Pathogenesis of Mumps Infection

C. Pathogenesis

Mumps is transmitted by droplet spread or by direct contact. The primary site of viral replication of the epithelium of the upper respiratory or the GI tract or eye. The virus quickly spreads to the local lymphoid tissue and a primary viraemia ensues, whereby the virus spreads to distant sites in the body. The parotid gland is usually involved but so may the CNS, testis or epididymis, pancreas and ovary. A few days after the onset of illness, virus can again be isolated from the blood, indicating that virus multiplication in target organs leads to a secondary viraemia Parotitis is the most frequent presentation, occurring in 95% of those with clinical symptoms. Occasionally, meningitis may precede parotitis by a week. Virus is excreted in the urine in infectious form during the 2 weeks following the onset of clinical illness. It is not known whether virus actually multiplies in renal tissues or whether the virus is of haematogenous origin. Life-long immunity is the rule after natural infection, but reinfections can occur and 1 - 2% of all cases are thought to be reinfections.
 

D. Clinical_Features

The incubation period is 16 - 18 days but may vary from 14 - 25 days. Parotid swelling develops in 95% of those with clinical illness. The rate of subclinical infection varies with age, but is on average 30%. In a small proportion of patients, the symptoms may resemble mild URTI. Typically, a prodromal illness consisting of headache, malaise, myalgia and low grade fever occurs 1 - 2 days before the onset of parotid enlargement. Patients with classic mumps develop enlargement of one parotid gland, followed 1 - 5 days later by enlargement of the contralateral gland. The patient complains of pain and tenderness in the area of the gland. The submandibular and sublingual glands may occasionally be involved. The parotid swelling starts to subside after 4 to 7 days. Virus shedding into the saliva begins a couple of days before the onset of parotitis and ends 7 to 8 days later.

Complications

All the other manifestations of mumps can be regarded as systemic complications of mumps rather than as true complications.

1. Meningitis ;- Aseptic meningitis occurs in 10% of patients with mumps but as many as 50% show abnormalities in the CSF. Mumps is the most frequent causative agent of aseptic meningitis, in many countries being responsible for 10 - 15% of all cases. Symptoms are indistinguishable from other types of aseptic meningitis and can start one week before parotid swelling before parotid swelling to 3 weeks after it. The CSF reveals a lymphocytosis of usually below 500 lymphocytes/mm³, normal or elevated protein. Virus can be isolated from the CSF during the first 2 to 3 days after onset. Later, specific antibodies can demonstrated in the CSF. Symptoms of meningitis subside 3 to 10 days after onset and recovery is usually complete. A study suggests that the majority of cases of meningitis occur without apparent parotiditis.
   
2. Encephalitis ;- encephalitis occurs rarely as a complication of mumps, where lesions are found in the brain and spinal cord. The incidence of encephalitis is around 1 in 6000 cases of mumps. Probably both direct viral invasion and allergic inflammatory reactions lie behind the nervous tissue damage. Clinical features suggesting encephalitis are convulsions, focal neurological signs, movement disorder and changes in sensory perception. Sometimes polio-like paralysis ensues and fatalities have been reported.
   
3. Hearing Loss ;- before vaccinations, mumps used to be one of the leading causes of hearing loss in children and young adults. In most cases, the hearing loss is transient but permanent dysfunction may occur. Hearing problems did not correlate with meningitis and appears to be due to direct damage tothe cochlea. The incidence of hearing loss is estimated to be in the region of 1 per 15,000 cases.
   
4. Orchitis and oophoritis ;- orchitis and oophoritis are more likely to occur after puberty where the incidence is 20 - 30%, and in 20 - 40% of cases, there is bilateral involvement. Men are much more likely to be affected than women.
   
5. Pancreatitis ;- the exact incidence of pancreatitis is hard to determine but is thought to be as high as 5%.
6. Arthralgia ;- arthralgia affecting a large joint may develop 2 weeks after parotitis. They are more frequent in young male adults.
7. Myocarditis ;- this can usually only be found on ECG examination in 10 - 15% of patients. Rarely, congestive heart failure and deaths have been reported.
8. Transient Renal Dysfunction ;- this is a frequent complication of clinical mumps. Cases of symptomatic nephritis following mumps are unusual.
9. Insulin Dependent Diabetes ;- there is some epidemiological evidence to suggest that mumps may be a triggering mechanism for IDDM. It is thought that immunological mechanisms may be involved and certain HLA-D haplotypes are particularly susceptible.
10. Abortion ;- if a pregnant woman contracts mumps during her pregnancy, there is increased risk for abortion. This is thought to be due to hormonal imbalances caused by virus infection.
11. Thyroiditis ;- there is evidence for a role of mumps virus in the causation of subacute thyroditis. However, the evidence is not strong.  

E. Laboratory Diagnosis

During mumps infection, several non-specific findings may be present in the blood. The WBC may be low with lymphocytes predominating. ESR and CRP may be normal or slightly elevated. Amylase levels may be elevated.

1. Serology ;- a serological diagnosis is usually made by finding a significant increase in Ab titres in 2 serum samples taken 10 - 14 days apart. In some cases, the detection of IgM may be used to diagnosis acute infection. Although only 1 serotype of mumps exist, cross-reactions between mumps virus and paramyxovirus makes serological results difficult to interpret on occasions. Several techniques are available :

1. CFT - the CFT is still the widely used for the diagnosis of mumps. Two antigenic preparations are commonly used, the V antigen (consists mainly of HN glycoprotein), and the S antigen (consists mainly of the NP). Antibodies against S appear early and are short-lived, whilst antibodies to V antigens appear slowly but persists longer. By comparing titres using the two different antigens, it is often possible to make a serological diagnosis early in the course of illness. However, due to problems with cross-reactivity, a paired serum sample is always needed for a reliable by CFT.
2. HAI - this test measures antibodies similar to those reacting with the V antigen in the CF test.
3. Neutralization test - virus neutralization has long been regarded as the most reliable serological marker for immunity but is very tedious to carry out and thus rarely used.
4. SRH - this technique has been adapted for use for the diagnosis of mumps.
5. Solid phase ELISA or RIA - various assays are available for the determination of IgM and IgG. However, capture IgM assays are liable to interference from Rheumatoid Factor. Elisa tests are useful in the measurement of mumps antibodies in CSF. The greater sensitivity allows the determination of the exact CSF/serum ratio and a ratio of greater than 100 signifies intrathecal synthesis. However, the blood-brain barrier should be intact and proper controls should be used. This may be an unrelated antibody or albumin.  

2. Virus Isolation ;- virus isolation may be carried out by allantoic inoculation of 6 day old embryonated eggs or by tissue culture methods. Virus can be isolated from the CSF during the first 2 - 3 days after the onset of disease, and is present in urine and saliva for 2 to 3 weeks. Monkey kidney cells are generally used for virus isolation where a CPE is seen which consists of the formation of syncytia and the focal rounding of cells. Virus identification can be performed by neutralization or inhibition of haemadsorption by specific sera.

Syncytial formation caused by mumps virus. Note the presence of red blood cells on the surface of the cell sheet (haemadsorption). Courtesy of Linda Stannard, University of Cape Town, S.A.

F. Management and Prevention

No specific treatment is available for mumps. Uncomplicated parotitis seldom require treatment except adequate. Some authorities recommend a short course of corticosteriods in severe cases. Mumps is the commonest cause of meningitis and encephalitis in many countries such as USA and Scandinavia and many countries have mumps vaccination as part of their vaccination program. At one time, there was some argument as to whether a vaccination program against mumps was necessary but the combination of mumps with rubella and measles in the same vaccine had swung the argument vastly in its favour. An inactivated vaccine was first used in the 1940s successfully. This has now been replaced by a live attenuated vaccine. The protection rate is over 95% and no adverse reactions are associated with the vaccine. In the USA, where more than 40 million doses of mumps vaccine have been administered, a cost-benefit analysis has been carried out. In a cohort of 1 million people, the vaccine would prevent over 74,000 cases of mumps and 3 deaths and the cost-benefit ratio is 7.4:1. Mumps vaccine is now routinely given as part of the MMR regimen in many countries to all infants.