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AimsNext generation sequencing (NGS) technology has been widely used in monitoring and identifying microbiomes in sewage. We aimed to evaluate the ability of NGS analysis in directly detecting enterovirus (EV) in sewage and to understand the diversity of EVs circulated in the residents in Weishan Lake region.Methods and resultsFourteen sewage samples were collected in Jining, Shandong Province, China from 2018 to 2019 and were parallelly investigated by the P1 amplicon-based NGS method and cell culture method. The results showed that 20 different serotypes belonging to species Enterovirus A (EV-A) (n = 5), EV-B (n = 13), and EV-C (n = 2) were identified by NGS in the sewage concentrates, which exceeded the number of types detected by cell culture method (n = 9). Echovirus 11 (E11), Coxsackievirus (CV) B5 and CVA9 were the most detected types in those sewage concentrates. Phylogenetic analysis revealed that E11 sequences obtained in this study belonged to genogroup D5 and had close genetic relationship with clinical sequences.ConclusionsVarious EV serotypes circulated in populations near Weishan Lake. The combination of NGS technology into environmental surveillance will greatly contribute to improving our knowledge about EV circulation patterns in the population.

Booster immunization is the following vaccination after a period of vaccine primary immunization schedule in order to maintain immunity against a certain pathogen. In this article, the immunological mechanism of booster immunization is elaborated, and the effectiveness and public health value of booster immunization for common vaccines is discussed. Subsequently, three hot issues of general concern in booster immunization are addressed, and the public health viewpoint that "Primary immunization of vaccines is fundamental, and booster immunization is the guarantee" is emphasized, so as to raise awareness of the importance and necessity of booster immunization as well as to provide scientific evidences for vaccine immunization practice.加强免疫是某些疫苗完成基础免疫一段时间后，为持续保持对某种病原体的免疫力而再次进行的接种。本文对疫苗加强免疫的一些基础理论和常见疫苗加强免疫的作用与效果进行阐述，探究了在加强免疫方面普遍关注的3个热点问题，重点强调了“做好疫苗基础免疫是根本，加强免疫是保障”的公共卫生观点，以期为提高对加强免疫重要性和必要性的认识、科学指导疫苗免疫工作实践提供科学参考。.

Norovirus (NoV) and human astrovirus (HAstV) are important causative agents of acute gastroenteritis in children and adults. They are comprised of multiple genotypes and attention should be paid to genotype changes or emergence of new genetic variants. To study the prevalence and diversity of NoV GI, GII, and HAstV circulating in eastern China, we conducted a three-year environmental surveillance in a coastal city of Yantai. Thirty-six sewage samples were collected, processed, and examined for the presence of viral genomes by PCR. The results showed that NoV GI, GII, and HAstV were detected in all 36 samples. Six NoV GI genotypes, 11 NoV GII genotypes, and 5 HAstV serotypes were identified; GI.6, GII.17, and HAstV-5 were the most prevalent types, respectively. Persistent existence of NoV GII.17 Kawasaki 308 variant was observed during whole study period. Phylogenetic analysis reflected multiple transmission lineages in local population for both viruses. Our results reflect continuous presence of enteric viruses in sewage, improve our understanding on their molecular epidemiology, and demonstrate surveillance on sewage is an effective approach in understanding the local circulation of enteric viruses.

Human sapovirus (SaV) is an important causative agent of nonbacterial gastroenteritis in humans. However, little is known about its circulation in China. To study the prevalence and diversity of human SaV genotypes circulating in eastern China, a 3-year environmental surveillance combined with next generation sequencing (NGS) technology was conducted. A total of 36 raw sewage samples were collected from January 2017 to December 2019 in Jinan and processed. Thirty-five (97.22%) samples were positive for human SaV genome in quantitative RT-PCR assay; 33 (91.67%) samples were positive in nested RT-PCR assay on partial capsid VP1 sequence and all amplicons were further analyzed separately by NGS. Among those, ten genotypes belonging to the genogroups of GI, GII, GIV, and GV were identified by NGS, including 4 major genotypes (GI.2, GI.1, GV.1 and GI.3) and 6 uncommon genotypes (GII.5, GII.1, GII.NA1, GII.3, GI.6 and GIV.1). A temporal switch of predominant genotype was observed from GI.2 to GI.1 around June 2019. Local and foreign sequences clustered together in some branches according to phylogenetic analysis, indicating frequent transmission of various lineages in different regions of the world. Environmental surveillance provides a comprehensive picture of human SaV in China. NGS-based environmental surveillance improves our knowledge on human SaV circulating in communities greatly and should be encouraged as a sensitive surveillance tool. Supplementary Information The online version contains supplementary material available at 10.1007/s12560-021-09469-x.

After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.

We present the results of environmental surveillance for poliovirus (PV) and non-poliovirus (NPEV) around the switch from trivalent to bivalent oral polio-vaccine (OPV) which occurred in China in May 2016. Sewage samples were collected in Jinan and Linyi city from 2015 to 2017. Enterovirus (EV) isolation, VP1 amplification, Sanger sequencing, and phylogenetic analyses were performed. Among105 sewage samples (36 in Jinan and 69 in Linyi), 101 were positive for EV, with 74.3% (78/105) PV-positive samples and 90.5% (95/105) NPEV-positive samples. A total of 893 EV isolates were obtained, including 326 (36.5%) PVs and 567 (63.5%) NPEVs. Echovirus (E) -11 was the most common serotype out of 18 detected NPEV types (120/567), followed by E-3 (75/567) and E-6 (74/567). PV2 vanished and PV3 came to be the ascendant PV type in sewage after May 2016. Eight PV isolates were judged as pre-vaccine-derived poliovirus (pre-VDPV) and no VDPV or wild PV isolates were monitored. Bayesian phylogenetics demonstrated global E-11 originated in 1876 and evolved with the estimated rate of 4.63 × 10–3 nucleotide substitutions per site per year (s/s/y). Multiple circulating clusters that originated at different times were coexisting in Shandong province. The most recently common ancestor of global coxsackievirus B5 could date back to 1867, at the evolutionary rate of 3.95 × 10–3 s/s/y. In conclusion, our study described the changes of PVs and NPEVs around the polio vaccine switch period and provided meaningful global molecular epidemiological data for further studies of EV-related diseases among the population.

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (1970年以来，山东省女性乳腺癌死亡率总体呈上升趋势。差别分解分析发现，1970—1990年代女性乳腺癌粗死亡率的微弱下降全部为非人口因素所致，1990年以后死亡率大幅上升为人口和非人口因素的共同作用，其中人口因素的贡献率逐渐上升，由2004—2005年的53.5%上升到了2011—2013年的59.5%，非人口因素的贡献率有所下降，由46.5%降到了40.5%。45~64岁是女性乳腺癌死亡的主要年龄段，占不同时期乳腺癌总死亡的40%~60%；其中55~64岁年龄组死亡率增长迅速，2011—2013年分别比1970—1974年、1990—1992年和2004—2005年上升了52.12%、115.19%和29.01%（

Two cases of epidemic situation of serogroup B meningitis in infants in Shandong Province in 2021 were investigated. Samples of cases and their close contacts were collected for isolation, culture and identification of对2021年山东省两起婴儿B群流脑疫情开展调查，采集病例及其密切接触者相关标本进行脑膜炎奈瑟菌（

Background: Measles caused by measles virus (MeV) is a highly contagious viral disease which has also been associated with complications including pneumonia, myocarditis, encephalitis, and subacute sclerosing panencephalitis. The current study collected33 strains from 2013 to 2019 in 13 cities of Shandong province and separate them into 2 group, outbreak cases and sporadic cases. Comparative of genetic characterization between 15 outbreak strains and 18 sporadic strains was made using nucleotide sequencing of the C-terminal region of the N protein gene(N-450). Results: The results showed that all 33 stains belonged to genotype H1a. The outbreak strains and sporadic strains distribute crossly in phylogenetic tree. Sequences alignment revealed some interesting G and A transversion, which change the amino acids, on sites 1317, 1422, 1543. The nucleotide sequence and amino acid homologies of 15 Shandong outbreak isolates were 98%–100% (0–10 nucleotide variation) and 97.7%–100%, for sporadic isolations, they are 97.3%–100% and 96.6%–100% respectively. The mean evolution rate of 15 outbreak isolations and 18 sporadic isolations was 4.73× 10-3 and 2.068× 10-3 substitutions per site per year separately, which is higher than the study made before 2002. Conclusions: This report compared epidemic and genetic characteristics of outbreak strains and sporadic strains, and raise evolutionary study of sporadic cases may be helpful for discovery of the possibility of outbreak, especially in the stage of measles elimination.

What is already known about this topic? After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. What is added by this report? Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. What are the implications for public health practices? Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

In the process of online prediction of multivariable non-stationary time series by kernel extreme learning machine (KELM), the dynamic characteristics of the system which are difficult to determine have always posed a big problem. We propose an online sequential prediction model with an adaptive forgetting factor (AFF) for multivariable time series to solve this problem. The multivariable time series instead of variable itself is reconstructed firstly. AFF is introduced into the objective function and can be adjusted iteratively and adaptively with the system changes. As a result, higher weight can be allocated for the fresh and more important samples while the old failure samples can be quickly forgotten. The model sparsification uses a fast leave-one-out cross-validation (FLOO-CV) method to set a prediction error threshold so that samples can be selected conditionally to form a dictionary. Besides, the dictionary parameters, including AFF and kernel parameters, are recursively updated simultaneously without increasing calculation complexity. The experimental results show that, compared with four fashionable KLEM methods, the proposed AFF-OSKELM has a better dynamic tracking ability and adaptability. Moreover, compared with single variable prediction, the spatial reconstructed multivariable has higher prediction accuracy and stability.

Totiviridae, a viral family of double-stranded RNA (dsRNA) viruses, contain a single dsRNA genome 4.6-7.0 kb in length. Totiviridae were initially only known to infect fungi and other eukaryotes as well as plants, but an increase in totiviruses has been detected in insects, mosquitoes, and bats. Here, we describe the isolation and characterization of a strain belonging to the family Totiviridae isolated from Culex tritaeniorhynchus in Kenli, China, in 2016. We isolated a totivirus from field-collected mosquitoes in China by cell culture in Aedes albopictus C6/36 cells, identified the virus by morphological observation and complete genome sequencing, and characterized it by phylogenetic analysis. Transmission electron microscopy identified icosahedral, non-enveloped virus particles with a mean diameter of 35-40 nm. The genome was 7612 bp in length, including two open reading frames (ORFs). ORF1 (5058 nt) encodes the capsid protein, while ORF2 (2216 nt) encodes the viral RNA-dependent RNA polymerase (RdRp). Nucleotide and amino acid homology analysis of isolate showed higher levels of sequence identity with isolate CTV_NJ2 (China, 2010) with 94.87% nucleic acid identity and 97.32% amino acid identity. The isolate was designated C. tritaeniorhynchus totivirus KL (CTV-KL). This is the first identification of a totivirus in a C. tritaeniorhynchus in northern China. Analysis of the virus's morphology, characteristic and genome organization will further enrich our understanding of the molecular and biological characteristics of dsRNA Totiviridae viruses.

Background: China contributes to almost half of the esophageal cancer cases diagnosed globally each year. However, the prognosis information of this disease in this large population is scarce. Methods: Data on a population-based cohort consisting of residents of Shandong Province, China who were diagnosed with esophageal cancer during the period from 2005 to 2014 were analyzed. The cancer-specific survival rates were estimated using Kaplan–Meier analysis. Discrete-time multilevel mixed-effects survival models were used to investigate socioeconomic status (SES) disparities on esophageal cancer survival. Results: The unadjusted 1-, 3-, and 5-year cause-specific survival rates were 59.6% [95% confidence interval (CI), 59.2%–59.9%], 31.9% (95% CI, 31.5%–32.3%), and 23.6% (95% CI, 23.1%–24.0%), respectively. Patients of blue-collar occupations had higher risk of esophageal cancer–related death than those of white-collar occupations in the first 2 years after diagnosis. Rural patients had higher risk of death than urban patients in the first 3 years after diagnosis. The risks of esophageal cancer–related death among patients living in low/middle/high SES index counties were not different in the first 2 years after diagnosis. However, patients living in high SES index counties had better long-term survival (3–5 years postdiagnosis) than those living in middle or low SES index counties. Conclusions: Socioeconomic inequalities in esophageal cancer survival exist in this Chinese population. Higher individual- or area-level SES is associated with better short-term or long-term cancer survival. Impact: Elucidation of the relative roles of the SES factors on survival could guide interventions to reduce disparities in the prognosis of esophageal cancer.

In actual clinical practice, infinite nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B virus (HBV) infection is unrealistic. The most commonly used endpoint is suppression of HBV DNA to undetectable levels with normalization of alanine aminotransferase. However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing the hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cut-off value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cut-off value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1,716 patients were included in this review. When the HBsAg levels at EOT were 100 IU/mL, the respective off-therapy virological relapse rates were 9.1%-19.6% (range) and 31.4%-86.8% (range) at ≥12 months off therapy, regardless of hepatitis B e antigen (HBeAg) status; the respective off-therapy clinical relapse rates were 15.4%-29.4% (range) and 48.1%-63.6% (range) at ≥12 months off therapy, regardless of HBeAg status; and the respective off-therapy HBsAg loss rates were 21.1%-58.8% (range) and 3.3%-7.4% (range) for HBeAg-negative patients at ≥39 months off therapy. Conclusion: Cessation of long-term NAs therapy before HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. An HBsAg level

Although vaccination is effective in preventing infection, pertussis remains endemic worldwide, including China. To lead better targeted prevention strategies, we examined dynamics of spatial and temporal patterns of pertussis transmission in Shandong, China, from 2009 to 2017. We used space-time cluster analysis, logistic regression analysis, and regression tree model to detect the changes in spatial patterns of pertussis infections in Shandong Province, China, between periods (2009–2011, 2012–2014, and 2015–2017). The yearly pertussis incidence rates dramatically increased by 16.8 times from 2009 to 2017. Shifting patterns of peaks of pertussis infections were observed over both time (from June–July to August–September) and space (from Linyi to Jinan), with increasing RR from 4.1 (95% CI: 2.3–7.4) (2009–2011) to 6.1 (95% CI: 5.6–6.7) (2015–2017) and obvious coincidence of peak time. West Shandong had larger odds of increased infections over the study period (odds ratio: 1.52 [95% CI: 1.05–2.17]), and pertussis had larger odds of spreading to east (odds ratio: 2.32 [95% CI: 1.63–3.31]) and north (odds ratio: 1.69 [95% CI: 1.06–2.99]) over time. Regression tree model indicated that the mean difference in yearly average pertussis incidence between 2009–2011 and 2015–2017 increased by more than 4-fold when the longitudes of counties are < 118.0°E. The geographic expansion of pertussis infection may increase the risk of epidemic peaks, coinciding with increased infections in the future. The findings might offer evidence for targeting preventive measures to the areas most in need to minimize the impact of the disease.

Enterovirus C96 (EV-C96) is a newer member of the species Enterovirus C. In this study, we determined the complete genome sequences of three EV-C96 isolates, one recovered from domestic sewage in 2013 and the other two isolated during surveillance of acute flaccid paralysis cases in 1991 and 2009, respectively. The complete genome sequences of these isolates were 75.6-84.2% identical to each other, 75.1-81.8% identical to the prototype strain, and 75.0-91.5% identical to other previously reported strains. Phylogenetic analysis of VP1 sequences revealed a high degree of genetic divergence among currently available EV-C96 sequences in the GenBank database, with an overall mean p-distance of 0.176. It is interesting to note that the 1991 strain 127/SD/CHN/1991 is the earliest EV-C96 isolate so far. Although EV-C96 is not frequently isolated during enterovirus surveillance, its great genetic diversity and the above findings suggest that this serotype has been circulating in China for many years.

Objectives: The hepatitis A vaccine (HepA) has been included in the national expanded program on immunization (EPI) in China since 2008. This study was performed to evaluate the change in dynamics of the seroepidemiology of hepatitis A virus (HAV) before and after the introduction of the program. Methods: The trends in seroepidemiology of anti-HAV antibodies were examined in Shandong Province, China, drawing on two population-based samples of persons aged 1–59 years, one obtained in the year 2006 (n = 6682) and the other in 2014 (n = 5095). Results: A dramatic increase in seroprevalence of anti-HAV antibodies from 30.76% (95% confidence interval (CI) 26.24–35.28%) to 77.46% (95% CI 74.04–80.87%) among children aged 1.5–7 years (born after HepA was recommended for routine childhood immunization), as well as an increase from 35.32% (95% CI 29.31–41.33%) to 66.69% (95% CI 55.59–77.80%) in subjects aged 8–14 years, was observed in 2014 when compared with 2006. By contrast, a decline in seroprevalence among subjects aged 15–29 years, as seen particularly in those 20–29 years of age, from 85.72% (95% CI 80.29–91.14%) to 69.24% (95% CI 62.02–76.45%), was found in this study. There was no statistically significant difference in seroprevalence between 2006 and 2014 among the subjects older than 30 years of age. Conclusions: The national HepA routine immunization program has had a positive effect, leading to an increase in anti-HAV seroprevalence among children in Shandong Province, China. More attention should be paid to young adults in the province. Keywords: Hepatitis A, Hepatitis A vaccine, Seroprevalence, Epidemiology

Background We assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer. Methods This was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8–11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose. Findings We enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p Interpretation This study offers evidence that two doses of sIPV administered at 4 and 8–11 months of age and three doses of sIPV administered at 2, 3, and 4 months of age both provide serological protection against poliomyelitis. Median reciprocal titres of polio antibodies were high overall, and were more related to the interval between doses than the number of doses, with the longer interval of the 2-dose schedule producing higher reciprocal titres than the shorter-interval 3-dose schedule. The protection provided by the 3-dose schedule is achieved earlier in life than the protection with the 2-dose schedule. Countries planning to use an IPV-only schedule in the post-eradication era can consider this 2-dose sIPV option as an immunogenic and dose-sparing strategy. Funding World Health Organization (from a grant from International PolioPlus Committee, Rotary International, Evanston, IL, USA).

In the process of online prediction of nonstationary time series by kernel extreme learning machine (KELM), two problems appear that the order of kernel matrix is increasing and the system dynamic characteristics are difficult to be determined. A sparse KELM state prediction model based on forgetting factor (FF) is proposed. Firstly, by introducing the forgetting factor, a new objective function is constructed to make the elements in the sparse dictionary have different weights according to the time distance, so as to ensure the effective tracking of the dynamic changes of the model. By studying the relationship between KELM and kernel recursive least-squares (KRLS), KRLS is extended to the online sparse KELM framework. To control the growth of network structure, and realize the recursion and update of dictionary parameters, the samples are sparse by using approximate linear dependence (ALD) criterion. The experimental results show that compared with KB-KELM, FOKELM, NOS-KELM and KRLSELM, FF-KRLSELM can reduce the average root mean square error by 48% and 36%, and the average relative error by 37% and 36%, and has good dynamic tracking ability and adaptability.

Objective To understand the genetic diversity and molecular epidemiology characteristics of group A Rotavirus (RVA) in domestic sewage through next generation sequencing (NGS), and to explore the feasibility and necessity of NGS method for RVA environmental surveillance. Methods In this study, two sewage samples from Jinan each quarter in 2019 were selected for concentration, RNA extraction, and then RT-PCR reaction. The amplified positive products were subjected to NGS. Finally, the results were analyzed for diversity and phylogeny. Results A total of 9 G-genotypes and 13 P-genotypes were detected. The Simpson diversity indices in autumn and winter were relatively high. Phylogenetic analysis showed that the dominant types G9 and P[8] were closely related to human-derived sequences. Conclusions This study proves that environmental surveillance as a means to understand the prevalence of RVA in the population is not only feasible but necessary. NGS based environmental surveillance greatly improves our understanding on RVA genetic diversity, and should be encouraged as a sensitive surveillance tool.

The Polio Endgame Strategy 2019–2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of emergence for vaccine-derived poliovirus (VDPV) or wild poliovirus (WPV). We reviewed the impact of the case-based acute flaccid paralysis (AFP) surveillance (1991 to 2018) and environmental surveillance (2011 to 2018) in polio eradication in Shandong province of China. Clinical characteristics of AFP cases and enterovirus (EV) investigation of research samples were assessed. During the period, 10,224 AFP cases were investigated, and 352 sewage samples were collected. The nonpolio AFP rate sustained at over 2.0/100,000 since 1997. Of 10,224 cases, males and young children experienced a higher risk of severe diseases, and 68.5% suffered lower limb paralysis. We collected 1,707 EVs from AFP cases, including 763 polioviruses and 944 nonpolio enteroviruses (NPEVs). No WPV was isolated since 1992. The AFP surveillance showed high sensitivity in detecting 143 vaccine-associated paralytic poliomyelitis (VAPP) cases and 6 VDPVs. For environmental surveillance, 217 (61.6%) samples were positive for poliovirus, and altogether, 838 polioviruses and 2,988 NPEVs were isolated. No WPV was isolated in environmental surveillance, although one VDPV2 was identified. Phylogenetic analysis revealed environmental surveillance had the capacity to detect a large scope of NPEVs. The case-based AFP surveillance will be indispensable for detecting VAPP cases and VDPV circulation in countries using oral polio vaccine. Environmental surveillance is advantageous in identifying EV circulation and responding to ongoing circulating VDPV outbreaks and should be expanded to complement the AFP surveillance. IMPORTANCE Interrupting wild poliovirus transmission and stopping circulating vaccine-derived poliovirus (cVDPV) outbreaks have been proposed as two global goals by the World Health Organization in the Global Polio Eradication Initiative (GPEI). This analysis, based on the 28-year acute flaccid paralysis (AFP) surveillance and 8-year environmental surveillance, provides continued high-quality surveillance performance in achieving the GPEI and detecting the circulation of enterovirus. Given the ongoing cVDPV outbreaks in the world, we present the surveillance capacity of environmental surveillance in capturing enterovirus circulation. The final poliovirus (especially VDPV) elimination has become increasingly complex, and the case-based AFP surveillance alone will lead to difficulties in early detecting dynamics of poliovirus transmission and monitoring the extent of environmental circulation. This study goes beyond previous work to provide a detailed comprehensive evaluation of the enterovirus surveillance and can be used to formulate a set of implementation plan and performance indicators for environmental surveillance.

IMPORTANCE: High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. OBJECTIVE: To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Shandong–Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. INTERVENTIONS: Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. MAIN OUTCOMES AND MEASURES: The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. RESULTS: Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P

Human astrovirus (HAstV) composes of classic HAstV serotypes 1-8 and recently discovered novel HAstV-MLB and HAstV-VA strains. A number of studies have demonstrated that wastewater analysis is an effective approach to understand the prevalence and diversity of enteric viruses in local population. However, a comprehensive analysis of classic and novel HAstVs in sewage is still lacking. In this study, sewage samples were collected monthly from Jinan, China during 2018-2019. Quantification of HAstV genomes was performed by real-time quantitative PCR. Different from previous studies which focused on partial ORF1b or ORF2 gene, complete ORF2 region of HAstV was amplified from sewage concentrates, and amplicons were subjected to next generation sequencing (NGS) and genetic analysis. This methodology allowed detection of 18 astroviruses, of which 7 (HAstV-1, -2, -4, -5, VA1, VA2, and VA3) were detected in all sewage samples. A new strain VA6 mapped to the HMO clade was identified in 20.8% of samples, with 82.4%-83.3% nucleotide identities to the closest strain VA5. The viral load of classic, MLB and VA clades in sewage samples ranged from 3.7 × 10

Stomach cancer is common in the Chinese population. The present study aimed to analyze the incidence and mortality as a result of stomach cancer in Shandong Province, in order to provide a reference for cancer prevention and control. We analyzed the incidence and mortality data of stomach cancer collected from 15 cancer registries in 2012. We calculated the crude, age‐standardized, and truncated incidence and mortality rates for the registered population, and estimated the numbers of new cases and deaths that might have occurred in the total provincial population by applying the age‐specific rates to the corresponding populations. The estimated numbers of new cases and deaths of stomach cancer were 36 796 and 25 343, respectively, among the total Shandong population in 2012. Both the incidence and mortality rates were higher in men than in women. The incidence in rural areas was similar with that in urban areas, whereas mortality was markedly higher in rural than in urban areas. Age‐specific incidence and mortality of stomach cancer increased with age, particularly after 40 years‐of‐age and peaked at 80–84 or ≥85 years‐of‐age. Stomach cancer is common in Shandong province, particularly among men and residents in rural areas. Targeted prevention, early detection, and treatment programs should be carried out.

Purpose: Almost half of the global esophageal cancer (EC) deaths occurred in China. This study aims to examine the geographic spread of EC mortality in two periods in a large Chinese population. Methods: Age-standardized mortality rates (ASMRs) for 140 county-level units in Shandong Province during the periods 1970-74 and 2011-13 were derived using data from the First National Cause-of-Death Survey and the Shandong Death Registration System, respectively. ASMRs were smoothed using Area-to-Area Poisson kriging technique. Spatial scan statistics were used to detect spatial clusters with higher EC mortality and clusters with greater temporal changes in EC mortality. Results: The provincial average ASMR decreased from 13.0 per 100,000 in 1970-74 to 5.8 in 2010-13. Almost all counties or districts have experienced a decrease in EC mortality, while the reduction was particularly pronounced in the mid-west region. This study has identified a geographical cluster with much higher EC mortality rates and the clustering pattern has largely unchanged over the past 40 years. Residents living in the cluster during 1970-74 were 2.7 (95% CI: 2.2-3.4) times more likely to die from EC than the rest of the province. The corresponding risk ratio for the 2011-13 cluster was 3.7 (95% CI: 2.8-5.0). Conclusions: This study detected a geographically defined subpopulation in Shandong, China with much higher risk of dying from EC. This spatial pattern has been consistent over the past few decades. The results suggest the key drives for geographic variations in esophageal cancer may not have changed.

Objective Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts both men and women. However, there is limited data on its genomic characterization in mainland China. The aim of this study was to understand the complete genomic diversity of HPV6 from patients with condyloma acuminatum (CA) and to explore the prevalence of different variant lineages/sublineages in eastern China. Methods CA samples were collected in 3 hospitals in Shandong Province, China from January 2020 to March 2021. DNA extraction, PCR amplification, Sanger sequencing and sequence assembly were performed on HPV6-positive samples. The complete genomes obtained in this study were analyzed phylogenetically with global HPV6 sequences in GenBank database using MEGA 11. Results A total of 55 complete genomic sequences of HPV6 were obtained in this study. They were classified as HPV6 variant lineage A (n = 20), sublineage B1 (n = 34) and sublineage B3 (n = 1) by phylogenetic analysis. Sequence alignment showed E1, E5A, E5B, L1, L2, LCR were relatively highly variable regions for sublineage B1 whereas E1, E5A, L2 for lineage A. Both phylogenetic trees of lineage A and sublineage B1 composed of two main branches. Chinese sequences of lineage A segregated into the major branch while those in sublineage B1 belonged to both branches. Genomic divergence between sequences from China and other countries was 0.00% - 0.33% in lineage A and 0.00% - 0.40% in sublineage B1. Conclusions This is the first study on HPV variant lineages circulating in mainland China. The results revealed that lineage A and sublineage B1 were prevalent and they had different highly variable regions. Further surveillance is needed to understand the dynamic change of different variants in the population.

The rubella vaccine has been included in the immunization program in Shandong province of China since 1995. Here we observed the rubella vaccine coverage, epidemiology, serosurvey, and virological surveillance data, in order to identify the challenges impeding the progress towards to its elimination following the implementation of rubella immunization over a 21-year period in Shandong province. We first noted that the annual increase in vaccination coverage resulted in decreased rate of rubella incidence, which was maintained at a low level. Second, the average age of rubella patients had shifted to the 15–29-year age group, making this group the main population affected by the rubella virus (RV). Third, more than 90% of the study population were immune to rubella. However, the positive rate of rubella IgG in some cities was relatively lower indicating that an insufficient proportion of individuals had been vaccinated. Finally, the transmission of the genotype 1E RV was gradually interrupted due to the implementation of rubella vaccination. Unfortunately, the endemicity of the imported genotype 2B RV was established due to the pockets with unvaccinated people. Therefore, comprehensive vaccination coverage of the population, combined with high quality monitoring of rubella, is necessary to achieve the rubella elimination goal.

// Zhentao Fu 1, * , Yingmei Li 2, * , Zilong Lu 1, * , Jie Chu 1 , Jiandong Sun 3 , Jiyu Zhang 1 , Gaohui Zhang 1 , Fuzhong Xue 4 , Xiaolei Guo 1, ** and Aiqiang Xu 1, ** 1 Department for Chronic and Non-Communicable Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China 2 The Second People's Hospital of Jinan, Jinan, China 3 School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia 4 School of Public Health, Shandong University, Jinan, China * The first three authors contributed equally to this work ** The last two authors contributed equally to this work Correspondence to: Xiaolei Guo, email: guoxiaolei@126.com Aiqiang Xu, email: aqxuepi@163.com Keywords: lung cancer, spatial scan statistics, mortality, epidemiology Received: March 27, 2017 Accepted: August 06, 2017 Published: September 21, 2017 ABSTRACT Lung cancer has long been a major health problem in China. This study aimed to examine the temporal trend and spatial pattern of lung cancer mortality in Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained from Shandong Death Registration System and three nationwide retrospective cause-of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson models was used to detect possible high-risk spatial clusters. The results show that lung cancer mortality rate in Shandong Province increased markedly from 1970-1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase was associated with both demographic and non-demographic factors. Several significant spatial clusters with high lung cancer mortality were identified. The most likely cluster was located in the northern region of Shandong Province during both 1970-1974 and 2011-2013. It appears the spatial pattern remained largely consistent over the last 40 years despite the absolute increase in the mortality rates. These findings will help develop intervention strategies to reduce lung cancer mortality in this large Chinese population.

Background Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial. Methods Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups. Results The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05). Conclusions This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment. Clinical trials registration NCT 02898922.

Several estimating equations for predicting 24-h urinary sodium (24-hUNa) excretion using spot urine (SU) samples have been developed, but have not been readily available to Chinese populations. We aimed to compare and validate the six existing methods at population level and individual level. We extracted 1671 adults eligible for both 24-h urine and SU sample collection. Mean biases (95% CI) of predicting 24-hUNa excretion using six formulas were 58.6 (54.7, 62.5) mmol for Kawasaki, &minus, 2.7 (&minus, 6.2, 0.9) mmol for Tanaka, &minus, 24.5 (&minus, 28.0, &minus, 21.0) mmol for the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) with potassium, &ndash, 26.8 (&minus, 30.1, &minus, 23.3) mmol for INTERSALT without potassium, 5.9 (2.3, 9.6) mmol for Toft, and &minus, 24.2 (&minus, 27.7, &minus, 20.6) mmol for Whitton. The proportions of relative difference &gt, 40% with the six methods were nearly a third, and the proportions of absolute difference &gt, 51.3 mmol/24-h (3 g/day salt) were more than 40%. The misclassification rate were all &gt, 55% for the six methods at the individual level. Although the Tanaka method could offer a plausible estimation for surveillance of the population sodium excretion in Shandong province, caution remains when using the Tanaka formula for other provincial populations in China. However, these predictive methods were inadequate to evaluate individual sodium excretion.

What is already known about this topic? After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. What is added by this report? Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. What are the implications for public health practices? Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

Pertussis has resurged in many countries over recent years, especially among adolescents and adults. This study assessed the effect of weather variability on resurging pertussis among different age groups in Jinan, China. Data on weekly pertussis notifications by age group and weather factors (mean temperature (MeanT), mean temperature standard deviation within a week (MeanT SD), diurnal temperature range (DTR) and relative humidity (RH)) were collected between 2013 and 2017. Distributed lag non-linear models (DLNMs) and regression tree models were used to examine the non-linear association between weather variability and pertussis infections. The 2-weeks cumulative relative risk (RR) of pertussis infections was 4.46 (95% confidence interval (CI): 2.33–9.51) in 0–4 age group, 6.25 (95% CI: 1.38–22.76) in 5–9 age group and 10.11 (95% CI: 2.83–39.07) in 10+ age group when MeanT was at 30.0 °C. MeanT SD (RR range in the three age groups: 2.82–5.83), DTR (RR range: 6.33–11.56) and RH (RR range: 2.02–7.43) also exert significant influence, with the highest risks at 10+ age group. Regression tree models showed the interactive effects of weather variability. The mean pertussis infections increased by over 1.7-fold in 0–4 years group when MeanT ≥14 °C, RH ≥57% and DTR ≥10 °C; by over 2.3-fold in 5–9 years group when MeanT ≥20 °C and MeanT SD ≥3 °C; by 2.0-fold in 10+ years group when MeanT ≥0.7 °C, DTR ≥8.3 °C and RH ≥74%. The study found significantly different associations between weather variability and pertussis infections by age group, and appeared to be stronger in 10+ years group. Continuing climate change, together with other risk factors such as low antibody levels among adolescents and adults, may facilitate pertussis resurgence. This supports previous suggestions of carefully reconsidering current vaccination programme to effectively curb the resurgence of pertussis.

Environmental surveillance has been used successfully in monitoring enterovirus (EV) circulation; however cell culture method may introduce a selective bias in those EV strains that are recovered from the environment. In this study, urban sewage samples were collected monthly in Jinan, China in 2018 and concentrated via membrane adsorption/elution method. A P1 seminested RT-PCR (RT-snPCR) and NGS method was developed, by which amplicons of 4000 nucleotide in length covering the entire P1 region of EVs were obtained from sewage concentrates and were further analyzed by next generation sequencing (NGS). In addition, for each sewage concentrate, two other assays - cell culture and NGS based partial VP1 amplicon sequencing - were conducted in parallel and compared. The results showed that the P1 RT-snPCR and NGS method generated the most data, with 32 serotypes identified belonging to species EV-A (n = 11), EV-B (n = 14), and EV-C (n = 7). These serotypes covered all those detected from the methods of cell culture (n = 10) and partial VP1 amplicon sequencing (n = 16). EV serotypes from acute flaccid paralysis surveillance correlated with those from sewage. Phylogenetic analysis on coxsackievirus B5, a common pathogen of meningitis, revealed close genetic relationship between environmental and clinical sequences. These results demonstrate sewage contains different EVs related to a variety of diseases. Traditional cell culture method underestimates the existence of some serotypes. NGS based environmental surveillance provides data which are consistent with those from clinical diseases, greatly improves our understanding on the actual circulation in the population, and should be encouraged for public health surveillance.

Esophageal cancer (EC) is a leading cause of cancer death in China. Within Shandong Province, a geographic cluster with high EC mortality has been identified, however little is known about how area-level socioeconomic status (SES) is associated with EC mortality in this province. Multilevel models were applied to EC mortality data in 2011–13 among Shandong residents aged 40+ years. Area-level SES factors consisted of residential type (urban/rural) of the sub-county-level units (n = 262) and SES index (range: 0–10) of the county-level units (n = 142). After adjustment for age and sex, residents living in rural areas had a 22% (95% CI: 13–32%) higher risk of dying from EC than those in urban areas. With each unit increase in the SES index, the average risk of dying from EC reduced by 10% (95% CI: 3–18%). The adjustment of area-level SES variables had little impact on the risk ratio of EC mortality between the high-mortality cluster and the rest of Shandong. In conclusion, rural residence and lower SES index are strongly associated with elevated risks of EC death. However, these factors are independent of the high mortality in the cluster area of Shandong. The underlying causes for this geographic disparity need to be further investigated.

Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) located in the IRG1 gene were genotyped in 1230 high-responders and 451 non-responders to hepatitis B vaccination. The SNPs rs17470171 and rs17385627 were associated with the immune response to hepatitis B vaccination (P = 0.014 and 0.029, respectively). In addition, the haplotypes G-A-A-A (rs614171-rs17470171-rs9530614-rs17385627, P = 0.0042, OR = 0.68) and A-A (rs17470171-rs17385627, P = 0.0065, OR = 0.72) exerted a protective role in the immune response to hepatitis B vaccination. Allele ‘A’ of rs17470171 and allele ‘A’ of rs17385627 show higher levels of expression for the IRG1 gene compared with allele ‘C’ of rs17470171 and allele ‘T’ of rs17385627 as demonstrated by luciferase reporter and overexpression assays. In addition, we observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele ‘A’ was more effective than rs17385627 allele ‘T’ at eliminating HBV in HepG2.2.15 cells. These findings suggest that polymorphisms in the IRG1 gene are associated with the immune response to hepatitis B vaccination. The antiviral effect of IRG1 was confirmed using HBV infection cell models. This article is protected by copyright. All rights reserved

Hepatitis E vaccine was available in China in 2012, but the priority population for immunization is not clear. In 2013, a hepatitis E outbreak occurred in a company of Shandong province, China where most employees moved from other provinces and dined at the company’s cafeteria. A total of fourteen (19%, 14/73) case-patients were identified, and three of them had symptomatic infection with one death. The proportion of symptomatic infection was much higher among those aged ⩾50years than those aged

This study aimed to explore the geographic distribution and risk clusters of pancreatic cancer mortality from 2011 to 2013 in Shandong, China, and to detect the differences between urban and rural areas. Our data were obtained from the Shandong Death Registration System (SDRS) and were adjusted according to the underreporting level. The distribution of mortality was displayed with GIS-based maps at the county level. The results showed an increasing trend in pancreatic cancer mortality from the western region to the eastern region of Shandong. Additionally, four significant risk clusters were detected, and the most likely cluster was focused in the northeastern and northern regions. Urban-rural differences in the mortality distribution and risk clusters were also detected. In conclusion, our study identified pancreatic cancer mortality clusters in Shandong in urban and rural areas; these results can contribute to the development of effective and targeted strategies to control pancreatic cancer in different areas.

This study aims to use big data (climate data, internet query data and school calendar patterns (SCP)) to improve pertussis surveillance and prediction, and develop an early warning model for pertussis epidemics. We collected weekly pertussis notifications, SCP, climate and internet search query data (Baidu index (BI)) in Jinan, China between 2013 and 2017. Time series decomposition and temporal risk assessment were used for examining the epidemic features in pertussis infections. A seasonal autoregressive integrated moving average (SARIMA) model and regression tree model were developed to predict pertussis occurrence using identified predictors. Our study demonstrates clear seasonal patterns in pertussis epidemics, and pertussis activity was most significantly associated with BI at 2-week lag (rBI = 0.73, p

This study explored how internet queries vary in facilitating monitoring of pertussis, and the effects of sociodemographic characteristics on such variation by city in Shandong province, China. We collected weekly pertussis notifications, Baidu Index (BI) data and yearly sociodemographic data at the city level between 1 January 2009 and 31 December 2017. Spearman's correlation was performed for temporal risk indices, generalised linear models and regression tree models were developed to identify the hierarchical effects and the threshold between sociodemographic factors and internet query data with pertussis surveillance. The BI was correlated with pertussis notifications, with a strongly spatial variation among cities in temporal risk indices (composite temporal risk metric (CTRM) range: 0.59–1.24). The percentage of urban population (relative risk (RR): 1.05, 95% confidence interval (CI) 1.03–1.07), the proportion of highly educated population (RR: 1.27, 95% CI 1.16–1.39) and the internet access rate (RR: 1.04, 95% CI 1.02–1.05) were correlated with CTRM. Higher RRs in the three identified sociodemographic factors were associated with higher stratified CTRM. The percentage of highly educated population was the most important determinant in the BI with pertussis surveillance. The findings may lead to spatially-specific criteria to inform development of an early warning system of pertussis infections using internet query data.

Background In recent years, several novel astroviruses have been discovered by molecular assays. Their prevalence in many parts of the world remains unclear. Objectives To investigate the existence and genetic diversity of novel astroviruses in China. Study design Stool specimens were collected from patients suffering gastroenteritis from two hospitals in Jinan city in 2016, and were screened for novel astroviruses by real-time RT-PCR assay. Positive samples were subject of ORF2-amplification by conventional RT-PCR and Sanger sequencing. In addition, 1 liter of sewage sample was collected monthly in 2016 and concentrated via the membrane adsorption/elution method. Partial ORF2 amplification, cloning and Sanger sequencing were conducted, and phylogenetic analysis was performed for genotyping all the obtained sequences. Results 18 of 635 specimens (2.8%) were positive for novel astrovirus detection by real-time RT-PCR assay and were further genotyped by Sanger sequencing as 13 MLB1, 4 MLB2, and 1 VA3. 100% (12/12) of sewage samples were positive for novel astroviruses by conventional RT-PCR. After cloning and sequencing, six known novel astroviruses (MLB1, MLB2, VA1, VA2, VA3, and VA5) were identified. VA2, MLB1, and VA1 were the most common subtypes being detected in 100.0% (12/12), 91.7% (11/12), and 91.7% (11/12) of the samples, respectively. Eighteen sequences that could not be classified into any known subtypes were found. Conclusions These results demonstrate the wide circulation and high diversity of novel astroviruses in Jinan, Shandong Province, China, and underline the significance of environmental surveillance combined with population-based surveillance for understanding the molecular epidemiology of enteric viruses.