Poliomyelitis

1. Poliomyelitis

2. Disease of semi-developed societies Occurs sporadically or in epidemics First described in Egypt, major cause of morbidity and mortality until 1960s Large epidemics in 1940s and 1950s in the developed world Poliomyelitis

3. HISTORY • 1789 - British physician Michael Underwood provides the first clinical description of polio, referring to it as "debility of the lower extremities.“ • 1840 - German physician Jacob von Heine published a 78-page monograph which not only describes the clinical features of the disease, but also notes that its symptoms suggest the involvement of the spinal cord. • 1908- Austrian physicians Karl Landsteiner and Erwin Popper make the first hypothesis that polio may be caused by a virus.

4. The word poliomyelitis is derived from polio = gray and myel = spinal cord). • Poliomyelitis is defined as an acute febrile illness, usually with meningitis and flaccid paralysis, but without objective evidence of a sensory defect or cortical damage. • Paralysis is an uncommon manifestation of viral CNS infection.

5. Causative Viruses • Polioviruses 1, 2, and 3 • NonpolioEnteroviruses - Sporadic: Coxsackievirus and Echovirus - Epidemic: Enterovirus 71 is the only non-polio serotype associated with large outbreaks (100s of cases of paralytic disease ) • West Nile Virus - This is clearly the most common cause of poliomyelitis in the United States in the past several years.

6. Pathogenesis and Pathology of Enteroviruses • Enteroviruses have similar pathogenesis but different target organs. • They inhabit the GI tract and rarely cause enteric disease. • The incubation period is usually between 7 and 14 days but may be as short as 2 days and as long as 35 days. • Viremia spreads the virus to involve target organs (spinal cord and brain, meninges, myocardium, skin)

7. Virus is excreted in the stools for several weeks and is present in the pharynx 1 to 2 weeks after infection. • Neural spread may occur in children who have unapparent infection at the time of tonsillectomy (bulbar paralysis). • The anterior horns are most prominently involved, but in severe cases the intermediate gray ganglia and even the posterior horns and dorsal root ganglia are often affected. • Viral rather than immunopathology is responsible for disease manifestations.

8. Clinical Syndromes • Asymptomatic Infection: The most common form (>90%) of infection. • Symptomatic Illness: Less than 10% of infections result in a recognized clinical illness. • Abortive Poliomyelitis (minor illness) • The most common form of the disease (5%). • The patient has only a minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, or sore throat in various combinations. The patient recovers in a few days.

9. Nonparalytic Poliomyelitis/ Aseptic Meningitis - It is seen in 1-2% of infections. - Stiffness and pain in the back and neck. - The disease lasts 2 to 10 days, and recovery is rapid and complete. - In a small percentage of cases, the disease advances to paralysis.

10. Meningitis and Mild Paresis - The disease sometimes progresses to mild muscle weakness that may be confused clinically with paralytic poliomyelitis. - In addition to poliviruses, viruses that cause this disease include Coxsackie B1 to B6, A7 and A9 and echoviruses 3, 4, 6, 9, 1, 14, 16, 18, 19, 25, 30, 31 and 33 and rarely enterovirus 70 and 71.

11. Paralytic Poliomyelitis - It usually occurs without an antecedent first phase. - The predominating sign is flaccid paralysis resulting from lower motor neuron damage. - Muscle involvement is usually maximal within a few days after the paralytic phase begins. - The maximal recovery usually occurs within 6 months, but it may take longer. - Paralytic disease is either spinal or bulbar poliomyelitis.

12. Painful muscle spasms and incoordination of non- paralysed muscles may occur • Involvement of the medulla may lead to respiratory paralysis and death • Paralysis usually develops over several days and some recovery may take place. • Any effects persisting for more than 6 months are usually permanent

15. Long Term Sequalae • Among children who are paralyzed by polio: - 30% make a full recovery - 30% are left with mild paralysis - 30% have medium to severe paralysis - 10% die

17. Post-Poliomyelitis Syndrome (PPS) • Progressive Postpoliomyelitis Muscle Atrophy (PPMA) • A recrudescence of paralysis and muscle wasting as a result of physiological and aging changes • An estimated 20-30% of polio survivors develop new symptoms approximately 35 years after their initial episode of polio (range 8-71 years). Most cases occur before the age of 60 years.

18. Symptoms are variable, and include muscular weakness, focal or generalized muscle atrophy, fatigue, pain and decreased ambulatory abilities. • The onset of PPS is correlated to the severity of the original disease. • May result from peripheral disintegration of individual nerve terminals in motor units that were reinnervated during recovery after the acute disease.

19. Criteria For Diagnosis of Post Polio Syndrome A prior episode of paralytic poliomyelitis EMG evidence of longstanding denervation A period of neurological recovery and functional stability preceding the onset of new problems (Usually >20 years)

20. Criteria for Diagnosis of Post Polio Syndrome Gradual or abrupt onset of new non-disuse weakness in previously unaffected or affected muscles May be associated with fatigue, muscle pain, joint pain, decreased function, etc. Exclusion of other conditions that may cause the above features

21. Pathophysiology Theories: • Remaining healthy motor neurons can no longer maintain new sprouts • Decompensation / chronic denervation and reinervation process. • Denervation exceeds reinervation

22. Motor neuronal loss due to reactivation of a persistant latent virus. Infection of the polio survivor’s motor neuron by a different enterovirus Loss of strength associated with aging, in already weakened muscles Theories (contd.)

23. Fatigue (most common) Weakness Muscle pain Gait disturbance Respiratory problems Swallowing problems Cold intolerance Sleep apnoea Main Clinical Features of PPS

24. Fatigue • Prominent in the early hours of the afternoon • Decreases with rest • Pathogenesis:Chronic pain / Muscle pain • Sleep disorders/ respiratory dysfunction • Difficulty in remembering/ concentrating • Decreased muscular endurance / Increased muscular fatigability • Generalized or muscular

25. Swallowing Problems: Subclinical asymmetrical weakness in the pharyngeal constrictor muscles almost always present in PPMA • Cold Intolerance: - Autonomic nervous system dysfunction? - May relate to sympathetic intermediolateral column damage during acute poliomyelitis - Peripheral component may include muscular atrophy leading to reduced heat production • Sleep Apnoea: diminished muscle strength of respiratory, intercostal & abdominal muscle groups

26. Laboratory Diagnosis • Virus isolation • Serology

29. No specific treatment is available except supportive measures in paralytic polio An ‘Iron Lung’ ward during a 1950s epidemic in Boston

30. Poliovirus Vaccine • 1955 Inactivated vaccine • 1961 Types 1 and 2 monovalent OPV • 1962 Type 3 monovalent OPV • 1963 Trivalent OPV • 1987 Enhanced-potency IPV (IPV)

31. Inactivated Polio Vaccine • Contains 3 serotypes of vaccine virus • Grown on monkey kidney (Vero) cells • Inactivated with formaldehyde • Contains 2-phenoxyethanol, neomycin, streptomycin, polymyxin B

32. Oral Polio Vaccine • Contains 3 serotypes of vaccine virus • Grown on monkey kidney (Vero) cells • Contains neomycin and streptomycin • Shed in stool for up to 6 weeks following vaccination

33. Inactivated Polio Vaccine • Highly effective in producing immunity to poliovirus • >90% immune after 2 doses • >99% immune after 3 doses • Duration of immunity not known with certainty

34. Oral Polio Vaccine • Highly effective in producing immunity to poliovirus • 50% immune after 1 dose • >95% immune after 3 doses • Immunity probably lifelong

37. Risks (Vaccine-associated Paralysis) - Maximum Risk (Study of 700 million doses) *1 per > 11 million vaccinees. *in a household contact 1 per 4 million vaccinees *in a community contact 1 for every 30 million vaccinees *Actual risk is lower

38. Epidemiology • Fecal oral route of transmission. • Humans are the only reservoir. • Poor hygiene and sanitation promote spread which is favored by warm weather. • Epidemics (water-borne less so food-borne) • Majority of infections are asymptomatic.

39. Bases of Confirmation of Suspected Cases During Outbreaks 1) Virus Isolation 2) Clinical Grounds 3) Epidemiologic 4) Outcome (Death) 5) Loss of Track

40. Epidemiology • Before the 20th century, there were sporadic cases of polio; no major outbreaks occurred • Before the sanitary movement,cities had open sewers or gutters which exposed individuals to the poliovirus • Generations of children were infected but protected (in part) by maternal antibodies • Diagnosis of polio was rare as symptoms were often indistinguishable from other childhood diseases

41. Cases of paralytic polio ironically began to rise due to changes in public sanitation and other health measures • The disease was more likely to take the paralytic formin older children or adults • In northern Europe and the USA, epidemics of paralytic polio began to appear in the late 19th and early 20th centuries, though small

42. An outbreak in the USA in the summer of 1916, 27,000 people paralyzed, and 6,000 deaths. It caused widespread panic and people deserted cities • Subsequently, epidemics were reported each summer with major ones during 1940s-50s • The worst epidemic occurred in 1952 ~ 58,000 cases, 3,145 deaths, 21,269 mild to disabling paralysis • More children died of polio in 1952 than any other infectious disease

43. Global Status 1988

44. Polio Eradication: Status in 1998

45. GLOBAL STATUS 2004

47. GLOBAL POLIO VIRUS CASES 1988 350, 000 1998 1,934 1999 1,186 2000 265 2001 211 2002 1919 2003784 2004 1,556 2005 1831

48. West Nile Virus • Severe neurologic illness categories -- Meningitis -- Encephalitis -- “Meningoencephalitis” -- Acute flaccid paralysis -- Emerging clinical syndromes • Movement disorders • Parkinsonism • Rhabdomyolysis

49. WNV-Associated Flaccid Paralysis • Previously described; not “new” syndrome • Relatively young; lack of premorbidity conditions • May have absence of fever, headache • Clinical hallmarks: • Onset during acute infection • Asymmetry of weakness • Absence of sensory changes • Elevation of CSF protein and WBC

50. WNV-Associated Flaccid Paralysis • Multiple alternative diagnoses (stroke, GBS, myopathy)—Rx with heparin, IVIG • Syndrome actually localized to spinal anterior horn cells —resultant poliomyelitis • Recognition could limit unnecessary diagnostic procedures and treatment • Little or no improvement (short-term)