VIROLOGY LECTURE FOURTEEN
MEASLES (RUBEOLA) AND MUMPS VIRUSES
Dr. Margaret Hunt
MBIM 650/720 LECTURE: 71
READING: Murray et al., Microbiology, 3rd Ed., Chapter 55
review of structure and properties of measles and mumps viruses.
Discussion of viral pathogenesis and disease, epidemiology,
prevention and treatment.
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. (Rubella
virus is a member of the Togavirus Family and is an enveloped,
non-segmented, positive-sense RNA virus with icosahedral symmetry.)
human parainfluenza viruses (HPIV 1-4)
measles and rubella vaccine (CDC)
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)
Infection is via an aerosol route and the virus is very contagious.
The virus replicates initially in the upper/lower respiratory tract. This
is 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.
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
Respiratory tract symptoms: running nose (coryza), cough
Koplik's spots on mucosal membranes - small (1-3mm),
irregular, bright red spots, with bluish-white speck at center - may get
enormous number, red areas may become confluent (see below).
Maculopapular rash (extends from face to extremities), seems to be
associated with T-cells targeting infected endothelial cells in small
blood vessels (see below).
Infection is prostrating.
Recovery is usually rapid, cell mediated response important (patients
with agamma-globulinemia recover normally).
Tends to be more severe in adults than children.
If patient has an
impaired cell-mediated immune response, there is continued growth in
lungs leading to giant cell pneumonia (such patients may not have a
rash). This is rare, but often fatal.
Since virus grows in
epithelia of the nasopharynx, middle ear, lung, all of these sites may
then be susceptible to secondary bacterial infection. Otitis media and
bacterial pneumonia are quite common.
Outcome 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
1 in 1000 cases may
get encephalitis a few days after the rash disappears. Most patients
(90%) survive encephalitis but there may be complications - deafness,
seizures, mental disorders.
Very rarely (7 in
1,000,000 cases) the patient may get subacute sclerosing panencephalitis
(SSPE). This develops 1-10 years after initial infection. It is a
progressive, fatal disease. Risk factors include acquiring primary measles
at an early age. The incidence of SSPE has decreased since vaccination.
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
ASPECTS OF MEASLES
replication of virus
a well nourished child with good medical care
a malnourished child with poor medical care
is quite common
is experienced more often and is more severe
Koplik's spots WHO/Immunization Action
Conjunctivitis Eyes of child with measles. CDC/Barbara Rice
lesions. There may be secondary bacterial infections of the eyes
and blindness may occur
Maculopapular rash Face of boy with measles. Third day of
This child shows a classic day-4 rash with measles. CDC/NIP/Barbara
hemorrhagic rashes (black measles)
increases malnutrition, halts growth and impairs recovery
Virus in urine
disease in a small proportion of patients
Major cause of
infant death (estimates of 1.5 million deaths per year)
Mims et al. Medical Microbiology, 1993
OTHER CONSEQUENCES OF
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.
replicates in the cytoplasm, but inclusions containing nucleocapsid
protein can 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.
Histopathology of measles pneumonia. Giant cells. CDC/Dr.
Edwin P. Ewing, Jr. email@example.com
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
is simpler but two samples are needed, one 10-21days post rash, and
so takes longer.
It is recommended that all suspect cases in the United States be confirmed
by laboratory testing
Almost all infected
individuals show signs of disease.
There is only one serotype of measles and a single natural infection gives
The main route of
infection is via inhalation. Measles virus is highly contagious. Note the
period of maximum contagiousness is the 2-3 day period before onset
There is an attenuated
virus vaccine. It is currently recommended to give a first dose of
the vaccine at 12-15 months. If given earlier, the recipient does not
mount a strong immune response to the vaccine. A second dose is
administered at 4-6 yrs 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 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.
No antiviral therapy
available for primary disease. Treat complications appropriately.
mump" - to grimace or grin, from the appearance of the patient as a
result of parotid gland swelling. (Note: Other agents can also cause
Association of State
and Territorial Directors of Health Promotion and Public Health Education
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
Pathogenesis of mumps Adapted from Mims et al Medical
Microbiology 1993. Mosby, 1993
ASPECTS OF MUMPS
of replication of virus
Inflammation, parotitis, in a child with mumps. CDC/NIP/Barbara
Virus is shed in saliva from 3 days before to 6 days after
symptoms are often absent or may be unilateral
|Up to 7 days
found in about 10% of cases.
Encephalitis is less common. Usually there is complete
recovery; nerve deafness is a rare complication
rigid tunica albuginea around testis makes orchitis more painful,
more damaging in male
||Common in adults
(20% in adult males), often unilateral; not a significant cause of
complication (There is a possible role in juvenile diabetes)
detectable in milk; mastitis in 10% post-pubertal females
from Mims et al. Medical Microbiology, Mosby, 1993
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.
The average time to
full manifestation of disease is 2-3 wks but there may be fever,
anorexia, malaise, myalgia during prodromal phase.
Symptoms of mumps:
Pain from parotitis
swelling persists 7-10 days
common in males, usually mild
Hearing loss, rare,
usually unilateral. May not have overt mumps. May improve with time
especially severe in adolescent and adult males, usually unilateral,
some degree of testicular atrophy, damage tends to be patchy, rarely
occurs, but very little evidence from controlled studies that mumps
plays any role in diabetes mellitus.
More severe in
immunity is important in recovery.
Approximately 30% of
infections are subclinical.
Parotitis is suggestive (30-40% infections). The disease is confirmed by
isolating the virus or by serology (HI, CF, enzyme immunoasssay).
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.
Man is the only known
natural host. Many (~30%) infections are subclinical. Single serotype.
Mumps is contagious
from ~7 days before infection and becomes clinically apparent at ~9
The vaccine virus does not spread to contacts and gives long-term
immunity. It is given as MMR vaccine (three live, attenuated viruses: mumps,
measles and rubella).
contraindicated in immunosuppressed patients and in pregnant women.
There is no
specific treatment for mumps.