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Without widespread vaccination, mumps is a common acute disease of children and young adults that is characterized by a nonpurulent inflammation of the salivary glands, especially the parotids. Severe manifestations may include pancreatitis, meningitis and encephalitis with hearing loss or deafness at any age and orchitis or oophoritis in young adults. Most disease manifestations are benign and self-limiting. Both symptomatic and asymptomatic mumps virus infections usually induce lifelong immunity. Rarely, reinfections with wild-type virus leading to typical mumps may occur.
Mumps virus shares many structural properties with the other paramyxoviruses.
Mumps virus belongs to the genus Paramyxovirus and exhibits most characteristics of the Paramyxoviridae. It occurs only in a single serotype and shares minor common envelope antigens with other Paramyxovirus species. The nucleotid-sequence homology between various mumps virus isolates is 90 to 99 percent.
Like other paramyxoviruses, mumps virus initiates infection by attachment of the HN protein to sialic acid on the cell-surface glycolipids and works together with the F protein to promote fusion with the plasma membrane. Following uncoating, the negative-sense viral RNA is transcribed by the RNA-dependent RNA polymerase to mRNAs followed by the synthesis of viral proteins which are essential for the continuation of the replication process. After assembly of the nucleocapsids (RNA, N, L, and P protein) in the cytoplasm, the maturation of the virus is completed by budding.
Mumps virus causes a systemic generalized infection that is spread by viremia with involvement of glandular and nervous tissues as target organs (Fig. 59-3
). The infecting virus probably enters the body through the pharynx or the conjunctiva. Local multiplication of the virus in epithelial cells at the portal of entry and a primary viremia precede a secondary viremia, lasting 2 to 3 days. The incubation period usually is 18 to 21 days, but may extend from 12 to 35 days. Recognizable symptoms do not appear in 35 percent of infected individuals. The virus is carried to the main target organs (various salivary glands, testes, ovaries, pancreas, and brain). Viral replication takes place in the ductal cells of the glands. It is not known how the virus spreads to the central nervous system. Studies in experimental animals suggest that indirect spread occurs by passage of infected mononuclear cells across the epithelium of the plexus to the epithelial cells of the plexus choroideus. Alternatively, direct spread of virus is possible.
Shedding of the virus in salivary gland secretions begins about 6 days before onset of symptoms and continues for another 5 days, even though local secretory IgA and humoral antibodies become detectable during that time. Shedding occurs also in conjunctival secretions and urine. During the first 2 days of illness, the virus may be recovered from blood. In cases of meningitis or early-onset encephalitis, virus can be detected in cerebrospinal fluid and cells during the first 6 days after onset of disease. The virus may persist in tissues for 2 to 3 weeks after the acute stage, despite the presence of circulating antibodies. The main pathogenic changes induced by mumps virus infection in the salivary glands and the pancreas are inflammatory reactions. When the testes are involved, swelling, interstitial hemorrhage, and focal infarcts (leading to atrophy of the germinal epithelium) may occur. Infection of the pancreas disturbs endocrine and exocrine functions, leading to diabetic manifestations and increased serum amylase levels. Mumps virus infection of the pancreas has been reported to be a triggering mechanism for onset of juvenile insulin-dependent diabetes mellitus (IDDM); however, a causal relationship has not been established.
The pathologic reaction to mumps virus infection of brain tissues is generally an aseptic meningitis. Less often, the infection involves the brain neurons (as in early-onset mumps encephalitis). Histopathologic findings are widespread and include neuronolysis and ependymitis, which may lead to deafness and obstructive hydrocephalus in children. One human case of chronic central nervous system mumps virus infection has been described. The late-onset (postinfectious) type of mumps encephalitis is attributed to autoimmune reactions. Histopathologic findings are characterized by perivascular accumulation of mononuclear leukocytes, demyelinization, and overgrowth of glial cells, with relative sparing of the neurons. These findings resemble those seen in postinfectious measles, rubella, and varicella encephalitis.
The most characteristic clinical feature of mumps virus infection is the edematous, painful enlargement of one or both of the parotid glands. Commonly, the submandibular salivary glands are involved and, less frequently, the sublingual glands. Pancreatitis is uncommon as a severe illness. Epididymo-orchitis develops in 23 percent of infected postpubertal males and may lead to atrophy of the affected testicles, although rarely to total sterility. Oophoritis develops in 5 percent of infected postpubertal women. Mumps meningitis occurs in up to 10 percent of patients with or without parotitis. Encephalitis has been reported to occur in 1 in 400 cases of mumps. Transient high frequency deafness is the most common complication (4 percent), and permanent unilateral deafness occurs infrequently (0.005 percent). Primary mumps virus infection in early pregnancy may lead to abortion, but there is no convincing evidence of an increased risk of congenital defects in humans.
Mumps virus infection is followed rapidly by interferon production and then by specific cellular and humoral immune responses. Interferon limits virus spread and multiplication, and its production ceases as virus levels decrease and humoral antibodies and cell-mediated immunity appear. Little is known about cell-mediated immunity to mumps virus; in contrast, the humoral antibody response is well understood.
IgM class-specific antibodies to mumps antigens develop rapidly within the first 3 days after onset of symptoms and persist for approximately 2 to 3 months. The IgG antibodies appear a few days later and persist for life. Circulating antibodies are responsible for the lifelong protection against recurrent disease, but reinfection may occur. Parainfluenza virus infections, particularly with type 3 virus, cause a rise of mumps antibody titers, contributing to the lifelong stability of the mumps antibody. Protective mumps antibody of the IgG class is transplacentally transferred to the newborn and persists in declining titers during the first 6 months of life.
Mumps occurs worldwide. In urban areas the infection is endemic with a peak incidence between January and May. Local outbreaks are common wherever large numbers of children and young adults are concentrated (institutions, boarding schools, and military camps). Epidemics occur every 2 to 3 years. In rural areas, mumps tends to die out until enough susceptible individuals have accumulated and the virus is reintroduced which may lead to large outbreaks. Humans are the only known hosts.
Infection is transmitted by salivary gland secretions, mainly just before and shortly after clinical onset. In asymptomatic infections, peak contagion occurs within a similar period. Mumps virus is transmitted usually by direct and close person-to-person contact and less often by the airborne route. School children (6 to 14 years old) are the main source of spread. Mumps infection is acquired later in childhood than are other paramyxovirus infections; 95 percent of individuals have antibody by age 15. As already mentioned, 35 percent of these infections are subclinical. In remote areas, a much lower percentage of children may be infected.
Active vaccination in the United States has reduced the incidence of reported mumps and mumps complications by more than 90 percent.
Typical cases of mumps involving the salivary glands can usually be diagnosed without laboratory tests. An etiologic diagnosis of other clinical manifestations without parotitis (e.g., meningitis, encephalitis, orchitis, and oophoritis) requires laboratory confirmation. Acute infections can be diagnosed by isolating the virus from saliva, cerebrospinal fluid or urine in cell culture. Serologic evidence of acute infection is obtained e.g. with the ELISA or an immunofluorescence test early after onset of symptoms by demonstrating IgM antibodies in the first serum and later by detecting a significant IgG antibody rise in paired sera. Reinfection after previous vaccination is recognized by high titers of mumps-specific IgG antibody, mostly in the absence of specific IgM. An alternative to antibody detection in serum is the detection of IgM and IgA antibody in saliva which in the acute phase of mumps compares satisfactorily with IgM antibody detection in serum.
In view of the long period of virus shedding and the 35 percent rate of subclinical infection, isolating patients with typical symptoms does little to prevent spread. Passive prophylaxis with mumps immunoglobulin prior to viremia is used for individuals at high risk, such as children with underlying disease, those in hospital wards, postpubertal males, and pregnant women. With the enzyme-linked immunosorbent assay (EIA), the immune status can be assessed in 3 hours so that immunoglobulin is given only to exposed seronegative (susceptible) individuals.
Active immunization against mumps is recommended for all children at 12 to 18 months of age in many countries. A combined live virus vaccine is available for mumps, measles, and rubella (MMR). The mumps component contains attenuated virus grown in chick embryo tissue culture. The vaccine containing Jeryl Lynn strain is well tolerated and safe in contrast to another strain (Urabe Am9). Usually it is effective only when maternal antibodies are absent. The seroconversion rate with the Jeryl Lynn vaccine strain used in the USA is >90 percent. The vaccine-induced antibody titers are lower than those following natural infection. This antibody protects generally against clinical disease but not against reinfection. Long-term vaccine-induced immunity seems to be maintained by inapparent (and sometimes also by apparent) reinfection with mumps wild-type virus and infections with other parainfluenza viruses. In spite of this, antibody may decline to very low or undetectable levels.
Mumps vaccination (two doses) has been responsible, e.g. in the USA for a 95 percent decrease in the annual incidence of reported mumps and mumps complications. To close vaccination gaps and to enhance antibody levels in previous vaccinees, a second dose of vaccine is recommended either at 6 or 12 to 13 years of age.
