Tag: DTaP

Making a Better Pertussis Vaccine

So we know that we need a better pertussis vaccine.

DTaP and Tdap just aren’t doing the job that they should be doing.

Whooping Cough is back, again.
Whooping Cough is back, again.

So when will we get one?

Making a Better Pertussis Vaccine

Since anti-vaccine folks are always talking about the 300 new vaccines in the pipeline, you would think that we would have had several new pertussis vaccines by now…

Unfortunately, we don’t.

What we do have is some good candidates, including:

  • new acellular pertussis vaccines, either with more antigens or an adjuvant
  • a new live attenuated nasal vaccine, BPZE1
  • new whole-cell vaccines with reduced endotoxin contents (so should have fewer side effects that then original whole-cell pertussis vaccine – DTP)

Before you get too excited, keep in mind that none of these vaccines will be available in your pediatrician’s office any time soon. Developing a new vaccine takes a lot of time.

BPZE1 has started phase 2a trials though.

What do we do until we get new pertussis vaccines?

“We should be more vigilant than we have been in the past to recognize and treat pertussis in all age groups so that transmission to young infants is reduced. Most important (although not discussed in this review) is to ensure that all pregnant women receive the Tdap vaccine between 27 and 36 weeks’ gestation with each pregnancy. Also, we should consider routinely administering Tdap vaccine every 3 years to all adolescents and adults who were primed with a DTaP vaccine.”

James D. Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines—Mistakes Made and Implications for the Future

We should keep using the pertussis vaccines we have!

Vaccines work, even when they aren’t as effective as we would like.

More on Making a Better Pertussis Vaccine

When Was the Last Case of Diphtheria?

Believe it or not, measles isn’t the only vaccine-preventable disease that is still around.

While you likely aren’t too surprised about the flu deaths and the cases of meningococcal disease, did you know that kids still get Hib, babies still get hepatitis B, and that there were three cases of human rabies and a case of diphtheria in the United States last year?

When Was the Last Case of Diphtheria?

Yes, diphtheria.

Diphtheria strikes unprotected children.

That’s despite the fact that the diphtheria vaccine has been around for over 100 years, long before it was combined with the first whole cell pertussis vaccine and the tetanus vaccine to form the DPT vaccine.

A vaccine that helped control respiratory diphtheria, which could lead to the formation of a pseudomembrane in a child’s airway, giving diphtheria the nickname of the “strangling angel.”

The last big outbreaks of diphtheria in the United States occurred in the 1970s, although sporadic cases had continued since, albeit at lower and lower levels each year. Eventually, endemic respiratory diphtheria was declared eliminated in 2009.

Still, we know that there have been some recent cases of diphtheria in the United States.

In April of 2014, a teen from Montgomery County, Ohio developed diphtheria.

And again in April of 2018, someone in Oklahoma developed diphtheria.

Why do we care about a few isolated cases?

Because we know how quickly diphtheria can come back if we stop vaccinating our kids!

Just look at what is happening in many other countries that once had these diseases under good control:

  • a 22-year-old unvaccinated women who died in Australia (2011)
  • an unvaccinated 3-year-old who died in Belgium (2016)
  • a family that became infected in South Africa in which at least one child died (August 2017)
  • at least 7 cases of diphtheria in Ukraine (2018)
  • an unvaccinated man in Australia who died (2018)
  • a case in Canada (2018)
  • 8 cases and 3 deaths in Columbia (2018)

Not to mention the large number of diphtheria deaths in Yemen, Venezuela, Haiti, and among Rohingya refugees.

Let’s not bring these diseases back. Vaccines are safe, with few risks, and obviously necessary.

More on the Last Case of Diphtheria

Are the Tdap and DTaP Vaccines the Same Thing?

You have probably already figured out the Tdap and DTaP aren’t the same vaccine, after all, if they were, why would they have different names, right?

Are the Tdap and DTaP Vaccines the Same Thing?

I bet you don’t know the difference between the two vaccines though.

Yes, they both are both combination vaccines that protect against diphtheria, tetanus, and pertussis.

The difference is that one (DTaP) is used as the primary series for infants and younger children (age 6 years and under) and the other (Tdap) is given to older children (age 7 years and above), teens, and adults.

Okay, that’s not the only difference.

The DTaP vaccine actually contains more diphtheria and pertussis antigens than Tdap, which is why it has the capital “D” and “P” in its name. The amount of tetanus toxoid antigens are about the same in both vaccines.

So Tdap contains the same amount of tetanus toxoid, plus a reduced amount of diphtheria and acellular pertussis antigens, as compared to DTaP.

While you would think that older children and adults would get the vaccine with the higher amount of antigens, since they are bigger, that’s not how this works. Vaccines typically start working at the injection site, so body size isn’t a key factor in determining the amount of ingredients.

As a booster dose of vaccine, the lower amount of antigens works just fine and helps reduce the risk of side effects from repeated doses that you might get with higher antigen counts.

More on Tdap vs DTaP

Does Getting the DTaP Vaccine Make You More Susceptible to Pertussis?

Wait, why would anyone think that getting vaccinated would make you more likely to get a vaccine-preventable disease?

Because there is a new pertussis outbreak in California and folks don’t understand how attack rates work…

Does Getting the DTaP Vaccine Make You More Susceptible to Pertussis?

We know that the latest pertussis vaccines aren’t the greatest, having issues with waning immunity.

They don’t actually make you more likely to get pertussis though, at least not relative to being unvaccinated.

“Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

What the above quote that anti-vaccine folks are misusing is actually saying is that kids who got DTaP vaccines will be more susceptible to pertussis compared to those who got DTwP, the older version of the vaccine. That’s what the whole article is about!

It is not that they will be more suspecptible to pertussis vs someone who was unvaccinated.

Dr. I: Anti-vax folks are misinterpreting that statement, not understanding that it means relative to kids who got DTwP. They think that you are saying that it is the DTaP vaccine itself that makes it more likely that a child will get pertussis, in general. Even relative to someone who is unvaccinated. I know it shouldn’t be necessary, but can you provide a simple quote to clarify this?

JDC: You are of course correct. I was asked to write-up the talk that I have given many times in the US and in many other countries. In the talk, right at the beginning, I mention that today there is 20 fold less pertussis than there was in the pre-vaccine era and that illness in vaccine failures is much less severe that illness in unvaccinated children. I also remember how wrong they were 30 years ago R/E alleged reactions to DTwP.

And if you read his latest article, The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future, especially if you read more than the abstract, you discover that’s what he is saying.

But what about linked-epitope suppression?

In “linked-epitope suppression,” memory B cells out-compete naive B cells for access to the Bordetella epitopes because they are more numerous and their receptors exhibit a higher antigen affinity. Linked-epitope suppression applies as the immune response to novel epitopes is suppressed by the strong response to initial components if they are introduced together.

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

Basically, the DTwP vaccine included many more epitopes or targets for antibodies to bind to than the newer DTaP vaccine. That’s why it worked better. And you don’t get a good response to non-vaccine epitopes or antigens.

Still, you at least have some memory B cells and antibodies after getting the DTaP vaccine, which is why the idea that getting vaccinated makes you more susceptible to pertussis is silly. You are still protected, even if the protection isn’t perfect.

That’s why Dr. Cherry recommends that folks continue to get vaccinated and protected!

“We should be more vigilant than we have been in the past to recognize and treat pertussis in all age groups so that transmission to young infants is reduced. Most important (although not discussed in this review) is to ensure that all pregnant women receive the Tdap vaccine between 27 and 36 weeks’ gestation with each pregnancy. Also, we should consider routinely administering Tdap vaccine every 3 years to all adolescents and adults who were primed with a DTaP vaccine. This suggestion is contrary to that in the current Advisory Committee on Immunization Practices recommendations. However, from the data available, this approach could be expected to decrease the circulation of B pertussis in adolescents and adults. Also, Tdap should be administered to all adolescent and adults exposed to B pertussis during a school or other group outbreak.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

He does recommend that we work on new pertussis vaccines though.

“Future cohorts would benefit from the development and use of live vaccines and less-reactogenic DTwP vaccines.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

But why are we using a vaccine that doesn’t work as well as the previous vaccine we had?

“Despite the fact that in all but 2 of the efficacy trials the DTwP vaccines had greater efficacy than did the DTaP vaccines being studied, DTaP vaccines were licensed and used in many countries throughout the world; DTaP vaccines had replaced DTwP vaccines. The urgency to adopt DTaP vaccines was driven largely by antivaccine activist groups such as “Dissatisfied Parents Together.” During the rush to adopt DTaP vaccines and tetanus, diphtheria, acellular pertussis vaccines for adults (Tdap), much of the history relating to human pertussis was overlooked.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

But the DTwP vaccines weren’t safe, right?

“The results of a number of controlled studies between 1979 and 2004 indicated that no risk of severe neurologic disease after DTwP vaccinations existed. It was noted by myself and Shields (a pediatric neurologist) that what was being called pertussis vaccine encephalopathy was not an encephalitis-like event but, instead, the first seizure or seizures of infantile epilepsy.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

No, the cases of encephalopathy that were being reported were not caused by the DTwP vaccine. And neither did the DTwP vaccine cause SIDS, as was also reported at the time.

“Since 1997, the DTaP vaccination policy has created a cohort of people (the number of which is expanding yearly) who are more susceptible to repeated clinical illness with B pertussis infection than are DTwP-vaccinated children. There is no feasible way to make this cohort less susceptible.”

JD Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines-Mistakes Made and Implications for the Future

And now, after helping create the current DTaP vaccination policy, anti-vaccine folks want to scare folks away from using the vaccine. Don’t let them. Don’t skip or delay this vaccine and leave your kids susceptible to getting diphtheria, tetanus, and pertussis.

More on Does Getting the DTaP Vaccine Make You More Susceptible to Pertussis?

VigiAccess Numbers in Context

Most people are familiar with VAERS, the Vaccine Adverse Event Reporting System.

They sometimes forget that it is only the Vaccine Adverse Event Reporting System for the United States.

Other countries have their own vaccine safety systems.

VigiAccess Numbers in Context

One of the biggest is VigiBase, the World Health Organization’s  global database for suspected adverse drug reactions, maintained by the Uppsala Monitoring Centre in Sweden.

“Information on suspected ADR should not be interpreted as meaning that the medicinal product in question, or the active substance(s), generally causes the observed effect or is unsafe to use.”

Not surprisingly, folks misuse VigiBase numbers, just like they misuse VAERS reports.

JB Handley needs help understanding VigiAccess reports.
JB Handley needs help understanding VigiAccess reports.

To look at the VigiBase reports, you can use VigiAccess.

“VigiAccess has a search interface that allows visitors to retrieve summary statistics on suspected adverse reactions to medicines and vaccines.”

Uppsala Monitoring Centre

While VigiBase “is at the heart of UMC’s signal detection and scientific research,” you aren’t going to learn much from VigiAccess.

“Geographically, only continent-level statistics are shown, due to issues relating to patient confidentiality and data protection in individual countries.”

Uppsala Monitoring Centre

The biggest problem?

You don’t know how many vaccines were given to all of those people.

For example, while it might sound like there have been a lot of adverse drug reaction reports for the DTaP vaccine, with 179,447 reports in VigiAccess, since those are worldwide reports since 1968, it is likely among many billions of doses of vaccines being given.

Most importantly though, as with VAERS, “The reports in VigiBase result from suspicions of a relationship between a drug and a reaction. No causal relation has been confirmed.”

So how do you put the numbers from VigiBase and VigiAccess in context?

If you consider that reports and safety signals from VigiBase, VigiMatch, VigiRank, and other tools used by the Uppsala Monitoring Centre continue to find that vaccines are safe, then to put the DTaP numbers in context, they help us know that vaccines are being well monitored for safety.

And since we know that these diseases haven’t disappeared, any further context, if you need it, would be that since vaccines are safe and necessary, then you should get yourself and your family vaccinated and protected.

More on VigiBase and VigiAccess

 

Did the US Government Lose a Landmark Vaccine Lawsuit?

Have you heard the big news in the anti-vaccine world?

The anti-vaccine world thinks that they won some landmark lawsuit.

Reagan didn’t do much for vaccines, but it isn’t fair to pin this one on him.

It seems that some folks think that the Department of Health and Human Services hasn’t been complying with federal vaccine safety mandates for 30 years.

The 1986 National Childhood Vaccine Injury Act includes a mandate for safer vaccines.
The National Childhood Vaccine Injury Act of 1986 includes a mandate for safer vaccines.

Really?

Which ones?

Did the US Government Lose a Landmark Vaccine Lawsuit?

While anti-vaccine folks are pushing this lawsuit victory (?) to make folks think that HHS has done absolutely nothing to promote vaccine safety in the last 30 years, that is obviously nonsense.

The lawsuit was actually just about the reporting requirements of paragraph (c) of section 2127 of the National Childhood Vaccine Injury Act of 1986.

It should be clear that the HHS has done plenty to promote vaccine safety though.

HHS Secretary Donna Shalala reported to the Senate Committee on Health Education Labor and Pensions in 1998.
HHS Secretary Donna Shalala actually reported to the Senate Committee on Health Education Labor and Pensions in 1998.

Even if no formal reports were filed, the HHS secretary did report to and appear before Congress. Come to think of it, they even sent some reports to Congress.

The Health Resources and Services Administration (HRSA), an agency of the U.S. Department of Health and Human Services, has commissioned almost a dozen reports about vaccine safety over the years.
The Health Resources and Services Administration (HRSA), an agency of the U.S. Department of Health and Human Services, has commissioned almost a dozen reports about vaccine safety over the years.

And the Health and Medicine Division (HMD) division (previously known as the Institute of Medicine (IOM) of the National Academies of Sciences, Engineering, and Medicine has published a number of vaccine safety reviews and reports under commission of HRSA, an agency of HHS.

Where do folks think that all of those IOM vaccine safety reports and reviews come from? Were they sent to Congress?

The Assistant Secretary for Health leads development of HHS-wide public health policy recommendations, oversees 11 core public health offices — including the Office of the Surgeon General and the U.S. Public Health Service Commissioned Corps, which has approximately 6,500 uniformed health officers who serve in nearly 600 locations around the world to promote, protect and advance the health and safety of our nation and our world. He also oversees three Presidential and 11 Secretarial advisory committees.
The Assistant Secretary for Health leads development of HHS-wide public health policy recommendations, oversees 11 core public health offices and three Presidential and 11 Secretarial advisory committees. We have had a National Vaccine Plan since 1994.

And also consider that:

Most importantly, new vaccines have been approved that protect our kids against many more now vaccine-preventable diseases.

HHS Settles Lawsuit Over Vaccine Safety Reporting

But wait, did the HHS even lose the lawsuit?

Not saying I'm surprised, but even Dr. Bob has bought into the idea that this lawsuit against HHS means something big.
Not saying I’m surprised, but even Dr. Bob has bought into the idea that this lawsuit against HHS means something big.

They actually didn’t.

They did settle a lawsuit though, a lawsuit which was then dismissed.

So like the CDC whistleblower movie that didn’t include a whistleblower, anti-vaccine folks think that they have a smoking gun about vaccine safety reports, except that it is very obvious that all kinds of reports about vaccine safety have been done over the years.

Vaccines are still safe. And they are still necessary.

What to Know About the HHS Vaccine Lawsuit

Although it does seem like HHS didn’t file the required formal reports and keep to the strict letter of the National Childhood Vaccine Injury Act of 1986, there is abundant evidence that they have actually done all of the work required to make sure that our vaccines are safe.

More on the HHS Vaccine Lawsuit

Can Vaccinated Children Be Asymptomatic Carriers of Pertussis?

Why do anti-vaccine folks like to talk about baboons so much?

“Did you know that a study showed that baboons injected with whooping cough vaccine became infected with whooping cough anyway – and silently spread the disease to other baboons for 35 days?”

Anti-vaccine Meme

Is it because baboons are used in the study of vaccines?

That’s part of it, at least when they can find a study where they can cherry pick the results to suit their needs.

The Baboon Study

Like most anti-vaccine talking points, this one about baboons, has some truth to it.

An adult male baboon.
An adult male baboon. Photo by Elizabeth Miller

There was a baboon study with the pertussis vaccine and it found that previously vaccinated baboons could develop asymptomatic carriage of the pertussis bacteria after they were intentionally infected.

Here is where it is important to note that an infection is different than a disease.

The example that many people are familiar with is tuberculosis. It is common to have a TB infection without any signs or symptoms and to not feel sick. The only reason we know that they have TB is because they had a positive TB test.

Unfortunately, about 5 to 10% of these people with TB infections can eventually develop TB disease, with coughing, weight loss, night sweats, fever, and chest pain, etc.

It is kind of the same with the baboons in the study. Twenty-four hours after two previously vaccinated baboons were inoculated with pertussis bacteria in the back of their nose and trachea, an unvaccinated baboon was put in each of their cages.

The vaccinated baboons continued to have pertussis bacteria in their noses, which the researchers had put there, for up to 35 days. And they were able to eventually pass the pertussis bacteria to the unvaccinated baboons in their cages. Vaccinated baboons also became infected or colonized after they were put in a cage with an intentionally infected unvaccinated baboon.

“…animals did not cough and showed no reduction of activity, loss of appetite, or other outward signs of disease.”

Warfel et al on Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

The vaccinated baboons were infected, but they never did develop symptoms of pertussis.

What Does The Baboon Study Mean?

One thing that is for sure – the baboon study found that the pertussis vaccines work. Only unvaccinated baboons got sick with pertussis.

But does this study explain our current outbreaks of pertussis?

Are vaccinated people becoming colonized and then getting others sick?

I guess it is possible, but we are not baboons in a cage with other baboons. How would we spread a respiratory disease, even if we did become colonized with the bacteria, if we don’t have symptoms?

It may explain part of our outbreaks though.

If vaccinated people do commonly become colonized with pertussis bacteria, then they might very well test positive for pertussis even though they don’t have symptomatic pertussis disease. So when they develop a cold or bronchitis and are found to have a positive pertussis test, then couldn’t that test just indicate that they have a pertussis infection and not disease, even though something else is actually causing their symptoms?

That’s what we think happens with strep carriers, right?

That’s kind of what the baboon study found. All of the baboons tested positive, but only the unvaccinated baboons had symptomatic pertussis disease.

“Baboons vaccinated with wP vaccines exhibit a level of protection that is intermediate between convalescent animals and aP-vaccinated animals. They exhibit no outwards signs of disease and are initially colonized to the same high level as aP-vaccinated animals but clear the infection more rapidly.”

Pinto et al on Pertussis disease and transmission and host responses: insights from the baboon model of pertussis.

It is interesting to note that the baboon study also found that baboons who had received whole cell pertussis vaccines also became carriers. They just didn’t stay carriers for as long as the baboons who got the newer acellular pertussis vaccine. But since they were still carriers, if asymptomatic transmission is such a big problem, wouldn’t it have been a big problem back in the day when everyone got whole cell pertussis vaccines?

The Debate Over Asymptomatic Carriage

Most vaccines prevent the spread of disease.

Do the pertussis vaccines?

Most folks still think so.

“The baboon model pioneered by Warfel et al. is without question a game-changer, shedding light on the impact of vaccination on disease and infection. However, the view it affords is clearer with respect to immunity and pathology than with respect to transmission. We point out that the extrapolation of the possibility of transmission from vaccinated baboons in the laboratory to the probability of transmission from vaccinated humans in the population is unwarranted. More work is needed to elucidate the relative transmissibility of infections in vaccinated vs. unvaccinated hosts. The evidence adduced above suggests, however, that vaccination with aP must have a strong effect on transmission as well as disease.”

Matthieu Domenech de Cellès et al on Epidemiological evidence for herd immunity induced by acellular pertussis vaccines

Even the author of the baboon study has said that “We agree that these data should not be directly extrapolated to pertussis transmission in humans. Although baboons are >96% genetically similar to humans, there are likely differences in how the species respond to vaccination and infection. We also agree that aP-vaccinated infected people are likely less efficient at transmitting pertussis compared with unvaccinated infected people, although it is not clear to what extent.”

Others think that asymptomatic carriage of pertussis might behind a lot of our recent outbreaks. Or at least what helps them grow so large.

Still, it is important to remember that unvaccinated folks do play a role in these outbreaks too. In a pertussis outbreak at a Florida preschool, in which most kids were vaccinated, the outbreak was started by a vaccine-exempt toddler.

And we have seen this in many other areas and it has been confirmed by many studies. Whatever else is contributing to pertussis outbreaks, like waning immunity, they are also associated with vaccine refusal.

“Counties with higher exemption rates had higher rates of reported pertussis among exempted and vaccinated children when compared with the low-exemption counties.”

Imdad et al. on Religious exemptions for immunization and risk of pertussis in New York State, 2000-2011.

But what if the DTaP and Tdap vaccines do cause folks to be asymptomatic carriers?

Even if that is true, understand that these vaccines don’t actually infect you, making you a carrier. They just might not prevent you from becoming a carrier if you are exposed to someone else with pertussis. While that might be a good reason to develop a new and better pertussis vaccine, it certainly isn’t a reason to skip or delay your child’s vaccines now.

Remember that even with our current outbreaks, rates of pertussis were much higher in the pre-vaccine era.

What to Know About Vaccines and Asymptomatic Carriers of Pertussis

The role of asymptomatic carriers and pertussis is controversial, but it certainly isn’t a reason to skip or delay your child’s vaccines.

More on the Vaccines and Asymptomatic Carriers of Pertussis