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Complications of measles are largely attributable to the pathogenic effects of the virus on the respiratory tract and
immune system ( Table 243-1 ). There are several factors that make complications more likely. Morbidity and
mortality from measles are greatest in patients <5 yr of age (especially <1 yr of age) and those >20 yr of age. In
developing countries, higher case-fatality rates have been associated with crowding, which is possibly attributable to
a larger inoculum dose following household exposure. 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. The clinical
severity of these complications frequently requires intubation and ventilatory support until the infection resolves.
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.
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
Diarrhea and vomiting are common symptoms associated with acute measles, and the gastrointestinal tract has diffuse
giant cell formation in the epithelium. Dehydration is a common consequence, especially in young infants and
children. 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 13/1,000 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 2040% 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 110 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 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 710 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.
SSPE is a rare disease and generally follows the prevalence of measles in a population. The incidence rate in the USA
in 1960 was 0.61 cases per million persons younger than 20 yr. By 1980 the rate had fallen to 0.06 cases per million.
Between 1956 and 1982 a total of 634 cases had been reported to the national SSPE registry. After 1982 about 5 cases
per year were reported annually in the United States and only 23 cases per year in the early 1990s. However,
between 1995 and 2000, reported cases in the USA increased and 13 cases were reported in 2000. Nine of the 13
cases occurred in foreign-born individuals. This resurgence may be the result of an increased incidence of measles
between 1989 and 1991. 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 713 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) 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-2b. 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 510%.

Virtually all patients eventually succumb to SSPE. Most die within 13 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. 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.

TABLE 243-1 -- Complications by Age for Reported Measles Cases, USA 19872000
<5 yr (n = 59 yr (n 1019 yr (n 2029 yr >30 yr (n
= 6,492) = 18,580)
(n = 9,161) = 4,069)

19,480 (29.1)



2,369 (12.8) 2,656




177 (0.3)

97 (0.3)

9 (0.1)

18 (0.1)

26 (0.3)

27 (0.7)


5,482 (8.2)


408 (6.3) 627 (3.4)

767 (8.4)

386 (9.5)


97 (0.1)

43 (0.2)

9 (0.1)

21 (0.2)

11 (0.3)


12,876 (19.2)


612 (9.4) 1,612 (8.7)



Otitis media

4,879 (7.3)


305 (4.7) 338 (1.8)

157 (1.7)

70 (1.7)


3,959 (5.9)

2,480 (8.6) 183 (2.8) 363 (2.0)

554 (6.1)

379 (9.3)

13 (0.1)