Analysis of Individual-Level Epidemic Data: Study of 2018-2020 Ebola Outbreak in Democratic Republic of the Congo

The 2018-2020 Ebola virus disease epidemic in Democratic Republic of the Congo (DRC) resulted in 3481 cases (probable and confirmed) and 2299 deaths. In this paper, we use a novel statistical method to analyze the individual-level incidence and hospitalization data on DRC Ebola victims. Our analysis suggests that an increase in the rate of quarantine and isolation by approximately 12% during the epidemic’s third and final wave was likely responsible for the eventual containment of the outbreak. The analysis further reveals that the total effective population size or the average number of individuals at risk for the disease exposure in three epidemic waves over the period of 24 months was around 19,000—a much smaller number than previously estimated and likely an evidence of at least partial protection of the population at risk through ring vaccination and contact tracing as well as adherence to strict quarantine and isolation policies.

Autocrine and paracrine interferon signalling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host

The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

Modelling of COVID-19 vaccination strategies and herd immunity, in scenarios of limited and full vaccine supply in NSW, Australia

Several vaccines for SARS-CoV-2 are expected to be available in Australia in 2021. Initial supply is likely to be limited, and will require a judicious vaccination strategy until supply is unrestricted. If vaccines have efficacy as post-exposure prophylaxis (PEP) in contacts, this provides more policy options. We used a deterministic mathematical model of epidemic response with limited supply (age-targeted or ring vaccination) and mass vaccination for the State of New South Wales (NSW) in Australia. For targeted vaccination, the effectiveness of vaccinating health workers, young people and older adults was compared. For mass vaccination, we tested varying vaccine efficacy (VE) and distribution capacities. With a limited vaccine stockpile of 1 million doses in NSW, if there is efficacy as PEP, the most efficient way to control COVID-19 will be ring vaccination, however at least 90% of contacts per case needs to be traced and vaccinated. Health worker vaccination is required for health system resilience. Age based strategies with restricted doses make minimal impact on the epidemic, but vaccinating older people prevents more deaths. Herd immunity can only be achieved with mass vaccination. With 90% VE, herd immunity can be achieved by vaccinating 66% of the population. A vaccine with less than 70% VE cannot achieve herd immunity and will result in ongoing risk of outbreaks. For mass vaccination, distributing at least 60,000 doses per day is required to achieve control. Slower rates of vaccination will result in the population living with COVID-19 longer, and higher cases and deaths.

Autocrine and paracrine interferon signaling as 'ring vaccination' and 'contact tracing' strategies to suppress virus infection in a host

The innate immune response, particularly the interferon response, represents a first line of defense against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signaling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signaling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signaling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signaling is not as effective; in contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signaling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as contact tracing or ring vaccination. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

Assessing the feasibility of Nipah vaccine efficacy trials based on previous outbreaks in Bangladesh

BackgroundNipah virus (NiV) is an emerging, bat-borne pathogen that can be transmitted from person-to-person. Vaccines are currently being developed for NiV, and studies funded to evaluate their safety and immunogenicity, so that they could possibly be used to contain outbreaks. An important unanswered question is whether it will be possible to evaluate the efficacy of vaccine candidates in phase III clinical trials in a context where spillovers from the zoonotic reservoir are infrequent and associated with small outbreaks. The objective of this study was to investigate the feasibility of conducting a phase III vaccine trial in Bangladesh, the only country reporting regularly NiV cases.MethodsWe used simulations based on previously observed NiV cases from Bangladesh, an assumed vaccine efficacy of 90% and other NiV vaccine target characteristics, to compare three vaccination study designs: (i) cluster randomized ring vaccination, (ii) cluster randomized mass vaccination, and (iii) an observational case-control study design.ResultsThe simulations showed that, assuming a ramp-up period of 10 days and a mean hospitalization delay of 4 days, it would take 516 years and over 163,000 vaccine doses to run a ring vaccination trial under current epidemic conditions. A cluster-randomized trial in the two most affected districts would take 81 years and 2.3 million vaccine doses. An observational case-control design in these two districts would require seven years and 2.5 million vaccine doses.DiscussionWithout a change in the epidemiology of NiV, ring vaccination or cluster-randomized trials are unlikely to be completed within a reasonable time window. In this light, the remaining options are: (i) not conducting a phase III trial until the epidemiology of NiV changes, (ii) identifying alternative ways to licensure such as observational studies or controlled studies in animals such as in the US Food and Drug Administration’s (FDA) Animal Rule.

Modelling the impact of a smallpox attack in India and influence of disease control measures

ObjectivesTo estimate the impact of a smallpox attack in Mumbai, India, examine the impact of case isolation and ring vaccination for epidemic containment and test the health system capacity under different scenarios with available interventions.SettingThe research is based on Mumbai, India population.InterventionsWe tested 50%, 70%, 90% of case isolation and contacts traced and vaccinated (ring vaccination) in the susceptible, exposed, infected, recovered model and varied the start of intervention between 20, 30 and 40 days after the initial attack.Primary and secondary outcome measuresWe estimated and incorporated in the model the effect of past vaccination protection, age-specific immunosuppression and contact rates and Mumbai population age structure in modelling disease morbidity and transmission.ResultsThe estimated duration of an outbreak ranged from 127 days to 8 years under different scenarios, and the number of vaccine doses needed for ring vaccination ranged from 16 813 to 8 722 400 in the best-case and worst-case scenarios, respectively. In the worst-case scenario, the available hospital beds in Mumbai would be exceeded. The impact of a smallpox epidemic may be severe in Mumbai, especially compared with high-income settings, but can be reduced with early diagnosis and rapid response, high rates of case finding and isolation and ring vaccination.ConclusionsThis study tells us that if smallpox re-emergence occurs, it may have significant health and economic impact, the extent of which will depend on the availability and delivery of interventions such as a vaccine or antiviral agent, and the capacity of case isolation and treatment. Further research on health systems requirements and capacity across the diverse states and territories of India could improve the preparedness and management strategies in the event of re-emergent smallpox or other serious emerging infections.

The Epidemiological Framework for Biological Invasions (EFBI): an interdisciplinary foundation for the assessment of biosecurity threats

Emerging microparasite (e.g. viruses, bacteria, protozoa and fungi) epidemics and the introduction of non-native pests and weeds are major biosecurity threats worldwide. The likelihood of these threats is often estimated from probabilities of their entry, establishment, spread and ease of prevention. If ecosystems are considered equivalent to hosts, then compartment disease models should provide a useful framework for understanding the processes that underpin non-native species invasions. To enable greater cross-fertilisation between these two disciplines, the Epidemiological Framework for Biological Invasions (EFBI) is developed that classifies ecosystems in relation to their invasion status: Susceptible, Exposed, Infectious and Resistant. These states are linked by transitions relating to transmission, latency and recovery. This viewpoint differs markedly from the species-centric approaches often applied to non-native species. It allows generalisations from epidemiology, such as the force of infection, the basic reproductive ratio R0, super-spreaders, herd immunity, cordon sanitaire and ring vaccination, to be discussed in the novel context of non-native species and helps identify important gaps in the study of biological invasions. The EFBI approach highlights several limitations inherent in current approaches to the study of biological invasions including: (i) the variance in non-native abundance across ecosystems is rarely reported; (ii) field data rarely (if ever) distinguish source from sink ecosystems; (iii) estimates of the susceptibility of ecosystems to invasion seldom account for differences in exposure to non-native species; and (iv) assessments of ecosystem susceptibility often confuse the processes that underpin patterns of spread within -and between- ecosystems. Using the invasion of lakes as a model, the EFBI approach is shown to present a new biosecurity perspective that takes account of ecosystem status and complements demographic models to deliver clearer insights into the dynamics of biological invasions at the landscape scale. It will help to identify whether management of the susceptibility of ecosystems, of the number of vectors, or of the diversity of pathways (for movement between ecosystems) is the best way of limiting or reversing the population growth of a non-native species. The framework can be adapted to incorporate increasing levels of complexity and realism and to provide insights into how to monitor, map and manage biological invasions more effectively.