Tag: diluents

A Toddler Has Died After Being Vaccinated in Cuba

No one expects to hear stories of kids dying after being vaccinated. Fortunately, these types of tragedies are very, very rare.

Still, even one is too many when it might have been prevented. After all, that’s why we vaccinate our kids in the first place. To protect them from life-threatening vaccine preventable diseases.

A Toddler Has Died After Being Vaccinated in Cuba

The Ministry of Health in Cuba released a statement a few days after her death:

“Between October 7 and 8 of this year, three one-year-old children were diagnosed with an adverse event associated with vaccination with PRS, which protects against Mumps, Rubella and Measles, this is applied according to official scheme to children one and six years old.

All had been vaccinated on October 7 at the “Betancourt Neninger” Polyclinic in the municipality of Habana del Este, province of Havana, and immediately after symptoms appeared, they were admitted and received medical attention by professionals of high scientific level in the Pediatric Hospitals ” Borrás Marfán ”and Centro Habana.

Through the active research carried out on all children vaccinated in that Health Area, two more children were detected with symptoms, which motivated their admission.

Painfully on October 9 at night, the one-year-old girl Paloma Domínguez Caballero dies, admitted to the “Borrás Marfán” Hospital as a result of complications. The remaining four children remain admitted: one with intensive attention, which is stable and the others evolve favorably.

The system of active surveillance of the events associated with vaccination carried out in the country has not identified any other children with symptoms.

The PRS vaccine has been used for years in Cuba, imported from India, is endorsed by the World Health Organization and certified by the Center for State Control of Medicines, Equipment and Medical Devices (CECMED).

A Commission of the Ministry of Public Health investigates the causes that caused this unfortunate event.”

Official Note from the Ministry of Public Health on adverse event associated with vaccination with PRS (computer translation)

So what happened?

Tragically, either because of errors or contamination, vaccines can rarely cause people to get sick, either if:

  • a reconstituted vaccine was used much after six hours – live vaccines can quickly become contaminated if they are kept and used for too long a time
  • vaccine diluents were mixed up – some vaccines need to be mixed before use and vaccination tragedies can occur when a dangerous medication is used instead of a vaccine’s standard diluent
  • vaccines were improperly handled – breaking the cold chain – or allowed to expire
  • a vaccine is given to someone with a true medical contraindication

In Samoa, the recent tragedy in which two toddlers died, we know that the vaccine diluent was mixed up with a powerful anesthetic.

It doesn’t sound like a diluent mixup happened in Cuba though.

“The mother told the news portal CiberCuba that the daughter’s arm began to swell the same day she was vaccinated. Then the vomits arrived. Less than 24 hours later I was already in intensive care, from where I did not come out alive again.”

Vacuna en mal estado suministrada en Cuba podría haber dejado 25 niños en estado de gravedad

With reports that the vaccines were possibly expired and the child getting sick later in the day, with swelling in her arm, it is more likely that there was some contamination, maybe in a vaccine vial itself.

A 10 dose vial of MMR from the Serum Institute of India Pvt. Ltd.
A 10 dose vial of MMR from the Serum Institute of India Pvt. Ltd.

Which vaccine?

The report says that it was the PRS vaccine – Parotiditis, Rubéola, and Sarampion – or MMR, which is usually available in 5 or 10 multi-dose vials when one dose vials aren’t available.

It was imported from India, which makes many of the vaccines that are used throughout the world, but any contamination likely would have occurred well after it was manufactured and shipped to Cuba.

In all of these cases, there is typically nothing inherently wrong with the vaccine itself.

“Cuba, a relatively poor and small country (population 11.2 million), has managed to bring about remarkable achievements in health in the past 30 years despite difficult fiscal restraints and limited resources.”

MacDonald et al on Infectious Disease Management: Lessons from Cuba

Interestingly, Cuba actually makes most of their other immunizations.

So why would they be using expired vaccines?

Was it a mistake?

Did someone use a leftover vial that had become contaminated with bacteria? Were the vaccines not refrigerated properly? Is it an isolated issue or part of a bigger breakdown in their healthcare system?

With four other sick kids, the use of a contaminated leftover vial that was part of an original 10 dose vial becomes one possible scenario.

We might get some answers if the vaccine vials had not been thrown away after they were used, and are still available for testing.

In Chapias, Mexico, after two infants died in 2015 after getting multiple vaccines, a vial was found to be contaminated with the Staphylococcus hominis bacteria.

A few years later, in 2017, 15 children died in South Sudan when unrefrigerated vaccine was mixed with a syringe that was reused over and over for four days and given to kids by untrained workers.

Again, these are very rare and isolated cases. Remember that billions of doses of vaccines are given each year without problems, saving millions of lives.

Hopefully we will soon learn what really happened to these children in Cuba, especially as that will hopefully help to make sure it doesn’t happen again.

Most importantly, don’t let these very rare tragedies scare you away from vaccinating and protecting your kids.

“The Cuban government has confirmed that five children suffered severe reactions and one of them — a 1-year-old girl — died after receiving a vaccine. The serum came from the same company in India that produced vaccines linked to the deaths of three other children following inoculations administered in Cuba in 2002.”

Child dies in Cuba after receiving vaccine made in India. It’s not the first time

We should remember what happened following the tragedy in Samoa. All vaccinations were unnecessarily suspended in the country for a time and MMR vaccinations were suspended for nine months!

What came next?

A measles epidemic that has already seen the death of one toddler!

The death of the girl in Cuba is a terrible tragedy, but folks shouldn’t make it any worse. There is almost certainly nothing wrong with the vaccines from India or any other vaccines in Cuba or anywhere else.

Vaccines are safe, with few risks.

Hopefully we can continue to work to eliminate even the rare risk of these kinds of awful tragedies too.

And no, this is not the MMR vaccine that is used in the United States in case anyone is wondering.

More on Vaccination Tragedies

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

Vaccination Tragedies are Rare

Vaccines work to prevent at least 2 to 3 million deaths each year worldwide.

Tragically, either because of errors or contamination, vaccines can sometimes actually cause people to get sick.

This can happen when health workers:

  • use a reconstituted vaccine after six hours – live vaccines can quickly become contaminated if they are kept and used for too long a time
  • mixup diluents – in addition to using the wrong diluent vaccination tragedies can occur when a dangerous medication is used instead of a vaccine’s standard diluent
  • improperly handle vaccines – breaking the cold chain
  • a vaccine is given to someone with a true medical contraindication

Fortunately, these situations are rare.

History of Vaccination Tragedies

With billions of doses of vaccines being given each year, it is likely not surprising that we see some problems. But when many of those vaccines are being given to kids, even one mishap, especially if it leads to life-threatening complications, is too many.

That’s why many safe guards have been put in place in the manufacturer and distribution of modern vaccines, so that we don’t see these types of vaccine tragedies:

  • the Cutter Incident, when, in 1955, at least 56 people developed polio and 5 children died after being vaccinated with inactivated polio vaccine that was poorly manufactured by Cutter Laboratories and still contained live polio virus
  • hepatitis-contaminated yellow fever vaccines – some lots of yellow fever vaccines used in the military in 1942 were unintentionally contaminated with the hepatitis B virus
  • the Lubeck Disaster – 75 children died and others got tuberculosis in 1929 Germany after there was a mixup between the BCG vaccine and the strain of Mycobacterium tuberculosis that causes tuberculosis. The BCG vaccine was supposed to be made with a weakened strain of Mycobacterium bovis bacteria instead.
  • the Bundaberg incident – 12 children died in Australia in 1928 after being given contaminated diphtheria vaccine from a multidose vial without preservative
  • tetanus contaminated smallpox vaccine in the 1890s and early 20th century

Although vaccines are much safer now, some rare incidents still occur.

Fifteen infants died and 75 children got sick in Syria in 2014 after they received a neuromuscular blocking agent, atracurium, instead of the measles vaccine they were supposed to get. How? The measles vaccine that was being used is mixed with a diluent, but instead of using the proper diluent, the health worker unintentionally used a bottle of atracurium instead.

In 2015, at least two kids died and 29 got sick in Chiapas, Mexico, among 52 children who were vaccinated. The children were reportedly given a BCG vaccine, the rotavirus vaccine, and/or a hepatitis B vaccine that day. However, the only vaccine that all of the sick children received in common was the hepatitis B vaccine. Since 130,000 doses from the same batch of vaccines had been given in the area, it was not thought to be a manufacturing problem or widespread issue. It was instead bacterial contamination of hepatitis B vaccine vials at that one clinic.

Fifteen children died in 2017 in a village in South Sudan after a poorly trained team that wasn’t adhering to WHO immunization safety standards used the same syringe to reconstitute measles vaccines over a four day period. They also didn’t keep the vaccine vials refrigerated.

“A single reconstitution syringe was used for multiple vaccine vials for the entire four days of the campaign instead of being discarded after single use. The reuse of the reconstitution syringe causes it to become contaminated which in turn contaminates the measles vaccine vials and infects the vaccinated children.”

Statement regarding findings of joint investigation of 15 deaths of children in Nachodokopele village, Kapoeta East County in South Sudan

As you can imagine, the conditions that led to these tragedies aren’t present when most kids get vaccinated.

Even in developing countries, most children get vaccinated by people adhering to WHO immunization safety standards. Why did they happened then? Both Syria and South Sudan have been rocked by war for years, leading to a breakdown in the ability to provide routine health care, even as basic as getting kids vaccinated. And Comunidad La Pimienta, Simojovel, Chiapas is a very poor part of southern Mexico.

These kinds of tragedies aren’t going to happen at your pediatrician’s office, as they don’t even have drugs like atracurium.

What Happened in Samoa?

In Samoa, four years after the deaths of the children in Syria, two children died within minutes of being vaccinated on the same day in the same hospital on the island of Savai’i.

Two toddlers died after being vaccinated at Safotu Hospital in Samoa.
Two toddlers died after being vaccinated at Safotu Hospital in Samoa.

Not surprisingly, as health officials investigate the cause, use of the MMR vaccine was suspended in Samoa.

So what happened?

On 4 June 2019, both nurses pleaded guilty to negligence causing manslaughter. On 2 August, both nurses were sentenced to five years in prison. During the sentencing hearing, it was confirmed that one of the nurses mixed the MMR vaccine powder with expired muscle relaxant anaesthetic instead of water for injection supplied in a vial with the vaccine. Eight Samoan speaking New Zealand nurses visited Samoa in June to provide training for vaccinating nurses at district hospitals.

Infant deaths in Samoa a tragic outcome from error preparing MMR vaccine

As suspected, since it happened so quickly, it ended up being a mix-up with the diluent, as happened in Syria. A five dose vial of MMR is used in Samoa, which means that unlike premixed vaccines, it does have to be mixed with a diluent.

Unfortunately, we are now hearing of a case in Cuba.

The Ministry of Health in Cuba released a statement a few days after her death:

“Between October 7 and 8 of this year, three one-year-old children were diagnosed with an adverse event associated with vaccination with PRS, which protects against Mumps, Rubella and Measles, this is applied according to official scheme to children one and six years old.

All had been vaccinated on October 7 at the “Betancourt Neninger” Polyclinic in the municipality of Habana del Este, province of Havana, and immediately after symptoms appeared, they were admitted and received medical attention by professionals of high scientific level in the Pediatric Hospitals ” Borrás Marfán ”and Centro Habana.

Through the active research carried out on all children vaccinated in that Health Area, two more children were detected with symptoms, which motivated their admission.

Painfully on October 9 at night, the one-year-old girl Paloma Domínguez Caballero dies, admitted to the “Borrás Marfán” Hospital as a result of complications. The remaining four children remain admitted: one with intensive attention, which is stable and the others evolve favorably.

The system of active surveillance of the events associated with vaccination carried out in the country has not identified any other children with symptoms.

The PRS vaccine has been used for years in Cuba, imported from India, is endorsed by the World Health Organization and certified by the Center for State Control of Medicines, Equipment and Medical Devices (CECMED).

A Commission of the Ministry of Public Health investigates the causes that caused this unfortunate event.”

Official Note from the Ministry of Public Health on adverse event associated with vaccination with PRS (computer translation)

What happened?

Unlike the case in Samoa and Syria, this one sounds like contamination.

It is known that vaccine vials can be contaminated with Staphylococcus bacteria if they are mishandled. Although Staphylococcus bacteria can directly cause infections, they can also release a toxin that can cause toxic shock syndrome (TSS).

There have been reports of TSS following vaccination in the past, usually with vaccines that don’t use preservatives, with symptoms developing over four to 24 hours.

Fortunately, these kinds of tragedies are very rar. Remember that billions of doses of vaccines are given each year without problems, saving millions of lives.

That some folks would use these rare tragedies to scare parents from vaccinating and protecting their kids is shameful. But that’s the modern anti-vaccine movement

What to Know About Vaccination Tragedies

Kids shouldn’t get sick or die after getting vaccinated. Fortunately, they rarely do, except in extreme circumstances that can make it more likely for errors to occur.

More on Vaccination Tragedies

When a Vaccine Doesn’t Count and Needs to Be Repeated

Of course, anti-vaccine folks are wrong when they say that vaccines don’t work.

Vaccines work and they work well to protect us from many different vaccine preventable diseases.

At least they do when you get the right vaccine at the right time and it is given properly. If an error is made, sometimes a vaccine dose needs to be repeated.

When a Vaccine Doesn’t Count and Needs to Be Repeated

While it would be unfortunate to have to repeat a vaccine dose, in most cases, if you didn’t, it would leave the child without full protection.

Why might a vaccine dose not count?

The Menomune vaccine has been discontinued, but this label is a good example of things to check before giving a vaccine.
The Menomune vaccine has been discontinued, but this label is a good example of things to check before giving a vaccine.

Although it doesn’t happen often, it is possible that:

  • the wrong vaccine was given
  • the vaccine was given too early, either before the next dose was due or when the child was too young. Although there is some leeway for when most vaccines can be given, there are still some specific rules to follow, especially the minimum time between doses, the earliest age you can get a dose, and the age requirement for booster doses. (sticking to the standard immunization schedule can help avoid these types of errors)
  • the vaccine was mixed improperly (many vaccines are now premixed, making this error less likely to occur)
  • part of the vaccine leaked out when it was being injected, which can happen when kids move, if they aren’t being held well as the shot is being given (rotavirus doses aren’t repeated if a child spits up though)
  • the vaccine had expired or had not been stored properly
  • two live vaccines (except for the typhoid vaccine) were given on separate days, but less than 28 days apart (again, sticking to the standard immunization schedule can help avoid this types of error)
  • the vaccine was given by the wrong route, although depending on the vaccine, this dose might still be valid (most vaccines, except hepatitis B and rabies)

Still, instead of a vaccine dose not counting, the much more common reason for a vaccine dose to be repeated is for folks to lose their vaccine records.

Do You Really Have to Repeat That Vaccine Dose?

Are you worried now that your kids might get a vaccine dose that has to be repeated?

Don’t be. It doesn’t happen very often.

It helps that we don’t actually have a one-size-fits-all immunization schedule and

  • there is a range of recommended ages for most vaccines
  • there is a range of recommended ages for catch-up immunization, which is basically an accelerated immunization schedule, which is why infants can typically start getting their vaccines as early as age 6 weeks and get the first few sets as early as 4 weeks apart

Also, you typically have a grace period, during which early vaccine doses will still count.

“…administering a dose a few days earlier than the minimum interval or age is unlikely to have a substantially negative effect on the immune response to that dose. Known as the “grace period”, vaccine doses administered ≤4 days before the minimum interval or age are considered valid…”

AICP on Timing and Spacing of Immunobiologics

The grace period doesn’t count for the rabies vaccine and while it is an ACIP guideline, it might be superseded by local or state mandates. The grace period also can’t be used to shorten the interval between two live vaccines, which must be at least 28 days.

One last way to get away without repeating an invalid dose would be checking your child’s titers.

When Do You Repeat the Invalid Vaccine Dose?

The next question that comes up after you realize that you have to repeat a dose of a vaccine is when should you repeat it?

It depends.

  • give the correct vaccine as soon as possible if the problem was that the wrong vaccine was given
  • repeat the dose as soon as possible if the problem was an expired, improperly stored, or a dose that had leaked out
  • if the dose was given too early, then you need to wait for the appropriate interval or when your child is old enough to get the dose. Keep in mind that when you repeat the dose, you would generally restart counting your interval from the invalid dose, not from the previous dose. That’s because the invalid dose might interfere with mounting a good immune response.

And in all cases, report the error to the ISMP National Vaccine Errors Reporting Program (VERP) or VAERS.

What to Know About Vaccine Errors

Although they aren’t common, vaccine errors sometimes lead to the need to repeat your child’s vaccines.

More on Vaccine Errors