Neisseria (Gram-negative cocci)

Gram negative

oxidase +

catalase +

grows on chocolate agar, not blood agar

Neisseria: Gram, oxidase, catalase, growth requirements

commensal

Most species of Neisseria are —

Neisseria gonorrhoeae —> gonorrhea

Neisseria meningitidis —> meningitis (but colonizes naso- and oropharynx without disease)

The two Neisseria species that are pathogenic to humans

Only in N. meningitidis, no capsule in N. gonorrhoeae

Capsule in Neisseria?

Outer membrane forms blebs (micelles of outer membrane shed during cell division) as it divides, and these blebs enhance inflammatory response and act as decoys for antibodies.

Role of blebs in Neisseria

lipooligosaccharide

Neisseria has this proinflammatory glycolipid in its cell wall

IgA1 (cleaves and inactivates secretory IgA1)

Neisseria has an — protease as a virulence factor

Pili (attach to non-ciliated epithelial cells, involved in conjugation, motility)

Opa (opacity) proteins (mediate strong binding to epithelial/phagocytic cells)

Porins (nutrient acquisition, interference with neutrophils and facilitation of invasion into epithelial cells)

These 3 virulence factors in Neisseria undergo phase and/or antigenic variation to evade antibodies

Entry through sexual contact, attach to and enter mucosal epithelial cells, then translocate to sub-epithelial space and establish an infection. Lipooligosaccharide induces secretion of TNF-a that is responsible for most symptoms of gonorrhea.

Pathogenesis of N. gonorrhoeae

1.Gonorrhea in Men – urethral infection

a.2-5 day incubation

b.purulent discharge, dysuria

c.most men exhibit acute symptoms

d.untreated, symptoms resolve in a few weeks

e.complications rare, include: prostatitis, epididymitis, abscesses

Presentation of gonorrhea in men:

Cervical infection

a.Primary site is endocervical columnar epithelial cells

b.>50% asymptomatic or have mild disease

c.symptoms:  vaginal discharge, dysuria, abdominal pain

d.10-20% of cases ascend reproductive tract and lead to complications like salpingitis, tubo-ovarian abscesses, PID, sterility

Presentation of gonorrhea in women:

N. gonorrhoeae, Chlamydia trachomatis

Primary causes (2) of pelvic inflammatory disease

It is an infection of female reproductive tract.

Presents with severe, prolonged menstrual symptoms with lower abdominal pain and tenderness, fever

Can cause irreversible damage to uterus and fallopian tubes

Inflammatory response lead to scarring of tissues; is a major cause of sterility

What is pelvic inflammtory disease?

4.Ophthalmia neonatorum

a.Conjunctivitis in newborns, contracted during vaginal birth

b.Lid edema, erythema, purulent discharge

c.Can lead to blindness

Complication seen in newborns of mothers with gonorrhea

Can lead to sepsis, infection of skin and joints

Affects 1-3% of infected women; very uncommon in men.

Clinical presentation: fever,

pustular rash on extremities with an erythematous base,

migratory arthralgias, suppurative arthritis (wrists, knees, ankles)

may include conjunctivitis

a leading cause of purulent arthritis in adults

What is a disseminated gonococcal infection (gonococcemia)?

Other manifestation of Neisseria gonorrhoeae in which infection spreads from follopian tube to liver capsule and/or abdominal wall

Leads to scarring of the liver capsule and adhesions between capsule and abdominal wall

Presents with abdominal pain, hepatic tenderness, inflammation

Fitz-Hugh-Curtis Syndrome:

Discharge, itching, bleeding, painful bowel movements

Presentation of anorectal gonorrhea

often asymptomatic but can cause sore throat, difficulty swallowing, fever

Rarely can lead to disseminated infection

Presentation of gonorrheal pharyngitis

Chlamydia

Gonorrhea is 2nd most common STI after —

50% for women, 20% for men

Risk of disease after single exposure to gonorrhea

Nucleic Acid Amplification Test (NAAT) (PCR-based tests)

Pros: fast, sensitive, and specific—can also detect chlamydia

Cons: no information gained about antibiotic sensitivity.

Gram Stain

Fast and effective but only in symptomatic men with urethral discharge

Culture

More time consuming and requires specific temperature range, but tests for abx sensitivity, which is crucial given increasing resistance.

Diagnosis of N. gonorrhoeae (3):

Antigenic variation of surface structures hard to overcome

Why there’s no vaccine for gonorrhea

Enters via respiratory secretions, then attaches to epithelial cells of nasopharynx.

Multiplies on cell surface, then invades epithelial cells, migrates to sub-epithelial space, then enters bloodstream and is protected by a capsule.

Inflammatory response to LOS leads to diffuse vascular damage; crosses BBB and enters CSF.

Pathogenesis of Neisseria meningitidis:

a.Infection of the meninges

b.Abrupt onset of headache, fever, nuchal rigidity (stiff neck), nausea/vomiting, decreased alertness, myalgias

•petechial rash may be present

c.Very young children:  presentation may be nonspecific

•fever, nausea/vomiting, irritability

d. Rapid progression

100% mortality if not treated promptly, <10% mortality with treatment

What is meningitis?

Low incidence but includes hearing loss, learning deficiencies, arthritis

Neurological sequelae seen in meningitis

This is a severe bloodstream infection (sepsis) caused by N. meningitidis, often leading to shock and multi-organ failure. Symptoms include a petechial rash (caused by thrombosis of small blood vessels) that may coalesce into larger hemorrhagic lesions referred to as purpura.

Disseminated intravascular coagulation and multi-organ involvement are present

Adrenal gland failure due to abnormal bleeding in adrenal glands (Waterhouse-Friderichsen Syndrome)

What is acute meningococcemia?

When bacteremia persists days/weeks

Symptoms: low-grade fever, arthritis, petechial rash

Milder, good prognosis with treatment

What is chronic meningococcemia?

Endemic worldwide, epidemics in developing countries

6 serotypes cause disease, in US mostly B, C, Y

Epidemiology of meningitis

humans are the only one

Reservoirs of N. meningitidis?

Those living in close quarters

Patients with asplenia, no capsule-specific antibodies, or those with complement deficiencies.

Risk factors for meningitis

Highest in children <1 year,

second peak in teens/college aged,

elderly also at risk

Population with highest incidence of meningitis

Gram stain: large numbers of diplococci

If in CSF=meningitis

If in blood=meningococcemia

Culture

Do this on selective and nonselective media, can detect bacteria in CSF, blood, sputum

Diagnosis of N. meningitidis

1.Start on broad spectrum drugs until disease agent identified

•IF SUSPECT MENINGITIS, DO NOT DELAY TREATMENT!!!

2.Meningococcemia, shock:  supportive care for affected organs

3.Prophylaxis:  close contacts of confirmed cases

anyone with direct exposure in preceding 7 days

Treatment of N. meningitidis

Gram negative diplococcus, strict aerobe

Moraxella catarrhalis: Gram, oxygen use, arrangement

1.Commonly colonizes URT in children

•increased prevalence in kids vaccinated against S. pneumo

2.Healthy adults not typically colonized

Moraxella catarrhalis: who is affected?

sinusitis, acute otitis media in otherwise healthy people

Bronchitis, bronchopneumonia in the elderly or patients with chronic pulmonary diseases

Moraxella catarrhalis: what diseases does it cause?

Usually treated empirically, grows at a lower temp than Neisseria and produces dry colonies on chocolate agar (distinguishing it from Neisseria)

Diagnosis of Moraxella catarrhalis: