Recommendations for UseThe IAPCOI acknowledges the morbidity and mortality burden of rotavirus and need for a rotavirus vaccine. Such a vaccine would be most needed in the national immunization program as the disease consequences are the most serious in the underprivileged. However the IAPCOI is concerned about (a) lack of immunogenicity studies from India where response
to other oral vaccines such as OPV has been observed to be
suboptimal
Till such data is available IAPCOI recommends use of the vaccine after one to one discussion with parents (Category 3). If the decision to administer the vaccine is taken, either vaccine may be chosen as they have similar efficacy and safety profiles as of currently available data. |
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Rotavirus is a major cause of diarrhea related morbidity and mortality in children worldwide. Although rotavirus illness rates are similar in both the developed and developing world and in children of all socioeconomic status, mortality due to rotavirus disease is more in the developing world and in the poor and malnourished. It has been estimated that rotavirus causes 6,10,000 under five deaths globally every year.
Rotavirus is an icosahedral RNA virus and seven serogroups have been described (A-G); Group A rotaviruses cause most human disease. The viral outer capsid is made of VP7 and VP4 proteins. The VP7 protein determines the G serotypes and the VP4 protein the P serotypes. Variability of genes coding for the VP7 and VP4 proteins is the basis for classification into genotypes. All G genotypes correspond with serotypes; there are more P genotypes then serotypes. Each rotavirus strain is designated by its G serotype number followed by P serotype number and then P genotype number in square brackets, e.g., G1P1A[8].
Epidemiologic studies from India indicate that 6-45% (median 20%) of all childhood diarrheas that need hospitalization are due to rotavirus. It is further estimated that rotavirus causes around 100,000 deaths in children below age 5 years annually in India. Seroepidemiologic studies show that G1, G2, G3 and G4 in combination with P8, P6 and P4 account for 65-70% of rotavirus infections in India. In addition to the common G and P serotypes, newer serotypes, mixed forms and untypable serotypes are frequently seen. Intra country differences exist between North, South, East and West.
The observation that initial infection with rotavirus prevents from subsequent severe infections has been the rationale for vaccine development. The first clinically licensed rotavirus vaccine (1998) was Rotashield, a live oral tetravalent vaccine comprising of three rhesus human reassortant and one rhesus rotavirus strain. This vaccine was withdrawn soon after licensure due to occurrence of vaccine associated intussusception.
Currently two live oral vaccines are licensed and marketed worldwide, RotarixTM and RotaTeqTM. A vaccine based on Indian neonatal strains is undergoing clinical trials. RotarixTM now available in India is a monovalent attenuated human rotavirus vaccine derived from the human rotavirus strain 89-12 grown in vero cells and contains the G1P1 [8] strain administered orally in a 2-dose schedule to infants of approximately 2 and 4 months of age. RotaTeqTM is a human bovine reassortant vaccine and consists of five reassortants between the bovine WC23 strain and human G1, G2, G3, G4 and P1A [8] rotavirus strains grown in vero cells and administered orally in a three dose schedule at 2, 4 and 6 months. Large phase 3 double blind placebo controlled trials with both vaccines in around 70,000 infants each (11 countries mainly US, Finland for Rotateq TM and Latin America and Finland for RotarixTM) have shown 85-98% efficacy against severe rotavirus gastroenteritis and 42-59% efficacy against hospitalization due to diarrhea of any cause.
Both vaccines have been demonstrated to be extremely safe with no increased risk of intussusception as compared to placebo. Shedding of the vaccine virus was observed in 10% of vaccinees with Rotateq and more than 50% of vaccinees with Rotarix. Similar high efficacy extends into the second year of follow up with the vaccine. Results from a recent trial with RotarixTM in 10,000 infants in Hong Kong, Singapore and Taiwan showed efficacy and safety similar to that seen in earlier trials. Both vaccines have been licensed and introduced into the national immunization program of several countries worldwide. Efficacy trials in developing countries of Africa and Asia are ongoing and results are awaited.
Studies show no interference between rotavirus vaccines and other childhood vaccines including IPV, pneumococcal, Hib, DTaP and Hep B. Data is insufficient for pertussis immunity. Immunogenicity studies about simultaneous administration of rotavirus vaccines with OPV are available for RotarixTM and RotateqTM, which show no reduction in immunogenicity against polio and no significant reduction in immunogenicity against rotavirus. Additionally an efficacy study shows no reduction in efficacy of RotarixTM against severe rotavirus gastroenteritis when co administered with OPV.
Vaccination should be strictly as per schedule discussed below, as there is a potentially higher risk of intussusception if vaccines are given to older infants. Vaccination should be avoided if age of the infant is uncertain. There are no restrictions on the infant’s consumption of food or liquid, including breast-milk, either before or after vaccination. Vaccines may be administered during minor illnesses. Though there is limited evidence on safety and efficacy of rotavirus vaccines in preterm infants, vaccination should be considered for these infants if they are clinically stable and at least 6 weeks of age as preterms are susceptible to severe rotavirus gastroenteritis.
Vaccination should be avoided in those with history of hypersensitivity to any of the vaccine components or previous vaccine dose. Vaccination should be postponed in infants with acute gastroenteritis as it might compromise efficacy of the vaccine. Immunocompromised infants are susceptible to severe and prolonged rotavirus gastroenteritis but safety and efficacy of either of the two vaccines in such patients is unknown. Risks versus benefits of vaccination should be considered while considering vaccination for infants with chronic gastrointestinal disease, gut malformations, previous intussuception and immunocompromised infants.
It is available as a lyophilized vaccine to be reconstituted with liquid diluent prior to administration. The vaccine and the diluents should be stored at 2 to 8° C and must not be frozen. The vaccine should be administered promptly after reconstitution as 1 ml orally. The first dose can already be administered at the age of 6 weeks and should be given no later than at the age of 12 weeks. The interval between the 2 doses should be at least 4 weeks. The 2-dose schedule should be completed by age 16 weeks, and no later than by 24 weeks of age. If the infant spits out or regurgitates the entire vaccine dose then the dose may be repeated at the same visit (as per drug insert of RotarixTM).
The vaccine is available as a liquid virus mixed with buffer
and no reconstitution is needed. It should be stored at 2 to
8° C. The recommended schedule is 3 oral doses at ages 2, 4
and 6 months. The first dose should be administered between
ages 6-12 weeks and subsequent doses at intervals of 4-8
weeks. Vaccination should not be initiated for infants aged
>12 weeks. All 3 doses should be administered before the age
of 32 weeks. The manufacturer does not recommend
readministration of vaccine if a dose is spit out or regurgitated.