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| BACTERIOLOGY | IMMUNOLOGY | MYCOLOGY | PARASITOLOGY | VIROLOGY | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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MICROBE RADIO |
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READING: |
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Revised October 2008 TEACHING OBJECTIVES Brief review of structure and properties of measles and mumps viruses. Discussion of viral pathogenesis and disease, epidemiology, prevention and treatment.
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INTRODUCTION 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 (figure 1A).
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Figure 1A Paramyxovirus structure |
PARAMYXOVIRUS FAMILY
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Figure 1B Reported cases of measles in the United States 1960-96 CDC |
MEASLES (RUBEOLA) 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. |
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WEB RESOURCES
Mumps, measles and
rubella vaccine Measles, Mumps, and Rubella -- Vaccine Use and Strategies for Elimination
of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization
Practices (ACIP)
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Uncomplicated disease is characterized by the following:
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.
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.
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Figure 2 The pathogenesis of measles. The virus invades the body via blood vessels
and reaches surface epithelium first in the respiratory tract where there are
only 1-2 layers of epithelial cells then in mucosae (Koplik's spots) and finally
in the skin (rash). Adapted from
Mims et al. Medical Microbiology, 1993, Mosby |
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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.
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3 A  B 
Histopathology of measles pneumonia. Giant cells.
CDC/Dr. Edwin P. Ewing, Jr. epe1@cdc.gov
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E
F
G
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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
(figure 3). There may also be nucleocapsid protein in the nucleus but the
significance of this is unknown. DIAGNOSIS The clinical picture is the first
part of diagnosis; that is exposure
plus upper respiratory tract symptoms, Koplik's spots (table 2) and rash (which is usually
quite characteristic for physicians familiar with measles).
This diagnosis is confirmed by
serodiagnosis,
RT-PCR 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. |
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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.
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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. |
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WEB RESOURCES CDC
(requires Acrobat) |
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. |
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Figure 4 Pathogenesis of mumps
Adapted from Mims et al Medical Microbiology 1993.
Mosby, 1993 |
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Complications of mumps CDC |
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 (figure 4 and table 3) include:
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Mumps epidemiology CDC
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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, RT-PCR 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. This was based on a small study (based on 12 children) and larger studies have failed to establish such a link. Among the findings in such studies reported by CDC (link) are:
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WEB RESOURCES
Facts about MMR vaccines and autism See also: |
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