POLIO ENDGAME STRATEGY IN INDIA

CONSIDERATIONS AND WAY FORWARD

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WE FIRST THANK TO THE DEDICATED VOLUNTEERS, WITHOUT THEM
POLIO ERADICATION IN INDIA IS NOT POSSIBLE

• Each national immunization day

involved:
• 225,000,000 doses of polio vaccine
• 172,000,000 children vaccinated
• 2,500,000 vaccinators
• 2,000,000 vaccine carriers
• 155,000 supervisors

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 Content
●Introduction
• Poliomyelitis disease
– Polio virus – Transmission, Pathogenecity
– Clinical course – Diagnostic challenges
– Complications
• Poliomyelitis eradication
– Global scenario ( Past & Current )
– Indian scenario ( Past & Current )
• Poliomyelitis vaccines
– Oral Polio Vaccine (OPV)
– Injectable Polio Vaccine (IPV)
– Comparison between OPV & IPV
• End game strategy
– What is the polio 'endgame'?
– Why is the world now rethinking
the Polio Endgame?
– What are the major elements of the 'New
Polio Endgame'?
• Polio Endgame Strategy in India
Considerations and Way Forward
3
Poliomyelitis crippled millions for
centuries is on the verge of eradication!
● Etymology
– Greek word: Polio (grey) + myelos (marrow)

• History
– First described in 1789 in Europe
– In next 100 years caused several
epidemics

• Impact of effective vaccines

– Rapid decline in polio incidence
– Only 3 countries are Polio endemic

• Global polio eradication in near future!

4
Poliovirus is a highly pathogenic virus has
3 serotypes & there is no heterotypic immunity!
● Member of Picornaviridae family
– Enterovirus
– Small viruses with an RNA genome
– 3 serotypes (P1, P2 & P3)
♦ No heterotypic immunity

• Inhabitant of GIT & stable at acidic pH

• Rapidly inactivated by

– Heat / Formaldehyde / Chlorine / UV

light

5
 Polio transmits via oro-fecal route!

• Humans are the only reservoirs

• Transmission
– Fecal-oral route
– No carriers

• Communicability
– Highly infectious for 7 - 10
days before & after onset
• No seasonality

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Poliovirus can cause paralysis in 10 days!

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8
 Behind every paralytic polio case
there are 100 to 1000 poliovirus infections!

• Incubation period
– 6 – 20 days

• 95% infections
– Inapparent infections

• 4 – 8%
– Abortive poliomyelitis

● 1 – 2%
– Nonparalytic meningitis

• <1%
– Flaccid paralysis

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 Paralysis is the major complication of
poliomyelitis!

• Complications
– Spinal polio
• 80% of paralytic cases
• Asymmetric paralysis of legs
– Bulbar polio
• 2% of paralytic cases
• Muscle weakness
– Bulbospinal polio
• 18% of cases
• Mixed morbidity

• Case Fatality Rate

– 2 – 5% (in children )
– 15 – 30% (in adults)

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Diagnosing poliomyelitis is a clinical challenge,
as many diseases & conditions cause AFP!
• Differential diagnosis of acute flaccid paralysis
– Commonest
• Gullian-Barre syndrome
• Transverse myelitis
– Infections
• Viral - Enteroviruses & other viruses

– Toxins
• Bacterial (e. g. Botulinm, Tetanus) & fungal
• Venoms (e. g. Ticks, spider, beetle, wasp & snake)
• Organic chemicals & pesticides

– Metabolic disorders
• Hypokalemia & Hypophosphatemia

– Traumatic neuritis (Post injection)

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 In 1988 the World Health
Assembly passed a resolution to
eradicate polio, launching the
Global Polio Eradication Initiative

In 1995,In India, 87 million children were vaccinated.

Global Status 1988

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GLOBAL STATUS 2004

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 Polio Eradication : 1988 - 2012
YEAR NO.OF POLIO
CASES
1988 350000
1993 1925
1988 : 1998 1934
350,000 1999 1186
cases 2000 265
> 125
2001 211
countries
2002 1919
2003 784
2004 1556
2005 1831
% cases decrease: > 99% 2006 2022
2007 1387
2008 1732
2009 1783
*2012 : 299 cases (as of 9th
Oct, 2012) 2010 1413
7 countries ( Endemic-3, Importation-4 )
2011 716
2012* 299
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SAW SEE Polio cases

2000

1750

1500

1250

1000

750

500

250

0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008*
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Rolling Towards the Success story

* as of 13th October
2012

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HOPE THIS IS
LAST POLIO CASE

Baby Rukhsar,
Howrah

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Finally, India achieved interruption
of transmission for Nearly 2 Years

So, India appears on track to

Stop Polio

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What has been the cost towards this achievement…???
MoH: India has spent INR1200 crores towards Polio control so far

International investment of over US$ 8 billion

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It took 75 years of scientific efforts for
eliminating polio from most part of the world!

Polio Virus

Jonas Salk Albert B. Sabin

created first injectable Created first oral polio vaccine
polio vaccine
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 In 1952 Prof. Salk created world’s first IPV!

• Tissue Culture Era (1950 – 1951)

• Cultivation in non-nervous tissue
• Plaque technique to improve yield
• Inactivated vaccines
– 1952 - 1953
• Prof. Salk – Safety & immunogenicity in animals & humans

– 1954
• Vaccine field trial by University of Michigan, US
• 1,829,916 children enrolled (US, Canada & Finland)

– 1955
• Trial results published – Safe & 70% effective
– 6 manufacturers permitted licenses

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In 1954 Prof. Sabin created world’s first OPV!
–1952
♦ Prof. Sabin identified characteristics of
candidate virus for OPV
♦ Developed neurovirulence model in
monkey
– 1957 - WHO recommended field trials

– 1958 - Singapore – 200,000 children vaccinated

– 1959 - USSR – 1,500,000 children vaccinated

– 1960 - > 100,000,000 children vaccinated

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 OPV protects the community
by conferring high level of herd immunity!

● Monodose (0.5 mL) in a plastic dispenser

• Live attenuated strains of 3 serotypes (10:1:3)

• Viruses replicate in intestine, lymph tissues

• Viruses excreted in stool up to 6 wks

• Herd immunity effect

– Persons coming in contact with fecal
material of a vaccinated child get
protected

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Though OPV is highly immunogenic vaccine,
it is a “hit / miss” vaccine, with associated risk
of VAPP!

● Immunogenicity & vaccine efficacy

– Highly immunogenic
♦ 1 dose - 50% recipients
♦ 3 doses - 95% recipients

– Produces intestinal immunity

• Prevent infection with wild virus

– Provides lifelong immunity

• Drawbacks
– “Hit / Miss” vaccine!
– Vaccine Associated Paralytic Poliomyelitis
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Risk of VAPP with OPV is rare, but……………………
immunodeficient children have 7000 times higher
risk!
• Vaccine Associated Paralytic Poliomyelitis (VAPP)
– Accounts for 95% of all cases of paralytic poliomyelitis
– Type of virus
• Type 3 (most cases in vaccinees) & Type 2 (most cases in
contacts)
– Risk of VAPP
• <1/1,000,000 )
– Cause
♦ Mutation / reversion of virus (revertant) to more neurotropic form

– Paralysis identical to that caused by wild virus

– At risk population
• Persons of > 18 years
• Immunodeficient children (e.g. malnutrition)
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 Risks of OPV
• Vaccine Associated Paralytic Poliomyelitis (VAPP),
• The global burden is estimated at
250–500 cases annually
• In 2000 in Hispaniola when 21 children were
paralysed, first cVDPV outbreak was identified
• Long term Carriers of VDPVs identified among
immunodeficient (iVDPVs) reseed in general
population
• In the Philippines in 2001 cVDPV outbreak in 3 and
in Madagascar in 2002, 4 children.
• Retrospective analyses documented cVDPV
circulation in Egypt 1988 -1993 30 cases
• So, they all have the potential to cause
Outbreaks in underimmunized
populations
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cVDPV Globally

http://www.polioeradication.org/
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Injectable Polio Vaccine

● IPV (Salk) 1955

● Enhanced IPV 1970’s
available since 1988 in US
used worldwide.
● Highly immunogenic >90%
protection 2 doses
Murdin AD, Vaccine 1996;14.,
Robertson, Lancet 1998;352

● 98-100%seroprotection
all 3 serotypes Vidor E,Ped.Infec
Dis.1997;16

● Ideal vaccine for individual

protection Thacker & Shendurnikar,IJP
2003;70

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 Risk of VAPP can be eliminated by
administrating IPV prior to OPV!

● Control of VAPP (Learning from US scenario)

– 1996
♦ ACIP recommended IPV followed by OPV
• Production of humoral immunity against polio vaccine virus

– 1998
• Fewer cases of VAPP

– 2000
• Exclusive IPV vaccination form 2000
– Elimination of shedding of live vaccine virus

– Elimination of VAPP

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IPV administration is safe during minor
illnesses, including diarrhoea & URTI!

• Minor illnesses
– Can be administered to a child with diarrhea
– Minor illness is not contraindications

• Breastfeeding
– No interference

• Special precautions
– Severe acute illness

● Contraindication
– Hypersensitivity to any vaccine component

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Most IPVs use vero cell substrate for virus growth &
the virus is inactivated by formaldehyde!

● Single dose prefilled syringe

Cell
Manufacturer Country
substrate
● Administered by IM injection
Novartis Italy Vero
France Vero
Sanofi Pasteur
• Contains all 3 serotypes of virus Canada & MRC -5
GSK Belgium Vero
National
• Inactivated with formaldehyde Biological Sweden Vero
Laboratory
• 2-phenoxyethanol as Netherlands
preservative Vaccine Netherlands Vero
Institute
• Traces of Rhesus Monkey
Statens Serum
neomycin, streptomycin & Denmark Kidney
Institute
polymyxin B & Vero

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 What is the polio 'endgame'?
The endgame: addressing risks due to the oral polio vaccine
(OPV) after eradication

● Vaccine-Associated Paralytic Poliomyelitis (VAPP): very rare adverse event.

● very rare event;

Outbreaks of circulating vaccine-derived poliovirus (cVDPV):

occurs when vaccine virus regains ability to paralyze

and circulate.
'After interruption of wild
poliovirus, continued use of OPV would compromise the goal of a polio-free world.

Expert Consultation on Vaccine-derived

Polioviruses (VDPVs), Sept 2003, Geneva

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Evolution of the 'Post-Eradication' Timeline
Last polio case OPV cessation

Years 0 2 4 6 8 10 12

Certification Wild virus

Certification
Commission '95 eradication

The 'endgame'
period

World Health Wild virus Certification & VDPV elimination & Post-OPV
Assembly (2008) eradication containment validation surveillance

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 Why is the world now rethinking
the Polio Endgame?
Recent developments allow a major
'rethink' of the endgame

• New bivalent vaccine (bOPV) outperforms trivalent OPV.

• New diagnostics show type 2 OPV is the main problem.

• New, very low cost 'IPV options' can allow all countries
to continue type 2 immunization if they want/need to.
36
Current Understanding of cVDPVs

circulating Vaccine-Derived Type 1 (79 cases)

Poliovirus Outbreaks Type 2 (450 cases)
(cVDPVs) 2000-2010 Type 3 (9 cases)

37
Affordable IPV options in the short-term,

1/5th of 1 dose of IPV can induce a 1/5th of 1 dose of IPV could be very
response in >90% of children affordable (<$0.5/dose)

Response* after 1 dose IPV price

(%, intradermal IPV, Cuba) ($ per dose)

100
90 $3
80
70
60
50 $0.6
40 < $0.3
30
20
10 Full-dose 1/5th fractional dose
0
P1 P2 P3
Current price Expected price
(low volume) (high volume**)

* includes seroconversion & priming ** assumes full dose price of < US$1.5/dose at high volume 38
 What are the major elements of the
'New Polio Endgame'?
New Polio Endgame: Guiding Principles

• phased removal of Sabin/OPV viruses, beginning

with highest-risk (type 2).

• elimination of type 2 in parallel by switching from

tOPV to bOPV for routine EPI & campaigns.

• introduction of 1 IPV dose to boost immunity prior

to a tOPV-bOPV switch & provide type 2 'priming'. 39
New 'Endgame' strategy: parallel risk management

Last wild polio case trivalent OPV cessation

Years 0 2 4 6 8 10 12

Sequential risk Wild virus Certification & VDPV elimination & Post-OPV
management eradication containment validation surveillance

Parallel risk Wild virus Certification &

management eradication containment

VDPV2 elimination & Post-OPV

validation surveillance

OPV2 cessation bivalent OPV 1&3

& IPV introduction (bOPV) cessation
40
Advantages of the New Approach

• accelerate type 1 & 3 eradication (with bOPV)

• address >90% of VDPV risk while surveillance &

response capacity is optimized

• substantially shorten the post-eradication phase

• boost routine immunization coverage (i.e. IPV at DPT3)

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 Polio Endgame Strategy in India
Considerations and Way Forward
● No WPV2 in India since 1999

● tOPV used in RI and during NIDs

● bOPV used in most SNIDs since Jan 2010

● Areas and populations with low routine immunization

coverage

● All cVDPVs in India due to type 2 in setting of low

immunity to type 2

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Last wild poliovirus cases by type, India

WPV2
24/10/1999
Aligarh (UP)

WPV3
22/10/2010
Pakur (JH)

WPV1
13/01/2011
Howrah (WB)

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 Current pattern of vaccine use-India

● tOPV
– EPI schedule: 6,10,14 wks
Birth dose for institutional births Assessed
– SIAs: 2 NIDs with tOPV each year tOPV3 coverage
by CES 2009
● bOPV A

– Introduced in Jan 2010

– Used extensively during SNIDs in high
risk states/ areas

70.4%

<60
60 - 70
70 - 80
>= 80
44
cVDPV cases, India 2009-2011

•cVDPV cases detected in 2009-10

•100% due to type 2

Type 2
District
2009 2010 2011
Badaun 3 0 0
Bulandshahar 2 0 0
Ghaziabad 0 1 0
Meerut 2 0 0
Moradabad 2 0 0
Pilibhit 4 0 0
Shahjahanpur 2 1 0
Total 15 2 0
45
 Low seroprevalence against poliovirus type 2
Results from different serosurveys
Moradabad AFP cases UP Moradabad UP & Bihar UP & Bihar
Nov 2007 Nov 08 – May 2009 Aug 2010 Aug 2011
(N=121) mid 09 (N=534) (N=1280) (N=1246)
(169)
Age 6-7 mo 6-11 mo 6-7 mo 6-7 mo 6-11 mo

Type 1 78% 96.5% 99% 98% 98.5%

Type 2 56% 33.7% 75% 65% 85%

Type 3 69% 42.6% 49% 77% 88.2%

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 Evaluated OPV3 coverage by district – DLHS 3 (2007-08)
and cVDPVs
S ta te .s h p
Uttar Pradesh D is tric t.s h p
0<- 25%
2 4 .9
225
5 -to4 950%
.9
550
0 -to7 475%
.9
7>=
5 - 75%
10 0

N
cVDPV type 2
W E

200 0 200 400 M i le s

S

10
tOPV tOPV tOPV tOPV
9 sNID NID NID sNID

7
Number of cases

tOPV 4

c VDPV type 2 3

0
J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D
2009 2010 2011
47
 iVDPV & aVDPV cases, India 2009 to 2012*

iVDPV aVDPV

State Type 1 Type 2 Type 3 State Type 1 Type 2

Chhattisgarh 1 Assam 1
Punjab 1 Bihar 3
Tamil Nadu 1 Karnataka 1
Uttar Pradesh 1 Madhya Pradesh 1
Odisha 1 Rajasthan 1
Total 1 3 1 Uttar Pradesh 4
West Bengal 1
Total 1 11

*: data as on 10 March 2012 ambiguous VDPV (aVDPV): origin uncertain e.g. single isolate from single AFP case, non-immunodeficient person 48
 tOPV-bOPV switch in India?
Considerations
● Pre-switch increase in type 2 immunity
● Rapidly improve routine immunization coverage
● Use of IPV in conjunction with bOPV/tOPV to reduce risk of
emergence and consequences of cVDPV
● Availability of vaccines
– IPV availability for use in routine immunization
– bOPV availability for routine immunization and SIAs
● Management of post-switch risks of type 2 VDPVs
● cVDPV type 2 circulation stopped everywhere & switch
synchronised globally

49
 Polio Endgame Strategy-India,
Possible Way Forward tOPV-
bOPV
switch

Polio
Last WPV certification
case

NID NID NID NID NID NID NID NID

IPV Post-
switch
Modelling, Research, Development Sabin
type 2
PQ/ licensing, stockpile risk mgt.

Certification standard surveillance, improved RI coverage

0
Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May

2011 2012 2013 2014

tOPV NID
50
 Conclusions
While the past cannot be re-enacted,
the future can certainly be redesigned
Sequential IPV/OPV schedules considered
1st phase transition towards all IPV
schedule in Routine Immunzation.
The program should attend
TO COUNTRY SPECIFIC NEEDS
And Not get overawed by Global needs
Hope this Debate will not only generate a
Nation wide Debate but also create the
Need in the best interest of country.

Ultimately success of the whole initiative will depend on

steps being taken now to improve the economics of IPV.
V Vashishtha RTC Series 2010(24) RSF India 51
HOPE THIS IS
THE HISTORICAL
LAST POLIO CASE
OF INDIA

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