Diarrhea, Gastroenteritis, Rotavirus Infections
Conditions
Keywords
Rotavirus, Gastroenteritis, Vaccination, Pediatrics
Brief summary
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.
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.
Interventions
OTHERNo intervention done
Not applicable because no intervention was done.
Sponsors
Institut National en Santé Publique du Québec
Ministere de la Sante et des Services Sociaux
GlaxoSmithKline
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Weeks to 3 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Matched VE Participants | From February 1, 2012 to May 31, 2014 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Vaccine Effectiveness of RV1 | From February 1, 2012 to May 31, 2014 | 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. |
Countries
Canada
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Rotavirus-negative All stool samples were initially tested for rotavirus via enzyme immunoassay. Patients with a negative result are included in this group. | 342 |
| Rotavirus -Positive All stool were initially tested for rotavirus via enzyme immunoassay. 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. | 32 |
| Total | 374 |
Baseline characteristics
| Characteristic | Rotavirus-negative | Rotavirus -Positive | Total |
|---|---|---|---|
| Age, Continuous | 12.6 months STANDARD_DEVIATION 6.3 | 16.6 months STANDARD_DEVIATION 6.5 | 13 months STANDARD_DEVIATION 6.4 |
| Region of Enrollment Canada | 342 participants | 32 participants | 374 participants |
| Rotavirus vaccination RV-vaccination 0 dose | 62 participants | 24 participants | 86 participants |
| Rotavirus vaccination RV-vaccination 1-dose | 26 participants | 1 participants | 27 participants |
| Rotavirus vaccination RV-vaccination ≥2 doses | 254 participants | 7 participants | 261 participants |
| Sex: Female, Male Female | 154 Participants | 20 Participants | 174 Participants |
| Sex: Female, Male Male | 188 Participants | 12 Participants | 200 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: From February 1, 2012 to May 31, 2014
Population: Rotavirus vaccination history by rotavirus disease status among matched VE participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotavirus-negative | Matched VE Participants | 0-Doses | 26 participants |
| Rotavirus-negative | Matched VE Participants | 1 Dose | 16 participants |
| Rotavirus-negative | Matched VE Participants | 2 Doses | 114 participants |
| Rotavirus-positive | Matched VE Participants | 0-Doses | 22 participants |
| Rotavirus-positive | Matched VE Participants | 1 Dose | 1 participants |
| Rotavirus-positive | Matched VE Participants | 2 Doses | 7 participants |
Other Pre-specified
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.
Time frame: From February 1, 2012 to May 31, 2014
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotavirus-negative | Vaccine Effectiveness of RV1 | 91.2 adjusted VE |
| Rotavirus-positive | Vaccine Effectiveness of RV1 | 92.5 adjusted VE |
95% CI: [0.02, 0.384]
95% CI: [0.018, 0.307]