Transcript N. gonorrhoeae

Pyogenic cocci
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]
Neisseriaceae
Name after the German physician A. L. S. Neisser, who
originally described the organism responsible for gonorrhea
Three genera: Neisseria, Eiknella and Kingella
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
Physiology and Structure
Gram-negative coccid-shaped (resemble coffee bean),
usually in pairs.
oxidase-positive; most catalase-positive
N. gonorrhoeae oxidizing glucose
N. meningitidis oxidizing glucose and maltose
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
N. gonorrhoeae does not grow on blood agar, but grow
on chocolate agar.
Physiology and Structure
Grow best under aerobic conditions
Meningococci and gonococci are rapidly killed by drying,
sunlight, moist heat and many disinfectants.
Poor survival at cooler temperature.
Peptidoglycan sandwiched between inner and outer membrane
Both meningococci and gonococci are encapsulated:
menigococci have a polysaccharide capsule (infection caused
by serogroup A, B, C, Y, W135); gonococci have a loose
capsule-like structure.
Antigenic structure
Pili: extend from cytoplasmic membrane; enhancing attachment
to host cells and resistance to phagocytosis; composed of
pilins; antigenically different among strains (distinct forms of
pilin that is highly variable in C-terminus) makes gonorrehea
vaccine difficult.
Porin proteins: integral membrane proteins that form channels
for nutrients to pass into cells and waste to exit; PorA and
PorB are expressed in N. meningtidis, but only PorB
expressed in N. gonorrhoeae; mediate resistance to
neutrophil and serum killing.
Opa proteins: membrane proteins; mediate binding to epithelial
and phagocytic cells; associated with opaque colonies which
recovered in patients with localized infection
(endocervcitis,etc); transparent colonies associated with
pelvic inflammatory disease and disseminated disease
Rmp proteins (reduction-modifiable proteins): stimulates
antibodies that block serum bactericidal activity.
Binding to human transferrin for iron that is essential for growth
and metabolism (other bacteria use siderophore for iron
binding)
Lipooligosaccharide (LOS): composed of lipid A, core
polysaccharide, but lack O-specific polysaccharide. Lipid A
possess endotoxin activity.
Rapid growth release outer membrane blebs: contain LOS and
surface protein; enhance endotoxin-mediated toxicity and
protect replicating bacteria
IgA1 protease: cleave hinge region of IgA; create
immunologically inactive Fc and Fab
b-lactamases
Pathogenesis and Immunity
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)
IgG3: predominant antibodies response to gonococcal infection
Meningococcal disease occurs in patients lack specific antibodies
(children younger than 2 years)
Patients with deficiencies in C5, C6, C7 and C8 of complement
system are 6000-fold greater risk for Meningococcal disease
Epidemiology
N. gonorrhoeae
Gonorrhea occurs naturally only in humans.
Gonorrhea is transmitted by sexual contact, often by women and
men with asymptomatic infections.
The most common sexually transmitted disease (second to
chlamydia)
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.
N. meningitidis
Endemic meningococcal disease occurs worldwide. Epidemics
occurs in developing countries.
In Europe and USA, serogroups B, C, Y predominate in meningitis
and meningococcemia.
In developing country, serogroups A and W135 predominate.
Serogroups Y and W135 commonly associated with meningococcal
pneumonia.
Humans are the only natural carriers.
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.
Clinical Diseases of N. gonorrhoeae
Gonorrhea
male: purulent urethral discharge after 2-5 days
incubation period; 95% of infected men have
acute symptoms; complications are rare, but
epididymi (附睪炎), prostatitis (攝護腺炎),
periurethral abscess may occur.
female: cervix is the primary site of infection; vaginal
discharge, dysuria, abdominal pain; 10-20% infected
women with salpingitis (輸卵管炎), tuboovarian
abscesses (輸卵管卵巢膿腫), pelvic inflammatory
disease.
Gonococcemia
Disseminated infection with septicemia and infection of skin
and joints
1-3% of infected women and much lower percent of infected
men
Symptoms: fever, migratory arthralgias (移動性關節痛) and
suppurative arthritis in wrists, knees and ankles, pustular
(膿泡) rash over the extremities
Other N. gonorrohea syndromes
Perihepatitis (肝周圍炎), purulent conjunctivitis (化膿性結膜炎),
ophthalmia neonatorum, anorectal gonorrhea, pharyngitis
Clinical Diseases of N. meningitidis
Meningitis
800 cases were reported in USA in 2010
Symptoms: begins suddenly with headache, meningeal signs
and fever; young children have nonspecific signs like fever and
vomiting
Mortality: nearly 100% if untreated; <10% in patients treated
promptly with appropriate antibiotics.
Neurologic sequelae: uncommon; hearing deficit.
Meningococcemia
A life-threating disease
Thrombosis (血栓形成) of small blood vessels and multiorgan
involvement
High fever and hemorrhagic rash
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.
Laboratory Diagnosis
N. gonorrhoeae
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 Thayer-Martin) 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.
N. meningitidis
Specimen: blood and cerebrospinal fluid (CSF). >107 bacteria/ml of
CSF are normally found in untreated patients.
Gram stain: gram-negative diplococci in PMNs.
Culture: alternative blood culture methods are required because
additives in the blood culture broths can be toxic for this organism.
Identification: acid formation with glucose and maltose, but not others.
Treatment, Prevention and Control
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. Combined
with 1-week dose of doxycycline or single dose of azithromycin for
dual infections with Chlamydia.
Chemoprophylaxis is ineffective except for newborn eye infections
(1% silver nitrate, 1% tetracycline or 0.5% erythromycin).
Protective immunity to reinfection does not develop due to the
antigenic variation of gonococci. This makes development of
effective vaccines difficult.
Rifampin, ceftriaxone, or ciprofloxacin can often eradicate the
carrier state and serve as chemoprophylaxis for preventing N.
meningitidis infection.
Vaccination of specific capsular polysaccharides of groups A,
C, Y, and W-135 is used for protecting susceptible persons
against infection.
- polysaccharide vaccine
- polysaccharide-protein conjugate vaccine (11-18 years old)
Outer membrane vesicle vaccines for group B (weak
immunogen) are being developed recently.