Intussusception-Rotavirus Vaccine Risk

6 October, 2011 by: colinparker

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Last time we spoke about intussusception and its treatment.  This week, we try to discover whether there is a real link between rotavirus vaccines and this rare cause of abdominal pain in infants.

Discussing vaccine efficacy and risks often engenders strong feelings from both sides of the river… the traditional believers AND the ‘anti-vaxxers’.  As with many controversies, it depends how you interpret the numbers – where your innate beliefs lie will influence how you see the data.  Join us as we try to walk the middle ground of objectivity…


Intussusception: Is Rotavirus Vaccination a real risk?

[cp] intro, disclaimer, overview

[cp] History: the RotaShield experience

Evidence – selected papers:
[rr] Belongia 2010 (USA surveillance)
[sf] TGA-Study 2011 (Australia)
[cp] Buttery 2011 (post-marketing surveillance Australia)
[sf] Patel 2011 NEJM (Mexico & Brazil)
[rr] Greenberg 2011 NEJM (editorial of Patel paper)
[cp] (similar studies/reports from numerous countries)

WHO position:
[cp] 2007 position paper
[rr] 2009 update of position paper (& NUVI implementation statement)
[sf] 2011 safety statement

Australian Health authorities’ position:
[cp] CMO letter 2011
[sf] Health Department Provider Info

Current practicalities:
[cp] Immunisation Handbook (Ch 3.18 Rotavirus)
[rr] Choice of vaccine
[sf] Timing of vaccination (catch-ups ?not allowed)
[cp] Both rotavirus infection and intussusception are Notifiable Diseases in (Western) Australia

[all] Summary, goodbye

ZDogg MD says: Immunize!

ZDoggMD \”Immunize!\” on YouTube

References

Belongia EA, Irving SA, Shui IM, Kulldorff M, Lewis E, Yin R, Lieu TA, Weintraub E, Yih WK, Li R, Baggs J; Vaccine Safety Datalink Investigation Group.
Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent, bovine-derived rotavirus vaccine.
Pediatr Infect Dis J. 2010 Jan;29(1):1-5. PubMed PMID: 19907356.

Rotavirus vaccination and risk of intussusception
Therapeutic Goods Administration
25 February 2011
http://www.tga.gov.au/safety/alerts-medicine-rotavirus-110225.htm

Buttery JP, Danchin MH, Lee KJ, Carlin JB, McIntyre PB, Elliott EJ, Booy R, Bines JE; PAEDS/APSU Study Group.
Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia.
Vaccine. 2011 Apr 5;29(16):3061-6. PubMed PMID: 21316503.

Patel MM, López-Collada VR, Bulhões MM, De Oliveira LH, Bautista Márquez A, Flannery B, Esparza-Aguilar M, Montenegro Renoiner EI, Luna-Cruz ME, Sato HK, Hernández-Hernández Ldel C, Toledo-Cortina G, Cerón-Rodríguez M, Osnaya-Romero N, Martínez-Alcazar M, Aguinaga-Villasenor RG, Plascencia-Hernández A, Fojaco-González F, Hernández-Peredo Rezk G, Gutierrez-Ramírez SF, Dorame-Castillo R, Tinajero-Pizano R, Mercado-Villegas B, Barbosa MR, Maluf EM, Ferreira LB, de Carvalho FM, dos Santos AR, Cesar ED, de Oliveira ME, Silva CL, de Los Angeles Cortes M, Ruiz Matus C, Tate J, Gargiullo P, Parashar UD.
Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil.
N Engl J Med. 2011 Jun 16;364(24):2283-92. PubMed PMID: 21675888.

Greenberg HB.
Rotavirus vaccination and intussusception–act two.
N Engl J Med. 2011 Jun 16;364(24):2354-5. PubMed PMID: 21675894.

Rotavirus Vaccines
World Health Organization
Weekly Epidemiological Record (WER) 10 August 2007, vol. 82, 32 (pp 285–296)
http://www.who.int/wer/2007/wer8232/en/index.html

Rotavirus Vaccines: an update
World Health Organization
Weekly Epidemiological Record (WER) 18 December 2009, vol. 84, 50 (pp 533–540)
http://www.who.int/wer/2009/wer8451_52/en/index.html

New and Under-utilized Vaccines Implementation (NUVI): Rotavirus
World Health Organization
Updated November 2009
http://www.who.int/nuvi/rotavirus/en/

Rotavirus vaccine and intussusception
Global Advisory Committee on Vaccine Safety
World Health Organization 2011
http://www.who.int/vaccine_safety/topics/rotavirus/rotarix_and_rotateq/Dec_2010/en/index.html
Extract from report of GACVS meeting of 8-9 December 2010, published in the WHO Weekly Epidemiological Report on 28 January 2011:http://www.who.int/wer/2011/wer8605/en/index.html

CMO Letter on Intussusception and rotavirus vaccine
Immunise Australia Program
Department of Health and Ageing (Australian Government)
http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/immunise-cmo-intussusception

Rotavirus vaccine and intussusception: Information for Immunisation Providers
Immunise Australia Program
Department of Health and Ageing (Australian Government)
http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/ITO135-cnt

The Australian Immunisation Handbook 9th Edition 2008
http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook-home
Rotavirus Chapter:
http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook-rotavirus

Australian national notifiable diseases and case definitions
Department of Health and Ageing (Australian Government)
http://www.health.gov.au/internet/main/publishing.nsf/Content/cdna-casedefinitions.htm

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One Response to “Intussusception-Rotavirus Vaccine Risk”
  1. To further expand on your excellent discussion on rotavirus vaccines and intussusception:

    While the benefits of vaccination against rotavirus has been well established, the recent study by Patel et al. (1) compared the historical intussusception data from the rotavirus vaccine, RotaShield, as approximately 1 case of intussusception in 10,000 recipients (2,3) to the current more favorable intussusception data for RV1 in Mexico and Brazil within 7 days of the first dose. This is misleading to the reader since a more recent re-evaluation of RotaShield (4) would indicate that the magnitude of the relative risk of intussusception with RotaShield may be dependent on the age at which the infants received their first dose of the rotavirus vaccine. In the RotaShield studies (2,3,4) the mean age of infants receiving their first dose was 97 days, in the Patel et al. report (1), the median age of infants receiving the first dose of RV1 was 68 days in Mexico and 64 days in Brazil. Because of the rapid increase in the background rate of intussusception in this age range, these age differences at first dose may be very significant. The background rate for intussusception tends to increase very rapidly after 2 months of age and peaks at or near 6 months of age worldwide. In the previous analysis of RotaShield (4), of the 71,000 infants that had received their first dose of RotaShield when they were younger than 60 days of age, there were no cases of intussusception within a 30 day period following their first dose. The majority (>80%) of intussusception cases associated with RotaShield within 7 days of receiving the vaccine occurred in infants that were older than 90 days of age on receiving their first dose. Therefore, the cited example of 1 case of intussusception in 10,000 recipients of RotaShield is only valid for older infants (mean age of 97 days) receiving their first dose. If the RotaShield data is analyzed for intussusception based on a younger age of vaccination (4), the safety data is very comparable to RotaTeq and Rotarix.

    The background rate of intussusception is basically zero at or near birth and a viable strategy to minimize or eliminate the risk of intussusception by immunizing infants against rotavirus during the neonatal period was proposed by leading rotavirus researchers a number of years ago (6) and has now been tested in a Phase II clinical trial in Ghana with 1,000 infants using a neonatal dosing protocol with RotaShield. Retrospective analyses (4) indicates that RotaShield may be safely administer to neonates and younger infants. This Phase II trial has been successfully completed and while not powered to evaluate the relative risks of intussusception, there were no cases of intussusception following the first dose. The results of the Phase II trial should be published in the near future.

    Neonatal immunization (administration of the first dose at or near birth) may be the only viable strategy to minimize or eliminate the risk of intussusception. This is the strategy that is being used by the International Medica Foundation to bring RotaShield back to the market as a safe, effective and affordable rotavirus vaccine.

    1. Patel MM, López-Collada VR, Bulhões MM et al. Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil. N Engl J Med 2011; 364:2283-2292
    2. Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med 2001;344:564-572
    3. Peter G, Myers MG. Intussusception, rotavirus, and oral vaccines: summary of a workshop. Pediatrics 2002;110:e67-e67
    4. Simonsen L, Viboud C, Elixhauser A, Taylor RJ, Kapikian AZ. More on RotaShield and intussusception: the role of age at the time of vaccination. J Infect Dis 2005;192:Suppl 1:S36-S43
    5. Buttery JP, Danchin MH, Lee KJ, et al. Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia. Vaccine 2011;29:3061-3066
    6. Kapikian AZ, Simonsen L, Vesikari T, et al. A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception. J Infect Dis 2005;192:Suppl 1:S22-S29

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