Transcript C. trachomatis

Chapter 47
Chlamydiaceae (披衣菌, 衣源體 )
Yu Chun-Keung DVM, PhD
Department of Microbiology
and Immunology
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)
Chlamydiaceae
Obligate intracellular organisms,
were once considered virus.
Possess inner and outer membranes
Contain DNA and RNA
Possess ribosomes
Synthesize proteins, nucleic acid, and
lipids, but cannot synthesize ATP.
Respond to wide-spectrum antibiotics,
but not to penicillin (lack peptidoglycan)
Unique development cycle
Two morphological distinct forms in
cytoplasmic phagosome:
(1) elementary body (300-400 nm),
resistant to harsh environmental
factor; bind to receptors of host cells and
stimulate uptake; metabolically inactive
but infectious,
(2) reticulate body (800-1000 nm),
reproductive form, divide by binary
fission, noninfectious.
Growth cycle
EBs → host cells → prevent
phagolysosomal fusion (if outer
membrane is intact) → EBs
reorganize into RBs within 6-8h
→ synthesis DNA, RNA,
proteins (but not ATP, so-called
energy parasite) → RBs
replicate by binary fission for
18-24h → RBs reorganize into
EBs 48-72h → cell rupture and
release of EB.
Histologic stains can detect phagosome with
accumulated RBs (inclusion)
1. Chlamydia trachomatis (砂眼披衣菌)
Infections only occur in humans
Two biovars (trachoma and LGV) and
19 serotypes (antigen differences in MOMP)
Biovars
Serotypes
Trachoma A to C
D to K
LGV
L1 to L3
Disease
Trachoma
Urethritis, cervicitis
Inclusion conjunctivitis
Neonatal conjunctivitis
Infant pneumonia
Lymphogranuloma
venereum
Pathogenesis
EBs enter the body via minute abrasions and
lacerations
Trachoma biovars primarily infect nonciliated
columnar, cuboidal, or transitional epithelial cells
(urethra, endocervix, endometrium, fallopian tube,
anorectum, respiratory tract, conjunctiva)
LGV biovars replicate in mononuclear
phagocytes in lymphatic system (formation of
granuloma, abscesses, or sinus tracts in LN
draining the site of primary infection)
Pathogenesis
Destruct cells during replication
Infection stimulates a severe
inflammatory response (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).
Trachoma (砂眼)
A chronic suppurative eye disease caused by
serotypes A,B,Ba,C.
Follicular conjunctivitis →scar →corneal
ulceration →pannus formation (翳, 音易)
(invasion of vessels into the cornea,) →blindness
Endemic in the Middle East, North Africa, and
India (dry and sandy regions); predominantly in
children. Leading global causes of blindness
(500 million infected, 7 to 9 million blinded).
Transmission: eye-to-eye by droplet, hands,
contaminated clothing, flies.
Urogenital infections
Venereal infections caused by serotypes of
D to K.
The most common sexually transmitted
bacterial disease in U.S. 2.8 million new
cases annually, largely in males (50 million
worldwide).
In women: 80% asymptomatic; bartholinitis,
cervicitis, pelvic inflammatory disease,
which can lead to sterility and ectopic
pregnancy.
In men: 25% asymptomatic; nongonococcal
urethritis (NGU)
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)
Urethritis caused by pathogens other
than gonococcus
C. trachomatis (35-50% of cases)
Ureaplasma urealyticum (10-30% of cases)
Mycoplasma hominis
Gardnerella vaginalis
Trichomonas vaginalis
Candida albicans
Herpesvirus hominis (?)
Cytomegalovirus (?)
Dual infections with both C. trachomatis
and Neisseria gonorrhoeae are common.
淋菌後尿道炎： symptoms of chlamydial
infection develop after successful treatment
of gonorrhea because the incubation
period is longer and the use of β–lactum
antibiotics to treat gonorrhea would be
ineffective against C. trachomatis
Adult Inclusion Conjunctivitis
(成人包涵性結膜炎)
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.
Auto-inoculation, oral-genital contact
Newborn Inclusion Conjunctivitis
25% infants acquired from
mothers with active genital
infections
Long (>12 months) disease
course if untreated and are at
risk for C. trachomatis
pneumonia
Infant Pneumonia
A diffuse interstitial pneumonia
Occur in 10-20% infants that
exposed to the pathogen at
birth
Rhinitis → staccato cough
(afebrile)
Reiter’s syndrome:
Urethritis, conjunctivitis,
polyarthritis
Usually occurs in young white
man
50-65% patients have chlamydial
genital infection at the onset of
arthritis
Lymphogranuloma venereum (LGV)
花柳性淋巴肉芽腫
A chronic sexually transmitted disease caused by
C. trachomatis L1, L2, L2a, L3.
More common in men, with male homosexuals
being the major reservoir.
Small, painless lesions at site of infection
(genitalia). Fever, headache, myalgia.
Swelling of regional lymph nodes (inguinal nodes),
painful buboes (橫瘻), rupture.
Proctitis 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
Cytology – Giemsa-stained cell scrapings

Quality of the specimen is important.
Specimens must be obtained from the involved
site; pus or exudate is inadequate.

Insensitive, nonspecific
Culture – HeLa, MaCoy, Hep-2 cells; iodine
strain to detect inclusions; the most
specific methods for diagnosis.
Iodine-stained Chlamydia trachomatis inclusion
bodies (arrows)
Chlamydial urethritis (elementary bodies in
direct smear of urethral cell, fluorescein antibody
stain)
Lab diagnosis
Nucleic acid amplification tests (NAATs) –
test of choice for lab diagnosis of C.
trachomatis infection
Serologic tests – limited value for adult
urogenital infections; good for LGV.

CF test or EIAs: genus-specific LPS, fourfold
increase or >1:256

MIF test: species- and serovar-specific antigen
(MOMPs)
2. Chlamydophilia pneumoniae
(肺炎披衣菌)
Was first isolated from the conjunctiva of a
child in Taiwan - TWAR stain.
An important cause of bronchitis,
pneumonia and sinusitis.
Infection is common, especially in adults
and transmitted person-to-person by
respiratory secretions.
Clinical disease
Most infections are asymptomatic or mild
- persistent cough.
Can’t be differentiated with other atypical
pneumonia - M. pneumoniae, Legionella
pneumophila, and respiratory viruses.
Detected in atherosclerotic lesions in
blood vessels. However, the role in the
development of atherosclerosis is not
clear.
(Koch’s postulate)
Lab diagnosis
Diagnosis is difficult
Do not grow in cell lines
NAATs are OK for use.
Complement fixation test (not
specific) or MIF test (specific)
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)
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 spread to and multiply in
reticuloendothelial cells of liver and spleen 
necrosis
Disseminate to lung and other organs via
circulation
Lmphocytic inflammation in lung, edema,
necrosis, mucous plugs  cyanosis and anoxia
C. psittaci has three forms of
infection
Asymptomatic infection
Transient flu-like illness: high fever,
headache, chills, myalgia
Serious pneumonia: non-productive
cough, rales, CNS involvement is
common, carditis, hepatomegaly,
splenomegaly
Diagnosis and treatment for
C. psittaci
Diagnosis: complement fixation
test with group antigen, fourfold
rise in specific antibody
Treatment: tetracyclines or
macrolides
Treat birds with chlortetracycline
HCl for 45 days.
C. trachomatis
C. pneumoniae
C. psittaci
Disease severe
Glycogen absent
No staining with iodine
Disease mild and chronic
Glycogen in inclusions
Inclusions can be stained
with iodine
Susceptible to sulfonamides Sulfonamide resistant
Chapter 45
Rickettsia and Orientia
Chapter 46
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
Chapter 45
Rickettsia and Orientia
General characteristics
G(-) bacilli, obligate intracellular
parasites.
Were thought to be virus: small
(0.3x1m), 800 genes.
True bacteria: DNA+RNA, binary fission,
sensitive to antibiotics, use host cell ATP.
Maintain in animal and arthropod
reservoirs.
Transmitted to humans by arthropod
vectors (ticks, mites, lice, fleas), and
maintained in arthropod hosts by
transovarian transmission.
Humans are accidental hosts: acquired
by arthropod bite or contact of
arthropod excreta with abraded skin.
The distribution of rickettsial diseases is
determined by the distribution of the
arthropod host/vector.
Pathogenesis
Rickettsia (also Ehrlichia) is unstable and die
quickly outside host cells.
Coxiella highly resistant to desiccation, remain
viable in environment for months to years.
No toxins, no immunopathology
Rickettsia replicate in endothelial cells,
cause cell damage and blood leakage, skin rash,
microthrombi, focal ischemia, hemorrhage.
Hypovolemia, hypoproteinemia, reduced
perfusion, organ failure.
After phagocytosis
Rickettsia and Orientia: degrade
phagosome membrane by producing
phospholipase; multiply in cytoplasm
Ehrlichia: multiply in cytoplasmic vacuoles
(= phagosomes)
Coxiella: multiply in phagolysosome
Spotted fever group of
Rickettsia and Orientia:
release during infection
Typhus group of Rickettsia:
release after cell lysis
Important Rickettsial Diseases
Spotted fever group
R. rickettsii
R. akari
RMSF (>90%)
Rickettsialpox (100%)
Typhus group
R. prowazekii
R. typhi
Epidemic typhus (40-80%)
Murine typhus (50%)
Scrub typhus group
O. tsutsugamushi Scrub typhus (<50%)
(Parentheses: % of rash, 紅斑)
Spotted fever 斑疹熱
Have a restricted geographic distribution; Rocky
mountain spotted fever (RMSF) is the prototype
of the group, caused by R. rickettsii.
Organisms are maintained in hard ticks (wood
tick and dog tick) by transovarian transmission.
Transmitted to humans by ticks (need 24-48h
to establish infection).
High fever, chills, headache, skin rash (>90%,
extremities to trunk)
GI symptoms, respiratory failure, encephalitis,
renal failure.
Diagnosis is urgent, because the
prognosis depends on the duration of
illness. (identify key clinical signs – rash)




Culture: tissue culture or embryonated eggs
(danger)
Microscopy: Giemsa stain; FA for biopsy
tissue specimens (rapid and specific)
Serology: Microimmunofluorescence (MIF),
detect antibodies against MOMP and LPS
antigens
Molecular diagnosis: PCR, not speciesspecific
Prevention/Control:
Tetracyclines (e.g., doxycline)
No vaccine
Prevent tick bites (can survive for
as long as 4 years without feeding)
Epidemic (louse-borne) typhus
流行性(蝨型)斑疹傷寒
R. prowazekii transmits from man to man by
human head and body lice.
Humans are the primary reservoir (lice die 2 to 3
wk after infection).
Epidemics occur among people living in crowded,
unsanitary condition - war, famine, or natural
disaster.
High fever, severe headache, chills, followed by a
generalized skin rash; complications: myocarditis
and CNS involvement.
O
Brill-Zinsser Disease
A recrudescent form of
epidemic typhus arising
years after the initial attack.
Diagnosis:

MIF test
T/P/C:

Tetracyclines, Chloramphenicol

Louse-control

Formaldehyde-inactivated vaccine
Endemic (murine) typhus
地方性(鼠類)斑疹傷寒
R. typhi transmits to man from
rodents reservoir hosts by rat flea.
Endemic all over the world, primarily
in warm, humid areas.
Fever, severe headache, chills, skin
rash (50%) on chest and abdomen
o
Diagnosis:

IFA test
T/P/C:

Tetracyclines, doxycycline,
Chloramphenicol

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, skin rash (<50%),
spread centrifugally to extremities.
Generalized lymphadenopathy, splenomegaly,
CNS complication, heart failure
O
別來無恙？
歲亦無恙耶？
民亦無恙耶？
王亦無恙耶？
<國策>「齊策‧四」
T/P/C:

Prompt treatment with
tetracyclines, doxycycline,
chloramphenicol

Avoid exposure to chiggers

No vaccine
Chapter 46
Ehrlichia, Anaplasma, Coxiella
Ehrlichia and Anaplasma
Infections of hematopoietic cells
Intracellular bacteria that lodge in
phagosomes of mononuclear and
granulocytic phagocytes, but not RBC.
multiply in phagosomes = morulae
Grow cycle: three stages - elementary body, initial
body, morula
Ehrlichia inclusions (peripheral blood smear, Wright-Giemsa)
Clinical diseases
1. Human monocytic ehrlichiosis
E. chaffeensis : infect blood monocytes
and mononuclear phagocytes in tissues
and organs
Vector - Lone Star tick
Reservoir - white-tailed deer, domestic
dogs
2. Canine granulocytic ehrlichiosis
E. ewingii
Vector - Lone Star tick
Reservoir -white-tailed deer, domestic dogs.
3. Human anaplasmosis
Anaplasma phagocytophilium : infect
bone marrow myeloid cell (i.e., neutrophils)
Vector - Ixodes ticks
Reservoir - small mammals
Clinical disease
Fever, headache, malaise, leukopenia,
thrombocytopenia
Skin rash (10 to 40%)
50% patients require hospitalization,
1 to 3% mortality
T/P/C:
Diagnosis is urgent. Prompt
treatment with doxycycline
No vaccine
Avoid tick-infested areas
Coxiella burnetii 蒲奈氏科克斯菌
Biologically and genomically distinct
from Rickettsia; more closely related
to Legionella and Francisella.
Obligate intracellular pathogen
Multiply in phagolysosome
Epidemiology
Can infect mammals, birds, and ticks
Primary reservoirs: farm animals, cats,
dogs, rabbits
Ticks are vector for disease in
animals but not in humans
Epidemiology
High concentrations of bacteria are present
in placenta of infected livestock.
Spores are able to survive in nature under
dry environmental conditions for months.
Transmit to man by the respiratory route
from contaminated soil, not from
arthropod vector.
Those handling pregnant or lactating cows
or sheep, drinking unpasteurized milk, or
working in slaughter-houses 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):
phase I antigen: LPS with a complex
carbohydrate, can block antibody binding;
infectious form
phase II antigen: modified LPS, expose surface
proteins to antibody, less infectious form
Formation of immune complex: cause of signs
and symptoms
Q fever
Most infections are mild or asymptomatic
Acute disease:


Pneumonia - high fever, severe headache, chill,
myalgias, resemble “atypical pneumonia”
Granulomatous hepatitis, hepatosplenomegaly,
Chronic disease: subacute endocarditis
with long incubation period and poor
prognosis
Diagnosis
Serologic tests (IFA, ELISA, CF)
Acute Q fever: IgM and IgG are
developed 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
Vaccine is available (single dose
with no booster immunization for
uninfected people)
96.5.14