Intussusception rotavirus vaccine

The first rotavirus vaccine was a tetravalent rhesus rotavirus strain. It was licensed in the United States in 1998 and subsequently withdrawn from the market due to an association with intussusception. A pentavalent human-bovine reassortant rotavirus vaccine was approved by the FDA in February 2006. The exact mechanism by which the vaccine produces an immune response is unknown however, this live virus vaccine replicates in the small intestines and induces immunity. 

Rotavirus — the most common cause of severe diarrhea in infanfs, with approximately 125 million cases worldwide per year and 600,000 deaths — vaccines have been linked with intussusceptions (a problem with the intestine in which one portion of the bowel slides into the next) at a rate of between 1 in 5000 and 1 in 11,000 infants. The only rotavirus vaccine approved in the United States, RotaShield (Wyeth-Ayerst), was withdrawn from market on October 22, 1999, about 1 year after licensure. 

Murphy TV, Smith PJ, Gargiullo PM, Schwartz B (2003), The first rotavirus vaccine and intussusception epidemiological studies and policy decisions, J. Infect. Dis. 187 1309-1313. 

Intussusception probably causally related to rotavirus vaccine (SEDA-23, 354) prompted studies to answer the question of whether polio vaccine could also cause intussusception. A workshop held in Atlanta on 15-16 June 2000 brought together experts from various fields with the primary investigators of the studies. The participants concluded that the available evidence favored rejection of a causal relation between OPV and intussusception (40). 

The epidemiology of hospitalizations and deaths associated with intussusception among US infants has been described (7). Such data could be useful for further clinical trials with newly developed rotavirus vaccines. 

Current prelicensure trials of newly developed rotavirus vaccines are taking into consideration the experiences gained during the licensure process of Rotashield. Phase 3 clinical trials have included over 10 000 volunteers in order to exclude the potential risk of intussusception. 

Centers for Disease Control and Prevention (CDC). Intussusception among recipients of rotavirus vaccine—... 

Kramarz P, France EK, Destefano F, Black SB, Shinefield H, Ward JI, Chang EJ, Chen RT, Shatin D, Hill J, Lieu T, Ogren JM. Population-based study of rotavirus vaccination and intussusception. Pediatr Infect Dis J 2001 20(4) 4I0-16. 

Intussusception after rotavirus vaccine was described as an example to underline the value of passive surveillance systems as an indicator for carefully designed follow-up studies. 

Rotavirus A. Intussusception B. Any sequel (including death) of the above events C. Events described in the manufacturers package insert as contraindications to additional doses of the vaccine 30 days Not applicable See package insert... 

Vaccines also may be used to boost specific immune processes directed against the bacteria themselves or against adherence appendages, cytotoxins, or enterotoxins. Currently available vaccines for typhoid fever in the United States are the parenteral Vi capsular polysaccharide vaccine, the oral live-attenuated Ty21a vaccine, and the older heat-phenol-inactivated parenteral vaccine. Only the older parenteral cholera vaccine is licensed for use in the United States, but it is not recommended owing to the low risk of cholera to the traveler and the limited efficacy of the vaccine. New oral five and killed vaccines are licensed outside the United States and are used by some travelers. The rotavirus vaccine, although effective, has presented complications in the form of rare cases of intussusceptions it is no longer marketed and thus is not recommended. ... 

The first vaccine (RotaShield) to prevent rotavirus infection was licensed for use in the United States in 1998, but it was withdrawn from the market after 1.5 million doses were administered owing to an increased rate of idiopathic intussusception. A number of rotavirus vaccines are under development, but the one that shows early promise is the rotavirus oral vaccine (Rotateq, Merck). This is a reassortant pentavalent vaccine with a backbone of bovine rotavirus and surface proteins of virus strains representing G types (G1-G4) and PI A. The preliminary results from the trial of 1946 healthy infants (aged 2 to 8 months) showed a level of protection of approximately 75%. ... 

A previous rotavirus vaccine, RotaShield, was approved by the FDA in 1998, but was removed from the market only a little more than a year later, after post-licensing studies had shown a risk of intussusception of 1 in 10000 recipients. 

Two second-generation rotavirus vaccine candidates (one composed of five human-animal reassortants, RotaTeq , and the other a monovalent attenuated human rotavirus vaccine, Rotarix ) were in development in 1999, and after 7 years of study, they were licensed by the European Medicines Agency (EMA), the Food and Drug Administration (FDA), and many other licensing authorities. Both vaccines are efficacious and both underwent extensive safety trials in more than 130000 children, in whom there was no association with intussusception. In the years since licensing, there have been substantial reductions in the rates of hospitalization and death from rotavirus in both developed and less-developed countries. As part of post-licensing safety follow-up, the possible effect of the widespread use of rotavirus vaccines on rates of intussusception has been monitored carefully [2V]. 

The risk of intussusception and other adverse events temporally connected with the administration of bovine-derived rotavirus vaccine (RotaTeq, manufactured by Merck) from May 2006 to May 2008 (see also SEDA-33, 662) has been studied in children aged 4-48 weeks [23 ]. Adverse events over the next 30 days were ascertained from in-patient, out-patient, and emergency department files cases of intussusception were validated by reviewing the medical records. The study population received 207621 doses of RotaTeq , of which 42% were first doses. Five children had computerized diagnosis codes for intussusception, and 6.75 cases were expected based on historical rates (RR = 0.74). There was no increased risk of intussusception or any other adverse event. Two of five children with suspected intussusception based on diagnosis codes met the case criteria after review of their medical records. The authors concluded that RotaTeq is not associated with an increased risk of intussusception. 

A WHO expert group has reported its view that post-marketing surveillance of both currently available rotavirus vaccines has detected a small increased risk of intussusception (about 1-2/100000 infants vaccinated) in some settings shortly after the first dose [2 ]. The risk is 5-10 times lower than that observed with the previously licensed vaccine, RotaShield, and the benefits of rotavirus immunization against severe diarrhea and death from rotavirus infection far exceed the risk of intussusception. After reviewing the... 

Patel MM, Lopez-Collada VR, Bulhoes MM, De Oliveira LH, Bautista Mdrquez A, Flannery B, and 30 other authors. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med 2011 364(24) 2283-92. 

Belongia EA, Irving SA, Shui IM. Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent, bovine-derived rotavirus vaccine. Pediatr Infect Dis J 2010 29 1-5. 

WHO. Rotavirus vaccine and intussusception report from an expert consultation. Wkly Epidemiol Rec 2011 86 317-21. 

Rasagiline, 31.270 Rasburicase, 31.203 Renin inhibitors, 30.242 Rhesus anti-D, prophylaxis, 13.297 Ribavirin - - interferon, 30.344 Ribostamydn, and aminoglycosides, 15.270 Rocuronium, allergic reactions, 26.150 and pholcodine, 31.249 Rotashield, intussusception, 23.354 Rotavirus vaccine, Kawasaki disease, 31.522 Rubella vaccine, joints, 11.295... 

Shui IM, Baggs J, Patel M, Parashar UD, Rett M, Belongia EA, et al. Risk of intussusception following administration of a pentavalent rotavirus vaccine in us infants. JAMA 2012 307(6) 598-604. 

Yen C, Tate JE, Steiner CA, Cortese MM, Patel MM, Parashar UD. Trends in intussusception hospitalizations among US infants before and after implementation of the rotavirus vaccination program, 2000-2009. J Infect Dis 2012 206(l) 41-8. 

Further studies have confirmed that there is an increased risk of intussusception associated with the use of rhesus rotavirus tetravalent vaccine (RRV-TV). The association has been assessed in infants in 19 states of the USA (8). Each infant hospitalized with intussusception between 1 November 1998 and 30 June 1999 was matched according to age with four healthy controls who had been born at the same hospital. The authors estimated that one case of intussusception would occur for every 4670-9474 infants immunized. 

The associahon of intussusception (IS) and rotavirus (RV) vaccination surfaced with the introduction of the first licenced RV vaccine, Rotashield . It has been a focus of interest during the development of Rotateq (RV5) and Rotarix (RVl), and in particular during the post-licensure surveillance of these vaccines. 

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