Greening) or No hemolysis on Sheep Blood Agar Plate (BAP)

A. GROUP D: ENTEROCOCCUS SPP.o Normal gut florao Grow in presence of 40% bile or 6.5% NaClo Inhibited but not killed by Penicillin. o Major Nosocomial Pathogens – Highly Resistant – Now also to Vancomycin***

B. STREPTOCOCCUS PENUMONIAEo Alpha hemolytic, Bile Soluble, Inhibited by Optochin**

C. GROUPS H AND K: VIRIDANS STREPTOCOCCIo Alpha hemolytic, Not Bile Soluble, Not inhibited by optochin.o Cause Dental Caries

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MODEL RESPIRATORY TRACT INFECTIONSHAEMOPHILUS AND BORDETELLA

HAEMOPHILUS INFLUENZA

I. BIOLOGICAL CHARACTERISTICSA. MORPHOLOGY

o Gram Negative Coccobacilluso Non-motileo Non-spore formingo Six Capsular Serotypes (A-F): Type B (polyriboylribitol phosphate, PRP or PRRP) causes most

acute infections

B. METABOLISMo Whole blood contains 2 factors Essential For Growth:

X Factor – Hemin, hematin, or protoporphyrin IX V Factor – NAD

o Aerobic, Facultative anaerobe

C. RESISTANCEo Easily killed by

50C for 30 minutes Desiccation Most antiseptics

II. VIRULENCE FACTORS1. Capsule prevents phagocytosis2. Endotoxin (LOS)

III. INFECTIOUS CYCLE Unimmunized children 2 months through 3 years are most susceptible Non-life threatening by age 10 Transmitted via droplet and fresh exudates

IV. DISEASES CAUSED BY H. INFLUENZA Begins as Nasopharyngitis Coryza, Cellulitis around cheek, Otitis meda, epiglottis. Infection to joints and meningitis.

V. LABORATORY DIAGNOSIS Positive Quellung Test establishes diagnosis Bile Solubility Test: Bile soluble

VI. TREATMENT Ampicillin

VII. PREVENTION Type B Capsular (PRP) Antigen Vaccine for children OVER 18 Months (Ti Antigen) Protein PRP Conjugate Vaccine for children UNDER 18 months (Td Antigen)

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VIII. OTHER RELATED SPECIESA. H. aegypticus Koch Weeks Bacillus, Purulent ConjunctivitisB. H. parainfluenza Subacute bacterial endocarditisC. H. suis Acute swine influenzaD. H. ducreyi Venereal disease chancroid

BORDETELLA PERTUSSIS (Whooping Cough)I. BIOLOGICAL CHARACTERISTICS

A. MORPHOLOGYo Gram Negative Coccobacillio Non-motile, Non-spore formingo Have Fibriae for attachment to cilia of respiratory epithelial cells

B. PHYSIOLOGYo Aerobico Inhibited by Fatty acids, sulfides, peroxideso Must be grown on media with charcoal, starch, blood, or ion exchange resins to bind inhibitors.

C. GENETICSo bvg AS genes control virulence factors

D. ANTIGENIC STRUCTUREo Fibriae, Filamentous hemaggultinin (FHA), Pertactin, LPS

E. RESISTANCEo Killed by

Drying 50C for 30 minutes Most antiseptics and disinfectants

II. INFECTIOUS CYCLE Childhood disease with highest incidence in children under 7 Highly communicable Transmitted via aerosols

III. DISEASES CAUSED Colonization of ciliated epithelium o nasopharynx Catarrhal Stage ( Most Contagious) lasts 10-14 days and is characterized by:

o Rhinitiso Sneezingo Mild Cough

Paroxysmal Stageo Last 1-6 weekso Severe coughing followed by “whoop” coughing

Convalescent Stageo Lasts weeks to months

Complicationso Secondary infections are possibleo Neurological complicationso Pneumothoraxo Hemorrhages

IV. LAB DIAGNOSIS Swat nasopharynx and plate onto Bordet Gengou Agar with and without penicillin

V. TREATMENT Erythromyocin, Tetracyclin, or Chloramphenicol Resistant to sufonamides and Penicillin

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VII. PREVENTION Whole Cell Vaccine (DTP) New Acellular Vaccines (DtaP)

SYSTEMIC ZOONOTIC INFECTIONS

I. BRUCELLOSISA. DESCRIPTION

o Zoonoses are diseases of vertebrate animals which are easily transmissible to man.o Not transmittable from man to man. o Systemic bacterial disease transmitted to humans by contact with unpasteurized milk o Characterized by continued, intermittent, or irregular fever and influenza like signs and symptoms

of malaise, anorexia, fever, and profound muscular weakness. “UNDULANT FEVER”B. ETIOLOGIC AGENTS

1. B. melitensis (goats)**2. B. abortus (cattle)3. B. suis (swine)4. B. canis (dog)

C. BIOLOGICAL CHARACTERISTICS1. Gram Negative Rod or Coccobacillus2. Non-motile, Non-sporeforming3. Facultative intracellular parasite4. Strict aerobe

D. PATHOTGENESISo Lesions are granulomatous characterized by mononuclear cell proliferation, fibrin deposition,

coagulation, necrosis, and fibrosis.E. TREATMENT

1. Timethorpim/Sulfamethozazole for 3 weeks + IM Gentamicin for 5 days – Children 8 or younger2. Doxycycline for 3 weeks + IM Gentamicin for 5 days – Children over 83. Oral Doxycycline and Rifampin for 30 days – Adults

II. PLAGUEA. DESCRIPTION

o An infectious disease of rodents and rabbits transmitted to humans by the bite of an infected flea.o “Black Death” Disease

B. ETIOLOGIC AGENT: YERSINIA PESTIS1. Gram Negative Coccobacillus - Marked bipolar staining and safety pin appearance 2. Facultative anaerobes3. Do Not Ferment Lactose4. Oxidase Negative5. Catalase Positive6. Non-Hemolytic7. 28C is optimal growth temperature

C. VIRULENCE FACTORS1. V-W antigens prevent phagocytosis2. Envelope (F-1) antigen prevents phagocytosis**3. Murine Toxin – produces shock4. Endotoxin – causes Febrile Response and Schwartzman reactions

D. DISEASES1. Buboes – Swollen lymph nodes2. Rapid rise in temperature, pneumonic signs, CNS abnormalities3. Pneumonic Plague – Pulmonary involvement from septic emboli

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E. TREATMENT1. Streptocycin2. Kanamycin3. Reporting to health authorities is Mandatory

F. PREVENTION1. Chemoprophylaxis with tetracycline recommend for those with a family history 2. Formalin killed vaccine for those with occupational exposure risk

III. TULAREMIA (FRANCISELLA TULARENSIS)

A. DESCRIPTIONo Infectious disease of wild animals especially rabbits that is transmitted to humans by direct

contact, arthropod vector transmission, and ingestion of contaminated meat.

B. BIOLOGICAL CHARACTERISTICS1. Gram Negative Coccobacillus with Bipolar Staining2. Obligate Aerobe3. 35C is optimal growth temperature4. Requires Cysteine and other growth factors

C. VIRULANCE FACTORS1. Jellison Type A – More virulent tick borne rabbit tularemia2. Jellison Type B – Waterborne rodent or sheep carried

D. DISEASESo Resemble those of plague with Primary Ulcer at site of entry and Lymphadenopathy.o 10% develop Painless, Non-Pruritic Rash

E. PATHOGENESIS AND HOST RESPONSE1. Ulceroglandular Form – Ulcer at site of infection2. Oculoglandular Disease – Site of infection is Conjunctival Sac with Papule Formation3. Typhoidal Type – Due to uncooked meat4. Pulmonary Disease5. Agglutinating IgM and IgG antibodies.

F. TREATMENT1. Streptomycin or Gentamicin2. Tetracycline and Chloramphenicol

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IV. ANIMAL BITE INFECTIONS

A. PASTEURELLA MULTOCIDA1. DESCRIPTION

Normal flora of nasopharynx of dogs and cats.2. ETIOLOGIC AGENT

i. Gram Negative Rod Shaped with bipolar stainingii. Non-hemolytic on blood agar

iii. 37C optimal temperature3. PATHOGENESIS AND HOST RESPONSE

i. Local infection at site of bite followed by regional lymphadenitisii. Cat bite progress to pyarthroses, necrotizing synovitis, and osteomyelitis

4. EPIDEMIOLOGYi. 1 to 2 million animal bites per year in the U.S.

5. TREATMENTi. Wound Irrigation

ii. Debridementiii. Suturingiv. Antibiotic prophylaxis and therapy for bite. Penicillin, Amoxicillin, Dicloxacillin.

B. DF-2 (CAPNOCYTOPHAGIA CANIMORSUS)1. DESCRIPTION

Gram Negative Opportunistic pathogen that can cause multiple organ disease in humans. Mostly due to dog bites

2. DIAGNOSIS Supported when severe sepsis develops after a bite in an immunodeficient patient Blood smears reveal Gram Negative Bacilli within Neutrophils

3. TREATMENT Penicillin G

C. STREPTOBACILLUS MONILIFORMIS

1. DESCRIPTION Found in pharynx of wild and lab rats Rat Bite Fever in laboratory workers after a bite Haverhill Fever in those with ingestion of contaminated milk Gram Negative, Non-encapsulated, Occurs in chains and filaments Most Distinguishing characteristic is Spontaneous Development of L-Phase Variants***

2. PATHOGENESIS AND HOST RESPONSE Maculopapular Rash develops in 48 hours*** along with acute arthritis

3. TREATMENT Pencillin G

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V. CAT SCRATCH DISEASE (CSD) - BARTONELLAA. INTRODUCTION

o Characterized by development of a Primary Inoculation Lesion at the site of Cat Scratch, followed by Subacute Regional Lymphadenitis. ***

o 50% only have Regional Lymphadenopathyo 10% have Perinaud’s Oculoglandular Syndrome (due to rubbing the eye after holding a cat)o Benign and Self limitingo Most common cause of chronic regional lymphadenitis in children

B. DESCRIPTIONo Motile**o Aerobico Gram Negativeo Warthin Starry Silver Imprgnations Stain and Brown Hopps Tissue Gram Staino BARTONELLA SPP.****

C. DIAGNOSISo Supported when following are met:

Exposure to cat Regional Lymphadenitis** Positive IFA test for B. henselae with titer greater than 1:64 in acute phase serum** Other causes of lymphadenopathy have been excluded.

D. EPIDEMIOLOGYo Primarily a disease of children with 60% of the patients being less than 12 years old**

E. TREATMENTo No specific treatment – Recover completely within monthso Treatment of cat with Doxycycline or Linicomycinseveral

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ENTERIC BACTERIA

Include Gram Negative Bacilli and Vibrios found normally in the Intestinal Tract. Gram Negative Bacilli - Coliforms

o Oxidase Negative**o Grow on MacConkey Agaro Characteristics used to differentiate rely on biochemical tests.o Antigens of the Cell Wall are used in diagnosis:

Somatic or “O” Antigens Flagella or “H” Antigens Capsule or “K” Antigens

Vibrioso Oxidase Positive**o Cause Cholera o Associated with vertebrate or invertebrate species in fresh and brackish waters

Campylobacterso Microaerophillico Oxidase positive**o Motileo Curved to Spiral rods

I. COLIFORMS Oxidase Negative** Lactose fermenters Normally found in large intestine

A. ESCHERICHIA COLI1. Indicator of fecal pollution of water, food, and dairy products.2. Diarrheal Disease and Meningitis in neonates due to K1 capsular antigen3. Enterotoxigenic E. coli (ETEC)

i. Acquired through ingestion of contaminated foodsii. Causes “Travelers diarrhea”

iii. Heat Labile Toxin (LT) – Increase cAMPiv. Heat Stable Toxin (ST) – Increase guanylyl cyclase

4. Enteropathogenic E. coli (EPEC)i. Gastroenteritis in infants of developing countries.

5. Enterohemorrhagic E. coli (EHEC)i. Blood in diarrhea

ii. No Fecal leukocytesiii. Sorbitol Negative (SMAC agar)iv. Undercooked ground beef is main cause**v. Hemolytic Uremic Syndrome (HUS) develops in 10% characterized by:

1. Microangiopathic Hemolytic Anemia2. Thrombocytopenia

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3. Thrombosis of Glomerular Capillaries6. Enteroinvasive E. coli (EIEC)

i. Dysentery – Fever, blood, small volume, pusii. Epithelial Invasion

7. Enteroaggregative E. coli (EAEC)i. Causes watery diarrhea

B. KLEBSIELLA1. K. pneumonia or K. oxytoca2. Non-motile, Ferments every sugar**3. Lobar pneumonia, urinary tract infection, wound infections

C. ENTEROBACTER1. E. cloacae and E. aerogenes2. Motile

D. SERRATIA1. S. marcescens2. Orange to Red pigment at room temperature3. Nosocomial infections

E. CITROBACTER1. C. freundii and C. koseri2. No intestinal infection

F. PROTEUS1. Swarms plate and Stinks**82. Lactose negative3. Urease positive

II. PRIMARY PATHOGENS

A. SHIGELLA1. Acute Bacillary Dysentery (Bowel movements, bloody stool, mucus, abdominal cramps, and tenesmus)2. Related to E. coli and cannot be differentiated with DNA hybridization3. Transmitted by fecal-oral route4. Antigen A S. dysenteriae5. Antigen B S. flexneri6. Antigen C S. boydii7. Antigen D S. sonnei – Often associated with Day Care Centers**8. Lactose Negative, Non-motile, Anaerogenic9. Smooth appearance forming colonies are Pathogenic

B. SALMONELLA1. Gram Negative, Aerobic2. Food borne infection is a major problem3. Gastroenteritis – Loose stools of moderate volume without blood for several weeks4. Bacteremia5. Enteric Fever – Typhoid Fever 6. Treatment includes Ampicillin, Streptomycin, and Tetracycline

III. OTHER ZOONOTIC GRAM NEGATIVE AGENTS - YERSINIOSISA. YERSINIA ENTEROCOLITICA AND YERSINIA PSEUDOTUBERCULOSIS

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B. Ingestion of contaminated food Acute Enteritis and AppendicitisC. Virulence Factors – AIL, YOP, and InvasinD. Neonates to 5 years Acute Gastroenteritis with watery diarrhea without bloodE. 5 – 15 years Acute mesenteric adenitisF. All ages Food poisoning

IV. VIBRIONACEAE A. GENERAL CHARACTERISTICS

1. Gram Negative Rods2. Motile with single Polar Flagellum3. Oxidase Positive 4. Grow on MacConkey Agar

B. VIBRIO1. VIBRIO CHOLERA

Low tolerance for acid 3 Serologic Subgroups (AB-Ogawa, AC-Inaba, ABC-Hikojima) Spread primarily in contaminated water Vomiting, watery diarrhea with Mucus Flecks (rice water stool)***

2. NON-CHOLERA VIBRIOS Caused by consumption of Raw Shellfish

3. VIBRIO PARAHEMOLYTICUS Gastroenteritis** Raw Seafood and Sashimi or contamination after cooking

4. VIRBIO VULNIFICUS ONPG positive Raw Oysters Gastroenteritis 16 hours after ingestion

C. CAMPYLOBACTER1. CAMPLYOBACTER JEJUNI

Sensitive to environmental stresses Found in Retail Chicken***, Raw milk, and Non-chlorinated water Infects mucosal surfaces of jejunum, ileum, and colon May cause Guillain-Barre Syndrome**

3. CAMPYLOBACTER FETUS Gastroenteritis and invasion of blood stream are more common

D. HELICOBACTER PYLORIo Urease producer, Ammonia to neutralize stomach acido Causes Gastritis, Gastric and Duodenal Ulcerso Precursor of gastric adenocarcinomao Treatment: Proton Pump Inhibitor (Omeprazole), Bismuth Compounds

E. PLEISOMONAS SHIGELLOIDESo Non-Lactose fermentero Genetically is more like E. coli than vibrioso Self limiting gastroenteritis

F. AEROMONAS HYDROPHILAo Gastroenteritis in healthy people, Septicemia in immunocompromised patients

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OPPORTUNISTIC ENVIRONMENTAL AND MISCELLANEOUS ORGANISMS

I. LEGIONELLA PNEUMOPHILA

A. BIOLOGICAL CHARACTERISTICS1. Gram Negative Bacilli2. Aerobic3. Catalase and Oxidase Positive4. Fastidious – High Cysteine and Low Sodium levels to grow5. Survive in tap water at room temperature for over a year

B. VIRULENCE FACTORSo Beta Lactamase Producer

C. INFECTIOUS CYCLEo Reservoir: Non-marine aquatic environments such as lakes and pondso Transmission: Aerosal to lungso Upper respiratory tract o Not communicable from human to human

D. PATHOGENESISo Inhaled Alveolar Macrophage Lyse macrophage after replication causing lung damage

E. DISEASESo Legionnair’s Disease - Patients present with Anorexia, Malaise, Headach, and a Rapid Fever to

39-40C. o Pontiac Fever – similar to Legionnair’s disease but more milder.

F. TREATMENTo Erythromycin

G. PREVENTIONo Hyperchlorination of water

II. PSUEDOMONADSA. CHARACTERISTICS

1.Grow on MacConkey agar2. Strict Aerobes3. Oxidase Positive4. Gram Negative, Motile with Polar flagellum

B. PSUEDOMONAS AERUGINOSA

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1. Blue Green Pigment2. 42C optimal temperature3. Fruity odor4. Pellicle (membranous surface film) in broth culture5. Lactose Negative6. Contaminates water – humidifiers and contact lens solutions

III. BURKHOLDERIAA. BURKHOLDERIA PSEUDOMALLEIL

o Gram Negativeo Aerobico Grow in watero Acquired by direct inhalation or inoculationo Meliodosis – acute pneumonia**o Glanders – Disease in horses with acute pulmonary lesions**

B. BURKHOLDERIA CEPACIAo Gram Negative, Aerobic, Grow in watero Causes Pulmonary Infection in cystic fibrosis

IV. STENOTROPHOMONAS MATOPHILIA Gram Negative, Aerobic, Grow in water, solutions, ice machines, etc Causes Bacteriemia, Pneumonia, Meningitis, Wound infections, Urinary tract infections

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MYCOBACTERIA

I. GENUS MYCOBACTERIUMA. CHARACTERISTICS OF GENUS MYCOBACTERIUM

1.Stain as Acid Fast (Gram Neutral/Positive) slim Rods2. Obligate Aerobes3. Non-Motile, Non-Spore Forming4. Very Slow Growing5. Unique Cell Wall Structure:

a. 2 backbones: Peptidoglycan and Arabinogalactanb. 60% lipid content, Very hydrophobicc. Development of mycolic acidsd. Outer envelope varies with species

6. Resistance to physical stress due to hydrophobic wall

B. ACID FAST STAIN1. Distinguishes Mycobacteria from other genera2. Once stained, cells resist Decolorization3. Classic Ziehl Neelsen Stain – Stain Red, other genera decolorize and counterstain blue

II. MYCOBACTERIAL DISEASEA. PATHOGENESIS

o By-Stander diseaseo Granulomas result from CMI processes. Bacilli multiply in macrophages. o Host damage results from Hypersensitivity to Mycoproteinso M. ulcerans is the Only Mycobacterium known to produce and Exotoxin**

B. DEFENSEo Cell mediated but incomplete (Macrophages kill intracellular mycobacteria)o Mycobacteria are Inhibited and Dormant, Not Killed. Must be actively contained for life

C. CLINICAL SYNDROMES1. Primary Infection

Handled well by host. Most lesions heal by fibrosis and organisms slowly die. Some remain for decades as opportunists

2. Reactivation Disease Reactivated due to immunosuppression, malnutrition, alcoholism, and diabetes

3.Granuloma Asymptomatic, rounded lesions Single or multiple Fibrous encapsulation of caseous lesion

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D. DIAGNOSTIC TOOLSo Purified Protein Derivative (PPD) skin test for Delayed Hypersensitivityo Acid Fast Smearw

III. MAJOR PATHOGENIC MYCOBACTERIA

A. MYCOBACTERIUM TUBERCULOSIS1. INTRODUCTION

o Causes Tuberculosis2. ETIOLOGIC AGENT

o Acid-Alcohol Fasto Wax D, cell wall oligomer is very strong immunoadjuvant**o Aerobic at 37C optimal**o Virulent strains show “Cording” on oleic acid albumin agar

3. HOST FACTORSo Multifactorial causation (genetic and environment influences)

4. CYCLE OF INFECTIONo Transmission from person to person via the aerosol route.o Respiratory tract to alveolus

5. PATHOGENESISo Tubercles result from Hypersensitivity to tuberculoproteins and depend on the concentration of

antigen at a location and the degree of tissue hypersensitivity.6. CLINICAL SYMPTOMS

o 80% is pulmonary tuberculosiso 90% it is asymptomatic or mild influenza like disease. o Chronic fever, weight loss, night sweats, and productive coughing with hemoptysis characterize

the disease***o Tuberculoma – Local lesions like Prosecutor’s Wart

7. DIAGNOSTIC STUDIESo Positive Niacin test confirms M. tuberculosis**

9. TREATMENTo Report the case to Public Health authoritieso Triple Chemotherapyo Isoniazid (INH) – inhibits synthesis of mycolic acids and mycobacterial DNAo Pyrazinamide (PZA) – Bactericidal, active against dormant mycobacteria at acid pHo Rifampin – blocks initiation of RNA transcriptiono Ethambutol – blocks syntheis of arabinogalactano Streptomycin – inhibits protein synthesiso Must use drugs in combinations or it is not useful.

B. MYCOBACTERIUM BOVIS1. ETIOLOGIC AGENT

o Produces tuberculosis in animals**2. CYCLE OF INFECTION

o Source: Infected cattle and their products, milk, cheese, meat.

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o Transmission: Ingestion or airborneo Primary site of colonization: Cervical and Mesenteric Lymph Nodes**

3. CLINCICAL SYNDROMEo Extrapulmonary lesions especially of cervical and mesenteric lympn nodes.

4. LABORATORY DIAGNOSISo DNA of M. bovis and M. tuberculosis have 100% homology with only a few different genetic

markers.o M. bovis is Niacin Negative**

7. TREATMENTo Same as M. tuberculosis

C. BACILLE OF CALMETTE AND GUERIN (BCG)1. VACCINE STRAIN

o Mutant of M. bovis isolated on a Glycerol-Potato-Bile Medium**o BCG vaccination is successful. Administration is Intradermal

2. BCG AS IMMUNOADJUVANTo Used as immunoadjuvant for superficial bladder cancer**

3. LABORATORY IDENTIFICATIONo Niacin Negative**

4. TREATMENTo With usual Antitubercular drugs

D. MYCOBACTERIUM LEPRAE1. ETIOLOGICAL AGENT

o Obligate Intracellular Parasiteo Slow multiplication within phagocytes, skin histiocytes, and Schwann cells. o Seen in armadillos and hedgehogs**

2. INFECTIOUS CYCLEo Much injury is due to denervation.

3. TREATMENTo Triple Therapy: Dapsone, Rifampin, Clofazimineo Treat until skin smears are free of bacilli

E. MYCOBACTERIUM ULCERANS1. CHARACTERISTICS

o Grows at 30C, NOT 37C**2. EPIDEMIOLOGY

o Usually in the Tropicso Reservoir: Plants of warm temperate rain foresto Source: Silt of shallow watero Transmission: Aerosolo Ulcerating Necrosis**

3. CLINICAL SYNDROMEo Begins as PainLess “Oil” or lump under skin. In a few weeks a shallow Ulcer with necrotic base

develops at the site of lump. ****4.TREATMENT

o Surgical excision and grafting o Antimicrobial treatment is often unsuccessful

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ACTINOMYCETES

Filamentous bacteria related to corynebacteria and mycobacteria and superficially resembling fungi. Grow as Gram Positive Some are Acid Fast Most are free living (soil). Anaerobic species are normally in the Mouth Some Aerobic species found in soil cause disease in humans and animals

I. ACTINOMYCOSIS Chronic Suppurative disease forming draining sinus tractsA. MORPHOLOGY AND IDENTIFICATION

o Typical finding is a Sulfur Granule in pus***o Gram positive colony surrounded by Eosinophillic “clubs”o A. israilii does not hydrolyze starch but A. bovis does.**o Catalase Negative

B. PATHOGENESIS AND PATHOLOGYo Found on teeth and tonsillar crypts

C. CLINICAL FINDINGSo Characteristic appearance is a Hard, Red, Non-tender Swelling that usually develops slowly.

Eventually drains forming a Chronic sinus extract with little tendency to heal****o Cervicofacial Disease – Swollen erythematous in the jaw area, producing draining fistulaso Throacic actinomycosis – Resembles subacute Pulmonary infection (mild fever, cough, purulent

sputum). Eventually lung tissue is destroyed, sinus tracts may erupt to chest wall, invasion of ribs. o Abdominal Actinomycosis – Follows a ruptured appendix or an ulcero Genital Actinomycosis – From intrauterine device most common in females.

D. DIAGNOSTIC LABORATORY TESTSo Sulfur granules under microscopeo Molar tooth shaped yellow colonies “looking like bread crumbs” on BHIA (brain heart infusion

blood agar). *****

II. NOCARDIOSIS Aerobic organisms that occur in soil Cauls Nocardiosis (human pulmonary disease that may spread to other parts of the body)A. MORPHOLOGY AND IDENTIFICATION

o Gram Positiveo Colonies are waxy or chalky winkled with pigmentation varying from yellow to red.

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o Urease Positive B. PATHOGENESIS AND CLINICAL FINDINGS

o Pulmonary Nocardiosis – begins as chronic lobar pneumonia and then spreads to rest of body.o Primary Cutaneous – Resulting Mycetoma is characterized by local subcutaneous swellingo Ocular – Infections from contaminated lenses or solution

III. ACTINOMYCOTIC MYCETOMA Localized granulomatous lesion with hypertrophy and draining sinus tracts.

ANAEROBES

ANAEROBES: FUNCTIONAL DEFINITION Fail to grow in air or 10% CO2 No superoxide dismutase or catalase Laminar flow

ANAEROBIC BACTERIA Part of normal flora, especially GI tract Outnumber aerobes 1000:1 Most infections are ENDOGENOUS and of Mixed aerobic/anaerobic etiology. Mixed Infections.

MIXED INFECTIONS Proximity to a mucosal site Pyogenic, very Foul Smelling Often due to predisposing conditions: surgery, injuries, contaminated wounds Clinical Clue: Profusion of mixed organisms on Gram Stain which fail to grow on routine culture**

COMMON MIXED INFECTIONS Head and neck Acute Necrotizing Ulcerative Gingivitis (ANUG) Abscesses Peritonitis Bites Aspiration pneumonia (Mendelson’s Syndrome) Gangrene

INFECTIONS WHICH SELDOM INVOLVE ANAEROBES Spontaneous peritonitis Urinary tract infection Meningitis Pharyngitis Bronchitis Pneumonia (except aspiration pneumonia) GI infections (except C. difficile)

ANAEROBIC BACTERIOLOGY Non-Spore Formers are Endogenous of Lower Virulence and tend to be opportunistic

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Spore Formers are Exogenous of Higher virulence due to Exotoxins ID cultured organisms by Gas Liquid Chromatography

CLINICAL APPROACH Never order anaerobic cultures from any site which has normal flora Prefer aspirates or biopsies to swabs Use anaerobic transport medium

ANAEROBIC GRAM POSITIVE COCCI: PEPTOSTREPTOCOCCUS Normal flora of GI, GU, and Skin Occasionally cause infections contiguous with mucosal sites Require 5-7 days to grow in culture Sensitive to most antibiotics

ANAEROBIC GRAM POSITIVE NON-SPORE FORMING RODS1. ACTINOMYCES2. PROPIONIBACTERIUM3. MOBILUNCUS4. LACTOBACILLUS5. EUBACTERIUM AND BIFIDOBACTERIUM

ACTINOMYCOSES Ray Fungus Non-acid fast, Fastidious, and Slow growing Normal flora of Upper Respiratory tract, GI tract, and Female genital tract. Not Skin! Chronic granulomatous infections with wood induration, multiple sinus tract formation, and sulfur granules Associated with disruption of normal mucosal barriers Endogenous 6 month therapy Cervicofacial – Lumpy Jaw Throacic – Secondary aspiration Abdominal – Metastatic Pelvic – From abdomen or associated with IUD CNS – Brain or epidural abscess

PROPIONIBACTERIUM Propionic acid is main fermentation product Normal flora of skin, conjunctiva, oropharynx and female genital trace Most common is P. acnes

MOBILUNCUS Rods with Pointed Ends Normally present in low numbers in female genital tract, Increase in bacterial vaginosis No LPS Sensitive to Vancomycin medication

LACTOBACILLUS Lactic acid is major fermentation product

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Normal flora of GI and GU tract Vancomycin resistant

ANAEROBIC GRAM NEGATIVE COCCI: VEILLONELLA Predominant anaerobe in oropharynx

ANAEROBIC GRAM NEGATIVE RODS1.BACTEROIDS – Clinically important2. PORPHYROMONAS – Assaccarolytic, Pigmented3. PREVOTELLA – Small, saccarolytic and bile sensitive4. FUSOBACTERIUM - Fusiform

VIRULENCE FACTORS Adhesion promotoes (capsules, pili) Antiphagocytic Factors (Capsules, Ig protease, LPS, succinic acid) Tissue Destroying Enzymes (Phospholipase C) Catalase and Superoxide Dismutase

BACTEROIDS FRAGILIS Gram Negative Rod Relatively O2 tolerant even though it is an anaerobe Opportunistic B-lactamase producer Penicillin resistant

FUSOBACTERIUM NECROPHORUM AND NUCLEATUM Fusiform Gram Negative Rods Normal flora of mouth, GI, and Vagina Cause pneumonia With oral spirochaetes, cause ANUG

VINCENT’S ANGINA ANUG Associated with stress and breakdown in oral hygiene Trench Mouth of WWI Mouth pain and Extreme Halitosis Treatment: Hydrogen peroxide with mouth rinses

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SPORE FORMING BACTERIACLOSTRIDIUM AND BACILLUS

CLOSTRIDIUM Gram Positive, Anaerobic, Spore Forming Highly Virulent due to exotoxins and enzyme production

1. CLOSTRIDIUM PERFRINGENS (C. WELCHII) 20% of clostridial isolates Most common member (80%) of the “Histoxic Clostridia” which cause Gas Gangrene A cause of Food poisoning Can be contaminant of blood cultures 5 toxin types (A-E) Defined on the basis of production of 4 main lethal toxins: , , e, t -toxin (phospholipase C) plays a major role in myonecrosis

GAS GANGRENE AKA CLOSTRIDIAL MYONECROSIS Toxin mediated breakdown of muscle tissue associated with bacterial growth Liquefaction of muscle, gas production, toxemia Rapidly progressive and life threatening** Requires Surgical debridement

CLOSTRIDIUM PERFRINGENS FOOD POISONING Type A strains are very common Improperly cooked meat or gravy Initial cooking activates spores. Ingested bacteria ensporulate in alkaline environment of small intestine,

releasing enterotoxin when they lyse Self limiting

ENTERITIS NECROTICANS: PIG-BEL OR DARMBRAND Severe necrosis of the small bowel due to -toxin of C. perfringens type C Affects mainly children at meat feasts Due to overeating particular meat in combination with semicooked yams (tyrpsin inhibitors) in the

malnourished (decrease pancreatic trypsin) Trypsin destroys -toxin

2. CLOSTRIDIUM SEPTICUM Very motile Aggressive bacteremia with metastatic myonecrosis. 80% of patients with bacteremia have an underlying malignancy Leukemia, lymphoma, cancer of large bowel

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3. CLOSTRIDIUM TETANI Found in soil and intestinal contents of animals Elaborates neurotoxin tetanospasmin, which produces spastic paralysis. A disease of unvaccinated. Often associated with minor puncture wounds Risus sardonicus, Trismus (Lockjaw) first, Then Opisthotonus (extended body, flexed arms)**** Treatment: Tetanus Antitoxin, Muscle Relaxants, Surgical Wound Care. Admit

4. CLOSTRIDIUM BOTULINUM Worldwide distributed in soil and aquatic habitats Can produce botulinum neurotoxin (BoNT), the most lethal poison known Acute Flaccid Paralysis 7 antigenic types of toxins (A-G) A, B, E, F cause most human botulism

BOTULISM BoNT acts at presynaptic junction and prevents release of Ach 4 Types:

o Food Borne – Ingestion of preformed toxino Wound – Wound infectiono Infant – Ingestion of sporeso Intestinal – Older children and adults

FOOD BORNE BOTULISM Usually home canned food, smoked fish BoNT is heat labile No taste or production of gas One case is an outbreak Treatment: Trivalent (ABE) botulinal antitoxin STAT! Intensive Ventilatory Care

WOUND BOTULISM - Treatment ABE antitoxin for adult cases Penicillin Respiratory support as required

INFANT BOTULISM Constipation is FIRST Sign Lethargy, weakness Floppy infant Occasional cause of SIDS Children <1 year should not be fed honey!

BOTOX Revolution in plastic surgery Small doses of BoNT injected directly into muscle for spasm (blepharospasm or strabismus) or for

cosmetic reasons Ever wonder why faces of Hollywood actors are not as expressive as they used to be? Bo Tox!

5. CLOSTRIDIUM DIFFICILE Major cause of Antibiotic Associated Diarrhea (AAD) and Pseudomembranous Colitis (PMC)****

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Most common cause of hospital acquired diarrhea Asymptomatic in 50% for infants <1year, decreases to 3% by age 3 Hospitalized patients become colonized, sometimes develop diarrhea, often after antibiotic therapy Toxin A, Toxin B. Substance that inhibits Bowel motility. EIA test available to detect toxins A and B. Most sensitive and specific test is toxigenic culture. Treatment: Discontinue antibiotic. Give Metronidazole. PO bacitracin is next step. Fecal transplant is last

resort. Avoid Vancomycin.

BACILLUS Large Gram Positive Rods, Spore forming, Aerobic**** Common in soil and water

1. BACILLUS CEREUS Soil organism Spores often contaminate rice. Bacteria are Motile Eye Infections – Usually secondary to foreign body** Food Poisoning – Emetic and diarrheal types**

FOOD POISONING Spores are activated by cooing and germinate if termpearture permits. Enterotoxin is produced during

growth phase. Emetic form associated with rice Diarrhoeal form associated with meat dishes and sauces Self limiting

2. BACILLUS ANTHRACIS Non-Motile** Nonhemolytic Medusa Head Colonies** Primarily pathogenic to herbivores Virulence factor genes (Capsule and toxin) are coded on plasmids The first bacterium shown to be causative of an infectious disease The first vaccine produced was attenuated B. antracis to protect sheep, BUT not the first vaccination.

BACILLUS ANTHRACIS TOXINS Toxin composed of 3 proteins:

o PA – protective antigeno EF – edema factor (adenylate cyclase)o LF – lethal factor

PA binds to specific cell receptors and forms channels to allow EF and LF into the cell Edema Toxin = PA + EF Lethal Toxin = PA + LF

ANTHRAX Cutaneous – Incubation forms Malignant Pustule*** Pulmonary (Woolsorters Disease) – Inhaled spores transported to macrophages to mediastinal lymph nodes

where they germinate and result in sepsis. Very rapid progression. Mortality 97% untreated, 75% with treatment.

Gastrointestinal – Very rare, contaminated meat

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ANTHRAX BIOTERRORISM Occurs in the US today with Mails

DIAGNOSIS AND TREATMENT OF ANTHRAX Cutaneous: Swab pustule for Gram and M’Fadyean stains and culture. Possible aerosol exposure: Treatment and nasal swab Pulmonary: Blood culture, paired blood for serology. Notify authorities Treatment – Ciprofloxacin or Doxycycline recommended, 60d course

SEXUALLY TRANSMITTED DISEASES

1. NEISSERIA GONORRHOEAE Gram Negative Diplococci, Usually intracellular Fastidious Does not tolerate desiccation or cold Cytochrome oxidase positive Oxidizes glucose, but not maltose nor lactose

N. GONORRHOEAE VIRULENCE FACTORS Por A protein (porin protein) type A bearing strains resist serum killing Opa proteins (opacity proteins) mediate adherence RMP proteins (reduction modifiable proteins) stimulate Ab that block serum killing LOS (lip-oligosaccharide) has lipid A and CO Pilin protein (pili) mediates initial attachment

N. GONORRHOEAE INFECTION SYNDROMES Urethritis/Cervicitis (occasionally pharyngitis and proctitis) Arthritis-dermatitis syndrome Monoarthritis (classically) Prepubescent females: Vaginitis

GONORRHOEA- “THE CLAP” Le Clapatier is a Paris Neighborhood Sexually acquired urethritis/cerrvicitis Incubation period 2-5 days Incidence has dropped dramatically in developed countries Profuse, inflammatory urethral discharge in males** Females often asymptomatic, but at risk for PID, DGI

COMPLICATIONS OF GONORRHOEA Disseminated Infection: Sepsis, skin, joints Fitz-Hugh-Curtis Syndrome (perihepatitis) Opthalmia neonatorum Pelvic inflammatory disease (chronic pelvic pain and sterility) Profuse Purulent Discharge**

DIAGNOSIS OF GONORRHOEA Urethral, Cervical, Throat, Rectal swabs Typical Gram Stain of Genital specimens Inoculation of Selective medium (Thayer-Martin) at bedside Gene probe commercially available, but gives no information on antibiotic resistance

TREATMENT Cefixime or Ciprofloxacin Ceftriaxone

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2. NEISSERIA MENINGITIDIS Not an STD Oxidizes Glucose and Maltose** Causes acute meningococcemia, meningitis and chronic meningococcemia Endemic in a belt across sub-Saharan Africa Rest of the world has sporadic cases and epidemic outbreaks

3. HAEMOPHILUS DUCREYI CHANCROID (Sof Chancre) – Painful Genital Ulcers + lymphadenopathy More common in tropics Gram Negative Short Rods, often in “school of fish” arrangement Can culture for confirmation Treatment same as gonorrhoea

4. KLEBSIELLA GRANULOMATIS Graunloma Inguinate – Chronic and progressively destructive infection of the skin and mucous membranes

of the external genitalia Similar to K. rhinoscleromatis (Slavic leprosy) and K. ozoaenae (chronic atrophic rhinitis) Diagnosis: Donovan Bodies (intracytoplasmic rods which stain with Giemsa Wright’s stain) Late Destructive lesions if untreated

5. SYPHILISA. PRIMARY SYPHILIS – ChancresB. SECONDARY SYPHILIS – Palms and soles, Condylomata lata, C. TERTIARY SYPHILIS – Gummata, Charcot’s JointD. CONGENITAL SYPHILIS – Hutchinson’s Teeth

DIAGNOSIS OF SYPHILIS Primary: Dark field of DFA microscopy of chancre fluid Seondary/Tertiary: Serology

o Nontreponemal (reaginic) –VDRLo Treponemal –TPI, MHA-TP, FTA-Abs

TREATMENT FOR SYPHILIS Benzathine penicillin G IM x 1-2 weekly doses IV penicillin G for congenital and late syphilis IV pen G is the only treatment for Neurosphyilis and for syphilis in pregnancy. Desensitize if allegoric Jerisch Herxheimer reaction

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SPIROCHAETES

1. TREPONEMA PALLIDUM Spirochaetes, Gram Negative Corkscrew rods with Axial flagella and an outer sheath Cannot be cultured on artificial media Primary, secondary, and tertiary stages Most chronic infectious disease: 1/3 rule Primary – Chancre at site of initial inoculation after 3 weeks, goes away! Secondary – Maculpapular eruption including palms and soles, condylmoata lata (6 months) Tertiary – Endarteritis obliterans Gummata (years)

2. TREPONEMA CARATEUM PINTA- Acute and chronic nonvenereal skin infection Skin discoloration leads eventually to depigmentation Found only in isolated rural populations living under crowded, unhygienic conditions in the American

tropics

3. BORRELIA Highly Motile spirochaetes Flagella beneath outer membrane Linear chromosomes Maintained in nature by cycling through wild animals and the ticks that feed upon them (except 2 species –

B. recurrentis and B. duttonii)

BORRELIA RECURRENTIS Louse-Borne (epidemic) Relapsing Fever** Now mainly in Africa (Ethiopian Highlands) Periods of fever lasting 2-9 days alternate with afebrile periods of 2-4 days Up to 10 relapses typical Diagnosis by finding spirochaetes on direct exam of peripheral blood during febrile periods Treatment: Tetracycline and Treat lice!

BORRELIA DUTTONII TICK BORNE (ENDEMIC) RELAPSING FEVER Similar to Louse Borne type but Sporadic Illness tends to last longer Most patients unaware of tick bite

BORRELIA BURGDORFERI: LYME DISEASE Ixodes Scapulatris – The Deer Tick 1st Stage – 3rd to 4 weeks, Flu like symptoms 2nd Stage – weeks to months, Arthralgia, arthritis, meningitis, Bell’s Palsy, painful radiculopathy, cardiac

conduction defects, myocarditis 3rd Stage – months to years, chronic arthritis and progressive CNS disease

DIAGNOSIS OF LYME DISEASE Erythema migrans** Visit to risk area

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Lack of known tick bites irrelevant ELISA, Western Blot, PCS

MANAGEMENT OF LYME DISEASE Tuck pants into socks. Inspect for ticks. Early – Penicillin or Doxycycline. Late – IM or IV Ceftriaxone

4. LEPTOSPIRA Worldwide either free living or associated with animal hosts Infection usually results from direct or indirect (water or soil) exposure to animal urine 1st Phase (1 to 2 weeks) – Fever, malaise. Decreases or disappears after 1 week 2nd Phase – Aseptic meningitis, hepatitis, nephritis, conjunctivitis, IgM titre increases Diagnoses – Seriology + urine and blood culture Treatment – Penicillin or Doxycycline effective if given early

5. SPIRLILLUM MINUS Common form of sporadic Rat-Bite Fever in Asia (Japan) Spirillary Fever or Soduku Distinctive Reddish Purple Skin Plaques Incubation period 1-3 weeks Previously healed bite wound reactivates when symptoms appear 10% untreated mortality

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CHLAMYDIA

CHLAMYDIA Small Obligate Intracellular Bacteria Unable to synthesize ATP – Energy Parasites Structurally similar to small Gram Negative bacteria Except Cell Wall contain No Peptidoglycan** Reproductive cycle different from other bacteria

UNIQUE REPRODUCTIVE CYCLE Intracellular form is the reticulate body RB divides repeatedly by Binary Fission until a large cytoplasmic inclusion is formed over 48 hours RB’s condense to form elementary bodies which are released into the environment by lysis of the host cell EB’s are phagocytosed by susceptible host cells The EB reorganizes into the larger RB

CHLAMYDIA SPECIES1. C. TRACHOMATIS2. C. PSITTACI3. C. PNEUMONIAE

1. CHLAMYDIA TRACHOMATIS Inclusion bodies stain with iodine 2 groups of serovars that cause different syndromes:

o A to K Trachoma Biovar (D to K cause genital tract infections)o L1, L2, L2a, and L3 Lymphogranuloma Venereum Biovar

TRACHOMA Servoars A, B, Ba, and C most common Chronic infection leads to scarring and trichiasis Leading cause of blindness in developing countries Easily prevented with intermittent medication

NON-GONOCOCCAL URETHRITIS/CERVICITIS Serotypes D-K usually Most common cause, especially in college students Females often asymptomatic, but at risk for PID Infertility, Chronic Pelvic Pain Neonates born to infected mothers at risk for inclusion conjunctivitis, occasionally infant pneumonia

LYMPHOGRANULMOA VENEREUM Uncommon in North America and Europe Transient papules on external genitalia followed in 1-2 months with PAINFUL inguinal and perirectical

Lymphadenopathy Groove Sign**

DIAGNOSIS Direct: Iodine staining ELISA, NA probes, NA amplification, Urine, Tissue culture

TREATMENT LGV – Tetracycline or Macrolide for 21 days

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Urethritis or Ocular Infections – 7 days Neonatal Conjunctivits or Pneumonia – Macrolide for 10 days

2. CHLAMYDIA PSITTACI Psittacosis (ornithosis) Transmitted by inhalation of dust contaminated with feces or respiratory secretions of infected birds

(History) Pneumonia often associated with headache and splenomegaly Diagnosis: 4x rise is CF Ab or IIF

TREATMENT FOR ORNITHOSIS Macrolide or Tetracycline for 7 to 10 days

3. CHLAMYDIA PNEUMONIAE Community acquired pneumonia, bronchitis, sinusitis Person to person transmission Common, but seldom diagnosed due to poor availability of reagents Tentalizing associations of high antibody titres with coronary atherosclerosis and asthma – trial underway.

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LISTERIA

LISTERIA MONOCYTOGENES First isolated 1926 by EGD Murray Gram Positive B-hemolytic Rod Oxidase Negative with Characteristic Tumbling End-over-End Motility at 22 degrees but Not at 37 degrees Primary habitats are soil and decaying vegetable matter Has been isolated from mammals, birds, crustaceans, fish, and insects Common contaminant of foods especially unpasteurized cheese (Mexican soft cheese) Tolerant of salt, Drying and refrigeration

PATHOGENESIS Primarily food borne Entry into enterocytes or M cells in Peyer’s patches mediated by internain proteins via surface

glycoproteins Phagolysosome acid activates exotoxins listeriolysin O and 2 kinds of phospholipase C Phagolysosome lyses, bacterium escapes into cytosol, and replicates ActA protein at one end of bacterium coordinates assembly of actin, which pushes bacterium through cell

membrane and into adjacent cell!

INFECTIONS Adults – Meningitis, encephalitis, sepsis, often with monocytosis Immunocompromised increased risk Tropism for CNS Pregnant – Influenza like illness, if untreated --> amnioitis, fetal infection Abortion, still birth, premature birth

DIAGNOSIS Meningitis very aggressive: 20-50% mortality, Neurologic sequelae common Lab often misidentified as Enterococcus Have high index of suspicion in meningitis or when Hx of suspect food ingestion Blood and CSF cultures

TREATMENT Resistant to Cephalosporins Treat with Ampicillin + Gentamicin Co-Trimoxazole for Penicillin Allergic patients

FOOD POISONING Listeriosis is an example of true food borne infection Primary infection syndromes of Listeria are NOT Gastroenteritis, unlike most forms of food poisoning Food poisoning originally thought (in error) to be due to Ptomaines (putresine and cadaverine)

FOOD POISONING SYNDROMES Heavy Metal Poisoning Toadstools (Amanita) Cereals infected with Claviceps purpura (ergot) Botulism Fish toxin poisoning (histamine, scromboid, ciguatera, fugu, paralytic shellfish)

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MYCOPLASMATACEAEMYCOPLASMA AND UREAPLASMA

CHARACTERISTICS Smallest free living organisms known Gram Negative in structure but not in staining No Cell Walls, Resistant to cell wall attacking antibiotics (penicillin) Cell membrane contains sterols, which must be in growth medium Slow growing Ubiquitous Frequently contaminate tissue cultures Pass through filters designed to trap bacteria Related to Clostridia Are anaerobes, but most not strict

MYCOPLASMA 100 species 11 primarily colonize and infect human

UREAPLASMA 6 species Primarily colonizes/infects humans

DISEASE ASSOCIATIONS Pneumonia – M. pneumoniae NGU – M. genitalium Postpartrum Fever – M. hominis and U. urealyticum Arthritis in immunosuppressed and hypogammaglobulinemic – M. hominis and U. urealyticum

1. MYCOPLASMA PNEUMONIAE 2nd most common cause of community acquired pneumnia 20% cases overall, 50% of pediatric cases Only 3% of infected develop pneumonia overall. Summer outbreaks every 3 to 4 years PATHOGENESIS:

o P1 protein adheres to neuraminic acid receptor on respiratory epitheliumo Organism remains extracellular o Mucosal damage occurs via H2O2o Cilia are paralyzedo Inflammatory infiltrate is lymphocytic, and contributes to pathology

CLINICAL FEATURES:o CXR – Looks worse than would expecto Anorexia, nausea, vomiting, diarrhea, musculoskeletal myalgia and arthralgiao Erythema mutiforme and other skin eruptionso Transient hemolytic anemiao Meningoencephalitis (70% hospitalized)o Relapses, persistent cough

DIAGNOSISo Culture: Slow, requires special media, Not widely usedo Serology: Complement Fixation Test, look for 4x rise in titres. Since symptoms develop slowly,

initial specimen may have high titreo Cold agglutinin Test

TREATMENTo B-lactam and sulfonamide drugs ineffective. Use Macrolides, Tetracycline and Fluoroquin.

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2. MYCOPLASMA GENITALIUM Sexually transmitted The most important cause of NGU after Chlamydia trachomatis Also found in high proportion of asymptomatic adults Treatment: Tetracycline or Macrolide for 7 days

3. MYCOPLASMA HOMINIS A genital commensal, sexually transmitted Postpartum sepsis – 10% of cases Sepsis in immunocompromised Arthritis in hypogammaglobulinemic Usually isolated from blood cultures TREATMENT

o Resistant to Macrolideso Infections in immunocompromised patients very hard to cure with antibiotics aloneo Immunocompromised – One of the last indications for antiserum prepared in animals

AIDS –ASSOCIATED MYCOPLASMAS? Isolated from AIDS patients Contribute to cell death with HIV in vitro Many informed investigators believe mycoplasmas are involved in AIDS

4. UREAPLASMA UREALYTICUM A genital commensal, Sexually Transmitted Very small colonies; splits urea Established roles in postpartum fever and arthritis in immunosupressed and hypogammaglobulinemic

patients Moderate evidence for causality: NGU, Infection stones, pneumonia/chronic lung disease in very low birth

weight infants

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