Diphtheria


 Diphtheria is a bacterial infection due to Corynebacterium diphtheriae, characterized by proliferation of the bacteria in the upper respiratory tract and systemic diffusion of the diphtheria toxin through the body.
– The infection is spread by droplets (coughing, sneezing, speaking) from the upper respiratory tract of a patient or carrier.
– The disease does not confer sufficient immunity. Immunisation protects against the effects of the toxin but does not prevent individuals from becoming carriers.

Clinical features

– Signs related to the infection:
• Pseudomembranous tonsillitis (grey, tough and very sticky membranes) with dysphagia and cervical adenitis, at times progressing to massive swelling of the neck;
• Airway obstruction and possible suffocation when the infection extends to the nasal passages, the larynx, the trachea and the bronchi;
• Fever is generally low-grade.

– Generalised signs due to the toxin, they determine the prognosis:
• Cardiac dysfunction (gallop on auscultation, arrhythmias), myocarditis with severe heart failure at times leading to cardiogenic shock;
• Neuropathies 1 to 3 months after the onset of the disease leading to difficulty with: swallowing (paralysis of the soft palate), vision (ocular motor paralysis), breathing (paralysis of respiratory muscles) and ambulation (limb paralysis);
• Oliguria, anuria and renal failure.

Laboratory

Confirmation is made by culturing a toxigenic strain of C. diphtheriae from a throat swab.

Treatment

– Careful examination of the throat.
– Strict isolation of patients; contact and droplet precautions for medical staff (gloves, gown, masks and handwashing).
– Administration of diphtheria antitoxin derived from horse serum. Do not wait for bacteriological confirmation any delay can diminish efficacy. Administer according to the Besredka method to assess possibility of allergy.

 Risk of an anaphylactic reaction, especially in patients with asthma. Close monitoring of the patient is essential, with immediate availability of equipment for manual ventilation (Ambu bag, face mask) and intubation, Ringer lactate and epinephrine.

Besredka method: inject 0.1 ml SC and wait 15 minutes. If there is no allergic reaction (no erythema at the injection site or a flat erythema of less than 0.5 in diameter, inject a further 0.25 ml SC. If there is no reaction after 15 minutes, inject the rest of the product IM or IV depending on the volume to be administered.

Doses are given as a function of the severity of illness, and the delay in treatment:

Clinical signs

Dose in units

Administration route

Laryngitis or pharyngitis
or duration < 48 hours

20 to 40 000


IM or IV infusion in 250 ml of 0.9% sodium chloride in 2 to 4 hours for doses of more than 20 000 UI.

Rhinopharyngitis

40 to 60 000

Severe form, cervical oedema
or duration ≥ 48 hours

80 to 100 000


– Antibiotherapy for 14 days (or according to length of treatment recommended by the national protocol):
• If the patient can swallow:
azithromycin PO
Children: 20 mg/kg once daily (max. 500 mg daily)
Adults: 500 mg once daily
or
erythromycin PO
Children: 30 to 50 mg/kg daily1
Adults: 1 g 2 times daily
or
phenoxymethylpenicillin (penicillin V) PO
Children under 1 year: 12.5 mg/kg 4 times daily (max. 500 mg daily)
Children from 1 to 6 years: 125 mg 4 times daily
Children over 6 years and adults: 250 mg 4 times daily

• If the patient cannot swallow, start with one of the treatments below and change as soon as possible to oral route with one of the oral treatments above to complete 14 days of treatment:
procaine benzylpenicillin IM1
Children: 50 000 IU/kg (= 50 mg/kg) once daily (max. 1.2 g daily)
Adults: 1.2 MIU (1.2 g) once daily 
 Never administer procaine benzylpenicillin by IV injection.
or, if  not available,
benzylpenicillin IM or slow IV (3 minutes)
Children: 50 000 IU/kg (= 30 mg/kg) every 6 hours (max. 4 MIU or 2.4 g daily)
Adults: 1 MIU (600 mg) every 6 hours
In penicillin-allergic patients, use erythromycin IV2 .

– Urgent intervention to secure an airway (intubation, tracheotomy) may be necessary in the event of laryngeal obstruction, cardiac or neurologic complications.

Management of close contacts

Close contacts include family members living under the same roof and people who were directly exposed to nasopharyngeal secretions of the patient on a regular basis (e.g. children in the same class, medical personnel).

– Throat culture; temperature and throat examination daily (7 days); exclusion from school or work until 48 hours of antibiotics have been completed.
– Antibiotherapy:
benzathine benzylpenicillin IM
Children under 30 kg (or under 10 years): 600 000 IU single dose
Children 30 kg and over (or 10 years and over) and adults: 1.2 MIU single dose
Benzathine benzylpenicillin should NEVER be administered by IV route.

In penicillin-allergic patients, use azithromycin or erythromycin PO as above for 7 days.

– Verify vaccination status:
• Less than 3 injections: complete with DTP, DT or Td according to age;
• 3 injections: if the last injection was given more than one year before, give a booster dose.
– Medical personnel in direct contact with patients: one dose of Td (booster).

Prevention

– Once the patient has recovered update their immunisations.
– Routine vaccination (EPI), for information: DTP: 3 doses at one month intervals before the age of 1 year, DTP booster one year later, and DT (diphtheria 30 IU/tetanus) at 6 years of age followed by 3 more Td (diphtheria 3 IU/tetanus) boosters at 10 year intervals.
– Mass vaccination (epidemic): update routine immunisations with DTP for children under 3 years of age; DT for children from 3 to 6 years of age; Td for children over 7 years of age and adults.



Footnotes
Ref Notes
1 For exact dosage according to age or weight, see erythromycin in the guide Essential drugs, MSF.
2 erythromycin IV infusion (60 minutes)
Children: 12.5 mg/kg every 6 hours (max. 2 g daily); adults: 500 mg every 6 hours
Erythromycin powder (1 g) should be reconstituted in 20 ml of water for injection only. Then, dilute each dose of erythromycin in 10 ml/kg of 0.9% sodium chloride in children less than 20 kg and in a bag of 250 ml of 0.9% sodium chloride in children over 20 kg and in adults. Do not dilute in glucose.


References

  1. Word Health Organization. Pocket book for hospital care in children: guidelines for the management of common childhood illnesses, 2013.
    http://apps.who.int/iris/bitstream/handle/10665/81170/9789241548373_eng.pdf;jsessionid=CE5C46916607EF413AA9FCA89B84163F?sequence=1 [Accessed 2 September 2018]