Gram Negative Cocci - Neisseria & Moraxella

Question 1

General features of gram neg cocci

Answer 1

1. Oxidase positive, purple colour rapidly appears when it touches filter paper with oxidase reagent

Question 2

Transmission of N. meningitidis

Answer 2

Carried in the nasopharynx

1. Respiratory droplets
2. Close contact eg kissing

Question 3

Virulence factors of N. meningitidis (2)

Answer 3

1. Lipo-oligosaccharide (LOS) - endotoxin in outer cell membrane, activates immune system - SIRS
2. Anti-phagocytic carbohydrate capsule - ≥13 serogroups incl A, B, C, Y, W-135 - immune system develops specific opsonic Ab for each - capsules used for vaccines

Question 4

Epidemiology of N. meningitidis

Answer 4

Outbreaks tend to occur

• at mass gatherings of people from diff communities
• at the “meningitis belt” across Africa (prone to short but large epidemics)

Question 5

Clinical presentations of N. meningitidis (4)

Answer 5

1. Meningococcemia - enters bloodstream, may progress to fulminant meningococcemia w hypotensive shock, SIRS, high mortality
   - not distinguishable from other causes of sepsis except that it is usually in otherwise well, young people + non-blanching rash
2. Acute Bacterial Meningitis - hematogenous spread to meninges, symptoms like headache, fever, photophobia, neck stiffness
3. Meningococcal rash - non-specific macular rash - petechiae (does not blanch when compressed under a glass - tumbler test) - leakage of blood from damaged vessels - purpura - ecchymoses, skin necrosis
   - look at conjunctivae & mucous membranes
4. Less commonly - pneumonia, pericarditis, endocarditis, conjunctivitis, arthritis, chronic meningococcemia (recurrent rash, fever, joint pain, must be treated as can develop into septicemia/meningitis - acute)

Question 6

Diagnosis of N. meningitidis (2)

Answer 6

1. Culture (blood, CSF, throat swab) (Gram stain - GNDC)

2. Molecular (antigen detection, PCR), sugar fermentation, mass spec

Question 7

Treatment of N. meningitidis (2)

Answer 7

1. Benzylpenicillin (does not clear throat carriage)

2. Ceftriaxone (broader spectrum, cephalosporin, clears throat carriage)

Question 8

Prevention of N. meningitidis (2)

Answer 8

1. Prophylaxis for close contacts, HCW
   - Rifampicin, ciprofloxacin - clear pharyngeal colonization (oral)
   - Ceftriaxone, often in pregnant contacts (injection)
   - Patient if treated w penicillin (reduce spread)
2. Vaccination
   - splenectomy (risk of infection by capsulated organisms), Hajj pilgrims, contact prophylaxis
   (A) polysaccharide (older) vaccine (purified capsular polysaccharide) - shorter term protection, does not prevent carriage or protect infants (not processed well in young immune systems)
   - quadrivalent vaccine for serogroups A, C, Y, W-135
   (B) conjugate (newer) vaccine (polysaccharide + protein) - longer protective response, effective in infants, protects against carriage
   - tetravalent (A, C, Y, W-135)
   - monovalent (C) vaccine

Question 9

Transmission of N. gonorrhoeae

Answer 9

Carried in urogenital sites, urethra, cervix, rectum, throat

1. Sexual intercourse
2. Possibly by fomites

Question 10

Virulence factors of N. gonorrhoeae (3)

Answer 10

1. Lipo-oligosaccharide
2. Fimbrae (& conjugation pili) - involved in attachment, expression can be turned on/off & antigenic composition can be changed - antigenic variation
3. Outer Membrane Proteins (OMPs) - variable expression, each can be independently turned on/off

Question 11

Clinical presentations of N. gonorrhoeae (6)

Answer 11

1. Males - Acute Urethritis, with discharge & dysuria (pain on urination)
   - repeated infections - fibrosis - blockage of urethra - urethral strictures
   - complication: may spread to epididymis - epididymitis
2. Females - often asymptomatic carriers, in endocervix
   - may have dysuria, vaginal discharge, intermenstrual bleeding
   - asc inf into uterus, fallopian tubes - acute salpingitis - spread further to cause acute PID - liver, FItz-Hugh-Curtis syndrome
3. Disseminated gonococcal infection (DGI) - fever, joint pain, small pustular skin lesions, due to entry into blood & spread
4. Prepubertal girls - Vulvovaginitis
5. Ophthalmia neonatorum/gonoccocal conjunctivitis (can also be caused by Ch. trachomatis) - due to infected mother
6. Homosexual men - Symptomatic proctitis (rectal inflam)

Question 12

Diagnosis of N. gonorrhoeae (3)

Answer 12

1. Samples - gram stain - req charcoal transport medium + chocolate agar/modified Thayer-Martin medium (CO2 enriched atmosphere, less interference from normal flora)
   - urethral, rectal, throat, endocervical (female)
   - gram stain of discharge from male w urethritis will show GNDC, but direct stain from female genital tract is less useful due to normal flora
2. Molecular diagnosis, nucleic acid tests eg PCR, sugar fermentation, mass spec
3. Patient with gonorrhoea likely has other STDs too!!

Question 13

Treatment & prevention of N. gonorrhoeae (1+4)

Answer 13

1. IM ceftriaxone + oral azithromycin together
   - empirical therapy in uncomplicated disease
   - high resistance rates to penicillin & cipro
2. No vaccine
3. Condoms, behaviour, education
4. Follow up sexual contacts
5. Prophylactic silver nitrate/antibiotic eyedrops for neonates

Question 14

Clinical presentations of Moraxella catarrhalis

Answer 14

Upper resp tract flora

1. Respiratory tract infections in those with predisposing conditions (pre-existing chest disease, immunocompromised)/Opportunistic chest infections

Question 15

Treatment of Moraxella catarrhalis

Answer 15

• almost all strains produce beta-lactamase - cannot use ampicillin & amoxicillin
  1. Co-amoxiclav (amoxicillin + clavulanate - beta lactamase inhibitor)