Analysing monkeypox epidemic drivers: Policy simulation and multi-index modelling across 39 nations.

Background: This study aimed to analyse the drivers of the monkeypox (Mpox) epidemic and policy simulation to support health care policies against the Mpox epidemic. Methods: We established a three-round selection mechanism for 164 factors using Lasso and negative binomial regression to investigate the correlation between significant drivers and the cumulative confirmed cases of Mpox. Policy simulation for each driver was evaluated, and the varying effects of implementation at different times were examined. Results: HIV/AIDS prevalence and air transport passengers carried were significant determinants of the risk of the Mpox epidemic across various countries, with regression coefficients of 1.417 and 0.766, respectively. A decrease in HIV/AIDS prevalence by 10, 20, 30, and 40% corresponded to reductions in the number of Mpox cases by 6.28, 6.55, 6.87, and 7.26%, respectively. Similarly, 20, 40, 60, and 80% travel restrictions led to reductions in Mpox cases by 7.16, 15.63, 26.28%, and 41.46%, respectively. Controlling air transport passengers carried in the first month could postpone outbreak onset by 0.5-2.0 months. Conclusions: Mpox prevention and control policies should primarily focus on travel restrictions during high disease-risk periods and flight suspensions from high-risk nations in combination with regular HIV/AIDS prevention and treatment strategies.

HIV viral suppression at different thresholds and duration of treatment in the dolutegravir treatment era in Sierra Leone: a nationwide survey.

INTRODUCTION: Viral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone. METHODS: We used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P < 0.05. RESULTS: Of the 2,253 patients recruited, 1,720 (76%) were women and 1,705 (76%) were receiving a fixed dose combination of tenofovir, lamivudine and dolutegravir. The median age and duration of anti-retroviral therapy (ART) was 36.0 (IQR, 28.0-45.0) years and 40.9 (IQR, 14.4-79.6) months, respectively. Using a threshold of HIV RNA < 1000 copies/mL, 1,715 (88.4%) patients on ART for more than 6 months were virally suppressed. Viral suppression rates were higher with dolutegravir-based (1,277, 89.5%) than efavirenz-based (418, 86.2%) ART. HIV RNA was < 200 copies/mL in 1,643 (84.6%) patients or < 50 copies/mL in 1,487 (76.6%) patients or between 50 and 999 copies/mL in 228 (11.7%) patients. Viral suppression rates at different ART durations (months) were as follows: 84.2% (≤ 3), 88.8% (4-6), 90.9% (6-12), and 88.1% (> 12). Viral suppression rates were higher for patients aged 40 or older (40-50 years: aOR 2.05, 95%CI 1.41-3.04, P < 0.01; 50-60 years: aOR 2.51, 95%CI 1.53-4.35, P < 0.01; >60 years: aOR 2.69, 95%CI 1.28-6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38-0.67, P < 0.01). CONCLUSION: We report a viral suppression rate of 88.4% among patients on treatment for at least 6 months, with higher rate of suppression with dolutegravir than efavirenz. Factors associated with virological suppression were age and gender, emphasizing the need for innovative differentiated ART delivery models to optimize viral suppression and achieve the 95% target.

Marginal effects of public health measures and COVID-19 disease burden in China: A large-scale modelling study.

China had conducted some of the most stringent public health measures to control the spread of successive SARS-CoV-2 variants. However, the effectiveness of these measures and their impacts on the associated disease burden have rarely been quantitatively assessed at the national level. To address this gap, we developed a stochastic age-stratified metapopulation model that incorporates testing, contact tracing and isolation, based on 419 million travel movements among 366 Chinese cities. The study period for this model began from September 2022. The COVID-19 disease burden was evaluated, considering 8 types of underlying health conditions in the Chinese population. We identified the marginal effects between the testing speed and reduction in the epidemic duration. The findings suggest that assuming a vaccine coverage of 89%, the Omicron-like wave could be suppressed by 3-day interval population-level testing (PLT), while it would become endemic with 4-day interval PLT, and without testing, it would result in an epidemic. PLT conducted every 3 days would not only eliminate infections but also keep hospital bed occupancy at less than 29.46% (95% CI, 22.73-38.68%) of capacity for respiratory illness and ICU bed occupancy at less than 58.94% (95% CI, 45.70-76.90%) during an outbreak. Furthermore, the underlying health conditions would lead to an extra 2.35 (95% CI, 1.89-2.92) million hospital admissions and 0.16 (95% CI, 0.13-0.2) million ICU admissions. Our study provides insights into health preparedness to balance the disease burden and sustainability for a country with a population of billions.

A novel humanized tri-receptor transgenic mouse model of HAdV infection and pathogenesis.

Human adenovirus (HAdV) is a highly virulent respiratory pathogen that poses clinical challenges in terms of diagnostics and treatment. Currently, no effective therapeutic drugs or prophylactic vaccines are available for HAdV infections. One factor contributing to this deficiency is that existing animal models, including wild-type and single-receptor transgenic mice, are unsuitable for HAdV proliferation and pathology testing. In this study, a tri-receptor transgenic mouse model expressing the three best-characterized human cellular receptors for HAdV (hCAR, hCD46, and hDSG2) was generated and validated via analysis of transgene insertion, receptor mRNA expression, and protein abundance distribution. Following HAdV-7 infection, the tri-receptor mice exhibited high transcription levels at the early and late stages of the HAdV gene, as well as viral protein expression. Furthermore, the tri-receptor mice infected with HAdV exhibited dysregulated cytokine responses and multiple tissue lesions. This transgenic mouse model represents human HAdV infection and pathogenesis with more accuracy than any other reported animal model. As such, this model facilitates the comprehensive investigation of HAdV pathogenesis as well as the evaluation of potential vaccines and therapeutic modalities for HAdV.

Evaluation of Metagenomics Next-Generation Sequencing as a Diagnostic Tool for Influenza Virus-Positive Respiratory Samples in Retired Fitness Players

The use of Metagenomics Next-Generation Sequencing (mNGS) as a diagnostic tool for respiratory infections, particularly in the context of retired fitness players, presents a novel avenue for optimizing healthcare and wellness in this unique population. Respiratory illnesses, including influenza, can have profound effects on the health and performance of retired athletes, making accurate and timely diagnosis paramount. In this study, we aimed to assess the applicability of mNGS in diagnosing influenza virus infections in retired fitness players. We collected and analyzed respiratory samples from this specific cohort, leveraging mNGS technology. Our research focused on evaluating mNGS's potential as a diagnostic tool compared to conventional methods. Our findings underscored the remarkable capabilities of mNGS. When compared to traditional diagnostic techniques, mNGS demonstrated superior sensitivity in detecting influenza virus-positive respiratory samples in retired fitness players. Additionally, mNGS facilitated the identification of not only known influenza strains but also previously undetected viral variants, offering a comprehensive view of the viral landscape. The utilization of mNGS as a diagnostic tool in the care of retired fitness players holds great promise in enhancing their health monitoring and overall well-being. This technology can aid in the early detection and precise characterization of respiratory infections, contributing to the timely implementation of targeted interventions and improving the quality of healthcare for this unique and health-conscious population. (AU)

Driving role of climatic and socioenvironmental factors on human brucellosis in China: machine-learning-based predictive analyses.

BACKGROUND: Brucellosis is a common zoonotic infectious disease in China. This study aimed to investigate the incidence trends of brucellosis in China, construct an optimal prediction model, and analyze the driving role of climatic factors for human brucellosis. METHODS: Using brucellosis incidence, and the socioeconomic and climatic data for 2014-2020 in China, we performed spatiotemporal analyses and calculated correlations with brucellosis incidence in China, developed and compared a series of regression and Seasonal Autoregressive Integrated Moving Average X (SARIMAX) models for brucellosis prediction based on socioeconomic and climatic data, and analyzed the relationship between extreme weather conditions and brucellosis incidence using copula models. RESULTS: In total, 327,456 brucellosis cases were reported in China in 2014-2020 (monthly average of 3898 cases). The incidence of brucellosis was distinctly seasonal, with a high incidence in spring and summer and an average annual peak in May. The incidence rate was highest in the northern regions' arid and continental climatic zones (1.88 and 0.47 per million people, respectively) and lowest in the tropics (0.003 per million people). The incidence of brucellosis showed opposite trends of decrease and increase in northern and southern China, respectively, with an overall severe epidemic in northern China. Most regression models using socioeconomic and climatic data cannot predict brucellosis incidence. The SARIMAX model was suitable for brucellosis prediction. There were significant negative correlations between the proportion of extreme weather values for both high sunshine and high humidity and the incidence of brucellosis as follows: high sunshine, [Formula: see text] = -0.59 and -0.69 in arid and temperate zones; high humidity, [Formula: see text] = -0.62, -0.64, and -0.65 in arid, temperate, and tropical zones. CONCLUSIONS: Significant seasonal and climatic zone differences were observed for brucellosis incidence in China. Sunlight, humidity, and wind speed significantly influenced brucellosis. The SARIMAX model performed better for brucellosis prediction than did the regression model. Notably, high sunshine and humidity values in extreme weather conditions negatively affect brucellosis. Brucellosis should be managed according to the "One Health" concept.

A Shigella sonnei clone with extensive drug resistance associated with waterborne outbreaks in China.

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health.

The combination of sodium alginate and chlorogenic acid enhances the therapeutic effect on ulcerative colitis by the regulation of inflammation and the intestinal flora.

Chlorogenic acid (CA) and sodium alginate (SA) each have good therapeutic effects on ulcerative colitis (UC) owing to their antioxidant and anti-inflammatory activity. This study aimed to investigate the effects of CA alone and in combination with SA on inflammatory cells and UC mice. In the Lipopolysaccharide (LPS)-induced RAW 264.7 inflammatory cell model, Nitric oxide (NO) and interleukin-6 (IL-6) levels were significantly lower after treatment with CA plus SA than with CA alone. In the DSS-induced UC mouse model, compared with CA alone, CA plus SA showed a better ability to alleviate weight loss, reduce the disease activity index (DAI), improve the colonic mucosa, reduce the expression of inflammatory factors in the serum and myeloperoxidase (MPO) in colonic tissue, increase superoxide dismutase (SOD) levels, protect the intestinal mucosa and regulate the abundance of Actinobacteriota, Lactobacillus, Bifidobacterium, Bacteroides, Subdoligranulum and Streptococcus. Thus, CA plus SA can improve the therapeutic efficacy of CA in UC by regulating inflammatory factors, oxidative stress, and the intestinal flora and by protecting ulcerative wounds. These findings broaden our understanding of the role of the combination of SA and CA in enhancing the effects of CA on UC and provide strategies for prevention and treatment.

Bearing Fault Diagnosis Using Piecewise Aggregate Approximation and Complete Ensemble Empirical Mode Decomposition with Adaptive Noise.

Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) effectively separates the fault vibration signals of rolling bearings and improves the diagnosis of rolling bearing faults. However, CEEMDAN has high memory requirements and low computational efficiency. In each iteration of CEEMDAN, fault vibration signals are added with noises, both the vibration signals added with noises and the added noises are decomposed with classical empirical mode decomposition (EMD). This paper proposes a rolling bearing fault diagnosis method that combines piecewise aggregate approximation (PAA) with CEEMDAN. PAA enables CEEMDAN to decompose long signals and to achieve enhanced diagnosis. In particular, the method first yields the vibration envelope using bandpass filtering and demodulation, then compresses the envelope using PAA, and finally decomposes the compressed signal with CEEMDAN. Test data verification results show that the proposed method is more effective and more efficient than CEEMDAN.

Using a grey relational analysis in an improved Grunow-Finke assessment tool to detect unnatural epidemics.

The Grunow-Finke epidemiological assessment tool (GFT) has several limitations in its ability to differentiate between natural and man-made epidemics. Our study aimed to improve the GFT and analyze historical epidemics to validate the model. Using a gray relational analysis (GRA), we improved the GFT by revising the existing standards and adding five new standards. We then removed the artificial weights and final decision threshold. Finally, by using typically unnatural epidemic events as references, we used the GRA to calculate the unnatural probability and obtain assessment results. Using the advanced tool, we conducted retrospective and case analyses to test its performance. In the validation set of 13 historical epidemics, unnatural and natural epidemics were divided into two categories near the unnatural probability of 45%, showing evident differences (p < 0.01) and an assessment accuracy close to 100%. The unnatural probabilities of the Ebola virus disease of 2013 and Middle East Respiratory Syndrome of 2012 were 30.6% and 36.1%, respectively. Our advanced epidemic assessment tool improved the accuracy of the original GFT from approximately 55% to approximately 100% and reduced the impact of human factors on these outcomes effectively.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Quantitative analysis of the impact of various urban socioeconomic indicators on search-engine-based estimation of COVID-19 prevalence.

Numerous studies have proposed search engine-based estimation of COVID-19 prevalence during the COVID-19 pandemic; however, their estimation models do not consider the impact of various urban socioeconomic indicators (USIs). This study quantitatively analysed the impact of various USIs on search engine-based estimation of COVID-19 prevalence using 15 USIs (including total population, gross regional product (GRP), and population density) from 369 cities in China. The results suggested that 13 USIs affected either the correlation (SC-corr) or time lag (SC-lag) between search engine query volume and new COVID-19 cases ( p <0.05). Total population and GRP impacted SC-corr considerably, with their correlation coefficients r for SC-corr being 0.65 and 0.59, respectively. Total population, GRP per capita, and proportion of the population with a high school diploma or higher had simultaneous positive impacts on SC-corr and SC-lag ( p <0.05); these three indicators explained 37-50% of the total variation in SC-corr and SC-lag. Estimations for different urban agglomerations revealed that the goodness of fit, R 2 , for search engine-based estimation was more than 0.6 only when total urban population, GRP per capita, and proportion of the population with a high school diploma or higher exceeded 11.08 million, 120,700, and 38.13%, respectively. A greater urban size indicated higher accuracy of search engine-based estimation of COVID-19 prevalence. Therefore, the accuracy and time lag for search engine-based estimation of infectious disease prevalence can be improved only when the total urban population, GRP per capita, and proportion of the population with a high school diploma or higher are greater than the aforementioned thresholds.

Corrigendum: A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

[This corrects the article DOI: 10.3389/fmicb.2021.779749.].

A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

Salmonella contamination of eggs and egg shells has been identified as a public health problem worldwide. Here, we reported an outbreak of severe gastrointestinal symptoms caused by Salmonella enterica serovar Enteritidis (S. enteritidis) in China. We evaluated the outbreak by using epidemiological surveys, routine laboratory testing methods, and whole genome sequencing (WGS). This outbreak occurred in a canteen in Beijing, during March 9-11, 2021, 225 of the 324 diners who have eaten at the canteen showed gastrointestinal symptoms. The outbreak had characteristical epidemiological and clinical features. It caused a very high attack rate (69.4%) in a short incubation time. All patients developed diarrhea and high fever, accompanied by abdominal pain (62.3%), nausea (50.4%), and vomiting (62.7%). The average frequency of diarrhea was 12.4 times/day, and the highest frequency of diarrhea was as high as 50 times/day. The average fever temperature was 39.4°C, and the highest fever temperature was 42°C. Twenty strains of S. enteritidis were recovered, including 19 from the patients samples, and one from remained egg fried rice. Antibiotic susceptibility test showed that the 20 outbreak strains all had the same resistance pattern. PFGE results demonstrated that all 20 strains bore completely identical bands. Phylogenetic analysis based on WGS revealed that all 20 outbreak strains were tightly clustered together. So the pathogenic source of this food poisoning incident may was contaminated egg fried rice. Resistance gene analysis showed that the outbreak strains are all multi-drug resistant strains. Virulence gene analysis indicated that these outbreak strains carried a large number of virulence genes, including 2 types of Salmonella pathogenicity islands (SPI-1 and SPI-2). Other important virulence genes were also carried by the outbreak strains, such as pefABCD, rck and shdA. And the shdA gene was not in other strains located in the same evolutionary branch as the outbreak strain. We speculated that this is a significant reason for the serious symptoms of gastroenteritis in this outbreak. This outbreak caused by S. enteritidis suggested government should strengthen monitoring of the prevalence of outbreak clone strains, and take measures to mitigate the public health threat posed by contaminated eggs.

Effects of molecular weight of chitosan on anti-inflammatory activity and modulation of intestinal microflora in an ulcerative colitis model.

This study investigated the therapeutic effects and mechanisms of chitosans (CSs) with different molecular weights on ulcerative colitis (UC). Three size classes of CSs (Mw ≤ 3, 50, and 200 kDa) were used in this study. The effect of large CSs (Mw ≤ 200 kDa) on UC was the best, followed by that of medium CSs (Mw ≤ 50 kDa), and that of small CSs (Mw ≤ 3 kDa) was the least in the LPS-induced Raw 264.7 cell model and DSS-induced UC mice model. The therapeutic mechanisms of three CSs are related to anti-oxidation, anti-inflammation, and regulation of immunoglobulin and intestinal flora by attenuating body weight loss, decreasing the disease activity index (DAI) and MPO activity, suppressing proinflammatory cytokines and IgG levels, down-regulating the level of oxidative stress, increasing anti-inflammatory cytokines, SOD activity and Prevotellaceae_UCG-001 levels, and reducing the abundance of Proteobacteria, Actinobacteria, and Escherichia-Shigella. In general, the molecular weight of CSs influences their efficacy against UC. CSs with an optimal molecular weight demonstrate good development prospects for ameliorating UC.

Source-tracking of the Chinese Chikungunya viruses suggests that Indian subcontinent and Southeast Asia act as major hubs for the recent global spread of Chikungunya virus.

BACKGROUND: Chikungunya fever, caused by the Chikungunya virus (CHIKV), has become a major global health concern, causing unexpected large outbreaks in Africa, Asia, Europe, and the Americas. CHIKV is not indigenous to China, and its origin in the country is poorly understood. In particular, there is limited understanding of the recent global spread of CHIKV in the context of the CHIKV epidemic. METHODS: Here we investigated a novel Chikungunya patient who came from Myanmar to China in August, 2019. Direct genome sequencing was performed via combined MinION sequencing and BGISEQ-500 sequencing. A complete CHIKV genome dataset, including 727 CHIKV genomes retrieved from GenBank and the genome sequenced in this study, was constructed. An updated and comprehensive phylogenetic analysis was conducted to understand the virus's origin, evolution, transmission routes and genetic adaptation. RESULTS: All globally distributed CHIKV genomes were divided into West Africa, East/Central/South African and Asian genotypes. The genome sequenced in this study was located in the Indian Ocean lineage, and was closely related to a strain isolated from an Australian patient who returned from Bangladesh in 2017. A comprehensive phylogenetic analysis showed that the Chinese strains mainly originated from the Indian subcontinent and Southeast Asia. Further analyses indicated that the Indian subcontinent and Southeast Asia may act as major hubs for the recent global spread of CHIKV, leading to multiple outbreaks and epidemics. Moreover, we identified 179 distinct sites, including some undescribed sites in the structural and non-structural proteins, which exhibited apparent genetic variations associated with different CHIKV lineages. CONCLUSIONS: Here we report a novel CHIKV isolate from a chikungunya patient who came from Myanmar to China in 2019, and summarize the source and evolution of Chinese CHIKV strains. Our present findings provide a better understanding of the recent global evolution of CHIKV, highlighting the urgent need for strengthened surveillance against viral diversity.

Pneumonia Patients Caused by Co-infection With SARS-CoV-2 and Human Adenovirus in China.

Objectives: To data, no patients with obvious epidemiological relationship co-infected with SARS-CoV-2 and other pathogens have been reported. Here, we investigated 10 patients caused by co-infection with SARS-CoV-2 and human adenovirus (HAdV), resulting in third-generation transmission. Materials and Methods: From Jan 15, 2020, we enrolled 10 patients with pneumonia in Hunan Province, China. Epidemiological, clinical, and laboratory investigation results from these patients were analyzed. An epidemiological investigation was performed to assess whether patient infections were linked using conventional methods and metagenomic sequencing. Results: The presence of co-infection with SARS-CoV-2 and HAdV was determined via RT-PCR and metagenomic sequencing. Phylogenetic analysis revealed that SARS-CoV-2 and HAdV genomes clustered together, with similar genetic relationships. The first patient likely became co-infected during meetings or travel in Wuhan. The patient transmitted the virus via dinners and meetings, which resulted in four second-generation cases. Then, a second-generation case transmitted the virus to her family members or relatives via presymptomatic transmission. Conclusions: This study described an example of co-infection with SARS-CoV-2 and HAdV in pneumonia patients, which caused third-generation cases and inter-regional transmission via meetings, household interactions, and dinner parties. We also observed the persistent and presymptomatic transmission of co-infection, which has the potential to make the continued control of the COVID-19 pandemic challenging. Continuous surveillance is needed to monitor the prevalence, infectivity, transmissibility, and pathogenicity of SARS-CoV-2 co-infection with other pathogens to evaluate its real risk.

Food-trade-associated COVID-19 outbreak from a contaminated wholesale food supermarket in Beijing.

The re-emerging outbreak of COVID-19 in Beijing, China, in the summer of 2020 originated from a SARS-CoV-2-infested wholesale food supermarket. We postulated that the Xinfadi market outbreak has links with food-trade activities. Our Susceptible to the disease, Infectious, and Recovered coupled Agent Based Modelling (SIR-ABM) analysis for studying the diffusion of SARS-CoV-2 particles suggested that the trade-distancing strategy effectively reduces the reproduction number (R0). The retail shop closure strategy reduced the number of visitors to the market by nearly half. In addition, the buy-local policy option reduced the infection by more than 70% in total. Therefore, retail closures and buy-local policies could serve as significantly effective strategies that have the potential to reduce the size of the outbreak and prevent probable outbreaks in the future.

Genetic Characterization of mcr-1-Positive Multidrug-Resistant Salmonella enterica Serotype Typhimurium Isolated From Intestinal Infection in Children and Pork Offal in China.

With the rapid emergence of plasmid-mediated colistin resistance gene mcr-1, the increased resistance of Salmonella has attracted extensive attention. This study reports on 11 multidrug-resistant Salmonella enterica serovar Typhimurium strains harboring mcr-1 in China. They all presented resistance to colistin, and additionally, one that was isolated from a child's stool sample was also resistant to ceftriaxone and azithromycin. We screened 1454 strains of Salmonella for mcr-1 gene through PCR, and these strains are all preserved in our laboratory. Antimicrobial sensitivity analysis was carried out for the screened mcr-1 positive strains. Genetic polymorphism analysis of S. Typhimurium was performed by using the Pulsed-Field Gel Electrophoresis (PFGE). The plasmids harboring mcr-1 were identified by S1-PFGE and southern blotting. Plasmid conjugation assays were used to analyze the transferability of colistin resistance. The plasmids harboring mcr-1 were characterized by sequencing and bioinformatic analysis. Eleven S. Typhimurium strains harboring mcr-1 with colistin resistance (MICs 4µg/ml) were detected, which were isolated from children and pig offal in China. All of them were multidrug-resistant strains. PFGE results revealed that the strains isolated from different samples or locations have identical genotypes. S1-PFGE and southern blotting experiments showed that three plasmids of different sizes (33, 60, and 250 kb) all carried the mcr-1 gene. The plasmid conjugation assays revealed that Salmonella acquired mcr-1 harboring plasmids by horizontal transfer. Sequencing and plasmid type analysis revealed that these plasmids were types IncX4, IncI2, and IncHI2. Among them, IncX4 and IncI2 plasmids had extremely similar backbones and contained one resistant gene mcr-1. IncHI2 plasmid contained multiple resistant genes including bla CTX-M, oqxB, sul, aph, aadA, and bla TEM. We identified 11 mcr-1 harboring S. Typhimurium strains in China and described their characteristics. Our findings indicate that the mcr-1 gene can effectively spread among intestinal bacteria by horizontal transfer of three types of plasmids. Moreover, the IncHI2 plasmid can also mediate the transfer of other drug resistance genes. These results reveal that constant surveillance of mcr-1 harboring S Typhimurium is imperative to prevent the spread of colistin resistance.