Enterovirus

Pembimbing :
dr. T Mirawati Sudiro, PhD
Penyaji :
Pranudiah Yulianti Ningtias - 2006626784

Kamis, 20 Oktober 2022

Introduction
 Human enteroviruses (EV) members of the Enterovirus genus of the family Picornaviridae
and are among the most common human viral infections.

 Their discovery had implications for all of virology because they indicated,

 first, that poliovirus (PV) grew in various tissue culture cells that did not correspond to
the tissues infected during the human disease and,

 second, that PV destroyed cells with a specific cytopathic effect (CPE).

The infectious virus is relatively resistant to many common laboratory disinfectants,

including 70% ethanol, isopropanol, dilute Lysol, and quaternary ammonium compounds
Introduction

 Poliomyelitis should be considered in all cases of pure motor paralysis

and is usually associated with
- normal or slightly elevated value for protein,
- normal sugar value, and
- moderate mononuclear pleocytosis in cerebrospinal fluid (CSF).

Real-time PCR is the primary test used to detect, even with very
small amounts of clinical specimens, such as CSF.
 Most EV infections cause only mild nonspecific disease, but infections
can frequently lead to serious illness and hospitalization, especially in
infants and in those who are immune-compromised.

 In addition, this group of viruses is the most common cause of aseptic

meningitis, the most frequent central nervous system (CNS) infection
History of Virus Discovery
 The first clinical descriptions of poliomyelitis were made in the 1800s, with
reports of cases of paralysis with fever

 this disease began with studies in the early 20th century.

 Viennese, Landsteiner and Popper proved the infectious nature of

poliomyelitis by inoculation of CNS tissue homogenates from human cases into
monkeys and successfully transmitting the clinical disease and its pathology
to a nonhuman host
History of Virus Discovery
 The control of polio began with the production of two different vaccines,

- the Salk inactivated polio vaccine (IPV) delivered via intramuscular injection
(licensed in 1955 in the United States [U.S.]) and

- the orally-delivered Sabin, live attenuated vaccine (oral polio vaccine [OPV],
licensed in 1961–1962).

Coxsackieviruses (CV) were first isolated from the feces of paralyzed

children following a poliomyelitis outbreak in 1947 in Coxsackie, New York, and
from cases of aseptic meningitis in 1948
 Virus Classification
The current classification for picornaviruses affecting humans

 Historically, the
classification of
EV into the
subgroups of
polioviruses, CVA,
CVB and
echoviruses
Biology
 Enteroviruses are small RNA viruses consisting of a small (~30 nm) spherical,
nonenveloped capsid that contains a single-stranded positive-sense RNA genome.

 Approximately 7,500 nucleotides long and encode a single open reading frame
for all viral capsid and functional proteins

 The icosahedral virus capsid, consisting of 60 protomers, is assembled from 12

identical pentamers.

 Each protomer is composed of the four virus proteins, VP1, VP2, VP3, and VP4.

 VP1, VP2, and VP3 constitute most of the capsid surface, whereas VP4 is located
in the interior of the capsid in close contact with the viral RNA
Mode of Transmission

 EV can be isolated from both the lower and upper alimentary tract and can be

transmitted by both fecal-oral and respiratory routes.

 Fecal-oral transmission may predominate in areas with poor sanitary

conditions, whereas respiratory transmission may be more important in more

developed areas
Mode of Transmission

 EV are transmitted in the same manner as are other viruses causing the
common cold—that is, by hand contact with secretions (e.g., on the hand of
another person) and autoinoculation to the mouth, nose, or eyes.

 Direct bloodstream inoculation, usually by laboratory accidents (e.g., needle

sticks), can result in EV infection

 Transmission within households has been well studied for PV and nonpolio EV.

 Enteroviruses are more prevalent in sewage from areas with low

socioeconomic conditions or with large proportions of young children with no
evidence of immunity to the virus type.
Epidemiology
 Important concept in understanding the epidemiology of the EV is variation:
by serotype, by time, by geographic location, and by disease.
 This concept is illustrated in surveillance studies of nonpolio EV infections.
For example, during 1970 to 2006, several major E30 epidemics
occurred in the U.S., from 1981 to 1982, 1990 to 1994, and 1997 to 1998
In temperate climates, EV are characteristically found during the summer and
early autumn, although outbreaks can continue into the winter.
In tropical and semitropical areas, circulation tends to be year-round or
associated with the rainy season.
 In the U.S., 36 years of surveillance indicated that 82% of EV isolations were
made during the five summer or fall months of June to October
PATHOGENESIS
 the primary site of infection  the epithelial cells of the respiratory or
gastrointestinal tract and the lymphoid follicles of the small intestine.

 Replication at the primary site of infection  followed by viremia  leading

to a secondary site of tissue infection.

 Secondary infection of the CNS results  aseptic meningitis or, rarely,

encephalitis or paralysis.

 Other tissue-specific infections can result  pleurodynia or myocarditis.

 Disseminated infection can lead to  exanthems, nonspecific myalgias, or

severe multipleorgan disease in neonates.
Incubation Times

 All polioviruses, group A and B coxsackieviruses, and echoviruses have

incubation times ranging from 2 to 35 days, with an average of 7 to 14 days

 The shortest incubation period, 12 to 72 h, has been reported for local

infections of the eye by EV70
Clinical Syndromes
Poliomyelitis

 The term poliomyelitis refers to the inflammatory damage due to infection of

the anterior horn cells of the spinal cord, recognized clinically as acute-onset,

lower-motor-neuron paralysis (or paresis) of one or more muscles.

 redefining poliomyelitis as spinal cord disease caused specifically by one or

another poliovirus serotype.

 Polioviruses may cause other diseases, but muscle paralysis due to myelitis is

the most important.

Poliomyelitis
 Until poliovirus infections were controlled by immunization, they were the

most common cause of acute flaccid paralysis (AFP), but this is no longer the

case in almost all countries

 Poliomyelitis may vary widely in severity from paresis of one or a few muscles

or paralysis of one or more limbs to quadriplegia and paralysis of the muscles

of respiration (diaphragm, intercostal muscles).

Poliomyelitis

 Most children recover from the acute illness, but some 70% continue to have

some residual motor weakness, which may vary from mild impairment to

complete flaccid paralysis.

 The permanent loss of motor neurons results in denervation atrophy of the

affected muscles
Post Polio Syndrome
 Delayed progression of neuromuscular symptoms (post-polio syndrome) may
occur 20 years or longer after the initial paralysis due to poliovirus.

 Post-polio syndrome is characterized by new muscle weakness associated with

dysfunction of surviving motor neurons.

 The illness is usually associated with deterioration of those nerves involved in

reinnervation during recovery from the original poliovirus infection.

 It does not appear that reactivation or replication of poliovirus is involved,

but current data are inconclusive, since no infectious virus has ever been
isolated
LABORATORY DIAGNOSIS

 If the clinical syndrome is already known to be associated with the detected

agent, then infection is taken as reasonable evidence of causation.

 If the agent is found in diseased tissue or a relevant body fluid (such as CSF),
that constitutes concrete evidence of invasion, hence causation.

 To rule out poliovirus infection in a paralytic case, two stool specimens should
be collected at least 24 hours apart during the first 14 days following onset of
paralysis.

 Isolation in culture remains the gold standard for poliovirus detection

Virus Isolation and Identification

 The traditional techniques for detecting and

characterizing EV rely on the time-consuming and
labor-intensive procedures of viral isolation in cell
culture and neutralization by reference antisera
 The best specimens for isolation of virus are, in order
of preference, stool specimens or rectal swabs,
throat swabs or washings, and CSF.
 Throat swabs or washings and CSF are most likely to
yield virus isolates if they are obtained early in the
acute phase of the illness.
Molecular Detection

 The methods of choice for EV detection in CSF and are widely used for a
patient with a clinical presentation of meningitis.

 In current practice, the most sensitive assays to detect enteroviruses use

molecular amplification methods such as RT-PCR
Serologic Diagnosis

 Serologic diagnosis of EV infection can be made by comparing antibody titers

in acute and convalescent phase (paired) serum specimens.

 In general, however, EV serodiagnosis is more relevant to epidemiologic

studies than to clinical diagnosis.

 A positive result with either IgM ELISA indicates a recent viral infection;
TREATMENT

 Antivirals

A number of specific antiviral compounds have been developed to target

enteroviral proteins and steps in the virus’ life cycle; none of these has received

regulatory approval, so there are currently no drugs available to treat

enterovirus infection.
Polio Eradication

 poliovirus infection has been radically altered by the widespread use of both
IPV and OPV.
 The recent activities of the Polio Eradication Initiative have eliminated
endemic poliovirus from most of the world.
 Since 1988, poliomyelitis from wild poliovirus has declined dramatically and in
the year 2015 remains endemic in only three countries in Africa and South
Asia.
 Four regions of the world—the Americas, the Western Pacific, Europe and
Southeast Asia—have been certified to be free of endemic poliovirus
transmission.
 One of the three serotypes of wild poliovirus (type 2) has already been
eliminated from the entire world.
Polio Eradication
 The eradication goal is attainable because humans are the only known
reservoir for poliovirus.
 The current global eradication program launched by WHO relies exclusively on
OPV for mass vaccination, but IPV is being introduced globally in 2015-2016.
 To achieve high vaccine coverage in all regions of the world, the Polio
Eradication Initiative also relies on supplemental immunization campaigns and
aggressive investigation of all suspected cases of AFP to identify wild PV
circulation.
 To ensure that no case of poliomyelitis is missed, every case of AFP in every
location in every country must be detected through clinical surveillance and
investigated virologically.
 Two stool samples should be collected on consecutive days, within 2 weeks
after the onset of paralysis, and processed for virus isolation
Circulating vaccine-derived polioviruses
(cVDPV).
 At least two dozen poliomyelitis outbreaks in 18 countries have been associated
with circulating vaccine-derived polioviruses (cVDPV).

 The outbreak strains were unusual because their capsid sequences were derived
from OPV.

 These viruses had recovered the capacity to cause paralytic poliomyelitis in

humans and to be transmitted efficiently among human population

 The discovery of cVDPVs has created urgency in planning a comprehensive post-

eradication immunization strategy and emphasizes the fact that the risk of polio
will not be eliminated until OPV vaccination stops
Reference

 Michael J. Loeffelholz, Richard L. Hodinka, Stephen A. Young & Benjamin A.

Pinsky. Clinical Virology Manual Fifth Edition. Washington, DC: ASM Press,
[2016]