Reappraisal of the Association of Intussusception with the Licensed Live Rotavirus Vaccine Challenges Initial Conclusions

Murphy, Brian R.; Morens, David M.; Simonsen, Lone; Chanock, Robert M.; Montagne, J. R. La; Kapikian, Albert Z.

doi:10.1086/367895

Cited by 113 publications

(64 citation statements)

References 28 publications

(39 reference statements)

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“…By generating reassortants with human RVs strains, a tetravalent RRV-based (serotype G1, G2, G3, and G4) vaccine (Rotashield; Wyeth Laboratories) was produced that was licensed and commercially used in infants and young children in the United States in 1998 to 1999 (7). Unfortunately, the vaccine was withdrawn from the market due to an association with an increased risk of intussusception in vaccinees (3,27,28). Our genomic analyses suggest that RRV may originate from the reassortment of a feline/canine ancestral RV with a Bovidae RV.…”

Section: Discussionmentioning

confidence: 99%

Simian Rotaviruses Possess Divergent Gene Constellations That Originated from Interspecies Transmission and Reassortment

Matthijnssens

Taraporewala

Yang

et al. 2010

J Virol

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Group A rotaviruses (RVs) are a major cause of acute dehydrating diarrhea in infants and children under the age of 5 years worldwide. These infections lead to approximately 527,000 deaths each year, the vast majority occurring in developing countries (33). RVs are also responsible for gastroenteritis in many other animal species, notably mammals and birds (16,38). RVs are members of the family Reoviridae and possess a genome consisting of 11 segments of double-stranded RNA (dsRNA). The prototypic genome of a group A RV encodes six structural proteins (VP) and six nonstructural proteins (NSP) (5). The mature RV virion is a nonenveloped triple-layered icosahedral particle. The inner most protein layer is formed by the core lattice protein VP2.Attached to the interior surface of the VP2 layer near the fivefold axes are complexes of the viral RNA-dependent RNA polymerase VP1 and the RNA capping enzyme VP3. Collectively, VP1, VP2, VP3, and the dsRNA genome form the core of the virion (5, 11). The core is surrounded by VP6, the sole constituent of the intermediate protein layer of the virion. The antigenic properties of VP6 are used in classifying RV isolates into groups. The outer protein layer of the virion is composed of trimers of the VP7 glycoprotein penetrated by spikes of the VP4 attachment protein (50). The properties of VP7 and VP4 form the basis of a dual classification system defining RV G types (glycosylated) and P types (protease sensitive), respectively. At present, 23 G genotypes and 31 P genotypes have been recognized in the literature based on sequence analyses (17,39,42,45,47). Recently, a comprehensive sequence-based classification system was established for the RVs which, together with a uniform nomenclature, allows each genome segment of the virus to be assigned to a particular genotype. In the comprehensive classification system, the acronym Gx-P[x]-Ix-Rx-Cx-Mx-AxNx-Tx-Ex-Hx defines the genotypes of VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 encoding genome segments (17, 18).

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Section: Discussionmentioning

confidence: 99%

Simian Rotaviruses Possess Divergent Gene Constellations That Originated from Interspecies Transmission and Reassortment

Matthijnssens

Taraporewala

Yang

et al. 2010

J Virol

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“…We have previously argued that most intussusception events associated with the use of RotaShield would likely have occurred at some point during infancy, even without exposure to RotaShield, and that receipt of the vaccine, therefore, did not change the overall risk of intussusception during the first year of life [11,12] (for other interpretations, however, see the studies by Murphy et al [13,14]). Nonetheless, the strong temporal association between intussusception and receipt of RotaShield represents a serious problem that must be addressed.…”

Section: Discussionmentioning

confidence: 99%

More on RotaShield and Intussusception: The Role of Age at the Time of Vaccination

et al. 2005

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Background. RotaShield, a vaccine intended to prevent severe rotavirus diarrhea, was withdrawn in July 1999, 9 months after it became available in the United States, because of a temporal association with intussusception events that occurred in vaccinated infants. We explore here the effect of age on the risk of intussusception.Methods. We reanalyzed a case-control database of the Centers for Disease Control and Prevention by use of a 21-day window, to define vaccine-associated events. We obtained data on vaccine use from the National Immunization Survey and estimated the age-stratified background incidence of intussusception by use of Healthcare Cost and Utilization Project data. We combined these data to estimate how absolute risk varies with age and to model the projected population-attributable risk associated with 3 different vaccination schedules.Results. We found that the incidence of intussusception associated with the first dose of vaccine increased with age. Infants у90 days old accounted for 80% of cases of intussusception associated with a first dose but had received only 38% of first doses. Modeling of the recommended schedule of vaccination at ages 2, 4, and 6 months projected 1 intussusception event/11,000-16,000 vaccine recipients; modeling of a 2-dose schedule beginning in the neonatal period projected 1 intussusception event/38,000-59,000 vaccine recipients.Conclusions. The practice of initiating immunization after age 90 days, which we call "catch-up" vaccination, contributed disproportionately to the occurrence of intussusception associated with the use of RotaShield. A fully implemented 2-dose vaccination schedule begun during the neonatal period would lead to, at most, a 7% increase in the incidence of intussusception above the annual background incidence.

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“…[4][5][6] Baseline intussuscepc c tion surveillance is needed in sites where trials of rotavirus vaccines are planned, and postclicensure intussusception surc c veillance may also be required by some licensing agencies. Intussusception is the invagination of the bowel by a more proximal segment.…”

Section: Introductionmentioning

confidence: 99%

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia

Bines

Liêm

Justice

et al. 2006

Bull World Health Organ

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Objective To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. Methods Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged < 2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged < 2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). Findings In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). Conclusion The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely. Voir page 574 le résumé en français. En la página 574 figura un resumen en español. IntroductionThe withdrawal of the first rotavirus vacc c cine to be licensed in the United States (RotaShield, Wyeth-Lederle Vaccines, Philadelphia, PA, United States), due to an unexpected association with intusc c susception, resulted in a major setback in the effort to reduce the global burden of rotavirus gastroenteritis.1-3 Although the risk of intussusception following imc c munization with RotaShield is low, it has posed a major challenge to the future development of a safe and effective vacc c cine.2 Largecscale clinical trials are now required to detect a risk of intussusception of < 1 in 10 000. [4][5][6] Baseline intussuscepc c tion surveillance is needed in sites where trials of rotavirus vaccines are planned, and postclicensure intussusception surc c veillance may also be required by some licensing agencies. Intussusception is the invagination of the bowel by a more proximal segment. The intussusception can be propelled disc c tally by peristalsis, resulting in intestinal obstruction and vascular compromise of the intestine. Prompt identification and reduction by air enema or hydrostatic enema or by surgery is vital to minimize the morbidity and mortality that may be associat...

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Reappraisal of the Association of Intussusception with the Licensed Live Rotavirus Vaccine Challenges Initial Conclusions

Cited by 113 publications

References 28 publications

Simian Rotaviruses Possess Divergent Gene Constellations That Originated from Interspecies Transmission and Reassortment

Simian Rotaviruses Possess Divergent Gene Constellations That Originated from Interspecies Transmission and Reassortment

More on RotaShield and Intussusception: The Role of Age at the Time of Vaccination

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia

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