What is Diphtheria?

Diphtheria is a rare toxin-mediated respiratory disease caused by the bacterium Corynebacterium diphtheriae (C. diphtheriae), an aerobic gram-positive bacillus. The production of the toxin only occurs when C. diphtheriae is affected by the specific virus which contains the genetic toxin information. When this happens, the serious disease will occur. There are four different types (biotypes) of C. diphtheriae – belfanti, gravis, intermedius, and mitis. All strains can cause toxin production that can lead to serious disease. 

Diphtheria causes a gray-green to black, thick fiber-like covering (pseudomembrane) in the back of the throat and on the tonsils. The pseudomembrane can restrict breathing and swallowing. Additional symptoms of the disease include swelling of the lymph nodes in the neck, sore throat, weakness, malaise, fever, and chills.  If the toxins enter the bloodstream, additional complications may occur, including neuritis, myocarditis, proteinuria, pneumonia, thrombocytopenia, and death. 

Diphtheria is contagious and is spread from person to person through respiratory secretions (coughing, sneezing). It can also be transmitted if a person touches a wound of a person with diphtheria, or from touching objects contaminated with the bacteria. Vaccinated individuals are still able to spread the bacteria because vaccination does not eliminate carriage of Corynebacterium diphtheriae in the back of the throat or on the skin. 

The incubation period of diphtheria ranges from one to 10 days but is generally between two and five days. The disease can affect any mucus membrane in the body, and symptoms will differ depending on the site. Areas that can be infected include the skin (cutaneous), anterior nasal passages, tonsils and pharynx, larynx, eye (ocular), external ear canal, and genitals.  Certain strains of diphtheria do not produce toxins and will generally result in mild to moderate inflammation of the throat.  Diphtheria can reoccur in individuals who have already had the disease. 

Cutaneous diphtheria is common in persons who reside in tropical countries. In the U.S., it is usually found among persons experiencing homelessness, and the strains are generally not toxin-producing. These infections typically present as ulcers or a scaling rash.  In 2019, the CDC updated their case definition of diphtheria to include cases of cutaneous diphtheria.  However, as of March 2021, no adequate data is available on the prevalence of cutaneous diphtheria in the United States. 

C. diphtheriae is exclusive to humans, and most who have it are asymptomatic. The disease is extremely rare in U.S. and other developed countries with good sanitation.  Between 1996 and 2017, there were 13 reported cases of respiratory diphtheria in the U.S. – five confirmed through culture and eight considered probable, as culturing was not completed. Of those cases, one fatality occurred in an international traveler who returned from an area where diphtheria is considered endemic. 

Globally, in 2017, there were 8,819 cases of diphtheria reported worldwide. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Is Diphtheria contagious?

Diphtheria spreads through respiratory droplets produced by a cough or sneeze from an infected person, or from someone who carries the bacteria, but has no symptoms. Vaccinated individuals are still able to spread the bacteria because vaccination does not eliminate carriage of Corynebacterium diphtheriae in the back of the throat or on the skin.  

Diphtheria can also be transmitted if a person touches a wound of a person with diphtheria or by touching objects contaminated with the bacteria.  Diphtheria can reoccur in individuals who have already had the disease. 

C. diphtheriae is exclusive to humans, and most who have it are asymptomatic. The disease is extremely rare in U.S. and other developed countries with good sanitation. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

What is the history of Diphtheria in America and other countries?

The earliest accounts of diphtheria date back to Hippocrates in the 4th century B.C. with epidemics of the disease first noted by Aetius in the 6^th century A.D. Monks in A.D. 856, 1004, and 1039 also described the epidemics, but the first descriptions of the diphtheria membrane did not occur until French physician Guillaume de Baillou recorded them in 1576. Additional documentation on diphtheria was recorded in the 17^th and 18^th centuries. 

The disease was formally named and described in detail in 1821 by French physician Pierre Bretonneau. Its name was derived from the Greek word Diphthera, meaning leather hide, and after the characteristic pseudomembrane found in the back of the throat of those affected by the disease. 

The bacteria responsible for diphtheria, Corynebacterium diphtheriae, was first identified in 1883 by Klebs. In 1884, Loeffler discovered that this bacterium could be cultured from the back of the throat.  In 1888, Emile Roux and Alexandre Yersin demonstrated that a component of C. diphtheriae, the diphtheria toxin, caused symptoms of diphtheria in animals. In the early 1890’s, Emil Behring and Shibasaburo Kitasato reported that serum taken from animals immunized against diphtheria toxin could be used to prevent and treat diphtheria. Behring went on to develop the first diphtheria antitoxin; however, his initial serum formulation was unsuccessful. The antitoxin became more effective once researchers began using horses to produce it. In 1897, Paul Erhlich developed a standardized unit of measurement for the diphtheria antitoxin.    While reportedly effective at treating diphtheria, horse-derived antitoxin was also associated with anaphylaxis and serum sickness.    

The use of the diphtheria antitoxin was questioned by certain physicians at the time, who expressed concerns that it was not necessarily safe or even effective. In 1907, Boston physician Dr. Charles E. Page reported that injecting disease to prevent disease was likely not the solution to treating diphtheria and other diseases. Page believed that improvements in cleanliness and sanitation would ultimately be more effective. 

Proper sanitation was also mentioned as a way to prevent diphtheria in an article published in the Journal of the American Medical Association in 1922. Dr. James Gordon Cumming noted that in the past 30 years, the mortality rate from diphtheria had decreased, but the incidence rate of the disease had not. 

When diphtheria was a common disease, approximately 40 percent of cases occurred in children under age five, and 70 percent among children under age 15.

In 1920, there were 147,991 reported cases of diphtheria in the U.S.  Rates, however, were declining and according to public health officials: 

“The simultaneous decline in diphtheria morbidity and mortality rates in all age groups of individual States located in different sections of the country, which began after a cyclic increase in incidence between 1915 and 1925, suggests the operation or influence of other factors besides, or in addition to, artificially induced immunity.”

In 1930, government officials reported that while widespread vaccination programs were occurring in some areas, while other areas had few programs. Yet after 1925, diphtheria morbidity and mortality rates decreased in all U.S. states simultaneously.  Public health officials reviewing the decline in diphtheria morbidity and mortality reported that:

“The great decline in mortality, the early date at which it was manifested, and the widespread area over which it has been experienced, all go to indicate that it is attributable largely to causes other than specific treatment and immunization. The remarkable reduction in morbidity and mortality since 1927, if viewed as a separate phenomenon, might be attributed in part at least to artificial immunization. That this has been a major factor, however, would seem to be quite improbable, as the recent acceleration of the decline has likewise been experienced over a wide area and, even in many cities in which immunization has been most extensively practised, the reduction has been far greater than can be satisfactorily explained by the numbers of persons immunized. Viewing all the available facts, the conclusion seems inevitable that other factors have played a major role.” 

During this time in Europe, outbreaks of a severe form of diphtheria were increasing. In 1926, Germany reported approximately 50,000 cases. That number significantly increased to 150,000 by 1936. By this time, researchers had confirmed the presence of at least 3 types of Corynebacterium diphtheriae – Mitis, gravis, and intermedius. Additionally, in some areas of Europe, strains of an atypical diphtheria bacteria were also noted but were reported as being milder and not usually associated with severe illness. 

Mitis strains in infants were associated with high mortality rates due to airway obstruction and lung involvement. Gravis and intermedius strains were associated with paralysis and heart issues, and these strains were considered more severe. 

The diphtheria antitoxin continued to be the treatment of choice; however, published research at the time questioned its effectiveness, and researchers stated that: 

“Not only are there these numerous records of unusually severe diphtheria, but there is no doubt that in many of these outbreaks the results of serum treatment have been singularly disappointing notwithstanding the great advances in the potency of antitoxic serum. So much is this the case that a considerable controversy has gone on in the European medical press on the value of anti-diphtheritic serum.”

In the U.S, the number decreased significantly and by 1943, 14,811 cases and 1,169 deaths were reported  and 8 out of 11 cases were diagnosed in adults.  A study published in 1950 reported that while diphtheria morbidity and mortality had decreased by 90 percent, cases had increased among adults. Additionally, mortality rates among all persons under the age of 20 declined nearly uniformly, but in most states, death rates of persons over the age of 20 did not significantly decrease when compared to the younger age group. The study’s author hypothesized that since diphtheria was no longer as widespread, symptoms of the disease in adults was not recognized early enough for treatment to be effective. 

An increase in the percentage of cases among adults was noted in both the U.S. and in Europe during this time, and while most public health officials attributed the shift in demographic to vaccination, historical data notes that this shift also occurred in areas that did not vaccinate. During World War II, many European countries experienced diphtheria outbreaks and it was estimated that in 1943, there were approximately one million cases, and at least 50,000 deaths. Many countries noted an increase in rates among adults. 

In the early 1940’s, Germany experienced a significant outbreak of diphtheria, and by 1943, over half the cases occurred among adults. Antitoxin treatment was found to be ineffective, even when administered early. Death rates among adults also increased, from 12 percent in 1939, to 48 percent in 1943. While some researchers suggested that vaccination of children against diphtheria was responsible for the age shift, this was not accurate, as diphtheria cases also rose significantly among children. Further, any vaccination strategies during World War II were likely very limited and would have had little to no impact on changing the age demographic of diphtheria. 

Researchers also suggested that the spike in diphtheria cases was likely due to living conditions during the war, which frequently resulted in water, food, and electricity shortages, and confinement in overcrowded bomb shelters. 

In the U.S. in 1953, there were 2,355 diphtheria cases and 156 deaths, indicating a death rate of 6.6 percent. Most cases of diphtheria were reported in the Southern U.S. States.  Cases continued to decrease until 1959, when a slight increase from one year earlier occurred. In 1959, there were 934 cases and 72 deaths, up from a total of 918 cases and 74 deaths one year earlier.  Most cases were among children ages five through nine, and most occurred in persons living in the South Central and South Atlantic States. 

Between 1960 and 1979, diphtheria continued to decrease; however, the decline was not as consistent. Sporadic outbreaks continued to occur, but the incidence rates were reported at 0.11 cases per 100,000 population. Between 1959 and 1970, most cases occurred in the Southern U.S. States, with Louisiana most impacted. Between 1971 and 1975, cases occurred more frequently in the Western states. Native Americans were most impacted and rates of diphtheria among this population were 20 times higher than rates among Caucasians, and three times higher than rates among African Americans. The higher rates among these populations were blamed on low socioeconomical status and poor hygiene. 

Cases among persons 15 years of age and older increased from 21 percent in 1960 to 48 percent between 1971 and 1981. Death rates between 1959 and 1970 were four times higher among children under five than for persons 20 years of age and older. 

In 1960, there were 918 diphtheria cases and 69 death, with 43 out of 50 states reporting cases.  By 1978, there only 76 cases and four deaths, with most cases occurring in Washington State.   

Between 1972 and 1975, an outbreak of diphtheria impacted Seattle, Washington, with most cases occurring in a poor section of the city known as “Skid Row”. This outbreak resulted in 558 cases, of which 74 percent were cutaneous diphtheria. Ninety-three percent of cases occurred in adults, with approximately 70 percent reporting frequent alcohol use. Most cases were among males (84 percent) and three deaths were reported, all among white males over the age of 47.  Of those infected who were under the age of 20, 80 percent had received the three recommended primary doses of diphtheria vaccine. 

During this outbreak, 39 percent of cases were among Native Americans and in 1973, a separate outbreak of cutaneous diphtheria occurred among Native American children residing in a rural area of Washington State. This outbreak infected 27 children, and 54 were found to be carriers of diphtheria.    

Since 1979, reporting of cutaneous diphtheria has not been consistent and in 1990, the CDC stated that cases of cutaneous diphtheria should not be reported.  There were only four reported cases of diphtheria in 1990. 

In the 1990s, the former Soviet Union experienced an outbreak of diphtheria with an estimated 115,000 cases and 3,000 deaths. Despite vaccination programs targeting diphtheria which had been ongoing since the 1950s, toxigenic strains of C. diphtheriae had continued to circulate in the environment. Many cases of diphtheria occurred among vaccinated individuals and researchers reported that a new biotype of C. diphtheriae and waning immunity were responsible for the outbreak. Additionally, they stated that vaccine supply, an adequate vaccine, and access to vaccine providers were not responsible for the outbreak. They also reported that social factors such as an increase in homelessness, crowded living conditions, and a susceptible military contributed to this outbreak. 

Between 1996 and 2017, there were 13 reported cases of respiratory diphtheria in the U.S. – five confirmed through culture and eight considered probable, as culturing was not completed. Of those cases, one fatality occurred in an international traveler who returned from an area where diphtheria is considered endemic. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Can Diphtheria cause injury and/or death?

There is a gap in medical knowledge in terms of predicting who will have a mild case of diphtheria and who will have a serious or even deadly case of it. Complications from diphtheria include myocarditis (inflammation of the heart wall), and neuritis (inflammatory of the peripheral nervous system). Additional complications include paralysis, which may result in respiratory insufficiency, and pneumonia. Infants who develop diphtheria are more likely to suffer from middle ear infections and respiratory complications related to airway blockage.

Death from diphtheria is estimated to occur in five to ten percent of all cases. Persons more at risk from death are those older than 40 years of age or less than five.¹

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Who is at highest risk for getting Diphtheria?

Diphtheria is extremely rare in U.S. and other developed countries with good sanitation.  Between 1996 and 2017, there were 13 reported cases of respiratory diphtheria in the U.S. – five confirmed through culture and eight considered probable, as culturing was not completed. Of those cases, one fatality occurred in an international traveler who returned from an area where diphtheria is considered endemic. 

Those at highest risk for developing diphtheria are persons who travel to countries where diphtheria is endemic and where sanitation is inadequate.  Those regions include Eastern Europe, the Middle East, Asia, the South Pacific, and countries including Haiti, the Dominican Republic, and Venezuela. 

Cutaneous diphtheria, a form of diphtheria that affects the skin, is commonly seen among persons who live in tropical climates or among persons experiencing homelessness.   

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Who is at highest risk for suffering complications from Diphtheria?

While diphtheria is extremely rare in U.S. and other developed countries with good sanitation,  it is still endemic in various areas including Eastern Europe, the Middle East, Asia, the South Pacific, and countries including Haiti, the Dominican Republic, and Venezuela. 

Death from diphtheria is estimated to occur in five to ten percent of all cases. Persons more at risk from death are persons older than 40 years of age or less than five. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Can Diphtheria be prevented and are there treatment options?

Diphtheria can be prevented by ensuring proper hygiene practices which include: 

· Frequent handwashing with soap and water

· Proper disposal of used tissues

· Avoiding use of items belonging to persons who may be ill

· Staying away from individuals who are sick

Treatment options for diphtheria include the use of diphtheria antitoxin, and antibiotics such as penicillin and erythromycin. 

Additional medical interventions may include: 

• Fluids by IV

• Oxygen

• Bed rest

• Heart monitoring

• Insertion of a breathing tube

• Correction of airway blockages

It is estimated that 90 percent of individuals who receive treatment for respiratory diphtheria will fully recover within four to six weeks. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

What is Diphtheria vaccine?

In the U.S. today, diphtheria vaccine is administered only in a combination shot (DTaP, DT, Tdap, Td) that contains vaccines for tetanus (T), diphtheria (D) and possibly pertussis (whooping cough) (P). It can also be found in combination with vaccines for polio, Haemophilus influenzae B (HIB), and hepatitis B (see below for descriptions).

The CDC’s Advisory Committee on Immunization Practices (ACIP) currently recommends administration of a diphtheria containing vaccine (DTaP) at two, four, and six months old; between 15 and 18 months old; and between four and six years old. Another booster dose is recommended at 11-12 years of age (Tdap). After a booster dose of Tdap vaccine, booster doses with a diphtheria toxoid (Td or Tdap) are recommended every ten years throughout a person’s life. 

While ACIP also recommends that pregnant women between 27- and 36-weeks gestation receive a dose of Tdap vaccine during each pregnancy, regardless of a previous history of Tdap vaccine,  this recommendation contradicts the information provided by the vaccine manufacturers. Boostrix vaccine is approved to be administered only as a single dose  and the Adacel package insert states that a second dose of Adacel vaccine may be administered if there has been at least an eight year interval between the first Tdap dose.  The product insert of both Boostrix and Adacel, the two available FDA licensed Tdap vaccines, also state that there are “no adequate and well-controlled studies” on the use of Tdap vaccine in pregnant women.   

Diphtheria Toxoid Vaccines Licensed for Use in the U.S.

The U.S. Food and Drug Administration has approved twelve different combination vaccine that include diphtheria toxoid vaccine. There are different rules for use of these vaccines by different age groups.

Following is a list of currently available vaccine combination shots that contain diphtheria toxoid vaccine with links to the manufacturer product inserts (click on the name of the product):

• Infanrix, a 3 in 1 combination shot containing diphtheria, tetanus toxoids, and acellular pertussis vaccine for children under 7 years of age. It is manufactured by GlaxoSmithKline.
• DAPTACEL, a 3 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis vaccine for children under 7 years of age. It is manufactured by Sanofi Pasteur Ltd.
• Pediarix, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccines for children under 7 years of age. It is manufactured by GlaxoSmithKline.
• Kinrix, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis and inactivated poliovirus vaccines for children 4 to 6 years old. It is manufactured by GlaxoSmithKline.
• Quadracel, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoid, acellular pertussis and inactivated poliovirus vaccine for children 4 to 6 years old. It is manufactured by Sanofi Pasteur
• Pentacel, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine for children under four years old. It is manufactured by Sanofi Pasteur Ltd.
• VAXELIS, a 6 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus b conjugate, and hepatitis B recombinant vaccine for children under 5 years of age. It is manufactured by MCM Vaccine Company. (Not currently available for use)
• Diphtheria and Tetanus Toxoid Adsorbed, a 2 in 1 combination shot containing diphtheria and tetanus toxoid for children under seven years old. It is manufactured by Sanofi Pasteur Ltd
• Adacel, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine for those 10 years or older. It is manufactured by Sanofi Pasteur Ltd.
• Boostrix, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine for those 10 years or older. It is manufactured by GlaxoSmithKline.
• TDVAX, a 2 in 1 combination shot containing tetanus and diphtheria toxoid for those 7 years of age or older. It is manufactured by MassBiologics
• TENIVAC, a 2 in 1 combination shot containing tetanus and diphtheria toxoid for those 7 years of age or older. It is manufactured by Sanofi Pasteur

Combination Vaccines

There are some doctors who limit the number of vaccines given simultaneously on the same day and will work as partners with parents to choose certain vaccine products and develop individualized schedules for vaccination. If you want your child to receive diphtheria vaccine but would prefer a 3 in 1 combination shot (diphtheria, tetanus, and pertussis) rather than a 4 in 1 or 5 in 1 combination shot, talk with your doctor.

If your doctor or the nurse administering vaccines refuses to have a discussion with you about vaccine products or schedules, you may want to consider consulting one or more other trusted health care professionals before making a vaccine decision.

Not all diphtheria-containing vaccines have been studied in clinical trials to prove the safety and effectiveness of giving the shot simultaneously with other licensed vaccines. Check the product inserts for more information about administering vaccines at the same time with other vaccines.

About Infanrix Vaccine in Brief

• Ages: Infanrix is a 3 in 1 shot (diphtheria, tetanus, acellular pertussis vaccine) given to children under age seven (see GlaxoSmithKline product insert for recommended schedule and other indications).
• Vaccine ingredients: Aluminum hydroxide, sodium chloride, polysorbate 80 (Tween 80), formaldehyde, modified Stainer-Scholte liquid medium, glutaraldehyde, fenton medium containing a bovine extract, modified Latham medium derived from bovine casein.
• Estimated Efficacy: Efficacy of diphtheria toxoid in Infanrix was based on immunogenicity (blood immune response) and was tested in only 45 infants one month following the completion of three doses of Infanrix vaccine. At this time, 100 percent of infants had a blood immune response to Infanrix
• Use with Other Vaccines: In clinical trials, Infanrix was given with HIB, pneumococcal, hepatitis B, inactivated polio or MMR vaccines. There is no information in the package insert about the safety or effectiveness of giving Infanrix simultaneously with inactivated or live influenza, rotavirus, varicella or hepatitis A vaccines.
• Commonly Reported Adverse Events: Pain, redness, and swelling at the site of the injection; drowsiness; irritability/fussiness; loss of appetite.
• Other Serious Reported Adverse Events: Hypotonic-hyporesponsive (collapse) episode; persistent cry for three or more hours; high fever, and convulsions (seizures). After licensure (post-marketing), reported adverse events included bronchitis, cellulitis, respiratory tract infection, lymphadenopathy, thrombocytopenia, anaphylactic reaction, encephalopathy, headache, hypotonia, ear pain, apnea, cough, angioedema, pruritus, rash, fatigue and Sudden Infant Death Syndrome (SIDS).
• Contraindications and precautions (Some reasons Infanrix should not be given to a child – See GlaxoSmithKline product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting 3 hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy;
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Infanrix vaccine product insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Infanrix vaccine;
  • The tip caps of prefilled Infanrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

NVIC NOTE: Some doctors only vaccinate children who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Infanrix. It is also not known whether Infanrix can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Infanrix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About DAPTACEL Vaccine in Brief

• Ages: DAPTACEL is a 3 in 1 shot (diphtheria, tetanus, acellular pertussis vaccines) given to children under age seven (see Sanofi Pasteur product insert for recommended schedule and other indications).
• Vaccine ingredients: Aluminum phosphate, formaldehyde, ammonium sulfate, modified Mueller-Miller casamino acid medium without beef heart infusion, glutaraldehyde, 2-phenoxyethanol, Stainer-Scholte medium, casamino acids, dimethyl-beta-cyclodextrin, Mueller’s growth medium.
• Estimated Efficacy: In a U.S study of children who received four doses of DAPTACEL vaccine at two, four, six and 15-17 months, after administration of the third dose of vaccine (at six months of age), 100 percent of vaccine recipients were found to have blood antibody levels indicative of protection. Following administration of the fourth dose of DAPTACEL, 96.5 percent of children sampled were found to have levels of blood antibodies considered to be protective against diphtheria disease.
• Use with Other Vaccines: In clinical trials, DAPTACEL was given with HIB, inactivated polio (IPV), hepatitis B, pneumococcal, and MMR or varicella vaccines. There is no information in the package insert about the safety or effectiveness of giving DAPTACEL simultaneously with inactivated or live influenza, rotavirus, or hepatitis A vaccines. DAPTACEL has been noted to reduce meningococcal antibody responses to Menactra when administered one month after Menactra. In cases where DAPTACEL and Menactra are to be administered, the vaccines are recommended to be given at the same time or else one month apart, with Menactra administered first.
• Commonly Reported Adverse Events: Injection site soreness, tenderness, redness, and increase in arm circumference; fussiness/irritability; inconsolable crying; decreased activity/lethargy.
• Other Serious Reported Adverse Events: Convulsions (seizures), including infantile spasms; bronchiolitis; pneumonia; meningitis; sepsis; irritability; unresponsiveness. After licensure (post-marketing), reported adverse events have also included cyanosis, nausea, diarrhea, cellulitis, and allergic reaction.
• Contraindications and precautions (Some reasons DAPTACEL should not be given to a child – See Sanofi Pasteur product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy).
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. DAPTACEL vaccine package insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering DAPTACEL vaccine.

NVIC NOTE: Some doctors only vaccinate children who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with DAPTACEL. It is not known whether DAPTACEL can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. DAPTACEL has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Pediarix Vaccine in Brief

• Ages: Pediarix is a 5 in 1 shot (diphtheria, tetanus, acellular pertussis, inactivated polio and recombinant hepatitis B vaccines) given to children under age seven (see GlaxoSmithKline product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum hydroxide, aluminum phosphate, aluminum salts, sodium chloride, polysorbate 80 (Tween 80), neomycin sulfate, polymyxin B, yeast protein, VERO cells, a continuous line of monkey kidney cells, calf serum and lactalbumin hydrolysate, fenton medium containing a bovine extract, modified Latham medium derived from bovine casein, formaldehyde, glutaraldehyde, modified Stainer-Scholte liquid medium.
• Estimated Efficacy: Antibody responses to diphtheria were tested one month following three doses of Pediarix administered in concomitantly with Hib vaccine and PCV7 (Prevnar 7) vaccine at two, four, and six months. At this time, 99.4 percent of vaccine recipients were found to have blood antibody levels considered to be protective against diphtheria.
• Use with Other Vaccines: In clinical trials, Pediarix was given with HIB conjugate vaccine (no longer licensed in the U.S.) or pneumococcal vaccines (PCV7). There is no information in the package insert about the safety or effectiveness of giving Pediarix simultaneously with inactivated or live influenza, rotavirus, or hepatitis A vaccines.
• Commonly Reported Adverse Events: Local injection site reactions (pain, redness, or swelling); fussiness, high fever (Pediarix is associated with higher rates of fever relative to separately administered vaccines. The prevalence of fever was highest on the day of vaccination and the day following vaccination).
• Other Serious Reported Adverse Events: High fever that required medical attention (In a safety study that evaluated medically attended fever after Pediarix or separately administered vaccines when co-administered with 7-valent pneumococcal and Hib conjugate vaccines, infants who received Pediarix had a higher rate of medical encounters for fever within the first four days following the first vaccination); febrile and afebrile convulsions (seizures); gastroenteritis, bronchiolitis; asthma, diabetes mellitus, and chronic neutropenia; anaphylactic reactions (hives, swelling, difficulty breathing, hypotension or shock), demyelinating diseases.
• Contraindications and precautions (Some reasons why Pediarix should not be given to a child – See GlaxoSmithKline product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Sensitivity to any component of Pediarix, including yeast or neomycin and polymyxin B (antibiotics);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Pediarix vaccine package insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • The tip caps of prefilled Pediarix syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Pediarix vaccine.

NVIC NOTE: Some doctors only vaccinate children who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Pediarix. It is not known whether Pediarix can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Pediarix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Kinrix Vaccine in Brief:

• Ages: Kinrix is a 4 in 1 shot (diphtheria, tetanus, acellular pertussis, inactivated polio vaccines) given to children four to six years old (see GlaxoSmithKline product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum hydroxide, VERO cells - a continuous line of monkey kidney cells, calf serum, lactalbumin hydrolysate, fenton medium containing a bovine extract, modified Latham medium derived from bovine casein, formaldehyde, modified Stainer-Scholte liquid medium, glutaraldehyde, sodium chloride, polysorbate 80 (Tween 80), neomycin sulfate, polymyxin B.
• Estimated Efficacy: The efficacy of the diphtheria toxoid component of Kinrix is estimated to be equal to that of Infanrix.
• Use with Other Vaccines: In clinical trials, Kinrix was administered simultaneously with the second dose of MMR or MMR and Varicella vaccine. There is no information in the product insert about the safety or effectiveness of giving Kinrix simultaneously with inactivated or live influenza, hepatitis B, or hepatitis A vaccines.
• Commonly Reported Adverse Events: Injection site pain, including redness, swelling and increase in arm circumference; drowsiness; fever; loss of appetite.
• Other Serious Reported Adverse Events: Gastroenteritis, dehydration, and cellulitis. After licensure (post-marketing) reported adverse event reports have also included apnea, collapse or shock-like state (hypotonic-hyporesponsive episode), convulsions (with or without fever), injection site vesicles; pruritus (intense itching); allergic reactions, including anaphylaxis; urticaria; angioedema; lympadenopathy, and thrombocytopenia.
• Contraindications and precautions (Some reasons why Kinrix should not be given to a child – See GlaxoSmithKline product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Severe allergic reaction to any component of Kinrix, including neomycin and polymyxin B (antibiotics);
  • The tip caps of prefilled Kinrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • If Guillain-Barré syndrome (GBS) occurred within 6 weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Kinrix vaccine. 

NVIC NOTE: Some doctors only vaccinate children who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Kinrix. It is not known whether Kinrix can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Kinrix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Quadracel Vaccine in Brief:

• Ages: Quadracel is a 4 in 1 shot (diphtheria, tetanus, acellular pertussis, inactivated polio vaccines) given to children four to six years old (see Sanofi Pasteur product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum phosphate, Stainer-Scholte medium, casamino acids, dimethyl-beta-cyclodextrin, MRC-5 cells, normal human diploid cells, CMRL 1969 medium supplemented with calf serum, modified Mueller’s growth medium, ammonium sulfate, modified Mueller-Miller casamino acid medium without beef heart infusion, formaldehyde, 2-phenoxyethanol, polysorbate 80, glutaraldehyde, neomycin, polymyxin B sulfate.
• Estimated Efficacy: The efficacy of the diphtheria toxoid vaccine component of Quadracel is estimated to be equal to that of DAPTACEL.
• Use with Other Vaccines: In clinical trials, Quadracel was administered simultaneously with the MMR and varicella. There is no information in the product insert about the safety or effectiveness of giving Quadracel simultaneously with inactivated or live influenza, hepatitis A, or hepatitis B vaccines.
• Commonly Reported Adverse Events: Injection site pain, including redness, swelling and increase in arm circumference; malaise; muscle pain; headache.
• Other Serious Reported Adverse Events: After licensure (post-marketing) reported adverse event reports have also included cyanosis; convulsions (with or without fever); injection site abscess; injection site cellulitis; pallor; screaming; allergic reactions, including anaphylaxis; urticarial, and dyspnea.
• Contraindications and precautions (Some reasons why Quadracel should not be given to a child – See Sanofi Pasteur product insert for complete list):
  • Serious allergic reaction following administration of a pertussis, tetanus, diphtheria, or polio containing vaccine or any ingredient of Quadracel vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Seizures within three days of a previous pertussis vaccination;
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Quadracel vaccine.

NVIC NOTE: Some doctors only vaccinate children who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Quadracel. It is not known whether Quadracel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Quadracel has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Pentacel Vaccine in Brief:

• Ages: Pentacel is a 5 in 1 shot (diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenzae b conjugate vaccines) for children under age five (see Sanofi Pasteur product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum phosphate, polysorbate 80, sucrose, formaldehyde, glutaraldehyde, bovine serum albumin, 2-phenoxyethanol, MRC-5 cells (a line of normal human diploid cells), CMRL 1969 medium supplemented with calf serum, Medium 199 without calf serum, modified Mueller and Miller medium, neomycin, polymyxin B sulfate, modified Mueller’s growth medium, ammonium sulfate, modified Mueller-Miller casamino acid medium without beef heart infusion, Stainer-Scholte medium, casamino acids, dimethyl-beta-cyclodextrin.

• Estimated Efficacy: Antibody responses to tetanus were tested one month following three doses of Pentacel at two, four, and six months. At this time, 98.8 percent of vaccine recipients were found to have blood antibody levels considered to be protective against diphtheria. Following a booster dose of Pentacel at 15-16 months, 100 percent of vaccine recipients were noted to have blood antibody levels considered protective against diphtheria.

• Use with Other Vaccines: In clinical trials, Pentacel was given with hepatitis B, pneumococcal, MMR or varicella vaccines. There is no information in the package insert about the safety or effectiveness of giving Pentacel simultaneously with inactivated or live influenza, rotavirus, or hepatitis A vaccines
• Commonly Reported Adverse Events: Systemic reactions that occurred in clinical trials in more than 50 percent of participants following any dose included fussiness/irritability and inconsolable crying; fever; injection site reactions, including tenderness, abscess and increase in arm circumference. Cases of encephalopathy and death occurred in clinical trials but were not causally attributed to Pentacel vaccine by investigators.
• Other Serious Reported Adverse Events: After licensure (post marketing), there have been reports of febrile and afebrile convulsions (seizures); bronchiolitis, gastroenteritis, dehydration, pneumonia, lethargy/somnolence; hypotonic/hyporesponsive episode (collapse); apnea, cyanosis, asthma.
• Contraindications and precautions (Some reasons why Pentacel should not be given to a child – See Sanofi Pasteur product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Severe allergic reaction to any component of Pentacel, including neomycin and polymyxin B (antibiotics);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Pentacel vaccine product insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Pentacel vaccine.

NVIC NOTE: Some doctors only vaccinate children, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Pentacel. It is not known whether Pentacel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Pentacel has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About VAXELIS Vaccine in Brief:

• Ages: VAXELIS is a 6 in 1 shot (diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, Haemophilus influenzae b (Meningococcal Protein Conjugate) and Hepatitis B (recombinant) vaccines for infants and children between six weeks through four years of age (prior to the fifth birthday) (see MCM company product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum, polysorbate 80, glutaraldehyde, formaldehyde, bovine serum albumin, neomycin, streptomycin sulfate, polymyxin B sulfate, yeast protein, ammonium thiocyanate, Mueller’s growth medium, Mueller-Miller casamino acid medium without beef heart infusion, ammonium sulfate, aluminum phosphate, Stainer-Scholte medium, Vero cells, extract of yeast, soy peptone, dextrose, amino acids, mineral salts, amorphous aluminum hydroxyphosphate sulfate.

• Estimated Efficacy: Diphtheria antibodies measured one month following administration of three doses of VAXELIS were found to be at 82.4 percent.
• Use with Other Vaccines: In clinical trials, VAXELIS was given with pneumococcal (Prevnar 13) and rotavirus (RotaTeq) vaccines. There is no information in the package insert about the safety or effectiveness of giving VAXELIS simultaneously with inactivated or live influenza, hepatitis A, measles, mumps, rubella (MMR), varicella, or measles, mumps, rubella and varicella (MMR-V) vaccines.

• Commonly Reported Adverse Events: Systemic reactions that occurred in clinical trials following any dose included injection site redness, swelling, and pain, fever, crying, decreased appetite, irritability, vomiting, and somnolence.
• Other Serious Reported Adverse Events: In the two U.S. clinical trials, six deaths were reported but were determined not to be attributed to VAXELIS by trial investigators. These deaths included sepsis, asphyxia, hydrocephalus, unknown cause, and two cases of sudden infant death syndrome (SIDS). As VAXELIS is not currently available for use in the United States, post-marketing data on serious adverse events are limited to those events considered to have a causal link to the vaccines containing the antigens of VAXELIS. These include anaphylaxis, hypersensitivity, seizures, including febrile seizures, and excessive swelling of the injected limb.
• Contraindications and precautions (Some reasons why VAXELIS should not be given to a child – See MCM Vaccine Company product insert for complete list):
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous dose of VAXELIS, any ingredient found in VAXELIS, or any other tetanus toxoid, diphtheria toxoid, pertussis-containing vaccine, hepatitis B vaccine, inactivated poliovirus vaccine, or H. influenzae type b vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering VAXELIS vaccine;
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision to vaccinate an infant born prematurely should be careful based on both the possible benefits and potential risks of vaccination.

NVIC NOTE: Some doctors only vaccinate children, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you do not want your acutely ill baby vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with VAXELIS. It is not known whether VAXELIS can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. VAXELIS has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Diphtheria and Tetanus Toxoid Adsorbed Vaccine in Brief:

• Ages: Diphtheria and Tetanus Toxoid Adsorbed is a 2 in 1 shot (diphtheria and tetanus) for children six weeks to six years of age (see Sanofi Pasteur product insert for recommended schedule and other indications). It is used in cases where pertussis vaccine should not be administered.
• Vaccine Ingredients: aluminum phosphate, isotonic sodium chloride, uracil, inorganic salts, vitamins, dextrose, formaldehyde, casein, cystine, maltose.

• Estimated Efficacy: Efficacy of diphtheria toxoid in Diphtheria and Tetanus Toxoid Adsorbed was based on immunogenicity (blood immune response) and tested in 137 infants only two months following the completion of three doses of the vaccine (given at two, four, and six months). 99 percent of infants were noted to have blood antibody levels considered protective against tetanus, two months following three doses of the vaccine.

• Use With Other Vaccines No clinical trials examined the safety or effectiveness of administering the vaccine with any other U.S. licensed vaccine.
• Commonly Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site, loss of appetite, crying, and fever. Adverse events were noted for only 24 hours following vaccination. In clinical trials, the Diphtheria and Tetanus Toxoid Adsorbed vaccine contained thimerosal (mercury).
• Other Serious Reported Adverse Events:  After licensure (post marketing) adverse event reports have included injection site pain, swelling and hypersensitivity; syncope; convulsion; somnolence; headache; rash; pallor; itching; lymphadenopathy;
• Contraindications and precautions (Some reasons why Diphtheria and Tetanus Toxoid Adsorbed should not be given to a child – See Sanofi Pasteur product insert for complete list):
  • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Diphtheria and Tetanus Toxoid Absorbed vaccine;
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision to vaccinate an infant born prematurely should be careful based on both the possible benefits and potential risks of vaccination.

NVIC NOTE: Some doctors only vaccinate children and adults, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you or your child are sick and do not want to get vaccinated, but your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Diphtheria and Tetanus Toxoid Adsorbed. It is not known whether Diphtheria and Tetanus Toxoid Adsorbed can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Diphtheria and Tetanus Toxoid Adsorbed has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About Adacel in Brief:

• Ages: Adacel is a 3 in 1 shot (tetanus, diphtheria, and acellular pertussis) used as a booster dose (Tdap) for children and adults 10 years and older (see Sanofi Pasteur product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum phosphate, formaldehyde, 2-phenoxyethanol, Stainer-Scholte medium, casamino acids, ammonium sulfate, modified Mueller’s growth medium, dimethyl-beta-cyclodextrin, glutaraldehyde, modified Mueller-Miller casamino acid medium without beef heart infusion.
• Estimated Efficacy: Blood antibody responses to diphtheria toxoid vaccine were tested one month following administration of a single booster dose of Adacel in persons between the ages of 11 and 64 years. 99.8 percent of vaccine recipients aged 11 through 17 and 94.1 percent of vaccine recipients aged 18 through 64 were found to have blood antibody levels considered protective against diphtheria disease.
• Use with Other Vaccines: In clinical trials, Adacel was given with hepatitis B or inactivated influenza vaccine. There is no information in the product insert about the safety or effectiveness of giving Adacel simultaneously with live influenza, meningococcal, HPV, MMR, varicella, hepatitis A, inactivated polio or other vaccines.
• Commonly Reported Adverse Events: In clinical trials, the most common reactions were pain and swelling at the injection site; fever (especially in adolescents); headache; body aches/muscle weakness; fatigue; chills; sore and swollen joints; nausea; lymph node swelling.
• Other Serious Reported Adverse Events: After licensure (post-marketing), adverse event reports have included severe injection site swelling, bruising, sterile abscess; facial palsy; convulsion; syncope (fainting); parasthesia; Guillain-Barre syndrome; myelitis; anaphylactic reaction; hypersensitivity reaction (angioedema, rash, hypotension); urticaria; muscle spasm; myocarditis.
• Contraindications and precautions (Some reasons why Adacel should not be given to a child or adult – See Sanofi Pasteur product insert for complete list):
  • Moderate or severe acute illness (with or without fever) until the illness resolves;
  • Serious allergic or hypersensitivity reaction to a previous shot;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • In adolescents, a progressive neurologic disorder, including progressive encephalopathy or uncontrolled epilepsy (convulsions);
  • In adults, an unstable neurologic condition, such as cerebrovascular events and acute encephalopathic conditions;
  • Severe allergic reaction to any component of Adacel;
  • If Guillain-Barré syndrome (GBS) occurred within 6 weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Adacel vaccine;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive Adacel more frequently than every 10 years;
  • The tip caps of prefilled Adacel syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

There are no adequate and well-controlled studies on the administration of Adacel in pregnant women in the United States. It is not known whether Adacel vaccine components are excreted in human milk and there is no available data on the effect of administrating Adacel on breast-fed infants or on milk production/excretion. Adacel has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility.

About Boostrix Vaccine in Brief:

• Ages: Boostrix is a 3 in 1 shot (tetanus, diphtheria, and acellular pertussis) used as a booster dose (Tdap) for children and adults 10 years and older (see GlaxoSmithKline product insert for recommended schedule and other indications).
• Vaccine ingredients: Aluminum hydroxide, sodium chloride, polysorbate 80, modified Latham medium derived from bovine casein, Fenton medium containing a bovine extract, formaldehyde, modified Stainer-Scholte liquid medium, glutaraldehyde.

• Estimated Efficacy: Antibody responses to diphtheria were tested one month following administration of a single booster dose of Boostrix in adolescents between the ages of 10 and 18 years. 99.9 percent of vaccine recipients were found to have blood antibody levels considered protective against diphtheria. When tested one month following administration in persons between 19 and 64 years of age, 98.2 percent of vaccine recipients were noted to have blood antibody levels considered to be protective against diphtheria.

• Use with Other Vaccines In clinical trials, Boostrix was given with inactivated influenza vaccine (Fluarix) and the meningococcal vaccine (Menactra). In both clinical trials, the antibody level for the pertussis component was determined to be lowered. There is no information in the product insert about the safety or effectiveness of giving Boostrix simultaneously with live influenza, MMR, varicella, HPV, hepatitis B, hepatitis A, inactivated polio or other vaccines.
• Commonly Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site, increase in arm circumference of injected arm; headache; fatigue; gastrointestinal symptoms.
• Other Serious Reported Adverse Events: One case of diabetes developed after Boostrix administration in clinical trials. After licensure (post marketing) adverse event reports have included extensive inflammation, swelling of injected limb; itching; encephalitis (brain inflammation); convulsion; facial palsy; lymphadenitis; lymphadenopathy; myocarditis; arthralgia; back pain; myalgia; urticaria; Henoch-Schonlein purpura.
• Contraindications and precautions (Some reasons why Boostrix should not be given to a child or adult – See GlaxoSmithKline product insert for complete list):
  • Serious allergic or hypersensitivity reaction to a previous shot;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • In adolescents and adults, a progressive neurologic disorder, including progressive encephalopathy or uncontrolled epilepsy (convulsions);
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering Boostrix vaccine;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive Boostrix more frequently than every 10 years;
  • The tip caps of prefilled Boostrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

NVIC NOTE: Some doctors only vaccinate children and adults, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you or your child are sick and do not want to get vaccinated, but your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with Boostrix. It is not known whether Boostrix can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Boostrix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility. There are no adequate and well-controlled studies on the administration of Boostrix in pregnant women in the United States.

About TDVAX Vaccine in Brief:

• Ages: TDVAX is a 2 in 1 shot (tetanus and diphtheria) for persons over the age of seven (see MassBiologics product insert for recommended schedule and other indications).
• Vaccine Ingredients: Thimerosal, aluminum phosphate, formaldehyde, modified Mueller's media which contains bovine extracts.

• Estimated Efficacy: Efficacy of diphtheria toxoid in TDVAX was based on immunogenicity (blood immune response) of six vaccine recipients tested after three doses of TDVAX were given as a primary series. All vaccine recipients were noted to have blood antibody levels considered protective against diphtheria. When administered as a booster dose, all 140 adolescent male vaccine recipients tested were noted to have blood antibody levels believed to be protective against diphtheria.

• Use with Other Vaccines: No clinical trials examined the safety or effectiveness of administering the vaccine with any other U.S. licensed vaccine.
• Commonly Reported Adverse Events: There is no pre-licensing clinical trial data on adverse events following TDVAX in the vaccine package insert.
• Other Serious Reported Adverse Events:  After licensure (post marketing) adverse event reports have included injection site pain, swelling, warmth, itching and hypersensitivity; fever; cellulitis; nausea; rash; joint and muscle pain; dizziness; convulsion; malaise; headache.
• Contraindications and precautions (Some reasons why TDVAX should not be given to a child or adult – See MassBiologics product insert for complete list):
  • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering TDVAX vaccine;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive TDVAX more frequently than every 10 years.

NVIC NOTE: Some doctors only vaccinate children and adults, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you or your child are sick and do not want to get vaccinated, but your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with TDVAX. It is not known whether TDVAX can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. TDVAX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

About TENIVAC Vaccine in Brief:

• Ages: TENIVAC is a 2 in 1 shot (tetanus and diphtheria) for persons over the age of seven (see Sanofi Pasteur product insert for recommended schedule and other indications).
• Vaccine Ingredients: Aluminum phosphate, formaldehyde, ammonium sulfate, sodium chloride, modified Mueller-Miller casamino acid medium without beef heart infusion, water.

• Estimated Efficacy: Efficacy of diphtheria toxoid in TENIVAC was based on evaluation of immunogenicity (blood immune response) in 17 vaccine recipients tested after two and three doses of TENIVAC given as a primary series. All vaccine recipients were noted to have blood antibody levels considered to be protective against diphtheria four weeks following the third dose of TENIVAC. When administered as a booster dose, 100 percent of persons between the ages of 11-18 years, 99.2 percent of adults between 19 and 59 years of age and 88.0 percent of adults 60 years of age and older were noted to have the minimally acceptable blood antibody levels believed to be protective against diphtheria.

• Use with Other Vaccines: No clinical trials examined the safety or effectiveness of administering the vaccine with any other U.S. licensed vaccine.
• Commonly Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site; fever; muscle weakness; joint pain; malaise; headache.
• Other Serious reported Adverse Events:  In pre-licensing clinical trials, serious adverse events included asthma, localized infection, stroke, chest pain, colonic polyp, cellulitis, angina pectoris, hip and wrist fracture, and cholecystitis. Three deaths occurred following administration of TENIVAC. Deaths were reported as cardiopulmonary arrest; myocardial infarction and septic shock; and unknown cause. After licensure (post marketing) adverse event reports have included Guillain-Barre Syndrome (GBS), injection site pain, swelling, warmth, itching, cellulitis and hypersensitivity; fever; lymphadenopathy; vomiting; dizziness; paresthesia; syncope; fatigue; peripheral edema; rash; joint and muscle pain; allergic and anaphylactic reactions.
• Contraindications and precautions (Some reasons why TENIVAC should not be given to a child or adult – See Sanofi Pasteur product insert for complete list):
  • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, careful assessment of the possible risks and potential benefits should be completed prior to considering TENIVAC vaccine;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive TDVAX more frequently than every 10 years;
  • The tip caps of prefilled TENIVAC syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • Administering TENIVAC vaccine more frequently than prescribed may result in an increased incidence and severity of adverse reactions.

NVIC NOTE: Some doctors only vaccinate children and adults, who are healthy and are not sick with a coinciding viral or bacterial infection at the time of vaccination. If you or your child are sick and do not want to get vaccinated, but your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

Animal reproduction studies have not been conducted with TENIVAC. It is not known whether TENIVAC can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. TENIVAC has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

What is the history of Diphtheria vaccine use in America?

Prior to a vaccine for diphtheria, one of the first treatments of diphtheria was a horse-derived antitoxin developed in the 1890s. This antitoxin was made by injecting the diphtheria toxin into horses to produce an antibody response. Blood was then drawn from the horses and the antitoxin serum was separated and purified for use in humans. The H.K. Mulford Company of Philadelphia was the first U.S. company to develop diphtheria antitoxin for commercial use. 

The diphtheria antitoxin, however, only produced short-term immunity, and in certain individuals, the injections resulted in fever, rash, joint pain, and anaphylaxis. This adverse reaction was referred to as “serum sickness” and seen in persons who received multiple doses of antitoxin. In 1913, Dr. Bela Schick introduced the Schick test, a procedure which involved injecting a small amount of diphtheria toxin in a solution into the arm to determine the necessity of the antitoxin. If redness at the injection site occurred, the use of the antitoxin was indicated. 

The first vaccine against diphtheria was developed by William Park of the New York City Health Department. Park combined the diphtheria antitoxin with diphtheria toxin and this combination was reportedly capable of triggering an antibody response. The use of this product, however, was questioned in the medical literature at the time due to reports of failure and harm. Serious side effects included serum sickness, anaphylaxis and even death.   

In 1923, two independent researchers, Gaston Ramon and Alexander Thomas Glenny, developed a method to inactivate the diphtheria toxin. This product, known as the diphtheria toxoid (DAT), was considered inferior to the toxin-antitoxin (TAT) because it did not produce a strong immune response.  Ramon also discovered that the use of formalin could decrease the toxic properties of the diphtheria toxoid while still maintaining its immunogenicity.  In 1926, Glenny and his colleagues discovered that adding the diphtheria antigen to alum (aluminum potassium sulphate) would enhance the immune response. 

In 1930, government officials reported that while widespread vaccination programs were occurring in some areas, other areas had few programs. However, after 1925, diphtheria morbidity and mortality rates decreased in all U.S. states at the same time.  Public health officials reviewing the decline in diphtheria morbidity and mortality reported that: 

“The great decline in mortality, the early date at which it was manifested, and the widespread area over which it has been experienced, all go to indicate that it is attributable largely to causes other than specific treatment and immunization. The remarkable reduction in morbidity and mortality since 1927, if viewed as a separate phenomenon, might be attributed in part at least to artificial immunization. That this has been a major factor, however, would seem to be quite improbable, as the recent acceleration of the decline has likewise been experienced over a wide area and, even in many cities in which immunization has been most extensively practised, the reduction has been far greater than can be satisfactorily explained by the numbers of persons immunized. Viewing all the available facts, the conclusion seems inevitable that other factors have played a major role.”

In the mid 1940’s, the diphtheria toxoid was combined with tetanus toxoid to create the tetanus- diphtheria (Td) toxoid vaccine and additionally combined with whole cell pertussis to create the diphtheria-tetanus-pertussis vaccine (DTP).  The newly created DTP combination vaccine was then absorbed onto aluminum salts when researchers discovered aluminum’s ability to enhance blood immune responses to both diphtheria and tetanus.  Numerous companies held licenses for tetanus toxoid vaccines in the mid 1940’s, however, product licensing was not indicative of product endorsement. Safety, purity, and potency (if tests were available to determine potency) were tested as part of licensing approval, however, product efficacy was not, and not required for product licensing. Companies that held tetanus toxoid vaccine licenses in 1945 included Parke Davis and Co., Sharp and Dohme, Cutter Laboratories, Lederle Laboratories and more. 

A diphtheria toxoid improperly manufactured by a Japanese pharmaceutical company in 1948 resulted in the toxoid reversing to toxin. Many children were harmed and killed because of this error. This disaster prompted vaccine manufacturers to put procedures into place to prevent a reoccurrence of this event. 

In 1966, the Public Health Service Advisory Committee on Immunization Practices (now the CDC’s Advisory Committee on Immunization Practices) published its first tetanus, diphtheria and pertussis vaccine recommendations and guidance for tetanus disease prevention pertaining to wound management. In this report, the Advisory Committee on Immunization Practices (ACIP) formally recommended that all infants receive three doses of diphtheria, tetanus, and pertussis vaccine (DTP) beginning between two and three months of age at intervals of four to six weeks. Additional booster doses were recommended at one year of age and between the age of three and six years, preferably prior to school entry. 

School children and adults not previously vaccinated with DTP were recommended to receive two doses of tetanus-diphtheria (Td) vaccine at four to six weeks intervals with a booster dose one year later, and routine booster doses every 10 years. The Td vaccine was recommended for use among schoolchildren and adults instead of the DTP vaccine. This recommendation was made due to the significant increase in adverse reactions that occurred with age following full doses of the diphtheria toxoid found in the DTP vaccine. 

In September of 1984, ACIP published its first adult vaccination guidelines. In this publication, adults not previously vaccinated with diphtheria toxoid vaccine were recommended to receive two doses of Td vaccine at least four weeks apart, followed by a booster dose one year later and routine booster doses every 10 years. In the case of wound management, Td vaccine was recommended if a person had not received a Td vaccine within five years. Persons previously vaccinated with the DTP primary series were recommended to receive the first booster dose of Td vaccine between the age of 14 and 16. 

The FDA approved the first acellular pertussis combination vaccine (DTaP) for use in the United States in 1991,  however, between 1991 and 1996, the whole cell diphtheria, tetanus, and pertussis (DPT) vaccine continued to be recommended for the first three primary doses at two, four, and six months of age.  The DTaP vaccine was only approved for use in children between the ages of 15 months and six years after completion of three primary doses of DPT.  

In 1995, the American Academy of Pediatrics (AAP) and ACIP published a harmonized childhood vaccine schedule   and decreased the recommended age of the adolescent booster dose of tetanus-diphtheria (Td) vaccine from 14-16 years, to age 11-12 years. ACIP stated that lowering the recommended age of the Td booster dose to 11-12 years of age would encourage a routine preadolescent healthcare visit where health care practitioners could administer additional vaccines such as a second MMR dose,  recommended in 1989 following a resurgence in measles cases related to MMR vaccine failure,  and the hepatitis B vaccine, in children not previously vaccinated. 

In 1997, ACIP updated its diphtheria, tetanus, and acellular pertussis vaccine (DTaP) recommendation, and recommended that all children receive five doses of DTaP vaccine, at two, four, six, 15-18 months and four to six years of age, in lieu of the highly reactive whole cell DPT vaccine. 

In 2005, the FDA approved two tetanus, diphtheria and acellular pertussis vaccines (Tdap), targeting adolescents and adults. Boostrix vaccine received initial approval for use in persons between 10 and 18 years of age, and Adacel received approval for use in individuals aged 11 through 64 years. Following FDA approval, ACIP promptly recommended that all 11-12-year old receive a dose of Tdap vaccine. This recommendation was made in response to the high number of pertussis cases and outbreaks occurring among adolescents due to the waning of vaccine acquired pertussis immunity. 

ACIP also recommended that all 11 to 18-year-old adolescents receive a dose of Tdap, including those already vaccinated with the previously recommended booster dose of tetanus-diphtheria (Td) vaccine at age 11-12. While a five-year interval between Tdap and Td vaccine administration was recommended due to the increased risk of both local and systemic reactions, ACIP stated that vaccination at an interval of less than five years was still acceptable. Additionally, ACIP encouraged health care practitioners to administer the newly approved Tdap vaccine at the same time as the newly licensed meningococcal conjugate vaccine (MCV4). This recommendation was made even though no safety or immunogenicity data existed to support the administration of both vaccines simultaneously. 

In 2006, ACIP recommended that all adults between the ages of 19 and 65 years receive a dose of Tdap vaccine. The Tdap vaccine was recommended as a one-time dose in lieu of the Td vaccine and administered if more than 10 years had passed since administration of Td vaccine. ACIP, however, reported that the Tdap vaccine could be administered at an earlier interval, to protect a person against pertussis. In their report, they also admitted that pre-licensing clinical trials of Adacel vaccine, the only Tdap vaccine FDA approved at the time for use in adults between 19 and 64 years of age, had purposely excluded all persons previously vaccinated with any vaccine containing tetanus or diphtheria toxoid and/or pertussis vaccine within the preceding five years, and that it was not known if vaccinating at an earlier interval than 10 years was actually safe. 

ACIP also acknowledged that adult safety studies of Adacel vaccine were not enough to be able to detect rare adverse events that might occur following vaccination. Tdap vaccine was also recommended for all women of childbearing age, and vaccination was encouraged prior to pregnancy or immediately postpartum. Additionally, all health care providers with direct patient contact were also recommended to receive Tdap vaccine if at least 2 years had passed since a previous dose of Td vaccine had been administered. 

In October of 2012, ACIP recommended that all pregnant women receive a Tdap vaccine during each pregnancy, between 27 and 36 weeks gestation.  At the time of this recommendation, ACIP acknowledged that “a theoretical risk exists for severe local reactions”  in pregnant women vaccinated frequently due to multiple pregnancies spaced closely together, but reported that current tetanus toxoid containing vaccines contained less tetanus toxin than previously recommended tetanus toxoid vaccines and stated that “the potential benefit of preventing pertussis morbidity and mortality in infants outweighs the theoretical concerns of possible severe adverse events.” 

In this recommendation, ACIP also acknowledged that no studies had ever examined the safety of administering Tdap vaccine to pregnant women during subsequent pregnancies, but reported that going forward, they planned to monitor both the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) to assess for adverse events, maternal adverse pregnancy outcomes and birth outcomes. 

The CDC currently recommends that all children receive five doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) at two, four, six, 15-18 months, and four to six years, with an adolescent booster dose of tetanus, diphtheria, and acellular pertussis vaccine (Tdap) at age 11-12. Adults not previous vaccinated with Tdap are recommended to receive one dose of the vaccine, and then continue to receive booster doses of tetanus-diphtheria (Td) vaccine or Tdap vaccine every 10 years.  All pregnant women are recommended to receive a Tdap vaccine between 27- and 36-weeks’ gestation, during each pregnancy, regardless of any previous Tdap vaccination. 

In 2017, the CDC reported that 94 percent of all 19 to 35-month-old children had received at least three doses of the diphtheria toxoid containing DTaP vaccine and 83 percent had received at least four DTaP vaccine doses.  Also in 2017, the CDC reported that 88.5 percent of all adolescents had received a booster dose of Tdap vaccine. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

How effective is Diphtheria vaccine?

According to the CDC, adults who receive three properly spaced diphtheria vaccines and infants who receive four, will develop antibodies considered protective against diphtheria approximately 95 percent of the time. The CDC also reports that the diphtheria vaccine has a 97 percent efficacy rate against clinical cases of diphtheria;  however they also state that “no randomized controlled clinical trial of the efficacy of diphtheria toxoid in preventing disease has ever been conducted”. 

Vaccinated individuals are still able to spread the bacteria because vaccination does not eliminate carriage of Corynebacterium diphtheriae in the back of the throat or on the skin.  

Between 2015 and 2018, an outbreak of diphtheria occurred in seven schools in Vietnam. Forty-six persons were diagnosed, and eight died. Vaccination status was not known for 85 percent of those affected; however, three of the eight who died had received at least two vaccine doses. Study authors expressed concerns that “Our finding of vaccinated people dying is particularly alarming because it might indicate a waning of vaccine-derived immunity.” 

A 2019 published review of diphtheria cases between 2000 and 2017 reported that 22 percent of cases occurred in fully vaccinated individuals and 13 percent among partially vaccinated individuals. This paper recommended that more emphasis was needed to ensure that children received the primary three doses of diphtheria and that adolescents and adults receive booster doses. 

Booster doses of diphtheria vaccine are recommended in the U.S. every 10 years;  however, a 2020 published study concluded that “Review of >11 billion person-years of incidence data revealed no benefit associated with performing adult booster vaccinations against tetanus or diphtheria.” 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Can diphtheria vaccine cause injury & death?

The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons, but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination.  However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving a DTaP/Tdap/Td vaccine or any other vaccine.

According to the CDC, possible side effects from DTaP vaccine include: 

• Pain, swelling, and redness at the injection site
• Fatigue
• Fussiness
• Fever
• Loss of appetite
• Vomiting
• Non-stop crying for 3 hours or longer
• Fever greater than 105 F
• Swelling of the entire vaccinated limb
• Severe allergic reaction
• death

According to the CDC, possible side effects from Tdap vaccine include: 

• Pain, redness, and swelling at injection site
• Ringing in the ears
• Headache
• Nausea, diarrhea, stomach ache, vomiting
• Joint pain
• Fatigue
• Fever
• Dizziness or fainting
• Severe allergic reaction
• Death

According to the CDC, possible side effects from Td vaccine include: 

• Pain, redness, and swelling at injection site
• Fever
• Fatigue
• Headache
• Nausea and vomiting
• Stomachache
• Ringing in the ears
• Vision changes
• Dizziness or fainting
• Severe allergic reaction
• Death

In 1994, the Institute of Medicine (IOM) reported that there was compelling scientific evidence to conclude that tetanus, DT and Td vaccines can cause Guillain-Barre syndrome (GBS) including death; brachial neuritis; and death from anaphylaxis (shock).  However, in 2012, the IOM committee reported that there was a lack of evidence to support or reject a causal association between GBS and tetanus, diphtheria toxoid and acellular pertussis vaccines.

This committee also reported a lack of evidence to support or reject a causal association between encephalopathy, encephalitis, infantile spasms, seizures, ataxia, autism, acute disseminated encephalomyelitis (ADEM), transverse myelitis, chronic inflammatory disseminated polyneuropathy, optic neuritis, onset of multiple sclerosis in adults, relapse of multiple sclerosis in adults, relapse of multiple sclerosis in children, opsoclonus myoclonus syndrome, or Bell ’s palsy and tetanus, diphtheria toxoid and acellular pertussis vaccines. There was, however enough evidence to convincingly support an association between anaphylaxis and tetanus, diphtheria toxoid and acellular pertussis vaccines. 

In 2017, researchers in Guinea-Bissau compared the mortality rates of diphtheria, tetanus, and whole cell pertussis (DTP) vaccinated infants between three and five months of age with children who were not yet vaccinated with the DTP vaccine and discovered that mortality rates from all causes were significantly higher among DTP vaccinated infants when compared to infants who were not yet vaccinated. Researchers also noted that if the oral polio vaccine (OPV) was administered simultaneously with the DTP vaccine, all-cause mortality rates decreased, however they were still significantly higher when compared to infants who had not yet been vaccinated. 

When the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended that all pregnant women receive a Tdap vaccine during each pregnancy, between 27- and 36-weeks’ gestation, in October of 2012, they acknowledged that a theoretical risk exists for severe local reactions  in pregnant women vaccinated more frequently due to multiple pregnancies spaced closely together. ACIP, however, also acknowledged that no studies had ever examined the safety of administering Tdap vaccine to pregnant women during subsequent pregnancies, but reported that going forward, they planned to monitor both the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) to assess for adverse events, maternal adverse pregnancy outcomes and birth outcomes. 

In 2018, ACIP reported that studies on the use of Tdap vaccine in pregnancy have not shown any “new or unexpected safety concerns”  but admitted that safety studies on Tdap vaccine administration during pregnancy at close intervals to another tetanus toxoid containing vaccine were limited. 

The Adacel vaccine product insert states that there are no adequate and well-controlled studies of Adacel administration in pregnant women in the U.S.  The product insert also states that for routine booster vaccination, a second dose of Adacel vaccine may be administered if eight years or more has passed since the first Tdap vaccine.  The Boostrix product insert states that safety and effectiveness of BOOSTRIX have not been established in pregnant women  and is FDA approved only to be administered as a single dose. 

Adverse reactions reported by vaccine manufacturers as listed in the vaccine package inserts:

Infanrix (Diphtheria, tetanus toxoids, and acellular pertussis vaccine manufactured by GlaxoSmithKline.)

• Frequently Reported Adverse Events: Pain, redness, and swelling at the site of the injection; drowsiness; irritability/fussiness; loss of appetite.
• Serious Reported Adverse Events:Hypotonic-hyporesponsive (collapse) episode; persistent cry for three or more hours; high fever, and convulsions (seizures). After licensure (post-marketing), reported adverse events included bronchitis, cellulitis, respiratory tract infection, lymphadenopathy, thrombocytopenia, anaphylactic reaction, encephalopathy, headache, hypotonia, ear pain, apnea, cough, angioedema, pruritus, rash, fatigue and Sudden Infant Death Syndrome (SIDS).

DAPTACEL (Diphtheria and tetanus toxoids and acellular pertussis vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: injection site soreness, tenderness, redness, and increase in arm circumference; fussiness/irritability; inconsolable crying; decreased activity/lethargy.
• Serious Reported Adverse Events:Convulsions (seizures), including infantile spasms; bronchiolitis; pneumonia; meningitis; sepsis; irritability; unresponsiveness. After licensure (post-marketing), reported adverse events have also included cyanosis, nausea, diarrhea, cellulitis, and allergic reaction.

Pediarix (Diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccine manufactured by GlaxoSmithKline.)

• Frequently Reported Adverse Events: Local injection site reactions (pain, redness, or swelling); fussiness, high fever (Pediarix is associated with higher rates of fever relative to separately administered vaccines. The prevalence of fever was highest on the day of vaccination and the day following vaccination.)
• Serious Reported Adverse Events: High fever that required medical attention; (In a safety study that evaluated medically attended fever after Pediarix or separately administered vaccines when co-administered with 7-valent pneumococcal and Hib conjugate vaccines, infants who received Pediarix had a higher rate of medical encounters for fever within the first 4 days following the first vaccination); febrile and afebrile convulsions (seizures); gastroenteritis, bronchiolitis; asthma, diabetes mellitus, and chronic neutropenia; anaphylactic reactions (hives, swelling, difficulty breathing, hypotension or shock), demyelinating diseases.

Kinrix (Diphtheria and tetanus toxoids, acellular pertussis and inactivated poliovirus vaccine manufactured by GlaxoSmithKline.)

• Frequently Reported Adverse Events: Injection site pain, including redness, swelling and increase in arm circumference; drowsiness; fever; loss of appetite.
• Serious Reported Adverse Events:Gastroenteritis, dehydration, and cellulitis. After licensure (post-marketing) reported adverse events have also included apnea, collapse or shock-like state (hypotonic-hyporesponsive episode), convulsions (with or without fever), injection site vesicles; pruritus (intense itching); allergic reactions, including anaphylaxis; urticaria; angioedema; lympadenopathy, and thrombocytopenia.

Quadracel (Diphtheria and tetanus toxoid, acellular pertussis and inactivated poliovirus vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: Injection site pain, including redness, swelling and increase in arm circumference; malaise; muscle pain; headache.
• Serious Reported Adverse Events: After licensure (post-marketing) reported adverse events have also included cyanosis; convulsions (with or without fever); injection site abscess; injection site cellulitis; pallor; screaming; allergic reactions, including anaphylaxis; urticarial, and dyspnea

Pentacel (Diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: Systemic reactions that occurred in clinical trials in more than 50 percent of participants following any dose included fussiness/irritability and inconsolable crying; fever; injection site reactions, including tenderness, abscess and increase in arm circumference.
• Serious Reported Adverse Events: Cases of encephalopathy and death also occurred during clinical trials. After licensure (post marketing), there have been reports of febrile and afebrile convulsions (seizures); bronchiolitis, gastroenteritis, dehydration, pneumonia, lethargy/somnolence; hypotonic/hyporesponsive episode (collapse); apnea, cyanosis, asthma.

VAXELIS (Diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus b conjugate, and hepatitis B recombinant vaccine manufactured by MCM Vaccine Company.)

• Frequently Reported Adverse Events: Systemic reactions that occurred in clinical trials following any dose included injection site redness, swelling, and pain, fever, crying, decreased appetite, irritability, vomiting, and somnolence

• Serious Reported Adverse Events: In the two U.S. clinical trials, 6 deaths were reported but were determined by trial investigators not to be attributed to VAXELIS. These deaths included sepsis, asphyxia, hydrocephalus, unknown cause, and two cases of sudden infant death syndrome. As VAXELIS is not currently available for use in the United States, post-marketing data on serious adverse events are limited to those events considered to have a causal link to the vaccines containing the antigens of VAXELIS. These include anaphylaxis, hypersensitivity, seizures, including febrile seizures, and excessive swelling of the injected limb.

Diphtheria and Tetanus Toxoid Adsorbed (Diphtheria and tetanus toxoid vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site, loss of appetite, crying, and fever. Adverse events were monitored for only 24 hours following vaccination.
• Serious Reported Adverse Events:  After licensure (post marketing) adverse events have included injection site pain, swelling and hypersensitivity; syncope; convulsion; somnolence; headache; rash; pallor; itching; lymphadenopathy.

Adacel (Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: In clinical trials, most common reactions were pain and swelling at the injection site; fever (especially in adolescents); headache; body aches/muscle weakness; fatigue; chills, sore and swollen joints; nausea, lymph node swelling.

• Serious Reported Adverse Events: After licensure (post-marketing), adverse events have included severe injection site swelling, bruising, sterile abscess; facial palsy; convulsion; syncope (fainting); parasthesia; Guillain-Barre Syndrome (GBS); myelitis; anaphylactic reaction; hypersensitivity reaction (angioedema, rash, hypotension); urticaria; muscle spasm; myocarditis.

Boostrix (Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine manufactured by GlaxoSmithKline.)

• Frequently Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site, increase in arm circumference of injected arm; headache; fatigue; gastrointestinal symptoms.
• Serious Reported Adverse Events: One case of diabetes developed after Boostrix administration in clinical trials. After licensure (post marketing) adverse events have included extensive inflammation, swelling of injected limb, nodule, itching; encephalitis (brain inflammation); convulsion; facial palsy; lymphadenitis; lymphadenopathy; myocarditis; arthralgia; back pain; myalgia; urticaria; Henoch-Schonlein purpura.

TDVAX (Tetanus and diphtheria toxoid vaccine manufactured by MassBiologics.)

• Frequently Reported Adverse Events: Pre-licensing clinical trial data on adverse events following TDVAX are not listed as part of the product insert.
• Serious Reported Adverse Events:  After licensure (post marketing) adverse events have included injection site pain, swelling, warmth, itching and hypersensitivity; fever; cellulitis; nausea; rash; joint and muscle pain; dizziness; convulsion; malaise; headache;

TENIVAC (Tetanus and diphtheria toxoid vaccine manufactured by Sanofi Pasteur.)

• Frequently Reported Adverse Events: In pre-licensure clinical trials, pain, redness, and swelling at the injection site; fever; muscle weakness; joint pain; malaise; headache.
• Serious Reported Adverse Events: In pre-licensing clinical trials, serious adverse events included asthma, localized infection, stroke, chest pain, colonic polyp, cellulitis, angina pectoris, hip and wrist fracture, and cholecystitis. Three deaths occurred following administration of TENIVAC. Deaths were reported as cardiopulmonary arrest; myocardial infarction and septic shock; and unknown cause. After licensure (post marketing) adverse events have included Guillain-Barre Syndrome (GBS), injection site pain, swelling, warmth, itching, cellulitis and hypersensitivity; fever; lymphadenopathy; vomiting; dizziness; paresthesia; syncope; fatigue; peripheral edema; rash; joint and muscle pain; allergic and anaphylactic reactions.

As of the March 29, 2024 data release, there have been 211,851 adverse events reported to the Vaccine Adverse Events Reporting System (VAERS) in connection with diphtheria and diphtheria-containing vaccines combined with additional vaccines since 1990, including 3,437 related deaths, 25,400 hospitalizations, and 3,768 related disabilities. However, the numbers of vaccine-related injuries and deaths reported to VAERS may not reflect the true number of serious health problems that occur develop after diphtheria vaccination.

Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to federal health agencies (VAERS), many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problems to VAERS. There is evidence that only between one and 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials, who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.       

As of April 1, 2024, there have been 6,487 claims filed so far in the federal Vaccine Injury Compensation Program (VICP) for 880 deaths and 5,607 injuries that occurred after diphtheria and diphtheria-containing vaccines combined with additional vaccines. Of that number, the U.S. Court of Claims administering the VICP has compensated 2,572 children and adults, who have filed claims for diphtheria vaccine associated injury.

The U.S. Government recognizes the following as injuries associated with DTP, DTaP, Tdap, DT, or Td vaccines: 

• Anaphylaxis occurring within 4 hours of vaccine administration
• Brachial Neuritis occurring within 2 and 28 days of vaccine administration
• Vasovagal syncope occurring within 1 hour of vaccine administration
• Encephalopathy and encephalitis occurring within 72 hours of vaccine administration
• Shoulder Injury Related to Vaccine Administration (SIRVA) occurring within 48 hours of vaccine administration

For more information on adverse reactions from combination pertussis, diphtheria and tetanus vaccines, visit the NVIC pertussis (whooping cough) webpage.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Who is at highest risk for complications from Diphtheria vaccine?

There is a gap in medical knowledge in terms of doctors being able to predict who will have an adverse reaction to diphtheria vaccination, and who will not.

The diphtheria toxoid vaccine is only available in combination with other routinely administered vaccines and most frequently combined with tetanus (DT, Td) and acellular pertussis vaccines (DTaP, Tdap). It is also found in combination with vaccines for polio, haemophilus influenzae B (HIB), and hepatitis B.

Infants born prematurely are at risk for apnea following intramuscular vaccination, which places them at higher risk for complications following vaccination. DTaP and DT vaccine product inserts state that the decision to vaccinate an infant born prematurely should take into consideration health status and the possible risks and potential benefits of vaccination.           

Persons with a history of Guillain-Barre Syndrome (GBS) within six weeks of receiving a tetanus containing vaccine may be at an increased risk of recurrent GBS illness following tetanus vaccination.                        Anyone who has experienced an arthus-like reaction (severe painful swelling of the injected arm) following a previous dose of tetanus toxoid vaccine are also considered to be at a greater risk of recurrent reaction and should not be vaccinated with tetanus toxoid vaccine more frequently than every 10 years.  All available diphtheria vaccines are combined with tetanus vaccines.

Residual milk allergens may persist following the manufacturing of DTaP and Tdap vaccines. While the CDC’s Advisory Committee on Immunization Practices (ACIP) does not consider a milk allergy to be a contraindication to vaccination and recommends both DTaP and Tdap vaccines for persons with known milk allergies, it does, however, strongly advise the monitoring of milk allergic patients due to the potential risk of anaphylaxis.  

Pre-licensing clinical studies of Adacel vaccine (Tdap) reported that when the vaccine was administered concomitantly with the Hepatitis B vaccine, there was an increase in reports of redness and swelling at the injection site and an increase of reports of swollen joints and body aches. Additionally, when Adacel was administered with the trivalent inactivated influenza vaccine (TIV), Fluzone, pain at the injection site was noted to be statistically higher when compared to the separate administration of Adacel vaccine. Rates of joint pain and swelling were also noted to be higher when Adacel was administered concurrently with Fluzone. As a result, persons who receive simultaneous vaccinations with one or more vaccines may be at a higher risk for adverse events. 

The TENIVAC (Td) vaccine product insert states that administering the vaccine more frequently than prescribed may result in the increased incidence and severity of adverse reactions. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Who should not get Diphtheria vaccine?

The diphtheria toxoid vaccine is only available in combination with other routinely administered vaccines and most frequently combined with tetanus (DT, Td) and acellular pertussis vaccines (DTaP, Tdap). It is also found in combination with vaccines for polio, haemophilus influenzae B (HIB), and hepatitis B.

The CDC’s Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of all infants and young children with the combination diphtheria, tetanus, and acellular vaccine (DTaP) at two, four, six, 15-18 months, and four to six years, however, children under the age of seven with a contraindication to pertussis vaccination are recommended to receive the diphtheria-tetanus toxoid vaccine (DT) in place of the pertussis containing DTaP vaccine. 

According to the CDC, diphtheria, tetanus, and acellular pertussis vaccines (DTaP) should not be administered to any person who has experienced a severe allergic reaction to a previous dose or to anyone with a severe allergy to any ingredient found within the vaccine. 

If a person has a previous health history of Guillain-Barré Syndrome (GBS) within six weeks of receiving a dose of a tetanus toxoid containing vaccine, or is considered moderately or severe ill, the CDC recommends that vaccination be given only if the potential benefits to vaccination outweigh the possible risks. Anyone who has experienced an arthus-type hypersensitivity reaction following a previous dose of a diphtheria or tetanus toxoid containing vaccine should not receive another tetanus-diphtheria (Td) vaccine more frequently than every 10 years. 

Any person who developed encephalopathy within seven days of vaccination with a pertussis containing vaccine (DTP, DTaP, Tdap) should not receive another pertussis containing vaccine (DTaP, Tdap). 

The CDC also states that DTaP vaccines should not be administered to any child who is experiencing the following conditions: 

• A progressive or unstable neurologic disorder, including infantile spasms
• Seizures that are not controlled
• Progressive encephalopathy

Contraindications and precautions to vaccination as listed in the vaccine manufacturer package inserts:

INFANRIX vaccine contraindications and precautions (Please see GlaxoSmithKline product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous diphtheria toxoid-, tetanus toxoid-, or pertussis-containing vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy;
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Infanrix vaccine product insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving Infanrix should be carefully considered prior to vaccination;
  • The tip caps of prefilled Infanrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

INFANRIX is FDA approved for use in infants and children between six weeks through six years of age. INFANRIX should not be administered to infants younger than six weeks or children older than six years of age.

DAPTACEL vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous diphtheria toxoid-, tetanus toxoid-, or pertussis-containing vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. DAPTACEL vaccine product insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination.
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving DAPTACEL should be carefully considered prior to vaccination. 

DAPTACEL is FDA approved for use in infants and children between six weeks through six years of age. DAPTACEL should not be administered to infants younger than six weeks or children older than six years of age.

Pediarix vaccine contraindications and precautions (Please see GlaxoSmithKline product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous dose of diphtheria toxoid-, tetanus toxoid-, pertussis-, poliovirus, or hepatitis B-, containing vaccine or any ingredient of Pediarix;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Sensitivity to any component of Pediarix, including yeast or neomycin and polymyxin B (antibiotics);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Pediarix vaccine product insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination.
  • The tip caps of prefilled Pediarix syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving Pediarix should be carefully considered prior to vaccination. 

Pediarix is FDA approved for use in infants and children between six weeks through six years of age. Pediarix should not be administered to infants younger than six weeks or children older than six years of age.

Kinrix vaccine contraindications and precautions (Please see GlaxoSmithKline product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous dose of any
  • diphtheria toxoid-, tetanus toxoid-, pertussis- or poliovirus-containing
  • vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Severe allergic reaction to any component of Kinrix, including neomycin and polymyxin B (antibiotics);
  • The tip caps of prefilled Kinrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving Kinrix should be carefully considered prior to vaccination. 

Kinrix is FDA approved for use in children between the ages of four and six years. Kinrix should not be administered to children younger than four years or older than six years of age.

Quadracel vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Serious allergic reaction following administration of a pertussis, tetanus, diphtheria, or polio containing vaccine or any ingredient of Quadracel vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Seizures within three days of a previous pertussis vaccination;
  • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving Quadracel should be carefully considered prior to vaccination. 

Quadracel is FDA approved for use in children between the ages of four and six years. Quadracel should not be administered to children younger than four years or older than six years of age.

Pentacel vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous pertussis vaccination;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy)
  • Severe allergic reaction to any component of Pentacel, including neomycin and polymyxin B (antibiotics);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Pentacel vaccine package insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving Pentacel should be carefully considered prior to vaccination. 

Pentacel is FDA approved for use in infants and children between six weeks through four years of age. Pentacel should not be administered to infants younger than six weeks or children older than four years of age.

VAXELIS vaccine contraindications and precautions (Please see MCM Vaccine Company product insert for complete list):

• • Temperature of 105 F. or higher within 48 hours of a previous pertussis vaccination, not attributable to another identifiable cause;
  • Collapse or shock-like state (hypotonic-hyporesponsive episodes) within 48 hours of a previous pertussis vaccination;
  • Persistent crying lasting three hours or more within 48 hours of a previous pertussis vaccination;
  • Convulsions with or without fever, occurring within three days of a previous pertussis vaccination;
  • Serious allergic reaction to a previous dose of VAXELIS, any ingredient found in VAXELIS, or any other tetanus toxoid, diphtheria toxoid, pertussis-containing vaccine, hepatitis B vaccine, inactivated poliovirus vaccine, or H. influenzae type b vaccine;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • Children with a progressive neurologic disorder (such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy);
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. VAXELIS vaccine package insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré syndrome (GBS) occurred within six weeks of receiving a tetanus containing vaccine, assessment of the possible risks and potential benefits of receiving VAXELIS should be carefully considered prior to vaccination.

VAXELIS is FDA approved for use in infants and children between six weeks through four years of age. VAXELIS should not be administered to infants younger than six weeks or children older than four years of age.

Diphtheria and Tetanus Toxoid Adsorbed vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • Apnea following intramuscular vaccination has been observed in some infants born prematurely. Diphtheria and Tetanus Toxoid Absorbed vaccine package insert warns that the decision to vaccinate an infant born prematurely should take into consideration both the potential risks and possible benefits of vaccination;
  • If Guillain-Barré Syndrome (GBS) occurred within 6 weeks of a previous tetanus toxoid vaccine, the risk of a recurrent case may be increased following vaccination with Diphtheria and Tetanus Toxoid Adsorbed.

Diphtheria and Tetanus Toxoid Adsorbed is FDA approved for use in infants and children between six weeks through six years of age. Diphtheria and Tetanus Toxoid Adsorbed should not be administered to infants younger than six weeks or children older than six years of age.

Adacel vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Moderate or severe acute illness (with or without fever) until the illness resolves;
  • Serious allergic or hypersensitivity reaction to a previous shot;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • In adolescents, a progressive neurologic disorder, including progressive encephalopathy or uncontrolled epilepsy (convulsions);
  • In adults, an unstable neurologic condition, such as cerebrovascular events and acute encephalopathic conditions;
  • If Guillain-Barré Syndrome (GBS) occurred within six weeks of a previous tetanus toxoid vaccine, the decision to administer Adacel should carefully examine the possible risk and benefits of Adacel prior to vaccination;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive Adacel more frequently than every 10 years;
  • The tip caps of prefilled Adacel syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

Adacel is approved to be administered in persons between the ages of 10 and 64 years of age. A second dose of Adacel may be administered if there has been an interval of at least eight years between a prior Tdap vaccine dose. Adacel should not be administered to children younger than 10 years or adults older than 64 years.

Boostrix vaccine contraindications and precautions (Please see GlaxoSmithKline product insert for complete list):

• • Serious allergic or hypersensitivity reaction to a previous shot;
  • Encephalopathy (coma, decreased level of consciousness, prolonged convulsions) within seven days of a previous pertussis vaccination not attributable to another identifiable cause;
  • In adolescents and adults, a progressive neurologic disorder, including progressive encephalopathy or uncontrolled epilepsy (convulsions);
  • If Guillain-Barré Syndrome (GBS) occurred within six weeks of a previous tetanus toxoid vaccine, the decision to administer Boostrix should carefully examine the possible risk and benefits of vaccination;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive Boostrix more frequently than every 10 years;
  • The tip caps of prefilled Boostrix syringes contain latex and may cause an allergic reaction in persons sensitive to latex.

Boostrix is approved to be administered as a single dose in persons older than 10 years. Boostrix should not be administered to children younger than 10 years of age.

TDVAX vaccine contraindications and precautions (Please see MassBiologics product insert for complete list):

• • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • If Guillain-Barré Syndrome (GBS) occurred within six weeks of a previous tetanus toxoid vaccine, the decision to administer TDVAX should carefully examine the possible risk and benefits prior to vaccination;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive TDVAX more frequently than every 10 years.

TDVAX is approved for use in adults and children seven years of age and older. TDVAX should not be administered to children younger than seven years.

TENIVAC vaccine contraindications and precautions (Please see Sanofi Pasteur product insert for complete list):

• • Serious allergic or hypersensitivity reaction to a previous shot, or to any diphtheria or tetanus toxoid vaccine;
  • If Guillain-Barré Syndrome (GBS) occurred within six weeks of a previous tetanus toxoid vaccine, the decision to administer TENIVAC should carefully examine the possible risk and benefits prior to vaccination;
  • Anyone who has experienced an Arthus-type hypersensitivity reaction following a previous dose of a tetanus toxoid vaccine should not receive TENIVAC more frequently than every 10 years;
  • The tip caps of prefilled TENIVAC syringes contain latex and may cause an allergic reaction in persons sensitive to latex;
  • Administering TENIVAC vaccine more frequently than prescribed may result in the increased incidence and severity of adverse reactions.

TENIVAC is approved for use in adults and children seven years of age and older. TENIVAC should not be administered to children younger than seven years.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

What questions should I ask my doctor about the Diphtheria vaccine?

NVIC’s If You Vaccinate, Ask 8! Webpage downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your child. If you review these questions before your appointment, you will be better prepared to ask your doctor questions. Also make sure that the nurse or doctor gives you the relevant Vaccine Information Statement (VIS) for the vaccine or vaccines you are considering well ahead of time to allow you to review it before you or your child gets vaccinated. Copies of VIS for each vaccine are also available on the CDC's website and there is a link to the VIS for vaccines on NVIC's “Quick Facts”  page.

It is also a good idea to read the vaccine manufacturer product insert that can be obtained from your doctor or public health clinic because federal law requires drug companies marketing vaccines to include certain kinds of vaccine benefit, risk and use information in product information inserts that may not be available in other published information. Diphtheria vaccine package inserts are located on the Diphtheria Disease & Vaccine Quick Facts page. 

Other questions that may be useful to discuss with your doctor before getting the diphtheria vaccine (DTaP, DT, Td, Tdap) are: 

• If other vaccines in addition to diphtheria vaccine are scheduled for my child at this office visit, am I allowed to modify the schedule so fewer vaccines are given at once?
• What should I do if my child has a high fever or appears very ill after vaccination?
• What other kinds of reaction symptoms should I call to report after diphtheria vaccination?
• If the diphtheria vaccine doesn’t protect my child, do I have any other options for preventing diphtheria infection?

Under the National Childhood Vaccine Injury Act of 1986, doctors and all vaccine providers are legally required to give you vaccine benefit and risk information before vaccination; record serious health problems following vaccination in the permanent medical record; keep a permanent record of all vaccines given, including the manufacturer’s name and lot number; and report serious health problems, injuries and deaths that follow vaccination to VAERS.

Remember, if you choose to vaccinate, always keep a written record of exactly which shots/vaccines you or your child have received, including the manufacturer’s name and vaccine lot number. Write down and describe in detail any serious health problems that develop after vaccination and keep vaccination records in a file you can access easily.

It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction report to federal health officials at the Vaccine Adverse Reporting System (VAERS). NVIC’s Report Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

NVIC Press Releases, Statements & Commentaries Related to Diphtheria

The Vaccine Reaction

Raines K. Asymptomatic Carriers of Diphtheria Identified in Canadian School The Vaccine Reaction Jul. 10, 2019.

Cáceres M. Woman Paralyzed by Tetanus-Diphtheria Vaccine Still ‘Firmly Pro-Vaccine’ The Vaccine Reaction Jan 30, 2019.

Jaxen J. Study: DTP Vaccine Associated With 212% Increased Infant Mortality Risk The Vaccine Reaction Mar. 21, 2017.

La Vigne P. Study: Febrile Seizure Risk Higher When Childhood Vaccines Given Simultaneously The Vaccine Reaction Jul. 26, 2016.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Diphtheria disease & vaccine quick facts

Quick Facts

Diphtheria

• Respiratory diphtheria is a rare bacterial infection with symptoms occurring 2-5 days after exposure. Symptoms include a sore throat, croupy cough, low-grade fever, runny nose, breathing problems, and a fiber-like coating on the tonsils, pharynx, or inside of the nose. Neck swelling (bull neck) is usually present in severe disease.  Complications include heart inflammation (myocarditis), neurologic inflammation (neuritis), kidney damage, and airway obstruction. Death occurs in 5-10 percent of respiratory cases. 
• Cutaneous diphtheria presents as infected skin lesions that lack a uniform appearance. It is most frequently seen in the tropics or among persons experiencing homelessness. Complications occur less often from this form of diphtheria. 
• Diphtheria is contagious and spreads from person to person through respiratory secretions (coughing, sneezing). It can also be transmitted if a person touches the wound of a person with diphtheria or from touching objects contaminated with the bacteria. Vaccinated individuals can still spread the bacteria because vaccination does not eliminate carriage of Corynebacterium diphtheriae in the back of the throat or on the skin. 
• Treatment options for diphtheria include the use of the diphtheria antitoxin and antibiotics such as penicillin and erythromycin. 
• While diphtheria is extremely rare in U.S. and other developed countries with good sanitation,  it is still endemic in various areas of the world, including Eastern Europe, the Middle East, Asia, the South Pacific, and countries such as Haiti, the Dominican Republic, and Venezuela. 

Diphtheria Vaccine

• There are 12 different diphtheria-containing vaccines licensed for use in the United States, with eight diphtheria combination vaccines available for use in infants and children. These combination vaccines may contain one or more of the following vaccines: pertussis, tetanus, hepatitis B, Hib, and/ or polio. For adults, four diphtheria combination vaccines are available, with two vaccines containing both tetanus and diphtheria toxoids approved for use in adults and children ages seven years and older and two vaccines containing tetanus and diphtheria toxoid and acellular pertussis approved for use in children and adults ages 10 years and older. 
• Adverse reactions to combination vaccines containing diphtheria include a temperature of 105F or higher, collapse/shock, persistent crying, convulsions, coma, uncontrolled epilepsy, progressive encephalopathy, and death.   
• Vaccinated individuals can still spread the diphtheria bacteria because vaccination does not eliminate carriage of Corynebacterium diphtheriae in the back of the throat or on the skin.  
• Using the MedAlerts search engine, as of the March 29, 2024 data release, there have been 211,851 reports of diphtheria vaccine reactions, hospitalizations, injuries, and deaths following diphtheria vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), including 3,437 related deaths, 25,400 hospitalizations, and 3,768 related disabilities. Some of the adverse reactions of the combination vaccines containing diphtheria include a temperature of 105 F. or higher, collapse or shock-like state (hypotonic-hyporesponsive episodes), persistent crying lasting three hours or more, convulsions with or without fever, and encephalopathy (coma, decreased level of consciousness, prolonged convulsions).
• As of April 1, 2024, there had been 6,489 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following diphtheria vaccination, including 880 deaths and 5,609 serious injuries.

Food & Drug Administration (FDA)

• Infanrix, manufactured by GlaxoSmithKline, is a 3-in-1 combination shot containing diphtheria, tetanus toxoids, and acellular pertussis vaccine for children under seven years of age.
• Daptacel, manufactured by Sanofi Pasteur Ltd., is a 3-in-1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis vaccine for children under seven years of age.
• Pediarix, manufactured by GlaxoSmithKline, is a 5-in-1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccines for children under seven years of age.
• Kinrix, manufactured by GlaxoSmithKline, is a 4-in-1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis, and inactivated poliovirus vaccines for children four to six years old.
• Quadracel, manufactured by Sanofi Pasteur, is a 4-in-1 combination vaccine containing diphtheria and tetanus toxoid, acellular pertussis, and inactivated poliovirus vaccine for children 4 to 6 years old.
• Pentacel, manufactured by Sanofi Pasteur Ltd., is a 5-in-1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, and Haemophilus b conjugate (tetanus toxoid conjugate) vaccines for children under four years old.
• VAXELIS, manufactured by MCM Vaccine Company, is a 6-in-1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus b conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) vaccine for children six weeks through four years of age.
• Diphtheria and Tetanus Toxoids Adsorbed, manufactured by Sanofi Pasteur Inc., is a 2-in-1 combination shot containing diphtheria and tetanus toxoid vaccine for children under seven years of age.
• Adacel, manufactured by Sanofi Pasteur Ltd., is a 3-in-1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine for those ten years or older.
• Boostrix, manufactured by GlaxoSmithKline, is a 3-in-1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine for those ten years or older.
• TDVAX, manufactured by MassBiologics, is a 2-in-1 combination vaccine containing tetanus and diphtheria toxoid for those seven years of age and older.
• TENIVAC, manufactured by Sanofi Pasteur Ltd., is a 2-in-1 combination vaccine containing tetanus and diphtheria toxoid for those seven years of age and older.

Centers for Disease Control (CDC)

• CDC Information on Diphtheria
• Td (DT) Vaccine Information Statement (VIS) 
• DTaP Vaccine Information Statement (VIS)
• Tdap Vaccine Information Statement (VIS)

Vaccine Reaction Symptoms & Ingredients

Our Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more.

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more.

Reporting a Vaccine Reaction

Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is the law. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

Selected Medical Literature and Resources

Slifka AM, Park B, Gao L, et al. Incidence of Tetanus and Diphtheria in Relation to Adult Vaccination Schedules. Clin Infect Dis. Feb. 2020; 72(2):285-292.

Blok BA, de Bree LCJ, Diavatopoulos DA et al. INTERACTING NON-SPECIFIC IMMUNOLOGICAL EFFECTS OF BCG AND Tdapf VACCINATIONS: AN EXPLORATIVE RANDOMIZED TRIAL. Clin Infect Dis. Mar. 2019; 70(3):455-463.

Aaby P, Mogensen SW, Rodrigues A, et al. Evidence of Increase in Mortality After the Introduction of Diphtheria-Tetanus-Pertussis Vaccine to Children Aged 6-35 Months in Guinea-Bissau: A Time for Reflection? Front Public Health Mar. 2018;6:79:1-10.

Mogensen SW, Andersen A, Rodrigues A et al. The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community: A Natural Experiment. EBioMedicine Mar. 2017;17:192-198.

Hamati-Haddad A, Fenichel GM. Brachial neuritis following routine childhood immunization for diphtheria, tetanus, and pertussis (DTP): report of two cases and review of the literature. Pediatrics Apr. 1997;99(4):602-3.

Bakshi R, Graves MC. Guillain-Barré syndrome after combined tetanus-diphtheria toxoid vaccination. J Neurol Sci. Apr. 1997;147(2):201-2.

Kumar V, Sidhu N, Roy S, Gaurav K. Myocarditis following diphtheria, whole-cell pertussis, and tetanus toxoid vaccination in a young infant. Ann Pediatr Cardiol. May-Aug 2018;11(2):224-226.

Wu SJ, Sun S, Li JY et al. Acute fulminant myocarditis after diphtheria, polio, and tetanus vaccination. Asian Cardiovasc Thorac Ann. Dec. 2006;14(6):e111-2.

O'Brien P, Wong RW. Optic neuritis following diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccination: a case report. J Med Case Rep. Nov. 2018;12(1):356.

Cabrera-Maqueda JM, Hernández-Clares R, Baidez-Guerrero AE et al. Optic neuritis in pregnancy after Tdap vaccination: Report of two cases. Clin Neurol Neurosurg. Sept. 2017;160:116-118.

Cumming JG. Is the Control of Diphtheria Leading to Eradication? JAMA Mar.1922; 78(9); 630-632.

Dauer CC. Trends in age distribution of diphtheria in the United States. Public Health Rep. Sept. 1950;65(38):1209-18.

Schuman LM, Doull JA. Diphtheria Infection and Morbidity in Cleveland, 1937-1939 Am J Public Health Nations Health Mar. 1940; 30(3 Suppl): 16–24.

McLeod J. THE TYPES MITIS, INTERMEDIUS AND GRAVIS OF CORYNEBACTERIUM DIPHTHERIAE A Review of Observations during the Past Ten Years Bacteriol Rev. Mar. 1943; 7(1): 1–41.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice. 
 

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