Diphtheria Toxin

Boston University
Research Occupational Health Program (ROHP)
617-358-7647

Agent

Diphtheria toxin is produced by corynebacterium diphtheriae, a noncapsulated gram (+) bacillus.  The toxin causes diphtheria complications in humans and can be lethal.  In the laboratory, the toxin release results from lysis of bacillus by a specific virus (bacteriophage).  It is a polypeptide with 2 subunits A & B toxins.

Disease/Infection

The diphtheria toxin (DT) is the major contributor to diphtheria illness and can cause nerve palsies, myocarditis and endocarditis.

Pathogenicity

The toxin enters cytoplasm by binding to heparin-binding EGF like growth factor on cell surface.  Once in a cell inhibition of protein synthesis occurs.  A small dose of toxin can be lethal.

Special Populations at Risk

Non vaccinated or immunocompromised persons

Biosafety Information

Risk Group/BSL
Risk Group BSL-2
Biosafety Level 2 Practices

Modes of Transmission

Transmission
Skin Exposure (Needlestick, bite, or scratch):Yes
Mucous Membrane Splash to Eye(s), Nose, or Mouth:Yes
Inhalation:Yes
Ingestion:Yes

Host Range/Reservoir
Humans

Symptoms
Diphtheria systemic infection causes fever, sore throat, weakness, and lymphadenopathy.  Diphtheria toxin skin exposure could cause cellulitis and necrotic lesion.  Injection into tissue could be distributed to distant organs causing cardiac or neurologic complications.  Death is possible if not treated.

Incubation Period
Incubation period is 2-5 days (range is 1-10 days)

Viability
Persists in environment

Survival Outside Host
The diphtheria toxin will persist until neutralized.

Information for Lab Workers

Laboratory PPE

Personnel protective equipment includes but is not limited to gowns with tight wrists and ties in back, disposable gloves, combination safety glasses and mask or a face shield.  Facilities for washing and changing clothing after work should be available.

Containment

Research should be conducted using Biosafety Level 2 practices, equipment, and facility design. Gloves and gowns should be worn when handling infected laboratory animals and when there is the likelihood of direct skin contact with infectious materials. Animal studies may be performed at ABSL-2. BSL-2 practices, containment equipment, and facilities are recommended for activities using clinical materials and diagnostic quantities of infectious cultures.

In Case of Exposure/Disease

  • For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…):
    • Medical Campus: call or have a coworker call the Control Center at 8–4144.
    • Charles River Campus: call or have a coworker call campus security at 617-353-2121.
      You will be referred to or transported to the appropriate health care location by the emergency response team. 
  • For lab exposures (needle sticks, bite, cut, scratch, splash, etc…) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7-hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
  • Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
  • Provide the ROHP medical surveillance wallet card to the physician.
  • If you sustain an injury, chemical exposure, or biological exposure in a BU laboratory: Implement the first aid steps on which you have been trained, i.e., washing the injury, etc. Refer to a chemical’s safety data sheet.
  • In case of emergency:  Follow BU Emergency Instructions
  • Immediate medical evaluation: Once you contact ROHP, a health care professional will perform a risk assessment, advise you on immediate first aid, and direct you to appropriate medical care.

Vaccination

CDC recommends vaccination to public every 10 years for all adults to maintain protection against diphtheria. Once an adult has received an initial dose of TDAP, a Td or Tdap should be provided for their booster doses. For researchers directly handling diphtheria toxin, it is recommended they receive vaccination every 5 years.

Laboratory workers handling large amounts of toxin (10% of the LD50 or more) can be monitored with annual anti-toxoid IgG levels following vaccination and booster when levels decline below 0.1 IU/ml or receive a vaccination every 5 years.

Information for First Responders/Medical Personnel

Public Health Issues

Protection from contact with diphtheria toxin is essential to exposed areas.

Diagnosis/Surveillance

Monitor for symptoms post exposure and attempt to defect toxin.

First Aid/Post Exposure Prophylaxis

Perform one of the following actions:

Skin Exposure (Needlestick or scratch):Immediately go to the sink and thoroughly wash the wound with soap and water for 15 minutes. Decontaminate any exposed skin surfaces with an antiseptic scrub solution.
Mucous Membrane Splash to Eye(s), Nose or Mouth:Exposure should be irrigated vigorously.
Inhalation:Exposed person should be moved to fresh air
Splash Affecting Garments:Remove garments that may have become soiled or contaminated and place them in a double red plastic bag

Treatment

Antibiotics are not useful.  Pre-exposure vaccination has been provided.  If not vaccinated, Td or Tdap administered at exposure efficacy is 95% long term.

If significant exposure the researcher should be referred to the Emergency Dept. to obtain anti-toxin which would be obtained from the Centers for Disease Control and Prevention (CDC). The CDC also provides telephone consultation for diagnosis and treatment questions. Providers can contact the CDC’s Emergency Operations Center at 770-488-7100 (or at www.cdc.gov/diphtheria/dat.html) after consulting with their state health department. DAT is available from CDC under an investigational new drug (IND) protocol.

References

Biosafety in Microbiological and Biomedical Laboratories (BMBL) sixth edition

Control of Communicable Diseases Manual. David L. Heymann. Washington DC, USA: American Public Health Association Press, 19th edition; 2008

CDC:  The Pink Book:  Course Textbook

Diphtheria, Epidemiology & Prevention of Vaccine Preventable Diseases, 12th Ed., 5/12

Harber, P., Baker, B. A., & Russi, M. (2022). Occupational Health for Higher Education and Research Institutions: A guide for employee health and student health programs. OEM Press.

https://www.cdc.gov/diphtheria/index.html

Revised: 8/28/25

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