Neisseria, Treponema pallidum and Clostridia

Neisseria

Gram-negative, kidney-shaped (coffee-bean) diplococci, often intracellular in neutrophils; oxidase-positive, catalase-positive; grow best in 5–10% CO₂ on chocolate agar or Thayer-Martin (selective); fragile (die quickly outside the body).

Both have IgA protease, pili and LPS (lipooligosaccharide); terminal complement (C5–C9) deficiency predisposes to recurrent infections with both.

Neisseria meningitidis

Virulence: polysaccharide capsule (main factor), endotoxin (LOS) (very high levels → shock, DIC), pili, IgA protease.

Epidemiology: carried in the nasopharynx of a minority of healthy people (more in crowded settings: hostels, barracks, Hajj and Umrah pilgrims); epidemics of serogroup A in the African "meningitis belt"; infants, adolescents and young adults most affected.

Diseases:

• Meningitis: fever, headache, neck stiffness, photophobia, vomiting, confusion; Kernig and Brudzinski signs; bulging fontanelle in infants.
• Meningococcal septicaemia (meningococcaemia): rapid onset fever, shock, non-blanching petechial or purpuric rash (glass test), DIC; Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhage with shock); can kill within hours.
• Complications: deafness, limb loss (gangrene), neurological damage.

Laboratory: CSF (turbid; high neutrophils, high protein, low glucose; Gram-negative diplococci), CSF and blood culture, PCR (useful after antibiotics), latex antigen tests, skin lesion scraping.

Management and prevention:

• Do not delay antibiotics: benzylpenicillin IM/IV in the community if meningococcal disease is suspected, then ceftriaxone (or cefotaxime) in hospital.
• Chemoprophylaxis for close contacts (household, kissing contacts): rifampicin (2 days), ciprofloxacin (single dose) or ceftriaxone (single IM dose; safe in pregnancy).
• Vaccines: conjugate ACWY (required for Hajj/Umrah), MenB, MenC; MenAfriVac in Africa.
• Notifiable disease.

Neisseria gonorrhoeae

Virulence: pili (adhesion; antigenic variation → repeated infections, no vaccine), Opa proteins, IgA protease, LOS, β-lactamase plasmids.

Diseases:

• Men: acute urethritis with purulent discharge and dysuria; epididymitis, prostatitis; urethral strictures.
• Women: often asymptomatic cervicitis; pelvic inflammatory disease (salpingitis → infertility, ectopic pregnancy), Fitz-Hugh-Curtis perihepatitis.
• Disseminated gonococcal infection: fever, pustular skin lesions on extremities, tenosynovitis, septic arthritis (commonest cause in young sexually active adults).
• Ophthalmia neonatorum: purulent conjunctivitis within 2–5 days of birth; can perforate the cornea → blindness. Prevented by eye prophylaxis (erythromycin or tetracycline ointment, povidone-iodine) and treating mothers.
• Pharyngitis, proctitis.

Laboratory: Gram stain of urethral pus in men (intracellular Gram-negative diplococci in neutrophils: highly specific); culture on Thayer-Martin (sensitivities); nucleic acid amplification tests (NAAT) on urine or swabs (most sensitive; also detect Chlamydia).

Treatment: ceftriaxone IM (single dose) per current guidelines, plus treatment for Chlamydia (co-infection common) if not excluded; treat partners.

Treponema pallidum (syphilis)

The organism

• Thin, tightly coiled spirochaete, motile (corkscrew); too thin for Gram stain.
• Seen by dark-field microscopy (from chancres and condylomata) or silver stain, direct fluorescent antibody.
• Cannot be cultured in artificial media (rabbit testes).
• Very sensitive to drying, heat and penicillin (no resistance has developed).
• Spread sexually, transplacentally (any stage of pregnancy; most likely in early syphilis), rarely by blood.

Stages

Congenital syphilis

Transplacental infection → stillbirth, hydrops, prematurity.

• Early (under 2 years): snuffles (bloody nasal discharge), rash (palms and soles, peeling), hepatosplenomegaly, jaundice, periostitis, pseudoparalysis.
• Late: Hutchinson teeth (notched incisors), mulberry molars, interstitial keratitis, eighth nerve deafness (Hutchinson triad), saddle nose, sabre shins, frontal bossing, rhagades.
• Prevented by antenatal serological screening and penicillin treatment of the mother.

Serological tests

Treatment

• Benzathine penicillin G IM: single dose (early syphilis) or three weekly doses (late latent, unknown duration).
• Neurosyphilis: IV benzylpenicillin (aqueous) for 10–14 days.
• Pregnancy: penicillin is the only reliable treatment (desensitise if allergic).
• Jarisch-Herxheimer reaction: fever, chills, headache, myalgia and worsening rash a few hours after the first dose, from release of treponemal antigens/endotoxin-like products as organisms die; most common in secondary syphilis; treated with antipyretics; also occurs in leptospirosis and relapsing fever.
• Contact tracing; screen for HIV and other STIs.

Clostridia

Gram-positive, spore-forming, obligate anaerobic bacilli; found in soil and the gut. Spores survive boiling; destroyed by autoclaving.

Clostridium tetani: tetanus

• Terminal spores ("drumstick" or tennis-racket appearance); spores enter wounds (puncture wounds, burns, dirty wounds, unhygienic delivery practices and umbilical cord care (neonatal tetanus), ear piercing, IV drug use).
• In anaerobic tissue, spores germinate and release tetanospasmin, which travels by retrograde axonal transport to the spinal cord and brainstem and blocks release of inhibitory transmitters (glycine and GABA) from Renshaw cells.
• Features: trismus (lockjaw) (often the first sign), risus sardonicus, neck and back stiffness, opisthotonos, painful generalised spasms triggered by noise or touch, dysphagia, laryngospasm, autonomic instability; consciousness preserved. Neonatal tetanus: day 3–14, baby stops sucking, spasms; high mortality.
• Diagnosis is clinical (culture often negative).
• Treatment: wound debridement, human tetanus immunoglobulin (HTIG) to neutralise unbound toxin, metronidazole (or penicillin), benzodiazepines for spasms, magnesium sulphate, airway and ventilation, quiet dark room; give tetanus toxoid (the disease does not give immunity).
• Prevention: tetanus toxoid in childhood (pentavalent vaccine in EPI) and boosters; TT/Td vaccination of women of childbearing age and pregnant women (prevents maternal and neonatal tetanus), clean delivery and clean cord care; wound management with toxoid ± immunoglobulin.

Clostridium botulinum: botulism

• Toxin blocks acetylcholine release at the neuromuscular junction and autonomic synapses (cleaves SNARE proteins); the most potent toxin known; destroyed by boiling (spores are not).
• Food-borne: preformed toxin in home-canned or preserved foods (vegetables, fish, meat), 12–36 hours after eating.
• Infant botulism: spores ingested (honey, dust) germinate in the infant gut: "floppy baby", constipation, weak cry, poor feeding. Do not give honey under 1 year.
• Wound botulism (IV drug users).
• Features: descending symmetrical flaccid paralysis starting with cranial nerves (diplopia, ptosis, dysarthria, dysphagia), dilated unreactive pupils, dry mouth, then limb and respiratory weakness; no fever, no sensory loss, alert.
• Treatment: antitoxin (equine for adults; human botulism immunoglobulin for infants), supportive ventilation.
• Therapeutic botulinum toxin (Botox): dystonia, spasticity, achalasia, hyperhidrosis, cosmetic.

Clostridium perfringens

• Large, non-motile, capsulated rods; spores rarely seen in tissue; double zone of haemolysis on blood agar; grows very fast.
• α-toxin = lecithinase (phospholipase C): destroys cell membranes → haemolysis and myonecrosis. Shown by the Nagler reaction (opacity on egg-yolk agar inhibited by antitoxin).
• Gas gangrene (clostridial myonecrosis): deep, contaminated, crushed or ischaemic wounds (war injuries, road accidents, septic abortion) → severe pain, swelling, crepitus (gas in tissue), bronze or black skin, foul serosanguinous discharge, shock. Treatment: urgent surgical debridement or amputation, high-dose penicillin + clindamycin, hyperbaric oxygen.
• Food poisoning: spores survive cooking of meat and gravy left warm; enterotoxin released in the gut → watery diarrhoea and cramps 8–16 hours later, without vomiting or fever; self-limiting.
• Enteritis necroticans (pigbel).

Clostridioides difficile

• Normal gut flora in some; spores spread in hospitals (hands, surfaces; alcohol gel does not kill spores: wash with soap and water; clean with chlorine).
• After antibiotics (clindamycin, cephalosporins, fluoroquinolones, co-amoxiclav) and PPIs, it overgrows and releases toxin A (enterotoxin) and toxin B (cytotoxin).
• Pseudomembranous colitis: watery diarrhoea, abdominal pain, fever, raised white cells; yellow-white plaques (pseudomembranes) on colonoscopy; can cause toxic megacolon and perforation.
• Diagnosis: stool toxin detection (EIA) with GDH antigen, PCR for toxin genes.
• Treatment: stop the culprit antibiotic; oral vancomycin or fidaxomicin (metronidazole only for mild disease when others unavailable); faecal microbiota transplant for recurrent disease; isolation.

Quick revision

• Neisseria: Gram-negative diplococci, oxidase +. Meningococcus: maltose +, capsule, vaccine. Gonococcus: glucose only, no capsule.
• Meningococcaemia: purpura, DIC, Waterhouse-Friderichsen; benzylpenicillin early; rifampicin/ciprofloxacin for contacts.
• Gonorrhoea: urethritis, PID, ophthalmia neonatorum (2–5 days); ceftriaxone.
• Syphilis: painless chancre → palms/soles rash, condylomata lata → latent → gumma, aortitis, neurosyphilis.
• VDRL/RPR: screen, monitor, false + in SLE. TPHA/FTA-ABS: confirm, lifelong.
• Benzathine penicillin; Jarisch-Herxheimer after first dose.
• Tetanus: glycine/GABA blocked → spasms, trismus; HTIG, metronidazole, toxoid.
• Botulism: ACh blocked → descending flaccid paralysis; honey in infants.
• C. perfringens: gas gangrene (lecithinase). C. difficile: pseudomembranous colitis (oral vancomycin).

Written by The House Job from standard microbiology references (Levinson's Review of Medical Microbiology and Immunology).

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