MMR teachig slides

1. single-stranded lipid enveloped RNA virus in the family Paramyxoviridae and genus
Morbillivirus
Highly contagious , less now due vaccine
humans are the only host of measles virus
2 most important in terms of induction of immunity are the hemagglutinin (H) protein and
the fusion (F) protein. The neutralizing antibodies are directed against the H protein, and
antibodies to the F protein limit proliferation of the virus during infection.
introduction of the measles vaccine 1963
The attack rate fell from 313 cases/100,000 population in 1956–60 to 1.3 cases/100,000
in 1982–88
Implementation of the 2 dose vaccine policy and more intensive immunization strategies
resulted in interruption of endemic transmission in the United States in 1993. The current
rate is <1 case/1,000,000 population.
through the respiratory tract or conjunctivae following contact with large droplets
viable virus may be suspended in air up to 1 hr after a source case leaves a room
necrosis of the respiratory tract epithelium small vessel vasculitis on the skin and on the
oral mucous membranes
Fusion of infected cells results in multinucleated giant cells, theWarthin-Finkeldey giant
cells that are pathognomonic for measles
incubation period,;
measles virus migrates to
regional lymph nodes 8-
12d
prodromal illness,
secondary viremia, Virus shedding begins in the prodromal phase. With onset of the
rash, antibody production begins and viral replication and symptoms begin to subside.
exanthematous phase,
recovery
[A primary viremia ensues that disseminates the virus to the reticuloendothelial system. A
secondary viremia spreads virus to body surfaces]
high fever, an enanthem, cough, coryza, conjunctivitis, and a prominent exanthem
The enanthem, Koplik spots, is the pathognomonic sign of measles and appears 1 to 4
days prior to the onset of the rash
discrete red lesions with bluish white spots in the center on the inner aspects of the
cheeks at the level of the premolars.
conjunctival folds and in the vaginal mucosa Symptoms increase in intensity for 2–4
days until the 1st day of the rash. The rash begins around the forehead (around the
hairline), behind the ears, and on the upper neck as a red maculopapular eruption. It
then spreads downward to the torso and extremities, reaching the palms and soles

2. in up to 50% of cases. The exanthem frequently becomes confluent on the face and
upper trunk ( With the onset of the rash, symptoms begin to subside and the rash
fades over about 7 days in the same progression as it evolved, often leaving a fine
desquamation of skin in its wake. Of the major symptoms of measles, the cough
lasts the longest, often up to 10 days. In more severe cases, generalized
lymphadenopathy may be present, with cervical and occipital lymph nodes especially
prominent.
In individuals with passively acquired antibody, such as infants or recipients of blood
products, a subclinical form of measles may occur. The rash may be indistinct, brief,
or, rarely, entirely absent. Likewise, some individuals who have received vaccine
when exposed to measles may develop a rash but few other symptoms. Persons
with inapparent or subclinical measles do not shed measles virus and do not
transmit infection to household contacts.
Children who had received the original formalin-inactivated measles vaccine at times
developed a more severe form of disease called atypical measles. Patients had
onset of high fever and headache followed by the appearance of a maculopapular
rash on the extremities that become petechial and purpuric and progressed in a
centripetal direction. The illness was frequently complicated by pneumonia and
pleural effusions. It is thought that atypical measles was caused by development of
circulating immune complexes that formed due to an abnormal immune response to
the vaccine
reduction in the total white blood cell count, with lymphocytes decreased more than
neutrophils.
IgM antibody appears 1–2 days after the onset of the rash and remains detectable for
about 1 mo
Viral isolation from blood, urine, or respiratory secretions can be accomplished by culture
DIFFERENTIAL DIAGNOSIS.
Exanthem subitum (in infants) and
erythema infectiosum (in older children) may also be confused with measles.
Mycoplasma pneumoniae and
group A streptococcus may also produce rashes similar to measles.
Kawasaki syndrome can manifest many of the same findings as measles but lacks
discrete intraoral lesions (Koplik spots) and a severe prodromal cough, and typically has
elevated neutrophils and acute-phase reactant levels. In addition, the characteristic
thrombocytosis of Kawasaki syndrome is absent in measles

3. . Drug eruptions may occasionally be mistaken for measles.
COMPLICATIONS.
. Morbidity and mortality from measles are greatest in patients <5 yr of age
(especially <1 yr of age) and those >20 yr of age.
Severe malnutrition in children results in suboptimal immune response and higher
morbidity and mortality with measles infection
Low serum retinol levels in children with measles have been shown to be
associated with higher measles morbidity and mortality in developing countries and
in the United States.
Measles infection lowers serum retinol, so subclinical cases of hyporetinolemia may
be made symptomatic during measles. Measles infection in immunocompromised
persons is associated with increased morbidity and mortality.
Pneumonitis occurs in 58% of patients with malignancy infected with measles, and
encephalitis occurs in 20%.
Pneumonia is the most common cause of death in measles. It may manifest as giant
cell pneumonia caused directly by the viral infection or as superimposed bacterial
infection. The most common bacterial pathogens are S. pneumoniae, H. influenzae,
and S. aureus. Following severe measles pneumonia, the final common pathway to
a fatal outcome is often the development of bronchiolitis obliterans.
Croup, tracheitis, and bronchiolitis are common complications in infants and toddlers
with measles.
Acute otitis media is the most common complication of measles and was of
particularly high incidence during the epidemic of the late 1980s and early 1990s
because of the relatively young age of affected children.
Sinusitis and mastoiditis also occur as complications.
Viral and/or bacterial tracheitis are seen and can be life threatening.
Retropharyngeal abscess has also been reported.

4. Measles infection is known to suppress skin test responsiveness to purified
tuberculin antigen. There may be an increased rate of activation of pulmonary
tuberculoses in populations of individuals infected with Mycobacterium tuberculosis.
Diarrhea and vomiting are common symptoms associated with acute measles, and
the gastrointestinal tract has diffuse giant cell formation in the epithelium.
Appendicitis may occur due to obstruction of the appendiceal lumen by lymphoid
hyperplasia.
Febrile seizures occur in <3% of children with measles.
Encephalitis following measles has been a long-associated complication, often with
an unfavorable outcome. Rates of 1–3/1,000 cases of measles have been reported,
with greater numbers occurring in adolescents and adults than in preschool or
school-aged children. This is a postinfectious immunologically mediated
process rather than due to a direct effect by the virus. Clinical onset begins
during the exanthem and presents with seizures (56%), lethargy (46%), coma (28%),
and irritability (26%).
Findings in cerebrospinal fluid include lymphocytic pleocyosis in 85% and elevated
protein concentration. Approximately 15% of patients die, and 20–40% suffer long-
term sequelae, including mental retardation, motor disabilities, and deafness.
Measles encephalitis in immunocompromised patients results from direct
damage to the brain by the virus. Subacute measles encephalitis presents 1–10
mo following measles in immunocompromised patients, particularly those with
AIDS, lymphoreticular malignancies, and immunosuppression. Signs and symptoms
include seizures, myoclonus, stupor, and coma. In addition to intracellular
inclusions, abundant viral nucleocapsids and viral antigen are seen in brain tissue.
Progressive disease and death almost always occurs.
A severe form of measles rarely seen now is hemorrhagic or “black measles.” It
presented with a hemorrhagic skin eruption and was often fatal. Keratitis, appearing
as multiple punctate epithelial foci, resolved with recovery from the infection.
Thrombocytopenia sometimes occurred following measles.
Myocarditis is a rare complication. Miscellaneous bacterial infections have been
reported, including bacteremia, cellulitis, and toxic shock syndrome. Measles during

5. pregnancy has been associated with high maternal morbidity, fetal wastage
and stillbirths, and congenital malformations in 3% of live born infants.
Subacute Sclerosing Parencephalitis (SSPE).
SSPE is a chronic complication of measles with a delayed onset and an outcome
that is nearly always fatal.
It appears to result from a persistent infection with an altered measles virus that is
harbored intracellularly in the CNS for several years. After 7–10 yr the virus
apparently regains virulence and attacks the cells in the CNS that offered the virus
protection. This “slow virus infection” results in inflammation and cell death, leading
to an inexorable neurodegenerative process.
While the age of onset ranges from <1 to <30 yr, the illness is primarily one of
children and adolescents.
Measles at an early age favors the development of SSPE: 50% of SSPE
patients had primary measles before 2 yr and 75% before 4 yr of age. Males are
affected twice as often as females, and there appear to be more cases reported from
rural rather than urban populations. Recent observations from the registry indicate a
higher prevalence among children of Hispanic origin. The pathogenesis of SSPE
remains enigmatic.
Factors that seem to be involved include defective measles virus and interaction
with a defective or immature immune system.
The virus isolated from brain tissue of patients with SSPE is missing 1 of the
6 structural proteins, the matrix or M protein. This protein is responsible for
assembly, orientation, and alignment of the virus in preparation for budding during
viral replication. Immature virus may be able to reside, and possibly propagate,
within neuronal cells for long periods. The fact that most patients with SSPE were
exposed at a young age suggests that immune immaturity is involved in
pathogenesis. In addition, the intracellular location of the virus sequesters it from the
immune system, especially from humoral immunity.
Clinical manifestations of SSPE begin insidiously 7–13 yr after primary measles
infection. Subtle changes in behavior or school performance appear, including
irritability, reduced attention span, or temper outbursts. This initial phase (stage I)

6. may at times be missed because of brevity or mildness of the symptoms. Fever,
headache, or other signs of encephalitis are absent. The hallmark of the 2nd
stage is massive myoclonus. This coincides with extension of the inflammatory
process site to deeper structures in the brain, including the basal ganglia.
Involuntary movements and repetitive myoclonic jerks begin in single muscle groups
but give way to massive spasms and jerks involving both axial and appendicular
muscles. Consciousness is maintained.
In the 3rd stage, involuntary movements disappear and are replaced by
choreoathetosis, immobility, dystonia, and lead pipe rigidity that result from
destruction of deeper centers in the basal ganglia. Sensorium deteriorates into
dementia, stupor, then coma. Stage IV is characterized by loss of critical centers that
support breathing, heart rate, and blood pressure. Death soon ensues. Progression
through the clinical stages may follow courses characterized as acute, subacute, or
chronic progressive.
The diagnosis of SSPE can be established through documentation of a compatible
clinical course and at least 1 of the following supporting findings: (1) measles
antibody detected in CSF, (2) characteristic electroencephalographic findings, or (3)
typical histologic findings and/or isolation of virus or viral antigen in brain tissue
obtained by biopsy or postmortem examination.
CSF analysis reveals normal cells but elevated IgG and IgM antibody titers in
dilutions of >1 : 8. Electroencephalographic patterns are normal in stage I, but in the
myoclonic phase suppression-burst episodes are seen that are characteristic of but
not pathogenomic for SSPE. Brain biopsy is no longer routinely indicated for
diagnosis of SSPE.
Management of SSPE is primarily supportive and similar to care provided to
patients with other neurodegenerative diseases. A recent large randomized clinical
trial compared the use of oral inosiplex (isoprinosine) alone to oral inosiplex and
intraventricular interferon-α2b. The treatment course for both groups was 6 mo.
While there were no differences in the rates of stabilization or improvement at 6 mo
(34% vs 35%), the study concluded that these rates were substantially better than
historically reported spontaneous improvement rates of 5–10%.
Virtually all patients eventually succumb to SSPE. Most die within 1–3 yr of onset
from infection or loss of autonomic control mechanisms. Prevention of SSPE
depends on prevention of primary measles infection through the use of vaccine.

7. SSPE has been described in patients who have no history of measles infection and
only exposure to the vaccine virus. However wild-type virus, not vaccine virus, has
been found in brain tissue of at least some of these patients, suggesting they had
had subclinical measles previously.
TREATMENT.
Management of measles is supportive. Antiviral therapy is not effective in the
treatment of measles in otherwise normal patients. Maintenance of hydration,
oxygenation, and comfort are goals of therapy. Antipyretics for comfort and fever
control are useful. For patients with respiratory tract involvement, airway
humidification and supplemental oxygen may be of benefit. Respiratory failure due to
croup or pneumonia may require ventilatory support. Oral rehydration is effective in
most cases, but severe dehydration may require intravenous therapy. Prophylactic
antimicrobial therapy to prevent bacterial infection is not indicated.
Measles infection in immunocompromised patients is highly lethal. Ribavirin is active
in vitro against measles virus. Anecdotal reports of ribavirin therapy with or without
intravenous gamma globulin suggest some benefit in individual patients. However,
no controlled trials have been performed, and ribavirin is not licensed in the United
States for treatment of measles.
VITAMIN A.
Vitamin A deficiency in children in developing countries has long been known to be
associated with increased mortality from a variety of infectious diseases, including
measles. In the United States, studies in the early 1990s documented that 22–72%
of children with measles had low retinol levels. In addition, 1 study demonstrated an
inverse correlation between the level of retinol and severity of illness. Several
randomized controlled trials of vitamin A therapy in the developing world and the
United States have demonstrated reduced morbidity and mortality from measles.
The American Academy of Pediatrics suggests vitamin A therapy for selected
patients with measles ( Table 243-2 ).
TABLE 243-2 -- Recommendations for Vitamin A Treatment of Children with Measles
INDICATIONS
• Children 6 mo to 2 yr of age hospitalized with measles and its complications (e.g., croup,
pneumonia, and diarrhea). (Limited data are available about the safety and need for

8. vitamin a supplementation for infants <6 mo of age.)
• Children >6 mo of age with measles who are not already receiving vitamin A supplementation
and who have any of the following risk factors:
• immunodeficiency
• clinical evidence of vitamin A deficiency
• impaired intestinal absorption
• moderate to severe malnutrition
• recent immigration from areas where high mortality rates attributed to measles have been
observed
REGIMEN
Parenteral and oral formulations of vitamin A are available in the USA. The recommended dosage,
administered as a capsule, is:
• Single dose of 200,000 IU orally for children ≥1 yr of age (100,000 IU for children 6 mo
to 1 yr of age)
• The dose should be repeated the next day and again 4 wk later for children with ophthalmologic
evidence of vitamin A deficiency
From the American Academy of Pediatrics, Committee on Infectious Disease: Vitamin A treatment
of measles. Pediatrics
PROGNOSIS.
In the early 20th century, deaths due to measles varied between 2,000 and 10,000,
or about 10 deaths per 1,000 cases of measles. With improvements in health care
and antimi crobial therapy, better nutrition, and decreased crowding, the death to
case ratio fell to 1 per 1,000 cases. Between 1982 and 2002, the CDC estimated
there were 259 deaths caused by measles in the United States, with a death-to-case
ratio of 2.5–2.8/1,000 cases of measles. Pneumonia and encephalitis were
complications in most of the fatal cases, and immunodeficiency conditions were
identified in 14–16% of deaths.
PREVENTION.

9. Patients shed measles virus from 7 days after exposure to 4–6 days after the onset
of rash. Exposure of susceptible individuals to measles patients should be avoided
during this period. In hospitals, standard and airborne precautions should be
observed for this period. Immunocompromised patients with measles will shed for
the duration of the illness, and isolation should be maintained throughout.
VACCINE.
Measles vaccine in the United States is available as a monovalent preparation or
combined with the rubella (MR) or measles-mumps-rubella (MMR) vaccine, which is
the recommended form in most circumstances ( Table 243-3 ). Following the
measles resurgence of 1989–1991, a 2nd dose of measles vaccine was added to
the schedule. The current recommendations include a 1st dose at 12–15 mo
followed by a 2nd at 4–6 yr of age. Seroconversion is slightly lower in children who
receive the 1st dose before or at 12 mo of age (87% at 9 mo, 95% at 12 mo, and
98% at 15 mo) because of persisting maternal antibody. For children who have not
received 2 doses by 11–12 yr of age, a 2nd dose should be provided. Infants who
receive a dose before 12 mo of age should be given 2 additional doses at 12–15 mo
and 4–6 yr of age. In any event, this 2nd dose of vaccine may be given anytime 4 wk
after the 1st dose.
TABLE 243-3 -- Recommendations for Measles Immunization[*]
CATEGORY RECOMMENDATIONS
Unimmunized, no history of measles
(12–15 mo of age)
A 2 dose schedule (with MMR) is recommended.
The first dose is recommended at 12–15 mo of age; the
2nd is recommended at 4–6 yr of age
Children 6–11 mo of age in epidemic
situations or prior to international travel
Immunize (with monovalent measles vaccine, or if not
available, MMR);reimmunization (with MMR) at 12–15
mo of age is necessary, and a 3rd dose is indicated at 4–6
y of age
Children 4–12 yr of age who have
received 1 dose of measles vaccine at
≥12 mo of age
Reimmunize (1 dose)
Students in college and other post–high
school institutions who have received 1
Reimmunize (1 dose)

10. CATEGORY RECOMMENDATIONS
dose of measles vaccine at ≥12 mo of
age
History of immunization before the 1st
birthday
Consider susceptible and immunize (2 doses)
History of receipt of inactivated
measles vaccine or unknown type of
vaccine, 1963–1967
Consider susceptible and immunize (2 doses)
Further attenuated or unknown vaccine
given with IG
Consider susceptible and immunize (2 doses)
Allergy to eggs Immunize;no reactions likely (see text for details)
Neomycin allergy, nonanaphylactic Immunize;no reactions likely (see text for details)
Severe hypersensitivity (anaphylaxis)
to neomycin or gelatin
Avoid immunization
Tuberculosis Immunize (see Tuberculosis);if patient has untreated
tuberculosis disease, start anti-tuberculosis therapy
before immunizing.
Measles exposure Immunize and/or give IG, depending on circumstances
(see text)
HIV-infected Immunize (2 doses) unless severely
immunocompromised (see text)
Personal or family history of seizures Immunize;advise parents of slightly increased risk of
seizures
Immunoglobulin or blood recipient Immunize at the appropriate interval (see Table
243-4)
American Academy of Pediatrics: Red Book:2006 Report of the Committee on Infectious
Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, p 446.
* IG, immune globulin;MMR, measles-mumps-rubella vaccine. See
text for details and recommendations for use of measles- mumps-
rubella-varicella (MMRV) vaccine.
Adverse events from the MMR vaccine include fever (usually 6–12 days following
vaccinations), rash in about 5% of vaccines, and, rarely, transient thrombocytopenia.

11. Children prone to febrile seizures may experience an event following vaccination, so
risks and benefits should be discussed with parents. Encephalopathy and autism
have not been shown to be causally associated with the MMR vaccine. Specifically,
MMR vaccine significantly diminishes the risk for SSPE.
Passively acquired, immunoglobulin may inhibit the immune response to live
measles vaccine, and administration should be delayed for variable amounts of time
based on the dose of immune globulin ( Table 243-4 ).
TABLE 243-4 -- Suggested Intervals Between Immune Globulin Administration and
Measles Immunization (MMR, MMRV, or Monovalent Measles Vaccine)
INDICATION FOR
IMMUNOGLOBULIN
DOSE INTERVAL,
MO[*]
ROUTE U or mL mg lgG/kg
Tetanus (as TIG) IM 250 U 10 3
Hepatitis A prophylaxis (as IG)
Contact prophylaxis IM 0.02 mL/kg 3.3 3
International travel IM 0.06 mL/kg 10 3
Hepatitis B prophylaxis (as
HBIG)
IM 0.06 mL/kg 10 3
Rabies prophylaxis (as RIG) IM 20 IU/kg 22 4
Varicella prophylaxis (as
VariZIG)
IM 125 U/10 kg
(maximum 625
U)
20–40 5
Measles prophylaxis (as IG)
Standard IM 0.25 mL/kg 40 5
Immunocompromised host IM 0.50 mL/kg 80 6
RSV prophylaxis (palivizumab
monoclonal antibody)
IM — 15 mg/kg
(monoclonal)
None
Cytomegalovirus immune
globulin
IV 3 mL/kg 150 6
Blood transfusion
Washed RBCs IV 10 mL/kg Negligible 0

12. INDICATION FOR
IMMUNOGLOBULIN
DOSE INTERVAL,
MO[*]
ROUTE U or mL mg lgG/kg
RBCs, adenine-saline added IV 10 mL/kg 10 3
Packed RBCs IV 10 mL/kg 20–60 5
Whole blood IV 10 mL/kg 80–100 6
Plasma or platelet products IV 10 mL/kg 160 7
Replacement (or therapy) of
immune deficiencies (as IGIV)
IV — 300–400 8
ITP (as IGIV) IV — 400 8
ITP IV — 1,000 10
ITP or
Kawasaki
disease
IV — 1,600–2,000 11
American Academy of Pediatrics: Red Book:2006 Report of the Committee on Infectious Disease,
27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, p 445.
*
H
B
I
G
,
h
e
p
a
ti
ti
s
B
I
G
;I

13. G
,
i
m
m
u
n
e
g
l
o
b
u
li
n
;I
g
G
,
i
m
m
u
n
o
g
l
o
b
u
li
n
G
;
I
G

14. I
V
,
I
G
i
n
tr
a
v
e
n
o
u
s
;I
T
P
,
i
m
m
u
n
e
(f
o
r
m
e
rl
y
t
e
r

15. m
e
d
“i
d
i
o
p
a
t
h
i
c
”
)
t
h
r
o
m
b
o
c
y
t
o
p
e
n
i
c
p
u
r
p
u

16. r
a
;
M
M
R
,
m
e
a
s
l
e
s
-
m
u
m
p
s
-
r
u
b
e
ll
a
;
M
M
R
V
,
m
e
a

17. s
l
e
s
-
m
u
m
p
s
-
r
u
b
e
ll
a
-
v
a
ri
c
e
ll
a
;
R
B
C
s
,
r
e
d
b
l

18. o
o
d
c
e
ll
s
;
R
I
G
,
r
a
b
i
e
s
I
G
;
R
S
V
,
r
e
s
p
ir
a
t
o
r
y
s

19. y
n
c
y
ti
a
l
v
ir
u
s
;
T
I
G
,
t
e
t
a
n
u
s
i
m
m
u
n
e
g
l
o
b
u
li
n

20. .
* These intervals should provide sufficient time for decreases in
passive antibodies in all children to follow for an adequate
response to measles vaccine. Physicians should not assume that
children are fully protected against measles during these intervals.
Additional doses of IG or measles vaccine may be indicated after
exposure to measles (see text).
Live vaccines should not be administered to pregnant women or immunodeficient or
suppressed patients. However, patients with HIV who are not severely
immunocompromised should be immunized. Because measles virus may suppress
the cutaneous response to tuberculous antigen, skin testing for tuberculosis should
be performed before or at the same time as administration of the vaccine. Individuals
infected with M. tuberculosis should be on appropriate treatment at the time of
administration of measles vaccine.
POSTEXPOSURE PROPHYLAXIS.
Susceptible individuals exposed to measles may be protected from infection either
by vaccine administration or immunization with immunoglobulin. The vaccine is
effective in prevention or modification of measles if given within 72 hr of exposure.
Immune globulin may be given up to 6 days following exposure to prevent or modify
infection. Immunocompetent children should receive 0.25 mL/kg intramuscularly and
immunocompromised children should receive 0.5 mL/kg. Immune globulin is
indicated for susceptible household contacts of measles patients, especially infants
<6 mo of age, pregnant women, and immunocompromised persons.