Impact of vaccination on Omicron's escape variants: Insights from fine-scale modelling of waning immunity in Hong Kong.

COVID-19 vaccine-induced protection declines over time. This waning of immunity has been described in modelling as a lower level of protection. This study incorporated fine-scale vaccine waning into modelling to predict the next surge of the Omicron variant of the SARS-CoV-2 virus. In Hong Kong, the Omicron subvariant BA.2 caused a significant epidemic wave between February and April 2022, which triggered high vaccination rates. About half a year later, a second outbreak, dominated by a combination of BA.2, BA.4 and BA.5 subvariants, began to spread. We developed mathematical equations to formulate continuous changes in vaccine boosting and waning based on empirical serological data. These equations were incorporated into a multi-strain discrete-time Susceptible-Exposed-Infectious-Removed model. The daily number of reported cases during the first Omicron outbreak, with daily vaccination rates, the population mobility index and daily average temperature, were used to train the model. The model successfully predicted the size and timing of the second surge and the variant replacement by BA.4/5. It estimated 655,893 cumulative reported cases from June 1, 2022 to 31 October 2022, which was only 2.69% fewer than the observed cumulative number of 674,008. The model projected that increased vaccine protection (by larger vaccine coverage or no vaccine waning) would reduce the size of the second surge of BA.2 infections substantially but would allow more subsequent BA.4/5 infections. Increased vaccine coverage or greater vaccine protection can reduce the infection rate during certain periods when the immune-escape variants co-circulate; however, new immune-escape variants spread more by out-competing the previous strain.

Nonlinear mixed models and related approaches in infectious disease modeling: A systematic and critical review.

The level of surveillance and preparedness against epidemics varies across countries, resulting in different responses to outbreaks. When conducting an in-depth analysis of microinfection dynamics, one must account for the substantial heterogeneity across countries. However, many commonly used statistical model specifications lack the flexibility needed for sound and accurate analysis and prediction in such contexts. Nonlinear mixed effects models (NLMMs) constitute a specific statistical tool that can overcome these significant challenges. While compartmental models are well-established in infectious disease modeling and have seen significant advancements, Nonlinear Mixed Models (NLMMs) offer a flexible approach for handling heterogeneous and unbalanced repeated measures data, often with less computational effort than some individual-level compartmental modeling techniques. This study provides an overview of their current use and offers a solid foundation for developing guidelines that may help improve their implementation in real-world situations. Relevant scientific databases in the Research4life Access initiative programs were used to search for papers dealing with key aspects of NLMMs in infectious disease modeling (IDM). From an initial list of 3641 papers, 124 were finally included and used for this systematic and critical review spanning the last two decades, following the PRISMA guidelines. NLMMs have evolved rapidly in the last decade, especially in IDM, with most publications dating from 2017 to 2021 (83.33%). The routine use of normality assumption appeared inappropriate for IDM, leading to a wealth of literature on NLMMs with non-normal errors and random effects under various estimation methods. We noticed that NLMMs have attracted much attention for the latest known epidemics worldwide (COVID-19, Ebola, Dengue and Lassa) with the robustness and reliability of relaxed propositions of the normality assumption. A case study of the application of COVID-19 data helped to highlight NLMMs' performance in modeling infectious diseases. Out of this study, estimation methods, assumptions, and random terms specification in NLMMs are key aspects requiring particular attention for their application in IDM.

Near zero background noise photoelectrochemical sensor based on sensitized signal probe CdS QDs-Dox intercalating double-stranded DNA for PEDV detection.

The highly sensitive detection method for porcine epidemic diarrhea virus (PEDV) is crucial for promptly identify infected pigs and effectively control the spread of the virus. In this study, the sensitization enhancement of organic photoactive material was combined with near zero background noise strategy for PEDV sensitive detection. A novel sensitized signal probe CdS quantum dots-doxycycline complex (CdS QDs-Dox) was prepared serving as a photoelectrochemical (PEC) probe embedded in dsDNA. Subsequently, a thiol-modified upstream inner primer (SH-FIP) was immobilized on the surface of electrode modified with gold nanoparticles (Au NPs) via Au-S bonding, enabling the loop-mediated isothermal amplification (LAMP) of PEDV on the electrode surface. The PEC probe (CdS QDs-Dox) embedded in the amplified dsDNA groove showed an increasing photocurrent signal with the rise of PEDV concentration, establishing a near-zero background LAMP-PEC sensing platform for PEDV detection. Under optimized conditions, the photocurrent intensity of this platform exhibited a good linear relationship with PEDV concentrations ranging from 0.0005 pg/µL to 10 pg/µL, achieving a detection limit as low as 0.17 fg/µL. This platform demonstrates outstanding specificity and sensitivity, thereby enabling precise quantitative detection of diverse pathogens.

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Integrating indicator-based and event-based surveillance data for risk mapping of West Nile virus, Europe, 2006 to 2021.

BackgroundWest Nile virus (WNV) has an enzootic cycle between birds and mosquitoes, humans being incidental dead-end hosts. Circulation of WNV is an increasing public health threat in Europe. While detection of WNV is notifiable in humans and animals in the European Union, surveillance based on human case numbers presents some limitations, including reporting delays.AimWe aimed to perform risk mapping of WNV circulation leading to human infections in Europe by integrating two types of surveillance systems: indicator-based and event-based surveillance.MethodsFor indicator-based surveillance, we used data on human case numbers reported to the European Centre for Disease Prevention and Control (ECDC), and for event-based data, we retrieved information from news articles collected through an automated biosurveillance platform. In addition to these data sources, we also used environmental data to train ecological niche models to map the risk of local WNV circulation leading to human infections.ResultsThe ecological niche models based on both types of surveillance data highlighted new areas potentially at risk of WNV infection in humans, particularly in Spain, Italy, France and Greece.ConclusionAlthough event-based surveillance data do not constitute confirmed occurrence records, integrating both indicator-based and event-based surveillance data proved useful. These results underscore the potential for a more proactive and comprehensive strategy in managing the threat of WNV in Europe by combining indicator- and event-based and environmental data for effective surveillance and public health response.

Impact of the COVID-19 pandemic on the codification of China's civil code.

The COVID-19 pandemic has spread widely around the world since 2019, wreaking havoc on social order in a global context. In China, the pandemic has not only provided new challenges to the government's capacity but also provided new issues for the Civil Code that is being compiled. The study adopts the research method of comparative analysis and combines the case study method, aiming to study the impact of the epidemic on the compilation of China's Civil Code. We found that the official Civil Code adds, deletes, and adjusts several articles compared to the Civil Code (Draft), five of which are relevant to the COVID-19 pandemic. The Civil Code was enacted at the time of the COVID-19 pandemic, which led to some of its provisions being affected by the COVID-19; the "COVID-19 provisions" not only provided legitimacy for the prevention and control of the pandemic but also improved China's system of governance of public health emergencies. This study exposes the legal loophole in the "COVID-19 provisions" in China's Civil Code and further suggests ways to fill the legal loophole.

Mathematical modeling of infectious diseases and the impact of vaccination strategies.

Mathematical modeling plays a crucial role in understanding and combating infectious diseases, offering predictive insights into disease spread and the impact of vaccination strategies. This paper explored the significance of mathematical modeling in epidemic control efforts, focusing on the interplay between vaccination strategies, disease transmission rates, and population immunity. To facilitate meaningful comparisons of vaccination strategies, we maintained a consistent framework by fixing the vaccination capacity to vary from 10 to 100% of the total population. As an example, at a 50% vaccination capacity, the pulse strategy averted approximately 45.61% of deaths, while continuous and hybrid strategies averted around 45.18 and 45.69%, respectively. Sensitivity analysis further indicated that continuous vaccination has a more direct impact on reducing the basic reproduction number $ R_0 $ compared to pulse vaccination. By analyzing key parameters such as $ R_0 $, pulse vaccination coefficients, and continuous vaccination parameters, the study underscores the value of mathematical modeling in shaping public health policies and guiding decision-making during disease outbreaks.

Changes in epidemiological and treatment-related characteristics among newly reported HIV/AIDS cases in an urban area in Shanghai, China from 2001 to 2019: A population-based retrospective study.

The HIV/AIDS epidemic has changed significantly over the past 40 years. Changes in AIDS intervention strategies over time and across regions may have influenced epidemiological characteristics and intervention strategies. The aim of the current study was to analyze the changes in multi-year epidemiological characteristics of newly reported HIV/AIDS cases in an urban area (the Fengxian District of Shanghai) from 2001 to 2019 based on the national AIDS comprehensive data information system and Shanghai Statistical Yearbook. In total, the average annual incidence of HIV/AIDS was 1.92 per 100,000 persons. The annual incidence fluctuated and tended to increase from 2001 to 2019 (χ2 = 128.38, p < 0.001). More male patients were reported compared to female patients, accounting for 82.9%. The proportion of patients over 65 years of age increased from 5% in 2009 to 12% in 2019. The majority of cases involved sexual contact (97.7%), early diagnosis (58.8%), full virologic suppression (72.9%), and early antiretroviral therapy (ART) (44.3%). Migrant patients have significantly increased over the years. There were significant differences between local and migrant patients in terms of the age at diagnosis, transmission route, and baseline CD4 count. The disparity in high-risk temporal clusters was also explored to indicate the delay of an epidemic between local patients and migrant patients. HIV remains at a low endemic level. AIDS prevention and control measures have been highly effective, and especially in virologic suppression of ART and early diagnosis. More efforts should be made to enhance early diagnosis and treatment among key vulnerable groups, including the elderly in the local population and young male migrants, and the scale of HIV/AIDS testing should be expanded to the general population to control HIV transmission.

Development and characterization of segment-specific enteroids from the pig small intestine in Matrigel and transwell inserts: insights into susceptibility to porcine epidemic diarrhea Virus.

Introduction: The critical early stages of infection and innate immune responses to porcine epidemic diarrhea virus (PEDV) at the intestinal epithelium remain underexplored due to the limitations of traditional cell culture and animal models. This study aims to establish a porcine enteroid culture model to investigate potential differences in susceptibility to infection across segments of the porcine small intestine (duodenum, jejunum, and ileum). Methods: Intestinal crypt cells from nursery pigs were cultured in Matrigel to differentiate into porcine enteroid monolayer cultures (PEMCs). Following characterization, PEMCs were enzymatically dissociated and subcultured on transwell inserts (PETCs) for apical surface exposure and infection studies. Characterization of region-specific PEMCs and PETCs included assessment of morphology, proliferation, viability, and cellular phenotyping via immunohistochemistry/immunocytochemistry and gene expression analysis. Subsequently, PETCs were inoculated with 105 TCID50 (50% tissue culture infectious dose)/mL of a high pathogenic PEDV non-S INDEL strain and incubated for 24 h. Infection outcomes were assessed by cytopathic effect, PEDV N protein expression (immunofluorescence assay, IFA), and PEDV N-gene detection (quantitative reverse transcription polymerase chain reaction, RT-qPCR). Results: No significant morphological and phenotypical differences were observed among PEMCs and PETCs across intestinal regions, resembling the porcine intestinal epithelium. Although PETCs established from different segments of the small intestine were susceptible to PEDV infection, jejunum-derived PETCs exhibited higher PEDV replication, confirmed by IFA and RT-qPCR. Discussion: This segment-specific enteroid culture model provides a reliable platform for virological studies, offering a controlled environment that overcomes the limitations of in vivo and traditional cell culture methods. Standardizing culture conditions and characterizing the model are essential for advancing enteroid-based infection models.

A useful parametric specification to model epidemiological data: Revival of the Richards' curve.

A useful parametric specification for the expected value of an epidemiological process is revived, and its statistical and empirical efficacy are explored. The Richards' curve is flexible enough to adapt to several growth phenomena, including recent epidemics and outbreaks. Here, two different estimation methods are described. The first, based on likelihood maximisation, is particularly useful when the outbreak is still ongoing and the main goal is to obtain sufficiently accurate estimates in negligible computational run-time. The second is fully Bayesian and allows for more ambitious modelling attempts such as the inclusion of spatial and temporal dependence, but it requires more data and computational resources. Regardless of the estimation approach, the Richards' specification properly characterises the main features of any growth process (e.g. growth rate, peak phase etc.), leading to a reasonable fit and providing good short- to medium-term predictions. To demonstrate such flexibility, we show different applications using publicly available data on recent epidemics where the data collection processes and transmission patterns are extremely heterogeneous, as well as benchmark datasets widely used in the literature as illustrative.

Mpox in People With Human Immunodeficiency Virus: Predictors of Diagnosis, Outcomes, and Vaccine Effectiveness in a Multisite Cohort.

INTRODUCTION: Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited. METHODS: We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt. FINDINGS: Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200-349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44-7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14-.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities. INTERPRETATION: PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia.

Thyroid cancer epidemiology in Ireland from 1994 to 2019 - Rising diagnoses without mortality benefit.

BACKGROUND: The epidemiology and management of thyroid cancer has changed radically in the recent past, with rising international incidence of early-stage papillary thyroid cancer (PTC) in particular. In this paper, we review the epidemiology of thyroid cancer in Ireland. METHODS: A retrospective cohort study of National Cancer Registry of Ireland data, 1994-2019. RESULTS: Records from 4158 patients were analysed. 73 % (n = 3040) were female. The average age was 50.4 years. Patient sex did not change over time (p = 0.662), while age decreased significantly (p < 0.0001). The most common diagnoses were PTC (n = 2,905, 70 %) and follicular thyroid carcinoma (n = 549, 13 %). Incidence rose over threefold (1.8-6.2 cases/100000 person-years). The incidence of T1 PTC rose over twelvefold (0.169-2.1 cases/100000 person-years), while the incidence of stage III and IV disease did not change significantly. Five-year disease-specific survival (DSS) was 85 % and varied significantly by diagnosis - 97 % for PTC versus 5 % for anaplastic thyroid carcinoma. Survival did not change significantly over time. Male sex was a risk factor for more advanced disease (p < 0.0001) but did not independently predict overall survival except in PTC (HR 1.6, p = 0.03). The use of radioactive iodine declined markedly from 49 % to 12.5 %. RAI improved DSS for PTC patients aged over 55 years (p = 0.02) without a notable effect on survival for those under 55 years (p = 0.99). CONCLUSION: The epidemiology and management of thyroid cancer in Ireland has changed dramatically in a manner reflective of international trends.

Quantifying age-specific household contacts in Aotearoa New Zealand for infectious disease modelling.

Accounting for population age structure and age-specific contact patterns is crucial for accurate modelling of human infectious disease dynamics and impact. A common approach is to use contact matrices, which estimate the number of contacts between individuals of different ages. These contact matrices are frequently based on data collected from populations with very different demographic and socio-economic characteristics from the population of interest. Here we use a comprehensive household composition dataset based on Aotearoa New Zealand census and administrative data to construct a household contact matrix and a synthetic population that can be used for modelling. We investigate the behaviour of a compartment-based and an agent-based epidemic model parametrized using these data, compared with a commonly used contact matrix that was constructed by projecting international data onto New Zealand's population. We find that using the New Zealand household data, either in a compartment-based model or in an agent-based model, leads to lower attack rates in older age groups compared with using the projected contact matrix. This difference becomes larger when household transmission is more dominant relative to non-household transmission. We provide electronic versions of the synthetic population and household contact matrix for other researchers to use in infectious disease models.

Diagnostics for detection and surveillance of priority epidemic-prone diseases in Africa: an assessment of testing capacity and laboratory strengthening needs.

In 2023, Africa experienced 180 public health emergencies, of which 90% were infectious diseases and 75% were related to zoonotic diseases. Testing capacity for epidemic-prone diseases is essential to enable rapid and accurate identification of causative agents, and for action to prevent disease spread. Moreover, testing is pivotal in monitoring disease transmission, evaluating public health interventions and informing targeted resource allocation during outbreaks. An online, self-assessment survey was conducted in African Union Member States to identify major challenges in testing for epidemic-prone diseases. The survey assessed current capacity for diagnosing priority epidemic-prone diseases at different laboratory levels. It explored challenges in establishing and maintaining testing capacity to improve outbreak response and mitigate public health impact. Survey data analysed diagnostic capacity for priority infectious diseases, diagnostic technologies in use, existing surveillance programmes and challenges limiting diagnostic capacity, by country. The survey result from 15 Member States who responded to the survey, showed high variability in testing capacity and technologies across countries and diverse factors limiting testing capacity for certain priority diseases like dengue and Crimean-Congo haemorrhagic fever. At the same time diagnostic capacity is better for coronavirus disease 2019 (COVID-19), polio, and measles due to previous investments. Unfortunately, many countries are not utilizing multiplex testing, despite its potential to improve diagnostic access. The challenges of limited laboratory capacity for testing future outbreaks are indeed significant. Recent disease outbreaks in Africa have underscored the urgent need to strengthen diagnostic capacity and introduce cost-effective technologies. Small sample sizes and differing disease prioritisation within each country limited the analysis. These findings suggest the benefits of evaluating laboratory testing capacity for epidemic-prone diseases and highlight the importance of effectively addressing challenges to detect diseases and prevent future pandemics.

An immuno-epidemiological model with non-exponentially distributed disease stage on complex networks.

Most of epidemic models assume that duration of the disease phase is distributed exponentially for the simplification of model formulation and analysis. Actually, the exponentially distributed assumption on the description of disease stages is hard to accurately approximate the interplay of drug concentration and viral load within host. In this article, we formulate an immuno-epidemiological epidemic model on complex networks, which is composed of ordinary differential equations and integral equations. The linkage of within- and between-host is connected by setting that the death caused by the disease is an increasing function in viral load within host. Mathematical analysis of the model includes the existence of the solution to the epidemiological model on complex networks, the existence and stability of equilibrium, which are completely determined by the basic reproduction number of the between-host system. Numerical analysis are shown that the non-exponentially distributions and the topology of networks have significant roles in the prediction of epidemic patterns.

Historical drivers of HCV Subtypes 1b and 3a in Thailand and 6f in Phetchabun, an HCV endemic area of the country.

The World Health Organization has set a target to eliminate viral hepatitis as a public threat by 2030. In pursuit of this goal, Thailand initiated a hepatitis C virus (HCV) microelimination project targeting Phetchabun province, a well-recognized high-burden HCV endemic area. However, the historical transmission dynamics of HCV in Phetchabun, and in Thailand in general, remain unclear. This study investigates the epidemic histories of HCV in Phetchabun, focusing on Subtypes 1b, 3a, and 6f, and their relationship with HCV in other regions of Thailand, using molecular phylogenetic analyses. Our results reveal nationwide the presence of Subtypes 1b and 3a, while Subtype 6f is mainly confined to Phetchabun. The initial spread of Subtype 1b was inferred to coincide with World War II and the period of suboptimal medical and hygienic standards in Thai blood transfusion services, suggesting a correlation between the two. The early expansion of Subtype 3a was, on the other hand, found to correlate with the epidemic of intravenous drug use in Thailand during the time of Vietnam War. The early expansion of Subtype 6f, in contrast, appears to coincide with the period of severe regional political conflict and social and economic instability. All these findings suggest the complex interplay between social determinants of health and HCV transmission. Post the mid-1990s/early 2000s, all subtypes showed significantly reduced population growth rates, aligning with improvements in blood transfusion safety standards, the nationwide "War on Drugs" policy, and enhanced accessibility to public healthcare and HCV treatments. These combined efforts likely have contributed to curbing the spread of HCV in Thailand. Nevertheless, our analyses reveal that the prevalence of HCV in Thailand remains high overall, emphasizing the need for further research and a nationwide approach to more effectively reduce the HCV burden in Thailand.

Addressing gaps in the diagnosis of TB in children.

Since 2000, efforts to develop new treatments for TB have been promising, but diagnosing TB, especially in children, remains a challenge. This issue of the Journal includes the first in a series of articles related to TB in children, highlighting new diagnostic tests that do not rely on sputum, and have great potential for improving diagnosis and treatment initiation. Key to a reduction in TB prevalence, experts are engaging with communities to find undiagnosed cases and combat the stigma of TB. International collaborations are also central to integrating novel diagnostics and providing support for these vulnerable populations.

Projecting the Dynamic Trends of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: Modeling the Epidemic in Sichuan Province, China.

Objective: Our study aimed to provide a comprehensive overview of the current status and dynamic trends of the human immunodeficiency virus (HIV) prevalence in Sichuan, the second most heavily affected province in China, and to explore future interventions. Methods: The epidemiological, behavioral, and population census data from multiple sources were analyzed to extract inputs for an acquired immunodeficiency syndrome (AIDS) epidemic model (AEM). Baseline curves, derived from historical trends in HIV prevalence, were used, and the AEM was employed to examine future intervention scenarios. Results: In 2015, the modeled data suggested an adult HIV prevalence of 0.191% in Sichuan, with an estimated 128,766 people living with HIV/AIDS and 16,983 individuals with newly diagnosed infections. Considering current high-risk behaviors, the model predicts an increase in the adult prevalence to 0.306% by 2025, projecting an estimated 212,168 people living with HIV/AIDS and 16,555 individuals with newly diagnosed infections. Conclusion: Heterosexual transmission will likely emerge as the primary mode of AIDS transmission in Sichuan. Furthermore, we anticipate a stabilization in the incidence of AIDS with a concurrent increase in prevalence. Implementing comprehensive intervention measures aimed at high-risk groups could effectively alleviate the spread of AIDS in Sichuan.

Epidemic Characteristics and Spatio-Temporal Patterns of HFRS in Qingdao City, China, 2010-2022.

Objective: This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City, China. Methods: Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic, seasonal decomposition, spatial autocorrelation, and spatio-temporal cluster analyses were performed. Results: A total of 2,220 patients with HFRS were reported over the study period, with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%. The male:female ratio was 2.8:1. 75.3% of patients were aged between 16 and 60 years old, 75.3% of patients were farmers, and 11.6% had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality: the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous, street/township-level hot spots that were mostly distributed in Huangdao, Pingdu, and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion: The distribution of HFRS in Qingdao exhibited periodic, seasonal, and regional characteristics, with high spatial clustering heterogeneity. The typical symptoms of "three red" and "three pain" in patients with HFRS were not obvious.

Chance-constrained stochastic optimal control of epidemic models: A fourth moment method-based reformulation.

This work proposes a methodology for the reformulation of chance-constrained stochastic optimal control problems that ensures reliable uncertainty management of epidemic outbreaks. Specifically, the chance constraints are reformulated in terms of the first four moments of the stochastic state variables through the so-called fourth moment method for reliability. Moreover, a spectral technique is employed to obtain surrogate models of the stochastic state variables, which enables the efficient computation of the required statistics. The practical implementation of the proposed approach is demonstrated via the optimal control of two different stochastic mathematical models of the COVID-19 transmission. The numerical experiments confirm that, unlike those reformulations based on the Chebyshev-Cantelli's inequality, the proposed method does not exhibit the undesired outcomes that are typically observed when a higher precision is required for the risk level associated to the given chance constraints.