Search

Background: Radio/chemotherapy and immune systems provide examples of hormesis, as tumours can be stimulated (or reduced) at low radio/chemical or antibody doses but inhibited (or stimulated) by high doses. Methods: Interactions between effector cells, tumour cells and cytokines with pulsed radio/chemo-immunotherapy were modelled using a pulse differential system. Results: Our results show that radio/chemotherapy (dose) response curves (RCRC) and/or immune response curves (IRC) or a combination of both, undergo homeostatic changes or catastrophic shifts revealing hormesis in many parameter regions. Some mixed response curves had multiple humps, posing challenges for interpretation of clinical trials and experimental design, due to a fuzzy region between an hormetic zone and the toxic threshold. Mixed response curves from two parameter bifurcation analyses demonstrated that low-dose radio/chemotherapy and strong immunotherapy counteract side-effects of radio/chemotherapy on effector cells and cytokines and stimulate effects of immunotherapy on tumour growth. The implications for clinical applications were confirmed by good fits to our model of RCRC and IRC data. Conclusions: The combination of low-dose radio/chemotherapy and high-dose immunotherapy is very effective for many solid tumours. The net benefit and synergistic effect of combined therapy is conducive to the treatment and inhibition of tumour cells. [ABSTRACT FROM AUTHOR]

Background: Epidemic zoning is an important option in a series of measures for the prevention and control of infectious diseases. We aim to accurately assess the disease transmission process by considering the epidemic zoning, and we take two epidemics with distinct outbreak sizes as an example, i.e., the Xi'an epidemic in late 2021 and the Shanghai epidemic in early 2022. Methods: For the two epidemics, the total cases were clearly distinguished by their reporting zone and the Bernoulli counting process was used to describe whether one infected case in society would be reported in control zones or not. Assuming the imperfect or perfect isolation policy in control zones, the transmission processes are respectively simulated by the adjusted renewal equation with case importation, which can be derived on the basis of the Bellman-Harris branching theory. The likelihood function containing unknown parameters is then constructed by assuming the daily number of new cases reported in control zones follows a Poisson distribution. All the unknown parameters were obtained by the maximum likelihood estimation. Results: For both epidemics, the internal infections characterized by subcritical transmission within the control zones were verified, and the median control reproduction numbers were estimated as 0.403 (95% confidence interval (CI): 0.352, 0.459) in Xi'an epidemic and 0.727 (95% CI: 0.724, 0.730) in Shanghai epidemic, respectively. In addition, although the detection rate of social cases quickly increased to 100% during the decline period of daily new cases until the end of the epidemic, the detection rate in Xi'an was significantly higher than that in Shanghai in the previous period. Conclusions: The comparative analysis of the two epidemics with different consequences highlights the role of the higher detection rate of social cases since the beginning of the epidemic and the reduced transmission risk in control zones throughout the outbreak. Strengthening the detection of social infection and strictly implementing the isolation policy are of great significance to avoid a larger-scale epidemic. [ABSTRACT FROM AUTHOR]

Background: China's Guangdong Province experienced a major dengue outbreak in 2014. Here we investigate if the weather conditions contributing to the outbreak can be elucidated by multi-scale models. Methods: A multi-scale modelling framework, parameterized by available weather, vector and human case data, was used to examine the integrative effect of temperature and precipitation variation on the effective reproduction number (ERN) of dengue fever. Results: With temperature in the range of 25–30 °C, increasing precipitation leads to an increase in the ERN with an average lag of 10 days. With monthly precipitation fixed, the more regular the pattern of rainfall (i.e. higher numbers of rainy days), the larger is the total number of adult mosquitoes. A rainfall distribution peaking in June and July produces a large ERN, beneficial to transmission. Climate conditions conducive to major outbreaks within a season are a combination of relatively high temperature, high precipitation peaking in June and July, and uninterrupted drizzle or regular rainfall. Conclusions: Evaluating a set of weather conditions favourable to a future major dengue outbreak requires near-future prediction of temperature variation, total rainfall and its peaking times. Such information permits seasonal rapid response management decisions due to the lags between the precipitation events and the realisation of the ERN. [ABSTRACT FROM AUTHOR]

Background: The Guangxi Zhuang Autonomous Region bears a relatively high burden of HIV/AIDS infection. The number of accumulatively reported HIV/AIDS cases in Guangxi is the third highest among 31 provinces or Autonomous Region from 2004 to 2007, changed to the second highest between 2011 and 2013, then returned to the third highest again after 2014. We aim to estimate the new infections and evaluate the real-time HIV epidemic in Guangxi, China, in order to reveal the rule of HIV transmission.Methods: Firstly, the number of annually reported HIV and AIDS cases, as well as the number of cases linked with CD4 data are extracted from the HIV/AIDS information system in China. Secondly, two CD4-staged models are formulated by linking the with-host information on CD4 level to between-host transmission and surveillance data. Thirdly, new HIV infections, diagnosis rates and undiagnosed infections over time are estimated by using Bayesian method and Maximum Likelihood Estimation method.Results: The data reveal that the newly reported cases have been decreasing since 2011, while lots of cases are identified at late CD4 stage. The data fitted results indicate that both models can describe the trend of the epidemic well. The estimation results show that the new and undiagnosed infections began to decrease from the period2006 - 2008. However, the diagnosis probabilities/rates keep at a very low level, and there are still a large number of infections undiagnosed, most of which have a large probability to be identified at late CD4 stage.Conclusions: Our findings suggest that HIV/AIDS epidemic in Guangxi has been controlled to a certain extent, while the diagnosis rate still needs to be improved. More attentions should be paid to identify infections at their early CD4 stages. Meanwhile, comprehensive intervention measures should be continually strengthened in avoid of the rebound of new infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic is complex and is developing in different ways according to the country involved.Methods: To identify the key parameters or processes that have the greatest effects on the pandemic and reveal the different progressions of epidemics in different countries, we quantified enhanced control measures and the dynamics of the production and provision of medical resources. We then nested these within a COVID-19 epidemic transmission model, which is parameterized by multi-source data. We obtained rate functions related to the intensity of mitigation measures, the effective reproduction numbers and the timings and durations of runs on medical resources, given differing control measures implemented in various countries.Results: Increased detection rates may induce runs on medical resources and prolong their durations, depending on resource availability. Nevertheless, improving the detection rate can effectively and rapidly reduce the mortality rate, even after runs on medical resources. Combinations of multiple prevention and control strategies and timely improvement of abilities to supplement medical resources are key to effective control of the COVID-19 epidemic. A 50% reduction in comprehensive control measures would have led to the cumulative numbers of confirmed cases and deaths exceeding 590,000 and 60,000, respectively, by 27 March 2020 in mainland China.Conclusions: Multiple data sources and cross validation of a COVID-19 epidemic model, coupled with a medical resource logistic model, revealed the key factors that affect epidemic progressions and their outbreak patterns in different countries. These key factors are the type of emergency medical response to avoid runs on medical resources, especially improved detection rates, the ability to promote public health measures, and the synergistic effects of combinations of multiple prevention and control strategies. The proposed model can assist health authorities to predict when they will be most in need of hospital beds and equipment such as ventilators, personal protection equipment, drugs, and staff. [ABSTRACT FROM AUTHOR]