for Pharmacists and Pharmacy Technicians

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1 Chapter 7: A Review of Measles, Mumps, and Rubella for Pharmacists and Pharmacy Technicians By: Katie Ingersoll, RPh, PharmD, and Staff Pharmacist for national chain. 4 Contact Hours Author Disclosure: Katie Ingersoll and Elite Professional Education, LLC do not have any actual or potential conflicts of interest in relation to this lesson. Universal Activity Number (UAN): H01-P Activity Type: Knowledge-based Initial Release Date: April 1, 2015 Expiration Date: April 1, 2017 Target Audience: Pharmacists in a community-based setting. To Obtain Credit: A minimum test score of 70 percent is needed to obtain a credit. Please submit your answers either by mail, fax, or online at Pharmacy.EliteCMEcom. Learning objectives After completion of this course, pharmacists and pharmacy technicians will be able to: Discuss the history and epidemiology of measles, mumps, and rubella. List the symptoms and complications of measles, mumps, and rubella. Describe the methods for diagnosing measles, mumps, and rubella. Discuss the treatment of measles, mumps, and rubella, including the use of post-exposure prophylaxis. Introduction The burden of contagious diseases has been significantly reduced through the use of successful vaccination programs in the United States. However, even significant achievements in infectious disease can be reversed. Measles, a highly contagious infectious disease, was considered eliminated from the United States in 2000, and for approximately 10 years, the majority of cases reported in the United States were imported from overseas. Despite this achievement, recent years have seen significant increases in the number of measles cases in the United States, increasing concerns that inadequate vaccination has created a resurgence of a disease that was once considered eliminated [1]. The most important tool available to health care providers (HCPs) in the United States to maintain low levels of contagious diseases is the use of vaccinations. Immunization rates in the United States are high, but gaps in care exist throughout the country. Questions regarding statements of credit and other customer service issues should be directed to This lesson is $ Educational Review Systems is accredited by the Accreditation Council of Pharmacy Education (ACPE) as a provider of continuing pharmaceutical education. This program is approved for 4 hours (0.4 CEUs) of continuing pharmacy education credit. Proof of participation will be posted to your NABP CPE profile within 4 to 6 weeks to participants who have successfully completed the post-test. Participants must participate in the entire presentation and complete the course evaluation to receive continuing pharmacy education credit. Describe the immunization schedule for vaccination against measles, mumps, and rubella. List the contraindications and precautions for vaccination against measles, mumps, and rubella. Discuss the efficacy of vaccination against measles, mumps, and rubella, and describe adverse reactions associated with immunization. Discuss strategies that can be used to improve immunization rates, including maintaining adequate records, reminding patients to vaccinate, and collaboration between the patient and provider. Economic and racial disparities exist, leaving vulnerable populations at a higher risk for contracting and transmitting contagious diseases. Maintaining high immunization rates, especially in vulnerable populations, is critical to sustaining low levels of vaccine-preventable illnesses, and immunization providers are perfectly poised to ensure that vaccinations are administered in a timely manner to everyone that needs them. Strict adherence to vaccination schedules and patient education on the safety of vaccinations, as well as the importance of immunizing, are essential to maintaining high immunization levels [2]. The contagious viral illnesses of measles, mumps, and rubella can be prevented through the appropriate use of vaccinations. This course serves as a review of the history, epidemiology, symptoms, treatment, and prevention of these three illnesses. Measles Definition Measles, also known as rubeola, is a viral infection that is transmitted through airborne respiratory droplets, such as with coughing or sneezing. It is characterized by high fever, conjunctivitis, coryza (runny nose), and cough, as well as a rash that appears 3 to 5 days after symptoms onset. The measles virus is highly contagious; up to 90% of History of measles Measles has a long history, with the first documentation of disease occurring in the 7th century. Measles was described as being more Page 85 people without previous immunity will become infected when exposed to measles. Prevention of measles can be achieved through the use of measles-containing vaccinations administered following recommended vaccination schedules [1, 3]. dreaded than smallpox by a Persian physician named Rhazes in the 10th century. Hundreds of years later in the 19th century, Peter Panum

2 discussed the lifelong immunity shown in patients who have recovered from the disease, as well as the incubation period between exposure and disease manifestation. After the virus was isolated from kidney Epidemiology of measles Before vaccination was made available in 1963, most people experienced measles infection before adulthood. Epidemic cycles occurred every 2 to 3 years, and while approximately 500,000 cases were reported annually, the actual infection rates were estimated to be between 3 and 4 million people annually. Over 50% of people experienced measles infection before age 6, and over 90% were infected by age 15. The highest incidence of infection was seen in children between 5 and 9 years old, with over 50% of cases occurring in this age range [1,3]. Once the vaccination against measles was released in 1963, a vaccination program was implemented to administer one dose of measles vaccination during childhood, to infants between the ages of 9 and 15 months. This program significantly reduced the incidence of measles in all age groups, with reported cases in the late 1960s and early 1970s decreasing to 22,000 to 75,000 per year. While the number of reported cases decreased drastically, outbreaks occurred in the 1980s in school-aged children who received a single dose of measles vaccination. This led the Advisory Committee on Immunization Practices (ACIP) to recommend a second dose of measles-containing vaccine in all children to induce immunity in the small subset of patients whose initial vaccination did not result in the development of antibodies. Major measles outbreaks occurred in the United States from 1989 to 1991, resulting in approximately 55,000 reported cases of measles. These outbreaks were largely associated with unvaccinated or inadequately vaccinated children, and led to increasing efforts to vaccinate all preschool-aged children against measles. The federal Vaccines for Children program was introduced in 1993 to increase access to vaccinations recommended by the ACIP, allowing eligible children under 19 years of age to receive recommended vaccinations at no cost. The result of these efforts to reduce the incidence of measles infection was a mere 309 reported cases of measles in Symptoms of measles The measles virus has a relatively long incubation period; the average onset of early symptoms after exposure to the virus is around 10 to 12 days. The first symptom is commonly a fever, which can peak as high as 103 F to 105 F, followed by the onset of runny nose (coryza), cough, and/or conjunctivitis. The measles virus is shed beginning with the early signs of infection and continuing through 3 to 4 days after onset of the measles rash, indicating the most contagious point of the infection. Koplik spots, a rash of blue-white spots on the bright red mucous membranes of the back of the mouth and throat, can often be seen within 2 to 3 days of symptom onset. Koplik spots are considered pathognomonic for measles, and can be an early sign of measles infection, often starting 1 to 2 days before the skin rash. tissue in 1954, the first live attenuated vaccination was developed and released in 1963 [3]. Measles cases reported annually continued to decrease, until measles was verified and declared as eliminated from the United States in 2000, with elimination defined as an interruption of continuous endemic transmission of measles lasting more than 12 months. Despite elimination, measles cases continued to occur throughout the early 2000s, largely due to importation of the virus from other countries and spread through unvaccinated persons. A total of 140 cases of measles were reported in 2008, the highest since While 89% of these cases were related to importation of disease from countries where outbreaks are ongoing, this number of cases was also related to increased transmission among improperly vaccinated persons after the virus was imported [1,3]. In January 2015, the California Department of Health received notification of an 11-year-old child that developed measles after a recent trip to Disneyland in California. Reports of other children developing measles after travelling to Disneyland came in, and as of February 11, 2015, a total of 125 cases of measles have been linked to this outbreak, with 110 occurring in California residents. Of the California residents, 45% were unvaccinated, 5% received 1 dose of measles-containing vaccine, 6% received 2 doses of measles-containing vaccine, and 43% had an unknown vaccination status. Approximately 25% of the unvaccinated patients were infants who were too young to receive measles vaccination, and 67% of the unvaccinated patients were not vaccinated due to personal beliefs. The source of this outbreak has not been identified, but specimens collected from affected patients revealed that the viral strain was the same strain that caused a large recent outbreak in the Philippines. Recent outbreaks have highlighted the importance of increasing awareness on the safety of immunizations and improving compliance with childhood vaccination schedules [4]. The measles skin rash is considered to be a maculopapular rash, or a rash characterized by a flat red area covered with small bumps. It appears approximately 14 days after exposure to the measles virus. It starts at the hairline and spreads downward, and may be associated with mild itchiness. It typically involves the face and neck within the first 3 days of onset, then spreads down and outward, reaching the hands and feet over the next 3 days, for a typical duration of 5 to 6 days total. Measles lesions initially turn white under the pressure of a fingertip, but after 3 to 4 days they no longer turn white with pressure. After 5 to 6 days, the rash tends to diminish in the order it appeared, starting with the hairline. Other symptoms of measles can include anorexia, diarrhea, and lymphadenopathy [3,5]. Complications of measles Complications are reported in approximately 30% of measles infections. Infants, young children, and adults over 20 years of age are at a higher risk of death from measles infection or its complications than adolescents or older children. Patients suffering from malnutrition, particularly vitamin A deficiencies (common in thirdworld countries), experience measles more severely. Patients with compromised immune systems, such as those with cancer or HIV/AIDS, can experience more severe or prolonged illness from measles, and may be at a higher risk of developing complications. They can also suffer from measles without the typical rash, and these patients can shed the measles virus for several weeks after the resolution of acute illness. Women who are pregnant may also be at a higher risk of severe measles or complications. They may be at a higher risk of premature labor, preterm delivery, low infant birth weight, and spontaneous abortion. Diarrhea is the most common complication, with approximately 8% of measles patients reporting this symptom. Pneumonia was reported in approximately 6% of cases between 1987 and 2000, and otitis media was reported in 7% of cases during this timeframe. Acute encephalitis was reported in approximately 0.1% of measles cases, and begins an average of 6 days after the onset of the measles rash. Symptoms of measles encephalitis include fever, stiff neck, headache, vomiting, headache, drowsiness, convulsions, or coma. Page 86

3 Encephalitis associated with measles is fatal in approximately 15% of cases, and residual neurologic damage can occur in up to 25% of cases. Rarely, persistent measles infection can lead to a neurologic condition called subacute sclerosing panencephalitis (SSPE). This degenerative neurologic disease is rare but often fatal, and is seen in 5 to 10 patients per million measles cases. Symptoms of SSPE are thought to be caused by a chronic measles infection of the brain and appear an average of 7 years after infection with measles, though it has been reported decades later. Symptoms often start with progressive deterioration of intellect and behavior, followed by ataxia, myoclonic seizures, and death. Widespread use of vaccinations against measles has virtually eliminated the occurrence of SSPE in the United States, though imported cases can still occur. The measles vaccine has not been shown to cause SSPE. Treatment of measles Treatment of measles should be focused on relieving symptoms through supportive care and preventing or addressing complications. While there are no antivirals approved by the U.S. Food and Drug Administration (FDA) for the treatment of measles, the measles virus has shown susceptibility to ribavirin, and has been used for cases of measles in severely immunocompromised individuals or those with SSPE. No controlled studies have evaluated this treatment and its use is considered to be experimental [7]. Maintaining adequate hydration to replace fluids lost through diarrhea or emesis is essential, and intravenous rehydration may be necessary in severely dehydrated patients. Fever management is also extremely important, and treatment with antipyretics such as acetaminophen may be necessary. Since vitamin A deficiency is associated with severe measles, the World Health Organization (WHO) recommends that all children with measles should be treated with vitamin A, regardless of the country in which they live. One dose of vitamin A should be given immediately Post-exposure prophylaxis People who have been exposed to measles that do not have evidence of immunity should be offered post-exposure prophylaxis to attempt to prevent or modify the course of measles. The primary treatment for post-exposure prophylaxis is the measles, mumps, and rubella (MMR) vaccine. The MMR vaccine is a live attenuated immunization that contains vaccinations against three viral illnesses: measles, mumps, and rubella. It is indicated for use in patients 12 months of age and older. Since it is a live vaccine, contraindications and precautions should be followed to ensure the appropriateness of vaccine administration; these issues are discussed in the following section. MMR vaccine used for post-exposure measles prophylaxis should be administered within 72 hours of initial exposure. If the MMR vaccine is not given within 72 hours of measles exposure, it should still be offered at any time after exposure to protect against further exposures. Page 87 Approximately 0.2% of measles cases result in death, often due to complications associated with the disease. Death is most commonly associated with pneumonia in children with measles, and acute encephalitis in adults. Modified measles can occur in patients who have received immune globulin for post-exposure prophylaxis, as well as in newborns who may have residual maternal antibodies. This form of measles has a longer incubation period, a mild acute phase, and a sparse rash that lasts for a short time. Hemorrhagic measles is rarely reported in the United States, but can be a severe form of the illness. Symptoms of hemorrhagic measles include high fever of 105 F to 106 F, hemorrhage into the skin and mucous membranes, delirium, seizures, and respiratory distress [1,3,5]. Diagnosis and laboratory testing for measles Patients presenting with febrile rash illnesses should be tested for measles, especially if they were exposed to another person with febrile rash illness or were recently travelling internationally. Suspected measles cases should be reported to the local health department within 24 hours. Confirmation of measles diagnosis through laboratory testing is necessary for all potential measles cases. Serum samples and throat swabs should be collected at first contact with any patient presenting with measles symptoms. The measles virus can also be present in urine and respiratory secretions; collecting and analyzing these samples can also improve the chances of detecting the measles virus. Measlesspecific IgM antibodies can be measured, but may be altered or missing in patients who received a measles-containing immunization. Measles RNA can be measured through real-time polymerase chain reaction (RT- PCR), and can also be used to confirm measles infection [5]. Throat swabs should be collected from patients with suspected measles and sent to state health department or the U.S. Centers for Disease Control and Prevention (CDC). Viral concentrations are highest within 3 days of rash onset, so collection of specimens should not be delayed. Protocols for collecting specimens from measles patients can be found at [3,6]. upon diagnosis and a second dose should be given 24 hours later. Children under 6 months of age should receive 50,000 IU per dose, those between 6 and 11 months of age should receive 100,000 IU per dose, and children older than 12 months should receive 200,000 IU per dose. Children exhibiting clinical signs of vitamin A deficiency should receive a third age-specific dose 2 to 4 weeks later. The use of vitamin A supplementation in measles patients is associated with a decrease in morbidity and mortality of approximately 50% [5,7]. Patients with measles should be isolated from other people for 4 days after rash development. In the health care setting, HCPs should follow airborne precautions during the period of communicability to minimize disease transmission, regardless of the immunization status of the HCP. Airborne precautions should be followed starting 3 to 5 days before the appearance of rash until 4 days after rash development; these precautions may need to be followed longer in immunocompromised patients. All staff entering the patient s room should wear a respirator, and patients with measles should be placed in single-patient airborne infection isolation rooms [5,7]. In the event of a measles outbreak among infants under 12 months of age, vaccination may be administered to infants as young as 6 months as an outbreak control measure. However, children who receive measles vaccination before 12 months of age should be revaccinated twice, once when they are between 12 and 15 months of age, and again when they are between 4 and 6 years of age. People at high risk of severe illness or complications from measles infection, such as pregnant women without evidence of immunity against measles, infants under 12 months, and severely immunocompromised individuals, should receive immune globulin (IG). All infants under 12 months of age who have been exposed to measles should receive immune globulin (intramuscular) (IGIM). Pregnant women without evidence of measles immunity who have been exposed to measles should receive immune globulin (intravenous) (IGIV) due to the high risk of severe measles and complications. Patients with

4 severely compromised immune systems who have been exposed to measles should receive IGIV regardless of their immunity status since they may not have received enough protection from the MMR vaccine. The recommended dose of IGIM is 0.5 ml/kg, with a maximum dose of 15 ml, and the recommended dose of IGIV is 400 mg/kg[5]. IG should be used to decrease the risk of infection and complications in high-risk patients who have been exposed to measles, and not used as an outbreak control measure. It should be given with priority to patients exposed to measles in close contact for prolonged periods of times, such as a caregiver of a measles patient. Health care workers without evidence of immunity that are exposed to measles should receive the MMR vaccine within 72 hours of exposure, or IG within 6 days of exposure. Exposed health care workers without measles immunity should be excluded from work from day 5 after Measles vaccination The measles virus was first isolated in 1954, leading to licensure of two vaccinations in 1963, an inactivated vaccine, and a live attenuated vaccine. The inactivated vaccine, known as the killed measles vaccine (KMV), was removed from the market in 1967 as it did not provide adequate protection against measles, and patients who received this vaccine developed atypical measles when exposed to the virus. Several iterations of the live attenuated Efficacy of measles vaccination After MMR vaccination, approximately 95% of children vaccinated at 12 months of age develop measles antibodies, and 98% of children vaccinated at 15 months of age develop measles antibodies. Between 2% and 5% of children who receive only a single dose fail to develop immunity to measles, which can be related to passive immunity present in the child, inappropriately stored vaccine, or inadequate records. Most patients who fail to develop a response to the first dose will develop a response to a second dose of MMR vaccine; approximately 99% of people who received 2 doses of MMR vaccine (with the first dose after their first birthday) will develop immunity. Vaccination schedule for children All children should receive 2 doses of measles-containing vaccine, separated by at least 4 weeks. The first dose should be administered between 12 and 15 months of age. Any doses administered before the child s first birthday should not be counted as part of the 2-dose series. The second dose should be administered between 4 and 6 years of age, often before the child enters school. Children should be re-evaluated at their 11- to 12-year-old recommended doctor visit to ensure they received 2 doses of measles-containing vaccine. If the child did not receive any doses, he or she should receive the first dose at this visit, and a second dose can be administered 28 to 90 days after the first, depending on the vaccine used initially. Written documentation of vaccinations with the date of receipt and vaccination administered should be the only accepted proof of vaccination. Those lacking adequate documentation should be vaccinated according to the immunization schedule [3]. MMRV is an immunization that adds varicella to the standard MMR vaccination. It is approved by the FDA for use in children 12 months to 12 years old, and should not be administered to children 13 years of Vaccination schedule for adults Adults born in or after 1957 should receive 2 doses of measlescontaining vaccine at least 4 weeks apart unless they have a contraindication or evidence of immunity to all three diseases. Birth before 1957 is considered to be acceptable evidence of immunity to measles, since the prevalence of measles before 1957 was so high. Adults born before 1957 that are attending college, working in the health care arena, or travelling internationally should consider 2 doses initial exposure until day 21 after last exposure, regardless of postexposure prophylaxis. After receiving IG, health care workers should not return to the health care setting right away, to minimize the potential for spreading disease and maintain the effectiveness of the IG. People returning to work in other settings should be evaluated on a case-by-case basis, depending on the intensity of close contact with the disease, the population they work with, and their immune status. Patients who receive post-exposure prophylaxis should be monitored for signs of measles for at least one incubation period. Patients refusing post-exposure prophylaxis should be excluded from the setting where measles is present; for example, children should be kept from school unless they receive post-exposure prophylaxis [5]. vaccine were licensed in the 1960s as developers attempted to decrease the incidence of adverse effects in vaccine recipients. The measles vaccine was combined with the mumps and rubella vaccines in 1971 to produce the MMR vaccination; single-antigen measles vaccinations are no longer available in the United States [3]. Vaccine-induced immunity develops a lower level of antibodies than natural disease, but the level of immunity to measles associated with vaccination appears to be long-term and probably life-long. Patients with low antibody titers after 2 immunizations who are revaccinated often develop a large amount of antibodies in recognition of the pathogens present in the vaccine, indicating a high likelihood of immunity from the original vaccinations. Revaccination is associated with an increase in measles antibody levels, but the increased level of antibodies may not be sustained [3]. age or older. Since 2 doses of varicella are recommended for children at the same intervals as MMR vaccine, the MMRV vaccination can be substituted for the separate MMR and varicella vaccines. However, the use of MMRV vaccine for the first dose at age 12 to 15 months has been associated with an increased risk of fever and febrile seizures as compared to separate doses of MMR and varicella vaccines administered in the same office visit. One additional febrile seizure occurred per 2,300 to 2,600 children who received MMRV vaccine compared to MMR and varicella vaccines administered separately. Therefore, providers should discuss the risks and benefits of using MMRV vaccine with parents and caregivers, and unless the adult expresses a strong preference for MMRV vaccine, the CDC recommends separate doses of MMR and varicella vaccines for the first dose in children 12 to 15 months old. Since 97% of febrile seizures occur in children less than 47 months of age, the MMRV vaccine is safer to use in children over age 4, and may be considered for the second dose of these vaccinations. If 2 doses of MMRV vaccine are indicated, they should be separated by at least 3 months [3,8]. of measles-containing vaccination due to the high risk of transmission associated with these settings, especially if they are lacking laboratoryconfirmed disease. Many colleges and health care facilities require documentation of immunity to measles or at least 1 dose of measlescontaining vaccination. Page 88

5 Blood testing for measles immunity does not need to be completed before vaccinating against measles unless the medical facility determines it to be cost-effective. Testing should only be done if there are systems Revaccination Revaccination is recommended in certain cases. Patients vaccinated before their first birthday, those who received a KMV between 1963 and 1967, those who received the KMV and were revaccinated with in place to ensure that patients who are determined to be susceptible to measles receive appropriate vaccination in a timely manner [3]. live vaccine less than 4 months later, and those vaccinated before 1968 with an unknown vaccine should be revaccinated with at least 1 dose of measles-containing vaccine [3]. Contraindications and precautions to the MMR vaccination The use of the MMR vaccine is contraindicated in patients who have experienced a severe allergic reaction to the vaccine or a vaccine component. Despite previous beliefs that severe egg allergies increased the risk of adverse reactions to the MMR vaccine, data suggest that anaphylactic reactions to the MMR vaccine are not associated with hypersensitivity to eggs but to other vaccine components such as gelatin. The risk of severe allergic reactions to the MMR vaccine when administered to patients with severe egg allergies is extremely low, and it is recommended in patients with egg allergies without special protocols. Pregnant women should not receive the MMR vaccine, and pregnancy should be avoided for 4 weeks after receiving it. Breastfeeding and close contact with pregnant women are not considered to be contraindications to the MMR vaccination. Patients who are severely immunocompromised should not receive the MMR vaccine, since replication of viruses in the vaccine can be prolonged in these patients, potentially leading to infection. Patients who are severely immunocompromised may include those with: Symptomatic HIV infection. Leukemia, lymphoma, or generalized malignancy. Chemotherapy or radiation treatment. Congenital immunodeficiency. Patients receiving high doses of corticosteroids (more than 2 mg/ kg per day or more than 20 mg per day for 14 days or more) are also considered immunocompromised and should avoid MMR vaccination for at least 1 month after cessation of corticosteroid therapy. Patients taking low doses, short-term therapy (less than 14 days), or topical treatments with corticosteroids may be vaccinated. Patients receiving high doses of corticosteroids given daily or every other day for less than 14 days can be considered candidates for MMR vaccination immediately after the end of corticosteroid treatment, but some experts recommend waiting for 2 weeks after the completion of therapy; these patients should be assessed on a case-by-case basis. Adverse reactions to MMR vaccination The most common adverse reaction to MMR vaccination is fever, and this reaction is most often associated with the measles component of the vaccine. Between 5% and 15% of patients receiving a MMR vaccine can develop a fever of 103 F or higher. The fever often occurs 7 to 12 days after vaccination and commonly lasts 1 or 2 days. Most patients who develop a fever in response to the MMR vaccine are otherwise asymptomatic. Studies comparing the use of MMR and MMRV vaccines in children 12 to 23 months old found that fevers were observed in 14.9% of patients who received a MMR vaccine and 21.5% of patients who received a MMRV vaccine. The use of separate MMR and varicella vaccinations in this population will help minimize the risk of fever. Vaccines containing measles and rubella have the potential to cause a transient rash. This rash often appears 7 to 10 days after vaccination, and has been reported in approximately 5% of vaccine recipients. The MMR vaccine can rarely cause low platelet counts, or thrombocytopenia, within 2 months of vaccination. It is estimated Leukemia patients who are in remission and have not received chemotherapy for a minimum of 3 months may receive MMR vaccination. Asymptomatic HIV-infected patients without severely compromised immune systems should be considered as candidates for MMR vaccination, due to the high risk of severe disease in these patients. Patients who have acute moderate to severe illnesses should wait until the illness has improved before receiving a MMR vaccine, to prevent complicating the management of severe illness with adverse reactions to the vaccines. Minor illnesses, such as ear infections, and concurrent antibiotic therapy are not considered contraindications to MMR vaccination. The use of products containing antibodies, such as whole blood, packed red blood cells, or IG, can alter the development of antibodies after MMR vaccination. The timeframe for delaying vaccination varies greatly depending on the concentration, quantity, and length of treatment with these products. The timeframe for vaccination in these patients should be considered on a case-by-case basis. Patients with a history of a low platelet count (i.e., thrombocytopenia) may be at a higher risk of developing thrombocytopenia after receiving MMR vaccination, although no deaths have been reported due to vaccine-induced thrombocytopenia. Benefits and risks should be considered in these patients to determine if vaccination is appropriate. Personal or family history of febrile seizures or epilepsy should be considered a precaution for MMRV vaccination. Since children less than 4 years old with this history are at a higher risk of developing febrile seizures, separate vaccinations for MMR and varicella should be administered in this age group to minimize risks. The MMR and MMRV vaccinations have the potential to suppress the response to tuberculin skin testing in patients infected with tuberculosis. If tuberculin skin testing is necessary, it can be administered at the same time as MMR or MMRV vaccinations; otherwise tuberculin skin testing should be delayed for at least 4 weeks after vaccination [3]. that this reaction occurs at a rate of one case per 30,000 to 40,000 vaccinations. The risk of developing thrombocytopenia may be higher in patients with a history of thrombocytopenia. Since the risk of thrombocytopenia is higher with measles or rubella infection than it is with vaccination, the benefits of vaccination often outweigh the risks. Joint pain, also known as arthralgia, and other joint symptoms have been reported in up to 25% of adult women who receive MMR vaccination, and are often associated with the rubella component of the vaccine. Minor injection site reactions have also been reported with MMR and MMRV vaccinations. To date, there is no evidence that MMR vaccination is linked to autism or other autism spectrum disorders. No increased risk of adverse effects has been noted following the administration of MMR vaccine in patients who are already immune to the diseases contained in the vaccine [3]. Page 89

6 Vaccine components The MMR and MMRV vaccinations are available in freeze-dried powder form and are reconstituted with preservative-free sterile water immediately before injection. The vaccines contain small amounts of Vaccine storage and administration The MMR vaccine can be stored in the refrigerator, at temperatures of 35 F to 46 F (2 C to 8 C), or in the freezer, between -58 F and +5 F (-50 C and -15 C). The MMRV vaccine must be stored in the freezer, due to the varicella component. MMR vaccines may be stored in the freezer alongside MMRV vaccines to prevent confusion and inappropriate storage of MMRV vaccines in the refrigerator. neomycin, sorbitol, gelatin, and human albumin. MMR and MMRV vaccines do not contain thimerosal [3]. Diluents may be stored in the refrigerator or at room temperature. Both vaccinations should be protected from light. Once reconstituted, the MMR vaccine must be used within 8 hours, and the MMRV vaccine must be used within 30 minutes. Reconstituted vaccine not used within these timeframes must be discarded. To administer the MMR vaccine, 0.5 ml should be injected subcutaneously behind the upper arm [3]. Mumps Definition Mumps is a contagious viral illness that is spread through respiratory droplets or contact with infected saliva. It is initially characterized by fever, headache, fatigue, loss of appetite, and muscle aches. These symptoms are followed by swelling of the salivary glands (parotitis), which are located under the ears or jaw on the sides of the face. History of mumps Hippocrates first described the symptoms of mumps thousands of years ago, in the 5th century BC. Before a vaccination was developed, outbreaks occurred every 2 to 5 years, especially among people aggregating in confined areas, such as school-aged children. Mumps outbreaks were incredibly common among military personnel in World War I. It was not until 1934 that Johnson and Goodpasture discovered that mumps was caused by an agent present in the saliva. This agent Epidemiology of mumps After the release of the live attenuated vaccine, mumps was classified as a nationally reportable disease in the United States in The introduction of the live vaccine significantly decreased reported mumps cases, from an estimated 212,000 cases in 1964 to an average of 3,000 cases per year between 1983 and A resurgence of mumps occurred in 1987, with 12,848 cases of mumps reported that year. The most commonly affected individuals during this time were children and young adults from 10 to 19 years of age. Many of the affected individuals during these outbreaks were born before the routine recommendation of mumps vaccination, and before comprehensive state immunization requirements for mumps were developed. Several outbreaks among populations who were highly vaccinated with 1 dose of mumps vaccine were also reported during this resurgence, demonstrating that 1 dose of the mumps vaccine may not be enough to prevent transmission of mumps. This led to the addition of a second dose to the vaccination recommendations. The number of reported cases of mumps declined steadily from 5,712 cases in 1989 to a mere 258 cases in However, a multistate outbreak of 6,584 cases occurred in 2006, mostly among Midwestern college Swelling in other parts of the body, such as the testicles and ovaries, can also be associated with mumps. Mumps can be prevented through the use of immunizations administered following recommended vaccination schedules [9]. was determined to be a virus, and it was first isolated in Isolation of the mumps virus allowed for the first vaccine to be developed in This single-entity inactivated vaccine provided only short-term immunity, and was replaced with a live attenuated vaccine created by Maurice Hilleman. He used viral strains that he was able to isolate from his own daughter s case of mumps, and called it the Jeryl Lynn strain. This live attenuated vaccine was released in 1967 [9]. students living in dormitories. The following 2 years saw low numbers of mumps cases, but another outbreak began in the summer of The 2009 outbreak began when an 11-year -old male picked up the virus in the United Kingdom, where an outbreak was occurring, and brought it back to New York, resulting in 3,502 reported cases of mumps. This outbreak was largely confined to Orthodox Jewish communities, which comprised 97% of the reported cases, with over 50% of cases occurring in children aged 5 to 17 years. Of the patients whose vaccination status was reported, 90% of patients received 1 dose of mumps-containing vaccine, and 76% of patients received 2 doses of the vaccine. High vaccination rates were thought to limit the size and extent of this outbreak [9]. Outbreaks of mumps are ongoing. In 2014, a mumps outbreak among professional hockey players and close contacts affected approximately 20 players, despite the widespread use of vaccination. Although cases of mumps can occur in vaccinated individuals, maintaining high vaccination rates is crucial to controlling outbreaks and preventing the spread of disease [10]. Symptoms of mumps The mumps virus is acquired through respiratory droplets or contact with infected saliva, and has an average incubation period of 14 to 18 days, though it can range from 12 to 25 days. During the incubation period, the virus replicates in the nasal passages and nearby lymph nodes. After the incubation period, the virus enters the bloodstream and can spread to various tissues, including the salivary glands, central nervous system, pancreas, ovaries, and testes. Inflammation can occur in infected tissues, leading to the characteristic symptoms of mumps as well as other complications [9,11]. When symptoms begin after the incubation period, they often start off as nonspecific symptoms, including low-grade fever, anorexia, myalgia, malaise, and headache. Viral spread to tissues leads to the most common distinguishing symptom of parotitis, or inflammation of the salivary glands located under the ear or jaw on the side of the face. Parotitis occurs in 30% to 40% of patients with mumps, and can occur on one or Page 90

7 both sides of the face. It tends to occur in the first 2 days of symptom onset and may be initially described as an earache or jaw tenderness. Mumps symptoms generally decrease after a week and often resolve 10 days after onset. Up to 20% of mumps infections may be Complications of mumps Due to the ability of the mumps virus to spread through the bloodstream to various tissues to cause inflammation, several complications can occur. Viral spread to the central nervous system can cause aseptic meningitis, or the presence of inflammatory cells in cerebrospinal fluid. Asymptomatic aseptic meningitis occurs in 50% to 60% of patients. Symptomatic aseptic meningitis is less common, occurring in up to 15% of patients, and is characterized by headache and stiff neck. Symptomatic cases often resolve within 3 to 10 days without residual effects, though cases of seizures, paralysis, and nerve palsies have been reported. Adults seem to be at a higher risk of aseptic meningitis than children, and males are affected more than females, at a ratio of 3 to 1. Up to 50% of mumps patients with aseptic meningitis can present without salivary gland swelling. Encephalitis, or inflammation of the brain, can also be caused by mumps, and has been reported at a rate of 5 cases of encephalitis per 1,000 cases of mumps. The prognosis for patients with encephalitis caused by mumps is generally good and permanent damage is rare, though neurologic damage and death are possible. Death as a result of mumps-induced encephalitis can occur in 1.4% of patients with encephalitis. Inflammation of the testicles, or orchitis, is the most common complication in male patients who are past puberty. Up to 50% of postpubertal males experience orchitis, and it often occurs after the onset of salivary gland swelling, but can occur before, simultaneously, or alone. It occurs in both testes in approximately 30% of cases. Orchitis often begins abruptly, with swelling and tenderness of the testes, nausea, vomiting, and fever. Swelling often resolves in 7 days, but tenderness can last for several weeks. Between 35% and 50% of mumps patients with orchitis experience some testicular atrophy. Development of complete sterility is rare, though decreased fertility can be seen in approximately 13% of patients. Inflammation of the female gonads is much less common than orchitis. Approximately 5% of females presenting with mumps after puberty experience ovarian inflammation, or oophoritis. Oophoritis Diagnosis and laboratory testing for mumps Mumps should be suspected based on the clinical presentation of the patient, especially in those presenting with salivary gland swelling or in males with testicular swelling. Laboratory confirmation of mumps is strongly recommended in all suspected patients. Swab samples should be collected from the salivary glands of suspected patients as soon as possible upon initial presentation; blood samples should also be collected for analysis. Treatment of mumps There are no FDA-approved medications to slow or reverse the viral progression of mumps. Treatment of mumps should be focused on relieving symptoms through supportive care and preventing or addressing complications. Patients should be encouraged to maintain adequate hydration. Acidic foods and liquids should be avoided as they may contribute to difficulty swallowing. Analgesics such as ibuprofen or acetaminophen may be used to alleviate headaches or discomfort associated with salivary gland swelling. Cold or warm packs can be applied topically to the salivary glands for comfort. Patients with orchitis may require stronger analgesics, and can use scrotal supports, ice packs, and bed rest to help control pain. asymptomatic. Between 40% and 50% of mumps patients experience only nonspecific symptoms or only respiratory symptoms. Patients who are infected with mumps are considered to be contagious from 3 days before until 4days after symptom onset [9]. may be confused with appendicitis, and has not been shown to cause impaired fertility. Inflammation of the pancreas, or pancreatitis, is also a possible complication of mumps. The occurrence of pancreatitis is infrequent, occurring in approximately 5% of mumps patients. Mumps-induced pancreatitis can be associated with transient and often reversible increases in blood sugar. Cases of diabetes mellitus caused by mumps have been reported, but the investigation of this relationship has not been conclusive. The mumps virus can cause hearing loss, and deafness is seen at a rate of approximately one case of deafness per 20,000 cases of mumps. Of those patients that develop hearing loss from mumps, approximately 80% present with one-sided hearing loss. Changes in hearing may be related to reactions in the vestibular system of the ear. The onset of hearing loss is often sudden and can be permanent or transient. Women who are pregnant when they become infected with mumps are at an increased risk of spontaneous fetal loss and fetal death, especially in the first trimester. Incidence rates of fetal loss have been reported to be as high as 27%. Mumps has not been found to cause congenital abnormalities. Widespread use of mumps vaccination has greatly reduced the incidence of this adverse reaction, but pregnant women should continue to remain cautious around known mumps cases. Changes in electrocardiogram readings that correlate with inflammation in the middle layer of the heart wall, known as myocarditis, can be seen in 3% to 15% of mumps patients. Myocarditis related to mumps is generally asymptomatic, but rare reports of symptomatic myocarditis have occurred, and more rarely, death has been reported. An average of one death caused by mumps per year has been reported from 1980 to Over 50% of these fatalities occurred in people over 19 years of age. Other complications of mumps include redness or swelling of the joints (arthritis), joint pain (arthralgia), and inflammation of the kidneys (nephritis) [9,11]. Enzyme immunoassay (EIA) can analyze the levels of immune system markers IgM or IgG, and is the most commonly used test to diagnose mumps. IgM antibody levels can be measured in the first few days of symptom onset, and peak approximately 7 days after symptom onset. However, like measles and rubella, IgM may be missing in patients who received any mumps-containing vaccinations, so negative test results should not be used to rule out mumps [9]. Patients with severe complications may need to consult with specialists based on their condition. For example, patients with encephalitis may need to consult with a neurologist for treatment. Since mumps is a contagious illness, the CDC recommends that mumps patients be isolated for 5 days after swelling of the salivary glands begins. Hospitalized mumps patients should be on droplet precautions to prevent the spread of disease [12,13]. Page 91

8 Post-exposure prophylaxis IG is not considered to be effective as post-exposure prophylaxis for mumps. A study assessing the effectiveness of a third dose of MMR vaccine as post-exposure prophylaxis to mumps was conducted during the 2009 New York outbreak among Orthodox Jewish patients. A third dose of MMR vaccine was administered to household contacts of infected patients within 5 days of onset of mumps in the infected patient, and attack rates were compared between 3-dose recipients Vaccination against mumps Following the release of the live attenuated mumps vaccine in 1967, the mumps vaccine was initially considered a low priority by the ACIP. Their recommendations were changed in 1972 to indicate that the vaccine was important for teenagers and adults who were highly affected by outbreaks. In 1977, the ACIP recommended that all children 12 and older should receive the mumps vaccine, to ensure Efficacy of mumps vaccination Immunization with the mumps vaccine allows for development of measureable antibodies in over 97% of patients. Studies conducted from 1973 to 1989 established that 1 dose of mumps or MMR vaccine proved an effectiveness of 75% to 91% against mumps. Due to the range of effectiveness of a single dose of mumps vaccine, a second dose to be given to children 4 to 6 years of age was recommended in 1989 to increase immunity in school-aged children. Vaccine-induced immunity is thought to last more than 25 years, and is believed to be lifelong [9,11]. An increase in cases of mumps among vaccinated patients prompted Dayan et al to research the efficacy of the mumps vaccine in They aggregated results from several studies that looked at vaccine effectiveness during outbreaks and found 23 studies that assessed the effectiveness of 1 dose of the mumps vaccine. They found that 1 dose created immunity that ranged based on the strain of mumps they studied. One dose was found to be 72% to 91% effective against the Jeryl Lynn strain, 54% to 93% effective against the Urabe strain, and 0% to 33% effective against the Rubini strain. Effectiveness of 2 doses was reported in 3 studies, and was found to range from 91% to 94.6%. Vaccine schedule Recommendations for the use of a MMR vaccine to induce mumps immunity follow the recommendations for measles and rubella. Children should receive their first vaccine after 12 months of age, and a second dose should be administered between 4 and 6 years of age, before the child enters school. Mumps-containing vaccine administered before 12 months of age should not be counted toward and 2-dose recipients. Attack rates were 0 among recipients of 3 doses of MMR vaccine, compared to 5.2% attack rates among 2-dose recipients, though these results were not found to be statistically significant. Study authors concluded that although a third dose did not produce significant effects, it might show some benefits in the context of certain outbreaks [9,14]. teenagers and adults would be protected. The 1980s saw further changes to mumps vaccine recommendations, to accommodate changes to the recommendations for measles vaccination, found in the combination MMR vaccine. Single-entity mumps vaccinations are no longer available in the United States [9,11]. The authors noted that there was evidence of immunity wearing off over time, which may have contributed to outbreaks of mumps. Dayan et al noted that several studies found people who received mumps vaccination more than 5 years before the outbreak were at a higher risk of contracting mumps than people vaccinated less than five years before an outbreak. In addition, differences between the vaccine strain and viral strains found in outbreaks were also considered to be a contributing factor to outbreaks. Many outbreaks were caused by the Rubini strain, against which the mumps vaccine was not found to be highly effective. Dayan et al noted that although vaccine effectiveness reported in clinical trials was higher than the effectiveness they found reported during outbreaks, there was still significant vaccine effectiveness when compared to unvaccinated individuals. Between 31% and 42% of unvaccinated people contracted mumps in comparison to 4% to 13% of people who received 1 dose of mumps vaccine, and 2% to 3% of people who received 2 doses of vaccine. The authors concluded that there is a need for more effective mumps vaccines, in addition to a review of the current policies surrounding vaccinations, to prevent future outbreaks [15]. completion of the vaccine schedule. All adults born after 1957 should have documentation of at least 1 dose of mumps-containing vaccine. Adults born before 1957 are presumed to have immunity to mumps, but those working in high-risk settings should ensure they have been immunized with at least 1 dose of MMR vaccine [9]. Adverse reactions to mumps component of vaccination The mumps portion of MMR vaccinations is associated with very few side effects. The majority of adverse effects reported with MMR vaccination are related to the measles or rubella portions of the vaccine. Rare cases of salivary gland swelling, testicular swelling, and fever have been reported. Allergic reactions to mumps-containing vaccine are possible, and can include rash and itching. If these symptoms occur, they are often transient and mild. Definition Rubella, also known as German measles or 3-day measles, is a viral infection that is transmitted through airborne respiratory droplets. The word rubella is a derivation of a Latin word meaning little red. The severity and characterization of rubella can vary greatly, with nearly half of infected patients presenting without symptoms. Age can Rubella Cases of central nervous system adverse events, including deafness, have been reported within 2 months of mumps vaccination, and are calculated to occur in approximately 1 case per 800,000 doses of mumps vaccine. However, the Institute of Medicine (IOM) concluded that there is not enough evidence to link the mumps vaccine with central nervous system adverse events [9]. determine the clinical manifestation of the disease. Younger children often experience mild symptoms, rash, and swelling of lymph nodes in the neck behind the ear, while older children and adults can experience arthritis, arthralgia, or thrombocytopenia. Page 92