Neisseria

王淑鶯微生物免疫學所國立成功大學醫學院

分機 : 5634

Email: sswang23@mail.ncku.edu.tw

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". 

Neisseria gonorrhoeae

Neisseria meningitidis

Important Human Pathogens

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.

NeisseriaN. gonorrhoeae (gonococcus): gonorrheaN. meningitidis: meningitis

Gram-negative cocci (kidney-

shaped), 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.

Morphology and Identification

www.buddycom.com

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)

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.

Antigenic structure

N. gonorrhoeae is capable of changing its surface antigens (particularly pilin) rapidly to avoid host defenses.

Back

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.

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)

Pathogenesis and PathologyGonococci 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.

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.

Epidemiology

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: 1% tetracycline, 0.5% erythromycin or 1% silver nitrate eye ointment.

(新生兒結合膜炎 )

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.

gonorrhea

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.

Immunity

Treatments

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 Thayer-Martin) and non-selective media (e.g., chocolate blood agar; for strains that are sensitive to vancomycin).

IdentificationN. 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)

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.

Antigenic structure

Pathogenesis, Pathology, and Clinical FindingMeningococci are human pathogen.

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 meningococcemiaHigh 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.

MeningitisSymptoms: 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

Protective immunity is the group- or type-specific, complement-dependent, bactericidal antibodies.

Serogroup B, whose capsule contains sialic acid, is relatively non-immunogenic.

Treatment

Penicillin G is the drug of choice.

Laboratory Diagnosis

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.

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).

Menigitis

back