Neisseria — Gonorrhoea & Meningitis

The genus Neisseria contains two obligate human pathogens that are perennial NEET PG favourites: Neisseria gonorrhoeae (gonococcus) and Neisseria meningitidis (meningococcus). Both are oxidase-positive, Gram-negative diplococci with a "kidney/coffee-bean" morphology, but they differ sharply in habitat, disease, capsule and prophylaxis. This sheet hammers the discriminating, exam-tested facts.

Genus overview & classification

Neisseria are aerobic, non-motile, non-sporing, Gram-negative diplococci that are oxidase-positive and catalase-positive. The two cells are flattened against each other, giving the classic kidney-bean or coffee-bean appearance. They are fastidious, capnophilic (need 5–10% CO₂), and die rapidly outside the host (autolysis due to powerful intracellular autolytic enzymes — hence specimens must be cultured promptly and never refrigerated).

The genus is differentiated mainly by carbohydrate (sugar) utilisation, which is one of the most repeated MCQ points.

Feature	N. gonorrhoeae	N. meningitidis
Capsule	Absent	Present (polysaccharide)
Glucose fermentation	Yes	Yes
Maltose fermentation	No	Yes
Plasmid	Often present (β-lactamase)	Usually absent
Normal flora	Never (always pathogen)	Nasopharynx (carrier state)
Vaccine	None	Available (conjugate/polysaccharide)
Transmission	Sexual / perinatal	Respiratory droplets
Main disease	STI, ophthalmia neonatorum	Meningitis, meningococcaemia

High-yield: Both ferment Glucose; only meningococcus ferments Maltose. Mnemonic: "MeninGococcus = Maltose + Glucose; Gonococcus = Glucose only." Both also reduce nitrite and N. lactamica (commensal) ferments lactose.

Common culture media (must-know)

• Selective medium — Thayer–Martin (Modified Thayer–Martin, MTM): chocolate agar + VCN(T) antibiotics — Vancomycin (suppresses Gram-positives), Colistin (suppresses other Gram-negatives), Nystatin (suppresses fungi), and Trimethoprim (suppresses swarming Proteus). Incubated in 5–10% CO₂.
• Martin–Lewis medium is a variant using anisomycin instead of nystatin.
• New York City (NYC) medium supports Neisseria and also genital mycoplasmas.
• Non-selective: chocolate agar and Mueller–Hinton.

High-yield: Thayer–Martin = chocolate agar + VCN. A frequently asked trap — vancomycin in the medium can suppress rare vancomycin-susceptible N. gonorrhoeae strains.

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Part A — Neisseria gonorrhoeae (Gonococcus)

Virulence factors

• Pili (fimbriae): primary adhesin to mucosal (columnar/transitional) epithelium; antigenically variable → no lasting immunity, reinfection common.
• Opa proteins (P.II): opacity-associated, tighter adhesion and invasion.
• Por (P.I) protein: porin; protects against intracellular killing.
• Lipo-oligosaccharide (LOS, not full LPS): endotoxin-like, causes mucosal damage; sialylation confers serum resistance.
• IgA1 protease: cleaves secretory IgA at the mucosa.
• β-lactamase (penicillinase): plasmid-mediated → PPNG (penicillinase-producing N. gonorrhoeae); reason penicillin is obsolete.

High-yield: Gonococcus is an obligate intracellular-surviving organism in polymorphs (neutrophils) — the Gram stain of urethral pus showing Gram-negative diplococci inside neutrophils is virtually diagnostic in symptomatic men.

Clinical features

Men: acute urethritis 2–7 days after exposure — purulent discharge + dysuria. Complications: epididymitis, prostatitis, urethral stricture.

Women: endocervicitis — often asymptomatic or mild (vaginal discharge, dysuria). The cervix, not vagina, is infected (squamous vaginal epithelium is resistant in adults; prepubertal girls get vulvovaginitis because of immature epithelium).

Disseminated gonococcal infection (DGI) / "arthritis–dermatitis syndrome": triad of migratory polyarthralgia, tenosynovitis, and pustular/haemorrhagic skin lesions; can progress to purulent monoarthritis (knee). Associated with terminal complement deficiency (C5–C9) and menstruation/pregnancy.

Important complications

Complication	Key point
Pelvic inflammatory disease (PID)	Ascending infection → infertility, ectopic pregnancy, chronic pelvic pain
Fitz-Hugh–Curtis syndrome	Perihepatitis → RUQ pain + "violin-string" adhesions between liver capsule and parietal peritoneum (laparoscopy)
Ophthalmia neonatorum	Acute purulent conjunctivitis in newborn, onset day 2–5, can perforate cornea → blindness
DGI	Arthritis–dermatitis, tenosynovitis; complement deficiency
Bartholinitis / tubo-ovarian abscess	Local glandular spread

High-yield: Fitz-Hugh–Curtis = perihepatitis with violin-string adhesions; caused by both gonococcus and Chlamydia trachomatis. Frequently tested as a PID complication.

Ophthalmia neonatorum — discriminating timeline

Chemical (silver nitrate) → day 1 → Gonococcal → day 2–5 (hyperacute, purulent, sight-threatening) → Chlamydial (inclusion conjunctivitis) → day 5–14 (commonest infective cause).

High-yield: Crede's method = 1% silver nitrate eye drops for prophylaxis at birth (now often replaced by erythromycin/tetracycline ointment because silver nitrate itself causes chemical conjunctivitis and does not cover Chlamydia).

Diagnosis & investigation of choice

• Specimen: urethral/endocervical swab; first-void urine for NAAT. Transport in Stuart's/Amies medium or inoculate directly; never refrigerate.
• Microscopy: Gram-stain — intracellular Gram-negative diplococci (sensitive & specific in symptomatic men; poor in women → culture/NAAT needed).
• Culture: MTM (Thayer–Martin); oxidase-positive, sugar fermentation. Culture remains the only test that gives antibiotic susceptibility, important in the era of resistance.
• Investigation of choice / most sensitive: NAAT (nucleic acid amplification test) — can be done on urine, dual-tests for Chlamydia.

High-yield: NAAT is the most sensitive test, but culture is preferred where drug resistance/susceptibility must be assessed and for medico-legal/extragenital sites.

Management / drug of choice

Because of widespread resistance (PPNG, fluoroquinolone resistance, emerging cephalosporin resistance), regimens have evolved:

• Uncomplicated gonorrhoea (current CDC, dual not always needed): Ceftriaxone 500 mg IM single dose (1 g if ≥150 kg). If chlamydial infection not excluded, add doxycycline 100 mg BD × 7 days (azithromycin previously used).
• Ophthalmia neonatorum: Ceftriaxone single dose + saline irrigation.
• PID: ceftriaxone + doxycycline + metronidazole.
• Always treat the sexual partner and screen for co-existing STIs (HIV, syphilis, Chlamydia).

High-yield: Drug of choice for gonorrhoea = ceftriaxone (3rd-gen cephalosporin). Penicillin and fluoroquinolones are no longer recommended empirically. There is no vaccine for gonococcus (capsule absent, pilus antigenic variation).

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Part B — Neisseria meningitidis (Meningococcus)

Serogroups & epidemiology

Classified by capsular polysaccharide into serogroups; A, B, C, W-135, X and Y cause most disease.

• Serogroup A — historically epidemic meningitis in the "meningitis belt" of sub-Saharan Africa and earlier in India.
• Serogroup B — common in developed countries; capsule is poorly immunogenic (mimics neural cell adhesion molecule), hence needs a protein-based (4CMenB) vaccine rather than polysaccharide.
• Serogroups A, C, W-135, Y — covered by quadrivalent conjugate vaccine (used for Hajj pilgrims, mandatory).

Humans are the only reservoir; asymptomatic nasopharyngeal carriage (up to 10–25%) is the source. Spread by respiratory droplets; peaks in winter/spring; outbreaks in crowding (hostels, military barracks, Hajj).

Virulence factors

• Polysaccharide capsule — antiphagocytic, the key virulence determinant.
• LOS endotoxin — drives the fulminant sepsis and DIC of meningococcaemia.
• IgA1 protease, pili, Opa/Opc — adhesion/colonisation.
• Acquisition of iron from transferrin/lactoferrin.

High-yield: Persons with terminal complement (C5–C9) and properdin deficiency, asplenia, and those on eculizumab are highly susceptible to recurrent/invasive meningococcal disease.

Clinical features

1. Meningitis — fever, headache, neck stiffness, photophobia, altered sensorium; Kernig and Brudzinski signs positive. Commonest cause of meningitis in adolescents/young adults.
2. Meningococcaemia — fulminant septicaemia with non-blanching petechial/purpuric rash (purpura fulminans), hypotension, DIC.
3. Waterhouse–Friderichsen syndrome (WFS) — overwhelming meningococcaemia → bilateral adrenal haemorrhage, refractory shock, DIC, and acute adrenal insufficiency. High mortality.

High-yield: Waterhouse–Friderichsen syndrome = bilateral haemorrhagic adrenal necrosis in fulminant meningococcaemia. Classic NEET PG one-liner.

CSF analysis — the key table

Parameter	Bacterial (pyogenic)	Viral	Tubercular
Appearance	Turbid/purulent	Clear	Cobweb/clear
Cells	↑↑ Neutrophils (polymorphs)	Lymphocytes	Lymphocytes
Protein	↑↑ (>100 mg/dL)	Normal/mild ↑	↑↑
Glucose	↓↓ (<40, low CSF:blood ratio)	Normal	↓
Pressure	↑	Normal/↑	↑

In meningococcal meningitis: turbid CSF, neutrophilic pleocytosis, high protein, low glucose, Gram-negative diplococci often intra- and extracellular.

Diagnosis & investigation of choice

• Specimen: CSF, blood (both before antibiotics if possible); throat swab for carriage; skin scraping/aspirate of petechiae.
• CSF must reach lab immediately at body temperature (37 °C) — organism is delicate and autolyses; do not refrigerate (contrast: most other specimens are refrigerated).
• Gram stain of CSF — Gram-negative diplococci within and outside neutrophils.
• Culture — blood agar, chocolate agar, MTM; oxidase +, ferments glucose and maltose.
• Latex agglutination / PCR of CSF — rapid antigen detection, useful when culture is negative (e.g., partially treated).
• Most definitive/confirmatory: culture; most rapid/sensitive when antibiotics already given: PCR.

High-yield: Meningococcal specimen handling = transport CSF without delay, at 37 °C, never refrigerated — a recurrent fact.

Management / drug of choice

Empirical (do not wait for culture): Ceftriaxone (or cefotaxime) IV — also covers pneumococcus and H. influenzae.

• Confirmed meningococcus: Ceftriaxone IV; penicillin G if susceptible.
• Add dexamethasone before/with first antibiotic dose (most benefit in pneumococcal; reduces neurological sequelae).
• Supportive care for shock/DIC; treat WFS with fluids, vasopressors, and hydrocortisone for adrenal insufficiency.

Chemoprophylaxis (very high-yield)

Given to close contacts of an index case (household, kissing, daycare, healthcare workers with mouth-to-mouth/intubation exposure):

Drug	Dose / note
Rifampicin	600 mg BD × 2 days (10 mg/kg children); turns secretions orange, avoid in pregnancy
Ciprofloxacin	500 mg single oral dose (adults)
Ceftriaxone	250 mg IM single dose — preferred in pregnancy

High-yield: Chemoprophylaxis flow → Rifampicin / Ciprofloxacin / Ceftriaxone. Ceftriaxone is the choice in pregnant contacts. The patient should also receive eradication therapy (ceftriaxone clears carriage; penicillin does not, so a treated patient still needs rifampicin/cipro to clear nasopharyngeal carriage).

Vaccination

• Conjugate quadrivalent (A, C, W-135, Y) — mandatory for Hajj/Umrah pilgrims and military recruits; given to asplenic, complement-deficient, and lab-workers.
• MenB (4CMenB / protein-based) — for serogroup B, which the polysaccharide vaccine cannot cover.
• Note: capsular polysaccharide vaccines are T-independent, poorly immunogenic in <2 years → conjugation overcomes this.

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Key differentials

• Other causes of urethral discharge: Chlamydia trachomatis (non-gonococcal urethritis, commonest co-infection), Mycoplasma genitalium, Trichomonas.
• Other causes of bacterial meningitis by age: Neonates — E. coli, Group B Streptococcus, Listeria; 6 months–6 years — S. pneumoniae, H. influenzae (declining with Hib vaccine); adolescents/young adults — meningococcus; elderly/immunocompromised — pneumococcus, Listeria.
• Petechial rash + fever DDx: meningococcaemia, Rocky Mountain spotted fever, leptospirosis, dengue, infective endocarditis.
• Moraxella catarrhalis — also an oxidase-positive Gram-negative diplococcus (commensal/respiratory pathogen) — a classic distractor; it does not ferment any sugars (asaccharolytic) and is DNase positive.

Recently asked / exam angle

• Sugar fermentation differentiation (glucose vs maltose) — repeatedly asked; N. lactamica ferments lactose (ONPG +).
• Composition of Thayer–Martin medium and the role of each VCN antibiotic.
• Specimen transport: "Which specimen must NOT be refrigerated?" → CSF for meningococcus.
• Waterhouse–Friderichsen syndrome — adrenal haemorrhage; single-best-answer image of haemorrhagic adrenals.
• Drug of choice for gonorrhoea (ceftriaxone) and why penicillin/quinolones are dropped (PPNG, resistance).
• Chemoprophylaxis agents and the pregnancy-safe choice (ceftriaxone).
• Why a patient treated with penicillin still needs chemoprophylaxis (penicillin doesn't eradicate carriage).
• Ophthalmia neonatorum timeline (gonococcal day 2–5 vs chlamydial day 5–14) and Crede's prophylaxis.
• Complement deficiency association with recurrent Neisseria infections and DGI.
• Fitz-Hugh–Curtis "violin-string" adhesions.
• Moraxella catarrhalis as the asaccharolytic oxidase-positive diplococcus distractor.

Rapid revision

1. Both Neisseria are oxidase-positive, Gram-negative diplococci; meningococcus has a capsule, gonococcus does not.
2. Glucose fermented by both; maltose only by meningococcus ("MeninGococcus = Maltose + Glucose").
3. Selective medium = Thayer–Martin (chocolate agar + Vancomycin, Colistin, Nystatin, Trimethoprim).
4. Gonococcus survives inside neutrophils; Gram stain of urethral pus diagnostic in symptomatic men.
5. Gonococcal complications: PID, Fitz-Hugh–Curtis (violin-string adhesions), ophthalmia neonatorum (day 2–5), DGI (arthritis–dermatitis).
6. Drug of choice for gonorrhoea = ceftriaxone; add doxycycline for Chlamydia co-infection; no gonococcal vaccine exists.
7. Meningococcus = leading cause of meningitis in adolescents/young adults; serogroup B needs a protein vaccine.
8. Waterhouse–Friderichsen syndrome = bilateral adrenal haemorrhage + shock in fulminant meningococcaemia.
9. CSF in meningococcal meningitis: turbid, neutrophilic, high protein, low glucose; transport at 37 °C, never refrigerate.
10. Empirical/definitive treatment of meningococcal meningitis = IV ceftriaxone/cefotaxime ± dexamethasone.
11. Chemoprophylaxis = rifampicin / ciprofloxacin / ceftriaxone; ceftriaxone in pregnancy; penicillin does not clear carriage.
12. Recurrent invasive Neisseria disease → suspect terminal complement (C5–C9)/properdin deficiency or eculizumab use; quadrivalent vaccine mandatory for Hajj pilgrims.