https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(15)00286-4/pdf

Rotavirus vaccines: a story of success

Observed‐to‐expected (OE) analyses, together with data mining algorithms1, 2, 3, 4, 5, 6, 7 and pharmacoepidemiological studies,8 are part of the quantitative pharmacovigilance toolkit for vaccines. While data mining algorithms generate hypotheses about potential safety concerns and pharmacoepidemiological studies test specific hypotheses or measure associations, OE analyses stand in between. The role of OE analyses is to refine previously detected signals when there is not enough information to determine whether further action is necessary.

In this paper, the focus is on the OE analyses of spontaneous reports, where the observed number of cases is obtained from a spontaneous reporting system and compared with the expected number of cases calculated based on background incidence rates from independent sources, such as epidemiological studies or national statistics. Note that disproportionality data mining algorithms estimate an “OE ratio” generated based on expected and observed numbers of cases from a single spontaneous reporting system.

The key requirements and statistical methods recommended for OE analyses are described in European guidelines.9, 10 Here, we discuss in more detail how to perform the analysis and deal with uncertainties. Although described here in the context of vaccines, the methodology and recommendations are in principle also applicable for other medicinal products, but additional complexities would then have to be considered. We will not discuss the use of OE analyses for sequential monitoring, which has been described elsewhere.11, 12

https://onlinelibrary.wiley.com/doi/pdf/10.1002/pds.3918

Pharmacoepidemiological considerations in observed-to-expected analyses for vaccines†

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.

Rotavirus vaccination in Brazil: effectiveness and health impact seven years

Intussusception is the most common cause of small bowel obstruction in young infants. Therefore a high index of suspicion and thorough knowledge of this condition is of major importance to be able to diagnose and treat this potentially life threatening condition. In this review we describe epdidemiology, etiology and clinical symptoms of intussuception. Furthermore, we describe diagnostic modalties, especially ultrasonography as the primary choice for diagnosis. In addition, non-operative treatment with different types of enema reduction techniques, and operative treatment by laparotomy and laparoscopy, and outcomes have been reviewed.

Intussusception in Children: A Clinical Review

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.

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

Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction. Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines. From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged. This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies. Clinical study identifier 999910/204 (SERO-EPI-IS-204)

/pdf/a-multi-country-study-of-intussusception-in-children-under-2-55ix75q29u.pdf

Ana L Jimenez

Papers

A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data