Describe the Neisseriae. Discuss meningococcal and gonococcal infection with their diagnosis, treatment and prevention.

General Features of the Neisseriae

• Gram-negative diplococci with adjacent flattened sides, giving a kidney or coffee-bean shape
• Oxidase positive and catalase positive — the oxidase test is the rapid presumptive identification
• Fastidious and delicate — they require enriched media (chocolate agar), a capnophilic atmosphere of 5 to 10% carbon dioxide, and are killed rapidly by drying, cold and sunlight. Specimens must therefore be plated immediately or sent in transport medium; they must never be refrigerated
• THAYER-MARTIN (or modified New York City) medium is chocolate agar made selective with vancomycin, colistin and nystatin, for isolation from sites with normal flora
• Sugar utilisation — meningococcus ferments glucose and maltose; gonococcus ferments glucose only

Neisseria Meningitidis

• Capsulated; serogroups A, B, C, W, X and Y cause nearly all disease. Group A caused the African "meningitis belt" epidemics; B and C predominate in Europe; A, B and C occur in India
• Man is the only reservoir; carriage in the nasopharynx is common (5 to 10%, higher in crowded conditions) and is usually harmless — disease is the exception, not the rule
• Transmission by respiratory droplets, favoured by crowding — hostels, barracks, pilgrimages and mass gatherings
• Clinical forms — meningitis (fever, headache, neck stiffness, photophobia, altered consciousness); meningococcaemia with a petechial and purpuric rash that does not blanch; and fulminant waterhouse-friderichsen syndrome — shock with bilateral adrenal haemorrhage and disseminated intravascular coagulation, which may kill within hours
• Complement deficiency of the terminal components (C5–C9) and asplenia predispose to recurrent meningococcal disease and should be sought after a second episode
• Diagnosis — lumbar puncture with Gram stain (gram-negative diplococci, often intracellular), culture of cerebrospinal fluid and blood, latex antigen detection and PCR (which remains positive after antibiotics)
• Treatment — ceftriaxone or benzylpenicillin, given immediately; in suspected meningococcal sepsis with a rash, the first dose should be given before transfer and before lumbar puncture
• Chemoprophylaxis of close contacts — rifampicin, ciprofloxacin or ceftriaxone, given promptly; and conjugate vaccines (ACWY and protein-based MenB), with vaccination required for Haj pilgrims

Neisseria Gonorrhoeae

• Non-capsulated; virulence depends on pili (adhesion, and antigenically highly variable), Opa proteins, IgA protease, and endotoxin. Antigenic variation of the pili is why infection confers NO lasting immunity and reinfection is common
• Transmission is almost exclusively sexual, and vertically at delivery; the organism does not survive outside the body
• In men — acute urethritis 2 to 5 days after exposure with purulent discharge and dysuria; complications are epididymo-orchitis, prostatitis and urethral stricture
• In women — frequently asymptomatic or mild (cervicitis, discharge), which is why it goes untreated and progresses to pelvic inflammatory disease with infertility, ectopic pregnancy and chronic pelvic pain. Perihepatitis (Fitz-Hugh-Curtis syndrome) may occur
• Ophthalmia neonatorum — acquired during passage through an infected birth canal; a purulent conjunctivitis within 2 to 5 days that rapidly causes corneal ulceration and blindness if untreated
• Disseminated gonococcal infection — fever, pustular skin lesions, tenosynovitis and migratory arthritis; associated with terminal complement deficiency
• Diagnosis — a Gram stain of urethral pus showing intracellular gram-negative diplococci within polymorphs is diagnostic in symptomatic men but insufficient in women; culture on Thayer-Martin with immediate plating; and nucleic acid amplification tests, which are now the most sensitive and can be done on urine
• Treatment — ceftriaxone intramuscularly, usually with azithromycin; resistance has developed to sulphonamides, penicillin, tetracyclines and fluoroquinolones in turn, and reduced cephalosporin susceptibility is now reported, so surveillance is essential

Comparison of the Two Pathogenic Neisseriae

Prevention and Applied Aspects

• Treat the sexual partners and screen for other sexually transmitted infections, particularly chlamydia, syphilis and HIV; co-infection with chlamydia is common, which is why dual therapy is given
• Syndromic management is used in India where laboratory facilities are limited, treating urethral or vaginal discharge for both gonococcus and chlamydia at the first visit
• Prevent ophthalmia neonatorum with prophylactic eye care at birth and by treating maternal infection antenatally; blindness from this cause is entirely preventable
• Any purulent conjunctivitis in the first week of life is gonococcal until proved otherwise, and requires systemic treatment, not merely drops
• Give the first antibiotic dose in suspected meningococcal disease before transfer; this single practice has measurably reduced mortality
• Investigate recurrent neisserial infection for terminal complement deficiency, and vaccinate such patients — a small group in whom a simple test changes lifelong management
• Plate gonococcal and meningococcal specimens immediately and never refrigerate them; the organisms are delicate, and a negative culture from a properly infected patient is usually a transport failure
• Vaccinate Haj and Umrah pilgrims against meningococcus, which is a requirement for entry and has prevented outbreaks associated with mass gatherings
• Gonorrhoea is often asymptomatic in women, so partner notification and treatment matter more than symptoms; the sequelae are borne almost entirely by women
• Gonococcal resistance has advanced through every drug class in turn, and there is now real concern about untreatable gonorrhoea; culture with sensitivities should be preserved wherever possible rather than relying only on molecular tests
• Do not delay the lumbar puncture beyond the antibiotic in suspected meningococcal disease — but equally, do not delay the antibiotic for the lumbar puncture; PCR and blood culture will usually still yield the diagnosis
• Look for the rash with the patient undressed and in good light, and use the tumbler test; early petechiae are sparse and easily missed on pigmented skin
• Meningococcal carriage is common and usually harmless, so throat swabbing of contacts is not useful; prophylaxis is given on the basis of exposure, not of carriage
• Give prophylaxis to close contacts within 24 hours — household members, those sharing a dormitory, and anyone with direct exposure to respiratory secretions including staff who intubated the patient
• Ceftriaxone is the preferred prophylaxis in pregnancy, since ciprofloxacin and rifampicin are avoided; and rifampicin reduces the effectiveness of oral contraceptives, which must be mentioned
• Screen for other sexually transmitted infections whenever one is found, and offer HIV testing with counselling; single-infection thinking misses the commonest pattern
• Ophthalmia neonatorum requires systemic treatment, not merely topical; and both parents must be examined and treated
• Chlamydial ophthalmia appears later than gonococcal — at 5 to 14 days rather than 2 to 5 — which is a useful clinical discriminator while awaiting laboratory confirmation
• Disseminated gonococcal infection presents as arthritis and skin lesions rather than as urethritis, and the genital infection may be silent, so it is regularly mistaken for a reactive or septic arthritis
• Meningococcal vaccines do not cover group B well in most formulations, because its capsule resembles human neural tissue; protein-based vaccines were developed specifically to solve that problem