Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception.

Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8-6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7-6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Risk of Intussusception After Rotavirus Vaccination: Meta-analysis of Postlicensure Studies.

BACKGROUND: Postlicensure surveillance studies suggest a small temporal increase in the risk for intussusception with both currently available rotavirus vaccines (RV1; Rotarix, GSK and RV5; RotaTeq, Merck & Co., Inc.). This meta-analysis was undertaken to provide a single overall estimate of the relative risk of intussusception during the 7-day period after administration of RV1 and RV5. METHODS: Meta-analysis based on estimates of relative risk and corresponding 95% confidence intervals from 5 postlicensure studies providing an estimate of risk of intussusception during the 7-day period after administration of dose 1 and/or dose 2 of RV1 and/or RV5, based on active and/or passive surveillance, for confirmed intussusception cases (Brighton or other method of case confirmation). For each vaccine, the relative risk of intussusception was estimated postdose 1 and postdose 2. Results were pooled using the inverse variance method using both fixed-effect and random-effect models. RESULTS: The overall estimate of relative risk of intussusception during the 7 days postdose 1 was 5.4 (95% confidence interval: 3.9-7.4, 3 studies) for RV1 and 5.5 (3.3-9.3, 3 studies) for RV5. The overall estimate of relative risk of intussusception during the 7 days postdose 2 was 1.8 (1.3-2.5, 4 studies) for RV1 and 1.7 (1.1-2.6, 3 studies) for RV5. CONCLUSIONS: This meta-analysis showed a similar increased risk of intussusception, during the first 7 days after administration of dose 1 and, to a lesser extent, dose 2, for both currently available rotavirus vaccines. This suggests that intussusception may be a class effect of currently available oral rotavirus vaccines.

Rotavirus vaccination in Brazil: effectiveness and health impact seven years post-introduction.

Before vaccine introduction in Brazil, rotavirus caused approximately 650,000 outpatient visits, 92,000 hospitalizations and 850 deaths annually among children aged <5 years. Brazil was one of the first countries to introduce rotavirus vaccination into the National Immunisation Program (NIP), in 2006, but estimated coverage (87.1%) for 2011 remained lower if compared with other routine immunizations (95%). Case-control studies reached effectiveness rates as high as 85%. Observational studies showed a significant reduction in gastroenteritis-related hospitalizations and deaths among children aged <1 year, at rates as high as 48 and 54%, respectively. There was a significant increase in the relative prevalence of G2P[4] genotype after vaccine introduction, reaching 100% of strains in some settings. A small increase in intussusception incidence was seen within 1 week following the second vaccine dose, but benefits far outweigh any potential risk. This article provides an in-depth review of postlicensure studies conducted in Brazil 7-year postintroduction.

Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico.

BACKGROUND: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants. METHODS: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis. RESULTS: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated. CONCLUSION: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Declaración del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología respecto a vacuna anti-rotavirus: Marzo 2006 / Rotavirus vaccine: statement of the Consultive Committee of Immunizations on behalf of The Chilean Infectious Diseases Society: March 2006

Se presenta una breve revisión de la epidemiología de la infección por rotavirus y de los antecedentes científicos de las vacunas Rotashield®, retirada del mercado luego de mostrar asociación con invaginación intestinal en EEUU, Rotateq® actualmente en fases finales de desarrollo y Rotarix®, recientemente licenciada en Chile. Considerando estos antecedentes, el Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología, indica sus conclusiones y recomendaciones en relación a la vacunación anti-rotavirus de lactantes en nuestro país.

Vacunas anti-rotavirus: al fin una realidad / New rotavirus vaccines: a reality at last

Rotavirus es la primera causa de diarrea aguda grave en niños bajo 3 años de edad en el mundo. Esta infección es responsable de 25 millones de consultas, 2 millones de hospitalizaciones y 440.000 muertes por año en niños con menos de 5 años. El desarrollo de vacunas anti-rotavirus ha sido un camino largo y tortuoso marcado por la abrupta caída de Rotashield® en 1999 debido a su asociación con invaginación intestinal. Luego de seis años de intensa investigación, el mundo celebra la licencia de dos nuevas vacunas que, a pesar de ser diferentes en su formulación y forma de administración, han demostrado ser seguras y no asociadas a invaginación intestinal, en estudios de Fase III de gran magnitud, que enrolaron más de 60.000 niños. Estas dos vacunas, Rotarix® de Glaxo SmithKline Biologicals y Rotateq® de Merck Sharp & Dohme son altamente eficaces contra diarrea grave causada por rotavirus de los serotipos más prevalentes en el mundo. La incorporación de estas vacunas, más temprano que tarde, especialmente en los países más pobres del mundo, requerirá de un esfuerzo conjunto de los gobiernos, laboratorios productores, organismos internacionales y no gubernamentales y fundaciones de beneficencia.

Lack of association between intussusception and oral polio vaccine in Cuban children.

Two exploratory investigations found an increased risk of intussusception after oral polio vaccine (OPV). A large, national, population-based study was undertaken in Cuba to investigate a possible association. Three hundred and thirty-five cases of intussusception in children under 2 years of age occurring in 1995-2000 were identified and their OPV records retrieved. The relative incidence (RI) of intussusception in defined periods up to 42 days after OPV in children under 1 year was estimated using the self-controlled case series method, controlling for age and season. The RI was not significantly raised in any of the time intervals examined within the 0-42 day period after OPV. For the period 0-42 days as a whole the RI was 1.11, 95% CI 0.74-1.67. This study does not support the hypothesis that OPV causes intussusception.