Marek Laskowski

Asymptomatic Transmission and the Dynamics of Zika Infection

Following the 2013–14 outbreak in French Polynesia, the Zika virus (ZIKV) epidemic spread widely to many countries where Aedes Aegypti as the main transmitting vector is endemic. The lack of a second wave of ZIKV infection in most affected regions may suggest that a sufficiently high level of herd immunity was reached during the first wave. We developed an agent-based transmission model to investigate the role of asymptomatic infection on the likelihood of observing a second wave, while accounting for its relative transmissibility. We found that, as the relative transmissibility of asymptomatic infection increases, a second wave is more likely to occur, despite an increase in the attack rate during the first wave. When the reproduction number varies between 1.9 and 2.8 based on estimates for Antioquia, Colombia, the attack rate varies between 4% and 26% for a low (below 10%) effectiveness of interventions in blunting the ZIKV transmission from symptomatic cases to mosquitoes. Moreover, the fraction of cases due to sexual transmission is estimated below 4% of the cumulative incidence. Our analyses underscore the need to quantify the transmissibility of asymptomatic infections, without which the overall attack rates and the level of herd immunity cannot be accurately estimated.

Influenza H3N2 variant viruses with pandemic potential: Preventing catastrophe in remote and isolated Canadian communities

OBJECTIVE To evaluate the impact of age-specific cross-reactive antibody protection levels on the outcomes of a pandemic outbreak of new variants of H3N2 influenza A viruses (H3N2v). METHODS We calibrated a previously validated agent-based model of human-to-human transmission of influenza viruses to project the outcomes of various protection levels in a remote and isolated Canadian community, when demographics are drawn from the Statistics Canada census data. We then compared the outcomes with a scenario in which demographic variables were shifted to resemble an urban structure. This comparative evaluation was conducted using in-silico computer simulations, where the epidemiological data were drawn from relevant estimates in published literature. RESULTS Simulations, using estimates of transmissibility for the 2009 H1N1 pandemic strain in the study population, show that the epidemic size is primarily affected by the cross-reactive protection levels of young children. A lower number of secondary infections at the early stages of an outbreak does not necessarily correspond to a lower epidemic size. CONCLUSIONS Demographic variables could play a significant role in determining the outcomes of an outbreak. The findings strongly suggest that, when an H3N2v-specific vaccine becomes available, children below the age of 17 should be prioritized for vaccination. This prioritization is essential in population settings with a low average age, including aboriginal communities in northern latitudes.

The Effect of Individual Movements and Interventions on the Spread of Influenza in Long-Term Care Facilities

Background. Nosocomial influenza poses a serious risk among residents of long-term care facilities (LTCFs). Objective. We sought to evaluate the effect of resident and staff movements and contact patterns on the outcomes of various intervention strategies for influenza control in an LTCF. Methods. We collected contact frequency data in Canada’s largest veterans’ LTCF by enroling residents and staff into a study that tracked their movements through wireless tags and signal receivers. We analyzed and fitted the data to an agent-based simulation model of influenza infection, and performed Monte-Carlo simulations to evaluate the benefit of antiviral prophylaxis and patient isolation added to standard (baseline) infection control practice (i.e., vaccination of residents and staff, plus antiviral treatment of residents with symptomatic infection). Results. We calibrated the model to attack rates of 20%, 40%, and 60% for the baseline scenario. For data-driven movements, we found that the largest reduction in attack rates (12.5% to 27%; ANOVA P < 0.001) was achieved when the baseline strategy was combined with antiviral prophylaxis for all residents for the duration of the outbreak. Isolation of residents with symptomatic infection resulted in little or no effect on the attack rates (2.3% to 4.2%; ANOVA P > 0.2) among residents. In contrast, parameterizing the model with random movements yielded different results, suggesting that the highest benefit was achieved through patient isolation (69.6% to 79.6%; ANOVA P < 0.001) while the additional benefit of prophylaxis was negligible in reducing the cumulative number of infections. Conclusions. Our study revealed a highly structured contact and movement patterns within the LTCF. Accounting for this structure—instead of assuming randomness—in decision analytic methods can result in substantially different predictions.

Antiviral Strategies for Emerging Influenza Viruses in Remote Communities

Background Due to the lack of timely access to resources for critical care, strategic use of antiviral drugs is crucial for mitigating the impact of novel influenza viruses with pandemic potential in remote and isolated communities. We sought to evaluate the effect of antiviral treatment and prophylaxis of close contacts in a Canadian remote northern community. Methods We used an agent-based, discrete-time simulation model for disease spread in a remote community, which was developed as an in-silico population using population census data. Relative and cumulative age-specific attack rates, and the total number of infections in simulated model scenarios were obtained. Results We found that early initiation of antiviral treatment is more critical for lowering attack rates in a remote setting with a low population-average age compared to an urban population. Our results show that a significant reduction in the relative, age-specific attack rates due to increasing treatment coverage does not necessarily translate to a significant reduction in the overall arrack rate. When treatment coverage varies from low to moderate, targeted prophylaxis has a very limited impact in reducing attack rates and should be offered at a low level (below 10%) to avoid excessive waste of drugs. Conclusions In contrast to previous work, for conservative treatment coverages, our results do not provide any convincing evidence for the implementation of targeted prophylaxis. The findings suggest that public health strategies in remote communities should focus on the wider availability (higher coverage) and timely distribution of antiviral drugs for treatment of clinically ill individuals.

A Perspective on Blockchain Smart Contracts: Reducing Uncertainty and Complexity in Value Exchange

The blockchain constitutes a technology-based, rather than social or regulation based, means to lower uncertainty about one another in order to exchange value. However, its use may very well also lead to increased complexity resulting from having to subsume work that displaced intermediary institutions had performed. We present our perspective that smart contracts may be used to mitigate this increased complexity. We further posit that smart contracts can be delineated according to complexity: Smart contracts that can be verified objectively without much uncertainty belong in an inter- organizational context; those that cannot be objectively verified belong in an intra- organizational context. We state that smart contracts that implement a formal (e.g. mathematical or simulation) model are especially beneficial for both contexts: They can be used to express and enforce inter-organizational agreements, and their basis in a common formalism may ensure effective evaluation and comparison between different intra-organizational contracts. Finally, we present a case study of our perspective by describing Intellichain, which implements formal, agent-based simulation model as a smart contract to provide epidemiological decision support.

Strategies for Early Vaccination During Novel Influenza Outbreaks.

Ongoing research and technology developments hold the promise of rapid production and large-scale deployment of strain-specific or cross-protective vaccines for novel influenza viruses. We sought to investigate the impact of early vaccination on age-specific attack rates and evaluate the outcomes of different vaccination strategies that are influenced by the level of single or two-dose vaccine-induced protections. We developed and parameterized an agent-based model for two population demographics of urban and remote areas in Canada. Our results demonstrate that there is a time period before and after the onset of epidemic, during which the outcomes of vaccination strategies may differ significantly and are highly influenced by demographic characteristics. For the urban population, attack rates were lowest for children younger than 5 years of age in all vaccination strategies. However, for the remote population, the lowest attack rates were obtained for adults older than 50 years of age in most strategies. We found that the reduction of attack rates following the start of vaccination campaigns during the epidemic depends critically on the disease transmissibility, suggesting that for a sufficiently high transmissibility, vaccine delivery after the onset of epidemic has little or no effect, regardless of the population demographics.

A First Step in the Co-Evolution of Blockchain and Ontologies: Towards Engineering an Ontology of Governance at the Blockchain Protocol Level

At the beginning of 2018, there is a growing belief that blockchain technologies constitute a revolutionary innovation in how we transfer value electronically. In that vein, blockchain may be a suitable complement to ontologies to achieve a big part of Tim Berners-Lee’s vision of the semantic Web. We believe that if this complementarity is to be achieved blockchain and ontologies must co-evolve. In this paper, we focus on what and how to engineer models, methods, designs, and implementations for this co-evolution. As a first step in this co-evolution, we propose a conceptual design of a governance ontology represented as meta-data tags to be embedded and instantiated in a smart contract at the blockchain protocol level. We develop this design by examining and analyzing smart contracts from the infamous The DAO experiment on the Ethereum blockchain. We believe there are two contributions of this paper: it serves to inform and implore the blockchain and ontology communities to recognize and collaborate with each other; and it outlines a roadmap for engineering artifacts to bridge the gap between blockchain community’s focus on protocol-level blockchain interoperability and the ontology community’s focus on semantic-level interoperability.

Strategies for halting the rise of multidrug resistant TB epidemics: assessing the effect of early case detection and isolation

Background The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control. Methods We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB. We implemented a 15-day isolation period following the start of treatment in active TB cases. The model was parameterized with the latest estimates derived from the published literature. Results We found that if high rates (over 90%) of TB case identification are achieved within 4 weeks of developing active TB, then a 15-day patient isolation strategy with 50% effectiveness in interrupting disease transmission leads to 10% reduction in the incidence of MDR-TB over 10 years. If transmission is fully prevented, the rise of MDR-TB can be halted within 10 years, but the temporal reduction of MDR-TB incidence remains below 20% in this period. Conclusions The impact of transmission reduction measures on the TB incidence depends critically on the rates and timelines of case identification. The high costs and adverse effects associated with MDR-TB treatment warrant increased efforts and investments on measures that can interrupt direct transmission through early case detection.

Individual movements and contact patterns in a Canadian long-term care facility

Contact networks of individuals in healthcare facilities are poorly understood, largely due to the lack of spatio-temporal movement data. A better understanding of such networks of interactions can help improve disease control strategies for nosocomial outbreaks. We sought to determine the spatio-temporal patterns of interactions between individuals using movement data collected in the largest veterans long-term care facility in Canada. We processed close-range contact data generated by the exchange of ultra-low-power radio signals, in a prescribed proximity, between wireless sensors worn by the participants over a two-week period. Statistical analyses of contact and movement data were conducted. We found a clear dichotomy in the contact network and movement patterns between residents and healthcare workers (HCWs) in this facility. Overall, residents tend to have significantly more distinct contacts with the mean of 17.3 (s.d. 3.6) contacts, versus 3.5 (s.d. 2.3) for HCWs (p-value < 10−12), for a longer duration of time (with mean contact duration of 8 minutes for resident-resident pair versus 4.6 minutes for HCW-resident pair) while being less mobile than HCWs. Analysis of movement data and clustering coefficient of the hourly aggregated network indicates that the contact network is loosely connected (mean clustering coefficient: 0.25, interquartile range 0–0.40), while being highly structured. Our findings bring quantitative insights regarding the contact network and movements in a long-term care facility, which are highly relevant to infer direct human-to-human and indirect (i.e., via the environment) disease transmission processes. This data-driven quantification is essential for validating disease dynamic models, as well as decision analytic methods to inform control strategies for nosocomial infections.

Assessing the benefits of early pandemic influenza vaccine availability: a case study for Ontario, Canada

New vaccine production technologies can significantly shorten the timelines for availability of a strain-specific vaccine in the event of an influenza pandemic. We sought to evaluate the potential benefits of early vaccination in reducing the clinical attack rate (CAR), taking into account the timing and speed of vaccination roll-out. Various scenarios corresponding to the transmissibility of a pandemic strain and vaccine prioritization strategies were simulated using an agent-based model of disease spread in Ontario, the largest Canadian province. We found that the relative reduction of the CAR reached 60% (90%CI: 44–100%) in a best-case scenario, in which the pandemic strain was moderately transmissible, vaccination started 4 weeks before the first imported case, the vaccine administration rate was 4 times higher than its average for seasonal influenza, and the vaccine efficacy was up to 90%. But the relative reductions in the CAR decreased significantly when the vaccination campaign was delayed or the administration rate reduced. In urban settings with similar characteristics to our population study, early availability and high rates of vaccine administration has the potential to substantially reduce the number of influenza cases. Low rates of vaccine administration or uptake can potentially offset the benefits of early vaccination.