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Pitzer, V.E. et al. Modeling rotavirus strain dynamics in developed countries to understand the potential impact of vaccination on genotype distributions. Proc. Natl. Acad. Sci. USA 108, 19353-19358

Department of Ecology and Evolutionary Biology and Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, NJ 08544, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2011; 108(48):19353-8. DOI: 10.1073/pnas.1110507108
Source: PubMed

ABSTRACT

Understanding how immunity shapes the dynamics of multistrain pathogens is essential in determining the selective pressures imposed by vaccines. There is currently much interest in elucidating the strain dynamics of rotavirus to determine whether vaccination may lead to the replacement of vaccine-type strains. In developed countries, G1P[8] strains constitute the majority of rotavirus infections most years, but occasionally other genotypes dominate for reasons that are not well understood. We developed a mathematical model to examine the interaction of five common rotavirus genotypes. We explored a range of estimates for the relative strength of homotypic vs. heterotypic immunity and compared model predictions against observed genotype patterns from six countries. We then incorporated vaccination in the model to examine its impact on rotavirus incidence and the distribution of strains. Our model can explain the coexistence and cyclical pattern in the distribution of genotypes observed in most developed countries. The predicted frequency of cycling depends on the relative strength of homotypic vs. heterotypic immunity. Vaccination that provides strong protection against G1 and weaker protection against other strains will likely lead to an increase in the relative prevalence of non-G1 strains, whereas a vaccine that provides equally strong immunity against all strains may promote the continued predominance of G1. Overall, however, disease incidence is expected to be substantially reduced under both scenarios and remain below prevaccination levels despite the possible emergence of new strains. Better understanding of homotypic vs. heterotypic immunity, both natural and vaccine-induced, will be critical in predicting the impact of vaccination.

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    • "Our findings also suggest rapid genotype cycling from in-season to out-of-season periods and, as noted by Pitzer et al.[26], this could be caused by relatively stronger homotypic immunity than heterotypic immunity in the population, which renders the less common genotypes increased fitness, permitting them to persist in the population[26,37]. Moreover, age increases among RVGE cases as the predominant genotype declines, and the rapid cycling to less common genotypes out of season may explain the proportional increase in two-to four-year-olds and those five years and older seen in our analysis out of season[26,27]. However, an increase in those five years and older out of season may also be influenced by delayed transmission to this group because of mixing and contact patterns in younger children and infants. "

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    • "Thus, it is expected that the use of vaccines having a single or limited number of viral or bacterial strains/types may influence the distribution of co-circulating pathogens in a population. A modeling of rotavirus strain dynamics in developed countries showed that vaccination that provides equally strong immunity against all strains may promote the continued predominance of G1 (Pitzer et al., 2011). Additionally, the concerns that G2[P4] strain was emerging after the introduction of RV1 in Latin America and Australia (Gurgel et al., 2008, 2007; Kirkwood et al., 2011a; Nakagomi et al., 2008), were subsequently dispelled by data showing sustained prevalence of G2P[4] in other countries in the same regions with low coverage of RV1 as well as from countries using RV5. "
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