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Indian Pediatr 2015;52: 906 |
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Why was there no Vaccine-associated
Intussusception in Indian Rotavirus Vaccine Trial?
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T Jacob John
President, Child Health Foundation, India.
Email: [email protected]
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Recently, two papers have been published on the phase 3 efficacy trial
of the Indian rotavirus vaccine (Rotavac) [1,2]. The study sites were
Delhi (urban), Pune (rural) and Vellore (urban and rural) [1,2]. A total
of 4532 infants were assigned to vaccine group and 2267 to placebo group
in this randomized, double-blind, placebo controlled study [1,2].
Vaccine efficacy (VE) against severe rotavirus gastroenteritis was 53.6
percent in the first year and 48.9 percent during the second year after
vaccination [1,2]. These results are comparable to VE of the other
licensed rotavirus vaccines in tropical developing countries [1,2].
Rotavirus vaccine-associated intussusception is
expected to occur within 7 to 14 or maximum 30 days after any dose in
the schedule. Among the 4500 infants given 3 doses of Rotavac, none
developed intussusception after dose 1 or 2 and during 100 days (>3
months) after third dose [1]. Although there was no vaccine-associated
intussusception in this study, we cannot extrapolate to suggest carte
blanche that Rotavac does not trigger intussusception.
Why was there no intussusception associated with
Rotavac in the study? There are three possible explanations for this
salutary safety record. First, the schedule was with three doses given
at 6, 10 and 14 weeks. This is the age with comparatively lower
frequency of spontaneous intussusception [3]. The prevalence begins to
rise from 20 weeks of age, which would be 5-6 weeks after the third dose
[3]. Second, the Indian rotavirus vaccine is derived from a naturally
occurring strain of human (neonatal nursery) rotavirus, unlike other
vaccines that are either bovine origin virus or laboratory manipulated
strains [1]. It is possible that the neonatal human strain is less prone
to trigger intussusception than other vaccine strains in use; this needs
to be explored in a larger study and in post-marketing surveillance.
Third, the risk of vaccine-associated intussusception is very small;
such a rare event may not have occurred in the sample size of 4,500,
purely due to chance.
In summary, the absence of vaccine-associated
intussusception in the vaccine trial is not to be taken as proof that
Rotavac will not trigger it when given to very large numbers of infants.
However, it gives the Government confidence that Rotavac is suitable for
inclusion in the Universal Immunization Programme (UIP). If and when the
Indian rotavirus vaccine is included in UIP, post-marketing surveillance
must be established to measure the risk of vaccine-associated
intussusception, particularly in infants given any dose beyond 14 weeks
of age.
References
1. Bhandari N, Rongsen-Chandola T, Bavdekar A, Jacob
J, Antony K, Taneja S, et al. Efficacy of a monovalent
human-bovine (116E) rotavirus vaccine in Indian infants: a randomized,
double-blind, placebo-controlled trial. Lancet. 2014;383:2136-43.
2. Bhandari N, Rongsen-Chandola, Bavdekar A, Jacob J,
Antony K, Taneja S, et al. Efficacy of a monovalent human-bovine
(116E) rotavirus vaccine in Indian children in the second year of life.
Vaccine. 2014; 32:A110-6.
3. Jehangir S, John J, Rajkumar S, Mani B, Srinivasan
R, Kang G. Inuessusception in southern India: comparison of
retrospective analysis and active surveillance. Vaccine 2014;
32(Suppl.1): A99-103.
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