A Discrete-Event, Simulated Social Agent-Based Network Transmission (DESSABNeT) model for communicable diseases: Method and validation using SARS-CoV-2 data in three large Australian cities

IMPORTANCE: During pandemics Agent Based Models (ABMs) can model complex, fine-grained behavioural interactions occurring in social networks, that contribute to disease transmission by novel viruses such as SARS-CoV-2. OBJECTIVE: We present a new agent-based model (ABM) called the Discrete-Event, Simulated Social Agent based Network Transmission model (DESSABNeT) and demonstrate its ability to model the spread of COVID-19 in large cities like Sydney, Melbourne and Gold Coast. Our aim was to validate the model with its disease dynamics and underlying social network. DESIGN: DESSABNeT relies on disease transmission within simulated social networks. It employs an epidemiological SEIRD+M (Susceptible, exposed, infected, recovered, died and managed) structure. One hundred simulations were run for each city, with simulated social restrictions closely modelling real restrictions imposed in each location. MAIN OUTCOME(S) AND MEASURE(S): The mean predicted daily incidence of COVID-19 cases were compared to real case incidence data for each city. R(eff) and health service utilisation outputs were compared to the literature, or for the Gold Coast with daily incidence of hospitalisation. RESULTS: DESSABNeT modelled multiple physical distancing restrictions and predicted epidemiological outcomes of Sydney, Melbourne and the Gold Coast, validating this model for future simulation work. CONCLUSIONS AND RELEVANCE: DESSABNeT is a valid platform to model the spread of COVID-19 in large cities in Australia and potentially internationally. The platform is suitable to model different combinations of social restrictions, or to model contact tracing, predict, and plan for, the impact on hospital and ICU admissions, and deaths; and also the rollout of COVID-19 vaccines and optimal social restrictions during vaccination

Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings

Epidemiology and clinical features of COVID-19 outbreaks in aged care facilities: A systematic review and meta-analysis

Background: COVID-19 outbreaks in aged care facilities (ACFs) often have devastating consequences. However, epidemiologically these outbreaks are not well defined. We aimed to define such outbreaks in ACFs by systematically reviewing literature published during the current COVID-19 pandemic. Methods: We searched 11 bibliographic databases for literature published on COVID-19 in ACFs between December 2019 and September 2020. Original studies reporting extractable epidemiological data as part of outbreak investigations or non-outbreak surveillance of ACFs were included in this systematic review and meta-analysis. PROSPERO registration: CRD42020211424. Findings: We identified 5,148 publications and selected 49 studies from four continents reporting data on 214,380 residents in 8,502 ACFs with 25,567 confirmed cases of COVID-19. Aged care residents form a distinct vulnerable population with single-facility attack rates of 45% [95% CI 32-58%] and case fatality rates of 23% [95% CI 18-28%]. Of the cases, 31% [95% CI 28-34%] were asymptomatic. The rate of hospitalization amongst residents was 37% [95% CI 35-39%]. Data from 21 outbreaks identified a resident as the index case in 58% of outbreaks and a staff member in 42%. Findings from the included studies were heterogeneous and of low to moderate quality in risk of bias assessment. Interpretation: The clinical presentation of COVID-19 varies widely in ACFs residents, from asymptomatic to highly serious cases. Preventing the introduction of COVID-19 into ACFs is key, and both residents and staff are a priority group for COVID-19 vaccination. Rapid diagnosis, identification of primary and secondary cases and close contacts plus their isolation and quarantine are of paramount importance. Funding: Queensland Advancing Clinical Research Fellowship awarded to Prof. Gulam Khandaker by Queensland Health's Health Innovation, Investment and Research Office (HIRO), Office of the Director-General

Subcellular Trafficking and Activity of Hyal-1 and Its Processed Forms in Murine Macrophages

The hyaluronidase Hyal-1 is an acid hydrolase that degrades hyaluronic acid (HA), a component of the extracellular matrix. It is often designated as a lysosomal protein. Yet few data are available on its intracellular localization and trafficking. We demonstrate here that in RAW264.7 murine macrophages, Hyal-1 is synthesized as a glycosylated precursor that is only weakly mannose 6-phosphorylated. Nevertheless, this precursor traffics to endosomes, via a mannose 6-phosphate-independent secretion/recapture mechanism that involves the mannose receptor. Once in endosomes, it is processed into a lower molecular mass form that is transported to lysosomes, where its activity could be detected using native gel zymography. Indeed, this activity co-distributed with lysosomal hydrolases in the densest fraction of a self-forming PercollTM density gradient. Moreover, it shifted toward the lower density region, in parallel with those hydrolases, when a decrease of lysosomal density was induced by the endocytosis of sucrose. Interestingly, the activity of the processed form of Hyal-1 was largely underestimated when assayed by zymography after SDS-PAGE and subsequent renaturation of the proteins, by contrast to the full-length protein that could efficiently degrade HA in those conditions. These results suggest that noncovalent associations support the lysosomal activity of Hyal-1.</p

Comparing the environmental efficiency of milk and beef production through life cycle assessment of interconnected cattle systems

peer-reviewedThe full text of this article will not be available in ULIR until the embargo expires on the 08/09/2020Dairy production has a substantial environmental impact. Currently, most studies analysing the environmental burdens of milk production employ attributional Life Cycle Assessment (LCA), for cradle to farm-gate analysis of dairy systems. This approach calculates environmental footprints per kg fat and protein corrected milk (FPCM). However, milk and beef production are inherently interconnected, and a narrow focus on milk production neglects wider synergies and trade-offs across cattle systems, outside dairy farm boundaries. For the first time, we applied an expanded boundary LCA of coupled dairy and beef production in Latin America, considering 1 kg FPCM plus 100 g of beef as functional unit (FU) to reflect the current global beef:milk demand ratio and taking into account the complexities of Costa Rican cattle production systems. Boundaries encompassed fattening of surplus dairy calves and incurred or avoided suckler-beef production needed to deliver the FU. A database of 552 Costa Rican farms (203 beef and 349 dairy farms) was analysed using a farm LCA model to generate results across five impact categories (Global Warming Potential – GWP; Eutrophication; Acidification; Abiotic Resource Depletion; and Land Occupation - LO). Normalised scores indicated that cattle systems contribute most strongly to per capita GWP and LO burdens. Cradle to farm-gate attributional LCA showed that milk produced by dual-purpose farms had the largest GWP and LO footprints, whilst specialist farms had the smallest footprints, per kg FPCM. The expanded boundary LCA showed that dual-purpose farms generated smaller GWP footprints per kg FPCM plus 100 g beef than specialised dairy farms, though still required more land. Key factors were the herd structure, influencing the amount of beef produced, and milk yields per animal, reflecting the level of dairy specialisation. This new evidence on the environmental efficiency of cattle production systems emphasises the imperative to consider both milk and beef production as well as multiple environmental pressures across interconnected milk and beef production systems when designing sustainable intensification mitigation strategies