Non-polio Enterovirus Infections

Michael Kramer, M.D.

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I. Virology
A. Classification and Host Range
1. The enteroviruses comprise one class of the
family Picornaviridae (table 1). They are
distinguished from other picornaviruses by their
acid stability. Enteroviruses are found in many
mammalian and non-mammalian hosts.
However, enteroviruses that infect humans
represent a distinct group that are not found in
other hosts.
II. Most human enteroviruses are subclassified into four
subclasses.
A. Inactivation
1. Unlike rhinoviruses, enteroviruses maintain
infectivity over a wide pH range (3-l0).
2. They are rapidly inactivated at temperatures
>500C.
III. Pathogenesis of Enterovirus Infections
A. Transmission
1. Infection results from ingestion of fecally
contaminated material or, less commonly, via
contact with respiratory secretions.
2. The incubation period is characteristically 3-5
days between infection and onset of non-
specific symptoms.
B. Infection and Viral Dissemination
1. Initial sites of replication include both the
pharynx and terminal ilium
2. Virus is shed from the upper respiratory tract
for 1-3 weeks, and from the feces for 38 weeks.
The period of maximum communicability is
during the first 2 weeks after infection.
C. Immunity to Infection
1. Immunity to enterovirus infection is serotype
specific.
2. Passive humoral antibody confers protection
from disease in low titer, and from both
infection and disease in high titer.
3. Humoral antibodies also have an important role
in the immune response to enterovirus
infection. Patients with isolated B cell
immunodeficiency are at risk of prolonged,
severe infections.
IV. Epidemiology
A. Epidemic and Endemic Behavior
1. Seasonal patterns
a. Although enterovirus infections occur
throughout the year, they are strikingly
more prevalent between June and October
in temperate climates.
The human enteroviruses are picornaviruses from the
family Picornaviridae. They are distinguished from the
other picornaviruses by the fact that they are acid
stable and survive transit through the gastrointestinal
tract and replicate in the intestinal tract unlike the other
picornaviruses. The various subgroups of
enteroviruses include polio, Coxsackie A viruses and
Coxsackie B viruses, and echoviruses.
The echo of course stands for enteric cytopathic
human orphan virus. The echoviruses cause a large
spectrum of disease.
Enteroviruses are transmitted via the fecal-oral route. It
is both direct and indirect transmission that can occur,
but they are ingested orally. There is an initial cycle of
replication that goes on both in the oropharynx, with
regards to shedding from the upper respiratory tract
and then a cycle of replication goes on in the ileum.
Replication is probably more efficient in the lower
gastrointestinal tract where more virus is shed for
longer periods of time in the feces than from the upper
respiratory tract. But, there is prolonged shedding after
infection, particularly from the gastrointestinal tract
where the virus may be shed in the feces for between
three and eight weeks. After a few days, there is an
asymptomatic minor viremia which seeds systemic
lymphoid tissue, such as bone marrow, lymphoid
tissue in the liver and spleen. There is another cycle of
replication that produces a major viremia. The major
viremia heralds the onset of fever and other symptoms
that we see with enterovirus infections. That is what
leads to seeding of the target organs such as the
central nervous system or the myocardium or other
target organs. The period of time between ingestion
and onset of symptoms is typically somewhere
between three and five days with a relatively brief
intervention period before onset of symptoms. But, then
there is another considerable period of time of which
the onset of these so-called end-organ symptoms,
such as polio and myocarditis, which may be as long
as nine to twelve days. Then again, the virus is shed in
stool characteristically for long periods of time.
Immunity to enteroviruses. Immunity is serotype
specific. Infection with the Coxsackie B1 incurs life long
immunity but not to the other Coxsackie B type II, III or
the others. Passive antibodies provide limited immunity
to disease. The passive antibodies are clearly very
protective if given during the incubation period, early on
in the incubation period. Secretory IgA develops within
about three weeks after infection and provides some
relative protection against re-infection. Re-infection
occurs readily even with the same serotype; it is just
that re-infections usually are asymptomatic when they
occur. Humoral and antibody and macrophage function
appear to be important effectors in terms of the
immune response to infection. Individuals that have
profound T-cell immunodeficiency syndromes, have
trouble with persistent and long progressive enterovirus
infections. Macrophage function is important. Cytotoxic
T-cell activity probably does not contribute to viral
clearance.
Epidemiology. There is a marked seasonal variation
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 2. Population immunity
a. Adults usually have a seroprevalence of
30-80% against the more common,
endemic enterovirus serotypes.
b. Periodic epidemics may result in
accumulation of a sufficient cohort of
susceptibles to sustain transmission of the
epidemic serotype.
B. Age and Socioeconomic Status
1. Incidence rates of infection and disease are
inversely proportional to age. Infants <12
months have the highest incidence of disease
2. Rates of infection and disease are also higher
among children of lower socioeconomic
classes.
C. Transmission
1. Both direct person-to-person transmission, and
indirect transmission (via contaminated
fomites, food, and water) probably occurs.
2. Transmission is most efficient in households
and families. Secondary attack rates for
infection of 30-90% within households.
V. Laboratory Diagnosis
A. Virus Isolation. Cell culture is labor intensive and
expensive.
B. Polymerase Chain Reaction (PCR)
1. PCR has superior sensitivity compared to cell
culture for identification of enteroviruses in
CSF.
2. Experience with other specimens is more
limited. PCR compares favorably to culture for
throat and serum specimens, but may be less
sensitive for urine specimens.
C. Serology
1. The micro-neutralization test is the standard
serologic method used for determination of
immunity.
a. Type specific
b. Both acute and convalescent sera required
c. Should not be used for diagnosis of acute
disease except when a specific serotype or
a small number of serotypes can be tested.
VI. Prevention and Treatment of Enterovirus Infections
A. Prevention
1. There are no vaccines available for non-polio
enterovirus infections
2. Passive immunoglobulin treatment (IVIG)
would probably prevent infection, but this would
be practical only in very isolated clinical
situations.
with a late summer, early fall predominance. Both
endemic and epidemic disease, the common
enterovirus types, the Coxsackie B types, the more
common echovirus types such a type 9 and type 11,
anywhere from 30-80% of adults tend to have
antibodies, so the antibody prevalence in the adult
population is high. Most of these infections occurred at
a very early age. We will find the highest infection rates
in children who come from the most disadvantaged
backgrounds.
Transmission occurs both directly person to person
and via indirect viral spread via fomites, and within
households there are very high secondary attack rates.
Secondary household attack rates are in the 50-90%
among susceptibles.
Seasonal occurrence of the enteroviruses. You get a
peak at the beginning and in the middle of the summer,
peaking in late August or early September. Then, a
marked drop off at the appearance of cool weather.
However, the enterovirus infections do occur at all
times of the year.
Marked peaks that occur in July, August, and
September, there was disease activity in every
calendar month of the year. The nadir for enterovirus
activity is March and April while the peak time is
August the early of September.
The ten or twelve most common types of enteroviruses
actually caused about 60-70% of all the disease. The
most common types being echo 9 and 11, and then the
Coxsackie B viruses are common.
Of the five most common types of enterovirus, the
Coxsackie viruses and echoviruses, some of these
viruses seem to be endemic and occur year after year
after year, very commonly. Others tend to occur very
infrequently and may only show up once every seven or
ten years, or in some cases even longer that. When
they do appear, they tend to be dominant causes of
disease as shown in the next slide.
Viruses like the Coxsackie B viruses or the others are
simply endemic and occur each year, year in, year out.
On the regional basis these outbreaks tend to be local
or regional. In this case of echo 30 here in the
Northeast there are other enteroviruses such as the
enterovirus 70, which can cause pandemics on a
worldwide basis.
The age incidence for the children under a year of age
is 82 cases per 100,000 is four times that for the next
age group, and then the age incidence levels off at a
fairly level rate up to the second and third decades of
life, and then may fall off thereafter. So, at least with
respect to aseptic meningitis, this is a disease that
occurs in all age groups, but there is a marked
increase in incidence that is detectable in children
under a year of age. Eighty percent of the disease
occurred in the first twenty weeks of life. So that it is
very clear that this is a disease of the very young.
Enterovirus disease is a disease of extremely young
children.
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 3. Nosocomial Infections
a. Hospital outbreaks reported, especially in
newborn nurseries
b. Simple hygienic measures such as
handwashing should reduce risk of
transmission; special isolation procedures
such as gowning and masking are not
warranted.
B. Treatment
1. No antiviral agents are currently licensed for
treatment of enterovirus infections.
VII. Infections in Infancy
A. Perinatal Infections
1. Incidence
a. In Nassau Co., NY, neonatal group B
coxsackievirus infection was estimated to
occur in 50/100,000 live births from 1970
to 1979.
b. Based on cases reported to the CDC
echovirus disease is slightly more common
than group B coxsackievirus disease (19).
2. Age onset
a. Echovirus disease onset <7 days of age
(peak 3-5 days)
b. Coxsackie B virus disease: onset <10 days
of age (peak 3-7 days)
3. Clinical Disease
a. Hepatitis
(1) This is a severe hepatitis that is unique
to newborns and is characterized by
rapid and extensive necrosis of the
liver and overwhelming hepatic failure
(2) The initial signs and symptoms include
lethargy, poor feeding, apnea and
jaundice. It is associated with
progression there marked elevation of
serum transaminases and severe
coagulopathy with widespread and
prolonged bleeding, progressive
anemia, marked prolongation of the
PT and PTT
(3) More than 80% of these infants die
within 1-3 weeks. Survivors may
develop cirrhosis and chronic hepatic
insufficiency.
(4) Echovirus 11 has been implicated in
the majority of reports (20), but cases
attributed to several other echoviruses
and the coxsackie B viruses are well
documented.
Virus isolation, of course, is the gold standard by which
we compare other methods. It is expensive. It takes at
least two to five days to see visible cytopathic effect in
most cell lines. There are some enteroviruses,
particularly many of the Coxsackie A serotypes that are
very difficult to isolate and culture. Type 1 and type 18
have never been isolated in cell cultures.
PCR has been applied principally to detection of
enterovirus RNA. The experience of PCR is very
positive. Whereas we can isolate virus from about 30%
of cerebrospinal fluid specimen of which we ultimately
make a diagnosis of enterovirus meningitis, PCR is
positive in as many as 80%. PCR will pick up
enterovirus in about two-thirds of CSF specimens that
are cultured negative. So that at least for CSF
specimen, PCR turns out to be far more sensitive than
culture and has the added advantage that there is a
turn around time of only one to two days. PCR is not
yet widely available commercially. It has not yet been
approved by the FDA. Serology, of course, has been
widely used, but is labor intensive, cumbersome,
difficult to do, and relatively insensitive. Even though
there are a number of tests available commercially,
serology is not widely used because it requires acute
and convalescent serum.
Treatment of enterovirus infections. There is no
currently available agent to treat any picornavirus
infection or any enterovirus infection. However, there
has been a lot of interest in the oxazolone compounds,
which are compounds that actually interpolate on the
capsid of the virus and stabilize the virus capsid and
prevent uncoating once it enters the cell. These
compounds are broadly reactive against many
enterovirus serotypes in vitro. They have been used
with impressive results in animal models and are now
just entering clinical testing. One compound called
Placinoral has been tested in adults with aseptic
meningitis. The drug had very impressive activity in
reducing the duration of signs and symptoms of aseptic
meningitis in adults, in studies that were done last
year. The drug is just now going into trial in children
and adolescents this year and probably will be going to
trial in young infants and neonates sometime within the
next couple of years. You will be hearing much more
about Placinoral in the future.
In neonates, serious infection is relatively uncommon,
but when it does occur it can often be very serious and
often fatal. In the neonatal period, when echovirus is
acquired intrapartum and perinatally, the onset of the
echoviruses is characteristically around three, four or
five days and almost always less than seven days. The
onset of the Coxsackie B disease would be a little bit
longer, and serious infections have been seen to last
up to ten days. But, rarely, if ever, do you see serious
disease in infants presenting beyond seven to ten days
of life. Almost all of these are probably perinatally
acquired from the mother, or in a small number of
cases, there have been serious cases of serious
disease reported with which viral infections have been
acquired nosocomially.
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b. Myocarditis
(1) May begin with non-specific signs
such as lethargy, poor feeding, or mild
respiratory distress. The onset of frank
myocarditis is often abrupt with
temperature instability, respiratory
distress, tachycardia, cyanosis,
arrhythmias, hepatomegaly, jaundice
and signs of poor peripheral
circulation. The ECG may show low
voltage and other electrophysiologic
abnormalities, and echocardiographic
studies often indicate poor left
ventricular or biventricular function
(2) Unlike older children and adults,
infants with group B coxsackievirus
myocarditis often develop concomitant
meningoencephalitis, pneumonia,
hepatitis, pancreatitis, or adrenalitis.
(3) Mortality among infants with
myocarditis alone is generally reported
to be 30-50%, but is higher when other
organs are involved.
(4) Virtually all cases are caused by the
coxsackie B viruses.
c. Meningocephalitis
(1) Signs and symptoms such as extreme
lethargy, seizures, hemiparesis, flaccid
paralysis, and coma help to
differentiate the more serious forms of
CNS involvement that often
accompany myocarditis or hepatitis
from the far more benign disease
observed with aseptic meningitis.
(2) Inflammation of the brain or spinal
cord can be found in about 2/3 of
infants dying with myocarditis.
Meningoencephalitis in the absence of
other organ involvement is quite rare.
d. Pneumonia
(1) A small number of infants have been
reported with severe pneumonia
caused by echovirus serotypes 6, 9,
and 11. Some of these cases have
been characterized by onset of
symptoms within hours of birth
suggesting prenatal exposure, and
associated with a high mortality rate.
Neonatal pneumonitis of lesser
severity has been described with
The echoviruses cause a very severe hepatitis
syndrome, which is termed disseminated disease. The
liver is the major target organ. Pneumonia is much less
common. Coxsackie B viruses have been associated
with myocarditis and sometimes encephalitis and
hepatitis, although it is unusual to see either
encephalitis or hepatitis occur in the absence of
myocarditis.
Peak onset is in the three, four, five day range,
suggesting that most of these infections had been
acquired at the time of delivery with a week incubation
period and peak at an early age.
Pathogenesis of neonatal enterovirus infections. Most
of these are acquired from the moms. The mothers
often do have symptoms late in pregnancy, particularly
with echovirus disease. These symptoms
characteristically are fever and onset of very intense
abdominal pain. Sometimes the infants have actually
been C-sectioned because of a misdiagnosis of
abruptio placenta. Nosocomial transmission has been
reported but most transmission is vertical, it probably
occurs intrapartum, at the time of delivery. We think
that the placenta actually acts as a very effective
barrier. Intrauterine infections do occur but they are
very uncommon. Most of the serious infections are
those with infection acquired at the time of delivery as
opposed to prior to delivery. The role of passively
acquired maternal antibody turns out to be critical, in
that, depending on the timing of the maternal infection
and whether or not she transmits IgG antibody across
the placenta to the newborn, the infant either gets into
very serious trouble with disease or remains
asymptomatic. What appears to determine whether or
not that happens is whether or not the infant has
acquired antibodies from the mom. So it all depends
on the timing of the maternal infection and at what
point she does or does not transmit antibody to the
fetus or the newborn infant.
The liver in echovirus disease is small, shrunken and
very hemorrhagic. There are a few small nests of
normal hepatocytes and the rest of this is just basically
coagulation and necrosis. Very serious, overwhelming
disease where presents with marked elevation of
serum transaminase and a severe coagulopathy. The
normal mortality unfortunately is about 80%.
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 echovirus serotypes 7 and 22.
B. Management
1. Acyclovir. Many of the presenting clinical
features of neonatal enteroviral disease cannot
reliably be distinguished from disseminated
HSV infection. Therefore, it is prudent to treat
with intravenous acyclovir until laboratory
studies confirm the diagnosis of enterovirus
infection.
2. Intravenous Immune Globulin (IVIG)
a. One infant has been reported with severe
echovirus hepatitis who survived after
receiving a large dose of IVIG.
b. It is reasonable to give a single infusion of
IVIG in a dose of 1-2 g/kg to infants with
clinical features strongly suggestive of
enterovirus myocarditis or hepatitis.
C. Non-Specific Febrile Illness With and Without
Aseptic Meningitis
1. Non-polio enteroviruses are the most
commonly WBC Cell Count identified cause
of fever without an apparent focus among
infants under a month of age who present for
emergent care. During the summer and fall
months,
enteroviruses account for at least 53-63% of
these cases.
2. Fever is often the sole examination finding
although some infants will present with other
non-specific findings such as irritability,
lethargy, poor feeding, vomiting, diarrhea,
exanthems, and signs of upper respiratory tract
infection. Upon evaluation, which for infants of
this age usually includes a full "septic workup",
approximately half of enterovirus infected
infants will have aseptic meningitis, although
there are no clinical features that distinguish
those with meningitis prior to performing the
lumbar puncture.
VIII. Central Nervous System Infections
A. Aseptic Meningitis
1. Viral meningitis is the most common infection
of the CNS. It is predominantly a disease of
infants less than a year of age.
2. The enteroviruses account for >90% of cases.
a. A prospective study conducted at three
Baltimore hospitals from 1986 to 1990
showed >90% of viruses isolated from
children under 2 years old are coxsackie B
viruses and echoviruses; coxsackie A

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 viruses appear to cause <3% of cases.
3. Clinical Presentation
a. In the older child and adult aseptic
meningitis presents with fever to 400 C,
headache, meningismus, nausea and
vomiting. Other signs of enterovirus
infection, i.e., rash, are present in a
minority of cases. Altered mentation,
seizures, and focal neurological signs are
unusual and suggest a diagnosis of
meningoencephalitis.
b. In infants less than a year of age, the
characteristic symptoms and signs of
meningitis are difficult to elicit by history
and exam. The most common symptoms
are fever and irritability. In practice, aseptic
meningitis is often diagnosed during the
clinical evaluation of febrile infants without
an apparent source of fever.
4. Diagnosis
a. The peripheral WBC and differential are
usually non-specific.
b. CSF examination
c. Virology
(1) Cell culture virus isolation rates from
the CSF have varied from 20% to 90%
in various reports. Viruses are less
often isolated from CSF than from the
GI tract. Enteroviruses are often
isolated from the oropharynx for 1-2
weeks after onset of symptoms, and
from the feces for 3-8 weeks
(2) The use of the polymerase chain
reaction (PCR) to detect enterovirus
RNA in CSF is likely to be more rapid
and more sensitive than cell culture
(41). Sawyer, et al, found that PCR
detected enteroviral RNA in 97% of
culture positive CSF specimens, and
in 66% of culture negative CSF
specimens from aseptic meningitis
patients.
5. Differential diagnosis
a. Partially treated bacterial meningitis
b. Parameningeal bacterial infection or brain
abscess
c. TB and fungal meningitis
d. Spirochetal meningitis (Lyme disease,
syphilis, leptospirosis)
6. Complications and Prognosis

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 a. Complete recovery is the rule, most infants
and children recover completely within 3-7
days of onset.
b. 12% patients with aseptic meningitis
develop signs of encephalitis during the
acute illness. Specific signs include
seizures (3.4%), weakness (1.0%), and
coma (3.7%). Most patients are teenagers
and young adults. Virtually all the
complications were associated with
coxsackieviruses and echoviruses.
c. In a Baltimore study of aseptic meningitis
among children <2 years of age, the acute
illness was complicated by either complex
seizures, physical evidence of increased
intracranial pressure, or coma in 25 (9%)
cases. However, these complications were
not associated with adverse long term
neurological sequelae.
d. Long Term Sequelae
(1) More recent studies with larger
numbers of cases and more
appropriate controls have found no
effect of viral meningitis on cognitive
development
7. Management
a. Admission
b. Treatment options
B. Encephalitis
1. Well described, but less common manifestation
of enterovirus infection.
a. 5-10% of aseptic meningitis patients have
symptoms or signs suggestive of
encephalitis such as diminished
consciousness, seizures.
b. Frank enterovirus encephalitis is reported
with multiple serotypes
2. Focal disease may mimic HSV encephalitis.
3. Prognosis is generally very good. Neurologic
sequelae and rare deaths reported.
C. Acute Myelitis (Poliomyelitis)
1. Sporadic cases of acute paralysis
indistinguishable from poliomyelitis have
occurred with many enterovirus serotypes.
2. Enterovirus 71 is the only non-polio serotype
associated with outbreaks of paralytic disease.
a. Causes coxsackie A virus-like disease in
newborn mice, but neurovirulent for
monkeys (unlike coxsackie A viruses).
b. Clusters of paralytic cases reported from

8
 many locations, including the U.S. (50).
c. Large outbreaks involving hundreds of
cases, mostly children < 6 y/o, reported
from eastern Europe and Russia.
IX. Exanthems
A. Rubelliform and morbilliform rashes
B. Hand-Foot-Mouth Syndrome
1. Hand-foot-mouth syndrome (vesicular
stomatitis with exanthem) is a relatively
common acute illness affecting mostly children
under 10 years of age. The characteristic
findings include fever, oral vesicles on the
buccal mucosa and tongue, and peripherally
distributed small, tender cutaneous lesions on
the hands, feet, buttocks and (less commonly)
genitalia.
2. The group A coxsackieviruses are recovered
most often from HFM syndrome patients.
Coxsackie A16 is especially common.
3. Differential diagnosis
a. Varicella
b. HSV stomatitis
4. Course. HFM syndrome usually resolves in 2-3
days without complication. Concomitant CNS
disease may occur when HFM syndrome is
caused by enterovirus 71.
X. Respiratory Infections
A. Acute Respiratory Disease
1. Febrile illness with URI ("summer gripe") is a
very common manifestation of enterovirus
infection that cannot be differentiated from
"colds" caused by rhinoviruses and other
respiratory viruses (54,55).
2. The role of enteroviruses in lower respiratory
tract disease (i.e., pneumonia) is less certain.
They can be considered rare causes of viral
pneumonia.
B. Herpangina
1. Herpangina is a vesicular exanthem of the
tonsillar fauces and soft palate, accompanied
by fever, sore throat, and pain with swallowing,
that principally affects children 3-10 years of
age. Most disease occurs during summer
outbreaks. Sporadic herpangina is less
common (56).
2. The coxsackie A viruses are the usual cause;
coxsackie B viruses and echoviruses have been
responsible for some outbreaks.
3. Differential diagnosis
a. Herpes simplex gingivostomatitis

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 b. Hand-foot-mouth syndrome
c. Aphthous stomatitis
C. Pleurodynia
1. Pleurodynia is an acute illness characterized by
fever and paroxysmal spasms of the chest and
abdominal muscles. Most cases occur during
summer outbreaks among adolescents and
adults.
2. Major epidemics occur at infrequent intervals,
typically 10-20 years apart.
3. Group B coxsackieviruses are the most
important cause. Coxsackie A viruses and
echoviruses are rarely implicated.
4. Differential diagnosis
a. Pneumonia
b. Pulmonary embolus
c. Myocardial infarction
d. Acute abdomen
XI. Other Clinical Diseases Associated with Enteroviruses
A. Myopericarditis
1. Background. Acute myopericarditis occurs at all
ages, but most often among healthy, often
athletic, adolescents and young adults. There is
a wide range of clinical manifestations and
outcomes.
2. Etiology and Pathogenesis
a. The enteroviruses are among the most
common identified causes of acute
myocarditis. Other agents include
adenoviruses, influenza A virus, EBV, VZV,
and mumps virus.
b. The group B coxsackieviruses are by far
the most prominent among the
enteroviruses, although disease due to
coxsackie A viruses, echoviruses, and
polioviruses is well documented.
c. The role of enteroviruses in cases of
dilated cardiomyopathy is uncertain.
d. Animal studies suggest the exercised
myocardium is at increased risk of more
severe infection.
3. Clinical Manifestations
a. Fever, malaise, dyspnea, chest pain, signs
of CHF
b. Pericardial friction rub observed in 35-80%
of cases
c. Cardiomegaly
d. ECG: ST-T elevation, T wave
abnormalities, arrhythmias
e. Ejection fraction

10
 f. Often misdiagnosed as myocardial
infarction
4. Management
a. Supportive care
b. Corticosteroids are often given, although
controlled studies indicate little or no long
term benefit.
5. Prognosis
a. Acute mortality <10%
b. Persistent cardiomegaly, failure 5-20%
c. Chronic constrictive pericarditis - rare
B. Acute Hemorrhagic Conjunctivitis
1. Acute hemorrhagic conjunctivitis (AHC) is a
highly contagious ocular infection characterized
by pain, lid edema, and subconjunctival
hemorrhages. It is self-limited and rarely leads
to permanent visual impairment. Worldwide
pandemics caused by enterovirus 70 and
coxsackie A24 have occurred mostly in tropical
coastal areas.
2. Transmission probably occurs via indirect
routes involving eye discharge and fingers,
towels, etc., rather than fecal-oral spread.
3. Differential diagnosis
a. Epidemic keratoconjunctivitis (due to
adenoviruses)
4. Course. AHC usually peaks in 2-3 days and
resolves within 10 days without complication. In
severe cases, keratitis may persist for several
weeks, but does not lead to permanent
scarring. Concomitant CNS disease may occur
when AHC is caused by enterovirus 70.
C. Pancreatitis
D. Hepatitis
E. Disease in Immunocompromised Persons
1. Persistent enterovirus infection
a. Patients at risk are those with profound B
cell immunodeficiency (X-linked
agammaglobulinemia, other inherited B
cell disorders, severe combined immune
deficiency, common variable
immunodeficiency).
b. The most common clinical manifestation is
chronic meningoencephalitis with slowly
progressive cognitive and neurologic
deterioration. More than half of patients
also have a chronic dermatomyositis
syndrome due to persistent infection of
skeletal muscle. Some patients also
develop hepatitis.

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 c. Most infections are caused by echoviruses,
but the group A coxsackieviruses and
group B coxsackieviruses have also
caused persistent infections.
2. Acute, overwhelming enterovirus infection
a. Neonates
b. Bone marrow transplantation
(1) Patients with acquired immune
deficiency syndrome (AIDS) appear to
have little or no increased risk from
enterovirus infections.

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4. Bodian D. A reconsideration of the pathgenesis of

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