Strong and consistent effects of waterbird composition on HPAI H5 occurrences across Europe.

Since 2014, highly pathogenic avian influenza (HPAI) H5 viruses of clade 2.3.4.4 have been dominating the outbreaks across Europe, causing massive deaths among poultry and wild birds. However, the factors shaping these broad-scale outbreak patterns, especially those related to waterbird community composition, remain unclear. In particular, we do not know whether these risk factors differ from those of other H5 clades. Addressing this knowledge gap is important for predicting and preventing future HPAI outbreaks. Using extensive waterbird survey datasets from about 6883 sites, we here explored the effect of waterbird community composition on HPAI H5Nx (clade 2.3.4.4) spatial patterns in the 2016/2017 and 2020/2021 epidemics in Europe, and compared it with the 2005/2006 HPAI H5N1 (clade 2.2) epidemic. We showed that HPAI H5 occurrences in wild birds in the three epidemics were strongly associated with very similar waterbird community attributes, which suggested that, in nature, similar interspecific transmission processes operate between the HPAI H5 subtypes or clades. Importantly, community phylogenetic diversity consistently showed a negative association with H5 occurrence in all three epidemics, suggesting a dilution effect of phylogenetic diversity. In contrast, waterbird community variables showed much weaker associations with HPAI H5Nx occurrence in poultry. Our results demonstrate that models based on previous epidemics can predict future HPAI H5 patterns in wild birds, implying that it is important to include waterbird community factors in future HPAI studies to predict outbreaks and improve surveillance activities.

[Epidemiological characteristics of diarrheagenic Escherichia coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai, 2014-2021].

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E. ) coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai and provide evidence for the development of disease control strategies. Methods: Based on multistage systematic sampling, diarrhea surveillance was conducted in 22 sentinel hospitals in Shanghai, the information about cases' demographic, clinical, and epidemiological characteristics were collected. Stool samples were collected for the detection and typing of diarrheagenic E. coli by local centers for disease control and prevention. The positive rate of diarrheagenic E. coli in different populations and seasons from 2014 to 2021 were analyzed. Statistical analysis was conducted by using χ2 test. Results: In 15 185 diarrhea cases, 8.05% (1 222/15 185) were positive for diarrheagenic E. coli. The positive rate was higher in men (8.74%, 684/7 824) than in women (7.31%, 538/7 361). The positive rate was highest in age group 15-29 years (9.14%, 335/3 665) and the annual positive rate was highest in 2021 (10.21%, 83/813), the differences were all significant (P<0.05). In the 1 264 strains of diarrheagenic E. coli analyzed through PCR, enterotoxingenic E. coli was the most frequently identified pathogen (50.24%, 635/1 264), followed by enteroadhesive E. coli (27.93%, 353/1 264), and enteropathogenic E. coli (21.36%, 270/1 264). The positive rate of diarrheagenic E. coli showed obvious seasonality with peak in summer (13.92%, 774/5 562) (χ2=495.73, P<0.001). Conclusions: Diarrheagenic E. coli has become a prominent pathogen in infectious diarrhea cases in Shanghai, the disease can occur all the year round with incidence peak during summer and autumn. Predominant subtypes included enterotoxingenic E. coli, enteroadhesive E. coli and enteropathogenic E. coli. Targeted prevention and control strategies are needed for diarrheagenic E. coli-induced infectious diarrhea in different age groups, seasons and for different types of infections.

[Analysis of parainfluenza virus infection in acute respiratory tract infection adult cases in Shanghai, 2015-2021].

Objective: To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV. Methods: Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR. Results: A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant (χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions: There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.

Host functional traits as the nexus for multilevel infection patterns.

Understanding pathogen transmission and infection patterns at multiple biological scales is a central issue in disease ecology and evolution. Here, we suggest that functional traits of host species readily affect infection patterns of species, communities, and landscapes, and thus serve as a linkage for multilevel studies of infectious disease.

[Changes in epidemic intensity of influenza during 2014-2020 in Shanghai].

Objective: To evaluate the performance of the influenza surveillance network and compare the epidemic intensity of influenza during 2014-2020 in Shanghai. Methods: Based on the weekly reports of influenza-like illness (ILI) and laboratory-confirmed influenza cases from January 1, 2014 to December 31, 2020. This study first evaluated the data reporting and specimen collection of ILI cases for each sentinel hospital, and then calculated the percentage of ILI (ILI%), the proportion of specimens tested positive for influenza, and the incidence of influenza among all ILI outpatient and emergency visits to measure the epidemic intensity of influenza. Finally, seasonal autoregressive integrated moving average (ARIMA) model was applied to quantify the changes in epidemic intensity of influenza in 2020. Results: The proportion of influenza surveillance sentinel hospitals with a score of less than 5 in the evaluation of ILI data reporting and samples collection were 9.68% and 21.05% in 2020 in Shanghai, respectively. ILI% was estimated to be 1.51% (95%CI: 1.50%-1.51%) and 2.31% (95%CI: 2.30%-2.32%), respectively for 2014-2019 and 2020; the proportion of specimens tested positive was 24.27% (95%CI: 24.02%- 24.51%) and 7.15% (95%CI: 6.78%-7.54%), respectively; and the incidence of influenza was 3.66‰ (95%CI: 3.62‰-3.70‰) and 1.65‰ (95%CI: 1.57‰-1.74‰), respectively. ARIMA model showed that ILI% was increased by 45.25% in 2020 in Shanghai, and the proportion of specimens tested positive and the incidence of influenza were reduced by 78.45% and 51.80%, respectively. Conclusions: In 2020, the performance of influenza surveillance system has changed, ILI% has increased, the proportion of specimens tested positive and the incidence of influenza has decreased in Shanghai. The change in the quality of influenza surveillance is also a potential factor affecting the epidemic intensity of influenza. In the future, the quality control of influenza surveillance network still needs to be further strengthened.

Functional traits explain waterbirds' host status, subtype richness, and community-level infection risk for avian influenza.

Species functional traits can influence pathogen transmission processes, and consequently affect species' host status, pathogen diversity, and community-level infection risk. We here investigated, for 143 European waterbird species, effects of functional traits on host status and pathogen diversity (subtype richness) for avian influenza virus at species level. We then explored the association between functional diversity and HPAI H5Nx occurrence at the community level for 2016/17 and 2021/22 epidemics in Europe. We found that both host status and subtype richness were shaped by several traits, such as diet guild and dispersal ability, and that the community-weighted means of these traits were also correlated with community-level risk of H5Nx occurrence. Moreover, functional divergence was negatively associated with H5Nx occurrence, indicating that functional diversity can reduce infection risk. Our findings highlight the value of integrating trait-based ecology into the framework of diversity-disease relationship, and provide new insights for HPAI prediction and prevention.

Risk factors for Lyme disease: A scale-dependent effect of host species diversity and a consistent negative effect of host phylogenetic diversity.

Biodiversity can influence disease risk. One example of a diversity-disease relationship is the dilution effect, which suggests higher host species diversity (often indexed by species richness) reduces disease risk. While numerous studies support the dilution effect, its generality remains controversial. Most studies of diversity-disease relationships have overlooked the potential importance of phylogenetic diversity. Furthermore, most studies have tested diversity-disease relationships at one spatial scale, even though such relationships are likely scale dependent. Using Lyme disease as a model system, we investigated the effects of host species richness and phylogenetic relatedness on the number of reported Lyme disease cases in humans in the U.S.A. at two spatial scales (the county level and the state level) using piecewise structural equation modelling. We also accounted for relevant climatic and habitat-related factors and tested their correlations with the number of Lyme disease cases. We found that species assemblages with more related species (i.e., host species in the order Rodentia) were associated with more Lyme disease cases in humans. Host species richness correlated negatively with the number of Lyme disease cases at the state level (i.e., a dilution effect), a pattern that might be explained by the higher number of reservoir-incompetent species at high levels of species richness at this larger spatial scale. In contrast, a positive correlation was found between species richness and the number of Lyme disease cases at the county level, where a higher proportion of rodent species was associated with higher levels of species richness, potentially amplifying the disease risk. Our results highlight that analyse at a single spatial scale can miss some impacts of biodiversity on human health. Thus, multi-scale analyses with consideration of host phylogenetic diversity are critical for improving our understanding of diversity-disease relationships.

[The crucial toxic components of ambient fine particles promoted the maturation and differentiation of megakaryocytes].

Objective: To reveal the crucial toxic components of ambient fine particles (PM2.5) that affect the maturation and differentiation of megakaryocytes. Methods: Human megakaryocytes were exposed to the organic fractions, metallic fractions and water-soluble fractions of PM2.5 at two exposure doses (i.e. actual air proportion concentration or the same concentration), respectively. The cell viability was performed to screen the non-cytotoxic levels of toxic components of PM2.5 using the CCK-8 assay. CellTiter-Blue assay, morphological observation, flow cytometry analysis and WGA staining assay were used to evaluate the cell morphological changes, occurrence of DNA ploidy, alteration in the expressions of biomarkers and platelet formation, which were key indicators of the maturation and differentiation of megakaryocytes. Results: Compared to the control group, both metallic and organic components of PM2.5 resulted in a lag in megakaryocytes with an increase in cell volume and the onset of DNA ploidy. Flow cytometry analysis showed that CD33 (the marker of myeloid-specific) decreased and CD41a (a megakaryocyte maturation-associated antigen) increased in metallic and organic components of PM2.5 treatment groups. Moreover, compared to the control group, budding protrusions increased in metallic and organic components of PM2.5 treatment groups. The water-soluble components had no effect on the maturation and differentiation of macrophages. Conclusion: Metallic and organic components of PM2.5 are the crucial toxic components that promote the maturation and differentiation of megakaryocytes.

[Research advances on the function of skin touch receptor Merkel cells].

The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.

Habitat loss exacerbates pathogen spread: An Agent-based model of avian influenza infection in migratory waterfowl.

Habitat availability determines the distribution of migratory waterfowl along their flyway, which further influences the transmission and spatial spread of avian influenza viruses (AIVs). The extensive habitat loss in the East Asian-Australasian Flyway (EAAF) may have potentially altered the virus spread and transmission, but those consequences are rarely studied. We constructed 6 fall migration networks that differed in their level of habitat loss, wherein an increase in habitat loss resulted in smaller networks with fewer sites and links. We integrated an agent-based model and a susceptible-infected-recovered model to simulate waterfowl migration and AIV transmission. We found that extensive habitat loss in the EAAF can 1) relocate the outbreaks northwards, responding to the distribution changes of wintering waterfowl geese, 2) increase the outbreak risk in remaining sites due to larger goose congregations, and 3) facilitate AIV transmission in the migratory population. In addition, our modeling output was in line with the predictions from the concept of "migratory escape", i.e., the migration allows the geese to "escape" from the location where infection risk is high, affecting the pattern of infection prevalence in the waterfowl population. Our modeling shed light on the potential consequences of habitat loss in spreading and transmitting AIV at the flyway scale and suggested the driving mechanisms behind these effects, indicating the importance of conservation in changing spatial and temporal patterns of AIV outbreaks.

[Advances in alternative methods upon the vision for toxicity testing in the 21st century].

With the increase of global chemical production and the aggravation of population exposure and health risks, higher requirements are put forward for chemical toxicity testing and safety evaluation.'Toxicity testing in the 21st century: a vision and a strategy' has greatly promoted the reform of toxicity testing. Toxicity testing in the new era has made great progress by using new models, new methods and new strategies, combined with interdisciplinary and high-tech advantages. While improving the efficiency of chemical toxicity testing, it also realizes more comprehensive, multi-level and high-quality data acquisition and toxicity evaluation, which provides strong support for the exploration of toxicity mode, toxicity mechanism and toxicity pathway. Focusing on the current alternative new methods of toxicity testing, this issue invites many scholars to introduce and summarize high-content analysis, three-dimensional (3D) cell culture technology, Ex vivo test, single cell sequencing and zebrafish experimental methods, in order to promote the leapfrog development of chemical toxicity testing and evaluation in China.

[Advanced progress of ex vivo biosensor assay in toxicological evaluation].

The ex vivo biosensor assay is developed to assess the health effects and toxicological mechanism of environmental pollutants with internal environment homeostasis changes by integrating the in vivo exposure evaluation, in vitro outcomes analysis, and systematic environment component screening. This toxicology testing model combines the real-world exposure of people in the field and the study of molecular mechanism exploration in lab experiments to overcome the shortcomings of a single toxicology method. It provides a new technique and perspective for toxicity testing and risk assessment in mesoscale between macroscopic population study and microscopic mechanism exploration.

Mammal assemblage composition predicts global patterns in emerging infectious disease risk.

As a source of emerging infectious diseases, wildlife assemblages (and related spatial patterns) must be quantitatively assessed to help identify high-risk locations. Previous assessments have largely focussed on the distributions of individual species; however, transmission dynamics are expected to depend on assemblage composition. Moreover, disease-diversity relationships have mainly been studied in the context of species loss, but assemblage composition and disease risk (e.g. infection prevalence in wildlife assemblages) can change without extinction. Based on the predicted distributions and abundances of 4466 mammal species, we estimated global patterns of disease risk through the calculation of the community-level basic reproductive ratio R0, an index of invasion potential, persistence, and maximum prevalence of a pathogen in a wildlife assemblage. For density-dependent diseases, we found that, in addition to tropical areas which are commonly viewed as infectious disease hotspots, northern temperate latitudes included high-risk areas. We also forecasted the effects of climate change and habitat loss from 2015 to 2035. Over this period, many local assemblages showed no net loss of species richness, but the assemblage composition (i.e. the mix of species and their abundances) changed considerably. Simultaneously, most areas experienced a decreased risk of density-dependent diseases but an increased risk of frequency-dependent diseases. We further explored the factors driving these changes in disease risk. Our results suggest that biodiversity and changes therein jointly influence disease risk. Understanding these changes and their drivers and ultimately identifying emerging infectious disease hotspots can help health officials prioritize resource distribution.

[Airway parameters and reference value range of high-resolution CT reconstruction in general population].

Objective: To investigate the measurement of small airways by high-resolution CT and image post-processing software. Screen and analyze the reconstructed airway parameters in order to find the best imaging biomarker parameters of small airway changes and calculate the reference value range; meanwhile, explore its influencing factors. Methods: From a water plant and a medical school, 169 cases of the general population aged 20 to 60 were selected as research objects, and questionnaire surveys and CT tests were performed, and CT data were reconstructed with image post-processing software. The reference value range of the general population was evaluated, and a linear mixed effect model was used to adjust the age, gender, height, BMI, and smoking status, and analyze the influencing factors of airway parameters. Results: The ratio of sixth-grade tracheal wall area to total tracheal area in the Left B1+2 to carina was (53.01±13.35) %, Left B9 to carina was (50.44±12.98) %, Right B1 to carina was (52.73±12.22) %, and Right B9 to carina was (52.93±11.85) %. The ratio of nineth-grade tracheal wall area to total tracheal area in the Left B1+2 to carina was (44.08±14.66) %, Left B9 to carina was (42.44±15.89) %, Right B1 to carina was (46.51±14.03) %, and Right B9 to carina is (43.54±15.87) %. BMI affect the area of the tracheal wall, all p value<0.05. Conclusion: High-resolution CT small airway morphology can make a preliminary assessment of the susceptible population of small airway-related diseases based on a range of reference values, and prevent and control it in combination with influencing factors.

[Practice and thinking of acute respiratory infection surveillance for the response of emerging respiratory diseases in Shanghai].

Shanghai Municipal Center for Disease Control and Prevention has implemented an active comprehensive surveillance project of acute respiratory infections in adults in Shanghai, including influenza like illness (ILI) and severe acute respiratory infection (SARI). By testing and identifying a variety of respiratory pathogens, it was found that influenza viruses were the main pathogens in 172 ILI cases in 2019. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 30.81%, 14.53% and 30.55%, respectively. The positive detection of influenza A (H1N1) pdm09 virus peaked in the first quarter. The positive rate of enterovirus/human rhinovirus was 6.40%, with a positive detection peak in the third quarter, while the positive rate of adenovirus was 4.65% with a positive detection peak in the second quarter of the year. Two human coronavirus (HCoV)-OC43 positive samples, 1 HCoV-HKU1 positive sample and 1 HCoV-NL63 positive sample were detected, respectively, and no HCoV-229E positive sample was detected. The detection rate of Staphylococcus aureus was 17.44%, and the detection rate of Klebsiellapneumoniae was 9.88%. Influenza viruses were also the main pathogens in 1 447 SARI cases. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 5.46%, 1.73% and 0.30%, respectively. The positive detection of influenza A (H1N1) pdm09 virus (17.50%) peaked in the first quarter. The total positive detection rate of enterovirus/human rhinovirus was 2.97%, the positive detection peaked in the first quarter. The positive rate of Mycoplasma pneumoniae was 3.25% and the positive rate of Legionella was 1.04%. 5 HCoV-229E positive samples, 10 HCoV-OC43 positive samples, 7 HCoV-HKU1 positive samples and 6 HCoV-NL63 positive samples were detected. Eight strains of Staphylococcus aureus, 4 strains of Pseudomonas aeruginosa and 3 strains of Klebsiella pneumoniae were detected after cultures. By implementing the active surveillance, we not only detected a case of human infection with avian influenza A(H7N9) virus in time, but also preliminary understood the pathogenic spectrum characteristics and seasonality of ILI and SARI in Shanghai. In recent years, the surveillance methods have been continuously improved and the number of sentinel hospitals has increased gradually. In particular, for the response to COVID-19, the Surveillance Information Reporting System of Acute Respiratory Infection based on HIS system has been promoted to cover the whole city, which might lay a foundation for the active surveillance and early warning of emerging infectious diseases in the future.

Effects of migration network configuration and migration synchrony on infection prevalence in geese.

Migration can influence dynamics of pathogen-host interactions. However, it is not clearly known how migration pattern, in terms of the configuration of the migration network and the synchrony of migration, affects infection prevalence. We therefore applied a discrete-time SIR model, integrating environmental transmission and migration, to various migration networks, including networks with serial, parallel, or both serial and parallel stopover sites, and with various levels of migration synchrony. We applied the model to the infection of avian influenza virus in a migratory geese population. In a network with only serial stopover sites, increasing the number of stopover sites reduced infection prevalence, because with every new stopover site, the amount of virus in the environment was lower than that in the previous stopover site, thereby reducing the exposure of the migratory population. In a network with parallel stopover sites, both increasing the number and earlier appearance of the stopover sites led to an earlier peak of infection prevalence in the migratory population, because the migratory population is exposed to larger total amount of virus in the environment, speeding-up the infection accumulation. Furthermore, higher migration synchrony reduced the average number of cumulative infection, because the majority of the population can fly to a new stopover site where the amount of virus is still relatively low and has not been increased due to virus shedding of infected birds. Our simulations indicate that a migration pattern with multiple serial stopover sites and with highly synchronized migration reduces the infection prevalence.

[Analysis of adenovirus infection in acute respiratory tract infection cases in Shanghai from 2015 to 2019].

Objective: To study the epidemiological characteristics and mixed infection of adenovirus in acute respiratory tract infections in Shanghai from 2015 to 2019, and to provide scientific basis for the prevention and control of adenovirus. Methods: Acute respiratory tract infections were collected from 3 hospitals in Shanghai from 2015 to 2019. Relevant information was registered and respiratory specimens were sampled for detection of respiratory pathogens by multiplex PCR. Results: A total of 1 543 cases of acute respiratory tract infection were included. The positive rate of adenovirus was 2.92%(45/1 543), the positive rates of influenza like illness (ILI) and severe acute respiratory illness (SARI) were 2.74%(29/1 058) and 3.30%(16/485), respectively. The positive rate of ILI during January-May 2019 was 5.43%(7/129), higher than that in the same period of 2015- 2018 (0.52%-4.48%) (Fisher's exact test value=8.92, P=0.036). The incidence of adenovirus-positive cases was mainly distributed in the first and second quarters, accounting for 62.22% (28/45). The difference of the incidence of adenovirus-positive cases in each quarter was significant (χ(2)= 12.52, P=0.006). The positive rate in the second quarter was highest (6.03%), which was higher than that in other quarters (1.89%-2.93%). There were significant differences among different age groups (χ(2)=16.94, P=0.001), and the positive rate decreased with age (χ(2)=10.16, P=0.001). The positive rate of 13-19 years old group (9.43%) was higher than that of other age groups (1.48%-4.81%). The positive rate of student group (12.07%) was higher than that of other occupations (2.61%). The difference was systematic (χ(2)=11.53, P=0.001). Mixed infection accounted for 31.11% (14/45) of 45 adenovirus positive cases. The mixed infection rates of ILI and SARI were 34.48% (10/29) and 25.00% (4/16), respectively. Among 14 cases of mixed infection, the main mixed infection pathogens of adenovirus were influenza A virus and coronavirus. Conclusion: Adenovirus surveillance should be further strengthened in adolescents with a focus on students and other key groups in the second quarter.