Chapter 19: Rickettsiae

1
Chapter 19 Rickettsiae

• Family Rickettsiaceae
• Genera Rickesttsia Ehrlichia
  Coxiella
• 5 categories of Rickettsial disease
• Typhus
• Scrub Typhus
• Trench Fever
• Spotted Fever
• Q Fever

2
Rickettsiae

• General Characteristics
• Small obligate intracellular parasites
• Grow ONLY inside living host cells
• Ultrastructure resembles Gram-negative bacilli
• Human transmission via arthropod vector-borne
  route
• Rodents ? arthropods (lice, ticks, fleas, mites)
  ? humans rodents (continues life cylce)
• Rickettsial diseases are generalized infections,
  w/ RASH usually being the prominent feature

3
Rickettsia

• Structural features simliar to typicla
  prokaryotic bacteria
• Small, rodlike or coccobacillary shape
• Typical double-layered, Gram-negative cell wall.
• Stain poorly in Laboratory best visualized under
  light microscope w/ either Giemsa or Macchiavello
  stain

4
Rickettsia

• Pathogenesis
• Insect vectors for human transmission arthropods
  such as fleas, ticks, mites, or lice
• Rodents, humans, or arthropods all can serve as
  reservoirs
• Multiply in salivary glands of ticks/mice gut
  of lice/fleas
• Affinity for endothelial cells of small blood
  vessels of circulatory system Bloodstream
  affinity in humans
• Causes obstruction of blood flow ? tissue
  necrosis
• Site of Bite Eschar (encrusted ulcer) ?
  necrotic tissue DIAGNOSTIC
• Site of bite point _at_ which Rickettsia enters
  the body becomes blackened
• Following bite, organisms taken into body by
  phagocytosis-like process
• Organisms multiply in both nucleus cytoplasm of
  host cell
• Host cells die, Rickettsia spread thru-out body
  via bloodstream or lymphatics
• Focal thrombi (blood clots) form in organs incl.
  skin
• Small hemorrhages hemodynamic disturbances
  create sxs of illness

5
Rickettsia

• Pathogenesis contd
• Except for agents of Trench Fever Epidemic
  Typhus, Rickettsia are zoonotic disease agents
  for which humans are accidental hosts
• After bite, predilection for cells that line
  small blood vessels (endothelial cells)
  bacterial multiply and spread along the blood
  vessels
• s/sxs result from inflammation and swelling of
  small blood vesssels
• Blockage /or reduced blood flow, come leakage of
  blood into surrounding tissues gt produces spots
  and rashes seen w/ most Rickettsial diseases

6
Rickettsia

• Clinical
• Rock Mountain Spotted Fever
• Etiological agent Rickettsia ricketsii
• m/c rickettsial disease in US, especially found
  in South Central states along Mid-Atlantic
  coast (high incidence in N. S. Carolina) also
  found in Russia.
• Reservoir rodents (mice, rats)
• Vector Tick Bite
• Rickettsia in saliva of tick, transfer to humans
  after bite
• Human infection initiated by bite of infected
  wood or dog tick
• Highest frequency of disease during warmer
  months, parallels tick activity
• Sxs develop 7 days after tick bite
• High fever malaise, then rash initially
  macular, but becomes petechial or hemorrhagic
• Rash starts on extremities, esp. palms and soles
  then rapid spread to entire body
• Fever, rash, NO eschar gtgtgt DEATH (hypotension,
  convulsions, cardiac arrest)
• Untreated cases vascular disturbances w/
  myocardial or renal failure possible
• Epidemiology children lt15 yoa peak 5-9 yrs.

7
Rickettsia

• Clinical
• Typhus Group
• Louseborne (epidemic) Typhus
• Etiological agent Rickettsia prowazekii
• Transmission person-to-person by infected human
  body louse that excretes organisms in feces
• Introduction of pathogen form lice facilitated by
  scratching the louse bites
• Ex. Infected human ? louse bites human and
  becomes infected sheds Rickettsia in feces ?
  bites another human ? feces on skin, scratching
  forces Rickettsia into wound ? 2nd human now
  becomes infected
• Disease is NOT maintained in the louse
  population lice serve as VECTORS, transmitting
  organism to humans
• Epidemics occur under conditions of displacement
  of people, crowding poor sanitation
• Sxs high fever, chills, severe HA rash
  possible
• Duration of Disease 2 weeks more severe in
  ederly
• Complications CNS (neurological involvement)
  dysfunction and myocarditis

8
Rickettsia

• Clinical
• Note Brill-Zinsser Disease (recrudescent
  typhus) mild form of typhus occurs in pts who
  previously recovered from 1 infection is latent
  infection, m/likely maintained in
  reticuloendothelial system carrier form
• Typhus Group
• Endemic (Murine) Typhus Fever
• Etiological agent Rickettsia typhi
• Reservoir Rodents (Rats)
• Vector flea feces or bite
• Transmission thru skin, respiratory tract,
  conjunctiva
• Milder form of Epidemic Typhus
• Natural infection is found in rats/mice and
  sporadically transmitted to humans no
  human-to-human transfer
• rare in US d/t good rodent control

9
Rickettsia

• Clinical
• Scrub Typhus Group
• Etiological agent Rickettsia tsutsugamushi
• Reservoir rodents
• Vector mite bite
• Typically seen in SE Asia and S. Pacific region
• Clinical maculopapular rash, Eschar untreated
  cases can lead to DEATH

10
Coxiella

• Distiguishing Characterisitics
• Grows in cytoplasmic vacuoles
• Stimulated by low pH of phagolysosome, but
  resistant to host degradative enzymes
• Extremely resistant to heat and drying persists
  outside host for long periods
• Causes disease in livestock (cattle, etc.)
• NOT transmitted to humans by arthropods but
  organism has been recovered from ticks.
• Human infection usually follows inhalation of
  infected dust in barnyards, slaughterhouses, etc

11
Coxiella

• Clinical
• Q Fever group
• Etiological agent Coxiella burnetti
• Reservoir cattle, sheep, rodents, ticks
• Vector contaminated aerosol (i.e., if a cow
  sneezes!)
• C. burnetti enters the body via mucous membranes,
  abrasions GIT via consumption of milk for
  infected animals
• Zoonosis b/c animal direclty transmits the
  organism to humans
• Reproduction w/in RT and dissemination is
  possible (untreated cases)
• Sxs high fever, cough, pneumonia, hepatitis
  all self-limiting usually rarely endocarditis
  (scarring of hrt. valves) and scarring of liver
• Classic Q fever is an interstitial pneumonitis,
  complicated by hepatitis, myocarditis, or
  encephalitis
• Laboratory Dx Serological assays
• Treatment Antimicrobials

12
Rickettsia

• Laboratory Identification/Dx
• Serologic Procedures ONLY
• Demonstration of rickettsia-specific Ab response
  during the course of the infection
• ? in specific Abs between acute convalescent
  stages of infection
• NO culture dangerous difficult
• Do not want to handle it in lab setting!
• Most diagnoses made by pt. hx clinical signs
• Treatment Prevention
• Antimicrobials effective in eradication
• Early tx is absolutely necessary
• No vaccines
• Person cleanliness/hygiene
• Eliminate/reduce an. reservoir avoid/reduce
  contact w/ arthropod vectors
• Delousing, rodent-proofing buildings, removing
  brush in tick- or mite-infested areas
• Wearing proper clothing, using tick repellants
• Frequent inspection of body for lice subsequent
  removal

13
Ehrlichia

• Similar to Rickettsia but these organisms
  parasitize leukocytes grow in cytoplasmic
  vacuoles formation of inclusion known as
  morulae
• Clinical Disease Ehrlichosis
• Reservoir rodents (mice, rats)
• Vector Ticks
• Etiological agents
• E. chaffeensis causes Human Monocytic
  Ehrlichiosis (HME)
• Anaplasma phagocytophilum causes Human
  Granulocytic Anaplasmosis (HGA)
• Clinical features acute fever, myalgia
  moderate-to-severe leukopenia and
  thrombocytopenia NO rash, usually
• Dx Ab assays, PCR
• Treatment Antimicrobial

14
Trench Fever Group

• NOT intracellular parasite can be cultured on
  artificial media
• Etiological agent Rochalimaea quintana
• Reservoir humans
• Vector body louse (lice)
• WWW I II virtually none today

15
Chapter 20 Fungi

• Mycology the study of fungi
• Fungi are widespread in nature 200,000 species
  identified
• Most fungi involved in decomposition of organic
  matter play important role in recycling organic
  compounds in nature
• Fungi are Eukaryotic organisms
• Unicellular morphology (Yeast) or Mulitcellular
  morphology ( Mold)

16
Fungi

• Yeasts (Unicellular morphology)
• Single, oval or spherical fungal cell
• Reproduction Asexual by budding
• Budding
• Division of nucleus
• Passage of one nucleus to a bud the balloons
  out from the mother cell
• Formation of wall between the bud and mother cell
• Daughter cell bud or blastospore
• Daughter cell initially smaller than mother cell
  but, it will increase in size produce own buds
• Molds (Filamentous morphology)
• Multicellular filamentous or tubular structures
• Reproduction asexual or sexual (main
  discriminating feature)

17
Fungi

• Growth of mold
• Germination of Condium (asexual reproductive
  unit in fungi) send out a filament that grows
  by elongation _at_ its tip
• Hyphae elongated filament the basic structure
  of growing molds
• Mycelium multiple branches of hypae mass of
  hypae
• Many nuclei located w/in each hypae
• Formation of Septae cross-walls w/in hypae
• Conidia terminal ends of hyphae seeds for
  new colonies molds reproduce by developing
  conidia on the hyphae
• Sexual reproduction
• 2 reproductive bodies connect haploid cells
  fuse to form diploid cells (spores) meiosis
• Resulting diploid cells become Spores
  reproductive elements formed from sexual
  reproduction
• Rare among the human fungal pathogens

18
Fungi

• Dimorphic Fungi
• Dimorphism the property of having 2
  morphological shapes dimorphic fungi have
  capability of 2 distinct forms dependent on
  temperature
• Temperature Dependent
• Yeast form 37C
• Mold or mycelial form 25C
• General characteristics
• Cell wall rigid thick NO PG
• 1 component is presence of sterol in cell wall
• No locomotion non-motile
• Distinguishing Morphological Characteristics
• Size, presence of a capsule, cell wall thickness,
  spores or conidia production

19
Fungi

• Growth Conditions
• Molds aerobic
• Yeasts facultative anaerobes
• Acid pH (4.0 ? 6.0)
• Selective Laboratory Media
• Sabourauds Dextrose Agar (SDA) low pH
• Dermatophyte Test Media (DTM) turns red in
  presence of all dermatophytes
• Birdseed Agar specific for ID of Cryptococcus
  neoformans ( agar turns brown) all other
  Crytpococcus spp turn it white
• Minimal Media
• Corn Meal Agar (ID of spore formation production
  of terminal conidia)
• Slide cultures undisturbed growth
• Colonial Morphology
• Molds dry, cotton-like masses
• Yeast moist, opaque, creamy colonies

20
Mycoses (Fungal Diseases)

• Superficial Mycoses
• surface infection
• Fungal diseases that grow on surface of skin
  nails
• Cutaneous Mycoses or Dermatomycoses
• Fungal infections of keratinous structures
  outer layers of skin, nails, in hair shafts
• Subcutaneous Mycoses
• Infections that penetrate below the skin
  involve the subcutaneous CT and bone tissue
• Systemic or Deep Mycoses
• Infections of internal organs from disseminated
  disease
• Opportunistic Mycoses
• Infections in compromised or immunosuppressed

21
Dermatomycoses

• ONLY contagious fungal infection/disease in
  humans not associated w/ death, just
  uncomfortable symptoms and characteristic lesions
• Dermatophytes fungi that invade keratinized
  cutaneous areas of the body
• Nails, hair and skin
• 3 Major Genera
• Microsporum
• Tichophyton m/c dermatophyte fungus
• Epidermophyton

22
Dermatomycoses

• Mode of Infection
• Hyphae grows into keratinized tissues of
  epidermis, into hair shaft, or into finger/toe
  nail
• Growth outward from infection site in concentric
  circles
• Enzyme production keratinase, elastase and
  collagenase
• Clinical Infections
• Tinea capitis (ringworm of scalp) Trichophyton
  Microsporum spp.
• Initial Sx inflammation itching of the scalp
• Mode of Infection hypae spread into keratinized
  areas of scalp hair follicle ? fungal growth
  weakens the hair ? breakage _at_ shaft ? ALOPECIA
  (hair loss) localized spotty
• Associated mostly w/ children (high transmission)

23
Dermatomycoses

• Clinical Infection
• Tinea Barbae (ringworm of the beard)
• Infection site bearded areas
• Superficial lesion scaly
• Severe infection development of deep pustules
• Result permanent hair loss
• Tinea pedis (ringworm of the foot, Athletes
  Foot) m/c in adolescents adults
• Trichophyton rubrum, Trichophyton mentagrophytes,
  Epidermophyton floccosum
• Sxs foot lesions
• Mode of infection growth between toes of small
  fluid-filled vesicles ? vesicles rupture ?
  development of shallow lesion that itch may
  become infected with bacterial (2 bacterial
  infection)
• Predisposing conditions public showers,
  swimming pools, failure to dry between toes.

24
Dermatomycoses

• Clinical Infections
• Tinea curis (ringworm of the groin, Jock Itch)
• E. floccosom T. rubrum
• Sxs lesions in groin or perianal area ? red,
  scaly, itchy and often dry
• Predisposing factors moisture in the groin
  area wet bathing suits, athletic supporter,
  tight fitting pants/slacks and obesity
• Tinea corporis (ringworm of the body)
• E. floccosum, spp. of Trichophyton Microsporum
• Infection site non-hairy areas of the body
• Sxs lesions are reddened, scaly, w/ papular
  eruptions
• Tinea unguium (ringwom of nails - onychomycosis)
• T. rubrum
• Infection sites fingernails and toenails
• Initial Sxs superficial white patches on nail
  beds puffy chalky
• Later Sxs thickening of the nail, accumulation
  of cheesy debris, cracking and discoloration of
  the nail

25
Dermatomycoses

• Diagnosis
• Clinical signs and symptoms
• Microscopic ID from tissue scraping samples
  presence of hyphae
• Tissue scraping 10 KOH (heated, then stain
  added) ? presence of septate hyphae visible under
  microscope
• Macroscopic ID
• Culture Dermatophyt Test Media (DTM) turns RED
• Culture Sabourauds Dextrose Agar (SDA)
• Treatment
• Non-Rx salves/ointments for symptomatic relief
• Good hygiene
• Oral antibiotic therapy
• Topical antifungal agent
• Note re-infection may occur over over gt not
  good host immune response

26
Subcutaneous Mycoses

• Fungal source normal inhabitants of soil or
  organic matter
• Introduction to host wound or abrasions of skin
• Deeper infection penetration to below skin
• Clinical Infections
• Sporotrichosis (Rose Gardners Disease)
• Causative agent Sporothrix schenckii
• Mode of infection traumatic implantation of
  fungus into skin ? painless papule _at_ inoculation
  site ? enlargement to form ulcerated lesion ?
  then possible spread to regional lymph nodes
  Lymphocutaneous sporotrichosis
• Lymphocutaneous Sporotrichosis
• Mode of infection fungus form multiple nodules
  after being spread by draining lymph node
  channels ? nodules may ulcerate ? untreated
  lesions last for years
• Occupational Risk Groups horticulturists,
  foresters, gardeners, farmers basket weavers

27
Systemic Mycosis

• True pathogens infect normal, healthy
  individuals
• Opportunisitic pathogens infect debilitated
  /or immunocompromised individuals
• Mode of Infection inhalation of spores ? lower
  respiratory tract ? germinate into yeast ?
  asymptomatic or 1 pulmonary infection that
  parallels TB ? disseminated to other organs d/t
  compromised defense mechanism
• NO person-to-person transmission only airborne
  route to humans from fungal spores
• Fungi growing in soil or on an. droppings produce
  conidia that be aerosolized and carried by
  air-borne route to humans

28
Systemic Mycosis

• Clinical Diseases
• Coccidioidomycosis
• Chronic, necrotizing mycotic infection of the
  lungs resembles TB pathologically
• Begins as a bronchopneumonia w/ its inflammatory
  infiltrate
• Disseminated to many site in immunocompromised
  pts skin, bones, meninges, liver, spleen
• Causative agent Coccidiodes immitis
• Dimorphic fungus that grows in soil of SW US
• Spore Arthrospores inhaled into alveoli and
  terminal bronchi, where they enlarge into
  spherules
• Spherules fill w/ endospored, which are released
  to form more spherules
• In Arizona 50 chance (after 10 yrs) person w/
  () serology to this b/c of exposure, NOT
  necessarily the disease

29
Systemic Mycosis

• Clinical Diseases
• Coccidioidomycosis
• Epidemiology
• SW US, particularly San Joaquin and Sacramento
  Valley of California, areas around Tucson and
  Phoenix in Arizona
• High incidence of infection disease may follow
  dust storm
• Coccidioidomycosis Valley Fever San Joaquin
  Valley Fever Desert Rheumatism
• Pathogenesis
• Inhalation of arthroconidia leads to 1 infection
• Asymptomatic in 60 individuals
• 40 self-limiting influenza-like illness
  fever, malaise, cough, arthralgia, HA
• Laboratory DX
• Culture specimen from sputum exudate from
  cutaneous lesions CSF, blood, urine, tissue
  biopsies
• Serology IgM Ab detection w/ latex
  agglutination
• Coccidioidin Skin Test ()
• Chest X-Ray analysis hilar lymphadenopathy
  along w/ pulmonary infiltrates, pneumonia,
  pleural effusions or nodules

30
Systemic Mycosis

• Clinical Diseases
• Histoplamosis
• m/c fungal disease in US
• Acute, necrotizing, caseous granuloma of the
  lungs
• Causative agent Histoplasma capsulatum
• Dimorphic fungus found in nature
• Multiplies extensively in areas where bird feces
  accumulate
• Fungus grows in soil ? formation of conidia ?
  airborne ? inhalation into the lungs ?
  germination into yeast-like cells ? engulfed by
  alveolar macrophages
• Infection acute, but benign and self-limiting
  or chronic, progressive and fatal
• Usu. Self-limiting flu-like syndrome (fever,
  chills, myalgia, HA, non-productive cough
• Dissemination rare but can occur to
  reticuloendothelial tissues (liver, spleen, BM
  lymph nodes)

31
Systemic Mycosis

• Clinical Diseases
• Hitoplasmosis
• Laboratory Dx
• Culture specimens include sputum, urine,
  scrapings from superficial lesions, BM aspirates
• Microscopic examination of fungus in macrophages
• Serology Tests for Abs to Histoplasmin Ag or
  yeast cells
• Skin Test Histoplasmin ()
• Epidemiology
• most prevalent in Ohio Mississippi River
  Valleys, including Central and Eastern States
• KC high risk area
• Reservoir Soils laden w/ bird, chicken, or bat
  droppings rich sources of the fungus (natural
  habitat)

32
Systemic Mycosis

• Clinical Diseases
• Blastomycosis
• Chronic granulomatous and suppurative disease of
  the lungs, resulting in small areas of
  consolidation
• Causative agent Blastomyces dermatitidis
• Fungus produces microconidia in soil, which
  become airborne and inhaled in lungs
• Germination into yeast cells
• Dissemination is rare, but can occur skin,
  bone, GU tract
• M/c in South Central and South Eastern US
• M/c clinical presentation pulmonary infiltrate
  w/ fever, malaise, cough, myalgia, night sweats

33
Opportunistic Mycoses

• Endogenous type infection caused by normal
  flora of respiratory tract, mouth, intestinal
  tract and vagina
• Opportunistic Infection
• Overgrowth of normal flora ? inflammation of
  epithelial surfaces (m/c oral cavity and
  vagina) ? dissemination to internal organs

34
Opportunistic Mycoses

• Clinical Diseases
• Cryptococcosis
• 1 disease of lungs w/ granulomas and
  consolidation
• Rapidly spreads to the meninges and brain,
  causing meningoencephalitis
• Etiological agent Cryptococcus neoformans
• Only systemic fungus that is NOT dimorphic
• Only true yeast unicellular pathogen of humans
• Epidemiology
• Occurs worldwide in nature found in very large
  s in dry pigeon feces
• Usually associated w/ immunosuppression AIDS,
  malignancy
• 2nd m/c fungal dis in AIDS pts (after
  candidiasis)
• Reservoir decomposing plant materials (soil) w/
  high N content from pigeon feces
• Pathogenesis
• Inhalation of yeast cells (encapsulated, dry,
  easily aerosolized)
• Influenza-like illness follows
• Immunosupressed yeast cells multiply and
  disseminated to CNS
• YEAST CELLS FOUND W/IN CSF

35
Opportunistic Mycoses

• Clinical Diseases
• Cryptococcus
• S/sxs MAJOR clinical manifestation chronic
  meningitis w/ spontaneous remissions and
  exacerbations
• Pt presentation
• HA
• Stiff neck
• Disorientation
• Lesions in skin, lungs
• Laboratory Dx
• CSF pressure and protein ?
• WBC count ?
• Glucose normal or low
• Diagnosis
• Specimens from CSF, sputum, blood, urine,
  exudates
• Culture
• Serology

36
Opportunistic Mycoses

• Clinical Diseases
• Candidiasis (candidiosis)
• Causative agent Candida albicans
• Normal flora of skin, vagina, and intestines
• Considered a yeast, but is Dimorphic (forms a
  true mycelium)
• Cutaneous Infections
• arise d/t hosts condition diabetes,
  immunological deficiencies, exposure of skin to
  moist environment
• Mode of infection
• Adherence to epithelial surfaces
• Fungal proliferation
• Invasion of epithelial tissue

37
Opportunistic Mycoses

• Cutaneous Infection w/ C. ablicans
• Thrush or Oral Candidiasis Most Common
  Candidiasis
• Symptomatic appearance white, adherent patches
  (pseudomembranes) attach to epithelial membranes
  of tongue, gums, cheeks, or throat FUNGAL MAT
  formation
• Pseudomembrane composition yeast, hyphae,
  epithelial debris
• Increased susceptibility Newborns
• Transmission Vertical - Mother?Child
• Vaginal Candidiasis m/c form of vaginal
  infection
• Sxs yellow to white milky discharge,
  inflammation, painful ulcerations itching
• Candidal overgrowth related to increased
  glucose content of vaginal secretions
• Assocd w/ - diabetic ?, pregnant ?, broad
  spectrum antibiotic tx

38
Opportunistic Mycoses

• Cutaneous Infection w/ C. ablicans
• Esophageal Candidiasis
• Complication of AIDS patients
• Sxs painful bleeding, ulcerations, nausea,
  vomiting
• General Candidiasis Infections
• Infections of epidermal tissue folds of skin on
  obese people (usual sites upper legs,
  underarms) tissue that remains wet
  (dishwashers) skin covered by wet diapers
  (diaper rash)

39
Opportunistic Mycoses

• Disseminated infection w/ C. albicans
• Cutaneous infection ? mutisystem disease
• Iatrogenic use of catheters of prosthetic
  devices
• Diagnosis
• Clinical symptoms
• Microscopic examination
• Macroscopic examination culture
• SDA (white- to cream-colored colny, pasty w/ a
  yeasty odor
• Corn Meal Agar visualization of spores
• Treatment Antifungals

40
Opportunistic Mycoses

• Clinical Diseases
• Asperigellosis
• Causative agent Aspergillus fumigatus
• Acute, invasive infection of lung dissemination
  to brain, GIT, other organs
• Non-invasive lung infection gives rise to
  aspergilloma (Fungal Ball) a mass of hyphal
  tissue that can form in lung cavities produced by
  other diseases, like TB
• Pneumocystis Pneumonia
• Causative agent Pneumocystis jiroveci
  Pneumocystis carnii
• Acute interstitial pneumonia w/ plasma cell
  infiltrates
• As disease progresses, pt. experiences weakness,
  dyspnea, and tachypnea leading to cyanosis Death
  can result from asphixiation
• m/c cause of DEATH in AIDS pts from Pneumocystis
  carinii pnuemonia