Indian Pediatr 2013;50: 1095-1108
Indian Academy of Pediatrics (IAP) Recommended
Immunization Schedule for Children Aged 0 through 18 years –
India, 2013 and Updates on Immunization
Vipin M Vashishtha, Ajay Kalra, Anuradha Bose, Panna
Vijay N Yewale, CP Bansal, Sailesh G Gupta
Indian Academy of Pediatrics, Advisory Committee on
Vaccines and Immunization Practices (acvip)
Correspondence to: Vipin M Vashishtha, Convener, IAP
Advisory Committee on Vaccines and Immunization Practices, Mangla
Hospital and Research Center, Shakti Chowk, Bijnor, Uttar Pradesh,
Justification: There is a
need to review/revise recommendations about existing vaccines in
light of recent developments in the field of vaccinology where new
developments are taking place regularly at short intervals.
Process: Following an IAP
ACVIP meeting on 3rd and 4th August, 2013, a draft of revised
recommendations for the year 2013 and updates on certain new vaccine
formulations was prepared and circulated among the meeting
participants to arrive at a consensus.
Objectives: To review and
revise recommendations for 2013 Immunization timetable for
pediatricians in office practice and issue statements on new vaccine
Recommendations: The major
change in the 2013 Immunization timetable was made in the
recommendations pertaining to pertussis immunization. Taking in to
the consideration of recent outbreaks of pertussis in many
industrialized countries using acellular pertussis (aP) vaccines and
subsequent finding of faster waning of the same in comparison to
whole-cell pertussis (wP) vaccines and superior priming with wP
vaccines than aP vaccines, the committee has now recommended wP
vaccines for the primary series of infant vaccination. Guidelines
are now also issued on the preference/selection of a particular aP
vaccine in case it is not feasible to use wP vaccine, and use of
Tdap vaccine during pregnancy. The administration schedule of
monovalent human rotavirus vaccine, RV1 has been revised to 10 and
14 weeks from existing 6 and 10 weeks. Recommendation is made for
the need of booster dose of live attenuated SA-14-14-2 JE vaccine.
Updates and recommendations are issued on new typhoid conjugate
vaccine, inactivated vero-cell culture derived SA-14-14-2 JE
vaccine, inactivated vero-cell derived Kolar strain, 821564XY JE
vaccine, and new meningococcal conjugate vaccines. This year the
recommended immunization schedule with range for persons aged 0
through 18 years is being published together instead of two separate
schedules. A subcategory of ‘general instruction’ is added in
footnotes. The comments and footnotes for several vaccines are
revised and separate instructions for ‘routine vaccination’ and
‘catch-up vaccination’ are added in the footnotes section wherever
Key words: Indian Academy of Pediatrics,
Advisory Committee on Vaccines and Immunization Practices,
Recommendations, Immunization Timetable 2013.
As stated earlier  it was decided in 2012 to
revise IAP Immunization Timetable every year. The IAP Advisory Committee
on Vaccines and Immunization Practices (ACVIP) has recently reviewed and
revised the recommended immunization schedules for children aged 0
through 18 years to ensure that the schedule reflects recommendations
based on recent evidence for licensed vaccines in the country. The
mid-term meeting of the IAP ACVIP was held on 3rd and 4th August, 2013
in New Delhi. IAP ACVIP members and invited experts who attended the
meeting are listed at the end of this paper. The aim of the meeting was
to discuss and debate recent developments in the field, to revise
recommendations for the IAP Immunization Timetable for the year 2013,
and to issue recommendations for newly licensed vaccines in the country.
Following the meeting, a draft of revised immunization schedule for the
year 2013 was prepared and circulated among the meeting participants to
arrive at a consensus.
Process for Issuing Recommendations
The detailed process behind issuing IAP
recommendations on immunization is described earlier . We reaffirm
that the recommendations of IAP are primarily for the pediatricians in
office practice. These recommendations provide guidelines to a
pediatrician on how best to utilize available licensed vaccines in their
office-practice settings. The members may use their own discretion while
using them in a given situation within the framework suggested . The
existing national immunization schedule and government policies are also
taken in to account while drafting recommendations.
AIMS AND OBJECTIVES
To revise IAP Immunization Timetable for the year
2013 and review and issue recommendations on the recently licensed
RECOMMENDATIONS FOR IAP IMMUNIZATION TIMETABLE, 2013
The IAP ACVIP has issued recommendations for the IAP
Immunization Timetable for the year 2013 that includes the following
major changes from last year:
A. Pertussis Immunization
IAP ACVIP has now issued following recommendations on
use of pertussis vaccines for office-practice in private health care:
Primary immunization: The primary infant series
should be completed with 3 doses of whole-cell pertussis (wP) vaccines.
Vaccination must start at 6 weeks. Acellular pertussis (aP) vaccines
should be avoided for the primary series of infant vaccination until or
unless there is a genuine compelling reason to use aP vaccine in a given
The recommendation on the use of wP vaccine in
primary immunization series is based on the experience with wP vaccines
in India and on demonstration of faster waning with aP vaccines in
comparison to wP vaccines, and superior priming with wP vaccines than aP
vaccines in studies conducted in the industrialized countries after
recent resurgence of pertussis in many of these countries using aP
vaccines. The evidences and reasons behind above recommendations are
discussed in detail in IAP Position Paper on Pertussis immunization .
The aP vaccine combinations should be avoided for the
primary series. However, the aP vaccines may be preferred to wP vaccines
in those children with history of severe adverse effects after previous
dose/s of wP vaccines or children with neurologic disorders, if
resources permit. The parents should be counseled about the probable
efficacy related disadvantages of using aP vaccines for the primary
series. The schedule is same as with wP (DTwP) vaccines. Like DTwP
vaccines, DTaP vaccines must not be used in children 7 years or older
because of increased reactogenicity.
Boosters: The 1st and 2nd booster doses of
pertussis vaccines should also be of wP vaccine. However, considering a
higher reactogenicity, aP vaccine/combination can be considered for the
boosters, if resources permit.
Choice of aP vaccines: Considering the strong
evidence in favor of superiority of multicomponent (³3)
aP vaccines in comparison to one- and two-component aP vaccines from
recent systematic reviews and meta-analysis , IAP unambiguously
recommends that if any aP containing vaccine is used, it must at least
have 3 or more components in the product, the more the better.
Tdap during pregnancy: Maternal immunization,
particularly of pregnant women may be an effective approach to protect
very young infants and neonates . IAP ACVIP therefore now suggests
immunization of pregnant women with a single dose of Tdap during the
third trimester (preferred during 27 through 36 weeks gestation)
regardless of number of years from prior Td or Tdap vaccination. Tdap
has to be repeated in every pregnancy irrespective of the status of
previous immunization (with Tdap). Even if an adolescent girl who had
received Tdap one year prior to becoming pregnant will have to take it
since there is rapid waning of immunity following pertussis
However, only single administration of Tdap is
permitted to all adolescents. Persons aged 7 through 10 years who are
not fully immunized with the childhood DTwP/DTaP vaccine series, should
receive Tdap vaccine as the first dose in the catch-up series; if
additional doses are needed, use Td vaccine. For these children, an
adolescent Tdap vaccine is not required.
B. Rotavirus immunization
Administration schedule of monovalent rotavirus
Monovalent (RV1) and pentavalent rotavirus (RV5)
vaccines when started at 8 weeks of age and given at 2 or 3 dose
schedule respectively, has been found to be highly effective in
preventing rotavirus gastroenteritis . WHO position paper 
recommends that 1st dose of rotavirus vaccination should be given with
1st dose of DPT vaccination both for RV1 and RV5, which effectively
means starting the schedule at 6 weeks in India. It is also known that
if rotavirus vaccines are to be co-administered with OPV in a setting
with an EPI vaccination schedule beginning at 6 weeks of age, the second
dose of RV1 may not be sufficient to provide adequate immunity against
severe rotavirus disease . The IAP committee on Immunization has
already expressed its concerns on the proper administration schedule of
rotavirus vaccines, particularly two-dose schedule of RV1 in India in
order to achieve higher yields in term of protective efficacy .
Several studies from South Africa, Vietnam, and
Philippines have indicated that the older the infant when they receive
the first dose of vaccine, the better the immune response in terms of
sero-conversion and GMCs . The titers of circulating maternal
antibody in the infants and OPV co-administration have a negative impact
on the immune response of the first rotavirus vaccine dose (lower sero-conversion
rates and reduced GMCs) . It is a well known fact that first dose of
RV1 administered at 6 weeks along with OPV is non-immunogenic. In a
study conducted in South Africa, the seroconversion of first dose of RV1
when administered at 6 weeks along with OPV was found to be only 13%,
whereas when the same dose was administered at 10 weeks along with IPV,
the seroconversion rose to 43% . In the same study, the
anti-rotavirus IgA antibody sero-conversion rates were higher for the
10-14 weeks schedule (55-61%) compared to the 6-10 weeks schedule
In Africa trial, the 2 dose and 3 dose schedule of
RV1 starting at 6 weeks of age showed that vaccine efficacy against
severe rotavirus diarrhea for the first year with 2 dose schedule was
58.7 (95% CI 35.7 -74) while for 3 dose schedule the same was 63.7 (95%
CI 42.4 – 77.8) . There was no difference on the first year efficacy
of both the schedules in Malawi, but a definite gradient favoring 3-dose
schedule in South Africa (81.5, 95% CI, 55.1-93.7 for 3-dose versus
72.2, 95% CI, 40.4-88.3 for 2-dose) . However, when second year
efficacy against severe rotavirus diarrhea was considered, there was
significant difference in the efficacy of the two schedules in both the
countries (85% for 3-dose versus 32% for 2-dose in South Africa, and 49%
versus 18%, respectively in Malawi) [8-10].
Most of the comparative studies with 2 versus 3 dose
schedule have employed RV1 in 10, 14 weeks instead of recommended 6, 10
weeks schedule [8-11]. An immunogenicity study from India has shown that
RV1 given in a 2 dose schedule, with 1st dose between 8 to 10 weeks and
2nd dose between 12 to 16 weeks is immunogenic and well tolerated in
healthy Indian infants . Pentavalent vaccine given in 3 doses has
shown adequate immunogenicity in Indian infants when started at 6 weeks
of age . A 3-dose schedule of RV 116E starting at 8 weeks
demonstrated a robust immune response . Two ongoing studies in
Pakistan and Ghana are studying the immunogenicity of 2 versus 3-dose
schedule of RV1.
Considering all the above mentioned facts, the IAP
ACVIP is of the opinion that if RV1 vaccine is to be administered in a
2-dose schedule, the first dose should start at 10 weeks of age instead
of 6 weeks in order to achieve better immune response. The second dose
can be administered at 14 weeks to fit with existing national
immunization schedule. However 3-dose schedule of any rotavirus vaccine
can start at 6 weeks of age with minimum interval of 4 weeks between the
C. Typhoid vaccination
Vi-polysaccharide conjugate typhoid vaccine (Typbar-TCV®}
by Bharat Biotech:
Typbar-TCV® is a Vi-capsular polysaccharide conjugate
typhoid vaccine conjugated with tetanus toxoid. The manufacturer has
used a dose of 25 µg/0.5 mL of Conjugate Vi Content polysaccharide which
is the highest having been used in other trials as well on conjugate
vaccine the world over.
According to the data submitted by the manufacturer,
a phase IIa/IIb study revealed no difference in the GMTs between two
doses (15µg/0.5 mL) and single (25 µg/0.5 mL) dose cohorts, and a single
dose of 25 µg/0.5 mL showed excellent immune response (100%
seroconversion). A phase III, randomized, multi-centric, controlled
trial was conducted to evaluate the immunogenicity and safety of the
test vaccine, Typbar-TCV® in a total of 981 healthy subjects and
compared with the typhoid vi capsular polysaccharide vaccine of the same
manufacturer (Typbar®) having similar amount of antigen per dose. The
study group receiving the test vaccine (Typbar-TCV®) was divided into
two cohorts i.e. ³6
months to £ 2
years (327 subjects) and >2 years to <45 years (654 subjects). Cohort–I
was single arm open label and all the subjects received single dose of
the test vaccine. Cohort-II was randomized double blind trial and the
subjects were recruited in to two groups who received single dose of
either test vaccine (340 subjects) or reference vaccine (314 subjects).
Immunogenicity results: In cohort-I, 98.05%
subjects showed seroconversion (³4-fold
titre rise) on day 42, and the geometric mean titres (GMTs) on day 0 and
42 were 9.44U/mL and 1952.03U/mL respectively. The GMTs were slightly
higher in the >1-2 years than in 6m to <1 year age group while no
difference was seen in seroconversion rates. In cohort-II, 97.29% and
93.11% subjects of test and reference vaccine groups respectively, were
titer rise) on day 42. Whereas the GMTs on day 42 in the test and
reference vaccine groups were 1301.44U and 411.11U, respectively (P=0.001).
Both seroconversion and GMTs were higher in younger (>2 to <15 years)
than older (15-45 years) age groups.
Long-term immunogenicity: The manufacturer has
planned a 3-year follow-up for seroconversion data of phase III. So far,
they have shared 18 months follow-up data which show significant waning
of GMTs and seroconversion levels in both the cohorts from day 42 levels
while 100% of subjects of test vaccine subjects were still seroprotected
(the protective level: Vi antibody > 7.4 Elisa unit/mL). Similar trend
was observed in the subgroup of cohort-II that received reference
Safety issues: No serious adverse event was
noted. The most common local and systemic events reported were pain at
injection site and fever, respectively in both the cohorts. Fever was
noticed in 10.0%, 4.28%, and 2.75% in cohort-I, test, and reference
vaccine groups of cohort-II, respectively. None of the enrolled subjects
were withdrawn from study for vaccine related adverse reaction. The
manufacturer has indicated to follow all subjects for up to 12 weeks
The vaccine has been licensed by the Drug Controller
General of India (DCGI) in August, 2013 for clinical use in India.
The IAP ACVIP has reviewed the above pivotal trial
(unpublished) and considers it to be a promising vaccine, fulfilling the
critical gap of providing protection under 2 years of age. However,
before a slot is created for the vaccine in the existing IAP
Immunization Timetable, the committee has pinpointed following issues to
1. The researchers have used a Vi-PS typhoid
vaccine from the same manufacturer as a reference vaccine above 2
years of age and have shown almost equal seroconversion and
significantly higher GMTs with the new Vi PS-conjugate vaccine in
children >2 years and adults, no comparative vaccine was used for
the cohort consisting of children <2 years of age. Though it may be
more difficult to identify a typhoid/non-typhoid vaccine that could
be used to maintain a double blind design in this age group, a
double-blind, randomized controlled trial would have been much more
2. It seems quite encouraging that almost similar
or higher level of seroconversion and GMTs were achieved below 2
years of age than in older children with the same vaccine, and
significantly higher (>3 folds) GMTs were achieved with the test
vaccine than the reference vaccine in older age group and adults.
Another Vi-PS vaccine from a different manufacturer (Typhim-Vi® from
Sanofi Pasteur) has demonstrated effectiveness in a large field
trial in Kolkata, India . The researchers have used a cut-off of
>7.4 Elisa unit/mL as a serologic correlate for protection. However,
it is still debatable and well known that there is no universally
accepted absolute correlate of protection for typhoid disease or
vaccine. Thus, there is need of a large field efficacy trial since
seroconversion is not a direct proxy for ultimate clinical
3. Though the test subjects below 2 years of age
could maintain reasonably good seroconversion even after 18 months
of follow-up, the GMTs waned significantly and were far below the
level achieved after the first dose. Hence, there may be a need of a
booster dose of the vaccine. The impact of booster dose on antibody
titres and exact timing of the same can only be determined after a
4. The vaccine is licensed to be given at age 6
months and above. The manufacturers have recommended single dose of
the vaccine at 9 months of age along with measles vaccine. However,
the committee believes there is a need of studying interference with
measles vaccine given to the subjects at 9 months before a universal
recommendation is made. Similar studies are needed with MMR vaccine
before recommending a booster of the vaccine at 15 months along with
5. The new Vi-PS conjugate vaccine was found more
than twice reactogenic (in term of fever) in children <2 years than
older children and adults and almost 3 times more reactogenic in
younger age group than the reference vaccine in older age group.
However, the reactogenicity was almost similar as expected with any
other vaccines given to infants. Nevertheless, the committee thinks
there is a need to monitor the reactogenicity profile of the vaccine
more closely and in higher number of subjects after licensure.
IAP recommendations for use
Considering the typhoid epidemiology in the country
and analyzing the available data of the vaccine, IAP recommends the new
Vi-PS conjugate vaccine below one year of age, preferably between 9-12
months (minimum age 6 months). Since the incompatibility data with
measles vaccine is not available, it would be prudent to maintain an
interval of at least 4 weeks with the former. The committee believes
there is a definite need of a booster dose during second year of life;
however, the available data is insufficient to specify exact timing of
the same. The committee stresses the need of large scale field
effectiveness trials in real life settings to establish superiority of
the product over the existing Vi-PS vaccines, and to ascertain
translation of higher GMTs and better seroconversion rates in to greater
D. Japanese Encephalitis vaccination
Live Attenuated SA-14-14-2 Vaccine
The IAP ACVIP reviewed the performance of SA-14-14-2
JE vaccine in India since its launch in 2006. Though this vaccine is not
available in private market for office use, the committee deemed it
necessary to respond to frequent queries from members on the critical
issue of a need of 2nd dose
(booster dose) of the vaccine.
The committee reviewed the efficacy of this vaccine
in India. A small case–control study from Lucknow, India found an
efficacy of 94.5% (95% CI, 81.5 to 98.9) after a single dose of this
vaccine within 6 months after its administration . However, data
from post marketing surveillance (PMS) in India (ICMR unpublished study)
showed that protective efficacy of the vaccine in India is not as high
as that seen in Nepal. According to the study, sero-conversion rates at
28 days after vaccination were 73.9% and 67.2% in all individuals and in
those who were nonimmune pre-vaccination, respectively. The protective
efficacy of the vaccine at one year was 43.1% overall and 35% for those
who were non-immune pre-vaccination, respectively . Preliminary
results of a recent case control study show an unadjusted protective
effect of 62.5% in those with any report of vaccination . According
to this report, the JE vaccine efficacy has been around 60% in Uttar
Pradesh and around 70% in Assam.
Inactivated Vero cell culture-derived SA 14-14-2 JE
vaccine (JE-VC), (IXIARO® and JEEV®)
(i) IXIARO® by Intercell AG: This
is an inactivated vaccine (JE-VC) derived from the attenuated SA
14-14-2 JEV strain propagated in Vero cells. This vaccine has been
evaluated in several clinical trials in adults and children in India
and in several other countries [18-20] IXIARO® has now been approved
by US FDA and EU for use in children from the age of 2 months
onwards [21, 22]. There is no efficacy data for IXIARO®, and the
vaccine has been licensed in pediatric age group especially for
travelers to Asian countries on the basis of a Phase III RCT
conducted in the Philippines , and favourable interim data from
a second Phase III trial in EU, U.S. and Australia . The safety
profile of the test vaccine was good, and its local tolerability
profile was more favorable than that of the mouse brain vaccines
(ii) JEEV-the Indian variant of IC51,
IXIARO: Biological E. Ltd. has launched a vaccine for the
endemic markets under the trade name JEEV® based on Intercell’s
technology and has already been WHO prequalified. In 2011, the BE
Ltd. India conducted a multi-centric open label randomized
controlled phase II/III study to evaluate safety and immunogenicity
of JEEV® vaccine in ~450 children (³1
to <3-year old) and compared to control Korean Green Cross Mouse
Brain Inactivated (KGCC) vaccine (unpublished). This study
demonstrated seroconversion (SCR) of 56.28% on day 28 and 92.42% on
day 56 in JEEV® vaccinated group. Non-inferiority of JEEV®
established against control in terms of proportion of subjects
seroconverted. GMTs in JEEV® group were significantly higher than
GMTs achieved in KGCC-JE vaccine group (218 vs 126). There was no
significant difference between the groups in proportion of subjects’
seroprotected, and in proportion of subjects reporting adverse
events between groups. JEEV® has been licensed by Drug Controller
General of India for use in prevention of JE virus infection in
children and adult population on the basis of its ability to induce
JEV neutralizing antibodies as a surrogate for protection.
Inactivated Vero cell culture-derived Kolar strain,
821564XY, JE vaccine (JENVAC®)
JENVAC® is a Vero cell culture derived, inactivated,
adjuvanted and thiomersal containing vaccine developed by Bharat Biotech
International Limited (BBIL). The original virus strain used in the
vaccine was isolated from a patient in the endemic zone in Kolar,
Karnataka, India by National Institute of Virology (NIV), Pune and later
transferred to BBIL for vaccine development.
A Phase II/III, randomized, single blinded, active
controlled study to evaluate the immunogenicity and safety of the
vaccine was conducted among 644 healthy subjects. Out of 644 subjects
212 were between the age of £50
to >18 years, 201 subjects were between the age of
£18 to >6 years and
231 subjects were between the age of
£6 to >1 years.
Subjects received two doses of the test vaccine or a single dose of a
reference vaccine (Live attenuated, SA 14-14-2 Chinese vaccine) as the
first dose and a placebo as the second dose.
The results revealed that even a single dose of the
test vaccine was sufficient to elicit the immune response. On 28th day,
the subjects who had received a single dose were 98.67% seroprotected
and 93.14% seroconverted (4 fold) for
³1 years, whereas the
corresponding figures for the reference vaccine were 77.56% and 57.69%,
respectively (p-value <0.001). There was no statistically significant
difference in all the 3 groups. The seroconversion (93.14% and 96.90%)
and seroprotection (98.67% and 99.78%) percentages on the 28th and 56th
day were not significantly different and similarly, no statistically
significant difference in these rates was noted amongst different age
groups. Higher GMTs were achieved in younger age groups. After the
second dose of the test vaccine, the GMTs increased exponentially from
day 28 (145) to day 56 (460.5) in £50
- ³1 years.
However, there was waning of both seroconversion and GMTs in both the
test vaccine and reference vaccine groups at 18 months. All the subjects
were followed up for 56±2 days. There was no serious adverse event or
adverse event of any special interest noted in the study.
IAP Recommendations for use
The vaccination against JE is not recommended for
routine use, but only for individuals living in endemic areas.
Live Attenuated SA-14-14-2 Vaccine: After
analyzing the recent Indian efficacy/effectiveness data, the academy
thinks there is a need of a second dose of the vaccine to provide more
complete and sustained protection. First dose of the vaccine can be
administered at 9 months along with measles vaccine and second at 16 to
18 months at the time of 1st
booster of DTP vaccine.
JEEV® by Biological E. Ltd: The committee
believes that although Biological E. India Ltd. has used the same
strain, adjuvant and technology in production of JEEV® as used by
Intercell AG in development of IXIARO®, the two vaccines cannot be
treated as the same product. Considering the proven efficacy and safety
profile of its parent vaccine in many countries over past many years,
and demonstration of good seroprotection in Indian trial, the committee
endorses use of this vaccine in India and recommends a primary schedule
of 2 doses of 0.25mL for children aged
£3 years and 2 doses
of 0.5mL for children >3 years, adolescents and adults administered
intramuscularly on days 0 and 28. However, the long term persistence of
protective efficacy and need of boosters are still undetermined. In
February 2011, ACIP approved recommendations for a booster dose of JE-VC
(IXIARO®) in adults.
JENVAC® by BBIL: The committee reviewed the data
provided by the manufacturer on the clinical trials of JENVAC® in India.
Although it lacks the experience of multinational trials of IXIARO® in
different settings, nevertheless the results of a pivotal phase II/III
study conducted in India appear satisfactory for issuing recommendations
for clinical use. The committee recommends two doses of the vaccine (0.5
ml each) administered intramuscularly at 4 weeks interval for the
primary immunization series for office practice starting from 1 year of
age. Since appreciable waning was noted in both seroconversion and
seroprotection rates, and GMTs were also waned significantly, there is
definitely a need of booster dose at later stage. The exact timing of
the booster along with feasibility of single dose for primary series can
be determined only after obtaining the long term follow-up data.
E. Meningococcal vaccination
Meningococcal conjugate vaccines (MCVs)
Currently two different types of meningococcal
conjugate vaccines (MCVs) are licensed in India. The first which is now
readily available in private market also, is a quadrivalent vaccine
Menactra® from Sanofi Pasteur, and another a monovalent serogroup A
vaccine from Serum Institute of India (SII).
Quadrivalent meningococcal polysaccharide-protein
conjugate vaccine (MenACWY-D, Menactra®,)
This is a quadrivalent (A,C,W135,Y) meningococcal
conjugate vaccine using diphtheria toxin as carrier protein
(A,C,W135,Y-D), and was licensed in US in 2005. However, it is licensed
in India only in 2012 for use among persons aged 2 through 55 years. In
2011, ACIP recommended a two-dose series of this vaccine for use in
children aged 9-23 months. It contains 4 µg each of A, C, Y and W-135
polysaccharide conjugated to 48 µg of diphtheria toxoid. A single dose
of 0.5 mL IM is recommended. Recent estimates of the effectiveness of
MenACWY-D, the first licensed quadrivalent vaccine suggest that within 3
to 4 years after vaccination, effectiveness is 80% to 85% [25, 26]. It
is associated with minor local side effects such as pain, and swelling.
Guillain-Barré Syndrome was noted as a possible but unproven risk in
some adolescents following immunization . Interference with PCV13
immune responses was noted when MenACWY-D and PCV13 were administered
simultaneously in patients with asplenia. Hence, it is now recommended
that at least one month interval should be kept between PCV13 and
MenACWY-D, and PCV13 should be administered first .
Monovalent serogroup A conjugate vaccine (PsA–TT,
Meningococcal Group A Conjugate Vaccine is a
lyophilized vaccine of purified meningococcal A polysaccharide
covalently bound to tetanus toxoid (TT) which acts as a carrier protein.
It contains 10 µg of group A polysaccharide conjugated to 10-33 µg
tetanus toxoid, with alum as adjuvant and thiomersal as preservative
. The vaccine is licensed in India since 2009 and prequalified by
WHO in 2010, but surprisingly, the company has not launched this
inexpensive vaccine (costing around half a cent to African nations) in
India so far. It has been used in large campaigns in Burkina Faso, Mali,
and Niger and is being progressively introduced in other countries of
the African meningitis belt .
It should be administered as a single intramuscular
injection of 0.5 mL to individuals 1-29 years of age . The possible
need for a booster dose has not yet been established. Persons who have
previously received a meningococcal A polysaccharide-containing vaccine
can be vaccinated with the conjugate vaccine.
The single intramuscular dose induces functional
antibody titres against meningococcal serogroup A which are
significantly higher and more persistent than those induced by a
corresponding polysaccharide vaccine [29-31].The immune response seems
to persist for a long time. The vaccine has also got a very good safety
profile. There is moderate level of evidence for protection of children
against Group A meningococcal disease in both children >12 months to <5
years, and in individuals ³5
years old . Furthermore, the vaccine has demonstrated a great
effectiveness when used in Africa in campaigns.
IAP position on use of meningococcal vaccines in
The current epidemiology and burden of meningococcal
diseases (MD) in India do not justify routine use of meningococcal
vaccines. Meningococcal vaccines are recommended only for certain
high-risk conditions and situations as enumerated below in children aged
2 years or more (3 months or older if risk of meningococcal disease is
high, e.g. outbreaks/ close household contact). Conjugate vaccines are
preferred over polysaccharide vaccines due to their potential for herd
protection and their increased immunogenicity, particularly in children
<2 years of age.
Sporadic outbreaks of meningococcal disease have been
recorded for last many decades in India. These outbreaks, particularly
the larger epidemics have almost universally been caused by serogroup A
meningococci . The committee believes that the new affordable
serogroup A-containing monovalent conjugate vaccine manufactured by SII
should have a critical role in containing future epidemics. The Academy
urges the Indian manufacturer to make this vaccine available in the
country also. The quadrivalent MenACWY-D should be employed in
individuals having certain high-risk conditions and situations
(mentioned below) and amongst international travelers.
IAP recommendations on dosage in different
categories: IAP now recommends the use of MCVs in different
categories as per following description:
A. During disease outbreaks:
Polysaccharide vaccines can be used to control outbreaks in countries
where limited economic resources or insufficient supply restrict the use
of MCVs . However, due to the limited efficacy of polysaccharide
vaccines in children <2 years of age, conjugate vaccines should be used
for protection of those aged 12–24 months, particularly for Men A
disease. Since majority of documented outbreaks in India are caused by
Men A, monovalent MCV, like PsA-TT should be employed in mass
B. Vaccination of persons with high-risk
(i) Children with terminal complement
component deficiencies: A two-dose primary series of MCV
administered 8–12 weeks apart is recommended for persons aged 24
months through 55 years with persistent deficiencies of the late
complement component pathway. A booster dose should be administered
every 5 years. Children who receive the primary series before their
seventh birthday should receive the first booster dose in 3 years
and subsequent doses every 5 years.
(ii) Children with functional/ anatomic
asplenia/ hyposplenia (including sickle cell disease):
Administer 2 primary doses of either MCV with at least 8 weeks
between doses for individuals aged 24 months through 55 years.
Vaccination should ideally be started two weeks prior to splenectomy.
(iii) Persons with Human
Immunodeficiency Virus: Administer two doses at at least 8 weeks
(iv) Laboratory personnel and
healthcare workers: who are exposed routinely to Neisseria
meningitides in solutions that may be aerosolized should be
considered for vaccination. A single dose of MCV is recommended. A
booster dose should be administered every 5 years if exposure is
(v) Adjunct to chemoprophylaxis: in
close contacts of patients with MD (health care workers in contact
with secretions, household contacts, day care contacts) single dose
of appropriate group MCV is recommended.
C. International travelers
(i) Students going for study abroad:
(mandatory in most universities in the USA) Some institutions have
policies requiring vaccination against MD as a condition of
enrollment. Persons aged £21
years should have documentation of receipt of a MCV not more than 5
years before enrollment. In US, ACIP recommends routine vaccination
of all adolescents with single dose of MCV4 at age 11-12 years, with
a booster dose at age 16 years (available online at
http://www.cdc.gov/vaccines/pubs/acip-list.htm). For further
details, follow the catch-up recommendations for meningococcal
vaccination of the destination country.
(ii) Hajj pilgrims: Vaccination in
the 3 years before the date of travel is required for all travelers
to Mecca during the annual Hajj. The quadrivalent vaccine is
preferred for Hajj pilgrims and international travelers as it
provides added protection against emerging W-135 and Y disease in
these areas. A single dose 0.5 ml IM is recommended in age group
(iii) Travelers to countries in the
African meningitis belt: A single dose of monovalent or
quadrivalent vaccine is recommended. Conjugate vaccine is preferred
to polysaccharide vaccine. A booster dose of MCV is needed if the
last dose was administered 5 or more years previously.
F. Poliovirus immunization
No change is made to the existing polio immunization
schedule. However, in the comment section of
Table 1 and in the
footnotes after Figure 1, extra-emphasis is given to the need of
vaccinating all eligible children with polio vaccines, IPV or OPV. The
Academy is committed to polio eradication initiative in the country.
This is to reaffirm again that the current IAP recommendations on polio
immunization are one suggested way to the practitioners on how to best
utilize available polio vaccines (OPV and IPV) in their office
practices. However, they may use the polio immunization schedule as
suggested by the Universal Immunization Program (UIP), if it is not
feasible to follow IAP schedule. The members/pediatricians are advised
to encourage administration of all OPV doses during the ongoing
campaigns, NIDs or SNIDs of GoI/NPSP.
G. Other changes
(i) Figures 1 and 2
of earlier schedule  are now combined to illustrate recommended
immunization schedule with range for persons aged 0 through 18
(ii) The footnotes of the two figures have
also now been merged. The recommendations contained in the footnotes
section is now divided in to two broad subheads, ‘routine
vaccination’ and ‘catch-up vaccination’ wherever applicable.
(iii) The footnotes section of all the
recommended vaccines is updated and revised with addition of new
information on many vaccines.
Major Changes in Recommendations
for IAP Immunization Timetable, 2013
• Whole-cell pertussis vaccines for primary infant series of immunization
• Acellular pertussis vaccines in certain specific circumstances/conditions only
• Multicomponent (≥3) aP vaccine products to be preferred over other aP vaccines
• Tdap vaccine recommended for pregnant women with every pregnancy
• Administration schedule of RV1 revised
• Two-dose schedule to begin at 10 weeks, 2nd dose at 14 weeks
• Guidelines are provided for the use of new Vi-polysaccharide conjugate typhoid vaccine
• Two doses of live attenuated SA-14-14-2 vaccine
• Guidelines are provided for the use of new inactivated JE vaccines, JEEV® and JENVAC ®
• Guidelines are provided for the use of new meningococcal conjugate vaccines
• Recommendations are issued on the dosage of meningococcal use in different categories
• Emphasis is given to the need of vaccinating all eligible children with polio vaccines
• Encouragement for administration of all OPV doses during campaigns
• Only single figure to illustrate recommended immunization schedule with catch-up range
for persons aged 0 through 18 years
• Footnotes are revised and updated.
Conflicts of interests: None. Funding:
IAP Advisory Committee on Vaccines & Immunization
Practices, 2013-14: Office-bearers: C.P. Bansal
(Chairperson), Rohit Agarwal (Co-chairperson), Vijay Yewale
(Co-chairperson), Vipin M. Vashishtha (Convener), Sailesh Gupta (lAP
Coordinator), Members: Shashi Vani, Anuradha Bose, Ajay Kalra, AK
Patwari, Surjit Singh; Consultants: Naveen Thacker, NK Arora,
Rajesh Kumar, HP Sachdev, VG Ramchandran, Ajay Gambhir; Rapporteur:
Panna Choudhury. Special invitees: Meenu Singh, PGIMER,
Chandigarh; Pravin J. Mehta, Mumbai, Treasurer, IAP.
1. Indian Academy of Pediatrics Committee on
Immunization (IAPCOI). Consensus recommendations on immunization and IAP
immunization timetable 2012. Indian Pediatr. 2012; 49:549-64.
2. Yewale V, Choudhury P, Thacker N, eds. IAP Guide
Book on Immunization. Mumbai: Indian Academy of Pediatrics; 2009-10.
3. Vashishtha VM, Bansal CP, Gupta SG. IAP position
paper on pertussis immunization. Indian Pediatr 2013;50:1001-9.
4. Payne DC, Boom JA, Staat MA, Edwards KM, Szilagyi
PG, Klein EJ, et al. Effectiveness of pentavalent and rotavuris
vaccines in concurrent use among US children <5 years of age ,
2009-2011. Clin Infect Dis. 2013;57:13-20.
5. WHO position paper. Rotavirus vaccines. Wkly
Epidemiol Rec. 2013;88:49-64.
6. Detailed Review Paper on Rotavirus Vaccines by
Ad-hoc group of experts on rotavirus vaccines. Available from:
Accessed on August 8, 2013.
7. Steele AD, De Vos B, Tumbo J, Reynders J, Scholtz
F, Bos P, et al. Co-administration study in South African infants
of a live-attenuated oral human rotavirus vaccine (RIX4414) and
poliovirus vaccines. Vaccine. 2010;28:6542-8.
8. Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten
M, Louw C, et al. Effect of human rotavirus vaccine on severe
diarrhea in African infants. N Engl J Med. 2010;362:289-98.
9. Cunliffe NA, Witte D, Ngwira BM, Todd S, Bostock
NJ, Turner AM, et al. Efficacy of human rotavirus vaccine against
severe gastroenteritis in Malawian children in the first two years of
life: a randomized, double-blind, placebo controlled trial.
Vaccine.2012; 30 (Suppl 1):A36-43.
10. Madhi SA, Kirsten M, Louw C, Bos P, Aspinall S,
Bouckenooghe A, et al. Efficacy and immunogenicity of two or
three dose rotavirus-vaccine regimen in South African children over two
consecutive rotavirus-seasons: a randomized, double-blind,
placebo-controlled trial. Vaccine. 2012;30 (Suppl 1):A44-51.
11. Steele AD, Reynders J, Scholtz F, Bos P, de Beer
MC, Tumbo J, et al. Comparison of 2 different regimens for
reactogenicity, safety, and immunogenicity of the live attenuated oral
rotavirus vaccine RIX4414 coadministered with oral polio vaccine in
South African infants. J Infect Dis. 2010; 202 (Suppl):S93-100.
12. Narang A, Bose A, Pandit AN, Dutta P, Kang G,
Bhattacharya SK, et al. Immunogenicity, reactogenicity and safety
of human rotavirus vaccine (RIX4414) in Indian infants. Hum Vaccin.
13. Lokeshwar MR, Bhave S, Gupta A, Goyal VK, Walia
A. Immunogenicity and safety of the pentavalent human-bovine(WC3)
reassortment rotavirus vaccine(PRV) in Indian infants. Hum Vaccin
14. Bhandari N, Sharma P, Taneja S, Kumar T, Rangsen-
Chandola T, Appaiahgari MB, et al. A dose-escalation safety and
immunogenicity study of live attenuated oral rotavirus vaccine 116E in
infants: a randomized, double-blind, placebo-controlled trial . J Infect
Dis. 2009; 200: 421-9.
15. Sur D, Ochiai RL, Bhattacharya SK, Ganguly NK,
Ali M, Manna B, et al. A cluster-randomized effectiveness trial
of Vi typhoid vaccine in India. N Engl J Med. 2009;361: 335-44.
16. Kumar R, Tripathi P, Rizvi A. Effectiveness of
one dose of SA 14-14-2 vaccine against Japanese encephalitis. N Engl J
Med. 2009; 360:1465-6.
17. Indian Council of Medical Research. Minutes of
the meeting of the Core Committee on Vaccines. Available from:
20Committee%20on%20Vaccines.pdf. Accessed on August 11, 2013.
18. Kaltenbock A, Dubischar-Kastner K, Schuller E,
Datla M, Klade C, Kishore T. Immunogenicity and safety of IXIARO (IC51)
in a Phase II study in healthy Indian children between 1 and 3 years of
age. Vaccine. 2010;28:834-9.
19. Schuller E, Jilma B, Voicu V, Golor G,
Kollaritsch H, Kaltenböck A, et al. Long-term immunogenicity of
the new Vero cell-derived, inactivated Japanese encephalitis virus
vaccine IC51 Six and 12 month results of a multicenter follow-up phase 3
study. Vaccine. 2008;26:4382-6.
20. Dubischar-Kastner K, Eder S, Kaltenboeck A, Klade
C, Schuller E, Wolfl G. Long term immunity following vaccination with
the inactivated Japanese encephalitis vaccine IXIARO and neutralizing
antibody response to a booster dose. 11th Conference of the
International Society of Travel Medicine; May 24-28, 2009, Budapest,
21. Intercell Announces Pediatric Approval of its
Japanese Encephalitis Vaccine in the U.S. Available from:
Accessed on October 3, 2013.
22. ACIP Unanimously Votes to Extend the
Recommendations for Use of IXIARO(R) Vaccine. Available from:http://www.reuters.com/article/2013/06/21/idUSnHUGd8
N0+72+ONE20130621. Accessed on October 3, 2013.
23. Dubischar-Kastner K, Eder S, Kaltenboeck A, Klade
C, Schuller E, Wolfl G. Safety and immunogenicity of the inactivated
Japanese encephalitis vaccine IXIARO®, IC51, in Filipino Children aged 2
months to <18 years. Presented at the 4th Northern European Conference
on Travel Medicine, June 2012, Abstract P.9. Available at
http://nectm.com/wp-content/uploads/BookofAbstracts. pdf. Accessed on
August 12, 2013.
24. Dubischar-Kastner K, Eder S, Kaltenboeck A, Klade
C, Schuller E, Wolfl G. Interim safety and immunogenicity data for the
inactivated Japanese encephalitis vaccine IXIARO®, IC51, in Children
from JE non-endemic countries. Presented at the 4th Northern European
Conference on Travel Medicine, June 2012, Abstract P.9. Available at
http://nectm.com/wp-content/uploads/BookofAbstracts.pdf. Accessed on
August 12, 2013.
25. Macneil JR, Cohn AC, Zell ER, Schmink S, Miller
E, Clark T, et al. Early estimate of the effectiveness of
quadrivalent meningococcal conjugate vaccine. Pediatr Infect Dis J.
26. Grading of scientific evidence – Table VI a & b
(efficacy of quadrivalent meningococcal conjugate vaccines). Available
ococcal_grad_efficacy.pdf. Accessed on August 14, 2013.
27. Kroger A. General Recommendations on
Immunization. ACIP Presentation Slides: February 2013 Meeting. Available
Accessed on August 16, 2013.
28. Meningococcal vaccines: WHO position paper,
November 2011. Wkly Epidemiol Rec. 2011; 86:521-39.
29. Kshirsagar N, Mur N, Thatte U, Gogtay N, Viviani
S, Préziosi MP, et al. Safety, immunogenicity, and antibody
persistence of a new meningococcal group A conjugate vaccine in healthy
Indian adults. Vaccine. 2007; 25 (Suppl 1):A101-7.
30. Sow SO, Okoko BJ, Diallo A, Viviani S, Borrow R,
Carlone G, et al. Immunogenicity and safety of a meningococcal A
conjugate vaccine in Africans. N Engl J Med. 2011;364:2293-304.
31. Hirve S, Bavdekar A, Pandit A, Juvekar S, Patil
M, Preziosi MP, et al. Immunogenicity and safety of a new
meningococcal A conjugate vaccine in Indian children aged 2-10 years: a
phase II/III double-blind randomized controlled trial. Vaccine.
32. Grading of scientific evidence – Table IV a & b
(efficacy of MenA conjugate vaccine). Available from:
pdf. Accessed on August 16, 2013.
33. Sinclair D, Preziosi MP, John TJ, Greenwood B.
The epidemiology of meningococcal disease in India. Trop Med Int Health.