Tag: rubella

What’s the Difference Between the MMR and MMR-II Vaccines?

As most folks know, the original MMR vaccine, which combined the separate measles, mumps, and rubella shots, was licensed way back in 1971.

It included the original rubella vaccine, which was made with a duck embryo derivative of HPV-77 that was attenuated by passing it 77 times in monkey kidney cells.

Wait, what?

HPV?

Before the new conspiracy theories start, no, not that HPV.

It stands for High Passage Virus.

What’s the Difference Between the MMR and MMR-II Vaccines?

And while the vaccine worked, it didn’t work as well and caused more side effects than a RA27/3 rubella vaccine that was already approved in Europe

“Over the next decade, accumulating evidence led to changes in the United States. First, the duck embryo and dog kidney vaccine strains caused significant joint reactions [24–27]. Second, reinfection on exposure to wild rubella virus was demonstrated frequently with all strains except the RA 27/3 vaccine [28–30]. Third, the good safety record of the RA 27/3 vaccine in Europe, plus the majority opinion of scientists, led the US Food and Drug Administration to license RA 27/3. Important pressure for this decision came from Dorothy Horstmann at Yale, who was convinced by her comparative studies of rubella vaccines [31], and by Maurice Hilleman at Merck, who sought a better rubella strain for measles-mumps-rubella (MMR) vaccine.”

Stanley Plotkin on The History of Rubella and Rubella Vaccination Leading to Elimination

So that’s it, they just changed out the rubella component for one that was safer and worked better.

The new and improved MMR-II vaccine was approved by the FDA in 1978.
The new and improved MMR-II vaccine was approved by the FDA in 1978.

And of course, they did the appropriate clinical trials and got FDA approval for this updated vaccine.

The control group didn't get a vaccine during the study.
The control group didn’t get a vaccine during the study.

But did they compare the vaccines against a saline placebo?

“The inclusion of a seropositive control group allowed the rates of reaction to be viewed against the background symptoms unrelated to vaccine administration.”

Polk et al on A controlled comparison of joint reactions among women receiving one of two rubella vaccines.

They actually went a little further, in a double-blind, controlled cohort study comparing it to folks who didn’t receive any vaccine at the time of the study!

Why so many joint issues with the vaccine?

The studies were in adults, who seemed to have more side effects with the vaccine. Still, the side effects, including arthritis, were transient.

What about the idea that it was studied long enough before being approved?

Both the rubella component and the MMR-II vaccine were studied both before and after being approved. In fact, the MMR-II vaccine is probably the most studied vaccine in history!

Believe it or not, they include placebo-controlled trials.

A double-blind, placebo-controlled, cross-over MMR study in twins!

What was the placebo in the Finland twin trial?

“The injections consisted of 0.5 ml of vaccine 2-5 or placebo (the same product including neomycin and phenol-red indicator but without the viral antigens) and were administered subcutaneously by the nurse to the left deltoid or gluteal region.”

Peltola et al on Frequency of true adverse reactions to measles-mumps-rubella vaccine. A double-blind placebo-controlled trial in twins.

If that doesn’t sound like a placebo to you, keep in mind that the MMR vaccine doesn’t contain that many ingredients. Remember, MMR doesn’t contain aluminum or thimerosal. And if the placebo didn’t contain the antigens, then it likely didn’t contain all of the things that went into getting those antigens in the vaccine, such as cell cultures and albumin, etc.

Still, some folks aren’t going to be satisfied unless there is a study with a saline placebo.

“The four other vaccines were commercial products of Merck Sharp & Dohme. The placebo consisted of vaccine diluent.”

Lerman et al on Clinical and Serologic Evaluation of Measles, Mumps, and Rubella (HPV-77: DE-5 and RA 27/3) Virus Vaccines, Singly and in Combination

The vaccine diluent?

What’s that?

It depends on the vaccine, but for MMR-II it’s sterile water.

“Placebo DTP consisted of sterile saline which was dispensed into sterile Tubex syringes.”

Deforest et al on Simultaneous Administration of Measles-Mumps-Rubella Vaccine With Booster Doses of Diphtheria-Tetanus-Pertussis and Poliovirus Vaccines

The MMR vaccine was even tested in placebo controlled trials with other vaccines!

And like other vaccines, the MMR vaccine has been found to be safe, with few risks, and is definitely necessary.

More on the the Difference Between the MMR and MMR-II Vaccines

Japan’s Rubella Outbreak Should Be a Warning About What Could Happen Here

Do you remember when we used to have rubella outbreaks in the United States?

There is a level 2 travel alert for Japan because of outbreaks of rubella.

Yeah, me neither, but in the rubella epidemics of the 1960s, rubella caused 2,100 neonatal deaths and 20,000 infants to be born with congenital rubella syndrome.

Japan’s Rubella Outbreak

Thanks to the rubella vaccine, the ‘R’ in the MMR, we rarely hear about rubella anymore.

Tragically, like measles and other vaccine-preventable diseases, rubella is coming back.

RubellaCongenital Rubella Syndrome
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There are still relatively few cases, but most of us would like to keep it that way.

The US had a big spike in rubella cases in the last 1980s.

We remember that with the return of measles in the late 1980s, rubella came back right along with it, causing 13 deaths and 77 cases of congenital rubella syndrome!

And that’s what is happening in many countries right now.

In Japan, for example, in addition to a rise in measles cases this year, they are seeing big outbreaks of rubella, with weekly totals exceeding 100 cases! These are numbers that are close to what they saw during outbreaks in 2013, a year that ended with 14,344 cases of rubella and 32 cases of congenital rubella syndrome.

Japan is on track to have a big rubella year.
Japan is on track to have a big rubella year.

And they are already reporting at least one case of congenital rubella syndrome, a 4 week old, which is not surprising, considering that they had nearly 3,000 cases of rubella last year.

A newspaper article in 1965 warned about the perils of rubella and congenital rubella syndrome.
A newspaper article in 1965 warned about the perils of rubella and congenital rubella syndrome.

Is that what we want to happen here too? Are folks looking forward to having to worry about babies being born with congenital rubella syndrome, a vaccine-preventable disease?

A vaccine-preventable disease that was declared eliminated in the United States in 2004.

More on Japan’s Rubella Outbreak

About those Stanley Plotkin Videos…

Stanley Plotkin is typically described as “a prominent figure in the history of vaccinology, whose work on vaccine development has led to a significant reduction in morbidity and mortality from infectious diseases in the second part of 20th century. “

Why?

For one thing, he developed the rubella vaccine that we still use today.

He also worked on vaccines against CMV, polio, chicken pox, rabies, and rotavirus.

What Did Stanley Plotkin Say While He Was Under Oath?

That’s not why anti-vaccine folks are talking about him these days, or maybe it is…

Mostly, they are misinterpreting comments he made during a videotaped deposition.

“Lori Matheson is fighting her ex-husband, Michael Schmitt, for the right to decide if their two-year-old daughter should be vaccinated.”

Michigan anti-vaccination case to goes to court

A videotaped deposition in a case involving parents who disagreed about vaccinating their daughter…

Even though it isn't his exact quote and anti-vaccine folks don't give you the full context of what he was talking about, it is clear that Dr. Plotkin simply meant that you can't prove a negative.
Even though it isn’t his exact quote and anti-vaccine folks don’t give you the full context of what he was talking about, it is clear that Dr. Plotkin simply meant that you can’t prove a negative.

What do anti-vaccine folks think he said?

“I would say it is logically true that you cannot say, you cannot point to proof that it doesn’t cause autism. ”

Stanley Plotkin, M.D.

No, he isn’t saying that vaccines are associated with autism.

“I could not say that as a, as a scientist or a logician. But I can say as a physician that, no, they do not cause autism, because as a physician, I have to take the whole body of scientific information into consideration when I make a recommendation for a child.”

Stanley Plotkin, M.D.

All he is saying is that you can’t definitively prove a negative.

One of the different things in communicating the fact that there is no link is that science and English are not really the same language. So when a scientist says, “We have no evidence that there’s a link between vaccines and autism,” what they’re really saying is, “We are as positive as someone can humanly be that there’s no link.”
Seth Mnookin explain it well – One of the different things in communicating the fact that there is no link is that science and English are not really the same language. So when a scientist says, “We have no evidence that there’s a link between vaccines and autism,” what they’re really saying is, “We are as positive as someone can humanly be that there’s no link.”

For example, just because I have never seen a black swan, I can’t use that as proof that black swans don’t exist somewhere. After all, I haven’t been everywhere.

“…scientists can be at a real disadvantage in this debate because they, by their nature, are careful in how they present their conclusions.”

Vaccines: Last Week Tonight with John Oliver (HBO)

What else do anti-vaccine folks have a problem with?

Remember the rubella vaccine he developed?

“After a detour to obtain credentials as a pediatrician, I returned to Wistarto work on rubella. Those years were fraught with advances and reverses, controversy and eventually vindication. The pandemic of CRS babies in 1964-65 was an important stimulus to research on the vaccine. “

Stanley Plotkin’s On the Occasion of the Presentation Of The 2002 Albert B. Sabin Gold Medal

During the rubella epidemic of 1964-65, there were 12.5 million rubella virus infections, which “resulted in 11,250 therapeutic or spontaneous abortions, 2,100 neonatal deaths, and 20,000 infants born with congenital rubella syndrome.”

And that’s just in the United States.

The controversy?

“There were only two fetuses involved in making vaccines. When fetal strains of, fibroblast strains were first developed, I was involved in that work trying to characterize those cells; but they were not used to make vaccines.”

Stanley Plotkin, M.D.

It is well known (this isn’t some shocking truth as some are trying to push) that some vaccines are made with fetal embryo fibroblast cells (the WI-38 and MRC-5 cells) from cell lines that are derived (they can replicate infinitely) from two electively terminated pregnancies (abortions) in the 1960s.

Those two fetuses weren’t the only two fetuses ever used in research though, they were just the only ones used to actually make vaccines.

“Human diploid cell strains (HDCSs) are batches of cells that are currently used for different purposes, including culturing viruses for the manufacturing of vaccines”

A brief history of human diploid cell strains.

They had to get to the point where they knew how to make vaccines in human cell lines though and that’s what he is talking about in the deposition.

“Q. In any event, so we have 76 in this study. Would you approximate it’s been a few hundred fetuses?


A. Oh, no, I don’t think it was that many. Probably not many more than in this paper. And I should stipulate that we had nothing to do with the cause of the abortion.”

It took some experimentation to find the right kind of cells and the right methods, but ultimately, they found that fetal embryo fibroblast cells were the best to use to grow many viruses.

Copies of those same cells are still used today.

What about the other “issues” brought up in the deposition?

Did he experiment on orphans, people who were mentally handicapped, or those who lived in third world countries?

“I don’t remember specifically, but it’s possible. And, again, I repeat that in the 1960s, that was more or less common practice. I’ve since changed my mind. But those were, that was a long time ago.”

Stanley Plotkin, M.D.

Those were different times, but Dr. Plotkin’s vaccine studies weren’t unethical and weren’t like what was done at Willowbrook, in which children were purposely exposed to hepatitis, with the justification that most of them ended up getting it anyway.

Surprisingly, in the early 1970s, there was still some debate about the ethics of doing experiments on children, and as you can see, using ableist language to describe children with a disability.
Surprisingly, in the early 1970s, there was still some debate about the ethics of doing experiments on children, and as you can see, using ableist language to describe children with a disability.

And from those times, experts developed the rules for how things are now done.

Ironically, anti-vaccine folks are pushing this stuff about Plotkin, but don’t understand why leaving kids completely unvaccinated and unprotected in a study is unethical.

“One is morally free to use the vaccine regardless of its historical association with abortion. The reason is that the risk to public health, if one chooses not to vaccinate, outweighs the legitimate concern about the origins of the vaccine. This is especially important for parents, who have a moral obligation to protect the life and health of their children and those around them.”

National Catholic Bioethics Center FAQ on the Use of Vaccines

Or why it’s immoral to push anti-vaccine propaganda or put others at risk to get a vaccine-preventable disease.

“Results indicate that the total number of cases of poliomyelitis, measles, mumps, rubella, varicella, adenovirus, rabies and hepatitis A averted or treated with WI-38 related vaccines was 198 million in the U.S. and 4.5 billion globally (720 million in Africa; 387 million in Latin America and the Caribbean; 2.7 billion in Asia; and 455 million in Europe). The total number of deaths averted from these same diseases was approximately 450,000 in the U.S., and 10.3 million globally (1.6 million in Africa; 886 thousand in Latin America and the Caribbean; 6.2 million in Asia; and 1.0 million in Europe).”

Olshansky et al on The Role of the WI-38 Cell Strain in Saving Lives and Reducing Morbidity

Dr. Plotkin’s work has helped save millions of lives.

“His achievements in vaccinology are on a scale that truly can be measured in lives saved and lives restored.”

On the Occasion of the Presentation Of The 2002 Albert B. Sabin Gold Medal

And that’s why anti-vaccine folks are attacking him.

More on Stanley Plotkin

How Often Should You Do Vaccine Titer Testing?

We sometimes hear about folks doing vaccine titer testing.

A vaccine titer is a blood test that can determine whether or not you are immune to a disease after you get a vaccine.

While that sounds good, after all, why not check and be sure, it has downsides. Chief among them is that the results aren’t always accurate.

That’s right. You can sometimes have a negative titer test, but still be immune because of memory B cells and the anamnestic response.

How Often Should You Do Vaccine Titer Testing?

So how often should you do vaccine titer testing?

It depends, but most folks might never have it done!

Why not?

Vaccines work very well, so you would typically not need to routinely check and confirm that you are immune after being vaccinated. And, this is also important, the vaccine titer tests don’t always work that well, titer testing isn’t available for all vaccines (you can’t do titer testing for Hib and pertussis), and the testing can be expensive.

So we usually just do the testing (a quantitative titer) for folks that are in high risk situations, including:

  • pregnancy – rubella titer only (HBsAg is also done, but that’s not a vaccine titer test, but rather to see if you are chronically infected with hepatitis B)
  • healthcare workers – anti-HBs (antibody to the hepatitis B surface antigen to confirm immunity after being vaccinated)
  • students in nursing school and medical school, etc. – anti-HBs
  • children and adults exposed in an outbreakmeasles, chicken pox, mumps, etc., but only if we are unsure if they were previously vaccinated and protected
  • after a needlestick injury, etc. – to confirm immunity to hepatitis B
  • babies born to a mother with hepatitis B – to confirm that their hepatitis B vaccine worked

Vaccine titer testing might also be done for:

  • internationally adopted children – to confirm that they are immune if we unsure about all of the vaccines the child got in other countries
  • children and adults with lost vaccine records – to confirm that they are immune, since we are unsure about all of the vaccines they got
  • evaluation of children and adults with immune system problems – to help identify what immune system problems they might have – typically involves checking pneumococcal titers, giving Prevnar, and then checking pneumococcal titers again
  • people at continuous or frequent risk for rabies – rabies titer testing every 6 months to 2 years
  • patients with inflammatory bowel disease, before starting immunosuppressive therapy – hepatitis A and hepatitis B titers, as they might be at increased risk for hepatitis

While checking titers is easy, it is sometimes harder to know what to do with the results you get.

Of all of these different titers, only one tells you that you are immune due to vaccination.
Of all of these different titers, only one tells you that you are immune due to vaccination.

It is especially important to know that:

  • most people don’t need to have their titers checked routinely if they are not in one of the high-risk groups noted above
  • it isn’t practical to get titers tested as a method of potentially skipping one or more doses of your child’s vaccines, after all, if the titer is negative, then you are still going to have to get vaccinated
  • a healthcare provider with a negative measles titer after two doses of the MMR vaccine does not need another dose of vaccine
  • a healthcare provider who has anti-HBs <10 mIU/mL (negative titer) after three doses of the hepatitis B vaccine should get another dose of vaccine and repeat testing in 1 to 2 months – if still <10 mIU/mL, they should then get two more doses of hepatitis B vaccine (for a total of 6 doses) and repeat testing. If still negative, these documented nonresponders will need HBIG as post-exposure prophylaxis for any future hepatitis B exposures, but no further doses of hepatitis B vaccine.
  • vaccinated women of childbearing age who have received one or two doses of rubella-containing vaccine and have rubella serum IgG levels that is not clearly positive should be administered one additional dose of MMR vaccine, with a maximum of three doses, and should not be tested again
  • postvaccination titer testing is not recommended after the chicken pox vaccine
  • in addition to not being able to test titers for pertussis and Hib immunity, it is becoming difficult to test poliovirus type 2 titers, as the test uses a live virus that isn’t routinely available anymore (type 2 polio has been eradicated)

Still think you need vaccine titer testing?

More on Vaccine Titer Testing

Did Your Rubella Titer Come Back Negative?

Two doses of the MMR vaccines give the great majority of people long lasting immunity to measles, mumps, and rubella. Well, measles and rubella anyway. Unfortunately, the mumps part of the vaccine has some issues with waning immunity.

Do you need to get your titers checked to make sure you are immune?

Usually not. Simply being fully vaccinated with the MMR vaccine is  good enough evidence that you are immune in most, but not all circumstances

Getting or being pregnant is one of those circumstances in which it is important to know for sure. It is really one of the only circumstances. Health care works are no longer routinely tested after they are vaccinated, as proof of vaccination is good evidence of immunity for the MMR vaccine.

The American College of Obstetricians and Gynecologists recommends that all pregnant women be screened for rubella.
The American College of Obstetricians and Gynecologists recommends that all pregnant women be screened for rubella.

That screening test is a rubella serum IgG levels or as it is more commonly known as, a titer level.

Non-Immune Rubella Titers

Why check it?

Because of the devastating effects of congenital rubella syndrome, all pregnant women are screened early in their pregnancy.

Babies with congenital rubella syndrome may have cataracts and many other birth defects.
Babies with congenital rubella syndrome may have cataracts and many other birth defects. Photo courtesy PHIL

Having a positive rubella titer, typically defined as a IgG level of ≥10 IU/mL, means that you are immune and protected.

But what if your rubella titer is negative? What if your level is <10 IU/mL?

We know that levels of vaccine-induced rubella antibodies can decrease over time, but unlike mumps and pertussis, this does not seem lead to waning immunity with rubella.

Still, the current recommendations from the Advisory Committee on Immunization Practices (ACIP) are that:

  1. Vaccinated women of childbearing age who have received one or two doses of rubella-containing vaccine and have a rubella serum IgG levels that is not clearly positive should be administered one additional dose of MMR vaccine, with a maximum of three doses.
  2. After this additional dose, they do not need to be retested for serologic evidence of rubella immunity.
  3. Since MMR is a live vaccine, the additional dose should not be given during pregnancy or within a month of when you plan to get pregnant. You can get it while you are breastfeeding though.

How much should you be concerned about a negative rubella titer?

Although congenital rubella syndrome is not uncommon in other countries that don’t routinely vaccinate for rubella, there has not been a case of congenital rubella syndrome in the United States since – 2017.

That’s right, we have actually had two cases of congenital rubella syndrome in the US this year! In past years, these cases have all been linked to pregnant women becoming infected outside the US though, as there are thought to be very few rubella infections locally.

And two cases is a far cry from when rubella caused 2,100 neonatal deaths and 20,000 infants to be born with congenital rubella syndrome during an epidemic in the mid-1960s, before the first rubella vaccine was available.

That’s because vaccines work.

Wait, then why do some of these folks have a negative titer when they are tested?

While the easy answer is to say that they aren’t immune, it is more complicated than that. For example, some of the negative results could be false negatives (a negative test result that really should be positive). Others could possibly have low antibody levels, but they are still immune. Still, since one dose of a rubella containing vaccine is only about 97% effective, some of them could be non-responders.

Will a second or third booster dose of vaccine help increase your antibody levels? Yes, but in this situation, they will likely just rise temporarily. The second or third dose of MMR isn’t technically a booster dose, but rather a dose for those who didn’t respond to the previous doses, particularly for the measles component.

Avoiding Rubella

With a negative rubella titer, especially if you have not been previously vaccinated with one or more rubella-containing vaccines, you should likely try to avoid anyone who might have rubella.

There aren’t a lot of guidelines on how to avoid rubella though.

If you want to avoid rubella, avoid folks who aren't vaccinated against rubella.
If you want to avoid rubella, avoid folks who aren’t vaccinated against rubella. Photo courtesy of PHIL

That probably surprises you, especially with all of the information out there on how to avoid the flu, measles, mumps, and other infectious diseases, but it shouldn’t.

Symptoms of a rubella infection can include swollen lymph glands, low grade fever, a mild case of pink eye, and a red rash that can be hard to see, unless the person is overheated, like after a bath. Most importantly, people with rubella can be contagious for another few weeks, even as all of the symptoms have gone away. Also, like most viral infections, they were contagious for a few days even before they developed their first symptoms. And, believe it or not, some people with rubella might have no symptoms at all and still be contagious.

So how do you avoid someone who doesn’t even know that they are sick and are still contagious?

You basically want to try and away from anyone who might become sick and contagious…

While that sounds impossible, avoiding kids and adults who are intentionally unvaccinated, especially those who are intentionally unvaccinated and have recently traveled out of the country, can be a good start.

And like someone with a medical exemptions to getting vaccinated, if you have been vaccinated and lost your immunity to rubella, feel free to hide in the herd. This is one of the reasons everyone gets vaccinated!

What to Know About Rubella Titers

Get vaccinated and follow the latest guidelines if you are pregnant and your rubella titer is negative.

More on Rubella Titers and Immunity