The optimal vaccination strategy to control COVID-19: a modeling study in Wuhan City, China.

BACKGROUND: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. METHODS: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (Reff) was used to estimate the transmission interaction in different age groups. RESULTS: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (Reff = 4.28), followed by group 2 to 3 (Reff = 2.61), and group 2 to 4 (Reff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old. CONCLUSIONS: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China.

Feasibility of controlling hepatitis E in Jiangsu Province, China: a modelling study.

BACKGROUND: Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province. METHODS: We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness. RESULTS: From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R2 = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days). CONCLUSIONS: HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

Effectiveness of potential antiviral treatments in COVID-19 transmission control: a modelling study.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy. METHODS: We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0-0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1-3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (fc) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15-44; 45-64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f). RESULTS: Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01-0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71-0.12%). CONCLUSIONS: Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups.

A five-compartment model of age-specific transmissibility of SARS-CoV-2.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model. METHODS: An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model. RESULTS: The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: ß43 = 7.71 × 10- 9; SAR43 = 3.86 × 10- 8), followed by group 3 to 4 (median: ß34 = 3.07 × 10- 9; SAR34 = 1.53 × 10- 8), group 2 to 2 (median: ß22 = 1.24 × 10- 9; SAR22 = 6.21 × 10- 9), and group 3 to 1 (median: ß31 = 4.10 × 10- 10; SAR31 = 2.08 × 10- 9). The lowest transmissibility was from age group 3 to 3 (median: ß33 = 1.64 × 10- 19; SAR33 = 8.19 × 10- 19), followed by group 4 to 4 (median: ß44 = 3.66 × 10- 17; SAR44 = 1.83 × 10- 16), group 3 to 2 (median: ß32 = 1.21 × 10- 16; SAR32 = 6.06 × 10- 16), and group 1 to 4 (median: ß14 = 7.20 × 10- 14; SAR14 = 3.60 × 10- 13). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: ß43 = 4.27 × 10- 8; SAR43 = 2.13 × 10- 7), followed by group 3 to 4 (median: ß34 = 1.81 × 10- 8; SAR34 = 9.03 × 10- 8). CONCLUSIONS: SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

Relative transmissibility of shigellosis among male and female individuals: a modeling study in Hubei Province, China.

BACKGROUND: Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscript m) and female (subscript f) individuals using a newly developed sex-based model. METHODS: The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017. A sex-based Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model was applied to explore the dataset, and a sex-age-based SEIAR model was applied in 2010 to explore the sex- and age-specific transmissions. RESULTS: From 2005 to 2017, 130 770 shigellosis cases (including 73 981 male and 56 789 female cases) were reported in Hubei Province. The SEIAR model exhibited a significant fitting effect with the shigellosis data (P <  0.001). The median values of the shigellosis transmission were 2.3225 × 108 for SARmm (secondary attack rate from male to male), 2.5729 × 108 for SARmf, 2.7630 × 10-8 for SARfm, and 2.1061 × 10-8 for SARff. The top five mean values of the transmission relative rate in 2010 (where the subscript 1 was defined as male and age ≤ 5 years, 2 was male and age 6 to 59 years, 3 was male and age ≥ 60 years, 4 was female and age ≤ 5 years, 5 was female and age 6 to 59 years, and 6 was male and age ≥ 60 years) were 5.76 × 10-8 for ß61, 5.32 × 10-8 for ß31, 4.01 × 10-8 for ß34, 7.52 × 10-9 for ß62, and 6.04 × 10-9 for ß64. CONCLUSIONS: The transmissibility of shigellosis differed among male and female individuals. The transmissibility between the genders was higher than that within the genders, particularly female-to-male transmission. The most important route in children (age ≤ 5 years) was transmission from the elderly (age ≥ 60 years). Therefore, the greatest interventions should be applied in females and the elderly.

Immunosuppressive effect of arsenic trioxide on islet xenotransplantation prolongs xenograft survival in mice.

The role of arsenic trioxide (As2O3) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT). The serum level of cytokines was determined by the enzyme-linked immunosorbent assay (ELIZA). The cell proliferation was measured by MTT assay. The mRNA levels were quantified with qRT-PCR. As2O3 prolonged the survival of the recipient mice but had no influence on body weight. As2O3 protected the function of xenograft in insulin secretion and suppressed immune rejection of recipient. As2O3 inhibited proliferation of T lymphocyte and increased the proportion of Foxp3+ regulatory T cells in recipient mice. As2O3 inhibited activation and promoted clonal anergy of T lymphocyte. As2O3 decreased total number of B cells and reduced partial antibody levels in recipient mice. As2O3 and leflunomide showed a synergistic effect in suppressing islet xenotransplant rejection. As2O3 prolongs islet xenograft survival by inhibiting cellular immune response, and increasing Foxp3+ regulatory T cells, while decreasing partial antibody levels in serum.

[Relationship Between LEP G2548A Polymorphism and Cholesterol Gallstone].

OBJECTIVES: To determine the associations of single nucleotide polymorphism (SNP) in leptin (LEP) genes and environmental factors with cholesterol gallstone in southeast Han populations. METHODS: A 1:2 matched case-control study was conducted involving 200 patients with cholesterol gallstone. Genotyping of the SNP was examined on the LightCycler480 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Multifactor dimensionality reduction (MDR) analysis was applied to examine the effects of potential gene-environment interactions. RESULTS: Three genotypes of LEP G2548A were obtained by HRM genotyping, including 52 cases of GG wild type, 192 cases of GA mutant heterozygosity and 356 cases of AA mutation homozygous type. The genotype distribution of the SNP locus in the control group was in line with the Hardy-Weinberg genetic balance (P>0.05). The AA genotype carriers of LEP G2548A had significantly higher serum leptin than the GA/GG genotype carriers (H=6.83, P<0.05). The conditional logistic regression revealed that high serum leptin [odds ratio (OR)=5.012, 95% confidence interval (CI): 3.248-7.734], AA genotype of LEP G2548A site (OR=2.292, 95%CI: 1.012-5.193), family history of gallstones (OR=2.984, 95%CI: 1.329-6.700), high SBP (OR=1.927, 95%CI: 1.140-3.255) and smoking (OR=1.717, 95%CI: 1.006-2.928) were predictors of cholesterol gallstone. However, regular drinking of strong tea (OR=0.552, 95%CI: 0.336-0.907) and exercise (OR=0.591, 95%CI: 0.395-0.882) were protecting factors for cholesterol gallstone. The results of MDR analysis indicated that tea drinking, genotype of LEP G2548A site and serum leptin formed the optimal gene-environment interaction model. CONCLUSIONS: Individuals who drink less tea, carry AA genotype and have high serum leptin are more susceptible to cholesterol gallstone.

[Synergistic effects of different types of smoking and other risk factors on risk of hepatocellular carcinoma in Xiamen, China].

OBJECTIVE: To evaluated the independent effects of different types of smoking exposure along with multiple risk factors for hepatocellular carcinoma (HCC) and determined whether the magnitude of smoking was modified by other risk factors, both in men and women. METHODS: We conducted a case-control study in Xiamen China. 345 HCC patients and 961 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. RESULTS: Cigars and pipes were not related to HCC among non-cigarette smokers. However, passive smoking exposure was associated with HCC in women: AOR, 2.35 (95%CI: 1.19 - 4.07). Regular cigarette smoking was associated with HCC in men: AOR, 2.27 (95%CI: 1.14 - 3.31). Cigarette smoking and chronic infection of hepatitis B virus showed positive additive model interactions in men: RERI (relative excess risk due to interaction) was 98.70 and AP (attributable proportion due to interactions) was 81.0%. Data on cigarette smoking with high AFB1-albumin adducts in women showed that the RERI was 2.69 and AP was 50.0%. CONCLUSION: We concluded that sex differences were seen in HCC relationship with cigarette smoking. Controlling of exposure to smoking might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.

[The study on the interactions between polycyclic aromatic hydrocarbon-albumin adducts and various risk factors to primary hepatocellular carcinoma].

OBJECTIVE: To explore the relationship between polycyclic aromatic hydrocarbon (PAH) exposure and hepatocellular carcinoma (HCC), and the interaction of PAH exposure and other HCC risk factors to HCC. METHODS: Baseline blood samples, collected from 345 HCC cases and 961 controls, were used to determine the level of PAH-albumin adducts by competitive enzyme-linked immunosorbent assay. Conditional logistic regression analysis was used to assess the effect of PAH-albumin adducts on risk of HCC. RESULTS: The mean level of PAH-albumin adducts was significantly higher in cases than in controls ((5.68 +/- 0.72) fmol/mg albumin vs (5.46 +/- 0.63) fmol/mg albumin) (u = 5.98, P < 0.01). When compared to subjects in the lowest quantile (< 1.76 fmol/mg albumin), there was an increase in risk of HCC, with adjusted ORs (95%CI) of 1.03 (0.65 - 1.60), 1.18 (0.76 - 1.78), 2.01 (1.42 - 2.82) for subjects in the second (1.76-fmol/mg albumin), the third (15.28-fmol/mg albumin), and the fourth quantile (> 34.21 fmol/mg albumin), respectively (chi(2)(trend) = 15.06, P < 0.01). There was a significant interaction between PAH-albumin adducts and HBsAg, family history of cancer and diabetes mellitus on HCC after adjusted for other risk factors, and relative excess risks due to the interaction (RERI) were 2.50 (u = 3.60, P < 0.01), 0.52 (u = 2.13, P < 0.05) and 0.88 (u = 2.26, P < 0.05), respectively. CONCLUSION: PAH-albumin adducts was related with HCC, and there is a trend of HCC prevalence increasing with the content of PAH-albumin adducts. There are interactions between PAH-albumin adducts and HBV infection, family history of cancer and diabetes mellitus on HCC.