Diphtheria

DIPHTHERIA

Dr. Jayaprakash Appajigol MD

Consultant Physician,KLE’s Hospital & MRC

Belgaum.

Diphtheria is a nasopharyngeal and skin infection caused by bacteria ‘Corynebacterium diphtheriae’.

DIPHTHERIA

Gram-positive bacillusClub-shaped bacilli Unencapsulated,Nonmotile,Nonsporulating

DIPHTHERIA

C. diphtheriae is transmitted via the aerosol route, usually during close contact with an infected person.

The incubation period for respiratory diphtheria is 2–5 days

Diphtheria toxin produced by tox+ strains of C. diphtheriae is the primary virulence factor in clinical disease.

The toxin is produced in the pseudomembranous lesion and is taken up in the bloodstream, from which it is distributed to all organ systems in the body.

tox+ strains of C.diphtheriae

Diphtheria toxin

Pseudomembranous formation

Toxin Enters Bloodstream

Systemic Effects

Binds to cell surface receptor

Toxin is internalized by receptor-mediated endocytosis and enters the cytosol

Irreversible inhibition of protein synthesis

Cell Death

DIPHTHERIA-Pathogenesis

Neutrophils and fibrin infiltration

Cell Death, Pseudomembrane formation


Mucosal ulcers with a pseudomembranous coating composed of Fibrin, dead cells, neutrophils, lyphocytes, plasma cells, bacteria

Initially white and firmly adherent, in advanced diphtheria the pseudomembranes turn gray or even green or black as necrosis progresses.

When To Suspect Diphtheria?

Severe pharyngitis, particularly when there is difficulty swallowing, respiratory compromise, or signs of systemic disease (e.g., myocarditis or generalized weakness).

DIPHTHERIA-APPROACH TO THE PATIENTThe leading causes of pharyngitis are Respiratory viruses (rhinoviruses, influenza viruses, parainfluenza viruses, coronaviruses, adenoviruses; ~25% of cases),

Group A streptococci (15–30%), group C streptococci (~5%), atypical bacteria such as Mycoplasma pneumoniae and Chlamydia pneumoniae (15–20% in some series), and other viruses such as herpes simplex virus (~4%) and Epstein-Barr virus (<1% in infectious mononucleosis).

Less common causes are acute HIV infection, gonorrhea, fusobacterial infection (e.g., Lemierre’s syndrome), thrush due to Candida albicans or other Candida species, and diphtheria.

Clinical diagnosis of diphtheria is based on the constellation- Sore throat; - Adherent tonsillar, pharyngeal, or nasal pseudomembranous lesions; and - Low-grade fever- And Isolation of C. diphtheriae or histopathologic isolation of compatible gram-positive organisms

DIPHTHERIA-Clinical Features

Centers for Disease Control and Prevention (CDC)Confirmed respiratory diphtheria : Laboratory proven or epidemiologically linked to a culture-confirmed caseProbable respiratory diphtheria: Clinically compatible but not laboratory proven or

epidemiologically linked

Carriers are defined as individuals who have positive cultures for C. diphtheriae and who either are asymptomatic or have symptoms but lack pseudomembranes

Apart from Sore throat and feverHead ache, Dysphagia, Voice change.Breathlessness and neck edema are poor prognostic signs.

Systemic manifestations due to arrhythmias and congestive cardiac failure due to myocarditis may be present

Tonsillopharyngeal region is the common site of pseudomembrane but rarely it may be located at larynx, nares, and trachea or bronchial passages

Bull-Neck Diphtheria: Massive edema of the submandibular and paratracheal region and is further characterized by foul breath, thick speech, and stridorous breathing

The diphtheritic pseudomembrane is gray or whitish and sharply demarcated and tightly adherent to underlying tissue. Attempt to remove causes bleeding.


Pseudomembrane

Bull-Neck Diphtheria

Cutaneous Diphtheria This dermatosis is characterized by punchedout ulcerative lesions with necrotic sloughing or pseudomembrane formation. The diagnosis requires cultivation of C. diphtheriae from lesions, which most commonly occur on the lower and upper extremities, head, and trunk.


Other Clinical Manifestations C. diphtheriae causes rare cases of endo carditis and septic arthritis, most often in patients with preexisting risk factors, such as abnormal cardiac valves, injection drug use, or cirrhosis.

DIPHTHERIA-ComplicationsAIRWAY OBSTRUCTION due to extension and sloughing of pseudomembrane.

Polyneuropathy and myocarditis are late toxic manifestations of diphtheria.

CARDIAC TOXICITY typically occurs after 1-2 weeks of illness following improvement in the pharyngeal phase of the disease.It may manifest as follows:Myocarditis is seen in as many as 60% of patients (especially if previously unimmunized) and can present acutely with congestive heart failure (CHF), circulatory collapse, or more subtly with progressive dyspnea, diminished heart sounds, cardiac chamber dilatation, and weakness. Atrioventricular blocks, ST-T wave changes, and various dysrhythmias may be evident.Endocarditis may be present, especially in the presence of an artificial valve.

DIPHTHERIA-ComplicationsNEUROLOGIC TOXICITY is proportional to the severity of the pharyngeal infection. Most patients with severe disease develop neuropathy.

Deficits include the following:Cranial nerve deficits including oculomotor, ciliary paralysis, facial, and pharyngeal, or laryngeal nervous dysfunction.

Occasionally, a glove and stocking peripheral sensory neuropathy is seen.

Most C diphtheriae associated neurologic dysfunction eventually resolves.

Peripheral neuritis develops anywhere from 10 days to 3 months after the onset of pharyngeal disease. It manifests initially as a motor defect of the proximal muscle groups in the extremities extending distally. Various degrees of dysfunction exist, ranging from diminished DTRs to paralysis

Other complications of diphtheria: Pneumonia, renal failure, encephalitis, cerebral infarction, pulmonary embolism, and serum sickness from antitoxin therapy

DIPHTHERIA-Lab DiagnosisCultivation of C. diphtheriae or toxigenic Corynebacterium ulcerans from the site of infection or on the demonstration of local lesions with characteristic histopathology.

MANAGEMENT STRATEGIES• Hospitalized in respiratory isolation rooms, with close monitoring of cardiac

and respiratory function.• ENT/Anesthesia consultation required for possible need for

tracheostomy/intubation.

DIPHTHERIA ANTITOXINPrompt administration of diphtheria antitoxin is critical in the management of respiratory diphtheria• Horse antiserum,• Extent of local disease, risk of complications of myocarditis and neuropathy,

reduction in mortality risk.ANTIMICROBIAL THERAPYInitiate prompt antibiotic coverage (erythromycin or penicillin) for eradication of organisms, thus LIMITING THE AMOUNT OF TOXIN PRODUCTION. Antibiotics HASTEN RECOVERY AND PREVENT THE SPREAD of the disease to other individuals.

DIPHTHERIA-Treatment

PROGNOSISRisk factors for death include

1.bullneck diphtheria; 2.myocarditis with ventricular tachycardia; atrial fibrillation; complete

heart block; 3.an age of >60 years or <6 months; 4.alcoholism; 5.extensive pseudomembrane elongation; and laryngeal, tracheal, or

bronchial involvement.

Cutaneous diphtheria has a low mortality rate and is rarely associated with myocarditis or peripheral neuropathy

DIPHTHERIA-Treatment

DIPHTHERIA-Vaccines

Prophylaxis Administration to Contacts

• Throat culture

• Antimicrobial prophylaxis should be considered for all

contacts, even those whose cultures are negative.The options are 7–10 days of oral erythromycin or one dose of IM benzathine

penicillin G (1.2 million units)

DIPHTHERIA- Prophylaxis

DIPHTHERIA- Conclusions

Gram-positive, Club-shaped bacilli, transmitted via the aerosol route.

Diphtheria toxin and pseudomembrane are the pathological factors for the disease.

Bull Neck Diphtheria carries poor prognosis

Polyneuropathy and myocarditis are late toxic manifestations of diphtheria

Diagnosis is by culture from the lesion or histopathology demonstration of characteristic lesion.

Treatment: Isolation, Administration of ANTITOXIN, Antibiotics, Airway management and management of complications.

Diphtheria vaccination is recommended once in 10 years in adults along with tetanus and pertussis (Tdap)

Diphtheria

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