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

However, enteroviruses that infect humans
represent a distinct group that are not found in
other hosts.

1. Unlike rhinoviruses, enteroviruses maintain
infectivity over a wide pH range (3-l0).
2. They are rapidly inactivated at temperatures

1. Infection results from ingestion of fecally
contaminated material or, less commonly, via
contact with respiratory secretions.

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.

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.

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.

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.

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.

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.

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. Should not be used for diagnosis of acute
disease except when a specific serotype or
a small number of serotypes can be tested.

2. Passive immunoglobulin treatment (IVIG)
would probably prevent infection, but this would
be practical only in very isolated clinical
situations.

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.