EpiVac Pink Book Netconference
Measles, Mumps, Rubella–2018
Tina Objio
QUOTES from 18 page document, not online.
These are the complications that are often associated with the measles in the U.S.: diarrhea is the most common, followed by otitis media or middle ear infection, and pneumonia. Encephalitis or inflammation of the brain and seizures are fairly uncommon and death occurs in about 0.2% of reported cases here in the U.S., which is about 2 deaths per 1,000 reported cases.
Mumps can infect several glands in the body, but parotitis, or inflammation of the parotid or salivary glands, is what we most often think of with mumps. The prodrome is nonspecific because the symptoms could be typical of many different conditions. They are myalgia or muscle aches, anorexia or loss of appetite, malaise or generalized discomfort, headache, and low-grade fever. Before vaccine was available, between 15% and 27% of persons who are infected with mumps had no symptoms at all.
The complications of rubella are not common, but they generally occur more often in adults than in children. Transient arthralgia or arthritis may occur in up to 70% of women infected with rubella, but it’s rare in children and adult males. And chronic arthritis due to rubella is very rare. Encephalitis occurs in 1 in 6,000 cases and again, is more common in female adults than anyone else. The most common hemorrhagic manifestation is thrombocytopenic purpura, which is bleeding into the skin with petechiae or red and purple spots and bruising in the skin. These symptoms are more common in children than adults and occur in about 1 in 3,000 cases. The other complications, orchitis, neuritis, or inflammation of the nerves, and progressive panencephalitis, or inflammation of the brain that results in loss of mental and motor function, are rare complications. No deaths have been reported in recent outbreaks here in the U.S.
Postvaccination serologic testing to verify an immune response is not recommended.
So now let’s look at the vaccines that protect against these diseases. There are no single-component measles, mumps, or rubella vaccines licensed in the U.S. MMR is the combined live vaccine that contains all three attenuated, or weakened, viral antigens. As long as there are no medical contraindications, MMR can be used in anyone 12 months of age and older and, in certain circumstances, for infants as young as 6 months of age, which I’ll discuss in a few minutes. The viruses in the vaccine are weakened so that they will not cause disease in a person with a competent immune system, but they will induce a protective immune response in most vaccinated persons.
MMRV is a combination live vaccine, contains attenuated measles, mumps, rubella, and varicella viral antigens…. It is not FDA-approved or ACIP-recommended for anyone 13 years of age or older.
Vaccine efficacy is inferred from MMR and varicella vaccines, so efficacy for the measles, mumps, and rubella components is considered to be the same as it would be for MMR vaccine. When manufacturers combine products they have to demonstrate noninferiority, which means the efficacy of the combined product is not inferior to the separate vaccines. The measles, mumps, and rubella components are the same as they are for MMR, but the varicella component contains seven to eight times as much varicella vaccine virus as does the single-component varicella vaccine. So you cannot just mix MMR and varicella vaccines and get MMRV. MMRV is supplied in single-dose vials and should only be administered subcutaneously after reconstitution with the supplied diluent.
The minimum age for a routine dose is 12 months. For international travel for a child who is at least 6 months of age, ACIP allows that a dose of MMR be administered; note this is an off-label use of the vaccine. The vaccine is not routinely recommended before 12 months of age because if maternal antibodies are present, they could interfere with the vaccine. But if the child is at high risk because of international travel, there’s a chance that the child may respond to the vaccine and the vaccine will not harm the child. However, a dose administered more than 4 days before the first birthday does not count as one of the 2 valid doses. So it should be repeated once the child is 12 months of age, as long as 4 weeks have elapsed.
The second dose is not really a booster dose, although it may boost the antibody titer in those who responded to the first dose. The main reason for the second dose is to produce immunity in persons who didn’t respond to the first dose.
Unless the parent or caregiver has a preference for MMRV, CDC recommends that separate MMR and varicella vaccines should be administered at separate sites for the first dose in children 12 through 47 months of age. For the second dose at 15 months through 12 years of age, or if the first dose is being given at 48 months of age or older, then MMRV is generally preferred because the risk of a febrile seizure is less. Note that this vaccine is not approved for use in people 13 years and older. MMR should be used for anyone 13 and older needing vaccination.
Adults born in 1957 or later need 1 dose or more of MMR unless they have other evidence of immunity. And again, pregnancy and immunosuppression would be contraindications to vaccination. It’s important to ensure that a woman who does not have evidence of immunity to rubella receives a dose of MMR after delivery before discharge.
And as I mentioned earlier, adults born before 1957 are generally presumed immune to measles, mumps, and rubella.
Health care providers with 2 documented, appropriately spaced doses of MMR are not recommended to be serologically tested for immunity. I’m going to say that one more time because we get a lot of questions. Health care providers with 2 documented, appropriately spaced doses of MMR are not recommended to be serologically tested for immunity. However, if they are tested and results are negative or equivocal for measles, mumps, and/or rubella, no additional MMR doses are recommended.
Transitioning from health care personnel back to the general population, revaccination with at least 1 dose of MMR is recommended for the following persons because they’re considered unvaccinated. Those vaccinated before the first birthday will still need 2 doses of MMR vaccine. Anyone vaccinated with killed measles vaccine or vaccinated from 1963 through 1967 with an unknown type of vaccine, or if they were vaccinated with immune globulin in addition to a further attenuated strain or with an unknown type of vaccine. Revaccination is not necessary if IG was given with Edmonston B vaccine. And persons vaccinated before 1979 with either killed mumps vaccine or a mumps vaccine of unknown type who are at high risk for mumps infection, like people who are working in a health care facility, should be considered for a revaccination with 2 doses of MMR vaccine.
After rubella or mumps exposure, postexposure prophylaxis with MMR vaccine or immune globulin has not been shown to be helpful, so ACIP does not recommend postexposure prophylaxis for those two diseases. Postexposure prophylaxis can be quite complicated; the ACIP recommendations provide detailed information on these recommendations.
Neomycin is an antibiotic that fights bacteria in the body.
MMR is contraindicated if someone has a history of a severe anaphylactic type reaction to neomycin or any component in the vaccine. This does not include eggs, but it does include gelatin; this also applies to MMRV. Neither MMR nor MMRV should be administered to women who are known to be pregnant or attempting to become pregnant. ACIP recommends that a patient of childbearing age be asked if they are pregnant or likely to become pregnant within the next 4 weeks. If the answer is yes, the woman should not be vaccinated. Because there is a theoretical risk to the fetus when the mother receives a live-virus vaccine, women should be counselled to avoid becoming pregnant for 4 weeks after receipt of MMR vaccine. The vaccine package insert recommends deferral of pregnancy for 3 months after vaccination, but ACIP’s off-label recommendation is 4 weeks.
If someone has a moderate or severe acute illness, they should not be vaccinated until their condition improves; this applies to all vaccines.
If someone has recently received an antibody-containing blood product, it could interfere with the immune response to the vaccine. The length of time to allow for these antibodies to clear the person’s system before vaccination depends on the concentration and quantity of the product. There’s a table of recommended intervals between antibody-containing products and measles-containing vaccine on page A24 of Appendix A in the Pink Book, and this table is also published in the ACIP General Best Practice Guidelines for Immunization.
A personal or family history of seizures for any reason is a precaution for MMRV, and I’ll discuss this more a little later.
Immunosuppression is generally a contraindication to a live-virus vaccine. Prevaccination HIV testing is not recommended before vaccination. As I showed on the adult immunization schedule for persons with medical conditions, persons who are HIV-positive can receive MMR if they are not severely immunosuppressed. Revaccination is recommended for persons with perinatal HIV infection if they were vaccinated before effective antiretroviral therapy, or ART. Once effective ART has been established with the patient, 2 appropriately spaced doses of MMR should be administered. And MMRV should not be used for persons who are HIV-positive. If vaccination is indicated, only use MMR. MMR vaccine should not be given to persons taking large daily doses of oral parenteral corticosteroids for more than 2 weeks and vaccination should be avoided for at least 1 month after high-dose therapy has stopped. Patients with leukemia in remission who have not received chemotherapy for at least 3 months may receive MMR. For someone who has received a hematopoietic cell transplant or a bone marrow transplant and is immunocompetent, MMR can be administered 24 months after the transplant.
Another consideration is persons who have a family history of congenital or hereditary immunodeficiency in first-degree relatives like their parents or their siblings, unless the immune competence of the potential vaccine recipient has been substantiated clinically or verified by a laboratory.
Until additional information is available, IGRA testing in the context of live-virus vaccine administration should be done as follows. Draw the blood for the IGRA, either on the same day as vaccination with the live-virus vaccine, or wait at least 4 weeks after the administration of the live-virus vaccine to draw the blood for the IGRA test.
Since all three components of MMR are live viruses, adverse reactions following vaccination are predictable and represent viral replication that leads to mild illness in susceptible vaccine recipients. Adverse reactions generally occur 7 to 10 days after vaccination. The most common reaction following vaccination is a low-grade fever in about 5 to 15% of recipients, which is usually attributed to the measles component in MMR, and might cause febrile seizures. The risk is approximately 1 case for every 3,000 to 4,000 doses of MMR vaccine administered. The rate is almost twice that for MMRV. A rash occurs in about 5% of recipients and lasts a day or two; it’s usually attributed to the measles component, but may also be caused by the rubella vaccine virus. The rash is much milder than the rash that occurs with disease. Thrombocytopenia or low platelet count occurs in 1 in 30,000–40,000 doses and it’s usually transient and benign. Lymphadenopathy, or swollen, tender lymph nodes, and allergic reactions are rare. Parotitis and deafness are rare reactions, usually attributed to the mumps component. Encephalopathy is believed to occur after 1 in a million doses or less; this is a very rare event.
Joint symptoms occur in up to 25% of rubella-susceptible women—less often in men and rarely in children. The most common joint symptoms reported after rubella or MMR vaccination are joint pain and frank arthritis-like joint swelling and redness in about 10% of vaccine recipients. These symptoms occur in approximately 70% of women after rubella disease. Symptoms usually occur between 1 and 3 weeks after vaccination and last between 1 day and 3 weeks and rarely recur. There have been some reports of persistent pain or chronic arthritis in women who received rubella vaccine, but several large studies have not found an association between chronic joint symptoms and rubella vaccination. Almost everyone becomes immune to rubella after the first dose, so in instances where a second or third dose is administered, only the small number of women who failed to respond to the first dose would be at risk for joint symptoms.
The concern about MMR vaccine and autism has been very well-studied. The Institute of Medicine, now called the Health and Medicine Division, reported finding no causal relationship between the MMR vaccine and autism; yet, there are still measles outbreaks attributed to these concerns. In July of 2017, an article was published about a measles outbreak that had occurred in April and May in Minnesota in a community with previously high vaccination coverage. Concerns about autism, the perceived increased rates of autism in a Somalia-American community, and the misunderstanding that autism was related to the MMR vaccine resulted in a decline in MMR vaccination coverage to a level low enough to sustain widespread measles transmission in the Somalia-American community following introduction of the virus. This outbreak demonstrates the challenge of combating misinformation about MMR vaccine.
Adverse reactions following MMRV are similar to MMR. However, compared to vaccination with MMR and varicella vaccines at the same visit, MMRV vaccination is associated with higher risk for fever and febrile seizures 5 through 12 days after the first dose among children 12 through 23 months of age. Fever of 102 degrees or higher within 42 days was reported in 22% of MMRV recipients compared to 15% of those who receive separate injections. The increased risk of fever following MMRV also results in an increased risk of febrile seizures. This is estimated to be 1 additional febrile seizure for every 2,300 to 2,600 MMRV doses administered to children 12 through 23 months of age. An increased risk of febrile seizures has not been observed following use of MMRV as the second dose in the MMR and varicella series. Studies suggest that children who have a personal or family history of febrile seizures or a family history of epilepsy are at increased risk for febrile seizures compared with children who do not have such histories. Children with a personal or family history of seizures generally should be vaccinated with separate MMR and varicella vaccines rather than the combined MMRV because the risk of using MMRV vaccine in this group of children generally outweighs the benefit of MMRV vaccine.
I do want to mention a few of the most common administration errors that we hear about with MMR and MMRV. The most common error we hear about is the wrong diluent being used for reconstitution. Only the sterile water sent by the manufacturer for reconstitution should be used. We also hear about MMRV being administered to persons 13 years of age or older. Remember, it’s only FDA-approved for use in persons 12 months to 12 years of age.
And finally, I can’t emphasize enough the importance of proper storage and handling, checking expiration dates, and proper administration technique. So just remember to be sure you’re following best practice guidelines when administering MMR or MMRV and any other vaccines. Any vaccine can lose its potency if not stored and handled properly and live vaccines are particularly fragile. MMR vaccine can be stored with other refrigerated vaccines or in the freezer. The diluent can be refrigerated or stored at room temperature, but it should never be frozen. MMR is a live vaccine, so it should be protected from light by keeping it in the original packaging until ready to administer. Once it’s reconstituted, the vaccine should be used as soon as possible. Store reconstituted vaccine in the vaccine vial in a dark place in the refrigerator and discard if not used within 8 hours. You should not draw reconstituted vaccine into a syringe until you’re ready to administer it.
Because MMRV contains varicella vaccine, it should be stored with other varicella-containing vaccines at the recommended freezer temperature. It should never be stored—even temporarily—using dry ice. If removed from the freezer, it can be stored for up to 72 continuous hours at refrigerator temperature, but if not used by then, it must be discarded. It should not be returned to the freezer. It should also be stored in the original packaging and protected from light. Use MMRV within 30 minutes of reconstitution or discard it, and never freeze reconstituted vaccine. The diluent for MMRV is the same as for MMR, and it should be stored at room temperature or refrigerated. Do not freeze the diluent.
MODERATOR: Okay, thank you. And they asked, though I think you covered this, but perhaps you can briefly repeat it, why does MMRV vaccine have substantially more—7 to 8 times more varicella virus titer in it—than does varicella vaccine when administered as a monovalent product?
TINA OBJIO: So when the vaccine manufacturers combine the antigens used in separate vaccines to make the combination vaccine, they have to demonstrate noninferiority. That means that the safety and efficacy are comparable to the separate vaccines and, in order to demonstrate noninferiority of MMRV, they found it necessary to use more of the live, attenuated varicella vaccine virus. So that’s why, you know, one just can’t mix your MMR vaccine and varicella vaccine to make your own dose of MMRV vaccine. Those have to be administered separately.
ONLY table of contents
Epidemiology and Prevention of Vaccine Preventable Diseases
https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/table-of-contents.pdf