Measles and Mumps virus

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Infections with measles, mumps and rubella viruses are confined to man and occur worldwide. They are all spread primarily via the aerosol route. Each of these viruses exists as a single serotype. MMR (mumps, measles, rubella) vaccine contains live, attenuated forms of all three of these viruses.

Measles and mumps viruses belong to the Paramyxovirus Family and are enveloped, non-segmented, negative-sense RNA viruses with helical symmetry

PARAMYXOVIRUS FAMILY

Paramyxovirus: Members- human parainfluenza virus1 (HPIV 1), human parainfluenza virus3 (HPIV 3). Glycoproteins: HN, F

Rubulavirus: Members- human parainfluenza virus2 (HPIV 2), human parainfluenza virus4 (HPIV 4), Mumps virus. Glycoproteins: HN, F

Morbillivirus : Members: measles. Glycoproteins-H, F

Pneumovirus: Members- respiratory syncytial virus. Glycoproteins- G,F

MEASLES (RUBEOLA)

The word measles is derived from the German word for blister.

Before the advent of the current measles vaccine, there were about 500,000 cases of measles in the United States per year; almost everyone got the measles. But since 1963, the number has fallen precipitously (figure 1B) with a low of only 86 cases in 2001, all of which seem to be imported. In the less developed world, measles still takes its toll with an estimated 30 million illnesses and 770,000 measles-caused deaths in 2000 of which 58% were in Africa

PATHOGENESIS AND DISEASE

Infection is via an aerosol route and the virus is very contagious. It replicates initially in the upper/lower respiratory tract, followed by replication in lymphoid tissues leading to viremia and growth in a variety of epithelial sites. The disease develops 1 - 2 weeks after infection.

Uncomplicated disease is characterized by the following:

Fever of 101 degrees Fahrenheit (38.3 C) or above

Respiratory tract symptoms: running nose (coryza) and cough

Conjunctivitis

Koplik's spots on mucosal membranes - small (1 - 3mm), irregular, bright red spots, with bluish-white speck at center. The patient may get an enormous number and red areas may become confluent.

Maculopapular rash which extends from face to the extremities. This seems to be associated with T-cells targeting infected endothelial cells in small blood vessels

The infection is prostrating but recovery is usually rapid. The peak of infectiousness is before the onset of obvious symptoms (Koplik’s spots, rash). Note some virus shedding occurs during the disease phase, so spread of the virus to other individuals can be somewhat reduced by minimizing contact with others.

The cell mediated response is important since patients with agamma-globulinemia recover normally. Measles tends to be more severe in adults and the very young (under 5 years of age) and is less severe in older children and teenagers.

Complications of measles

If a patient has an impaired cell-mediated immune response, there is continued growth of the virus in the lungs leading to giant cell pneumonia (such patients may not have a rash). This is rare, but often fatal. The reason for the giant cells is that, since F protein can function at physiological pH, it can facilitate cell-cell fusion.

Since virus grows in epithelia of the nasopharynx, middle ear and lung, all of these sites may then be susceptible to secondary bacterial infection. Otitis media and bacterial pneumonia are quite common.

The outcome of the disease is affected by the nourishment of the patient and access to medical care. Measles is still a major killer in underdeveloped countries and several studies in areas with severe vitamin A deficiency problems have found that vitamin A treatment of children with measles has resulted in reduction in morbidity and mortality. Pneumonia accounts for 60% of deaths from measles.

One in 1000 cases may get encephalitis a few days after the rash disappears. Most patients (90%) survive encephalitis but there may be complications such as deafness, seizures and mental disorders.

SUB-ACUTE SCLEROSING PAN ENCEPHALITIS

Very rarely (7 in 1,000,000 cases) the patient may get subacute sclerosing panencephalitis (SSPE). This develops 1 to 10 years after the initial infection. It is a progressive, usually fatal disease and those who survive are severely impaired mentally and physically. First signs are behavioral, followed by loss of motor control and coordination. There are jerky movements known as myoclonic seizures. As the disease progresses speech and swallowing are affected and vision may be impaired. The course of the disease may be a few weeks although it may also last for years.

Risk factors include acquiring primary measles at an early age (usually under two years). The incidence of SSPE has decreased since vaccination against measles was initiated. SSPE is associated with defective forms of the virus in the brain and so it is difficult to isolate infectious virus from such patients. Certain viral proteins are often not expressed, the M protein being frequently absent.

OTHER CONSEQUENCES OF MEASLES INFECTION

Measles can cause temporary defects in the immune response; for example, tuberculin-positive individuals may temporarily give a negative response. There may be reactivation of herpes or exacerbation of tuberculosis with natural measles, but this does not seem to happen with the vaccine strain.

Measles virus replicates in the cytoplasm, but inclusions containing nucleocapsid protein can also accumulate in the nucleus. It is not known if this has any effect on the host cell, but histologically typically giant cells with cytoplasmic and nuclear inclusion bodies are seen.

DIAGNOSIS

The clinical picture is the first part of diagnosis; that is exposure plus upper respiratory tract symptoms, Koplik's spots and rash (which is usually quite characteristic for physicians familiar with measles).

This diagnosis is confirmed by serodiagnosis or isolation. Serodiagnosis by IgG levels is simpler than isolation but two samples are needed, one 10 to 21days post rash, and so takes longer. There is now also an IgM test. It is recommended that all suspect cases in the United States be confirmed by laboratory testing

EPIDEMIOLOGY

Almost all infected individuals show signs of disease. There is only one serotype of measles and a single natural infection gives life-long protection. The main route of infection is via inhalation. Measles virus is highly contagious and the period of maximum contagiousness is the 2 to 3 day period before onset of the rash.

PREVENTION

There is an attenuated virus vaccine that is grown in chicken embryo fibroblast culture. It is currently recommended to give a first dose of the vaccine at 12 to 15 months. If given earlier, the recipient does not mount a strong immune response to the vaccine. A second dose is administered at 4 to 6 years of age, before the recipient enters kindergarten or first grade. This reduces the proportion of persons who remain susceptible due to primary vaccine failure. The vaccine gives long term immunity and the vaccine virus does not spread from the vaccinee.

Immune serum globulin can be used for at risk patients during an outbreak; that is those less than 1 year old or with impaired cellular immunity.

Measles vaccine can cause problems (e.g. fatal giant cell pneumonia) in those with severely compromised cell-mediated immunity. No inactivated vaccine is available, due to past problems in which subsequent infection with naturally acquired measles was sometimes associated with an atypical, severe form of measles.

TREATMENT

No antiviral therapy available for primary disease. Complications should be treated appropriately.

MUMPS

The name comes from the British word "to mump", that is grimace or grin. This results from the appearance of the patient as a result of parotid gland swelling although other agents can also cause parotitis. Clinically, mumps is usually defined as acute unilateral or bilateral parotid gland swelling that lasts for more than two days with no other apparent cause.

Mumps is caused by a paramyxovirus. There is one serotype of the virus and in an affected patient it can be found in most body fluids including cerebro-spinal fluid, saliva, urine and blood. The virus can be grown in cell cultures and in eggs.

PATHOGENESIS AND DISEASE

Mumps is very contagious and is probably usually acquired from respiratory secretions and saliva via aerosols or fomites. The virus is secreted in urine and so urine is a possible source of infection. It is found equally in males and females. Before 1967, most mumps patients were under 10 years of age but since the advent of the attenuated vaccine, the remaining cases occur in older people with almost half being 15 years of age or older.

Virus infects upper/lower respiratory tract leading to local replication. The virus spreads to lymphoid tissue which, in turn, leads to viremia. The virus thus spreads to a variety of sites, including salivary, other glands and other body sites (including the meninges).

The average time to full manifestation of disease is 2 - 3 weeks but there may be fever, anorexia, malaise, myalgia during prodromal phase. Many mumps infections (up to 20%) result in no symptoms at all and about half of infections result only in the primary respiratory symptoms.

The symptoms of mumps include:

Fever

Parotitis. Pain from parotitis swelling persists for 7 - 10 days. This is the most common feature of mumps and is seen in about 40% of patients. It may be unilateral or bilateral depending on which salivary glands are infected by the virus.

Meningitis. Aseptic meningitis is usually mild. About three times as many males than females get this . In about half of patients the meningitis is asymptomatic. In symptomatic meningitis, which occurs in about 15% of patients, there is stiff neck and headache which usually resolves in up to 10 days with no further problems. Mumps-related meningitis is more severe in adults. In very rare cases mumps can result in encephalitis.

Deafness. Mumps was a leading cause of acquired deafness before the advent of mumps vaccines but nevertheless hearing loss is rare (one in every 20,000 mumps cases). It is usually unilateral. The patient may not, in fact, have overt mumps. Deafness may improve with time but is usually permanent.

Orchitis (testicular inflammation). This is especially severe in adolescent and adult males and occurs in about 50% of cases. Sometimes, it occurs along with parotitis. The painful swelling diminishes after about seven days but tenderness can last for weeks. In 70% of cases, orchitis is unilateral and results in some degree of testicular atrophy. Damage tends to be patchy and rarely causes infertility.

Pancreatitis. This is an infrequent side effect of mumps. There is transient hyperglycemia that resolves. However, there is very little evidence from controlled studies that mumps plays any role in diabetes mellitus although outbreaks of diabetes have been reported after mumps outbreaks.

Myocarditis. Myocarditis is observed from electrocardiograms in a minority of patients but is usually otherwise asymptomatic.

Rare complications. These include nephritis, arthralgia (joint pain) and arthritis (joint inflammation)

Mumps is more severe in adults and it seems that cell-mediated immunity is important in recovery. On average, one person dies per year in the United States now that most people are vaccinated.

DIAGNOSIS

Approximately 30% of infections are sub-clinical. Parotitis is suggestive as it occurs in 30 - 40% of infections but there are other causes of parotitis. The disease is confirmed by isolating the virus or by serology. Hemagglutination inhibition, radial hemolysis and complement fixation assays are rather insensitive. Better is enzyme immunoassay which detects IgM or IgG. The level of IgM rise during the prodromal phase and peak at about seven days. Normally, when testing for IgG a specimen is taken during the acute disease and then during the convalescent phase. The latter should show a higher antibody titer than the former.

Complement fixing antibody to the S (soluble) antigen (nucleocapsid protein) is seen for a few months after infection and is used to diagnose a recent infection. However, one needs to be careful as there is some cross reaction with other human parainfluenza virus nucleocapsid proteins. CF antibody to the viral envelope (V antigen) persists.

EPIDEMIOLOGY

Man is the only known natural host and the disease is found worldwide. There is no 'carrier state'. Since many (about 30%) infections are sub-clinical, spread is usually via these persons. Mumps is contagious from about 7days before the infection becomes clinically apparent and continues until about 9 days afterwards.

PREVENTION

Until the development of the highly effective attenuated vaccine, mumps was a very common disease.; for example, there were 212,000 reported case in the United States in 1964. Occurrence dropped to about 3,000 cases by the mid 1980's which is about one case per 100,000 population. In 2001, there were 231 United States cases. In 1986/87, there was a jump in mumps in people in the 10 - 19 years age group (12,848 cases) which was attributable to the fact that these people were born before routine immunization. Vaccine failure may also have contributed.

The vaccine virus, which is made in chick embryo fibroblasts, does not spread to contacts and gives long-term immunity (greater than 95% efficacy with immunity lasting more than 25 years). It is usually given as MMR vaccine that contains three live, attenuated viruses: mumps, measles and rubella. It is also available as a single virus preparation or combined with the rubella vaccine. Normally, two doses separated by four weeks are recommended for children more than one year of age.

Vaccine is contraindicated in immunosuppressed patients and in pregnant women, although there is no evidence that the vaccine can damage the fetus. Also people who have severe allergic reactions after a previous mumps vaccination should not receive the MMR vaccine.

The virus is rapidly inactivated by organic solvents such as chloroform and ether (as would be expected of enveloped viruses) and also by UV light and formaldehyde.

TREATMENT

There is no specific treatment for mumps.

MMR VACCINE AND AUTISM

There have been reports in the media linking autism to administration of the MMR vaccine which used to contain thimerosal as a preservative. Thimerosal contains mercury. There are no data that connect thimerosal to any disorder including autism. Nevertheless, the use of mercury-containing preservatives has ceased in the United States. The American Academy of Pediatrics has issued a statement repudiating such a connection