2006; 8(3) : 187

INDIAN JOURNAL OF IJPP

PRACTICAL PEDIATRICS
IJPP is a quarterly subscription journal of the Indian Academy of Pediatrics
committed to presenting practical pediatric issues and management up
dates in a simple and clear manner
Indexed in Excerpta Medica, CABI Publishing.

Vol.8 No.3 JUL.-SEP. 2006

Dr. A. Balachandran Dr. K.Nedunchelian
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 189

TOPIC OF INTEREST - VACCINES

Issues in EPI /IAP immunization schedule 190
- Raju C Shah, Bharat Prajapati
Newer vaccines (I) 197
- Nitin K Shah
Adverse events following immunization 208
- Indra Sekar Rao M
Polio Eradication / How near and how far? 220
- Vipin M Vashishtha, Naveen Thacker
Hepatitis vaccines - Current concepts 232
- Ashish Bavdekar, Sheila Bhave
Rabies vaccines - Current concepts 239
- Tapan Kumar Ghosh
Medico legal issues in emergency room 155
- Mahesh Baldwa
Journal Office: Indian Journal of Practical Pediatrics, IAP-TNSC Flat, F Block, Ground Floor, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for ordinary letters: The Editor-in-Chief, Indian Journal of Practical Pediatrics, Post Bag No.524,
Chennai 600 008.
Address for registered/insured/speed post/courier letters/parcels and communication by various
authors: Dr. A. Balachandran, Editor-in-chief, Indian Journal of Practical Pediatrics, F Block, No. 177,
Plot No. 235, 4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
Indian Journal of Practical Pediatrics 2006; 8(3) : 188

RADIOLOGIST TALKS TO YOU

Hepatomegaly and hepatic masses - II 246
- Vijayalakshmi G, Elavarasu E, Porkodi, Malathy K, Venkatesan MD
CASE STUDY
Milroys disease 250
- Farzana Beg, Ajit Saxena, Imteyaz Ahamed Khan, Siray N Huda,
Faisal Haque
Necrotizing Fascitis 252
- Shrishu R Kamath, Anjul, Rajeswari, Balaji V, Suchitra Ranjit,
Radha Rajagopalan
Mckusick - Kaufman: Hydrometrocolpos polydactaly -
A rare syndrome 256
- Sridharan S, Pradip Vincent, Ramesh S.
PRACTITIONERS COLUMN
Is there a need for regular ultrasound in every infant? 262
- Janani Sankar, Alka Sophia Rao, Nammalwar BR, Vijayakumar M,
Muralinath S.
PICTURE QUIZ 265
EMERGING EPIDEMICS
Chikungunya - Is it a threat? 266
QUESTION AND ANSWER 268
NEWS AND NOTES 196, 207, 219, 231, 238, 245, 249,
251, 255, 261, 264, 267

FOR YOUR KIND ATTENTION

* The views expressed by the authors do not necessarily reflect those of the sponsor or publisher.
Although every care has been taken to ensure technical accuracy, no responsibility is accepted for errors
or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are the
responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board

Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road, Egmore,
Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works, 9, Iyyah Street,
Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.

2

EDITORS DESK
Greetings from the Journal Committee of
IJPP. This issue is dedicated to important topics
on Vaccines. The journal committee sincerely
thanks Dr.Nitin K Shah, President, IAP - 2006
for accepting to be the Guest Editor for this issue.
With his vast experience and rich knowledge in
immunization, he has carefully chosen the topics
and authors for this current issue.
Issues on EPI and immunization schedule
is compiled by Dr.Raju C Shah, et al. They have
covered the general principles to be followed in
vaccination, various schedules, principles of
vaccine scheduling, and immunzation in special
circumstances.
The topic on Newer vaccines has been
written by Dr.Nitin K Shah. He has stated that
H.influenzae b and pneumococcus are common
causes of invasive bacterial infections in children.
He has mentioned that conjugated Hib vaccine
has good immunogenicity and efficacy and it can
be given as 3 primary doses and 1 booster dose
along with DPT and OPV and the conjugated
pneumococcal vaccine given as 3 primary doses
at 2, 4, 6 months and a booster at 15 months has
high efficacy against invasive disease. He has
also stated that Influenza virus A can lead to severe
illness,hospitalization and even deaths among high
risk populations, and they should be targetted with
inactivated influenza vaccine.
In his article on Adverse events following
immunization Dr.Indra Sekhar Rao has discussed
the various adverse events that can occur
following the routine immunization. He has
warned all medical personnel handling vaccines
to be aware that no vaccine is perfectly safe and
adverse events can occur following any
immunization.
3
2006; 8(3) : 189
The topic on Polio eradication / How
near and how far? is well narrated by
Dr.Vipin Vashishtha, et al. The main aim of the
polio eradication programme is to interrupt wild
polio virus (WPV) transmission globally. They
have warned that failure to achieve this will pose
a threat to all the nations as evidenced by the
recent reporting of large number of cases in non-
endemic countries. The various problems
pertaining to this and the possible solutions for
present and future are discussed by them.
The article on Hepatitis vaccines - Current
concepts is contributed by Dr.Ashish Bavdekar,
et al. They have stated that some regions in the
country have shown an epidemiologic shift of HAV
infection from early childhood to adolescents and
adults. They stress the definite role of HA vaccine
in these regions to prevent epidemics and protect
against severe HAV infection in adulthood. The
effectiveness of the vaccine in reducing the burden
of hepatitis B disease is well demonstrated in
countries adopting the universal immunization
program. Hepatitis B vaccination not only prevents
HBV infection but also associated chronic liver
disease and hepatocellular carcinoma.
Rabies is said to be a disease of antiquity
known to mankind from time immemorial.The
prevention of rabies by vaccination dates back to
Louis Pasteur. Dr.Tapan Kumar Ghosh has given
a detailed account in the article Rabies vaccine -
Current Concepts.
We thank all the authors for their
contributions to Practitioners column, Case
study and Question and Answer column. Our
sincere thanks to Dr.Vijayalakshmi, et al. for their
continued, contribution to Radiologist talks to
you column. The next issue will also cover some
more topics on vaccines.
Indian Journal of Practical Pediatrics
VACCINES
ISSUES IN EPI / IAP IMMUNIZATION
SCHEDULE
* Raju C Shah
** Bharat Prajapati
Abstract : Immunization programme should be
epidemiologically relevant, immunologically
competent, technologically feasible, economically
viable and socially acceptable. This article covers
general principles in vaccination, various
schedules, principles underlying vaccine
scheduling, and immunization in special
cicumstances.
Key words : Schedules, Principles, Special
Circumstances.
Every nation designs its own immunization
schedule depending on epidemiology, health
infrastructure and socio economic conditions of
the country. For any immunization programme to
be successful the national schedule should be such
that it is epidemiologically relevant,
immunologically competent, technologically
feasible, economically viable and socially
acceptable.
EPI was proposed by WHO in 1974. In India
it was launched in 1978. In 1985 Government of
India launched Universal Immunization
Programme (UIP). Under this the emphasis was
shifted from under five to under one.
* Immediate Past President, IAP
** Junior Consultant
Ankur Institute of Child Health,
Ashram Road, Ahmedabad 380009
4
2006; 8(3) : 190
Schedule means a time table which is
necessary for achieving uniform and regular
response and optimal coverage. It is a way of
ordering priorities in accordance with childrens
ability to acquire immunity, the epidemiology of
disease and antigenic qualities of the vaccine.
Certain general principles should be observed
while performing vaccination.
1. An interval of 4 weeks is necessary between
two doses or two different vaccines unless
specific short interval is stated for a vaccine.
2. Vaccines can be given at all ages as per
requirement.
3. Generally the child should not be very sick
at time of vaccination.
4. Separate syringes and needles are required
for each prick.
5. Vaccine must be properly preserved
maintaining the cold chain.
6. While giving more than one vaccine at a time,
their compatibility must be known.
Universal Immunization Programme (UIP)
launched in 1985 in India covers six vaccine
preventable diseases. BCG, OPV, DPT and
Measles are the vaccines administered totalling
five injections during infancy. With the launch of
Pulse Polio Programme, an infant may receive,
up to 7 doses of OPV. The Indian Academy of
Pediatrics-Committee on Immunization (IAPCOI)
has suggested that EPI should be supplemented
by hepatitis B, MMR, and typhoid vaccines.

Principles underlying vaccine
scheduling
Optimal response to a vaccine depends on
multiple factors. These include the following.
Nature of vaccine
Certain vaccines (Inactivated vaccines,
toxoids, recombinant subunit and polysaccharide
conjugate vaccines) require administration of more
than two doses for development of an adequate
and persisting antibody response. Toxoids (i.e.
tetanus and diphtheria) require periodic
reinforcement of booster doses to maintain
protective antibody concentrations. Unconjugated
polysaccharide vaccine does not induce T-cell
memory and hence repeated doses do not produce
substantial boosting. However, when conjugated
with a protein carrier, the effectiveness of
polysaccharide vaccine improves by inducing
T-cell dependent immunity.
Immunogenicity and potential
interference by passively transferred
maternal antibody
The timing of the first immunization is a
compromise between the developing immunity by
the infants immune system and the risk of infection
from virulent organisms. Maternal transplacental
IgG antibodies are protective in the first few
months of life. In early infancy the protection is
partial for some diseases (pertussis), and
satisfactory against others (measles and rubella).
BCG (Bacille Calmette Guerin), OPV (Oral
Polio Vaccine) and Hepatitis B (Hep. B) vaccines
can be given at birth. BCG elicits a CMI and
maternal CMI is not transferred transplacentally.
Maternal antibodies in the babys circulation
against OPV are weakly inhibitory in nature and
hence OPV can establish local gut infection in a
significant proportion of recipients. Hepatitis B
vaccine is strongly immunogenic and can
overcome the maternal antibodies. Live measles
vaccine, mumps and rubella are inhibited by
maternally derived antibodies till around 9 to 12
months of age.
5
2006; 8(3) : 191
Local disease epidemiology
The optimal age for starting immunization
depends upon both immunological maturity and
local disease epidemiology. In developing countries
where tuberculosis and poliomyelitis may affect
young children, immunization should be started
soon after birth. In communities where pertussis
and diphtheria are still a problem this vaccine
should be given as DTP (diphtheria, tetanus,
pertussis) early in infancy since cases before
6 months of age have a greater morbidity and
mortality. When measles is a major threat, vaccine
should be given early, despite the risk that the
response may not be optimal. The most
appropriate age for measles vaccination depends
upon the age-specific measles attack rate in a
particular county. In India this age is 9 months.
Changing epidemiology of diseases
With effective vaccination program, there is
a shift to the right in the age group affected by
some vaccine preventable disease. It has been
observed that now measles is affecting older
children and whooping cough is being seen more
in adults. These changes may make vaccination
programs prolonged or even lifelong.
Simultaneous administration of
vaccines
The simultaneous administrations of live and
inactivated vaccines have produced
seroconversion rates and rates of adverse reactions
similar or those observed when the vaccines are
administered separately. Routinely simultaneous
administration of all vaccines is recommended for
children who are of the appropriate age to receive
them and for whom no specific contraindications
exist at the time of the visit.
Combination vaccines
Use of combination vaccines can reduce the
number of injections required at a single visit. Use
of licensed combination vaccines is preferred over
separate injection of their equivalent component
vaccines.
Indian Journal of Practical Pediatrics 2006; 8(3) : 192

Adverse reactions Table 2: National immunization

schedule of India (UIP)
Certain vaccines produce increased rates of
local or systemic reactions in certain recipients Age Vaccine
when administered too frequently. This has been
At birth BCG, OPV
observed with adult tetanus-diphtheria toxoid (dT),
pediatric diphtheria-tetanus toxoid (DT), and 6 Weeks DTP1, OPV1
tetanus toxoid (TT). 10 Weeks DTP2, OPV2
14 Weeks DTP3, OPV3
Vaccine failure
9 Months Measles
Approximately 90-95 percent recipients of a
16-18 Months DTP booster, OPV4
single dose of MMR vaccine develop protective
antibody within 2 weeks of the dose. Similarly, a 5 Years DT
second dose of varicella is recommended in 10 Years TT
recipients of >13 years of age, since 16 Years TT
approximately 20 percent fail to respond to the
first dose and 99 percent of recipients seroconvert
after two doses. Table 3: Indian Academy of
Pediatrics Immunization Schedule
Issues in schedule for specific
vaccines Vaccine Age Recommended

1. DTP: IAP recommends that all children less BCG Birth 2 weeks
than 1 year should be actively immunized with OPV Birth, 6, 10, 14 weeks,
three doses of DTP vaccine followed by 2 booster 16 18 months, 5 years
doses at 18 month and 5 year of age. IAP DTP Birth, 6, 10, 14 weeks,
recommends DTP at 5 years (2nd booster), which 16 18 months, 5 years
is logical looking at its comparative safety in recent
Hepatitis B Birth, 6 weeks, 6 months
or 6 , 10, 14 weeks
Table 1: WHO Expanded program on
Immunization Hib Conjugate 6, 10, 14, weeks
16 18 months
Age Vaccine
Measles 9 months plus
Birth BCG, OPV0, Hep. B1
MMR 15 months
6 Weeks OPV1, DTP1, Hep. B2
Typhoid 2 years
10 Weeks OPV2, DTP2
TT/Td 10, 16, years
14 Weeks OPV3, DTP3, Hep. B3
2 doses of TT Pregnancy
6 Months Measles*
9 Months Measles* Additional Vaccines*
10 Months Yellow fever Varicella Above 1 Year
18 Months DTP 4 Hepatitis A Above 1 Year
* Extra early dose given in situation of high risk * These are not routinely recommended
given in all countries at risk
6

studies. DT is recommended after 7 years of age
whenever there is need to give even one antigen
and Td/TT after 10 years of age. Surveys also
indicate that tetanus tends to infect more people
as they age . Hence, booster doses shall be given
in adults also at regular interval of 10 years or on
exposure to serious injury.
2. Polio vaccine: IAP recommends the five dose
schedule, ZERO DOSE at birth, 3 doses at 6,
10 and 14 weeks and fifth dose at 9 months along
with measles vaccine. Although IAP finds the need
and requests for the availability of IPV in India, it
has not been licensed in the country till date. A
five dose OPV regimen plus two to three dose
pulse would increase the number of doses to 7 to
8 in infancy, 10 to 11 by second year and so on.
This approach, although recommended for
adoption in India was rejected in favour of the
3 dose regimen and multiple NIDs and subnational
IDs.
3. Hepatitis B vaccine: HB vaccine may be given
in any of the following schedules.
(i) Birth, 4 to 6 wks and 6 months
(ii) Birth, 6 and 14 weeks
(iii) 6,10, and 14 weeks
If the mother is known to be HbsAg negative,
HB vaccine can be given along with DTP at 6,10
and 14 weeks. If the mothers HbsAg status is
not known, it is important that HB vaccination
should begin within a few hours of birth so that
peinatal transmission can be prevented. Any one
of the following schedules may be used for this
purpose-birth, 6 and 14 weeks or birth, 1 and 6
months. If the mother is HbsAg positive (and
especially HbeAg positive), the baby should be
given Hepatitis B immune globulin (HBIG) within
24 hours of birth, along with HB vaccine (at birth,
6 and 14 weeks, or birth, 1 and 6 months). If
HBIG is not available (or is unaffordable), HB
vaccine may be given at 0,1 and 2 months with
an additional optional dose between 9-12 months.
7
2006; 8(3) : 193
It has been suggested that in infancy the third
dose of HB vaccine should be given at least
16 weeks after the first dose, at least 8 weeks
after the second dose and not before 6 months of
chronological age, as it presumably gives longer
lasting immunity. The vaccination schedule need
not be changed for preterm and small-for-dates
babies.
4. Measles vaccine: Ideal vaccination strategy is
to choose the right time so as to close the gap of
vulnerability to natural wild virus infection.
Vaccination given too early, before waning of
maternal antibodies would result in failure of
vaccine uptake. On the other hand delayed
vaccination will leave many children predisposed
to measles infection. Considering all these factors
IAP has advocated two dose schedule where
second dose is recommended as MMR at
15 months of age.
Immunization in special
circumstances
1. Immunization in preterm infants
In general, all vaccines may be administered
as per schedule according to the chronological age
irrespective of birth weight or period of gestation.
Very low birth weight babies can be given
immunization after initial stabilization.
2. Children receiving corticosteroids
Children receiving oral corticosteroids in high
doses (e.g. Prednisolone 2 mg/kg/day) for more
than 14 days should not receive live virus vaccines
until the steroid has been discontinued for at least
one month. Killed vaccines are safe but may not
be completely effective in such situations. Patients
receiving small doses, short course, on topical or
inhaled steroid therapy should not be denied their
age appropriate vaccines.
3. Children awaiting splenectomy
Children with loss of splenic function are at
high risk of serious infections with encapsulated
Indian Journal of Practical Pediatrics 2006; 8(3) : 194

organisms. If splenectomy is being planned,
immunization with pneumococcal, Hib and
meningococcal vaccines should be initiated 2 to 4
weeks prior to splenectomy.
4. Vaccination in children with HIV infection
Children infected by HIV are particularly
vulnerable to severe recurrent or unusual
infections by vaccine preventable pathogens. It
must be emphasized that routine immunizations
seem to be generally safe in such children, but
the immune responses may be suboptimal.
Development of an immune response following
vaccination would depend upon the degree of
immunodeficiency at that point of time. Immune
attrition associated with viral replication may
particularly interfere with memory responses.
Consideration should be given to re-administering
childhood immunization to such children when
their immune status has improved following anti-
retroviral therapy.
Table no. 4 summarizes the recommendations of
WHO/UNICEF and the Advisory Committee on
Immunization Practices (ACIP).
5. Vaccination schedule for children not
immunized in time
It may be noted that vaccination catch-up
regimens may be difficult to construct for older
children and must necessarily be individualized.
Table 5 depicts the suggested schedule which may
be followed in cases of children who have not
been offered any immunization.
It may be noted that Measles/MMR vaccines
may as well be given at the first visit itself (along
with the other vaccines). The third dose of HB
vaccine may be given 6 month after the first dose,
if patient compliance is not a problem.

Table 4. Vaccination recommendations in HIV infected children

VACCINE WHO/UNICEF ACIP
Symptomless Symptomatic Children with
HIV infection HIV infection HIV/AIDS
BCG Yes* (At birth) No No
DTP Yes (At 6,10,14weeks) Yes Yes (but use DTPa)
OPV Yes (At 0, 6,10, 14 Yes No (use inactivated polio
weeks) vaccine)
Measles Yes (At 6 & 9 months) Yes Yes (but contraindicated
if CD4+ is < 15%)
Hepatitis B Yes (As for Yes Yes
uninfected children)
Hib Yes
Pneumococcal Yes
Influenza Yes (but not below
6 months of age)
Varicella Yes
Meningococcal Yes
Empty cells imply there are no current recommendations

8
 2006; 8(3) : 195

6. Lapsed immunization illnesses (e.g. fever, diarrhea, respiratory infection)

There is no need to restart a vaccine series
regardless of the time that has elapsed between
individual doses. Immunizations should be given
at the next visit as if the usual interval had elapsed
and the immunization schedule should be
completed at the next available opportunity. In
case of unknown or uncertain immunization status,
however, it is appropriate to start the schedule as
for an unimmunized child.
7. Missed opportunity for immunization
This is defined as a situation when child visits
a health care facility and is not immunized. Minor
and malnutrition should not be construed as
contraindications to immunization. Any dose not
given at the recommended age should be given at
any subsequent visit when indicated and feasible.
8. Simultaneous administration of multiple
vaccines.
Both killed and live vaccines can be
administered simultaneously without decreasing
the efficacy of the individual vaccines. However,
prudence demands that the vaccines be
administered at different sites using separate
needles for each component.

Table 5. Vaccination schedule for an unimmunized child

Age Less than 5 years More than 5 years

First visit BCG, OPV, DTP, HBV TT/Td, HBV

2nd visit (1 month later) OPV, DTP, HBV TT/Td, HBV

3rd visit (1 month later) OPV, DTP, HBV HBV, MMR

Measles/MMR, Typhoid Typhoid

1Yr later OPV, DTP -

Every 3 Years Typhoid booster Typhoid booster

Table 6. Vaccination schedule in adolescents

Vaccine Age
1. Diptheria/Tetanus Toxoid (Td) Boosters at 10 and 16 Years
2. Rubella vaccine 1 dose to girls at 12-13 years of age
OR
MMR Vaccine 1 dose at 12-13 years of age, if not given earlier
3. Hepatitis B Vaccine 3 doses at 0,1 and 6 months, if not given earlier
4. Typhoid Vaccine Vi-polysaccharide vaccine every 3 years
5. Varicella Vaccine* 1 dose upto 13 years, and 2 doses (at 4-9 weeks interval)
after 13 years of age (if not given earlier)
6. Hepatitis A Vaccine* 2 doses 0 and 6 months
* Only after discussing with the parents on a one-to-one basis

9
Indian Journal of Practical Pediatrics
9. Immunization of adolescents
Adolescence should be considered an
appropriate age for top-up immunization as well
as for administration of certain vaccines which
may not have been indicated earlier. However,
this should always be done after careful counseling.
10. Vaccination of children with bleeding
disorders or those receiving anticoagulants
23G or smaller needles should be used for
injection and the parents should be asked to apply
firm and sustained pressure, without rubbing, for
at least 5 minutes.
11. Breastfeeding and vaccination
Breastfeeding does not adversely affect
immunization and is therefore, not a
contraindication for any vaccine. Neither
inactivated nor live vaccines administered to a
lactating woman affect the safety of breastfeeding
for infants. There is no risk of transmission of
Hepatitis B virus from an HBsAg carrier mother
to her baby through breast milk.
Points to remember
* National Immunization schedule is
designed according to disease epidemiology,
health infrastructure and socio economic
conditions.
* General principles should be observed while
performing vaccination.
* It may be necessary to adopt some
modifications under special circumstances
like immuno compromised states, lapsed
immunisation, etc.
NEWS AND NOTES
PPSA: Pediatric Procedural Sedation and Analgesia Course 3rd December, 2006
Course Director: Dr. Suresh Gupta, Sir Ganga Ram Hospital, New Delhi - 110 060.
Phone : 9811426628, 28312656, 28312591 Email: drguptasuresh@yahoo.co.in
10
2006; 8(3) : 196
Bibliography
1. Committee on Immunization and infectious
diseases. Immunity, Immunization &
Infectious diseases. 1994. 16-32.
2. IAPCOI Update on immunization policies,
guidelines and recommendations. Indian
pediatircs. 2004 : 41 : 239-244.
3. WHO Global programme for vaccines and
Immunization. Immunization policy. Geneva:
WHO,1996.
4. IAP Committee on Immunization 2003-2004.
IAP Guide Book on Immunization, 3rd ed. New
Delhi, Cambridge Press, 2005; pp 39-45.
5. Obaro SK, Pugatch D, Luzuriaga K.
Immunogenicity and effficacy of childhood
vaccines in HIV-1 infected children. Lancet
Infect Dis 2004; 4(8): 510- 518.
6. Colditz GA, Brewer TF, Brekey CS, et al.
Efficacy of BCG vaccine in the prevention of
tuberculosis. JAMA 1994;271 (9):698-702.
7. Seth V, Kumar M, Lodha R. BCG vaccination.
In: seth V, Kabra SK (Eds).Essentials of
nd
Tuberculosis in children 2 ed. New Delh,
Jaypee Brothers Medical Publishers (P) Ltd,
2001;371-581.
8. Fine PE, Rodrigues LC. Modern vaccine
Mycobacterial disease. Lancet 1990;335:
1016-1020.
9. CDC vaccine Adverse Event Reporting
systemUnited States, MMWR 1990;39:
730-733.
10. Fritzell B.Polysaccharide vaccine against
Haemophilus influenzae b conjugated to
tetanus protein. Immunol Med 1991;8:176-
183.
11. CDC. Prevention of varicella. Recommen-
dations of the Advisory Committee on
Immunization Practices (ACIP). MMWR
1996;45(RR-11):1-36.

VACCINES
NEWER VACCINES (I)
*Nitin K Shah
Abstract: H.influenzae type b and pneumococcus
are common causes of invasive bacterial
infections in children. Conjugated Hib vaccine
has good immunogenicity and efficacy. The
recommended schedule is 3 primary doses and
one booster dose along with DPT and OPV.
Polyvalent polysaccharide pneumococcal vaccine
cannot be used in children less than 2 years of
age and in healthy adults it has an efficacy of
70% against invasive disease. Conjugated
pneumococcal vaccine given as 3 primary doses
at 2, 4, 6 months and a booster at 15 months has
high efficacy against invasive disease. Influenza
virus A can lead to severe illness, hospitalization
and even deaths among high risk populations,
who should be targetted with inactivated
influenza vaccine. Due to frequent antigenic drift
of the virus, the development of vaccine also
would require periodic changes. Intranasally
administered live cold adapted influenza trivalent
(CAIV-T) vaccine is also found to be effective.
Key words: Hib, Pneumococcal, Influenza,
Vaccines
H. Influenzae b vaccine
H. Influenzae type b infection is a common cause
of invasive and non-invasive severe bacterial
infections in children less than 5 years of age like
* President, Indian Academy of Pediatrics, 2006
Co-chairperson,
IAP Committee on Immunization, 2005-06
Mumbai
11
2006; 8(3) : 197
bacteremia, meningitis, pneumonitis, arthritis,
epiglottitis etc. The pathogen is a commensal in
the upper respiratory tracts of healthy
humans1,2. In the developing countries it is still a
major cause of morbidity and mortality due to
non-inclusion of Hib in the national immunization
schedule.
Disease burden: 3-5% of children in west are
carriers of Hib, whereas this figure is as high as
15%-30% in developing countries. 95% of the
Hib infection occurs before the age of
5 years. IBIS study done in India has shown that
76% of Hib occurs before the age of 1 year with
the peak at 6-9 months3. It is estimated that the
incidence of invasive Hib disease in India is
around 50-60/100,000 children less than 5 years
of age2. It is estimated that 3 million cases of Hib
infection occur every year world over and 0.375
million of them die due to Hib1,4. In India only
hospital based data is available which have shown
that 30-45% of cases of pyogenic meningitis and
8-12% of cases of pneumonia in children are due
to Hib disease as shown in Table I 2,5. This is
similar to data from Europe before mass
vaccination in these countries.
Meningitis: Of the cases of pyogenic meningitis,
30% is caused by Hib as per IBIS study and
30-45% as per the study done in Vellore. The
mortality in developing countries is as high as
30-50% as compared to 3-5% in the West. Of the
survivors, 30-40% have some sequelae like
deafness, epilepsy or motor deficiencies1,3.
Pneumonia: Up to 40% of cases of Hib present
as pneumonia in developing countries1. Various
studies done from India have shown Hib as a cause
Indian Journal of Practical Pediatrics
of pneumonia in 8-46% 2. It is difficult to prove
the etiological agent as blood culture is positive in
less than 10% of cases as most of the pneumonia
cases are non-invasive.
Others: 8-12 % of total Hib cases present as
epiglottitis. It is commonly seen in developed
countries but virtually not seen in developing
countries. Similarly skin infections involving face
is rarely seen in countries like India but was
commonly seen in west before mass
vaccination 1.
Drug resistant Hib: Since 1970, drug resistant
Hib strains have emerged posing therapeutic
challenges. In India, initial cases of drug resistant
Hib disease were reported from Chandigarh in
19901. Since then Vellore has reported that 42.5%
of the Hib isolates were MDR strains in 19922, 5,
Nagpur reported 80% MDR isolates in 19966 and
IBIS reported 56% resistance to chloramphenicol
and 40% resistance to ampicillin in 19993.
Prevention: 3 million cases with 0.37 million
deaths world over is a huge toll due to Hib disease
in children. Increasing drug resistance has added
to the mortality and cost as 3 rd generation
cephalosporins are required now to treat these
patients. Excellent vaccines are available in the
form of conjugate Hib vaccines since 1980. The
western world has eliminated Hib disease with
universal immunization. That makes this vaccine
a strong contender as the 8th vaccine to be included
in to the National Schedule for immunization.
Hib vaccines
The newer conjugated Hib vaccines have
been highly successful with excellent tolerance,
safety, immunogenicity and efficacy as proved in
several trials world over.
There are 4 types of conjugate Hib vaccines
depending on the protein carrier used; PRP-OMP
(using outer membrane protein of meningococcus)
is not used due to poor immunogenicity, PRP-D
12
2006; 8(3) : 198
(using diphtheria toxoid) is also given up for
primary schedule due to poor immunogenicity,
HbOC (using CRM 197 mutant diphtheria toxin)
and PRP-T (using tetanus toxoid). HbOC and
PRP-T are the only vaccines available in India.
There is one more brand available which has
HbOC with adjuvant.
Immunogenicity and clinical efficacy: 98-100%
of the vaccinees achieve anti-PRP antibody titers
of > 0.15 mcg/ml in the serum which is taken as
protective in a short term basis and nearly 100%
of them achieve the same after the booster dose
given at 15 months. The GMC achieved at the
end of 4 dose series is as high as 60-90 mcg/ml1.
These high titers translate into near 100% clinical
efficacy as shown in various trials world over1.
High coverage with the vaccine has also resulted
in significant drop in the carrier state not in those
vaccinated but even in un-vaccinated children
which means that routine vaccination program
leads to herd immunity1. This also means that it
is possible to eradicate Hib by including it in the
National Schedule. In US there was 95-98% drop
in the incidence of Hib disease with the use of
HbOC and PRP-T vaccines1. Similar experience
was noted in Finland and UK which almost
eliminated Hib disease with mass vaccination in
just 2-3 years of its use 1,7.
Schedule: Hib vaccines are available as ready to
use liquid (HbOC) or as lyophilized powder
(PRP-T) in 0.5 ml of volume. It is given by IM
route over the antero-lateral aspect of the thigh or
over deltoid region. It should be preserved at
2-80C in the refrigerator. It should not be frozen
and if frozen by mistake, it should be discarded.
The cost of the vaccine at present is Rs. 250-300
per dose. It is available as unit dose or as a
multi-dose vial. 3 primary doses are given at 6,
10 and 14 weeks along with the OPV/DTP vaccine
followed by a booster at 15-18 months. If the
child comes after 6 months of age only 2 primary
doses at 4-6 weeks interval are given followed by

the booster at 15 months. Similarly if the child
comes after 1 year he receives only one primary
dose followed by a booster at 15-18 months. After
the age of 15 months, only one dose is required1.
It is preferable to use Hib/DPT/Hepatitis B
combination vaccine instead of giving these
vaccines separately as appropriate.
Side effects: Hib conjugate vaccines are one of
the safest vaccines proved in many studies.
Local : 3-5% of the vaccinees develop local pain,
10% develop redness, 2-4 % develop swelling.
These are mild in nature and lasts for 1-2 days.
One can use paracetamol for pain 1,8.
Systemic : 10-15% of the vaccinees develop fever
which is mild, lasts for 1-2 days and responds to
paracetamol. Other side effects include loss of
appetite in 15-20%, restlessness in 15-20%,
excessive crying in 20-22%, vomiting in 7-10%
and diarrhea in 10-15% of cases. Again these
symptoms are mild and self limiting 1,8.
IAP recommendation: Indian Academy of
Pediatrics Committee of Immunization strongly
recommends that Hib vaccine needs serious
consideration for inclusion in the national
immunization schedule, while awaiting disease
burden studies. However, the cost of vaccination
is considered prohibitive9.
Pneumococcal vaccine
Pneumococcus is a common organism causing
invasive bacterial disease, especially in children
less than 2 years and elderly adults (above the
age of 65 years). In west, now it is the commonest
organism causing invasive bacterial disease in
children, as Hib is virtually eradicated with
universal Hib vaccination. Interest existed in
developing pneumococcal vaccine since 1940s till
penicillin became available. With the emerging
resistance to penicillin and other drugs of late,
there is resurgence of interest in pneumococcal
vaccine, especially after the success of conjugation
13
2006; 8(3) : 199
technique used for Hib vaccine. This has led to
availability of highly efficacious conjugate
pneumococcal vaccine which is creating history
in western world.
Pneumococcus: Pneumococcus has more
than 90 serotypes grouped into more than
45 serogroups. Most serotypes do not have cross
protection. Of these, 10 serotypes cause more than
90% of childhood infections and include serotypes
4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 3, 7. Of
these, type 1 is the commonest serotype seen in
India as per IBIS study10.
Disease spectrum: Pneumococcus can lead to
invasive diseases like bacteremia, meningitis,
pneumonitis or local infections like non-bacteremic
pneumonia, acute otitis media (AOM), cellulitis,
arthritis, peritonitis etc. 30-50% of school age
children are carriers for one or more serotypes.
In adults, carrier rate varies from 6-30%. From
nasopharynx it can spread locally or systemically
leading to various types of clinical diseases. In
west, the first contact with pneumococcus occurs
at 6 months of age whereas in developing countries
it can occur as early as 17 days! The peak
incidence of pneumococcal disease is seen at
6-24 months of age.
Incidence of invasive disease in children less than
5 years varies from 25-50 per100,000 in Europe
to 90/100,000 in USA to 500/100,000 in Gambia
and Apache Indians11.
90% of bacteremia, 30-50% of pneumonia,
30-45% of pyogenic meningitis and 30-60% of
all bacterial AOM are caused by pneumococcus.
The mortality rate of invasive disease is 6% to
20% and there are sequelae like CNS sequelae in
survivors of meningitis and deafness in children
with recurrent AOM.
In India, it is estimated that pneumococcus leads
to 50,000 - 75,000 cases of meningitis11. IBIS
study showed that of the pneumococcal invasive
Indian Journal of Practical Pediatrics
diseases 30% present as meningitis, 30% as
pneumonia and 30% as bacteremia, peritonitis and
others10. At this rate one expects pneumococcus
also to cause 50,000 - 75,000 cases of invasive
pneumonia, 50,000 - 75,000 cases of other types
of invasive disease, 10 times more cases of non-
bacterial pneumonia and 100 times more cases of
AOM.
Bacterial resistance: Cases of penicillin resistance
were reported first in 1970s. Since then the
resistance has spread world over. More than 40%
of the isolates from invasive diseases and nasal
carriers are penicillin resistant in countries like Sri
Lanka and Taiwan, whereas the same in USA
and Europe is 10-40%. In India and Australia it is
less than 10%. IBIS study done in India showed
that intermediate penicillin resistance was seen in
1-4 % of serotypes in India. The resistance has
been increasing over last two decades. In USA it
increased from 4% in 1980 to 30% in 1990.
Pneumococci are resistant to other drugs too like
TMP/SMX, chloram-phenicol, and even 3 rd
generation cephalosporins.
Serotypes 6B, 9V, 14, 19F and 23F are
responsible for most of the resistant infections and
are covered by the 7 valent conjugate vaccine.
Infection with resistant forms means use of higher
dose of antibiotic or use of alternate drugs like
cefotaxime or vancomycin to prevent mortality.
One of the main reasons for increasing drug
resistance is misuse of antibiotics10, 11.
Unconjugated pneumococcal vaccines
23 valent plain polysaccharide vaccine is
available since last few decades. Being non-T cell
dependent it cannot induce good immune
response. The immune response is IgM type, short
lived, has low titers, affinity and avidity, does not
induce local IgA immunity and does not have
boosting effect in spite of repeated doses.
Hence, this vaccine cannot be used in children
below 2 years of age when it is most required. At
14
2006; 8(3) : 200
best it has efficacy of 70% in healthy adults against
invasive disease and only 56% in those > 65
years of age. It has poor efficacy against non-
bacteremic pneumonia and doubtful, if any,
efficacy against AOM, carrier state or immune
compromised hosts.
Conjugated pneumococcal vaccine
7, 9 and 11 valent conjugated pneumococcal
vaccines have been developed and of this 7 valent
CRM 197 conjugated vaccine is commercially
available in the west. Other carrier proteins tried
include tetanus toxoid, diphtheria toxoid and outer
membrane protein of meningoccus. None of them
are commercially available at present.
Content : 7 valent vaccine contains 2 ug of each
serotypes 4, 9, 14, 18C, 19F, 23F and 4 ug of
6B, that is total of 16 mg of antigen in 0.5 ml of
vaccine. 9 valent vaccine contains additional
serotypes 1, 5 and 11 valent vaccine in addition
has serotypes3,7,10,12.
Safety : 7 valent conjugate vaccine given to infants
is a very safe vaccine. Mild local reactions are
seen in 30-35% of patients and include redness,
warmth, pain, induration and tenderness. Severe
local reactions of > 2.5 cm diameter are seen in
5-6% of patients. The reactions are less than those
seen with DPwT and same as seen with DTaP,
Hib/MMR vaccines 12,13.
Fever of > 38oC is seen in 25-35% of recipients
whereas fever of > 39oC is seen in < 5% of
patients. Rare adverse reactions like febrile
convulsion, breath holding spasms are same as
seen with any other vaccine and are more of a
coincidence. Severe adverse reactions are
unknown to occur with this vaccine 12,13.
Immunogenicity: Rise in GMT following
3 primary doses is statistically better than controls
for each serotype with 4.4 to 27.0 fold rise in
titers. 92-100% of vaccines develop GMT of
> 0.15mg/ml and 90-91% >1.0 mg/ml. Pre

booster titers are better than pre-primary titers
for all serotypes. Post-booster titers rise by 5-15
fold. GMT rises to 2.3-9.7 mg/ml and 96-100%
recipients have GMT of > 0.15 mg/ml and
84-100% > 1.0 mg/ml. Types 4 and 6B are the
most immunogenic serotypes 13.
Clinical Efficacy
Invasive disease: In a study done by Black et al
in California, USA, children were given 3 primary
doses at 2, 4, 6 months followed by a booster at
15 months of 7 valent conjugate pneumococcal
vaccine. The efficacy against invasive
pneumococcal disease was 97.4% which remained
as high as 97.4% at 1 year follow up12.
Pneumonia: The same study done by Black
et al also looked at efficacy against clinically
diagnosed pneumonia 12. The efficacy was 11.4%
against any pneumonia diagnosed clinically, 13.8%
against any pneumonia with X-ray taken, 33%
against any pneumonia with some abnormalities
on X-ray and 63% against pneumonia with
consolidation of > 2.5 cm on X-ray of chest (which
is likely to be caused by pneumococcus more than
other pathogens).
Acute Otitis Media: Besides the study done by
Black et al, one more study by Eskola et al looked
at efficacy against AOM. They studied culture
proven cases of AOM by doing myringotomy in
patients diagnosed to have AOM with middle ear
fluid as per WHO guidelines 14. Both the studies
found nearly similar efficacy of 57 66.7%
against vaccine serotype AOM. It was 7.8 -8.9%
against any AOM episode. It was more efficacious
against recurrent AOM especially the ones that
need tube placement in the middle ear.
Carrier state and herd immunity: Studies have
shown nearly 50% reduction in the carriage with
vaccine types which however is counterbalanced
by similar 50% increase in the non-vaccine types
carriage leading to no net change in the prevalence
of carriage rates 15.
15
2006; 8(3) : 201
Schedule : Children presenting before 7 months
of age are given 3 primary doses at 2, 4 and
6 months or 2, 3, 4 months or at 6, 10, 14 weeks
depending on local schedule, and a booster at
12-15 months. Children coming for the first time
between 7-12 months are given 2 primary doses
at 4-8 weeks interval and a booster at 12-15
months. Children presenting between 12-24
months for the first time are given 2 doses at 4-8
weeks interval. It is given IM over deltoid or lateral
aspect of thigh. It is to be stored at 2-8o C and the
shelf life is 2 years.
Coverage in India and other problems: Main
problem is coverage of prevailing serotypes.
7 valent vaccine will have coverage of > 90%
serotypes in USA, 75% in Europe, 51% in India,
and 45% in Pakistan. Similar figures with 9 valent
vaccine will be 71% in India, 30% in Dhaka
(Bangladesh) and 61% in Pakistan and with
11 valent vaccine 75% in India, 51% in Dhaka,
and 61% in Pakistan. Hence we need 9 or
11 valent vaccine or even more valent vaccine
for good global coverage 10.
The other problems are high cost which needs to
come down. There may be need to increase the
dose of some antigens like 19F serotype. Long
term follow up will prove the efficacy over years
and need for further booster if any. For timely
completion it has to be given simultaneously along
with other childhood vaccines. Some studies of
combined CRM 197 vaccine along with HbOC/
DPT have proved to be safe and efficacious. We
need more studies on such combinations. We also
need clear cut studies showing its benefits in older
children, adults and immune compromised hosts
especially HIV infected patients. Study done in
Africa using 9 valent vaccine has shown good
efficacy in spite of high local prevalence of HIV
in children13 Lastly, we need to update information
on the prevailing serotypes. For this, we need
continued surveillance of pneumococcal disease
globally.
Indian Journal of Practical Pediatrics
Influenza vaccines
After the discovery of influenza A virus in
1933, efforts were on to develop a vaccine against
influenza as it was realized that the disease could
be devastating during pandemics and epidemics
amongst military forces. The first influenza vaccine
was invented in 1945 and since then the mankind
is in the search of the ideal flu vaccine. Currently
there is a lot of interest generated in the influenza
vaccine due to the fear that the next pandemic of
influenza is long overdue and it could be due to
spread of avian influenza [A (H5N1)].
Disease burden: 30-50% of influenza cases can
be asymptomatic. Classical influenza is a mild but
bothersome illness with 3-5 days of high fever,
respiratory tract symptoms, myalgia and
GI symptoms which are more commonly seen in
children. It also leads to morbidity, school
absenteeism and loss of work hours. At times the
disease can lead to complications like acute otitis
media (AOM), croup, sinusitis, pneumonia,
exacerbation of underlying chronic conditions like
respiratory or cardiac disease, Reyes syndrome
in patient on long term aspirin therapy, toxic shock
syndrome, myocarditis or pericarditis, myositis
and myoglobinuria, and rarely CNS morbidity like
encephalitis, GBS or chronic encephalopathy as
reported from Japan. These complications are
more common in certain high risk populations
leading to more severe illness, morbidity,
hospitalization and even deaths. These at risk
groups are the ones which are the target for
influenza vaccination at present 16.
In temperate climate influenza typically has onset
in winter, whereas in tropics it is seen throughout
the year with one or two peaks during winter and
summer. While pandemics do lead to sudden
increase in the number of cases and mortality,
cumulatively more cases and deaths occur in the
inter-pandemic interval. Type C influenza is very
mild and hence is not included in the vaccine.
Type B influenza is significant and hence is a part
of the vaccine. Fortunately type B virus does not
16
2006; 8(3) : 202
mutate easily and hence does not need change
from year to year. Type A virus mutates easily
and constantly due to point mutations in the HA
and NA antigens called as antigenic drift. This
ensures that enough pool of susceptible population
is available for the epidemics to occur from time
to time. This also means the need to change the
vaccine and the need to vaccinate annually.
Exchange of genes between two different types
of type A viruses in a host like pig co-infected
with both the viruses leads to antigenic shift which
leads to pandemics. The worst pandemic was the
Spanish flu in 1918-1919 caused by type A
(H1N1) which killed more than 20 million people,
mainly young adults. This was then followed by
Asian pandemic due to type A (H2N2) in 1957,
Hong Kong flu pandemic due to type A (H3N2)
in 1968, and partial pandemic due to reintroduction
of type A (H1N1) in 1977 which still co-circulates
with type A (H3N2) even now. Another pandemic
was possibly averted by culling millions of
chickens infected with type A (H5N1) avian virus
which had threatened to transmit directly to
humans. The cases of avian flu keep on occurring
still since then and epidemic within the birds is
rapidly spreading in the world keeping the threat
of another pandemic alive 16.
During an epidemic 10-20% of the population
suffers from disease which can be as high as
40-50% in an institutional breakout. Usually the
cases start in the school going children which then
spreads to the older individuals. The attack rates
are 19-20% in general population, 30-40% in
school age children, 1-19% in elderly population
and 80-90% in institutionalized people.
Hospitalization, complications and mortality are
higher in children < 2 years old besides the elderly
> 65 years of age. This has led to recent
recommendation of routine annual vaccination of
healthy children aged 6 months 23 months by
the Advisory Committee on Immunization
Practices (ACIP) in US and other western
countries 16.

Influenza Vaccines
The first influenza vaccine was invented in 1945
for use during World War II. The initial vaccine
was whole virion vaccine which though effective
was highly reactogenic with lots of side effects
especially in children. Since 1970s only sub-virion
vaccines like the split or the sub-unit vaccines are
used especially in children. Sub-virion vaccines
are prepared by using a solvent which dissolves
or disrupts the lipid layer of the virion which leads
to availability of the HA and NA without the
envelope or the other proteins like NP and M
proteins which are known to lead to side effects.
Of late safer, more convenient and more efficacious
live intra-nasal cold-adapted vaccines have been
made available and licensed for use. The vaccines
are grown on chicken eggs. Now the
manufacturers also use MKCD or the Vero cell
lines. It is also possible to make the HA and the
NA antigens by DNA recombinant technique;
however this has not been tried commercially.
Though the virions have many antigens,
hemagglutinin (HA) is the most important antigen
as the anti-HA antibodies are protective in nature.
Anti-NA antibodies though can not prevent the
disease, can reduce the severity of the disease.
Other proteins like the nucleoprotein (NP) or the
matrix protein (M) can lead to side effects as also
the intact lipid envelope. Hence anti-HA antibodies
are measured as a immune correlate of efficacy.
Inactivated influenza vaccine
Contents : The current vaccine is a trivalent
vaccine. It contains inactivated type A (H3N2),
type A (H1N1) and type B viruses. In children
whole virion vaccines are not recommended.
Current vaccines are subunit or split vaccines
manufactured by disrupting the whole virion
envelope by chemical process. The vaccine
contains 7.5 mg of HA of each of the virus type/
dose in 0.25 ml of volume for children < 3 years
and 15 mg/dose in 0.5 ml volume for older children
17
2006; 8(3) : 203
and adults. It also contains traces of thiomerosal
as preservative. Since 1990s type B virus is
showing two different HA antigens leading to the
question whether we need now a quadrivalent
vaccine 16.
Vaccine manufacture and time frame : The
manufacture of influenza vaccine is literally a race
against time. The seed virus representing the
current circulating virus for both the northern and
the southern regions is provided by WHO and
the manufacturing of the vaccine is completed in
the next 6 months so that it is available in time for
the next influenza season 16.
Dose and route: The vaccine is given by IM
route. SC and ID routes lead to less efficacy and
more side effects. The dose is 0.25 ml for a child
<3 years and 0.5 ml for >3 years of age. Children
< 8 years of age are given 2 doses for the first
time at 6-8 weeks interval and one dose in the
subsequent years, whereas > 8 years old are
always given only one dose.
Stability and storage: The vaccine should be
stored at 2-80C. The vaccine is stable at this
temperature for at least 2 years. However as the
vaccine is changed every year due to mutation of
the virus, the shelf life of the vaccine is only one
year.
Immunogenicity: Anti HA titers of > 1:32-40 are
protective. More than 90% of the young vaccinees
sero-convert. Vaccine also may produce secretory
IgA antibody acting locally. The Japan model has
shown that herd immunity may develop if
sufficient target population is vaccinated.
Efficacy and effectiveness: The efficacy of the
study depends on the match between the vaccine
types and the circulating types, outcome measure
used to calculate the efficacy and from year to
year. It is difficult to compare studies with one
another as the outcome measure used to calculate
efficacy differs from study to study. In one study
Indian Journal of Practical Pediatrics
the efficacy was found to be 86% against culture
proved cases, 34% against clinical definition using
influenza like illness and 10% against any upper
respiratory tract infections 17.
A meta-analysis done on effectiveness in > 65
years old showed the effectiveness to be 33%
against Influenza like illness, 33% against
hospitalization due to pneumonia or influenza and
50% against mortality due to any cause 18. In
studies done in < 65 years the effectiveness has
been shown to be 56-70 % against influenza like
illness in a military population, 70-79% in culture
proved influenza illness. The overall efficacy
appears to be as high as 70-90% in young
people 16,19.
In elders > 65 years with chronic medical illnesses
the effectiveness against hospitalization has been
shown to be 29% in those with chronic heart and
lung disease, 32% in those with metabolic diseases
like diabetes, rheumatologic disease, renal diseases
or strokes compared to 49% in those who were
healthy. Same study showed a decrease in
mortality of 49%, 64% and 55% in respective
groups 20.
Various studies have been done in children. In a
study done in US over 5 seasons, the effectiveness
against influenza like illness was found to be 77-
91% in 1-15 years old, 54% in 3-6 years old and
100% in 10-18 years old. Similar efficacy of
70-83% has been found in studies done in Italy,
UK and Japan 16. Efficacy seems to be lower in
children, 2 years old. The efficacy against
influenza acute otitis media has been found to be
30%. There are very few studies of efficacy in
children with chronic medical illnesses. In one
study the efficacy against influenza was found to
be 22-54% in 2-5 years old and 60-78% in 7-14
years old 16.
Duration of immunity: Natural infection leads
to long term immunity for decades. Vaccine leads
to sero-conversion in 90% of the vaccinees. The
immunity lasts for 1-3 years. The second dose
18
2006; 8(3) : 204
does not lead to boosting effect. The antibody
levels drop by next 6 months in 50% of the
vaccinees. In any case due to high level of mutation
the vaccine has to be changed every year, and in
that sense the protection lasts for only 1 year
needing revaccination annually.
Safety: 65% of the vaccinees develop local side
effects like pain, induration and redness for
24-48 hours which usually is mild and responds
to paracetamol. Less than 15% develop systemic
side effects like fever, myalgia etc, usually in
young children with first dose. Rare side effects
include acute GBS (excess of 1/100,000 doses)
which was first noticed with the Swine vaccine
used in 1976. The current vaccines are safe and
do not lead to increase in cases of acute GBS 16.
Contraindications: The vaccine is
contraindicated in children < 6 months of age,
pregnant women in the first trimester, those with
severe reactions with previous doses and those
with severe egg allergy.
Cost: There are 3 brands available commercially.
Each dose costs Rs.700.
Indications: Influenza vaccine is used liberally
in the Western world. In fact is considered an
under-utilized vaccine in US. Initially the focus
was on vaccination of those who are at high risk
for complications following influenza and those
who are in contact with these at high risk people
as they can transmit influenza to them. As the
epidemiological studies in US have shown that
even healthy children < 2 years are at as much
risk of complications, hospitalizations and deaths
following influenza as the other at risk elders, in
2000 vaccination was encouraged for routine
use for all children < 2 years of age. In 2004 it is
now recommended for all children < 2 years of
age. The current recommendations of ACIP in
US are shown in Table 1 16. Many other western
countries also follow these guidelines and vaccinate
routinely all children < 2 years of age.

IAP Recommendations: IAP does not
recommend routine influenza vaccination of
children < 2 years old. It recommends to use
influenza vaccine for all the children with high
risk diseases as listed in Table 1 except asthma
unless oral steroid dependant. This is partly
because of lack of data of disease burden and its
severity in Indian children and partly because
influenza is in the lower priority in childhood
vaccination program where we are still struggling
to include more important vaccines like MMR,
Hib, HepatitisB and Typhoid vaccines in our
national schedule.
Live Cold Adapted Influenza Vaccine - Trivalent
(CAIV-T):
Live attenuated influenza vaccines are made
to make it more safe, efficacious, physiological
and convenient. The cold adapted live vaccine
CAIV-T is licensed since June 17, 2003 in US
and other western countries. It is still not marketed
in India. It is adapted by serial passages in such a
way that there is limitation to its replication only
in the colder upper airway and not in the lower
airway when given intra-nasally. This leads to local
immunity in airway without chances of systemic
infection or side effects. It contains
107 TCIDs/dose of each of the type A (H3N2),
type A (H1N1) and type B influenza viruses in
0.5 ml volume to be given intra-nasally by a
syringe like device in the dose of 0.25 ml in each
of nostrils21.
Efficacy and effectiveness: In a study done on
15-71 months old children over 2 years, the
efficacy against type A (H3N2) was found to be
95% in first year and 100% in the second year;
against type B it was 91% in first year and 100%
in the second year; against any type it was 93%
in first year and 100% in the second year. Type
A/Sydney variant not included in the vaccine was
seen in the second year and the efficacy against
that variant was 86%. Type A (H1N1) was not in
19
2006; 8(3) : 205
circulation during the study period and hence was
tested for challenge after vaccination, the efficacy
against such challenge was found to be 83%.
Efficacy against culture proved acute otitis media
was found to be 98% and that against culture
proved LRTI was 95%22.
Safety : 20 trials done on over 20,000 subjects
Table 1: ACIP recommendations for
influenza vaccination (modified)
A) At risk group:
a) > 65 years of age
b) Residents of nursing homes or chronic care
facilities
c) 6 months - 64 years of age with chronic
medical conditions like:
i) Chronic pulmonary condition including
asthma
ii) Chronic cardiac conditions
iii) Chronic metabolic conditions including
diabetes mellitus
iv) Chronic renal diseases
v) Hemoglobinopathies
vi) Immune compromised including HIV
infected
d) 6 months 18 years on long term aspirin
therapy
e) Pregnant women after the first trimester
f) Children of 6 months 23 months
B) Persons who can transmit influenza to as
risk group patients:
a) Health care workers
b) Employees of the nursing home and other
chronic health care facilities
c) Home care workers looking after the at
risk group at home
d) Contacts at home for all those at risk
including contacts of children 6 months
23 months
C) 50-64 years old
Indian Journal of Practical Pediatrics
using over 28,000 doses which included 15,000
children has shown that local side effects were
similar to the placebo and < 10% subjects
developed mild side effects like URI, low fever
or lethargy. Study in high risk group showed that
the side effects were not more in asthmatics, HIV
patients or elderly patients with high risk diseases.
In asthmatics there was no change in any of the
scores of asthma after the use of the live vaccine21.
Indications: At present this vaccine is indicated
only in healthy people between 5-49 years of age.
It is not indicated for < 5 years, > 50 years and
those with high risk diseases. Hence the inactivated
influenza vaccine is indicated for the prevention
of influenza and related complications in those at
high risk, whereas the live vaccine is primarily
indicated for prevention of influenza in healthy
young adults.
Contraindications: The live vaccine is
contraindicated in the following:
a) < 5 years old
b) > 50 years old
c) 5-50 years old with high risk diseases
d) Any one with reactive airway disease
e) Any one on long term aspirin therapy
f) Pregnant women
g) Patient with acute GBS
h) Immune compromised individuals
Points to remember
Conjugated Hib vaccine has good
immunogenicity and efficacy.
Conjugated pneumococcal vaccine given in
a schedule of 3 primary doses and 1 booster
dose is found to have high efficacy.
High risk populations should be targetted
with influenza vaccine.
References
1) Wegner JD, Booy R, Heath PT et al.
Epidemiological impact of conjugate vaccines
on invaseive disease caused by Hemophilus
20
2006; 8(3) : 206
influenzae type b. In Levine MM, Woodrow
GC, Kaper JB (eds): Newer Generation
vaccines. USA, Marcel Dekker Inc, 1999, pp
489 502.
2) John TJ, Cherian T, Raghupathy P. Hemophilus
influenzae disease in children in India : a
hospital perspective. Pediatr Infect Dis J
1998;17(9):51695171.
3) Invasive Hemophilus influenzae disease in
India: a preliminary report of prospective
multihospital surveillance IBIS. Pediatr Infect
Dis J 1998;17:31723175.
4) Bijlwer H. World wide epidemiology of
Hemophilus influenzae meningitis;
industrialised versus non industrialised
countries. Vaccine 1991;9:5559.
5) Singh R, Thomas S, Chellam K, et al.
Occurrence of multiple antimicrobial
resistance among Hemophilus influenzae type
b is causing meningitis. Indian J Med Res
1992;95:230233.
6) Agarwal V, Jaivi D, Patnaik A, et al.
Characterisation of invasive Hemophilus
influenzae isolated in Nagpur, Central India.
Indian J Med Res 1996;103:296298.
7) Peltola H, Kilpi T, Anttila M. Rapid
disappearance of Hemophilus influenzae type
b meningitis after routine childhood
immunisation with conjugate vaccines. Lancet
1992;340:592-594.
8) Schmitt HJ, Zepp F, Miischenborn S, et al.
Immunogenecity and reactogenecity of a
Hemophilus influenzae type b tetanus
conjugate vaccine when administered
separately or mixed with concomitant
diphtheria-tetanus-toxoid and acellular
pertussis vaccine for primary and for booster
immunisation. Eur J Pediatr 1998;157: 208-
214.
9) Update on Immunization Policies, Guidelines
and Recommendations. Indian Pediatr
2004;41:239-244.
10) Invasive bacterial infection surveillance (IBIS)
group. International Clinical Epidemiology
Network (INCLEN) : Prospective multicentre
 2006; 8(3) : 207

hospital surveillance streptococcus
pneumoniae disease in India. Lancet 199; 353:
1216-1221.
11) Murray CJL, Lopez AD. Global burden of
disease and injury series: Global health
statistics. Cambridge: Harvard University
Press, 1994.
12) Black S, Shinefield SH, Fireman B, et al.
Efficacy, safety and immunogenicity of
heptavalent pneumococcal conjugate vaccine
in children. Pediatr Infect Dis J 2000, 19: 187-
195.
13) Rennels MB, Edwards KM, Keyserling H, et
al. Safety and immunogenicity of Heptavalent
pneumococcal vaccine conjugated to CRM
197 in United States infants. Pediatrics 1998;
101: 604-611.
14) Eskola J, Kilpi T, Palmu A, et al. Efficacy of a
pneumococcal conjugate vaccine against acute
otitis media. N Engl J Med 2001; 344: 403-
409.
15) Dagan R, Melamed R, Muallem M, et al.
Reduction of nasopharyngeal carriage of
pneumococci during the second year of life
by a heptavalent conjugate pneumococcal
vaccine. J Infect Dis 1996; 174: 1271-1278.
16) Fukuda K, Roland AL, Carolyn BB, Nancy JC.
Inactivated influenza vaccines. In Plotkin SA,
Orenstein WA (eds): Vaccines. USA, Elsevier
Inc, 2004, pp 339-370.
NEWS AND NOTES
17) Bridges CB, Thompson WW, Meltzer MI, et
al. Effectiveness and cost benefit of influenza
vaccination of healthy working adults:a
randomized controlled trial. JAMA 2002;
284:1655-1663.
18) Vu T, Farish S, Jenkins M, Kelly H. A meta-
analysis of effectiveness if influenza vaccine
in persons aged 65 years and over living in the
community. Vaccine 2002; 20: 1831-1836.
19) Pyhala R, Haanpaa M, Kleemola M, et al.
Acceptable protective efficacy of influenza
vaccination in young military conscripts under
circumstances of incomplete antigenic and
genetic match. Vaccine 2001; 19:3252-3260.
20) Nochol KL, Wouremna J, Stenberg T. Benifits
of influenza vaccination for low-,
intermediate- and high-risk senior citizens.
Arch Intern Med 1998; 158: 1776-1998.
21) Robert BB, Husein FM, Paul MM. Influenza
vaccine - Live. In Plotkin SA, Orenstein WA
(eds): Vaccines. USA, Elsevier Inc, 2004; pp
371-388.
22) Belshe RB, Gruber WC, Mendelman PM, et
al. Efficacy of vaccination with live attenuated,
cold adapted, trivalent, intranasal influenza
virus vaccine against a variant (A/Sydney) not
contained in the vaccine. J Pediatr 2000;
136:168-175.

8th NATIONAL CONGRESS ON PEDIATRIC CRITICAL CARE (NCPCC)

Dates : 10th, 11th and 12th November 2006
CONFRENCE FEES Till June Till August Till October
15th 2006 15th 2006 15th 2006 Spot
IAP Intensive Care Member Rs.2000 Rs.2500 Rs.3000 Rs.4000
IAP Member Rs.2250 Rs.2750 Rs.3250 Rs.4000
Non IAPMember /
Foreign delegate Rs.2500 Rs.3000 Rs.3500 Rs.4000
PG Student Rs.1400 Rs.1700 Rs.2000 Rs.4000

Payment is by Demand Draft only, payable to NCPCC Bangalore. Cheques not accepted.
Contact for further details: Dr.Girish HC, Organizing Secretary, NCPCC Bangalore KR Hospital, 979,
25th Main Road, BSK 1st Stage, 50 Feet Road, Bangalore 560050. Mobile: 98452-72933
21
Indian Journal of Practical Pediatrics
VACCINES
ADVERSE EVENTS FOLLOWING
IMMUNIZATION
* Indra Shekhar Rao M
Abstract : Several scientific, ethical and statutory
obligations are fulfilled before introducing a
vaccine in the field. However no vaccine is
perfectly safe and adverse events can occur
following immunization. The adverse events may
be minor or major, true or coincidental. The various
adverse events that can occur following the routine
immunization are dicussed in this article.
Guidelines for vaccinations, reporting of adverse
events following immunization (AEFI), parent
education and efficient resuscitation equipments
are vital components essential to make
immunization a most effective public health tool
in child survival programme.
Keywords : AEFI, Safe Vaccination.
The success story of child health in the last
century attributes to immunization as the main
component which has enhanced and improved the
child survival all over the world. Vaccines used in
National Immunization Programmes are extremely
safe and effective. Several scientific, ethical, and
statutory obligations are fulfilled by the
manufacturers; elaborate field trials regarding safety
and protection offered by individual vaccines are
established before it is recommended for routine
use. However no vaccine is perfectly safe and
adverse events can occur following immunization.
In addition to the vaccines themselves, being
* Professor & Head, Dept. of Pediatrics,
Institute of Child Health, Niloufer Hospital,
Hyderabad, A.P.
22
2006; 8(3) : 208
products of biological nature, the process of
immunization is also a potential source for
adverse events1-3.
An adverse event following immunization
(AEFI) is any adverse event that is believed to
be caused by immunization. Reported adverse
event can be a true adverse event or a
coincidental event. For the purpose of these
guidelines AEFIs are classified into five
categories as shown in Table 1.
Immunization can cause adverse events
from the inherent properties of vaccine (Vaccine
reaction) or some error in Immunization process
(Programme error) The event may be unrelated
to the immunization but have temporal
association (Coincidental event). Anxiety
related reactions can raise fear or pain of the
injection rather than the vaccine. In some cases
the cause of AEFI remains unknown.
The adverse event following the
immunization may be minor and is the one
which is expected but not severe enough to
cause discomfort during short duration of time,
e.g. pain or fever after DPT vaccination;
whereas a severe or rare event following the
vaccine may be in the form of unexpected
anaphylactic shock or introduction of active
disease e.g. anaphylaxis following measles
vaccine. Another type of hypothetical and
vaccine related scare has casual rather than
causal relationship with the adverse effect and
usually are concerning the issues which are of
controversial nature occurring in vaccinated
children though not directly related to the vaccine
as shown in Table 2.
 2006; 8(3) : 209

Table 1. Classification of adverse events following immunization (AEFIs)

Vaccine reaction Event caused or precipitated by the vaccine when given correctly,
caused by the inherent properties of the vaccine.
Programme error Event caused by an error in vaccine preparation, handling, or
administration.
Coincidental Event that happens after immunization but not caused by the vaccine
a chance association.
Injection reaction Event from anxiety about, or pain from, the injection itself rather than
the vaccine
Unknown Events cause cannot be determined.

Table 2. Adverse events following immunization

Anticipated reaction (Minor reaction) Pain, fever following DPT vaccination
Severe reaction (rare event) Disseminated BCG infection, anaphylaxis
Vaccine controversies and casual relationship MMR vaccination and autistic syndrome.

Table 3. Common, minor vaccine reactions and treatment

Vaccine Local reaction Fever>380C Irritability, malaise
(pain, swelling, and systemic
redness) symptoms

BCG 90-95% - -
Hib 5-15% 2-10% -
Hepatitis B Adults 15% 1-6% -
Children 5%
Measles / MMR / MR 10% 5-15% 5% (Rash)
Oral Poliomyelitis (OPV) - <1% <1%
Tetanus / DT / Td 10% 10% 25%
Pertussis (DTP-Whole cell) Upto 50% Upto 50% Upto 55%
Treatment Cold compress at Give extra fluids Give extra fluids
injection site Tepid sponge or Paracetamol
Paracetamol bath
Paracetamol

23
Indian Journal of Practical Pediatrics 2006; 8(3) : 210

The common vaccine reactions are due to
the immune response of the host and sometimes
due to vaccine components (e.g. Aluminium
adjuvant and preservatives). An ideal vaccine
reduces these reactions to a minimum while
inducing the best possible immunity. These
anticipated reactions occur within a day or two of
immunization and they are listed in Table 3.
The rare vaccine reactions usually do not lead
to long-term problems. Anaphylaxis while
potentially fatal is treatable without leaving any
long-term effects. These are listed in Table 4.
The vaccine scare related adverse events
have a very casual link and are most often
hypothetical. These are listed in Table 5.
Another notable component of adverse
events following immunization is due to
programme errors that result from errors and
accidents in vaccine preparation, handling or
administration. The identification and correction
of these errors are of great importance which
would otherwise lead to a cluster of other events
associated with immunization. The most common
programme error is an infection as a result of non

Table 4. Rare vaccine reactions, onset interval and rates

Vaccine Reaction Onset Number of
interval reactions per doses
BCG Suppurative lymphadenitis 2-6 months 1 in 1000-10000
BCG osteitis 1-12 months 1 in 3000 to 1 in
100 million
Disseminated BCG infection 1-12 months 1 in 1 million
Hib None known
Hepatitis B Anaphylaxis 0-1 hour 1 in 6-900000
Measles / MMR / Febrile seizures 6-12 days 1 in 3000
MR Thrombocytopenia 15-35 days 1 in 30000
Anaphylaxis 0-1 hour 1 in 1000000
Encephalopathy 6-12 days <1 in 100000
OPV Vaccine associated paralytic 4-30 days 1 in 2.4-3 million
poliomyelitis
Tetanus Brachial neuritis 2-28 days 0.5-1 in 100000
Anaphylaxis 0-1 hour 1 in 100000 to
1 in 2500000
Tetanus- None extra to tetanus
Diphtheria reactions
Pertussis (DTP- Persistent (>3 hours 0-24 hours 1 in 15 to 1 in 1000
Whole cell) inconsolable screaming)
Seizures 0-2 days 1 in 1750 to
1 in 12500
Hypotonic, hyporesponsive 0-24 hours 1 in 1000-33000
episode (HHE)
Anaphylaxis 0-1 hour 1 in 50000
Encephalopathy 0-2 days 0-1 in 1 million
(note: risk may be zero)

24
 2006; 8(3) : 211

sterile injection e.g. abscess which may have a Each vaccine administered in the
systemic effect or blood borne infection e.g.HIV, immunization programme has specific
Hepatitis B etc. These are listed in Table 6. complications most of which are anticipated and

Table 5. Vaccination scares

Hepatitis B Multiple sclerosis, lupus, diabetes
Whole-cell pertussis Encephalopathy, epilepsy, learning disorders
Diphtheria, tetanus and pertussis
Cot death/Sudden Infant Death Syndrome (SIDS)
Inactivated polio vaccine HIV infection
Influenza Diabetes mellitus
Hemophilus influenza type b Diabetes mellitus
Measles, Mumps and Rubella Autistic spectrum disorder, inflammatory bowel disease,
Childhood arthropathy
Rubella Ethical concerns because grown in cells from an aborted fetus
Thiomerosal containing vaccines Neuro-developmental disorders, autism
Aluminium containing vaccines Muscular fibrosclerosis
Various vaccines Diseases of unknown, or only partially understood etiology, e.g.
asthma, autism, inflammatory bowel disease, cot death, chronic
fatigue syndrome, immune deficiency, leukemia, autoimmune
diseases, learning disorders, increase in violent crime.
Table 6. Programme errors leading to adverse events
Non-sterile injection Infection
Reuse of disposable syringe or needle Local suppuration at injection site,
Improperly sterilized syringe or needle abscess, cellulitis, systemic infection, sepsis,
Contaminated vaccine or diluent toxic shock syndrome, transmission of blood
Reuse of reconstituted vaccine at subsequent borne virus (HIV, hepatitis B or hepatitis C).
session
Vaccine prepared incorrectly
Vaccine reconstituted with incorrect diluent Local reaction or abscess from inadequate
shaking
Drugs substituted for vaccine or diluent. Effect of drug (e.g. muscle relaxant, insulin)
Immunization injected in wrong site
Subcutaneous instead of intradermal for BCG Local reaction or injection site abscess.
Too superficial for toxoid vaccine
(DPT, DT, TT)
Gluteal region (
Sciatic nerve damage vaccine efficacy.
)
e.g. hepatitis B
Vaccine transported/stored incorrectly. Increased local reaction from frozen vaccine
(and ineffective vaccine).
Contraindications ignored Avoidable severe vaccine reaction.

25
Indian Journal of Practical Pediatrics
mild. However some of them are serious adverse
reactions which have to be anticipated and
immediate remedial measures must be given.
Vaccine complications and their management:
BCG
Anticipated Reactions: Nodule formation at
the site of vaccination (3-6 weeks) which liquefies,
ulcerates and heals by tiny scar (10-12 weeks)
Adverse Reactions
Local:
a) Persistent discharging sinus at the site of
vaccination
b) Regional axillary adenitis (below 2 cm, no
treatment). Fluctuant, more than 2 cms- INH
(3-6 months) / Excision.
c) BCG Complex: Local lymphadenitis +
Positive Mantoux reaction + Paratracheal
Lymphnode. Treat with RHZ (2 months) +
RH (7 months)
Systemic: Disseminated infection, T.B.
Osteomyelitis, Scrofuloderma. Treat like
tuberculosis.
Table 7. Differential diagnosis of anaphylactic shock
Anaphylaxis These reactions must be distinguished from syncope, breath holding spells,
anxiety which are common benign reactions which only require
symptomatic treatment.
Syncope (Fainting) Breath holding spells Anxiety
Sudden onset of pallor, Occurs after 6 months
loss of consciousness, of age
collapses to ground. Follows a painful
stimuli
Continuous cry, holds
his breath, cyanosis,
convulsion.
2006; 8(3) : 212
DPT
Anticipated Reactions: Pain, discomfort,
fever, induration (treatment-analgesics +
antipyretics paracetamol 15 mg/kg/dose).
Adverse Reactions: Incessant cry (more than
3 hours), febrile convulsions, hyperpyrexia,
hyporesponsive hypotensive shock like state
acute encephalopathy, anaphylactic shock. (The
differential diagnosis of anaphylactic shock
following DPT or any other vaccine is discussed
in Table 7.
Treatment of anaphylactic shock : Place the
patient in recumbent position and elevate the feet.
a) Clear the airway, establish breathing
(O2 supplementation and bag valve mask
application) and maintain circulation.
b) Injection Adrenaline (1:1000) 0.01 ml/kg.
S.C./I.M. (severe cases). Repeat dose at 20
min. intervals.
c) Volume expanders (20 ml / kg normal saline
or R.L. 20 ml/kg over 20 minutes) followed
by plasma or fresh blood 20 ml / kg.
Anaphylaxis
Sweating Itchy urticarial rash, facial flushing
Panic Progressive edema involving face,
mouth and body parts
Excessive Respiratory symptoms: Sneezing,
crying coughing / wheezing, airway
obstruction.
Hypotension: Shock
26

d) Dopamine (5-10 micro grams/kg/minute) and
Dobutamine (5-40 micro grams/kg/min).
e) Monitor vital signs.
f) Other measures: To reduce the absorption of
vaccine from injection site:
a. Placing a tourniquet above vaccination site.
b. Local adrenaline to reduce vaccine
absorption (only in vaccines given through
S.C. route).
OPV
AEFI almost none
Very rarely vaccine associated paralytic
poliomyelitis (VAPP)
In contacts: 1 in 3 million vaccine doses
In recipients: 1 in 2 million vaccine doses.
IPV
Local reactions: Erythema, induration,
Patients sensitive to streptomycin/neomycin might
develop hypersensitive reactions as IPV contains
streptomycin and neomycin.
Measles
Anticipated Reactions: Mild fever, rash,
coryza (upto 4-7 days following vaccination)
Treatment: Paracetamol
Adverse Reactions:
a) Toxic shock syndrome (TSS) due to
contamination of measles vaccine by Staph.
aureus.
b) Exaggeration of T.B.
c) Encephalitis
Toxic shock syndrome: It occurs due to
contamination of measles vaccines with Staph.
aureus due to usage of unsterile syringes, needles/
and using a reconstituted vaccine vial for more
than one session.
27
2006; 8(3) : 213
Clinical features: (can occur after 30 minutes to
few hours after vaccination) Fever, vomiting,
diarrhea, shock.
Treatment: Should be treated as medical
emergency.
a) ORS, paracetamol (home treatment)
b) I.V. fluids (RL or Normal Saline), Antibiotics
(Cloxacillin 100 200 mg/kg/day in divided
doses), steroids, antipyretics, supportive
therapy
MMR
Anticipated Reactions: Mild fever, rash, febrile
seizures
Mumps
Adverse reactions: Fever (Rarely, encephalopathy,
seizures, G.B.S, parotid swelling, hemolytic uremc
syndrome, aseptic meningitis).
Rubella
Adverse reactions: Arthralgia, lymphadenopathy,
fever, sore throat; rarely thrombocytopenia and
peripheral neuropathy
Hepatitis B vaccine
Local reactions: Soreness at the site of injection
Systemic reactions: Mild fever, myalgia, arthralgia,
rarely anaphylaxis
Hepatitis A vaccine
Local reactions: Soreness, induration
Systemic reactions: Headache, nausea, loss of
appetite
Typhoid vaccine
1) A.K.D. vaccine (Acetone Killed)
Local reactions: Pain, swelling, tenderness
Systemic reactions: Headache, nausea, fever and
relapse of chronic diseases like rheumatoid arthritis
and compensated cardiac conditions
Indian Journal of Practical Pediatrics
2) Vi capsular polysaccharide vaccine
Local reactions: Mild pain, swelling for 1 day
3) Ty 21 A (Oral)
Local reactions: Diarrhea, vomiting
Systemic reactions: Transitory exanthema
Tetanus Toxoid (T.T.):
Repeated TT injections after trivial injuries
can lead to reduced immunogenecity,
hypersensitivity, hemolytic anemia, amyloidosis.
Also increase risk to hemorrhagic disease of
newborn.
Hib vaccine
Local reactions: Mild redness, pain and swelling
Varicella vaccine
Local reactions: Papulo vesicular eruption in less
than 4% of vaccinees.
Systemic reactions: Mild fever, headache,
pneumonitis, arthropathy.
Rabies Vaccine
1) Nervous tissue vaccine
Local reactions: Pain, redness, itching, abscess
formation
Systemic reactions: Fever, headache, giddiness,
palpitation, shock, generalised urticaria.
Neuro-paralytic complications (1:5,500): Cranial
nerve paralysis, paralysis of limbs, ascending
paralysis, encephalopathy
Treatment of complications: Discontinue the
vaccine, bed rest, steroids, further vaccination if
required by tissue culture vaccine.
2) Tissue culture vaccine
Local reactions: Soreness
Systemic reactions: Headache, fever, anaphylaxis,
rarely transient neuroparalytic illness (Guillain
Barre type)
28
2006; 8(3) : 214
Meningococcal vaccine
Local reactions: Inflammation
Systemic reactions: Anaphylaxis rarely
Pneumococcal vaccine
Local reactions: Swelling, redness, pain
Systemic reactions: GBS, anaphylaxis, relapse of
ITP
Japanese Encephalitis vaccine
Local reactions: Redness, swelling, pain
Systemic reactions: Fever, headache
Influenza vaccine
Local reactions: Pain, swelling
Systemic reactions: Rarely GBS (1 in 100,000)
Vaccines and controversies
Thiomerosal and Vaccines: Thiomerosal, a
mercury based preservative used in some vaccines,
is an organic compound containing 49.6% of
ethylmercury by weight. It has been used in very
small amounts in some vaccines to prevent
bacterial and fungal contamination. This organic
compound of mercury is in two forms,
ethylmercury (Thiomerosal) which doesnt
accumulate in the body because its half life is 7-
10 days and is rapidly converted in the body to
inorganic mercury which is excreted in the stool;
and methylmercury which is more potent as it
accumulates in the body because the time taken
for the body to eliminate it is about 50 days.
The safe level of mercury consumption lies
somewhere between 0.7 gs/kg/week (Environ-
mental protection agency, USA) to 3.3 gs/kg/
week (WHO). The total intake of 175 micrograms
of ethylmercury occurs in a child who is given all
routine vaccines, is equivalent to 1.9 gs/kg/week.
This level is well below the WHO limit for
methylmercury which is converted to
ethylmercury and rapidly excreted4.
 2006; 8(3) : 215

The Global Advisory Committee on Vaccine a single study that has shown a risk of MMR
safety ( GAVSC ) of WHO has concluded that vaccine causing autism but there have been many
There is currently no evidence of mercury toxicity studies that cant find a risk. No correlation exists
in infants, children or adults exposed to Thimerosal between the prevalence of MMR vaccination and
containing vaccines, and there is no reason to the rapid increase in the risk of autism over the
change current immunization practices with time7. The surveys revealed that the apparent rise
Thimerosal containing vaccines on grounds of in cases of autism substantially reflects the
safety5. adoption of a much broader concept of autism
and improved identification of children with
Various studies in Denmark, Sweden, United
autism8.
States and UK and the evidence there upon
indicated that autism and neurodevelopmental In conclusion, there is no epidemiological
disorders are not associated with Thimerosal in evidence for a casual association of Measles,
the vaccines. Mumps and Rubella vaccines with autism. MMR
vaccination is not associated with an increased
MMR and autism risk of pervasive developmental disorders in
Autism is a developmental disorder, a children 9.
situation where childs growth and development, Vaccines and contraindications
physically and emotionally doesnt progress as it
is expected, which usually appears in second year Vaccines might cause adverse reactions. It
of life and MMR is given around that age of is often difficult to prove definite cause effect
1-2yr6. relationship between the act of vaccination and
subsequent complication. However, following
Autism is well known condition long before guidelines will help in deciding vaccine
the MMR vaccine was used. There has not been administration as shown in Table 8.
Table 8. Vaccines and contra-indications
1. Avoid: Live vaccine a) Immunodeficient individuals
b) Immuno suppressant therapy
c) Chronic debilitating illness
Avoid: DPT (1st dose) a) Progressive neurologic disease
b) Uncontrolled seizure disorder
Avoid: Rubella vaccine during pregnancy
Avoid: Antibiotics effective against S. typhi: 1 week prior / after Ty 21a vaccination
If person is sensitive to vaccines containing egg protein (eg. Measles vaccine) should not be given
2. Delay: Live vaccine a) Measles / MMR for 6 weeks following
immunoglobulin therapy
b) Severe febrile illness.
3. Discontinue: DPT in case of severe post-vaccinial reactions
4. Do not stop vaccination in: a) Malnutrition
b) Moderate fever
c) Respiratory infections
d) Mild diarrhea
e) Any benign ailment

29
Indian Journal of Practical Pediatrics
Guidelines for safe vaccination
1) Select proper vaccine. Follow manufacturers
instructions (dose / route / administration)
2) Maintenance of cold chain.
3) Informing the mother regarding vaccine
benefits and their anticipated reactions.
4) Obtain consent before vaccination.
5) Keep the child under observation for 30 min.
after vaccination. Be equipped and gear up
to treat any untoward reactions. Have always
resuscitation kit ready.
6) Use desired injection procedure i.e. load the
vaccine into appropriate syringe size, discard
the needle used for drawing and use a fresh
needle for injection (1 syringe and 2 needles
for each vaccination)
7) Dont mix vaccines in single syringe unless
permitted by the manufacturer and the drug
authorities Use different syringes for different
vaccines. Use different sites for injection.
8) Once a live vaccine has been administered
wait for 4-6 weeks period for another vaccine
administration.
9) Use zig-zag method of administration or Z
technique to prevent track formation.
10) Always use anterolateral aspect of thigh in
young children and deltoid area for older
children for injections. Avoid gluteal region.
11) Avoid fomentation/ vigorous rubbing after
vaccination.
12) Document every vaccination procedure in the
immunization card and keep a copy of it.
13) Complete the vaccination schedule as per
immunization calendar. Remind the mother
regarding next date.
30
2006; 8(3) : 216
14) There is no need to restart immunization
within a year of administering the first dose
of multidose vaccine e.g. HIB, DPT etc., if
the child is not brought for immunization on
suggested date.Continue and complete the
schedule.
The best way to minimize the adverse events
following the immunization is to anticipate the
expected type of reaction for a specific vaccine
and to identify the events that are probably
unrelated to the vaccination.
Prevention and Treatment of Vaccine
Reaction
It is mandatory for the person administering
the vaccine to have sufficient knowledge regarding
vaccines and expected side effects and to inform
parents thoroughly regarding such adverse effects
which may however occur very rarely. It is also
essential to be prepared and to always have a kit
with life saving drugs and equipments at each place
of vaccination.
Advice on managing the common reactions
should be given to parents as well as the
instructions to return if there are more serious
symptoms. This will help to reassure parents
about immunization and prepare them for common
reactions. Programme errors are preventable and
detract from the overall benefit of the
Immunization Programme. Identification and
correction of these errors are of great importance.
WHO guidelines to avoid programme errors are
as follows:
Vaccines must only be reconstituted with the
diluent supplied by the manufacturer.
Reconstituted vaccines must be discarded at
the end of each immunization session and
never retained.
No other drugs or substances should be stored
in the refrigerator of the immunization centre.
 2006; 8(3) : 217

Immunization workers must be adequately
trained and closely supervised to ensure that
proper procedures are being followed.
Careful epidemiological investigation of an
AEFI is needed to pinpoint the cause and to
correct immunization practices.
Reporting AEFIs
The reportable AEFI must include any death
or serious event believed by the public or health
worker to be caused by Immunization. Table 9
gives the list of reportable AEFIs. The minor
common reactions such as local reactions, fever,
and self limiting systemic symptoms need not be
reported. It is important for the persons
administering the vaccine to advise the parent /
patient at the time of immunization that these
reactions are expected and advise them how to
manage these common reactions (e.g. paracetamol
to treat fever). For more serious problems patient
should be advised to return or to seek medical
attention and to allow detection of AEFI. More
importantly they should be advised not to delay
treatment of a coincidental illness falsely attributed
as vaccine reaction. Severe local reactions
especially if occurring in clusters should be
reported as they can be markers for programme
errors or for problems with specific vaccine lots.
When to report? Who should report?
Reporting should be done as quickly as
possible so that an immediate decision on the need

Table 9. List of Reportable AEFIs

Occurring within 24 hours of
immunization
Occurring within 5 days of
immunization
Occurring within 15 days of
immunization
Occurring within 3 months of
immunization
Occurring between 1 and 12 months Lymphadenitis
after BCG immunization
No time limit
Anaphylactoid reaction (acute hypersensitivity reaction)
Anaphylaxis
Persistent (more than 3 hours) inconsolable screaming
Hypotonic hyporesponsive episode (HHE)
Toxic shock syndrome (TSS)
Severe local reaction
Sepsis
Injection site abscess (bacterial/sterile)
Seizures, including febrile seizures (6-12 days for measles/
MMR; 0-2 days for DTP)
Encephalopathy (6-12 days for measles / MMR; 0-2 days
for DTP)
Acute flaccid paralysis (4-30 days for OPV recipient; 4-75
days for contact)
Brachial neuritis (2-28 days after tetanus containing
vaccine)
Thrombocytopenia (15-35 days after measles / MMR)
Disseminated BCG infection
Osteitis/Osteomyelitis
Any death, hospitalization, or other severe and unusual
events that are thought by health workers or the public to be
related to immunization

31
Indian Journal of Practical Pediatrics
for action and investigation can be made. Private
physicians and hospitals should also report events
that come to the notice. In the community,
peripheral health worker or supervisor should
report to the district office.
The report should contain at a minimum:
Description of the event
Timing of the event in relation to
immunization.
Vaccines given
Patients identifying details.
The routine vaccination programme should
continue while awaiting the completion of the
reporting and investigation.
Responding to AEFIs
Private physicians and the health workers
need to know how to recognize, treat and report
AEFI-immediately as per the guidelines discussed
earlier. It is always wiser to keep the community
informed, investigate fully and avoid making the
premature statement about the cause of the event.
Always safeguard the public during investigation
with continuing immunization.
Communicating with the media
The media plays an important role in public
perception. The media are more interested in
stories that will attract attention, hence there is
tendency to dramatize and personalize the event.
It is easy for the media to create sense of panic
and outrage about the events which are unrelated
to immunization (co-incidental). The guiding
principle dealing with media must be one of
honesty and building of trust and one should show
empathy and caring, honesty and openness,
dedication and commitment, whenever possible
positive terms like immunization safety or vaccine
safety should be used. Key messages have to be
32
2006; 8(3) : 218
prepared before media contact and they should
include some of these facts.
That benefit of immunization in preventing
disease is well proven
It is very risky not to immunize (risk of
disease and complications)
Vaccine-preventable diseases caused millions
of death and/or disability before the
introduction of vaccines, and that situation
would return without continued use of
vaccines.
Vaccines do cause reactions, but these are
rarely serious and hardly ever cause long-
term problems.
Immunization safety is of paramount
importance, and any suspicion of a problem
is investigated (Advantage of well established
immunization safety surveillance)
The AEFI is currently being investigated, but
is likely to be coincidental/due to a local
problem (depending on type of event), and
the immunization programme must continue
to keep the population safe from disease.
The Immunization Safety and Safe Injection
Practices
The issues concerning the practices and
policies dealing with various aspects of correct
administration of vaccines focus on minimizing
the risk of transmission of disease and maximizing
the effectiveness of the vaccine. The term
encompasses the spectrum of events from proper
manufacture to correct administration which
includes both injection safety and vaccine safety.
The Immunization safety project includes the
WHO, UNICEF, UNAIDS, World bank, PATH,
Bill and Melinda Gates Children Vaccine
Programme, USAID and CDC who are the main
partners and financial supporters.

The project has main areas of focus.
1) Vaccine safety
2) Research and development of safe thermo
stable vaccines.
3) Access to safe vaccine delivery and safe
disposal.
4) Identification and management of risks related
to immunization, development of resource
material, training of all EPI managers in the
surveillance and management of adverse
events following immunization.
5) Strengthening of monitoring system for
vaccine adverse event reporting system
(VAERS).
Conclusion
The Immunization focus as established by
the WHO has objective to eliminate sickness and
death caused by vaccine preventable diseases
through the development of strong, sustainable
National Immunization Programmes, capable of
delivering high quality vaccines in a safe and
effective way to all children.
Points to remember
No vaccine is perfectly safe and adverse
events can occur following any vaccination
Effective resuscitation facilities should be
available to tackle and adverse event if
occurs.
Safe and efficient immunization practices
with thorough knowledge of the vaccines,
well maintained cold chain, proper parent
education and efficient resuscitation
equipment are vital components essential
to make immunization most cost effective
public health tool in child survival
programmes.
NEWS AND NOTES
NATIONAL CONFERENCE OF PEDIATRIC RHEUMATOLOGY, SURAT, SEPTEMBER 30, 2006
Enquiries to: Dr.Ketan Shah, Email: ketanhet@mail.com
33
2006; 8(3) : 219
References
1. Rao I. Vaccination complications, their
management and contraindications. Pediatr
clini India 2001; 36:30-35.
2. Immunization safety surviveillence.
Guidelines for managers of immunization
programmes on reporting and investigating
adverse events following immunization.
Manalia: WHO: 1999.
3. Adverse events following immunization. In:
Parthasarathy A, Lokeshwar MR, Shah NK
st
(Eds). Immunization digest.1 edn. New Delhi.
Jaypee Brothers Medical Publishers (P)
Ltd.2004;pp59-62.
4. Ball LK, Ball R, Pratt RD. An assessement
thimerosal use in childhood vaccines:
Pediatrics. 2001;107:1147-1154.
5. Clements CJ, Ball LK, Ball R, Pratt RD.
Thimerosal in vaccines: Is removal warranted?
Drugs safety. 2001;24:567-574.
6. Madsen KM, Lauristen MB, Pedersen CB, et
al. Thimerosal and the occurrence of autism:
negative ecological evidence from Danish
population- based data. Pediatrics
2003;112:604-606.
7. Taylor B, Miller E, Lingam R, Andrews N,
Simmons A, Stowe J. Measles, Mumps and
Rubella vaccination and Bowel Problems or
Developmental Regression in children with
Autism: Population Study. Brit Med J 2002;
324:393-396.
8. Kaye J et al. Mumps measles and rubella
vaccine and the incidence of autism recorded
by general practitioners: a time trend analysis.
Bri Medi J 2001;322:460-463.
9. Taylor V, Miller E, Farrington CP, Prtropoulos
MC, Farot-Mayaud I, LI J, Waight PA. Autism
and meales, mumps and rubella vaccine : No
epidemiological evidence for a causal
association. Lancet 1999;353:2026-2029.
Indian Journal of Practical Pediatrics
VACCINES
POLIO ERADICATION / HOW NEAR
AND HOW FAR?
* Vipin M. Vashishtha
** Naveen Thacker
Abstract : In the on-going struggle on polio
eradication the main aim is to interrupt wild
polio virus (WPV) transmission globally. Failure
to achieve this will pose a threat to all the nations
as evident by the recent reporting of large number
of cases in non-endemic countries. Evaluation
initiative has made good impact in the two most
stubborn states of Bihar and Uttar Pradesh in
India with substantial reduction in the number
and geographical areas with WPV. The threats
to ongoing eradication initiative may be in the
form of importation of WPV and vaccine
associated paralytic poliomyelitis. Reasons
behind delay in achieving polio erradication like
vaccine failure, programmatic set backs,
peculiarity of type 1 virus in endemic regions,
neglect of routine imminization and accessibility
problems are discussed and possible solutions
for present and future are offered.
Key words : Polio eradication, Situation
analysis, India, Worldwide
In 1988, when poliovirus was endemic in
more than 125 countries, World Health Assembly
resolution 41.28 established the goal of global
eradication of poliomyelitis by 2000. In 1999, the
Health Assembly, in resolution WHA 52.22, urged
* Consultant Pediatrician,
Mangal Children Hospital, Bijnor, UP
** Consultant Pediatrician,
Convener, IAP Committee on Polio Eradication
IAP President-Elect, 2006
Gandhidham
34
2006; 8(3) : 220
all member states to accelerate eradication
activities. At that time, three of the six WHO
regions - the Americas, Europe and Western
Pacific- had successfully interrupted transmission
of poliovirus. By 2003, the number of polio
endemic countries decreased to six (Afghanistan,
Egypt, India, Niger, Nigeria and Pakistan) from a
high of 125 in 19881. At the beginning of 2006,
this number has further reduced to an all time
low of four as so far Egypt and Niger have not
had indigenous poliovirus for more than 12
months2. However, during 2002-2005, a total of
21 previously polio free countries were affected
by importation of wild poliovirus (WPV) type 1
from the six remaining endemic countries
(primarily Nigeria). Four countries (Indonesia,
Somalia, Sudan and Yemen) had out breaks of
more than 100 polio cases3. For the first time in
the history of Global Polio Eradication Initiative
(GPEI), the number of cases in the non-endemic
countries was higher than in the endemic countries
(1048 vs 848 as of February, 2006). This reflects
progress in endemic countries and the great
vulnerability of polio free countries, where low
coverage of routine immunization (RI) failed to
protect their polio-free status4.
Hence, the current overall scenario provides
mixed signals- there are ample indicators of
achieving ultimate objectives and goal in
immediate future where as continued setbacks
tend to dampen the euphoria and remind us to
tread the path with utmost caution.
The Goal and Objectives of Eradication
The original targets of GPEI when the
initiative was undertaken in 1988 were:
 2006; 8(3) : 221

No cases of clinical poliomyelitis associated

Containment of all polioviruses

with wild poliovirus, and

Stop AFP surveillance after 3yrs

Stockpile & Response
No WPV circulation world wide (including

Coordinated cessation of OPV after 3 yrs of

Interruption of wild Poliovirus transmission

in sewage or drinking water) in presence of
the ability to detect one should it be

Surveillance & Response

? IPV use in RI/ No IPV/
circulating.
Since then various elaborate modifications
were made to final goal and the most recent
published goal is to ensure

of last VDPV
that poliovirus transmission is interrupted
globally through coordinated national and
international action;
that the full humanitarian and economic
benefits of eradication are realized;

last wPV
that the lessons and infrastructure from its
implementation are utilized in the
strengthening of health systems and control
of other important diseases5.
There is definite, perceptible shift from the
original goal. The enforcing agencies and polio-
partners are no longer talking of complete absence
of WPV from the world including the environment, Fig 1. Proposed cascade of events to be observed
which was far more ambitious and unrealistic goal before achieving true eradication of polio
as the world has come to realize now.
This new strategic plan has identified four The state of polio eradication - Situation
key objectives and milestones5 analysis

1. Interruption of WPV transmission, In 2005, the world moved several critical

2. Achieving certification of Global Polio
Eradication,
3. Developing products for the Global OPV
Cessation Phase,
4. Mainstreaming the Global Polio Eradication
Initiative
The strategic plan, 2004-2008 has also set a
timeline for all the above-enumerated objectives.
A modified step-ladder type figure
demonstrating each important event is depicted
in Figure 1.
35
milestones closer to polio eradication, including
the successful introduction of the powerful new
monovalent OPV(mOPV) vaccines, visible
progress in the hardest endemic areas, and an end
to west and central Africas epidemic (outside
Nigeria/ Niger). As stated earlier, the number of
countries with indigenous polio has dropped to 4,
as Egypt and Niger have not had indigenous
poliovirus for more than 12 months now2.
Between 1988 and 2004, global eradication
efforts reduced the number of polio cases from
350,000 annually to a low of 1,189 cases. In 2005,
Indian Journal of Practical Pediatrics 2006; 8(3) : 222

the number of cases rose again to 1932 (as of 21st fundamentalist religious organizations of the
February 2006), at the peak of the epidemic country severely affected the drive against polio
originating in northern Nigeria and infecting 21 eradication and at least ensured that the project is
previously polio free countries between 2003 and going to be delayed for further few years4,6. This
20053. temporary suspension resulted not only in huge
immunization gap in young children in northern
Nigeria (40.7 %), Yemen (24.8 %), states of the country where between 40-50 % of
Indonesia (15.7 %) and Somalia (9.6 %) are the children have not received any doses of OPV
countries responsible for more than 90% of global but also introduced wild poliovirus (type 1) in to
wild poliovirus cases in 2005 (Table 1). 21 previously polio free countries, followed by
Table 1: Polio cases from 22 February intercontinental spread to Middle East and Asia
2005 to 21 February 2006 (Fig. 2). Out of these 21 countries, in 8 countries
imported virus did not result in sustained
Name of Status Number of transmission and they either had only 1case
country WPV cases (Botswana, Eritrea, Lebanon, Togo) or had
Nigeria Endemic 788 detected a small number of separate cases not
Yemen Importation 478 directly linked genetically or epidemiologically
Indonesia Importation 302 (Benin, Cameroon, Nepal, Saudi Arabia). In the
Somalia Importation 184 remaining 13 countries, imported WPV caused
India Endemic 66 multiple case outbreaks. In 8 of these 13 countries,
Pakistan Endemic 27 transmission is considered to have stopped
Sudan Importation 27 (Burkina Faso, Central African Republic, Chad ,
Ethiopia Importation 22 Cote dIvore, Ghana, Guinea, Mali, Sudan). The
Angola Importation 10 remaining 5 countries (Yemen, Indonesia,
Niger Importation 10 Somalia, Angola and Ethiopia) are still having
Afghanistan Endemic 7 sustained transmission and 3 of them (Yemen,
Nepal Importation 4 Indonesia, and Somalia) are still contributing wild
Mali Importation 3 virus cases and already had large out breaks7.
Chad Importation 2
The Progress in India and the Sub-continent
Eritrea Importation 1
Cameroon Importation 1 The eradication initiative has made handsome
Total cases 1932 progress in India till last year, particularly in the
states of Bihar and to some extent in Uttar Pradesh
Nigeria continues to be the greatest obstacle (U.P.)- the two most stubborn endemic foci in
in making world free from polio. Extensive the country. The number of WPV cases declined
transmission of both type 1 and type 3 poliovirus from 1600 cases in 2002 to 66 cases in 2005, and
continues in the northern part of the country. With number of infected districts has gone down from
788 cases reported in 2005, Nigeria accounted 159 districts in 2002 to only 35 districts in 20058.
for >40 % of global cases. The southern part of
the country is polio free, as no indigenous polio However, 2006 brought us disappointing news as
transmission has occurred in 20052. Suspension far as situation in UP is concerned. Already by
of all forms of polio activities during 2003-2004 mid-July the number (136) has reached double
period owing to fierce resistance from some that of the whole year of 2005. The wild virus

36

tally in UP now reflects a staggering figure of 185
cases (as of 18th August 2006). Cases in UP are
concentrated around Moradabad district.
Moradabad, JP Nagar, Bareilly, Badaun, and
Rampur account for 80% of the cases to date in
UP and 70% of cases in India as a whole.
Moradabad and JP Nagar alone have reported 56
cases, greater than 50% of the UP total. While
cases have been concentrated in a fairly restricted
area of western UP, more recently geographical
spread has occurred and it is likely that there will
be numbers of cases reported across UP in the
9
coming months .
The situation in Bihar stands in marked contrast
to UP. 12 of the 13 cases from Bihar had onset in
the first 4 months of the year. Since
April 19 only one case has been reported, in Patna.
9
Transmission in Bihar is clearly very restricted .
There is dj vu of what we had seen in 2002. In
2000 and 2001 there was promise, with the then
Fig. 2. Wild poliovirus (WPV) cases in 2005 and WPV importation routes during 2002-2005 worldwide
Source : CDC
37
2006; 8(3) : 223
lowest numbers on record namely 265 and 268,
that things were going well, but 2002 turned out
an outbreak year. Four years later, the situation
looked good towards the end of 2005, but then
and outbreak has developed now. So, there is
growing anxiety, as we are not able to reach the
goal of eradication even in 2006, six years overdue
from the original target year of 2000. Previously
1998 and 2002 were years of upswing in numbers
of cases; now 2006 shows the same pattern
4 years later. This is disconcerting. Had
transmission continued but the number of cases
was less than in 2005, optimism would have
10
prevailed .
Bihar, the other hot spot polio endemic state,
has for the first time surpassed the U.P. tally last
year (30 vs. 29 cases). The situation in Bihar
stands in marked contrast to UP. 12 of the 13
cases from Bihar had onset in the first 4 months
of the year. Since April 19 only one case has been
Indian Journal of Practical Pediatrics
reported, in Patna. Transmission in Bihar is clearly
very restricted. The wild virus activity, it seems,
has confined to only these two states. The AFP
surveillance sensitivity has improved substantially
since mid 2004, and genetic sequences data
indicate that transmission is substantially restricted,
with only two P-1 genetic clusters circulating in
2005 (down from 10 in 2003 and 4 in 2004),
whereas only one cluster of P-3 virus was
responsible for all four P-3 cases in western U.P .
9 Apart from Pakistan and Afghanistan, two
Pakistan (27 cases) and Afghanistan (7 cases),
the other two endemic countries of the
subcontinent, have shown remarkable progress in
2005. In 2005, 27 cases were reported in Pakistan
compared with 53 of the same period in 2004.
The primary risk to Pakistans polio eradication
efforts remains restricted access due to insecurity
in some areas of the country, most notably the
2
tribal areas bordering Afghanistan .
However, while Pakistan continued to show good
control (only 13 cases in 2006, till 18th August),
the situation in Afghanistan deteriorated
alarmingly. Afghanistan has seen a six-fold rise in
the number of polio cases over last year
(25 cases confirmed in 2006, compared to 4 cases
in the same period in 2005). All but one of these
cases is in the southern region of the country,
where the current security situation has made it
nearly impossible for health teams to reach
11
children . The transmission of virus is made easier
by frequent population movements into and from
neighbouring Pakistan, one of the three other
polio-endemic countries. This corridor of
transmission stretches from the Southern Region,
into Pakistans Balochistan and northern Sindh/
southern Punjab. In response, Afghanistan and
Pakistan continue to synchronize Supplementary
Immunization Activities (SIAs) .
11
Pakistan has only reported 13 cases so far in 2006.
In Pakistan, wild poliovirus is surviving only in
minority-underserved populations, including
nomadic groups and other mobile populations,
38
2006; 8(3) : 224
generally in less well-populated areas.
Transmission survives in these groups because
children have not been consistently reached during
immunization activities. The priority for the
programme in Pakistan now is to identify these
groups and access them during the remaining
rounds in 2006, to ensure that transmission is
completely stopped by the end of the year.
other countries of the sub-continent-Bangladesh
(10 cases so far till 18th August 2006) and Nepal
(1 case) have reported importation of wild virus
from India. Bangladesh had been polio-free for
five years before the first case was confirmed in
March of this year-an importation from India
(Bihar). That one case sparked the three NIDS
which reached 96% of the 22 million children aged
under five. This, however, has not stopped the
outbreak with a further 10 cases being confirmed
in the past month11. Nepal has also reported one
case again an imported wild virus from Bihar
(India).
The new strategies to tackle imbroglio in
western UP
The first necessary step is to realize that higher
quality performance is essential in western UP
than everywhere else10. The primary players are
the government, the health system officers, the
staff and the volunteers, facilitators, social
mobilisers and monitors. It is not that they have
not done their job reasonably well, but that they
must do it even better. All partner agencies must
work harder and work together and work in
unison.
The second step is to maximize the use of the
monovalent OPV, which has better efficacy for
the given type (here type1), than trivalent OPV.
The government has already progressed in this
direction. A birth dose of OPV has been introduced.
Monovalent OPV will replace trivalent OPV in
the endemic communities. It will certainly

improve vaccine efficacy of OPV but perhaps not
to the level that will result in herd effect and
interruption of transmission10.
A third step to improve protection in the very
young is to give the inactivated polio vaccine
(IPV), which is highly immunogenic with 3 doses
and sufficiently immunogenic even with 2 doses10.
The Drugs Controller General of India has
appreciated this need and has very recently
licensed IPV for use in India. IPV has potential
role in the long term, but let us look at the short-
term need, opportunity and tactic. Ideally IPV
should be enmeshed with routine vaccination
schedule, 3 doses per infant, but we know that
the coverage will be dismally low. In the
immediate future we can use IPV to expedite the
process of infant immunization and thereby
supplement the vaccine efficacy. For that purpose
a campaign mode may be the only way. The
introduction of IPV, if and when it comes, should
be an additional intervention, without in any way
diluting whatever is being achieved by OPV9,10.
Threats to ongoing eradication initiative
The polio eradication initiative is
characterized by multiple setbacks, frequent
delays, scarcity of funds, and religious opposition.
However, the greatest threat to on going program
is now posed by the following phenomena.
1. Importation of wild virus to polio free
countries
As stated earlier, the most significant
development of 2005 was importation of large
number of WPVs from endemic countries to polio
free countries. This phenomenon will continue to
occur until endemic WPV transmission is
interrupted globally. It is simply not sufficient to
achieve zero polio status; more arduous task
would be to maintain this status, year after year.
As happened in Indonesia- after remaining polio
free for 10 consecutive years, the country
39
2006; 8(3) : 225
witnessed first case of imported WPV in May
2005 and before any outbreak response measure
could be taken, epidemic engulfed six more
provinces of the country leading to moe than 300
clinical cases!7
The risk of importation is highest for countries
adjacent to endemic countries, but importations
over long distances also occur. Globalization and
international migration pose a risk for re-
introduction of WPV for all countries. Inability to
achieve and / or maintain high routine
immunization (RI) coverage in the absence of
periodic NID, predisposes some countries with
imported WPV to re-establishment of polio
transmission within their borders3,4,7.
2. Vaccine associated paralytic poliomyelitis
(VAPP)
VAPP is one of the few inherent weaknesses
of the OPV. In the face of diminishing burden of
WPV cases every year, we have now reached a
state where burden posed by VAPP has become
much greater than the wild virus itself. Already,
voices of dissent asking for more transparency
on actual burden of VAPP in the country and
demanding compensation for the victims of VAPP
are emanating from different quarters12. Most
experts believe that the risk is lower in India and
put it around 100-200 cases per year13,14.
In recent times, a new variant of VAPP called
imported VAPP is documented in an
unvaccinated US adult, who traveled abroad15.
This highlights the previously unrecognized risk
for paralytic polio among unvaccinated persons
exposed to OPV during travel abroad.
3. Circulating vaccine derived polioviruses
(cVDPV)
This is yet another looming threat posed by
continuous use for OPV and again highlights the
inherent weakness and risk of using live oral
vaccine. Fortunately, in India, there is no instance
Indian Journal of Practical Pediatrics
of cVDPV so far but continued use of OPV
perpetuates this risk at every location. Many
experts believe that even the discontinuation of
OPV may pose a risk for the development of
cVDPV during the 3-5 years period after cessation
of OPV16. World over, seven outbreaks of cVDPV
have been recognized most recent being in
Indonesia. Hence, both VAPP and cVDPV are
ethically incompatible with eradication17.
Reasons behind the delay
When GPEI was launched in 1988, the year
2000 was set as the target year to achieve the
goal of polio eradication and certification of
eradication by 200518. However, with the frequent
set backs suffered in last few years particularly in
developing, third world countries, the first deadline
is already a matter of history19. Strong voices of
dissent questioning the achievements of GPEI so
far and dubbing it as yet another exercise in
mismanaging the health priorities and programs
in developing countries in the era of globalization
have started emanating20.
1. Poor efficacy of OPV in endemic regions
(Vaccine failure)
OPV was the right choice to begin the
massive, synchronized global exercise and it did
deliver goods in restricting the wild poliovirus to
certain limited geographical regions. It has certain
inherent weaknesses like VAPP and cVDPVs.
But, the greatest drawback of OPV is its
unpredictable immune response in a vaccinee.
Even after administration of 10 doses, one can
not be sure whether the vaccinee has developed
adequate immune protection or not. For example,
in India in 2005, 33% of children with confirmed
polio had received 10 or more doses 16 .
Historically, it is believed that control of
poliomyelitis can be achieved by properly
immunizing 80-85 % of the at risk population 21.
In some high-risk districts of western U.P., despite
achieving coverage as high as 96.5 %, OPV failed
40
2006; 8(3) : 226
to break wild virus transmission and 7.25 %
children of a study group failed to show
seroconversion to any of the three sero-subtypes22.
Though it could also be due to over reporting of
the coverage to some extent.
The OPV has geographic variation in
efficacy- high in industrialized nations, low in
Taiwan, and Oman, lower still in many developing
countries23 due to host factors like concomitant
infections, malnutrition, programmatic factors like
cold chain maintenance failures and environmental
factors, requiring substantially more doses to
seroconvert for such an individual5. In the foci of
persistent transmission, the efficacy may be the
lowest. Low vaccine efficacy spells low
effectiveness and low herd effect; all factors that
make the vaccine a poor match to the task of
interrupting the transmission of the most
transmissible among wild poliovirus types namely
type 123. India, Pakistan, Egypt, and to some
extent Nigeria, provide the toughest challenge to
effectiveness of OPV in halting the wild virus
transmission. High population density, sub-optimal
sanitation, concurrent enteroviral infection,
interference among 3 sero-subtypes of Sabin
viruses, sub-optimal practices of vaccine handling,
poor coverage and at times over-reporting of the
coverage which gives a false sense of security
along with tropical climates combine to lead to
failure to curtail the transmission of wild
poliovirus5,19.
Hence, OPV was the right tool to start with
but we all failed to anticipate the current
shortcoming of the vaccine in final phase of the
GPEI, particularly in some most hostile geographic
regions. As a result, neither alternate strategy nor
other options were envisaged to deal with current
imbroglio24. Though, monovalent OPV might
salvage the situation to some extent, it is also not
devoid of some of the most inherent deficiencies
of its precursor. The presumed failure of OPV to
combat ongoing transmission of wild virus in few

pockets of endemic countries like India despite
using it very aggressively in its most potent form
pose the greatest challenge to the ultimate success
of GPEI.
2. Programmatic hiccups
Failure to reach all children below five years
of age in some highly endemic regions, suspension
of all forms of polio activities in Nigeria in 2003-
2004, resistance to OPV among some religious
community in India and Nigeria, poor quality of
SIAs, inadequate engagement and involvement
of the general community, failure launch an
effective, aggressive IEC, lack of co-ordination
amongst enforcing agencies, programmatic fatigue
and inertia are the main factors that halted the
swift progression of the initiative25,26.
3. Peculiar epidemiology of type 1 poliovirus
in endemic regions
The vast difference in the epidemiology and
environmental factors in different parts of the
world provided conducive ground and force for
wild virus transmission. The strategy adopted in
the regions where force of transmission is low did
not work in places with high force of transmission
such as India, Egypt and Nigeria 27. Wild
polioviruses have been eliminated nearly from all
low-income countries with low or moderate force
of transmission with lesser efforts. However, high
density of population, relatively high birth rates
and consequent high density of infants and
toddlers- the most efficient amplifiers and
transmitters of WPV, poverty, low literacy, low
living standards with poor sanitation and hygiene
form a milieu of formidable high force of
transmission in these last remaining endemic
countries23,27. Interventions that worked in other
poor communities and countries may not be
sufficient to overcome such exceedingly high force
transmission. We failed to recognize this
geographic variation in behavior of wild poliovirus,
especially type 1, and are now facing the prospects
41
2006; 8(3) : 227
of losing control over the eradication imitative.
4. Neglect of routine immunization (RI)
Routine immunization (RI) is unarguably the
weakest link and probably is the most neglected
area of the four pronged eradication strategy.
The current strategy has put all the emphasis on
SIAs. It seems the strategist do not have much
faith on the effectiveness of RI and by increasing
the frequency of SIAs, they have indeed left
nothing for the strengthening of RI19. This is
certainly a major setback. Even if transmission is
broken and zero polio status is achieved through
high quality SIAs, it is ultimately RI that will
determine the herd immunity and will thwart
any attempt of importation of the disease in the
community. As the recent episode of importation
of WPV in 21 previously polio free countries
shows, the 8 countries with no sustained WPV
transmission after importation of the virus differed
considerably in RI status from 13 countries where
transmission following importation was
sustained7. According to WHO /UNICEF estimate
for 2003, the median vaccination coverage with 3
dose of OPV (OPV 3) by 12 months of age in the
8 countries without sustained spread was 83%,
compared with a median coverage of 52 % in the
other 13 countries (P = 0.001)7. Hence, the
robust RI would be the greatest deterrent to the
greatest threat to polio free status the importation
of wild viruses! The current status of RI in some
of the highly endemic countries is indeed pitiable25.
5. Conflict, social unrest and accessibility
problem
Conflict among community and presence of
political vacuum in certain war affected countries
like Sudan, Afghanistan, and Angola have already
adversely affected the ongoing eradication
campaign. Afghanistan, Pakistan, Sudan and
Somalia are the few countries where major
security risks have made covering the entire
population for vaccination extremely challenging.
Indian Journal of Practical Pediatrics
Frequent floods in Bihar (India) and fierce
resistance by some religious communities in
northern Nigeria have also made the task of
volunteers more difficult.
6. Lack of foresight and flexibility
The greatest flaw of the current strategy was
almost exclusive and over reliance on OPV to
achieve the goal. The conceivers of the program
failed miserably to even anticipate OPVs limitation
in final stages of polio eradication in some of the
most stubborn regions of the world. Apart from
keeping the option of using monovalent OPV in
final stages and during post eradication phase, they
failed to device an alternate strategy to break wild
virus transmission where OPV was found wanting
and quite unequal to the task. The enforcing
agencies did fail to anticipate the current scenario
in endemic countries where intense, high force
transmission of type 1 WPV almost rendered the
OPV redundant.
How far is the goal?
Undeniably, the whole initiative has made a
remarkable progress in terms of over 90 %
reduction in WPV cases ( from 350,000 in 1998
to 1932 cases in 2005) and an impressive
curtailment in total number of endemic countries
(125 to 4 by 2005). Three WHO regions have
already been declared polio free, WPV type 2
has not been isolated anywhere in the world since
October 1999, WPV type 3 has only very few
clusters confined to few endemic countries
only2,19. But the fact remains that even after 18
years of uninterrupted global efforts; we have still
not been able to accomplish the first task the
interruption of wild virus transmission from half
of the globe!
As we all know that merely making any
country polio free is not sufficient. Certification
is conducted on a regional basis. Each region can
consider certification only when all countries in
42
2006; 8(3) : 228
the area demonstrate the absence of WPV
transmission for at least three consecutive years
in the presence of excellent surveillance. As of
now, none of the remaining three WHO regions
have achieved polio free status even for a single
year. Worse, the recent re- introduction of
type1 WPV into several previously polio free
countries have further compounded the worries
associated with the plan. Some countries like
Indonesia after remaining polio free for 10 years
had to restart all the suspended activities of SIA
from the scratch once again. Hence, a most honest
and dispassionate analysis of the performance of
GPEI would reveal that the proposed eradication
plan is quite a complex issue.
How to move forward?
The first and foremost objective for the year
2006 is to urgently halt the ongoing intense wild
virus transmission in remaining endemic countries
and at the same time, to maintain a high level of
immune coverage in most polio free countries,
particularly those bordering with endemic ones.
Quickly stopping polio outbreaks in previously
polio free countries should top our agenda. The
WHO Advisory Committee on Polio Eradication
(ACPE) recommends that any polio free country
that detects imported WPV should immediately
obtain a risk assessment by an international expert
group and prepare a large scale response plan
(within 72 hours of case confirmation) and conduct
three large scale house-to-house immunization
campaigns using type-specific mOPV, initiating the
first round within 28 days of confirmation of the
case7. If we do not stick to these guidelines, the
world would soon experience more instances of
inter-continental importation and rapid resurgence
of polio worldwide. The only deterrent to prevent
importation of WPV is a robust RI coverage.
Hence, addressing low RI rates in certain polio
free countries should take the top most priority.
However, apart from these established
measures, we must look for certain unconventional

approaches. What they could be? Though ground
implementation of some of them may seem
unfeasible, but the current situation definitely
warrants some serious consideration to these
innovative albeit unconventional options. After all,
desperate situation demands desperate measures
and we all must know the time is fast running
out. We cannot afford to push the deadline beyond
a certain limit.
A. Targeted use of IPV
Use of IPV in post eradication phase is quite
complex- depending upon the will and resources
of an individual country. But what is the use of
IPV in the ongoing, pre eradication phase of GPEI
in some most challenging endemic regions of the
world such as India. We have already exercised
the option of maximizing immune response of
OPV by using monovalent type 1 and type 3 OPV
in endemic states of UP and Bihar. But even that
intervention, it seems, failed to break the deadlock.
What next then? Targeted use of currently
available IPV in local endemic areas, preferably
in combination with DPT may not only boost the
sagging RI state but can also augment OPV in
halting the ongoing intense wild virus transmission.
This move might also take care of circulating
VDPV and VAPP the two inherent weaknesses
of its oral counterpart. The fear of most western
agencies involved with GPEI, whether developing
countries with tropical settings will be able to
achieve good coverage (i.e. more than 90 %) with
IPV is not quite unfounded. However, with a lesser
effort than in some northern states of India (UP
and Bihar), most southern states of the country
(Tamil Nadu and Kerala, particularly) are able to
achieve >95% coverage of third dose of DPT17.
Hence, with good programmatic management
similar results can be achieved in endemic states
also. The DPT- IPV combination in RI along with
OPV supplied through SIAs would greatly enhance
the chances of rapidly breaking WPV transmission
in endemic regions. Indian studies had already
43
2006; 8(3) : 229
shown very high efficacy of IPV and low efficacy
of OPV in tropical settings. On the other hand,
western studies showed complete safety of IPV
but not of OPV17.
B. New polio vaccines for end game and
post eradication phase
The current IPV is made from three wild
poliovirus strains (Mahoney type 1, MEF type 2
and Saukett type 3). The risk of accidental or
intentional release of wild strains from IPV
manufacturing sites would pose a significant risk
to the polio-free world. Hence, ultimately, we
would need to part away with current IPV also to
make the gains of polio eradication permanent.
What would be the next option then? Development
of new vaccine candidates to tackle the biosafety
concerns would be most prudent approach. Why
didnt we look for this option earlier? Why did
we continue to rely heavily only on the two
vaccines developed some 50 years ago despite
knowing their inherent weakness and formidable
challenges ahead. This is indeed a mystery.
Instead, we should have looked for safer, more
efficacious and cheaper polio vaccines. We all
knew well in 1999 that the proposed goal of
eradication would be unachievable in 2000. Yet
no attempt was made device better strategies.
The work on new polio vaccines was started
in mid-1980s where various types of poliovirus
antigens were investigated in depth for their
immunogenicity. They included peptides, proteins
and vector vaccines using vaccinia 28. The
conclusion at the time was that none of these
approaches offered a practical way forward, and
the existence of two highly effective vaccines
made further development in a manufacturing or
marketing sense unlikely. This is believed to
remain the case at present, but it might be of interest
to revisit capsid formation by non-polio expression
systems such as DNA vaccines for post
eradication era. This would be the only vaccine
Indian Journal of Practical Pediatrics
type not associated with risk of poliovirus
infection.
Though DNA polio vaccine appears to be
the most desirable one to use, currently the most
exciting prospect seems to be the development of
IPV from the virus strains used for making Sabin
OPV. The Sabin-IPV made from, live,
attenuated strains of OPV, would have lower
transmissibility. Three manufacturers (Japanese,
Chinese and Indian) of the world are currently
involved in its manufacturing but so far are not
able to develop a licensed product. Even WHO
has recently shown great interest in SabinIPV
and urged acceleration of studies demonstrating
its safety, efficacy, attenuation and possible use
in near future 29 . Potential difference in
immunogenicity and antigenicity between Sabin
and conventional IPV strains need to be
investigated and may necessitate modification in
order to achieve equivalent protection.
In addition to live strains for which there is
clinical experience, there are a number of other
strains designed on molecular biological principles,
which are likely to be suitable for consideration
as new IPV seeds28. Over the past 20 years the
molecular basis of the attenuation of the Sabin
vaccine strains has been studied in detail, and it is
considered possible to exploit this understanding
to create new live attenuated strains.
Points to remember
1. The GPEI despite experiencing frequent
setbacks, delays and new evolving
challenges has made handsome progress
towards achieving its final goal.
2. New emerging threats like importation of
wild virus to polio free countries and
epidemics of circulating VDPVs have
compounded the problems of the initiative.
3. There is urgent need to rapidly halt the
ongoing intense wild virus transmission in
44
2006; 8(3) : 230
endemic countries that call for more
flexibility in approach and to venture in to
some unconventional, innovative
interventions.
4. The program initiators must do a thorough
dispassionate reappraisal of the whole
strategy and should set new targets and
timelines.
References
1. CDC. Progress toward interruption of wild
poliovirus transmission world wide, January
2004- 2005. MMWR 2005; 54: 408-412
2. World Health Organization. Polio eradication
monthly situation report- February 2006.
Available at www.polioeradication.
www.polioeradicationorg/casecount.asp .
Accessed on February 20, 2006.
3. CDC. Resurgence of wild poliovirus type 1
transmission and consequences of
importation- 21countries 2002 2005.
MMWR 2006 ; 55 (06):145-150.
4. Vashishtha VM, Shah RC, Thacker N and John
TJ. Importation: The greatest threat to polio
free countries. Bulletin of Polio Eradication
Committee, Indian Academy of Pediatrics
2005, (December)2: 13-15.
5. World Health Organization. Global Polio
Eradication Initiative Strategic Plan 2004-
2008. Weekly Epidemiol Rec 2004;79:55-57.
6. CDC. Progress towards poliomyelitis
eradication, Nigeria, January 2004-July 2005.
MMWR 2005; 54: 873- 877.
7. World Health Organization. Resurgence of
wild poliovirus type 1 transmission, and effect
of importation into polio free countries, 2002-
2005. Weekly Epidemiol Rec 2006(7), 81:
63-68.
8. National Polio Surveillance Project, India.
Available at http://www npspindia.org
Accessed on February 21, 2006.
9. Conclusions and Recommiutations. Special
Interim Meeting of the India Expert Advisory

Group for Polio Eradication, New Delhi, India,
th
28 July, 2006.
10. John TJ, Shah NK, Thacker M, Vashishtha VM.
Editorial. Polio eradication: Learn from failure
to create success. Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics 2006 (August) Vol 3 (In press).
11. Global polio Eradication Initiative-
Country Profile. Available at http://
www.polioeradication.org/countries.asp
Accessedx on August 19, 2006.
12. Paul Y, Dawson A. Some ethical issues arising
from polio eradication programs in India.
Bioethics 2005; 19 (44): 393-406.
13. John TJ. A developing country perspective on
vaccineassociated paralytic poliomyelitis.
Bull WHO 2004; 82: 53-57.
14. Shah RC, John TJ, Thacker N, and Vashishtha
VM. Vaccine associated paralytic
poliomyelitis (VAPP). Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics, 2005; 2: 6-7.
15. CDC. Imported vaccine associated paralytic
poliomyelitis United States, 2005. MMWR
2006 3; 55(4): 97- 99.
16. John TJ, Shah RC, Shah NK, Thacker M,
Vashishtha VM. Editorial. Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics 2005 2 :2-3.
17. John TJ. Will India need inactivated poliovirus
vaccine (IPV) to complete polio eradication?
Indian J Med Res 2005; 122: 365-367.
18. The Global Eradication of Polio- A polio free
world in 2005. Available at http://
www.polioeradication.org/strategies.aso http:/
/wwwpolioeradication Accessed on February
20, 2006.
NEWS AND NOTES
APLS: The Pediatric Emergency Medicine Course
Contact Course Director: Dr. Suresh Gupta, Sir Ganga Ram,Hospital, New Delhi - 110 060.
Phone : 9811426628, 28312656, 28312591
2006; 8(3) : 231
19. Thacker N, Vashishtha VM, and Krishna SA.
Polio eradication: How far we have reached
and where have we gone wrong? Pediatr Today
2005; (8): 320-24.
20. Sathyamala C, Mittal O, Das Gupta R and Priya
R. Polio eradication initiative in India:
Deconstruction the GPEI. Int J Health Ser
2005; 35(2): 361-83.
21. Nightangel O. recommenation for a national
policy onpoliomyelitis vaccination. N Eng J
Med 1977;297:249.
22. Hasas AS, Malik A, Shukla I and Malik MA.
Antibody levels against polioviruses in children
following pulse polio immnization program.
Indian Pediatr 2004;41:1040-1044.
23. John TJ. Polar Spectrum of problems in polio
eradication. Indian J Med Res 2004;120:133-
135.
24. Vashishtha VM. But do we have other option?
Indian J Pediatr 2004;71:183-184.
25. Thacker N. Shendurnikar N. Current status of
polio eradication and future prospects. Indian
J Pediatr 2004;71:241-245.
26. John TJ, Thacker N. Despande JM. Setbacks
in polio eradication in India: Reasons and
Remedies. Indian Pediatr 2003;40:195-203.
27. John TJ. The vicissitudes of global eradication
of polio. Indian J Med Res 2004;120:133-135.
28. World Health Organization. New polio
vaccines for the post-eradication era.
Department of vaccines and Biologicals,
Geneva 2000. Available at at http://
www.who.int/vaccines-documents/ Accessed
on February 24, 2006.
29. World Health Organization. AACPE
recommendations. Weekly Epidemiol Rec
2004;79:401-408.
24-25 March 2007
Email: drguptasuresh@yahoo.co.in
45
Indian Journal of Practical Pediatrics
VACCINES
HEPATITIS VACCINES - CURRENT
CONCEPTS
*Ashish Bavdekar
**Sheila Bhave
Abstract: Hepatitis A is the commonest cause of
acute sporadic hepatitis and acute liver failure
in Indian children. Atypical clinical manifesta-
tions, co-infections and acute infections in adults
are being increasingly reported. Some regions
in the country have shown an epidemiologic shift
of HAV infection from early childhood to
adolescents and adults. HA vaccination has a
definite role in these regions to prevent epidemics
and protect against severe HAV infection in
adulthood. Both the inactivated and live
attenuated HA vaccines are safe, immunogenic
with long-lasting protective efficacy. Hepatitis
B vaccination not only prevents HBV infection
but also associated chronic liver disease and
hepatocellular carcinoma. Many vaccination
schedules have been used, with similar
immunogenicity. Effectiveness of the vaccine in
reducing the burden of hepatitis B is well
demonstrated in countries adopting the universal
immunization program. Hepatitis E vaccine is
undergoing clinical trials while the hepatitis C
vaccine is still in early experimental stage.
Key words: Hepatitis A, B, C, E; Vaccines
Five different viruses appear to target the liver
and produce liver disease as their main
* Consultant Pediatric Gastroenterologist,
Liver & Gastroenterology Unit,
K.E.M. Hospital, Pune.
** Consultant in Pediatric Research,
Department of Pediatrics,
K.E.M. Hospital, Pune.
46
2006; 8(3) : 232
manifestation. Hepatitis A virus (HAV) and
hepatitis E virus (HEV) are non-enveloped RNA
viruses that are spread predominantly by fecal
oral transmission and cause acute hepatitis in
children and adults. Hepatitis B virus (HBV) and
hepatitis C virus (HCV) are enveloped viruses
causing acute as well as chronic hepatitis. Their
route of transmission is usually parenteral though
HBV may also have a horizontal transmission
among young children. Hepatitis D virus (HDV)
is a defective virus that co-infects and requires
HBV for its expression. Vaccines against HAV and
HBV are now routinely available while vaccines
against HEV and HCV are still in various phases
of development. The hepatitis vaccines have two
purposes : to prevent the morbidity and occasional
mortality associated with acute hepatitis virus
infection and to reduce the occurrence of chronic
hepatitis, cirrhosis and hepatocellular carcinoma.
This article briefly reviews the current status of
hepatitis vaccines.
Hepatitis A vaccines
Hepatitis A (HA) is the commonest cause of
acute sporadic hepatitis and acute liver failure in
Indian children. Generally the disease is mild and
self limited. However, recently, atypical
manifestations like significant ascites, edema,
pleural effusions, skin rashes, firm to hard
hepatosplenomegaly, prolonged recovery, severe
anemia and coagulopathy are commonly seen.
Co-infections of HAV with other infections like
HEV, HBV, typhoid fever, dengue fever,
malaria, etc are also increasingly encountered1.
HA vaccines were originally recommended
for high risk groups only. These included travellers

to endemic countries, children with chronic liver
disease, health personnel, persons using clotting
factor concentrates, etc. However nowadays, in
many countries, the vaccine is increasingly added
to vaccination programs in areas of intermediate
endemicity for HAV. In some regions of India,
recent studies have indicated evidence of
epidemiological shift (shift of age of infection from
children to older age groups) of HA infection
especially in the higher socioeconomic groups2.
With continuing economic development and
subsequent improvement in sanitation and hygiene,
more and more areas will show this shift. These
areas are at risk for epidemic outbreaks in children
and adults as was recently reported in Kerala. In
these vulnerable populations, HA vaccination has
a definite role to prevent epidemics and protect
against severe HAV infection in adulthood. The
Indian Academy of Pediatrics (IAP) has
recommended HA vaccine as an additional vaccine
to be offered to children > 1 year of age belonging
to high socio-economic strata.
Humans are the only known reservoir for
hepatitis A virus. Thus, the virus could theoretically
be eradicated if a widespread immunization
program is implemented. Several hepatitis A (HA)
vaccines are available including the formalin-
inactivated vaccines with and without aluminum
hydroxide as an adjuvant, live attenuated vaccine,
and combined hepatitis A and hepatitis B vaccine.
Inactivated vaccines: Currently four inactivated
vaccines are available worldwide. All these
vaccines are safe, well tolerated, highly
immunogenic and licensed for children aged
> 1 year (except in USA where it is licensed for
children > 2 years of age). The vaccine is
administered intramuscularly in the deltoid region.
The previous three-dose immunization regimen
of 0, 1 and 6 months has been replaced by a two-
dose schedule, given at 0 and 612 months. The
adult dose (> 18 years) is generally twice that of
the pediatric dose. Most studies demonstrate a
47
2006; 8(3) : 233
seroconversion rate of 95-100% (defined as an
anti-HAV antibody level of >20 mIU/mL) after
vaccination in both adults and children 3,4. Anti-
HAV antibodies immediately after immunization,
though 10 to 100 fold lower than that following
natural infection are still very high than the
minimum titer required for protection against HA
infection. There is a gradual decline in antibodies
over time and mathematical modelling studies
assuming a constant rate of decline in antibodies,
suggest that antibody may persist for 2030
years 5. Infants under the age of 1 year with
maternal anti-HAV achieve slightly lower
seroconversion rates (93100%) and lower
geometric mean titres. Nevertheless, studies in
such infants reveal a substantial and rapid
(anamnestic) immune response to HAV antigen,
suggesting that protection may be long lasting even
when anti-HAV is no longer detectable6. This
suggests the existence of a robust recall response
and long-lasting immune memory that make
booster immunization of immunocompetent
individuals unnecessary 7 . The antibody
concentration achieved with the HA vaccine is
much greater than the concentrations reached with
protective doses of immune globulin (IG) and the
response is also much more long-lasting.
A toddlers-only universal immunization program
in Israel using inactivated HA vaccine has not only
reduced the annual incidence rate of hepatitis A
from 50.4 per 100,000 to 2.2 per 100,000 but
also demonstrated marked herd protection8.
Reduced immunogenicity: Seroconversion rate
is less in persons with chronic liver disease (93%),
immunocompromised state (88%), HIV infection
(77%), transplant recipients (26%) and elderly
(65%)9.
Adverse reactions: The HA vaccines have an
excellent safety profile. Reported adverse events
in children have been local pain at the injection
site (15-19%), feeding problems (8%), headache
(4%), injection site induration (4%). There were
Indian Journal of Practical Pediatrics 2006; 8(3) : 234

no accounts of elevations in serum transaminases. effects. A 3-dose schedule of 0, 1 and 6 months

Vaccinating already immune persons did not is suggested using the pediatric vaccine for children
increase the risk of adverse events10. between the ages of 1-15 years and the adult
Simultaneous administration with other vaccine after 15 years. Recent studies have looked
vaccines: The inactivated HA vaccine can be into the possibility of using only 2 doses of the
given concurrently with vaccines for diphtheria, pediatric or adult vaccine for better compliance11,12.
polio, tetanus, hepatitis B, typhoid, cholera, While the results of these studies are quite
Japanese encephalitis, rabies, or yellow fever encouraging, more data is needed before the 2-
without adversely affecting immunogenicity or dose schedule can be recommended. Information
safety. It is recommended that the injections be on the duration of antibody response following
given at different sites. The vaccine can be given vaccination with a combined vaccine, and role of
with immune globulin at different sites. booster is not yet clear. This vaccine has a role in
Combined Hepatitis A and B vaccine: Clinical catchup vaccination of children who have missed
trials evaluating a combined HA and hepatitis B hepatitis B vaccination in infancy (Table 1).
vaccine have shown consistently high
seroconversion rates with no appreciable adverse Post-exposure prophylaxis: The efficacy of
hepatitis A vaccine as post exposure prophylaxis
Table 1. Immune prophylaxis for Hepatitis infections
Infection Passive Active Comments
Immunisation Immunisation
Hepatitis A Immunoglobulin Inactivated vaccines IG protection short lasting (3-5 months)
(IG) and expensive. Recommended for
Live attenuated for post-exposure prophylaxis within
vaccine 2 weeks of exposure
Both vaccines safe, immunogenic and
provide long term protection.
Hepatitis B HB Immune Recombinant DNA HBIG indicated for babies of HBsAg
Globulin (HBIG) vaccines +ve mothers and post-exposure
prophylaxis
HB vaccines safe and immunogenic
Indicated for universal immunization
Combined HA and Combined vaccine useful for catch-up
HB vaccine vaccination
Hepatitis D IG ineffective No specific vaccine Prevention of HBV infection by HB
vaccine will prevent HDV infection
Hepatitis C IG ineffective. Vaccine in IG not recommended for post exposure
experimental stages prophylaxis
Hepatitis E Role of IG Phase II, III studies IG from plasma collected in HEV non
unclear ongoing endemic areas not protective. IG from
plasma collected in HEV endemic areas
unknown efficacy

48

in outbreak settings without accompanying
immunoglobulin is still unclear. One small study
has shown a protective efficacy of 79% when
given within 8 days of symptom onset of the index
case while other studies have shown that vaccine
alone may be insufficient 13.
Live Attenuated Vaccines: The use of attenuated
live HA vaccines has been evaluated in both
animals and humans. The attenuated H2 strain
HAV originating from the feces of a 12 year old
child with hepatitis A has undergone extensive field
trials in China and is now available in India. It is a
freeze dried live vaccine licensed for subcutaneous
use in children > 1 year of age. The vaccine
induces not only neutralizing antibody but also
cell mediated immune response. The vaccine is
well tolerated and highly immunogenic.
Seroconversion in subjects 2 months and 10 years
after vaccination was 98.6% and 80.2%
respectively14. There were no major side effects,
and elevations in serum transaminases were not
noted. In regions in China where mass vaccination
programs have been introduced, there has been
over 95% reduction in Hepatitis A related
morbidity and no cases of HA has been reported
since 199914. At KEM Hospital, Pune, a 96%
seroconversion rate was observed in a study of
144 children between the ages of 1-12 years
immunized with a single dose of the live attenuated
hepatitis A vaccine. (unpublished observations).
The vaccine is given as 0.5 ml sub-cutaneoulsy
and only single dose is recommended by the
manufacturers.
Hepatitis B (HB) vaccine
The first HB vaccine was derived from
HBsAg particles of chronic hepatitis B carriers.
Though this vaccine had excellent immunogenicity
and safety, the plasma origin was of concern.
Hence recombinant vaccines produced by cloning
the HBV S gene in yeast cells are now being
49
2006; 8(3) : 235
widely used all over the world. HB vaccines are
available as single antigen formulations or fixed
combinations with other vaccines hepatitis A,
hemophilus influenzae type B, DPT and IPV.
Seroconversion: Protective anti-HBs antibody
levels of at least 10mIU/ml appear in 90% of
healthy adults and 95% of infants and children
after vaccination. Administration of HB vaccine
with other childhood vaccines does not produce
any significant interference in antibody responses
and vaccines made by different manufacturers are
interchangeable. Increasing age, obesity, smoking,
chronic renal failure, renal dialyses, organ
transplant recipients and immunosuppressed
individuals are at risk for reduced response15.
Duration of protection: Anti-HBs levels decrease
over time and 50-80% of vaccinees may have
levels below 10mIU/ml 12 years after
vaccination 16. However there have been no
symptomatic hepatitis B cases among this group.
This is probably due to priming of memory cells,
which are capable of eliciting an anamnestic
response when challenged. Post vaccination testing
1-2 months after the last vaccine dose is not
required except in newborns of HBsAg mothers,
health care workers and individuals with risk
factors for poor response.
Need for booster doses: Booster doses are not
routinely recommended for persons with normal
immune status but may be necessary in the
individuals with risk factors for poor response.
Annual anti-Hbs testing and booster doses when
anti-HBs level drops to below 10mIU/ml may be
considered in this group.
Effectiveness: As long-term follow-up studies are
now available, the beneficial effects of HB vaccine
are now increasingly apparent. In Taiwan, the
prevalence of HBsAg positivity among children
15 -20 years old decreased from 9.8% (born before
universal immunization program) to 0.7% (born
Indian Journal of Practical Pediatrics
after universal immunization program). 12-14%
of babies born to HBeAg positive mothers and
3-4% of the babies born to ani-HBeAg positive
mothers became carriers following vaccination (as
compared to 86-96% and 10-12% without
vaccination respectively). The incidence of
hepatocellular carcinoma per 100,000 also declined
from 0.7 in 1981-86 to 0.36 in 1990-9413.
Safety: The currently licensed HB vaccines are
safe. Mild adverse reactions are reported in 1-3%
and include low grade fever, pain at injection site,
headache, myalgia etc. Estimated anaphylaxis
incidence is 1 per 1.1 million vaccine doses.
Association between HB vaccination and Guillain
Barre syndrome or multiple sclerosis is not proven.
Rarely illnesses like chronic fatigue syndrome,
leucoencephalitis, optic neuritis, transverse
myelitis, rheumatoid arthritis, auto-immune
disorders, type I diabetes, alopecia have been
reported after HB vaccination but no causality
has been demonstrated17.
New vaccines: A commercially available triple
recombinant mixed particle vaccine containing pre-
S1 and pre-S2 regions has been shown to be
immunogenic in nave individuals and previous
non-responders18. A two dose regimen has been
found to be as effective as the three dose one. Its
present role is still unclear. Other newer vaccines
in various stages of development are single dose
controlled microparticle release vaccine, oral
vaccines, vaccines using newer adjuvants like
MF-59, live recombinant vaccines and DNA
vaccines. These vaccines are still in experimental
stages.
Schedule of vaccination: WHO has
recommended that all countries provide universal
HBV immunization programs for infants and
adolescents. They have suggested the following
options for introducing HB vaccine in the
immunization schedule19.
a) In areas of low perinatal transmission (low
HBeAg prevalence) - HB vaccine given at 6,10,14
50
2006; 8(3) : 236
weeks either as single antigen or as a combined
vaccine.
b) In areas of significant perinatal transmission
(high HBeAg prevalence) HB vaccine at birth,
6, and 14 weeks (3 dose schedule) or birth, 6, 10,
and 14 weeks (4 dose schedule).
IAP recommendation: IAP has recommended
two HB vaccine schedules for all babies (except
those born to HBsAg +ve mothers) - birth, 6 and
14 weeks or 6, 10 and 14 weeks.
For babies born to HBsAg positive mothers,
HB vaccine should be initiated from birth onwards,
followed by 2 more doses at 6 weeks and 14
weeks along with HB immunoglobulin (HBIG)
which should be given within 12 hours of birth. If
HBIG is not available, then HB vaccine alone must
be given preferably in a four doses schedule at
birth, 6 weeks, 10 weeks and 12 months.
Interrupted vaccine schedules: An interruption
in the vaccination schedule does not require
restarting the vaccination series or adding extra
doses. The missed doses should be administered
as soon as possible.
Vaccine induced escape mutants: Some infants
get infected with HBV despite an adequate anti-
HBs response to vaccine. These are commonly
due to HBV S gene mutants. These mutants are
detected in less than 5% of infants receiving HB
vaccine and only 10-40% of vaccine failures are
due to HBV S mutants. In Taiwan, prevalence of
HBV S mutants in HBsAg positive children
increased from 7.8% in 1984 to 28% in 199420.
Careful epidemiological surveillance is necessary
to monitor this increasing prevalence of escape
mutants and establish continuing efficacy of the
conventional HB vaccines.
Hepatitis E vaccine
Hepatitis E is a common cause of acute
hepatitis in adults and is now also increasingly

reported in children throughout Asia, Middle East
and North Africa. In India, besides causing regular
water-borne epidemics, HEV accounts for 23-28%
of acute sporadic viral hepatitis in children and
40-53% in adults. It is a water borne disease with
a possibility of zoonotic spread of the virus since
several non-human primates, pigs, cows, sheep
and rodents are susceptible to the infection. The
case fatality rate can be 1 3% in non pregnant
patients and upto 20% among pregnant women.
Once an effective HE vaccine is available, its role
would have to be defined.
The development of attenuated or killed
vaccine is not currently possible due to lack of
self-cultured system for replication of HEV, though
some cell lines have been reported for culturing
and isolating HEV in vitro. Therefore, a nucleic
acid based vaccine or a recombinant protein
vaccine is needed. At present no commercially
prepared vaccine exists. However, several studies
for the development of an effective vaccine against
Hepatitis E are in progress. HEV is a spherical
non enveloped particle having 3 open reading
frames (ORFs). IgG HEV antibody to ORF3
wanes during convalescence, while that to the
ORF2 persists for several years making it a
candidate for a vaccine against HEV. Only one
vaccine has progressed to the stage of clinical trials.
This is the 56ku recombinant vaccine developed
at the NIH, USA. Phase I trials have found it to
be safe and immunogenic in 88 American
volunteers and 44 Nepalese volunteers. Phase II,
Phase III trials are underway in Nepal. Once an
effective HE vaccine is available, the vaccination
strategy would have to be defined.
Hepatitis C vaccine
The development of an effective hepatitis C
vaccine has been slow due to lack of a susceptible
small animal, a high degree of hepatitis C virus
(HCV) genomic diversity and failure to produce
high quantities of HCV in tissue culture. Clinically
51
2006; 8(3) : 237
adequate vaccines against HCV are not yet
available but protection against homologous strains
of the virus has been achieved in animal studies.
Declaration of conflict
The authors have received grant support
from GlaxoSmithKline Biologicals for non-
hepatitis vaccine trials and from Wockhardt Ltd
for a clinical trial of live attenuated hepatitis A
vaccine.
Points to remember
1. Inactivated and live attenuated HA vaccines
are safe and immunogenic
2. HA vaccine should be offered to children
from higher socioeconomic groups, as they
are most likely to benefit from this vaccine
3. Universal Hepatitis B vaccination
programs are effective in reducing
morbidity and burden of Hepatitis B
4. Hepatitis E and C vaccines are still in
various stages of development
References
1. Bavdekar AR, Bhave SA, Pandit AN.
Hepatitis A : treatment and its prevention. In :
Thapa BR, edi, Recent advances in Pediatric
Clinical Gastroenterology. Chandigarh,
Relume Printec, 2001; pp 282-286.
2. Arankalle VA. Hepatitis A vaccsine strategies
and relevance in the present scenario. Indian J
Med Res 2004; 119(5):3-6.
3. Just M, Berger R. Reactogenicity and
immunogenicity of inactivated hepatitis A
vaccines. Vaccine 1992; 10(1) : S110-113.
4. Balcarek KB, Bagley MR, Pass RF, Schiff ER,
Krause DS. Safety and immunogenicity of an
inactivated hepatitis A vaccine in preschool
children. J Infect Dis 1995; 171 (1): S70-72.
5. Van Herckk, Van Damme P. Inactivated hepatitis
A vaccine-induced antibodies: followup and
Indian Journal of Practical Pediatrics
estimates of long-term persistence. J Med
Virol 2001;63:1-7.
6. Dagan R, Amir J, Mijalovsky A, et al.
Immunization against hepatitis A in the first
year of life: priming despite the presence of
maternal antibody. Pediatr Infect Dis J 19,
10451052.
7. Van Damme P, Banatvala J, Fay O, et al.
Hepatitis A booster vaccination: is there a
need?. Lancet 2003; 362:1065-1071.
8. Dagan R. Leventhal A, Anis E, Slater P, Ashur
Y, Shouval D. Incidence of Hepatitis A in Israel
following universal immunization of toddlers.
JAMA 2005;295:202-210.
9. Craig A, Schaffner W. Prevention of
hepatitis A with the hepatitis A vaccine. NEng
/ Jmed 2004;350:76-81.
10. Prevention of hepatitis A through active or
passive immunization: Recommendations of
the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep
1999;48:1-37.
11. Duval B, Gilca V, Boulianne N, Deceuninck G,
Rochette L, De Serres G. Immunogenicity of
two paediatric doses of monovalent hepatitis
B or combined hepatitis A and B vaccine in 8-
10-year-old children. Vaccine. 2005; 23(31):
4082-4087.
12. Kurugol Z, Mutlubas F, Ozacar T. A two-dose
schedule for combined hepatitis A and B
vaccination in children aged 6-15 years.
Vaccine2005;23(22):2876-2880.
NEWS AND NOTES
INDIAN ACADEMY OF PEDIATRICS - CHILDHOOD DISABILITY GROUP
In association with IAP Kerala, Indian Academy of Pediatrics-Childhood Disability Group initiates
Newborn Hearing Screening Programme in 4 Districts of Kerala. Ernakulam, Calicut, Trivandrum
& Kottayam. This initiative is the first of its kind in India.
Dr. Abraham K. Paul,
Chairman,
IAP-Childhood Disability Group.
52
2006; 8(3) : 238
13. Karayiannis P, Main J, Thomas H. Hepatitis
vaccines. Br Med Bull 2004;70:29-49.
14. Zhuang F, Qian W, Mao Z, et al. Persistent
efficacy of live attenuated hepatitis A vaccine
(H2 strain) after a mass vaccination program.
Chin Med J 2005;118(22):1851-1856.
15. Poland G, Jacobsen R. Prevention of
Hepatitis B with the Hepatitis B vaccine. NEng
/ Jmed 2004;351:2832-2838.
16. West DJ, Watson B, Lichtman J, Hesley TM,
Hedberg K. Persistence of immunologic
memory for twelve years in children given
hepatitis B vaccine in infancy. Pediatr Infect
Dis J 1994; 13:745-747.
17. A comprehensive Immunisation strategy to
eliminate transmission of Hepatitis B virus
infection in the United States.
Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR
Recomm Rep 2005;54:1-33.
18. Zuckerman JN, Zuckerman AJ. Recombinant
hepatitis B triple antigen vaccine: Hepacare.
Expert Rev Vaccines 2002;1:141144.
19. WHO. Wkly Epidemiol Rec 2004;79(28):
255263
20. Hsu HY, Chang MH, Liaw SH, Ni YH, Chen
HL. Changes of hepatitis B surface antigen
variants in carrier children before and after
universal vaccination in Taiwan. Hepatology
1999; 30:1312-1317.
Dr. S.S. Kamath,
Secretary,
IAP-Childhood Disability Group.

VACCINES
RABIES VACCINE CURRENT
CONCEPTS
* Tapan Kumar Ghosh
Abstract: Several breakthroughs have taken place
since the invention of rabies vaccination by
Louis Pasteur. Semples neural tissue vaccine
(NTV) has been in use in India for nearly a
century. Modern tissue culture vaccines or
purified avian tissue vaccine have replaced the
NTV. WHO has approved two intramuscular
(Essen protocol and Zagreb protocol) and two
intradermal regimes (Oxoford ID protocol and
Thai Red Cross Society - ID protocol, ie, TRC -
ID protocol). The updated TRC - ID protocol
and KIMS-ID protocol are also suitable for Indian
population. Passive immunization by Human
Rabies Immunoglobulin (HRIG) and Equine
Rabies Immunoglobulin (ERIG), their usage,
advantages, disadvantages and failure of RIG
treatment are also discussed in this article.
Key words: Rabies vaccine, Intramuscular,
Intradermal
Rabies is a disease characterised by acute
viral encephalitis. It is said to be a disease of
antiquity known to mankind from time
immemorial.
The prevention of rabies by vaccination was
started with Louis Pasteurs anti-rabies vaccine
which was the suspension of infected rabbit spinal
cord that had been dried over caustic potash for
different period of time, at least 2 weeks time
* Scientific Coordinator
Institute of Child Health, Kolkata
53
2006; 8(3) : 239
was needed to make it non-infective. Fermi in
1908 introduced a new method in which the
vaccine was treated with carbolic acid. Fermis
method introduced uniformity of vaccine and
simplicity of preparation. In 1911, Sir David
Semple, the then director of Central Research
Institute (CRI ) Kasauli evolved the method
of preparation of dead carbolized vaccine and
since then this Semples Neural Tissue Vaccine
(NTV) has been used for nearly one century in
India.
The original neural tissue vaccine was made
from brain of the adult animal. Serial changes in
rabies vaccines took place after that and the neural
tissue vaccines was then prepared from the brain
of suckling mouse. The idea was to reduce the
content of adult myelin to avoid the incidence of
neuroparalysis. In 1956, the avian tissue vaccine
was also used successfully e.g., duck embryo
vaccine and ultimately the era of modern tissue
culture vaccine started.
WHO Expert Committee on Rabies in its
7th report has recommended abandoning the use
of neural tissue vaccine due to its serious side
effects like development of neuroparalysis
attributed to high content of myelin 1. This
recommendation was given after the availability
of modern tissue culture vaccine for the last four
decades. Following the recent ruling of Supreme
Court of India to phase out the use of NTV and
ultimately stop its use altogether in India from
2005, the production and use of NTV are stopped
and the only option left is to use modern tissue
culture vaccine (MTCV) or purified avian tissue
vaccine.
Indian Journal of Practical Pediatrics
Rabies vaccines Current Concepts
Modern Tissue Culture Vaccine
Vaccination with modern tissue culture
vaccine is the standard of practice in rabies
immunization today and MTCV is available for
2 decades in India. This is the best vaccine as
regards to safety, potency, convenience and has
several advantages over the age old NTV, ie.,
nerve tissue vaccine.
Advantages 2
Modern tissue culture vaccines (MTCV) are
highly potent, more immunogenic and less
reactogenic in comparison to neural tissue vaccine
(NTV) e.g., (i) High titer of antibody production
in shorter period, (ii) Development of detectable
antibodies within 10 days, (iii) Persistence of
antibody for longer time, (iv) Much less allergic
reactions to protein content, (v) Less number of
injections needed, which are spaced and not given
daily, (vi) Longer shelf life, (vii) Almost nil neuro-
paralytic incidence, (viii) Lack of local side effects
of NTV like, local pain, swelling, redness, abscess
formation etc, (ix) Excellent tolerance and safety
profile, (x) Capability of pre-exposure application.
Vaccine strains, production, quality control
and antigenic content Two vaccine strains are
now in use viz. Pitman Moore strain and Flury-
LEP-C25 strain. The Pitman Moore strain is
adapted to human diploid cells and vero cells.
Flury-LEP-C25 strains are adapted to primary
chick embryo cell lines.
The cell lines are infected with vaccine virus
and incubated. After incubation, the cells are tested
for heme-adsorbing viruses as well as other
extraneous agents. For vaccines derived from avian
embryos, their freedom from avian viruses and
adenoviruses is also demonstrated. The harvests
obtained are pooled, homogenized and inactivated,
usually by beta propiolactone (BPL). After
inactivation, purification and concentration, the
54
2006; 8(3) : 240
vaccine is lyophilized and the final product is
subjected to same tests of quality control as are
recommended by WHO for lyophilized neural
tissue vaccines.
Each final dose of tissue culture vaccine must
contain 2.5 IU as determined in a mouse protection
test. Nowadays liquid vaccine namely, liquid
human diploid cell vaccine is also available in India.
Various protocols of modern tissue culture
vaccines
There are various protocols or regimes of using
modern tissue culture vaccine in animal bite cases,
of which WHO has approved 2 intra-muscular
and 2 intradermal regimes.
1. Intramuscular Regimes: Two intramuscular
regimes approved are Essen protocol and Zagreb
protocol.
(1a) Essen protocol : The six dose schedule spread
over a period of three months was recommended
at an International Conference on Rabies, held at
Essen, Germany, and is popularly known as Essen
schedule. Nowadays in place of 6 doses, 5 doses
are recommended i.e. on days 0, 3, 7, 14 and 28.
The dose on day 90 is optional and is only used
in cases of immunodeficiency, extremes of age
and presence of debilitating condition. Day 0
indicates the date of the first injection. The dose
of purified chick embryo cell vaccine (PCECV)
and human diploid vaccine (HDCV) is 1 ml and
in case of purified vero cell vaccine it is 0.5 ml.
Table 1 shows the Essen Protocol for rabies
vaccination.
Table 1. Essen protocol
Day of Vaccination No.of doses
Day 0 1
Day 3 1
Day 7 1
Day 14 1
Day 28 or Day 30 1
Day 90 1

(1b) Zagreb protocol : Another intra-muscular
regime is Zagreb protocol or short IM protocol,
where 2 doses are given at separate sites on day 0
and subse-quently single dose given on day 7 and
day 21, so 4 doses are given in 3 sittings. This is
an equally effective schedule, though not
recommended in countries like India, which are
considered as the hyperendemic for rabies. This
schedule induces early and enhanced immune
response initially but when given along with RIG
leads to poor development of antibodies on long
term3. Table 2 shows the Zagreb schedule of rabies
vaccination.
Table 2. Zagreb protocol
Day of No. of Doses
vaccination
Day 0 2 extensive use of this most cost effective schedule
Day 7 1 Thai Red Cross Society has brought down the
Day 21 1 incidence of rabies death drastically in Thailand
(1c) Pre exposure intramuscular schedule:
In pre-exposure IM schedule 3 doses are
recommended in India. First dose is given on day
0, 2nd on day 7 and 3rd on day 28. The dose used
is the same as used for post-exposure prophylaxis.
Booster dose is indicated at the end of 1st year
and then every 3 years, though it is better to
estimate the antibody titer if possible before giving
the boosters (if titer is less than 0.5 IU/ml, the
booster is indicated). Pre-exposure prophylaxis is
only possible with MTCV. The pre-exposure is
given to high risk groups like (i) veterinarians (ii)
laboratory personnel working with rabies virus,
(iii) medical and paramedical personnel treating
rabies patients, (iv) dog catchers/dog pound
workers, (v) forest staff, (vi) zoo keepers,
(vii) postmen,(viii) policemen, (ix) courier boys,
(x) school children in endemic countries4 etc.
2. Intradermal regimes
Though there are 2 regimes approved by
WHO namely, 8 doses Oxford regime and 2 doses
55
2006; 8(3) : 241
Thai Red Cross (TRC-ID) regime, there are other
protocols too. These two intradermal (ID)
schedules have been found to be equally
immunogenic and effective if given by experienced
hands5. This has been studied and found cost
effective in bringing down the mortality due to
rabies and unfortunately are yet not widely
practiced6,7.
(2a) 2-2-2-0-1-1 (Thai Red Cross Intradermal
Schedule or TRC-ID Schedule): Two ID doses,
one on each deltoid region, are given on day 0,
day 3 and day 7; and one ID dose on any one
site of deltoid on day 28 and day 90. No dose is
given on day 14. One ID dose should be 1/5th
the quantity of IM dose depending on vaccine,
though 0.1 ml of purified chick embryo cell vaccine
is also used successfully in Thailand. With the
in last one decade. We should think of this cost
effective schedule in our country. We should plan
to give training to the personnel to make him/her
a skilled worker in vaccine centers and help our
country to avail of this opportunity of using cell
culture vaccine in animal bite cases at a much
cheaper cost. Table 3 shows TRC-ID schedule.
Recently Drug Controller General of India has
approved this schedule with PVRV or PCEC
vaccines in centers where there are 50 cases of
postexposure cases per day.
(2b) Updated TRC-ID Schedule8: TRC-ID
Schedule is modified by omitting the dose on day
90 and 2 doses are given on day 28 in place of
1 dose. Table 4 shows the updated TRC-ID
Schedule. This schedule is also recommended by
DCGI as above.
(2c) Kempegowda Institute of Medical Sciences
Bangalore, has tried another modified regime
of TRC-ID Schedule Their work is also very
well appreciated by the medical fraternity. This is
Indian Journal of Practical Pediatrics 2006; 8(3) : 242

Table 3. TRC-ID Schedule or 2-2-2-0-1-1 Schedule*

Day of PVRV** PCECV*** No. & Site of
Immunization Injection
Day 0 0.1 ml 0.2 ml 2 : Left and right deltoids
or anterolateral thighs
Day 3 0.1 ml 0.2 ml - do -
Day 7 0.1 ml 0.2 ml - do -
Day 14 None None None
Day 30 0.1 ml 0.2 ml 1 : deltoid
or anterolateral thigh
Day 90 0.1 ml 0.2 ml - do -
* This schedule is also practiced officially in Philippines and Sri Lanka
** Purified Vero Cell Vaccine
*** Purified Chick Embryo Cell Vaccine
Table 4. Updated TRC-ID schedule or Table 5. KIMS Bangalore Modification
2-2-2-0-2-0 schedule of TRC-ID Schedule or 2-2-2-2-2-0
schedule
Day 0 - One ID dose x 2 sites
Day 0 - One ID dose x 2 sites
Day 3 - One ID dose x 2 sites
Day 3 - One ID dose x 2 sites
Day 7 - One ID dose x 2 sites
Day 7 - One ID dose x 2 sites
Day 14 - No dose
Day 14 - One ID dose x 2 sites
Day 28 - One ID dose x 2 sites Day 28 - One ID dose x 2 sites
Day 90 - No dose Day 90 - No dose

an effective schedule for India, a highly endemic
country for Rabies6. In this schedule 2 ID doses
are given on all the days i.e. day 0, day 3, day 7,
day 14 and day 28. Table 5 shows KIMS
Bangalore Modification of TRC-ID Schedule.
(2d). 8-0-4-0-1-1 schedule (Oxford schedule or
Warell and Nicholson schedule)7 : One ID dose
is 0.1 ml each given on 8 sites on day 0. The sites
are deltoids (two), lateral side of thighs (two),
suprascapular regions (two) and lower quadrant
of abdomen on either side (two). No dose is given
on day 3. Then 4 doses are given on day 7, the
sites are deltoids and thighs on either side. No
dose is given on day 14. One dose is given on day
28 and on day 90. Table 6 shows the 8-dose ID
Schedule.
56
(2e) Pre-exposure ID schedule for prophylaxis.
Here 0.1 ml of PCEC is given on day 0, day 7
and day 21/28. So total 3 ID doses are given.
Table 7 shows pre-exposure ID schedule.
The volume per intradermal site is usually
one-fifth of IM dose
(a) 0.1 ml of PVRV (Purified vero cell vaccine,
0.5 ml vial)
(b) 0.2 ml of PCECV (Purified chick embryo cell
vaccine 1 ml vial)
(c) 0.1 ml of PCECV may also be considered for
use by National health authorities as approved by
WHO
Report of multicentric study with ID schedule has
already published in India, approved by National
 2006; 8(3) : 243

Table 6. 8-0-4-0-1-1 Intradermal schedule (Oxford schedule) or Warell and

Nicholson schedule)
Day of PCECV No of Site of injection
Immunization doses
Day 0 0.1 ml 8 Deltoid (2), anterolateral thigh (2),
lower quadrant of abdomen (2),
suprascapular region (2)
Day 3 - NiL -
Day 7 0.1 ml 4 Deltoid (2), anterolateral thigh (2)
Day 14 - Nil -
Day 28 0.1 ml 1 Deltoid (1)
Day 90 0.1 ml 1 Deltoid (1)

Table 7. Pre-exposure ID schedule for prophylaxis

Schedule PVRV (Dose in ml) PDEV/PCEC(Dose in ml)

D0 D7 D 21/28 D0 D7 D 21/28

Intradermal 0.1 0.1 0.1 0.1 0.1 0.1

OR
Intramuscular 0.5 0.5 0.5 1.0 1.0 1.0

Institute of Communicable Disease (NICD), New
Delhi and actively supported by Association for
Prevention and Control of Rabies in India
(APCRI), Bangalore9. It is felt by many that the
implementation of ID schedule is the only
economical, scientific and viable alternative to use
MTCV at all anti-rabies clinics of India and very
recently DCGI has started giving permission to
MCID schedule in a phased manner.
Rabies Immunoglobulin (RIG)
The discussion on anti-rabies vaccination cannot
be complete without mentioning the role of RIG
in prevention of rabies. RIG infiltration is the
passive method of protection, whereas the
vaccination is the active mode of protection. Both
57
are important specially in the category III (WHO)
cases where there is (are) transdermal wound(s).
There are 2 types of rabies immunoglobulin
namely, (i) Human rabies immunoglobulin (HRIG)
and (ii) Equine rabies immunoglobulin (ERIG).
The dose of HRIG is 20 IU/kg of body weight
whereas the dose of ERIG is 40 IU/kg of body
weight. It is to be kept in mind that a skin test
prior to application of ERIG is medicolegally very
important. RIG neutralizes rabies virus on contact.
RIG gives a coating to the virus so that it cannot
enter the nerve ending resulting in reduction or
total obliteration of inoculated virus.
Choice of RIG: Though HRIG represents the
gold standard for passive immunization, the cost
of HRIG is exorbitantly high making it impossible
Indian Journal of Practical Pediatrics
to afford by majority of patients of our country.
Supply of HRIG is also erratic. ERIG is an
acceptable alternative. The crude anti-rabies serum
(ARS) is related with high incidence of
anaphylactic reaction and induction of serum
sickness. Now the crude ARS has been replaced
by purified and pepsin-digested product which is
far safer and can be used with confidence. The
increased production of highly purified equine
immunoglobulin (ERIG) should be promoted to
provide an alternate effective solution to the
problems of supplies of human immunoglobulin
(HRIG) and the cost involved1. One study shows
that the incidence of adverse reaction is as low as
2.4% with anaphylactic reaction of 0.2% 10.
Another study shows 1.7% serum sickness
reaction in a series of 297 cases 11. In Thai
population it was reported by Wilde et al to be as
low as 0.81%6. Presently the purified ERIG
preparation has been available and produced by
Indian manufacturers. CRI, Kasauli also produces
a small quantity ARS which is insufficient for a
vast country like India.
Failure of RIG treatment: Failure occurs if RIG
is not used locally but administered only
systemically. Local infiltration of the wound is
essential in order to neutralize virus before it can
enter the nerve endings. Other causes of RIG
treatment failure are: (i) Insufficient quantity of
RIG used. (ii) Time interval from the time of bite
to RIG administration if it is unusually delayed.
Theoretically as well as practically RIG
administration should start simultaneously with
first dose of vaccine administration but not in same
site. Use of RIG after 7 days of bite or after 3
doses of vaccination may result in failure. (iii)
Same site of injection of RIG and anti-rabies
vaccine (ARV). (iv) When infiltration of some
wounds are not done. It has been experienced
especially in children that quantity of RIG
calculated according to body weight is small and
insufficient in a good number of cases where
wounds are extensive. So, inexperienced person
58
2006; 8(3) : 244
may leave some wounds without infiltration with
RIG. It is better to dilute the RIG 2 to 3 folds
with normal saline in this type of cases so that all
wounds can be covered. (v) RIG is administered
alone without the use of vaccines This is most
unscientific decision. The rationale of use of RIG
is to neutralize the virus immediately as 7 to 14
days time is taken for ARV (MTCV) to achieve
the desired antibody level but RIG has no long
standing effect which vaccines can only achieve.
Points to remember
1. Modern tissue culture vaccines are the only
suitable vaccines for rabies prophylaxis
2. Intradermal (ID) schedules approved by
WHO are found to be equally immuno-
genic and should be adopted in all anti
rabies clinics in our country in view of their
efficacy and cost effectiveness. This will be
introduced in phased manner
3. Local administration of rabies immuno-
globulin (Human or Equine) is indicated
in all cases of transdermal wounds along
with rabies vaccination.
References
1. WHO Experts Committee on Rabies, Seventh
Report. WHO Techn Rep Series 709. Geneva
: WHO, 1994 68-70.
2. Ghosh TK. Rabies Control How to Make
MTCV Cost Effective at Individual and
Community Level. In : Ghosh TK, ed.
Infectious Diseases in Children and Newer
Vaccines, Part 1. Kolkata : IAP Infectious
Diseases Chpater, 2003; 159-165.
3. Dutta AK, Kanwal SK. Rabies and its
prevention. J Assoc Prev Control Rabies India
1999; 1(1): 5-13.
st
4. Background Document and Slide Text. 1
National Workshop for APCRI Training in
Modern WHO approved Rabies Prophylaxis
st
held on 31 March 2001 at National Institute
of Mental Health and Neurosciences.
Bangalore : Association for Prevention and
 2006; 8(3) : 245

Control of Rabies in India. 2001; slide no.35-
36.
5. Madhusudana SN. Recent advances in Rabies.
In : Proceedings of the Conference II on
Rabies Prevention and Management,
Kathmandu. November 20-24, 2003: 17-20.
6. Wilde H, Chomchey P, Prakongsri S,
Punyarathabandhu P. Safety of equine rabies
immunoglobulin. Lancet 1987; 2 : 1285.
7. Warell MJ, Nicholson KG, Sitharasami P,
Udomaskadi D. Economical multiple site
intradermal immunisation with human diploid
cell strain vaccine is effective for post-
exposure rabies prophylaxis. Lancet 1985; 1 :
1059-1062.
8. Ghosh TK. Beginning of the end of the rabies
in India. Bulletin of Infectious Diseases
Chapter of Indian Academic of Pediatrics.
2005; 5 : 1-5.
9. Madhusudana SN, Editor. Peoceedings of
National Seminar on ID Rabies Vaccination
Bangalore 2003, Bangalore , APCRI; 2005.
10. Tripathi KK, Madhusudana SN. Safety of equine
rabies immunoglobulin. Vaccine 1989; 7 : 372-
373.
11. Goswami A. Safety and tolerance of equine
rabies immunoglobulin in the Indian
popu lation. J Assoc Prev Control Rabies India
2000; 1 : 30-34

NEWS AND NOTES

ANNUAL CONVENTION
NATIONAL NEONATOLOGY FORUM
TAMILNADU CHAPTER
4th & 5th November 2006.
Theme : COMPREHENSIVE NEWBORN CARE

Venue : Hotel Green Park, Chennai

Conference Secretariat :
Dr. J. Kumutha, Organising Secretary
22, Temple Street, Alagappa Nagar, Kilpauk, Chennai 600010
Ph-044-26446431 E-mail: githkarthi@yahoo.co.in / Dr_kumutha@yahoo.com
Registration Before
30-09-2006 Spot
Delegate Fees
(Include CME) 750 1,000
PG student 500 1,000
NRP 500 -
Transport Workshop 500 -
Nurse Workshop 250 -
Accompanying Person 600
D.D should be drawn in favour of CHENNAI NEOCON 2006 payable at Vijaya Bank,
Kilpauk, Chennai

59
Indian Journal of Practical Pediatrics 2006; 8(3) : 246

RADIOLOGIST TALKS TO YOU

HEPATOMEGALY AND HEPATIC multiple, found incidentally and do not require

MASSES- 2 any further investigaton2.
*Vijayalakshmi G Sometimes they are large and present a more
**Elavarasu E complex appearance (Fig 2). There are echogenic
**Porkodi areas because of closely packed channels and
***Malathy K fibrosis, cystic areas because of hemorrhage and
***Venkatesan MD lysis of thrombi and bright specks because of
calcification. There may be tubular structures
Primary liver tumors are rare and malignant
representing venous channels, more in the
liver tumors are generally more common than
periphery. These are seen better with Doppler
benign tumors. In neonates and infants one should
though flow may be too slow to give a good
always think of benign tumors like cavernous
Doppler signal. On CT they are seen as low
hemangiomas and hemangioendotheliomas.
attenuated or isodense lesions. On contrast
Among malignant tumors, hepatoblastoma is seen
administration they show peripheral nodular
in children less than five and the extremely rare
enhancement. Later films will show central
hepatocellular carcinoma after ten years of age1.
enhancement. Hemangiomas are hypointense on
Metastases to the liver must also be considered in
T1 weighted images and hyperintense on T2
the differential diagnosis.
images. Inhomogeneity may also be seen as in
Tumors of the liver look so much alike in ultrasound.
imaging that it is often confusing. There are certain The infantile hemangioendothelioma has an
classical findings for each type that are not seen interesting appearance. In ultrasound they are seen
in all cases. However, one easily identifiable lesion
is a cavernous hemangioma when it is seen as a
solid, echogenic, round lesion mostly situated in
the peripheral parts of the liver (Fig.1).
Hemangiomas consist of multiple vascular
channels lined by endothelium.Therefore there are
multiple interfaces reflecting the ultrasound beam
which is why it appears bright. They are often

* Addl.Professor
** Tutor in Radiology
*** Reader
**** Professor
, Department of Radiology,
Chenglepet Medical College Hospital, Chenglepet Fig. 1. Cavernous hemangioma
60

as multiple hypoechoic lesions 3,4,5 (Fig 3).
Bloodflow through the lesion is so much that the
preferential flow into the tumor reduces flow to
the peripheries of the body. The aorta is of normal
or increased caliber proximal to the take-off of
the hepatic artery while distally it appears thin.The
Fig. 2. Complex cavernous hemangioma in
a newborn with Jaundice
Fig. 3. Infantile hemangioendothelioma
61
2006; 8(3) : 247
hepatic artery is also wider6,7. The patient may
present with high-output cardiac failure.On CT
they are seen as hypodense areas in the plain
images (Fig 4). Late films after contrast show
brilliantly enhancing lesions that are so typical of
this lesion8 (Fig 5). MRI shows similar features.
Fig. 4. Infantile hemangioendothelioma CT
plain
Fig. 5. Infantile hemangioendothelioma - CT
contrast
Indian Journal of Practical Pediatrics
Fig. 6. Hepatoblastoma
The hepatoblastoma is a solid tumor (Fig 6)
that may have a heterogenous appearance.
Calcifications may be present in some histological
types. After contrast, in CT, they show patchy
enhancement. Hepatoblastomas may look very
much like a large, complex hemangioma9,10. In
that case only histological diagnosis will give the
answer. However, if fine-needle biopsy yields
only some blood and endothelial cells it is either a
non-diagnostic sample or a case of hemangioma.
Therefore we are left with the same differential
diagnosis. Alphafetoprotein levels may help in these
cases. VMA levels can help in metastatic
neuroblastomas.
62
2006; 8(3) : 248
Thus diagnostic evaluation of liver tumors
needs an integrated approach combining clinical
features, laboratory tests and radiological imaging.
References
1. Weinberg AG, Finegold MJ. Primary hepatic
tumors in childhood. In: Finegold MJ, ed.
Pathology of neoplasia in children and
adolescents. Philadelphia: WB Saunders,
1986;333.
2. Jabra AA, Fishman EK, Taylor GA. Hepatic
masses in infants and children: CT evaluation.
AJR 1992;158:143-149.
3. Siegel MJ. Liver and biliary tract. In Siegel Mj,
ed. Pediatric Sonography. 2nd ed. New York,
Raven Press, 1995;186-187.
 2006; 8(3) : 249

4. Boon LM, Bourrows PE, Paltiel HJ, et al.
Hepatic vascular anomalies in infancy: a
twenty-seven-year experience. J Pediatr
1996;129:346-354.
5. Paltiel HJ, Patriquin HB, Keller MS, et al.
Infantile hepatic hemangioma: doppler US.
Radiology 1992;182:735-742.
6. Abuhamad AZ, Lewis D, Inati MN, et al. The
use of color flow doppler in the diagnosis of
foetal hepatic hemangioma. J ultrasound
Med.4.22,1933.
7. Mejides AA, Adra Am, OSullivan Mj,
Nicholas MC. Prenatal diagnosis and therapy
for foetal hepatic vascular malformation.
Obstet Gynecol 1995;85:85
8. Lucaya J, Enriquez G, Amat L, Gonzalex-
Rivero MA. Computed tomography of infantile
hepatic hemangioendothelioma. AJR
1985;144:821-826.
9. King SJ, Babyn PS,Greenberg ML, et al: Value
of CT in determing the reectbility of
hepatoblastoma before and after
chemotherapy. AJR Am J Roentgenol 1993;
160(4):793-798.
10. Miller J, Greenspan B. Integrated imaging of
hepatic tumours in children. Part I. Malignant
lesions (primary and metastatic). Radiology
1985;145:83-90.

NEWS AND NOTES

COMPED 2006
FIRST NATIONAL CONFERENE OF COMMUNITY PEDIATRICS
(SUBCHAPTER OF IAP)
Date: 11th & 12th November 2006
Organized by: IAP Chhattisgarh State Branch & IAP Raipur Branch
Venue: Hotel Babylon International, VIP Road, Raipur.
Registration Fee Upto 31st Oct. 2006 SPOT
Delegates IAP Rs.1,000/- Rs.1,200/-
Delegates Non-IAP Rs.1,200/- Rs.1,400/-
Postgradyate student Rs. 800/- Rs.1,000/-
Demand draft should be sent in favour of COMPED 2006 payable at Raipur (c.g.)
*Scientific paper on community pediatrics are invited for presentation before 15th October 2006
Contact : Dr. Ashwani Agrawal, Organizing Secretary, C/O Swapnil Nursing Home, Civial Lines,
Raipur (c.g.) 492001. Phone no. : 0771-2424111, 0771-2593093 Mobile no. 94252 08789
E-mail : drakagr_r@yahoo.co.in or annopve@yahoo.com

Karnataka State PEDICON 2006, Karnataka October 7-8, 2006

Contanct : Dr. Nitin Tikare, Organizing Secretary, Dr. Bidaris Ashwini Hospial. B.L.D.E. Road,
Bijapur 586 103, Karnataka.
Ph. : (H) 08352 - 261128. Mo. 09844363382. E-mail : pedicon2006@rediffmail.com

63
Indian Journal of Practical Pediatrics 2006; 8(3) : 250

CASE STUDY

MILROYS DISEASE distension. There was no history of dyspnoea on

exertion, no cyanosis, no redness or warmth over
*Farzana.Beg the swelling. His mother and maternal great
*Ajit Saxena grandmother had similar swelling of their feet.
*Imteyaz Ahmad Khan
*Siraj N Huda On examination: He was lethargic, pale, not
*Faisal Haque dyspnoeic, with no facial dysmorphism and had
bilateral pitting pedal oedema of his feet.(Fig1).
Abstract: Milroys disease is a rare familial System examination was normal.
disorder of the lymphatic vessels characterized
by hypoplasia of the lymphatics, presenting as
congenital lymphoedema. We report a toddler who
presented with disturbing cough and increasing
pallor of a short duration and swelling of both
his feet since birth. On treatment the presenting
symptoms improved but the pedal oedema
persisted.
Key words: Lymphoedema, Milroys disease.
Milroys disease is due to hypoplasia or
aplasia of the lymphatic vessels and constitutes
5-10% of primary lymphoedema. It usually occurs
from birth or may be noted later in life it is more
common in females and presents as bilateral pedal
oedema. Prevention of complications is important Fig. 1. Pedal oedema in mother and child
in the management of Milroys disease and surgery Invesitgations: The complete blood count
plays a very minor role. showed Hb of 6.8Gm/dl, total WBC 16,000 cells/
Case summary: A one year four months old boy cumm with a differential of 73% neutrophils. The
born to consanguineous parents was brought with renal function tests and serum transaminases were
cough and increasing pallor of 8 days duration. normal. Total protein was 5.3Gm/dl with albumin
His parents had noted swelling of his feet since 2.9 Gm/dl. X ray chest showed consolidation of
birth which was non progressive and not the right upper lobe which resolved with
associated with puffiness of face or abdominal antibiotics. Ultrasound of the abdomen was normal.
Colour doppler of the lower limb for both the
* Dept. of Pediatrics & Radiodiagnosis
child and his mother did not identify any
J.N.Medical College. arteriovenous malformation. He was prescribed
A.M.U., Aligarh, Uttar Pradesh. iron supplements and his mother was advised
64

regarding diet. He responded to therapy but the
swelling of his feet persisted.
Discussion: The eponym Milroys disease was
given by Sir William Osler and hereditary
lymphoedema of the legs described by Nonne in
1891. In 1892 Milroy described a 31 years
clergyman who had returned from India with
swelling of his legs. Milroy studied the 250 years
family records of this patient and identified 22
patients in his family. Meige described the same
condition in 1898.
Primary lymphoedema can be of different types
depending on the age of onset. Milroys disease
(Nonne-Milroy Syndrome)usually occurs soon
after birth or within the first year of life. Meige
syndrome is a non congenital familial
lymphoedema which occurs during puberty. It also
involves the feet but is not associated with
intestinal lymphangiectasia. Lymphoedema
praecox is the most common type and constitutes
80% of primary lymphoedema and occurs before
the age of 35years. Lymphoedema tarda occurs
after the age of 35years.
Syndromic Lymphoedema: Several syndromes can
be associated with lymphoedema in children.
They are Turners, Noonans, Klienfelter, Downs,
Amniotic band syndrome and Klippel Trenuay
Weber syndrome and Lymphoedema Distichiasia
Syndrome.
Milroys disease has a predilection for females
and there is usually a positive family history. The
oedema in Milroys disease is described as a
brawny swelling which pits on pressure and is
soft to touch. It is restricted to the dorsum of the
feet. The right leg being involved more than the
left. It may involve the arms, hands, face and
also the intestinal lymphatics. The intestinal
NEWS AND NOTES
RAJ PEDICON 2006 11th & 12th November 2006
Contact : Dr. J.N. Sharma, Email: drsharmajn@rediffmail.com
65
2006; 8(3) : 251
involvement may result in protein losing
enteropathy. Some have associated cystic
hygroma of the neck or pulmonary
lmphangiectasia. The disease is inherited as
autosomal dominant with incomplete penetrance
(about 50%). A tyrosine kinase receptor, specific
for lymphatic vessels has been reported to be
abnormally phosphorylated in patients with
Milroys disease. The gene for this disease,
VEGFR3 Vascular Endothelial Growth Factor
Receptor 3(FLT4), has been mapped to the
telemeric part of chromosome arm 5q in the region
5q34-q35. The complications of Milroys disease
include cellulitis, lymphangitis, bacteremia,
chylothrax, chylous ascites, protein losing
enteropathy and lymphangiosarcoma. The
diagnosis is usually clinical but lymphangiography,
lymphoscintigraphy and MRI are useful
techniques. The management of Milroys disease
is supportive and includes excercises, elastic
stockings, bandages, gentle message, elevated
positioning of legs and pneumatic compression.
Cellulitis has to be treated adequately with
antibiotics. Surgery has a very limited role in the
management of Milroys disease.
Reference
1. Dale RF. The inheritance of primary
lymphoedema. J Med Genet 1985;122:274-
278.
2. Ko Ds, Lerner R, Klose G, Cosimi AB.
Effective treatement of lymphedema of the
extremities. Arch Surg 1998;133:452-458.
3. Mortimer PS, Swollen lower limb -
lymphoedema. Br Med J 2000;320:1527-
1530.
4. Tiwari A, Cheng KS, Buttun M. Diffrential
dignosis invariyable and current treatment of
lowe limb lymphoede. Arch Surg
2003;138:152-161.
Indian Journal of Practical Pediatrics
CASE STUDY
NECROTIZING FASCITIS
*Shrishu R Kamath
*Anjul
*Rajeshwari
**Balaji V
***Suchitra Ranjit
****Radha Rajagopalan
Abstract: A 14 year old child presented with
necrotizing fascitis following a trivial trauma.
The presentation was of toxic shock syndrome
with multiorgan dysfunction. Aggressive early
debridement, targeted antibiotics and supportive
PICU care played a key role in his recovery.
Keywords: Necrotizing fascitis, Multiorgan
dysfunction, Toxic shock syndrome.
Necrotizing fascitis is a potentially life threatening
condition characterized by rapidly advancing local
tissue destruction and systemic toxicity. The onset
is acute with swelling of the skin and subcutaneous
tissues followed by systemic toxicity. Early
debridement and antibiotic therapy help in early
recovery. We present a child with necrotising
fascitis who had a stormy course necessitating a
co-ordinated multi-disciplinary approach to
management.
Case report
A 14 year old adolescent boy was brought
with history of fall in the toilet 14 days earlier,
* Registrar, Peditric Intensive Care Unit
** Surgeon, Department of Vascular Surgery
*** HOD, Pediatric Intensive Care Unit
**** Head of Pediatric Department
Apollo Hospitals, Chennai.
66
2006; 8(3) : 252
following which there was a progressively
increasing swelling of thigh along with yellowish
discoloration of eyes. As the boy developed
decreased urine output he was admitted.
On examination in the Emergency Room, he
was well nourished, had icterus and was toxic.
His vitals were stable and capillary refill time was
2 seconds. He had generalized swelling of the right
thigh which was extending till the upper half of
the calf. This swelling was warm, tense and tender.
There was a small discolored patch of 3 x 2 cms
in the back of the thigh. Physical examination
revealed an enlarged liver 3cm below the right
costal margin without spleno megaly. Other
systems were normal.
A possible diagnosis of cellulitis with hepatic
and renal dysfunction was considered. He was
admitted to the PICU for observation. Over the
next 4 hours there were subtle changes in his vital
parameters. He remained afebrile, oriented and
normotensive but developed progressive
tachycardia and effortless tachypnoea. The heart
rate increased from 90/minute to 130/minute and
respiratory rate went up to 40/minute from a
baseline of 20 breaths per minute. However, he
continued to have a good urine output and
remained well oriented and afebrile. There was
also a progressive increase in the size of the
discolored patch on the back of his thigh along
with the appearance of surrounding blebs. Evolving
toxic shock resulting from necortising fascitis was
considered on account of the presence of skin
necrosis with progressive changes in vital
parameters.
Blood gas analysis revealed significant
metabolic acidosis with compensatory respiratory

Fig. 1. The picture depicts the extent of tissue destruction and debridement being done.
alkalosis. This explained the tachypnoea and
supported the diagnosis of septic shock.
Aggressive fluid resuscitation was initiated and
central line was inserted in the inernal jugular vein
for CVP (Central Venous Pressure) monitoring.
Despite adequate fluid resuscitation his CVP
remained low (4mmHg) suggesting the presence
of capillary leak.
Further fluids were administered, but acidosis
persisted. He developed respiratory distress and
hypotension. He was electively intubated and
ventilated in order to facilitate full fluid
resuscitation and reverse the rapid deterioration
in his vital parameters.
At this time his total counts were
42,000/cmm with predominant polymorphs.
He had thrombocytopenia (Platelet count -
97,000/cmm). His urea was 178mg/dl and
creatinine 1.8 mg/dl. His total bilirubin was
17.3mg/dl and direct bilirubin was 14.4mg/dl
SGPT was 351U/L and SAP was 8031U/L,
GGTP was 351U/L with albumin of 2.3gm/dl and
67
2006; 8(3) : 253
globulin of 3.2gm/dl. His coagulation parameters
were deranged, Prothrombin time was 58 secs
(Control13secs), Activated Partial
Thromboplastin Time was 98secs (Control
30secs). His urine myoglobulin and haemoglobin
were negative. Echo cardiogram was normal.
Doppler of the affected limb was normal. Culture
and ASO titers were non contributory.
Maximal dose antibacterials were initiated
with Piperacillin/Tazobactum and Clindamycin.
Child was taken up for immediate fasciotomy and
wound debridement. Infectious disease
consultation was sought and was advised
intravenous gamma globulin in addition to the
antibiotics. Appropriate blood products were
administered. 48 hours post surgery, fever
appeared for the first time with a further increase
in total white cell count and recurrence of
metabolic acidosis. A Computed Tomography
Scan (CT) of the thigh showed reappearance of
pus pockets with no intra-abdominal extension.
The child was taken up for re-debridement and
following this, rapid and steady improvement in
Indian Journal of Practical Pediatrics
clinical and laboratory parameters allowed weaning
off from ventilation and vasoactive support by
day 4 of his PICU stay. He required prolonged
hospital stay on account of the need for multiple
sittings for skin-grafting.
Discussion
Necrotising Fascitis: Since 1980s there was
marked increase in the recognition and reporting
of necrotising fascitis and associated toxic shock
syndrome. The British tabloids coined the
termFlesh Eating Bacteria to describe invasive
necrotising infections caused by Group A
Streptococcus(GAS). Necrotising soft tissue
infections are potentially life threatening conditions
characterized by rapidly advancing local tissue
distribution and systemic toxicity. Tissue necrosis
differentiates this condition from cellulitis. In
cellulitis, an inflammatory process involves the
subcutaneous tissue but does not destroy it.
Necrotising soft tissue infection presents with early
cutaneous signs. However the extent of cutaneous
signs may be disproportionate to the rapidity and
degree of destruction of subcutaneous tissue.
Streptococcus pyogenes and Staphylococcus
aureus are the most common agents. Occasionally
other gram positive cocci and or rarely Escherichia
coli may be responsible. In patients who are
Table 1. CDC case definition of Necrotising Fascitis
Suspected case
1. Necrosis of tissue with involvement
of the fascia plus
2. Serious systemic disease including
one or more of the following:
a. Death
b. Shock(Syst BP<90mmHg)
c. DIC
2006; 8(3) : 254
immunocompromised or have diabetes mellitus,
a number of fungal or bacterial agents may be
involved. These are Pseudomonas aeruginosa,
Aeromonas hydrophila, Enterobateriaceae,
Legionella spp, the Mucorales, particularly
Rhizopus spp. It may be polymicrobial with a
mixture of anerobic and aerobic bacteria. Infection
may be due to any one single organism or
combinations of organisms such as Clostridium,
E.coli, Klebsiella, Proteus and Aeromonas. In the
absence of toxic shock syndrome, streptococcal
necrotising fascitis is seldom fatal but may be
associated with substantial morbidity.
The most common location of necrotising
fascitis is on the extremities, abdomen and perineal
region. In neonates, the commonest predisposing
factors are omphalitis and balanitis occurring after
circumcision. Predisposing factors are
immunosuppression, extremes of age, diabetes
mellitus, neoplasia or vascular surgery. A healthy
individual may acquire infection by blunt trauma,
abrasions, laceration, hypodermic needle injection
or following a surgical procedure.
Clinical manifestations : The onset of
necrotizing fascitis is abrupt with local swelling,
erythema and tederness resulting from the
destruction of subcutaneous tissues, fascia and
Definite case
1. 1+2and serologic confirmation of group A
streptococcal infection by a 4 fold rise against:
a.Streptolysin O
b.DNAse B
2. 1+2 and histologic confirmation of gram-postive
cocci in a necrotic soft tissue infection.
68

sometimes muscles. Skin changes occur 48 hours
later when ill-defined cutaneous erythema and
edema may be seen. Constitutional signs are
frequently out of proportion to the visible
cutaneous sings. Fluid filled bullae appear and
finally, frank tissue gangrene, ischaemia and
necrosis occur. Vesiculation or bulla, crepitus and
local anaesthesia are ominous and indicative of
advanced disease. Significant systemic toxicity
may accompany necrotising fascitis including
shock, organ failure and death. Rapid progression
to death can occur within hours.
In an extremity, a compartment syndrome
may develop which will manifest as tight edema,
pain on movements and loss of distal sensation
and pulses. This is a surgical emergency. Definitive
diagnosis is made by surgical exploration. Necrotic
fascia and sub cutaneous tissue are gray and offer
minimal resistance to probing. MRI and CT scan
aid in delineating the extent and tissue planes of
involvement, but these procedures should not
delay surgical intervention. During surgery, frozen
section incisional biopsy may help to delineate
margins of involvement.
Treatment : Early supportive care and
debridement by surgery are paramount. All
devitalized tissue has to be removed to freely
bleeding edges and repeat surgery may be required
until no necrotic tissue remains. Antibiotic therapy
should be initiated as soon as possible. Initial
therapy with broad spectrum antibiotics is
NEWS AND NOTES
FIFTH NATIONAL CME IN NEONATOLOGY, NEW DELHI.
February 10-11, 2007
Contact: Dr.Ramesh Agarwal, Assistant Professor,
Department of Pediatrics, All India Institute of Medical Sciences,
New Delhi - 110 029.
Tel.: 011-26593621 Fax : 011-26862663
E-mail : aranag@rediffmail.com
69
2006; 8(3) : 255
necessary. Crystalline penicillin has been
hypothesized to Inoculum effect where by it is
suggested that large inocula reach the stationery
phase of growth sooner than smaller inocula and
pencillin cannot act during the stationery phase.
Use of intravenous gamma globulin is also
effective and is thought to act by decreasing toxin
production.
The greater efficacy of clindamycin may be
multifactiorial: It is not affected by inoculums size
or stage of growth. Clindamycin is a potent
suppressor of toxin synthesis. It facilitates
phagocytosis of organism by inhibiting M-protein
and all enzymes involved in cell wall synthesis
and degradation, longer post antibiotic effect and
suppresion of synsthesis.
Bibliography
1. Bisno AL, Steven DL: Strepcoccal infections
of skin and soft issues. N Engl.J.Med 1996;
334:240
2. Brogan TV, Nizet V, Werldhaisen JH et al:
Group A Streptococcus necrotising fascitis
complicating varicella : A series of ten patients
Pediatr Infect Dis J 1995; 14:588
3. Steven DL: Invasive group A Streptococcal
infections: The past, present and future, Pediatr
Infect Dis J 1994; 13:561
4. Stevens DL: Streptococcal Toxic Shock
Syndrome: Spectrum of disease , pathogenesis
and new concepts in treatment. http://
www.cdc.gov/ncidod/EID/volno3/stevens.htm
Indian Journal of Practical Pediatrics
CASE STUDY
MCKUSICK - KAUFMAN:
HYDROMETROCOLPOS
POLYDACTALY - A RARE SYNDROME
*Sridharan S
**Pradip Vincent
***Ramesh S
Abstract : Discovery of an abdominal mass in a
neonate presents a challenging problem in
diagnosis and treatment. We present a neonate
with a large midline abdominal mass. Clinically
and sonologically it was proven to be
hydrometrocolpos. She also had polydactyly.
Hence a possible diagnosis of McKusick
Kaufman syndrome was made. The pit falls in
diagnosis of McKusick Kaufman syndrome is
highlighted. A single stage abdominoperineal
vaginal pull through for the repair is possible
but necessary steps to prevent vaginal stenosis
which should be followed are also discussed.
Keywords : Hydrometrocolpos, McKusick
Kaufman syndrome, Abdominoperineal vaginal
pull-through.
Case history
A term appropriate for gestational age female
baby with birth weight of 2.8 kg was born by an
emergency LSCS, indication being decreased fetal
movements with meconium stained liquor. The
affected child is the second child born to second
* Senior Consultant Pediatric Surgeon
** Surgical Resident
*** Consultant Pediatric Anaesthesiologist
Kanchi Kamakoti CHILDS Trust Hospital,
Nungambakkam, Chennai.
70
2006; 8(3) : 256
degree consanguineous parents. The mother had
polydactaly. The other sibling, a girl child, is
normal.
The antenatal ultrasound showed
hydrometrocolpos with hydronephrosis of right
kidney with paranephric pseudocyst. Apgar scores
were 7 and 9 at 1 and 5 minutes respectively.
Child was referred within 4 hours of birth with
evidence of large midline abdominal mass. The
baby passed meconium immediately after birth
and was voiding urine well.
Cardiovascular system examination was
normal. Limb examination revealed an extra digit
in right upper limb and left lower limb. Left lower
limb edema was also seen.
Physical examination revealed a distended
tense abdomen with dilated veins over the
abdomen (Fig.1). Palpation revealed a tensely
cystic to firm swelling occupying the umbilical and
suprapubic regions partly extending in to the
epigastric and right and left hypochondria. At the
upper pole of the swelling a firm to hard mass
was palpable whenever the child cried. Bladder
was also palpable as it was pushed forward.
External genitalia showed a single opening
(common urogenital sinus) between the labia.
There was no bulge. Clitoris appeared normal but
separate vaginal and urethral orifices were not
made out. Ano rectum was normal.
Characteristically the mass persisted even after
bladder catheterization.
A neonate with midline abdominal mass with
post axial polydactaly and a urogenital sinus with
absent vagina with a pre op provisional diagnosis
 2006; 8(3) : 257

of hydrometrocolpos the possiblity of The neonate didnot exhibit any problem both
McKusickKaufmann syndrome was thought. during induction and recovery from anesthesia.
Preoperative work up : Hematological The surgical procedure done was a single stage
investigations were normal. Sonogram revealed a abdominoperineal vaginal pull through with
right kidney (5x 2.5 cm) with grade II parenchymal creation of a new vagina at the normal position
change and dilated collecting system with (Figs. 2 and 3).
perinephric collection. Left kidney showed 2 to 3
Per operative findings: (1) A huge 20x 15cm
cortical cysts again with dilated collecting system.
dilated vagina with uterus, thick walled with
Echo cardiogram showed a small patent foramen
mucoid material approximately 150 ml. (2) Distal
ovale. A thorough genital / vaginal examination
atretic vagina (Fig. 4). (3) Normal ovaries and
was also done.
Fallopian tubes and (4) Bladder compressed
Anaesthetic work up : The major problem for anteriorly and a 6 Fr tube passed in to the bladder
anaesthesia for Mckusick Kaufman syndrome are draining clear urine.
the abdominal distension, large abdominal mass
causing circulatory and ventilatory dysfunction
associated congenital heart anomalies and some
times upper air way problems1. Preoperative echo
ruled out any congenital heart defects.

Fig. 2. Shows the bladder infront, uterus

behind and decompressed vagina in between
(stays on the vagina)

Fig. 3. Post surgery shows the bladder

catheterized, opened new vagina and a dilator
Fig. 1. Neonate with distended abdomen in the anus.
71
Indian Journal of Practical Pediatrics 2006; 8(3) : 258

Before After

Fig. 4. Line diagram showing anatomy of perineum before and after surgery

Follow up : A stent was kept in the neovagina

but on the sixth day it slipped out. From second
week child underwent routine vaginal dilatation.
On day 36 child had abdominal distension, hence
a sonoguided decompression of vagina with
cannula along with vaginal dilatation carried out.
Three months after surgery child developed
abdominal distension along with difficulty to void
urine. Sonogram revealed a recurrence of the
swelling. Hence a redo abdominoperineal vaginal
pull through was done (Fig. 5 & 6). This time an
indwelling sialastic tube was kept for more than 6
weeks followed by daily dilatations for 6 months. Fig. 5. Recurrent hydrometrocolpos after the
Child is regularly being followed up and in the vagina stenosed
last follow up underwent removal of the extra
digits.

Discussion
Hydrometrocolpos is a pathological distension
of uterus and vagina with excessive amount of
fluid in presence of distal vaginal outflow
obstruction2. It can be divided into secretory and
urinary type depending on the type of fluid, mucus
or urine3. The urinary type is related to a urogenital
sinus or cloacal anamoly, where as the secretory
type is related to the vaginal obstruction3. Vaginal
obstruction results from disorder of vertical and Fig. 6. Redo abdominoperineal - Vaginal pull
lateral fusion of mullerian ducts4. through

72
 2006; 8(3) : 259

Fig. 7

73
Indian Journal of Practical Pediatrics
Table 1. Classification of vaginal anomalies and treatment2
Type Anomaly
I Low hymenal obstruction
II Mid Plane Transverse membrane /septum
III Distal Vaginal atresia and high obstruction
IV Vaginal atresia with persistence of
Urogenital sinus
V Vaginal atresia with cloacal anomaly
The aim of surgical treatment is distal vaginal
drainage, which can be achieved by a perineal
procedure in most cases. Laparotomy is indicated
in cases of high vaginal atresia, urogenital sinus
or cloacal anomalies which require a pull through
procedure5,6.
Mc Kusick- Kaufmann Syndrome (MKKS)
and Bardet Biedel Syndrome (BBS)
First described by McKusick in 1964 and
1968; Kaufman in 1972 did a more
comprehensive description. It comprises of
hydrometrocolpos, polydactaly and congenital
heart defects and overlaps with Bardet- Biedel
syndrome (BBS) comprising of retinitis
pigmentosa or retinal dystrophy, polydactaly,
nephropathy, obesity, mental retardation, renal
and genital anomalies7.
MKKS is inherited in an autosomal recessive
pattern8. They are caused by the mutations in the
MKKS gene. Locus mapped to 20 p12 close to
the jagged 1 gene8.
So far about 60 cases of MKKS have been
reported7. Hydrometrocolpos is present in 80-95%
of females. Postaxial polydactaly is present in 90%
of cases. Congenital heart defects are seen in only
10% of cases. Mental prognosis in MKKS is
favourable9,10,11.
The similarities of MKKS and BBS indicate
that the MKKS gene products are likely to act in
74
2006; 8(3) : 260
Treatment
Hymenectomy
Abdominoperineal repair
Abdominoperineal vaginal pull-through
Abdominoperineal vaginal pull-through
Abdominoperineal vaginal pull-through
and rectal pull through
the same developmental pathway and to interact
with the proteins involved in the pathogenesis of
BBS7.
There are no phenotypic features in the
neonatal period that may show reliable
differentiation between MKKS and BBS as
hydrometrocolpos and polydactaly are common
to both syndromes7. The consequences of this
are straightforward. As long as genetic tests for
MKKS or BBS are unavailable routinely, genetic
counseling for parents of newborns with
hydrometrocolpos and polydactyly should be much
more cautious, even when congenital heart defect
is present, considering the poor visual prognosis
of BBS and the risk of mental impairment9. A
firm diagnosis of MKKS should be deferred to
5 to 10 years and the possibility of delayed
complications should be discussed accordingly.
Similarly, this clinical overlap in infancy makes it
necessary to establish systematic ophthalmolo-
gical and neurodevelopmental follow up of all
newborns presenting as MKKS10.
Conclusion
Hydrometrocolpos is a rare congenital
anamoly. A proper work up of the type of anamoly
is to be done before surgery. It is possible to do a
single stage abdominoperineal vaginal pull-
through12,13. After this it is advisable to keep a
indwelling sialastic tube to prevent adhesion.
Regular dilatation should be done for maintaining
 2006; 8(3) : 261

the patency of the vagina. As differentiation from
BBS is not possible, genetic counselling and long
term follow up are recommended.
References
1. Tekin I,OK G,Genc A, Tok D. Anesthetic
management in McKusick-Kaufman syndrome.
Paediatr Anaesth 2003; 13:167-170.
2. Gupta D. Hydrometrocolpos. In: New born
nd
surgery, 2 Edn,Ed, Prempuri, Oxford
University press, London 2003; pp. 875-882.
3. Jan HP, Kvist Nina, Nielsen OH.
Hydrometrocolpos current views on
pathogenesis and management. J Urol 1984;
132: 537-540.
4. Anthony S. Vaginal obstruction. Semin in Paed
surg 2000; 9: 128-134.
5. Ramenofsky M, Raffensperger JG. An
abdomino perineal vaginal pull -through for
definitive treatment of hydrometrocolpos.
J Paed Surg 1971 ; 6: 381.
6. Gerald CT, Victor MF. Hydrocolpos causing
urinary obstruction. J Urol 1964 ; 92 : 127
132.
7. David A, Bitoun P, Lacombe D, et al.
Hydrometrocolpos and polydactaly:a common
neonatal presentation of Bardet-Biedel and
McKusick-Kaufman syndromes. J Med Genet
1999;36:599-603.
8. Stone DL, Agarwala R, Schaffer, et al. Genetic
and physical mapping of the McKusick-
Kaufman syndrome. Hum Mol Genet 1998;
7:475-481.
9. Schaap C, de Die- Smulders CE, Kuijten RH,
Fryns J. McKusick Kaufman syndrome : The
diagnostic challenge of abdominal distension
in the neonatal period. Eur J Pediatr 1992 ;
151:583-585.
10. Lurie IW, Wulfsberg EA. The Mckusick-
Kaufman syndrome : Phenotypic variation
observed in familial cases as a clue for the
evaluation of sporadic cases. Genet Couns
1994 ; 5 : 275-281.
11. Chitayat D, Hahm SY, Marion RW. Further
delineation of the McKusick- Kaufman
hydrometrocolpos polydactyly syndrome.
Am J Dis child 1987;141: 1133-1136.
12. Graivier L, McKay D, Katz A. Hydrocolpos,
vaginal atresia and urethro vaginal fistula in a
Neonate : Abdomino perineal vaginal pull
through. J Paed Surg 1977; 12: 605-607.
13. Hendren Hardy. Further experience in
reconstructive surgery for cloacal anomalies.
J Paed Surg 1982; 17: 695-717.

NEWS AND NOTES

NCPID 2006
IX National Conference of Pediatirc Infectious Diseases
Theme : Pediatric infections - Basics and beyond
Date : 14-15 October 2006 Venue : Hotel Green Park, Chennai
Organised by Infectious Diseases Chapter - IAP
Host IAP-Tamil Nadu State Chatpter
in coordination with IAP - Chennai City Branch
Conference Secretariat :
NCPID2006
IX National Conference of Pediatric Infectious Diseases, Ground Floor, F-Block, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. Tamilnadu.
Phone : (O) 044-28191524, 044-42696885 Email : ixncpid2006@yahoo.co.in
75
Indian Journal of Practical Pediatrics
PRACTITIONERS COLUMN
IS THERE A NEED FOR REGULAR
ULTRASOUND IN EVERY INFANT?
*Janani Sankar
*Alka Sophia Rao
**Nammalwar BR
**Vijayakumar M
***Muralinath S
Congenital abnormalities of the renal and
urinary tract of the fetus constitute about
2030% of all fetal abnormalities1. The frequency
of infant mortality due to genito-urinary
malformations is about 10 per 10000 live births1.
The early antenatal diagnosis of these
abnormalities by ultrasonographic examination
and early postnatal intervention improves
considerably the prognosis of children having such
divergences in their renal and urinary tract1. Some
of the defects are even amenable to intrauterine
interventions. The anomalies that are not detected
antenatally get detected during a routine sonogram
done for indications like UTI, PUO and recurrent
abdominal pain during infancy. At times the
pediatrician is in for a surprise when anomalies
like dysplastic kidneys and single kidneys are
identified. There is a strong indication for regular
ultrasound in every infant coming under the review
of pediatrician, as early detection and treatment
reduces the future morbidity related to renal
diseases and dysfunction. We feel that this
approach will help us to reduce the expenditure
* Pediatrician
** Consultant Pediatric Nephrologist
*** Radiologist
Kanchi Kamakoti CHILDS Trust Hospital,
Nungambakkam, Chennai.
76
2006; 8(3) : 262
involved in treating these children at later years
when they present with the end result, the chronic
kidney disease in adulthood.
Our experience and opinion
We had conducted an analysis to find out
the frequency of renal anomalies, detected by
ultrasonogram done for renal and non-renal
indications and to analyse the type of anomalies
and their modes of presentation as well as to assess
the co-relation of the type of anomalies with clinical
presentation.
A total number of 2889 abdominal sonograms
were done between January to December
2001.Out of this 223 (7.7%) children had renal
anomalies. Sixty-eight (30.49%) children were less
than 1 year, 62 (27.8%) were between 1-3 years,
49 (21.9%) between 3- 6 years and 44 (19.7%)
were in more than 6 years age group. The male
to female ratio was 2:1.
Some important observations made in this
study were as follows (Table-1). Failure to thrive
and recurrent vomiting were the symptoms in
50.3% of children with small kidneys. Recurrent
abdominal pain was the presentation in 44.8% of
ectopic kidneys. No specific urinary symptoms
were documented in 15.5% of hydronephrosis,
55.2% of ectopic kidneys and 73.2% of renal
agenesis. No specific urinary symptoms could be
documented in 77.0% of anomalies that were
detected in children more than 6 years of age.
Indications for ultrasonograms by convention
include; 1) follow up of antenatally detected
anomalies 2) in pyrexia of unknown origin, to
locate the site of infection, 3) recurrent abdominal

Table 1. Observations from abnormal ultrasonograms
Renal anomaly Follow-up Recurrent Recurrent
found scan done* vomiting abdominal pain thrive
Bifid Coll. system # - -
Agenesis - -
Ectopic Kidney - -
Small Kidneys - 27.8%
Hydronephrosis 72% - -
* Follow up scan done for antenatally detected anomalies
# Bifid collecting system
pain, 4) in dysmorphic features like ear anomalies
and vertebral anomalies to rule out associated renal
anomalies and 5) in recurrent culture positive
urinary tract infection to assess the renal status.
Not infrequently major or minor renal anomalies
are identified in them.
Discussion
To establish the prevalence of renal
abnormalities in school children an epidemiological
study of 132,686 school children, including 69,903
boys and 62,783 girls, was conducted from March
1987 to May 1988 in the City of Taipei3. Renal
abnormalities were detected in 645 students
(0.5%). There were 256 (39.6%) hydronephrosis,
103 (15.9%) unilateral renal agenesis, 128 (19.8%)
unilateral small kidneys, 90 (13.9%) renal cystic
disorders, 30 (4.6%) ectopic kidneys and 38
(5.8%) other abnormalities. Surgically correctable
lesions were demonstrated in 50 of these children.
In another study by Sheih CP et al, rapid renal
ultrasonography was found to effectively detect
some renal abnormalities initially and then
prevalence could be established with further
investigations3. In the present study renal anomaly
without specific urinary symptoms were found in
7.7% of children and bifid collecting system was
77
2006; 8(3) : 263
Failure to Culture No Specific
positive UTI urinary
symptoms
- - 65.5% 34.5%
- 13% 13.8% 73.2%
44.8% - - 55.2%
- 22.5% - 49.7%
- 12.5% 15.5%
the commonest anomaly seen (42.8%) followed
by small sized kidneys (29.2%), hydronephrosis
(8.7%) and rotational anomalies (9.0%) and others.
(Table-2)
Studies have recommended the routine use
of ultrasound in healthy infants because a
significant number of infants harbor silent urinary
tract abnormalities that can be detected by
ultrasound at a low cost 4. This study supports
our observation that in children more than 6 years
diagnosis of renal anomalies without specific
urinary symptoms was noted in 77% of children.
Every second patient with a solitary kidney
suffers from renal disease. This accumulation of
renal diseases of varying origin makes special care
for these children necessary5. This observation is
very true and it is our duty to protect those with
single kidney from developing infection,
hypertension and end stage renal disease.
Counseling of parents is also important. As renal
anomalies can get missed during routine prenatal
sonogram and early detection of these anomalies
can prevent progression of disease and prevention
of end stage renal disease and considering the easy
availability and non-invasiveness of ultra
sonogram, routine post- natal sonogram should
Indian Journal of Practical Pediatrics
Table 2. Various renal anomalies detected incidentally
Type of anomaly
Bifid collecting system
Small sized kidneys
Hydronephrosis
Rotational anomalies
Ectopic kidney
Renal agenesis (unilateral)
Miscellaneous (Horse-shoe kidney, fused kidneys)
be done as a part of health screening programmes
in children3.
Conclusion
References
From our experience and opinion from
literature we could derive the following conclusions
Renal anomalies may be detected without
specific urinary symptoms in children with
recurrent vomiting, failure to thrive and
recurrent abdominal pain.
Early diagnosis of major anomalies helps in
initiation of treatment and prevention of
complication and end stage renal disease.
Considering the number of anomalies without
specific urinary symptoms identified during
sonogram done for other indications, we feel
postnatal sonograms during infancy should
be routinely advised in the following
situations; family history of renal anomalies,
previous fetal loss/neonatal deaths and
presence of other congenital anomalies.
NEWS AND NOTES
MP PEDINEOCON 06
Venue: Gwalior Date: 2nd & 3rd December 2006
For futher details contact: email: mppedicon06@yahoo.co.in
78
2006; 8(3) : 264
Percentage of children
42.8%
29.2%
8.75%
9%
4.25%
4.5%
1.5%
Its routine need in every infant to reduce
future morbidity and mortality can be obtained
clearly only with multicentric analysis.
1. Todarova M,Buzalov S,Vasilev . Prenatal
Diagnosis of Bilateral Fetal Renal
Polycystosis. Akush ginekol 2000; 39: 53-55
(Medline ref)
2. Gunn TR, Mora JD, Pease P.Antenatal diagnosis
of urinary tract abnormalities by
ultrasonography after 28 weeks gestation:
incidence and outcome. Am J Obstet Gynecol
1995; 172: 479-486.
3. Sheih CP, Liu MB, Hung CS, Yang KH, Chen
WY, Lin CY. Renal abnormalities in
schoolchildren. Pediatrics 1989; 84 (6):1086-
1090.
4. Donovan JM, Ney KG, Maizels M. Urosound.-
In-office ultrasonography for pediatric
urology. Urol Clin North Am 1989; 16(4): 841-
855.
5. Beyer HJ, Hofmann V, Brettschneider D .
Value of ultrasound in the treatment of solitary
kidneys in infancy and childhood. Prog Pediatr
Surg 1989; 23:3-17.
 2006; 8(3) : 265

PICTURE QUIZ

3 year old girl with history of tilting of head to the right and inability to abduct the right eye;
following a short duration of fever

What is the diagnosis, aetiology and prognosis?

Compiled by:
*Ganesh R, **Deenadayalan M, ***Lalitha Janakiraman

*Resident in Pediatrics, **Junior Consultant in Pediatrics,

***Senior Consultant Pediatrician
Kanchi Kamakoti CHILDS Trust Hospital
12-A, Nageswara Road, Nungambakkam, Chennai - 600 034.
Tamilnadu.

Answer on page: 268

79
Indian Journal of Practical Pediatrics
EMERGING EPIDEMICS
CHIKUNGUNYA - IS IT A THREAT?
What is chikungunya fever?
Chikungunya fever is a viral disease
transmitted to humans by the bite of infected
mosquitoes. Chikungunya virus (CHIKV) is a
member of the genus Alphavirus, in the family
Togaviridae. CHIKV was first isolated from the
blood of a febrile patient in Tanzania in 1953,
and has since been identified repeatedly in west,
central and southern Africa and many areas of
Asia, and has been cited as the cause of numerous
human epidemics in those areas since that time.
The virus circulates throughout much of Africa,
with transmission thought to occur mainly
between mosquitoes and monkeys.
What type of illness does
chikungunya virus cause?
CHIKV infection can cause a debilitating
illness, most often characterized by fever,
headache, fatigue, nausea, vomiting, muscle pain,
rash, and joint pain. The term chikungunya is
Swahili for that which bends up.
The incubation period (time from infection
to illness) can be 2-12 days, but is usually 3-7
days. Silent CHIKV infections (infections
without illness) do occur; but how commonly this
happens is not yet known.
Acute chikungunya fever typically lasts a few
days to a couple of weeks, some patients have
prolonged fatigue lasting several weeks.
Additionally, some patients have reported
incapacitating joint pain, or arthritis which may
last for weeks or months. The prolonged joint
pain associated with CHIKV is not typical of
80
2006; 8(3) : 266
dengue. Co-circulation of dengue fever in many
areas may mean that chikungunya fever cases are
sometimes clinically misdiagnosed as dengue
infections, therefore the incidence of chikungunya
fever could be much higher than what has been
previously reported.
No deaths, neuroinvasive cases, or
hemorrhagic cases related to CHIKV infection
have been conclusively documented in the
scientific literature.
CHIKV infection (whether clinical or silent)
is thought to confer life-long immunity.
How do humans become infected
with chikungunya virus
CHIKV is spread by the bite of an infected
mosquito. Mosquitoes become infected when they
feed on a person infected with CHIKV. Monkeys,
and possibly other wild animals, may also serve
as reservoirs of the virus. Infected mosquitoes
can then spread the virus to other humans when
they bite.
Aedes aegypti (the yellow fever mosquito),
a household container breeder and aggressive
daytime biter which is attracted to humans, is the
primary vector of CHIKV to humans. Aedes
albopictus (the Asian tiger mosquito)may also play
a role in human transmission is Asia, and various
forest-dwelling mosquito species in Africa have
been found to be infected with the virus.
How is chikungunya virus infection
treated?
No vaccine or specific antiviral treatment for
chikungunya fever is available. Treatment is
symptomaticrest, fluids, and ibuprofen,
 2006; 8(3) : 267

naproxen, acetaminophen, or paracetamol may
relieve symptoms of fever and aching. Aspirin
should be avoided
Infected persons should be protected from
further mosquito exposure (staying indoors and/
or under a mosquito net during the first few days
of illness) so that they cant contribute to the
transmission cycle.
What can people do to prevent
becoming infected with chikungunya
virus?
The best way to avoid CHIKV infection is
to prevent mosquito bites. There is no vaccine or
preventive drug. Prevention tips are similar to
those for dengue or West Nile virus:
Use insect repellent containing an DEET or
another EPA-registered active ingredient on
exposed skin. Always follow the directions
on the package.
Wear long sleeves and pants (ideally treat
clothes with permethrin or another repellent).
Have secure screens on windows and doors
to keep mosquitoes out.
Get rid of mosquito breeding sites by
emptying standing water from flower pots,
buckets and barrels. Change the water in pet
dishes and replace the water in bird baths
weekly. Drill holes in tire swings so water
drains out. Keep childrens wading pools
empty and on their sides when they arent
being used.
Additionally, a person with chikungunya fever
or dengue should limit their exposure to
mosquito bites in order to avoid further
spreading the infection. The person should
stay indoors or under a mosquito net.
Source : WWW.cdc.gov/travel

NEWS AND NOTES

PHOCON 2006
X NATIONAL PAEDIATRIC HAEMATOLOGY ONCOLOGY CONFERENCE
Date: 16th-18th November 2006
Venue: Christian Medical College, Vellore, Tamil Nadu
Registration Fee Till 15.10.06 SPOT
IAP Member Rs.1,000/- Rs.1,200/-
PG Student* Rs. 800/- Rs. 900/-
Non-IAP Member Rs.1,200/- Rs.1,500/-
Accompanying person Rs. 600/- Rs. 600/-
All payments to be made by Demand Draft, in favour of Phocon 2006 payable at Vellore.
Leni G Mathew Mammen Chandy
Organizing Secretary Chairperson
For further details contact : Leni G Mathew, Organizing Secretary, PHOCON 2006,
Child Health Unit I, Christian Medical College and Hospital, vellore 632 004, Tamil Nadu.
Tel: 91-416-2283350 Fax: 91-416-2232103 eimail: lenimathew@cicvellore.ac.in

81
Indian Journal of Practical Pediatrics 2006; 8(3) : 268

QUESTION AND ANSWER

Q.No.1. A male child 1 year 3 months, 8 kg
attended a clinic (Indian Red Cross Society) for
2nd dose of Hepatitis B vaccine, which is 3 months
after the 1st dose. The mother was requested to
take the first dose again and then 2nd and 3rd dose
after one and 6 month of the first dose. Kindly
let me know what is the Hepatitis B vaccination
schedule suggested for this child?
Dr.Pradyut Mondal
Khoshbagan, Burdwan, West Bengal.
A.No.1. This is a very wrong immunization
practice; all 3 doses of hepatitis B vaccine can be
completed within one year of starting the 1st dose.
So the correct schedule that should have been
followed in this child is to have given the 2nd dose
when the mother reported after 3 months after
the 1st dose and complete the 3rd dose at 4 weeks
(28 days) intervals after the 2nd dose. Being an
aluminium adjuvanted vaccine the completion of
3 doses within 1 year of starting the 1st dose is
equally immunogenic. It has been categorically
proved that the immuogenicity of Hepatitis B
vaccine is 96-98% by whatever schedule the
vaccine is administered. viz birth, 6, 14 weeks,
6,10,14 weeks; 0,1,2 months or 0,1,6 months.
Further no booster doses are necessary as
protective titer is enhanced to more than 10mIU,
when it falls below the protective level due to
anamnestic response.
Prof.Dr.A.Parthasarathy
Retd. Clinical Professor
MMC, Chennai.

PICTURE QUIZ

Answer for the picture quiz

Diagnosis is right lateral rectus palsy

Acquired isolated abducens nerve palsy in children is rare. The aetiology is usually post- viral. Other
less common causes are trauma, tumor and meningitis. This condition is generally benign and
resolves spontaneously within 2 weeks to 2 months. In this child, it was probably post viral and she
recovered completely within 2 months.

82
 2006; 8(3) : 269

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

SUBSCRIPTION TARIFF
IJPP
JOURNAL OFFICE Official Journal of the Indian Academy of Pediatrics
IAP TNSC Flat, Ground Floor, F Block, A quarterly medical journal committed to practical
Halls Towers, 56/33 Halls Road, Egmore, pediatric problems and management update
Chennai 600 008. For office use
Phone: +91-44-28190032, 42052900.
Email: ijpp_iap@rediffmail.com Ref. No.
Cash / DD for Rs.
Enter ONE year
Subscription DD No.
for TEN years
Receipt No. & Date

Name ..................................................................................................................................

Address ................................................................................................................................

...............................................................................................................................................

City ...............................................................State ................................................................

Pin .............................. Phone (R) ...................................... (O)............................................

Mobile ...................................... Email ...................................................................................

Designation ................................................. Qualification........................................................

I am enclosing a DD No. .. dated drawn on .................

favoring Indian Journal of Practical Pediatrics for Rs

Signature
Subscription rate

Individual Annual Rs.300/- Send your subscription, only by crossed demand draft,
Ten Years Rs.3000/- drawn in favour of INDIAN JOURNAL OF PRACTICAL
PEDIATRICS, payable at Chennai and mail to
Institution Annual Rs.400/- Dr.A.BALACHANDRAN, Editor-in-Chief, F Block,
Ten Years Rs.4000/-
No.177, Plot No.235, 4th Street, Anna Nagar East,
Chennai - 600 102, Tamilnadu, India.
Foreign Annual US $ 50/-
83
Indian Journal of Practical Pediatrics 2006; 8(3) : 270

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

ADVERTISEMENT TARIFF
Official Journal of the Indian Academy of Pediatric - A quarterly medical journal
committed to practical pediatric problems and management update

Name ...................................................... FULL PAGE

Address .................................................. B/W Colour*

............................................................... Ordinary 5,000 10,000
............................................................... Back cover - 15,000
...............................................................
Second cover - 12,000
City .........................................................
Third cover - 12,000
State ............................... Pin................

* Positives of the advertisements should be given by the company.

Signature
Kinldy send your payment by crossed demand draft only drawn in favour of
Indian Journal of Practical Pediatrics and art work / matter to

MANAGING EDITOR
Indian Journal of Practical Pediatrics
IAP-TNSC Flat, Ground Floor,
F Block, Halls Towers,
56 (Old No.33), Halls Road,
Egmore, Chennai - 600 008. India
Phone : 044-2819 0032, 044-42052900
Email : ijpp_iap@rediffmail.com

84
 2006; 8(3) : 271

Indian Journal of
Practical Pediatrics IJPP
Subscription Journal of the
Indian Academy of Pediatrics

JOURNAL COMMITTEE NATIONAL ADVISORY BOARD

Editor-in-Chief President, IAP

Dr. A.Balachandran Dr.Nitin K Shah
Executive Editor
President 2007, IAP
Dr. K.Nedunchelian
Managing Editor Dr.Naveen Thacker
Dr. Malathi Sathiyasekaran Editor, Indian Pediatrics
Associate Editors
Dr. Panna Choudhury
Dr. N.C.Gowrishankar
Dr. P.Ramachandran Members

Dr. C.V.Ravisekar Dr. Arati Deka

Dr. V.Sripathi Dr. B.K.Bhuyan
Dr. S.Thangavelu
Dr. C.Kamaraj
Executive Members
Dr.Kul Bhushan Sharda
Dr. G. Durai Arasan
Dr. Mahesh Kumar Goel
Dr. Janani Sankar
Dr. S.Lakshmi Dr. M.A.Mathew
Dr. V.Lakshmi Dr. Mukesh Kumar Khare
Dr. (Major) K.Nagaraju Dr. Subhash Singh Slathia
Dr. T. Ravikumar Emeritus Editors
Dr. S.Shanthi
Dr. A.Parthasarathy
Dr. So.Shivbalan
Dr. B.R.Nammalwar
Dr. C.Vijayabhaskar
Dr. M.Vijayakumar
Dr. Deepak Ugra
(Ex-officio)

85
Indian Journal of Practical Pediatrics 2006; 8(3) : 272

Indian Academy
of Pediatrics
IAP Team - 2006 Kailash Darshan,
Kennedy Bridge,
Mumbai - 400 007.
President Karnataka
Dr.Nitin K Shah Dr.M.Govindaraj
President-2007 Dr.R.Nisarga
Dr.Naveen Thacker Dr.Santosh T Soans
President-2005 Kerala
Dr.Raju C Shah Dr.Guhan Balraj
Vice President Dr.M.A.Mathew
Dr.VN.Tripathi Dr.T.U.Sukumaran
Secretary General Madhya Pradesh
Dr.Deepak Ugra Dr.Mukesh Kumar Khare
Treasurer Dr.C.P.Bansal
Dr.Rohit C Agrawal Maharashtra
Editor-in-Chief, IP Dr.Anand K Shandilya
Dr.Panna Choudhury Dr.Tanmay Amladi
Editor-in-Chief, IJPP Dr.Vijay N Yewale
Dr.A.Balachandran Dr.Yashwant Patil
Joint Secretary Manipur
Dr.Bharat R Agarwal Dr.K.S.H.Chourjit Singh
Members of the Executive Board Orissa
Andhra Pradesh Dr.B.K.Bhuyan
DR K Umamaheswara Rao Punjab
Dr.P.Venkateshwara Rao Dr.Kul Bhushan Sharda
Dr.P.Sudershan Reddy Rajasthan
Assam Dr.Prem Prakash Gupta
Dr.Arati Deka Dr.Ashok Gupta
Bihar Tamilnadu
Dr.Sachidanand Thakur Dr.K.Chandrasekaran
Chhattisgarh Dr.M.P.Jeyapaul
Dr.Pradeep Sihare Dr.K.Nedunchelian
Delhi Uttar Pradesh
Dr.Ajay Gambhir Dr.Mahesh Kumar Goel
Dr.Sunil Gomber Dr.V.N.Tripathi
Gujarat Dr.Vineet K Saxena
Dr.Baldev S Prajapati West Bengal
Dr.Satish V Pandya Dr.Nabendu Choudhuri
Haryana Dr.Sutapa Ganguly
Dr.Verender N Mehendiratta Services
Jammu and Kashmir Brig. Vipin Chandar
Dr.Subhash Singh Slathia IAPs Spl. Representative
Jharkhand Dr.Anupam Sachdeva
Dr.Bijay Prasad A.A.A.
Dr.Kamlesh K Shrivastava
86