eMedicine Specialties > Emergency Medicine > Infectious Diseases

Diphtheria

Allysia M Guy, MD, Staff Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center, Brooklyn, New York
Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate at Brooklyn

Updated: Oct 5, 2009

Introduction

Background

C diphtheria is responsible for both endemic and epidemic diseases, and it was first described in the 5th century BC by Hippocrates. Diphtheria manifests as either an upper respiratory tract or cutaneous infection and is caused by the aerobic gram-positive bacteria, Corynebacterium diphtheria. The infection usually occurs in the spring or winter months. It is communicable for 2-6 weeks without antibiotic treatment.^1,2 People who are most susceptible to infection are those who are not completely immunized or have low antitoxin antibody levels and have been exposed to a carrier or diseased individual. A carrier is someone whose cultures are positive for the diphtheria species but does not exhibit signs and symptoms. Studies show that as the number of asymptomatic carriers decrease, the number of diphtheria cases consequently decline.^1,3

C diphtheria is a nonencapsulated, nonmotile, gram-positive bacillus. Pathogenic strains can result in severe localized upper respiratory infection, localized cutaneous infections, and rarely systemic infection.

Photomicrograph depicts a number of gram-positive Corynebacterium diphtheriae bacteria, which had been stained using the methylene blue technique. The specimen was taken from a Pai's slant culture.

Pathophysiology

Overcrowding, poor health, substandard living conditions, incomplete immunization, and immunocompromised states facilitate susceptibility to diphtheria and are risk factors associated with transmission of this disease.⁶ Human carriers are the main reservoir of infection; however, case reports have linked the disease to livestock.^5,4 Infected patients and asymptomatic carriers can transmit C diphtheria via respiratory droplets, nasopharyngeal secretions, and rarely fomites.^1,2 In the case of cutaneous disease, contact with wound exudates may result in the transmission of the disease to the skin as well the respiratory tract.⁴

Immunity from exposure or vaccination wanes over time. Inadequate boosting of previously vaccinated individuals may result in increased risk of acquiring the disease from a carrier, even if adequately immunized previously. Additionally, since the advent of widespread vaccination, cases of nontoxigenic strains causing invasive disease have increased.⁷

C diphtheria adheres to mucosal epithelial cells where the exotoxin, released by endosomes, causes a localized inflammatory reaction followed by tissue destruction and necrosis. The toxin is made of two joined proteins.² The B fragment binds to a receptor on the surface of the susceptible host cell, which proteolytically cleaves the membrane lipid layer enabling segment A to enter.¹ Molecularly, it is suggested that the cellular susceptibility is also due to diphthamide modification, dependent on human leukocyte antigen (HLA) types predisposing to more severe infection. The diphthamide molecule is present in all eukaryotic organisms and is located on a histidine residue of the translation elongation factor 2 (eEF2). eEF2 is responsible for the modification of this histidine residue and is the target for the diphtheria toxin (DT).

Fragment A inhibits an amino acid transfer from RNA translocase to the ribosomal amino acid chain, thus inhibiting protein synthesis is required for normal host cell functioning.¹ DT causes a catalytic transfer of NAD to diphthamide, which inactivates the elongation factor, resulting in the inactivation eEF2, which results in protein synthesis blockage and subsequent cell death.^8,2

Local tissue destruction enables the toxin to be carried lymphatically and hematologically to other parts of the body. Elaboration of the diphtheria toxin may affect distant organs such as the myocardium, kidneys, and nervous system. Nontoxigenic strains tend to produce less severe infections; however, since widespread vaccination, case reports of nontoxigenic strains of C diphtheria causing invasive disease have been documented.¹

Frequency

United States

Since the introduction and widespread use of diphtheria toxoid in the 1920s, respiratory diphtheria has been well controlled, with an incidence of approximately 1000 cases reported annually. Before vaccination, at least 200,000 cases occurred annually in the United States.⁹

Diphtheria remained endemic in some states through the 1970s, with reported incidence rates of greater than 1.0 per million population in Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington.¹ Most of these infections were attributed to incomplete vaccination.

In the United States, diphtheria currently occurs sporadically, mostly among the Native American population, homeless people, lower socioeconomic groups, and alcoholics.⁶ Immigrants and travelers from regions with ongoing epidemics are also at risk.⁶

International

According to the World Health Organization (WHO), diphtheria epidemics remain a health threat in developing nations.² The largest epidemic recorded since widespread implementation of vaccine programs was in 1990-1995, when a diphtheria epidemic emerged in the Russian Federation, rapidly spreading to involve all Newly Independent States (NIS) and Baltic States. This epidemic caused more than 157,000 cases and 5000 deaths according to WHO reports.^10,11 Disproportionately high rates of death were observed in individuals older than 40 years, and 5,000 deaths were reported. This epidemic accounted for 80% of cases reported worldwide during this time period.¹²

From 1993-2003, a decade long epidemic in Latvia resulted in 1359 reported cases of diphtheria with 101 deaths. The incidence fell from 3.9 cases per 100,000 cases in 2001 to 1.12 cases per 100,000 population in 2003. Most cases were registered in unvaccinated adults.

From 1995-2002, 17 cases of cutaneous diphtheria due to toxigenic strains were reported in the United Kingdom.¹²

Many case reports in the literature describe epidemics in sub-Saharan Africa, France, India, and the United States.^13,14

Mortality/Morbidity

Before the introduction of vaccine in the 1920s, the incidence of respiratory disease was 100-200 cases per 100,000 population in the United States and has decreased to approximately 0.001 cases per 100,000 population.^9,1

The most widely quoted diphtheria mortality rate is 5-10%. It may reach higher than 20% in children younger than 5 years and adults older than 40 years. Immunization patterns have the most influence on mortality patterns. Mortality rates have not changed significantly over the past few decades. Most deaths occur on days 3-4 secondary to asphyxia with a pharyngeal membrane or due to myocarditis. Mortality rates of 30-40% have been reported for bacteremic disease.⁹

Race

No racial predilection for diphtheria has been reported.

Sex

No significant differences exist between the incidence of diphtheria in males and females. In certain regions of the world, however, women may have lower immunization rates than males. Female infants and young children account for the majority of deaths in endemic regions.

Age

Historically, diphtheria has been primarily a disease of childhood, affecting populations younger than 12 years. Infants become susceptible to the disease at age 6-12 months after their transplacentally derived immunity wanes.¹⁵ Since the advent of diphtheria vaccination, cases of pediatric disease have declined dramatically. Recently, however, diphtheria has shifted into the adolescent and adult population, most notably in ages 40 and older accounting for most new cases.¹¹ This is primarily due to incomplete immunization status, including never being immunized, inefficient vaccine or response to vaccination, and not receiving a booster after previous vaccination. According to immunologic studies, one must have an antitoxin level of greater 0.1 IU/mL for adequate immunity.¹⁶ Additionally, adolescents and adults may exhibit an atypical presentation of the disease, thus potentially obscuring the diagnosis.⁷

Immunization schedules have recently changed requiring a toxoid booster at age 11-12 and every 10 years thereafter. The toxoid booster, without tetanus, is approved for pregnant women if their antitoxin titers are less than 0.1 IU/mL.^17,16

Clinical

History

Onset of symptoms of respiratory diphtheria typically follows an incubation period of 2-5 days (range, 1-10 d).^9,1 Symptoms initially are general and nonspecific, often resembling a typical viral upper respiratory infection (URI). Respiratory involvement typically begins with sore throat and mild pharyngeal inflammation. Development of a localized or coalescing pseudomembrane can occur in any portion of the respiratory tract. The pseudomembrane is characterized by the formation of a dense, gray debris layer composed of a mixture of dead cells, fibrin, RBCs, WBCs, and organisms.

The characteristic thick membrane of diphtheria infection in the posterior pharynx.

Cervical edema and cervical lymphadenopathy from diphtheria infection produce a bull's neck appearance in this child. Source: Public Domain www.immunize.org/images/ca.d/ipcd1861/img0002.htm.

Cutaneous diphtheria is a disease characterized by indolent, nonhealing ulcers covered with a gray membrane. The ulcers are often co-infected with Staphylococcus aureus and group A streptococci. This form of the disease is seen with increasing frequency in poor inner-city dwellers and alcoholics. The lesions of cutaneous diphtheria are infectious, and bacteria from cutaneous lesions have been found to cause pharyngeal infections and thus serve as a reservoir for infection.

• Patients with diphtheria may present with the following complaints
  • Low-grade fever (rarely >103°F) (50-85%) and chills
  • Malaise, weakness, prostration
  • Sore throat (85-90%)
  • Headache
  • Cervical lymphadenopathy and respiratory tract pseudomembrane formation (about 50%)
  • Serosanguineous or seropurulent nasal discharge, white nasal membrane
  • Hoarseness, dysphagia (26-40%)
  • Dyspnea, respiratory stridor, wheezing, cough
• Respiratory diphtheria may quickly progress to respiratory failure due to airway obstruction or aspiration of pseudomembrane into the tracheobronchial tree.
• Cutaneous diphtheria often develops at a site of previous trauma or a primary dermatologic disease. It follows an indolent course, typically lasting weeks to months. Occasionally, it may cause respiratory diphtheria.¹⁵

Physical

General: Patient has a low-grade fever but is toxic in appearance, and also may have a swollen neck.

Pharyngeal diphtheria:

• Patients may present with general symptoms of fever, halitosis, tachycardia, and anxiety.
• Tonsils and pharynx: Pharyngeal erythema and edema, thick, gray, leathery membrane variably covers the tonsils, soft palate, oropharynx, nasopharynx, and uvula. Attempts at scraping the pseudomembrane causes bleeding of the underlying mucosa.
• Neck: Extensive anterior and submandibular cervical lymphadenopathy imparts a bull's neck appearance. The patient may hold his or her head in extension. It can occasionally also be associated with dysphonia.
• Respiratory distress manifesting as stridor, wheezing, cyanosis, accessory muscle use, and retractions.

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.¹⁸
• Atrioventricular blocks, ST-T wave changes, and various dysrhythmias may be evident.
• Endocarditis may be present.

Neurologic 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 stocking and glove peripheral sensory neuropathy pattern can be observed.
• 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.¹⁹
• Other systems involvement: Diphtheria is occasionally seen in the female genital tract, conjunctivae, or ear.
• Invasive disease may manifest in multiple organ system disease, though this is rare.^1,3
• Cutaneous diphtheria begins as a painful lesion resembling an erythematous pustule, which breaks down to form an ulcer covered with a gray membrane.^4,15

Causes

The following factors may predispose to diphtheria infection:

• Incomplete or absent immunization, which is especially important in the adult population, and as well the pediatric population in underdeveloped countries, may predispose to infection. In some cases, immunity does not prevent infection but lessens the severity of the disease.⁹
• Antitoxin titers decrease over time and immunity wanes, thus older people who have not received booster vaccination are more susceptible to contract the disease from carriers. Studies suggest if titer level is greater than 0.1 UI/mL, then an individual is characterized as immune from infection.
• Low herd immunity, possibly leading to increasing circulation of nontoxigenic strains 
• Travel to endemic areas or regions with current epidemics
• Immunocompromised states - Due to pharmacologic immune suppression, disease states including HIV, or relative compromise such as from diabetes or alcoholism
• Low socioeconomic status
• Large-scale population movements - Implicated in the spread of the epidemic in the Newly Independent States of the former Soviet Union²⁰
• Poor healthcare care system infrastructure
• Overcrowding - Homeless shelters, jails

Differential Diagnoses

Other Problems to Be Considered

Tonsillitis
Peripheral nerve palsies
Vincent angina
Septic arthritis
Myocarditis
Acute renal failure
Sepsis

Workup

Laboratory Studies

• To establish the diagnosis of C diphtheriae, it is vital to both isolate C diphtheriae in culture media and to identify the presence of toxin production.²
• Bacteriologic testing
  • Gram stain shows club-shaped, nonencapsulated, nonmotile bacilli found in clusters.
  • Immunofluorescent staining of 4-hour cultures or methylene blue–stained specimen may sometimes allow for a speedy identification.
  • Cultures: Inoculation of tellurite or Loeffler media with swabs taken from the nose, pseudomembrane, tonsillar crypts, any ulcerations, or discolorations. Identification is accomplished through observation of colony morphology, microscopic appearance, and fermentation reactions. Any diphtheria bacilli isolated must be tested for toxin production.
  • Obtain throat and pharyngeal swabs from all close contacts.⁹
• Toxigenicity testing is aimed to determine the presence of toxin production.
  • Elek test detects the development of an immunoprecipitin band on a filter paper impregnated with antitoxin and then is laid over an agar culture of the organism being tested.¹⁰
  • Polymerase chain reaction (PCR) assays for detection of DNA sequence encoding the A subunit of tox+ strain are both rapid and sensitive.
  • Once diphtheria infection has been established, the Centers for Disease Control and Prevention (CDC) should be contacted, and further testing may be requested.
• Other laboratory studies
  • CBC may show moderate leukocytosis.
  • Urinalysis (UA) may demonstrate transient proteinuria.
  • Serum antibodies to diphtheria toxin prior to administration of antitoxin: Low levels cannot exclude the possibility of the disease; high levels may protect against severe illness (concentrations of 0.1 to 0.01 IU are thought to confer protection).⁹
  • Serum troponin I levels seem to correlate with the severity of myocarditis.²¹

Imaging Studies

• Chest radiograph and soft tissue neck radiography/CT or ultrasonography may show prevertebral soft tissue swelling, enlarged epiglottis, and narrowing of the subglottic region.
• Echocardiography may demonstrate valvular vegetations; however, this systemic manifestation of diphtheria is rare.^22,21

Other Tests

• ECG may show ST-T wave changes, variable heart block, and dysrhythmia.

Procedures

• Endotracheal intubation
• Surgical airway - Cricothyroidotomy or tracheostomy
• Laryngoscopy, bronchoscopy as indicated in intubated patients
• Electrical pacing for high-grade conduction disturbances

Treatment

Prehospital Care

Careful assessment of airway patency and cardiovascular stability. Patients should be transported to the nearest hospital.

Emergency Department Care

Treatment of diphtheria should be initiated even before confirmatory tests are completed due to the high potential for mortality and morbidity.

• Isolate all cases promptly and use universal and droplet precautions to limit the number of possible contacts.
• Secure definite airway for patients with impending respiratory compromise or the presence of laryngeal membrane. Early airway management allows access for mechanical removal of tracheobronchial membranes and prevents the risk of sudden asphyxia through aspiration. Consider involving ENT or operating room personnel for intubation and securing of airway if there is suspicion for loss of the airway or respiratory failure.
• Maintain close monitoring of cardiac activity for early detection of rhythm abnormalities. Initiate electrical pacing for clinically significant conduction disturbance and provide pharmacologic intervention for arrhythmias or for heart failure.
• Provide 2 large-bore IVs for patients with a toxic appearance; provide invasive monitoring and aggressive resuscitation for patients with septicemia.
• Initiate 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.
• Neutralize the toxin as soon as diphtheria is suspected. Diphtheria antitoxin is a horse-derived hyperimmune antiserum that neutralizes circulating toxin prior to its entry into the cells. It prevents the progression of symptoms. The dose and route of administration (IV vs IM) are dependent on the severity of the disease. This antitoxin must be obtained directly from the Centers for Disease Control and Prevention (CDC). Antitoxin is only available in the United States. 
• Diphtheria disease does not confer immunity; thus, initiation or completion of immunization with diphtheria toxoid is necessary.
• Obtain throat and nasal swabs from persons in close contact with the suspected diphtheria victim; administer age-appropriate diphtheria booster.
• Initiate antibiotic therapy with erythromycin or penicillin for chemoprophylaxis in a patient with suspected exposure. Throat cultures should be repeated in 2 weeks after treatment.
• Studies suggest that erythromycin might be superior in the eradication of the carrier state, but treatment failure may occur.

Consultations

• Centers for Disease Control and Prevention (CDC), to report the case and to secure help in obtaining antitoxin and as well for testing and typing of toxin if indicated
• Infectious disease service and neurology
• Cardiology, for assistance in managing cardiac complications
• Critical care service, for admission into the ICU
• ENT/anesthesia, for airway control
• Surgery, for assistance in obtaining a surgical airway if needed in a nonemergent fashion
• Pulmonary, for bronchoscopy for pseudomembrane removal or obstruction

Medication

Patients with active disease as well as all close contacts should be treated with antibiotics. Treatment is most effective in the early stages of disease and decreases the transmissibility and improves the course of diphtheria. Additionally, close contacts, such as family members, household contacts, and potential carriers, must receive chemoprophylaxis regardless of immunization status or age. This entails treatment with erythromycin or penicillin for 14 days and post treatment cultures to confirm eradication.³

The CDC has approved macrolides such as erythromycin as first-line agents for patients older than 6 months of age. However, macrolide therapy has been associated with an increase in pyloric stenosis in children younger than 6 months, especially treatment with erythromycin. Intramuscular penicillin is recommended for patients who will be noncompliant or intolerant to an erythromycin course.

The horse serum antitoxin is given to anyone suspected to have diphtheria and can be administered without confirmation from cultures, as it is most efficacious early during the course of the disease.

Antitoxins

Diphtheria antitoxin was first used in the United States in 1891, derived from a horse serum, it neutralizes unbound exotoxin. It is to be administered as soon as diphtheria suspected. It can only be obtained from the CDC and is not available internationally. Administer immunization toxoid booster, as the antitoxin does not influence immunity.

Diphtheria antitoxin

Neutralizes toxin before it enters cells. Dose given depends on site of infection and length of time patient is symptomatic. In United States, diphtheria antitoxin (DAT) is available from the CDC. Contact diphtheria duty officer at 404-639-8255 from 8 am to 4:30 pm (EST) or at 404-639-2889 all other times. Report all suspected cases of diphtheria to local and state health departments.

Dosing

Adult

20,000-40,000 U IV over 60 min for laryngeal or pharyngeal disease of <48 h duration
40,000-60,000 U for nasopharyngeal lesions
80,000-120,000 U for extensive disease with duration of 3 or more days or edema of the neck (bull's neck)
Administer IM for less severe disease
Test all patients with a 1:10-1:100 dilution of DAT SC; if an immediate reaction occurs, administer epinephrine; hypersensitivity to horse serum is not a contraindication to antitoxin injection; desensitize subjects with increasing doses of diluted DAT

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Approximately 10% of patients may develop serum sickness; hypersensitivity reactions can include anaphylaxis, requiring epinephrine treatment

Macrolides

Erythromycin and penicillin are both recommended for the treatment of diphtheria. Some studies suggest that erythromycin may be better at eradication of the carrier state. Penicillin is recommended in household contacts who may not comply with the duration of erythromycin treatment. An increased incidence of pyloric stenosis is associated with administration of erythromycin to infants younger than 6 months. It is believed that azithromycin may be a better macrolide treatment in this population, though there are a few case reports describing pyloric stenosis in infants treated with azithromycin for pertussis infections.

The treatment of endocarditis requires the addition of an aminoglycoside.

Erythromycin (E-Mycin, Ery-Tab)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
Age, weight, and severity of infection determine proper dosage in children. When bid dosing is desired, one half the total daily dose may be taken q12h. Double the dose for more severe infections.
Has the added advantage of being a good anti-inflammatory agent by inhibiting migration of polymorphonuclear leukocytes.

Dosing

Adult

2 g/d IV divided bid or 2 g/d PO divided qid for 14 d

Pediatric

20-50 mg/kg/d IV divided bid; not to exceed 2 g/d; alternately, 40-50 mg/kg/d PO divided qid for 14 d

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis; decreases metabolism of repaglinide, thus increasing serum levels and effects

Contraindications

Documented hypersensitivity; caution in myasthenia gravis, impaired liver function, QT prolongation, cardiomyopathy, or bradycardia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Antibiotic, Penicillin

Penicillin may be used for treatment, prophylaxis, and eradication of diphtheria in carriers. However, resistant strains and transmission from penicillin-treated carriers has been reported.

Penicillin G benzathine (Bicillin L-A, Permapen)

Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. Effective treatment for systemic diphtheria.

Dosing

Adult

Penicillin V: 250 mg PO qid for 10 d
Penicillin G benzathine: 1,200,000 U/d IM for 10 d

Pediatric

<30 lb: 60 mg PO (penicillin V) qid for 10 d; 300,000 U/d IM (penicillin G benzathine) for 10 d
30-60 lb: 125 mg PO (penicillin V) qid for 10 d; 600,000 U/d IM (penicillin G benzathine) for 10 d

Interactions

Probenecid can increase penicillin effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness of penicillin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Follow-up

Further Inpatient Care

• Provide supportive care, continuation of antibiotic treatment, and antipyretics for fever.
• Closely observe for development of primary or secondary bacterial pneumonia.
• Perform serial ECGs to detect cardiac abnormalities.
• Provide physical therapy for patients with neurologic dysfunction.
• Patients with endocarditis may require valve replacement.
• Respiratory isolation may be indicated.
• Monitor for serum sickness or hypersensitivity reactions in patients treated with DAT.

Further Outpatient Care

Complete age-appropriate immunization schedule. Treat all household and other close contacts with antibiotics as mentioned above. All suspected and confirmed carriers should be treated with erythromycin or penicillin for 14 days. Follow-up pharyngeal cultures must be obtained post treatment, confirming eradication of the bacterium.³

Inpatient & Outpatient Medications

• Bronchodilators (may be beneficial for patients with mild respiratory symptoms)
• Antipyretics
• Antibiotics - Penicillin, erythromycin

Transfer

• Intensive care unit admission is recommended for patients with impending respiratory compromise.
• Isolation may be indicated.

Deterrence/Prevention

• The Global Pertussis Initiative formed in 2001 is the task force working towards global immunizations and disease prevention in infants, adolescents, and adults for diphtheria, pertussis, and tetanus. 
• The 4 forms of the diphtheria toxoid are as follows: DTaP, Tdap, DT, and Td. The childhood vaccination is called DTaP. Adult vaccination form is Tdap. These toxoid vaccinations are combined with acellular pertussis and tetanus vaccine.²³
  • DTap is given at 2 months, 4 months, 6 months, 15-18 months, and 4-6 years. The uppercase D denotes the full strength of tetanus toxoid (7-8 Lf units).²⁴
  • DT does not contain pertussis and is given to children who have had previous adverse reactions to the acellular pertussis incorporated vaccine.
  • Td is a vaccine for adolescents and adults given as a booster every 10 years or when an exposure has occurred. The lowercase d denotes reduced strength diphtheria toxoid (2.0-2.5 Lf units). It is given to those older than 7 years.^25,17
  • Tdap is recommended for adolescents aged 11 or 12 years, or in place of one Td booster in older adolescents and adults aged 19-64 years. Boostrix is Tdap approved for adolescents aged 10-18, and Adacel is Tdap approved for those aged 19-64 years. Adacel is used for adult vaccination and is recommended by the CDC in the adult vaccination schedule since 2007.¹⁷ These immunization schedules have been modified due to trends of pertussis increasing in the adolescent and adult populations. Therefore, Tdap Boostrix and Adacel are now recommended in the immunization schedule for prevention of endemics associated with pertussis and diphtheria.²⁶
• Contact/respiratory isolation is indicated for prevention and deterrence of spreading the infection.

Complications

• Respiratory failure due to pseudomembrane formation or aspiration, tissue edema, and necrosis
• Cardiac - Myocarditis, cardiac dilatation and failure, mycotic aneurysm, endocarditis
• Rhythm disturbances - Heart block, including AV dissociation and dysrhythmias
• Secondary bacterial pneumonia
• Cranial nerve dysfunction and peripheral neuropathy, total paralysis
• Optic neuritis
• Septicemia/shock (rare)
• Septic arthritis, osteomyelitis (rare)
• Metastasis of infection to distant sites such as spleen, myocardium, or CNS (rare)
• Death

Prognosis

• Cardiac involvement is associated with a very a poor prognosis, particularly AV and left bundle-branch blocks (mortality rate 60-90%).
• Bacteremic disease carries a mortality rate of 30-40%.
• High mortality rate is seen with invasive disease.
• High mortality rates are seen in individuals younger than 5 years and in those older than 40 years.

Patient Education

• Widespread awareness of the need for universal immunization is indicated.
• Stress the importance of seeking medical attention in all cases of contact with suspected diphtheria cases.

Miscellaneous

Medicolegal Pitfalls

• Failure to recognize diphtheria and to promptly treat those infected and their close contacts
• Failure to recognize cardiac dysrhythmias
• Failure to secure the airway in the face of impending respiratory failure from obstructive pseudomembrane
• Failure to admit patients to appropriate hospital setting
• Failure to isolate infected patients or to identify and treat carriers

Multimedia

Media file 1: The characteristic thick membrane of diphtheria infection in the posterior pharynx.

Media file 2: Cervical edema and cervical lymphadenopathy from diphtheria infection produce a bull's neck appearance in this child. Source: Public Domain www.immunize.org/images/ca.d/ipcd1861/img0002.htm.

Media file 3: Photomicrograph depicts a number of gram-positive Corynebacterium diphtheriae bacteria, which had been stained using the methylene blue technique. The specimen was taken from a Pai's slant culture.

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Keywords

diphtheria, diphtheria symptoms, diphtheria causes, diphtheria treatment, diphtheria prevention, C diphtheriae, var , mitis, intermedius, gravis, diphtheria vaccine, diphtheria toxoid

Contributor Information and Disclosures

Author

Allysia M Guy, MD, Staff Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center, Brooklyn, New York
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Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate at Brooklyn
Mark A Silverberg, MD, FACEP, MMB is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine
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Steven A Conrad, MD, PhD, Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center
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Barry J Sheridan, DO, Chief, Department of Emergency Medical Services, Brooke Army Medical Center
Barry J Sheridan, DO is a member of the following medical societies: American Academy of Emergency Medicine
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CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
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The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Elzbieta Pilat, MD, Lorenzo Paladino, MD, and Malini K Singh, MD, to the development and writing of this article.

The authors and editors of eMedicine gratefully acknowledge the medical review of this article by Joseph U Becker, MD.

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