Diphtheria, Tetanus and H. influenzae b

Clinical Background

Clostridium tetani is a slender, gram-positive, sporulating, anaerobic bacillus.

C. tetani spores are ubiquitous in the environment and usually enter body through puncture wounds, lacerations, abrasions or burns
If bacilli find a suitable deep wound with reduced oxidation (anaerobic conditions), they germinate, releasing toxin
- Toxin is disseminated via blood and lymphatics
- Clinical manifestations of tetanus are due to toxin
Manifestations
- Tetanus is characterized by intermittent tonic spasms of voluntary muscles
- Neonatal tetanus occurs secondary to unsterile treatment of umbilical cord associated with inadequately immunized mothers
- When tetanus results in death, cause is usually interference with respiration
- The death rate among reported cases of tetanus is about 30%
- Tetanus in the U.S. mostly affects older adults not adequately immunized

Corynebacterium diphtheriae is an aerobic gram-positive rod.

Causes diphtheria - a contagious, airborne infection
Manifestations
- Diphtheria is characterized by
  - Formation of fibrinous pseudo-membranes, usually on respiratory mucosa
    - Pseudomembrane formation is sine qua non for disease
    - Primary infection most often tonsillopharyngeal, but may be laryngeal, nasal or tracheobronchial
  - Myocardial and neural tissue damage secondary to exotoxin produced by diphtheria bacteria
- In addition to respiratory form, diphtheria includes cutaneous form
  - Occurs in pre-existing dermatoses
  - Produces lesions resembling other cutaneous bacterial infections

H. influenza is a gram-negative coccobacillus.

6 major typable serotypes (a-f)
Nontypeable strains also
Causes meningitis, epiglottitis, otitis media, sinusitis, cellulitis and pneumonia
Majority of disease (except pneumonia) affects children

Prevention

Prevention for all of these diseases is vaccination
Pre- and one-month post vaccination titers may be used for testing of suspected antibody deficiency states

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Diphtheria & Tetanus Antibodies, IgG

ARUP #: 0050595

Methodology: Multi-Analyte Fluorescent Detection

Use:

For diphtheria antibody titer, order with diphtheria antibody, IgG to:
- Determine patient's response to protein toxoid (majority of antibody falls within IgG/subclass 1)
- Diagnose antibody deficiency in patients with recurrent infections, especially sinopulmonary and gastrointestinal

For tetanus antibody titer, order with tetanus antibody, IgG to:
- Determine whether vaccine recipient responded to vaccine with protective levels of antibodies
- Determine IgG antibody titers to tetanus and diphtheria toxoids and H. Influenzae PRP simultaneously

Limitations:

Follow-up:

If concentrations of IgG, IgM, and IgA are low, low normal or even normal, and antibody deficiency still strongly suspected, determine IgG subclass and response to protein antigens such as diphtheria, tetanus toxoid, and Haemophilus influenzae as well as to pure polysaccharide antigens such as unconjugated pneumococcal vaccine

Test name: Diphtheria, Tetanus, and H. Influenzae b Antibodies, IgG

ARUP #: 0050779

Methodology: Multi-Analyte Fluorescent Detection

Use:

Determine whether vaccine recipient responded to vaccine and whether protective antibody levels have been reached

Determine IgG antibody titers to tetanus and diphtheria toxoids and H. Influenzae PRP simultaneously

Limitations:

Follow-up:

If concentrations of IgG, IgM, and IgA are low, low normal or even normal, and antibody deficiency still strongly suspected, determine IgG subclass and response to protein antigens such as diphtheria, tetanus toxoid, and influenzae as well as to pure polysaccharide antigens such as unconjugated pneumococcal vaccine

Test name: Diphtheria Antibody, IgG

ARUP #: 0050210

Methodology: Multi-Analyte Fluorescent Detection

Use:

For diphtheria antibody titer, order with diphtheria and tetanus antibodies, IgG to:
- Determine patient's response to protein toxoid (majority of this antibody falls within IgG/subclass 1)
- Diagnose antibody deficiency in patients with recurrent infections (especially sinopulmonary and gastrointestinal infections)

Limitations:

Follow-up:

If concentrations of IgG, IgM, and IgA are low, low normal or even normal, and antibody deficiency still strongly suspected, determine IgG subclass and response to protein antigens such as diphtheria, tetanus toxoid, and influenzae as well as to pure polysaccharide antigens such as unconjugated pneumococcal vaccine

Test name: Tetanus Antibody, IgG

ARUP #: 0050535

Methodology: Multi-Analyte Fluorescent Detection

Use:

For tetanus antibody titer, order with diphtheria and tetanus antibodies, IgG to:
- Determine whether recipient responded to vaccine and whether protective antibody levels reached
- Determine IgG antibody titers to tetanus and diphtheria toxoids and H. influenzae PRP simultaneously

Limitations:

Follow-up:

If concentrations of IgG, IgM, and IgA are low, low normal or even normal, and antibody deficiency still strongly suspected, determine IgG subclass and response to protein antigens such as diphtheria, tetanus toxoid, and influenzae, as well as to pure polysaccharide antigens such as unconjugated pneumococcal vaccine

Additional Tests Available

Test name: Haemophilus influenzae b Antibody, IgG

ARUP #: 0050542

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Additional Information

Pre-vaccine and 1-month post immunization samples should be run simultaneously, clearly marked as pre-vaccine or post-vaccine and dated.

Responder status is determined by ratio of a one-month, post-vaccination sample to a pre-vaccination concentration of IgG antibodies.

References

Guidelines

(1) Pertussis vaccination: use of acellular pertussis vaccines among infants and young children.(2) Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as a five-dose series. (Addendum) Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 1997 Mar 28 (revised 2000 Nov; addendum released 2003 Sep 26) . 25 pages. NGC:003288

Childhood immunizations. American College of Preventive Medicine - Medical Specialty Society. 1997 (revised 2003 Aug). 7 pages. NGC:003164

Cited References

Attygalle D, Rodrigo N. New trends in the management of tetanus. Expert Rev Anti Infect Ther. 2004;2(1):73-84.

Godfroid F, Denoel P, de Grave D, Schuerman L, Poolman J. Diphtheria-tetanus-pertussis (DTP) combination vaccines and evaluation of pertussis immune responses. Int J Med Microbiol. 2004;294(5):269-276.

Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type b conjugate vaccines. Immunology. 2004;113(2):163-174.

Rhee P, Nunley MK, Demetriades D, Velmahos G, Doucet JJ. Tetanus and trauma: a review and recommendations. J Trauma. 2005;58(5):1082-1088.

Swingler G, Fransman D, Hussey G. Conjugate vaccines for preventing Haemophilus influenzae type b infections. Cochrane Database Syst Rev. 2003;(4):CD001729.

General References

Dorsey MJ, Orange JS. Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy. Ann Allergy Asthma Immunol. 2006;97(5):590-595.

Gregory DS. Pertussis: a disease affecting all ages. Am Fam Physician. 2006;74(3):420-426.

Leung AK, Robson WL, Davies HD. Pertussis in adolescents. Adv Ther. 2007;24(2):353-361.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Pickering JW, Martins TB, Schroder MC, Hill HR. Comparison of a multiplex flow cytometric assay with enzyme-linked immunosorbent assay for auantitation of antibodies to tetanus, diphtheria, and Haemophilus influenzae Type b. Clin Diagn Lab Immunol. 2002;9(4):872-876.

Medical Reviewers

Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah

Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah

Comprehensive Review: November 2007
Last Update: September 2008