Vaccines

Understanding the Disease

Diphtheria is a serious disease that can cause death through airway obstruction, heart failure, paralysis of the muscles used for swallowing and pneumonia. It is caused by the bacterium Corynebacterium diphtheriae, which produces toxins that cause cell death both at the site of infection and elsewhere in the body.

Diphtheria usually begins with a sore throat, slight fever, and swollen neck. Most commonly, bacteria multiply in the throat, where a grayish membrane forms. This membrane can choke the person. Sometimes, the membrane forms in the nose, on the skin, or other parts of the body. The bacteria can release a toxin that spreads through the bloodstream and may cause muscle paralysis, heart and kidney failure, and death. Approximately 5% of people who develop diphtheria (500 out of every 10,000) die from the disease and many more suffer permanent damage.

In the 1920s, before the diphtheria vaccine, there were 100,000 to 200,000 reported cases in the United States each year. Because of the high level of immunization, only about one case of diphtheria occurs each year in the United States. However, in areas where the immunization rate has recently fallen (such as Eastern Europe and the Russian Federation), tens of thousands of people are suffering from diphtheria. The bacterium is still here—even though we do not see many cases. Our children are protected by being immunized and by everyone else being immunized too.

The diphtheria toxoid (inactivated toxin) vaccine offers the greatest protection against this disease. The fully immunized person who is exposed can become a carrier of the bacterium but may only develop a mild case, or may not get sick at all. But if not fully vaccinated, the risk of getting severely ill is 30 times higher.

Available Vaccines

No diphtheria-only vaccine is available. The diphtheria vaccine is available as:

• DTaP (Diphtheria, Tetanus, acellular Pertussis vaccine)
• DTaP in combination with Haemophilus influenzae type b (Hib) vaccine
• DTaP in combination with hepatitis B and inactivated polio vaccines
• DTaP in combination with Hib, hepatitis B and inactivated polio vaccines
• DT or Td (in combination with tetanus vaccine)
• Tdap (Tetanus, reduced diphtheria, acellular Pertussis)

Vaccines containing the whole cell pertussis component (DTP) are no longer recommended for use in the United States and are not listed here although they are used in many other countries. Vaccines containing lower amounts of diphtheria toxoid—abbreviated with a small d—are utilized in persons 7 years of age or older.

Product Name: Diphtheria and tetanus toxoids adsorbed (DT)
Manufacturer: Sanofi Pasteur
Year licensed: 1984

Product Name: Tetanus and diphtheria toxoids adsorbed for adult use (Td)
Manufacturers (Year licensed): Massachusetts Public Health Biologic Laboratories (1970), Sanofi Pasteur (1978)

Product Name: Decavac^TM (Tetanus and Diphtheria Toxoids Adsorbed for Adult Use - preservative free)  (Td)
Manufacturer: Sanofi Pasteur
Year licensed: 2004

Product Name: Tripedia® (DTaP)
Manufacturer: Sanofi Pasteur
Year licensed: 2001

Product Name: Infanrix® (DTaP)
Manufacturer: GlaxoSmithKline
Year licensed: 1997

Product Name: TriHIBit® (DTaP and Hib conjugate vaccine)
Manufacturer: Sanofi Pasteur
Year licensed: 2001

Product Name: Daptacel^TM (DTaP)
Manufacturer: Sanofi Pasteur
Year Licensed: 2002

Product Name: Pediarix^TM (DTaP, hepatitis B, and inactivated polio vaccines for use for the first 3 doses of DtaP (but not the booster dose) in children 6 weeks through6 years of age)
Manufacturer: GlaxoSmithKline
Year licensed: 2002

Product Name: Pentacel^TM (DTaP, Hib conjugate, hepatitis B, and inactivated polio vaccines)
Manufacturer: Sanofi Pasteur
Year licensed: 2008

Product Name: Boostrix^TM (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed for use in persons 10 yearof age and older) (Tdap)
Manufacturer: GlaxoSmithKline Biologicals
Year licensed: 2005

Product Name: Adacel^TM (Tetanus and Diphtheria Toxoids Adsorbed for use in 11 years of age and older)
Manufacturer: Sanofi Pasteur
Year licensed: 2005

All DTaP vaccines are available containing no or only trace amounts of thimerosal. DT & Td are both available as vaccines containing thimerosal preservative, containing trace amounts of thimerosal, or as thimerosal-free vaccines. For information on the thimerosal content in these vaccines, see the Food and Drug Administration at www.fda.gov/cber/vaccine/thimerosal.htm#t3

History of the Vaccine

In the mid-1940s, the diphtheria toxoid (inactivated toxin) vaccine was combined with vaccines against tetanus and pertussis. The combined DTP vaccine soon was routinely used in the United States, but is no longer recommended.

In 1991, the Food and Drug Administration licensed the DTaP (diphtheria-tetanus-acellular pertussis) vaccine. While DTP vaccine was made using whole cells of the pertussis germ, DTaP is made using only small, purified pieces of the germs. Fewer side effects have been reported with the DTaP vaccine than with DTP. In 1991, DTaP was licensed for only the fourth and fifth doses in the series, and in 1997 it was licensed for all five doses.

Two reduced diphtheria toxoid vaccines containing acellular pertussis vaccine were licensed by the Food and Drug Administration for use in older individuals in 2005. These vaccines are abbreviated Tdap.

There are 2 licensed vaccines that combine DTaP with other vaccine components, permitting a reduction in injections.

Who Should and Should Not Receive the Vaccine

Who should receive the vaccine?

• Most infants and children younger than seven years of age should receive DTaP beginning at two months of age.
• For children who are younger than 7 years of age for whom there is a reason to not give a pertussis-containing vaccine, the TD can be administered. Children seven to nine years of age who are incompletely immunized, should receive Tdap. Previously unimmunized children between the ages of seven and nine, also should receive a dose of Td one to two months later and then another dose of Td 6 to 12 months later.
• Children between 11 and 18 years of age should receive a dose of Tdap. The preferred age for Tdap vaccination is 11-12 years. Detailed recommendations for the use of Tdap for preteens and adolescents are available from the CDC.
• Adults 19-64 years of age should also receive a single dose of Tdap (ADACEL) to replace a single dose of Td for booster immunization if their most recent tetanus toxoid-containing vaccine was 10 or more years earlier. Tdap may be given at an interval shorter than 10 years since the last tetanus and diphtheria toxoids-containing vaccine in order to protect against pertussis, especially for:
  • Women <65 years of age who might become pregnant.
  • Women who have not previously received Tdap (including those who are breast feeding) should receive Tdap as soon after birth as is feasible. Many experts also recommend that Tdap be considered for pregnant teenagers.
  • Adults who have or anticipate having close contact with an infant aged <12 months should receive a single dose of Tdap and trivalent inactivated influenza vaccine. Ideally the vaccines should be given at least 2 weeks before contact.
  • Health-care personnel who have direct patient contact should receive a single dose of Tdap.

• Td vaccine should be administered every 10 years to provide continued immunity against diphtheria and tetanus.

Detailed recommendations for the use of Tdap in adults are available from the CDC.

Who should not receive the vaccine?

• Those with a history of a serious allergic reaction (such as anaphylaxis) to any of the vaccine components.
• Those with a history of encephalopathy (e.g. coma or prolonged seizures) not attributable to an identifiable cause within 7 days of administration of a vaccine with pertussis components should not receive a pertussis-containing vaccine.

People with the following conditions should discuss with their health care professional whether they should receive these vaccines:

• Moderate or serious reaction after receiving DTP or DTaP in the past
• Seizure or have a parent or sibling who has had a seizure (the risk of fever and seizure is much less with the new DTaP vaccines than with DTP).
• Brain problem that is unstable or getting worse
• People who are moderately or severely ill should consult with their physician before receiving any vaccine.

This vaccine is recommended by:

• Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention
• American Academy of Pediatrics
• American Academy of Family Physicians

The complete childhood immunization schedule can be found at:
http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm

Dose Schedule

A DTaP vaccine is given to most children at two, four, and six months of age. A fourth dose of DTaP is given between 15 and 18 months (17-20 months for Daptacel), and a fifth dose is given at age four to six years. PediarixTM can only be given for the first three doses a child receives. TriHIBit® is only licensed for use as a booster dose for children 15-18 months of age. Pentacel is not licensed for use in children over 4 years of age.

If the fourth dose was given after age four years, then no fifth dose is needed.

Receiving combination vaccines from different manufacturers, which may include different component vaccines, can make the dose schedule more complex. However, since giving combination vaccines means fewer shots overall for a child, healthcare providers will usually choose to administer them. Healthcare professionals should attempt to select vaccines for their patients, especially children who have been seen by others, based on what they have already been given.

Children younger than age seven who should not receive the pertussis vaccine should receive the DT (diphtheria-tetanus) vaccine.

Between the ages of seven and nine, Tadp—which contains the same amount of tetanus vaccine as DTaP or DT, but contains much less diphtheria toxoid—is given to protect against tetanus, and diphtheria and pertussis. Previously unimmunized children between the ages of seven and nine, also should receive a dose of Td one to two months later and then another dose of Td 6 to 12 months later.

At age 11-12 years, a booster shot of tetanus-diphtheria-acellular pertussis (Tdap) is needed. It should be given no later than 16 years of age. Every 10 years thereafter, a booster of Td is needed to maintain protection against diphtheria and tetanus.

One booster dose of Tdap is recommended for adults to replace a Td booster. Every 10 years thereafter, a booster of Td is needed to maintain protection against diphtheria and tetanus.

Effectiveness of the Vaccine

The DTaP vaccine is 95% effective in preventing all three diseases that it immunizes against—diphtheria, tetanus and pertussis. It is also about 95% effective in preventing diphtheria, while the protection rates are lower for pertussis and higher for tetanus. Immunity against diphtheria lasts about 10 years; therefore a booster dose of Td (tetanus-diphtheria) vaccine is needed every 10 years to maintain immunity. If exposed to diphtheria, partially immunized individuals can acquire the disease, although generally it is less severe than in unimmunized people.

Known Side Effects

The DTP vaccine is no longer recommended in the United States. DTaP is now recommended because the rates of all reactions following the DTaP vaccine are lower than with DTP; however, if a person had a serious adverse reaction related to DTP, they should not be given DTaP.

Vaccines, particularly pertussis-containing vaccines have been incorrectly blamed for many things in the past. For example, the evidence does not support a casual role for DTaP vaccines as a cause of asthma, autism, type 1 diabetes, brain damage, or sudden infant death syndrome (SIDS). Severe encephalopathy (brain injury) within 7 days after DTaP vaccination is usually explainable by another cause but is also considered a reason to omit the pertussis component in subsequent doses of vaccine.

Half of those vaccinated with DTaP will experience no side effects at all. About half of those vaccinated will experience mild reactions such as soreness where the shot was given, fever, fussiness, reduced appetite, tiredness, or vomiting. Some children may experience a temporary swelling of the entire arm or leg where DTaP was given; this reaction is more common after the fourth or fifth dose of DTaP but does not indicate that it will happen again after the next dose.

Although a single case of recurrent Guillain-Barre syndrome (GBS) after multiple doses of tetanus toxoid has been documented, analyses of cases of GBS found by active surveillance found no increased risk of GBS within 6 weeks following immunizations with tetanus toxoid-containing vaccines.

The rate of severe allergic reactions after DTaP is unknown but these occurred rarely after DTP vaccine so they are theoretically possible.

In rare cases (about 100 children out of 10,000 shots given, or about 1%) children have moderate reactions such as prolonged crying, fever of 105 degrees or higher, seizure, or the child becoming limp, pale, and less alert. Children who have had these reactions after DTaP have had no sequelae.

Studies have shown that children who receive the Hib vaccine in combination with or at the same time as the DTaP vaccine are no more likely to experience side effects than children who only receive the DTaP vaccine.

Related Issues

Outbreaks of diphtheria in eastern Europe and the Russian Federation occured when immunization levels fell. Outbreaks of pertussis have occurred when immunization levels have fallen largely as a consequence of misinformation claims about DTaP vaccine. To read more about this see Do Vaccines Cause That?! A Guide for Evaluating Vaccine Safety Concerns.

Key References and Sources of Additional Information

• American Academy of Pediatrics, Committee on Infectious Diseases. (2009). Red Book: Report of the Committee on Infectious Diseases (28th ed.). Elk Grove Village, IL..
• Centers for Disease Control and Prevention (CDC). Vaccine Information Statements (VIS).
• CDC. (1997). Pertussis vaccination: Use of acellular pertussis vaccines among infants and young children: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR, 46(RR-7),1-25.
• CDC. (2000). Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as afive-dose series: Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR, 49 (RR-#13).
• CDC (2006). Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR, 55(No. RR-3).
• CDC (2006). Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel.. MMWR 55(RR-#17).
• CDC. (2008). Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus, and Haemophilus b conjugate vaccine and guidance for use in infants and children. MMWR 57(39); 1079-80.

• CDC. (2011). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices. MMWR 60(1): 13-15.
• CDC frequently updates immunization schedules:
  • For infants and children: http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm.
  • For preteens and adolescents: http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm
  • For adults: http://www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm

CDC Information

http://www.cdc.gov/vaccines/pubs/default.htm#vis