immunization programme (UIP) in its recent move has decided to introduce
pentavalent vaccine in selected states.1
When given separately, it needs 9 shots 3 for DPT+3 for Hep-b +3 for
Hib to provide protection against all the above-mentioned diseases. Pentavalent
vaccine reduces it to 3 shots. Besides providing immunity and protection
quickly and safely, it reduces cost, 1 occupational-environmental hazards as
well as cause less distress and inconvenience for the children and their parents.
Active immunization against vaccine preventable
diseases have played a crucial role in bringing down the burden of these
diseases and indirectly reducing the cost of medical care involved in treating
these conditions and their related complications. Presently, on a programmatic
basis, the universal immunization programme (UIP) in India provides free
immunization services against tuberculosis, poliomyelitis, diphtheria,
pertussis, tetanus, hepatitis B, measles, mumps and rubella.
The pentavalent vaccine, consisting H. Influenzae B
(Hib) component in addition to DPT and Hep B is currently in vogue in private
practice all across India. The introduction of this vaccine in government
programme is still in conceptual stages due to a lot of debate regarding the
safety of Hib component in the vaccine.
Monitoring and surveillance of AEFI due to
pentavalent vaccine in the UIP requires in depth analysis before it can be
approved for further use. Very few prospective studies in Maharashtra have
taken incidence of AEFI in pentavalent vaccine recipients as their primary
research question. Hence, this study will be conducted to
assess the incidence of AEFI among children who received the pentavalent
Safety monitoring of vaccines used in routine
programmes on immunisation is important in all settings. As the rates of
vaccine preventable diseases decrease, even minor common adverse events in
children causes a lot of concern in the parents. Identification, detection,
prevention and appropriate communication of adverse events following
immunisation (AEFI) are therefore essential to preserve the integrity of
immunisation programmes and protect public health.
To add pneumonia due to Haemophilus Influenzae B (Hib) to the list of vaccine preventable
diseases on a national basis the pentavalent vaccine (DPT+HepB+Hib) is proposed
to be used. This vaccine is in use by civilian practitioners since a decade. As
a part of Universal Immunization Program, it is introduced in two states only
(Kerala and Tamil Nadu), as a pilot project in Dec 2011. However, there is a
lot of debate in the country about the relevance of the pentavalent vaccine in
general and the Hib component in particular, in view of reports of deaths in
children following immunization with the vaccine in these two states 3.
A public interest litigation (PIL) has also been filed in the Delhi High Court
against the use of the vaccine by a group of eminent pediatricians 4.
This concern gains more relevance in the light of reports of deaths and severe
adverse events following immunization (AEFI) due to pentavalent vaccine usage
in Pakistan, Sri-Lanka and Bhutan 4, 5. This vaccine had faced a
lot of scrutiny and subsequent withdrawal from the govt programme in Sri-Lanka
in 2008 6.
For western countries where the incidence of
complicated and serious Hib infections is higher compared to that in Asian
countries, the use of pentavalent vaccine in routine immunization is
understandable. In fact, the introduction of the pentavalent vaccine and other
Hib containing vaccines have greatly reduced the annual incidence of meningitis
and severe Hib pneumonia in countries like USA and Gambia 7, 8 But
in Asia and the Indian sub-continent, it is believed that there is a lot of
natural immunity in the children under 5 years of age owing to exposure to
subclinical cases and cross-reactivity to other H.Influenzae species. As per
one community based study, the incidence of complicated Hib disease in India is
as low as 0.007 percent 9.
Also the efficacy of the pentavalent vaccine in comparison to separately
given vaccines is low 10. Hence, it is believed that Introduction
of this vaccine in the national programme in the face of proven low incidence
of invasive disease, absence of benefit from Hib vaccination demonstrated in
the probe studies from Asia and the evidence of strain replacement in the West,
appears to be a profligate exercise in futility 11.
DPT is an established combination vaccine used in
India on a backdrop of high disease burden and adequate country specific
research. And any new vaccine finds it convenient to get combined with DPT and
get introduced into the markets. But combination vaccines should be introduced
only after a lot of scrutiny and deliberate understanding of the ‘profit’ of
single visit by parents for vaccinating against multiple diseases versus the
‘loss’ of safety and efficacy. For example, the varicella vaccine in
combination with MMR was tried, but resulted in raised instances of febrile
seizures in the recipients 12. Similarly, for adults, the
combination of hepatitis A with typhoid vaccine proved inefficient in
comparison to both the vaccines given separately 13. Using a combination of Hep B and Hib along
with DPT thus raises further questions.
However, the argument against the anticipated
apprehensions of AEFI in pentavalent vaccine recipients is that the state of
Goa has been using it in state funded immunization program without any
difficulty of reports of severe AEFI/deaths. Same is the case with private
practitioners, but authentic data in this group is not readily available.
Several studies conducted on the issue in developing countries also reflect a
similar opinion 14. The UNICEF suggests that that in remote areas
with poor access to medical care, 10 per cent cases of pneumonia die 15.
In the Sri Lankan episode of 2008 mentioned earlier,
a detailed investigation by the WHO revealed that no serious AEFI were
attributable to the vaccine as such 6. The non-fatal but serious
AEFI like the hypotonic-hypo responsive episode (HHE) did occur, but it is an
established side effect of Pertussis (whole cell), Hep B as well as Hib
vaccines. In Sri Lanka, the survey concluded, in comparison to the previous
four years, there had been an increased reporting of deaths temporally
following vaccination in 2008. The reasons for increased reporting are unclear,
but the number of deaths temporally following vaccination is not above what
would be expected by chance alone based on the background neonatal and infant
mortality rates. Further, the panel concluded based on its preliminary review
of the “HHE-like” cases reported in Sri Lanka that although HHE was
apparently unrecognized in Sri Lanka prior to the use of the liquid pentavalent
vaccine, the reported cases do not show an increase above the expected
reporting rate of HHE following similar vaccines.
Further, the WHO also recommends that the H.
Influenzae conjugate vaccine should be included in routine immunization
programmes 16. However, some authorities believe that such a
universal advocacy by the WHO for a disease which has varied epidemiological
trends country-wise and without accounting for limited resources of country
like India is questionable 17.
Thus the present environment in the country is
reeked with lack of faith in the vaccine at the national level on one side and
the advocacy of making it available to the poorer classes free of cost on the
other. The surveillance and reporting of
AEFI has thus become a highly relevant issue in current scenario 18.
It may be the reason
itself (causal association), or, there might be some other factors (temporal
association/coincidental adverse event) for which the complications are
reported. Adverse events following immunization (AEFI) are well established
with DPT, Hep-B and Hib vaccine separately in various studies but when given in
combination as pentavalent vaccine, data on AEFI with this is still lacking. If
there is any reduction in proportion of
various minor and major AEFI after pentavalent Vaccination in comparison to
separate vaccines? It is utmost important to monitor reactogenicity of vaccine
used in immunization programme. To establish and maintain the faith of
community in immunization programme, identification, detection, prevention and
appropriate communication is necessary.19
term “AEFI” merely denotes a temporal relationship between vaccination and
adverse events. This relationship need not to be causal from an expert point of
view. But community mostly perceived it as causal.19
Rationale of the study
fill this gap in knowledge we plan to carry an observational epidemiological
study. Despite every care, vaccine given to infant can cause adverse events.
Our study investigated the reported AEFI with pentavalent vaccine. Infants were
actively followed up for this purpose.
is lack of documentary evidence for the same especially in this part of the
world. Hence, this study aimed to study adverse events following immunization
with pentavalent second dose Indian population”