• Gram positive cocci in pairs, short chains, and grape like clusters
• Grow best aerobically but can grow anaerobically using fermentative pathways
• Relatively simple nutritional requirments: Blood agar is used for primary isolation-hemolytic reactions
• Colony color: white
• Catalase +
• Coagulase -
• Glucose Fermentation +
• Mannitol Fermentation -
• Novobiocin sensitive
• Common as normal skin flora
• Occassional disease resulting from foreign body colonization (shunts, catheters, joint protheses) which can lead to bacteremia, and endocarditis
• Frequently methicillin-resistant (MRSE) 

• Gram positive cocci in pairs, short chains, and grape like clusters
• Grow best aerobically but can grow anaerobically using fermentative pathways
• Relatively simple nutritional requirments: Blood agar is used for primary isolation-hemolytic reactions
• Common as normal skin flora
• Important cause of UTI in young sexually active females
• Colony color: white
• Catalase (+)
• Coagulase (-)
• Glucose Fermentation (-)
• Mannitol Fermentation (V)
• Novobiocin Sensitivity (resistant)

• Gram positive cocci in pairs, short chains, and grape like clusters
• Grow best aerobically but can grow anaerobically using fermentative pathways
• Relatively simple nutritional requirments: Blood agar is used for primary isolation-hemolytic reactions
• Colony color: pale yellow, orange, or golden
• Catalase (+)
• Coagulase (+)
• Glucose Fermentation (+)
• Mannitol Fermentation (+)
• Novobiocin sensitive
• May normal flora in anterior nares
• Transient on the skin surface
• Some colonization on moist skin areas
• Cellular Antigens
• Peptidoglycan-inflammatory
• Teichoic acid-inflammatory
• Protein A-major protein component of cell wall covlently linked to peptidoglycan.  Nonspecific interaction with Fc of some immunoglobulin. Anti-phagocytic
• Capsule-anti-phagocytic
• Hemolytic/Cytolytic toxins:
• RBC hemolytic-iron acquisition
• Kills/inhibits phagocytic cells
• Tissue necrosis
• α -toxin: major exotoxin nearly all human strains
• Channel forming toxin
• Most important extracellular virulence factor elevated levels in CA-MRSA strains
• Non-hemolytic/Cytolytic toxins:
• attack white cells ONLY
• Kills/inhibits phagocytic cells
• Tissue necrosis
• Panton-Valentine Leukocidin (PVL):
• Kills neutrophils, macrophages
• Highly associated with CA-MRSA strain
• No added virulence
• Leukocidin A/B:
• Major contribution to MRSA pathogenesis in murine model
• Kills neutrophils, macrophages
• Exo-enzymes: coagulase, penicillinase, hyaluronidase, lipases, nucleases, staphylokinases (fibrinolysin)
• Transmission often from normal flora
• Self contamination
• Person-to-person
• Infections from another skin disease (person to person)
• Clinical Manifestations
• Cutaneous infections
• Scalded Skin Syndrome
• Toxic Shock Sydrome
• Food Poisoning
• Pneumonia
• Metastatic Infections
• Arthritis
• Endocarditis

• Folliculitis, boils, carbuncles, wound infections
• Most common bacterial infection in humans
• Can be superfical or Deep
• Frequent abscess formation, occasional spread via fascitis (necortizing fascitis)
• Extreme inflammation, pain, purulent
• May disseminate to bloodstream-sepsis can occur
• Eyelid infection-conjunctivitis, sticky eye in neonates
• Impetigo
• Encrusted pustuls on superifical layers of skin
• Frequently seen in younger children 

• Exfoliative Toxin: lysis of attachment between cells of the granular layer of the epidermis 
• Bacteria is not present in the bloodstream but rather the toxin is present in the bloodstream
• Local infection, systemic toxemai
• Most common in neonates and children < 4 yrs
• Generalized exfoliative dermatitis: generalized painful erythema and dramatic bullous desquamation of large areas of skin.  Focus of infection may be distant.
• Bollus impetigo-localized version of the syndrome with infection at the site of the lesion

• Toxic shock syndrome toxin 1:
• SUPERANTIGEN
• Non-specific interaction of T cells and macrophages
• Potent inducer of TNF and IL-1, systemic inflammation
• enterotoxin activity
• Localized infection, systemic toxemia
•  Local infection: tampon, wound, boil: with systemic toxemia
• High Fever
• Vomiting/diarrhea
• Development of a characteristic rash
• Systemic toxemia-induced hypotension leads to cardiac and renal failure
• Rare bacteremia-no bacteremia classically
• Delayed desquamation of feet and hands

• Enterotoxins:
• six serotypes present
• Heat stable
• Stimulates emetic receptor in abdominal viscera
• Common form of food poisoning in US
• Ingestion of pre-formed toxin elaborated by enterotoxin -producing strains growing in foods
• Typical Foods: custard or cream filled pastries, chicken salad, processed meats, cottage cheese, sauces etc.
• Rapid onset of symptoms 2-6 hours 
• Vomiting, severe cramps, variable diarrhea

• Seen in Children < 1 yr and immunocompromised (cystic fibrosis etc)
• Increased in number of highly virulent MRSA infections in apparently normal individuals (necrotizing pneumonia)
• Fulminant disease, high mortality rate (50%)
• Consolidation or necrosis with formation of multiple abscesses   

• Any area of the body
• Often following skin/tissue infections
• Osteomyelitis
• Most frequent organism causing osteomyelitis
• Male Children under age of 12
• Especially in long bones of legs
• Hematogenous spread from a primary focus (wound or boil)
• Direct spread from a tissue puncture wound pentrating to the bone
• Spine may be infected with para-meningeal involvement (aseptic meningitis) 

• 50% of all cases of bacterial arthritis
• Dissemination from skin infection or from osteomyelitis
• Direct inoculation during intra-articular injections
• Destruction of articular cartilage, permanent joint deformity  

• 50% are hospital acquired from bacteremia following a primary infection of the skin, respiratory tract, or other body site inculding MRSA
• Common in patients with diabetes mellitus, cardiovascular disease, granulocyte disorders, immunological defiencies, prior valve damage
• Mitral and aortic valve damage is most common: splinter hemorrages and janeway lesions present
• Tricuspid valve in IV drug abusers, lung abscesses
• Usually a continuous bacteremia
• Difficult to treat with antibiotics
• Often requires valve replacement
• 40-80% mortality with antibiotics  

• Sample must be "clean"
• Direct Examinaion-Gram stain (sterile sites only)
• Culture-blood agar, B-hemolytic, yellow colonies
• Rapid Slide agglutination kids (protein A)
• Phage typing
• PCR assays
• Antibiotic sensitivites: MRSA ID and molecular typing
• 85-90% are B-lactamase positive (plasmid)
• Some vancomycin resistance

• Clean wounds, drain abscesses, remove foreign bodies
• Topical antibiotics fro impetigo (bacitracin, mupirocin)
• HA-MRSA: Vancomycin alone or with rifampin
• CA-MRSA:
• skin tissue: TMP/SMX or clindamycin, doxycycline
• Pneumonia, endocarditis, arthritis: vancomycin or linezolid
• Prevention:
• Proper handwashing
• Eliminate carriers
• 7-day treatment with combination of
• Daily Bactroban Nasal (mupirocin)
• Daily chlorhexidine baths
• NO VACCINES

• Primarily USA 100
• NO increased virulence
• exreme antibiotic resistance

• USA 300 and USA 400 strains
• INCREASED virulence
• Moderate antibiotic resistance  

• Gram positive cocci
• Never considered norma flora
• Cellular Antigens
• Peptidoglycan- inflammatory
• Teichoic Acid
• Lipoteichoic Acid
• M Protein- Major protein antigens > 60 serotypes
• Main virulence factor
• Fibrillar molecule composed of two alpha helical cahins
• Inhibits complement fixation, resistance to phagocytosis
• Protein G
• Capsule-anti-phagocytic
• Cytolytic Toxin: RBC hemolytic, kills phagocytic cells, tissue nerosis
• Streptolysin O:
• Produced by nearly all strains
• Oxygen Labile
• Channel forming toxin
• Potent antigen
• Streptolysin S
• Produced by nearly all strains
• Oxygen Stable
• Small peptide
• Non-antigenic
• Pyrogenic Exotoxins-fever producing
• SpeA and SpeC
• Super antigens
• Inflammatory
• Erythrogenic toxins- rash and fever of scarlet fever
• SpeA associated with most severe disease
• Only by strains lysogenized by specific phage
• Shock and organ failure of strep toxic sock syndrome
• Stimulates cytokine production in macrophages
• SepB- inflammatory
• Transient on the skin surface
• Transmission is person-to-person
• Respiratory Droplets
• Exchanging Secretions
• Touching skin, carrier on hands
• URT and skin infections primarily inc children (5-15 yr old)
• Healthy people can get invasive GAS but immunocompromised are more likely to get GAS
• Clinical Manifestations and Pathogenesis
• Pharyngitis
• Scarlet Fever
•  Pneumonia
• Impetigo
• Erysipelas
• Necrotizing fascitis
• Streptococcal toxic shock syndrome
• Puperal sepsis
• Acute rheumatic fever
• Acute glomerulonephritis
• PANDAS

• Encrusted pustules on superficial layers of skin
• Associated with certain M protein serotypes

• Acute lymphangitis of the skin (may be complication of impetigo)
• Painful, hot, rapidly spreading, inflamed area with an advancing bright red margin-may spread to fascia (spreads laterally)
• Most often present on the face and lower extremities (primarily infants, elderly) 

• Enter throuh a break in the skin
• Bacteria follow a path along the fascia between the subcutaneous tissue and muscle
• Rapid swelling, red-to-purple-to blue, large blisters
• Skin dies, muscle may be infected, gangrene
• Bacteremia (60%),
• May progress to streptococcal toxic shock syndrome  

• Complication of bactermia and or agressive soft tissue infection
• Historically in older patients with multiple medical problems
• Now seen in persons of all ages with no underlying disease
• Associated with systemic production of  pyrogenic exotoxins
•  Fever, rash, vomitign/diarrhea/ hypotension, leading to cardic and renal failure, shock and death

• Historical "child-bed-fever"
• Spread to uterus after delivery
• Endometritis, bacteremia
• Toxic Shock Syndrome  

Acute Rheumatic Fever

ARF

Acute Glomerulonephritis

AGN

• Inflammatory reaction seen after a Group A skin or pharyngial infection
• Seen primarily in children
• Average of 1-2 weeks in pharyngeal
• 2-3 weeks in skin
• Well defined group of M serotypes
• Deposition of immune complexes in kidney, fix C, inflammation
• Must document Step A etiology to confirm origin

• Direct Examination-Gram stain-sterile sites only
• Culure-blood agar (24 hours) 
• Serology-important for establishing streptococcal etiology for AGN
• Antibiotic Sensitivity-usually unnecessay b/c almost all strains are sensitive to penicillin
• Most resistant to TMP-SMX
• Resistance to macrolides increasing

• Penicillin G or V
• Any B-lactams
• Invasive disease-higher doses of penicillin often better response with added clindamycin or erythromycin
• Surgical debridement
• Typically resistant to TMP/SMX
• No Vaccines 

• Gram (+) rods
• Chinese characters
• Not acid Fast
• Produce lipases to degrade lipis for cutrients
• Anaerobic
• Normal flora of skin (sebacecous follicles)
• Overgrowth of normal flora in response to nutrient stimulation (lipids) causing inflammation
• Disease follows increase in bacterial numbers, usually 1-3 years before sexual maturity
• Bacterial numbers are in direct relation to the amount of lipid sebaceous gland sebum secretions at the time of pubrty
• Less common in people over 25 yrs 
• Inflammatory mediators from bacterial cell wall products and extracellular enzymes along with faty acids from pliase action on lipids
• Intense local inflammatory response
• Papules, pustules, and nodulocystic lesions typical of this disease
• Treatment:
• Comedonal acne-blackheads, white heads, no inflammation
• Topical lipid dyring colutions-tretinon
• Mild inflammatory acne-small papules or pustules
• Topical for above + topical antibiotics/antiseptics: erythmycin or clindamycin _ benzoyl peroxide
• Inflammatory acne, commedones, papules or pustules
• Tpoical for above + oral antibiotics (doxycycline, minocycline, tetracycline, etc)
• Accutane is bad: birth defects, depression, IBD
• NO vaccine

• Free-living in the soil and water
• Growth within amoebae
• Chronic diseases
• Opportunistic infections only
• Number of cases increasing, particularly in AIDS patients
• Tuberculosis-like disease in presentation and pathogenesis

• Superficial skin lesions
• Associated with fish tanks
• "Swimming pool granulomas"
• Growth in macrophages
• Pigmented
• Optimum temp is 32 C
• Nodular skin lesions, break in skin is necessary

• Fast growing
• wound
• systemic
• pulmonary disease
• non-pigmented

• Pulmonary disease (AIDS patients)
• Skin/tissue granulomas
• Break in skin with exposure to soil necessar
• An example is a puncture wound with rose thorn

• Acid Fast
• Slow growing
• Extracellular pathogen
• DNA analysis suggests a recent divergence from M. marinum with the acquisition of a plasmid that codes for a potent lipophilic toxin (mycolactone)
• Cytotoxic-tissue necrosis, leading to spreading ulceration.  Lethal for most cells
• Anti-inflammatory/immunosupressive-little fever, no early granulomatous lesion
• fills phagocytic cells etc
• Mycolactone toxins are found in fish//amphiban pathogens but this is the only human pathogen mycolactone is found in
• Aquatic environmental habitat
• Human to human transmission
• Aquatic environmental habitat following trauma usually on the legs or arms
• Buruli ulcer disease (Bairnsdale ulcer disease in Australia)
• Higher incidence in Children < 12 years
• Swimming in rivers is a risk
• In US only seen in recent immigrants

• Caused by Mycobacterium ulcerans
• Pre-Ulcerative Stage
• Inoculation into the tissue via a break in the skin
• Incubation period: 2 weeks to 3 years
• Average 2-3 months
• Replication extracellularly in dermis and subcutaneous tissue with production of the mycolactone toxin
• Tissue necrosis
• Immunosupression
• Disease manifests initially as a firm, non-tender nodule (1-2 cm) at site of trauma
• Ulcerative Stage
• Within 1-2 months the nodules erode forming a painless, continuously spreading ulcerative lesion as the bacteria spread into new tissue
• Ulcerations can involve as much as 15% of the patients skin surface
• Inflammatory cels are scarce in the active lesions
• phagocytic cells that migrate to the lesion are killes by the mycolactone toxin
• May include dissemination via bloostream with widespread damage
• Infection may destroy nerves, appendages,and blood vessels
• Ocassionally invade the bone
• Delayed treatment leads to significant cosmetic and or functional disabilites
• Untreated lesions tend to heal over months or years by a cell mediated granulomatous response with delayed-type hypersensitivity and scarring

Mycobacterium ulcerans

Diagnosis/Treatment/Prevention

• Diagnosis: made on presentation
• Acid fast stain of tissue
• Culture (6-8 weeks(
• PCR
• Treatment: Requires rapid diagnosis and initiation for good response
• Surgery to remove infected tissue
• Skin grafts may be required
• Combined antibiotic therapy: rifampin plus streptomycin or amikacin for 8 weeks
• Heat packs 40 C on wounds or skin gradts
• M. ulceranshas poor growth at 37 C
• Prevention:
• No vaccines
• Preventative wound care

• Not Gm (-) but outer membrane has glycolipids
• Can NOT be grown on lab media
• Does NOT grow well at 37 C
• Optimum growth at 25-33 C
• Obligate intracellular pathogen that multiplies slowly
• Mononuclear phagocytosis especially histiocytes in the skin
• Schwann cells of the nerves
• Humans are the primary natural host
• Also foung in armadillos, and certain Monkeys
• Person-person transmission
• Respiratory droplets
• Long incubation period-average 2-5 years
• Range 3 months - 20 years
• Most people are resistant to infections, children are more suspectible
• Anyone with a defect in cell mediated immunity is at risk

• Caused by Mycobacterium leprae
• After respiratory exposure the bacteria are able to invade into the bloodstream
• Bacteremia but no systemic inflammation
• No sepsis
• Migration to the skin-preference for cooler areas of the body with the temperature < 37 C
• Growth as an obligate intracellular pathogen that multiplies very slowly
• Mononuclear phagocytes, especially the histiocytes in the skin
• Schwann Cells of the nerves
• Tuberculoid leprosy
• Benign, non-prgressive
• Rapid onset of asymmetric loss of nerve functions
• Macular skin lesions-may have hypo-pigmentation
• Few bacteria in the lesions
• Positive lepromin skin test
• Cell mediated immune response intact
• Borderline leprosy
• Transition from tuberculosis to lepromatous stages
• Skin lesions more extensive
• Bacteria increasing
• Cell mediated immunity is decreasing
• Lepromatous Leprosy
• Rapid progressive course
• Nodular skin lesion
• Slow, symmetric nerve involvement with loss of the sense of touch, leading to injury with hands and feet
• Abudant bacteria in skin lesions, continuous bacteremia
• Negative lepromin skin test
• Cell mediated immune response is markedly depressed

Mycobacterium leprae

Diagnosis/Treatment/Prevention

• Diagnosis:
• Symptoms, type, and distribution of lesions, endemic area
• Acid-fast stains: skin lesions and tissue
• Lepromin skin test useful only for tuberculoid leprosy
• New DNA probes with PCR
• Treatment
• Traditional therapy: 4,4-diaminodiphenylsulfone (DDS or dapsone)
• Life time treatmet
• Resistance is increasing (40%)
• Combined Treatment
• Dapsone/rifampin/clofazimine-lepromatous
• Dapsone/rifampin-tuberculoid
• 1-2 years or until skin smears are negative
• Prevention
• Early detetion and treatment
• No Vaccine

• Dermatophytes
• Grow only as septate filamentous fungi
• Smooth walled, club shaped macroconidia
• ABSENCE of microconidia
• Chlamydospores and arthrospores
• Arthrospoores are significant in transmission

• Dermatophytes
• Grow only as septate filamentous fungi
• Prominent microconidia
• Rough walled, spindle shaped macroconidia
• Arthrospores ae more significant in transmission

• Dermatophyte
• Grow only as septate filamentous fungi
• Prominent microconidia
• Few smooth-walled cylindrical, club-shaped or cigar shpaed macroconidia
• chlamydospores and arthrospores
• Arthrospores are significant in transmission

• Keratinophilic fungi
• Keratinase t degrade keratin in the skin, hair, and nails
• Elastase and proteinases present
• Microsporum species secrete pteridine that fluoresces bright blue-green under long wave UV light
• Woods lamp-diagnostic
• Associated with humans, animals, or soil
• Transmitted to humans via
• direct contact with infected tissue (human or animal)
• Human contact with soil
• Indirectly through contaminated surfaces or objects (hair brushes)
• Arthrospores are produced in high amounts in tissues are are VERY infectious
• Microconidia and macroconidia are potentially infecios
• May affect both normal and immunocompromised
• Risk of invasion deeper into the body in immunocompromised
• Moist areas provide the most favorable environment for establishment of fungal infections
• When arthospores or conidia are transmitted to the new host they germinate and the hyphae invade into the keratinized tissue in order to obtain nutrients
• Endothrix Pattern of growth: fungal hyphae grow inside the hair shaft, eventually breaking off the hair and leaving a block dot (T. tonsurans)
• Ectothrix growth: Fungal hyphae grow on the outer surface of the hair shaft an results in scaly patterns with ahir loss ( M.canis)
• Favus pattern of growth: Most aggressive type of scalp hair infection, hyphae growing inside the hair shaft, with production of air bubbles withn the hair.  yellow thick crusts and inflammation produce scarring. (T. schoenleinii)
• No invasion into healthy living tissue, except in severely immunocompromised patietns
• Inflammation and pathology result from the production of extracellula enzymes and other metabolic by-products that induce an inflammatory response, with redness, swelling, and itching
• The classic lesion is red, scaly with an advancing border with a greater degree of inflammation at the margins (termed an actived border), often with central clearing.
• Seen on the trunk, arms, legs
• Itching is a major symptoms
• Scalp infections may lead to patches of hair loss (alopecia)

• Infection of the scalp hair and skin
• Transmission fostered by poor hygiene, ovrcrowding, and contaminated items
• Seen mainly in children
• Scalp scaling, scalp pruitus, occipital adenopathy, and diffue or pathy alopecia
• Most caused by T. tonsurans
• Non-fuoescent

• Infection of the face
• Lesions seen on non-bearded parts of the face
• Some classic lesions, others less distinct
• May be confused with other skin lesions
• T. tonsurans most common in US
• T. mentagrophytes and T. rubrum in Asia

• Infection of the mustache, beard area, and neck
• Caused by zoophilic and anthropophilic species
• Farm workers often effected from exposure to animals
• T. verrucosum (cattle) most common
• M. canis, M. mentagrophytes

• Infections of the trunk, arms, legs
• Usually demonstrates the classic "ringworm" lesion with central clearing
• Seen in adults and children
• Hot humid climates
• T. rubrum, M. tonsurans (anthropophillic) and M. canis, T. verrucosum (zoophilic), M. gypseum

• Infection of the palms of the hands
• Diffusely dry, scaly, erythematous
• T. rubrum-may be an extension of Athlete's foot

• Infection of the groin "jock itch"
• E. floccosum, T. rubrum

• Infection of the soles of the feet and interdigital web "Athlete's foot"
• Interdigital form: most common, lesions with fissuring, maceration between toes
• Plantar skin becomes clinically scaly and thickened with hyperkeratosis and erythema of soles, feet and sides of feet
• Vesiculobullous form: characterized by vesicles, pustules, and coems bullae in an inflammatroy patern on the soles
• T. rubrum
• T. interdigitale
• T. mentagrophytes

• Infection of the nails (onychomycosis)-feet (most common) or hands
• Thickened, broken, discolored, and dystrophic nails
• Nail plate may be separated from the nail bed
• T. rubrum
• T. mentagrophytes
• Dermatophyte form and non-dermatophyte forms

• Non-dermatophyte
• Malassezia furfur
• Lipophilic yeast that is normal flora of the skin
• Hyperpigmented macules thatcoalesce to form scaling plaques, usually NOT itchy
• Stimulus for the disease unknown
• Often resolves spontaneously
• Also associated wtih seborrheic dermatitis and dandruff

• Hortaea werneckii
• Inoculation onto the skin from soil, growing as a filamentous fungus in the stratum corneum in moist areas
• Growth on lipids
• Tolerates increased salt, low pH
• Generally the infection is asymptomatic (rare itching), appears as brown-to-black macule, beginning as a small  dark spot and enlarging slowly (weeks to months) to several centimeters with times
• Lesionsare typically located on the soles of feet or palms of the hands

• Piedra hortae
• Inoculation onto the skin and hair from the soil growing as a filamentous fungus on the hair shaft, particularly the scalp hair.
• Infection is asymptomatic, but the fungal growth and firm adhering black to brown nodules on the hair shafts can weaken the hair causing breakage
• Rare in US occurs in tropical and subtropical regions

• Caused by Trichosporon
• The dimorphic yeast is common in the soil but being recognized as a member of the normal flora of the human skin, nails, mouth, and GI tract
• Transmission of infection is not known
• Infected hair occurs minly in the pubic, beard, scalp areas
• Fungal noduleson the hair shaft are white-to-light brown, easily removed
• Infections are most common in temperat climates, common in parts of southern US
• T. cutaneum causes superficial skin infections
• Cutaneous lesions
• Onychomycosis
• Disseminated infections-resulting in positive blood cultures
• endocarditis
• meningitis
• Has significant intrinsic resistnace to amphotericin B, azoles, and echinocandins

Diagnosis/Treatment/Prevention

of

Dermatophyte and Non-Dermatophyte Fungi

• Acute and Chronic inflammatory response are important for maintaining the superficial nature of the infections
• Inflammatory environment with iflux of neutrophils is not favorable for fungal replication
• Diseases with impaired neutrophil response (diabetes) have a higher risk for dermatophyte infection, particularly onychomycosis
• Cell mediated immune response seems to be critical for defense and recovery
• AIDS patients may be extensively infected and disseminated dermatomycoses are also observed only in AIDS patients
• Diagnosis
• Woods light examination-only useful if + M. canis infection
• Direct microscopic examination-skin scrapings, hair, nail scrapings
• KOH treatment to degade keratinized tissue, observe directly or stained
• skin biopsy
• Observe for branching, septate hyphae, with arthospores, for skin biopsy observe for prominent neutrophils in stratum corneum
• Culture-results are slow-2 weeks
• Treatment
• Historically treated with oral griseofulvin
• Newer azoles and allyamines are more effective and work well together
• Tinea corporis, cruris, or pedis treatment
• mild: topical butenafine Lotrimin Ultra, terbinafine (Lamisil)
• 2-3 weeks
• extensive: oral terbinafine (Lamisil)
• 2 weeks- 4 months
• Tinea capitis treatment: oral terbinafine-4-8 weeks
•  Onychomycosis Treatment: oram terbinafine-6-12 weeks
• Pityriasis (tiea) versicolor treatment- topical or oral ketoconazole or fluconazole
• Trichosporon treatment- intrinsic resistance to many anti-fungal drugs
• Hortaea/Piedraia treatment- topical anti fungals

• Organsim: Sporothrix schenckii
• Thermally dimorphic fungus
• "Rose handlers disease"
• 37 C: Growth as oval to cigar shaped yeast cells. This is observed is tissue
• 25 C: Growth as filamentous fungi with hyaline hyphae (septate), conidophores and conidia.
• Conidiophores are sympodial and arise at right angles to the hyphae. Conidia are arranged in rosette like clusters at the tip of conidiophores
• Skin trauma, usually to extremities
• Appearance of a reddish, necrotic, nodular papule at the inoculation site.  Appears 1-10 weeks after the injury
• Lesion will usually suppurate, ulcerate, anc become chronic
• Frequent spread along the lymphatics with additional ulcerating nodules appearing
• Disseminaton may occur in AIDS patients and other immunocompromised persons
• May also cause a primary inhalaton pneumonia in these latter patients
• Diagnosis:
• Direct microscopic examination: observe for yeast vs. hyphae (pigmented vs. hyaline)
• Culture: results are slow
• Treatment:
• Surgical excision or cryocurgery of infected lesions is usually necessary
• Recommended antimicrobial therapy (generall long term due to slow response)
• Cutaneous/lymphonodular-itraconazole (3-6 months)
• Pulmonary-itraconazole (6-12 months)
• Meningitis-amphotericin B followed by itraconazole

• Organsims: Fonsecaea, Phialophora, Cladosporium, Rhinocladiella
• Dimorphic (nutrient not temperature)
• Tissue: thick walled, dark brown rounded sclerotic cells known as Muriform cells or Medlar bodies. Divide by planar splitting not budding
• Lab agar media- grow as dematiaceous (dark brown) hyphae (septate) forming slow growing, dark, velvety colonies with a black reverse at 25 or 37 C. 
• Seen world wide but higher in tropics and subtropics
• Commin in men who work outside in rural areas
• Skin trauma from thorns or splinters usually to extremities. Often not remembered since skin trauma occurs several years before lesions appear
• Lesions start as a small scaly bump that slowly develops  into a raised crusted lesion with a dry warty appearance. The center of the lesion may clear partially
• Slow spread (2mm/year) to healthy skin with new satellite nodular lesions and plaques
• The limb may be very swollen (elephantiasis) and covered with various nodular scaly or verrucous lesions that resemble cauliflower
• Rarely disseminates via bloodstream to the brain.
• Treatment:

• Surgical excision or cryocurgery of infected lesions is usually necessary
• Recommended antimicrobial therapy (generall long term due to slow response)

• Organisms: Exophiala, Wangiella, Phialophora, Alternaria, Bipolaris etc
• All species grow with dematiaceous hyphae septate in tissue. Some species produce both hyphae and yeast in tissue
• Very diverse group of at least 71 species from 39 genera.  Identification based on microscopic sporulation in conidia production
• Subcutaneous Infection:
• Skin trauma from thorns, splinters, or soil
• Generally a single swollen cystic granulomatous lesion or abscess develops at the site of implantation. 
• Immune compromised patients can develop multiple lesions with odules and ulcers
• Similar implantation of spores can occur in the eyes, corneal lesions
• Respiratory/Disseminated Infections
• Inhalation of fungal spores to:
• Nasal cavity-lesions on the nasal septum
• Sinuses-Sinusitis, often associated with allergic rhinitis or immunosupression
• Lungs-pneumonia seen with immunosupression
• Dissemnation via the bloostream to brain. Meningitis is most common
• Treatment:
• Surgical excision or cryocurgery of infected lesions is usually necessary
• Recommended antimicrobial therapy (generall long term due to slow response)

• Organisms: Pseudoallescheria, Madurella, Acremonium
• Diverse group of fungi
• All species grow as filamentous fungi in tissue but form masses of fungi that appear as tiny balls or grains with white or black draining pus
• Madura Foot
• Usually involves the feet, following implantation of fungal spores from the soil
• Initially a simple primary lesion, develops as a small painless lump under the skin.  Fungal growth is slow but is locally invasive, indolent and tumor like, eventually involving the underlying muscle and bone.
• Eventually multiple subcutaneous lesions consist of abscesses, granulomatous lesions
• Middle of the lesion caves in, ulcerates and discharges pus (white or black grains).  The grains are the hallmark.
• Lesions can eventually cause considerable deformity
• Treatment:
• Surgical excision or cryocurgery of infected lesions is usually necessary
• Recommended antimicrobial therapy (generall long term due to slow response)

• Spiral shape due to peptidoglycan
• Outer envelope similar to GM (-) bacteria but NO LPS
• Periplasmic flagella- very actively motile, seems to be required for virulence
• Very long, very thin (too thin to see with light microscope)
• Must use dark field microscopy or silver impregnation for Treponema and Leptospira
• Blood smears-wright or giemsa for Borrelia
• Difficult to grow in vitro
• Extracellular pathogens
• How they evade the host immune response is now known in most cases

• Seen in humans with disease
• Transmission is person-person via sexual contact
• Rate 6X more commin in men
• Biggest increase seen in men having sex with men
• HIV/AIDS have accelerated stages, increased severity, increased neurosyphilis

• Penetration of mucous membranes by T. pallidum, multiplication at site of infection with proliferation in regional lymph nodes. 
• Extracellular
• Development of chancre at site of entry within 2-10 weeks
• Sinlge lesion at site of contact (may be oral)
• Smooth base, sharply demarcated walls "hard chancre"
• Painless
• Enlarged inguinal lymph nodes
• Highly infectous, full of spirochetes
• Darkfield/silver stain of skin scrapings-positive
• If untreated spontaneous healing within 3-6 weeks
• Some patients do not develop disease beyond primary stage
• Good antibody response against organism-positive serology

• Dissemination of T. pallidum throughout the body with multiplication in lymph nodes, liver, joints, muscles, skin, and mucous membranes
• Extracellular
• Development of muco-cutaneous lesions within 1-3 months after the primary chancre
• Rash on palms and soles
• Alopecia-pathy hair loss
• Papules in genital area
• Skin lesions any where on body
• Lesions in the mouth
• Highly infectious
• Painless
• Flu like illness, fever, sore throat, headache, and lymphadenopathy
• May last 2-6 weeks
• 1-3 relapses in 25% of untreated patients
• Some patients do not develop disease beyond the secondary stage

• Asymptomatic period between secondary and tertiary disease
• Early latency < 4 years
• Long latency > 4 years
• No clinical symptoms but positive serology

• Varied symptoms " The great pretender"
• Development of gummas (granulomatous lesions) > 10 years after primary syphilis
• Spirochetes absent (immunopathology)
• occurs in 25-40% of untreated patients
• Skin and bone affected
• CNS (neurosyphilis)-brain and or spinal cord (tabes dorsalis)
• Progressive mental deterioration, insanity
• Muscular incoordination, sensory disturbances
• Acute pain
• Paralysis of leg muscles
• Acute abdominal pain
• cardiovascular system (commonly aorta)

• Infection of te fetus-usually after 16th week of gestation
• 100% risk of transmission if woman has primary
• 90% risk of transmission if woman has secondary
• 30% with ealy latent
• no risk with late latent or tertiary syphilis
• Fatal in 25-50% of cases without antibiotic syphilis
• Early congenital symptoms (< 2 years of age, chronic infection)
• low birth weight
• Cutaneous lesion and mucoid patches on palms and soles
• Snuffles-highly infectous mucoid nasal discharge
• Hepatosplenomegaly
• nephritis
• Long bone involvement
• multiple organ failure
• Late congenital symptoms (> 2 yrs of age)
• Stigmata (visible evidence of disease, permanent defects)
• Hutchinson triad:
• Hutchinson's teeth-notched permanent incisors
• Interstitial keratitis-chronic inflammation of the cornea
• Deafness
• Saddle nose
• Boney deformities
• Similar to tertiary syphilis

Diagnosis/Treatment/Prevention

Syphilis

• Culture and Gm stain NOT possible due to small size
• Non-treponemal antigen tests-screening
• Cardiolipin-lecithin-cholesteol suspension as antigen
• Detects nonspecific IgM, IgG antibodies called reagin
• May be negative in tertiary syphilis
• Subject to false positives
• Treponemal antibody test-confirmation
• Fluorescent treponemal antibody absorbed (FTA-ABS)
• T. pallidum as antigen
• Once positive remains so for life
• Reported as negative or positive
• Specific and sensitive
• Treatment:
• Penicillin G-preferred for treatment of all stages of syphilis
• Primary/seconday/early latency-1 dose of 2.4 million units IM
• Neurosyphilis-3-4 million units IV every 4 hours for 10-14 days
• Jarisch-Herxheimer reaction-acute febrile reaction < 24 hours of start of penicillin
• Alternative: azithromycin

• Non-venereal contact
• Bejel (endemic syphilis):
• caused by endemicum
• middle east, africa
• Acquired in early childhood
• Lesions primarily in the mouth
• Mouth to mouth transmission
• Pinta
• Caused by T. carateum
• Central and South America
• Hyperpigmented lesions
• Skin to skin transmission
• Yaws
• Caused by T. pertenue
• Tropical forests worldwide
• Resembles syphilis in course of disease
• skin to skin transmission
• Dissemination like T. pallidum possible

• Granuloma inguinale (Donovanosis)
• Intracellular, pleomorphic Gm (-) bacteria
• One of more nodules that erode to form beefy-red, painless, slowly spreading granulomatous ulcers that bleed easily
• Uncommon in US but much more connon in tropical/subtropical regions such as India, New Guinea, Austilia, Caribeban, Brazil
• Dianosis - microscopic observation of Donovan bodies (intracellular bacteria)
• Treatment- doxycycline, fluoroquinolones

• Gm (-) diplococci
• Obligate parasites of the respiratory and genital tract of humans
• Obligate aerobes (do NOT ferment carbohydrates), catalase (+), oxidase (+) (high cytochrome oxidase activity)
• Sensitive to adverse environemntal conditions-drying, cold, UV light
• Special growth media (chocolate agar) required
• Increased CO₂ required

• Gm (-) diplococci
• Obligate parasites of mucosal surfaces (female genital, intestinal, URT)
• Never considered normal flora
• LPS- endotoxin, cytotoxin, no O-antigen
• Outer Membrane Proteins- major adhesins, vaccine development
• Pili (fimbriae)-major adhesin, major virulence factor, Vaccine target
• Large strain to strain antigenic variation (problem for vaccine)
• NO capsule
• Exoenzymes- IgA protease, B-lactamase (10% os strains)
• Sexual transmission, transmission to newborn during birth
• 25% risk of transmission from a single exposure
• Uncomplicated Infections- mucosa surface/ submucosal invasion, inflammation
• Lots of pus present
• Males
• Urethra, pharynx (homosexuals), conjunctiva (newborn)
• Urethritis is painful, very likely to be diagnosed early
• Females
• Endocervix, rectum, conjunctiva (newborn)
• Infection is often asymptomatic, leading to delayed treatment
• Complicated infections- Chronic infections, spread to adjacent tissues if primary infection is not treated
• Males
• Chronic prostatitis
• Urethral strictures
• Uncommon in US
• Females
• Pelvic inflammatory disease-often a mixed infection with syphilis
• Occurs in 20% of untreated primary infections
• Infertility, ectopic pregnancies
• Abscesses, peritonitis
• Disseminated Infections
• Spread via lymphatics to bloodstream
• No sepsis due to lack of capsule
• Foci of infection at other body sites
• 1% of untreated primary infections
• Arthritis and or tenosynovitis-extremities
• Dermatitis-often a single lesion on arms or hands
• Endocarditis-rare occasions
• No sepsis
• If arthritis/tenosynovitis and dermatitis is present this is diagnostic

Diagnosis/Treatment/Prevention

N. gonorrhoeae

• Diagnosis in MEN
• Urethral exudate, pharyngeal swab
• Gm stain(Gm (-) diplococci and nertrophils) on urethral exudate-diagnostic
• Culture on chocolate agar with antibiotics, increased CO2
• Identification of isolates: + oxidase test
• DNA amplification/detection: Urine test can also identify syphilis
• Diagnosis in Females-endocervical swab, rectal swab
• Gm stain-not appropriate
• Culture on chocolate agar with antibiotics, increased CO2
• • Identification of isolates: + oxidase test
• DNA amplification/detection: Urine test can also identify syphilis
• Disseminated infections (male or female)- blood, synovial fluid
• Gm stain on synovial fluid
• Culture-chocolate agar + CO2 (no normal flora)
• Treatment of uncomplicated Infections: two drug therapy due to drug resistance and co-infection with chlamydiae
• Ceftriaxone (250 mg IM single dose) + doxycycline ( 7 days)
• Fluoroquinolones-increased resistnace
• Spectinomycin-especially for penicillinase producing strains
• Treatment of Neonatal and Disseminated Infections- Penicillin G (IV) and ceftriaxone (IV, IM)
• Pelvic Inflammatory Disease- combined broad spectrum antimicrobial therapy
• Ceftriaxone/cefoxitin (IM/IV) + doxycycline (oral) ±metronidazole
• Clindamycin (IV) + gentamicin (IV or IM) + doxycyline (oral)
• Prevention
• No successful vaccine
• Public Health offcials-trace all sexual contacts
• Education
• Prophylaxis-erythromycin ointment for newborn eyes

• Obligate intracellular bacteria
• Host target cell-columnar epithelial cells lining mucous membranes of humans and animals
• Urethra
• Endocervix
• Endometrium
• Fallopian Tubes
• Rectum
• Respiratory Tract
• Conjunctiva
• Cellular Location-phagosome of the host cell
• Inhibit phagosome-lysosome fusion
• Appears as an inclusion in the cell
• Pathogenesis of infections if due to persistent inflammation-alternating cycles of host cell destruction and chlamydial growth.
• Elementary Body (EB)
• Infectious
• Responsible for attachment and entry
• Inhibits phagolysosomal fusion
• Rigid cell wall-lacks traditional peptidoglycan but has disulfide cross-linking of the major outer membrane protein
• Tough, survives environmental stress "spore like"
• Reticulate Body (RB)
• Metabolically active form within phagosome
• Divides by binary fission
• Osmotically fragile-do not survive in environement
• Enlarging phagosome full of dividing and differentiating RBs is called an inclusion
• Gm (-) membrane but no peptidoglycan (LPS is present)
• Genus specific LPS (all Chlamydia have the same major LPS antigen)
• Species specific antigen-heat labile protein
• Type specific antigen (serovars)-MOMP a heat liabile protein on the surgace of EB.  Each serovar cause different disease

• Phase 1
• Transmission of mucosal secretions from an infected person or animal
• Attachment of infectious RBs to host epithelial cells
• Endocytosis within phagosome
• Inhibition of phagolysosomal fusion
• Phase 2
• Primary differentiation of EBs into RBs by 9 hours post infection
• Phase 3
• Growth and Binary fission of RBs
• Genus specific antigen on surface of infected cells within 18 hours
• Inclusions are present (phagosome filled wiht RBs)
• Phase 4
• Secondary differentiation of RBs to EBs bu 24 hours post infection
• Phase 5
• Release of infectious EBs by host cell lysis or exocytosis at 40 hours post infection, transmission to other susceptible hosts

• Direct microscopic examination of specimens for cytoplasmic inclusions-Giemsa or iodine
• Direct microscopic detection of chlamydial antigens in epithelial cell inclusions
• Fluorescein or enzyme labeled monoclonal antibody
• DNA amplification/detection-in combinaton with ghonerra
• Isolation in cell culture- McCoy fibroblasts or epithelial cells-examine for inclusions

Chlamdia trachomatis servars A-C

Trachoma

• Leading, preventable cause of blindness in the world
• Common in poverty-stricken regions of Africa and southeast Asia
• Spread from child to child in a household by flies, dirty clothing, fingers
• Early Disease in children (< 2 years of age)
• Inflammation within the epithelial cells of the conjunctivae
• Begins as purulent conjunctivtis and develops into a follicular keratoconjunctivitis
• Development of Blindness-may no occur into 40 yrs of age, chronic disease
• Scarring of the conjunctiva as a result of follicular necrosis
• Deformity of the eyelids- turning in of eyelashes
• Abrasion of the cornea-ultimately resulting in blindness
• Ingrowth of new blood vessels into cornea
• Repeated infections over time-extensive lymphoid proliferation with formation of lymphoid follicles
• Treatment:
•  Topical tetracycline ointment 2X day for 6 weeks- compliance problem
• Erythromycin-single oral dose (expensive but more reliable
• Surgery to correct lid deformities
• No vaccines

Chlamydia trachomatis servars D-K

Genital Tract Infections

• Human to human transmission via sexual contact
• Most common sexually transmitted pathogen
• Replication in epithelial cells
• Nongonococcal Urethritis (NGU)- males
• Infection of the urethra-causes inflammation
• Clear to purulent discharge-sometimes not noticeable
• Begins 7-10 days after sexual contact
• Gm stain reveals neutrophils and NO organisms
• Pain upon urination in 50%
• If left untreated it may be followed by epididymitis
• Cervicitis-females
• Cervix most commonly affected site with inflammation
• May have mucoid or purulent discharge-often not noticeable
• 75% asymptomatic with no noticeable discharge
• Acute Pelvic Inflammatory Disease- often co-infected with N. gonorrhoeae
• Untreated infections may spread to the uterus and Fallopian tubes
• Inflammation in these new areas of colonization
• subacute or chronic with mild abdominal pain and unimpressive tenderness
• Scarring of Fallopian tubes leading to infertility and ectopic pregnancy
• Reiter's Syndrome "The patient can't see, can't pee, and can't bend the knee"
• Primary bacterium wiht this syndrome
• HLA-B27 linkage
• reactive arthritis, urethritis and uveitis following active disease
• Occurs most often in men
• Also seen in infections from Salmonella, Shigella, Campylobacter, and Yersinia
• Treatment is prescribed on the basis of clinical diagnosis or as a co-treatment for gonorrhea
• Doxycycline is most widely used
• Erythromycin/Azithromycin-alternative for pregnant women
• No vaccines
• Treat sex partners of infected pateints (contact within 30 days of onset of symptoms)

Chlamydia trachomatis serovars D-K

Venereal Infections in Neonates

• Inclusion Conjunctivitis
• Purulent conjunctivitis that heals without scarring
• Eyes become infected during passage through the birth canal
• Incubation of 5-21 days after birth
• Opthalmia Conjunctivitis
• Purulent conjunctivitis occuring usually within the first 10 days of life
• Pneumonia
• Infected during passage through birth canal
• Develops at 3-11 weeks of age
• Cough and little fever
• Often preceded by inclusion of conjunctivitis

Chlamydia trachomatis serovars L1-L3

Lymphogranuloma Venereum (LGV)

• Seen in tropical and subtropical areas of Africa and Asia
• Seen in homosexual males in US
• Incubation period usually 1-3 weeks after intercourse
• Incubation period may be longer
• Small painless ulcer at the site of sexual contact (angogenital area in male homosexual)
• Ulcer heals in a few days but bacteria invade systemically
• 2-6 weeks later development of inguinal lymphadenopathy with painful lymph nodes
• Granulomatous micorabscesses in lymph nodes
• If untreated: leads to chronic infection
• Colorectal fistulas and strictures
• Difficult to dianose because it is rare and can look like other diseases
• Genital or lymph nodes swap or aspirates-nucleic acid detection, serology
• Treat with Doxycycline
• 3 weeks
• No vaccine

Chlamydia pneumoniae

Community Acquired Pneumonia

• Person to person spread via respiratory secretions
• Most infections in school aged children and young adults
• Accountss for 10% of community acquired pneumonia
• Also infects animals
• Begins with URT symptoms: pharyngitis, sinusitis, otitis media
• Progresses to bronchitis-mild to severe atypical pneumonia
• Must distinguish from Mycoplasma pneumoniae
• Treat with doxycycline
• Can treat with Azithromycin-will cover other atypical pneumonia agents: Legionella and Mycoplasma
• No vaccines

Chlamydia psittaci

Psittacosis-Community acquired Pneumonia

• Inhalation of chlamydiae from infected birds (dead or alive) and their droppings
• Psittacine birds: parrots, parakeets, pigeons, turkeys
• Infection is often mild or aymptomatic but can be fatal
• Elderly are more likely to have a symptomatic infection
• Unilateral, lower lobe interstitial pneumoniae
• Atypical pneuomonia
• Can disseminate systemically to liver, spleen, heart, and CNS
• More common in immunosupressed pateints
• Treat with doxycycline
• Azithromycin-covers the other atypical pneumonia pathogen-Legionella and Mycoplasma
• No Vaccine

• Gm (-)
• Obligate intracellular growth
• Rickettsial genome: Similar to mitochondria.  Thought to be the closest living relative to mitochondria and are believed to be involved in the endosymbiotic process of eukaryotic evolution. 
• No genes for glycolysis
• No genes involved in biosynthesis
• No genes involved in regulation of amino acids and nucleosides
• All of these functions are provided by the host

• Rocky Mountain Spotted Fever
• Host Target Cell: Vascular Endothelium
• Intracellular location: Cytoplasm
• Can travel cell to cell without exiting hose cell via actin polymerization
• Transmitted to rodents, dogs, and humans by the bite of the adult domestic dog tick.
• Most common and most severe tickettsial disease in Western hemisphere
• Found in 38 states including KY.  Most common in South Atlantic and Ozark regions (North Carolina and Oklahoma)
• 2/3 in children under age of 15
• Tick must be attached for 24-48 hours for bacterial transfer
• Spring-summer transmission
• Symptoms appear 5-7 days after tick bite
• Fever, headache (severe and frontal)
• Macular, maculopapular, petichial rash
• extremities to trunk-centripetal
• may become necrotic
• Vasculitis- growth of Rickettsia in endothelial cells causing ststemic inflammation
• Perivascular infiltration of mononuclear cells, plasma cells, and macrophages → leakage → thrombosis → microinfarction → vascular necrosis
• Shock, multiple organ failure (especially renal)
• Death in 20% if untreated or delayed treatment
• Diagnosis
• Clinical Presentation-progression of rash from extremities to trunk
• History of tick bite
• Rapid detection in tissue (skin scraping)
• Direct immunofluorescence microscopy
• PCR
• Serology to confirm diagnosis-to slow for primary diagnosis
• Treatment-doxycycline
• Treatment needs to be intitiated early to get a goodresponse
• No Vaccine

• Boutonneuse fever- Southern Europe, Africa, Middle East
• Transmitted from rodents and dogs by tick bite

• Host Target Cell: Vascular Endothelium
• Intracellular location: Cytoplasm
• Allows cell to cell spread via actin tail to avoid the immune response
• Rickettsial Pox
• First identified in NY in 1946
• Transmitted from house mice by the bite of a mite
• Highest risk in urban areas with mice infecstations
• Replication in endothelial cells, less sever tehn rocky mountain spotted fever
• Lesion develops with a black crusty scab at the site of tick or mite bite
• Lymph node swelling
• Chills, fever, adn headache accompanied by a maculopapular rash
• Usually mild course with rare fatalities
• Lesion to recovery period is over three weeks

• Epidemic Typhus-louse borne
• Africa, Asia, South America
• Human louse vector (no animal reservoir)
• Human to human disease
• Louse feces-rubbed into bite, suberficial abrasion or inhaled
• Delousing with DDT helped to lower deaths in WWII
• Sylvatic typhus-exposure to flying squirrels
• Eastern US
• Louse or flea vector (animal to human)
• Milder disease than epidemic typhus
• Brill-Zinsser-reoccurance of a mild disease months or years after primary epidemic typhus
• Rickettsai typhi and R. felis
• Endemic typhus (Murine typhus)
• Flea borne from rodents
• Risk for travelers
• Clinical Manifestations of all typhus disease are similar only differing in speed and severity
• Symptoms appear 5-10 days after louse or flea bite
• Fever, headache, myalgia
• Macular, papular rash
• Trunk to extremities-centrifungal
• Vasculitis of small vessels of many organs (especially the liver)-causing systemic inflammation
• Clotting abnormalities, shock, multiple organ failure, death
• Milder symptoms in Brill-Zinsser disease, sylvatic typhus, and murine typhus
• Diagnosis
• Clinical presentation-progression of rash from trunk to extremities
• Rapid detection in tissue (skin scrapings0-speed is important
• Direct immunofluorescence microscopy
• PCR
• Serology to confirm diagnosis-too slow for primary diagnosis
• Treatment-doxycycline
• No Vaccine

• Scrub Typhus
• Mite (chigger) vector from mice or other rodents
• Seen in areas of low vegetation or "scrub"
• Typhus like disease
• Incubation period 6-21 days
• Fever and headache
• Localized escher at site of bite
• Macular, papular rash
• Trunk to extremities (centrifigal)
• Usually mild, rare fatalities

• Human Monocytic ehrlichiosis (HME)
• Common in KY, common in eastern US
• Incidence highest in adults
• Lone star and dog ticks-deer is natural host
• Replication in bloodstream monocytes and tissue macrophages
• Incubation period 3-4 weeks after tick bite
• Rash seen in 50% of patients
• Leukopenia and thrombocytopenia
• Systemic inflammation
• Fever, Headache, Vomiting
• Death in 2-5 % of cases
• Diagnosis:
• Presentation with history of tick bite
• Part of Tick-borne serology panel
• Treatment-doxycycline
• No Vaccine

• Human granulocytotropic anaplasmosis (HGA)
• Diagnosis:
• • Presentation with history of tick bite
  • Part of Tick-borne serology panel
• Treatment-doxycycline
• No Vaccine
• Common in KY, common in upper midwest
• Deer ticks (cotransmitted with Lyme disease)
• Deer is natural host
• Repliation in circulating granulocytes
• More acute than HME
• Incubation period 1 week after tick bite
• Rash is rare
• Leukopenia and thrombocytopenia
• Systemic inflammation
• Fever, headache, confusion
• Death in 7-10%

• Newly discovered
• Replication in granulocytes
• Same tick vector as HME

• Cat-Scratch Disease
• Cats are often asymptomatically infected
• Transmitted by a cat bite or scratch (contaminated with saliva)
• Normal humans can be infected but peopel with immunocompromised conditions are more likely than others to have complications
• Extracellular pathogen
• Some new evidence for replication in endothelial cells
• Cat scratch disease- normal individuals
• Primary skin papule or pustule at inoculation sire (3-10 days after scratch/bite)
• Painful lymphadenopathy in axillary or cervical lymph node
• Fever
• Most resolve without treatment but may become chronic if untreated
• Cat Scratch Disease in Immunocompromised
• Bacillary angiomatosis-vascular proliferative disorder of the skin and visceral organs. Appears as red nodular lesions
• Bacillary peliosis hepatitis (also spleen)- cystic, blood filled spaces in the liver
• Bacteremia
• Sepsis
• Endocarditis
• Diagnosis
• History of contact with a cat and the presence of a scratch/bite
• Histopathology of lymph nodes, serology, slow growth on lab media.  Extracellular bacterium
• Treatment-azithromycin, FQs
• Treatment of HIV patients is slow and relapses are common
• No vaccine

• Trench Fever
• Extracellular pathogens
• Human to human via body lice
• Unusual in US
• Distinctive symptom is bone pain especially in shins
• Macular rash, headache, fever

• Oroya fever
• Intracellular in RBC
• Human to human via sandfly vector
• Andes Mountains
• Severe hemolytic anemia
• High fatality

• Q fever
• Rarely associated wtih an insect vector
• Primarily an infection in aminal populations
• Spread via contact with urine, feces, milk, placentas
• Human disease is via inhalation of aerosols or dust contaiminated with C. burnetti
• "Spore Like"- very hardy in the environment
• One of the MOST infectious known bacteria
• 1-10 bacteria infectious dose
• Potential biological warfare agent
• Ingestion of infected unpasteurized milk or food
• Patients wtih prosthetic or damaged heart valves are at high risk b/c endocarditis is a clinical manifestation
• Clinical Manifestations
• Mild asymptomatic disease
• Acute Disease-respiratory with systemic spread-typical presentation
• Febrile illness, fever, chills, headache, chest pain
• Mild atypical lobar or interstitial pneumonia
• Hepatosplenomegaly with granulomas
• Usually self limited, lasts several weeks
• Chronic disease-months to years after primary infection
• Endocarditis-typical presentation
• Chronic hepatitis
• osteomyelitis
• Poor prognosis, may be fatal
• No rash in any disease presentation
• Replication in macrophages (live, lung, spleen)
• No vasculitis
• Serology is useful to diagnosis chronic disease
• New rapid PCR based test approved for defense department
• Treatment: doxycycline
• Q fever endocarditis: doxycycline + hydrochloroquine for 18 months
• Vaccin is available in Australia for high risk occupations
• killed whole cell preparation
• Not approved in US

• Spirochete
• Lyme Disease
• White-footed mouse and deer-main animal reservoirs
• Primary tick borne disease in US
• Transmitted by deer ticks-nymphal life stage
• Highest risk in Northeast adn upper midwest
• In California transmitted by western black legged tick
• Tick must be attached for 24-48 hours for transmission of bacteria
• May-August transmission
• Extracellular pathogen
• Primary Stage- erythema migrans (EM)
• Annular bulls eye skin rash
• Rash occurs in 60-80% but most often is atypical form
• Rash may fade or reoccur at sites distant from tick bite
• Headache, fever, myalgia, lymphadenopathy
• Proliferation of bacteria in the tissue at the site of the tick bite, initial dissemination
• Seconday Stage-Early disseminated, neurologic and cardiac symptoms
• Usually 2 weeks - 3 months after the initial tick bite
• Result of dissemination and replication of the bacteria throughout hte body
• May be a disseminated rash-not at the site of bite
• Chronic fatigue
• Neurologic symptoms-facial nerve palsy, peripheral neuropathy, meningitis
• Cardiac symptoms-carditis, atrioventricular block
• Tertiary Stage-late or chronic lyme disease-arthritis
• Weeks-years after the primary infection
• Migratory pain in joints, especially knees (arthritis)
• Chronic memory loss, other neurologic complaints
• Chronic muscle pain
• Chronic and destructive in patients with HLA-DR4 or HLA-DR2
• Immunopathological process
• Cannot culture bacteria from the joint fluid
• Post lyme Syndrome
• Chronic lyme disease even after appropriate treatment
• 10-20% of patients
• Fatigue
• joint pain
• Muscle aches
• cognitive impairments
• "Antibiotic therapy has not proven to be useful and is not recommended"
• Congenital Lyme Disease
• Transplancental transmission
• Stillbirths, birth defects, mental retardation
• Rare

Diagnosis/Treatment/Prevention

Lyme Disease

• Diagnosis
• Based on clinical grounds-classical rash
• Medical history of tick bite or travel to sites of likely exposure
• Serology-Elisa followed by western blot
• Treatment
• Prophylaxis-engorged tick in endermic area: doxycycline
• Primary Stage: oral doxycycline or amoxicillin or cefuroxime 14-21 days
• Early neurological symptoms: oral doxycycline or amoxicillin or IV deftriaxone (14-21 days)
• Lyme carditis- IV ceftriaxone or Pen G (14-28 days)
• Meningitis/encephalitis: IV ceftriaxone or Pen G (14-28 days)
• Lyme arthritis (without neurological symptoms): oral deoxycycline or amonicillin (30-60 days) or IV ceftriaxone or Pen G (14-28 days)
• Late Neurological symptoms-no treatment
• Post Lyme syndrome-no treatment beyond standard therapy
• No vaccine
• Old vaccine: LYMErix-recombinant outer surface protein
• Two IM doses 1 month apart and third dose one year later
• Very effective no longer available ince 2002
• Reported side effects: arthritis, myalgia

• B. recurrentis- transmitted by human body louse (human to human) not common in US
• B. hermsii, B. parkeri-transmitted by sfot ticks in US
• Tick Born Relapsing Fever (TBRF)
• Most cases are in the summer months
• Incubation period: 1 week after louse of tick bite
• Primary febrile attack-persists for 3-6 days with high fever, headache, muscle pain
• Asymptomatic interval of 6-10 days
• 1-4 relapses due to antigenic variation
• Spirochetes disseminate in the body replicating extracellularly
• Spirochetes express surface exposed immunodominant antigen called variable major proteins. > 26 different VMP
• Antibody response to initial VMP develops and removes borreliae from blood causing asymptomatic interval
• Transposition of new vmp into expression site: immune response does not recognize new vmp; borreliae will multiply and disease symptoms will relapse
• Diagnosis-blood Giemsa stain-microscopic observation of spirochetes in bloos
• Serology and culture are difficult due to antigenic variation
• Treatment-Doxycycline
• No Vaccine

• Leptospirosis (Weil's disease)
• Reservoir: dogs are a major source; other domestic animals too
• Animals are infected and shed large numbers of spirochetes in their urine contaminating water and soil where they survive for months
• Swimming or washing in natural bodies of water is a risk
• Worldwide distribution
• Site of entry: skin and mucus membranes
• No lesions
• Incubation period: 8-12 days
• Primary Disease:
• mild septicemia
• Fever, headache
• Diverse presentaton and symptoms
• Asymptomatic interval due to antibody clearance of leptospires from all tissues except kidneys and aqueous humor of eye
• Secondary disease
• return of symptoms (immune stage)
• Depends on organs involved
• Anicteric (90% of patients)-fever, mild meningitis, uveitis, other organ involvement
• Icteric (Weilds disease) (10% of patients)
• Jaundice
• Hemorrhage
• renal failure
• death in 5-40% of cases
• Diagnosis-blood or urine cultures
• Treatment: Pen G or doxycycline
• No Vaccine

• Gm (-) rods and coccobacilli
• Bipolar staining "safety pin appearance"
• PLAGUE
• LPS endotoxin-septic shock
• Capsule (Fral glycoprotein) essential for growth
• Anti phagocytic
• Extracellular
• V and W antigens: outer membrane proteins
• Anti phagocytic
• Extracelular
• Intracellular growth in macrophages
• Has both intracellular and extracellular periods in disease process
• Facultative intracellular parasite
• Wild rodents are a reservoir (prairie dogs0
• Trasmission to humans via
• Bites of rodent fleas
• Direct contact
• Aerosols
• Bubonic Phase-2-6 days after flea bite
• Y. pestis travels vai lymphatics from site of the flea bite to lymph nodes (intracellular phase)
• Inguinal or axillary lymph nodes usually
• Survives and grows in macrophages- intracellular phase
• Production of bubo (swollen lymph nodes becomes filled with pus)
• Will eventually spread to blood stream
• Septicemic (extracellular) Phase-LPS endotoxin induced
• Disseminated intravascular coagulation- necrossi "black death"
• Septic Shock
• Pneumonic (extracellular phase)-systemic spread to lungs
• Pneumonia with organisms in alveolar spaces and sputum
• May arise from inhalation of infectious respiratory droplets (bio terrorism agent)
• Person to person spread
• Diagnosis-
• culture in biosafety level 3 labs
• Immunofluorescence using Fral antibody: rapid
• Serology: 4 fold rise in antibody to Fral antigen
• Treatment/Prevention
• Isolationg of patients
• Streptomycin or gentamycin
• Poor prognosis is therapy is delayed
• Vaccine: killed whole bacteria contains Fral fragement
• Only in high risk situations

Yersinia enterocolitica

Yersinia pseudotuberculosis

• Enterocolitis
• LPS endotoxin
• Gm (-) rods and coccobacilli
• Bipolar staining "safety pin appearance"
• Yops-anti-phagocytic
• Do not replicate in macrophages
• No capsule
• Present in aquatic and animal reservoirs
• Fecal-oral transmission via ingestion of food or water contaminated (often times milk)
• Occurs in children mostly
• Reiter syndrome: Can't see, can't pee, can't bend the knee.  HLA-B27 positive individuals
• Gastroenteritis
• Following ingestion, invasion of the mucosathrough M cells multiply in Peyes patches
• Enter mesenteric lymph nodes-intense inflammation (pain resembeling appendicictis)
• May have septicema (abscesses in liver and spleen)

• Tularemia
• Small Gm(-) coccobacillus
• bipolar staining
• Capsule-antiphagocytic, protects while bacteria is extracellular
• Facultative intracellular parasire-macrophages
• Widely distributed in animals especially rabbits
• Transmission via handeling of infected animals, tick bite from infected animal, ingestion of animal meet
• Ulceroglandular disease-most common
• focal ulcer at the site of entry
• Regional lymphadenopathy
• Intracellular growth in macrophages
• Resembles bubo plaque
• Typhoidal Disease-acquired by eating undercooked infected meat. Intracellular
• Oropharyngeal Disease-pneumonia, intracellular (bioterrorism agent)
• Ocularglandular Disease-wiping eyes with contaminated hands. Intracellular
• All infections can enter the blood stream and become extracellular
• May be fatal without treatment
• Diagnosis-culture specimens in lab-biosafelty level 3
• Treatment: streptomycin or gentamycin
• Prevention: Live attenuated vaccine-only for high risk
• No person to person transmission

• Brucellosis
• Undulant Fever
• Small Gm(-) coccobacilli, weakly staining
• Faculative intracellular pathogens within macrophages
• Taxonomy is based on the animal they primarily infect
• Grow slowly on complex media containing serum or blood
• Growth of B. abortus is enhanced by erythritol-found in uterus and placental tissue
• Found in wild domestic animals
• Transmission is from infected animals in urine, milk, vaginal secretions, placental tissue
• Ingestion
• Direct Contact
• Inhalation
• Chronic febrile illness with either an abrupt or more often insidous onset
• Symptoms are severe and prolonged with B. melitensis and self-limtied with B. abortus
• Fever and malaise may persist for weeks
• Series of relapses "undulant fever"
• Targer organs
• lungs if inhales
• Lymph nodes
• Spleen
• Liver
• Bone marrow
• minute granulomas-hallmark lesions
• Diagnosis is based on immunological reactions
• Serology
• Brucellergin DHT skin test
• Treatment: > 6 weeks: doxycycline + streptomycin or gentamycin
• Prevention: Aminal immunization-live attenuated