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Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

ABSTRACT: Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes.

SUBMITTER: Pitzer VE

PROVIDER: S-EPMC4685644 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

Pitzer Virginia E VE Bilcke Joke J Heylen Elisabeth E Crawford Forrest W FW Callens Michael M De Smet Frank F Van Ranst Marc M Zeller Mark M Matthijnssens Jelle J

Scientific reports 20151221

Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the und ...[more]

PMID: 26687288

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Project description:IntroductionThe rotavirus (RV) vaccine Belgium Impact Study (RotaBIS) evaluated the vaccine effect on RV-related hospital care in children up to 5 years old over a period of 13 years. Different forces were identified that influence the reduction in hospital care. Our analysis aims to report on the current RotaBIS dataset and explore through model simulation whether, how, and when the results could have been improved.MethodsAs performed in previous assessments, this analysis evaluated RV-related events per year, per age group, RV nosocomial infections, hospitalization duration, and herd effect. It subsequently identified results that were surprising or unexpected. To know whether those data could have been improved through specific interventions, we developed a model with the forces acting on the disease transmission and the vaccine effect on RV-related hospital care. Scenario analysis of the forces should explain the current findings and identify ways to optimize the results.ResultsThe RotaBIS data show that annual RV-related hospital cases (n = 1345 pre-vaccination) dropped by 70% (95% confidence interval [CI] 66-74%) by year 5 (n = 395) after vaccine introduction, and by 84% (95% CI 79-89%) by year 10 (n = 217). The herd effect during the first year was limited to 14% extra gain. During the last 5 years, small disease increases were seen biennially. The simulation model indicates that higher vaccine coverage of the major transmitters during the peak season of the first year of vaccination could have reduced RV-related hospital care by nearly 90% at 5 and 10 years after vaccine introduction owing to a higher herd effect. The smaller peaks observed in recent years would have been dramatically reduced.ConclusionThe current RotaBIS data show a maintained reduction, around 76%, in RV hospitalization cases. Simulations show that these results could have been improved to an important extent with a more optimal initiation of the vaccination program.Trial registrationClinicalTrials.gov identifier, NCT01563146 and NCT01563159.

Project description:BACKGROUND: Tanzania currently rolls out vaccination against rotavirus-diarrhea, a major cause of child illness and death. As the vaccine covers a limited number of rotavirus variants, this study describes the molecular epidemiology of rotavirus among children under two years in Dar es Salaam, Tanzania, prior to implementation of vaccination. METHODS: Stool specimens, demographic and clinical information, were collected from 690 children admitted to hospital due to diarrhea (cases) and 545 children without diarrhea (controls) during one year. Controls were inpatient or children attending child health clinics. Rotavirus antigen was detected using ELISA and positive samples were typed by multiplex semi-nested PCR and sequencing. RESULTS: The prevalence of rotavirus was higher in cases (32.5%) than in controls (7.7%, P<0.001). The most common G genotypes were G1 followed by G8, G12, and G4 in cases and G1, G12 and G8 in controls. The Tanzanian G1 variants displayed 94% similarity with the Rotarix vaccine G1 variant. The commonest P genotypes were P[8], P[4] and P[6], and the commonest G/P combination G1 P[8] (n?=?123), G8 P[4] and G12 P[6]. Overall, rotavirus prevalence was higher in cool (23.9%) than hot months (17.1%) of the year (P?=?0.012). We also observed significant seasonal variation of G genotypes. Rotavirus was most frequently found in the age group of four to six months. The prevalence of rotavirus in cases was lower in stunted children (28.9%) than in non-stunted children (40.1%, P?=?0.003) and lower in HIV-infected (15.4%, 4/26) than in HIV-uninfected children (55.3%, 42/76, P<0.001). CONCLUSION: This pre-vaccination study shows predominance of genotype G1 in Tanzania, which is phylogenetically distantly related to the vaccine strains. We confirm the emergence of genotype G8 and G12. Rotavirus infection and circulating genotypes showed seasonal variation. This study also suggests that rotavirus may not be an opportunistic pathogen in children infected with HIV.

Project description:BackgroundRotavirus is a leading cause of morbidity and mortality in young children worldwide. In China, the universal immunization of children with the rotavirus vaccine has not been introduced, and the two globally distributed vaccines (RotaTeq and Rotarix) are not licensed in the country. We aim to determine the prevalence and strain diversity of rotavirus in children with diarrhea aged ≤ five years across China.Materials and methodsSentinel-based surveillance of acute diarrhea was conducted at 213 participating hospitals in China from January 1, 2009, through December 31, 2015. Group A rotavirus (RVA) was tested by using enzyme-linked immunosorbent assays, and G- and P-genotype of RVA were tested by RT-PCR methods.ResultsOf 33,616 children with diarrhea, 10,089 (30%) were positive for RVA; RVA-associated diarrhea was identified in 2247 (39.5%, n = 2247/5685) inpatients and 7842 (28.1%, n = 7842/27931) outpatients. Children living in low-middle-income regions suffered from the highest burden of rotavirus, with 40.7% of diarrhea cases attributed to rotavirus infection, followed by 31.3% in upper-middle-income and 11.2% in high-income regions. The majority of children (88.9%, n = 8976/10089) who tested positive for RVA were children aged ≤ 2 years. The seasonal peak of RVA was in the winter. Among all 2533 RVA strains genotyped, five strain combinations, G9P[8], G3P[8], G1P[8], G2P[4] and G3P[4], contributed to 71.3% (1807/2533) of the RVA-associated diarrhea cases. The predominant strain of RVA has rapidly evolved from G3P[8] and G1P[8] to G9P[8] in the recent years, with the proportion of G9P[8] having increased remarkably from 3.4% in 2009 to 60.9% in 2015.ConclusionsThe burden of diarrhea attributed to rotavirus is high in China, highlighting the potential value of vaccination. The rapid shift of RVA strains highlights the importance of conducting rotavirus surveillance to ensure that currently marketed vaccines provide protective efficacy against the circulating strains.

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Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

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Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

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