Research

Vaccine-associated paralytic poliomyelitis in India during

1999: decreased risk despite massive use of oral polio vaccine
Kathryn A. Kohler,1 Kaushik Banerjee,2 W. Gary Hlady,3 Jon K. Andrus,4 & Roland W. Sutter5

Objective Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but serious consequence of the administration of oral polio
vaccine (OPV). Intensified OPV administration has reduced wild poliovirus transmission in India but VAPP is becoming a matter of
concern.
Methods We analysed acute flaccid paralysis (AFP) surveillance data in order to estimate the VAPP risk in this country. VAPP was
defined as occurring in AFP cases with onset of paralysis in 1999, residual weakness 60 days after onset, and isolation of vaccine-related
poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4 and 40 days after receipt of OPV.
Findings A total of 181 AFP cases met the case definition. The following estimates of VAPP risk were made: overall risk, 1 case per 4.1
to 4.6 million OPV doses administered; recipient risk,1 case per 12.2 million; first-dose recipient risk, 1case per 2.8 million; and
subsequent-dose recipient risk, 1 case per 13.9 million.
Conclusion On the basis of data from a highly sensitive surveillance system the estimated VAPP risk in India is evidently lower than that
in other countries, notwithstanding the administration of multiple OPV doses to children in mass immunization campaigns.
Keywords Poliovirus vaccine, Oral/adverse effects/administration and dosage; Poliomyelitis/chemically induced/epidemiology;
Paralysis/epidemiology; Poliovirus/isolation and purification; Risk assessment; India (source: MeSH, NLM ).
Mots cles Vaccin antipoliomye litique Sabin/effets inde sirables/administration et posologie; Poliomyelite anterieure aigue /
induit chimiquement/e pidemiologie; Paralysie/e pidemiologie; Poliovirus/isolement et purification; Evaluation risque; Inde
(source: MeSH, INSERM ).
Palabras clave Vacuna antipolio oral/efectos adversos/administracion y dosificacion; Poliomielitis/inducido qumicamente/
epidemiologa; Paralisis/epidemiologa; Poliovirus/aislamiento y purificacion; Medicion de riesgo; India (fuente: DeCS, BIREME ).
Bulletin of the World Health Organization 2002;80:210-216.

Voir page 215 le resume en francais. En la pagina 216 figura un resumen en espanol.

Introduction
In 1988 the World Health Assembly resolved to eradicate
poliomyelitis globally by 2000 (1). India began implementing
polio eradication strategies in 1995 (2), and in 1999 introduced
additional rounds of national immunization days (NIDs) and
increased reliance on house-to-house visits for the administration of oral polio vaccine (OPV). The objective of NIDs is
to decrease widespread poliovirus circulation rapidly by mass
immunization campaigns with OPV, lasting only a few days
and targeting all children under 5 years of age regardless of their
vaccination history.
Vaccine-associated paralytic poliomyelitis (VAPP) is a
rare adverse event following the administration of OPV. In
England and Wales, the estimated risk of VAPP in 198591
was 1 case per 1.4 million OPV doses administered (3). In the
USA, VAPP risk estimates ranged from 1 case per 2.5 million
doses of OPV distributed in 198089 (4) to 1 case per
3.2 million doses distributed in 197384 (5). Data from the
acute flaccid paralysis (AFP) surveillance system in Latin
America showed an estimated VAPP risk of 1 case per 1.5

2.2 million doses administered in 198991 (6). These studies

demonstrated that the risk was substantially increased
following receipt of the first dose of OPV and that children
with B-cell immunodeficiency disorders were at highest risk
for VAPP (4). Reports from Romania (7, 8) suggested that
multiple injections could increase the risk of VAPP (provocation or aggravation poliomyelitis) and raised the question of
whether mass immunization campaigns might be associated
with an elevated VAPP risk.
In 1999 India accounted for over half the cases of polio
occurring globally. The number of polio cases attributable to
wild poliovirus infection in this country has rapidly declined as
efforts to eradicate the disease have progressed. The
proportion of cases of paralysis caused by receipt of OPV or
contact with an OPV recipient can be expected to increase as
the vaccine continues to be used extensively in both routine
and supplemental immunization activities.
Except in Latin America in 198991 (6), VAPP risk has
not been assessed in tropical countries where polio is endemic.
A decrease in the immunogenicity of OPV has been reported in

Epidemiologist, Polio Eradication Branch, Global Immunization Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta,
GA 30333, USA (email: [email protected]). Correspondence should be addressed to this author.
2
National Surveillance Coordinator, National Polio Surveillance Project, World Health Organization Regional Office for South-East Asia, New Delhi, India.
3
Project Manager, National Polio Surveillance Project, World Health Organization Regional Office for South-East Asia, New Delhi, India.
4
Regional Adviser, Vaccines and other Biologicals, World Health Organization Regional Office for South-East Asia, New Delhi, India.
5
Chief, Polio Eradication Branch, Global Immunization Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Ref. No. 01-1135
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World Health Organization 2002

Bulletin of the World Health Organization 2002, 80 (3)

Vaccine-associated paralytic poliomyelitis in India

tropical climates (9). This could alter the risk of VAPP in
developing tropical countries relative to estimates from the
USA or Europe. In the present analysis, national AFP
surveillance data are used to describe VAPP cases in India in
1999 and to estimate overall and recipient VAPP risk.

Methods
Study population
Active surveillance for AFP was established in October 1997.
International performance standards were met and in May
1998 they began to be surpassed, i.e. the non-polio AFP rate
was at least 1 case per 100 000 population under 15 years of age.
AFP is defined as any case of acute-onset flaccid paralysis in a
child under 15 years of age without another obvious cause,
such as trauma, or any case of paralytic illness occurring in any
person, regardless of age, in whom poliomyelitis is suspected.
AFP cases are detected by active surveillance. This involves
over 11 000 health care institutions reporting weekly (10).
When an AFP case is identified and reported to the
surveillance system, epidemiological and clinical information is
collected at both an initial investigation and 60 days after the
onset of paralysis. Two stool specimens are collected within
14 days after the onset of paralysis for virological testing. All
AFP cases reported to the surveillance system in 1999 were
eligible for this analysis.

Case definition
AFP cases in which wild poliovirus was isolated from any stool
sample were classified as confirmed polio cases and were
excluded from the VAPP case definition. VAPP was defined as
occurring in AFP cases if there was residual weakness 60 days
after the onset of paralysis, if vaccine-related poliovirus was
isolated from any stool sample, and if no wild poliovirus was
isolated from any stool sample. A subset of recipient VAPP
cases was defined as those VAPP cases with an interval of 4 to
40 days between the receipt of OPV and the onset of paralysis.
There is no standard case definition of VAPP. An interval of 4
40 days was chosen to define recipient VAPP in order to
improve comparability with previous studies (6). Because the
available data from the Indian surveillance system did not
include contact and exposure histories, VAPP cases not
meeting the criteria for recipient VAPP were classified as nonrecipient VAPP cases. Many of these would have been
considered as cases of contact VAPP in other studies.

network underwent an annual accreditation process coordinated by WHO (12).

Standard procedures were used to isolate viruses from
stool suspensions by culture in a rhabdomyosarcoma and HEp2C cell monolayer (13). In the second half of 1999, Hep-2C cells
were replaced by L20B cells (14). Neutralization tests involving
the use of high-titre equine sera were performed in order to
determine serotypes. Poliovirus isolates were further characterized as vaccine-related or wild by hybridization with genotypic
probes (15) and by polymerase chain reaction analyses (16).

Risk estimates
Data from the national surveillance system showed that the
non-polio AFP rate in children under 15 years of age was 1.8/
100 000, well above the benchmark of at least 1 case per
100 000 required to demonstrate that an AFP surveillance
system is operating with sufficient sensitivity to meet
international standards. The risks of overall VAPP and
recipient VAPP were estimated. The risk of recipient VAPP
was further categorized as following first or subsequent OPV
doses. In order to calculate the overall VAPP risk the estimated
number of OPV doses administered via both routine
immunization and NIDs was used as the denominator.
Routine immunization in India includes three OPV doses
given at 6, 10 and 14 weeks of age and a birth or zero dose for
institutional births. On the basis of data for 199798 obtained
from the Ministry of Health and Family Welfare it was assumed
that, of the annual birth cohort of 25 million infants, 8.3 million
(33.3%) were institutional births and that, of these, 6.1 million
(73%) received four doses of OPV by way of routine
immunization, giving a total of 24.3 million doses. For the
remaining 16.7 million (66.7%) of the birth cohort, 73%
(12.2 million) were assumed to have received three routine
OPV doses, giving a total of 36.5 million routine doses. The
total number of routine OPV doses administered in 1999 was
thus estimated to be 60.8 million.
NIDs were held in January, October, November and
December 1999. An additional subnational round was held in
March 1999 in areas with confirmed wild poliovirus cases. The
numbers of children under 5 years of age who received OPV in
each of these rounds are given in Table 1. Approximately
672.6 million supplemental OPV doses were administered
during NIDs in 1999. Altogether, therefore, some 733.4 million OPV doses were administered during the year, either
routinely or during NIDs.

Data
The database of the Indian AFP surveillance system included
demographic, virological and clinical information. The data
were used to arrive at the final classification of confirmed or
discarded cases of poliomyelitis.
All cases of AFP should be investigated within 48 hours
of being reported. An investigator confirmed whether each
case was one of AFP and completed a standard case
investigation form. The data collected as part of the
investigation included the date of onset of paralysis, the age
of the child, its immunization history, and the clinical history
and findings (signs and symptoms). Investigators also
arranged for the collection of stool specimens and their
transportation to the national polio laboratory network for
virus isolation and subsequent differentiation of wild virus
and vaccine-related strains (11). All the laboratories in the

Bulletin of the World Health Organization 2002, 80 (3)

Table 1. National and subnational immunization days, India,

1999
Children aged 05 years receiving OPVa

Date
17 January 1999

134 889 848

14 March 1999

106 937 384

24 October 1999

141 490 011

21 November 1999

142 263 569

19 December 1999

147 030 690

Total

672 611 502

a
b

Oral polio vaccine.

Subnational immunization day.

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Research
In order to calculate the risk of recipient VAPP
following the first OPV dose it was assumed that all infants
received at least one dose of OPV during the first year of life.
Thus the birth cohort of 25 million in 1999 was used as the
denominator. For the calculation of the VAPP risk following
subsequent OPV doses the denominator was the number of
OPV doses administered in 1999 minus the number of first
doses, i.e. 708.4 million subsequent doses (733.4 million
minus 25 million).
The data were analysed by means of Epi Info (v. 6.04,
Centers for Disease Control and Prevention, Atlanta,
Georgia, USA) and SAS (v. 6.12, Cary, North Carolina,
USA). They are presented as means and standard deviations
or as medians with ranges; t-tests for differences in
proportions involved using the Yates corrected P-value or
the two-tailed Fishers exact P-value; the KruskalWallis test
was used for nonparametric comparisons. Statistical significance was defined as P < 0.05.

Results
A total of 9576 AFP cases were reported to the national
surveillance system in India, in 1999. Of these, 4127 (43.1%)
had residual weakness at follow-up examination 60 days after
the onset of paralysis. The 952 cases in which wild poliovirus
was isolated in at least one stool sample were excluded. The
subsequent analysis was restricted to the 271 cases with
vaccine-related poliovirus isolated in any stool sample. Of
these, 87 cases (32.1%) in which OPV was received after the
onset of paralysis and before stool collection and 3 cases (1.1%)
with an unknown number of OPV doses were excluded. Thus
there remained 181 VAPP cases which formed the basis for
this analysis.
Of these cases, 60 (33.1%) developed paralysis between
4 and 40 days after receiving OPV and were classified as
recipient VAPP. For 8 cases (4.4%) there was no information
on the date of the last OPV dose and the number of OPV doses
received; for 13 cases (7.2%) there was no information on the
date of the last OPV dose but it was known that OPV had been
administered at least once. Two risk calculations were made,
one including the 21 cases with unclear immunization histories
and one excluding them, so as to obtain a range of overall
VAPP risk.

Total VAPP cases

For the 181 total VAPP cases the median age was 2 years (range
37 days to 13.4 years), the median number of OPV doses

before the onset of paralysis was 4 (range 014), and 87.3% of

the cases occurred in children under the age of 5 years
(Table 2). Fever was present at the time of onset of paralysis in
67.4% of the VAPP cases; 70.2% of the cases had asymmetric
paralysis. Where only a single virus was isolated, vaccinerelated poliovirus type 3 (33.1%) and type 1 (32.6%) were most
frequently isolated in the stools of VAPP cases, followed by
poliovirus type 2 (21.5%) (Table 3). Mixtures of two or three
poliovirus types were present in 12.7% of all VAPP cases. Of
the 23 cases in which mixtures were isolated, nine (39.0%) had
mixtures of types 1 and 3, six (26.1%) had mixtures of types 1
and 2, six (26.1%) had mixtures of types 2 and 3, and two
(8.7%) had mixtures of types 1, 2 and 3. The age distribution of
cases is given in Fig. 1.

Recipient VAPP cases

The median age of the 60 recipient VAPP cases was 1.2 years
(range 39 days 2555 days (7 years)) and the median number of
OPV doses was 4 (range 114) (Table 2). Asymmetric paralysis
was present in 68.3%; 65.5% had fever at the time of onset of
paralysis; 93.3% were under 5 years of age. Type 3 virus was
isolated in 41.7% of cases, type 1 in 31.7%, and type 2 in 15.0%
(Table 3). Mixtures of two types of poliovirus were present in
7 cases (11.7%): types 1 and 2 were isolated in three of these
cases (42.9%), types 1 and 3 in one case (14.3%), and types 2
and 3 in three cases (42.9%).

Date of onset of paralysis

The onset of VAPP showed clear peaks during October and
November 1999, when national mass immunization campaigns were held, and there were smaller peaks in January,
March and December (Fig. 2). Recipient cases made up a larger
proportion of the total VAPP cases in January, February,
November and December. In October and March, however,
recipient cases made up a small proportion of the total despite
the fact that national or subnational campaigns were held in
these months.

OPV doses
Of the 60 recipient VAPP cases, nine (15.0%) had received
1 dose of OPV, four (6.7%) had received 2 doses, 15 (25%)
had received 3 doses, and 32 (53.3%) had received more than
3 doses (Fig. 3). The nine first-dose recipient VAPP cases were
significantly younger than the remaining 51 who had received
at least 2 doses (199 + 139 days vs 749 + 577 days, Kruskal
Wallis P < 0.001) but did not differ with respect to the

Table 2. Comparison of recipient VAPPa cases (n = 60) and non-recipient VAPP cases (n = 121), India, 1999
Variable

All VAPP

Recipient VAPP

Non-recipient VAPP

Pvalue

Age (days)

933 + 844

665 + 569

1063 + 924

0.003

No. of OPV doses

4.5 + 3.2

4.6 + 3.1

4.4 + 3.3

0.62

41/60 (68.3%)

84/118 (71.2%)

0.83

Asymmetric paralysis

125/178 (70.2%)

Fever

120/178 (67.4%)

38/58 (65.5%)

82/120 (68.3%)

0.84

Age < 5 years

158/181 (87.3%)

56/60 (93.3%)

102/121 (84.3%)

0.14

Data are presented as means + standard deviations (continuous variables) or as proportions with presence of attributes.
a
Vaccine-associated paralytic poliomyelitis.
b
Figures in parentheses are percentages.

212

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Vaccine-associated paralytic poliomyelitis in India

Table 3. Isolates of vaccine-related polioviruses from VAPPa cases, India, 1999
No. with
an isolate
All VAPP
All recipient VAPP
All non-recipient VAPP
a
b
c
d
e

No. with:
Type 1
b

No. with mixtures

of isolates

Type 2

Type 3

39 (21.5%)

60 (33.1%)

23c (12.7%)

181

59 (32.6%)

60

19 (31.7%)

9 (15.0%)

25 (41.7%)

7d (11.7%)

121

40 (33.1%)

30 (24.8%)

35 (28.9%)

16e (13.2%)

Vaccine-associated paralytic poliomyelitis.

Figures in parentheses are percentages.
Six mixtures of types 1 and 2, six of types 2 and 3, nine of types 1 and 3, two of types 1, 2 and 3.
Three mixtures of types 1 and 2, three of types 2 and 3, one of types 1 and 3.
Three mixtures of types 1 and 2, three of types 2 and 3, eight of types 1 and 3, two of types 1, 2 and 3.

presence of fever at the time of onset of paralysis, asymmetric

paralysis, or isolation of the three types of poliovirus.

Estimated risk of VAPP

Table 4 shows the estimated risks of overall and recipient
VAPP. The overall risk (n = 181) was estimated to be 1 case per
4.1 million OPV doses administered. The risk of recipient
VAPP (n = 60) was estimated to be 1 case per 12.2 million
doses administered. The risk of first-dose recipient VAPP
(1 case per 2.8 million doses) was higher than the risk of
subsequent-dose recipient VAPP (1 case per 13.9 million
doses). The overall VAPP risk was recalculated after exclusion
of (i) the 13 cases for which there was no information on the
date of the last OPV dose but for which there was a record of at
least one dose, and (ii) the 8 cases for which there was no
information on the date of the last OPV dose and on the total
number of doses received. This gave an overall VAPP risk of
1 case per 4.6 million doses administered. The risk of recipient
VAPP was unchanged, as there was no information on the
interval between the administration of OPV and the onset of
paralysis for the 21 excluded cases.

Discussion
The results indicated that there were similarities in VAPP
between India and industrialized countries, i.e. small risk, and
first-dose risk higher than subsequent-dose risk. However, in
India the median number of OPV doses before the onset of
VAPP was higher than in industrialized countries and the
children with recipient VAPP were older. The limitations of
the data made it impossible to consider contact VAPP
separately and to assess the contribution of provocation by
injection, if any, to the VAPP risk estimates.
Despite extensive exposure to OPV during mass
vaccination campaigns and in the routine immunization
programme, the overall estimated risk of VAPP in India was
lower than that in Latin America (1 case per 1.52.2 million
doses administered) (6), England and Wales (1 case per
1.4 million doses administered) (3), and the USA (1 case per
2.53.2 million doses distributed) (4). In the United Kingdom
and the USA, OPV has been given solely through routine
health services. In Latin America, however, mass immunization campaigns were conducted in order to supplement routine
immunization. The magnitude of the mass immunization
campaigns in India has been unprecedented, each NID having
reached at least 125 million children every year since 1996 (17).
Exposure to OPV has thus been intense.
Bulletin of the World Health Organization 2002, 80 (3)

213

Research
Table 4. Risk of VAPPa, India, 1999

Table 5. Factors potentially associated with increased or

decreased VAPPa risk in India
Risk of:

Recipient VAPP
Overall risk

First-dose risk

1/12.2 million (60)

c

Subsequent-dose risk
a
b

c
d

e
f

Total VAPP
e

1/4.1 million (181)

1/2.8 million (9)

1/13.9 million (51)

Vaccine-associated paralytic poliomyelitis.

Overall risk denominator is total number of OPV doses distributed over one year
as routine immunization and through national mass immunization campaigns
(733.4 million).
First-dose risk denominator is annual birth cohort (25 million).
Subsequent-dose risk denominator is total number of OPV doses distributed
annually minus annual birth cohort (708.4 million).
Numbers in parentheses are numbers of cases.
Overall VAPP risk, excluding 21 cases with unknown OPV immunization
histories, is 1 case per 4.6 million.

Increased VAPP risk

Decreased VAPP risk

Intense and frequent OPV

exposure during national
immunization days

Early exposure to wild poliovirus,

resulting in type-specific immunity
(protection from vaccine-related virus)

Provocation poliomyelitis
(multiple injections)

Early exposure to vaccine-related

virus (routine immunization at birthb and
6, 10, and 14 weeks)

Aggravation poliomyelitis

Increased maternally-derived antibody

titerres in infants (most mothers repeatedly
exposed to wild poliovirus)
Lower OPV immunogenicity, particularly
for type 3 component, in developing
countries (permits P2 type-specific
immunity to develop first, providing
some cross-immunity to P3)

The somewhat lower risk of VAPP observed in India

relative to estimates from Latin America, the United Kingdom,
and the USA, may be attributable to several factors present in
India and other countries in which polio is endemic (Table 5).
First, the force of wild poliovirus infection, as measured by the
average age of infection (18), is substantially higher than in
industrialized countries. Viral exposure occurs at an earlier age,
when many infants are still protected by maternally-derived
antibodies, which would be expected to prevent both paralytic
poliomyelitis and VAPP. Infants in India remain under the
protection of maternally derived antibodies longer than those
residing in industrialized countries, since mothers are likely to
be exposed to wild poliovirus on many occasions. Moreover,
vaccine-related virus exposure is frequent and repeated even
among unvaccinated infants and children (19). The routine
OPV immunization schedule in India is skewed towards the
younger ages, which induces active immunity against polio at
an early age. These factors lead to decreasing susceptibility to
polio with increasing age, which is reflected by the age
distribution of the disease (2). All of these factors would be
expected to reduce the VAPP risk in countries where polio is
endemic. However, as the force of wild poliovirus infection
decreases the proportion of all polio cases attributable to
VAPP can be expected to increase.
As expected, giving large numbers of supplemental OPV
doses during mass immunization campaigns caused the
estimated risk of subsequent-dose VAPP to diminish by
selectively increasing the magnitude of the denominator
without changing the numerator. The estimated risk of firstdose recipient VAPP was substantially higher than that of
subsequent-dose recipient VAPP. However, the distribution
of OPV doses given to all recipient VAPP cases showed that of
the 60 recipient VAPP cases, 9 (15%) had received only 1 dose
and 32 (53.3%) had received 4 or more. Of the 113 nonrecipient VAPP cases for which there were data on the number
of doses, 61 (54%) had received 4 or more OPV doses. This
high proportion of VAPP cases that had received at least
4 doses possibly reflected lower OPV immunogenicity, which
has been documented in developing countries (9, 20). It is also
possible that the OPV administered in India was of lower
potency and that deficiencies in the cold-chain were
responsible for reduced potency. Some VAPP cases in our
214

Vaccine-associated paralytic poliomyelitis.

Birth dose recommended for institutional births.

study may not have received potent OPV until their third or
fourth dose, at which point they would have been susceptible
and consequently could have developed VAPP. Nevertheless,
the supplementation of routine immunization with OPV doses
from regular mass campaigns has markedly reduced wild
poliovirus transmission in India and remains an essential
strategy for eradication in all remaining countries in which
polio is endemic.
Our data showed increased numbers of VAPP cases
during October and November 1999 and smaller peaks during
January, March and December, all months during which mass
immunization campaigns were conducted. The increased
numbers of VAPP cases during the winter months probably
resulted from the massive amounts of OPV administered
throughout the country during this season of low transmission
of wild poliovirus. In each of these months, recipient VAPP
cases accounted for approximately half of all VAPP cases.
However, the proportion changed from March to October,
when recipient VAPP cases made up only a small proportion of
the total. This change may have been partly attributable to the
misclassification of non-VAPP cases as VAPP cases in
instances where AFP actually had other causes.
Type 1 poliovirus was isolated in a high proportion of
VAPP cases. This had not been expected because of findings in
other populations. The proportion of type 1 VAPP cases was
similar in months when NIDs were held and in months when
they were not held (31% and 35.4% respectively of all VAPP
cases; 31.9% and 30.8% respectively of all recipient VAPP
cases). With the exception of three cases of VAPP involving
type 1 poliovirus in a district of Uttar Pradesh where onset
began on 59 November, there was no apparent temporal or
geographical clustering. Similar results emerged from a
previous study (6) in which type 3 was the most common
serotype, occurring in 50% of recipient VAPP cases, while type
1 occurred in 34.6%. In our recipient VAPP cases, type 3 was
isolated most frequently (48.3%), followed by type 1 (38.3%).
It is important to note that while type 1 poliovirus was
frequently isolated in our VAPP cases, we used a conservative
case definition and thus some of these type 1 cases may not
have been cases of true VAPP.
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Vaccine-associated paralytic poliomyelitis in India

The Indian AFP surveillance system is primarily a tool
for monitoring progress in the eradication of wild poliovirus
transmission. It is not designed to collect comprehensive data
for the assessment of VAPP risk. The misclassification of cases
may have resulted from incomplete detection of either wild or
vaccine poliovirus, incomplete vaccination histories, and
inaccurate assessment of residual paralysis. OPV-derived virus
isolated in the stools of AFP cases with other causes is
expected and is not proof of a causative link between paralysis
and vaccine use. A subset of the VAPP cases identified for
these analyses had final diagnoses suggesting that they were
unlikely to be true VAPP cases, e.g. Guillain-Barre syndrome.
However, the data from the surveillance system were not
complete and it was not possible to exclude any presumptive
VAPP cases that had probable non-polio final diagnoses at 60day follow-up. As a result, the inclusion of these cases may have
led to an overestimation of the VAPP risk. The most accurate
risk estimates in this analysis are those relating to recipient
VAPP, particularly first-dose recipient VAPP, for which
comparisons between studies in different countries are most
easily made.
At least one stool specimen was collected from 92.7% of
the 9576 AFP cases with onset of paralysis in 1999, and two
were collected from 90.7% of them. Two adequate stool
samples were collected within 14 days of the onset of paralysis
for 6739 (70.4%) of the reported AFP cases. The case
definition required isolation of vaccine-related virus in at least
one stool sample and the lack of wild poliovirus in any stool
sample. However, no constraints were placed on the number
of adequate stool samples required. It is possible that VAPP
cases were missed because either no stool samples were
collected, inadequate samples were collected and testing could
not be done, or only one sample was collected and tested
negative for vaccine-related virus. Similarly, it is possible that
wild virus was not detected in cases with inadequate stool
samples. All WHO network polio laboratories in India meet
WHO accreditation criteria and stool samples are carried by
hand from the field to laboratories in order to minimize transit
time and maintain the reverse cold chain. Inadequate specimens are thus not likely to result from reverse cold chain failure
or laboratory error, and the misclassification of viral isolation
results is likely to be minimal, particularly when two adequate
stool samples are obtained. It should be noted that the overall
stool collection rate in India during 1999 was similar to that in
the sample used to estimate VAPP risk in the USA. At least one
stool specimen was taken for poliovirus isolation within
14 days of the onset of paralysis from 57 (71.3%) of the
80 VAPP cases meeting the case definition in the USA in
198089 (4). However, our VAPP case definition, which
required the isolation of vaccine-related virus, was more
specific than that used in the USA, where the isolation of
vaccine-related virus was not required. It is possible that we
missed some VAPP cases because of missing data (inadequate

stool samples); the result of this would have been to

underestimate the VAPP risk.
Several assumptions were made in estimating the
denominators for risk calculations. During NIDs, immunization booths may erroneously report the number of OPV doses
administered on the basis of the number of empty OPV vials at
the end of the day rather than on the number of doses
administered. This may have contributed to our estimated
VAPP risk being lower than the values obtained in Latin
America and the United Kingdom. Furthermore, it is difficult
to determine accurately the denominator for subsequent-dose
recipient VAPP, particularly in countries such as India where
extremely large numbers of children are immunized during
mass immunization campaigns at least twice a year. We could
not differentiate between VAPP associated with routine
immunization doses and that associated with mass campaigns,
as these data were not collected by the surveillance system.
Additionally, it was not possible to conduct a more detailed
examination of the VAPP cases in order to determine whether
they had typical polio paralysis at 60-day follow-up or whether
they had recovered at a later time. It was therefore likely that
non-VAPP cases were included in the analyses and that the
estimated VAPP risks were thus inflated.
The data from the AFP surveillance system in India
show a lower risk of VAPP than in other populations, despite
intense and repeated exposure to many more doses of OPV
than in industrialized countries. These findings in a tropical
developing country where polio is endemic are particularly
significant since wild poliovirus transmission is rapidly
decreasing in India and in other countries where the disease
is endemic, and where providers and parents are increasingly
concerned about VAPP. The risk of paralytic disease from wild
poliovirus infection still far outweighs the risk of VAPP in
countries where polio is endemic, and experience has shown
that OPV, particularly when distributed in mass campaigns, is
an essential tool for rapidly raising herd immunity and
interrupting wild poliovirus transmission. The results of this
analysis and of analyses from other populations indicate that
the risk of VAPP remains quite small even when OPV is
administered to large numbers of children through mass
immunization campaigns. Efforts should therefore be intensified with a view to achieving the goal of global polio eradication
by the end of 2002 and the subsequent discontinuation of OPV
vaccination to ensure that no child will ever again experience
paralytic disease, disability and death associated with either wild
poliovirus or vaccine-related poliovirus. n
Acknowledgements
The authors thank Harry Hull for his valuable comments on
the manuscript and Sunita Durrani for her assistance with data
management.
Conflicts of interest: none declared.

Resume
Poliomyelite paralytique associee a` la vaccination en Inde pendant lannee 1999 : diminution du risque
malgre lutilisation massive du vaccin oral
Objectif La poliomyelite paralytique associee a` la vaccination
(PPAV) est une consequence rare mais grave de ladministration de vaccin antipoliomyelitique oral (VPO). Lintensification
Bulletin of the World Health Organization 2002, 80 (3)

de la vaccination par le VPO a reduit la transmission du

poliovirus sauvage en Inde mais la PPAV devient un sujet de
preoccupation.
215

Research
Methodes Nous avons analyse les donnees de surveillance
concernant la paralysie flasque aigue (PFA) afin destimer le risque
de PPAV dans ce pays. La PPAV a ete definie comme poliomyelite
paralytique observee parmi les cas de PFA avec debut de la
paralysie en 1999, faiblesse musculaire residuelle 60 jours apre`s le
debut de la paralysie et isolement dun poliovirus de type vaccinal.
Les cas de PPAV chez les sujets recemment vaccines constituaient
un sous-ensemble de cas chez lesquels la paralysie debutait entre
4 et 40 jours apre`s ladministration du VPO.
Resultats Au total, 181 cas de PFA repondaient a` la definition de
cas de PPAV. Les estimations de risque suivantes ont ete faites :

risque global, 1 cas pour 4,1 a` 4,6 millions de doses de VPO

administrees ; risque chez les sujets recemment vaccines, 1 cas
pour 12,2 millions ; risque chez les sujets ayant recemment recu la
premie`re dose de vaccin, 1 cas pour 2,8 millions ; risque chez les
sujets ayant recemment recu une dose ulterieure de vaccin, 1 cas
pour 13,9 millions.
Conclusion Le risque estime de VAPP en Inde, calcule dapre`s les
donnees dun syste`me de surveillance tre`s sensible, est a` levidence
plus faible que dans dautres pays, malgre ladministration de
doses multiples de VPO aux enfants dans le cadre de campagnes de
vaccination de masse.

Resumen
Poliomielitis paraltica de origen vacunal en la India durante 1999: reduccion del riesgo pese al uso masivo
de la vacuna antipoliomieltica oral
Objetivo La poliomielitis paraltica de origen vacunal (PPV) es una
consecuencia infrecuente pero grave de la administracion de la
vacuna antipoliomieltica oral (OPV). La intensificacion de la
administracion de OPV ha reducido la transmision del poliovirus
natural en la India, pero la PPV esta empezando a suscitar
preocupacion.
Metodos Analizamos los datos de vigilancia de la para lisis
flaccida aguda (PFA) a fin de estimar el riesgo de PPV en el
pa s. Se establecio que deb an considerarse PPV los casos de
PFA con inicio de la para lisis en 1999, debilidad residual 60
d as despue s del comienzo de las manifestaciones, y
aislamiento del poliovirus vacunal. Los casos de PPV de
receptores se identificaron con el subgrupo en el que la

para lisis se hab a iniciado entre 4 y 40 d as despue s de la

administracio n de OPV.
Resultados En total, 181 casos de PFA satisficieron la definicion
de caso. Se hicieron las siguientes estimaciones del riesgo de PPV:
riesgo global, 1 caso por 4,14,6 millones de dosis de OPV
administradas; riesgo de receptor, 1 caso por 12,2 millones; riesgo
de receptor de primera dosis, 1 caso por 2,8 millones; y riesgo de
receptor de dosis subsiguientes, 1 caso por 13,9 millones.
Conclusion A juzgar por los datos suministrados por un sistema
de vigilancia altamente sensible, el riesgo estimado de PPV en la
India es claramente menor que el correspondiente a otros pases,
pese a la administracion de multiples dosis de OPV a los ninos
durante las campanas de inmunizacion masiva.

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