Dr. Abdulaziz medicine15/5/2030

Diphtheria .

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Definition Diphtheria is an acute, toxin-mediated disease

caused by toxigenic Corynebacterium diphtheriae

It’s a very contagious and potentially life-threatening bacterial disease.

It’s a localized infectious disease, which usually attacks the throat and nose mucous membrane

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Etiology C. diphtheriae is an aerobic gram-positive bacillus.

Pleomorphic, club-end Non-spore-forming Non-acid-fast Non-motile

Epidemiology Transmission

Transmission is most often person-to-person spread from the respiratory tract (by small droplet when coughing or sneezing).

Rarely, transmission may occur from skin lesions or articles soiled with discharges from lesions of infected persons.

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Epidemiology Sources of infection

Patients and asymptomatic carriers Patients: Transmission time is variable,

usually persist 12 days or less, and seldom more than 4 weeks, without antibiotics.

Diphtheria occurs worldwide, but clinical cases are more prevalent in temperate zones, and in socioeconomic conditions of poor personal hygiene, crowding and limited access to medical care.

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Pathogenesis and pathology

Susceptible persons may acquire toxigenic diphtheria bacilli in the nasopharynx, skin, middle ear or anterior nares.

The organism produces a toxin that inhibits cellular protein synthesis and is responsible for local tissue destruction and pseudomembrane formation.

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Pathogenesis and pathology

The pseudomembrane consists of coagulated fibrin, inflammatory cells, destructed mucous tissues and bacteria.

The pseudomembrane in larynx, trachea or bronchia may have the potential for airway obstruction.

The toxin is responsible for the major complications of myocarditis and neuritis, and can also cause low platelet

counts (thrombocytopenia) and protein in the urine (proteinuria).

It was eradicated from much of the developed world by mass vaccination in the mid-20th century.

Recent outbreaks have occurred in the former Soviet Union and continue to occur in South-east Asia.

Diphtheria

Clinical features

The average incubation period is 2-4 days.

The disease begins insidiously with a sore throat.

Despite modest fever there is usually marked tachycardia.

The diagnostic feature is the 'wash-leather' elevated greyish-green membrane on the tonsils. It has a well-defined edge, is firm and adherent, and is surrounded by a zone of inflammation.

There may be swelling of the neck ('bull-neck') and tender enlargement of the lymph nodes.

Clinical features of diphtheria

Acute infection Membranous tonsillitis or Nasal infection or Laryngeal infection or Skin/wound/conjunctival infection (rare)

Complications Laryngeal obstruction or paralysis Myocarditis Peripheral neuropathy

Pharyngeal diphtheria

Insidious onset of exudative pharyngitis Exudate spreads to form adherent

“pseudomembrane” can lead to respiratory obstruction and death by

asphyxiation

Fever not high, but patient appears toxic

Pharyngeal Diphtheria: Local Features

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Pharyngeal diphtheria

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Pharyngeal diphtheria

Pharyngeal Diphtheria: Distant Complications

Myocarditis Cardiac arrythmias in acute phase Sudden death Prolonged damage and arrythmia

Neuropathy Motor neuropathy Paralysis of soft palate from 3rd

week Eye muslces, limbs, diaprhagm after

5th week Spontaneous resolution

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Laryngeal diphtheria Laryngeal diphtheria can be either an

extension of the pharyngeal form (often) or the only site involved (rarely).

Symptoms include mild fever (with little absorption of toxin), dyspnea, hoarseness, and a barking cough.

The pseudomembrane can lead to airway obstruction, coma, and death.

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Laryngeal diphtheria

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Anterior nasal diphtheria

The onset is indistinguishable from that of the common cold and is usually characterized by a mucopurulent nasal discharge (containing both mucus and pus) which may become blood-tinged.

A white pseudomembrane usually forms on the nasal septum.

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Cutaneous and Other site diphtheria

Skin infections are quite common in the tropics and are probably responsible for the high levels of natural immunity found in these populations.

Skin infections may be manifested by a scaling rash or by ulcers with clearly demarcated edges and pseudomembrane.

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Cutaneous (skin) diphtheria

Death from acute circulatory failure may occur within the first 10 days.

About 25% of survivors of the early toxaemia may later develop myocarditis with arrhythmias or cardiac failure

Neurological involvement occurs in 75% of cases.

usually starts after 10 days with palatal palsy.

Paralysis of accommodation often follows, manifest by difficulty in reading small print.

Generalised polyneuritis with weakness and paraesthesia may follow in the next 10-14 days.

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Laboratory findings Routine examination

Leukocytosis, 10~20 G/L, neutrophil is dominant. Low platelet count (thrombocytopenia), rise profiles of the serum enzyme tests and proteinuria were

found in serious cases. Bacteriological examinations

Smear and gram stain can found C. diphtheriae, but can not identify from the diphtheroids.

Fluorescent antibody-stain can found toxigenic C. diphtheriae, favourable for early diagnosis, but definitive diagnosis (false positive).

C. diphtheriae can be cultured from the swabs from nose, pharynx or other sites.

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Treatments Treatment should begin once appropriate swabs

have been taken before waiting for microbiological confirmation.

Strict isolation Use antitoxin and antibiotics for neutralization of

free toxin, elimination of further toxin production and to control local infection.

Use supportive interventions during disintoxication.

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Treatments Diphtheria antitoxin

Diphtheria antitoxin, produced in horses. It will not neutralize toxin that is already

fixed to tissues, but will neutralize circulating toxin.

Early use will prevent progression of disease.

The earlier, the better.

Diphtheria antitoxin

In a severely ill patient the risk of anaphylactic shock is outweighed by the mortal danger of diphtheritic toxaemia, and up to 100 000 U of antitoxin are injected intravenously if the test dose has not given rise to symptoms. For disease of moderate severity, 16 000-40 000 U i.m. will suffice, and for mild cases 4000-8000 U

reactions to this foreign protein include a potentially lethal immediate anaphylactic reaction and a 'serum sickness' with fever, urticaria and joint pains, which occurs 7-12 days after injection.

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Treatments Antibiotics

Prevention of further toxin production. Control local infection. Reduction of transmission.

Penicillin (1200 mg 6-hourly i.v.) or amoxicillin (500 mg 8-hourly) should be administered for 2 weeks to eliminate C. diphtheriae.

Erythromycin orally or by injection (40-50 mg/kg/day; maximum, 2 gm/day) for 14 days.

prevention

Active immunisation should be given to all children.

If diphtheria occurs in a closed community, contacts should be given erythromycin.

All contacts should also be immunised or given a booster dose of toxoid.

Pneumococcal infection

Strep. pneumoniae (the pneumococcus) is the leading cause of community-acquired pneumonia globally and one of the leading causes of infection-related mortality.

Otitis media, meningitis and sinusitis are also

frequently due to Strep. pneumoniae. Asplenic individuals are at risk of fulminant

pneumococcal disease with purpuric rash.

Vaccination of infants with pneumococcal vaccine decreases Strep. pneumoniae infection in infants and in their relatives.

The polysaccharide pneumococcal vaccine is used in individuals predisposed to Strep. pneumoniae infection and the elderly, but only modestly reduces pneumococcal bacteraemia and does not prevent pneumonia.

All asplenic individuals should receive vaccination against Strep. pneumoniae.

Anthrax

B. anthracis was the first recognised bacterial pathogen described by Koch and became the model pathogen for 'Koch's postulates'

It is a Gram-positive organism with a central spore. The spores can survive for years in soil.

EPIDEMIOLOGY Anthrax is an endemic zoonosis in many

countries; it causes human disease following inoculation

of the spores of Bacillus anthracis. Infection is commonly acquired from contact

with animals, particularly herbivores. The ease of production of B. anthracis spores

makes this infection a candidate for biological warfare or bioterrorism.

Clinical features

There are three recognised forms of infection with Bacillus anthracis:

cutaneous anthrax gastrointestinal anthrax inhalational (pulmonary) anthrax

Cutaneous anthrax

This skin lesion is associated with occupational exposure to anthrax spores during processing of hides and bone products.

It accounts for the vast majority of clinical cases.

Spores are inoculated into exposed skin. A single lesion develops as an irritable papule on an oedematous haemorrhagic base. This progresses to a depressed black eschar.

Despite extensive oedema, pain is infrequent.

Gastrointestinal anthrax

This is associated with the ingestion of meat products that have been contaminated or incompletely cooked.

The caecum is the seat of the infection, which produces nausea, vomiting, anorexia and fever, followed in 2-3 days by severe abdominal pain and bloody diarrhoea.

Toxaemia and death can develop rapidly thereafter.

Inhalational anthrax

This form of the disease is extremely rare, unless associated with bioterrorism.

Without rapid and aggressive therapy at the onset of symptoms, the mortality is 50-90%.

Fever, dyspnoea, cough, headache and symptoms of septicaemia develop 3-14 days following exposure.

Typically, the chest X-ray shows only widening of the mediastinum and pleural effusions which are haemorrhagic. Meningitis may occur.

Management

B. anthracis can be cultured from skin swabs from lesions.

Skin lesions are readily curable with early antibiotic therapy. ciprofloxacin (500 mg 12-hourly) until penicillin susceptibility is confirmed; the regimen can then be changed to benzylpenicillin with doses up to 2.4 g i.v. given 4-hourly or phenoxy-methylpenicillin 500-1000 mg 6-hourly administered for 10 days.

The addition of an aminoglycoside may improve the outlook in severe disease.

In view of concerns about concomitant inhalational exposure, particularly in the era of bioterrorism, a further 2-month course of ciprofloxacin 500 mg 12-hourly or doxycycline 100 mg 12-hourly orally is added.

Prophylaxis with ciprofloxacin (500 mg 12-hourly) is recommended for anyone at high risk of exposure to anthrax spores.