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Effectiveness of self-financed rotavirus vaccines on acute gastroenteritis primary care episodes using real-world data in Spain: a propensity score–matched analysis of cohort study

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Abstract

The objective of this study was to estimate, by a novel spatiotemporal approach in an environment of non-funded rotavirus (RV) vaccines, the RV vaccine effectiveness (VE) to prevent acute gastroenteritis primary care (AGE-PC)–attended episodes, demonstrating how indirect protection leads to underestimation of direct VE under high vaccine coverage (VC). This population-based retrospective cohort study used electronic healthcare registries including all children 2 months–5 years old, born from 2009 to 2018 in the Valencia Region (Spain). Direct RV VE preventing AGE-PC episodes was estimated using propensity score matching and Poisson regressions stratified by VC, adjusted by age and calendar season. Indirect VE was estimated by Poisson regression comparing AGE-PC rates in unvaccinated children among the different VC levels. A total of 563,442 children were included for the RV VC estimation; of them, 360,576 were included in the birth-cohort for VE analysis. RV VC showed strong variability among districts and seasons, rising on average from 21% in 2009/2010 to 55% in 2017/2018. The highest direct VE was found in vaccinated children from districts with 0–30% RV VC (16.4%) and the lowest in those from districts with ≥ 70% RV VC (9.7%). The indirect protection in unvaccinated children raised from 6 to 16.6% for those living with 20–30% and ≥ 70% VC, respectively.

Conclusion: Considering that RV is the causative agent in 20% of AGE cases, a direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with VC over 70% because of indirect protection.

What is Known:

• The effectiveness of RV vaccines preventing hospitalizations due to RV-acute gastroenteritis (RV-AGE) has been extensively studied. However, RV also burdens the primary care (PC) setting, and data on vaccine effectiveness (VE) in preventing AGE-PC visits are scarce.

• The RV vaccine distribution in Spain (non-funded), with large differences in vaccine coverage (VC) among healthcare districts, provides an ideal scenario to assess the actual VE in preventing AGE-PC consultations, including the direct and indirect protection.

What is New:

• A direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with high VC because of indirect protection.

• These findings, together with existing data on the impact on hospitalizations due to RV-AGE, offer valuable insights for implementing vaccination initiatives in countries that have not yet commenced such programs.

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Data availability

Authors agree to make data and materials supporting the results presented in the paper available upon reasonable request.

Abbreviations

AGE:

Acute gastroenteritis

AGE-PC:

Acute gastroenteritis primary care

HCSB:

Healthcare seeking behaviour

ICD-9-MC:

55International Classification of Diseases, Ninth Revision, Clinical Modification coding system

ICD-10-MC:

International Classification of Diseases, Ninth Revision, Clinical Modification coding system

PC:

Primary care

PSM:

Propensity score matching

RV:

Rotavirus

RVAGE:

Gastroenteritis due to RV

SMD:

Standardized mean differences

VC:

Vaccine coverage

VE:

Vaccine effectiveness

VID:

The Valencia healthcare Integrated Databases

VIS:

Vaccine Information System

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Funding

Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme LLC.

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Authors and Affiliations

  1. Vaccine Research Unit, Fundación Para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, FISABIO-Public Health, Avda. Cataluña, 21. 46020, Valencia, Spain

    Mónica López-Lacort, Cintia Muñoz-Quiles, Javier Díez-Domingo & Alejandro Orrico-Sánchez

  2. CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain

    Mónica López-Lacort, Cintia Muñoz-Quiles, Javier Díez-Domingo & Alejandro Orrico-Sánchez

  3. Universidad Católica de Valencia San Vicente Mártir, Carrer de Quevedo, 2, 46001, Valencia, Spain

    Javier Díez-Domingo & Alejandro Orrico-Sánchez

Authors
  1. Mónica López-Lacort
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  2. Cintia Muñoz-Quiles
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  3. Javier Díez-Domingo
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  4. Alejandro Orrico-Sánchez
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Contributions

AOS is the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article.

MLL contributed to study conception and design; data acquisition, data cleaning, analysis, and interpretation; drafting the article, revising it critically for important intellectual content and final approval of the version to be published. MLL takes responsibility for the integrity of the data and the accuracy of the data analysis and serves as principal author.

CMQ contributed to data acquisition, analysis and interpretation; drafting the article and revising it critically for important intellectual content; and final approval of the version to be published. CMQ takes responsibility for communicating with the Editorial Office and all other co-authors as corresponding author.

AOS and JDD contributed to study design; drafting the article or revising it critically for important intellectual content; and final approval of the version to be published.

Corresponding author

Correspondence to Cintia Muñoz-Quiles.

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Data sharing statement

Authors agree to make data and materials supporting the results presented in the paper available upon reasonable request.

Conflict of interest

MLL, CMQ, AOS and JDD ever received travel grants to attend meetings sponsored by pharmaceutical companies. JDD has been principal investigator in clinical trials sponsored by SPMSD, MSD, GSK and Pfizer. JDD acted as Advisor for GSK and SPMSD.

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Communicated by Tobias Tenenbaum

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López-Lacort, M., Muñoz-Quiles, C., Díez-Domingo, J. et al. Effectiveness of self-financed rotavirus vaccines on acute gastroenteritis primary care episodes using real-world data in Spain: a propensity score–matched analysis of cohort study. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05536-0

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