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Transcript
Microbiology 2011
May 16, 2011
Yu Chun-Keung
Chapter 46
Chlamydiaceae (披衣菌/衣源體)
Chapter 44
Rickettsia and Orientia (立克氏體)
Chapter 45
Ehrlichia, Anaplasma, Coxiella
Chapter 46 Chlamydiaceae
Obligate intracellular organisms
Were once considered virus, true bacteria
Contain DNA and RNA
 Possess ribosomes, synthesize proteins, nucleic acid,
and lipids, but cannot synthesize ATP.
 Binary fission
 Susceptible to numerous antibiotics, but not to penicillin
(lack peptidoglycan)

Cell wall:
Genus-specific LSP
 Major outer membrane protein (MOMP) – species
specific antigens, serological variants (serovars)

Unique development cycle
Two morphological distinct
forms in cytoplasmic
phagosome:
(1) elementary body (300-400
nm), resistant to harsh
environmental factors;
infectious, bind to receptors of
host cells and stimulate uptake;
cannot replicate
(2) reticulate body (800-1000
nm), reproductive form,
metabolically active,
noninfectious.
Histologic stains can detect phagosome
with accumulated RBs (inclusion)
Family Chlamydiaceae
Genus Chlamydia:
C. trachomatis (砂眼披衣菌)
Genus Chlamydophilia:
C. pneumoniae (肺炎披衣菌)
C. psittaci (鸚鵡熱披衣菌)
1. Chlamydia trachomatis (砂眼披衣菌)
Infections only occur in humans
Two biovars and 18 serovars (antigenic differences in
MOMP)
Biovars
Serovars
Trachoma A to C
D to K
LGV
L1 to L3
Disease caused
Trachoma
Urethritis, cervicitis,
Inclusion conjunctivitis,
Neonatal conjunctivitis,
Infant pneumonia
Lymphogranuloma
venereum
Pathogenesis
EBs enter the body via minute abrasions and
lacerations
Trachoma serovars primarily infect nonciliated
epithelial cells (urethra, endocervix, endometrium,
fallopian tube, anorectum, respiratory tract,
conjunctiva)
LGV serovars replicate in mononuclear
phagocytes (more invasive); formation of
granuloma in lymph nodes draining the site of
primary infection, abscesses, or sinus tracts
formation
Pathogenesis
Direct destruction of cells during replication
Proinflammatory cytokine response
stimulates a severe inflammation
(accumulations of neutrophils, lymphocytes
and plasma cells).
No long-lasting immunity after infection
Re-infection induces a vigorous
inflammatory response with subsequent
tissue damage (blindness and sterility).
(1) Trachoma (砂眼)
A chronic keratoconjuctivitis caused by serovars A,
B, Ba, C.
Diffuse follicular conjunctivitis → eyelid inward →
eyelashes abrade cornea → corneal ulceration
→pannus formation (invasion of vessels into the
cornea) →blindness
Endemic in the Middle East, North Africa, and
southern Asia (crowded and poor sanitation
regions); predominantly in children. Leading global
causes of preventable blindness (>150 million
infected, 6 million blinded).
Transmission: eye-to-eye by droplet, hands,
contaminated clothing, flies.
Epidemiology
Worldwide; in USA bacterial STD: Chlamydia >
Neisseria gonorrhoeae > Syphilis
Extremely sensitive to drying or disinfectants,
cannot be spread through contact with
inanimate objects
Not highly contagious, 30% change of infection
after a single sexual contact
Can be acquired congenitally or by transfusion;
bacteremia can persist for > 8 years
Incidence of late syphilis has markedly
decreased, primary and secondary syphilis
remain high
(2) Urogenital infections
Venereal infections caused by serovars of D to K.
The most common sexually transmitted bacterial
disease in U.S. 2.8 million new cases annually (50
million worldwide).
In women: 80% asymptomatic as reservoir;
bartholinitis, cervicitis, endometritis, salpingitis,
urethritis, which can lead to sterility and ectopic
pregnancy.
In men: 25% asymptomatic; nongonococcal
urethritis (NGU; urethritis caused by pathogens
other than gonococcus )
Nongonococcal
urethritis
1. Mild
2. Slow and prolonged
3. Dysuria is mild
4. Urethral discharge is
clear or white, thin
and mucoid
Gonorrhea
1.
2.
3.
4.
Severe
Acute
Severe dysuria
Purulent
discharge
Nongonococcal Urethritis (NGU)
C. trachomatis (35-50% of cases)
Ureaplasma urealyticum (10-30% of cases)
Mycoplasma hominis
Gardnerella vaginalis
Trichomonas vaginalis
Candida albicans
Post-gonococcus urethritis

Dual infections of C. trachomatis and Neisseria
gonorrhoeae are common.

Symptoms of chlamydial infection develop after
successful treatment of gonorrhea.

Reason: longer incubation period + β-lactam antibiotics
are ineffective for C. trachomatis
Reiter’s syndrome

Urethritis, conjunctivitis, polyarthritis, mucocutaneous
lesion

Usually occurs in young white man

Initiated by genital infection with C. trachomatis.
(3) Adult Inclusion Conjunctivitis
Acute follicular conjunctivitis with
mucopurulent discharge
Mostly occur in sexually active adults
(18-30 yr) with genital infection with
serotypes A, B, Ba, D to K.
Acquired by auto-inoculation, oral-genital
contact
(4) Newborn Inclusion Conjunctivitis
25% infants acquired from mothers
with active genital infections
Swollen and hyperemic eyelids
Long (>12 months) disease course if
untreated and are at risk for C.
trachomatis pneumonia
(5) Infant Pneumonia
A diffuse interstitial pneumonia
Occur in 10-20% infants that
exposed to the pathogen at
birth
(6) Lymphogranuloma venereum (LGV)
花柳性淋巴肉芽腫
A chronic sexually transmitted disease caused by C.
trachomatis L1, L2, L2a, L2b, L3.
More common in men, with male homosexuals being the
major reservoir.
Small, painless lesions (papule or ulcer) at site of infection
(genitalia). Fever, headache, myalgia.
Inflammation and swelling of regional lymph nodes
(inguinal nodes) - painful buboes (橫瘻), rupture, fistulas
formation.
Proctitis (直腸炎) is common in women.
Resolve spontaneously or progress to ulceration or genital
elephantiasis (象皮病).
Bubonic plague – Inguinal buboes with edema
Lab diagnosis
Symptomatic infections are easier to diagnosis
than asymptomatic infections as more chlamydiae
present in specimen.
For trachoma: cytology – Giemsa-stained cell
scrapings

Quality of the specimen is important. Specimens must be
obtained from the involved site; pus or exudate is
inadequate.
For genital infections: culture – HeLa, MaCoy,
Hep-2 cells

Iodine stain to detect inclusions (=RBs)

The most specific methods for diagnosis.
Iodine-stained Chlamydia trachomatis inclusion
bodies (arrows)
Lab diagnosis
Nucleic acid amplification tests (NAATs)

Test of choice for lab diagnosis of C. trachomatis
infection

First-void urine / urethral discharge

Amplification of a specific sequence, then detecting with
a species-specific probe
Serologic tests

Good for LGV. Limited value for adult urogenital
infections, cannot differentiate between current and past
infections;

CF test or EIAs: genus-specific LPS as antigen, fourfold
increase or >1:256

MIF test: species- and serovar-specific antigen (MOMPs)
T/P/C
Resistance to penicillin (lack peptidoglycan)
Doxycycline for LGV
Azithromycin or doxycycline for ocular and
genital infections in adult
Erythromycin for newborn conjunctivitis
and pneumonia
Improve sanitary conditions – essential for
prevention
Safe sex practices
2. Chlamydophilia pneumoniae
Was first isolated from the conjunctiva of a
child in Taiwan - TWAR strain.
An important cause of sinusitis, pharyngitis,
bronchitis, and pneumonia.
Infection is common, especially in adults
and transmitted person-to-person by
respiratory secretions.
Clinical disease
Most infections are asymptomatic or mild persistent cough.
Cannot be differentiated with other
atypical pneumonia - Mycoplasma
pneumoniae, Legionella pneumophila, and
respiratory viruses.
Detected in atherosclerotic lesions in
blood vessels. However, the role in the
development of atherosclerosis is not
clear.
Lab diagnosis
Diagnosis is difficult
Do not grow in cell lines used for isolation of
C. trachomatis
NAATs are OK with large inter-laboratary
variation.
Micro-immunofluorescence (MIF) test

The only acceptable serodiagnotic test (specific)

A single IgM titer > 1:16 (=recent infection) or a
fourfold increase in IgG titer (paird acute and
convalescent phase sera)
T/P/C
Macrolides (erythromycin), doxycycline
Ubiquitous present, control is difficult
3. Chlamydophilia psittaci
(鸚鵡熱披衣菌)
Caused Psittacosis (parrot fever).
The natural reservoir is any species of
birds (Ornithosis, 飼鳥病)
Also infect sheep, goats, cows, and
humans
High risk groups: veterinarians,
zookeepers, pet shop workers, employees
of poultry industry.
Pathogenesis
Inhalation of dried bird excrement, urine, or
respiratory secretions; person-to-person
transmission is rare.
Bacteria first spread to and multiply in
reticuloendothelial cells of liver and spleen 
necrosis
Then hematogenous spread to lung and other
organs via circulation
Lmphocytic inflammation in lung, edema, necrosis,
mucous plugs in bronchioles cyanosis and
anoxia
Clinical disease
Asymptomatic infection
Flu-like illness: high fever, headache, chills,
myalgia
Serious pneumonia
CNS involvement is common (headache,
encephalitis, convulsion, coma),
GI symptoms (nausea, vomiting, diarrhea),
hepatomegaly, splenomegaly
Diagnosis for C. psittaci
Complement fixation test of paired acute and
convalescent phase sera
Confirmed by species-specific MIF test
Treatment for C. psittaci
Tetracyclines or macrolides
No need of isolation of patients and prophylaxia
No vaccine available
Treat birds with chlortetracycline HCl for 45
days.
Chapter 44
Rickettsia and Orientia
Chapter 45
Ehrlichia, Anaplasma, Coxiella
Rickettsia Howard Ricketts
Ehrlichia
Paul Ehrlich
Coxiella
Harold Cox
(Historically classified in Rickettsiaceae)
Order Rickettsiales
Family Rickettsiaceae
Genena Rickettsia
Orientia
Family Anaplasmataceae
Genena Ehrlichia
Anaplasma
Neorickettsia
Wolbachia
Rickettsia (also Ehrlichia) is unstable and die
quickly outside host cells.
Coxiella highly resistant to desiccation, remain
viable in environment for months to years.
Obligate intracellular parasites. After phagocytosis
Rickettsia and Orientia: degrade phagosome
membrane by producing phospholipase, multiply in
cytoplasm and nucleus of endothelial cells
Ehrlichia and Anaplasma: multiply in cytoplasmic
vacuoles (= phagosomes) of hematopoietic cells
Coxiella: multiply in phagolysosome of monocytes
and macrophages
Chapter 44 Rickettsia and Orientia
G(-) bacilli, with a minimal peptidoglycan layer
(stain poorly with Gram stain) and LPS (weak
endotoxin activity)
Maintain in animal and arthropod reservoirs
(ticks, mites, lice, fleas by transovarian
transmission).
Transmitted to humans by arthropod vectors
Humans are accidental hosts: acquired by
arthropod bite or contact of arthropod excreta
with abraded skin
Pathogenesis
No toxins, no immunopathology
Rickettsia replicate in endothelial cells,
cause cell damage and blood leakage,
vasculitis, microthrombi, focal ischemia,
hemorrhage, skin rash.
Hypovolemia, hypoproteinemia, reduced
perfusion, organ failure.
Important Rickettsial Diseases
Spotted fever group 斑疹熱
R. rickettsii
R. akari
RMSF (>90%)
Rickettsialpox (100%)
Typhus group 斑疹傷寒
R. prowazekii
R. typhi
O. tsutsugamushi
Epidemic typhus (40-80%)
Murine typhus (50%)
Scrub typhus (<50%)
(Parentheses: % of rash, 紅斑)
The distribution of rickettsial diseases (restricted
area or worldwide) is determined by the distribution
of the arthropod hosts/vectors.
Rocky mountain spotted fever
(RMSF)
Have a restricted geographic and seasonal
distribution, corresponding to tick activity.
R. rickettsii is maintained in hard ticks (wood tick
and dog tick) by transovarian transmission.
Transmitted to humans by tick bite (need >6h to
establish infection).
High fever, chills, headache, skin rash (>90%,
extremities to trunk)
Respiratory failure, encephalitis, renal failure.
Diagnosis is urgent, identify key clinical signs – rash;
the prognosis depends on the duration of illness
fatality 10-25% if untreated
Culture: buffy coat of blood or skin biopsy; tissue
culture or embryonated eggs (danger)
Microscopy: Giemsa stain; FA staining of biopsy
tissue specimens for antigen detection
Serology: microimmunofluorescence (MIF), detect
antibodies against MOMP and LPS antigens; both
specific and sensitive
Nucleic acid-based tests: PCR + gene sequencing
of a variety of genes
The traditional Weil-Felix test: not recommended
for use
Treatment /Prevention/Control:
Appropriate therapy would result in
good prognosis (e.g., doxycycline)
No vaccine
Prevent tick bites (can survive for as
long as 4 years without feeding)
Rickettsialpox
R. akari
Infections are transmitted to humans from rodents
reservoir by bite of infected mites (transovarian
transmission)
Cosmopolitan distribution
Clinical disease – biphasic

Papule at site of bite, ulceration, eschar formation (焦痂)
(differentiate with cutaneous anthrax)

High fever, severe headache, chills, sweats, myalgias,
photophobia, generalized rash (100%), complete healing
2-3 wks.
Epidemic (louse-borne) typhus
流行性(蝨型)斑疹傷寒
R. prowazekii
Humans are the primary reservoir with person-toperson transmission by human louse (the
bacteria kill the lice 2 to 3 wk after infection; no
transovarian transmission).
Epidemics occur among people living in crowded,
unsanitary condition - war, famine, or natural
disaster.
High fever, severe headache, myalgias, skin rash
(20-80%), complete recovery >3 months
Brill-Zinsser Disease
Bacteria may remain for years.
A recrudescent, mild form of
epidemic typhus arising years
after the initial attack.
Diagnosis:

MIF test for detection of antibody
T/P/C:

Tetracyclines, Chloramphenicol

Louse-control

A formaldehyde-inactivated
vaccine is available
Endemic (murine) typhus
地方性(鼠類)斑疹傷寒
R. typhi transmits to man from rodent
reservoir hosts by the bite of rat flea and
cat flea.
Endemic all over the world, primarily in
warm, humid areas.
Fever, severe headache, myalgias, chills,
skin rash (50%) on chest and abdomen
for 3 weeks.
Diagnosis:

IFA test for detection of antibody
T/P/C:

Tetracyclines

Pest control

No vaccine
Scrub typhus 叢林斑疹傷寒
A rickettsial disease caused by Orientia
tsutsugamushi (恙蟲病立克次體菌)
Transmitted to humans by red mites (chiggers)
Organisms are maintained in mites by
transovarian transmission.
Endemic in eastern Asia, Australia, and Japan.
Fever, severe headache, myalgias, skin rash
(<50%), spread centrifugally to extremities.
Generalized lymphadenopathy, splenomegaly,
CNS complication, heart failure
2010.11.20
T/P/C:

Prompt treatment with
doxycycline

Avoid exposure to chiggers

No vaccine
Order Rickettsiales
Family Rickettsiaceae
Genena Rickettsia
Orientia
Family Anaplasmataceae
Genena Ehrlichia
Anaplasma
Neorickettsia
Wolbachia
Chapter 45 Ehrlichia and Anaplasma
Intracellular bacteria that
lodge in phagosomes of
mononuclear and
granulocytic phagocytes.
Grow cycle: three stages elementary body, reticulate
body, morulae in
phagosome (can be
detected by Giemsa or
Wright stains)
Ehrlichia inclusions (peripheral
blood smear, Wright-Giemsa)
Clinical disease
1. Human monocytic ehrlichiosis
E. chaffeensis : infect blood monocytes
and mononuclear phagocytes in tissues
and organs
Vector - Lone Star tick, no transovarian
transmission
Reservoir - white-tailed deer, domestic
dogs, foxes, coyotes, wolves
2. Canine granulocytic ehrlichiosis
E. ewingii : infect granulocytes
Vector - Lone Star tick
Reservoir -white-tailed deer, domestic dogs
Humans are accident host
3 .Human anaplasmosis
Anaplasma phagocytophilum : infect
neutrophils, eosinophils, basophils
Vector - Ixodes ticks
Reservoir - small mammals
Clinical disease
Fever, headache, malaise, myalgias,
leukopenia, thrombocytopenia,
elevated transaminases
Skin rash (10 to 40%)
50% patients require hospitalization,
2 to 3% mortality
Diagnosis
Diagnosis is urgent.
Stain poorly with Gram stain.
Giemsa stain of blood smear for moralae

monocytic ehrlichiosis: 10% (+)

granulocytic ehrlichiosis and anaplasmosis:
20-80% (+)
DNA amplification test: specific and sensitive
Serology: cross-reactivity
T/P/C:
Prompt treatment with
doxycycline
No vaccine available
Avoid tick-infested areas
Coxiella burnetii
Biologically and genomically distinct from
Rickettsia and Anaplasma; more closely
related to Legionella.
Obligate intracellular pathogen

Small cell variants (SCV): extremely resistant
to environmental stress, infectious form

Large cell variants (LCV): multiply in
phagolysosome in monocytes or macrophages
Epidemiology
Zoonosis
Can infect mammals, birds, and ticks
Primary reservoirs: farm animals, cats,
dogs, rabbits
Infection is common in livestock, but
symptomatic disease is rare.
Ticks are vector for disease in animals
but not in humans
Epidemiology
Extremely stable in harsh environmental
conditions
Are able to survive in soil and milk for months to
years.
High concentrations of bacteria are present in
placenta of infected livestock.
Transmit to man by the respiratory route from
contaminated soil or ingestion of contaminated
unpasteurized milk.
Ranchers, veterinarians, and food handlers are
at highest risk.
Pathogenesis
Target tissue is the lung, proliferate in
phagolysosomes of infected cells, then
disseminate to other organs
Undergo antigenic variation (cell wall LPS):

Infectious forms possess phase I antigen: LPS
with a complex carbohydrate, can block
antibody binding

phase II antigen is the product of the gene of
phase I antigen after deletion: a modified LPS,
expose surface proteins to antibody
Q fever
Most infections are mild or asymptomatic
Acute disease:

Mild, flulike, <5% requires hospitalization

Fever, pneumonia, hepatitis, diffuse
granulomas in involved organs
Chronic disease: subacute endocarditis
exclusively in patients with valvular heart
disease or immunosuppression; mortality
65% if untreated
Diagnosis
Serologic tests (IFA, ELISA, CF)
Acute Q fever: antibodies are developed
primarily against phase II antigen.
Chronic Q fever: antibodies against both
phase I and II antigens are elicited.
(phase I antigen: weak antigenic)
T/P/C:
Doxycycline for prolonged period
Vaccines are available

single dose with no booster
immunization for uninfected people
for adverse reaction will happen in
previously infected individuals.
96.5.14