Abstract
Background
Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus ...hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old.
Methods
Articles published from January 1, 2006 to December 31, 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQRs).
Results
We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR, 46–74) in rotavirus hospitalizations, 36% (IQR, 23–47) in AGE hospitalizations, and 36% (IQR, 28–46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR, 28–45) before rotavirus vaccine introduction and 20% (IQR, 20–20) 4 years after introduction.
Conclusions
Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation.
105 peer-reviewed articles from the first 14 years of rotavirus vaccine implementation show substantial reductions in rotavirus and acute gastroenteritis hospitalizations, with the largest decreases in countries with low child mortality and higher coverage, and among younger age groups.
Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) ...as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Each year, 31 major known pathogens acquired in the United States caused an estimated 9.4 million episodes of foodborne illness. Additional episodes of illness were caused by unspecified agents, ...including known agents with insufficient data to estimate agent-specific illness, known agents not yet recognized as causing foodborne illness, substances known to be in food but of unproven pathogenicity, and unknown agents. To estimate these additional illnesses, we used data from surveys, hospital records, and death certificates to estimate illnesses, hospitalizations, and deaths from acute gastroenteritis and subtracted illnesses caused by known gastroenteritis pathogens. If the proportions acquired by domestic foodborne transmission were similar to those for known gastroenteritis pathogens, then an estimated 38.4 million (90% credible interval CrI 19.8-61.2 million) episodes of domestically acquired foodborne illness were caused by unspecified agents, resulting in 71,878 hospitalizations (90% CrI 9,924-157,340) and 1,686 deaths (90% CrI 369-3,338).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Swine enteric coronaviruses are a group of most significant pathogens causing diarrhea in piglets with similar clinical symptoms and pathological changes. To develop a simple, rapid, accurate, and ...high-throughput detection method for diagnosis and differential diagnosis on swine enteric coronaviruses, specific primers and probes were designed based on the highly conserved regions of transmissible gastroenteritis virus (TGEV) N, porcine epidemic diarrhea virus (PEDV) M, porcine deltacoronavirus (PDCoV) M, and porcine enteric alphacoronavirus (PEAV) N genes respectively. A TaqMan-probe-based multiplex real-time RT-qPCR assay was developed and optimized to simultaneously detect these swine enteric coronaviruses. The results showed that the limit of detection can reach as low as 10 copies in singular real-time RT-qPCR assays and 100 copies in multiplex real-time RT-qPCR assay, with all correlation coefficients (
R
2
) at above 0.99, and the amplification efficiency at between 90 and 120%. This multiplex real-time RT-qPCR assay demonstrated high sensitivity, extreme specificity, and excellent repeatability. The multiplex real-time RT-qPCR assay was then employed to detect the swine enteric coronavirus from 354 field diarrheal samples. The results manifested that TGEV and PDCoV were the main pathogens in these samples, accompanied by co-infections. This well-established multiplex real-time RT-qPCR assay provided a rapid, efficient, specific, and sensitive tool for detection of swine enteric coronaviruses.
Universal rotavirus (RV) vaccination is expected to reduce hospitalizations for acute gastroenteritis (GE) of children by eliminating most of severe RVGE, but it does not have any effect on norovirus ...(NV), the second most common causative agent of GE in children. After the introduction of the RV vaccine into the National Immunization Programme (NIP) of Finland in 2009, we conducted a prospective 2-year survey of GE in children seen in Tampere University Hospital either as outpatients or inpatients and compared the results with a similar 2-year survey conducted prior to NIP in the years 2006–2008. Compared with the pre-NIP 2-year period, in 2009–2011, hospitalizations for RVGE were reduced by 76 % and outpatient clinic visits were reduced by 81 %. NVGE showed a slight decreasing trend and accounted for 34 % of all cases of GE seen in hospital in pursuance of RVGE having decreased to 26 % (down from 52 %). In cases admitted to the hospital ward, RV accounted for 28 % and NV accounted for 37 %.The impact of RV vaccination was reflected as a 57 % decrease in all hospital admissions and 62 % decrease in all outpatient clinic visits for GE of any cause.
Conclusion
: RV vaccination in NIP has led to a major reduction of hospital admissions and clinic visits due to RVGE, but has had no effect on NVGE. After 2 years of NIP, NV has become the leading cause of acute GE in children seen in hospital.
The Luminex Gastrointestinal Pathogen Panel (xTAG® GPP) detects in one assay the most common gastroenteritis-causing pathogens and toxins, namely adenovirus 40/41, norovirus genogroup (NG) I/II, ...rotavirus A, Clostridium difficile toxin A/B, Campylobacter sp., Escherichia coli O157, Enterotoxigenic E. coli heat-labile enterotoxin/heat-stable enterotoxin, Salmonella sp., Shiga-toxin producing E. coli, Shiga-like toxin (Stx) 1/2, Shigella sp., Vibrio cholerae, Yersinia enterocolitica, Cryptosporidium sp., Entamoeba histolytica and Giardia sp. In this study, we compared the results that were obtained by testing 393 faecal samples, collected during November and December 2011 at our laboratory, using the xTAG® GPP assay with the results of the routine diagnostic procedure. This procedure includes culture for bacteria and real-time PCR for viruses and parasites, but only if the test was requested by the clinician. If the clinician did not request the test for an xTAG® GPP-positive target, real-time PCR assays were used to confirm xTAG® GPP positivity. Discrepant results were also tested with real-time PCR assays. A total of 83 targets were detected in 76 samples using xTAG® GPP. The xTAG® GPP assay detected 43 additional positives compared with the routine diagnostic procedure, of which 11 targets could not be confirmed by real-time PCR. The non-confirmed targets were Campylobacter (one sample), Salmonella (four samples), Shigella (one sample) and E. histolytica (five samples). The xTAG® GPP was shown to be a convenient and sensitive assay for detection of 15 major gastrointestinal pathogens in a single molecular test, but for detection of E. histolytica and Salmonella, a confirmatory assay is indicated.
Porcine transmissible gastroenteritis virus (TGEV) is one of the major etiological agents of viral enteritis and fetal diarrhea in suckling piglets. In this study, a TGEV JS2012 strain was isolated ...from the feces of piglets in Jiangsu Province, China. The phylogenetic analysis showed that TGEV JS2012 was placed between the Purdue and the Miller clusters. Analysis of recombination confirmed that TGEV JS2012 is a natural recombinant strain between Miller M6 and Purdue 115. Similar to Miller M6, virulent Purdue and China strain TS, in S gene the JS2012 maintained genetic integrity and the characteristics of the TGEV virulent strains. In vivo, TGEV JS2012 caused 100% mortality in newborn piglets, indicating the strong pathogenicity of this isolate. These results reveal that the JS2012 is a novel natural recombinant TGEV with high virulence. Our findings provide valuable information about genetic diversity and infection mechanism of the coronavirus family.
•TGEV JS2012 strain was isolated from the feces of piglets in China.•TGEV JS2012 is a natural recombinant strain between Miller M6 and Purdue 115.•TGEV JS2012 caused 100% mortality in newborn piglets.
The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence ...has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience.
The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members.
PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms.
Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.
The intestinal organoid culture system is a pathbreaking working model for investigating pathogen-host interactions in the intestines. However, due to the limitations of the first generation of ...intestinal organoids, basal-out structure and growth in Matrigel, most pathogens can rarely attach to the apical membrane directly and hardly initiate infection. In this study, we first developed a next-generation porcine intestinal organoid culture system, characterized by an apical membrane on the surface, called apical-out. To investigate the infectivity and antiviral immune responses of this apical-out porcine intestinal organoid, a swine enteric virus, transmissible gastroenteritis virus (TGEV), was employed to inoculate the culture system. Both reverse transcription-quantitative PCR (RT-qPCR) and immunofluorescence assay (IFA) analysis demonstrated that TGEV replicated in the apical-out porcine intestinal organoid culture system. Additionally, our results illustrated that TGEV infection significantly upregulated the expression levels of alpha interferon (IFN-α), IFN-λ1, interferon-stimulated gene 15 (ISG15), ISG58, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) in this culture system. Hence, we successfully developed a porcine intestinal apical-out organoid culture system, which will facilitate the investigation of pathogen-host interactions in pig intestines.
Intestinal organoids are a newly developed culture system for investigating pathogen-host interactions. Intestinal organoid models have been widely used since their development, because the results obtained from this type of culture model better represent physiological conditions than those from well-established cell lines. The three-dimensional (3D) porcine intestinal organoid model was reported in 2018 and 2019 for the investigation of intestinal pathogens. However, those organoid culture models were basal-out intestinal organoids, which are not suitable for porcine enteric virus research because they invade the intestines via the apical side of epithelial cells on villi. In this study, we developed a porcine apical-out intestinal organoid culture system and verified its infectivity, type I and type III interferon (IFN) antiviral responses, and inflammatory responses following infection by a swine enteric virus. Our results imply that this apical-out porcine intestinal organoid culture system is an ideal model for the investigation of interactions between swine enteric viruses and the intestines.
Abstract Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with ...inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication. Phosphorylation of NF-κB subunit p65 and proinflammatory cytokine production were greatly decreased after knockdown of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) or its adaptors MAVS and STING, while only slight reduction was observed in cells following silencing of Toll-like receptor adaptors, MyD88 and TRIF. Furthermore, TGEV infection significantly upregulated mRNA expression of RIG-I and MDA5. Taken together, our results indicate that the RLR signaling pathway is involved in TGEV-induced inflammatory responses.
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