A joint-threshold Filippov model describing the effect of intermittent androgen-deprivation therapy in controlling prostate cancer.

Intermittent androgen-deprivation therapy (IADT) can be beneficial to delay the occurrence of treatment resistance and cancer relapse compared to the standard continuous therapy. To study the effect of IADT in controlling prostate cancer, we developed a Filippov prostate cancer model with a joint threshold function: therapy is implemented once the total population of androgen-dependent cells (AC-Ds) and androgen-independent cells (AC-Is) is greater than the threshold value ET, and it is suspended once the population is less than ET. As the parameters vary, our model undergoes a series of sliding bifurcations, including boundary node, focus, saddle, saddle-node and tangency bifurcations. We also obtained the coexistence of one, two or three real equilibria and the bistability of two equilibria. Our results demonstrate that the population of AC-Is can be contained at a predetermined level if the initial population of AC-Is is less than this level, and we choose a suitable threshold value.

Prediction of the next major outbreak of COVID-19 in Mainland China and a vaccination strategy for it.

After the widespread prevalence of COVID-19 at the end of 2022 in Mainland China, a major concern is when will the second major outbreak occur and with what prevalence and fatality rates will it be associated with, as peoples' immunity from natural infection subsides. To address this, we established an age-structured model considering vaccine and infection-derived immunity, fitted an immunity-waning curve, and calibrated the model using the epidemic and vaccination data from Hong Kong in 2022. The model and the situation of the first major epidemic in Mainland China were then used to predict the prevalence rate, fatality rate and peak time of the second wave. In addition, the controlling effects of different vaccination strategies on the second major outbreak are discussed. Finally, a characterization indicator for the level of population immunity was provided. We conclude that if the prevalence of the first major epidemic was 80%, the prevalence rate of the second major outbreak would be about 37.64%, and the peak time would have been July 2 2023. Strengthening vaccination can effectively delay the peak of the second wave of the epidemic and reduce the prevalence.

Lessons drawn from Shanghai for controlling highly transmissible SARS-CoV-2 variants: insights from a modelling study.

BACKGROUND: The continuous emergence of novel SARS-CoV-2 variants with markedly increased transmissibility presents major challenges to the zero-COVID policy in China. It is critical to adjust aspects of the policy about non-pharmaceutical interventions (NPIs) by searching for and implementing more effective ways. We use a mathematical model to mimic the epidemic pattern of the Omicron variant in Shanghai to quantitatively show the control challenges and investigate the feasibility of different control patterns in avoiding other epidemic waves. METHODS: We initially construct a dynamic model with a core step-by-step release strategy to reveal its role in controlling the spread of COVID-19, including the city-based pattern and the district-based pattern. We used the least squares method and real reported case data to fit the model for Shanghai and its 16 districts, respectively. Optimal control theory was utilized to explore the quantitative and optimal solutions of the time-varying control strength (i.e., contact rate) to suppress the highly transmissible SARS-CoV-2 variants. RESULTS: The necessary period for reaching the zero-COVID goal can be nearly 4 months, and the final epidemic size was 629,625 (95%CI: [608,049, 651,201]). By adopting the city-based pattern, 7 out of 16 strategies released the NPIs more or earlier than the baseline and ensured a zero-resurgence risk at the average cost of 10 to 129 more cases in June. By adopting the district-based pattern, a regional linked release can allow resumption of social activity to ~ 100% in the boundary-region group about 14 days earlier and allow people to flow between different districts without causing infection resurgence. Optimal solutions of the contact rate were obtained with various testing intensities, and higher diagnosis rate correlated with higher optimal contact rate while the number of daily reported cases remained almost unchanged. CONCLUSIONS: Shanghai could have been bolder and more flexible in unleashing social activity than they did. The boundary-region group should be relaxed earlier and more attention should be paid to the centre-region group. With a more intensive testing strategy, people could return to normal life as much as possible but still ensure the epidemic was maintained at a relatively low level.

The resurgence risk of COVID-19 in China in the presence of immunity waning and ADE: A mathematical modelling study.

The mass vaccination program has been actively promoted since the end of 2020. However, waning immunity, antibody-dependent enhancement (ADE), and increased transmissibility of variants make the herd immunity untenable and the implementation of dynamic zero-COVID policy challenging in China. To explore how long the vaccination program can prevent China at low resurgence risk, and how these factors affect the long-term trajectory of the COVID-19 epidemics, we developed a dynamic transmission model of COVID-19 incorporating vaccination and waning immunity, calibrated using the data of accumulative vaccine doses administered and the COVID-19 epidemic in 2020 in mainland China. The prediction suggests that the vaccination coverage with at least one dose reach 95.87%, and two doses reach 77.92% on 31 August 2021. However, despite the mass vaccination, randomly introducing infected cases in the post-vaccination period causes large outbreaks quickly with waning immunity, particularly for SARS-CoV-2 variants with higher transmissibility. The results showed that with the current vaccination program and 50% of the population wearing masks, mainland China can be protected at low resurgence risk until 8 January 2023. However, ADE and higher transmissibility for variants would significantly shorten the low-risk period by over 1 year. Furthermore, intermittent outbreaks can occur while the peak values of the subsequent outbreaks decrease, indicating that subsequent outbreaks boosted immunity in the population level, further indicating that follow-up vaccination programs can help mitigate or avoid the possible outbreaks. The findings revealed that the integrated effects of multiple factors: waning immunity, ADE, relaxed interventions, and higher variant transmissibility, make controlling COVID-19 challenging. We should prepare for a long struggle with COVID-19, and not entirely rely on the COVID-19 vaccine.

Controlling Multiple COVID-19 Epidemic Waves: An Insight from a Multi-scale Model Linking the Behaviour Change Dynamics to the Disease Transmission Dynamics.

COVID-19 epidemics exhibited multiple waves regionally and globally since 2020. It is important to understand the insight and underlying mechanisms of the multiple waves of COVID-19 epidemics in order to design more efficient non-pharmaceutical interventions (NPIs) and vaccination strategies to prevent future waves. We propose a multi-scale model by linking the behaviour change dynamics to the disease transmission dynamics to investigate the effect of behaviour dynamics on COVID-19 epidemics using game theory. The proposed multi-scale models are calibrated and key parameters related to disease transmission dynamics and behavioural dynamics with/without vaccination are estimated based on COVID-19 epidemic data (daily reported cases and cumulative deaths) and vaccination data. Our modeling results demonstrate that the feedback loop between behaviour changes and COVID-19 transmission dynamics plays an essential role in inducing multiple epidemic waves. We find that the long period of high-prevalence or persistent deterioration of COVID-19 epidemics could drive almost all of the population to change their behaviours and maintain the altered behaviours. However, the effect of behaviour changes fades out gradually along the progress of epidemics. This suggests that it is essential to have not only persistent, but also effective behaviour changes in order to avoid subsequent epidemic waves. In addition, our model also suggests the importance to maintain the effective altered behaviours during the initial stage of vaccination, and to counteract relaxation of NPIs, it requires quick and massive vaccination to avoid future epidemic waves.

Home quarantine or centralized quarantine? A mathematical modelling study on the COVID-19 epidemic in Guangzhou in 2021.

Several outbreaks of COVID-19 caused by imported cases have occurred in China following the successful control of the outbreak in early 2020. In order to avoid recurrences of such local outbreaks, it is important to devise an efficient control and prevention strategy. In this paper, we developed a stochastic discrete model of the COVID-19 epidemic in Guangzhou in 2021 to compare the effectiveness of centralized quarantine and compulsory home quarantine measures. The model was calibrated by using the daily reported cases and newly centralized quarantined cases. The estimated results showed that the home quarantine measure increased the accuracy of contact tracing. The estimated basic reproduction number was lower than that in 2020, even with a much more transmissible variant, demonstrating the effectiveness of the vaccines and normalized control interventions. Sensitivity analysis indicated that a sufficiently implemented contact tracing and centralized quarantine strategy in the initial stage would contain the epidemic faster with less infections even with a weakly implemented compulsory home quarantine measure. However, if the accuracy of the contact tracing was insufficient, then early implementation of the compulsory home quarantine with strict contact tracing, screening and testing interventions on the key individuals would shorten the epidemic duration and reduce the total number of infected cases. Particularly, 94 infections would have been avoided if the home quarantine measure had been implemented 3 days earlier and an extra 190 infections would have arisen if the home quarantine measure was implemented 3 days later. The study suggested that more attention should be paid to the precise control strategy during the initial stage of the epidemic, otherwise the key group-based control measure should be implemented strictly.

The effectiveness of various control strategies: An insight from a comparison modelling study.

Several local outbreaks have occurred and been suppressed with the dynamic zero-COVID policy and widely promoted vaccination program implemented in China. The epidemic duration and final size vary significantly in different cities, which may be attributed to different implementation patterns and intensities of non-pharmaceutical interventions (NPIs). It's important to capture the underlying mechanism to explore more efficient implementation patterns of NPIs in order to prevent the future resurgence. In this study, outbreaks caused by Delta variant in Xi'an, Yangzhou and Guangzhou in 2021 are chosen as the examples. A novel model dividing the population into three groups is proposed to describe the heterogeneity of control interventions. The model is calibrated and key parameters related to NPIs are estimated by using multi-source epidemic data. The estimation results show a lower transmission probability but a higher initial reproduction number in Xi'an. Sensitivity analysis are conducted to investigate the impact of various control measures in different epidemic phases. The results identify the vital role of enhancing closed-off management, strengthening tracing and testing intensities, on shortening the epidemic durations and reducing the final size. Further, we find that sufficiently implemented closed-off management would prevent the city from lockdown. Strengthening the tracing other than the testing strategy in the initial stage is more effective on containing the epidemic in a shorter duration with less infections.

Discrete epidemic modelling of COVID-19 transmission in Shaanxi Province with media reporting and imported cases.

The large-scale infection of COVID-19 has led to a significant impact on lives and economies around the world and has had considerable impact on global public health. Social distancing, mask wearing and contact tracing have contributed to containing or at least mitigating the outbreak, but how public awareness influences the effectiveness and efficiency of such approaches remains unclear. In this study, we developed a discrete compartment dynamic model to mimic and explore how media reporting and the strengthening containment strategies can help curb the spread of COVID-19 using Shaanxi Province, China, as a case study. The targeted model is parameterized based on multi-source data, including the cumulative number of confirmed cases, recovered individuals, the daily number of media-reporting items and the imported cases from the rest of China outside Shaanxi from January 23 to April 11, 2020. We carried out a sensitivity analysis to investigate the effect of media reporting and imported cases on transmission. The results revealed that reducing the intensity of media reporting, which would result in a significant increasing of the contact rate and a sizable decreasing of the contact-tracing rate, could aggravate the outbreak severity by increasing the cumulative number of confirmed cases. It also demonstrated that diminishing the imported cases could alleviate the outbreak severity by reducing the length of the epidemic and the final size of the confirmed cases; conversely, delaying implementation of lockdown strategies could prolong the length of the epidemic and magnify the final size. These findings suggest that strengthening media coverage and timely implementing of lockdown measures can significantly reduce infection.

Impact of Hospital Bed Shortages on the Containment of COVID-19 in Wuhan.

The global outbreak of COVID-19 has caused worrying concern amongst the public and health authorities. The first and foremost problem that many countries face during the outbreak is a shortage of medical resources. In order to investigate the impact of a shortage of hospital beds on the COVID-19 outbreak, we formulated a piecewise smooth model for describing the limitation of hospital beds. We parameterized the model while using data on the cumulative numbers of confirmed cases, recovered cases, and deaths in Wuhan city from 10 January to 12 April 2020. The results showed that, even with strong prevention and control measures in Wuhan, slowing down the supply rate, reducing the maximum capacity, and delaying the supply time of hospital beds all aggravated the outbreak severity by magnifying the cumulative numbers of confirmed cases and deaths, lengthening the end time of the pandemic, enlarging the value of the effective reproduction number during the outbreak, and postponing the time when the threshold value was reduced to 1. Our results demonstrated that establishment of the Huoshenshan, Leishenshan, and Fangcang shelter hospitals avoided 22,786 people from being infected and saved 6524 lives. Furthermore, the intervention of supplying hospital beds avoided infections in 362,360 people and saved the lives of 274,591 persons. This confirmed that the quick establishment of the Huoshenshan, Leishenshan Hospitals, and Fangcang shelter hospitals, and the designation of other hospitals for COVID-19 patients played important roles in containing the outbreak in Wuhan.

Optimal media reporting intensity on mitigating spread of an emerging infectious disease.

Mass media reports can induce individual behaviour change during a disease outbreak, which has been found to be useful as it reduces the force of infection. We propose a compartmental model by including a new compartment of the intensity of the media reports, which extends existing models by considering a novel media function, which is dependent both on the number of infected individuals and on the intensity of mass media. The existence and stability of the equilibria are analyzed and an optimal control problem of minimizing the total number of cases and total cost is considered, using reduction or enhancement in the media reporting rate as the control. With the help of Pontryagin's Maximum Principle, we obtain the optimal media reporting intensity. Through parameterization of the model with the 2009 A/H1N1 influenza outbreak data in the 8th Hospital of Xi'an in Shaanxi Province of China, we obtain the basic reproduction number for the formulated model with two particular media functions. The optimal media reporting intensity obtained here indicates that during the early stage of an epidemic we should quickly enhance media reporting intensity, and keep it at a maximum level until it can finally weaken when epidemic cases have decreased significantly. Numerical simulations show that media impact reduces the number of cases during an epidemic, but that the number of cases is further mitigated under the optimal reporting intensity. Sensitivity analysis implies that the outbreak severity is more sensitive to the weight α1 (weight of media effect sensitive to infected individuals) than weight α2 (weight of media effect sensitive to media items).

A two-thresholds policy to interrupt transmission of West Nile Virus to birds.

This paper proposes a model of West Nile Virus (WNV) including threshold control policies concerning the culling of mosquitoes and birds under different conditions. Two thresholds are introduced to estimate whether and which control strategy should be implemented. For each mosquito threshold level [Formula: see text] the dynamical behaviour of the proposed non-smooth system is investigated as the bird threshold level [Formula: see text] varies, focusing on the existence of sliding domains, the existence of pseudo-equilibria, real or virtual of the endemic equilibria, global stability of these steady states, and the most interesting case of the occurrence of a novel globally asymptotically stable pseudo-attractor. The model solutions ultimately converge to a real equilibrium or a pseudo-equilibrium (if it exists), or a pseudo-attractor if no equilibrium is real and no pseudo-equilibrium exists. Here within, we show that the free system has a single stable endemic equilibrium under biologically reasonable assumptions, and show that when the control system has: (1) a bird-culling threshold that is above the bird equilibrium, culling has no advantage; (2) a bird-culling threshold that is below the bird equilibrium, but a mosquito-culling threshold that lies above the mosquito equilibrium, the infected bird population can be reduced but the infected mosquito population will remain the same; (3) a bird-culling threshold and a mosquito-culling threshold that both lie below their respective equilibrium values of the free system, then both the infected bird and mosquito populations can be reduced to lower levels. The results suggest that preset levels of the number of infected birds and infected mosquitoes can be maintained simultaneously when threshold values are chosen properly, which provides a possible control strategy when an emergent infectious disease cannot be eradicated immediately.