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Initial symptoms of mumps are nonspecific, with myalgia, anorexia, malaise, headache, and low-grade fever often seen. The classic clinical manifestation of mumps is enlargement of the parotid gland, which may be unilateral or bilateral. Other salivary glands may be enlarged as well. However, more than half of mumps cases are manifest only by nonspecific symptoms without parotitis. The clinical presentation varies by age group, and asymptomatic infection is common, occurring in up to 20% of cases. Mumps may present with predominantly respiratory symptoms in up to half of cases in children under 5 years old, while parotitis (inflammation of the salivary glands) is more typically seen among school-aged children.
Complications of mumps include those resulting from inflammation of glandular tissues (e.g., orchitis, oophoritis, and pancreatitis) and neurologic complications. Orchitis, usually unilateral, occurs in 20–30% of postpubertal males; testicular atrophy may occur, but sterility is rare. Pancreatitis is reported to occur in about 4% of mumps cases. It is usually mild. An association with diabetes has been suspected but has not been established. Central nervous system involvement as manifested by cerebrospinal fluid pleocytosis is common in mumps infection, occurring in 50–60% of patients. Aseptic meningitis occurs in up to 10% of patients with mumps, with clinical manifestations of severe headache, photophobia, and neck stiffness, often accompanied by nausea and vomiting. Recovery is usually complete and without sequelae in 3–10 days, although many patients require hospitalization. Sensorineural hearing loss occurs in an estimated 1 in 20 000 cases; onset is usually sudden, and hearing loss is permanent. Encephalitis is rare but may result in permanent sequelae such as paralysis, seizures, or hydrocephalus. About 1% of cases of mumps encephalitis are fatal. Serious complications can occur in the absence of parotitis; (Plotkin, 2003; CDC, 2007).
During the first trimester of pregnancy, mumps infection may result in fetal death. There is no increase in congenital malformations among infants born to women who experienced mumps infection during pregnancy, but an association between endocardial fibroelastosis and intrauterine or postnatal mumps infection has been reported.
Mumps virus was first identified by Johnson and Goodpasture in 1934. It is an enveloped, single-stranded RNA virus in the paramyxovirus family. Mumps virus is related to parainfluenza and Newcastle disease viruses, and antibodies to these viruses may cross-react with mumps virus.
The mumps virus genome encodes seven genes. The hemaglutinin-neuraminidase (HN) protein and fusion protein (F) are both surface glycoproteins. The HN protein mediates adsorption of the virus to the host cell, and the F protein mediates the fusion of lipid membranes, allowing the nucleocapsid to enter the cell. Antibodies to the HN protein neutralize the infectivity of the mumps virus. The other five structural proteins are not thought to be important in generating a protective immune response. The gene that encodes the small hydrophobic protein (SH) is the most variable part of the mumps genome. Sequencing of the SH gene forms the basis of the genotyping of mumps viruses (Plotkin, 2003).
Mumps viruses are inactivated by heat, organic solvents, nonionic detergents, oxidizing agents, formalin, drying, and ultraviolet radiation.
Mumps occurs worldwide, and humans are the only natural hosts for mumps virus. Mumps is transmitted by respiratory droplets. In temperate climates in the absence of vaccination there was a strong seasonal pattern, with peak incidence in late winter and early spring, but seasonality has not been reported in tropical countries. The disease is somewhat less contagious than measles and varicella, based on both observational studies and the higher average age of infection of mumps. The incubation period averages 16–18 days, with a range of 14–25 days. Although virus may be isolated over a more extended period, the disease is considered to be communicable from three days before, to the fourth day of, active disease.
In the absence of vaccination, mumps is a common cause of illness of children and adolescents, with highest incidence rates usually seen among 5to 9-year-olds. In countries with a large enough population to sustain endemic transmission, outbreaks are typically seen every two to five years, but outbreaks may be less frequent in isolated or island populations. When an outbreak occurs in a population in which there are many susceptible adults, mumps may lead to high complication rates.
In countries that have achieved high coverage with effective vaccines, mumps has been reduced dramatically (Galazka et al., 1999). In several countries, outbreaks have occurred 10–15 years following introduction of mumps vaccine, with disease occurring in cohorts that were missed as programs were implemented. As mumps virus circulation decreased, children who were not vaccinated had less opportunity to acquire natural disease and therefore remained susceptible. A single dose of vaccine may be effective in 75–90% of children. Some countries that have achieved high, sustained coverage utilizing a two dose schedule of mumps vaccine have reported elimination of indigenous circulation of mumps. However, recent outbreaks have been reported in some countries in spite of high coverage with two doses of vaccine. These outbreaks have tended to occur in settings of close contact where exposure may be intense (e.g., on college campuses) and are of limited size, compared to outbreaks in unvaccinated populations.
Acute mumps infection may be diagnosed by isolation of mumps virus from clinical specimens. The virus can be isolated from saliva, urine, or cerebrospinal fluid (CSF) in a variety of cell lines as well as in embryonated eggs. The preferred sample for virus isolation is a swab from the parotid duct, or the duct of another affected salivary gland. Mumps virus can also be detected by the polymerase chain reaction (PCR); (Plotkin, 2003; CDC, 2007).
The diagnosis can also be confirmed serologically by demonstration of mumps-specific IgM antibodies or by demonstrating a significant rise in mumps-specific IgG antibody levels between acute and convalescent titers. However, in persons who have previously received mumps vaccine but not achieved full immunity to infection, the IgM antibody response may be transient or not occur. A negative serologic test, especially in a vaccinated person, does not eliminate the possibility that mumps is the cause of illness because of the lack of sensitivity of available assays. In the absence of an alternative diagnosis, a person with an illness meeting the clinical case definition of mumps should be reported as a mumps case (CDC, 2007).
Although a number of different serologic assays have been described, the most commonly used serologic test is the enzyme immunoassay (EIA). The sensitivity and specificity of the different EIAs vary, but cross-reactivity with other paramyxoviruses limits their specificity and available IgM EIAs are of low sensitivity – from 24–51% in one recent evaluation (Krause et al., 2007).
Mumps can be prevented by vaccination. Live, attenuated mumps vaccines have been available since the 1960s.
Many different strains have been developed, several of which are currently widely used. Other strains are used only in the country in which they were developed, and some are no longer used. Although one mumps vaccine is no longer recommended because it was found to not provide long-term protection (the Rubini strain, used during the 1990s in some countries in Europe), the most important factors differentiating current mumps vaccines are reactogenicity (the frequency and severity of adverse reactions), availability, and cost.
Mumps vaccine is most frequently administered as a trivalent vaccine, combined with measles and rubella vaccines (MMR), but is also available as monovalent mumps vaccine and bivalent measles–mumps vaccine (MM). In some countries measles, mumps, and rubella vaccines are combined with live attenuated varicella vaccine as a quadrivalent vaccine, MMRV. The minimum amount of virus in a mumps vaccine is set by the national control authority in the country where the vaccine is produced. Mumps vaccines also contain additives, such as sorbitol or gelatin, which are used as stabilizers, and neomycin. The vaccines are supplied as lyophilized powder.
Several mumps vaccines have been found to be composed of more than one clone of attenuated mumps virus. The significance of this finding is unclear. One mumps vaccine, RIT 4385, was derived from one of the two strains that comprise the Jeryl-Lynn mumps vaccine. Other mumps vaccines that contain more than one clone of virus are the Urabe and the Leningrad-3 mumps vaccines. It is unknown whether the heterogeneity of these vaccines contributes in a significant way to the vaccines’ efficacy or adverse event profile.
Mumps vaccine is temperature-sensitive, and the cold chain must be maintained from the time of manufacture until the vaccine is administered. Lyophilized vaccine should be kept frozen at -20ºC or refrigerated between +2ºC and +8ºC until used; if the vaccine contains varicella vaccine, storage and handling requirements may differ. Diluent may be stored at refrigerator temperature or at room temperature. Mumps vaccine should be protected from light both before and after reconstitution. After reconstitution, the vaccine should be administered promptly or stored at +2ºC and +8 ºC for up to 8 h. If reconstituted vaccine is not used within 8 h, the vaccine must be discarded (CDC, 2007).
The Jeryl-Lynn vaccine, named after the child from whom the virus was initially isolated, was developed in the United States and licensed in that country in 1967. It has been the only vaccine used in the United States since the 1970s. The Jeryl-Lynn vaccine contains two different clonal lines of attenuated mumps virus. Studies in industrialized countries have demonstrated that a single dose of Jeryl-Lynn vaccine results in seroconversion in 80–100% of recipients. Postlicensure studies in the United States have found that the effectiveness of one dose of the vaccine ranged from 75–91% in prevention of clinical mumps disease. The Jeryl-Lynn vaccine has not been associated with an increased incidence of aseptic meningitis.
The RIT 4385 mumps vaccine was derived from one of the virus clones contained in the Jeryl-Lynn vaccine. The immunogenicity of the RIT 4385 vaccine appears to be similar to the Jeryl-Lynn vaccine, but there are no comparative data on efficacy or effectiveness.
The Leningrad-3 vaccine was developed in the former Soviet Union and has been used since 1974 in the former Soviet Union and other countries. Among children 1–7 years of age, the Leningrad-3 vaccine produced seroconversion in 89–98% of vaccine recipients, and vaccine efficacy in the range of 91–99%. Information on the incidence of aseptic meningitis following receipt of the Leningrad-3 vaccine is not available.
The Leningrad-Zagreb vaccine was produced in Croatia, from further attenuation of the Leningrad-3 vaccine strain. The Leningrad-Zagreb vaccine is currently produced in both Croatia and India and has been used in many countries. The Leningrad-Zagreb vaccine has been demonstrated to be highly immunogenic, with seroconversion in 87–100% of vaccine recipients, and reported efficacy of 97–100%. Aseptic meningitis has been associated with the Leningrad-Zagreb vaccine, and vaccine strain virus has been isolated from the CSF of aseptic meningitis cases following receipt of vaccine. When MMR vaccine containing the Leningrad-Zagreb mumps vaccine has been used in mass campaigns, clusters of aseptic meningitis cases among recently vaccinated persons have been observed, disrupting immunization programs and stressing health-care services.
The Urabe Am9 vaccine was developed in Japan and first licensed in that country in 1979. Subsequently it was licensed in several European countries and Canada and was manufactured both in Japan and in Europe. Immunogenicity studies in many countries have been formed, with seroconversion rates of 85–100% in most reports. Vaccine effectiveness of 73–87% has been reported. Aseptic meningitis among persons who had recently received the Urabe vaccine was reported in Canada beginning in 1986. Subsequent molecular studies demonstrated the presence of Urabe vaccine strain in the cerebrospinal fluid of these cases, and the vaccine’s license was withdrawn in Canada in 1990. In the United Kingdom, it was estimated that 1 in 11 000 recipients of the Urabe vaccine developed aseptic meningitis, and in 1992 the Public Health Service stopped purchasing the vaccine. When MMR containing Urabe vaccine has been used in mass immunization campaigns, clusters of aseptic meningitis cases have been observed, challenging both the immunization program and the health-care system.
Other mumps vaccines are also in use in Asia. The S79 vaccine was developed in China, and more than 100 million doses have been administered in that country. Several other vaccines, including the Hoshino, Torii, Miyahara, and NKM-46 strains, have been developed and used in Japan.
Persons who have experienced a severe allergic reaction following a prior dose of mumps vaccine or to a vaccine component (e.g., gelatin, neomycin) generally should not be vaccinated with mumps vaccine. In the past it had been thought that persons with a history of anaphylactic reactions to egg antigens were at increased risk of serious reactions after receipt of mumps vaccine produced in chick embryo fibroblasts. However, it is now recognized that most anaphylactic reactions to mumps vaccines are not due to hypersensitivity to egg antigens but to other components of the vaccine, especially gelatin. Mumps vaccine may be administered to egg-allergic persons without special protocols.
Because mumps is a live virus vaccine, mumps vaccines should not be administered to persons with immune deficiency or immunosuppression. However, MMR can be administered to persons infected with human immunodeficiency virus who are not severely immunocompromised. Mumps vaccine should not be administered to pregnant women, although the risk is theoretical.
The most common adverse events following mumps vaccination are headache, fever, and parotitis. In a large comparative study reported by dos Santos et al. (2002), parotid enlargement was reported among 3% of children vaccinated with MMR containing the Leningrad-Zagreb mumps vaccine, 1% of children receiving MMR containing Urabe vaccine, and <1% of recipients of MMR containing the Jeryl-Lynn strain. Other manifestations of mumps disease (e.g., orchitis, sensorineural deafness) are infrequently reported following mumps vaccination. Aseptic meningitis following vaccination has been reported at different frequencies, reflecting in part differences in study design, diagnostic criteria, clinical practice, and susceptibility of the population studied, but also differences in the reactogenicity of the vaccines (Bonnett et al., 2006). The onset of aseptic meningitis usually occurs 2–3 weeks after vaccination, with a median interval of 23 days (range 18–34 days). To date, cases of vaccine-associated aseptic meningitis have been self-limited, with full recovery without sequelae. Meningoencephalitis and other more severe forms of neurological involvement, as are rarely seen with mumps disease, have not been reported in association with mumps vaccine.
The World Health Organization recommends routine mumps vaccination in countries with a well-established, effective childhood vaccination program and the capacity to maintain high vaccination coverage (80% or higher) with measles and rubella vaccines and in which the reduction of mumps incidence is a public health priority. WHO considers measles control and the prevention of congenital rubella syndrome to be higher priority than mumps control; thus, countries should consider the burden of mumps disease, including the socioeconomic impact, in deciding whether to introduce mumps into national immunization programs. According to WHO, two doses of mumps vaccine are required for long-term protection (WHO, 2007b).
As of December 2004, the World Health Organization reported that 109 of 192 Member States included mumps vaccine in their routine national immunization programs. Of the 109, 89 countries routinely administer two doses of mumps vaccine. Mumps vaccine was used routinely in 26 of 27 ‘developed’ countries, but none of the 50 countries classified as ‘least developed’ routinely used the vaccine. Of the 109 countries using mumps vaccine routinely, 105 use trivalent measles-mumps-rubella vaccine. In Kazakhstan, Turkmenistan, and Uzbekistan, single-antigen mumps vaccine is used, and both single antigen and bivalent measles-mumps vaccine are used in the Russian Federation (WHO, 2005).
Most national immunization schedules call for the first dose of vaccine to be given to children at age 12–18 months and a second dose after a minimum interval of one month, usually given before entry into school (WHO, 2007b).
In order to obtain high coverage for multiple cohorts quickly and to protect susceptible older children, adolescents, and adults, many countries have conducted mass immunization campaigns as part of the introduction of MMR into the national immunization program. When a mumps vaccine that is associated with a higher risk of aseptic meningitis (e.g., the Urabe or Leningrad-Zagreb vaccine) is used in a mass immunization campaign, careful planning is required to address the expected adverse events. Guidelines for monitoring, investigating, and managing aseptic meningitis cases should be developed, and health-care workers should receive training on expected rates of adverse events and how to communicate risk (WHO, 2007a; b).
Surveillance for mumps should be conducted to support national objectives for mumps control. When mumps is endemic, WHO recommends routine monthly reporting of aggregated case counts, and that only outbreaks should be investigated. In countries that have achieved high immunization coverage with mumps vaccine and low disease incidence, surveillance should be conducted to identify high-risk populations and to prevent and detect outbreaks of disease. This requires case-based surveillance, with investigations of individual cases of mumps. In countries that have established a goal of interrupting mumps transmission, intensive case-based surveillance of every suspected mumps cases should be conducted (WHO, 2003).
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