Elimination of VaccineAssociated Paralytic Poliomyelitis United States Lorraine

Elimination of Vaccine-Associated Paralytic Poliomyelitis – United States Lorraine N. Alexander, RN MPH National Immunization Program Centers for Disease Control

Objectives • To provide background on poliovirus vaccines, U. S. vaccination policy & changing epidemiology of polio • To describe U. S. success in eliminating vaccine-associated paralytic polio with the transition to an all-IPV schedule

Background

Poliovirus Vaccines • Inactivated poliovirus vaccine (IPV) – Developed in the 1950 s; IM injection – Trivalent IPV licensed in 1955 • Oral poliovirus vaccine (OPV) – Live attenuated-virus vaccine – Licensed in the early 1960 s • Monovalent OPV (m. OPV) type 1 -- 1961 • m. OPV types 2 and 3 -- 1962 • Trivalent OPV licensed in 1963

Poliovirus Vaccines: OPV vs. IPV • OPV selected as polio vaccine of choice in the US -- 1962 – Easier and cheaper to administer – Vaccine spread to contacts – Induces immunity quickly and reliably – Induces gut immunity – “lack of untoward reactions” • IPV continued to be available in US

Paralytic Poliomyelitis United States, 1951 -1959 Poliomyelitis Cases IPV licensed * YEAR

No. of Paralytic Polio Cases Paralytic Poliomyelitis United States, 1960 -1969 type 1 m. OPV type 2 OPV type 3 m. OPV t. OPV 0 2 25 18 12 YEAR 7 9 7 6 5

No. of Paralytic Polio Cases Paralytic Poliomyelitis United States, 1970 -1979 YEAR

No. of Paralytic Polio Cases Paralytic Poliomyelitis United States, 1980 -1989 YEAR

Poliovirus Vaccine Policy -- 1990 s • 1995 ACIP: – • 1996 ACIP: – – • increase reliance on IPV Adopt a sequential schedule of IPV-OPV All-OPV or all-IPV schedule acceptable 1999 ACIP: – – Exclusive use of IPV, beginning January 2000 OPV should be used only for special circumstances (e. g. polio outbreak)

Poliovirus Vaccine Policy -- Impact • Wyeth Lederle – Sole manufacturer of OPV (Orimune) in US – Ceased production & distribution of Orimune in December, 1999 • OPV no longer available in US

Epidemiology of Polio – United States, 1990 -2003

Data Sources • National polio surveillance system – – Maintained by CDC since 1955 Voluntary reporting-- local & state health depts Vaccine Adverse Events Reporting System National Vaccine Injury Compensation Program • Reviewed polio cases with onset between 1990 -2003

Paralytic Poliomyelitis: Clinical Case Definition • Acute onset of flaccid paralysis – – One or more limbs Decreased/absent tendon reflexes No apparent cause No sensory or cognitive loss

Paralytic Poliomyelitis: Confirmed Case Definition • Meets clinical case definition • Neurological deficit present 60 days after onset of symptoms • unless death has occurred, • or follow-up status unknown

Paralytic Poliomyelitis: Case Classification • Vaccine-associated paralytic polio (VAPP): Temporal association between exposure to OPV and onset of symptoms Median-slide

Estimation of VAPP Risk • Overall risk: ratio of VAPP cases per OPV doses distributed in USA – Recipient – Contact – Immunodeficient • Risk by dose: – First OPV (OPV 1) dose risk – Subsequent OPV dose risk

Results • 130 suspect cases reported, 1990 -2003 • 61 confirmed paralytic poliomyelitis • 59 VAPP • 1 indeterminate (1991) • 1 imported (1993) • Last VAPP case occurred in 1999.

VAPP Cases by Epidemiologic Classification, 1990 -1999 Epidemiological classification Total Sporadic (n = 43) OPV recipient 27 OPV contact 13 Community acquired 3 Immunodeficient (n =16) OPV recipient 14 OPV contact 2 Total 59

Sporadic VAPP Cases, by Age, United States, 1990 -1999 (N= 43)

Immunodeficient VAPP Cases, by Age, United States, 1990 -1999 (N=16)

Interval from OPV Exposure to VAPP Onset, United States, 1990 -1999 Epi Classification Median days Range (days) Sporadic Recipients 26 3 -61 Sporadic Contacts 28 10 -39 Immunodeficient 63 2 -398 Onset- slide

Poliovirus (PV) Types Isolated, VAPP Cases, United States, 1990 -1999 No. (%) of polio isolates* with indicated with poliovirus type Epidemiologic Classification PV 1 PV 2 PV 3 Total Sporadic 5 9 14 28 (72%) Immunodeficient 2 8 1 11 (28%) Total 7 (18%) 17 (44%) 15 (38%) 39 (100%)

VAPP Case Severity, United States, 1990 -1999 • Sixty-day follow-up of 59 VAPP cases: – 11 (19%) minor involvement – 31 (54%) significant involvement – 13 (22%) severe – 3 (5%) died – 1 unknown

Ratio of one VAPP case to number OPV doses distributed (in millions), United States, 1990 -1999 Case classification All doses Sporadic, all 1: 4. 0 Recipient 1: 6. 4 Contact Immunodeficient 1: 13. 3 1: 10. 8 Recipient 1: 12. 4 Contact 1: 86. 6 Total *First dose ratio/subsequent dose ratio. 1: 2. 9

Number and proportion of VAPP cases by implicated OPV dose, 1990 -1999 Epidemiological classification OPV 1 No. (%) Subsequent OPV No. (%) Sporadic OPV recipient 23 (85) 4 (15) OPV contact 7 (54) 6 (46) 3 (100) Community acquired n/a * Immunodeficient OPV recipient 4 (29) 10 (71) OPV contact 1 (50) 35 (59) 24 (41) Total * Implicated doses are assumed to be subsequent doses if unknown.

VAPP and Non-VAPP Cases, United States, 1990 -2004 IPV-OPV Schedule VAPP cases All-IPV Schedule Year

VAPP cases OPV doses in millions Poliomyelitis Cases, and OPV doses distributed, United States, 1990 -2004 Year

VAPP Cases during Sequential Schedule, United States, 1990 -2004 IPV-OPV VAPP cases All-IPV Year

Study Limitations • Denominator issue: Not all OPV doses distributed may have been administered • Some clinical cases of paralysis may have been misclassified as paralytic poliomyelitis or mis-categorized

Conclusions • The US has had a very successful polio vaccination program since the 1960 s: – Last indigenous wild polio case -- 1979 – Last imported wild poliovirus case -- 1993 • VAPP cases predominated by 1980 s • Vaccine policy change – transition from OPV to IPV – led to elimination of VAPP

Current Status • Keep polio immunity levels high • Maintain vigilance in detecting and responding to a potential poliomyelitis case • Development of polio vaccine stockpile to respond to outbreaks

Acknowledgements • Co-authors: Jane Seward; Tammy Santibanez; Roland Sutter; Mark Pallansch; Olen Kew; Rebecca Prevots; Peter Strebel; Melinda Wharton; Walt Orenstein • Support from CDC colleagues: Rex Ellington; Barry Sirotkin; Trudy Murphy; Jim Alexander

Extra Slides

Background • Poliovirus vaccines • Epidemiology of polio • Vaccine policy decisions

Paralytic Poliomyelitis United States, 1960 -1969 No. of Cases type 1 m. OPV type 2 m. OPV type 3 m. OPV t. OPV YEAR

Polio Vaccine Policy -- 1960 s • Surgeon General investigation • Advisory Group report: – Polio cases “compatible with the possibility of having been induced by the vaccine” – Risk higher in adults – Majority of cases associated with type 3 m. OPV

Poliovirus Vaccine Policy -- 1970 s • Institute of Medicine (IOM) report, 1977: – Continue routine use of OPV– except in those with contraindications to OPV – IPV as an option for all others

Poliovirus Vaccine Policy -- 1980 s • Most US polio cases were vaccineassociated • Enhanced IPV was licensed in US, 1988 • IOM report, 1988: – Continue primary reliance on OPV

Poliovirus Vaccine Policy -- 1990 s • In 1995 ACIP voted increase reliance on IPV but postponed decision – working group formed – model presented to IOM: predicted to reduce VAPP by 43 -51% • Sequential schedule proposed as a transition towards all-IPV

Poliovirus Vaccine Policy -- 1990 s • In June 1996, ACIP voted to adopt a sequential schedule of IPV-OPV – An all-OPV or all-IPV schedule was acceptable —if parents are informed • Jan 1999, it was noted that cases of VAPP continued to occur – A revised recommendation, endorsed by AAP stated that only all-IPV schedule was acceptable

Poliovirus Vaccine Policy -- 1990 s • • In June 1999, ACIP recommended exclusive use of IPV as of January 2000 OPV should be used only for special circumstances (e. g. polio outbreak)

Objectives of Study • Review the epidemiology of paralytic poliomyelitis since 1990 • Impact of polio vaccine policy changes

Study Methods • Sources of Data • Case Definition • Estimation of VAPP Risk

Paralytic Poliomyelitis: Case Classification (1) • Sporadic: immune-competent • Epidemic: epidemiological link to another case • Immune-deficient: immunologically abnormal person • Imported: case in a person who has entered the US within 30 days

Estimation of OPV Doses Administered, by Dose, 1990 -1996 • OPV 1 administered = annual birth cohort • Subsequent doses administered = (OPV doses distributed) - birth cohort

Estimation of OPV Doses Administered, by Dose, 1997 -1999 • OPV 1 doses = (NIS estimate of % of children who received OPV 1) X (annual birth cohort) • Subsequent doses = (Number of doses OPV distributed) – (OPV 1 doses)

Study Results • Cases characteristics; epidemiologic, clinical and laboratory • VAPP risk estimates • VAPP cases outcomes • Graphics: – Poliomyelitis and vaccine changes, 1990 s – VAPP and OPV doses distributed – VAPP and vaccine policy recommendations

Study Results • Cases characteristics; epidemiologic and clinical data • VAPP risk estimates • VAPP cases outcomes • Graphics: – Poliomyelitis and vaccine changes, 1990 s – VAPP and OPV doses distributed – VAPP and vaccine policy recommendations

Study Results • Number of cases, demographic, epidemiologic, and clinical data • VAPP risk estimates • VAPP cases severity outcomes • Graphic results • Study Limitations