1. Enterovirus infection associate professor Kantemirova M.G.

2. Enteroviruses are a genus of RNA viruses associated with several human and mammalian diseases : 66 serological human enterovirus serotypes.RNA virusesserotypes Four main groups of enteroviruses: polioviruses - 3 Coxsackie A viruses (CA) - 23 Coxsackie B viruses (CB) - 6 echoviruses - 28 ( 5 other enteroviruses)

3. Etiology and epidemiology 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

4. Enteroviruse infection Group of diseases caused by enteroviruses and characterized by symptoms of intoxication and clinical polymorphizm.

5. 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.febrile

6. Clinical forms of enteroviruse infection aseptic meningitis in childrenaseptic meningitis Pleurodynia is characerized by severe paroxysmal pain in the chest and abdomen, along with fever, and sometimes nausea, headache, and emesis.Pleurodynia Acute hemorrhagic conjunctivitis can be caused by enteroviruses.Acute hemorrhagic conjunctivitis Encephalomyocarditis in newborns

7. 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.Pericarditismyocarditisdyspneachest painArrythmias 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.Herpanginafeversore throatmalaisedysphagiaheadache Hand, foot and mouth disease is a childhood illness Hand, foot and mouth disease

8. 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.Encephalitisechovirus 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.Bornholm disease[1]diseaseCoxsackie B viruschronic fatigue syndrome Enteroviral exantema

9. Enteroviral epidemic exantema

10. haemorrhagic rash maculo- petechial rash

11. Hand-foot-mouth syndrome. Vesicular elements 1-3 mm with hyperemic ring, rapid turns into erousion (on the hands, feet, fingers, toes, mouth vucouse)

12. Hand-foot-mouth syndrome. Vesicular rash on the palm and lips. Moderate toxicosis, fever Epidemic or sporadic cases

13. Hand-Foot-and-Mouth Disease

15. 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.Herpanginafeversore throatmalaisedysphagiaheadache Enlargement of reginal lymph nodes

16. Diagnosis 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

17. Treatment Bed rest in acute period Antiviral drugs, interferons and it’s inductor,Ig, IHIG Pathogenetic, symptomatic treatment: antipyretics, diuretics, analgesics ….

18. Poliomyelitis (polio, infantile paralysis, HEINE-MEDINA disease ) HEINE-MEDINA

19. 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.

20. Etiology Poliovirus – RNA enterovirus. Three immunological serotypes (1,2,3) 1 st type – the most paralytogenic and epidimic. Well resistant to external factors, alive for a long time in sewage

21. 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.

22. 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

23. 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.immunizationimmunityIgAantibodiestonsilsIgG IgM central nervous system

24. Pathogenesis virus Pharyngeal, intestinal Mucose, replication Lymph nodes, intestinal follicles replication Priemery viremia replication in inner organs (Ret.endot.S) Secondary viremia CNS – motoneurons of anterior horns of spinal cord And motor nuclei of craniocerebral nerves, cerebral membrane, motor cortex

25. 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.

26. 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

27. 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 1988World Health Organizationeradicate - 483 cases in 2001, -1000 cases in 2005 - 1,606 - in 2009

28. 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

29. 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.

30. Aseptic meningitis Signs: headache, neck, back, abdominal and extremity pain, fever, vomiting, lethargy and irritability, neck stiffness, tremor, horizontal nystagmus,weakness in some muscleslethargy 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

31. 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

32. Major illness Only 0,5-1%-of patients develops paralytic form Incubation period – 7-14 days (range 5-35 days) Paralytic P. 1.Preparalytic period (1-6 days) 2.Paralytic period (1-2 weeks) 3.Recovery period (up to 2 ys) 4.Residual period ( after 2 ys)

33. 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.difficulty swallowingmuscle painreflexesparesthesia Cerebrospinal fluid: cell-protein dissociation 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.

34. Major illness

35. 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 affectedsensation 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).asymmetricalproximallydistallyfingertipstoes CSF; protein-cells dissociation

36. The location of motor neurons in the anterior horn cells of the spinal column

37. Spinal form Low limbs paralysis with muscles atrophy

38. Spinal form Left leg paresis, absence of skin folds

39. Spinal form Affected chest muscles: parasis and paralysis of intercostals‘ muscles, breathing lesions Affected abdomen muscles:frog-like abdomen» Affected left shoulder muscles

40. The location and anatomy of the bulbar region

41. 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, pneumoniaglossopharyngeal nervevagus nerve accessory nervemucus

42. 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

43. Recovery period Appearance of movements Decrease of painful syndrom Decrease of vegitative disorders irregular recovery of muscle’s functions

44. 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

45. Diagnosis 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

46. Differential diagnosis Acute flaccid enterovirus paralysis Facial neuritis Serous meningitis (viral and bacterial) Meningoencephalitis Polineuropathy in diphtheria Congenital myasthenia Polyradiculoneuritis

47. Treatment There is no cure for polio.cure 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

48. 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

49. Prevention 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.

50. 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 4 th -30 th 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