1

POLIO THEN AND NOWancient Egypt and contemporary southern Asia

1Egyptian stele, 14th century BC Wikipedia, 2009

POLIOMYELITIS REVISITEDan epidemiological and historical perspective (to 1973)Neal Nathanson, University of Pennsylvania

• Polio emerges: ancient history and the early outbreaks, through 1916

• Polio triumphant: annual epidemics in the United States, 1916-1955

• Polio in retreat: IPV to first eradication, 1955-1973

2

1973

• Polio deconstructed: epidemiological enigmas and explanations

2

EMERGENCE OF POLIO AS AN EPIDEMIC DISEASEUnited States, 1885-1916

3Lavinder et al Public Health Bulletin #1, 1918

EMERGENCE OF EMERGENCE OF POLIO AS AN EPIDEMIC DISEASE

the world, 1880-1916

4

Lavinder et al Public Health

Bulletin #1, 1918

3

EMERGENCE OF POLIO AS AN EPIDEMIC DISEASEfirst enigma

OBSERVATIONOBSERVATION• Between the years 1890 and 1910 polio appeared

as an epidemic disease in the USA and many European countries?

ENIGMA• What explains the transition from a sporadic to an

5

epidemic disease?

POLIO DECONSTRUCTEDepidemiological enigmas and hypotheses

HYPOTHESIS• Poliovirus was ubiquitous prior to appearance of epidemic polio: • Poliovirus was ubiquitous prior to appearance of epidemic polio:

epidemics do NOT reflect an increase in the number of polio infections• Appearance of polio epidemics does NOT reflect an increase in

virulence of poliovirus• The appearance of epidemic poliomyelitis was due to a delay in initial

infection from infancy to childhood• Infants infected prior to age 6-12 months were protected against

paralysis by maternal antibody while toddlers were not

6

EVIDENCE TO TEST THE HYPOTHESIS• Seroepidemiological comparison of pre- and post-epidemic regions• Comparison of two populations in a single city: Casablanca, 1947-1953• Sero-epidemiology in pre-epidemic population: Casablanca, 1953

4

POLIO DECONSTRUCTEDpoliovirus is ubiquitous prior to the emergence of epidemic polioinfections are delayed in regions where polio is epidemic

7Paul WHO Monograph 26, 1955

1953 seroepidemiology

POLIO DECONSTRUCTEDpolio incidence in two populations in a single city: Casablanca, 1947-1953

European MoroccanEuropean Moroccan

Population 125,000 530,000

Paralytic polio cases, 1947-1953 117 25

Average annual attack rate per 100,00013.4

Epidemic0.7

Pre-epidemic

8

1953 cases by age group

0-1 8 9

2-9 15 2

10-39 5

Paul and Horstmann Am J Trop Med Hyg 1955, 4: 512

5

POLIO DECONSTRUCTEDage-specific poliovirus antibody prevalenceMoroccan population, Casablanca, 1953

+ 100 100N

T PO

LIO

AB

, 1:1

0+

40

60

80

40

60

80

9Paul and Horstmann Am J Trop Med Hyg 1955, 4: 512

AGE IN YEARS0 5 10 15 20 25 30

PER

CEN

0

20

0

20

POLIO DECONSTRUCTEDPre-existing serum antibody will confer protection against paralytic poliomyelitis at a titer of ≥1:4

Percent Unvaccinated

placebo children

Vacccinated children

protection against

paralytic poliomyelitis

Number of paralytic cases

40

14(40 expected

if no 65%

10

protection)

Percent seroconversions ≥ 1:4

0% 65%

Francis et al. 1954 Field Trial of poliovirus vaccine, 1957

6

POLIO TRIUMPHANT: ANNUAL EPIDEMICSPolio age distribution, Massachusetts, 1912-1952

1912-16 1925-29 1935-39 1948-52

PER

CEN

T

40

60

80

100

0-45-9 10 +

11Dauer Pro NY Acad Sci 1955, 61: 943

P

0

20

POLIO TRIUMPHANT: ANNUAL EPIDEMICSParalytic polio incidence, USA, 1915-1954

000

14

RA

TE P

ER 1

00,0

6

8

10

12

14

12Serfling and Sherman Pub Hlth Rep 1953, 68: 453; and CDC, 1955

1915 1920 1925 1930 1935 1940 1945 1950 1955

AN

NU

AL

0

2

4

7

POLIO TRIUMPHANT: ANNUAL EPIDEMICS second enigma

OBSERVATIONS• After its appearance polio became an annually

recurring epidemic disease (USA, 1900-1954)• During this period the age distribution increased

quite dramatically, evolving from “infantile paralysis” into a disease mainly of children and young adults

13

ENIGMA• Why did the age distribution evolve?• Did the advancing age of infection result in an

overall increase in incidence?

POLIO DECONSTRUCTEDepidemiological enigmas and hypotheses

HYPOTHESISHYPOTHESIS• Improved sanitation and personal hygiene reduced

the probability of transmission and led to a delay in the age of infection (USA, 1900-1950)

• The data are unclear whether this led to an increase in overall incidence of paralytic poliomyelitis

EVIDENCE TO SUPPORT THE HYPOTHESIS

14

EVIDENCE TO SUPPORT THE HYPOTHESIS• Studies of the case:infection ratio by age• Polio incidence in New York City, 1910-1954

8

POLIO DECONSTRUCTEDAge-specific paralytic case:infection ratio

AgeNumber of

seroconvertersParalytic

casesCases per 100 seroconverters

<1 450 3 0.66

1-2 1,000 10 1.00

3-4 741 12 1.62

5 9 1 042 25 2 40

15

5-9 1,042 25 2.40

10-14 716 13 1.82

TOTAL 3,949 63 1.59

Melnick and Ledinko Am J Hyg 1953, 58: 207

POLIO DECONSTRUCTEDAverage annual polio incidence, New York City, 1910-1952

LIO

00

25

GE

AN

NU

AL

POL

ENC

E PE

R 1

00,0

0

10

15

20

16

1910 1920 1930 1940 1950

AVE

RA

GIN

CID

E

0

5

Siegel et al. NE J Medicine 1955, 252: 752

9

POLIO TRIUMPHANT: SEROTYPE DIFFERENCESFrequency of isolates from poliomyelitis cases, by serotype, USA, 1952data by regions with different overall attack rates

Regions by attack rates per 100,000

Number of isolates

Percent of isolates

Type 1 Type 2 Type 3

445-103 270 94% 4% 2%

94-43 156 77% 10% 13%

17Shelokov et al Proc NY Acad Sci 1959, 61: 998

40-16 235 77% 20% 3%

15-4 133 59% 28% 13%

POLIO DECONSTRUCTEDthird enigma

OBSERVATIONTh th t f li i t i • The three serotypes of poliovirus appear to vary in epidemic significance: type 1; type 2; type 3

• Wild type 2 poliovirus has been eradicated while types 1 and 3 have not

ENIGMA

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• Is this due to differences in environmental survival; infectivity; viremogenicity; neuro-invasiveness; or neurovirulence?

10

POLIO TRIUMPHANT: SEASONALITYPoliomyelitis cases by month, New England, 1915-1954

AL 35

NT

OF

AN

NU

AL

TOTA

10

15

20

25

30

NEW ENGLANDPEAK MONTH: 31%TROUGH MONTH: 0.3%

19

MONTHD J F M A M J J A S O N D J F M

PER

CEN

0

5

Serfling and Sherman Pub Hlth Rep 1953, 68: 453; and CDC, 1955

POLIO TRIUMPHANT: A DREAD DISEASEPast images from the USA

20

11

POLIO TRIUMPHANT: A FRIGHTENING SPECTERIron lung ward at Rancho los Amigos, Downey, California, USA, 1953

21

POLIO DECONSTRUCTEDfourth enigma

OBSERVATIONS• Polio seasonality is marked in cold climates and peaks in late

summer• Seasonality is marked for many viral diseases but peaks occur at

different times of yearHYPOTHESIS• Seasonality does NOT reflect differences in human activity• Seasonality reflects seasonal differences in humidity but NOT in

temperature

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EVIDENCE• Rotaviruses (another enterovirus) has totally different seasonality• Polio seasonality is associated with seasonal changes in indoor

humidity, but not in tropics where humidity is constant and high• Environment duration of poliovirus infectivity is much greater at

elevated relative humidity and constant temperature (20C)

12

POLIO DECONSTRUCTEDSeasonality of polio and rotaviruses, USA

L POLIOVIRUS

OF

AN

NU

AL

TOTA

10

15

20

25

30

35PEAK

AUG-SEPROTAVIRUS

PEAKMAR-APR

23Serfling and Sherman Pub Hlth Rep 1953, 68: 453; Torok et al. Ped Inf D J 1997, 16: 941

MONTHD J F M A M J J A S O N D J F MPE

RC

ENT

0

5

10

POLIO DECONSTRUCTEDSeasonality, New England and Hawaii compared

HAWAIINEW ENGLAND

OF

AN

NU

AL

TOTA

L

20

30

40

50

VE H

UM

IDIT

Y (%

)

40

60

80HUMIDITY

HAWAIIPEAK:TROUGH 3:1

NEW ENGLANDPEAK:TROUGH 100:1

OF

AN

NU

AL

TOTA

L

20

30

VE H

UM

IDIT

Y (%

)

40

60HUMIDITY

24

MONTHD J F M A M J J A S O N D J F M

PER

CEN

T O

0

10

20

REL

ATI

V

20

40

POLIO

Nathanson and Martin Am J Epidemiology 1979, 110: 672

MONTHD J F M A M J J A S O N D J F M

PER

CEN

T O

0

10

REL

ATI

V

20

POLIO

13

POLIO DECONSTRUCTEDPoliovirus survival at 20C is sensitive to reduced humidity

25Hemmes et al Ant V Leeuwanhoek 1962, 28: 221

POLIO IN RETREAT: IPV TO FIRST ERADICATIONPolio incidence, USA, 1952-1979

1955 INACTIVATEDPOLIOVIRUS VACCINE

ALY

TIC

CA

SES

100

1000

10000

1972 ERADICATIONWILD POLIOVIRUS

1963 ORALPOLIOVIRUS VACCINE

26

1950 1955 1960 1965 1970 1975 1980

PAR

A

10

WILD POLIOVIRUS

Nathanson and Martin Am J Epidemiology 1979, 110: 672

1973-1982IMPORTEDORVACCINE-ASSOCIATEDPOLIO

14

POLIO DECONSTRUCTEDfifth enigma

OBSERVATIONS• Prior to the introduction of polio vaccine in 1955, ~16% of the Prior to the introduction of polio vaccine in 1955, 16% of the

population (24 million) were susceptible to polio• In the USA, by 1970, vaccination programs (IPV and OPV) had reduced

susceptibles to ~2.6% of the population (>5 million)• It was assumed that the residual susceptible group would continue to

circulate wild polioviruses: control not eradicationHYPOTHESIS• IPV and OPV-induced “herd immunity” that reduced circulation of wild

polioviruses

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• Seasonality played a key role in the disappearance of wild polioviruses in the USA

EVIDENCE• Both OPV and IPV reduced circulation of wild polioviruses?• Wild polioviruses faded out during winter trough?• Stepwise fadeouts in individual States

POLIO DECONSTRUCTEDObserved polio incidence, USA, 1958-1961vs expected based on pre-vaccine incidence, 1951-1954

E t d if Expected if

Polio incidence by yearExpected if no

vaccine

Expected if 65% IPV

protectedObserved

1958 27,316 11,794 3,795

1959 28,224 10,191 6,358

1960 28,964 8,964 2,556

1961 29,521 8,471 1,002

1958 1961 114 025 39 420 13 711

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1958-1961 114,025 39,420 13,711

Percent of baseline 100% 35% 12%

Vaccine protection: (% immunized with IPV) X (% IPV efficacy)

Stickle Am J Pub Hlth 1964, 54:1222

15

POLIO DECONSTRUCTEDCalculated perpetuation of wild polioviruses during seasonal trough in New England, 1950 and 1970

Pre-vaccine Post-vaccinePre-vaccine1950

Post-vaccine1970

Total population 1,000,000 1,000,000

Polio susceptible population 160,000 26,000

Annual polio infections 20,000 1,000

29

Polio infections per generation period at seasonal trough(0.1% of annual total)

20 ~1

Nathanson J Infectious Diseases 1984 6 (S2): S308; Stickle Am J Pub Hlth 1964, 54:1222

POLIO DECONSTRUCTEDStates reporting any polio, USA, 1960-1973

1963ORAL POLIOVIRUS VACCINE INTRODUCED

REP

OR

TIN

G A

NY

TIC

PO

LIO

MYE

LITI

S

20

30

40

50VACCINE INTRODUCED

1973WILD POLIOVIRUS

ERADICATED

30

1960 1962 1964 1966 1968 1970 1972

STAT

ES

PAR

ALYT

0

10

Nathanson and Martin Am J Epidemiology 1979, 110: 672

16

FINIS

31