Transcript N. gonorrhoeae

Neisseria
王淑鶯
微生物免疫學所
國立成功大學醫學院
分機: 5634
Email: [email protected]
Reference:
Chapter 29 in Medical Microbiology
(Murray, P. R. et al; 6th edition, 2009)
Neisseria
• German physician A. L. S. Neisser, who
originally described the organism
response for gonorrhea
Albert Ludwig Sigesmund Neisser was born as
the son of a well known Jewish physician, Moritz
Neisser. Neisser began his medical studies in
Breslau in 1872. Neisser originally planned to
become a specialist in internal medicine, but
there was no opening for assistants in Biermer's
clinic. It was therefore purely by chance that he
turned to dermatology and became an assistant
physician to in the dermatology clinic originally
founded by Heinrich Koebner. He worked here
for two years, and it was here, in 1879, Neisser
discovered the gonococcus.
Neisser's discovery occurred in the wake of the rapid
development of the new field of bacteriology. It was
made possible in large part by his close association
with Ferdinand Cohn , the botanist who also gave
invaluable help to Robert Koch. Cohn taught him
Koch's smear tests for the identification of bacteria.
He at first called the microorganism that he thus
observed "micrococcus"; they were then given the
name "gonococcus" by Paul Ehrlich. Although his
discovery was extremely important, it was not until
the advent of penicillin that this widespread disease
could be controlled. His students called him the
"father of gonococcus".
Important Human Pathogens
Neisseria gonorrhoeae
Neisseria meningitidis
Other species normally colonize mucosal surfaces
of oropharynx and nasopharynx and occasionally
anogenital mucosal membranes. These species
have limited virulence and generally produce
disease only in compromised patients.
Neisseria
N. gonorrhoeae (gonococcus): gonorrhea
N. meningitidis: meningitis
Morphology and Identification
Gram-negative cocci (kidneyshaped), usually in pairs.
Human pathogens (i.e. N.
gonorrhoeae and N.
meningitidis) are typically
found associated with or
inside PMN cells. They are
able to multiply inside the
phagocytes, epithelial and
endothelial cells.
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Morphology and Identification
Both meningococci and gonococci are encapsulated:
menigococci have a polysaccharide capsule; gonococci have a
loose capsule-like structure.
Grow best under aerobic conditions
Produce cytochrome oxidase (oxidase-positive).
Meningococci and gonococci grow best in medium containing
complex organic substances (e.g. blood, hemin, and animal
proteins), and in a humid atmosphere containing 5% CO2.
Meningococci and gonococci are rapidly killed by drying,
sunlight, moist heat and many disinfectants.
Poor survival at cooler temperature.
N. gonorrhoeae (Gonococcus)
Antigenic structure
1. Pili: enhancing
attachment to host cells
and resistance to
phagocytosis; antigenically
different among strains,
and a single strain can
make many antigenically
distinct forms of pilin.
2. Por proteins: form porins
and mediate resistance to
neutrophil and serum
killing.
3. Opa: associated with
opaque colonies; an outer
membrane protein
functioning in attachment to
host cells.
4. Rmp: stimulates antibodies
that block serum bactericidal
activity.
5. Lipooligosaccharide (LOS):
lacking long-antigenic side
chains; endotoxic.
6. Other proteins.
N. gonorrhoeae is capable of changing its surface antigens
(particularly pilin) rapidly to avoid host defenses.
Pathogenesis
Attachment to mucosal cells (requires pili)
Invade into the cells and multiply (Opa mediates
tighter association with and invasion of host cells;
Por inhibits phagolysosome fusion)
Pass through the cells into the subepithelial space
Establish infection (LOS stimulates inflammatory
response; Rmp blocks bactericidal activity)
Lipopolysaccharide (LPS)
is also called endotoxin.
LPS is composed of lipid A, core
polysaccharide, and O-specific
polysaccharide.
Lipid A anchors LPS in the lipid
bilayer. It causes symptoms
associated with endotoxin.
O-specific polysaccharide can be
used to identify certain species
and strains.
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Pathogenesis
and Pathology
Gonococci attack
mucous membrane of
the genitourinary tract,
eye, rectum, and throat,
producing acute
suppuration that lead to
tissue invasion; this is
followed by chronic
inflammation and
fibrosis.
Epidemiology
Gonorrhea occurs only in humans.
Gonorrhea is transmitted by sexual contact, often by
women and men with asymptomatic infections.
Women have a 50% risk of acquiring the infection with a
single exposure to an infected man while men have a
20% risk in the same situation.
95% infected men and 50% infected women have acute
symptoms. So, asymptomatic carriage is more common
in women than in men.
Rectal and pharyngeal infections are more commonly
asymptomatic than genital infections.
Symptoms
1. Male: urethritis with yellow, creamy pus
and painful urination. The process may
extend to the epididymis (附睪炎).
As suppuration subsides in untreated
infection, fibrosis occurs, sometimes
leading to urethral strictures (sterility).
2. Female: infection starts from the
endocervix (子宮頸內膜) , and results in
vagina discharge, dysuria (排尿困難) , and
abdominal pain. Uterine tubes may be
involved, causing salpingitis (輸卵管炎),
fibrosis, and obliteration of the tubes (20%
may become infertile). When gonococcal
cervicitis is either asymptomatic or
unrecognized, the patient may progress to
pelvic inflammatory disease (PID).
3. Gonococcal ophthalmia neonatorum :
bilateral conjunctivitis often follows vaginal
delivery from an infected mother. The
symptoms are eye pain, redness, and a
purulent discharge. The organism can
cause permanent injury to the eye in a
very short time; prompt recognition and
treatment are essential to avoid blindness.
prevention: tetracycline, erythromycin or
silver nitrate.
4. Gonococcal bacteremia (1-3% of infected
women and much lower percent of infected
men) can lead to fever, pustular (膿泡)
rash over the extremities, tenosynovitis (腱
鞘炎) and suppurative arthritis.
Frequency
In United States
• Incidence is 360,000 infections reported in 2006.
• The reported rate is approximately 240 cases per 100,000
population.
• The rate of gonorrhea is much higher in African compared
to other racial groups.
• The rate is associated with socioeconomic and behavioral
factors.
Frequency
International
• Disease rates are unknown for most developing
countries.
• The incidence is substantially lower in most
European countries.
• The indigenous gonorrhea has virtually been
eliminated in Sweden.
• The median prevalence of gonorrhea has been
estimated to be 10% in Africa, 5% in Latin America,
and 4% in Asia.
Age
• In the United States, the highest rates of gonorrhea
are found in young (15-24 y) unmarried persons and
in groups of low educational and socioeconomic
status.
• Infection in children is a marker for child sexual
abuse.
Immunity
Treatments
Repeated gonococcal
infections are common,
because protective
immunity to reinfection
does not develop due to
the antigenic variation of
gonococci. This makes
development of effective
vaccines difficult.
Resistance to penicillin G (PPNG:
penicillinase-producing N.
gonorrhoeae) and tetracycline is
common. Resistance to
fluoroquinolones has also become
prevalent.
Ceftriaxone can be used for
uncomplicated gonorrhea.
In gonococcal infections other than
urethritis in men, cure should be
established by follow-up, including
cultures from the involved sites.
Laboratory Diagnosis
Gram stain (gram-negative
diplococci in PMNs):
Sensitive (>90%) and specific
(98%) for men with purulent
urethritis.
Less sensitive for
asymptomatic men (<60%).
Relatively insensitive for both
symptomatic and
asymptomatic women.
* Negative results must be
confirmed by culture.
Culture:
Avoid drying of specimen
(genital or rectal) and low
temperature. Direct inoculation
of specimens onto prewarmed
media is preferred.
Inoculate both the selective
media (e.g., modified ThayerMartin) and non-selective
media (e.g., chocolate blood
agar; for strains that are
sensitive to vancomycin).
Identification
N. gonorrhoeae is distinguished from other species by acid
production from oxidation of glucose, but not from other sugars.
Direct detection of N. gonorrhoeae in clinical specimens by
PCR with specific primers.
Prevention and Control
Chemoprophylaxis is ineffective except for eye infections.
Areas with high incidence of PPNG: Asia, parts of Africa and
some places in USA.
Infection rate can be reduced by:
1. avoiding multiple sexual partners;
2. early diagnosis and treatment;
3. finding cases and contacts through education
and screening of population at high risk.
4. combined with doxycycline or azithromycin for dual
infections with Chlamydia
Neisseria meningitidis
(meningococcus)
Antigenic structure
1. Capsular polysaccharide: more than 13 serogroups
have been identified (serogroups A, B, C, X, Y, and
W135 are most commonly isolated).
2. Pili (allow bacterial colonization of nasopharynx).
3. Outer membrane proteins: these are analogues to the
Por and Opa proteins of gonococci.
4. Lipooligosaccharide (LOS): responsible for diffuse
vascular damage in meningococcal infections.
Pathogenesis, Pathology, and Clinical Finding
Meningococci are pathogenic only for humans under
natural conditions.
Like gonococci, meningococci are able to invade the
epithelial cells. The capsule of meningococci protects the
bacteria from phagocytic destruction.
Nasopharynx is the portal of entry
attach to epithelial
cells with the aid of pili (may colonize without producing
symptoms)
reach the blood stream, producing
bacteremia.
Upper respiratory tract infection.
Fulminant meningococcemia.
(腦膜炎球菌血症)
Fulminant meningococcemia
High fever and hemmorrhagic rash.
There may be disseminated intravascular coagulation (血
管內凝集) with shock, and circulatory collapse
(Waterhouse-Friderichsen syndrome: bilateral destruction
of adrenal gland.)
Meningitis is the most common complication of
meningococcemia.
A milder septicemia with low-grade fever, arthritis, and
petechial skin lesions that persist for days or weeks may
be observed.
Other syndromes: pneumonia, arthritis, and urethritis.
Meningococcemia can be prevented by specific bactericidal
antibodies in serum.
Meningitis
Symptoms: begins suddenly, with intense headache,
vomiting, and stiff neck, and progress to coma within
a few hours.
Mortality: nearly 100% if untreated; <10% in patients
treated promptly with appropriate antibiotics.
Neurologic sequelae:
uncommon; hearing deficit.
Skin lesions in a patient
with meningococcemia
Immunity
Laboratory Diagnosis
Protective immunity is the
group- or type-specific,
complement-dependent,
bactericidal antibodies.
Specimen: blood and cerebrospinal
fluid (CSF). >107 bacteria/ml of
CSF are normally found in
untreated patients.
Serogroup B, whose
capsule contains sialic
acid, is relatively nonimmunogenic.
Gram stain: gram-negative
diplococci in PMNs.
Treatment
Culture: alternative blood culture
methods are required because
additives in the blood culture broths
can be toxic for this organism.
Penicillin G is the drug of
choice.
Identification: acid formation with
glucose and maltose, but not others.
Epidemiology, Prevention, and Control
Meningococcal meningitis occurs in epidemic (in developing countries)
and sporadic cases (in developed countries).
Transmitted by respiratory droplets among people in close contact
(family members; soldiers in military barracks; direct contact with the
respiratory secretions of an infected person.) Reduction of personal
contacts in a population with a high carrier rate is important for
prevention.
Rifampin, ceftriaxone, or ciprofloxacin can often eradicate the carrier
state and serve as chemoprophylaxis.
Persons with deficiencies in the complement system are at high risk
for meningococcal disease.
Vaccination of specific capsular polysaccharides of groups A, C, Y,
and W-135 is used for protecting susceptible persons against infection.
Outer membrane vesicle vaccines for group B are being developed
recently.
Areas with frequent
epidemics of meningococcal
disease. This is known as
the Meningitis Belt of Africa,
and visitors to these locales
may benefit from meningitis
vaccine.
Large-scale outbreaks rates
as high as 400-500 cases
per 100,000 population
(compared to 1-2 cases per
100,000 population in USA).