Genetic characterizations and molecular evolution of human norovirus GII.6 genotype during the past five decades.

The norovirus genotype GII.6 is circulating in the population with a relatively high prevalence, but in-depth molecular characterization studies of GII.6 are needed. In this study, norovirus GII.6 sequences were retrieved and analyzed to demonstrate the molecular characterizations of norovirus GII.6. The results show that GII.6 VP1 gene can be divided into three variants and all variants cocirculated in humans in the past decades. The intragenotypic showed no growth trend over time. Since the overall evolutionary rate was 3.432 × 10-3 substitutions/site/year, the infer most recent common ancestor was estimated as 1913. Only a few amino acid sites were recognized to be under positive selection pressure. The mean effective population size was stable in the recent years. The variant C (especially 87 GII.P7-GII.6 strains) had a higher evolutionary rate and more sites under positive selection pressure compared to other variants. NS4 protein had the higher diversity than other nonstructural proteins, and VP1 and VP2 genes had the same phylogenetic relationships. This study provides a systematic description of genetic characterizations and molecular evolution of GII.6. Research on norovirus molecular epidemiology should be pursued to enrich the genomic data of the diverse genotypes and improve their analysis.

Understanding Mumps Dynamics: Epidemiological Traits and Breakthrough Infections in the Population under 15 Years of Age in Jiangsu Province, China, 2023.

Despite coverage of two doses of mumps-containing vaccines, mumps epidemics persist among children and young adults in China. This study aimed to analyze the epidemiological characteristics of mumps in Jiangsu Province, with a particular focus on breakthrough cases among high-incidence groups. Mumps cases reported in 2023 were systematically collected from the Infectious Disease Surveillance and Reporting System. A comprehensive descriptive epidemiological analysis was performed to elucidate the characteristics of the reported cases. A joinpoint regression (JPR) model was utilized to identify the temporal trends across various periods. Subsequently, immunization information for cases under 15 years of age was obtained through the Jiangsu Province Vaccination Integrated Service Management Information System to identify breakthrough cases and conduct exploratory analyses. A total of 4142 mumps cases were reported in Jiangsu Province in 2023, yielding an annual incidence rate of 4.86/100,000. A total of 81.75% of the cases were students and childcare children, and the gender ratio was 1.5:1 (male/female). The JPR model analysis of weekly reported cases identified five distinct trend segments (1st: 1-8, weekly percent change (WPC) = 26.67 *; 2nd: 9-28, WPC = 3.11 *; 3rd: 29-34, WPC = -5.31; 4th: 35-37, WPC = 15.48; 5th: 38-52, WPC = -4.06 *), and the gender subgroups demonstrated similar trends to the overall pattern. Notably, 89.14% (3692/4142) of the total cases were among individuals under 15 years, with 96.02% (3545/3692) having been vaccinated against mumps. The number of single-dose breakthrough cases (SdBCs) was approximately fourfold (2847/698) that of two-dose breakthrough cases (TdBCs). The main population composition of TdBCs was children aged 0-5 years old, and the classification was dominated by childcare children and scattered children. The median time interval between initial immunization and onset were shorter in TdBCs than in the SdBCs group, and the median time interval between the last immunization and onset was interestingly similarly shorter. However, these situations were interestingly reversed in 105 laboratory-confirmed breakthrough cases. Therefore, the current vaccination strategies have demonstrated tangible effectiveness in preventing and controlling mumps. However, the high incidence of breakthrough cases among high-risk pediatric populations indicates that mumps immunization strategies still deserve more attention and research for better herd protection.

Molecular Evolution of RNA-Dependent RNA Polymerase Region in Norovirus Genogroup I.

Norovirus is the leading viral agent of gastroenteritis in humans. RNA-dependent RNA polymerase (RdRp) is essential in the replication of norovirus RNA. Here, we present a comprehensive evolutionary analysis of the norovirus GI RdRp gene. Our results show that the norovirus GI RdRp gene can be divided into three groups, and that the most recent common ancestor was 1484. The overall evolutionary rate of GI RdRp is 1.821 × 10-3 substitutions/site/year. Most of the amino acids of the GI RdRp gene were under negative selection, and only a few positively selected sites were recognized. Amino acid substitutions in the GI RdRp gene accumulated slowly over time. GI.P1, GI.P3 and GI.P6 owned the higher evolutionary rates. GI.P11 and GI.P13 had the faster accumulation rate of amino acid substitutions. GI.P2, GI.P3, GI.P4, GI.P6 and GI.P13 presented a strong linear evolution. These results reveal that the norovirus GI RdRp gene evolves conservatively, and that the molecular evolutionary characteristics of each P-genotype are diverse. Sequencing in RdRp and VP1 of norovirus should be advocated in the surveillance system to explore the effect of RdRp on norovirus activity.

Influencing factors and adverse outcomes of virologic rebound states in anti-retroviral-treated individuals with HIV infection.

Antiretroviral therapy (ART) aims to inhibit HIV replication, decrease CD4 T cell loss, and immune function recovery in order to reduce the morbidity and mortality associated with the infection. Treatment should also, improve quality of life and control HIV spread. However, incomplete viral suppression still occurs during ART. Viral suppression and virological failure (VF) thresholds vary between studies in terms of virological rebound (VR) states using different detection thresholds. Further understanding of influencing factors and adverse outcomes in various VR states should provide important guidance for HIV treatment.

Post-marketing safety surveillance for both CRM197 and TT carrier proteins PCV13 in Jiangsu, China.

Background: This study is to evaluate the safety of two kinds of PCV13 carriers by monitoring the occurrence of adverse event following immunization (AEFI) after the launch of two kinds of PCV13 carriers in Jiangsu Province, China. Methods: The AEFI Information System (CNAEFIS) of mainland China was used to monitor the incidence and classification of adverse reactions of the CRM197-carrier protein PCV13 and TT-carrier protein PCV13 vaccines. Results: There was no statistical difference between the cumulative reported incidence of AEFI between the two vaccines from 2020 to 2022 (χ2 = 1.991, p < 0.158). 96.62% of the AEFIs were classified as common reactions; rare reactions and coincidental events only accounted for 2.99 and 0.39% of all the AEFI cases, respectively. Redness (2.6 cm-5 cm) is the commonest symptom at the injection site for both vaccines. More than 97% of AEFIs occurred between 30 min and 3 days after administration for both types of PCV13. Conclusion: Both vaccines perform well in terms of safety. We did not identify any new/unexpected safety concern from the NAEFISS during a 4 years timespan.

Mumps-specific antibody persistence in children aged 3-7 years immunized with two doses of mumps-containing vaccines: A prospective cohort study in Jiangsu Province, China.

Mumps reemergence has been reported in developed countries with high levels of two-dose mumps-containing vaccine (MuCV) coverage. The effectiveness of the two-dose MuCV may be compromised by limitations in the persistence of immunity. This prospective cohort study evaluated the persistence of immunity of a two-dose MuCV in children aged 3-7 years from 2015 to 2020. Persistence of antibody to mumps, determined as the geometric mean antibody concentration (GMC), and seropositivity were analyzed for both repeated measurements from three follow-ups and on each cross-section, respectively. A total of 105 eligible subjects were recruited. Their overall seropositivity rate was relatively high and stable (92.4%-84.8%), while the overall GMC decreased from 547.6 U/ml to 333.3 U/ml. Analysis of waning immunity in 91 participants showed a significant and consistent downward trend for GMC, which differed significantly in boys and girls. The overall seropositivity rate decreased slightly from 2015 (95.6%) to 2016 (92.3%) but both were significantly higher than in 2018 (84.6%). The rates in girls remained stable, while those in boys declined to 75% in 2018. The seropositivity rate of the cross-section level decreased from 95.4% to 86.4% in 4 years. Although two-dose MuCV may result in a high level of immunity, antibody concentrations decay over 2 years after the second dose. Children with waning immunity after receiving two doses, especially boys, require further surveillance at 4 years and later to avoid future mumps epidemics.Clinical trial registration: NCT02901990.

Trends in global burden of diseases attributable to lead exposure in 204 countries and territories from 1990 to 2019.

Background: Lead hazards are ubiquitous in the environment, and lead exposure has been proved to damage human health. Nevertheless, there is limited data on the global burden of diseases attributable to lead exposure. In this study, we evaluated the temporal-spatial trend of disease burden caused by lead exposure in 204 countries and territories from 1990 to 2019. Methods: Based on Global Burden of Disease (GBD) Study 2019, deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR) and DALYs rate (ASDR) were estimated by region, country, sex and age. The estimated annual percentage change (EAPC) was calculated to assess the temporal trends of ASMR and ASDR between 1990 and 2019. Results: Global deaths increased from 0.53 (95% UI: 0.31, 0.77) to 0.90 (95% UI: 0.55, 1.29) million, and the number of DALYs increased from 16.02 (95% UI: 10.32, 22.17) to 21.68 (95% UI: 13.81, 30.30) million between 1990 and 2019. China, India and Bangladesh were top three countries with the largest number of deaths and DALYs in 2019. The ASMR (per 100,000 population) decreased from 14.47 (95% UI: 8.40, 21.43) to 11.48 (95% UI: 7.00, 16.49) with EAPC of -0.75 (95% UI: -0.87, -0.64), and the ASDR (per 100,000 population) decreased from 378.01 (95% UI: 240.55, 524.18) to 267.52 (95% UI: 170.57, 373.44) with EAPC of -1.19 (95% UI: -1.32, -1.07). Most of disease burden of lead exposure occurred in the men and elderly population. Stroke and ischemic heart disease were two key sources of disease burden of lead exposure. Also, a negative association between sociodemographic index (SDI) and disease burden of lead exposure was observed. Conclusions: Lead exposure poses a significant disease burden globally, and is still a great threat to public health. Primary prevention measures of reducing lead exposure in the environment are essential.

Factors correlated with targeted prevention for prediabetes classified by impaired fasting glucose, impaired glucose tolerance, and elevated HbA1c: A population-based longitudinal study.

Background: There is still controversy surrounding the precise characterization of prediabetic population. We aim to identify and examine factors of demographic, behavioral, clinical, and biochemical characteristics, and obesity indicators (anthropometric characteristics and anthropometric prediction equation) for prediabetes according to different definition criteria of the American Diabetes Association (ADA) in the Chinese population. Methods: A longitudinal study consisted of baseline survey and two follow-ups was conducted, and a pooled data were analyzed. Prediabetes was defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or elevated glycosylated hemoglobin (HbA1c) according to the ADA criteria. Robust generalized estimating equation models were used. Results: A total of 5,713 (58.42%) observations were prediabetes (IGT, 38.07%; IGT, 26.51%; elevated HbA1c, 23.45%); 9.66% prediabetes fulfilled all the three ADA criteria. Among demographic characteristics, higher age was more evident in elevated HbA1c [adjusted OR (aOR)=2.85]. Female individuals were less likely to have IFG (aOR=0.70) and more likely to suffer from IGT than male individuals (aOR=1.41). Several inconsistency correlations of biochemical characteristics and obesity indicators were detected by prediabetes criteria. Body adiposity estimator exhibited strong association with prediabetes (D10: aOR=4.05). For IFG and elevated HbA1c, the odds of predicted lean body mass exceed other indicators (D10: aOR=3.34; aOR=3.64). For IGT, predicted percent fat presented the highest odds (D10: aOR=6.58). Conclusion: Some correlated factors of prediabetes under different criteria differed, and obesity indicators were easily measured for target identification. Our findings could be used for targeted intervention to optimize preventions to mitigate the obviously increased prevalence of diabetes.

Genetic Characterizations and Molecular Evolution of the Measles Virus Genotype B3's Hemagglutinin (H) Gene in the Elimination Era.

Measles virus (MeV) genotype B3 is one globally significant circulating genotype. Here, we present a systematic description of long-term evolutionary characterizations of the MeV genotype B3's hemagglutinin (H) gene in the elimination era. Our results show that the B3 H gene can be divided into two main sub-genotypes, and the highest intra-genotypic diversity was observed in 2004. MeV genotype B3's H gene diverged in 1976; its overall nucleotide substitution rate is estimated to be 5.697 × 10-4 substitutions/site/year, and is slowing down. The amino acid substitution rate of genotype B3's H gene is also decreasing, and the mean effective population size has been in a downward trend since 2000. Selection pressure analysis only recognized a few sites under positive selection, and the number of positive selection sites is getting smaller. All of these observations may reveal that genotype B3's H gene is not under strong selection pressure, and is becoming increasingly conservative. MeV H-gene or whole-genome sequencing should be routine, so as to better elucidate the molecular epidemiology of MeV in the future.

Effect of Metabolic Health and Obesity Phenotype on Risk of Diabetes Mellitus: A Population-Based Longitudinal Study.

BACKGROUND: Epidemiologic evidence on body mass index (BMI)-metabolic status phenotypes and diabetes risk remains controversial, especially for metabolically healthy obesity (MHO). We aimed to examine the effect of metabolic health and obesity phenotype on diabetes risk in the Chinese population. METHODS: A population-based cohort study was carried out. The baseline survey was conducted in 2017, with two follow-up visits in 2018 and 2020. Diabetes was defined based on the criteria of the World Health Organization. Robust generalized estimating equation models with a binary distribution using a log link and exchange structure were applied for the pooled analysis sample. RESULTS: A total sample of 9623 observations was pooled for the longitudinal data analysis. The average follow-up time was 1.64 years per person and the overall incidence density of diabetes was 6.94% person-years. Decreased diabetes risk was found in metabolically healthy overweight phenotype (RR = 0.65; 95% CI = 0.47-0.90) and no significant associations were detected for the MHO individuals (RR = 0.99; 95% CI = 0.63-1.53) compared with those of metabolically healthy normal weight, in contrast to metabolically unhealthy normal weight (MU-NW) (RR = 1.81; 95% CI = 1.28-2.55), metabolically unhealthy overweight (MU-OW) (RR = 2.02; 95% CI = 1.57-2.61) and metabolically unhealthy obesity (MUO) (RR = 2.48; 95% CI = 1.89-3.26) phenotypes. Significant associations between BMI-metabolic status phenotypes and diabetes were found in both males and females. CONCLUSION: The MUO phenotype needs to be accorded much more importance. MU-NW and MU-OW are also important component for targeted prevention. Our findings can be targeted for optimizing preventive strategies to mitigate the obviously increased prevalence of diabetes.