Guidelines and Recommendations on
Citing the Evidence
The IAP has published its updated Policies, Guidelines
and Recommendations on Immunization 2003 (1). However
unlike the recommendations of the Centre for Disease
Control Advisory Committee on Immunization Practice (2),
the document published by the IAP cites no references.
In the sphere of Evidence-Based-Medicine, the evidence
from ‘expert committee reports or opinions and / or
clinical experience of respected authorities’,
represents Category IV evidence. The strength of the
recommendations based on category IV evidence, is the
lowest Grade D, according to the categories of evidence
described by Eccles and Manson (3).
We believe the recommendations of the IAP expert
committee must surely be evidence-based, but the
references may have been omitted due to persuasions of
brevity. The committee should therefore be able to
provide the references on request and this would improve
the strength of its recommendation.
We seek to enquire about the evidence-base for 3 of the
1. There is controversy about the mortality from
Hepatitis B in India. The WHO has suggested that 250,000
die due to the disease each year (4, 5). The projection
made by the Indian Council of Medical Research (ICMR)
suggests that about 5000 die from Hepatitis B each year
(6). We have recently published in the Lancet, how the
WHO figure can be arrived at, by wrongly extrapolating
data from Taiwan (7).
The cost-benefit equation is different, depending which
figure is accepted. It is crucial to know what figure
for mortality the IAP expert committee used, for its
cost-benefit evaluation, before recommending hepatitis B
vaccine to the government for inclusion in the UIP.
2. With regard to the timing of hepatitis B vaccination,
we notice a subtle shift in policy, from the IAP policy
in 2001 (8). The old policy suggested, ‘the first dose
at birth with subsequent two doses at 6 week and 14
weeks of age’. It stated, “It is important to note that
the first dose at birth is essential to prevent
perinatal transmission. If the first dose at birth is
missed, it should be given at 6 weeks, 10 weeks and 14
weeks of age.” The 2003 recommendation starts instead by
stating “We wish to emphasize the fact that in our
country, horizontal transmission of the disease appears
to be an important mode of transmission of the disease
along with vertical ie. mother to child (transmission).”
We have looked for evidence that has appeared since the
Policy Statement of 2001, for the assertion that,
“horizontal transmission is an important mode of
transmission”. There are few good studies looking at
this issue after the 2001 recommendation. An old study
by Nayak et al (9) suggested that one third of chronic
hepatitis B carriers acquired infection by perinatal
spread and the remaining acquired infection in early
childhood “very likely from contact with perinatally
infected children”. Prevention of vertical spread is
thus crucial both to prevent mother-to-child
transmission and also child-to-child transmission.
Aggarwal et al (10) have done calculations, using
primary data that is available in the abstract of the
paper by Nayak et al (9) and suggested that 86% of
chronic hepatitis B infection in India occur in
offspring of mothers who lack HBsAg and so delayed
vaccine would be effective. We discuss the issue of this
distortion of the findings of Nayak et al, in the Indian
Journal of Gastroenterology (11). It will be interesting
to know if the IAP has come across other strong evidence
of horizontal transmission prompting this change in
3. The 2003 policy suggests that Hib vaccine should be
offered to all children. It states that Hib is a vaccine
that merits active consideration to be included in the
UIP. We find this surprising. International literature
is awash with evidence that the incidence of Hib disease
is extremely low in India.
In Gambia, Hib vaccination brought down the incidence of
Hib meningitis from 200 per 100 000 to just 20 per 100
000(12). In India even without immunization, the
incidence of Hib disease is 9 per 100 000, according to
a large, prospective, population based study, conducted
by the WHO recently (13).
The 4 year IBIS study in 6 referral hospitals in India,
after employing sophisticated culture techniques to
isolate the organism, also found a remarkably low
incidence of Hib disease (14, 15). In the journal
Vaccine, we have described how cross-reactive-antigens
may be responsible for the low incidence of invasive Hib
disease in India (16).
After the two studies quoted above (13, 14.) there can
be little argument that the incidence of the disease is
truly low in India. It would be useful to know if the
IAP has taken cognizance of these 2 studies, in which
members of the expert committee may have participated.
Like Yellow-fever-vaccine is not routinely recommended
in India because the risk of disease is low, must we not
abandon Hib vaccine use, with its low risk of disease?
Members of the IAP are extremely proud of the editorial
independence of its journal and for its high standards
(17). It is fitting that the evidence-base of what is
published here, is discussed in the journal itself. We
hope this can be done with reference to literature, and
without taking issues of science at a personal level.
-Noopur Baijal, Jacob M Puliyel, Department of
Pediatrics, St Stephens Hospital
Tis Hazari, Delhi 110054
Academy of Pediatrics Committee on Immunization.
Update on Immunization Policies, Guidelines and
Recommendations Indian Pediatrics 2004; 41:239-244
Advisory committee on Immunization practices and the
American Academy of Family Physicians. General
recommendations on immunization.
MMWR Morb Mortal Wkly Rep. 2002 ;51(RR02):1-36.
M, Manson J. How to develop cost-conscious
Health Technol Assess. 2001;5(16):1-69
MA, Kane M Routine hepatitis B immunization in
India: cost-effectiveness. Indian J Pediatr
MA, McCann L. Policy analysis of the use of
Hepatitis B, Hemophilus influenzae type B,
Streptococcus pneumoniae- conjugate and Rotavirus
vaccines in the National Immunization Schedules.
Health Economics. 2000; 9: 19-35
V, Mohandas KM. Epidemology of digestive tract
cancers in India 111 – Liver. Indian J Gstroenterol
Puliyel JM Plea to restore public funding for
Committee on Immunization Indian Academy of
Pediatrics. Update Policies, Guidelines and
Recommendations on immunization - 2001
NC, Panda SK, Zuckerman AJ, Bhan MK, Guha DK.
Dynamics and impact of perinatal transmission of
hepatitis B in India J Med Virol 1987;21:137-45
Aggarwal R, Naik SR. Prevention of hepatitis B
infection: the appropriate strategy for India.
Natl Med J India. 1994;7:216-20.
M, Jindal K, Abraham N, Aruldas , Puliyel JM.
Hepatitis B immunization:cost calculation in a
community –based study in India Indian J
Adegbola RA, Usen SO, Weber M,Lloyd-Evans N, Jobe K,
Mullholland KPWJ et al.Hemophilus influenza type b
meningitis in The Gambia after introduction of a
conjugate vaccine. Lancet 1999;354:1091-2
JP, Levine O, Santosham M. Global reduction of Hib
disease: what are the next steps? Proceedings of the
meeting Scottsdale, Arizona, September 22-25, 2002.
J Pediatr. 2003;143(6 Suppl):S163-87.
Invasive Bacterial Infections Surveillance (IBIS)
Group of the International Clinical Epidemiology
Network. Are Haemophilus influenzae infections a
significant problem in India? A prospective study
and review. Clin Infect Dis. 2002 1;34:949-57.
Steinhoff MC. Invasive Haemophilus influenzae
disease in India: a preliminary report of
prospective multihospital surveillance. IBIS
(Invasive Bacterial Infections Surveillance) Group.
Pediatr Infect Dis J. 1998 Sep;17(9 Suppl):S172-5.
Puliyel JM, Agarwal KS, Abed Abas F. Natural
immunity to Haemophilus influenza b in infancy in
Indian children. Vaccine. 2001 14;19:4592-4.
P, Choudhury P Declaring competing interest. Indian
Pediatrics 2003;40: 3-6
With reference to ‘Recommenations’ of IAP Committee on
Immunization (1), I would like to offer few comments.
The committee has stated that to get “an optimum immune
response the recommended interval between second and
third dose of HB vaccine should be at least 8 weeks”.
However, to devise an ideal schedule of HB vaccine and
to take the maximum immunoprotective benefits, it is
also imperative that the last dose of any HB schedule,
be it 3-dose or 4-dose, should not be administered
before 6 months of chronologic age (2). This
recommendation is based to achieve the high boosting
effects on consequently maximum possible GMT levels of
antibodies (2). Hence, any HB schedule concluding before
6 months of age would only offer less than maximum
possible immune benefits to the vaccinee. Further, the
stated option of 0, 1 and 2 months for adolescent
vaccination also does not confirm to the criteria of
minimum interval between 2nd and 3rd dose of HB vaccine.
The recommendation of starting HB vaccination of preterm
and small-for-dates babies at birth is still debatable
and might not confer adequate protection if given to
infants weighing <2000 grams at birth. These infants
would need an extra dose of HB vaccine if vaccination
started at birth (2).
The committee has recommended Government of India (GOI)
to include Vi- polysaccharide vaccine in its national
immunization schedule. However, this is to be noted that
all the available typhoid vaccines in the market today
including Vi-polysaccharide vaccine, are only moderately
efficient (50-70%) in traditional target groups of
children under 5 years of age (3). Thus, before coaxing
GOI to manufacture and include this vaccine in national
immunization schedule, it would be more appropriate to
wait till a more efficient, conjugate version of current
Vi-vaccine is available in the market. Alternatively,
the government should be urged to explore possibilities
of developing the same in the country.
The recommendation that Hib vaccine “needs serious
consideration for inclusion in the national immunization
schedule, while awaiting disease burden studies” is a
lucid example of contradictory statement and almost
amounts to oxymoronic proposition. How could a vaccine
be recommended against any disease for universal
adoption without first ascertaining and quantifying the
disease burden caused by the disease itself?
4- Hepatitis A vaccination:
The committee has recommended Hepatitis A vaccine to
children at 2 years of age. Most of the recent Indian
studies have shown that there is gradual decline of
maternally acquired anti-HAV antibodies after birth and
reach their nadir around 12-24 months (4, 5). This is
the most vulnerable period for a child to contract the
disease. Thus, to cover the most susceptible population,
it would be prudent to use the vaccine during this
period i.e. between 12-24 months of age.
The dose of Hepatitis A vaccine mentioned in the article
reflects the dose recommended by only one vaccine
manufacturer, however, the dose of the vaccine marketed
by other manufacturer is different.
Contrary to committee’s conclusion that pneumococcal
vaccine is not indicated for universal immunization in
our country at present, the limited epidemiological data
show that this vaccine is indeed urgently needed in the
country (6). In fact, the disease burden posed by
Pneumococcal disease both in terms of morbidity and
mortality far outweighs the one inflicted by Hib disease
in the country. However, non-availability of a good
conjugate vaccine consisting of all the prevailing
serotypes responsible for serious disease in the country
and exorbitant cost of the vaccine available elsewhere
in the world are altogether different issues.
Recommendations to Ministry of Health, GOI:
The first and foremost recommendation to GOI should be
to initiate efforts to generate authentic data on
epidemiology of those vaccine preventable diseases (VPDs)
on which adequate data are lacking, such as, Hib and
Pneumococcal diseases. The government needs to be
recommended to sponsor multicentric trials to generate
indigenous data, both hospital and community based on
The committee should also stress the government the need
of starting efforts in the direction of making certain
vaccines, not available in India but needed most here
such as conjugate Pneumococcal vaccines (available
elsewhere in the world) and the vaccines against
Rotavirus and other diarrheal diseases and RSV vaccines
(currently under process of development) available in
India at affordable prices.
-Vipin M. Vashishtha,
(For references, kindly visit our website
www.pediascene.com or write to editor).
1-Committee on Immunization, Indian Academy f
Pediatrics. Update on immunization policies, guidelines
and recommendations. Indian Pediatr 2004; 41: 239-244.
2-American Academy of Pediatrics. In Pickering LK, ed.
2003 Red Book; Report of the Committeeon Infectioud
Diseases. 26th edn Elk Grove Village, IL: American
Academy of Pediatrics; 2003.
3-World Health Organization. Typhoid vaccines. WHO
position paper. Weekly Epidemiological Record, 2000,
4- Dutta AK, Aggarwal A, Kapoor AK, Ray GN, Batra S.
Sero-epidemiology of Hepatitis A in children in Delhi.
Indian J Pediatr 2000; 67:77-79.
5-Mittal SK, Rastogi A, Kumar N, Talukdar B, Kar P.
Seroprevalence of Hepatitis A in children-Implication
for Hepatitis A vaccine. Trop Gastroenterol 1998; 19:
6- Prospective multicentre hospital surveillance of
streptococcus pneumoniae disease in India. Invasive
bacterial infection surveillance (IBIS) group,
Internatinal clinical epidemiology network (INCLEN).
Lancent 1999; 353: 1216-1221.