Exploring barriers to influenza vaccine uptake and recommendation among healthcare providers in the community in China: A qualitative study.

Healthcare providers (HCPs) are recommended for priority influenza vaccination due to their high risk of contracting influenza. HCPs greatly aid in targeted population immunization campaigns. Therefore, understanding the factors that influence HCPs' decisions to get vaccinated and to recommend influenza vaccination is essential. However, there currently needs to be more evidence on this topic in China. Qualitative interviews using a semi-structured interview method were conducted with 180 HCPs from urban community hospitals and town hospitals in four cities in Shandong Province during August 2023. The interview content was analyzed using thematic analysis to identify the variables impacting the vaccination and recommendation practices of HCPs, as well as their suggestions for improving vaccination services. The results will help support the future development of precise intervention measures as well as focused education and training.

Spatial-temporal drivers and incidence heterogeneity of hemorrhagic fever with renal syndrome transmission in Shandong Province, China, 2016-2022.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province. METHODS: The epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions. RESULTS: The total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence. CONCLUSIONS: The autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Antibody and transcription landscape in peripheral blood mononuclear cells of elderly adults over 70 years of age with third dose of COVID-19 BBIBP-CorV and ZF2001 booster vaccine.

BACKGROUND: In the context of the COVID-19 pandemic and extensive vaccination, it is important to explore the immune response of elderly adults to homologous and heterologous booster vaccines of COVID-19. At this point, we detected serum IgG antibodies and PBMC sample transcriptome profiles in 46 participants under 70 years old and 25 participants over 70 years old who received the third dose of the BBIBP-CorV and ZF2001 vaccines. RESULTS: On day 7, the antibody levels of people over 70 years old after the third dose of booster vaccine were lower than those of young people, and the transcriptional responses of innate and adaptive immunity were also weak. The age of the participants showed a significant negative correlation with functions related to T-cell differentiation and costimulation. Nevertheless, 28 days after the third dose, the IgG antibodies of elderly adults reached equivalence to those of younger adults, and immune-related transcriptional regulation was significantly improved. The age showed a significant positive correlation with functions related to "chemokine receptor binding", "chemokine activity", and "chemokine-mediated signaling pathway". CONCLUSIONS: Our results document that the response of elderly adults to the third dose of the vaccine was delayed, but still able to achieve comparable immune effects compared to younger adults, in regard to antibody responses as well as at the transcript level.

Spatiotemporal distribution and environmental influences of severe fever with thrombocytopenia syndrome in Shandong Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. The purpose of this study was to describe the spatiotemporal distribution of SFTS and to identify its environmental influencing factors and potential high-risk areas in Shandong Province, China. METHODS: Data on the SFTS incidence from 2010 to 2021 were collected. Spatiotemporal scan statistics were used to identify the time and area of SFTS clustering. The maximum entropy (MaxEnt) model was used to analyse environmental influences and predict high-risk areas. RESULTS: From 2010 to 2021, a total of 5705 cases of SFTS were reported in Shandong. The number of SFTS cases increased yearly, with a peak incidence from April to October each year. Spatiotemporal scan statistics showed the existence of one most likely cluster and two secondary likely clusters in Shandong. The most likely cluster was in the eastern region, from May to October 2021. The first secondary cluster was in the central region, from May to October 2021. The second secondary cluster was in the southeastern region, from May to September 2020. The MaxEnt model showed that the mean annual wind speed, NDVI, cattle density and annual cumulative precipitation were the key factors influencing the occurrence of SFTS. The predicted risk map showed that the area of high prevalence was 28,120 km2, accounting for 18.05% of the total area of the province. CONCLUSIONS: The spatiotemporal distribution of SFTS was heterogeneous and influenced by multidimensional environmental factors. This should be considered as a basis for delineating SFTS risk areas and developing SFTS prevention and control measures.

Transmission of SARS-CoV-2 Omicron Variant under a Dynamic Clearance Strategy in Shandong, China.

SARS-CoV-2 Omicron caused a large wave of COVID-19 cases in China in spring 2022. Shandong was one of the most affected regions during this epidemic yet was also among those areas that were able to quickly contain the transmission. We aimed to investigate the origin, genetic diversity, and transmission patterns of the Omicron epidemic in Shandong under a dynamic clearance strategy. We generated 1,149 Omicron sequences, performed phylogenetic analysis, and interpreted results in the context of available epidemiological information. We observed that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to majority of local cases. We found evidence suggesting that some local clusters were potentially associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. We identified a BA.1.1 genome with the R493Q reversion mutation in the spike receptor binding domain, potentially associated with an escape from vaccine and Omicron infection elicited neutralizing immunity. Our findings illustrated how the dynamic clearance strategy constrained this epidemic's size, duration, and geographical distribution. IMPORTANCE Starting in March 2022, the Omicron epidemic caused a large wave of COVID-19 cases in China. Shandong was one of the most affected regions during this epidemic but was also among those areas that were able to quickly contain the transmission. We investigated the origin, genetic diversity, and transmission patterns of Omicron epidemic in Shandong under a dynamic clearance strategy. We found that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to most local cases. We found evidence suggesting that some local clusters were associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. Our study illustrated the transmission patterns of Omicron epidemic in Shandong and provided a looking glass onto this epidemic in China.

Humoral immunity and transcriptome differences of COVID-19 inactivated vacciane and protein subunit vaccine as third booster dose in human.

Under the background of the severe human health and world economic burden caused by COVID-19, the attenuation of vaccine protection efficacy, and the prevalence and immune escape of emerging variants of concern (VOCs), the third dose of booster immunization has been put on the agenda. Systems biology approaches can help us gain new perspectives on the characterization of immune responses and the identification of factors underlying vaccine-induced immune efficacy. We analyzed the antibody signature and transcriptional responses of participants vaccinated with COVID-19 inactivated vaccine and protein subunit vaccine as a third booster dose. The results from the antibody indicated that the third booster dose was effective, and that heterologous vaccination with the protein subunit vaccine as a booster dose induced stronger humoral immune responses than the homologous vaccination with inactivated vaccine, and might be more effective against VOCs. In transcriptomic analysis, protein subunit vaccine induced more differentially expressed genes that were significantly associated with many important innate immune pathways. Both the homologous and heterologous boosters could increase the effectiveness against COVID-19, and compared with the inactivated vaccine, the protein subunit vaccine, mediated a stronger humoral immune response and had a more significant correlation with the innate immune function module, which provided certain data support for the third booster immunization strategy.

Factors Associated With Severe Fever With Thrombocytopenia Syndrome in Endemic Areas of China.

Objective: To explore the influence of climatic, environmental and socioeconomic factors on SFTS occurrence in Shandong Province, China. Methods: We used generalized additive model to estimate the association between SFTS cases and climatic factors, environmental factors and socioeconomic factors, including annual average temperature, precipitation, land cover, normalized difference vegetation index, altitude, population density, meat production, milk production, and gross domestic product (GDP). Results: There were a total of 4,830 cases reported in 100 (70.9%) counties and districts in Shandong Province from 2010 to 2020. The results showed that the annual average temperature, precipitation, forest and grassland coverage rate, altitude and meat production (square root transform) had a reversed "V" relationship with SFTS occurrence, with the inflection points around 12.5-13.0°C in temperature, around 650 mm in precipitation, around 0.3 in forest and grassland coverage rate, around 300 m in altitude, and around 200-300 tons in meat production (square root transform), respectively. SFTS occurrence had a "V" relationship with milk production (square root transform) and GDP (square root transform), with the inflection points around 100-200 tons in milk production (square root transform), and around 150,000-200,000 yuan in GDP (square root transform), respectively. Conclusions: Climatic, environmental, and socioeconomic factors contributed to the heterogeneous distribution of SFTS in Shandong Province, and the influence of these factors on SFTS occurrence was nonlinear.

Correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri and the sul genes.

ABSTRACT: The aim of this study was to discuss the correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri (S. flexneri) and the antibiotic resistance genes sul1, sul2, and sul3 and SXT element.From May 2013 to October 2018, 102 isolates of S. flexneri were collected from the clinical samples in Jinan. The Kirby-Bauer (K-B) test was employed to determine the antibiotic susceptibility of the S. flexneri isolates. The antibiotic resistance rate was analyzed with the WHONET5.4 software. The isolates were subject to the PCR amplification of the sul genes (sul1, sul2, and sul3) and the SXT element. On the basis of the sequencing results, the correlation between the sulfamethoxazole-trimethoprim resistance of the S. flexneri isolates and the sul genes was analyzed.The antibiotic resistance rates of the 102 S. flexneri isolates to ampicillin, streptomycin, chloramphenicol, tetracycline, and sulfamethoxazole-trimethoprim were 90.2%, 90.2%, 88.2%, 88.2%, and 62.7%, respectively. The antibiotic resistance rates of these isolates to cefotaxime, ceftazidime, and ciprofloxacin varied between 20% and 35%. However, these isolates were 100% susceptible to cefoxitin. Positive fragments were amplified from 59.8% (61/102) of the 102 S. flexneri isolates, the sizes of the sul1 and sul2 genes being 338 bp and 286 bp, respectively. The sequence alignment revealed the presence of the sul1 and sul2 genes encoding for dihydrofolate synthase. The carrying rate of the sul1 gene was 13.7% (14/102), and that of the sul2 gene was 48.0% (49/102). No target gene fragments were amplified from the 3 isolates resistant to sulfamethoxazole-trimethoprim. The sul3 gene and SXT element were not amplified from any of the isolates. The testing and statistical analysis showed that the resistance of the S. flexneri isolates to sulfamethoxazole-trimethoprim correlated to the sul1 and sul2 genes.The acquired antibiotic resistance genes sul1 and sul2 were closely associated with the resistance of the 102 S. flexneri isolates to sulfamethoxazole-trimethoprim.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in SARS-CoV-2 Naïve and Recovered Individuals Vaccinated With Inactivated Vaccine.

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the host's molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

Imported dengue serotype 1 outbreak in a non-endemic region, China, 2017: A molecular and seroepidemiological study.

OBJECTIVES: Beginning in June 2017, numerous dengue virus (DENV) infections occurred in the Jining City of Shandong Province, formerly a dengue-free region in East China. We sought to describe the clinical and epidemiological features of this outbreak. METHODS: We reviewed the clinical records and epidemiological data regarding a case series of patients diagnosed with DENV in Jining City, from June 30 to September 14, 2017. Diagnosis was confirmed by molecular method, culture, or rapid diagnostic tests. Sequencing of the DENV envelope gene or the whole viral genome was performed for 11 patients. Additionally, neutralizing antibodies against DENV was measured among patients and residents from their same villages. RESULTS: Data from 150 patients were evaluated in this outbreak. None were diagnosed with dengue hemorrhagic fever or dengue shock syndrome. The patients' ages ranged between 2-88 years (median 51 years, [IQR=37.5-64.3]), and 100 (66.7%) were female. Epidemiological analyses implicated a man who had visited Saudi Arabia as the likely source of the outbreak. Phylogenetic studies identified DENV serotype 1. Most of the patients demonstrated increases of neutralizing antibody titers one year after infection compared with titers three months after infection. The residents living in dengue-affected villages had a significant higher seroprevalence of 21.2% (95%CI 16.9-25.5) than residents (3.2%, 95%CI-0.36-6.7) living in a non-dengue-affected village. CONCLUSIONS: This report documents the first dengue outbreak in Shandong Province, China, in more than 60 years. It underscores the need for medical providers to record patients' travel histories and to consider dengue in their differential diagnoses.

Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China.

Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

Analysis of the laboratory indexes and risk factors in 189 cases of severe fever with thrombocytopenia syndrome.

The current study aimed to analyze the clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) and to explore the risk factors of critical patients. From 2016 to 2018, we collected the hospitalized diagnosed cases with SFTS in Jinan infectious disease hospital of Shandong University and analyzed by the descriptive epidemiological method. According to the prognosis, they were divided into general group and severe group. The epidemiological characteristics, clinical features, and laboratory indexes of these 2 groups of patients were compared and analyzed at the first visit. The risk factors related to the severity of the disease were analyzed by univariate Logistic regression. In total, 189 cases of SFTS were treated during the period and 33 deaths occurred in the severe group, with the fatality rate of 17.46%. The patients' age (χ = 8.864, P < .01), ALT (Z = -2.304, P = .03), AST (Z = -3.361, P < .01), GLU (t = -4.115, P < .01), CK (Z = -3.964, P < .01), CK-MB (Z = -2.225, P = .03), LDH (Z = -3.655, P < .01), α-HBDH (Z = -2.040, P = .04), APTT (t = -3.355, P < .01), BUN (Z = -2.040, P = .04), Cr (Z = -3.071, P = .01), and D-dimer (Z = -2.026, P = .04) in the severe group were higher than that in the normal group, but the blood platelet (PLT) counts were significantly lower (Z = -2.778, P < .01) than that in the normal group. With the neuropsychiatric symptoms (OR = 24.083, 95% CI = 6.064-95.642), skin bleeding point (OR = 30.000, 95% CI = 6.936-129.764), multiple organ dysfunction (OR = 34.048, 95% CI = 7.740-149.782), past medical history (OR = 3.792, 95% CI = 1.284-11.200), and fasting glucose elevation (OR = 1.359, 95% CI = 1.106-1.668) could predict the severity of the SFTS. In summary, the abnormality of the laboratory index, the special clinical manifestations, and the past medical history of SFTS patients were the important basis for judging the patient's serious condition.

Resistance characteristics of CTX-M type Shigella flexneri in China.

The present study was to identify the drug resistance, resistance mechanism and the extended-spectrum ß-lactamase (ESBLs) genotypes of Shigella flexneri (S. flexneri) in Jinan. Susceptibility tests were performed by MIC-determination. The genotypes of ß-lactamase were identified using PCR and DNA sequencing. The resistance transfer ability of the ESBL-producing strains was examined by conjugation tests. A total of 105 S. flexneri isolates were collected, and 34 (32.4%) were ESBL-producing isolates. All ESBL-producing isolates were susceptible to cefoxitin and imipenem, and 35.3% isolates were resistant to ciprofloxacin. ESBL-producing isolates showed high level resistant to ampicillin (100%), cefotaxime (100%), tetracycline (100%), chloramphenicol (100%), trimethoprim/sulfamethoxazole (100%), ceftazidime (73.5%) and cefepime (73.5%). Three types of ß-lactamase genes (blaTEM, blaOXA and blaCTX-M) were identified in all ESBL-producing isolates, and the genotypes were confirmed as blaTEM-1 (23/34), blaOXA-30 (34/34), blaCTX-M-14 (9/34) and blaCTX-M-15 (25/34) by sequencing. In conclusion, the Shigella strains isolated in Jinan are cross-resistant and multi-drug resistant. The main genotypes of ESBLs are CTX-M-14 and CTX-M-15.

Two Coxsackievirus B3 outbreaks associated with hand, foot, and mouth disease in China and the evolutionary history worldwide.

BACKGROUND: Coxsackievirus B3 (CV-B3) is usually associated with aseptic meningitis and myocarditis; however, the association between CV-B3 and hand, foot, and mouth disease (HFMD) has not been clearly demonstrated, and the phylogenetic dynamics and transmission history of CV-B3 have not been well summarized. METHOD: Two HFMD outbreaks caused by CV-B3 were described in Hebei Province in 2012 and in Shandong Province in 2016 in China. To analyze the epidemiological features of two CV-B3 outbreaks, a retrospective analysis was conducted. All clinical specimens from CV-B3 outbreaks were collected and disposed according to the standard procedures supported by the WHO Global Poliovirus Specialized Laboratory. EV genotyping and phylogenetic analysis were performed to illustrate the genetic characteristics of CV-B3 in China and worldwide. RESULTS: Two transmissible lineages (lineage 2 and 3) were observed in Northern China, which acted as an important "reservoir" for the transmission of CV-B3. Sporadic exporting and importing of cases were observed in almost all regions. In addition, the global sequences of CV-B3 showed a tendency of geographic-specific clustering, indicating that geographic-driven adaptation plays a major role in the diversification and evolution of CV-B3. CONCLUSIONS: Overall, our study indicated that CV-B3 is a causative agent of HFMD outbreak and revealed the phylogenetic dynamics of CV-B3 worldwide, as well as provided an insight on CV-B3 outbreaks for effective intervention and countermeasures.

Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China.

Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains (n = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the VP1 gene from a larger CVA4 collection (n = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, VP1 was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of VP1 was estimated to be 5.12 × 10-3 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in VP1 gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China.

Study on the association between drug­resistance and gene mutations of the active efflux pump acrAB­tolC gene and its regulatory genes.

The aim of the present study was to investigate the correlation between the multi­drug resistance of Shigella flexneri and the drug­resistant gene cassette carried by integrons; in the meanwhile, to detect the associations between drug­resistance and gene mutations of the active efflux pump acrAB­tolC gene and its regulatory genes, including marOR, acrR and soxS. A total of 158 isolates were isolated from the stool samples of 1,026 children with diarrhoea aged 14 years old between May 2012 and October 2015 in Henan. The K­B method was applied for the determination of drug resistance of Shigella flexneri, and polymerase chain reaction amplification was used for class 1, 2 and 3 integrase genes. Enzyme digestion and sequence analysis were performed for the variable regions of positive strains. Based on the drug sensitivity assessment, multi­drug resistant strains that were resistant to five or more antibiotics, and sensitive strains were selected for amplification. Their active efflux pump genes, acrA and acrB, and regulatory genes, marOR, acrR and soxS, were selected for sequencing. The results revealed that 91.1% of the 158 strains were multi­resistant to ampicillin, chloramphenicol, tetracycline and streptomycin, and 69.6% of the strains were multi­resistant to sulfamethoxazole/trimethoprim. The resistance to ceftazidime, ciprofloxacin and levofloxacin was <32.9%. All strains (100%) were sensitive to cefoxitin, cefoperazone/sulbactam and imipenem. The rate of the class 1 integron positivity was 91.9% (144/158). Among these class 1 integron­positive strains, 18 strains exhibited the resistance gene cassette dfrV in the variable region of the strain, four strains exhibited dfrA17­aadA5 in the variable region and 140 strains exhibited blaOXA­30­aadA1 in the variable region. Four strains showed no resistance gene in the variable regions. The rate of class 2 integron positivity was 86.1% (136/158), and all positive strains harboured the dfrA1­sat1­aadA resistance gene cassette in the variable region. The class 3 integrase gene was not detected in these strains. The gene sequencing showed the deletion of base CATT in the 36, 37, 38, 39 site in the marOR gene, which is a regulatory gene of the active efflux pump, AcrAB­TolC. Taken together, the multi­drug resistance of Shigella flexneri was closely associated with gene mutations of class 1 and 2 integrons and the marOR gene.