Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study.

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

The relationship between compartment models and their stochastic counterparts: A comparative study with examples of the COVID-19 epidemic modeling.

Deterministic compartment models (CMs) and stochastic models, including stochastic CMs and agent-based models, are widely utilized in epidemic modeling. However, the relationship between CMs and their corresponding stochastic models is not well understood. The present study aimed to address this gap by conducting a comparative study using the susceptible, exposed, infectious, and recovered (SEIR) model and its extended CMs from the coronavirus disease 2019 modeling literature. We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations. Based on this equivalence, we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment. The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics. However, it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs. Additionally, we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents. This model offered a balance between computational efficiency and accuracy. The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling. Furthermore, the results had implications for the development of hybrid models that integrated the strengths of both frameworks. Overall, the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

Modelling the preventive treatment under media impact on tuberculosis: A comparison in four regions of China.

Preventive treatment for people with latent Tuberculosis infection (LTBI) has aroused our great interest. In this paper, we propose and analyze a novel mathematical model of TB considering preventive treatment with media impact. The basic reproduction number R0 is defined by the next generation matrix method. In the case without media impact, we prove that the disease-free equilibrium is globally asymptotically stable (unstable) if R0<1(R0>1). Furthermore, we obtain that a unique endemic equilibrium exists when R0>1, which is globally asymptotically stable in the case of permanent immunity and no media impact. We fit the model to the newly reported TB cases data from 2009 to 2019 of four regions in China and estimate the parameters. And we estimated R0=0.5013<1 in Hubei indicating that TB in Hubei will be eliminated in the future. However, the estimated R0=1.015>1 in Henan, R0=1.282>1 in Jiangxi and R0=1.930>1 in Xinjiang imply that TB will continue to persist in these three regions without further prevention and control measures. Besides, sensitivity analysis is carried out to illustrate the role of model parameters for TB control. Our finding reveals that appropriately improving the rate of timely treatment for actively infected people and increasing the rate of individuals with LTBI seeking preventive treatment could achieve the goal of TB elimination. In addition, another interesting finding shows that media impact can only reduce the number of active infections to a limited extent, but cannot change the prevalence of TB.

Environmental Contamination of SARS-CoV-2 Delta VOC by COVID-19 Patients Staying in the Hospital for More Than Two Weeks.

Background: Patients infected with SARS-CoV-2 Delta VOC have a longer course of disease. We detected the air, surfaces, and patient's personal items in the wards of the second hospital of Nanjing during the outbreak of the COVID-19 Delta Variant to identify the environmental contamination, which provides a theoretical basis for the prevention and control of COVID-19 variation beads in the future. Methods: In the cross-sectional study, we collected and analyzed clinical features, demographic and epidemiological data, laboratory and swab test results, and surface and air samples of 144 COVID-19 cases. Results: The time from symptom onset to surface sampling was 25 days (IQR, 21 to 33 days). Positive throat swabs were detected in 52(36.1%) patients, of which only 8(5.6%) patients had N or ORF1a/b genes Ct value <35 on the surface sampling day. Among the 692 environmental surface and air specimens collected from 144 COVID-19 cases, 3 specimens (3/692, 0.4%) related to 5 cases (3.5%, 5/144) were detected positive on RT-PCR. Overall, bedside tables (2/144, 1.4%) were most likely to be contaminated, followed by toilet seats (1/81, 1.2%). Conclusion: The environmental contamination by SARS-CoV-2 Delta VOC-infected cases with disease duration of more than two weeks is limited.

COVID-19 transmission driven by age-group mathematical model in Shijiazhuang City of China.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established a with age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

Annual incidence and fatality rates of notifiable infectious diseases in southeast China from 1950 to 2022 and relationship to socioeconomic development.

Background: Over the past 70 years, China has advanced significantly in the prevention and treatment of infectious diseases while simultaneously undergoing a socioeconomic transformation, making it a useful source of data for analysing relationships between public health policy and the control of infectious diseases. Methods: We collected data on the incidence of notifiable infectious diseases and associated fatalities in Jiangsu province in southeast China from the Provincial Center for Disease Control and Prevention, Provincial Institute of Parasitic Diseases, and the Nationwide Notifiable Infectious Diseases Reporting Information System. We compared data from different historical periods using descriptive statistical methods, joinpoint regression, and correlation analysis. Results: During 1950-2022, 75 754 008 cases of 46 notifiable infectious diseases were reported in Jiangsu, with an average annual incidence was 1679.49 per 100 000 population and a fatality rate of 1.82 per 1000 persons. The incidence of classes A-B decreased (average annual percent change (AAPC) = -2.1) during the entire study period, while the incidence of class C increased (AAPC = 10.8) after 2004. The incidence of intestinal diseases (AAPC = -4.4) and vector-borne and zoonotic diseases (AAPC = -8.1) decreased rapidly, while the incidence of sexually transmitted and blood-borne diseases (AAPC = 1.8) increased. The number of medical and health institutions and the per capita gross domestic product correlated negatively with the annual incidence of diseases in classes A-B, but not with fatality rates. Conclusions: Although the annual incidence of many severe infectious diseases has decreased in Jiangsu since 1950, the incidence of sexually transmitted and blood-borne diseases increased. Socioeconomic growth and sustainable investment in health systems are associated with better control of infectious diseases.

Dynamic modeling and data fitting of climatic and environmental factors and people's behavior factors on hand, foot, and mouth disease (HFMD) in Shanghai, China.

Background: Hand, foot, and mouth disease (HFMD) appear to be a multi-wave outbreak with unknown mechanisms. We investigate the effects of climatic and environmental factors and changes in people's behavior factors that may be caused by external factors: temperature, relative humidity, and school opening and closing. Methods: Distributed lag nonlinear model (DLNM) and dynamic model are used to research multi-wave outbreaks of HFMD. Climatic and environmental factors impact on transmission rate ß(t) is modeled through DLNM and then substituted into this relationship to establish the dynamic model with reported case data to test for validity. Results: Relative risk (RR) of HFMD infection increases with increasing temperature. The RR of infection first increases and then decreases with the increase of relative humidity. For the model fitting HFMD dynamic, time average basic reproduction number [R0] of Stage I (without vaccine) and Stage II (with EV71 vaccine) are 1.9362 and 1.5478, respectively. Temperature has the highest explanatory power, followed by school opening and closing, and relative humidity. Conclusion: We obtain three conclusions about the prevention and control of HFMD. 1) According to the temperature, relative humidity and school start time, the outbreak peak of HFMD should be warned and targeted prevention and control measures should be taken. 2) Reduce high indoor temperature when more than 31.5 oC, and increase low relative humidity when less than 77.5% by opening the window for ventilation, adding houseplants, using air conditioners and humidifiers, reducing the incidence of HFMD and the number of infections. 3) The risk of HFMD transmission during winter vacations is higher than during summer vacations. It is necessary to strengthen the publicity of HFMD prevention knowledge before winter vacations and strengthen the disinfection control measures during winter vacations in children's hospitals, school classrooms, and other places where children gather to reduce the frequency of staff turnover during winter vacations.

Effects and interaction of temperature and relative humidity on the trend of influenza prevalence: A multi-central study based on 30 provinces in mainland China from 2013 to 2018.

Background: Evidence is inefficient about how meteorological factors influence the trends of influenza transmission in different regions of China. Methods: We estimated the time-varying reproduction number (Rt) of influenza and explored the impact of temperature and relative humidity on Rt using generalized additive quasi-Poisson regression models combined with the distribution lag non-linear model (DLNM). The effect of temperature and humidity interaction on Rt of influenza was explored. The multiple random-meta analysis was used to evaluate region-specific association. The excess risk (ER) index was defined to investigate the correlation between Rt and each meteorological factor with the modification of seasonal and regional characteristics. Results: Low temperature and low relative humidity contributed to influenza epidemics on the national level, while shapes of merged cumulative effect plots were different across regions. Compared to that of median temperature, the merged RR (95%CI) of low temperature in northern and southern regions were 1.40(1.24,1.45) and 1.20 (1.14,1.27), respectively, while those of high temperature were 1.10(1.03,1.17) and 1.00 (0.95,1.04), respectively. There were negative interactions between temperature and relative humidity on national (SI = 0.59, 95%CI: 0.57-0.61), southern (SI = 0.49, 95%CI: 0.17-0.80), and northern regions (SI = 0.59, 95%CI: 0.56,0.62). In general, with the increase of the change of the two meteorological factors, the ER of Rt also gradually increased. Conclusions: Temperature and relative humidity have an effect on the influenza epidemics in China, and there is an interaction between the two meteorological factors, but the effect of each factor is heterogeneous among regions. Meteorological factors may be considered to predict the trend of influenza epidemic.

Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.

BACKGROUND: Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet. METHODS: This multicentre, open-label phase 3 trial, done in 15 centres in six provinces (Jiangsu, Hunan, Anhui, Chongqing, Yunnan, Shandong) in China, aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV in healthy adults (members of the general population with no acute febrile disorders, infectious disease, serious cardiovascular diseases, serious chronic diseases or progressive diseases that cannot be controlled) at least 18 years old, who had received two doses of inactivated COVID-19 vaccine as their primary regimen. This study contained a non-randomly assigned safety cohort and a centrally randomly assigned (1:1) immunogenicity subcohort. The patients in the immunogenicity subcohort received aerosolised Ad5-nCov (aerosolised Ad5-nCoV group) or inactivated vaccine (inactivated COVID-19 group) The primary endpoints were the incidence of adverse reactions within 28 days following the booster vaccination with aerosolised Ad5-nCoV in the safety population (collected through a daily record of any solicited or unsolicited adverse events filled by each participant) and the geometric mean titre of neutralising antibodies at day 28 after the booster dose in the immunogenicity subcohort (measured with a pseudovirus neutralisation test). This study was registered with ClinicalTrials.gov, NCT05204589. FINDINGS: Between Jan 22, 2022, and March 12, 2022, we recruited 11 410 participants who were screened for eligibility, of whom 10 267 (99·8%) participants (5738 [55·9%] men, 4529 [44·1%] women; median age 53 years [18-92]) received the study drugs: 9847 (95·9%) participants in the open-label cohort to receive aerosolised Ad5-nCoV, and 420 (4·1%) in the immunogenicity subcohort (212 in the aerosolised Ad5-nCoV group and 208 in the inactivated vaccine group). Adverse reactions were reported by 1299 (13%) of 10 059 participants within 28 days after receiving the booster vaccination with aerosolised Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants in the aerosolised Ad5-nCoV group had a significantly higher level of the neutralising antibodies against omicron BA.4/5 (GMT 107·7 [95% CI 88·8-130·7]) than did those in the inactivated vaccine group (17·2 [16·3-18·2]) at day 28. INTERPRETATION: The heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Impact of antibody-level on viral shedding in B.1.617.2 (Delta) variant-infected patients analyzed using a joint model of longitudinal and time-to-event data.

Knowledge of viral shedding remains limited. Repeated measurement data have been rarely used to explore the influencing factors. In this study, a joint model was developed to explore and validate the factors influencing the duration of viral shedding based on longitudinal data and survival data. We divided 361 patients infected with Delta variant hospitalized in Nanjing Second Hospital into two groups (≤ 21 days group and > 21 days group) according to the duration of viral shedding, and compared their baseline characteristics. Correlation analysis was performed to identify the factors influencing the duration of viral shedding. Further, a joint model was established based on longitudinal data and survival data, and the Markov chain Monte Carlo algorithm was used to explain the influencing factors. In correlation analysis, patients having received vaccination had a higher antibody level at admission than unvaccinated patients, and with the increase of antibody level, the duration of viral shedding shortened. The linear mixed-effects model showed the longitudinal variation of logSARS-COV-2 IgM sample/cutoff (S/CO) values, with a parameter estimate of 0.193 and a standard error of 0.017. Considering gender as an influencing factor, the parameter estimate of the Cox model and their standard error were 0.205 and 0.1093 (P = 0.608), the corresponding OR value was 1.228. The joint model output showed that SARS-COV-2 IgM (S/CO) level was strongly associated with the risk of a composite event at the 95% confidence level, and a doubling of SARS-COV-2 IgM (S/CO) level was associated with a 1.38-fold (95% CI: [1.16, 1.72]) increase in the risk of viral non-shedding. A higher antibody level in vaccinated patients, as well as the presence of IgM antibodies in serum, can accelerate shedding of the mutant virus. This study provides some evidence support for vaccine prevention and control of COVID-19 variants.

Study on the COVID-19 epidemic in mainland China between November 2022 and January 2023, with prediction of its tendency.

The prediction system EpiSIX was used to study the COVID-19 epidemic in mainland China between November 2022 and January 2023, based on reported data from December 9, 2022, to January 30, 2023, released by The Chinese Center for Disease Control and Prevention on February 1, 2023. Three kinds of reported data were used for model fitting: the daily numbers of positive nucleic acid tests and deaths, and the daily number of hospital beds taken by COVID-19 patients. It was estimated that the overall infection rate was 87.54% and the overall case fatality rate was 0.078%-0.116% (median 0.100%). Assuming that a new COVID-19 epidemic outbreak would start in March or April of 2023, induced by a slightly more infectious mutant strain, we predicted a possible large rebound between September and October 2023, with a peak demand of between 800,000 and 900,000 inpatient beds. If no such new outbreak was induced by other variants, then the current COVID-19 epidemic course in mainland China would remain under control until the end of 2023. However, it is suggested that the necessary medical resources be prepared to manage possible COVID-19 epidemic emergencies in the near future, especially for the period between September and October 2023.

Impact of inactivated COVID-19 vaccines on lung injury in B.1.617.2 (Delta) variant-infected patients.

BACKGROUND: Chest computerized tomography (CT) scan is an important strategy that quantifies the severity of COVID-19 pneumonia. To what extent inactivated COVID-19 vaccines could impact the COVID-19 pneumonia on chest CT is not clear. METHODS: This study recruited 357 SARS-COV-2 B.1.617.2 (Delta) variant-infected patients admitted to the Second Hospital of Nanjing from July to August 2021. An artificial intelligence-assisted CT imaging system was used to quantify the severity of COVID-19 pneumonia. We compared the volume of infection (VOI), percentage of infection (POI) and chest CT scores among patients with different vaccination statuses. RESULTS: Of the 357 Delta variant-infected patients included for analysis, 105 were unvaccinated, 72 were partially vaccinated and 180 were fully vaccinated. Fully vaccination had the least lung injuries when quantified by VOI (median VOI of 222.4 cm3, 126.6 cm3 and 39.9 cm3 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001), POI (median POI of 7.60%, 3.55% and 1.20% in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001) and chest CT scores (median CT score of 8.00, 6.00 and 4.00 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001). After adjustment for age, sex, comorbidity, time from illness onset to hospitalization and viral load, fully vaccination but not partial vaccination was significantly associated with less lung injuries quantified by VOI {adjust coefficient[95%CI] for "full vaccination": - 106.10(- 167.30,44.89); p < 0.001}, POI {adjust coefficient[95%CI] for "full vaccination": - 3.88(- 5.96, - 1.79); p = 0.001} and chest CT scores {adjust coefficient[95%CI] for "full vaccination": - 1.81(- 2.72, - 0.91); p < 0.001}. The extent of reduction of pulmonary injuries was more profound in fully vaccinated patients with older age, having underlying diseases, and being female sex, as demonstrated by relatively larger absolute values of adjusted coefficients. Finally, even within the non-severe COVID-19 population, fully vaccinated patients were found to have less lung injuries. CONCLUSION: Fully vaccination but not partially vaccination could significantly protect lung injury manifested on chest CT. Our study provides additional evidence to encourage a full course of vaccination.

Association of Endocrine-Disrupting Chemicals with All-Cause and Cause-Specific Mortality in the U.S.: A Prospective Cohort Study.

Wide exposure to endocrine-disrupting chemicals (EDCs) poses a great risk on human health. However, few large-scale cohort studies have comprehensively estimated the association between EDCs exposure and mortality risk. This study aimed to investigate the association of urinary EDCs exposure with mortality risk and quantify attributable mortality and economic loss. Multivariable Cox proportional hazards regression models were performed to investigate the association of 38 representative EDCs exposure with mortality risk in the National Health and Nutrition Examination Survey (NHANES). During a median follow-up of 7.7 years, 47,279 individuals were enrolled. All-cause mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, cadmium, antimony, cobalt, and monobenzyl phthalate. Cancer mortality was positively associated with cadmium. Cardiovascular disease (CVD) mortality was positively associated with 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 2-hydroxyfluorene. Nonlinear U-shaped relationships were found between all-cause mortality and cadmium and cobalt, which was also identified between 2-hydroxyfluorene and CVD mortality. J-shaped association of cadmium exposure with cancer mortality was also determined. EDCs exposure may cause 56.52% of total deaths (1,528,500 deaths) and around 1,897 billion USD in economic costs. Exposure to certain phthalates, polycyclic aromatic hydrocarbons, phytoestrogens, or toxic metals, even at substantially low levels, is significantly associated with mortality and induces high economic costs.

High Cytomegalovirus Viral Load Is Associated With 182-Day All-Cause Mortality in Hospitalized People With Human Immunodeficiency Virus.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with increased mortality in persons with HIV (PWH). It is less clear whether CMV infection is still associated with mortality when routinely screened and adequately treated. METHODS: This retrospective cohort study recruited 1003 hospitalized adults with HIV with CD4 cell counts <200 cells/µL from May 2017 to June 2021. Blood CMV DNA was routinely measured and CMV DNAemia was treated if end-organ disease occurred. CMV viral load was categorized into below the limit of quantification (BLQ; <500 IU/mL), low viral load (LVL; 500-10 000 IU/mL), and high viral load (HVL; ≥10 000 IU/mL) groups. We compared the 182-day all-cause mortality among different groups. RESULTS: The median (IQR) CD4 cell count of patients was 33 (13-84) cells/µL. The prevalence of CMV DNAemia was 39.8% (95% CI: 36.7-42.9%) and was significantly associated with CD4 cell count. The 182-day all-cause mortality was 9.9% (95% CI: 8.0-11.7%). Univariable analysis showed that, compared with BLQ, LVL and HVL were associated with 1.73-fold and 3.81-fold increased risks of mortality, respectively (P = .032 and P < .001). After adjustment for predefined confounding factors, HVL but not LVL was still associated with increased risk of mortality (adjusted hazard ratio: 2.63; 95% CI: 1.61-4.29; P < .001). However, for patients on effective antiretroviral therapy, the impact of HVL on 182-day mortality was not significant (P = .713). CONCLUSIONS: High CMV viral load in hospitalized PWH was associated with higher mortality, even when identified early by screening. Optimalization of the management for those patients needs to be explored in future studies.

Study and prediction of the 2022 global monkeypox epidemic.

The World Health Organization (WHO) declared monkeypox as a public health emergency of international concern (PHEIC) on July 23, 2022, their highest level of alert. This raised concerns about the management of the global monkeypox outbreak, as well as the scientific analysis and accurate prediction of the future course of the epidemic. This study used EpiSIX (an analysis and prediction system for epidemics based on a general SEIR model) to analyze the monkeypox epidemic and to forecast the major tendencies based on data from the USA CDC (https://www.cdc.gov) and the WHO (https://www.who.int/health-topics/monkeypox). The global outbreak of monkeypox started in the UK on May 2, 2022, which marked the beginning of an epidemic wave. As of October 28, 2022, the cumulative number of reported cases worldwide was 77,115, with 36 deaths. EpiSIX simulations predict that the global monkeypox epidemic will enter a low epidemic status on March 1, 2023 with the cumulative number of confirmed cases ranging from 85,000 to 124,000, and the total number of deaths ranging from 60 to 87. Our analysis revealed that the basic reproduction number (R0) of monkeypox virus (MPXV) is near to 3.1 and the percentage of asymptomatic individuals is 13.1 %-14.5 %, both of which are similar to the data for SARS. The vaccination efficiency against susceptibility (VEs) of individuals who have had monkeypox is âˆ¼ 79 %, and the vaccination efficiency against infectiousness (VEi) of individuals who have had monkeypox is âˆ¼ 76 %-82 %. The mean incubation period for monkeypox is 8 days. In total, 94.7 % of infected individuals develop symptoms within 20 days and recover within 2 weeks after the confirmation of symptoms. Simulation results using EpiSIX showed that ring vaccination was remarkably effective against monkeypox. Our findings confirmed that a 20-day isolation for close contacts is necessary.

Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients.

Although considerable interest in metagenomic next-generation sequencing (mNGS) has been attracted in recent years, limited data are available regarding the performance of mNGS in HIV-associated central nervous system (CNS) infection. Here, we conducted a retrospectively analyzing of the cerebrospinal fluid (CSF) mNGS reports and other clinical data from 80 HIV-infected patients admitted to the Second Hospital of Nanjing, China from March, 2018 to March, 2022. In our study, CSF mNGS reported negative result, mono-infection, and mixed infection in 8.8, 36.2, and 55% of the patients, respectively. Epstein-Barr virus (EBV), positive in 52.5% of samples, was the most commonly reported pathogen, followed by cytomegalovirus (CMV), John Cunningham virus (JCV), torque teno virus (TTV), cryptococcus neoformans (CN), toxoplasma Gondii (TE), and mycobacterium tuberculosis (MTB). 76.2% of the EBV identification and 54.2% of the CMV identification were not considered clinically important, and relative less sequence reads were reported in the clinical unimportant identifications. The clinical importance of the presence of TTV in CSF was not clear. Detection of JCV, CN, or TE was 100% suggestive of specific CNS infection, however, 60% of the MTB reports were considered contamination. Moreover, of the 44 (55%) mixed infections reported by mNGS, only 4 (5%) were considered clinical important, and mNGS failed to identify one mixed infection. Additionally, except for MTB, CSF mNGS tended to have high sensitivity to identify the above-mentioned pathogens (almost with 100% sensitivity). Even all the diagnostic strategies were evaluated, the cause of neurological symptoms remained undetermined in 6 (7.5%) patients. Overall, our results suggest that mNGS is a very sensitive tool for detecting common opportunistic CNS pathogen in HIV-infected patients, although its performance in CNS tuberculosis is unsatisfactory. EBV and CMV are commonly detected by CSF mNGS, however, the threshold of a clinical important detection remains to be defined.

The impact of supplementary immunization activities on measles transmission dynamics and implications for measles elimination goals: A mathematical modelling study.

BACKGROUND: Measles has re-emerged globally due to the accumulation of susceptible individuals and immunity gap, which causes challenges in eliminating measles. Routine vaccination and supplementary immunization activities (SIAs) have greatly improved measles control, but the impact of SIAs on the measles transmission dynamics remains unclear as the vaccine-induced immunity wanes. METHODS: We developed a comprehensive measles transmission dynamics model by taking into account population demographics, age-specific contact patterns, seasonality, routine vaccination, SIAs, and the waning vaccine-induced immunity. The model was calibrated by the monthly age-specific cases data from 2005 to 2018 in Jiangsu Province, China, and validated by the dynamic sero-prevalence data. We aimed to investigate the short-term and long-term impact of three-time SIAs during 2009-2012 (9.68 million and 4.25 million children aged 8 months-14 years in March 2009 and September 2010, respectively, and 140,000 children aged 8 months-6 years in March 2012) on the measles disease burden and explored whether additional SIAs could accelerate the measles elimination. RESULTS: We estimated that the cumulative numbers of measles cases from March 2009 to December 2012 (in the short run) and to December 2018 (in the long run) after three-time SIAs (base case) were 6,699 (95% confidence interval [CI]: 2,928-10,469), and 22,411 (15,146-29,675), which averted 45.0% (42.9%-47.0%) and 34.3% (30.7%-37.9%) of 12,226 (4,916-19,537) and 34,274 (21,350-47,199) cases without SIAs, respectively. The fraction of susceptibles for children aged 8-23 months and 2-14 years decreased from 8.3% and 10.8% in March 2009 to 5.8% and 5.8% in April 2012, respectively. However, the fraction of susceptibles aged 15-49 years and above 50 years increased gradually to about 15% in 2018 irrespective of SIAs due to the waning immunity. The measles elimination goal would be reached in 2028, and administrating additional one-off SIAs in September 2022 to children aged 8-23 months, or young adolescents aged 15-19 years could accelerate the elimination one year earlier. CONCLUSIONS: SIAs have greatly reduced the measles incidence and the fraction of susceptibles, but the benefit may wane over time. Under the current interventions, Jiangsu province would reach the measles elimination goal in 2028. Additional SIAs may accelerate the measles elimination one year earlier.

Dynamics of a stochastic HBV infection model with drug therapy and immune response.

Hepatitis B is a disease that damages the liver, and its control has become a public health problem that needs to be solved urgently. In this paper, we investigate analytically and numerically the dynamics of a new stochastic HBV infection model with antiviral therapies and immune response represented by CTL cells. Through using the theory of stochastic differential equations, constructing appropriate Lyapunov functions and applying Itô's formula, we prove that the disease-free equilibrium of the stochastic HBV model is stochastically asymptotically stable in the large, which reveals that the HBV infection will be eradicated with probability one. Moreover, the asymptotic behavior of globally positive solution of the stochastic model near the endemic equilibrium of the corresponding deterministic HBV model is studied. By using the Milstein's method, we provide the numerical simulations to support the analysis results, which shows that sufficiently small noise will not change the dynamic behavior, while large noise can induce the disappearance of the infection. In addition, the effect of inhibiting virus production is more significant than that of blocking new infection to some extent, and the combination of two treatment methods may be the better way to reduce HBV infection and the concentration of free virus.