Diphtheria, Tetanus and Pertussis: The Diseases & Vaccines

Diphtheria, Tetanus and Pertussis: The Diseases & Vaccines

Diphtheria, tetanus and pertussis are prevented by a childhood vaccine, called DTaP, and a vaccine for adolescents and adults, called Tdap. A version for adults is also available without the pertussis component, called Td.

The diseases

Diphtheria

What is diphtheria?

The dangers associated with diphtheria come from the toxin released by the bacterium, Corynebacterium diphtheriae. The toxin makes it difficult for children to breathe and swallow because it causes a membrane to form in the throat. In fact, diphtheria used to be called the “strangling angel” of children because the membrane resembled angel wings. The toxin can also attack the heart, kidneys and nerves.

Incidence of diphtheria

In the 1920s, diphtheria was a common cause of death in children and adolescents. At its peak, about 150,000 cases of diphtheria occurred in the United States every year. The diphtheria vaccine, first used in the United States in the early 1940s, has virtually eliminated the disease. Now we see fewer than one case a year.

Outbreaks still occur around the world and typically coincide with a drop in immunization rates.

Tetanus

What is tetanus?

Tetanus is another disease caused by toxin released from a bacterium called Clostridium tetani. Tetanus is the only vaccine-preventable disease that you cannot catch from someone else. This means if you are not vaccinated, your risk of tetanus will be the same even if every other person is vaccinated. 

Tetanus bacteria live in the soil and usually enter the body through punctures or wounds that are not kept clean. The bacteria can also enter when tissues have been damaged, such as from burns, frostbite, or gangrene. Items that could have tetanus bacteria on them include nails or pieces of glass that were lying on the ground. 

Because children are playful and adventurous, they can get injuries that expose them to tetanus bacteria. This chance for exposure makes it important to immunize them against tetanus. Handwashing and bathing do little once the bacteria actually get under the skin.

Once under the skin, the bacteria make a toxin that causes muscle spasms. These spasms can affect the throat and jaw making it difficult to breathe. In some cases these spasms and breathing problems cause suffocation. Tetanus is sometimes called lockjaw because of the muscle spasms in the throat and jaw. The tetanus toxin can also damage the heart.

Eradication, or complete elimination, of tetanus will not be possible through vaccination because of its presence in the soil and the fact that it does not spread from one person to another. This also means there is no protection from herd immunity, so people are not protected from this disease even if everyone around them has been vaccinated.

Two populations most affected by tetanus

Two groups are most often affected by tetanus: adults and newborns. Which group is most at risk depends on where they live. In developed countries, tetanus is more likely in adults who have injured themselves. In the developing world, infants are at greater risk. Infections in newborns result from poor sanitation during or after delivery. Tetanus in newborns is called neonatal tetanus. Efforts to eliminate deaths from neonatal tetanus are making progress, but work remains.

Pertussis

What is pertussis?

Pertussis is one of the most contagious diseases. It is caused by a bacterium known as Bordetella pertussis. Pertussis makes people cough uncontrollably. The cough can be so violent that people with pertussis can crack ribs, break blood vessels, or develop hernias. A hernia occurs when an organ breaks through a muscle or tissue into a space where it should not be. Pneumonia or seizures can also develop. Pertussis is particularly dangerous for young children because of their small breathing tubes. Mucus caused by the infection makes breathing even more difficult. As children try to catch their breath, it causes a “whooping” sound. This is why pertussis is sometimes called whooping cough. Young infants can also experience bouts of apnea in which they briefly stop breathing.

Pertussis is unusual in that most children catch the disease from adults and not from other children. People do not always realize how common pertussis is, and adults often do not seek medical care. Even if they do, they may not be diagnosed with pertussis, especially if they wait until they have had the cough for a few weeks. As a result, cases of pertussis are often undercounted. Cases of pertussis decreased during COVID-19 as people isolated. Since then, cases have been increasing. For example, in 2023, cases were double those in 2022. More than 35,000 cases occurred in 2024 — five times higher than in 2023 — and 10 people died. Six of the 10 were children less than 1 year of age. Sadly, because cases are undercounted, it is likely that many more people in the U.S. had pertussis.

  • Anjuli Gans, MD: I remember as a trainee, one of the first children I ever admitted to the pediatric ICU was a baby with pertussis; a 5-month-old, whose parents had chosen to delay vaccines. And I was so struck by how significant the symptoms were.

    Paul Offit, MD: It's a frightening disease. What happens is children, especially young children because their windpipes are narrower, get clogged with this thick, tenacious mucus. So, they cough, cough, cough, but they can't really cough up the mucus because it's so thick. And so, cough, cough, cough, cough. Stop breathing. And then they breathe in through this narrow windpipe, which causes that whooping sound. But you're worried that they're not going to breathe in because you’re watching them sort of cough, cough, cough; stop; turn blue. It's just frightening.

    Anjuli Gans, MD: I remember just sitting up on call and I would hear it, you know, doors and doors away and just being so struck by, like you say, that frightening cough sound. And I'm a mom of young kids now, and I can't imagine being a parent in that situation. Thinking about seeing your kids sick is so hard, and also knowing that you maybe could’ve done anything more to prevent it or to help them get through it, can be really challenging.

    Paul Offit, MD: Right, and there's really not much else you can do other than supportive care. We give antibiotics, but really the main reason we give antibiotics is to prevent that child from continuing to shed bacteria. So, it's more in trying to prevent him or her from infecting others than treating that disease. I mean, once they're at the point where they have this paroxysmal coughing, there's really not much you can do other than hope for the best.

    Anjuli Gans, MD: Yeah, absolutely. And knowing that it's not just that acute illness too, but that those kids can have coughs that linger for weeks and months after. They can have post-inflammatory wheezing, you know. It's not just the acute illness on its own, too, it's thinking about all of the other effects later on.

    Have you seen a lot of older adults get pertussis? Is that something that you've had experience with?

    Paul Offit, MD: I think pertussis is a common disease in older adults, so we never identify it, or we often don't identify it. But, you know, it's the same thing. Cough, cough, cough. It's miserable. It's often referred to as the 100-day cough. Sometimes the coughing can be so bad that you have sort of broken blood vessels in the eye or you break a rib. I mean, it can be that bad. And I think it equally important is the fact that then that adult can bring the disease back into the home. It's interesting, most infectious diseases, the child gives it to the adult, but this is one of those diseases often where the adult gives it to the child.

    Anjuli Gans, MD: It's interesting, too, because I see a lot of newborns in clinic, and so when I'm talking with families, I often will say it's sort of a family protection we can offer them. So, we have a lot of conversations about the adults around them, grandparents, things like that, getting the vaccine too.

    Paul Offit, MD: Right. You want to protect especially that young child. It’s the young child who is at greatest risk.
Transcript Transcript

Watch as Drs. Paul Offit and Anjuli Gans from CHOP talk about the symptoms of pertussis and its lingering effects, how adults can spread the infection to infants, how to protect newborns from whooping cough, and more.

Read personal stories about pertussis.

 

Why is pertussis sometimes called the “100-day cough?”

The cough caused by pertussis is its most recognizable symptom. Severe coughing spells can cause vomiting and prevent people from sleeping. These spells can also cause nosebleeds or cracked ribs. People can have up to 15 severe coughing spells per day. The coughing spells often last for months. This is why pertussis has been called the “100-day cough.”

Five things you should know about pertussis include:

  • Pertussis is highly contagious. Eight of 10 non-immune people will be infected when exposed to someone with the disease.
  • Pertussis is commonly misdiagnosed and underdiagnosed.
  • You can get pertussis more than once. Protection from the vaccine fades over time, and people who get pertussis can get it again.
  • Older children and adults commonly spread pertussis to infants and young children.
  • Pertussis can be particularly harmful, even deadly, for infants.
Misdiagnosis, underdiagnosis, and fading immunity

Experts are aware that the actual number of pertussis infections each year is much greater than the number diagnosed. That’s because of:

  • Misdiagnoses: Pertussis bacteria are only detected at the beginning of the infection, so the test may be negative by the time someone seeks medical care.
  • Underdiagnoses: Many adults who are ill do not go to the doctor, so they are never diagnosed with pertussis.
  • Fading immunity: Booster doses are needed after vaccination to maintain immunity, and people can get pertussis more than once.
Susceptible infants

Although a pertussis infection can interfere with day-to-day life, adults tend to recover. Unfortunately, infants and young children are not always as lucky. Narrow breathing tubes and severe coughing episodes caused by pertussis can result in breathing problems for babies. If they can’t get enough air, they turn blue as they struggle to breathe. Sadly, some of them do not survive.

Infants too young to get a vaccine are most likely to suffer severe effects of pertussis. We have two ways to protect them in the interim:

  • “Borrowed” immunity — Pregnant women should get a single dose of Tdap vaccine between 27 and 36 weeks of gestation to boost the level of pertussis antibodies in their blood. These antibodies will be passed to the baby through the placenta before birth. Getting the Tdap vaccine as early during this window of 27 to 36 weeks as possible will maximize the quantity of antibodies the baby may have at the time of birth.
  • Limited exposure — If someone is ill, particularly with symptoms that include coughing, they should stay away from the baby as much as possible. Family members who will be with the new infant for extended periods can get a single dose of Tdap vaccine if they have not already had one, but they should still limit their time with the baby if they are ill.
Mom with child coughing

Pertussis Q&A
Woman and child gardening

Tetanus Q&A

Tetanus Special Topics Q&A

The vaccines

DTaP, Tdap, and Td Vaccines

The DTaP and Tdap vaccines both protect against three bacterial infections: diphtheria, tetanus and pertussis. The Td vaccine only protects against two: diphtheria and tetanus. The vaccines also vary in terms of who should get them and the amount of vaccine proteins they each contain:

  • DTaP: The DTaP vaccine is given to infants and young children in a series of five shots ─ at 2 months, 4 months, 6 months, 15 to 18 months, and again at 4 to 6 years of age. Infants are not considered protected until they have had the first three doses, called the primary series. The later two doses are booster doses.
  • Tdap: When older adolescents and adults got DTaP, some would have severe swelling of the arm where the vaccine was given. Studies suggested this was due to antibody levels to diphtheria. The Tdap vaccine has lower amounts of both diphtheria and pertussis proteins. It is much less likely than DTaP to cause this severe swelling as well as pain, redness and tenderness at the injection site. The Tdap vaccine is recommended for most people 11 years and older who have not previously received it. Adults should get a dose of Tdap or Td every 10 years as well as if they have a wound that warrants tetanus vaccination.
  • Td: The Td vaccine is the one people commonly think of when they need a tetanus booster. Like Tdap, it contains lower amounts of diphtheria protein to reduce side effects in adults. Adults should get a dose of Tdap or Td every 10 years as well as if they have a wound that warrants tetanus vaccination. 

Diphtheria vaccine

How is the diphtheria vaccine made?

The bacteria that cause diphtheria makes a harmful protein, called a toxin. The toxin is what makes people sick. So, people need an immune response to this toxin to be protected. The diphtheria vaccine is made by treating the diphtheria toxin with a chemical, so it can’t cause disease. The treated toxin is called a "toxoid." Once injected, the toxoid causes an immune response to the toxin, but it doesn't cause disease.

What are the side effects of the diphtheria vaccine?

The diphtheria vaccine can cause mild side effects such as pain or soreness where the shot was given. A small number of people will also have a low-grade fever. About 3 of every 100 children experience swelling of the limb where the vaccine was given after the fourth or fifth dose of DTaP vaccine. Studies have suggested that this occurs when children have high levels of antibodies against diphtheria. It is because of this swelling that older adolescents and adults are recommended to get Tdap instead of DTaP.

Tetanus vaccine

How is the tetanus vaccine made?

The bacteria that cause tetanus makes a harmful protein, called a toxin. The name of the tetanus toxin is tetanospasmin. The toxin is what makes people sick. So, people need an immune response to this toxin to be protected against tetanus. The tetanus vaccine is made by treating the tetanus toxin with a chemical, so it can’t cause disease. The treated toxin is called a "toxoid." Once injected, the toxoid causes an immune response to the toxin, but it doesn't cause disease.

What are the side effects of the tetanus vaccine?

Like the diphtheria vaccine, the tetanus vaccine can cause mild side effects such as pain or soreness where the shot was given. A small number of people will also have a low-grade fever.

The tetanus vaccine is also a rare cause of a severe allergic reaction. It is estimated that this allergic reaction could occur in about 1 of every 1 million people who get the tetanus vaccine. The allergic reaction can include hives, difficulty breathing or lower blood pressure. The allergic reaction can be treated with medication.

Pertussis vaccine

How is the pertussis vaccine made?

The bacteria that cause pertussis make several harmful proteins, called toxins. The toxin is what makes people sick. So, people need an immune response to some of these toxins to be protected against pertussis. The pertussis vaccine is made by treating two to five of these toxins with a chemical. The treated toxins are called "toxoids." Once injected, the toxoids cause an immune response against the toxins, but they don't cause disease.

The latest version of the pertussis vaccine was released in the fall of 1996. This vaccine is called the "acellular" pertussis vaccine. To reflect this change, a lowercase “a” has been added to the name of vaccines that include pertussis (e.g., DTaP and Tdap). 

  • Acellular pertussis vaccine (currently used in U.S.): This version takes advantage of advances in protein chemistry and protein purification, so it has only two to five proteins.
  • Whole-cell pertussis vaccine (no longer used in U.S.): This version contained a killed form of the whole pertussis bacteria. It had about 3,000 proteins and sugars.

The “whole cell” pertussis vaccine caused a fair number of severe side effects (see “What are the side effects of the pertussis vaccine?”). The newer “acellular” version causes fewer severe side effects because of its increased purity.

This change is one of the main reasons that children who receive all of the recommended vaccines today experience a lower antigenic challenge than children in the 1980s did. Antigens are the parts of a vaccine that our immune systems react to. This means while the number of vaccines has increased over time, babies’ immune systems are responding to fewer challenges from vaccines. Find out more about antigenic challenges: Webpage | Infographic (in Spanish).

What are the side effects of the pertussis vaccine?

The pertussis vaccine used before 1996 was called the "whole cell" vaccine. It had a high rate of mild and severe side effects. Mild side effects included pain and tenderness where the shot was given, fever, fussiness and drowsiness. These side effects occurred in as many as one-third to one-half of children who got the vaccine. Severe side effects also occurred. About 1 of every 100 doses caused persistent, inconsolable crying, high fever (greater than 105 degrees), or hypotonic-hyporesponsive syndrome, a condition in which a child can become listless and lethargic with poor muscle tone. And 1 of every 1,750 doses led to seizures caused by fever (called “febrile seizures”).

The pertussis vaccine used in the U.S. today is called the “acellular” pertussis vaccine. It has been in use in the United States since 1996. Mild side effects, such as pain and tenderness at the injection site, occur in about one-third of children. These usually occur after the fourth or fifth dose. This version has much lower rates of severe side effects. Severe reactions can include high fever (105 degrees or higher), fever-associated seizures, inconsolable crying, or hypotonic-hyporesponsive syndrome, a condition in which a child can become listless and lethargic with poor muscle tone. The symptoms of this syndrome can last for several hours and be scary for parents watching their child experience this, but they do not cause permanent harm. (see "Are vaccines safe?" page). The more severe reactions listed for “acellular” pertussis vaccine occur in about 1 of every 10,000 doses instead of 1 of every 100 doses as was the case for “whole cell” pertussis vaccine.

The change to “acellular” pertussis vaccine improved its safety, but it also led to decreased vaccine effectiveness. Children who receive the “acellular” pertussis vaccine become susceptible more quickly than those who received the “whole cell” version. It is unlikely that we would return to using the “whole cell” version because of its side effects. It is more likely that additional booster doses would be recommended until a more effective vaccine can be developed without returning to higher rates of side effects.

Other questions you might have

Should babies who cry uncontrollably after DTaP vaccine receive additional doses?

Babies who experience uncontrollable crying after the DTaP vaccine are considered to have a “precaution” to getting future doses of the vaccine. A vaccine precaution means that the baby can still receive future doses of the DTaP vaccine, but the family and the child’s doctor should discuss the relative risks and benefits before any additional doses are given.

The relative benefits of the vaccine may still outweigh the risks for a few reasons. First, pertussis is still fairly common. Second, young children are at the greatest risk for complications, and third, children need the first three doses to gain protection. Previous experience has shown that in most cases, infants who experience inconsolable crying after the first dose of DTaP do not experience the same reaction after later doses.

Should teenagers and adults get the pertussis vaccine?

Pertussis is common in teenagers and adults. So, a vaccine to prevent pertussis in teenagers and adults is of great benefit. The “whole cell” pertussis vaccine (DPT) and the "acellular" pertussis vaccine for young children (DTaP) had high rates of side effects when given to people older than 7 years of age. To address this, another version was made for older children and adults. It is called the Tdap vaccine. The “d” and the “p” are lowercase because this version contains lower amounts of the diphtheria (“d”) and pertussis (“p”) toxoids. These changes improved the side effect rates in older children, teens and adults.

Adolescents and adults can spread pertussis to infants who are too young to have received the DTaP vaccine. For this reason, it is important for adolescents and adults around a baby to be up to date on Tdap vaccine. Parents, grandparents and childcare providers should all have at least one dose of Tdap vaccine. In addition, when it is time for a “tetanus booster,” ask for Tdap instead of Td to boost your immunity against not only diphtheria and tetanus but also pertussis.

Notably, a dose of Tdap is recommended between 27 and 36 weeks of gestation during each pregnancy. This is to increase the level of maternal antibodies against pertussis. Those antibodies are passed to the baby to provide some level of protection until the baby can get the DTaP vaccine at 2 months, 4 months, and 6 months of age. (Also see “Vaccine considerations for new and expectant parents.”)

How can I protect my newborn from pertussis?

Pertussis can be a dangerous disease for a new baby. Because of their small airways and the amount of mucus caused by infection with pertussis, babies have trouble breathing. They often turn blue during their coughing spells. Every year in the U.S., children die from pertussis. Most are young babies who have not been fully immunized. In 2024, 10 deaths were caused by pertussis. Six of those were in children less than 1 year of age.

There are several things that you can do to help protect your baby from pertussis:

  • Get vaccinated during pregnancy: The Tdap vaccine is recommended between 27 and 36 weeks of gestation during each pregnancy. Although any time during this window is acceptable, the vaccine should be received as early as possible during this window to improve protection for the baby. If you are past 36 weeks in your pregnancy, be sure to ask for the Tdap vaccine before being discharged from the hospital to decrease the chance of getting pertussis and giving it to your baby.
  • Vaccinate the baby when they are old enough: Babies get a vaccine to protect them from pertussis when they are 2 months, 4 months, and 6 months of age. They get another dose at 15 to 18 months.
  • Before vaccination: Make sure that adults and siblings who will be around the baby are up to date on pertussis vaccine. Keep people who are ill, especially those with a cough, away from the baby. Notably, people are not only contagious in the first few weeks of the severe coughing stage, but also in the one- to two-week period before the cough begins. During this period, symptoms may resemble those of a cold (e.g., runny nose, sneezing, occasional cough).
  • Limit potential for exposure: Limit how many people the baby is around, and make sure people wash their hands. 

You can find more tips for protecting babies before they are vaccinated in these resources:

If I had whooping cough as a child, do I still need to get the vaccine before being around an infant?

Protection after a pertussis infection is not lifelong. That means people can get pertussis more than once. Because infants are at higher risk for complications and death from pertussis, those who will be around them should have a single dose of Tdap vaccine if they did not have that vaccine before.

If I had the DTP vaccine as a child, do I need the booster vaccine for pertussis?

Yes. Adults who have not previously gotten the Tdap vaccine should get a single dose. Adults can also get Tdap instead of Td when they need a tetanus booster. This will also increase their protection against pertussis. 

Pregnant women should get one dose of Tdap vaccine between 27 and 36 weeks of gestation during each pregnancy because pertussis can be fatal to young infants. Although any time during this window is fine, it is better to get the dose earlier rather than later during the window to increase the level of protection for the baby.

The Tdap vaccine is also recommended for all adolescents 11 to 12 years old.

Relative risks and benefits

Do the benefits of the diphtheria vaccine outweigh its risks?

Diphtheria is an extremely rare cause of disease in the United States. Between 1996 and 2018, 14 cases of diphtheria and one death occurred in the U.S. The death occurred in 2003 after an unvaccinated man returned from a trip to Haiti. Most cases of diphtheria are among recent travelers. There have been no cases in U.S. residents that have not recently traveled since 1999. On the other hand, cases and deaths continue to occur in other parts of the world. 

The diphtheria vaccine has no serious side effects. So, although the risk of disease and death from diphtheria is very small, the risk of severe adverse reactions or death from the diphtheria vaccine is zero. 

For these reasons, the benefits of the diphtheria vaccine outweigh its risks.

Do the benefits of the tetanus vaccine outweigh its risks?

Tetanus is an uncommon cause of disease in the United States. But it’s probably not as rare as you may think. Between 2013 and 2022, an average of 30 cases of tetanus was reported each year in the United States, and 13 people died during those years. 

The tetanus vaccine can be a very rare cause of a short-lived allergic reaction called “anaphylaxis.” But the tetanus vaccine does not cause death. Because most of the disease and death from tetanus occurs in the elderly, it is important to get booster shots every 10 years. 

For these reasons, the benefits of the tetanus vaccine outweigh its risks. 

Do the benefits of the pertussis vaccine outweigh its risks?

Several years ago, negative publicity surrounding the “whole cell” pertussis vaccine caused its use to decrease in many areas of the world. One example was Japan. In 1975, children stopped receiving the pertussis vaccine. In the three years before the vaccine was discontinued, there were 400 cases and 10 deaths from pertussis. In the three years after the pertussis vaccine was discontinued, there were 13,000 cases and 113 deaths from pertussis. Although the side effects of the “whole cell” pertussis vaccine were high, no child ever died from that vaccine. The “acellular” pertussis vaccine used today has even fewer side effects.

The Japanese Ministry of Health realized how costly its error had been and quickly reinstituted use of pertussis vaccine. Sadly, the children of Japan proved that the benefits of pertussis vaccine clearly outweighed its risks during the three years after vaccine use was stopped.

In the U.S., pertussis is quite common. In 2024, more than 35,000 cases and 10 deaths resulted from pertussis. However, because of underdiagnosis and misdiagnosis, the number of cases is likely to be much higher. Sadly, most of the deaths from pertussis occur in young infants who struggle to breathe. They can turn blue or stop breathing for a short time as they struggle. 

The “acellular” pertussis vaccine has fewer proteins and causes fewer side effects. It does not cause any deaths.

For these reasons, the benefits of the pertussis vaccine clearly outweigh its risks.

Diseases risks

Diphtheria

  • Damage to heart, kidneys and nerves
  • Can be fatal

Tetanus

  • Severe muscle spasms
  • If muscles in throat and neck spasm, it may lead to suffocation and death
  • Heart damage

Pertussis

  • Uncontrollable coughing for weeks or months.
  • Severe coughing attacks can cause vomiting, cracked ribs, broken blood vessels or hernias, which occur when an organ breaks through a muscle or tissue into a space where it shouldn’t be.
  • Pneumonia or seizures.
  • Bouts of apnea during which young infants stop breathing.
  • Can be fatal.

Vaccine risks

  • Pain, redness and swelling at the injection site
  • Mild fever
  • Fussiness, fatigue, lack of appetite
  • Nausea, vomiting, diarrhea, stomach ache
  • Extensive swelling of the limb where the shot was given (about 3 in 100 people following fourth or fifth dose)
  • Severe reactions (about 1 in 10,000 people):
    • Fever of 105 degrees or higher
    • Fever-associated seizures
    • Inconsolable crying
    • Hypotonic-hyporesponsive syndrome, a condition in which a child can become listless and lethargic with poor muscle tone for several hours

References

  • Orenstein WA, Offit PA, Edwards KM and Plotkin SA. Diphtheria Toxoid in Plotkin's Vaccines, 8th Edition. 2024, 298-310.
  • Orenstein WA, Offit PA, Edwards KM and Plotkin SA. Tetanus Toxoid in Plotkin's Vaccines, 8th Edition. 2024, 1117-1141.
  • Orenstein WA, Offit PA, Edwards KM and Plotkin SA. Pertussis Vaccines in Plotkin's Vaccines, 8th Edition. 2024, 763-815.
  • 2024 Provisional Pertussis Surveillance Report, Jan. 2025.
  • Pertussis Cases by Year (1922-2023), April 24, 2025.

Specific topic references

Pertussis vaccine and neurologic complications

Top KA, Brna P, Ye L, Smith B. Risk of seizures after immunization in children with epilepsy: a risk interval analysis. BMC Pediatr 2018;18:134.
The authors analyzed the risk of seizures after immunization in children with epilepsy less than 7 years of age. Nearly half of the immunization visits that occurred after epilepsy diagnosis were characterized by receipt of DTaP. The risk of seizures was not increased 0-14 days after any vaccine. The authors concluded that children with epilepsy do not appear to be at increased risk of seizures following immunization. These findings suggest that immunization is safe in children with epilepsy.

Lateef TM, Johann-Liang R, Kaulas H, Hasan R, Williams K, et al. Seizures, encephalopathy, and vaccines: experience in the National Vaccine Injury Compensation Program. J Pediatr 2015;166:576-581  
The authors described the demographic and clinical characteristics of children younger than 2 years of age for whom claims were filed with the National Vaccine Injury Compensation Program (VICP) alleging seizure disorder or encephalopathy or both during a one-year period. In 80 percent of these claims, a pertussis-containing vaccine was implicated, and four times more often related to the whole-cell pertussis vaccine. Seizure disorder was the primary condition for which compensation was sought and less than half of the claimants were known to have been febrile at the time of presentation. A significant number of children with alleged vaccine injury had pre-existing neurologic or neurodevelopmental abnormalities. Among those developing chronic epilepsy, many had clinical features suggesting that the epilepsy had a genetic basis.

Daley MF, Yih WK, Glanz JM, Hambidge SJ, Narwaney KJ, et al. Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP-IPV) vaccine. Vaccine 2014;32:3019-3024.
The authors examined the risk of serious, but uncommon, adverse events after receipt of DTaP-IPV in more than 200,000 children 4-6 years of age during a four-year period via the Vaccine Safety Datalink project. Receipt of DTaP-IPV did not significantly increase the risk of meningitis/encephalitis, seizures, stroke, Guillain-Barré syndrome, Stevens-Johnson syndrome, anaphylaxis, serious allergic reactions, or serious local reactions.

Sun Y, Christensen J, Hviid A, Li J, Vedsted P, et al. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type b. JAMA 2012;307(8):823-831.
The authors evaluated the risk of febrile seizures and epilepsy in more than 300,000 children who received DTaP-IPV-Hib at ages 3, 5, and 12 months in Denmark during a six-year period. DTaP-IPV-Hib vaccination was not associated with an increased risk of febrile seizures in children within seven days following receipt of vaccine compared with those children beyond seven days of vaccination. Sub-analyses indicated an increased risk of febrile seizures on the day of the first two vaccinations, although absolute risk was small. DTaP-IPV-Hib vaccination was not associated with an increased risk of epilepsy.

Huang WT, Gargiullo PM, Broder KR, Weintraub ES, Iskander JK, et al. Lack of association between acellular pertussis vaccine and seizures in early childhood. Pediatrics 2010;126(2):e263-e269.
The authors investigated the incidence of seizures following receipt of DTaP during a 10-year period in more than 430,000 children aged 6 weeks to 23 months. They found no significant increase in the risk of seizures following receipt of DTaP.

Yih WK, Nordin JD, Kulldorff M, Lewis E, Lieu TA, et al. An assessment of the safety of adolescent and adult tetanus-diphtheria-acellular pertussis (Tdap) vaccine, using active surveillance for adverse events in the Vaccine Safety Datalink. Vaccine 2009;27:4257-4262.
The safety of Tdap was monitored weekly among subjects aged 10-64 years during 2005-2008 with specific attention to encephalopathy-encephalitis-meningitis, paralytic syndromes, seizures, cranial nerve disorders, and Guillain-Barré syndrome (GBS).  No evidence of an association between Tdap and any of these adverse events was found during a three-year-surveillance period that included more than 660,000 Tdap doses. GBS and cranial nerve sub-analyses found no statistically significant temporal clustering within 42 days after vaccination.

Ray P, Hayward J, Michelson D, Lewis E, Schwalbe J, et al. Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study. Pediatr Infect Dis J 2006;25:768-773.
The authors investigated the possible relationship between whole-cell pertussis (DTP) or measles (MMR) vaccination and encephalopathy, encephalitis, and Reye syndrome by evaluating 15 years of health records from four health maintenance organizations in the United States, which encompassed nearly 2.2 million children. DTP and MMR vaccines were not associated with an increased risk of encephalopathy, encephalitis, or Reye syndrome after vaccination. Additionally, a clinically distinctive pertussis vaccine-induced encephalopathy was not detected, which was consistent with other studies.

Le Saux N, Barrowman NJ, Moore DL, Whiting S, Scheifele D, et al. Decrease in hospital admissions for febrile seizures and reports of hypotonic-hyporesponsive episodes presenting to hospital emergency departments since switching to acellular pertussis vaccine in Canada: a report from IMPACT. Pediatrics 2003;112:e348-e353.
The authors compared the incidence of hospital admissions for febrile seizures and hypotonic-hyporesponsive episodes (HHEs) presenting to hospital emergency departments before and after transition from DTP to DTaP in Canada. Hospital admissions secondary to pertussis vaccine-related febrile seizures and HHEs associated with pertussis vaccine decreased by 79 percent and 60-67 percent %, respectively.

Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, et al. The risk of seizures after receipt of whole-cell pertussis or measles, mumps and rubella vaccines. N Engl J Med 2001;345:656-661.
The authors investigated the relationship between DTP and MMR and the risk of a first seizure, subsequent seizures and neurodevelopmental disability in children. During the three-year period, more than 340,000 DTP vaccines and more than 130,000 MMR vaccines were administered. Receipt of DTP vaccine was associated with an increased risk of febrile seizures only on the day of vaccination (six to nine febrile seizures per 100,000 children vaccinated). Receipt of MMR vaccine was associated with an increased risk of febrile seizures eight to 14 days after vaccination (25-34 febrile seizures per 100,000 children vaccinated). DTP and MMR were not associated with an increased risk of non-febrile seizures. Children with febrile seizures after vaccination were not found to be at a higher risk for subsequent seizures or neurodevelopmental disabilities as compared with their unvaccinated counterparts. The authors concluded that the increased risk of febrile seizures secondary to DTP and MMR do not appear to be associated with any long-term, adverse consequences.

Goodwin J, Nash M, Gold M, Heath TC, Burgess MA. Vaccination of children following a previous hypotonic-hyporesponsive episode. J Paediatr Child Health 1999;35:549-552.
Hypotonic-hyporesponsive episodes (HHE) were once considered a contraindication to pertussis vaccination in Australia. In this study, the authors evaluated the safety of further vaccination in children who had experienced an HHE (95 percent  experienced with whole-cell pertussis and 80 percent after the first dose). Researchers found no HHE or serious reactions after subsequent DTaP, DTP, or DT. The authors concluded that previously healthy children who experience HHE reactions can safely continue standard vaccination schedules.

Vermeer-de Bondi PE, Labadie J, Rumke HC. Rate of recurrent collapse after vaccination with whole cell pertussis vaccine: follow up study. BMJ 1998;316:902-903.
The authors conducted a follow-up study of 84 children in the Netherlands with reported collapse after their first whole cell pertussis vaccination (DTP) to determine the rate of recurrence in those who received subsequent doses of DTP. None of the children had recurrent collapse, and other adverse events were only minor.

Greco D, Salmaso S, Mastrantonio P, Giuliano M, Tozzi A, et al. A controlled trial of two acellular vaccines and one whole cell vaccine against pertussis. N Engl J Med 1996;334:341-348.
The authors compared the efficacy and safety of two acellular pertussis vaccines with whole-cell pertussis and DT alone in more than 14,000 children within six to 28 weeks of life. DTwP was found to have a significantly higher rate of local and systemic reactions, including local swelling and tenderness, irritability, fever, persistent crying for ≥ 3 hours, and hypotonic/hyporesponsive episodes with those receiving DTaP. Events following receipt of DTaP were similar to the control group that received DT alone. Seizures were either infrequent or did not occur in the vaccine groups.

Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334:349-356.
The authors compared the efficacy and safety of a two-component acellular pertussis vaccine, a five-component acellular pertussis vaccine, a whole-cell pertussis and DT alone in more than 9,000 children within the first six months of life. DTP was found to have a significantly higher rate of local and systemic reactions, including protracted crying, cyanosis, fever, and local reactions compared with both DTaP vaccines and DT. DTaP rates of these events were similar to the control group who received DT alone. Seizures occurred infrequently in the 48 hours after any vaccine receipt, and rates were similar among all groups.

Rosenthal S, Chen R, Hadler S. The safety of acellular pertussis vaccine vs whole-cell pertussis vaccine. Arch Pediatr Adolesc Med 1996;150:457-460.
In December 1991, the FDA licensed the first diphtheria, tetanus toxoid, and acellular pertussis vaccine (DTaP) for use in children aged 15 months to 7 years. In this study, the authors analyzed post-marketing surveillance data submitted to the Vaccine Adverse Event Reporting System (VAERS) between late 1990 and late 1993 to determine whether serious but uncommon adverse events are less frequent after DTaP as compared with whole-cell pertussis (DTP) vaccine receipt. An estimated 27 million DTP doses (with or without Haemophilus influenzae type b vaccine) and 5 million DTaP doses were administered during this period. DTaP was associated with significantly fewer total adverse event reports, as well as significantly fewer reports of subcategory adverse events (fever, seizures or hospitalization), compared with DTP.

Gale JL, Thapa PB, Wassilak SGF, Bobo JK, Mendelman PM, et al. Risk of serious acute neurological illness after immunization with diphtheria-tetanus-pertussis vaccine. JAMA 1994;271:37-41.
The authors prospectively identified children between mid-1987 and mid-1988 in Washington and Oregon states to evaluate the association between receipt of whole-cell pertussis vaccine and serious acute neurological illness within seven days of vaccination. Among an estimated 368,000 DTP vaccines administered, no increased risk of serious acute neurological illness including complex febrile seizures, afebrile seizures, infantile spasms, or acute encephalitis/encephalopathy was detected.

Blumberg DA, Lewis K, Mink CM, Christenson PD, Chatfield P, et al. Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers and persistent crying. Pediatrics 1993;91:1158-1165.
The authors prospectively evaluated children in Los Angeles, California, between 1986 and 1990 to determine causes and risk factors for severe DTP reactions within 48 hours of vaccine receipt. Children with seizures had a high rate of personal and family histories of seizures, and 90 percent  had documented fevers. Persistent crying was associated with painful local reactions. Neither lymphocytosis nor hypoglycemia occurred. No biologically active pertussis toxin was found in the acute sera of children experiencing possible severe DTP reactions. As acellular pertussis vaccines have less endotoxin, which is thought to lead to febrile seizures, the authors concluded that use of acellular vaccines should lead to a reduction in DTP-related seizures due to a decrease in febrile events. Acellular pertussis vaccines also have lower local and systemic reaction rates compared with the whole cell vaccine utilized in this study; therefore, persistent crying may also be reduced.

Griffin MR, Ray WA, Mortimer EA, Fenchel GM, Schaffner W. Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine. JAMA 1990;263:1641-1645.
The authors evaluated the risk of seizures and other neurological events, including encephalopathy, following DTP immunization in Denmark in more than 38,000 children who received about 107,000 DTP immunizations in the first three years of life. The authors found no increased risk of febrile or afebrile seizures in the 0- to three-day window following immunization when compared with 30 or more days after vaccine receipt. Two cases of encephalitis were reported, but onset occurred more than two weeks after vaccine receipt.

Griffith AH. Permanent brain damage and pertussis vaccination: is the end of the saga in sight? Vaccine 1989;7:199-210.
The author provides an overview of the pertussis vaccine and controversies surrounding its possible link to permanent brain damage.  Reports of permanent brain damage thought secondary to receipt of the pertussis vaccine were published in the 1950s through 1970s. Most notably, a case series suggesting permanent brain damage secondary to pertussis vaccination out of the National Hospital for Sick Children by Kulenkampff and colleagues was the subject of a United Kingdom television documentary in 1974 that resulted in a significant decline in vaccination rates and a consequent resurgence of pertussis in England. Repercussions from this documentary in the UK included the establishment of expert panels and sponsored research teams by the Department of Health and Social Security to examine existing clinical data and to carry out prospective studies including the North West Thames study (see Pollock, et al, Lancet 1983 data reported below) and the National Childhood Encephalopathy Study (NCES).

The NCES evaluated reported cases of defined serious neurological disorders arising in children between 2 and 36 months of age admitted to the hospital between mid-1976 and mid-1979 in the UK. These researchers estimated the attributable risk of neurological damage after pertussis immunization to be 1 in 310,000-330,000 injections, but the report was limited by certain structural biases and incomplete information; furthermore, these results could not be reproduced in subsequent studies.

The Kulenkampff and NCES data were reexamined in the High Court of Justice, London, in the wake of neurologic damage claims brought to the court. Regarding the Kulenkampff data, more than half of the cases either could not be linked to pertussis vaccination (e.g., DT given instead of DTP), had normal outcomes, or were found to have alternative causes. Reexamination of the NCES data showed

  1. No previously normal child suffered permanent brain damage with an onset within 48 hours of vaccination
  2. No evidence supported the notion that previously neurologically abnormal children had a greater risk than normal children of suffering an event within a short period following vaccination
  3. Of the 12 previously normal cases of “serious neurological disorder” with onset within the first 48 hours, 10 were cases of febrile convulsions and those with prolonged convulsions were normal at follow-up
  4. If the cases of Reye’s syndrome and of viral origin were excluded— given that they are not caused by DTP — no cases of permanent brain damage or death were linked to the vaccine
  5. The figure of 1 in 310,000 or 330,000 given as the attributable risk of permanent brain damage following DTP vaccine could not be supported
  6. Evidence supports that on rare occasions, DTP causes febrile convulsions

Livengood JR, Mullen JR, White JW, Brink EW, Orenstein WA. Family history of convulsions and use of pertussis vaccine. J Pediatr 1989;115:527-531.
The authors evaluated data from the CDC Monitoring System for Adverse Events Following Immunization during the period of 1979 to 1986 to determine the risk of neurologic events after vaccination with DTP in patients with a family history of convulsions compared with those without a family history. Children with a family history of seizures had an increased risk of neurologic events, primarily febrile convulsions, after DTP receipt, but this increase in risk may reflect a nonspecific familial tendency for convulsions rather than a specific vaccine effect as well as selection bias. Given the rare occurrence of neurologic events after DTP vaccination, the generally benign outcome of febrile convulsions that accounted for more than 75 percent  of the events, and the risk pertussis caused by not vaccinating people with a family history of convulsions, the authors concluded that a history of convulsions in a close relative should not be a contraindication to the pertussis vaccination. Rather, prevention of post-vaccination fever may be warranted in these children.

Baraff LJ, Shields WD, Beckwith L, Strome G, Marcy SM, et al. Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow up evaluation. Pediatrics 1988;81(6):789-794.
In a previous prospective study (Cody, et al Pediatrics 1981), the authors found that minor reactions (e.g., local redness, swelling, fever, etc.) were more common following DTP immunization than DT. Among more than 15,000 DTP injections, nine children developed seizures and nine developed hypotonic-hyporesponsive episodes though no sequelae were detected following these possible temporal reactions. The authors completed a follow-up evaluation six to seven years later in 16 of these children to determine if any had evidence of neurologic impairment too subtle to have been detected at the time of their initial evaluation.  All 16 children were considered to be normal by their parents and — as determined by their school performance — had no evidence of serious neurologic damage.

Shields WD, Nielsen C, Buch D Jacobsen V, Christenson P, et al. Relationship of pertussis immunization to the onset of neurologic disorders: a retrospective epidemiologic study. J Pediatr 1988;113:801-805.
The authors examined the temporal relationship between onset of neurologic disorders and the time of pertussis vaccine in children immunized with either DTP or monovalent pertussis at different ages. They found no relationship between the age of onset of epilepsy and scheduled age of administration of pertussis vaccine; however, a relationship existed between scheduled age of administration and first febrile seizure, which occurred more commonly with the third dose in the series between 10-15 months of age. No relationship between pertussis immunization and the occurrence of central nervous system infections was noted.

Walker AM, Jick H, Perera DR, Knauss TA, Thompson RS. Neurologic events following diphtheria-tetanus-pertussis immunization. Pediatrics 1988;81(3):345-349.
The authors assessed the frequency of serious neurologic events following administration of 106,000 DTP immunizations in children between 1977 and 1983. They found no cases of acute unexplained encephalopathy temporally associated with vaccination. The onset of one serious seizure disorder occurred within three days of immunization, with 1.13 cases expected on the basis of chance alone.  The incidence of recorded febrile seizures in the immediate post-immunization period was 3.7 times that in the period 30 days or more after immunization.

Bellman MH, Ross EM, Miller DL. Infantile spasms and pertussis immunisation. Lancet 1983;321(8332):1031-1034. 
The authors investigated the possible role of pertussis immunization and other factors in the etiology of infantile spasms reported to the National Childhood Encephalopathy Study between 1976 and 1979 in England, Scotland and Wales. No significant association was found between infantile spasms and pertussis immunization in the 28 days following vaccination.  

Corsellis JA, Janota I, Marshall AK. Immunization against whooping cough: a neuropathological review. Neuropathol Appl Neurobiol 1983;9(4):261-270. 
The authors examined published data on childhood deaths which were thought to be due to receipt of the pertussis vaccine and identified an additional 29 children in England and Wales whose deaths between 1960 and 1980 had been reported as occurring in relation to DTP and had post-mortem examinations. Deaths occurred within three weeks or up to 12 years after DTP receipt. Upon autopsy, various cerebral abnormalities were found; however, none of the cases in this study or in previous published reports had demonstrated a recurring pattern of inflammatory or other damage that could be accepted as a specific reaction to pertussis immunization. Reactive changes that were occasionally found appear to be indistinguishable from those seen in other infantile encephalopathies.

Pollock TM and J Morris. A 7-year survey of disorders attributed to vaccination in North West Thames Region. Lancet 1983;1(8327):753-757.
The authors examined the relationship between pertussis and other vaccines and neurological problems over a seven-year period. All children reported to have serious or unusual vaccine reactions, regardless of severity, had records investigated and were physically examined by an area health authority medical officer four weeks after the original report; and all children, except for those with mild symptoms, had a developmental examination six months after the report. In a group of hundreds of thousands of children and more than 400,000 DTP immunizations, 20 reports of convulsions within three weeks of DTP were reported and three-quarters of the reports were febrile seizures within 48 hours of immunization; all children were developmentally normal on follow-up. Twelve neurological disorders were reported to have occurred within eight weeks of DTP receipt; 11 of which had either infantile spasms, infectious etiology, or epilepsy, none of which were linked to DTP. The authors concluded that their study does not support the claim that DTP produces a syndrome characterized by a previously healthy child who presents with continuous screaming, collapse, convulsion and arrested mental development.

Melchior JC. Infantile spasms and early immunization against whooping cough: Danish survey from 1970 to 1975. Arch Dis Child 1977;52:134-137. 
The authors examined the relationship between immunization and the onset of infantile spasms over a six-year period in Denmark after a change in its immunization program. Previously, DTP vaccine had been administered at 5, 6, and 15 months of age, but was changed in 1970 to monovalent pertussis vaccine at 5 weeks, 9 weeks, and 10 months of age. The authors found no differences in the age at onset of infantile spasms between immunized and non-immunized children; half of all cases in each group began before 5 months of age despite children immunized before 1970 not receiving the first dose until 5 months of age.

Reviewed by Paul A. Offit, MD, on May 8, 2025