Direct and Indirect Effects of Rotavirus Vaccination: Comparing Predictions from Transmission Dynamic Models

Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8–2.9 times more than expected from the direct effects of the vaccine alone (28–50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1–1.7 times more than expected from the direct effects (54–90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research.

[1]  P G Smith,et al.  Assessment of the protective efficacy of vaccines against common diseases using case-control and cohort studies. , 1984, International journal of epidemiology.

[2]  S. Grinstein,et al.  Epidemiology of rotavirus infection and gastroenteritis in prospectively monitored Argentine families with young children. , 1989, American journal of epidemiology.

[3]  D. Bernstein,et al.  Protection of adults rechallenged with a human rotavirus. , 1990, The Journal of infectious diseases.

[4]  D. Sack,et al.  Evidence that protection against rotavirus diarrhea after natural infection is not dependent on serotype-specific neutralizing antibody. , 1992, The Journal of infectious diseases.

[5]  M E Halloran,et al.  Interpretation and estimation of vaccine efficacy under heterogeneity. , 1992, American journal of epidemiology.

[6]  D. Bernstein,et al.  Protection against rotavirus disease after natural rotavirus infection. US Rotavirus Vaccine Efficacy Group. , 1994, The Journal of infectious diseases.

[7]  R. J. Gilbert,et al.  Food poisoning: notifications, laboratory reports, and outbreaks--where do the statistics come from and what do they mean? , 1996, Communicable disease report. CDR review.

[8]  R. Glass,et al.  Rotavirus infection in infants as protection against subsequent infections. , 1996, The New England journal of medicine.

[9]  L. Moulton,et al.  The protective effectiveness of natural rotavirus infection in an American Indian population. , 1998, The Journal of infectious diseases.

[10]  Laura C Rodrigues,et al.  Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance , 1999, BMJ.

[11]  K. Mølbak,et al.  Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa. , 2002, The Journal of infectious diseases.

[12]  T. Vesikari,et al.  Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants. , 2004, Vaccine.

[13]  C. Castillo-Chavez,et al.  An age-structured epidemic model of rotavirus with vaccination , 2006, Journal of mathematical biology.

[14]  J. Heyse,et al.  Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. , 2006, The New England journal of medicine.

[15]  W. Edmunds,et al.  Impact of Model, Methodological, and Parameter Uncertainty in the Economic Analysis of Vaccination Programs , 2006, Medical decision making : an international journal of the Society for Medical Decision Making.

[16]  T. Vesikari,et al.  Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. , 2006, The New England journal of medicine.

[17]  T. Vesikari,et al.  Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study , 2007, The Lancet.

[18]  C. Macken,et al.  Modeling targeted layered containment of an influenza pandemic in the United States , 2008, Proceedings of the National Academy of Sciences.

[19]  R. Mikolajczyk,et al.  Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases , 2008, PLoS medicine.

[20]  D. Nokes,et al.  Rotavirus within day care centres in Oxfordshire, UK: characterization of partial immunity , 2008, Journal of The Royal Society Interface.

[21]  Felix Espinoza,et al.  Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study , 2008, The Lancet.

[22]  N. Nagelkerke,et al.  Male Circumcision for HIV Prevention in High HIV Prevalence Settings: What Can Mathematical Modelling Contribute to Informed Decision Making? , 2009, PLoS medicine.

[23]  Pejman Rohani,et al.  Resolving the impact of waiting time distributions on the persistence of measles , 2010, Journal of The Royal Society Interface.

[24]  Cécile Viboud,et al.  Demographic Variability, Vaccination, and the Spatiotemporal Dynamics of Rotavirus Epidemics , 2009, Science.

[25]  S. Hajat,et al.  Temperature-dependent transmission of rotavirus in Great Britain and The Netherlands , 2010, Proceedings of the Royal Society B: Biological Sciences.

[26]  A. Galvani,et al.  Impact of transmission dynamics on the cost-effectiveness of rotavirus vaccination. , 2009, Vaccine.

[27]  Manish M Patel,et al.  Decline and Change in Seasonality of US Rotavirus Activity After the Introduction of Rotavirus Vaccine , 2009, Pediatrics.

[28]  J. Gray,et al.  A mathematical model of the indirect effects of rotavirus vaccination , 2009, Epidemiology and Infection.

[29]  M. Levine,et al.  Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial , 2010, The Lancet.

[30]  Manish M Patel,et al.  Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P[4] strains in Brazil. , 2010, The Journal of infectious diseases.

[31]  Manish M Patel,et al.  Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study , 2010, BMJ : British Medical Journal.

[32]  C. Steiner,et al.  Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states. , 2010, The Journal of infectious diseases.

[33]  J. C. de Moraes,et al.  Hospital-based Surveillance to Evaluate the Impact of Rotavirus Vaccination in São Paulo, Brazil , 2010, The Pediatric infectious disease journal.

[34]  M. Boily,et al.  Understanding differences in predictions of HPV vaccine effectiveness: A comparative model-based analysis. , 2010, Vaccine.

[35]  E. Flem,et al.  Dynamic model of rotavirus transmission and the impact of rotavirus vaccination in Kyrgyzstan. , 2010, Vaccine.

[36]  M. Kundi,et al.  Universal Mass Vaccination Against Rotavirus Gastroenteritis: Impact on Hospitalization Rates in Austrian Children , 2009, The Pediatric infectious disease journal.

[37]  W. Edmunds,et al.  Modelling the seasonality of rotavirus disease and the impact of vaccination in England and Wales. , 2010, Vaccine.

[38]  A. Curns,et al.  Infant rotavirus vaccination may provide indirect protection to older children and adults in the United States. , 2011, The Journal of infectious diseases.

[39]  Manish M Patel,et al.  Decline in Rotavirus Hospitalizations and Health Care Visits for Childhood Diarrhea Following Rotavirus Vaccination in El Salvador , 2011, The Pediatric infectious disease journal.

[40]  R. Pitman,et al.  Handling uncertainty in dynamic transmission models. , 2011, Vaccine.

[41]  J. D. Mascarenhas,et al.  Effectiveness of the Monovalent G1P[8] Human Rotavirus Vaccine Against Hospitalization for Severe G2P[4] Rotavirus Gastroenteritis in Belém, Brazil , 2011, The Pediatric infectious disease journal.

[42]  J. Tate,et al.  Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US Counties, 2006-2009. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[43]  Benjamin A Lopman,et al.  Uptake, Impact, and Effectiveness of Rotavirus Vaccination in the United States: Review of the First 3 Years of Postlicensure Data , 2011, The Pediatric infectious disease journal.

[44]  S. Lambert,et al.  Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule , 2011, The Pediatric infectious disease journal.

[45]  P. van Damme,et al.  Rotavirus Vaccines in Belgium: Policy and Impact , 2011, The Pediatric infectious disease journal.

[46]  Laura C Rodrigues,et al.  Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice , 2011, Gut.

[47]  M. Porwal,et al.  Decline in rotavirus hospitalisations following introduction of Australia's national rotavirus immunisation programme , 2011, Journal of paediatrics and child health.

[48]  Manish M Patel,et al.  Remarkable Postvaccination Spatiotemporal Changes in United States Rotavirus Activity , 2011, The Pediatric infectious disease journal.

[49]  Alison P Galvani,et al.  Impact of rotavirus vaccination on epidemiological dynamics in England and Wales. , 2012, Vaccine.