Biases in Routine Influenza Surveillance Indicators Used to Monitor Infection Incidence and Recommendations for Improvement.

Background: Monitoring how the incidence of influenza infections changes over time is important for quantifying the transmission dynamics and clinical severity of influenza. Infection incidence is difficult to measure directly, and hence, other quantities which are more amenable to surveillance are used to monitor trends in infection levels, with the implicit assumption that they correlate with infection incidence.

Methods: Here, we demonstrate, through mathematical reasoning using fundamental mathematical principles, the relationship between the incidence of influenza infections and three commonly reported surveillance indicators: (1) the rate per unit time of influenza-like illness reported through sentinel healthcare sites, (2) the rate per unit time of laboratory-confirmed influenza infections and (3) the proportion of laboratory tests positive for influenza ('test-positive proportion').

Investigation of P. vivax elimination via mass drug administration: A simulation study.

Plasmodium vivax is the most geographically widespread malaria parasite. P. vivax has the ability to remain dormant (as a hypnozoite) in the human liver and subsequently reactivate, which makes control efforts more difficult.

Challenges in the case-based surveillance of infectious diseases.

To effectively inform infectious disease control strategies, accurate knowledge of the pathogen's transmission dynamics is required. Since the timings of infections are rarely known, estimates of the infection incidence, which is crucial for understanding the transmission dynamics, often rely on measurements of other quantities amenable to surveillance. Case-based surveillance, in which infected individuals are identified by a positive test, is the predominant form of surveillance for many pathogens, and was used extensively during the COVID-19 pandemic.

Spatial information allows inference of the prevalence of direct cell-to-cell viral infection.

The role of direct cell-to-cell spread in viral infections-where virions spread between host and susceptible cells without needing to be secreted into the extracellular environment-has come to be understood as essential to the dynamics of medically significant viruses like hepatitis C and influenza. Recent work in both the experimental and mathematical modelling literature has attempted to quantify the prevalence of cell-to-cell infection compared to the conventional free virus route using a variety of methods and experimental data. However, estimates are subject to significant uncertainty and moreover rely on data collected by inhibiting one mode of infection by either chemical or physical factors, which may influence the other mode of infection to an extent which is difficult to quantify.

Opportunities to strengthen respiratory virus surveillance systems in Australia: lessons learned from the COVID-19 response.

Disease surveillance data was critical in supporting public health decisions throughout the coronavirus disease 2019 (COVID-19) pandemic. At the same time, the unprecedented circumstances of the pandemic revealed many shortcomings of surveillance systems for viral respiratory pathogens. Strengthening of surveillance systems was identified as a priority for the recently established Australian Centre for Disease Control, which represents a critical opportunity to review pre-pandemic and pandemic surveillance practices, and to decide on future priorities, during both pandemic and inter-pandemic periods.

A hybrid transmission model for Plasmodium vivax accounting for superinfection, immunity and the hypnozoite reservoir.

Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection.

Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia.

Background: Australian states and territories used test-trace-isolate-quarantine (TTIQ) systems extensively in their response to the COVID-19 pandemic in 2020-2021. We report on an analysis of Australian case data to estimate the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission.

Methods: Our analysis uses a novel mathematical modelling framework and detailed surveillance data on COVID-19 cases including dates of infection and dates of isolation.

Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections.

Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria.

Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a 'National Plan' to reopening.

The availability of COVID-19 vaccines promised a reduction in the severity of disease and relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden of COVID-19. We were asked to define vaccine coverage thresholds for Australia's transition to easing restrictions and reopening international borders. Using evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine coverage targets.

Mathematical models of Plasmodium vivax transmission: A scoping review.

Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of the P. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.

Key Challenges for Respiratory Virus Surveillance while Transitioning out of Acute Phase of COVID-19 Pandemic.

To support the ongoing management of viral respiratory diseases while transitioning out of the acute phase of the COVID-19 pandemic, many countries are moving toward an integrated model of surveillance for SARS-CoV-2, influenza virus, and other respiratory pathogens. Although many surveillance approaches catalyzed by the COVID-19 pandemic provide novel epidemiologic insight, continuing them as implemented during the pandemic is unlikely to be feasible for nonemergency surveillance, and many have already been scaled back. Furthermore, given anticipated cocirculation of SARS-CoV-2 and influenza virus, surveillance activities in place before the pandemic require review and adjustment to ensure their ongoing value for public health.

Seasonality as a driver of pH1N12009 influenza vaccination campaign impact.

Although the most recent respiratory virus pandemic was triggered by a Coronavirus, sustained and elevated prevalence of highly pathogenic avian influenza viruses able to infect mammalian hosts highlight the continued threat of pandemics of influenza A virus (IAV) to global health. Retrospective analysis of pandemic outcomes, including comparative investigation of intervention efficacy in different regions, provide important contributions to the evidence base for future pandemic planning. The swine-origin IAV pandemic of 2009 exhibited regional variation in onset, infection dynamics and annual infection attack rates (IARs).

Superinfection and the hypnozoite reservoir for Plasmodium vivax: a general framework.

A characteristic of malaria in all its forms is the potential for superinfection (that is, multiple concurrent blood-stage infections). An additional characteristic of Plasmodium vivax malaria is a reservoir of latent parasites (hypnozoites) within the host liver, which activate to cause (blood-stage) relapses. Here, we present a model of hypnozoite accrual and superinfection for P.

How effective were Australian Quarantine Stations in mitigating transmission aboard ships during the influenza pandemic of 1918-19?

The influenza pandemic of 1918-19 was the most devastating pandemic of the 20th century. It killed an estimated 50-100 million people worldwide. In late 1918, when the severity of the disease was apparent, the Australian Quarantine Service was established.

Improving estimates of waning immunity rates in stochastic SIRS models with a hierarchical framework.

As most disease causing pathogens require transmission from an infectious individual to a susceptible individual, continued persistence of the pathogen within the population requires the replenishment of susceptibles through births, immigration, or waning immunity. Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers from infection. If, initially, the prevalence of disease increases (that is, the infection takes off), the number of infectives will usually decrease to a low level after the first major outbreak.

Individual variation in vaccine immune response can produce bimodal distributions of protection.

The ability for vaccines to protect against infectious diseases varies among individuals, but computational models employed to inform policy typically do not account for this variation. Here we examine this issue: we implement a model of vaccine efficacy developed in the context of SARS-CoV-2 in order to evaluate the general implications of modelling correlates of protection on the individual level. Due to high levels of variation in immune response, the distributions of individual-level protection emerging from this model tend to be highly dispersed, and are often bimodal.

Choice of spatial discretisation influences the progression of viral infection within multicellular tissues.

There has been an increasing recognition of the utility of models of the spatial dynamics of viral spread within tissues. Multicellular models, where cells are represented as discrete regions of space coupled to a virus density surface, are a popular approach to capture these dynamics. Conventionally, such models are simulated by discretising the viral surface and depending on the rate of viral diffusion and other considerations, a finer or coarser discretisation may be used.

Understanding the impact of disease and vaccine mechanisms on the importance of optimal vaccine allocation.

Vaccination is an important epidemic intervention strategy. However, it is generally unclear how the outcomes of different vaccine strategies change depending on population characteristics, vaccine mechanisms and allocation objective. In this paper we develop a conceptual mathematical model to simulate strategies for pre-epidemic vaccination.

Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020.

As of January 2021, Australia had effectively controlled local transmission of COVID-19 despite a steady influx of imported cases and several local, but contained, outbreaks in 2020. Throughout 2020, state and territory public health responses were informed by weekly situational reports that included an ensemble forecast of daily COVID-19 cases for each jurisdiction. We present here an analysis of one forecasting model included in this ensemble across the variety of scenarios experienced by each jurisdiction from May to October 2020.

Enhanced viral infectivity and reduced interferon production are associated with high pathogenicity for influenza viruses.

Epidemiological and clinical evidence indicates that humans infected with the 1918 pandemic H1N1 influenza virus and highly pathogenic avian H5N1 influenza viruses often displayed severe lung pathology. High viral load and extensive infiltration of macrophages are the hallmarks of highly pathogenic (HP) influenza viral infections. However, it remains unclear what biological mechanisms primarily determine the observed difference in the kinetics of viral load and macrophages between HP and low pathogenic (LP) viral infections, and how the mechanistic differences are associated with viral pathogenicity.

A modelling approach to estimate the transmissibility of SARS-CoV-2 during periods of high, low, and zero case incidence.

Against a backdrop of widespread global transmission, a number of countries have successfully brought large outbreaks of COVID-19 under control and maintained near-elimination status. A key element of epidemic response is the tracking of disease transmissibility in near real-time. During major outbreaks, the effective reproduction number can be estimated from a time-series of case, hospitalisation or death counts.

Real-time analysis of hospital length of stay in a mixed SARS-CoV-2 Omicron and Delta epidemic in New South Wales, Australia.

Background: The distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the 'length of stay') is a key factor in determining how incident caseloads translate into health system burden. Robust estimation of length of stay in real-time requires the use of survival methods that can account for right-censoring induced by yet unobserved events in patient progression (e.g.

A Multiscale Mathematical Model of Plasmodium Vivax Transmission.

Malaria is caused by Plasmodium parasites which are transmitted to humans by the bite of an infected Anopheles mosquito. Plasmodium vivax is distinct from other malaria species in its ability to remain dormant in the liver (as hypnozoites) and activate later to cause further infections (referred to as relapses). Mathematical models to describe the transmission dynamics of P.