From gut to liver: unveiling the differences of intestinal microbiota in NAFL and NASH patients.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The gut microbiota plays a pivotal role in the pathogenesis of NAFLD, yet the detailed characteristics and ecological alterations of gut microbial communities during the progression from non-alcoholic fatty liver (NAFL) to NASH remain poorly understood. Methods: In this study, we conducted a comparative analysis of gut microbiota composition in individuals with NAFL and NASH to elucidate differences and characteristics. We utilized 16S rRNA sequencing to compare the intestinal gut microbiota among a healthy control group (65 cases), NAFL group (64 cases), and NASH group (53 cases). Random forest machine learning and database validation methods were employed to analyze the data. Results: Our findings indicate a significant decrease in the diversity of intestinal flora during the progression of NAFLD (p < 0.05). At the phylum level, high abundances of Bacteroidetes and Fusobacteria were observed in both NAFL and NASH patients, whereas Firmicutes were less abundant. At the genus level, a significant decrease in Prevotella expression was seen in the NAFL group (AUC 0.738), whereas an increase in the combination of Megamonas and Fusobacterium was noted in the NASH group (AUC 0.769). Furthermore, KEGG pathway analysis highlighted significant disturbances in various types of glucose metabolism pathways in the NASH group compared to the NAFL group, as well as notably compromised flavonoid and flavonol biosynthesis functions. The study uncovers distinct microbiota characteristics and microecological changes within the gut during the transition from NAFL to NASH, providing insights that could facilitate the discovery of novel biomarkers and therapeutic targets for NAFLD.

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration.

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.

Spatiotemporal modulation of nitric oxide and Notch signaling by hemodynamic-responsive Trpv4 is essential for ventricle regeneration.

Zebrafish have a remarkable ability to regenerate injured hearts. Altered hemodynamic forces after larval ventricle ablation activate the endocardial Klf2a-Notch signaling cascade to direct zebrafish cardiac regeneration. However, how the heart perceives blood flow changes and initiates signaling pathways promoting regeneration is not fully understood. The present study demonstrated that the mechanosensitive channel Trpv4 sensed the altered hemodynamic forces in injured hearts and its expression was regulated by blood flow. In addition to mediating the endocardial Klf2a-Notch signal cascade around the atrioventricular canal (AVC), we discovered that Trpv4 regulated nitric oxide (NO) signaling in the bulbus arteriosus (BA). Further experiments indicated that Notch signaling primarily acted at the early stage of regeneration, and the major role of NO signaling was at the late stage and through TGF-ß pathway. Overall, our findings revealed that mechanosensitive channels perceived the changes in hemodynamics after ventricle injury, and provide novel insights into the temporal and spatial coordination of multiple signaling pathways regulating heart regeneration.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. METHODS: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. FINDINGS: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). INTERPRETATION: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. FUNDING: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Integrating host transcriptomic signatures for distinguishing autoimmune encephalitis in cerebrospinal fluid by metagenomic sequencing.

BACKGROUND: The early accurate diagnoses for autoimmune encephalitis (AE) and infectious encephalitis (IE) are essential since the treatments for them are different. This study aims to discover some specific and sensitive biomarkers to distinguish AE from IE at early stage to give specific treatments for good outcomes. RESULTS: We compared the host gene expression profiles and microbial diversities of cerebrospinal fluid (CSF) from 41 patients with IE and 18 patients with AE through meta-transcriptomic sequencing. Significant differences were found in host gene expression profiles and microbial diversities in CSF between patients with AE and patients with IE. The most significantly upregulated genes in patients with IE were enriched in pathways related with immune response such as neutrophil degranulation, antigen processing and presentation and adaptive immune system. In contrast, those upregulated genes in patients with AE were mainly involved in sensory organ development such as olfactory transduction, as well as synaptic transmission and signaling. Based on the differentially expressed genes, a classifier consisting of 5 host genes showed outstanding performance with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95. CONCLUSIONS: This study provides a promising classifier and is the first to investigate transcriptomic signatures for differentiating AE from IE by using meta-transcriptomic next-generation sequencing technology.

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection.

Background and objectives: Disease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms. Methods: COVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers. Results: The oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway. Conclusion: The oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19.

Suppression of innate and acquired immunity in severe hand foot and mouth disease caused by EV71 infections in children.

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role. Transcriptomes of peripheral blood mononuclear cells from EV71-infected patients (n = 45) and healthy controls (n = 36) were examined. Immune pathways were up-regulated in patients with mild disease symptoms (n = 11, M) compared to the healthy controls (n = 36, H), demonstrating an effective anti-viral response upon EV71 infection. However, in patients with severe symptoms (n = 23, S) as well as severe patients following treatment (n = 11, A), their innate and acquired immune pathways were down-regulated, indicating a global immunity suppression. Such immune suppression characteristics could thus provide an opportunity for early EV-71 infection prognosis prediction. Based on our cohort, an SVM model using RNA-seq expression levels of five genes (MCL1, ZBTB37, PLEKHM1P, IFNAR2 and YEATS2) was developed and achieved a high ROC-AUC (91·3%) in predicting severe HFMD. Meanwhile, qPCR fold-changes method was performed based three genes (MCL1, IFNAR2 and YEATS2) on additional cohort. This qPCR method achieved a ROC-AUC of 78.6% in predicting severe HFMD, which the patients could be distinguished in 2-3 h. Therefore, our models demonstrate the possibility of HFMD severity prediction based on the selected biomarkers that predict severe HFMD effectively.

Evaluation of Cell-Free DNA-Based Next-Generation Sequencing for Identifying Pathogens in Bacteremia Patients.

Rapid detection of bloodstream pathogens would greatly facilitate clinicians to make precise antimicrobial treatment in patients with bacteremia. In this study, 114 plasma samples were collected from patients with identified or suspected bacteremia, and pathogens were detected by the conventional blood culture (BC) and cell-free DNA metagenomics next-generation sequencing (cfDNA mNGS). The present study indicated that 76% (38/50) of positive conventional blood culture (BC+ group) patients were positively detected by cfDNA mNGS, and only 4% were mismatched between cfDNA mNGS and conventional bacteria culture. Pathogens in 32.8% of suspected bacteremia patients with negative conventional blood culture (BC- group) were determined accurately by cfDNA mNGS combined with analyzing the patients' clinical manifestations. Escherichia coli and Klebsiella pneumoniae were the most detected pathogens in identified bacteremia patients by cfDNA mNGS. 76.2% (16/21) of E. coli and 92.3% (12/13) of K. pneumoniae in bacteremia patients were identified by conventional blood cultures that were also detected by cfDNA mNGS. This study demonstrated that genomic coverage of E. coli and K. pneumoniae were more often detected in BC+ group patients and genomic coverage of Acinetobacter johnsonii and Paucibacter sp. KCTC 42545 was more often detected in BC- group patients. In conclusion, cfDNA mNGS could rapidly and precisely provide an alternative detection method for the diagnosis of bacteremia.

Ercc2/Xpd deficiency results in failure of digestive organ growth in zebrafish with elevated nucleolar stress.

Mutations in ERCC2/XPD helicase, an important component of the TFIIH complex, cause distinct human genetic disorders which exhibit various pathological features. However, the molecular mechanisms underlying many symptoms remain elusive. Here, we have shown that Ercc2/Xpd deficiency in zebrafish resulted in hypoplastic digestive organs with normal bud initiation but later failed to grow. The proliferation of intestinal endothelial cells was impaired in ercc2/xpd mutants, and mitochondrial abnormalities, autophagy, and inflammation were highly induced. Further studies revealed that these abnormalities were associated with the perturbation of rRNA synthesis and nucleolar stress in a p53-independent manner. As TFIIH has only been implicated in RNA polymerase I-dependent transcription in vitro, our results provide the first evidence for the connection between Ercc2/Xpd and rRNA synthesis in an animal model that recapitulates certain key characteristics of ERCC2/XPD-related human genetic disorders, and will greatly advance our understanding of the molecular pathogenesis of these diseases.

Microbial and human transcriptional profiling of coronavirus disease 2019 patients: Potential predictors of disease severity.

The high morbidity of patients with coronavirus disease 2019 (COVID-19) brings on a panic around the world. COVID-19 is associated with sex bias, immune system, and preexisting chronic diseases. We analyzed the gene expression in patients with COVID-19 and in their microbiota in order to identify potential biomarkers to aid in disease management. A total of 129 RNA samples from nasopharyngeal, oropharyngeal, and anal swabs were collected and sequenced in a high-throughput manner. Several microbial strains differed in abundance between patients with mild or severe COVID-19. Microbial genera were more abundant in oropharyngeal swabs than in nasopharyngeal or anal swabs. Oropharyngeal swabs allowed more sensitive detection of the causative SARS-CoV-2. Microbial and human transcriptomes in swabs from patients with mild disease showed enrichment of genes involved in amino acid metabolism, or protein modification via small protein removal, and antibacterial defense responses, respectively, whereas swabs from patients with severe disease showed enrichment of genes involved in drug metabolism, or negative regulation of apoptosis execution, spermatogenesis, and immune system, respectively. Microbial abundance and diversity did not differ significantly between males and females. The expression of several host genes on the X chromosome correlated negatively with disease severity. In this way, our analyses identify host genes whose differential expression could aid in the diagnosis of COVID-19 and prediction of its severity via non-invasive assay.

Identification of a 3-Gene Model as Prognostic Biomarker in Patients With Gastric Cancer.

Objective: Although the incidence of gastric cancer (GC) is decreasing, GC remains one of the leading cancers in the world. Surgical resection, radiotherapy, chemotherapy, and neoadjuvant therapy have advanced, but patients still face the risk of recurrence and poor prognosis. This study provides new insights for assessment of prognosis and postoperative recurrence of GC patients. Methods: We collected paired cancer and adjacent tissues of 17 patients with early primary GC for bulk transcriptome sequencing. By comparing the transcriptome information of cancer and adjacent cancer, 321 differentially expressed genes (DEGs) were identified. These DEGs were further screened and analyzed with the GC cohort of TCGA to establish a 3-gene prognostic model (PLCL1, PLOD2 and ABCA6). At the same time, the predictive ability of this risk model is validated in multiple public data sets. Besides, the differences in immune cells proportion between the high- and low-risk groups were analyzed by the CIBERSORT algorithm with the Leukocyte signature matrix (LM22) gene signature to reveal the role of the immune microenvironment in the occurrence and development of GC. Results: The model could divide GC samples from TCGA cohorts into two groups with significant differences in overall and disease-free survival. The excellent predictive ability of this model was also validated in multiple other public data sets. The proportion of these immune cells such as resting mast cells, T cells CD4+ memory activated and Macrophages M2 are significantly different between high and low risk group. Conclusion: These three genes used to build the models were validated as biomarkers for predicting tumor recurrence and survival. They may have potential significance for the treatment and diagnosis of patients in the future, and may also promote the development of targeted drugs.

Knockout of Shelterin subunit genes in zebrafish results in distinct outcomes.

As the core component of telomeres, the Shelterin complex interacts with telomerase and the CST complex and plays a crucial role in maintaining telomere structure. Perturbation of Shelterin subunits results in telomere damage and subsequent genomic instability, which leads to aging as well as multiple human diseases. Recently, zebrafish have been widely utilized to model human diseases. To establish appropriate zebrafish models of Shelterin-related human disorders, we generated knockout zebrafish of the Shelterin subunit genes acd, pot1, tinf2, terf1 and pinx1 using the CRISPR/Cas9 technology and analyzed the effects of gene deficiency on zebrafish development in detail. We discovered that tinf2, terf1 and pinx1 homozygous mutants could grow to adulthood normally, whereas acd and pot1 homozygous mutant larvae died between 12 and 15 dpf without obvious abnormalities. A few acd-/- mutants survived to adulthood and displayed several premature aging-like phenotypes, including male sterility, cachectic dwarfism and reduced lifespan. Overall, our study established a variety of telomere-deficient zebrafish mutant strains and provided novel animal models for further exploring the relationship between telomeres and aging as well as the pathogenesis of human diseases associated with telomere deficiency.

Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing.

Helicobacter pylori infection is a prevalent infectious disease, associated with many gastric diseases, including gastritis, gastric ulcer, and gastric cancer. To reveal the characteristics of the gastric microbiome in patients infected with H. pylori, we performed metagenomic shotgun sequencing of stomach swab samples from 96 patients and then conducted metagenomic association analyses between alterations in the gastric microbiome and H. pylori infection status. The overall composition of the gastric microbiota in H. pylori-infected individuals was distinctly different from the negative controls; H. pylori became the dominant species after colonizing the human stomach and significantly decreased the α-diversity of the gastric community (P < 0.05, Wilcoxon rank-sum test). We also identified 6 HPI-associated microbial species (FDR < 0.05, Wilcoxon rank-sum test): Stenotrophomonas maltophilia, Stenotrophomonas unclassified, Chryseobacterium unclassified, Pedobacter unclassified, Variovorax unclassified, and Pseudomonas stutzeri. Furthermore, 55 gastric microbial pathways were enriched in the H. pylori-positive group, whereas only 2 pathways were more abundant in the H. pylori-negative group: dTDP-L-rhamnose biosynthesis and tetrapyrrole biosynthesis (FDR < 0.05, Wilcoxon rank-sum test). Gastritis was not associated with non-H. pylori species in the stomach (P > 0.05, Wilcoxon rank-sum test). This study revealed alterations in gastric microbial taxa and function associated with HPI in the Chinese population, which provides an insight into gastric microbial interactions and their potential role in the pathological process of gastric diseases.

Comparison of Intraocular Antibody Measurement, Quantitative Pathogen PCR, and Metagenomic Deep Sequencing of Aqueous Humor in Secondary Glaucoma Associated with Anterior Segment Uveitis.

PURPOSE: To identify viral pathogens in patients with secondary glaucoma associated with anterior segment uveitis and compare metagenomic deep sequencing (MDS) with enzyme-linked immunosorbent assay (ELISA) combined with Witmer-Desmonts coefficient (WDC) evaluation and real-time quantitative polymerase chain reaction (qPCR) on investigating pathogens in aqueous humor. METHODS: Aqueous humor from 31 patients, including 22 Posner-Schlossman Syndrome and 9 other anterior uveitis, was assessed pathogens by ELISA combined with WDC evaluation, virus deoxyribonucleic acid (DNA) detection by real-time qPCR and MDS. RESULTS: Viral pathogens (HCMV or VZV or RV) were detected in 19 out of 31 eyes (61.3%) by real-time qPCR or WDC evaluation. MDS revealed the presence of HCMV DNA sequences in three PSS patients. CONCLUSION: Virus is an important pathogen in secondary glaucoma associated with anterior segment uveitis. MDS is a potential etiologic diagnosis tool to seek intraocular viral pathogens for secondary glaucoma associated anterior segment uveitis.

Metatranscriptomic Analysis Reveals Disordered Alterations in Oropharyngeal Microbiome during the Infection and Clearance Processes of SARS-CoV-2: A Warning for Secondary Infections.

This study was conducted to investigate oropharyngeal microbiota alterations during the progression of coronavirus disease 2019 (COVID-19) by analyzing these alterations during the infection and clearance processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnosis of COVID-19 was confirmed by using positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR). The alterations in abundance, diversity, and potential function of the oropharyngeal microbiome were identified using metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 47 patients with COVID-19 (within a week after diagnosis and within two months after recovery from COVID-19) and 40 healthy individuals. As a result, in the infection process of SARS-CoV-2, compared to the healthy individuals, the relative abundances of Prevotella, Aspergillus, and Epstein-Barr virus were elevated; the alpha diversity was decreased; the beta diversity was disordered; the relative abundance of Gram-negative bacteria was increased; and the relative abundance of Gram-positive bacteria was decreased. After the clearance of SARS-CoV-2, compared to the healthy individuals and patients with COVID-19, the above disordered alterations persisted in the patients who had recovered from COVID-19 and did not return to the normal level observed in the healthy individuals. Additionally, the expressions of several antibiotic resistance genes (especially multi-drug resistance, glycopeptide, and tetracycline) in the patients with COVID-19 were higher than those in the healthy individuals. After SARS-CoV-2 was cleared, the expressions of these genes in the patients who had recovered from COVID-19 were lower than those in the patients with COVID-19, and they were different from those in the healthy individuals. In conclusion, our findings provide evidence that potential secondary infections with oropharyngeal bacteria, fungi, and viruses in patients who have recovered from COVID-19 should not be ignored; this evidence also highlights the clinical significance of the oropharyngeal microbiome in the early prevention of potential secondary infections of COVID-19 and suggests that it is imperative to choose appropriate antibiotics for subsequent bacterial secondary infection in patients with COVID-19.

Intestinal microbiota has important effect on severity of hand foot and mouth disease in children.

BACKGROUND: The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. METHODS: We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. RESULTS: We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. CONCLUSIONS: Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.

The Origin and Molecular Epidemiology of Dengue Fever in Hainan Province, China, 2019.

There was an outbreak of Dengue fever on September 5, 2019, in Hainan Province, which has not been endemic for 28 years. We aim to describe the clinical and epidemiological features of the 2019 outbreak in Hainan Province and identify the cause. All type 1 Dengue fever cases that occurred in this outbreak of Hainan exhibited mild clinical symptoms. The epidemiological investigations indicate that the outbreak might originate from workers in the Xiuying area, Haikou City, form a concentrated outbreak, and then spread out. Bayesian phylogenies results and epidemiological data were used to infer a likely series of events for the dengue virus's potential spread and trace the possible sources. The strains' sequences were close to a sequence from the nearby Guangdong province, supporting the hypothesis that the dengue virus was imported from Guangdong province and then spread across Hainan province. Furthermore, it is interesting that two other strains didn't group with this cluster, suggesting that additional introduction pathways might exist. The study indicated that the dengue fever epidemic presented two important modes in Hainan. Firstly, epidemics prevalence was caused by imported cases, and then endogenous epidemics broke out in the natural epidemic focus.