Vaccine Effectiveness of RV1 in a Naïve Population

Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) in young children. The cumulative risk of GE hospitalizations and hospital stays of < 24 hours is 1/25, which would amount to 13,600 Canadian children < 5 years. The incidence of nosocomial RV infections is an average of 8/10,000 patient-days in children < 5 years. An immunization program with a live-attenuated monovalent oral RV vaccine (RV1 - Rotarix® from GSK) will be implemented, free of charge, in the Province of Quebec in November 2011. To provide an accurate portrait of the disease and give critical information to the public health agencies as they struggle to control costs, we aim to evaluate the accuracy of surveillance for RV and other diseases with similar characteristics; estimate selection bias in passive laboratory-based surveillance; and estimate the agreement between surveillance time-series created from passive and active surveillance data sources.

Study Overview

• Status: Completed
• Conditions: Gastroenteritis; Diarrhea; Rotavirus Infections
• Intervention / Treatment: Other: No intervention done

Detailed Description

In November 2011, Quebec implemented a publicly-funded RV1 vaccination program with its routine administration at 2 and 4 months of age. From February 1, 2012 - May 31, 2014, we conducted prospective, active surveillance for acute rotavirus gastroenteritis at The Montreal Children's Hospital and Centre Hospitalier Universitaire Sainte-Justine, located in Montreal, and Centre Hospitalier Universitaire de Sherbrooke, located in Sherbrooke. Active surveillance was approved by Research Ethics Boards at each hospital.

• Study Type: Observational
• Enrollment (Actual): 374

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • The Montreal Children's Hospital
    • Montréal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre hospitalier universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The Montreal Children's Hospital and the CHU Sainte-Justine are the 2 main pediatric hospitals in Montreal. With these 3 sites, 30% of the Quebec birth cohort will be captured and, given the concentration of children in the Montreal area, the participating hospitals will ensure that the study remains efficient in terms of resources. We elected Sherbrooke as an intermediate area; Montreal will represent an urban population.

Description

Inclusion Criteria:

• Child less than 3 years old

Cases:

• Acute gastroenteritis (within 7 days of hospital visit)
• able to provide a stool specimen for RV ELISA testing
• Rotavirus positive

Controls:

• Visited the ED or admitted for a non-rotavirus gastroenteritis
• Visited the ED or admitted for acute respiratory infections without gastroenteritis symptoms

Exclusion Criteria:

• Immunocompromised children
• Prior history of intussusception
• Admission to NICU between 6 to 15 weeks of life, for >6 weeks
• Child less than 56 days of life (8 weeks)
• Child vaccinated with Rotateq (Merck)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rotavirus-negative; Patients with a negative result for rotavirus via enzyme immunoassay (EIA). No intervention done.	Other: No intervention done; Not applicable because no intervention was done.
Rotavirus-positive; Patients with a positive result for rotavirus via enzyme immunoassay (EIA). Rotavirus-positives were confirmed via real-time reverse-transcriptase polymerase chain reactions (RT-PCR). RT-PCR results were used in the event of discordant EIA results. Rotavirus genotyping was performed. No intervention done.	Other: No intervention done; Not applicable because no intervention was done.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Matched VE Participants	RV1 vaccine effectiveness (VE) was investigated using a subset of active surveillance participants age-eligible to receive 2-doses of RV1 vaccine, defined as participants (i) <15 weeks of age as of program implementation (November 1, 2011), and (ii) ≥16 weeks of age at symptom onset. These ages corresponded to the maximum recommended age of administration for the first RV1 dose at program implementation, and the recommended age of second dose administration, respectively. We estimated RV1 VE of 2- versus 0-doses and ≥1- versus 0-doseto prevent rotavirus hospitalization or emergency visits. Only valid RV1 vaccinations administered ≥14 days prior to symptom onset were considered. Children vaccinated with RV5 (private market,minimal penetrance) were excluded.	From February 1, 2012 to May 31, 2014

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine Effectiveness of RV1	RV1 vaccine effectiveness (VE) was investigated using a subset of active surveillance participants age-eligible to receive 2-doses of RV1 vaccine, defined as participants (i) <15 weeks of age as of program implementation (November 1, 2011), and (ii) ≥16 weeks of age at symptom onset. These ages corresponded to the maximum recommended age of administration for the first RV1 dose at program implementation, and the recommended age of second dose administration, respectively. Only valid RV1 vaccinations administered ≥14 days prior to symptom onset were considered. RV1 VE was estimated as (1 - exposure odds ratio) × 100. Based upon our sampling scheme, the exposure odds ratio from our analyses approximates the rate ratio.	From February 1, 2012 to May 31, 2014

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: GlaxoSmithKline; Institut National en Santé Publique du Québec; Ministere de la Sante et des Services Sociaux
• Investigators: Principal Investigator: Caroline Quach-Thanh, MD, MSc, McGill University Health Centre/Research Institute of the McGill University Health Centre; Study Director: Caroline Quach-Thanh, MD, MSc, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Doll MK, Buckeridge DL, Morrison KT, Gagneur A, Tapiero B, Charest H, Quach C. Effectiveness of monovalent rotavirus vaccine in a high-income, predominant-use setting. Vaccine. 2015 Dec 16;33(51):7307-7314. doi: 10.1016/j.vaccine.2015.10.118. Epub 2015 Nov 3.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 4, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimate): November 8, 2011

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Gastroenteritis; Pediatrics; Vaccination; Rotavirus
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Reoviridae Infections; Diarrhea; Gastroenteritis; Rotavirus Infections
• Other Study ID Numbers: MCH-ID-11-01