REVIEW

Polio Eradication in India

T. N. Dhole • Vikas Mishra

Received: 18 October 2011 / Accepted: 14 November 2011 / Published online: 1 March 2012

� The National Academy of Sciences, India 2012

Abstract The Global Polio Eradication Initiative gained

a great success in India in the last one year, especially on

the epidemiology of type 1 wild poliovirus (WPV), by the

intensive use of monovalent oral polio vaccine (OPV) type

1. However, failure to completely interrupt the transmis-

sion of type 1 and persistence of type 3 WPV in western

Uttar Pradesh and Bihar are still causes of concern. The

year 2010 was very crucial for polio eradication in India; as

good control over transmission of type 1 wild polio virus

was achieved. While mOPV1 is a sharper tool against

WPV1, bOPV seems to be adequate against WPV3; hence

there may not be any more need for mOPV3. Thus, the key

to success lies in intelligent and imaginative use of the

three OPVs, i.e. mOPV1, bOPV and tOPV, against WPV

types 1 and 3, and circulating vaccine derived polio virus

types 1, 2 and 3. Serious consideration should be given to a

contingency plan to the use of inactivated polio vaccine or

non OPV in endemic areas.

Keywords Epidemiology � Inactivated polio vaccine �Oral polio vaccine � Vaccine derived polio virus �Wild poliovirus

Introduction

Global eradication of polio is not possible without taking care

of circulation of wild polio virus in India, Pakistan, Afghan-

istan and Africa. India’s original goal was to eliminate polio

by the year 2000—the gift of a polio free world to the children

of the 21st century. That goal was missed for wild polioviruses

(WPV’s) type 1 and type 3 and these two serotypes are still in

circulation. The Government of India then revised the goal in

2005 and extended to 2015 [1]. By the year 2010, a good

decline in the number of polio cases has been observed in Uttar

Pradesh and Bihar [2].

In 2003 the formal view of the officers of the Health

Ministry and National Polio Surveillance Project (NPSP)

which was the reason for lack of success was ‘‘failure to

vaccinate’’ an adequate proportion of children [3–5]. Both

efficacy and protection of trivalent vaccine (tOPV) in children

of temperate climate was questioned [6–8]. The mucosal

response to tOPV was doubted and felt that there was need of

inactivated polio vaccine IPV [7]. In 2005 the failure of vac-

cine was officially acknowledged and monovalent vaccine

OPV (mOPV) types 1 and 3 were licensed for the first time in

India. It has been shown long back by Indian scientists that the

vaccine efficacy (VE) of trivalent oral polio vaccine (tOPV)

was very low against WPV types 1 and 3 and that it was 2–3

times higher in mOPV 1 and 3, respectively [9–11]. In India

the trial for monovalent vaccine was carried out in 2003 and

2004 in Ahmedabad, Indore and Bhopal. The conclusion of

trial was drawn on basis of the minimum excretion of the

vaccine virus inversely proportion to large amount of the

intestinal antibody present in the fecal sample by plaque

counting assay.

Epidemiology

The disease of poliomyelitis has a long history. The first

example may even have been more than 3000 years ago. An

Egyptian stele dating from the 18th Egyptian dynasty

(1580–1350 BCE) shows a priest with a deformity of his leg

characteristic of the flaccid paralysis typical of poliomyelitis.

T. N. Dhole (&) � V. Mishra

Department of Microbiology, Sanjay Gandhi Post Graduate

Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

e-mail: tndhole@gmail.com

123

Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133

DOI 10.1007/s40011-011-0010-0

The first known clinical description of poliomyelitis is

attributed to Michael Underwood, a British physician, who in

1789 reported observing an illness which appeared to target

primarily children and left those afflicted with residual

debility of the lower extremities. Initial outbreaks in Europe

were documented in the early 19th century and outbreaks in

the United States were first reported in 1843. However, it was

not until the early 20th century that the number of paralytic

poliomyelitis cases reached epidemic proportions [12]. The

polio is in circulation in India since ages especially in Uttar

Pradesh and Bihar because of poor sanitation and high pop-

ulation density. If one looks at the picture of different villages

of Uttar Pradesh and Bihar, old paralytic cases of acute flaccid

paralysis (AFP) can easily be found. This indicates that the

polio virus has survived and circulated in these areas for years.

This circulating virus has made victim of polio cases time to

time depending upon the immunity in general population.

Molecular Epidemiology of Wild Poliovirus

Circulation in India

The role of molecular surveillance in eradication initiatives

of poliomyelitis has proven to be an extremely powerful

tool for assessing the transmission pathways, monitoring

quality of the national immunization program, assessing

vaccine coverage and monitoring the success of eradication

strategies. The polio virus has three serotypes; PV1, PV2

and PV3 (Figs. 1, 2), sufficient genetic clusters [11] have

been observed in each serotype (Fig. 3). The genotype and

cluster, lineage and sublineage are the operational taxo-

nomic units for molecular surveillance. For all practical

purposes, VP1-906 nt has been sequenced and compared

[13]. It is essential to know the indigenous baseline geno-

type/cluster/lineage circulating in different states of India

and to monitor the changes with accelerated efforts for

elimination of these lineages.

Currently the Polio virus wild type 1 has three clusters

with multiple lineages circulating in different parts of India

while wild type 3 has four clusters with few lineages. P2

wild polio virus has already been eradicated from India

[14]. Surveillance for poliomyelitis is a dynamic process

and continuous monitoring of appearance and disappear-

ance of different lineages in any given region is imperative.

The most effective and useful strategy of strain surveil-

lance is crossing over from endemic to relatively non-

endemic area. Depending upon the effective and optimal

immunization coverage, circulation of indigenous lineage

may persist or disappear. The close similarity of sequences

within each lineage indicates good quality of surveillance.

Some of the wild poliovirus strains may disappear without

surfacing for more than 2 years (silent transmission) or

may appear as importation from other countries. It is a

barometer of current status of polio eradication which helps

in refining the strategies to achieve the goal in shortest

possible time.

An Update on Epidemiology

In May 1988, during the World Health Assembly, Minister

of health of all member states of the World Health Orga-

nization (WHO) voted to launch global goal to eradicate

polio. As a result of this global polio eradication initiative

started and estimated global incidence of polio decreased

by more than 99% with three WHO regions (Americas,

Western Pacific and Europe) being certified polio-free [15].

Intensive polio eradication program in the South–East

Asia Region (SEAR), with the use of tOPV, led to the

substantial decrease in the number of polio cases. By 2001,

Fig. 1 Poliovirus serotypes. Three immunologically distinct types of

PV, PV-1, PV-2 and PV-3 have been recognized. Strains which cause

severe paralysis are known as wild poliovirus (PV1-wild, PV2-wild

and PV3-wild). Sabin PV1, PV2 and PV3 strains are used as efficient

vaccine known as Vaccine derived poliovirus. Adapted from www.

http://wenliang.myweb.uga.edu

Fig. 2 Structure of poliovirus. Poliovirus genome consists of a single

molecule of single stranded RNA, *7,500 nucleotides long. It acts

like mRNA in infected cell and is translated into a single large

polypeptide. This polypeptide is cleaved by virus coded enzymes into

capsid proteins (VP1, VP2, VP3 and VP4) and non-structural proteins

which include proteases and RNA-dependent RNA polymerase.

Partially adapted from ‘‘Poliovirus proves IRES-istible in vivo’’ [60]

124 Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133

123

poliovirus circulation in India was limited primarily to

northern states of Uttar Pradesh and Bihar, with 268 cases

reported nationwide [16]. However, a major resurgence

occurred in 2002 with 1,600 cases nationwide [16–18]

(Figs. 4, 6), of which majority of cases i.e. 1,363 (85%)

were from Uttar Pradesh and Bihar only [16]. This resur-

gence was attributed to the decline in OPV coverage in

critical areas with vaccination coverage of children in

\15% houses in some districts [17]. Thus, a large number

of children were missed in areas with high population

density resulting in a very large birth cohort of susceptible

individuals in areas of poor sanitation.

Frequent Importation of Strains

The frequent importation has been observed from polio

endemic countries to relative non endemic countries as

well as interstate within India. In India, frequent importa-

tion have been observed to neighboring areas like Nepal to

Bihar, Bihar to Bangladesh, Uttar Pradesh to Mumbai and

other nearby states [19]. The importation of virus has been

observed mainly in those countries from where the OPV

vaccine coverage is low in general population after eradi-

cation (Fig. 5).

VE in Northern States

Repeated OPV not only potentiates the immune response

of the child but may produce immune paralysis. The

immunogenicity of OPV varies region to region, the sero-

conversion rate and protection in children of Bihar and

Uttar Pradesh are below the Indian standard [20, 21]. The

herd effect of OPV is also quite low in developing

Fig. 3 Genetic relationship of

wild poliovirus type 1 detected

in India (Complete VP1

sequences). Adapted from

National Polio Surveillance

Project (NPSP), India

Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133 125

123

countries like India [21]. Vaccine viruses are less infectious

than their wild counterparts and spread to non-immune

children (contact immunization) is another reason. Both of

these factors are weak in children of Uttar Pradesh and

Bihar. Therefore, virtually every child must be vaccinated

with repeated doses of OPV to ensure personal protection

but it is difficult to achieve where primary immunization is

weak. If the immunization rates fall after achieving high

level of immunity in the polio-free community, risk of

large outbreaks increase rapidly among the growing

cohorts of non-immune children. The routine immunization

with OPV will no longer outweigh the burden of diseases

Fig. 4 Monthly incidence of

wild poliovirus cases in India

with national, sub-national and

large scale immunization.

Adapted from National Polio

Surveillance Project (NPSP),

India

• Wild virus type 1• Wild virus type 3• Wild virus type 1 and 3

Endemic countries Case or outbreak following importation (last 6 months)Case or outbreak following importation (6-12 months)

Fig. 5 Tracing virus transmission pathways. Adapted from National Polio Surveillance Project (NPSP), India

126 Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133

123

either due to paralysis caused by OPV (vaccine associated

paralytic polio), or outbreak caused by circulating vaccine-

derived poliomyelitis (cVDPV) [22].

The mucosal immunity induced by OPV in India varies

by location, serotype, and vaccine formulation [10]. The

present discrepancies in tOPV versus IPV is debatable

based on scientific merit and demerit, advantage versus

disadvantage of their use in two highly populated states of

the country [23]. The tOPV/Monovalent OPV (mOPV) has

reduced the circulation of wild poliovirus from major part

of the country without making significant impact in their

circulation in 107 sub-districts of Uttar Pradesh and Bihar.

Therefore the success of tOPV cannot be ignored, but its

small amount inherent problem of the vaccine needs to be

addressed. It is difficult to maintain the high level of

immunity in the community with tOPV because of sero-

conversion, GI immunity and sustaining the high level of

antibody for protection. The polio eradication stands for,

eradication of wild as well as vaccine strain from the

community. Therefore prolonged use of tOPV will invite

innumerable problems like frequent importation of wild

strains, occurrence of circulating cVDPV’s and vaccine-

associated paralytic poliomyelitis (VAPP), circulation of

Sabin strains in the community [24–26].

Recent studies have shown that the VE of IPV is very

high and it is completely safe to use [27, 28]. Where VE of

OPV is problematic, IPV provides predictably high VE.

However, the areas which are of concern with IPV devel-

opment and implementation are the choice of appropriate

adjuvant to be used in IPV [29–31], population immunity

[27], assessment of risks of paralytic diseases due to

poliomyelitis in the post eradication era [32]. The above

needs methodical evaluation for policy making and rec-

ommendation of IPV.

Risk Associated With OPV Vaccine Use

Seroconversion Studies in Children Given OPV

A number of studies have shown that seroconversion fre-

quency is less than expected after giving tOPV [26, 33, 34].

WHO has tried to overcome serious problem with subop-

timal efficacy of OPV by dividing tOPV into monovalent

vaccines. Since 2005, two vaccines, mOPV1 and mOPV3,

were used to immunize children. The selection of vaccine

type was in accordance with the prevailing wild virus type

circulation in the different parts of Uttar Pradesh and Bihar.

The epidemiological data generated with this strategy

seems very promising as there is drastic reduction in cir-

culation of P1 wild while still the detection rate of P3 wild

strain remains static [35].

The above diminishing of one strain while static detection

rate of other strain depicts a possible pattern. Prioritization of

eradication of P1 type wild strain tend to minimize the

attention on eradication of other variants, which subsequently

lead to the emergence of P3 wild, P2 cVDPV and P1 cVDPV

isolates (Fig. 6). Thus in policy making further changes has

been incorporated, which states maintenance of the equal

pressure on the eradication of all three strains of wild polio

viruses, while trying to eradicate at least one.

Recent studies of WHO has shown the servoconversion

rate of mOPV-1 and mOPV-3 is 99 and 95%, respectively.

The study advocates, that there is no need to opt for IPV as

IPV is no way better than OPV as far as seroconversion is

concerned. The question remains to be answered that,

whether 99% seroconversion is cumulative effect of repe-

ated vaccination or 99% were above the protection level

and sustaining the same level for period of at least 3 years.

The seroconversion is easy to achieve but difficult to sus-

tain above the protection level, especially in settings where

children are malnourished, school dropout rate is high and

there is least or no education [21, 36, 37]. Frequent waxing

waning would result snacking of virus in the community

from highly immunized population to relatively under

immunized population after prolonged gap.

Emergence of Vaccine Derived Polio viruses (VDPVs)

Rare cases of paralytic polio occur due to the Sabin strain,

called as vaccine derived poliovirus (VDPV). VDPVs can

cause paralytic polio in humans and have the potential for

sustained circulation. VDPVs resemble WPVs biologically

and differ from the majority of vaccine related poliovirus

(VRPV) isolates by having genetic properties consistent

with prolonged replication or transmission. Because

poliovirus genomes evolve at a rate of approximately 1%

per year, VRPVs that differ from the corresponding OPV

strain by [1% of nucleotide positions (VP1 genomic

region) are presumed to have replicated for at least 1 year

in one or more persons after administration of an OPV

dose. This is substantially longer than the normal period of

vaccine virus replication of 4–6 weeks in an OPV reci-

pient. Poliovirus isolates are grouped into three categories,

based on the extent of divergence of the VP1 nucleotide

region compared with the corresponding OPV strain:

(a) VRPVs (\1% divergent [types 1 and 3] or \0.6%

divergent [type 2]);

(b) VDPVs (VRPVs that are[1% divergent [types 1 and

3] or [0.6% divergent [type 2] from the correspond-

ing OPV strain).

(c) WPVs (no genetic evidence of derivation from any

vaccine strain).

There are three types of VDPV

(A) Circulating vaccine-derived poliovirus (cVDPV).

Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133 127

123

(B) Immunodeficiency-related vaccine-derived poliovi-

rus (iVDPV).

(C) Ambiguous vaccine-derived poliovirus (aVDPV).

Circulating vaccine-derived poliovirus (cVDPV) On very

rare occasions, if a population is seriously under-immu-

nized, there are enough susceptible children for the

excreted vaccine-derived polioviruses to begin circulating

in the community. These viruses are called cVDPV which

has 1–15 nucleotide (nt) substitution of RNA at VP1 region

from other enteroviruses [38, 39] (Figs. 2, 7). The lower

the population immunity, the longer these viruses survive.

The longer they survive, the more they replicate, change,

and exchange genetic material with other enteroviruses as

they spread through a community. If a population is fully

immunized against polio, it will be protected against the

spread of both wild and vaccine strains of poliovirus.

Episodes of cVDPV are rare. Between 2000 and 2009—a

period in which nearly 10 billion doses of oral polio vaccine

were given worldwide—14 cVDPV outbreaks occurred,

resulting in 428 polio cases (Fig. 8). In the same period, wild

poliovirus paralyzed nearly 14,000 children [40].

Fig. 6 Geographical distribution of wild polio virus cases in India (1998–2011). Adapted from National Polio Surveillance Project (NPSP),

India

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123

Clinically, the picture in cVDPV is indistinguishable from

wild poliovirus strains. The cVDPV can be detected easily as

they will show discordant intratypic differentiation (ITD)

results. In ELISA, optical density fails to differentiate between

wild and vaccine strains or will show double reactive test.

ELISA is a very sensitive technology to pickup phenotypic

changes occurred in P1 strain but is not equally sensitive to

pick up the changes that occur in P2 and P3. Therefore from

January 2009 WHO introduced the Real time PCR based

detection and characterization of wild and vaccinated viruses

for ITD as well as for cVDPV’s of P1, P2 and P3 types [41].

This has expedited the reporting time from 14 to 7 days after

receiving the stool sample in the laboratory.

The potentially growing risks of VDPV emergence

highlight the need for a well coordinated synchronous

cessation of OPV use worldwide. The need to stop OPV

use is driven not only by the risks of VDPV emergence and

spread but also by continued global occurrence of 250–500

cases of VAPP annually. Both VAPP and VDPV risks are

the consequences of the intrinsic genetic instability of the

Sabin OPV strains and of the strong negative selection

against key genetic determinants of attenuation when OPV

replicates in the human intestine [42].

Immunodeficiency related vaccine derived poliovirus (iV-

DPV) Prolonged replication of vaccine-derived viruses has

been observed in a small number of people with rare immune

deficiency disorders. Because they are not able to mount an

immune response, these people are not able to clear the intes-

tinal vaccine virus infection, which is usually cleared within 6

to 8 weeks. They therefore excrete iVDPVs for prolonged

periods.

The occurrence of iVDPVs is very rare. Only 42 cases

have been documented worldwide. Of these, most stopped

excretion within 6 months or died. Three people excreted

the virus for more than 5 years.

Ambiguous vaccine derived poliovirus (aVDPV) aVDPVs

are vaccine-derived polioviruses that are either isolated from

people with no known immunodeficiency, or isolated from

sewage whose ultimate source is unknown. Very little is known

about them.

Acute Transient Paralysis

The large number of acute/transient paralysis have occurred in

children following the vaccination in National Immunization

Fig. 7 Evolutionary

relationship of type 2 VDPV

using VP1 sequences. Adapted

from National Polio

Surveillance Project (NPSP),

India

Proc. Natl. Acad. Sci. Sect B. Biol. Sci. (January–March 2012) 82(1):123–133 129

123

Day’s (NID’s) and Sub-National Immunization Day’s

(SNID’s) and mopping up within first 3 days of vaccine

delivery [43, 44] (Fig. 4). A large number of stool samples

from these AFP cases were routinely sent for laboratory

investigations; where isolation of vaccine viruses has con-

firmed the role of OPV in AFP after vaccination. Although the

vaccine viruses are enough attenuated as evident by their

genetic analysis [45, 46], the hotspots in vaccine viruses

should be investigated to find out the possibilities of any

change/mutation following immunization.

Vaccine Delivery

The vaccine delivery needs a perfect organization and syn-

chronization between the deliverer and the recipient. Most of

the village heads are illiterate and do not have any docu-

mentation about the recent births and deaths. In the absence of

such epidemiological data, there are virtually no pre-prepa-

ration for implementation and delivery of vaccines and thus

entire program become highly disorganized. Missing of

children in every drive becomes very high following door to

door campaign and further it is very difficult to have a match

between first and second immunization drive. Most vaccina-

tors are not well trained, illiterate and do not have the ability to

motivate the parents for the benefits associated with vacci-

nation [47]. Thus whole purpose behind the safe delivery of

vaccine has been defeated.

Injectable Polio Vaccine (IPV)

The first vaccine against polio virus was developed by

Jonas Salk (1952), consisting of inactivated whole virions

of polioviruses, without any adjuvant [48, 49]. Today IPV

is prepared by growing the wild strains of polioviruses in

tissue culture medium in continuous culture flasks to have a

40-, 8- and 32-D antigen units for the three PV1, PV2 and

PV3 virus types, respectively [50, 51]. The viruses are

grown in MRC-5 cells (diploid cell origin), a line of normal

human diploid cell by micro-carrier technique in serum

free medium of M-199. After clarification and filtration,

viral suspension has been concentrated by ultra-filtration

and purified. After intradermal injection, the IPV is sup-

posed to raise the IgG neutralizing antibodies in the blood

and will also infiltrate the IgG’s and secretary IgA’s in the

intestinal lumen [52]. The neutralizing antibody will not

only inactivate the vaccine viruses as well as wild viruses,

thus it will confer total protection against circulating vac-

cine and wild strains. The IPV has been advised to be given

in two doses, 2 months apart, with alternate oral polio

vaccine [53]. It has been advised to be given in primary

immunization along with DPT [9].

The modern IPV is highly immunogenic, but how much

systemic antibodies will infiltrate at gut level is not known.

We still do not know whether the gut immunity in IPV will

be able to prevent the colonization of Sabin strains in initial

period of eradication while switching over from OPV to

Fig. 8 Geographical distribution of vaccine-derived polioviruses. Adapted from ‘‘update on vaccine-derived polioviruses-worldwide, July 2009–

March 2011

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IPV in a phased manner. However, its immunogenicity is

dampened by the presence of maternal antibodies in the

young infants, especially up to 8 weeks. Two doses

(0.5 ml) of IPV have been given, preferably by subcuta-

neous injection and at an interval of 8 or more weeks to

induce antibody response in virtually 100% children [54].

The booster doses will be given at the age of 4–6 years

[55]. However, OPV would be needed to control any future

outbreak of wild polio viruses.

The main shortcoming for the use of IPV in developing

countries involves the trained vaccinator for injecting

(subcutaneous, intramuscular or intradermal). The disad-

vantage of using needles for injecting vaccines involves

pain at the site of administration, logistical difficulties,

safety and disposal concerns.

New Trials for IPV

Countries like Cuba and Oman are testing the viability of

fractional doses and evaluating serologic response to 1/5th of a

standard dose with intradermal jet injector, which uses no

sharps and can be reset manually without use of batteries [56–

58]. If these studies prove successful, they would confer non-

inferior serologic and mucosal immunity at 1/5th of the cost of

the current IPV dose and could be administered by the vol-

unteers with an innovative and painless tool.

Future Strategies

This is the crucial time to discuss and plan for the future

vaccination strategy rather than waiting till WPV elimi-

nation is achieved. Phased introduction of IPV is required

in the RI (Routine Immunization) programs of southern

states where WPV transmission has already halted years

ago, followed gradually by universal use in RI all over the

country (when Uttar Pradesh and Bihar are also polio-free)

[59]. OPV used thereafter should be confined to three-

annual pulses through NIDs, until confirmed cessation of

the WPV transmission. There is urgent requirement to

chalk out a clear strategy on how to deal with the issues

like OPV cessation plans, global synchronization versus

regional/national synchronization, duration of AFP sur-

veillance, tackling of future outbreaks of both wild and

vaccine viruses, role of IPV in controlling future outbreaks

of cVDPVs, development of safe and affordable IPV etc.

Conclusions

Tremendous progress has been made in the global fight

against polio virus since 1988. A number of initiatives have

been implemented in India to intensify efforts to interrupt

transmission of WPV. Advocacy efforts have been

strengthened; mOPV1 to bOPV has been introduced in

January 2010 and they were used in campaigns in high-risk

areas. New strategies are being developed for switching

over for IPV from OPV with greater focus on 107 sub

districts of Northern India. The Polio eradication from

India is now mainly dependent on states of Uttar Pradesh

and Bihar as how quickly the transmission chains of WPV

is interrupted from these areas.

The areas which are of concern with IPV development and

implementation are the choice of appropriate adjuvant to be

used in IPV, VE, population immunity, assessment of risks of

paralytic diseases due to poliomyelitis in the post eradication

era. The above needs methodical evaluation for policy

making and recommendation of IPV. Although it is one of

the toughest tasks ever but polio eradication from India is

showing light of hope in near future. As per the new direc-

tives received from WHO, Indian manufacturers are

encouraged to prepare the IPV from Sabin polio virus strains

instead of their counterpart wild strains. Since the protein

yield of Sabin strain in tissue culture is low, therefore we

have to look for suitable adjuvant to enhance the antibody

response. At present we do not have any manufacturer in

India, except Panacea Biotech, who has some experience in

manufacturing IPV. Importing IPV vaccine from outside

India will be very expensive as we might need billion doses

to eradicate polio. Till date no indigenous manufacturer is

available for bulk and safe production of IPV. The intra-

dermal (non oral) polio vaccine which might be used in

future for polio eradication would have enumerable advan-

tage over wild as well as cVDPV.

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