Paediatrics chapters
Diphtheria
Diphtheria in children: Corynebacterium diphtheriae and its toxin, how it spreads, the adherent grey membrane, bull neck and laryngeal obstruction, myocarditis and neuropathy, diagnosis, antitoxin and antibiotics, and control by vaccination.
- Diphtheria is caused by toxin-producing Corynebacterium diphtheriae (Gram-positive club-shaped rods), spread by droplets from cases and, mostly, carriers; the bacteria stay on the mucosa and their exotoxin (made only by strains carrying a phage gene) forms an adherent grey pseudomembrane that bleeds when removed.
- Pharyngeal disease gives mild fever but a toxic child, tachycardia out of proportion, sometimes bull neck; laryngeal spread causes stridor and obstruction; the absorbed toxin causes myocarditis (weeks 2-6) and neuropathy (palatal palsy first, then eye and limb muscles).
- Treat on clinical suspicion: antitoxin early (dose by extent and duration), penicillin or erythromycin, airway support, rest with serial ECGs; isolate, culture and treat carriers and contacts; prevent with DPT (pentavalent) vaccination and boosters.
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Overview
Diphtheria is an acute toxin-mediated infection of the upper respiratory tract (and sometimes skin) caused by Corynebacterium diphtheriae. The bacteria stay at the surface, but their exotoxin kills local tissue to form a membrane and travels in the blood to damage the heart and nerves. It still causes outbreaks among unvaccinated children in Pakistan. Exams test the membrane, bull neck, the complications and their timing, antitoxin, and contact management.
Organism
- Corynebacterium diphtheriae: a Gram-positive, non-motile, club-shaped rod with a beaded look.
- Biotypes: gravis, mitis, intermedius (and belfanti); gravis tends to cause more severe disease.
- Only strains infected by a bacteriophage (beta phage) carrying the toxin gene produce toxin; non-toxigenic strains can become toxigenic.
- Grows on Loeffler serum medium and tellurite agar.
- Sensitive to penicillin; killed by heat and disinfectants.
Toxin
- An extremely potent inhibitor of protein synthesis in host cells.
- Locally: hyperaemia, oedema and death of surface epithelium, which with fibrin, white cells and bacteria forms the pseudomembrane.
- Absorbed toxin targets the myocardium, peripheral nerves, kidneys, liver and adrenals.
- Once bound to cells, toxin cannot be neutralised: hence early antitoxin.
Transmission and epidemiology
- Humans only: mucous membranes and skin.
- Spread by droplets and respiratory secretions; also from skin lesions and, briefly, contaminated objects.
- Carriers matter more than cases: Park estimates about 95 carriers for every 5 clinical cases; nasal carriers shed most.
- Vaccination prevents disease, not carriage (the vaccine is a toxoid against the toxin, not the bacterium).
- Incubation: 2-6 days (Akbar 2-4 days).
- Affects mainly children aged 1-5 years; in well-vaccinated communities the age shifts to older children and adults.
- More common in winter, crowding, poor hygiene and low vaccine coverage.
- Akbar: mortality in immunised or partly immunised patients is about one-tenth of that in the unimmunised.
Clinical diagnosis
Pharyngeal (faucial) diphtheria: the commonest and most toxic form
- Insidious onset: mild to moderate fever, malaise, headache; sore throat is not prominent.
- Grey (greyish-white to dirty grey) membrane on one or both tonsils, often spreading to the uvula, soft palate and pharynx.
- The membrane is adherent; trying to lift it causes bleeding.
- Toxic, prostrated child with dull sensorium even though fever is modest.
- Pulse faster than the fever explains (early toxic effect on the heart).
- Bull neck: enlarged cervical nodes plus brawny oedema of the neck soft tissues; marks severe disease.
- Difficulty swallowing; palatal palsy may follow (nasal voice, nasal regurgitation).
Laryngeal diphtheria
- Usually spread down from the pharynx.
- Hoarseness, brassy (croupy) cough, stridor, recession; anxiety and cyanosis.
- Can cause suffocation unless the airway is secured by intubation or tracheostomy.
Nasal diphtheria
- The mildest form, but infectious.
- Serosanguineous or blood-stained nasal discharge, often one-sided, with excoriation of the upper lip; a white membrane may be seen on the septum. Mimics a nasal foreign body.
Cutaneous diphtheria
- Chronic, non-healing, punched-out ulcer with a grey-brown membrane; common in the tropics.
- Little toxicity, but an important reservoir.
In diphtheria the fever is low and the sore throat mild, but the child looks very ill. In streptococcal tonsillitis the fever is high and swallowing is painful, and the exudate wipes off without bleeding.
Differential diagnosis of a membrane on the throat
| Condition | Distinguishing features |
|---|---|
| Streptococcal tonsillitis | High fever, painful swallowing, non-adherent exudate |
| Infectious mononucleosis | Generalised lymphadenopathy, splenomegaly, atypical lymphocytes, positive Paul-Bunnell test |
| Oral thrush | White patches on tongue and cheeks, little systemic upset |
| Herpetic stomatitis | Painful shallow ulcers on gums, tongue and cheeks |
| Agranulocytosis | White membrane; diagnosis from very low neutrophil count |
| Epiglottitis (for laryngeal form) | Very toxic, high fever, drooling, "cherry-red" epiglottis |
| Viral croup | Prominent barking cough, non-toxic, low fever |
"Grey, glued, gory and goes beyond the tonsil": the diphtheria membrane is grey, adherent, bleeds when lifted and spreads past the tonsil.
Complications
| Complication | Timing | Features |
|---|---|---|
| Airway obstruction | Early | Laryngeal membrane, bull neck; aspiration of membrane |
| Toxic myocarditis | Day 2 to week 6 (commonest in weeks 2-6; circulatory failure often in week 2) | Rapid thready pulse, faint heart sounds, gallop, hepatomegaly, heart failure; arrhythmias and heart block (prolonged PR, ST-T changes, complete block) |
| Palatal and pharyngeal palsy | Weeks 1-2 | Nasal voice, nasal regurgitation, choking |
| Ocular palsy | Week 3 | Diplopia, squint, blurred vision (loss of accommodation) |
| Peripheral neuritis | Weeks 5-7 | Limb weakness, lost tendon reflexes; can resemble Guillain-Barre (similar CSF); recovers fully if the child survives |
| Respiratory paralysis | Weeks 6-8 | Needs ventilation |
| Others | Any time | Secondary bronchopneumonia (laryngeal form), renal involvement (albuminuria, transient), hepatitis, adrenal haemorrhage, low platelets |
Toxic myocarditis is the leading cause of death (Akbar: 50-60% of deaths). A tachycardia out of proportion to fever is an early warning; do serial ECGs.
Neuropathy follows a set order: palate first (week 1-2), eyes next (week 3), limbs last (weeks 5-7), and it always recovers if the child survives.
Investigations
- Throat and nasal swabs (taken from beneath the edge of the membrane if possible) for culture on Loeffler and tellurite media; results take 16-48 hours.
- Toxin testing of the isolate (virulence testing) confirms a toxigenic strain.
- Direct smear is unreliable; finding staphylococci or streptococci does not exclude diphtheria.
- Cultures may be negative after antibiotics.
- Blood count: white count normal or slightly raised; possible low platelets and haemolysis.
- ECG at presentation and repeatedly.
Do not wait for culture: treat on clinical suspicion, because delay in antitoxin increases toxin binding.
Management
Aims
Neutralise circulating toxin, stop further toxin production, control local infection, support the patient through toxic damage, and prevent spread.
1. Diphtheria antitoxin (DAT)
- Give as early as possible (ideally within 48 hours); it neutralises only unbound toxin.
- Equine (horse) serum: test for sensitivity first and keep adrenaline ready for anaphylaxis.
- Give as a single IV dose (repeated horse serum increases sensitisation).
- Dose depends on extent and duration, not weight (Akbar):
| Disease | Antitoxin dose |
|---|---|
| Cutaneous diphtheria | About 20,000 units |
| Limited pharyngeal disease of 2 days or less | 20,000-40,000 units |
| Moderate nasopharyngeal disease (Park) | 40,000-60,000 units |
| Extensive disease, 3 days or more, bull neck | 80,000-100,000 units |
2. Antibiotics
- Penicillin (benzyl penicillin) or erythromycin (Akbar: erythromycin 40-50 mg/kg/day orally or IV).
- They stop toxin production and spread, but are not a substitute for antitoxin.
- Repeat cultures after treatment to confirm clearance (resistance, especially to erythromycin, can occur).
3. Supportive care
- Airway: intubation or tracheostomy for laryngeal obstruction, before the child is exhausted.
- Strict bed rest for 2-3 weeks, longer with myocarditis; activity can worsen myocarditis.
- ECG 2-3 times a week for 4-6 weeks; treat heart failure and arrhythmias.
- Nasogastric feeding when palatal or pharyngeal palsy threatens aspiration.
- Ventilation for respiratory muscle paralysis.
- Fluid and electrolyte balance.
4. Isolation and notification
- Droplet precautions for pharyngeal disease; contact precautions for skin disease.
- Isolate until two (Akbar: three) consecutive nose and throat cultures, 24 hours apart, are negative after antibiotics stop.
- Notify all suspected cases to the health authorities.
Recovery from diphtheria does not guarantee immunity (Akbar: about half do not develop it), so vaccinate the child during convalescence.
Carriers and contacts
Carriers
- Detected only by culture of nose and throat swabs.
- Treat all carriers: erythromycin orally (Park: a 10-day course is most effective) or a single IM dose of benzathine penicillin.
- Keep at home until cultures are negative.
Contacts
- Examine daily for about a week; take nose and throat swabs.
- Give prophylactic penicillin or erythromycin.
- Immunisation: a booster if the last dose was more than a few years ago (Park: more than 2 years); a full course if unimmunised.
- Start treatment at once if a contact develops signs.
Vaccination and prevention
- Diphtheria toxoid (formalin-treated toxin, adsorbed on aluminium) given as DPT, now within the pentavalent vaccine (DPT + hepatitis B + Hib) in Pakistan's EPI at 6, 10 and 14 weeks, IM in the anterolateral thigh. Some provinces add a booster; check the current national schedule at the Federal Directorate of Immunization (EPI Pakistan) (checked 8 Nov 2026).
- Older children and adults receive the low-dose adult-type (Td) preparation, which carries far less diphtheria toxoid.
- Protective level: antitoxin of at least about 0.01 units/mL.
- Because vaccination does not prevent carriage, coverage must stay high; boosters maintain immunity.
- Store DPT-containing vaccines at 2-8°C; never freeze.
Expect: C. diphtheriae as a Gram-positive club-shaped rod whose toxin depends on a bacteriophage gene; droplet spread with carriers as the main reservoir; a grey, adherent membrane that bleeds when removed and extends beyond the tonsil; low fever, toxic child and tachycardia out of proportion; bull neck; laryngeal obstruction; myocarditis (weeks 2-6) as the commonest cause of death; palatal palsy then ocular palsy then peripheral neuritis; culture on Loeffler and tellurite media; early antitoxin after sensitivity testing with dose by extent, plus penicillin or erythromycin; bed rest with serial ECGs; treatment of carriers with erythromycin; vaccination after recovery; DPT/pentavalent and Td.
Quick revision
- C. diphtheriae: Gram-positive club rod; toxin via beta-phage gene; man only host.
- Droplets; carriers outnumber cases; vaccine does not stop carriage.
- Grey adherent membrane, bleeds on removal; low fever, toxic child; bull neck.
- Laryngeal form: croupy cough, stridor; secure the airway early.
- Myocarditis weeks 2-6 (main killer); palate weeks 1-2, eyes week 3, limbs weeks 5-7.
- Swabs for Loeffler and tellurite culture; treat before results.
- Antitoxin early, single IV dose after sensitivity test; penicillin or erythromycin.
- Isolate, notify, treat carriers, protect contacts; vaccinate survivors; DPT/pentavalent.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Park's Preventive and Social Medicine).
FAQ
Why is antitoxin given before the culture result?
Antitoxin can only neutralise toxin that has not yet entered cells, and toxin keeps being made and absorbed from the membrane. Waiting 1-2 days for culture lets more toxin bind to heart and nerves.
Why does the membrane bleed when removed?
It is formed from dead epithelium, fibrin and white cells that are firmly stuck to the inflamed tissue underneath; pulling it off tears the small vessels beneath.
Why does a vaccinated child still sometimes carry C. diphtheriae?
The vaccine is a toxoid that produces antibody against the toxin, not against the bacterium, so it prevents disease but not colonisation of the throat.
Does a child who recovers from diphtheria need vaccination?
Yes. Natural infection often fails to produce lasting immunity, so the child should be vaccinated during recovery.