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Indian Pediatr 2016;53: S14-S19 |
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Cross-sectional Serologic Assessment of
Immunity to Poliovirus in Differential Risk Areas of India:
India Seroprevalence Survey - 2014
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Mohammad Ahmad, Sunil Bahl and Abhishek Kunwar
From World Health Organization (WHO) – Regional
Office for South East Asia, New Delhi, India.
Correspondence to: Dr Mohammad Ahmad, National
Professional Officer, Research- Vaccine Preventable Diseases, WHO India,
New Delhi, India.
Email: [email protected]
Received: January 23, 2016;
Initial review: March 01, 2016;
Accepted: April 23, 2016.
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Objective: To assess the seroprevalence against all three poliovirus
serotypes in traditional high risk areas in Bihar, lowest routine
immunization coverage areas in Madhya Pradesh and migrant population
living in Mumbai urban slums.
Design: Cross-sectional Survey.
Setting: Subjects selected by
house to house visit (community based) and transported to government
health facilities for further study procedures.
Participants: 1137 randomly
selected healthy infants 6-11 months of age residing in the selected
high-risk areas.
Methods: Serum samples from the
study site were shipped to Enterovirus Research Centre (ERC), Mumbai to
determine the neutralizing antibodies against all three poliovirus
serotypes. Children with a reciprocal antibody titer
³1:8
were considered seropositive to the specific poliovirus.
Results: Overall, seroprevalence
in all the three study areas was 98%, 98% and 91% against poliovirus
type-1, type-2 and type-3, respectively. Bihar had a seroprevalence of
99%, 99% and 92% against type-1, type-2 and type-3 respectively.
Corresponding figures for Madhya Pradesh and Mumbai were 98%, 99% and
88% and 98%, 97% and 94%, respectively.
Conclusions: The study found high
seroprevalence against all three poliovirus types not only in the
traditional high-risk areas for polio in India, but even in the areas
known to have low routine immunization coverage and among the migratory
clusters living in Mumbai urban slums. Type-2 seroprevalence was found
to be high. These findings are reassuring against the threat of
emergence of circulating vaccine derived polioviruses (cVDPVs) in the
country subsequent to switch from trivalent oral polio vaccine to
bivalent oral polio vaccine in the routine immunization schedule from
April 2016.
Keywords: India, Poliovirus, Seroprevalence,
Vaccine derived poliovirus.
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W HO South-East Asia Region was
certified polio-free in March 2014, three years after the last polio
case due to wild poliovirus in the Region was reported from India. [1].
However, India still faces the risk of wild poliovirus (WPV) importation
and spread and the risk of paralysis from vaccine derived polio virus
(VDPV) in areas with low population immunity [2,3]. To mitigate these
risks, India continues its efforts to raise population immunity against
polio through mass vaccinations and efforts to improve routine
immunization coverage. To assess the population immunity against
poliovirus, India conducted regular seroprevalence studies in the
highest risk areas during 2007-2012 [4]. The serosurvey conducted in
2012 in high-risk areas of Uttar Pradesh (UP) and Bihar showed improving
type-2 immunity even while sustaining high levels of seroprevalence to
type 1 and 3 [5].
All previous serosurveys in India have been conducted
in the traditional reservoirs of poliovirus transmission in UP and
Bihar. Apart from these traditional risk areas, areas with low routine
immunization coverage and moving populations pose additional risk of WPV
importation and emergence of cVDPVs. This seroprevalence study against
poliovirus was conducted among infants residing in Bihar, Madhya Pradesh
(MP) and Mumbai. This serosurvey in India during August 2014 was the
first after South East Asia Region of WHO including India was certified
polio free in March 2014. The study assessed the seroprevalence to all
three poliovirus serotypes in three categories of risk areas and
compared the seroprevalence between 2014 and 2012.
Methods
Study Design
The study was a cross-sectional seroprevalence of
neutralizing antibodies against all three poliovirus types in infants
6-11 months of age staying in high risk areas for poliovirus
transmission. Children with antibody levels
³ 1:8 dilution for
each poliovirus types were considered seropositive.
Target population: Risk area categories for the study
The study was conducted in three different categories
of risk; 1- traditional high risk areas for polio (Bihar), 2- state with
low routine immunization coverage (Madhya Pradesh) and 3- urban slum
areas with large migratory population (Mumbai). Five highest risk
districts from Kosi riverine areas of Central Bihar were selected. These
districts posed extreme challenges to the polio eradication program in
India and were among the last vestiges of polio transmission in India
with maximum WPV circulation during 2005-2011 in Bihar [6,7]. Another
five districts with lowest routine immunization coverage in MP as per
the Annual Health Survey (AHS), 2011-2012 were included [8]. Eight
municipal wards from Mumbai city were selected due to intense migration
of population in the city. Almost 55% of Mumbai inhabitants live in
slums with migration mainly from UP and Bihar and neighboring countries
like Bangladesh, Nepal, Pakistan and Sri Lanka [9,10].
Sample size and study area selection
Keeping in view the objectives of the study, 360
subjects were proposed to be enrolled in each risk area category, giving
a total sample of 1080 subjects in the whole study. This gave a power of
80%, a
error at 5% and 95% confidence level and compensating for subjects with
dry tap or hemolysis during blood collection and processing. Microplans
of the supplementary immunization activity (SIA) teams carrying out
polio vaccination campaigns were used to randomly select study areas and
houses to be visited to screen and select study subjects. Of all the SIA
team areas in the study districts/wards, a total of 60 SIA team areas
were randomly chosen in Bihar, MP and Mumbai. A random house from all
the houses in the selected SIA team area was allotted to the study staff
to start the screening for the subjects. Moving consecutively as per the
SIA microplan, the study staff selected six children from each SIA team
area to enroll 360 infants in each study location.
Inclusion criteria, screening and selection of
subjects
All 6-11 month old, healthy infants residing in the
study area and whose parents provided consent were eligible for the
study. About 3-5 days prior to actual enrollment, the field study staff
visited the households in their respective polio vaccination team areas
to screen age-eligible children, starting with a randomly allotted first
house. On actual study days, a surveillance medical officer (SMO) of WHO
India-NPSP visited households of age-eligible children to select
study-eligible subjects and transported them to the designated study
sites with their family members.
Study procedures
The study was implemented after approval from the
Institutional Ethics Committee (IEC) of Enterovirus Research Center
(ERC), Mumbai and the Ethics Review Committee (ERC) at WHO, Geneva.
Study sites were set up at government health facilities (PHC/health
posts etc.). At the study site, a study physician obtained written
signed consent from participants’ parents and administered a short
questionnaire. A pediatric resident then collected blood by venepuncture
in a vaccutainer tube with clot separator. Blood samples were allowed to
clot at room temperature and centrifuged. Serum was separated in
cryovials and stored below -20°C. At the end of study, all cryovials
with serum were shipped in dry ice to the Enterovirus Research Centre
(ERC), Mumbai where samples were processed to determine neutralizing
antibodies against all three poliovirus serotypes using Sabin
polioviruses in a modified micro-neutralization assay following a
standard protocol. Serial two-fold dilutions of test serum sample are
reacted with 100 CCID50 of each of the three poliovirus types to
determine the highest dilution that neutralizes the virus infectivity
50% of the time. HEp-2(C) cells are used to detect virus infectivity.
The test requires an incubation period of 5 days. All samples for polio
antibodies were tested in triplicate beginning at a 1:8 dilution.
Specimens were randomized by district and site across the test runs.
Analysis of Results
Based upon an estimated 28-30 days half-life of
maternal antibodies for polio, it is assumed that maternal antibodies
will have decayed to undetectable levels by 6 months. Therefore, all
children with a reciprocal antibody titer
³1:8 were considered
seropositive to the specific poliovirus.
Results
Enrolment
A total of 76,822 houses were visited during initial
screening and 2,890 age-eligible infants were identified. Of this, 1,137
infants were enrolled in the study. Test results for poliovirus
neutralizing antibodies were available from 1,110 subjects (Fig.
1). These subjects were almost equally distributed in the age group
of 6-7 months (N=374), 8-9 months (N=366) and 10-11 months
(N=370).
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Fig. 1 Subject enrolment overview.
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OPV doses received by children
Overall, the study children in Bihar, MP and Mumbai
received a median of 3 routine doses (tOPV) and 4 doses of OPV (2 bOPV+
2 tOPV) through polio campaigns. Infants in Bihar received maximum
median OPV doses (4 through routine and 5 through polio campaigns)
compared to Mumbai (3 and 4) and MP (3 and 2). Overall, only 6.4%
infants in the study received less than 4 OPV doses. No infant from
Bihar received less than 4 doses of OPV (tOPV+bOPV through routine
immunization and polio campaigns), whereas 5.6% infants from Mumbai and
13.8% infants from MP received less than 4 OPV doses. Three quarter
infants from Bihar, about one-third from Mumbai and none from MP
received 8 or more OPV doses (Table I).
TABLE I Percent Subjects By OPV (Topv+Bopv) Doses Received
Doses received |
Bihar |
MP |
Mumbai |
Total |
Total cumulative % |
0 |
0.0 |
0.3 |
0.3 |
0.2 |
0.2 |
1 |
0.0 |
1.4 |
0.0 |
0.5 |
0.6 |
2 |
0.0 |
3.3 |
2.1 |
1.8 |
2.4 |
3 |
0.0 |
8.8 |
3.2 |
4.0 |
6.4 |
4 |
1.6 |
11.8 |
5.4 |
6.2 |
12.6 |
5 |
3.0 |
34.8 |
10.7 |
16.0 |
28.7 |
6 |
5.9 |
39.7 |
19.8 |
21.7 |
50.4 |
7 |
13.5 |
0.0 |
23.0 |
12.3 |
62.6 |
8 |
27.2 |
0.0 |
19.5 |
15.7 |
78.3 |
9 |
26.2 |
0.0 |
15.8 |
14.1 |
92.3 |
10 |
22.6 |
0.0 |
0.3 |
7.7 |
100.0 |
Total |
371 |
365 |
374 |
1110 |
100 |
subjects (N) |
Risk-area category wise seroprevalence
Overall, seroprevalence across the study areas in
Bihar, MP and Mumbai was 98.3%, 98.1% and 91.1% against poliovirus
type-1 (P1), type-2 (P2) and type-3 (P3) respectively. Bihar had a
seroprevalence of 98.9%, 98.9% and 91.6% against P1, P2 and P3,
respectively. Corresponding figures for MP and Mumbai were 97.8%, 99.2%
and 88.0% and 98.1%, 97.3%, and 93.6% respectively (Fig. 2).
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Fig. 2 Seropositivity against three
polioviruses types.
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Age-wise seroprevalence
The youngest age group (6-7 months) had
seropositivity rates of 97.3%, 97.9% and 86.9% against P1, P2 and P3
respectively, compared to 98.7%, 97.3% and 93.5% among infants 10-11
months of age. P3 seroprevalence was significantly high in 10-11 months
infants compared to 6-7 months subjects (Table II).
TABLE II Percent Seroprevalence Against Polioviruses by Age Groups
Age Poliovirus type |
6-7 mo |
8-9 mo |
10-11 mo |
P value* |
Type 1 |
97.3 |
98.9 |
98.7 |
0.20 |
Type 2 |
97.9 |
99.2 |
97.3 |
0.62 |
Type 3 |
86.9 |
92.9 |
93.5 |
0.00 |
Total subjects (N) |
374 |
366 |
370 |
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*P value for seroprevalence between 6-7 & 10-11 months. |
Comparison of seroprevalence against poliovirus
during 2012 and 2014
In 2012, a similar seroprevalence study was conducted
in the high risk areas of UP and Bihar. A significant improvement in
2014 was observed in overall seroprevalence against all three poliovirus
serotypes compared to the 2012 serosurvey (Table III).
Bihar was included in 2012 and 2014 serosurvey. The seroprevalence in
Bihar increased from 96.7% in 2012 to 98.9% in 2014 against type-1 (P=0.03).
Similar increase was also observed for type-2 (98.9%, 89.4%, P<0.01)
and type-3 (91.6%, 86.2%, P<0.001).
TABLE III Percent Seroprevalence against Polioviruses during 2012 and 2014 Serosurveys
|
Overall seroprevalence |
Seroprevalence in Bihar |
Study areas (Year) |
UP, Bihar |
Bihar, MP & Mumbai |
P value |
Bihar (2012) |
Bihar (2014) |
P value |
Poliovirus types |
(2012) |
(2014) |
|
|
|
|
Type 1 |
96.8 |
98.3 |
0.02 |
96.7 |
98.9 |
0.03 |
Type 2 |
88.8 |
98.1 |
0.00 |
89.4 |
98.9 |
0.00 |
Type 3 |
87.0 |
91.1 |
0.00 |
86.2 |
91.6 |
0.01 |
Number of subjects (N) |
1250 |
1110 |
|
620 |
371 |
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Type 2 seroprevalence by number of tOPV doses |
Seroprevalence against type-2 poliovirus steadily
increased with number of tOPV doses, reaching as high as 97.0% with 4
tOPV doses. Infants from Madhya Pradesh showed the highest
seroprevalence of 98.0% with 3 or lesser tOPV doses; reaching 100% with
5 or more tOPV doses. Four doses of tOPV gave a seroprevalence of 98.3%,
96.6% and 95.4% in Mumbai, Bihar and MP respectively (Table IV).
TABLE IV Percent Type-2 Seroprevalence against Polioviruses by tOPV Dose
tOPV doses |
0-3 doses |
4 doses |
>=5 doses |
Study area |
|
|
|
Bihar |
93.8 |
96.6 |
98.4 |
Madhya Pradesh |
98.0 |
95.4 |
100.0 |
Mumbai |
91.8 |
98.3 |
98.8 |
Total |
94.2 |
97.0 |
99.0 |
Discussion
Unlike previous seroprevalence studies in India, the
current seroprevalence study included additional areas with low RI
coverage and areas with sizable mobile/migrant populations, apart from
traditional reservoir areas of poliovirus transmission. Due to intensive
SIAs in Bihar, 76% infants in the present study received
³8 doses of OPV.
Infants in Bihar received a median of 4 routine tOPV doses compared to 3
in MP and Mumbai. In the post-polio-free certification period the levels
of humoral immunity against type-1 poliovirus not only continues to be
high in the traditional high risk areas of Bihar (99%) but also high in
the lowest routine coverage areas of MP (98%) and in slum areas with
migratory populations in Mumbai (98%). This high seroprevalence should
be protective against any poliovirus spread from any potential type-1
importations from polio endemic countries [19]. Type-2 seroprevalence is
high (>97%) in all the three risk areas; the highest seroprevalence
against type-2 recorded since 2007 [20]. This improvement in the type-2
immunity is also a testimony of India’s efforts to improve routine
immunization in the recent years [21]. Type-3 immunity takes the maximum
effort to develop as evident in the present study also [22]. Infants in
the age group of 10-11 months had significantly higher seroprevalence
for type-3 compared to 6-7 month olds. However, no such differences were
observed between the age groups for type -1 and type-2 seroprevalence.
This could be attributed to better opportunity of 10-11 months infants
to be covered with bOPV through the SIAs compared to 6-7 month infants.
Bihar was common study area for the serosurveys
during 2012 and 2014. The seroprevalence in Bihar significantly improved
during 2014 compared with 2012 for all three poliovirus serotypes
(type-1: 98.9% Vs 96.7%, P=0.03; type-2: 98.9% vs 89.4%,
P<0.001; type-3: 91.6% vs 86.2%, P=0.01) [5].
Similar improvement is observed when all the areas of 2012 serosurvey
(UP and Bihar) are compared with the entire risk category areas of 2014
serosurvey (Bihar, MP and Mumbai). This improved seropositivity is seen
despite reduced number of OPV doses in 2014. Further analysis of results
in this study shows that for children in Bihar who received 5 doses, OPV
efficacy has significantly improved in 2014 compared to 2012 (P<0.01).
The immunogenicity of OPV seems to have improved in countries of the
Indian subcontinent during the past 5–10 years, from fairly low baseline
values. Improvements in access to clean water, improved sanitation or
rising socioeconomic status could have contributed to this [23].
We would have liked to understand the population
immunity against polioviruses in areas with known social, political and
geographical challenges where polio surveillance quality is also known
to be weak. But due inherent operational complexity and security
concerns, this was an important limitation of our study.
High seroprevalence rates against all three
poliovirus types in all risk areas as demonstrated in the present study
would mitigate India’s most important risks of poliovirus spread upon
any importation and emergence of cVDPVs. In areas with low RI coverage,
the additional tOPV doses given through NIDs have provided adequate
back-up to keep type-2 immunity high in these areas. Low type-2
seroprevalence had led to outbreaks of cVDPV2 in India in 2009-10 [19].
Along with strengthened routine immunization, NIDs should be continued
in India until global polio free certification to mitigate the risk of
VDPV emergence/circulation. Similar seroprevalence studies are
recommended in India after the tOPV-bOPV switch to understand the
population immunity in dynamically changing vaccine and vaccination
scenario during the polio endgame.
Acknowledgments: World Health Organization
provided funding and technical oversight for the study. We thank and
appreciate the study coordinators Dr AK Gurha, Dr Rahul Shimpi and Dr
Vivek Pardeshi for providing oversight and coordination in their risk
category areas, and all the Medical officers of the WHO India- National
Polio Surveillance unit, India for their dedicated involvement in the
study. We thank the Dr Jagadish Deshpande and his team at the
Enterovirus Research Centre, Mumbai for testing the serum samples to
determine antibodies against poliovirus. Finally, this study would not
have been accomplished without the manpower and logistics support from
the Health departments in Bihar, Madhya Pradesh and Maharashtra.
Contributors: MA: conception and design of the
project, finalising the study protocol, SOPs, trainings of study staff,
leading the field implemetation of the project including monitoring and
supervision, data management and data analysis and manuscript writing;
SB: conception and design of the project, finalising the study protocol,
data management and data analysis and manuscript writing; AK: finalising
the study protocol, SOPs, trainings of study staff, facilitating field
implemetation, monitoring and supervision and manuscript writing.
Funding: Funding by WHO,
(SEIND1409199–8.1–61730); Competing interest: None stated.
What Is Already Known?
• Prior to polio-free certification, the
seroprevalence against poliovirus types 1 & 3 was high in the
traditional high risk areas of transmission in India.
What This Study Adds?
• In 2014 (post-polio-free period), the seroprevalence is
high not only against poliovirus types 1 & 3 but also against
type-2 in the traditional high risk areas in India, as well as
in the areas with low routine coverage and migratory clusters
living in urban slums.
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