Microbiology Week 3 Exam 3
Terms in this set (174)
Inherently virulent-can cause disease in healthy individual
Host's immune status determines the severity of the disease
Histoplasma capsulatum var capsulatum and var duboisii
Mold; thin, branching septate hyphae that produce microconidia and tuberculate macroconidia what you would see in nature
Parasitic phase; small, budding yeast cell often found inside macrophages what you would see in pts
Grows in soil with high nitrogen content contaminated with bat/bird excreta
Common in the midwestern U.S. especially in the Ohio and Mississippi River valleys
Lung is the portal of entry and Organisms phagocytosed by macrophages, Yeast can replicate intracellularly, Immunocompetent host contain the infection
95% of infections asymptomatic, 5% acute pneumonia
<1% progressive disseminated disease that may be life threatening
Associated with AIDS
Thermal Dimorphism: yeast in person, if can prevent switch to yeast no disease symptoms in animal studies
Resides in Host Macrophages, Organism facilitates uptake, Modulation of phagolysosomal pH remains 6-6.5 and not 5
Iron and Calcium uptake facilitated
Cell wall can influence growth of pathogen in macrophage leading to release
Histoplasmosis Diagnosis and Treatment
Serology could test positive if had earlier
Histopathological examination of infected tissue-valuable in detection of disseminated disease; intracellular yeast
Culture blood, bone marrow, sputum
Amphotericin B followed by itraconazole
systemic mycoses, Blastomyces dermatitidis
Mold; septate hyphae with pyriform microconidia at rm temp (histo had mac too)
Parasitic phase; large yeast cells with broad-based budding in pt at body temp much larger than histo not found in macro
North America parts of Africa, Endemic in the Ohio and Mississippi Valleys
Natural disease of dogs and horses, Can be cultured from soil
Primary infection of lung is often asymptomatic
Mild flu like illness that resolves
Progressive pulmonary disease
Classic form of blastomycosis is chronic cutaneous involvement, skin ulcerates from inhaling this into lung
Fairly uncommon in AIDs patients but very aggressive, aids get histo
Thermal dimorphism (small hyphae to larger yeast cells)
Modulation of yeast and host system interactions, WI-1 surface glycoprotein only on yeast cells, virulent shed a this protein and is less easily cleared by immune sys
Presentation of surface antigen modulates the T-helper pathway, virulent sheds smaller WI-1 protein to stimulate Th2 response which means being successful
Blastomycosis Diagnosis and Treatment
Serology not very useful
Culture; abscess fluid, sputum if systemic
Microscopic examination of tissue- large broad-based budding yeast cells
For mild forms itraconazole
Mold; filamentous mold that fragments to form infectious arthroconidia, some hyphae makes spores like these and fragment these out
Parasitic phase; Multinucleated spherical structure called a spherule. Spherule bursts open to release infectious endospores, diagnostic
North, Central and South America: Semiarid regions of California, Arizona and Texas, San Joaquin Valley fever, Routinely isolated from the soil
Can be the most virulent of systemics
Self-limited, mild febrile to moderately severe respiratory disease
In a small percentage of patients can become a progressive pulmonary or disseminated disease often involving the meninges or skin
Hydrophobic protein (hydrophobins) prevent phagocytosis. Not going to find in mac
Th2 response stimulated
Urease to help in intracellular survival
Extracellular proteinases that likely allow invasion
Coccidioidomycosis Diagnosis and Treatment
Diagnosis: Serology (antibody - CF, ID) is useful
Culture sputum or tissue samples, conversion from mold phase to spherules
Microscopic identification of spherules in biopsy material
CF tests are useful
Agar diffusion tests also
Amphotericin B followed by oral azole
Extrapulmonary - oral azole therapy
Meningeal coccio. Fluconazole - amph B only if azoles fail
Caused by dimorphic pathogen
Found primarily in South America and Latin America
Culture yields mold with small microconidia and chlamydospores. Yeast form is large with multiple budding cells.
Itraconazole is treatment of choice.
Refractory forms can be given amphotericin
Most important group of opportunistic fungi
4th most common nosocomial bloodstream infections
Normal flora of humans
incidence is increasing
Diseases of the skin and nails
Mucosal surfaces of the mouth, vagina, esophagus and bronchial tree
Disseminated disease of many organ systems including the brain and heart
Associated with AIDS patients
Humans have strong innate immunity - disease results from impaired immunity or physiological deficiencies
Bud - hyphae transition, makes pseudohyphae
Adherence can localize in organs and mucosal surfaces
Cell surface hydrophobicity
Cell wall mannans
Proteases and phospholipases good for adherence, invasion, dissemination
Candidiasis Diagnosis and Treatment
Diagnosis: Yeast, pseudohyphae, septate hyphae in tissues
Culture positive specimens from normally sterile tissues, normal flora but finding in places where it shouldn't be
Topical treatment of cutaneous disease
Systemic disease; amphotericin B alone or in combination with 5-fluorocytosine.
Grows as a budding yeast cell with acidic mucopolysaccharide capsule that can prevent phagocytosis
Associated with the excreta of pigeons but does not seem to infect the birds
Associated with AIDS
Most common cause of fungal meningitis
Asymptomatic pulmonary infection
Systemic disease fatal if left untreated
Meningitis-most frequently diagnosed form of cryptococcosis, Headache, mental status changes, fever
Growth at 37 degrees
Polysaccharide capsule prevents phago
Melanin not sure why matters
Mating type yeast have mating types that when undergo meiosis and mating, not sure how pathogenic as well
Cryptococcosis Diagnosis and Treatment
Antigen detection in spinal fluid
India ink detection of encapsulated yeast cells in CSF
Culture of specimens (blood or csf)
Amphotericin B plus 5-fluorocytosine
Aspergillus sp. A. fumigatus, A. flavus
Grows as a mold with characteristic conidiophores
Common environmental organism
Opportunistic infection as a result of immunological/physiological status of individual
Allergic bronchopulmonary disease
Fungal colonization of pulmonary cavities as hyphae
Invasive disease involving many organs-often rapidly fatal
Cells secrete elastase, proteases and catalase that may play a role in pathogenesis
Gliotoxin inhibits phagocytosis and T- cell activation
Conidia bind to fibrinogen and laminin to set up residence.
Neutrophil function important in clearing infection, can down-regulate this function
Aspergillosis Diagnosis and Treatment
Invasive disease; culture that produce septate hyphae that branch at regular intervals
Invasive disease requires aggressive chemotherapy
Rhizobium sp., Absidia sp., Mucor sp.
Coenocytic hyphae (no septae), produce asexually via sporangia
Ubiquitous in the environment
Fairly rare disease but 70-100% fatal.
Rhinocerebral zygomycosis: Initiates in the paranasal sinuses that can invade into the brain in diabetic patients, GI, lung, subcutaneous infections in immunosuppressed patients, Burn patients colonize damaged tissue and then become invasive especially blood vessels
Microscopic examination of infected tissues reveals hyphal filaments
Culture not very reliable
Aggressive chemotherapy of invasive disease
Pneumocystis Carinii Pneumonia
Closely related phylogenetically to fungi
Trophic form is a uninucleated sporocyst or a mature spore case containing eight spherical spores
Subclinical infection in healthy people is frequent
AIDS patients develop and interstitial pneumonitis with plasma cell infiltrates, Death as a result of asphyxiation
Pneumocystis Diagnosis and Treatment
Diagnosis: Morphological identification of organisms in tissue stained with Gomori methanamine silver or Giemsa
Trimethoprim-sulfate-methoxazole or pentamidine isethionate
Lab Methods for Diagnosing Fungal Disease
Conventional Microbiologic Methods
Direct microscopy (Gram, Giemsa, and Calcofluor stains)
Culture from sample from patient
Routine stains (H&E)
Special stains (GMS, PAS, mucicarmine) stains can help visualize
In situ hybridization looking for fungal aspects in the sample
Molecular (Still not routinely used)
Direct detection (nucleic acid amplification)
Cell wall components
organism part of the normal flora; hypopigmented lesions occur on upper torso or abdomen; diagnosis made by microscopy; yeast-like cells and hyphae seen; topical azoles for treatment
causative agent produces melanin; found primarily as yeast and hyphae; discolorized spots appear on the skin; topical therapy
superficial hair infection; hard nodules found on hair shafts; these nodules contain asci (spores); condition of poor hygiene; washing
superficial hair infection; soft, pasty cream-colored growth along hair shafts; microscopic examination shows presence of hyphal cells
Diseases of the skin, hair and nails
Restricted to keratinized layers
Can invoke cellular immune responses, sometimes secondary bacterial infections
Not necessarily life threatening but do need to treat
Ringworm or Tinea (worm or moth)
Tinea Pedis (foot); tinea capitis (scalp); tinea manus (hands); tineas unguium (nails); tinea corporis (body)
Caused by agents named dermatophytes
Three Genera involved including Microsporum, Trichophyton, Epidermophyton
41 species recognized as causing disease - anthrophilic, zoophilic and geophilic
Epidermophyton - Macroconidia (clusters, smooth walled)
Microsporum - Macroconidia (large and thick)
Trichophyton - Macroconidia (rare, smooth, thin walled); microconidia (spherical, teardrop shaped)
Classified into three categories: geophilic, zoophilic and anthropophilic
Anthropophilic cause chronic relatively noninflammatory infections more difficult to cure, not understood why, lesser reaction but more difficult to treat.
Ringworm is classic presentation, Alopecia can be present along with scatter papules, vesicles and kerions and Onychomycosis for nails
Laboratory Diagnosis - Alkali Treatment and microscopy, Culture necessary to identify the agent involved
Treatment- Skin infections treated topically with azole derivatives, Hair and nail infections can be treated orally with griseofulvin for better still intraconazole or terbinafine
Subcutaneous Mycoses Key Properties
Comprise a wide range of fungal infections characterized by the development of lesions at the sites of trauma, usually org implanted
Many bacterial infections present the same way and mimic fungal infections. Need to differentiate
These infections may be difficult to treat.
Most subcutaneous fungal infections are rare in the U.S.
Chronic infection characterized by nodular and ulcerative lesions developing along the lymphatic glands that drain the primary site
Initial site of infection is a small nodule that may ulcerate
Secondary lymphatic nodules appear about 2 weeks later especially if left untreated
Causative agents are heterogenous group of organisms found in the soil.
Sporothrix schenckii is causative agent, Thermally dimorphic (hyphae or yeast), Mycelial colonies grow rapidly
Microscopic - narrow, septate hyphae with oval conidia, Yeast form may be cigar shaped.
Associated with warmer climates and Associated with forest work, mining and gardening
Laboratory Diagnosis: Definitive diagnosis requires culturing of infected tissue
Budding yeast at 35 degrees and mould at 25 degrees
In tissue, appears as pleomorphic budding yeast but not seen often
Asteroid bodies may be seen in tissue
Treatment: Classic treatment is KI in saturated solution. Effective and cheap. Given 3-4 weeks daily.
Current treatment now is itraconazole
Characterized by warty nodules that appear at inoculation sites, due to blunt force trauma
Common in Tropics
Dematiaceous (earth bound) fungi responsible
Organisms are pigmented
Diverse forms upon culturing
However, in tissue all form muriform cells (sclerotic bodies) brown in color
Chronic, pruritic, progressive and resistant to treatment
Presentation ranges from flat plaques to verrucous lesions
Established infections appear as warty cauliflower growths
Copper colored spherical cells are seen in tissue.
Isolation in culture of one of the agents
Antifungal treatment tends to be ineffective due to advanced state at presentation. Usually these patients have let it go too long.
Itraconazole and terbinafine are best, Heat and cryotherapy, Skin cancer can develop often times req amputation
Chronic, granulomatous, infectious process caused by fungi
Granules or grains in aggregates are observed, asteroid bodies
Amputation often indicated
Subcutaneous Zygomycosis and Subcutaneous Phaehyphomycosis
Medically Important Spirochetes
Subspecies pallidum- syphilis
Subspecies endemicum- bejel
Subspecies pertenue- yaws
Genome sequence analysis suggests that certain repeat motifs may be associated with sexual transmission
T. carateum- pinta
T. denticola, T. macrodentium, T. oralis- normal flora in mouth
Treponema Pallidum Key Properties
Very Slender (0.15 um) hard to see with microscope
Cannot grow in cell-free culture
Very slow replication rate
May be seen by darkfield microscopy (too thin for Gram stain)
Very sensitive to drying and disinfectants
Very sensitive to penicillin
Acquired by direct mucosal contact with primary/secondary lesion
Transmission occurs in ~1/3 of such contacts
Primary lesions may occur on oral or rectal mucosa
Organism can penetrate intact mucosa or damaged epithelium
30-70,000 cases per year in U.S. (2001)
12 million worldwide
homosexual men account for more than 50% of cases
Incubation period 10-90 days, Chancre forms at site of initial penetration
May include rectum, oral cavity, and cervix
"Hard Chancre" usually has raised, regular borders, a hard base, and some ulceration, Begins as papule and prgresses to ulcer
Chancre is painless unless secondary infection present
Multiple chancres occur in 25% of cases, Lesions with irregular borders may occur, Painless regional adenopathy common, Chancre is highly infectious heals in 4-6 weeks
Local penetration of skin (microabrasions) and mucous membrane, followed by spread to local lymph nodes and bloodstream
Histology of lesion shows infiltration of PML and macrophages, endarteritis and periarteritis
Outer membrane proteins aid in adherence to host cells
Hyaluronidase aids tissue penetration by "ungluing" connective tissue
Organisms become coated with fibronectin, inhibiting phagocytosis
Macrophage phagocytosis and killing of T. pallidum is enhanced by specific antibodies
Can overlap with primary chancre
Flu-like syndrome may precede rash when spreading systemically and body reacting
Rash occurs 2-10 weeks postinfection and can recur later
Appearance variable, but rash usually present on palms and soles, Lesions are infectious
~10% develop condylomata lata (raised gray or white lesions) in warm, moist areas (commonly perianal)
High titers of treponemal/nontreponemal antibodies present
Other symtoms (variable):"moth-eaten" alopecia, hepatitis, gastrointestinal inflammation, renal abnormalities, synovitis, uveitis
CNS involvement occasionally seen usually later
1/3 of patients may spontaneously clear infection after this stage
Women more likely to be asymptomatic so less likely to notice and progress to secondary
MSM may have lesions that are not as noticeable and often proceed to secondary
Hyperkeratosis of the epidermis and capillary proliferation with endothelial swelling
In the deeper dermis: perivascular infiltration by monocytes, plasma cells, and lymphocytes occurs.
Asymptomatic period of variable length after resolution of secondary syphilis
No sexual transmission
Transmission to fetus possible
Can occur months or years after infection
Not infectious- few organisms present
Soft, granulomatous masses (gummas) with central necrosis can cause widespread tissue destruction
Damage to skin, bones, joints, heart, nervous system, etc. Rarely heal spontaneously
May represent autoimmune or delayed-type hypersensitivity reaction
CNS involvement: Headache, fever, stiff neck, vomiting indicate meningitis, Dementia and paralysis may occur
May be fatal or cause permanent disability
Transplacental transmission can occur at any time
Can often be prevented by antibiotic treatment
Most fetuses die in utero, Surviving infants may develop symptoms of secondary and tertiary syphilis
Symptoms often appear 2-10 weeks after birth
"snuffles"- chronic rhinitis with whitish discharge, sometimes bloody very persistent
rash may appear 1-2 weeks after snuffles: may be severe with desquamation, more severe than would see in adults
Those surviving secondary syphilis may suffer tooth and bone malformation, blindness, deafness, CNS abnormalities, mental retardation such as interstitial keratitis and saber shins
Facial abnormalities include depressed nose bridge, short maxilla and protuberant mandible, Hutchinson's teeth- hypoplastic, notched
Syphillis Differential Diagnosis
Must consider genital herpes or Haemophilus ducreyi as alternative diagnoses (primary chancre)
Secondary syphilis: Infectious mononucleosis, Herpes zoster, Rubella or measles, Rocky mountain spotted fever, Various other skin diseases
Tertiary syphilis: Tuberculosis, Leprosy, sarcoidosis
Treponema Pallidum Diagnosis
Detection of spirochetes in primary/secondary lesions
Darkfield microscopy only useful on genital lesions if done immediately
Fluorescent antibody test more specific and useful on genital, oral, and rectal specimens, varies in availability
Detection of treponemal antibodies possible during early infection
Detection of nontreponemal antibodies like anti-cardiolipin
Non-Treponemal Diagnostic Tests
Tests use antigen comprised of cardiolipin, lecithin, and cholesterol
These molecules may be incorporated into T. pallidum membrane
VDRL (Venereal Disease Research Laboratories) slide test: No advantages over RPR, except in diagnosis of neurosyphilis
RPR (Rapid Plasma Reagin): Visual readout easier, Plasma can be used, Greater antigen stability due to slight modifications
Advantages: fast, easy to perform, reverts to negative 6-18 mos after successful treatment
prone to false positives because measuring host substances, Low sensitivity in early primary syphilis
Treponemal Diagnostic Test
Fluorescent treponemal antibody test (FTA-ABS): killed T. pallidum + serum+ fluorescent α-human IgG. Patient's serum must be pre-adsorbed with Reiter spirochetes
Advantages: High specificity, sensitivity; becomes positive very early in infection
Disadvantages: Requires whole T. pallidum; Cost; not useful for monitoring therapy, fall slower
T. pallidum hemagglutination (TPHA) or particle agglutination: RBC (or particles) treated to adsorb T. pallidum antigens. RBC clump when exposed to serum containing antitreponemal antibodies.
Advantages: similar to above, but not positive quite as early in infection, not as sensitive but easier
Disadvantages: similar to above
These tests can remain pos for life even after the infection is cleared.
Newer Tests for Syphillis
Rapid serological tests: Include EIA and immunochromatography formats, Can be performed in the clinic, Sensitivity can rival traditional tests
PCR: Sensitivity is low overall, Best sensitivity on lesion swabs because lots of org there
Treponema Pallidum Treatment and Prevention
Benzathine penicillin G (long acting) is the drug of choice: Single i.m. dose sufficient for early infection, Prolonged treatment required for tertiary or latent
Tetracycline or doxycycline (oral, 2 weeks) are alternatives, but not effective in neurosyphilis and can't be given to pregnant women
Oral azithromycin is effective, but some resistance noted
Jarisch-Herxheimer reaction: Fever, headache, malaise, Frequently occurs ~24 hours following antibiotic treatment due to lysis of organisms and body producing cyctokines, Resolves within 24 hours
Re-testing at 6 and 12 months recommended
No vaccine is available
Prevention solely by limiting contact with infected individuals
Bejel/ Endemic Syphillis
Was (is?) present in Africa, Asia, and Australia
Spread by contaminated eating utensils
Begins in mouth, then causes raised, eroding lesions on trunk and legs.
Inflammation of leg bones common.
Gummas of nose and soft palate develop later
Primarily a disease of children and Can cause severe disability
Still present in tropical regions of Africa, Indonesia, Guyana
Affects skin and bones
Spread by contact with lesions or eye gnats
Raspberry-like growths on skin may exude watery, highly infectious fluid.
Subcutaneous growths may occur later, and can cause deformity and disability.
Was (is?) present in Mexico, South America, Phillipines
Spread by contact with lesions
Initial raised papule, followed by flat, reddened areas and changes in pigmentation. Only involves skin.
Neurological and cardiac complications are rare.
Fungal Classification, Structure, and Replication
Diverse group of organisms, only 100 cause disease
Eukaryotic organisms - saprobes (live on decaying matter), symbionts (mutual advantage to living together), commensals (one benefits) and parasites (one benefits the other may be harmed).
Fungi Kingdom - Important Classes involved in human disease include: Zygomycetes, Ascomycetes, Archiascomycetes, Basidiomycetes and the Deuteromycetes.
Fungal Classes Human Disease
Zygomycetes, Ascomycetes, Archiascomycetes, Basidiomycetes and the Deuteromycetes.
Fungi can produce asexual spores.
Fungi can also produce spores by a sexual process
Fungi in the Zygomycetes, Ascomycetes, Archiascomycetes, and Basidiomycetes produce sexual and asexual spores.
Form producing sexual spores = teleomorph
Form producing asexual spores = anamorph
Deuteromycetes produce no known sexual spores.
Teleomorph and anamorph names are different but normally the anamorph name is used clinically.
Fungal Classification by Disease
Superficial mycoses - outer layers of the skin and hair affected, usually not very dangerous
Cutaneous and subcutaneous mycoses - only keratinized layers infected for cutaneous. Deeper layers affected for subcutaneous and spread is unusual. Usually very treatable.
Endemic mycoses - these systemic infections involve the lung and subsequent spread to other parts of the body. Organisms primarily found in the Ascomycetes Class, most dangerous ones, cause diseases in healthy people
Opportunistic mycoses -usually wont cause disease in healthy people
Mechanisms of Fungal Pathogenesis
Ergot Alkaloids: Inflammation and necrosis smooth muscle stimulants: cramps and pain
Psychotropic and other Agents: Psilocybin: "shrooms"
Aflatoxinsz: Turkey X disease caused death in turkey
can cause cancer
Hypersensitivity Diseases: allergies
Colonization and Disease (mycoses): superficial, cutaneous, subcutaneous, systemic
Primary Fungal Pathogens
Only 4 primary pathogens known and they cause blastomycosis, histoplasmosis, coccidiodomycosis, and paracoccidiodomycosis
Fungal General Virulence Factors
Limited understanding of how Fungi cause disease.
Some putative virulence factors to be discussed later include:
Adherence to tissue
Growth at 37 degrees, in yeast form
Cell wall mannans
Proteases allow cells to move deeper
Binding to ECM facilitates growth and tropism in parts of the body
Resistance to phagocytosis
Survival in macrophages
Antifungal Agent Classes
Produced by Streptomyces species, cyclic macrolide lactones, bind to sterols
Amphotericin B is the only clinical useful polyene
Pores may form in membrane after drug inserts or oxidation events affect membrane
Nystatin a related drug less potent
Binds to ergosterol in preference over cholesterol
AmpB with or without lipid formulation (lipid formulation help with solubility), Given IV, topical
Binds to Ergosterol causing oxidative damage to membrane and/or pores
Broad spectrum - works against most fungi
Toxicity include kidney and systemic side affects.
Primarily used for systemic infections that can kill patient, but meds have side effects
Largest group of commercially available antifungals.
Broad spectrum of activity, lots of research in this class
Inhibit synthesis of ergosterol
Triazoles (fluconazole, itraconazole and voriconazole)
Inhibit lanosterol 14 alpha demethylase, an enzyme important in ergosterol formation.
limited spectrum, serious side affects, clinical uses limited, second-line agent, often use in case of resistance
first generation triazole with excellent oral bioavailability and low toxicity. Better spectrum of action than ketoconazole. Important in treatment of candidiasis, cryptocococcis, and coccidiodomycosis. Good complement to amphotericin B
broad spectrum of activity, treatment of choice for non-meningeal histoplasmosis, blastomycosis and paracoccidiodomycosis. Second line treatment of aspergillosis.
new agent, broad spectrum action, primary indication for aspergillosis and massive candidiasis.
Novel selective class of lipopeptides that inhibit cell wall synthesis.
Caspofungin, micafungin, anidulafungin.
Caspofungin approved for treatment of invasive aspergillosis and candidiasis; others still being investigated.
Newer drug need to investigate the side effects further so only in very serious disease
Flucytosine is the only available antifungal agent acting as a antimetabolite.
FC becomes FU in cytoplasm and than to FUA which competes with uracil for RNA synthesis and has effect on DNA synthesis.
Used primarily with other agents.
Terbinafine active systemically and naftifine active topically
Inhibits conversion of squalene to lanosterol
Used for athletes foot
Oral agent in treatment of infections caused by dermatophytes.
Second line agent. Newer agents like itraconazole and terbinafine are being used.
Combination Therapy Mechanisms
Inhibit different steps in the same pathway (ergosterol)
Increase penetration of one agent by permeabilizing with another.
Inhibit transport of agent out of the cell.
Inhibit different targets in the same cell.
Rickettsia Key Properties
cytoplasmic membrane-peptidogylcan-outer membrane- LPS (cross-reactive)
Replicates in cytoplasm of eukaryotic cell
Cytoplasmic vesicle = Morulae
Insect bite (bac in saliva) or scratching insect feces into skin
Local necrotic lesion usually not seen
Infection of endothelium of small blood vessels
Direct endothelium damage (vasculitis) allows RBCs to surrounding tissues (skin rash, petechial rash)
Stupor may lead to terminal shock due to hypovolemia, hypoproteinemia caused by loss of plasma into tissues leads to reduced perfusion of organs and to organ failure.
Clinical History: time of year
fever, distribution of rash
Giemsa stain or fluorescent antibodies
Presence of Rickettsia (morulae)
Patient's sera reacts with Proteus stains OX-19 and OX-K
Western blot of Rickettsia LPS react with patient's antibodies (only do in severe cases)
Rickettsia Treatment and Prevention
Chloramphenicol or tetracycline
Toxic in children
Sanitation: rodent control
Prompt treatment probably before lab results
Rocky Mountain Spotted Fever
To humans via bite from hard tick 24-48 hr. contact with feeding tick
To activate avirulent rickettsiae in tick salivary glands
Dermacentor andersoni (wood tick, rodents) in Rocky mountains
Dermacentor variabilis (dog tick, dogs) in eastern states and west coast
Summer months (April-October) when ticks most active
800 cases per year
North Carolina and Oklahoma = one third of cases
Symptoms: Fever, chills, headache, myalgia
Spread of rash from extremities to trunk
Starts out on ankles and/wrists
Hypovolemia and hypoproteinemia
Loss of plasma into tissues which can lead to organ failure
Treatment: tetracylines, chloramphenicol
Sequela: 20% mortality due to delayed diagnosis, typically in pts with no rash
Prevention: protective clothing, tick repellents, remove ticks
Primarily from human to human via body louse (Pediculus humanus)
Eastern US: flying squirrels to humans via flea (?)
Recrudescence (Brill-Zinsser disease): years after initial infection, typically WWII vets because trench disease if came down with typhus before will have mild typhus like syndrome that usually resolves on its own
Sporadic disease in United States
Symptoms: Fever, headache, chills, myalgia, arthralgia
Rash on trunk of body
Stupor can get CNS symptoms
Recrudescent (reactivation): Brill-Zinsser disease
Laboratory: serology takes 3 to 4 wks
Treatment: tetracyclines, chloramphenicol
Prevention: louse-control; formaldehyde-inactivated typhus vaccine only recommended for those likely to come in contact with bac
R. typhi/ murine typhus
Rodent populations to humans via rat flea
Rare in United States
50-100 cases/year: most in Gulf States, especially Texas
Travelers from temperate or subtropical climates
Symptoms: Fever, headache, myalgia, cough
Spread of rash from trunk to extremities
Tetracycline, chloramphenicol, doxycycline
Rodent control difficult: too wide-spread
Also know as tsutsugamushi fever
Maintained by transovarial transmission, passed in generations
Endemic in Southeast Asia
Chigger bites are small and usually not notice. Patient will likely have no recollection of being bitten.
Cough with infiltrates on chest radiograph. Severe disease can mimic SARS.
Flu like symptoms.
The Weil Felix test is poor at detecting Scrub Typhus.
The drug most commonly used is doxycycline;
but chloramphenicol is an alternative.
Azithromycin is used in antibiotic resistant cases and with children and pregnant women.
Chlamydiciae Key Properties
Obligate, intracellular parasites
Small (pass through 0.45 um filter)
Two distinct morphological forms:
Elementary Body (EB)
Reticulate Body (RB)
Chlamydia Trachomatosis Species
2 human biovars: Trachoma and LGV
Trachoma Infects nonciliated epithelial cells found on mucous membranes of urethra, endocervix, fallopian tubes, anorectum, respiratory tract, and conjunctiva
Lymphogranuloma verenum biovar can replicate in mononuclear phagocytes present in lymphatic system, can also infect epithelial cells and causes more severe disease
Causes ocular and genital infections, pneumonia and LGV.
Direct destruction of host cell during replication
Infection can last many months and can spontaneously clear.
Establishment of persistent/latent infection
Nutrient deprivation, antibiotics, and IFN-g can stimulate development of persistent, non-replicating form (EB), that can re-enter the normal developmental cycle when conditions are favorable.
The host inflammatory immune response: No long-lasting immunity allows for re-infection and chronic inflammation, Re-infection induces a vigorous inflammatory response with subsequent tissue damage, Potent inducer of IFN-g and IL-1
Chlamydia Trachomatis Trachoma Diseases
Adult inclusion conjunctivitis
(chronic keratoconjunctivitis), Trachoma Biovar (A-C serotypes)
Endemic in Africa, Middle East, S. Asia, & S. America
Leading cause of preventable blindness, 2nd cause of blindness after cataract.
Infection occurs predominantly in children in endemic areas
Infection is reduced in older children and adolescents, incidence of blindness continues to increase through adulthood as disease progresses.
Poor sanitation, hygiene, and crowded living conditions promote transmission
Transmitted eye-to-eye by droplets, hand, contaminated fomites, flies, respiratory droplets, and fecal contamination
Chronic follicular conjunctivitis with diffuse inflammation that involves the entire conjunctiva
Scarring of conjunctiva due to repeated infections
Eyelids and eyelashes turn inward (trichiasis) resulting in corneal abrasion
Overtime, corneal ulceration, scarring, pannus formation leads to blindness
Adult Inclusion Conjunctivitis
Acute follicular conjunctivitis in sexually active adults
Associated with genital infections that precede eye involvement
Transmitted by autoinoculation with genital secretions, or direct inoculation by an infected partner
Mucopurulent discharge, keratitis, corneal infiltrates, and occasionally some corneal vascularization
Corneal scarring can occur in chronic infections, but infection usually resolves without complications. Usually acute.
Urogenital Infections in Women
Most genital track Chlamydial infections in women are
asymptomatic, but have serious consequences.
sexual intercourse with an infected male has an incidence in excess of 30% for becoming infected
Young age has increased risk, possibly due to cervix not fully mature
Women infected with Chlamydia are up to 5 times more likely to become infected with HIV, if exposed. Tissue damage and inflammation makes easier to infect
Infection generally begins in cervix and/or urethra, ascends to uterus and/or fallopian tubes if untreated—Pelvic inflammatory disease.
Symptomatic infection characterized by
mucopurulent discharge and hypertrophic ectopy
that develops 1-3 wks after infection,
inflammation of cervix
Postcoital bleeding, abnormal menstrual bleeding, dysuria
Untreated or undetected infections can progress to uterus and/or fallopian tubes resulting in pelvic inflammatory disease (PID).
40% of untreated (undiagnosed) women will develop PID.
Permanent damage of tissue/organs in urogenital tract
Chronic pelvic pain (~18%)
2/3 of tubal infertility due to C. trachomatis
tubal occlusion due to inflammation or scarring
Ectopic pregnancy due to salpingitis (9%)
1/3 of ectopic pregnancies attributed to C. trachomatis
Ectopic preg also a result of occlusion of the fallopian tubes
Infection during pregnancy can result in preterm labor, premature rupture of membranes, low birth weight, neonatal death, post-partum endometriosis. Could also pass infection to neonate.
Acquired through passage of infant through an infected birth canal
25%-50% of exposed newborns develop conjunctivitis
Eye infection develops 5 - 12 days after birth
Self-limiting: spontaneous resolution between 3 - 12 months
Infants who are untreated or topically treated are at risk for pneumonia
10% - 20% of exposed newborns develop diffuse interstitial pneumonia
Onset 2 - 3 wks after birth
Characterized as an afebrile illness with
Rhinitis and development of staccato cough
Infection can persist for several months
Urogenital Infections in Men
Generally "symptomatic" (25% -50% asymptomatic)
Responsible for 35 - 50% of nongonococcal urethritis
Symptoms: Less purulent discharge than gonoccocal, dysuria, pyuria, develop between 1 - 3 weeks after infection
Dual infections (C. trachomatis and N. gonorrhoeae) are common because chlam so prevalentsc
Symptoms for Chlamydial infection may appear after treatment for gonorrhea
Affects young white men (25 - 40 years of age)
lower incidence in women (5% of total) and African-American men.
Symptoms: urethritis, conjunctivitis, polyarthritis, and mucocutaneous lesions,
Associated with Chlamydial infections, although Shigella, Yersinia, and Campylobacter acquired through digestive track have also been implicated
50 -60% of patients have a chlamydial infection, 80% seropositive
Hereditary factor (HLA-B27 in 80% of patients)
Sexually transmitted disease
Acute LGV generally affects men primarily because symptomatic infection is less common in women.
Prevalent in Africa, Asia, and South America, sporadic in N. America, Australia, and Europe.
In US, 200-500 cases per year (homosexual men being the reservoir).
A new variant (L2b) was discovered among homosexual men in Amsterdam in 2003.
LGV is a systemic disease caused by the Chlamydia trachomatis serovars L1 to L3.
Systemic manifestations including fever, malaise, chills, anorexia, myalgia, arthralgia, meningismus, and headache.
More invasive than disease caused by the urogenital serovars (D-K)
LGV can manifest as
1) an inguinal syndrome, with genital ulceration and inguinal lymphadenopathy (buboes) and subsequent suppuration
2) an anogenitorectal syndrome, with proctocolitis and hyperplasia of intestinal and perirectal lymphatic tissue.
Common in women resulting from lymphatic spread from cervix or vagina
Spread by anal intercourse or lymphatic spread from urethra
Lymphogranuloma Verenum Stages
Stage 1: A painless primary lesion develops 1 - 4 weeks after infection.
penis, urethra, glans, scrotum, vaginal wall, cervix, vulva
Stage 2: Inflammation and swelling of lymph nodes draining the site of infection.
Lymph nodes become painful buboes that can rupture into draining fistulas.
Frequently affects inguinal lymph node
Can resolve at this stage
Stage 3: If left untreated, a chronic ulcerative phase may develop. Genital ulcers, fistulas, strictures, and genital elephantiasis develop
Ocular Lymphogranuloma verenum
LGV serotype implicated in Parinaud's oculogranuloma conjunctivitis
Conjunctival inflammation accompanied by nearby swollen lymph nodes
More Chlamydiae present in specimen from symptomatic infections: Obligate, intracellular nature of Chamydia requires a need to obtain specimen from infected site
A specimen of pus or exudate is inadequate.
Heat sensitivity can destroy specimen
Cytology: Examine Giemsa-stained cell scrapings
for presence of inclusions. Problem: Insensitive and not recommended
Culture: Most specific method, but only ~70% sensitive. Specimens are added to cultures of susceptible cells and the infected cells are examined for the presence of iodine-staining inclusion bodies or fluorescent-staining of MOMP or LPS.
Problem: Detection compromised in certain specimens or loss of viability during specimen manipulation/transport
Antigen Detection: Direct immunofluorescence, or ELISA Use antibodies to detect LPS or MOMP
Problem: Asymptomatic patients and male urethral
samples tend to have low bacterial loads.
Antigenic determinants (LPS) may be shared with other bacteria
Serology : Limited value, do not distinguish between current or past infection, IgM levels not useful because patients often do not produce these antibodies. Exceptions: Infants with chlamydial pneumonia LGV patients-- produce a vigorous antibody response
Nucleic Acid Probes (Molecular probes):
Non-amplified: Measure presence of species-specific 16S RNA Rapid and relatively inexpensive
Problem with sensitivity (low bacterial load)
Amplification techniques (NAAT): i.e. PCR
Considered the test of choice for laboratory diagnosis
90-98% sensitive and very specific if properly monitored
Problems include presence of inhibitors in specimens and cross-contamination of samples.
Tests are available to detect Chlamydia in samples from endocervical swabs, urethral swabs, urine.
Tetracyclines: Doxycycline 2X per day for 7 days (CDC), LGV for 21 days
Macrolides: Azithromycin, one dose, Erythromycin is recommended for children under 9 yrs of age, pregnant women, and patients unable to tolerate tetracyclines, Erythromycin should be prescribed for newborn conjunctivitis (10 - 14 day course), Pregnant women: erythromycin base 500 mg orally 4 times a day for 7 days
Fluoroquinolones: Ofloxacin for 7 days (not recommended for pregnant women, children or adolescents)
Sulfonamide derivative (Sulfisoxazole)
Chlamydia trachomatis is resistant to aminoglycosides (too slow acting), vancomycin and b-lactam antibiotics (penicillins & cephalosporins).
Only one Biovar (TWAR, single serotype)
No animal reservoir was been identified
Causes sinusitis, pharyngitis, bronchitis, and pneumonia,
Most infections are usually asymptomatic or mild
Symptoms are difficult to differentiate from other respiratory infections
Transmitted by respiratory secretions
May have a role in atherosclerosis
Infects smooth muscle, endothelial cells of coronary artery, and macrophages
Has been detected in atherosclerotic plaques by various techniques
Not detected in normal non-atherosclerotic tissue
Mechanism of pathogenesis not known:
Plaques may result from inflammatory responses to chronic infection
Chlamydophila Pneumoniae Diagnosis
Diagnosis of C. pneumonia is difficult
Do not grow well in standard cell lines used in Chlamydia diagnosis.
Will grow in Hep-2 cell line, but it is not used in most clinical labs.
Nucleic Acid detection (PCR) is successful, but no commercial kit available.
Serological diagnosis is also available using the microimmunofluorescence test (MIF) to specifically detect C.pneumonia MOMP. (IgM titer 1:16, 4 fold increase)
Chlamydophila Pneumoniae Treatment
Treatment of C. pneumonia is similar to Chlamydia
Macrolides (erythromycin, azithromycin, clarithromycin)
Tetracyclines (tetracycline, doxycycline)
Not susceptible to sulfonamides
Difficult because organism is ubiquitous
Primarily a pathogen of birds (ornithosis), but can also infect sheep, cows, goats, and humans
In humans, it causes psittacosis (parrot fever)
Transmitted by inhalation of dried bird excrement, urine or respiratory secretions (bird-person), person-person transmission is rare.
After incubation of 5 - 14 days, headache, high fever, chills, malaise, myalgia, and pulmonary involvement are observed.
Central nervous system involvement is common, usually consisting of headaches, but encephalitis, convulsions, coma, and death may occur in severe cases.
Fewer than 25 cases are reported annually in the US, very rare.
Diagnosed based on serologic findings
Treated with tetracycline and macrolides (not susceptible to sulfonamides).
Prevented by the control of infections in domestic birds and imported pet birds (treat birds with tetracycline for 45 days)
Bacillis Key Properties
Gram-positive, endospore-forming rods, catalase positive (Clostridia negative big distinguishing characteristic)
Aerobic to facultative anaerobe (Clostridia obligate anaerobes)
Most soil habitats, most innocuous to humans, ubiquitous
Some produce antibiotics (bacitracin, polymyxins, vanc & other polypeptides)
B. subtilis is the "E. coli" model for Gram positives
Contains two main pathogens (anthracis, cereus) and one important agricultural member (thuringiensis); all three very phylogenetically related and hard to distinguish
No person to person spread
Major naturally-occurring anthrax areas are tropical, subtropical (India, Pakistan, Africa, South America)
Lots animal reservoirs but no arthropod vector needed due to spores
Spores in soil so will see outbreaks in livestock
anthracis: highly virulent
cereus: low virulence- wound infection and food poisoning
thuringiensis: No disease; insecticides
Bacillis Virulence Plasmids
pXO1-182 kb (Anthrax toxin)
Edema Factor (EF)
Lethal Factor (LF)
Protective Antigen (PA)
pXO2 -96 kb (Capsule): Composed of poly-(D-
glutamic acid), single antigenic type-poorly immunogenic b/c aa polymer, anti-phagocytic, Production enhanced in the presence of Na+-bicarbonate-Produced primarily in vivo
Anthrax Toxin (Tri-partite A-B type toxin)
Protective Antigen (PA) - required for EF and LF binding to host cells; protective; vaccine candidate
Edema Factor (EF) - Adenylate cyclase, activated by host Ca-calmodulin; causes edema Bordetella pertussis also has an adenylate cyclase homologous to B. anthracis EF
Lethal Factor (LF) - Zn metalloprotease: Cleaves MAPK, Causes release of cytokines from Macrophages- lethal shock, not sure of mech
Bacillus Anthracis Disease
Wool Sorter's Disease
abrasions 95% cases papule (2 - 5 d post inf) Vesicle filled with black fluid. Head, Hands; Forearm. Regional Lymph nodes to blood stream (100 million/ ml) to death (20%)
Spores deposited in abrasion, insect bite
Germinate, vegetative cells multiply and produce toxin
Vesicle appears, contains serous fluid which later becomes hemorrhagic and blue-black (eschar)
Ruptures, leaving round sharp-edged ulcer with hemorrhagic necrotic tissue
5-20% of untreated patients develop septicemia and generalized infection
Wool Sorter's Disease
(inhalation) - Pulmonary, fever, malaise, cough, septicemia, death within 24 h nearly 100% fatal
Diagnosis made Post-Mortum
Dust particles contaminated with spores are inhaled, deposit in terminal alveoli
Spores engulfed by macrophages, transported to regional LN (mediastinal)
Germinate; vegetative cells produce toxin and capsule
Extensive necrotic hemorrhage, multiple organs involved, Meningitis by crossing BBB
Death rapid and near 100% even with Tx!
Invariably fatal. Organisms enter blood through intestine
Results from ingestion of contaminated meat
Organisms or spores penetrate oropharynx/intestinal mucosa
Deposited in submucosal tissue, multiply and produce toxin
Usually extends to regional LN, systemic symptoms develop
Death in 50-90% despite Tx
Bacillus Anthracis Diagnosis
Culture from lesions, blood; suspect bioterrorism for
inhalation cases because very rare
Inject blood into guinea pig or mouse
India ink or direct fluorescent antibody (capsule)
Lysis by gamma phage
PCR analysis of variable number of tandem repeats; high clonality a problem
Bacillus Antracis Treatment and Prevention
Ciprofloxacin (preferred), doxycycline, penicillins
Therapy must be administered early before bacteria get to >3 x 108/ml once to this level cant overcome toxin effects
Vaccines: PA vaccine (PA protective, but not as good as live spores) called anthrax vaccine adsorbed (AVA) 6 shot subcutaneously for military and lab workers with yearly boosters, acapsulate live spore vaccine (Sterne) for herds in endemic areas
Bacillus Cereus Key Properties
b-Hemolytic (cereolysin), no capsule, not lysed by gamma phage, no anthrax toxin; motile
Normal soil inhabitant, but can be isolated from foods (grains & spices).
Wound & ocular infections; rare systemic infection (IV-catheter); food poisoning
Two types of food-borne intoxications (as opposed to infections): Emetic and Diarrheal.
Emetic: nausea, vomiting, & abdominal cramps; incubation period of 1 to 6 hours (ingestion of toxin). It resembles Staphylococcus aureus food poisoning in its symptoms (rapid development) and incubation period (short). Patient recovers in 8-10 h. Caused by preformed heat-stable enterotoxin (Emetic toxin or Cereulide) (<5000 Daltons, cyclic peptide). Mechanism: potassium ionophore of mitochondria (similar to valinomycin); inhibits NK cells. Protease resistant; rice/pasta dishes implicated
Diarrheal: abdominal cramps and diarrhea with an incubation period of 8 to 16 hours. Diarrhea may be a small volume or profuse and watery. Resembles food poisoning caused by Clostridium perfringens. Patient recovers in 24 h, Hauge (1955) consumed vanilla sauce spiked with 9.2 x 107 CFU/ml and developed diarrhea within 16 h.
caused by heat-labile enterotoxin (50 kDa; hemolysin= cereolysin), produced after vegetative growth in intestine.
Activates intestinal adenylate cyclase and causes intestinal fluid secretion. Protease sensitive. Meat-based dishes responsible
Brucella Key Properties
Small Gram negative coccobacilli aerobic, alpha proteobacteria, oxidase & urease positive
Malta fever, undulant fever, Bang's disease (abortions in livestock, esp. cattle), brucellosis
Slow-growing- 1 week for culture + CO2; likes erythritol
Zoonotic disease, ingestion of contaminated animal products, no human to human
Potential biowarfare agent (class III pathogen!)
most common lab accident
can be aerosolized
Variety of animal reservoirs
Disease complications can occur in almost any organ
Worldwide distribution but rare in US due to control measures/vaccination of animals.
In animals, chronic lifelong infection
Replication within reproductive organs (prefers erythritol): sterility and abortion
Large number of Brucella shed in milk
Bacteria enter the body - through abrasion or mucosa
Macrophage ingests Brucella
Brucella survive and replicate with macrophage
Infected macrophage migrates to local lymph node ('Trojan Horse') to pretty much any organ of body
Other macrophage become infected with Brucella
Spread of Brucella via lymphatic system/blood
Brucella resists complement-mediated killing by serum
Organs become seeded with Brucella (mainly macrophage-type cells in organs) GI (70% infected people), liver (nearly all), skeletal, CNS
Granulomas can form in infected organs
Unusual symptoms: depression, neuroses, strange taste in mouth
Any organ may be involved
Intermittent fever-night sweats/chills ("Undulant Fever"), Muscle aches, headache, malaise, inability to concentrate, GI problems
Acute or chronic-symptoms may recur for months/years
Brucella Species and Disease
B. melitensis: more severe and acute disease
B. suis: more likely to produce suppurating granulomas in lymphatic tissue; chronic disease
B. abortus: less severe; more likely to be subclinical; suppurative complications
B. canis: least virulent for humans- mild disease; suppurative complications
Acquired by breaks in skin, inhalation
Acquired by ingestion of unpasteurized dairy products (eg. unpasteurized goat milk from Mexico = B. melitensis) - incidence in US is higher in Texas, California
Brucella Virulence Factors
Brucella LPS: Unusual structure, Contributes to resistance to antimicrobial peptides. O-antigen of LPS: required for virulence, Strains with O chain: "smooth" more virulent, Strains without O chain: "rough" Required for survival within phagocytic cells
Type IV' secretion system - required for persistence in macrophage
Symptoms nonspecific: important to obtain detailed history (occupation, ingestion of high-risk food, etc.).
Blood/bone marrow aspirates (handle with care!) plated on blood agar w/10% CO2.
Gram negative, non-motile, aerobic, rod-shaped bacteria.
Antibodies in patient
Uncommon in US, so usually referred to state public health lab for definitive identification.
Brucella Treatment and Control
Treatment: doxycycline in combination with streptomycin, rifampin, or gentamicin 3-6 weeks (relapses common with doxy alone because static, not cidal; relapses not due to resistance but inadequate therapy/patient compliance)
For pregnant women or children <8 yr: trimethoprim-sulfamethoxazole+rifampin
No human vaccine available: Current animal B. abortus/B. melitensis dangerous for humans.
Vaccinate livestock (B. abortus RB51; no vaccine against B. suis or B. canis) and test-and-control removal of infected animals
Quarantine imported animals
Pasteurize dairy products/avoid raw milk
Safety precautions for laboratory workers (biosafety level 3 required)
Protective clothing by abattoir workers
Anaplasma phagocytophilum (formerly E. phagocytophila)
Ehrlichia Key Properties
Gram-negative (poorly stained)
No LPS and no peptidoglycan
Morulae: membrane enclosed mass of bacteria
Intracellular replication (morulae)
Protected from immune response
Survival in phagocytic vacuole
Infection of hemopoietic cells
Picks specific leukocyte it wants to go after then binds and induces phago in vesicles and phago lyse and inhibit maturation so wont degrade bac
Cells divide eventually enough intracell bac that will kill the cell and escape out
Prevents phago and lysos fusion aka maturation
Lone Star Tick (Amblyomma americanum): white-tailed dear in south-central United States
Human monocytic ehrlichiosis: Monocytes and mononuclear phagocytes, macrophages causes Flu-like symptoms, gastrointestinal (50%), rash (30-40%)
Immune pathology creates most of disease (flulike symptoms)
Ixodes ticks: white-footed mouse, chipmunks in northeast and central Atlantic states
Canine granulocytic ehrlichiosis: Prevalent in dogs, infects neutrophils, Human accidental host in neutrophils
Similar to human monocytic ehrlichiosis due to symptoms
Raw fish flat worms prevalent in east Asia
Acute fever, looks like infectious mononucleiosis
Ixodes ticks: white-footed mouse, chipmunks in northeast and central Atlantic states
Human anaplamosis (human granulocytic ehrlichiosis): Infects bone marrow neutrophils causes Flu-like symptoms; gastrointestinal (<50%), rash (<10%)
Ehrlichia Diagnosis and Treatment
Serology and PCR
Cytology: intracellular organisms (morulae: formation of the intracellular bodies unique to infection process)
Treatment: Doxycycline before laboratory confirmation
Prevention: Avoid ticks and raw seafood
similar to Rocky Mountain spotted fever so use doxy so covers both
Coxiella Burnetti Key Properties
LPS: phase variation
Forms spores that are released from infected cells
Spores stay in the environment for months especially in feces, What allows to not have arthropod vector can just breathe it in
Worldwide: Stable spores in the environment, Mostly a disease of animals (wild or domestic)
Most human disease from contact with farm animals from Accidental inhalation (dried feces, animal placenta) or Ingestion of unpasteurized milk
20-30 cases/year USA
Mainly West coast (think hippies want to drink unpast milk)
Proliferated in respiratory tract
Disseminates to other organs
Chronic infections often manifest as endocarditis
Infects alveolar mac and resident mac of lung causes damage to the lung
Flu like symptoms and pneumonia with semiprod cough
Not treated in time can disseminate and chronic infections manifest in endocard sometimes up to 20 yrs post acute infection
Acute infection: Q fever: Sudden onset headache, high fever, chills, myalgia, Respiratory involvement (mimics Mycoplasma pneumoniae, e.g., atypical pneumonia)
Chronic infection: Subacute endocarditis (on damaged heart valve)
Coxiella Diagnosis and Treatment
Diagnosis: serology or PCR performed by reference laboratories
Francisella Key Properties
Facultative intracellular, gram negative, non-motile, coccobacillus (round or oblong)
Low infective dose (10 organisms) High morbidity (95%) and High mortality (up to 60% in untreated cases)
mammals and arthropod vectors
no person to person
4 identified subspecies of Francisella tularensis:
Francisella tularensis subspecies tularensis:
Has the highest mortality rate (up to 60% in untreated pneumonic cases) localized to north america common in US
Francisella tularensis subspecies holarctica:
High morbidity rate but lower mortality rate, typically found in Northern Europe
Francisella tularensis subspecies novicida:
Only causes disease in immuno-compromised individuals, first case out of this hospital
Francisella tularensis subspecies mediasiatica: Recently identified subspecies, rarely causes disease in humans, currently no documented cases
Francisella can invade a variety of cells including: Macrophages, Neutrophils, Dendritic cells, Hepatocytes, Epithelial cells, Erythrocytes
Francisella pathogenicity island is a Type 6 secretion system that is critical for cellular invasion into cytosol and intracellular replication
Immune evasion allows the organism to persist in the host: Invasion and inactivation of immune cells slows generation of immune response, Stimulation of host cells to make anti-inflammatory components alter immune response, Alter LPS structure to evade immunological detection
This is the most common form of tularemia and usually occurs following a tick or deerfly bite or after handing of an infected animal. A skin ulcer appears at the site where the organism entered the body. The ulcer is accompanied by swelling of regional lymph glands very painful, usually in the armpit or groin.
Similar to ulceroglandular tularemia but without an ulcer. Also generally acquired through the bite of an infected tick or deerfly or from handling sick or dead animals.
Pneumonic (most serious)
This is the most serious form of tularemia. Symptoms include cough, chest pain, and difficulty breathing. This form results from breathing dusts or aerosols containing the organism. It can also occur when other forms of tularemia (e.g. ulceroglandular) are left untreated and the bacteria spread through the blood stream to the lungs.
Specimens should be examined for evidence of the tularemia if a person:
Presents with symptoms suggestive of tularemia like Fever, lympadenopathy, flu like symptoms, ulcers, non-productive cough; Has recent travel history to tularemia infected areas and/or Has been bitten by fleas, flies or mosquitos, Encountered dead animals
Bacteria will grow on specific enriched laboratory mediums: Francisella grows slowly so treatment should be started before results
No rapid diagnostic currently available
Francisella infections need to be reported to CDC and local health officials.
Streptomycin and Gentamicin for 10 days
Doxycycline, Choramphenicol and Ciprofloxacin are also effective, though they should be used for 14-21 days
For prophylactic treatment Doxcycline or ciprofloxacin is perferred
There is a vaccine, however it is not FDA approved and does not proved effective immunity against type A F. tularensis (made avirulent first then virulent in mice but not humans)
Yersinia Key Properties
Gram negative, Rod shaped bacterium
Facultative anaerobe with bipolar safety pin staining
Can be found both intracellular and extracellular
wild rodents and rats are the reservoir
transferred when flea bites infected rat then human
If into lungs can be aerosolized and moved human to human
Yersinia pestis has three plasmids that encode: Virulence factors, Type III secretion system and effectors, LcrV, F1 Capsule
Several proteins then contribute to the maintenance of the bacteria in the flea digestive tract, among them the hemin storage (Hms) system and Yersinia murine toxin (Ymt).
Yersinia Pestis Disease
Bubonic plague is the most common type. It is caught when an infected flea bites a person. The victim then develops swollen and tender lymph glands, fever, headache, chills, and weakness. The disease does not spread between people.
Septicemic plague occurs when plague bateria multiply in the blood. It can occur on its own or may be a combination of pneumonic and bubonic plague. Symptoms include fever, chill, abdominal pain, shock, bleeding into the skin and organs. It is not spread between people.
Pneumonic plague is caused by inhaling the bacteria. It begins as a severe pneumonia with high fever, chills, and cough. Without prescription antibiotics, respiratory failure and death may occur within 12 to 24 hours after the initial symptoms appear. It spreads directly from person to person through the air (e.g., cough, sneeze).
Specimens should be examined for evidence of the plague if a person: Presents with symptoms suggestive of plague like Fever, lympadenopathy, flu like symptoms, Has recent travel history to plague infected areas and/or Has been bitten by fleas
Gram staining of cultures should see classic safety pin morphology from Bubo or Blood or Sputum- though they may contain many other bacteria
Bacteria will grow on general laboratory medium, Culture can be stained for expression of F1 antigen, Yersinia grows slowly so treament should be started before results
Yersinia pestis infections need to be reported to CDC and local health officials.
Yersinia Treatment and Prevention
Antibiotic therapy: Gentamicin, Streptomycin, Tetracycline
Prophylactic treatment Given to people who have close exposure to known plague cases, or report flea bite during a plague outbreak, Use tetracylines or sulfonamides
No current FDA approved vaccine
Control Flea and rat populations and Use flea control on pets and Insect repellents
Burkholderia Key Properties
Gram negative, rod shaped motile aerobic bacterium
Bipolar staining characteristic
Can be found both intracellular and extracellular
cat b bioterrorism agent
There are many Burkholderia species with many being environmentally friendly.
Two species are classified as Category B Bioterrorism Agents
Burkholderia pseudomallei -the causative agent of melioidosis
Burkholderia mallei- the causative agent of glanders
Both strains contain two chromosomes: Chromosome 1 contains mostly housekeeping and metabolism genes, Chromosome 2 contains virulence factors
Both strains contain a variety of virulence factors: Type IV pili used for attachment, Type III secretion to secrete effector molecules into host cells, Type VI secretion system does same as 3, Capsule for passive protection against antibodies and phago
Burkholderia pseudomallei has an efflux pump making it resistant to many antibiotics, efflux pump is extremely effective (need very strong long term antibio)
Most cases present with acute febrile illness with severe pneumonia and sepsis
Can have asymptomatic carriers that can develop into acute melioidosis years later
Typically manifests with abscess formation on internal organs
Affected adults typically have and underlying predisposing condition, most prevalent of which is diabetes mellitus.
Caused by pseudomallei
Acquired by inhalation, through cuts in the skin and occasionally through ingestion.
The symptoms of glanders depend upon the route of infection with the organism. The types of infection include localized, pus-forming cutaneous infections, pulmonary infections, bloodstream infections, and chronic suppurative infections of the skin. Generalized symptoms of glanders include fever, muscle aches, chest pain, muscle tightness, and headache. Additional symptoms have included excessive tearing of the eyes, light sensitivity, and diarrhea.
Horses are the primary carrier for this agent and responsible for transmitting disease to other animals and humans
Medical history of patient demonstrate travel to endemic area or worked with horses
Culture of organism from blood, sputum or pus
An indirect hemagglutination assay is the most widely used serologic test.
Melioidosis (pseudomallei so hard to treat) require initial treatment of ceftazidime, imipenem or meropenem treatment followed by 20-24 weeks of oral trimethoprim-sulfamethoxazole.
Burkholderia mallei is sensitive to tetracyclines, ciprofloxacin, streptomycin and gentamicin (mallei so no efflux pumps)
No current vaccines avaliable.
Y. pestis (plague)
Parasites (Giardia, Cryptosporidium, ringworm)
Viruses (West Nile, Hantavirus, EEE, WEE, VEE, Herpes B, Rabies)
Listeria Monocytogenes Key Properties
Gram positive, facultative (can utilize oxygen); small short rods, motile at room temp but not really at 37
Facultative intracellular pathogen (can grow in host cells)
Usually acquired by ingestion of contaminated food
Cause mild influenza-like disease with GI symptoms in healthy adults
Can cause serious disease such as meningitis in pregnant women, individuals with impaired cellular immunuty, and neonates
Grows at 4oC!, normal refrigeration temp
Ubiquitous in soil, water, vegetation and intestines of mammals, birds, fish, insects
Infection can cause animals to abort
Some animals show neurologic symptoms
Healthy adult (nonpregnant) animals usually asymptomatic
Asymptomatic carriers in humans and mammals; ~5% of human stool contains Listeria.
Humans are not important route of transmission.
Major mode: ingestion of contaminated (especially undercooked/raw) food products.
Infectious dose in healthy mammals: 103-109 bacteria
Pregnant women at higher risk (up to 1/3 of cases)
Mother-child transplacentally or via infected birth canal
Other risk factors include immunosuppression, age, diabetes, etc.
Cross-infection in neonatal nurseries (rare)
Other human-human spread not documented
Variable acid resistance- range of infectious doses
InlA- promotes M cell/enterocyte invasion via host glycoprotein receptors (e.g. cadherins)
InlB- allows invasion of more cell types
Phagocytic uptake by professional phagocytes (independent of InlA)
Listeria enters the liver via macrophages and can replicate in hepatocytes, Hepatocyte lysis results in bacteremia, Placenta and brain may be exposed
Listeriolysin O (Llo)+ phospholipases- permit lysis of vacuole and escape into cytoplasm, Acidification of phagosome activates enzymes, Does not lyse cytoplasmic membrane; bacterium stays intracellular
ActA- directs assembly of actin at one end of bacterium promotes movement of bacterium through cell via actin polymerization, promotes formation of filopodia which are engulfed by adjacent , Cycle repeats in adjacent cell
Cell-mediated immunity (activated macrophages) important for clearance of this pathogen because of its intracellular tropism.
mild impairment of cell mediated immunity in mother permits replication and spread
Infection can be transmitted transplacentally: 22% stillbirth or neonatal death.
Early onset disease: acquired by aspiration of infected amniotic fluid before birth: Granulomatosis infantiseptica- numerous abscesses and granulomas prognosis not great
Late onset: colonization of neonate by organisms in vagina. Neonate infected at birth: Occurs 2-3 weeks after birth
Usually results in meningitis with septicemia.
Most healthy adults: asymptomatic
mild influenza-like illness, gastrointestinal symptoms; self-limiting
Pregnant women, elderly, immunocompromised are most at risk: bacteremia/sepsis or meningitis, Listeria has a tropism for brain
Meningitis in immunocompromised patients/pregnant women: mortality rate : 22%!
Bacteremia- May follow febrile enterocolitis, Most deadly in immunocompromised patients and neonates, Less fatal in pregnant women but often leads to abortion.
Brain stem encephalitis; high mortality; healthy adults (unusual)
Brain abscess (10% of listerial CNS disease); high mortality
Endocarditis: high mortality; adults
Listeria Treatment, Prevention, Control
For individuals at risk, avoid soft cheeses; reheat ready-to-eat foods (i.e., hot dogs) to very hot
Thoroughly wash raw vegetables
Thoroughly cook raw food from animals
Penicillin or ampicillin + gentamycin
Early antibiotic treatment of infected pregnant women can increase chances of delivering healthy child.
No vaccine available
Bartonella Key Properties
Gram negative rod
Stains poorly with Gram stain
Human or animal reservoirs
Often spread by insect vectors
Bartonella bacilliformis: 'Carrión's disease'
Bartonella henselae: 'Cat-scratch fever'
Bartonella quintana: 'Trench fever'
Henselae and Quintana cause secondary infections in AIDs patients
Complex interplay with host
Facultative intracellular pathogens
Prefers highly vascularized tissue.
Targets: endothelial cells & erythrocytes
Invades, alters, parasitizes("hemotrophy"), and destroys erythrocytes
Stimulates pathological angiogenesis
Bartonella Bacillaformis Disease
'Carrión's disease' Disease largely restricted to South America - Andes region of Peru, Ecuador, Colombia.
Acute hematologic disease - 3 -12 weeks after inoculation.
Mild form - febrile illness that may not be recognized or even asymptomatic
Persistent asymptomatic bacteremia in survivors - are asymptomatic humans the reservoir
Carrion's Disease Phase I
High fever, chills anorexia, prostration, headache, mental status changes
Profound anemia from erythrocyte destruction, vomiting, hepatic/GI dysfunction (anemia and GI prob), End organ ischemia
Without antibiotics, high mortality ~10% mortality in modern era
Carrion's Disease Phase II
"Verruga Peruana" ("Peruvian warts")
Occurs if acute infection was not treated with antibiotics.
Skin lesions- blood-filled, bulbous, ulcerating, bleeding.
Globally endemic can get anywhere, Well-adapted to cats/felids (a natural host)
Cats: bacteremia in the absence of disease or mild disease
Cat-to-cat transmission: cat flea (Ctenocephalides felis)
"Cat-scratch" disease in humans, Humans are 'incidental' host
Transmission to humans is via cat, not via flea
Bartonella Henselae Disease
In general, mild infections in immunocompetent humans.
3-10 days following contact with infected animal (usually kitten/feral cat):
Primary cutaneous papule/pustule.
Regional lymphadenophathy (near infection site) that is unilateral.
May have low grade-fever, fatigue, headache, sore throat, headache, rash, muscle aches.
Parinaud's oculoglandular syndrome possible
Immunocompromised humans: more severe disease (bacillilary angiogenesis)
Outbreaks in WWI & WWII "5 day fever": trench warfare/POW camps/concentration camps
Later, sporadic occurrence in developing countries after disasters
Recently, emerged in homeless populations ("Urban trench fever") more likely to have head or body lice, Poor hygeine/poor sanitation
Predisposes to human encounter with vector/reservoir.
At risk: homeless, inmates, healthcare workers caring for infected individuals
Headache, Relapsing fever (~5 day intervals), Truncal rash, Join paint, Shin pain, Bacillary angiomatosis, Endocarditis (can be fatal)
More serious skin lesions possible
In HIV patients- cutaneous/subcutaneous lesions, bone lesions
Vascular proliferative disorder
Typically seen in HIV-infected or immunocompromised patients
Skin lesions: subcutaneous or dermal nodules, papules - skin colored, red, purple.
B. quintana: Involves skin, lymph, spleen, liver.
B. henselae: Skin subcutaneous tissue, bone
Bartonella Diagnosis and Treatment
Presenting symptoms Can be nonspecific and perplexing, Important to obtain patient history (contact with animal, travel, etc.)
Identification through PCR methods and Serological methods
Culture of organism. Takes ~7 days for colonies to appear.
Treatment not required for mild cases
Optimal treatment regimen is uncertain
Possible treatments include: azithromycin, clarithromycin, rifampin, trimethoprim/sulfamethoxazole, clarithromycin
Addition of gentamycin may be useful for hepatosplenic disease
Pateurella Multocida Key Points
Gram negative coccobacillus, worldwide distribution
Commensal organism in household pets (cat/dog)
Acquired by bite/scratch
Wound infection/soft tissue infection may be polymicrobial
More severe disease in individuals with underlying disease
Skin, soft tissue, joint infections: Usually occur after cat or dog bite, Inflammation, pain and swelling within 24 hr, Regional lymphadenopathy, Prognosis excellent if infection remains localized
Complications: Necrotizing fasciitis, cellulitis possible, Abscesses, Osteomyelitis
Uncommon: bacteremia, sepsis, septic arthritis
Respiratory tract infections: Second in frequency to skin/soft tissue infections, Mostly Pasteurella multocida, Patient typically has underlying respiratory tract infection, ~30% mortality rate
Central nervous system infections: Rare; usually elderly and neonates
Pateurella Diagnosis and Treatment
Treatment (most infections): Penicillin
Septic arthritis: frequent drainage of joints and antimicrobial therapy.
Difficult to culture
Rat Bite Fever
Rodents Oropharyngeal Cavity= reservoir
Rat Bite Fever
Incubation period: ~10 days after bite
Starts abruptly with Nonspecific symptoms: fever, chills, vomiting, arthralgias, myalgias
Rash appears after initial symptoms usually on the extremities including palms and soles, maculopapular
Complications: endocarditis, myocarditis, sepsis, meningitis, abscess in different organs.
Children: diarrhea/weight loss
25% mortality if untreated
Rat Bite Fever Diagnosis and Treatment
Obtain exposure history
Febrile patient, rash, rat exposure can suggest rat-bite fever
Visualization of pleomorphic bacilli from blood smears, pus, joint fluid
ELISA and PCR
Treat with ampicillin, cefotaxime, azithromycin, or doxycycline
(notice not penicillin as in previous diseases)
grazing mammals, many types of infections in immunocomp
dog or cat bite; possible septicemia
Eikenella corrodens: human bite wounds
human bite wounds
DONT BITE ME EIK
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