Transcript Enterovirus infection

Enterovirus infection
associate professor Kantemirova
M.G.
• Enteroviruses are a genus of RNA
viruses associated with several human and
mammalian diseases : 66 serological human
enterovirus serotypes.
• Four main groups of enteroviruses:
polioviruses - 3
Coxsackie A viruses (CA) - 23
Coxsackie B viruses (CB) - 6
echoviruses
- 28
( 5 other enteroviruses)
Etiology and epidemiology
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Small in size, RNA
Well resistant to external condition
Sensitive to ultraviolet, high Tº
The source: sick person and carries
Mode of transmission: fecal-oral, droplets
The route:air droplets, water, food, direct
contact, transplacental
Susceptibility is high
Peak incidence – in children aged 3-10
years,but may be in neonatal period
(encephalomyocarditis)
Immunity – serotype specific
Season: spring-summer and summer-autumn
Enteroviruse infection
Group of diseases caused by enteroviruses
and characterized by symptoms of
intoxication and clinical polymorphizm.
Clinical forms of enteroviruse infection
• Poliomyelitis
• Nonspecific febrile illness is the most
common presentation of enterovirus
infection. Other than fever, symptoms
include muscle pain, sore throat,
gastrointestinal distress, and headache.
Abdominal discomfort may also be
reported in some patients.
Clinical forms of enteroviruse infection
• aseptic meningitis in children
• Pleurodynia is characerized by severe
paroxysmal pain in the chest and
abdomen, along with fever, and
sometimes nausea, headache, and
emesis.
• Acute hemorrhagic conjunctivitis can be
caused by enteroviruses.
• Encephalomyocarditis in newborns
Clinical forms of enteroviruse infection
• Pericarditis and/or myocarditis are typically caused by
enteroviruses; symptoms consist of fever
with dyspnea and chest pain. Arrythmias, heart failure,
and myocardial infarction have also been reported.
• Herpangina is caused by Coxsackie A virus, and
causes a vesicular rash in the oral cavity and on the
pharynx, along with high fever, sore throat, malaise,
and often dysphagia, loss of appetite, back pain,
and headache. It is also self limiting, with symptoms
typically ending in 3–4 days.
• Hand, foot and mouth disease is a childhood illness
Clinical forms of enteroviruse infection
• Encephalitis is rare manifestation of enterovirus
infection; when it occurs, the most frequent
enterovirus found to be causing the it
is echovirus 9.
• Bornholm disease - epidemic myalgia[1] is
a disease caused by the Coxsackie B virus A
2007 study suggested that acute respiratory or
gastrointestinal infections associated with
enterovirus may be a factor in chronic fatigue
syndrome.
• Enteroviral exantema
Enteroviral epidemic exantema
Enteroviral epidemic exantema
haemorrhagic rash
maculo- petechial rash
Hand-foot-mouth syndrome.
• Vesicular elements 1-3 mm
with hyperemic ring, rapid
turns into erousion (on the
hands, feet, fingers, toes,
mouth vucouse)
Hand-foot-mouth syndrome.
• Vesicular rash on the palm and
lips.
• Moderate toxicosis, fever
• Epidemic or sporadic cases
Hand-Foot-and-Mouth Disease
Hand-Foot-and-Mouth Disease
Herpangina
• Herpangina is caused by
Coxsackie A virus, and causes
a vesicular rash in the oral
cavity and on the pharynx,
along with high fever, sore
throat, malaise, and
often dysphagia, loss of
appetite, back pain,
and headache. It is also self
limiting, with symptoms
typically ending in 3–6 days.
Enlargement of reginal lymph
nodes
Diagnosis
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Epidemic cases
Summer-autumn incidence
Prolong fever with 2 peacks
polymorphous clinical peacture
Laboratory findings
PCR - faeces , nasopfaryngeal discharges
IFA, serological tests (RN, RCB) –antibodies
increase
Treatment
• Bed rest in acute period
• Antiviral drugs, interferons and it’s inductor,Ig,
IHIG
• Pathogenetic, symptomatic treatment:
antipyretics, diuretics, analgesics ….
Poliomyelitis
(polio, infantile paralysis,
HEINE-MEDINA disease)
Definition
An acute viral infection with wide range of
manifestations :nonspesifis minor illness
and major illness (aseptic meningitis – non
paralytic P; paralytic P – flaccid weakness
of various muscular groups) –
antroponosis.
Etiology
• Poliovirus – RNA enterovirus.
• Three immunological serotypes (1,2,3)
• 1st type – the most paralytogenic and
epidimic.
• Well resistant to external factors, alive for
a long time in sewage
Epidemiology
• The source of P.- sick person and carries;
The most danger is non(in)apparent or abortive forms.
Even in epidemics the ratio of nonapparent to clinic
cases is 100:1
Mode of transmission: main - fecal-oral (water,
food,direct contact) additional – droplets (first 1-2
(weeks)
• The contagious period: is not defined. Polioviruses are
revealed in paitient’s stool for 6-8 weeks. After recovery
– may be a carrie.
• Susceptibility - any age. 90% paralytic cases - children
under 5-7 ys
• Season: summer-autumn
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Epidemiology
• Factors for promotion virus circulation:
- poor sanitation and hygine
- low level of vacination
- immunodificiency
- malnutrition
Predisposing factors to paralytic forms:
- tonsillectomy, adenoidectomy
- toot extraction
- lumbar puncture
Immunity
• Individuals who are exposed to the virus, either
through infection or by immunization with polio
vaccine, develop immunity. In immune
individuals, IgA antibodies against poliovirus are
present in the tonsils and gastrointestinal tract
and are able to block virus replication; IgG and
IgM antibodies against PV can prevent the
spread of the virus to motor neurons of the
central nervous system. Infection or vaccination
with one serotype of poliovirus does not provide
immunity against the other serotypes, and full
immunity requires exposure to each serotype.
Pathogenesis
virus
Pharyngeal, intestinal
Mucose, replication
replication in inner
organs (Ret.endot.S)
Secondary viremia
Lymph nodes,
intestinal follicles
replication
Priemery viremia
CNS – motoneurons of anterior horns of
spinal cord
And motor nuclei of craniocerebral nerves,
cerebral membrane, motor cortex
• The site and severity of paralysis depends on
the degree of neural lesions. The process is
reversible in the stage of perineuclear and
neuclear infiltration. If more than 1/3
motoneurons undergo necrosis paralyses
becomes irreversible. Muscels innervated with
damaged neurons undergo athrophy due to
denervation of skeletal muscles.
Classification
I. Minor illness (without NS involvement):
abortive
II. Major illness (with NS involvement):
1. nonparalytic P: meningeal form
2. paralytic P: - spinal form
- bulbar (bulbar-spinal)
- encephalic form
Incidence
• According to World Health Organization, a
global effort to eradicate polio by
widespread vaccination leads to reduction
the number of annual diagnosed cases by
99%: - 350,000 cases in 1988
- 483 cases in 2001,
-1000 cases in 2005
- 1,606 - in 2009
Incidence
• Asymptomatic - 90–95%
• Minor illness - 4–8%
• Non-paralytic aseptic meningitis - 1-2%
• Paralytic poliomyelitis - 0.1–0.5% (1%):
Spinal polio - 79% of paralytic case
Bulbospinal polio - 19% of paralytic cases—
Bulbar polio - 2% of paralytic cases
Incubation period – 7-14 days (range 5-35 days
Minor illness
• Inaparent – without clinical signs
• Abortive: lasts for 1-4 days – moderate
fever, headache, sore throat, nausea,
vomiting, loss of appetite, vague
abdominal pain.
Aseptic meningitis
• Signs: headache, neck, back, abdominal and extremity
pain, fever, vomiting, lethargy and irritability, neck
stiffness, tremor, horizontal nystagmus,weakness in
some muscles
• Tripod sign – on asking the child to sit up unassisted,
he writhes from side to side, flexes the knees and places
his hand behind him
• Kiss the knee test: the kness are kept down and the
child is asked to kiss his knees; he can’t do it due to
stiffness and pain of his spine
• Head drop sign: the hands placed under the
patient’s shoulder, the trunk is rised
Aseptic meningitis
• Cerebrospinal fluid: cell-protein dissociation –
increased cells - up to 200-300 leucocytes
predominately lymphocytes and mild elevation of
protein.
Intracranial pressure is increased.
• Lumbar puncture in this case can promote the
development of paralytic form
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Major illness
Only 0,5-1%-of patients
develops paralytic form
Incubation period – 7-14
days (range 5-35 days)
Paralytic P.
Preparalytic period (1-6
days)
Paralytic period (1-2
weeks)
Recovery period (up to 2
ys)
Residual period ( after 2
ys)
Preparalytic period
• High or moderate fever, headache, stiffness in the back
and neck, asymmetrical weakness of various muscles,
sensitivity to touch, difficulty swallowing, muscle pain,
loss of superficial and deep reflexes, paresthesia (pins
and needles), irritability, constipation, or difficulty
urinating; Tripod sign, Kiss the knee positive test, Head
drop sign.
• Cerebrospinal fluid: cell-protein dissociation
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Paralysis generally develops one to ten days after early
symptoms begin, progresses for two to three days, and
is usually complete by the time the fever breaks.
Major illness
Paralytic period
• Sudden morning paralysis -the muscles become weak,
floppy and poorly controlled, and finally completely
paralyzed –flaccid paralysis
• Progression to maximum paralysis is rapid (two to four
days), and is usually associated with fever and muscle
pain
• Deep tendon reflexes are also affected, and are usually
absent or diminished; affected limbs –
pale,cold,cyanotic,soon-atrophy
• sensation (the ability to feel) in the paralyzed limbs,
however, is not affected
• more often the paralysis is asymmetrical. Any limb or
combination of limbs may be affected—one leg, one
arm, or both legs and both arms. Paralysis is often more
severe proximally than distally (the fingertips and toes).
• CSF; protein-cells dissociation
The location of motor neurons in the anterior
horn cells of the spinal column
Spinal form
• Low limbs paralysis
with muscles atrophy
Spinal form
• Left leg paresis, absence of skin folds
Spinal form
• Affected chest muscles:
parasis and paralysis of
intercostals‘ muscles,
breathing lesions
• Affected abdomen
muscles:frog-like abdomen»
• Affected left shoulder
muscles
The location and anatomy of the bulbar
region
Bulbar form - life-threatened
• damage of the cranial nerves neuclei
(glossopharyngeal nerve, vagus nerve,
accessory nerve) causes difficulty breathing,
speaking and swallowing; fluids regargitation,
nasal speech, voice hoarseness; arrhythmia,
increase and fall of BP-shock, irrigular breathing,
; control of upper neck movement. Due to the
effect on swallowing, secretions of mucus may
build up in the airway causing suffocation,
atelectasis, pneumonia
Pontine form
• Nuclei of the facial nerve and motor part of of the
trigeminal nerve are affected
• symptoms include facial weakness(paresis) or paralysis
of mimic muscles
Recovery period
• Appearance of
movements
• Decrease of painful
syndrom
• Decrease of vegitative
disorders
• irregular recovery of
muscle’s functions
Residual period
• crude contracture and
skeletal deformities,
scoliosis,osteoporosis
• Growth retardation of
affected limb
• Persistent prominent
flaccid paralysis
• Muscles atrophy
• Disturbances of liquor
circulation
• Vegetative disturbances
Diagnosis
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Epidemic anamnesis
Clinical peacture
Electromyography
Laboratory findings
LP – increased ICP, cell-protein (first 1-2
weeks), than protein-cell dissociation (2d – 3d
weeks)
• PCR, virusological findings
• Serological – increase in specific antibodies
titer > 4 times
Differential diagnosis
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Acute flaccid enterovirus paralysis
Facial neuritis
Serous meningitis (viral and bacterial)
Meningoencephalitis
Polineuropathy in diphtheria
Congenital myasthenia
Polyradiculoneuritis
Treatment
• There is no cure for polio.
• Strict bed rest with physiological position for affected
limbs, change of position every 2 hours
• Interferons
• Pathogenetic:Патогенетическое
– dehydration (lasics, diacarb)
– nonsteroid antiinflammatory drugs
– trental, curantil
– vasoective neurometabolits (instenon, actovegin)
– polyvitamins
– in sever cases – corticosteroids, antibiotics
– analgetics
Treatment
• hydrotherapy, electrotherapy, massage and passive
motion exercises
• surgical treatments such as tendon lengthening and
nerve grafting
• Devices such as rigid braces and body casts
• Orthopedic surgery
Prevention
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Nonspecific – strong control for all cases of flaccid paralysis
Patient isolation for 4-6 weeks
Current and terminal disinfection in place of infection
Quarantine for contacts 21 days
Immediate vaccination in focus of infection all susceptible
under 5 ys.
• Spesific active vaccunation: live attenuated (weakened) oral
polio vaccine (OPV)-Three doses of live-attenuated OPV
produce protective antibody to all three poliovirus types in more
than 95% of recipients ; inactivated (killed) polio vaccine (IPV).
very rare (about 1 case per 750,000 vaccine recipients) the
attenuated virus in OPV reverts into a form that can
paralyze.Most industrialized countries have switched to IPV
Vaccination starts at 3 months - 4,5 - 6 months (thrice in 30-45
days). Revaccination -18 months, 20 months, 14 ys.
Vaccine associated Polio
Develops in immune compromised individuals and
when the attenuated virus in OPV reverts into a form
that can paralyze.
Diagnostic criteria.
The onset the disease on 4th-30th days after
vaccination. For contacts this period prolonged to 60
days.
Flaccid paresis and paralysis without sensory loss with
persistent consequences (>2 months)
absence of progredient course (worsening)
Isolation of antigens similar to vaccinated strain virus
and specific antibodies increase in 4 times