The epidemiology and evolutionary dynamics of massive dengue outbreak in China, 2019

IntroductionIn 2019, China experienced massive dengue outbreaks with high incidence and expanded outbreak areas. The study aims to depict dengue’s epidemiology and evolutionary dynamics in China and explore the possible origin of these outbreaks.MethodsRecords of confirmed dengue cases in 2019 were obtained from the China Notifiable Disease Surveillance System. The sequences of complete envelope gene detected from the outbreak provinces in China in 2019 were retrieved from GenBank. Maximum Likelihood trees were constructed to genotype the viruses. The median-joining network was used to visualize fine-scale genetic relationships. Four methods were used to estimate the selective pressure.ResultsA total of 22,688 dengue cases were reported, 71.4% of which were indigenous cases and 28.6% were imported cases (including from abroad and from other domestic provinces). The abroad cases were predominantly imported from Southeast Asia countries (94.6%), with Cambodia (3,234 cases, 58.9%), and Myanmar (1,097 cases, 20.0%) ranked as the top two. A total of 11 provinces with dengue outbreaks were identified in the central-south of China, of which Yunnan and Guangdong provinces had the highest number of imported and indigenous cases. The primary source of imported cases in Yunnan was from Myanmar, while in the other ten provinces, the majority of imported cases were from Cambodia. Guangdong, Yunnan and Guangxi provinces were China’s primary sources of domestically imported cases. Phylogenetic analysis of the viruses in outbreak provinces revealed three genotypes: (I, IV, and V) in DENV 1, Cosmopolitan and Asian I genotypes in DENV 2, and two genotypes (I and III) in DENV 3. Some genotypes concurrently circulated in different outbreak provinces. Most of the viruses were clustered with those from Southeast Asia. Haplotype network analysis showed that Southeast Asia, possibly Cambodia and Thailand, was the respective origin of the viruses in clade 1 and 4 for DENV 1. Positive selection was detected at codon 386 in clade 1.ConclusionDengue importation from abroad, especially from Southeast Asia, resulted in the dengue epidemic in China in 2019. Domestic transmission between provinces and positive selection on virus evolution may contribute to the massive dengue outbreaks

Impact of a Local Vision Care Center on Glasses Ownership and Wearing Behavior in Northwestern Rural China: A Cluster-Randomized Controlled Trial

Visual impairment is common among rural Chinese children, but fewer than a quarter of children who need glasses actually own and use them. To study the effect of rural county hospital vision centers (VC) on self-reported glasses ownership and wearing behavior (primary outcome) among rural children in China, we conducted a cluster-randomized controlled trial at a VC in the government hospital of Qinan County, a nationally-designated poor county. All rural primary schools (n = 164) in the county were invited to participate. Schools were randomly assigned to either the treatment group to receive free vision care and eyeglasses, if needed, or control group, who received glasses only at the end of the study. Among 2806 eligible children with visiual impairment (visual acuity ≤ 6/12 in either eye), 93 (3.31%) were lost to follow-up, leaving 2713 students (45.0% boys). Among these, glasses ownership at the end of the school year was 68.6% among 1252 treatment group students (82 schools), and 26.4% (p < 0.01) among 1461 controls (82 schools). The rate of wearing glasses was 55.2% in the treatment group and 23.4% (p < 0.01) among the control group. In logistic regression models, treatment group membership was significantly associated with spectacle ownership (Odds Ratio [OR] = 11.9, p < 0.001) and wearing behavior (OR = 7.2, p < 0.001). County hospital-based vision centers appear effective in delivering childrens’ glasses in rural China

Cardiovascular mortality risk attributable to ambient temperature in China.

OBJECTIVE: To examine cardiovascular disease (CVD) mortality burden attributable to ambient temperature; to estimate effect modification of this burden by gender, age and education level. METHODS: We obtained daily data on temperature and CVD mortality from 15 Chinese megacities during 2007-2013, including 1,936,116 CVD deaths. A quasi-Poisson regression combined with a distributed lag non-linear model was used to estimate the temperature-mortality association for each city. Then, a multivariate meta-analysis was used to derive the overall effect estimates of temperature at the national level. Attributable fraction of deaths were calculated for cold and heat (ie, temperature below and above minimum-mortality temperatures, MMTs), respectively. The MMT was defined as the specific temperature associated to the lowest mortality risk. RESULTS: The MMT varied from the 70th percentile to the 99th percentile of temperature in 15 cities, centring at 78 at the national level. In total, 17.1% (95% empirical CI 14.4% to 19.1%) of CVD mortality (330,352 deaths) was attributable to ambient temperature, with substantial differences among cities, from 10.1% in Shanghai to 23.7% in Guangzhou. Most of the attributable deaths were due to cold, with a fraction of 15.8% (13.1% to 17.9%) corresponding to 305,902 deaths, compared with 1.3% (1.0% to 1.6%) and 24,450 deaths for heat. CONCLUSIONS: This study emphasises how cold weather is responsible for most part of the temperature-related CVD death burden. Our results may have important implications for the development of policies to reduce CVD mortality from extreme temperatures

Novel KCNJ10 Compound Heterozygous Mutations Causing EAST/SeSAME-Like Syndrome Compromise Potassium Channel Function.

Inwardly rectifying K+ channel 4.1 （Kir4.1）, encoded by KCNJ10 , is a member of the inwardly rectifying potassium channel family. In the brain, Kir4.1 is predominant in astrocytic glia and accounts for the spatial buffering of K+ released by neurons during action potential propagation. A number of studies have shown that mutations in KCNJ10 are associated with SeSAME/EAST syndrome, which is characterized by seizures, ataxia, sensorineural deafness, and electrolyte imbalance. Herein, we identified two siblings presenting with seizures and motor delays in one outbred kindred. Customized targeted-exome sequencing showed that both affected siblings are compound heterozygous for two KCNJ10 missense mutations （NM002241.4: c.601G > A: p.A201T and c.626T > C: p.I209T）. Prediction tools suggested that both amino acid substitutions were deleterious or disease causing. Further functional studies showed that Chinese hamster ovary （CHO） cells expressing either A201T and/or I209T Kir4.1 channels exhibited lower K+ currents, indicating compromised Kir4.1 biological function. Intriguingly, the A201T but not I209T mutation decreased total and cell surface Kir4.1 levels. Kir4.1 channels with the A201T mutation were unstable and degraded through lysosomal pathway. In conclusion, these data indicated that both A201T and I209T mutations disrupt Kir4.1 activity and are the cause of SeSAME/EAST-like syndrome in the siblings

Host Immune Responses to a Viral Immune Modulating Protein: Immunogenicity of Viral Interleukin-10 in Rhesus Cytomegalovirus-Infected Rhesus Macaques

, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10.As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva.This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1) it is highly immunogenic during natural RhCMV infection, and (2) neutralizing antibodies to rhcmvIL-10 do not cross-react with rhesus cIL-10. Exceedingly low rhcmvIL-10 antibodies in saliva further suggest that the oral mucosa, which is critical in RhCMV natural history, is associated with suboptimal anti-rhcmvIL-10 antibody responses