Measles, mumps, and rubella

What is the impact of antibiotics or vaccines in the prevention and control of measles, mumps, and rubella?

Measles, mumps and rubella are highly contagious respiratory viruses, although many are mild to moderate infections in children. Measles, however, can be a significant cause of morbidity and mortality. Associated sequelae in children include ear infections (10%), pneumonia (5%), and death (0.1%). In the U.S. every year there are about 50 cases. However, most of these are acquired abroad. Outbreaks associated with non-vaccinated populations are still common in Europe, in part related to recent decline in acceptance of the vaccine. Despite an efficacious vaccine, globally there are approximately 164,000 deaths per annum, mostly in developing countries.

Rubella is of particular importance because of its association with birth defects (20%). This occurs with maternal infection in the first trimester of the pregnancy.

Complications associated with mumps are uncommon; however it has been reported as a cause of encephalitis and infertility especially in men.

Droplet precautions are indicated for mumps and rubella. Health-care associated infections with these agents, although rare, still occur. There is evidence that health-care workers are at higher risk of infections compared to the general population (RR 19, 95% CI 7.4, 45.4, p< 0.01). During the 2006 mumps outbreak in the U.S., there were several health care related exposures.

From 2001 to 2008 there were 27 reported measles cases transmitted in health care facilities. This amounted to 5% of all U.S. measles cases in 2005 and 11% of cases in 2008. In 2008, Arizona had the largest U.S. nosocomial outbreak of measles (n=14). In three Arizona hospitals, almost 8,000 health care workers were exposed, of whom 25% had no documentation of immunity to measles in their occupational health records. These workers were serologically screened and 5% of employees born prior to 1957 and 11% born after were susceptible to measles.

Hospital associated transmission of mumps can occur as well. The last well-documented occurrences of this was in Tennessee in 1986 and 1987 with transmission of mumps in two hospital emergency departments, infecting six health care workers, and in two long-term care facilities resulting in nine infected patients.

Which antibiotic or vaccine preparation is key to the prevention and control of measles, mumps, and rubella?

Mumps, measles, and rubella infections are prevented by the use of the three-in-one, live attenuated mumps, measles and rubella vaccine.

Measles vaccination has decreased mortality considerably. From 2000 to 2008, mortality was decreased by almost 78%, from 733,000 associated deaths to 164,000. The global goal is to vaccinate all children with two doses of measles. Measles vaccination costs less than one U.S. dollar.

Isolation precautions need to be implemented as soon as a case is suspected because of the higher risk of infections among health-care personnel; a valid history of vaccination or previous disease should be on record.

Which are the common antibiotics or vaccines used to prevent and control measles, mumps, and rubella, and what are key distinguishing features of each?

These infections are usually prevented by the combination of the three live-attenuated viruses. The vaccine is called MMR. More recently (2005) the MMRV vaccine was licensed which also includes coverage for vermicelli.

Available vaccines and the features that distinguish them, including efficacy and safety.

The MMR vaccine is made by combining three live-attenuated viruses. Measles vaccine is prepared by using the Edmonston-Enders strain growth in chicken embryos, although human diploid cells are also used; most of them contain small doses of antibiotics (neomycin 25 mg). There are around 10 strains used for the preparation of the mumps vaccine with the Jerry strain being the most commonly used. The rubella vaccine is prepared using the RA 27/3 strain (Plotkin).

Drugs currently under development and what is known about them.

MMRV was licensed in 2005 and is recommended for children less than 13 years of age. The first dose is given at 12 months and the second at 4 to 6 years of age. It has been associated with a high risk of fever and fever-associated seizures (1/250). Children over 13 should receive MMR and varicella vaccine in different vaccine administrations.

What are the controversies about the key agents, if any, and what are the pros and cons for each drug?

The major controversy around MMR vaccination, particularly of the measles vaccine component, is the public concern related to a possible association with autism and inflammatory bowel disease. Nevertheless, a careful examination of the evidence has shown no significant relationship between autism and measles vaccination.

Are there specific guidelines for the use of some or all of these agents?

Vaccination guidelines

Vaccination of children

Two doses of measles vaccine, as a combination MMR vaccine, separated by at least 4 weeks, are routinely recommended for all children. All persons born during or after 1957 should have documentation of at least one dose of MMR or other evidence of measles immunity. The first dose of MMR should be given on or after the first birthday. Any dose of measles-containing vaccine given before 12 months of age should not be counted as part of the series. Children vaccinated with measles-containing vaccine before 12 months of age should be revaccinated with two doses of MMR vaccine, the first of which should be administered when the child is at least 12 months of age.

A second dose of MMR is recommended to produce immunity in those who failed to respond to the first dose. The second dose of MMR vaccine should routinely be given at age 4 to 6 years, before a child enters kindergarten or first grade. The recommended visit at age 11 or 12 years can serve as a catch-up opportunity to verify vaccination status and administer MMR vaccine to those children who have not yet received two doses of MMR.

The second dose of MMR can be administered as soon as 1 month (i.e., minimum of 28 days) after the first dose. Children who have already received two doses of MMR vaccine at least 4 weeks apart, with the first dose administered no earlier than the first birthday, do not need an additional dose when they enter school. Children without documentation of adequate vaccination against measles, mumps, and rubella or other acceptable evidence of immunity to these diseases when they enter school should be admitted after receipt of the first dose of MMR. A second dose should be administered as soon as possible, but no less than 4 weeks after the first dose.

Adults born in 1957 or later

Adults born in 1957 or later who do not have a medical contraindication should receive at least one dose of MMR vaccine unless they have documentation of vaccination with at least one dose of measles-, mumps- and rubella-containing vaccine or other acceptable evidence of immunity to these three diseases. With the exception of women who might become pregnant and persons who work in medical facilities, birth before 1957 generally can be considered acceptable evidence of immunity to measles, mumps, and rubella.

Adults at increased risk of exposure

Certain groups of adults may be at increased risk for exposure to measles and should receive special consideration for vaccination. These include persons attending colleges and other post-high school educational institutions, persons working in medical facilities, and international travelers.

Persons who work in medical facilities are at higher risk for exposure to measles than the general population. All persons who work within medical facilities should have evidence of immunity to measles, mumps, and rubella. Because any healthcare personnel (i.e., medical or nonmedical, paid or volunteer, full time or part time, student or nonstudent, with or without patient-care responsibilities) who is susceptible to measles or rubella can contract and transmit these diseases, all medical facilities (i.e., inpatient and outpatient, private and public) should ensure measles and rubella immunity among those who work within their facilities (a possible exception might be a facility that treats only elderly patients considered at low risk for measles and rubella and their complications).

Adequate vaccination for measles, mumps, and rubella for healthcare personnel born during or after 1957 consists of two doses of a live measles- and mumps-containing vaccine and at least one dose of a live rubella-containing vaccine. Healthcare personnel needing a second dose of measles-containing vaccine should be revaccinated at least 4 weeks after their first dose.

For unvaccinated personnel born before 1957 who lack laboratory evidence of measles, mumps and/or rubella immunity or laboratory confirmation of disease, healthcare facilities should consider vaccinating them with two doses of MMR vaccine at the appropriate interval (for measles and mumps) and one dose of MMR vaccine (for rubella), respectively. For unvaccinated personnel born before 1957 who lack laboratory evidence of measles, mumps and/or rubella immunity or laboratory confirmation of disease, healthcare facilities should recommend two doses of MMR vaccine during an outbreak of measles or mumps and one dose during an outbreak of rubella.

Serologic screening need not be done before vaccinating for measles and rubella unless the medical facility considers it cost-effective. Serologic testing is appropriate only if tracking systems are used to ensure that tested persons who are identified as susceptible are subsequently vaccinated in a timely manner. Serologic testing for immunity to measles and rubella is not necessary for persons documented to be appropriately vaccinated or who have other acceptable evidence of immunity. If the return and timely vaccination of those screened cannot be assured, serologic testing before vaccination should not be done.

People who travel

Persons who travel outside the United States are at increased risk of exposure to measles. Measles is endemic or epidemic in many countries throughout the world. Although proof of immunization is not required for entry into the United States or any other country, persons traveling or living abroad should have evidence of measles immunity. Adequate vaccination of persons who travel outside the United States is two doses of MMR.

Revaccination, prevention of MMR, allergic reactions, pregnancy

Revaccination is recommended for certain persons. The following groups should be considered unvaccinated and should receive at least one dose of measles vaccine:

1) Persons vaccinated before the first birthday

2) Those vaccinated with killed measles vaccine (KMV)

3) Those vaccinated with KMV followed by live vaccine less than 4 months after the last dose of KMV

4) Those vaccinated before 1968 with an unknown type of vaccine (the vaccine may have been KMV) or

5) All people vaccinated with IG in addition to a further attenuated strain or vaccine of unknown type (revaccination is not necessary if IG was given with Edmonston B vaccine.

Live measles vaccine provides permanent protection and may prevent disease if given within 72 hours of exposure. Immune globulin (IG) may prevent or modify disease and provide temporary protection if given within 6 days of exposure. The dose is 0.25 mL/kg body weight, with a maximum of 15 mL intramuscularly. The recommended dose of IG for immunocompromised persons is 0.5mL/kg of body weight (maximum 15 mL) intramuscularly. IG may be especially indicated for susceptible household contacts of measles patients, particularly contacts younger than 1 year of age (for whom the risk of complications is highest). If the child is 12 months of age or older, live measles vaccine should be given about 5 months later when the passive measles antibodies have waned. IG should not be used to control measles outbreaks.

Persons who have experienced a severe allergic reaction (anaphylaxis) to a vaccine component or following a prior dose of measles vaccine should generally not be vaccinated with MMR. In the past, persons with a history of anaphylactic reactions following egg ingestion were considered to be at increased risk for serious reactions after receipt of measles- or mumps-containing vaccines, which are produced in chick embryo fibroblasts. However, data suggest that anaphylactic reactions to measles- and mumps-containing vaccines are not associated with hypersensitivity to egg antigens but to other components of the vaccines (such as gelatin). The risk for serious allergic reactions following receipt of these vaccines by egg-allergic persons is extremely low, and skin-testing with vaccine is not predictive of allergic reaction to vaccination. Therefore, MMR may be administered to egg-allergic children without prior routine skin testing or the use of special protocols.

MMR vaccine does not contain penicillin. A history of penicillin allergy is not a contraindication to vaccination with MMR or any other U.S. vaccine.

Women known to be pregnant should not receive measles vaccine. Pregnancy should be avoided for 4 weeks following MMR vaccine. Close contact with a pregnant woman is NOT a contraindication to MMR vaccination of the contact. Breastfeeding is NOT a contraindication to vaccination of either the woman or the breastfeeding child.

Replication of vaccine viruses can be prolonged in persons who are immunosuppressed or immunodeficient. Severe immunosuppression can be due to a variety of conditions, including congenital immunodeficiency, HIV infection, leukemia, lymphoma, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or large doses of corticosteroids. Evidence based on case reports has linked measles vaccine virus infection to subsequent death in at least six severely immunocompromised persons. For this reason, patients who are severely immunocompromised for any reason should not be given MMR vaccine. Healthy susceptible close contacts of severely immunocompromised persons should be vaccinated.

People receiving large daily doses of corticosteroids

In general, persons receiving large daily doses of corticosteroids (2 mg/kg or more per day, or 20 mg or more per day of prednisone) for 14 days or more should not receive MMR vaccine because of concern about vaccine safety. MMR and its component vaccines should be avoided for at least 1 month after cessation of high-dose therapy. Persons receiving low-dose or short-course (less than 14 days) therapy, alternate-day treatment, maintenance physiologic doses, or topical, aerosol, intra-articular, bursal, or tendon injections may be vaccinated. Although persons receiving high doses of systemic corticosteroids daily or on alternate days during an interval of less than 14 days generally can receive MMR or its component vaccines immediately after cessation of treatment, some experts prefer waiting until 2 weeks after completion of therapy.

People with leukememia, HIV, acute illnesses

Patients with leukemia in remission who have not received chemotherapy for at least 3 months may receive MMR or its component vaccines.

Measles disease may be severe in persons with HIV infection. Available data indicate that vaccination with MMR has not been associated with severe or unusual adverse reactions in HIV-infected persons without evidence of severe immunosuppression, although antibody responses have been variable. MMR vaccine is recommended for all asymptomatic HIV-infected persons and should be considered for symptomatic persons who are not severely immunosuppressed. Asymptomatic children do not need to be evaluated and tested for HIV infection before MMR or other measles-containing vaccines are administered. A theoretical risk of an increase (probably transient) in HIV viral load following MMR vaccination exists because such an effect has been observed with other vaccines. The clinical significance of such an increase is not known.

MMR and other measles-containing vaccines are not recommended for HIV-infected persons with evidence of severe immunosuppression. MMRV is not approved for and should not be administered to a person known to be infected with HIV.

Persons with moderate or severe acute illness should not be vaccinated until the illness has improved. This precaution is intended to prevent complicating the management of an ill patient with a potential vaccine adverse reaction, such as fever. Minor illness (e.g., otitis media, mild upper respiratory infections), concurrent antibiotic therapy, and exposure to or recovery from other illness is not contraindications to measles vaccination.

References

“AAP – American Academy of Pediatrics (1997). “Measles””. Red Book: Report of the Committee on Infectious Diseases. vol. 344. 1997.

““Measles, mumps, rubella-vaccine use and strategies for elimination of measles, rubella and congenital rubella syndrome and control of mumps””. MMWR: Morbidity and Mortality Weekly Report. vol. 47. pp. 1-57.

“CDC (1996). Centers for Disease Control and Prevention. “Measles pneumonitis following measles–mumps–rubella vaccination of a patient with HIV infection, 1993””. MMWR: Morbidity and Mortality Weekly Report. vol. 45. 1996. pp. 603-6.

“CDC, Centers for Disease Control and Prevention. Measles: Epidemiology and Prevention of Vaccine-preventable diseases”. The Pinkbook: Course textbook. April 2011.

Chen, R.T, Moses, J.M, Markowitz, L.E, Orenstein, W.A. “(1991). “Adverse events following measles–mumps–rubella and measles vaccinations in college students””. Vaccine. vol. 9. pp. 297-299.

Steingart, KR, Tomas AR Dykewicz, CA, Redd, SC. “Transmission of measles virus in healthcare settings during a communitywide outbreak”. Infect Control Hosp Epidemiol. vol. 20. 1999. pp. 115-19.

“WHO Report on vaccine safety.whqlibdoc.who.int/hq/2000/WHO_V&B_00.36”. pp. 54-72.

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