Emergent variant modeling of the serological repertoire to norovirus in young children.

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens.

An analysis of 45 large-scale wastewater sites in England to estimate SARS-CoV-2 community prevalence.

Accurate surveillance of the COVID-19 pandemic can be weakened by under-reporting of cases, particularly due to asymptomatic or pre-symptomatic infections, resulting in bias. Quantification of SARS-CoV-2 RNA in wastewater can be used to infer infection prevalence, but uncertainty in sensitivity and considerable variability has meant that accurate measurement remains elusive. Here, we use data from 45 sewage sites in England, covering 31% of the population, and estimate SARS-CoV-2 prevalence to within 1.1% of estimates from representative prevalence surveys (with 95% confidence). Using machine learning and phenomenological models, we show that differences between sampled sites, particularly the wastewater flow rate, influence prevalence estimation and require careful interpretation. We find that SARS-CoV-2 signals in wastewater appear 4-5 days earlier in comparison to clinical testing data but are coincident with prevalence surveys suggesting that wastewater surveillance can be a leading indicator for symptomatic viral infections. Surveillance for viruses in wastewater complements and strengthens clinical surveillance, with significant implications for public health.

SARS-CoV-2 infection risk during delivery of childhood vaccination campaigns: a modelling study.

BACKGROUND: The COVID-19 pandemic has disrupted the delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to the staff delivering vaccination, the children being vaccinated, and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks. METHODS: We modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees, and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening. RESULTS: Infection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32 to 45% for vaccinators and 0.3 to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6 to 5.3% and 0.1 to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening. CONCLUSIONS: SARS-CoV-2 infection risks to vaccinators, vaccinees, and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.

Predicted norovirus resurgence in 2021-2022 due to the relaxation of nonpharmaceutical interventions associated with COVID-19 restrictions in England: a mathematical modeling study.

BACKGROUND: To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. METHODS: Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. RESULTS: We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. CONCLUSIONS: Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Estimating the minimum number of SARS-CoV-2 infected cases needed to detect viral RNA in wastewater: To what extent of the outbreak can surveillance of wastewater tell us?

There is increasing interest in wastewater-based epidemiology (WBE) of SARS-CoV-2 RNA to serve as an early warning system for a community. Despite successful detection of SARS-CoV-2 RNA in wastewaters sampled from multiple locations, there is still no clear idea on the minimal number of cases in a community that are associated with a positive detection of the virus in wastewater. To address this knowledge gap, we sampled wastewaters from a septic tank (n = 57) and biological activated sludge tank (n = 52) located on-site of a hospital. The hospital is providing treatment for SARS-CoV-2 infected patients, with the number of hospitalized patients per day known. It was observed that depending on which nucleocapsid gene is targeted by means of RT-qPCR, a range of 253-409 positive cases out of 10,000 persons are required prior to detecting RNA SARS-CoV-2 in wastewater. There was a weak correlation between N1 and N2 gene abundances in wastewater with the number of hospitalized cases. This correlation was however not observed for N3 gene. The frequency of detecting N1 and N2 gene in wastewater was also higher than that for N3 gene. Furthermore, nucleocapsid genes of SARS-CoV-2 were detected at lower frequency in the partially treated wastewater than in the septic tank. In particular, N1 gene abundance was associated with water quality parameters such as total organic carbon and pH. In instances of positive detection, the average abundance of N1 and N3 genes in the activated sludge tank were reduced by 50 and 70% of the levels detected in septic tank, suggesting degradation of the SARS-CoV-2 gene fragments already occurring in the early stages of the wastewater treatment process.

Tooling-up for infectious disease transmission modelling.

In this introduction to the Special Issue on methods for modelling of infectious disease epidemiology we provide a commentary and overview of the field. We suggest that the field has been through three revolutions that have focussed on specific methodological developments; disease dynamics and heterogeneity, advanced computing and inference, and complexity and application to the real-world. Infectious disease dynamics and heterogeneity dominated until the 1980s where the use of analytical models illustrated fundamental concepts such as herd immunity. The second revolution embraced the integration of data with models and the increased use of computing. From the turn of the century an emergence of novel datasets enabled improved modelling of real-world complexity. The emergence of more complex data that reflect the real-world heterogeneities in transmission resulted in the development of improved inference methods such as particle filtering. Each of these three revolutions have always kept the understanding of infectious disease spread as its motivation but have been developed through the use of new techniques, tools and the availability of data. We conclude by providing a commentary on what the next revoluition in infectious disease modelling may be.

Projected early spread of COVID-19 in Africa through 1 June 2020.

For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later.