Number of COVID-19 cases required in a population to detect SARS-CoV-2 RNA in wastewater in the province of Alberta, Canada: Sensitivity assessment.

With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.

Early warning and rapid public health response to prevent COVID-19 outbreaks in long-term care facilities (LTCF) by monitoring SARS-CoV-2 RNA in LTCF site-specific sewage samples and assessment of antibodies response in this population: prospective study protocol.

INTRODUCTION: The COVID-19 pandemic has an excessive impact on residents in long-term care facilities (LTCF), causing high morbidity and mortality. Early detection of presymptomatic and asymptomatic COVID-19 cases supports the timely implementation of effective outbreak control measures but repetitive screening of residents and staff incurs costs and discomfort. Administration of vaccines is key to controlling the pandemic but the robustness and longevity of the antibody response, correlation of neutralising antibodies with commercial antibody assays, and the efficacy of current vaccines for emerging COVID-19 variants require further study. We propose to monitor SARS-CoV-2 in site-specific sewage as an early warning system for COVID-19 in LTCF and to study the immune response of the staff and residents in LTCF to COVID-19 vaccines. METHODS AND ANALYSIS: The study includes two parts: (1) detection and quantification of SARS-CoV-2 in LTCF site-specific sewage samples using a molecular assay followed by notification of Public Health within 24 hours as an early warning system for appropriate outbreak investigation and control measures and cost-benefit analyses of the system and (2) testing for SARS-CoV-2 antibodies among staff and residents in LTCF at various time points before and after COVID-19 vaccination using commercial assays and neutralising antibody testing performed at a reference laboratory. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta Health Research Ethics Board with considerations to minimise risk and discomforts for the participants. Early recognition of a COVID-19 case in an LTCF might prevent further transmission in residents and staff. There was no direct benefit identified to the participants of the immunity study. Anticipated dissemination of information includes a summary report to the immunity study participants, sharing of study data with the scientific community through the Canadian COVID-19 Immunity Task Force, and prompt dissemination of study results in meeting abstracts and manuscripts in peer-reviewed journals.

Cost-effectiveness of palivizumab compared to no prophylaxis in term infants residing in the Canadian Arctic.

BACKGROUND: Hospital admissions for respiratory syncytial virus infection result in large health expenditures for Inuit infants. Palivizumab has been shown to be highly effective in reducing such admissions in preterm Inuit infants. We performed a cost-effectiveness analysis estimating the incremental cost-effectiveness ratio (ICER) for palivizumab prophylaxis per admission related to respiratory syncytial virus avoided in healthy term infants across the Canadian Arctic. METHODS: We compared universal palivizumab prophylaxis in term infants less than 6 months of age to no prophylaxis in 8 Arctic regions: the Northwest Territories, Nunavut, Nunavut without Iqaluit, the 3 subregions of Nunavut (Kitikmeot, Kivalliq and Qikiqtaaluk), the Qikiqtaaluk Region without Iqaluit, and Nunavik (northern Quebec). Costs were acquired from the territorial governments, hospitals and contracted agencies. The perspective is that of the public payer, with a 6-month timeline. In scenario A, universal prophylaxis was provided until the end of the respiratory syncytial virus season, and in scenario B, infants received prophylaxis until 5 months of age. The ICERs of scenario A were compared with those of scenario B. RESULTS: Under scenario A, the cost per admission avoided was as high as $546 115 in the Northwest Territories, compared with a cost savings of $36 145 in the Kitikmeot Region. Under scenario B, the ICER showed cost savings of $48 549 in the Kitikmeot Region and $2731 in the Kivalliq Region, with low ICERs in Nunavik of $15 601. INTERPRETATION: Considerable cost savings were found for the Kitikmeot Region with universal palivizumab prophylaxis in term infants with both scenarios, whereas cost savings were found for the Kivalliq Region with scenario B. Stopping prophylaxis at 5 months of age was a more cost-effective strategy in all regions except the Kitikmeot Region. Nunavik had low ICERs, and prophylaxis should be considered for this region.

Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE): epidemiology, emerging organisms, and economics.

BACKGROUND: Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. METHODS/DESIGN: This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. DISCUSSION: This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.

Determination of the relative economic impact of different molecular-based laboratory algorithms for respiratory viral pathogen detection, including Pandemic (H1N1), using a secure web based platform.

BACKGROUND: During period of crisis, laboratory planners may be faced with a need to make operational and clinical decisions in the face of limited information. To avoid this dilemma, our laboratory utilizes a secure web based platform, Data Integration for Alberta Laboratories (DIAL) to make near real-time decisions.This manuscript utilizes the data collected by DIAL as well as laboratory test cost modeling to identify the relative economic impact of four proposed scenarios of testing for Pandemic H1N1 (2009) and other respiratory viral pathogens. METHODS: Historical data was collected from the two waves of the pandemic using DIAL. Four proposed molecular testing scenarios were generated: A) Luminex respiratory virus panel (RVP) first with/without US centers for Disease Control Influenza A Matrix gene assay (CDC-M), B) CDC-M first with/without RVP, C) RVP only, and D) CDC-M only. Relative cost estimates of different testing algorithm were generated from a review of historical costs in the lab and were based on 2009 Canadian dollars. RESULTS: Scenarios A and B had similar costs when the rate of influenza A was low (< 10%) with higher relative cost in Scenario A with increasing incidence. Scenario A provided more information about mixed respiratory virus infection as compared with Scenario B. CONCLUSIONS: No one approach is applicable to all conditions. Testing costs will vary depending on the test volume, prevalence of influenza A strains, as well as other circulating viruses and a more costly algorithm involving a combination of different tests may be chosen to ensure that tests results are returned to the clinician in a quicker manner. Costing should not be the only consideration for determination of laboratory algorithms.