Download Rickettsia, Chlamydia, Mycoplasma, Legionella, and Gardnerella

Obligate Intracellular
Pathogen
Rickettsia
Chlamydia
D. Rickettsia - Virus-like bacteria Infect
cells lining the capillaries (intracellular).
Transmitted by insects (arthropods).
Defective bacteria - leaky plasma
membranes, very small 0.3-1.0
micrometers. Ex. Rocky Mountain Spotted
Fever, typhus, Q fever.
E. Chlamydia - “virus-like” (intracellular)
Spread from one human to the next. Very
small: 0.2-0.7 micrometers. Defective
bacteria - can’t make their own ATP.
Complicated reproductive cycle. Diseases:
blindness, urethritis, and pneumonia.
Rickettsia
Chlamydia
F. Mycoplasma Sometimes form long strands
that resemble fungi in microscopic
appearance.
• No cell walls - instead contains
sterols.
• Ameboid locomotion - disease:
“walking” pneumonia
• The smallest bacteria - 0.2
micrometers
Mycoplasma “fungus-form”
Chlamydia & Rickettsia
General Characteristics
• Obligate intracellular organisms
• Can not be cultured on agar plates
• Dependant on a host for survival
Rickettsia
• Intracellular, gram negative organism
• Requires host to replicate and survive
• Cause febrile illness through the bite of
an arthropod
• Patient often presents with a rash
• Posses a cell wall
Rickettsia and Related Organisms
Disease
Agent
Arthropod Vector
Rocky Mountain spotted fever
Rickettsia rickettsii
Wood tick
Rickettsial pox
Rickettsia akari
House mouse mites
Murine typhus
Rickettsia typhii
Rat flea
Epidemic typhus
Rickettsia prowazekii
Human body louse
Scrub typhus
Orientia tsutsugamushi
Chigger mites
Ehrlichiosis
Ehrlichia chaffeenis
Lone star tick
Q fever
Coxiella burnetti
None- spead by inhalation
Family Rickettsiaceae:
Genera
• Zoonotic infection
– Human microbial pathogens ~61% zoonotic
– Rickettsia are arthropod-borne infections
• Spotted Fever Group
– Rickettsia rickettsii – Rocky Mountain spotted
fever; rodent, tick
• Typhus Group
– Rickettsia typhi – Endemic typhus; rodent, flea
– Rickettsia prowazekii – Epidemic typhus;
mammal, louse
Rickettsia: Gram Stain
and Culture
• Gram (-) small, pleomorphic coccobacilli
• Gram stain poorly, observed by Giemsa
stain of infected cell
• Grow in phagocytic, nonphagocytic cells
• Lab culture in embryonated eggs or cell
tissue culture (similar for virus)
• Cultivation costly and hazardous; aerosol
transmission occurs easily
Chlamydia, Rickettsia, Virus
Rickettsia: Lab ID
• Giemsa, or Immunofluorescence
assay (IFA) - direct detection
MO in tissue
• Weil-Felix reaction –
Nonspecific test
– Rickettsial antibody agglutinate
Proteus vulgaris
– Presumptive evidence of typhus
group infection
– Not very sensitive or specific,
many false positives
• Agglutination or Complement
Fixation (CF) assay - use
specific Rickettsial antigen,
test for infection and antibody
Rickettsia: Virulence Factors
• Induced phagocytosis, intracelluular
growth – protected from host immune
clearance
• Replicates in endothelial cells – cell
damage, vasculitis
• Recruitment of actin - intracellular spread
Rickettsia: Infection and Disease
• Disease
worldwide, USA
• Arthropod
reservoir/vector
(tick, mite, louse,
flea)
• Diseases
characterized by
fever, headache,
myalgias, usually
rash
R. rickettsii: Rocky Mountain
Spotted Fever (RMSF)
• USA ~500-1000 cases/year
• Ticks must remain attach for hours
• Incubation 7 days - headache, chills,
fever, aching, nausea
• Followed by maculopapular rash on
extremities (including palms and
soles), spread chest, abdomen
• If untreated
– Petechial rash, hemorrhages skin and
mucous membranes
– Vascular damage, MO invades blood
vessels
– Death up to 20%, due to kidney or heart
failure
Rocky Mountain Spotted Fever
Rickettsia: Typhus Group
• Incubation 5-18 days
• Symptoms - severe headache, chills, fever,
maculopapular rash (subcutaneous
hemorrhaging as MOs invade blood vessel)
• Rash begins on upper trunk; spread to
whole body except face, palms of hands,
soles of feet
• Lasts ~2 weeks
• Patient may have prolonged convalescence
R. typhi : Endemic Typhus
Fever
• “typhus” “fever”
• Disease worldwide in warm, humid areas
(Gulf states, So Cal.; S. America, Africa,
Asia, Australia, Europe)
• Murine typhus - rat primary reservoir,
transmitted to human by rat flea
• Disease occurs sporadically
• Clinically same, but less severe than
epidemic typhus
• Restricted to chest, abdomen; generally
uncomplicated, lasts <3 weeks
• Low fatality
R. prowazekii : Epidemic
Typhus Fever
•
•
•
•
Disease C & S Americas, Africa; less common USA
Human, squirrel primary reservoir
Transmitted by louse; bites, defecates in wound
At risk - people living in crowded, unsanitary
conditions; often war, famine, natural disaster
• Complications - myocarditis, CNS dysfunction
• Mortality high untreated cases, up to 20%
• Brill-Zinsser disease - individual may harbor MO,
latent infection with occasional relapses
Rickettsia: Treatment and
Prevention
• RMSF
– Doxycycline drug of choice
– Avoid ticks, wear protective clothing, use
insect repellents, insecticides
– In infested areas, check and remove ticks
immediately
• Typhus Fever
– Doxycycline effective
– Improve personal hygiene and living conditions,
reduce lice by insecticides, control rodent
population
– Inactivated vaccine for epidemic typhus
Laboratory Diagnosis of
Rickettsial Disease
• Immunohistochemical detection
• Serological tests
• PCR
Family Chlamydiaceae: Genera
Chlamydia trachomatis – STD, eye
infection
Chlamydophila pneumoniae – pneumonia
Chlamydophilia psittaci – pneunomia
(psittacosis); birds, humans
Obligate intracellular parasite
Cell wall similar G(-) bacilli, lack
peptidoglycan
Energy parasites, use ATP of host cell
Chlamydia Characteristics
• Unique growth cycle because they are
deficient in independent energy metabolism
• Replication involves elementary body (EB) and
reticulate body (RB)
– EB’s are infectious and non-metabolically
acitve
– RB’s are noninfectious and metabolically
active
Chlamydia: Life Cycle –
Elementary Body (EB)
• Circular, infectious form; 300-400 nm
• Metabolically inactive
• Resistant to harsh environments
• 0 hour - EB binds to host cell, induced phagocytosis
• Outer membrane of EB prevents lysosome fusion, survives
in phagosome
• 8 hours - EB reorganizes into Reticulate Body (RB)
Chlamydia: Life Cycle –
Reticulate Body (RB)
• Noninfectious form, larger, less dense, 800-1000
nm
• Metabolically active
• 8-30 hours
–
–
–
–
Synthesize new materials
Multiply by binary division
Form inclusion body
Reorganize, condense into EB
• 35-40 hours - cell lyses, releases EB, begins cycle
again
Chlamydia: Lab ID
• Stain tissue
– Giemsa stain
– Direct fluorescent
antibody (DFA)
– ELISA
– Less sensitive
• Cell culture
– More sensitive method
– Grow MO in tissue
culture, stain infected
cells
• DNA amplification test
– Recently developed
– Specific, sensitive
– Now routine test of choice
Chlamydia: Virulence
Factors
• Intracellular replication – protected from
host immune defense
• Prevent fusion of phagolysome – evades
phagocytic killing
• Repeated infections by C. trachoma result
in cell pathology
• Serotypes A-K and L1, L2, L3 - serotype
identifies strain’s clinical manifestation
Chlamydia pneumoniae
• Important respiratory pathogen (acute
respiratory disease, pneumonia, and
pharyngitis)
• Common (50% of adults have antibodies)
• College age students most susceptible
• Implicated in asthma
• Risk factor for Guillain-Barre’ syndrome
• Reinfection common
• Biphasic clinical picture
– Prolonged sore throat and hoarseness,
followed by flu-like lower respiratory
symptoms
– Pneumonia and bronchitis
Chlamydia trachomatis
• Most commonly sexually transmitted
bacterial pathogen in U.S.
– Only HPV is a more commonly sexually
transmitted disease
– Major cause of sterility in U.S.
– May be transmitted to newborns during
delivery
• Results in conjunctivitis
• Other sites of infection
– Trachoma – infection of the conjunctiva,
resulting in scarring and blindness (Mostly
in India and Egypt)
– Lymphogranuloma venereum
• Infects lymph nodes
Chlamydia psittaci
• Causes psittacosis (parrot fever)
• Identification based on history of close contact with
birds and serologic evaluation
“parrot” “parrot fever”
Naturally infects avian species
Mild to severe respiratory infections
Human infection by contact infected bird
Infection - subclinical to fatal pneumonia
Commonly causes atypical pneumonia with fever,
chills, dry cough, headache, sore throat, nausea, and
vomiting
Chlamydia trachomatis:
Trachoma
•
•
•
•
•
•
•
•
•
“rough” “trachoma” granulations on conjunctiva
Serotypes A-C
Single, greatest cause blindness developing countries
Infections mainly children (reservoir), infected first
three months life
Transmission eye-to-eye, direct contact (droplet, hand,
clothing, fly)
Chronic infection, reinfection common
Conjunctival scarring, corneal vascularization
Scars contract, upper lid turn in so eyelashes cause
corneal abrasions
Leads to secondary bacterial infections, blindness
C. trachomatis: Lymphogranuloma Venereum
• Venereal disease, occurs developing, tropical areas
• Primary stage - painless lesion (vesicle or an ulcer) occurs
site of entry in few days, heals with no scarring; but
widespread dissemination
• Secondary stage - occurs 2-6 weeks later, symptoms of
regional suppurative lymphadenopathy (buboes), may drain
for long time, accompanied by fever and chills. Arthritis,
conjunctival, CNS symptoms
• Tertiary stage - urethrogenital perineal syndrome;
structural changes, such as non-destructive elephantiasis of
the genitals, rectal stenosis
C. trachomatis:
• Urogenital tract infection - serotypes D-K
• Major cause of nongonococcal urethritis;
frequently found concomitantly with N.
gonorrhoeae
• In males - urethritis, dysuria, sometimes
progresses to epididymitis
• In females - mucopurulent cervical inflammation,
can progress to salpingitis and PID
C. trachomatis: Inclusion
Conjunctivitis
• Newborns and adults
• Genital tract infection source of eye
infection (serotypes D-K)
• Benign, self-limited conjunctivitis, heals
with no scarring
• Newborns infected during birth process:
– 1-2 weeks, mucopurulent discharge
– Lasts 2 weeks, subsides
– Some develop afebrile, chronic pneumonia
• In adults – causes an acute follicular
conjunctivitis with little discharge
Chlamydia: Treatment and
Prevention
• Genital tract infection and conjunctivitis:
– Adult - azithromycin or doxycycline, prompt
treatment of patients and partners
– Newborn – erythromycin
– Public Health education
• Trachoma:
– Need prompt treatment, prevent reinfection
– Systemic tetracycline, erythromycin; long term
therapy necessary
– Improve living, sanitary conditions
– Difficult to prevent endemic disease in
developing countries due to lack of resources,
medical care
Laboratory Diagnosis
• If cultured, must be in cells
• Direct microscopic examination to find
EB’s
– visualized with fluorescein-conjugated
antibodies
• Enzyme immunoassay
• Nucleic acid probes with and without
amplification (PCR)
• Serologic tests are method of choice for
detection (Four-fold rise in titer)
Case Study 9 - Questions
• 1. Why is penicillin ineffective against
Chlamydia? What antibiotic can be used to
treat this patient?
• 2. Describe the growth cycle of Chlamydia.
What structural features make the EBs
and RBs well suited for their environment?
• 3. Describe the differences among the
three species in the family Chlamydiaceae
that cause human disease.
Normal Flora:
Commensals are regularly found in certain human
microbiotopes. The normal human microflora is thus
the totality of these commensals. Table 1.7 lists the
most important microorganisms of the normal flora
with their localizations.
Bacteria are the predominant component of the normal
flora. They proliferate in varied profusion on the
mucosa and most particularly in the gastrointestinal
tract, where over 400 different species have been
counted to date.
The count of bacteria per gram of intestinal content is 101–105 in
the duodenum, 103–107 in the small intestine, and 1010–1012 in the
colon. Over 99% of the normal mucosal flora are obligate
anaerobes, dominated by the Gram-neg. anaerobes. Although life is
possible without normal flora(e.g., pathogen-free experimental
animals), commensals certainly benefit their hosts. One way they do
so is when organisms of the normal flora manage to penetrate into
the host through microtraumas, resulting in a continuous stimulation
of the immune system. Commensals also compete for living space
with overtly pathogenic species, a function known as colonization
resistance .On the other hand, a potentially harmful effect of the
normal
flora
is
that
they
immunocompromised individual.
can
also
cause
infections
in