Medicine › Infectious Diseases

Viral gastroenteritis research and epidemiology

Works Count: 83079

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Description

This cluster of papers focuses on the epidemiology, pathogenesis, and vaccine development for gastrointestinal viral infections, particularly rotavirus and norovirus. It covers topics such as global distribution, strain diversity, molecular detection methods, and the impact of vaccination on disease burden.

Keywords

Rotavirus; Norovirus; Gastroenteritis; Vaccine; Infection; Epidemiology; Diarrhea; Genotyping; Pathogenesis; Molecular Detection

Changing patterns of infectious disease

2000-08-17

Mitchell L. Cohen

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Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens

1990-02-01

Vera Gouvêa , Roger I. Glass , Patricia Woods +4 more

The rotavirus gene segment coding for the major outer capsid glycoprotein vp7 was amplified directly from stool specimens by the polymerase chain reaction (PCR). Double-stranded RNA extracted from stool samples … The rotavirus gene segment coding for the major outer capsid glycoprotein vp7 was amplified directly from stool specimens by the polymerase chain reaction (PCR). Double-stranded RNA extracted from stool samples was used as the template for reverse transcription, which was followed immediately and in the same reaction mix with amplification, using the Taq polymerase. Various conditions were examined to optimize the yield of the amplified gene. The concentrations of MgCl2, dimethyl sulfoxide, and template RNA were critical. The choice of primer pairs allowed amplification of the entire segment or specific portions. By using type-specific primers derived from distinct regions on the gene, we devised a PCR typing method in which each human serotype virus produced a characteristic segment size, readily identifiable in agarose gels. The PCR typing method was applied to 10 rotavirus reference strains, including all 6 known human serotypes (serotypes 1, 2, 3, 4, 8, and 9), and to 34 stool specimens previously serotyped by an enzyme immunoassay with monoclonal antibodies. An absolute correlation was found between the molecular and serologic methods. In addition, 14 stool specimens nonserotypable by an enzyme immunoassay with monoclonal antibodies could be typed by the PCR method. Besides the application for rotavirus detection and typing directly from stools, the PCR method provides a rapid and efficient means of obtaining large quantities of cDNA suitable for sequencing, cloning, and other genetic studies, precluding the need for cell culture and virus purification.

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Identification of group A rotavirus gene 4 types by polymerase chain reaction

1992-06-01

Jon R. Gentsch , Roger I. Glass , Patricia Woods +5 more

Five genetically distinct human rotavirus (HRV) gene 4 groups have been described on the basis of comparative nucleotide sequencing and the predicted amino acid sequences, and at least four of … Five genetically distinct human rotavirus (HRV) gene 4 groups have been described on the basis of comparative nucleotide sequencing and the predicted amino acid sequences, and at least four of them represent distinct VP4 antigenic types. To identify each gene 4 type and investigate its distribution in HRV isolates from patients with diarrhea, we developed a polymerase chain reaction (PCR) typing method using sequence information available for four genetically distinct gene 4 types. Rotavirus double-stranded RNAs (dsRNAs) isolated from stool samples were first reverse transcribed and amplified by PCR by using two oligonucleotide primers that correspond to regions that are highly conserved among all known HRV gene 4 types. The 876-bp dsDNA products were then reamplified by PCR in the presence of a cocktail containing one conserved plus-sense primer and four type-specific minus-sense primers (selected from the hypervariable region of gene 4), resulting in products of 345, 483, 267, and 391 bp corresponding to gene 4 types 1, 2, 3, and 4, respectively. This method reliably identified the gene 4 types of 16 well-characterized HRV isolates. Our results were independently confirmed for all 16 strains by reverse transcription and PCR amplification of HRV dsRNA in the presence of alternate type-specific primer pairs. For direct gene 4 typing of HRV in stool samples, we developed a method to extract rotavirus dsRNA from stool specimens by using glass powder. Our results suggest that gene 4 typing will be useful in providing more a complete characterization of HRV strains of epidemiologic or vaccine-related interest.

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A Receptor for Tumor Necrosis Factor Defines an Unusual Family of Cellular and Viral Proteins

1990-05-25

Craig A. Smith , Terri Davis , Dirk Anderson +6 more

Tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) bind surface receptors on a variety of cell types to mediate a wide range of immunological responses, inflammatory reactions, and anti-tumor … Tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) bind surface receptors on a variety of cell types to mediate a wide range of immunological responses, inflammatory reactions, and anti-tumor effects. A cDNA clone encoding an integral membrane protein of 461 amino acids was isolated from a human lung fibroblast library by direct expression screening with radiolabeled TNF-alpha. The encoded receptor was also able to bind TNF-beta. The predicted cysteine-rich extracellular domain has extensive sequence similarity with five proteins, including nerve growth factor receptor and a transcriptionally active open reading frame from Shope fibroma virus, and thus defines a family of receptors.

The mucosal immune system: from fundamental concepts to vaccine development

1992-01-01

Jerry R. McGhee , Jiří Městecký , Mark T. Dertzbaugh +3 more

The pig: a model for human infectious diseases

2011-12-09

François Meurens , Artur Summerfield , Hans Nauwynck +2 more

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Rotavirus and Severe Childhood Diarrhea

2006-02-01

Umesh D. Parashar , Christopher J. Gibson , Joseph Bresee +1 more

Studies published between 1986 and 1999 indicated that rotavirus causes approximately 22% (range 17%-28%) of childhood diarrhea hospitalizations. From 2000 to 2004, this proportion increased to 39% (range 29%-45%). Application … Studies published between 1986 and 1999 indicated that rotavirus causes approximately 22% (range 17%-28%) of childhood diarrhea hospitalizations. From 2000 to 2004, this proportion increased to 39% (range 29%-45%). Application of this proportion to the recent World Health Organization estimates of diarrhea-related childhood deaths gave an estimated 611,000 (range 454,000-705,000) rotavirus-related deaths.

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Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity

2014-09-09

Paul Browne , Dhia Chandraratna , Ceri Angood +4 more

Multiple sclerosis (MS) is one of the world's most common neurologic disorders, and in many countries it is the leading cause of nontraumatic neurologic disability in young adults. Despite this, … Multiple sclerosis (MS) is one of the world's most common neurologic disorders, and in many countries it is the leading cause of nontraumatic neurologic disability in young adults. Despite this, global information on the epidemiology of MS and the availability of resources and services for people with MS is scarce in many regions of the world. The first Atlas of MS , published in 2008 as a joint project of the Multiple Sclerosis International Federation (MSIF) and the World Health Organization (WHO),1 endeavored to fill this knowledge gap with information from 112 countries. Here, we outline important updates in the recently launched Atlas of MS 2013: Mapping Multiple Sclerosis around the World. 2 The authors thank Bernard Uitdehaag, PhD (VU University Medical Center, the Netherlands); Ed Holloway (Multiple Sclerosis Society, UK); Lekha Pandit, MD, PhD (Nitte University, India); and Mario Battaglia, MD (Associazione Italiana Sclerosi Multipla, Italy) of the MSIF Atlas of MS Study Group Committee who developed the templates used to collect the data for this manuscript.

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Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG)

2011-05-19

Jelle Matthijnssens , Max Ciarlet , Sarah M. McDonald +7 more

Norwalk virus: How infectious is it?

2008-06-12

Peter Teunis , Christine L. Moe , Pengbo Liu +5 more

Abstract Noroviruses are major agents of viral gastroenteritis worldwide. The infectivity of Norwalk virus, the prototype norovirus, has been studied in susceptible human volunteers. A new variant of the hit … Abstract Noroviruses are major agents of viral gastroenteritis worldwide. The infectivity of Norwalk virus, the prototype norovirus, has been studied in susceptible human volunteers. A new variant of the hit theory model of microbial infection was developed to estimate the variation in Norwalk virus infectivity, as well as the degree of virus aggregation, consistent with independent (electron microscopic) observations. Explicit modeling of viral aggregation allows us to express virus infectivity per single infectious unit (particle). Comparison of a primary and a secondary inoculum showed that passage through a human host does not change Norwalk virus infectivity. We estimate the average probability of infection for a single Norwalk virus particle to be close to 0.5, exceeding that reported for any other virus studied to date. Infected subjects had a dose‐dependent probability of becoming ill, ranging from 0.1 (at a dose of 10 3 NV genomes) to 0.7 (at 10 8 virus genomes). A norovirus dose response model is important for understanding its transmission and essential for development of a quantitative risk model. Norwalk virus is a valuable model system to study virulence because genetic factors are known for both complete and partial protection; the latter can be quantitatively described as heterogeneity in dose response models. J. Med. Virol. 80:1468–1476, 2008. © 2008 Wiley‐Liss, Inc.

VIRUS PARTICLES IN EPITHELIAL CELLS OF DUODENAL MUCOSA FROM CHILDREN WITH ACUTE NON-BACTERIAL GASTROENTERITIS

1973-12-01

R F Bishop , G. P. Davidson , Ian Holmes +1 more

Human susceptibility and resistance to Norwalk virus infection

2003-04-14

Lisa C. Lindesmith , Christine L. Moe , Séverine Marionneau‐Lambot +6 more

Superspreading and the effect of individual variation on disease emergence

2005-11-01

James O. Lloyd‐Smith , Sebastian J. Schreiber , Peter Ekkehard Kopp +1 more

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Global burden of childhood pneumonia and diarrhoea

2013-04-01

Christa L. Fischer Walker , Igor Rudan , Li Liu +6 more

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Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease

2015-01-01

Jason Norman , Scott A. Handley , Megan T. Baldridge +7 more

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A DNA transfection system for generation of influenza A virus from eight plasmids

2000-05-09

Erich Hoffmann , Gabriele Neumann , Yoshihiro Kawaoka +2 more

We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the … We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the RNA polymerase I (pol I) promoter and terminator sequences. This entire pol I transcription unit is flanked by an RNA polymerase II (pol II) promoter and a polyadenylation site. The orientation of the two transcription units allows the synthesis of negative-sense viral RNA and positive-sense mRNA from one viral cDNA template. This pol I–pol II system starts with the initiation of transcription of the two cellular RNA polymerase enzymes from their own promoters, presumably in different compartments of the nucleus. The interaction of all molecules derived from the cellular and viral transcription and translation machinery results in the generation of infectious influenza A virus. The utility of this system is proved by the recovery of the two influenza A viruses: A/WSN/33 (H1N1) and A/Teal/HK/W312/97 (H6N1). Seventy-two hours after the transfection of eight expression plasmids into cocultured 293T and MDCK cells, the virus yield in the supernatant of the transfected cells was between 2 × 10 5 and 2 × 10 7 infectious viruses per milliliter. We also used this eight-plasmid system for the generation of single and quadruple reassortant viruses between A/Teal/HK/W312/97 (H6N1) and A/WSN/33 (H1N1). Because the pol I–pol II system facilitates the design and recovery of both recombinant and reassortant influenza A viruses, it may also be applicable to the recovery of other RNA viruses entirely from cloned cDNA.

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Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

1999-01-01

Karen L. Kotloff , Jonathan P. Winickoff , B Ivanoff +5 more

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we … Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.This article presents a review of the literature published between 1966 and 1997 on Shigella infection. The purpose of the review is to provide data on the global morbidity and mortality caused by the infection and to plan strategies of prevention and treatment. The data obtained from this literature were used to calculate the number of Shigella infection cases and the associated mortality occurring worldwide each year, by age and by clinical category. The burden of Shigella infection was also estimated by serogroup and serotype. A sensitivity analysis was performed to estimate the high and the low range of morbid and fatal cases in each category (mild cases remaining at home, moderate cases requiring outpatient care and severe cases demanding hospitalization). The result of the calculations and analysis revealed that the annual number of Shigella infections throughout the world was estimated to be 164.7 million. 163.2 million occurred in developing countries, with 1.1 million deaths, and 1.5 million occurred in industrialized countries. More than half of the episodes and death affects children under 5 years of age. In comparing developing countries against industrialized countries, the median of isolates are S. flexneri (60% vs. 16%), S. sonnei (15% vs. 77%), S. dysenteriae (6% vs. 1%), and S. boydii (6% vs. 2%). The predominant serotype of S. flexneri in developing countries is 2a, followed by 1b, 3a, 4a, and 6, while in industrialized countries most isolates are S. flexneri 2a and unspecified type 2 strains.

Redefining Chronic Viral Infection

2009-07-01

Herbert W. Virgin , E. John Wherry , Rafi Ahmed

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Broadly Reactive and Highly Sensitive Assay for Norwalk-Like Viruses Based on Real-Time Quantitative Reverse Transcription-PCR

2003-04-01

Tsutomu Kageyama , Shigeyuki Kojima , Michiyo Shinohara +5 more

We have developed an assay for the detection of Norwalk-like viruses (NLVs) based on reverse transcription-PCR (RT-PCR) that is highly sensitive to a broad range of NLVs. We isolated virus … We have developed an assay for the detection of Norwalk-like viruses (NLVs) based on reverse transcription-PCR (RT-PCR) that is highly sensitive to a broad range of NLVs. We isolated virus from 71 NLV-positive stool specimens from 37 outbreaks of nonbacterial acute gastroenteritis and sequenced the open reading frame 1 (ORF1)-ORF2 junction region, the most conserved region of the NLV genome. The data were subjected to multiple-sequence alignment analysis and similarity plot analysis. We used the most conserved sequences that react with diverse NLVs to design primers and TaqMan probes for the respective genogroups of NLV, GI and GII, for use in a real-time quantitative RT-PCR assay. Our method detected NLV in 99% (80 of 81) of the stool specimens that were positive by electron microscopy, a better detection rate than with the two available RT-PCR methods. Furthermore, our new method also detected NLV in 20 of 28 stool specimens from the same NLV-related outbreaks that were negative for virus by electron microscopy. Our new assay is free from carryover DNA contamination and detects low copy numbers of NLV RNA. It can be used as a routine assay for diagnosis as well as for elucidation of the epidemiology of NLV infections.

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The global burden of typhoid fever.

2004-05-01

John A. Crump , Stephen P. Luby , Eric D. Mintz

To use new data to make a revised estimate of the global burden of typhoid fever, an accurate understanding of which is necessary to guide public health decisions for disease … To use new data to make a revised estimate of the global burden of typhoid fever, an accurate understanding of which is necessary to guide public health decisions for disease control and prevention efforts.Population-based studies using confirmation by blood culture of typhoid fever cases were sought by computer search of the multilingual scientific literature. Where there were no eligible studies, data were extrapolated from neighbouring countries and regions. Age-incidence curves were used to model rates measured among narrow age cohorts to the general population. One-way sensitivity analysis was performed to explore the sensitivity of the estimate to the assumptions. The burden of paratyphoid fever was derived by a proportional method.A total of 22 eligible studies were identified. Regions with high incidence of typhoid fever (>100/100,000 cases/year) include south-central Asia and south-eastAsia. Regions of medium incidence (10-100/100,000 cases/year) include the rest of Asia, Africa, Latin America and the Caribbean, and Oceania, except for Australia and New Zealand. Europe, North America, and the rest of the developed world have low incidence of typhoid fever (<10/100,000 cases/year). We estimate that typhoid fever caused 21,650,974 illnesses and 216,510 deaths during 2000 and that paratyphoid fever caused 5,412,744 illnesses.New data and improved understanding of typhoid fever epidemiology enabled us to refine the global typhoid burden estimate, which remains considerable. More detailed incidence studies in selected countries and regions, particularly Africa, are needed to further improve the estimate.

Visualization by Immune Electron Microscopy of a 27-nm Particle Associated with Acute Infectious Nonbacterial Gastroenteritis

1972-11-01

Albert Z. Kapikian , Richard G. Wyatt , Raphael Dolin +3 more

A 27-nm particle was observed by immune electron microscopy in an infectious stool filtrate derived from an outbreak in Norwalk, Ohio, of acute infectious nonbacterial gastroenteritis. Both experimentally and naturally … A 27-nm particle was observed by immune electron microscopy in an infectious stool filtrate derived from an outbreak in Norwalk, Ohio, of acute infectious nonbacterial gastroenteritis. Both experimentally and naturally infected individuals developed serological evidence of infection; this along with other evidence suggested that the particle was the etiological agent of Norwalk gastroenteritis.

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Full Genome-Based Classification of Rotaviruses Reveals a Common Origin between Human Wa-Like and Porcine Rotavirus Strains and Human DS-1-Like and Bovine Rotavirus Strains

2008-01-24

Jelle Matthijnssens , Max Ciarlet , Erica Heiman +7 more

ABSTRACT Group A rotavirus classification is currently based on the molecular properties of the two outer layer proteins, VP7 and VP4, and the middle layer protein, VP6. As reassortment of … ABSTRACT Group A rotavirus classification is currently based on the molecular properties of the two outer layer proteins, VP7 and VP4, and the middle layer protein, VP6. As reassortment of all the 11 rotavirus gene segments plays a key role in generating rotavirus diversity in nature, a classification system that is based on all the rotavirus gene segments is desirable for determining which genes influence rotavirus host range restriction, replication, and virulence, as well as for studying rotavirus epidemiology and evolution. Toward establishing such a classification system, gene sequences encoding VP1 to VP3, VP6, and NSP1 to NSP5 were determined for human and animal rotavirus strains belonging to different G and P genotypes in addition to those available in databases, and they were used to define phylogenetic relationships among all rotavirus genes. Based on these phylogenetic analyses, appropriate identity cutoff values were determined for each gene. For the VP4 gene, a nucleotide identity cutoff value of 80% completely correlated with the 27 established P genotypes. For the VP7 gene, a nucleotide identity cutoff value of 80% largely coincided with the established G genotypes but identified four additional distinct genotypes comprised of murine or avian rotavirus strains. Phylogenetic analyses of the VP1 to VP3, VP6, and NSP1 to NSP5 genes showed the existence of 4, 5, 6, 11, 14, 5, 7, 11, and 6 genotypes, respectively, based on nucleotide identity cutoff values of 83%, 84%, 81%, 85%, 79%, 85%, 85%, 85%, and 91%, respectively. In accordance with these data, a revised nomenclature of rotavirus strains is proposed. The novel classification system allows the identification of (i) distinct genotypes, which probably followed separate evolutionary paths; (ii) interspecies transmissions and a plethora of reassortment events; and (iii) certain gene constellations that revealed (a) a common origin between human Wa-like rotavirus strains and porcine rotavirus strains and (b) a common origin between human DS-1-like rotavirus strains and bovine rotaviruses. These close evolutionary links between human and animal rotaviruses emphasize the need for close simultaneous monitoring of rotaviruses in animals and humans.

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Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants

2010-01-27

Shabir A. Madhi , Nigel A. Cunliffe , A. Duncan Steele +7 more

Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.We conducted a randomized, … Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.).

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Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study

2013-05-14

Karen L. Kotloff , James P. Nataro , William C. Blackwelder +7 more

Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis

2014-06-26

Sharia M. Ahmed , Aron J. Hall , Anne E. Robinson +5 more

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Food-borne diseases — The challenges of 20years ago still persist while new ones continue to emerge

2010-01-25

Diane G. Newell , Marion Koopmans , Linda Verhoef +7 more

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Global Illness and Deaths Caused by Rotavirus Disease in Children

2003-05-01

Umesh D. Parashar , Erik Hummelman , Joseph Bresee +2 more

Abstract To estimate the global illness and deaths caused by rotavirus disease, we reviewed studies published from 1986 to 2000 on deaths caused by diarrhea and on rotavirus infections in … Abstract To estimate the global illness and deaths caused by rotavirus disease, we reviewed studies published from 1986 to 2000 on deaths caused by diarrhea and on rotavirus infections in children. We assessed rotavirus-associated illness in three clinical settings (mild cases requiring home care alone, moderate cases requiring a clinic visit, and severe cases requiring hospitalization) and death rates in countries in different World Bank income groups. Each year, rotavirus causes approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000–592,000 deaths (median, 440,000 deaths) in children <5 years of age. By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 60 will be hospitalized, and approximately 1 in 293 will die. Children in the poorest countries account for 82% of rotavirus deaths. The tremendous incidence of rotavirus disease underscores the urgent need for interventions, such as vaccines, to prevent childhood deaths in developing nations.

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Foodborne Illness Acquired in the United States—Major Pathogens

2010-12-27

Elaine Scallan , Robert M. Hoekstra , Frederick J. Angulo +5 more

Estimates of foodborne illness can be used to direct food safety policy and interventions. We used data from active and passive surveillance and other sources to estimate that each year … Estimates of foodborne illness can be used to direct food safety policy and interventions. We used data from active and passive surveillance and other sources to estimate that each year 31 major pathogens acquired in the United States caused 9.4 million episodes of foodborne illness (90% credible interval [CrI] 6.6-12.7 million), 55,961 hospitalizations (90% CrI 39,534-75,741), and 1,351 deaths (90% CrI 712-2,268). Most (58%) illnesses were caused by norovirus, followed by nontyphoidal Salmonella spp. (11%), Clostridium perfringens (10%), and Campylobacter spp. (9%). Leading causes of hospitalization were nontyphoidal Salmonella spp. (35%), norovirus (26%), Campylobacter spp. (15%), and Toxoplasma gondii (8%). Leading causes of death were nontyphoidal Salmonella spp. (28%), T. gondii (24%), Listeria monocytogenes (19%), and norovirus (11%). These estimates cannot be compared with prior (1999) estimates to assess trends because different methods were used. Additional data and more refined methods can improve future estimates.

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X-ray Crystallographic Structure of the Norwalk Virus Capsid

1999-10-08

B. V. Venkataram Prasad , Michele E. Hardy , Terje Dokland +3 more

Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a … Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded β-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor–Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.

2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis

2011-11-14

Jacqueline E. Tate , Anthony Burton , Cynthia Boschi-Pinto +3 more

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European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases Evidence‐Based Guidelines for the Management of Acute Gastroenteritis in Children in Europe

2014-04-01

Alfredo Guarino , Shai Ashkenazi , D Gendrel +3 more

ABSTRACT Objectives: These guidelines update and extend evidence‐based indications for the management of children with acute gastroenteritis in Europe. Methods: The guideline development group formulated questions, identified data, and formulated … ABSTRACT Objectives: These guidelines update and extend evidence‐based indications for the management of children with acute gastroenteritis in Europe. Methods: The guideline development group formulated questions, identified data, and formulated recommendations. The latter were graded with the Muir Gray system and, in parallel, with the Grading of Recommendations, Assessment, Development and Evaluations system. Results: Gastroenteritis severity is linked to etiology, and rotavirus is the most severe infectious agent and is frequently associated with dehydration. Dehydration reflects severity and should be monitored by established score systems. Investigations are generally not needed. Oral rehydration with hypoosmolar solution is the major treatment and should start as soon as possible. Breast‐feeding should not be interrupted. Regular feeding should continue with no dietary changes including milk. Data suggest that in the hospital setting, in non–breast‐fed infants and young children, lactose‐free feeds can be considered in the management of gastroenteritis. Active therapy may reduce the duration and severity of diarrhea. Effective interventions include administration of specific probiotics such as Lactobacillus GG or Saccharomyces boulardii , diosmectite or racecadotril. Anti‐infectious drugs should be given in exceptional cases. Ondansetron is effective against vomiting, but its routine use requires safety clearance given the warning about severe cardiac effects. Hospitalization should generally be reserved for children requiring enteral/parenteral rehydration; most cases may be managed in an outpatients setting. Enteral rehydration is superior to intravenous rehydration. Ultrarapid schemes of intravenous rehydration are not superior to standard schemes and may be associated with higher readmission rates. Conclusions: Acute gastroenteritis is best managed using a few simple, well‐defined medical interventions.

Linguistic theory and psychological reality

1979-08-01

Ruth A. Berman

Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine

2006-01-04

Timo Vesikari , David O. Matson , Penelope H. Dennehy +7 more

Rotavirus is a leading cause of childhood gastroenteritis and death worldwide.We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of … Rotavirus is a leading cause of childhood gastroenteritis and death worldwide.We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events.The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent).This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

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Norovirus classification and proposed strain nomenclature

2005-12-16

Du-Ping Zheng , Tamie Ando , Rebecca L. Fankhauser +3 more

Measuring the optimal exposure for single particle cryo-EM using a 2.6 Å reconstruction of rotavirus VP6

2015-05-29

Timothy Grant , Nikolaus Grigorieff

Biological specimens suffer radiation damage when imaged in an electron microscope, ultimately limiting the attainable resolution. At a given resolution, an optimal exposure can be defined that maximizes the signal-to-noise … Biological specimens suffer radiation damage when imaged in an electron microscope, ultimately limiting the attainable resolution. At a given resolution, an optimal exposure can be defined that maximizes the signal-to-noise ratio in the image. Using a 2.6 Å resolution single particle cryo-EM reconstruction of rotavirus VP6, determined from movies recorded with a total exposure of 100 electrons/Å(2), we obtained accurate measurements of optimal exposure values over a wide range of resolutions. At low and intermediate resolutions, our measured values are considerably higher than obtained previously for crystalline specimens, indicating that both images and movies should be collected with higher exposures than are generally used. We demonstrate a method of using our optimal exposure values to filter movie frames, yielding images with improved contrast that lead to higher resolution reconstructions. This 'high-exposure' technique should benefit cryo-EM work on all types of samples, especially those of relatively low-molecular mass.

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Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine

2004-10-14

Norma Santos , Yasutaka Hoshino

A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and … A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and P serotypes/genotypes throughout the world. The temporal and geographical distribution of human rotavirus G and P types was reviewed by analysing a total of 45571 strains collected globally from 124 studies reported from 52 countries on five continents published between 1989 and 2004. Four common G types (G1, G2, G3 and G4) in conjunction with P[8] or P[4] represented over 88% of the strains analysed worldwide. In addition, serotype G9 viruses associated with P[8] or P[6] were shown to have emerged as the fourth globally important G type with the relative frequency of 4.1%. When the global G and/or P type distributions were divided into five continents/subcontinents, several characteristic features emerged. For example, the P[8]G1 represented over 70% of rotavirus infections in North America, Europe and Australia, but only about 30% of the infections in South America and Asia, and 23% in Africa. In addition, in Africa (i) the relative frequency of G8 was as high as that of the globally common G3 or G4, (ii) P[6] represented almost one-third of all P types identified and (iii) 27% of the infections were associated with rotavirus strains bearing unusual combinations such as P[6]G8 or P[4]G8. Furthermore, in South America, uncommon G5 virus appeared to increase its epidemiological importance among children with diarrhea. Such findings have (i) confirmed the importance of continued active rotavirus strain surveillance in a variety of geographical settings and (ii) provided important considerations for the development and implementation of an effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the formulation of next generation multivalent vaccines).

Practice Guidelines for the Management of Infectious Diarrhea

2001-02-01

Richard L. Guerrant , Thomas Van Gilder , Theodore S. Steiner +7 more

The widening array of recognized enteric pathogens and the increasing demand for cost-containment sharpen the need for careful clinical and public health guidelines based on the best evidence currently available.Adequate … The widening array of recognized enteric pathogens and the increasing demand for cost-containment sharpen the need for careful clinical and public health guidelines based on the best evidence currently available.Adequate fluid and electrolyte replacement and maintenance are key to managing diarrheal illnesses.Thorough clinical and epidemiological evaluation must define the severity and type of illness (e.g., febrile, hemorrhagic, nosocomial, persistent, or inflammatory), exposures (e.g., travel, ingestion of raw or undercooked meat, seafood, or milk products, contacts who are ill, day care or institutional exposure, recent antibiotic use), and whether the patient is immunocompromised, in order to direct the performance of selective diagnostic cultures, toxin testing, parasite studies, and the administration of antimicrobial therapy (the latter as for traveler's diarrhea, shigellosis, and possibly Campylobacter jejuni enteritis).Increasing numbers of isolates resistant to antimicrobial agents and the risk of worsened illness (such as hemolytic uremic syndrome with Shiga toxin-producing Escherichia coli O157:H7) further complicate antimicrobial and antimotility drug

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Systematic Literature Review of Role of Noroviruses in Sporadic Gastroenteritis

2008-08-01

Manish M. Patel , Marc‐Alain Widdowson , Roger I. Glass +3 more

Abstract We conducted a systematic review of studies that used reverse transcription–PCR to diagnose norovirus (NoV) infections in patients with mild or moderate (outpatient) and severe (hospitalized) diarrhea. NoVs accounted … Abstract We conducted a systematic review of studies that used reverse transcription–PCR to diagnose norovirus (NoV) infections in patients with mild or moderate (outpatient) and severe (hospitalized) diarrhea. NoVs accounted for 12% (95% confidence interval [CI] 10%–15%) of severe gastroenteritis cases among children <5 years of age and 12% (95% CI 9%–15%) of mild and moderate diarrhea cases among persons of all ages. Of 19 studies among children <5 years of age, 7 were in developing countries where pooled prevalence of severe NoV disease (12%) was comparable to that for industrialized countries (12%). We estimate that each year NoVs cause 64,000 episodes of diarrhea requiring hospitalization and 900,000 clinic visits among children in industrialized countries, and up to 200,000 deaths of children <5 years of age in developing countries. Future efforts should focus on developing targeted strategies, possibly even vaccines, for preventing NoV disease and better documenting their impact among children living in developing countries, where >95% of the deaths from diarrhea occur.

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Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis

2006-01-04

Guillermo M. Ruiz‐Palacios , Irene Pérez‐Schael , F. Raúl Velázquez +7 more

The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.We studied 63,225 healthy infants from 11 Latin American countries … The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

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Microbial Ecology and Evolution: A Ribosomal RNA Approach

1986-10-01

G J Olsen , David Lane , Stephen J. Giovannoni +2 more

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute … Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More

World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis

2015-12-03

Martyn Kirk , Sara M. Pires , Robert E. Black +7 more

Background Foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most … Background Foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases. Methods and Findings We synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990–2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5–2.9 billion) cases, over one million (95% UI 0.89–1.4 million) deaths, and 78.7 million (95% UI 65.0–97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23–36%) of cases caused by diseases in our study, or 582 million (95% UI 401–922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5–37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70–251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52–177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49–6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne. Conclusions Foodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings.

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Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000–2013

2016-04-08

Jacqueline E. Tate , Anthony Burton , Cynthia Boschi-Pinto +1 more

Background. Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and … Background. Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children <5 years of age from 2000 to 2013. Methods. We searched PubMed using the keyword "rotavirus" to identify studies that met each of the following criteria: data collection midpoint in year 1998 or later, study period of a 12-month increment, and detection of rotavirus infection by enzyme immunoassay in at least 100 children <5 years of age who were hospitalized with diarrhea and systematically enrolled through active surveillance. We also included data from countries that participated in the World Health Organization (WHO)–coordinated rotavirus surveillance network between 2008 and 2013 that met these criteria. To predict the proportion of diarrhea due to rotavirus, we constructed a multiple linear regression model. To determine the number of rotavirus deaths in children <5 years of age from 2000 to 2013, we multiplied annual, country-specific estimates of the proportion of diarrhea due to rotavirus from the regression model by the annual number of WHO-estimated child deaths caused by diarrhea in each country. Results. Globally, we estimated that the number of rotavirus deaths in children <5 years of age declined from 528 000 (range, 465 000–591 000) in 2000 to 215 000 (range, 197 000–233 000) in 2013. The predicted annual rotavirus detection rate from these studies declined slightly over time from 42.5% (95% confidence interval [CI], 37.4%–47.5%) in 2000 to 37.3% (95% CI, 34.2%–40.5%) in 2013 globally. In 2013, an estimated 47 100 rotavirus deaths occurred in India, 22% of all rotavirus deaths that occurred globally. Four countries (India, Nigeria, Pakistan, and Democratic Republic of Congo) accounted for approximately half (49%) of all estimated rotavirus deaths in 2013. Discussion. While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.

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Intussusception among Infants Given an Oral Rotavirus Vaccine

2001-02-22

Trudy V. Murphy , Paul Gargiullo , Mehran S. Massoudi +7 more

Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases … Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus–human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System.

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Bergey's manual of determinative bacteriology

1975-05-01

Thomas C. Cheng

Replication of human noroviruses in stem cell–derived human enteroids

2016-08-26

Khalil Ettayebi , Sue E. Crawford , Kosuke Murakami +7 more

The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the … The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the leading cause of gastroenteritis worldwide. We report the successful cultivation of multiple HuNoV strains in enterocytes in stem cell–derived, nontransformed human intestinal enteroid monolayer cultures. Bile, a critical factor of the intestinal milieu, is required for strain-dependent HuNoV replication. Lack of appropriate histoblood group antigen expression in intestinal cells restricts virus replication, and infectivity is abrogated by inactivation (e.g., irradiation, heating) and serum neutralization. This culture system recapitulates the human intestinal epithelium, permits human host-pathogen studies of previously noncultivatable pathogens, and allows the assessment of methods to prevent and treat HuNoV infections.

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Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

2017-06-28

Timothy P. Sheahan , Amy Sims , Rachel L. Graham +7 more

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses in vitro and in vivo. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses in vitro and in vivo.

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Genetic Analysis of Human Norovirus Strains in Japan in 2016–2017

2018-01-18

Koo Nagasawa , Yuki Matsushima , Takumi Motoya +7 more

In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution … In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the VP1 gene and RdRp region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains VP1 gene and RdRp region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the VP1 gene and RdRp region were around 10-3 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the VP1 gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.

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Structure of the RNA-dependent RNA polymerase from COVID-19 virus

2020-04-10

Yan Gao , Liming Yan , Yucen Huang +7 more

The COVID-19 RNA-synthesizing machine Many in the scientific community have mobilized to understand the virus that is causing the global coronavirus disease 2019 (COVID-19) pandemic. Gao et al. focused on … The COVID-19 RNA-synthesizing machine Many in the scientific community have mobilized to understand the virus that is causing the global coronavirus disease 2019 (COVID-19) pandemic. Gao et al. focused on a complex that plays a key role in the replication and transcription cycle of the virus. They used cryo–electron microscopy to determine a 2.9-angstrom-resolution structure of the RNA-dependent RNA polymerase nsp12, which catalyzes the synthesis of viral RNA, in complex with two cofactors, nsp7 and nsp8. nsp12 is a target for nucleotide analog antiviral inhibitors such as remdesivir, and the structure may provide a basis for designing new antiviral therapeutics. Science , this issue p. 779

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Human Retroviruses and Aids - 1999

1999-01-01

Carla Kuiken , Brian Foley

a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been … a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. In addition to the general descriptions below of the parts of the compendium, the user should read the individual introductions for each part.

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Norovirus Gastroenteritis

2009-10-28

Roger I. Glass , Umesh D. Parashar , Mary K. Estes

Noroviruses are now recognized as the leading cause of epidemics of gastroenteritis and an important cause of sporadic gastroenteritis among both children and adults. In the United States, more than … Noroviruses are now recognized as the leading cause of epidemics of gastroenteritis and an important cause of sporadic gastroenteritis among both children and adults. In the United States, more than 90% of the outbreaks of gastroenteritis for which the cause could not previously be identified can now be attributed to this virus. Understanding the nature of immunity to the norovirus is a key determinant for future improvements in the control and prevention of this viral infection.

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Monoclonal antibodies: their place in applied medicine and their role in the newest infectious disease – history, present, and future. Literature review

2025-06-25

Petar Atanasov , Maria Moneva-Sakelarieva , Yozlem Ali Kobakova +7 more | Pharmacia

Monoclonal antibodies (mAbs) are immunoglobulins with practically absolute specificity (monospecificity) for a particular antigen (epitope). Over the past three decades, monoclonal antibodies have undergone a remarkable transformation, evolving from their … Monoclonal antibodies (mAbs) are immunoglobulins with practically absolute specificity (monospecificity) for a particular antigen (epitope). Over the past three decades, monoclonal antibodies have undergone a remarkable transformation, evolving from their use predominantly as research tools to becoming increasingly powerful therapeutic agents in medical practice. Personalized therapy and targeted treatment of diseases form the cornerstone of modern medicine’s revolutionary capabilities. Monoclonal antibodies are a shining example of personalized therapy, developed based on deep and continuously growing knowledge in the fields of immunology, molecular biology, and biochemistry. The accepted nomenclature for monoclonal antibody names indicates their origin: murine (-omab), chimeric (-ximab), humanized (-zumab), or recombinant (-umab). Monoclonal antibodies belong to the IgG class. Monoclonal antibodies of this class possess specific properties and advantages. They are characterized by optimal pharmacokinetics, stability, and low immunogenicity (especially recombinant forms), a low toxicity profile, and the capacity for large-scale production of specific monoclonal antibodies targeting diverse antigens. The mechanisms of action of monoclonal antibodies include direct cell toxicity, immune-mediated cell destruction, vascular destruction, and immunomodulatory functions. The pathophysiology of many conditions treated with monoclonal antibodies is equally intricate, involving numerous cells and molecules. Monoclonal antibodies, in general, are characterized by good tolerance. The scientific community continues its efforts to enhance their efficacy, reduce their immunogenicity, and optimize their pharmacokinetic properties, as well as attempts to achieve oral (mucosal) bioavailability. The use of monoclonal antibodies in modern medicine is continuously expanding, with their incorporation into therapeutic regimens for numerous severe non-malignant diseases such as asthma, atopic dermatitis, migraine, hypercholesterolemia, osteoporosis, bacterial infections (e.g., anthrax), and viral infections (such as COVID-19). Efforts are being directed not only at improving the structural and functional properties of existing monoclonal antibodies but also at creating new types of antibodies with smaller molecular weights and higher specificity. As a next generation of nanobiotechnology, natural and synthetic nanobodies have been utilized in numerous fields of biomedicine, including as biomolecular materials, for various biological studies, and in medical diagnostics and immunotherapy. Monoclonal antibodies and antibody-based molecules offer a reliable opportunity to effectively counter emerging viral pathogens and antibiotic-resistant bacteria. When administered to patients with a healthy immune system, they can provide necessary prophylaxis against specific diseases, acting as vaccine-like molecules and promoting long-term, antimicrobial-specific immune responses. Monoclonal antibodies have been identified as a potentially effective therapy for preventing the progression of COVID-19 in patients at high risk of developing severe disease.

First report of inter-species recombinant Gyroviruses in Chinese urban companion animals with cross-species transmission risks

2025-06-25

Zhibin Zhang , Xin Xu , Dandan Li +4 more | Frontiers in Veterinary Science

Environmental stress drives clearance of a persistent enteric virus in mice

2025-06-25

Christin Herrmann , Kimberly Zaldaña , A. Lustig +4 more | Nature Microbiology

Immunotherapeutic potential of Dalbergia sissoo and Aegle marmelos extracts for managing colibacillosis in neonatal calves in Rajasthan, India

2025-06-24

T. C. Nayak , Ajit Singh , Shweta Gupta +3 more | Molecular Biology Reports

Egress-enhancing mutation reveals the inefficiency of non-enveloped virus cell exit

2025-06-24

Valerie J. Rodriguez-Irizarry , Robert W. Maples , Julie K. Pfeiffer | PLoS Biology

Viruses encounter a range of selective pressures, but inefficiencies during replication can be masked. To uncover factors that limit viral replication, we used forward genetics to enrich for a murine … Viruses encounter a range of selective pressures, but inefficiencies during replication can be masked. To uncover factors that limit viral replication, we used forward genetics to enrich for a murine norovirus (MNV) mutant with faster replication. We sequentially harvested the earliest progeny in cultured cells and identified a single amino acid change in the viral NS3 protein, K40R, that was sufficient to enhance replication speed. We found that the NS3-K40R virus induced earlier cell death and viral egress compared with wild-type virus. Mechanistically, NS3-K40R protein disrupted membranes more efficiently than wild-type NS3 protein, potentially contributing to increased mitochondrial dysfunction and cell death. Immunodeficient mice infected with NS3-K40R virus had increased titers, suggesting that increasing egress did not reduce fitness in vivo. Overall, by using a forward genetic approach, we identified a previously unknown inefficiency in norovirus egress and provide new insights into selective pressures that influence viral replication and evolution.

Zoonotic and Environmental Sources of Infant Enteric Pathogen Infections Identified with Longitudinal Sampling

2025-06-23

Abigail Harvey Paulos , John Mboya , Jeremy Lowe +7 more | Environmental Science & Technology

Many enteric pathogens that infect young children can be zoonotic, yet the exposure risk of domestic animals living in close proximity to young children is poorly understood. Here, we longitudinally … Many enteric pathogens that infect young children can be zoonotic, yet the exposure risk of domestic animals living in close proximity to young children is poorly understood. Here, we longitudinally measured 33 enteric pathogens in child stool, animal feces, and the household environment (n = 28,743 pathogen-sample observations) to investigate pathogen transmission between animals and children under two in pastoralist communities in rural Northern Kenya. Children were typically infected with 1 enteric pathogen by 3 months of age, and pathogen burden increased with age; 85% of enteric pathogens detected in child stool were also detected in animal feces. New infections in children were associated with preceding household detection of the same pathogen in soil (Odds ratio: 8.8, 95% confidence interval: 3.3-23) and on child hands (odds ratio: 5.0, 95% confidence interval 1.1-17). Regression modeling revealed transmission of pathogens from poultry, dog, and ruminant feces to household soil, and between child hands and child stool. Our results provide new evidence that domestic animals in the household environment contribute to early life enteric pathogen exposure, and that child hand hygiene could substantially prevent animal-child transmission.

Localized impact of zinc and probiotics on antibiotic-associated diarrhea in children: a perspective from southern Iran

2025-06-23

Mohammad Bagher Rahmati , Razie Khodadadzade , Mehran Ahmadi +1 more | Deleted Journal

Incidence of Human Sapovirus Outbreaks in Beijing, China, 2014–2021: Predominance of Genotypes GII.3 and GI.2

2025-06-23

Lingyu Shen , Yu Fan , Hanqiu Yan +7 more | Emerging Microbes & Infections

The study aimed to analyze epidemiological, clinical, and genome characteristics of acute gastroenteritis (AGE) outbreaks caused by sapovirus in Beijing. Epidemiological and clinical characteristics of sapovirus detected by RT-qPCR were … The study aimed to analyze epidemiological, clinical, and genome characteristics of acute gastroenteritis (AGE) outbreaks caused by sapovirus in Beijing. Epidemiological and clinical characteristics of sapovirus detected by RT-qPCR were collected from AGE surveillance. Descriptive statistics were used for epidemiological analysis, and both genotype identification and sequence analysis were conducted on the VP1 regions, RNA-dependent RNA polymerase regions, and whole genomes. From 2014 to 2021, sapovirus was the second most common pathogen in AGE outbreaks, causing 216 outbreaks (6.85%) with peaks in 2017, 2019, and 2021. The predominant outbreaks occurred in kindergartens (76.39%, 165) and primary schools (18.98%, 41) within urban (62.96%, 136) and suburban (35.19%, 76) by person-to-person transmission (97.73%, 172). Outbreaks in outer suburbs lasted longer duration[median 7 days, IQR: 6-8)]. Comprehensive schools (21.62%, IQR: 10.00-35.00%) and kindergartens (18.18%, IQR: 13.51-22.72%) showed higher attack rates. Clinical symptoms included vomiting (97.27%, 1,462), diarrhea (18.44%, 277), fever (8.32%, 125), nausea (28.72%, 432), and abdominal pain (33.94%, 510). Vomiting prevalence was higher in children aged ≤5 years (96.94%, 983/1,014), while diarrhea prevalence was higher in those >5 years (31.29%, 153/489). Eight genotypes (GI.1-3, 5, 6; GII.1, 3, 5) were identified, and the predominant genotype changed from GII.3 (2016-2019) to GI.2 (2020-2021). Phylogenetic analysis revealed emerging clades in GII.3 and GI.2, with nucleotides and amino acids mutations confirmed by whole-genome sequencing. Therefore, sapovirus is a significant AGE pathogen in Beijing, China, warranting its inclusion in surveillance among sporadic outbreaks of AGE in China necessitating genotyping and whole-genome sequencing.

Detection of Murine Norovirus on Fresh Produce Through a CRISPR/Cas13a RNase-Based Capsid Integrity Assay

2025-06-21

Axel Ossio , José Ángel Merino-Mascorro , Juan S. León +2 more | Food and Environmental Virology

Microbiological and Biochemical Characterization of Plant Based Vegan Curd

2025-06-21

Vichitra Kaushik , Ram Kumar Pundir , Rekha Yadav | Microbiology Research Journal International

Curd is a traditional food which is high in nutrition and helps in boosting immunity. Curd has-been consumed worldwide and has health gut bacteria that fights against harmful pathogenic bacteria. … Curd is a traditional food which is high in nutrition and helps in boosting immunity. Curd has-been consumed worldwide and has health gut bacteria that fights against harmful pathogenic bacteria. Curd is coagulated using milk. Since some people experience lactose intolerance, plant based curd is advised for their intake. In this study we will explore the good gut bacteria and other microorganisms present in the homemade vegan curd. This plant-based curd is made of peanut milk and rice milk and Green chilli pedicels are added for fermentation process that helps in curdling of milk. Peanuts are rich in antioxidants and they have health gut bacteria and fibres. Rice contains bacteria like Bacilli Green chillies consist of Lactobacilli and is also a starter for lactose fermentation. The homemade Vegan curd is rich in protein and carbohydrates. This research involved creating peanut curd from peanut milk using green chillies as a starter. Both the total bacterial count and the total yeast mold count were measured. Vegan curd, which serves as a plant-based substitute for dairy yogurt, has the potential to contain harmful microorganisms. Such contamination arises when undesirable bacteria and fungi proliferate in the product.

Beyond Cold Chain: Exploring Bacterial-Viral Interactions and Disinfection Strategies for Norovirus Persistence on Organic Lettuce under Temperature Fluctuations

2025-06-21

Xinyun Chen , Weiguo Hong , Peng Tian +4 more | Journal of Hazardous Materials

Epidemiology, Prevention and Control of Foodborne Microbial Pathogens

2025-06-20

Gabriel Augusto Marques Rossi , Juliano Gonçalves Pereira , Márcia Nitschke | Microorganisms

Foodborne diseases are caused by the consumption of food or water contaminated with bacteria and their toxins, viruses, parasites, or chemical substances [...] Foodborne diseases are caused by the consumption of food or water contaminated with bacteria and their toxins, viruses, parasites, or chemical substances [...]

Unresolved Chronic Diarrhea: The Importance of Maintaining a Broad Differential

2025-06-20

Victoria Gregorio , Narayanan Venkatasubramani | Clinical Pediatrics

Genomic insight of avian reovirus circulating among desi-chickens in Tamil Nadu, South India.

2025-06-20

M Pranay , A. Balasubramaniam , P. Ponmurugan +2 more | PubMed

Avian reovirus (ARV) is a major causative agent of viral arthritis (VA), tenosynovitis, and malabsorption syndrome (MAS) in chickens, with significant economic consequences due to growth retardation, reduced production performance, … Avian reovirus (ARV) is a major causative agent of viral arthritis (VA), tenosynovitis, and malabsorption syndrome (MAS) in chickens, with significant economic consequences due to growth retardation, reduced production performance, and immunosuppression. Despite routine vaccination of breeder chickens against ARV, cases of VA and MAS continue to be reported in commercial flocks in recent years. Moreover, there is a lack of recent data on the genetic characteristics of circulating field ARV strains in India. In light of these concerns, a study was conducted to investigate the involvement of ARV in chickens exhibiting clinical signs suggestive of VA or MAS. Samples were collected from 27 commercial broiler and desi-chicken flocks across the mid-western region of Tamil Nadu, South India. Molecular confirmation was performed using reverse transcription polymerase chain reaction (RT-PCR) targeting a partial region of the σC gene within the S1 segment. Of the 27 flocks sampled, only two samples - both from desi-chickens aged two and three weeks - tested positive for ARV. Sequence analysis of these positive samples, compared against available ARV sequences in GenBank (including vaccine strains) revealed that the identified strains clustered within ARV genogroup II. This represents the first report of cluster II ARV in India, indicating the circulation of genetically distinct ARV strains in Indian poultry populations. These findings underscore the need for routine molecular surveillance of ARV genotypes in India and highlight the potential mismatch between circulating field strains and current vaccine strains. Comprehensive genotype monitoring is essential to upgrade vaccine design and implement effective control strategies for ARV-associated diseases in Indian poultry production.

CRISPR-Cas12a/RPA Dual-Readout Assay for Rapid Field Detection of Porcine Rotavirus with Visualization

2025-06-20

Xinjie Jiang , Yun Huang , Yi Jiang +3 more | Viruses

PoRV is a significant etiological agent of neonatal diarrhea in piglets, resulting in substantial economic losses within the global swine industry due to elevated mortality rates and reduced productivity. To … PoRV is a significant etiological agent of neonatal diarrhea in piglets, resulting in substantial economic losses within the global swine industry due to elevated mortality rates and reduced productivity. To address the urgent need for accessible and rapid diagnostics in resource-limited settings, we have developed a CRISPR/Cas12a-based assay integrated with recombinase polymerase amplification (RPA) for the visual detection of PoRV. This platform specifically targets the conserved VP6 gene using optimized RPA primers and crRNA, harnessing Cas12a’s collateral cleavage activity to enable dual-readout via fluorescence or lateral flow dipsticks (LFDs). The assay demonstrates a detection limit of 102 copies/μL within 1 h, exhibiting no cross-reactivity with phylogenetically related pathogens such as Transmissible Gastroenteritis Virus (TGEV). By eliminating reliance on thermal cyclers or specialized equipment, this method is fully deployable in swine farms, veterinary clinics, or field environments. The lateral flow format provides immediate colorimetric results that require minimal technical expertise, while the fluorescence mode allows for semi-quantitative analysis. This study presents a robust and cost-effective platform for decentralized PoRV surveillance in swine populations, addressing the critical need for portable diagnostics in resource-limited settings and enhancing veterinary health management.

Virome profiling of long-tailed marmots reveals tissue tropism and cross-species transmission of a diversity of uncharacterized mammalian viruses

2025-06-20

Yi Le , Yan Liang , Guangzhi Yan +6 more | Research Square (Research Square)

<title>Abstract</title> Background Anthropogenic land conversion and population encroachment into wildlife habitats are amplifying zoonotic risks through intensified human-livestock-wildlife contacts. As ecologically resilient rodents exhibiting dynamic population fluxes, long-tailed marmots (<italic>Marmota … <title>Abstract</title> Background Anthropogenic land conversion and population encroachment into wildlife habitats are amplifying zoonotic risks through intensified human-livestock-wildlife contacts. As ecologically resilient rodents exhibiting dynamic population fluxes, long-tailed marmots (<italic>Marmota caudata</italic>) are crucial viral reservoirs in Central Asian ecosystems. Their sympatric coexistence with domestic herds creates sustained spillover risks, yet comprehensive virome characterization remains fragmented. This study pioneers a whole-virome profiling strategy to comprehensively characterize the viral diversity of 101 wild <italic>M. caudata</italic> across five habitats in Xinjiang, addressing critical knowledge gaps in rodent-borne zoonoses under anthropogenic pressures. Results Our study identified 3,314 viral contigs spanning 21 families, with intestinal and lung samples exhibiting the highest viral diversity. Organ-specific tropism was characterized by preferential niches, notably adenoviral predominance in intestinal ecosystems and herpesviral selectivity for lymph node microenvironments. Phylogenetic reconstruction revealed cross-species transmission of rotavirus and ephemerovirus from bovines to marmots, along with identification of 72 novel viruses expanding taxonomic diversity across 17 species and 2 genera. Particularly, two novel coronaviruses showing lung tropism are sufficiently divergent to be new subgenus candidates within the genus <italic>Betacoronavirus</italic>. Conclusions This comprehensive virome profiling delineates the ecological niches of marmot-associated viruses and identifies a diversity of uncharacterized mammalian viruses, including taxonomically novel lineages and multiple potential zoonotic pathogens requiring prioritized attention. These findings expand our understanding of the circulation dynamics and diverse background of marmot viruses, providing important reference data for developing surveillance frameworks and prevention strategies targeting zoonotic risks associated with this ecologically pivotal species.

Corrigendum: Commentary: Risk factors and early markers for echovirus type 11 associated haemorrhage-hepatitis syndrome in neonates, a retrospective cohort study

2025-06-20

Haider Al‐Hello , Soile Blomqvist , Carita Savolainen‐Kopra | Frontiers in Pediatrics

Replication of human enteric viruses from wastewater in saliva cell lines

2025-06-19

Sharon C Kosgei , Olivia N Birch , R. Rodríguez +2 more | The Science of The Total Environment

2023–2024년 대구ㆍ경북 수인성 및 식품매개감염병 유행 현황

2025-06-19

Seul Koo , Sookhyun Kim , Myung-Jae Hwang +3 more | Public Health Weekly Report

Inactivation of Influenza A Viruses (H1N1, H5N1) During Grana-Type Raw Milk Cheesemaking: Implications for Foodborne Transmission Risk

2025-06-18

Ana Moreno , Stefano Pongolini , Giuseppe Merialdi +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Background The detection of H5N1 highly pathogenic avian influenza virus (HPAIV) in lactating dairy cattle in the United States, with high viral titers in raw milk, has raised concerns … Abstract Background The detection of H5N1 highly pathogenic avian influenza virus (HPAIV) in lactating dairy cattle in the United States, with high viral titers in raw milk, has raised concerns about potential zoonotic transmission through the consumption of unpasteurized milk and raw-milk dairy products. While inactivation studies exist for pasteurized milk, data on virus persistence during the manufacture of raw-milk cheeses remain scarce. Aim To evaluate the survival and inactivation of avian influenza viruses (AIV), including both low pathogenic (LPAIV, H1N1) and highly pathogenic (HPAIV, H5N1) strains, during the production and ripening of Grana-type hard cheeses made from raw cow’s milk. Methods Experimental cheesemaking was conducted using raw milk artificially contaminated with A/duck/Italy/281904-2/06 (H1N1; 107.75 EID 50 /mL) or A/duck/Italy/326224-2/22 (H5N1 clade 2.3.4.4b; 106.75 EID 50 /mL). Cheeses were produced in accordance with Parmigiano Reggiano production standards and ripened for 30 days at 5–6 °C. Viral presence was assessed in finished cheeses by inoculation on SPF embryonated chicken eggs (ECE), hemagglutination (HA) assay, and monoclonal antibody-based ELISA. Results No infectious virus was detected in any cheese sample produced from contaminated milk following two blind passages in SPF-ECE. Both HA and ELISA tests yielded negative results, indicating complete inactivation of the virus. Conclusion This study demonstrates that the traditional Grana-type cheese production process— including curd cooking, acidification, and ripening—effectively inactivates both LPAIV and HPAIV, even at high contamination levels. These findings support the microbiological safety of hard cheeses made from raw milk with regard to AIV, contributing to risk assessment and food safety policies during avian influenza outbreaks.

Genetic diversity of norovirus in Shenzhen Based on continuous surveillance from 2016 to 2022

2025-06-18

Xin Wang , Wanqiu Liu , Mingda Hu +7 more | Frontiers in Cellular and Infection Microbiology

Introduction Norovirus is a key pathogen of acute gastroenteritis and poses a significant burden on both the economy and public health. This study focuses on continuous monitoring of norovirus in … Introduction Norovirus is a key pathogen of acute gastroenteritis and poses a significant burden on both the economy and public health. This study focuses on continuous monitoring of norovirus in Shenzhen, China, from 2016 to 2022, aiming to analyze the epidemic characteristics and genetic diversity of norovirus in the context of global sequence data. Methods The study was based on data collected from local sentinel hospitals. It involved analyzing the demographic, spatial, and temporal distribution of norovirus infections. Phylogenetic analysis was conducted, and genotype dynamics were compared across geographic levels. Mutations affecting protein stability were evaluated, and recombination analysis was performed to identify critical breakpoints and fragments for norovirus. Results The study found that norovirus primarily infected infants under 3 years old, with epidemics occurring in winter and concentrated in developed districts. Phylogenetic analysis revealed both similarities and differences in the evolutionary patterns of various genotypes at different geographical levels. Mutations in the VP1 protein, based on the protein structure of GII.4_Sydney[P31], provided insights into the evolutionary trends of key genotypes. Additionally, recombination analysis identified important breakpoints and fragments for norovirus. Discussion The findings offer valuable insights to evolution and transmission of norovirus. These results can serve as a reference for future research, and they may aid in vaccine development efforts aimed at controlling norovirus outbreaks.

Antiviral Activity of Biocompatible Bionanocatalysts against Rotavirus

2025-06-18

T. López , Francisco J. Padilla-Godínez , G. De Rosa +1 more | ACS Omega

Impact of the COVID-19 pandemic and typhoid conjugate vaccine introduction on typhoid fever in Nepal

2025-06-18

Dipesh Tamrakar , Shivram Naga , Esther Jung +7 more | medRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Background While typhoid conjugate vaccines (TCV) offer promise for reducing risk in endemic settings, their population-level impact remains unclear. In 2022, Nepal introduced TCV nationally on the heels of … ABSTRACT Background While typhoid conjugate vaccines (TCV) offer promise for reducing risk in endemic settings, their population-level impact remains unclear. In 2022, Nepal introduced TCV nationally on the heels of the COVID-19 pandemic, which disrupted healthcare services, surveillance, and potentially typhoid transmission dynamics, complicating vaccine impact evaluation. We investigated the impact of TCV introduction amid shifting typhoid burden during the pandemic. Methods We analyzed blood culture data from four Kathmandu Valley health facilities, comparing culture positivity for Salmonella Typhi across three periods: pre-pandemic (January 2018-March 2020); pandemic, pre-vaccine introduction (April 2020-April 2022); post-vaccine introduction (May 2022-April 2024). We used multivariable logistic regression to assess S . Typhi positivity, adjusting for month and site, stratified by TCV-eligible children and older, TCV-ineligible populations. Results Between January 2018 and April 2024, 62,236 blood cultures were performed. S . Typhi blood culture positivity decreased from 2.11% pre-pandemic to 0.59% during the pandemic (p < 0.001) and remained low at 0.69% after TCV introduction. Among TCV-eligible children (15 months to 15 years), odds of S . Typhi positivity during the pandemic were 47% lower than the pre-COVID period (aOR 0.53, 95% CI 0.29-0.90) and continued to decrease by 76% post-TCV introduction (aOR 0.24, 95% CI 0.10-0.55). In contrast, among vaccine-ineligible individuals (≥16 years), odds of positivity during the pandemic were 78% lower than the pre-COVID period (aOR 0.22, 95% CI 0.16-0.30) but increased by 59% following TCV rollout (aOR 1.59, 95% CI 1.13-2.27). Sensitivity analyses restricted to pathogen-positive cultures yielded similar results. Conclusion S . Typhi blood culture positivity declined sharply during the pandemic before TCV introduction. The subsequent rollout of TCV substantially reduced typhoid burden in vaccine-eligible children; however, rising cases among older, vaccine-ineligible populations following the relaxation of pandemic measures highlights the need for additional control measures such as improved water and sanitation infrastructure and broader age eligibility for typhoid vaccination. AUTHOR SUMMARY Typhoid fever is a serious illness caused by bacteria that spread through contaminated food and water. In 2022, Nepal introduced a new typhoid vaccine for children, just as the country was recovering from the COVID-19 pandemic. The pandemic transformed how people accessed healthcare and may have also affected how typhoid spread. We wanted to understand how both the pandemic and the vaccine rollout influenced typhoid infections over time. Using results from four hospitals in the Kathmandu Valley between 2018 and 2024, we compared the number of typhoid cases before the pandemic, during the pandemic before typhoid vaccine introduction, and after typhoid vaccine introduction. We found that typhoid cases dropped sharply during the pandemic, even before the typhoid vaccine introduced. After the vaccine was introduced, typhoid continued to decline in children who were eligible for the vaccine. However, cases increased in people who were not vaccinated. Our findings show that the vaccine helped protect the age group that received it, but highlights the need for additional interventions such as improvements to sanitation and clean water infrastructure, and expanding vaccine access to more age groups to control typhoid in the future.

Comparison of classic and novel human astrovirus MLB and VA seroprevalence in HIV and non-HIV cohorts in South China demonstrates high seroreactivity to classic human astrovirus, which is associated with HIV infection

2025-06-18

J.-W. Wang , Bin-Yi Liu , Sisi Liu +5 more | Microbiology Spectrum

ABSTRACT Human astroviruses (HAstVs), including classic and novel clades (MLB, VA), are enteric pathogens with increasing clinical significance, particularly in immunocompromised populations. This cross-sectional study investigated HAstV seroprevalence and antibody … ABSTRACT Human astroviruses (HAstVs), including classic and novel clades (MLB, VA), are enteric pathogens with increasing clinical significance, particularly in immunocompromised populations. This cross-sectional study investigated HAstV seroprevalence and antibody response profiles in 197 individuals (101 HIV-positive and 96 HIV-negative) from Guangdong Province, South China. Recombinant HAstV1, MLB2, and VA1 spike proteins were expressed in Escherichia coli , structurally validated using AlphaFold2, and used in enzyme-linked immunosorbent assays-based serology with minimal cross-reactivity confirmed in murine models. Cohort study showed that HIV-positive individuals exhibited significantly higher HAstV1 seroreactivity (median OD450: 0.93 vs 0.64, P = 0.047) and an ordinal logistic regression revealed greater odds of stronger antibody responses to HAstV1 (adjusted odds ratio [aOR] = 1.91, P = 0.027). In contrast, VA1 seroprevalence was lower in HIV-positive participants (median OD450: 0.73 vs 1.02, P = 0.026), with reduced odds of high reactivity (aOR = 0.61, P = 0.089). In addition, VA1 demonstrated the highest overall seroprevalence (78.68%), followed by MLB2 (77.16%) and HAstV1 (75.13%), and significant associations between co-exposure to MLB2 and VA1 were observed by regression analysis (aOR = 1.60, P = 0.010). Together, these findings highlight distinct HIV-associated seroreactivity shifts in HAstV immunity, underscoring the regional importance of classic HAstV1 and the need for clade-specific surveillance in high-risk populations. IMPORTANCE Human astroviruses (HAstVs) are increasingly implicated in severe systemic and neurological infections, yet their seroepidemiology in immunocompromised populations remains poorly characterized. This study provides critical insights into the divergent immune responses to classic and novel HAstV clades among people living with HIV (PLWH) in southern China. We demonstrate that PLWH displayed heightened antibody responses to classic HAstV1 but reduced reactivity to MLB2, suggesting HIV-driven immune dysregulation may selectively boost infection with classic HAstV strains. These findings highlight the need for targeted surveillance and improved diagnostics for HAstV infections in high-risk populations.

Preparation and Serological Evaluation of an Inactivated Trivalent oil emulsion vaccine for Avian Fowl Adenovirus (FAdV) containing -8a, 8b, and 11 serotypes

2025-06-18

Fatimah Ibrahim , Hasnaa Maged , Mahmoud Ibrahim +4 more | Research Square (Research Square)

<title>Abstract</title> In recent years, inclusion bodies hepatitis (IBH) caused by fowl adenovirus (FAdV) species D and E led to significant economic losses in the poultry sector, worldwide. Therefore, this study … <title>Abstract</title> In recent years, inclusion bodies hepatitis (IBH) caused by fowl adenovirus (FAdV) species D and E led to significant economic losses in the poultry sector, worldwide. Therefore, this study aimed to assess the immunogenicity of an inactivated trivalent FAdV vaccine prepared with different payloads (107 TCID50, 106.8 TCID50, 106.5 TCID50) in commercial broiler chickens. The effects of booster immunization and thiomersal addition on the titers of developed antibodies were also evaluated. The virus propagated on liver primary cells for virus isolation and virus infectivity. Our results showed that group which vaccinated with a higher payload of the virus presented a prolonged immune response till the 6th week, compared to birds which were vaccinated with lowest dose of the virus of the trivalent vaccine. Also, birds which were vaccinated with the same vaccine containing thiomersal as a preservative, showed no significant reduction in immune response. For booster immunization, only high payload (107 TCID50 of each serotype/bird) increased the antibodies titers, specially at 2th and 3rd week post-vaccination. The obtained results suggested that the trivalent inactivated FAdv serotype 8a/8b/D vaccine at 107 TCID50 concentration of each serotype/bird at priming and booster vaccination could be used for the prevention and control of IBH.

Refining the role of ROTEM in ulcerative colitis: A critical perspective

2025-06-18

S. Uma Maheswari , Suprabhat Giri | Indian Journal of Gastroenterology

Identification and molecular characterization of subgroups GI.1 and GI.2 of Feline calicivirus in cats (Felis silvestris catus) from Metropolitan Region of Chile

2025-06-17

José Pizarro-Lucero , Marcela González , Claudia Yáñez +3 more | Microbial Pathogenesis

Integrative Structure of Norovirus NS3 Suggests a Role in RNA Transport

2025-06-17

Meryl Haas , Jake T. Mills , Cynthia Kelley +7 more | bioRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Human noroviruses (HuNoVs) are the leading global cause of non-bacterial gastroenteritis, yet no vaccines or antiviral therapies are currently approved 1 . The viral non-structural protein NS3 is a … ABSTRACT Human noroviruses (HuNoVs) are the leading global cause of non-bacterial gastroenteritis, yet no vaccines or antiviral therapies are currently approved 1 . The viral non-structural protein NS3 is a membrane-bound AAA+ ATPase of superfamily 3 (SF3) with multiple proposed roles in the norovirus replication cycle. However, the structure of NS3, and the mechanisms by which it contributes to genome replication and membrane remodeling, have remained unknown. We engineered a soluble, hexameric, and catalytically active form of NS3 and determined its cryo-EM structure in the presence of a nucleotide analogue at 2.9 Å resolution. The structure adopts a split lock-washer architecture characteristic of AAA+ motors that operate via a hand-over-hand translocation mechanism 2 . Modeling of the nucleotide-binding site reveals conserved features governing ATP binding and hydrolysis. Using integrative modeling with AlphaFold3, we generated a full-length, membrane-associated model of NS3, in which an N-terminal transmembrane domain, central helical bundle, and AAA+ motor form a continuous conduit. This model supports a role for NS3 as a candidate membrane-spanning RNA translocase that couples ATP hydrolysis to genome movement. This structural framework helps address long-standing gaps in our understanding of norovirus replication and establishes a basis for mechanistic studies and structure-guided antiviral design.

Rotavirus alphagastroenteritidis: Circulating Strains After the Introduction of the Rotavirus Vaccine (Rotarix®) in Luanda Province of Angola

2025-06-17

Daniela De Vita , Cristina Santiso-Bellón , Manuel Lemos +7 more | Viruses

Rotavirus alphagastroenteritidis (R. alphagastroenteritidis) remains the leading cause of pediatric diarrhea. Although Angola introduced Rotarix®, the human monovalent R. alphagastroenteritidis vaccine since 2014 as part of its routine childhood immunization … Rotavirus alphagastroenteritidis (R. alphagastroenteritidis) remains the leading cause of pediatric diarrhea. Although Angola introduced Rotarix®, the human monovalent R. alphagastroenteritidis vaccine since 2014 as part of its routine childhood immunization program, no follow-up study has been conducted. The aim of this study was to evaluate the distribution of R. alphagastroenteritidis genotypes among children under five years of age, hospitalized with acute gastroenteritis (AGE), after the introduction of the rotavirus vaccine. To achieve this goal, stool samples collected between 2021 and 2022 from children under 5 years of age diagnosed with AGE at six hospitals in Luanda Province were analyzed. The R. alphagastroenteritidis-antigen immunochromatographic test (SD Bioline™, Abbott, Chicago, IL, USA) was performed, and 121 positive samples were genotyped. Ten samples were randomly selected for further Sanger sequencing. The results showed that the G9P[6] was the most prevalent genotype (17.3%), followed by G9P[8] (16.5%), G2P[4] (14.9%), G3P[6] (13.2%), G8P[6] (11.5%), and less frequently G12P[8] (9.1%), G1P[6] (4.1%), and G1P[8] (2.5%). The genotype combinations G3P[6], G8P[6], and G12P[8] were detected for the first time in Luanda Province. In conclusion, the emergence of new genotype combinations supports the need for continuous surveillance to identify the trend in R. alphagastroenteritidis infection and the emergence of new strains circulating in Luanda Province in the post-vaccination period.

HPAI virus transmission is shaped by inter-specific social network structure

2025-06-17

Jamie Dunning , Anna Gamża , Josh A. Firth +4 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract The emergence of zoonotic and epizootic disease from communities of wild animals is a recurrent threat to human and animal health, to food and economic security. This is particularly … Abstract The emergence of zoonotic and epizootic disease from communities of wild animals is a recurrent threat to human and animal health, to food and economic security. This is particularly true for disease systems that involve many interacting species, where the varied ecological and behavioural diversity of those species interact, driving complex pathways of transmission, and where sampling many species across time and space is difficult. As a consequence, surveillance of disease across communities of wild animals is largely reliant on responsive, rather than preventative, sampling after an outbreak event. Here, we inferred social networks of wild birds using five years of bird survey data from a county in Northern England. We mapped 8,162 links between 159 species, and combined this with Highly Pathogenic Avian Influenza virus (HPAIV) genomic similarity measures from 35 host species, measured over 388 sequences. Inter-specific social network position predicted similarity between viral genomes, consistent with HPAIV transmission between species that co-occur in the wild. Our results have important applications for surveillance and prioritization of zoonotic and epizootic disease, and provide an empirical basis for future theoretical and species trait-based evaluation of pathogen spread among ecological communities.

Development of an efficacious oral peptide vaccine against infection with the carcinogenic liver fluke Opisthorchis viverrini

2025-06-17

Wuttipong Phumrattanaprapin , Ahmed O. Shalash , Mariusz Skwarczyński +4 more | Vaccine

The Originally Established PBE Cell Line as a Reliable In Vitro Model for Investigating SIV Infection and Immunity

2025-06-16

Xi-Chen Bai , Kohtaro Fukuyama , Leonardo Albarracín +7 more | International Journal of Molecular Sciences

Previously, we developed a porcine bronchial epithelial cell line designated as PBE cells and demonstrated that this cell line possesses functional Toll-like receptor 3 (TLR3), triggering the expressions of interferons … Previously, we developed a porcine bronchial epithelial cell line designated as PBE cells and demonstrated that this cell line possesses functional Toll-like receptor 3 (TLR3), triggering the expressions of interferons (IFNs), antiviral factors, and inflammatory cytokines after its stimulation with the synthetic double-stranded ARN poly(I:C). In this work, we aimed to further characterize the PBE cell line as a reliable in vitro model for investigating swine influenza virus (SIV) infection and immunity. We evaluated the capacity of two SIV subtypes, H1N1 and H3N2, to replicate and induce cytopathic effects in PBE cells and to modulate the expressions of IFNs, antiviral factors, inflammatory cytokines, and negative regulators of the TLR signaling. We demonstrated that PBE cells are susceptible to both H1N1 and H3N2. SIV infected PBE cells inducing notable cytopathic effects as shown by the alteration of transepithelial electrical resistance (TEER) and cilia. Both SIV subtypes replicated in PBE cells in similar proportion and altered TEER values in comparable magnitudes. However, SIV H3N2 induced higher alterations of cilia than H1N1. SIV infection induced changes in all the immune factors evaluated in PBE cells. We detected quantitative differences when the subtypes H1N1 and H3N2 were compared. The fold expression changes of IFN-β, Mx1, Mx2, IFITM1, OAS1, OAS2, and OASL were higher in PBE cells infected with H3N2 than in cells challenged with H1N1. In addition, although both subtypes stimulated IL-8 expression, only the H3N2 induced IL-6 in infected PBE cells. SIV H1N1 and H3N2 also upregulated the expressions of the negative regulators A20, BCL-3, and MKP-1, while only H1N1 increased SIGIRR and Tollip. Immortalized respiratory cell lines from pigs can be useful in vitro systems for the study of viral infections and immune responses. These studies are of importance in the context of influenza infections not only for the agricultural field because pigs are natural hosts of these viruses but also because these animals serve as intermediate reservoirs of viruses that can threaten humans' health. We demonstrated here that the PBE cell line can be a useful in vitro model to study SIV infection and immunity.

Uncovering protein conformational dynamics within two‐component viral biomolecular condensates

2025-06-16

Alice Colyer , Julia Acker , Alexander Borodavka +1 more | Protein Science

Abstract Biomolecular condensates selectively compartmentalize and organize biomolecules within the crowded cellular milieu and are instrumental in some disease mechanisms. Upon infection, many RNA viruses form biomolecular condensates that are … Abstract Biomolecular condensates selectively compartmentalize and organize biomolecules within the crowded cellular milieu and are instrumental in some disease mechanisms. Upon infection, many RNA viruses form biomolecular condensates that are often referred to as viral factories. The assembly mechanism of these viral factories remains poorly defined but involves transient, non‐stoichiometric protein/RNA interactions, making their structural characterization challenging. Here, we sought to investigate the structural dynamics and intermolecular interactions of the key proteins responsible for condensate formation upon rotavirus infection, namely NSP2 (an RNA chaperone) and NSP5 (an intrinsically disordered protein [IDP]), using a combination of hydrogen–deuterium exchange mass spectrometry (HDX‐MS), native MS, and biophysical tools. Our data reveal key structural features of intrinsically disordered NSP5 that are vital for condensate assembly and highlight inter/intra‐protein interactions involved in condensate assembly. Moreover, we demonstrate that within a condensate there are altered conformational dynamics within the C‐terminal region of NSP2, which has previously been shown to play a role in regulating its RNA chaperoning activity, and in the disordered regions of NSP5. We propose that altered conformational dynamics in NSP2 and NSP5 are critical for regulation of RNA annealing within a biomolecular condensate and for condensate assembly/client recruitment, respectively. Combined, our data demonstrate that the unique environment within a biomolecular condensate can tune functionally important protein conformational dynamics, which may play a crucial role in the replication of rotaviruses.

Aptamer-Functionalized Gold Nanoparticle Assay for Rapid Visual Detection of Norovirus in Stool Samples

2025-06-16

Maytawan Thanunchai , Sirikwan Sangboonruang , Natthawat Semakul +3 more | Biosensors

Norovirus (NoV), a leading cause of acute gastroenteritis worldwide, imposes significant morbidity and economic burdens across all age groups. Timely and accurate laboratory diagnosis is crucial for effective outbreak control … Norovirus (NoV), a leading cause of acute gastroenteritis worldwide, imposes significant morbidity and economic burdens across all age groups. Timely and accurate laboratory diagnosis is crucial for effective outbreak control and patient management. However, current diagnostic methods often require specialized equipment, technical expertise, and considerable time. To address these challenges, we developed a visual detection method utilizing gold nanoparticles (AuNPs) functionalized with the SMV25 aptamer specific to the NoV capsid protein. Detection relies on MgCl2-induced changes in the color and absorbance of these aptamer-functionalized AuNPs. The assay exhibited a good linear relationship between the A630/A520 absorbance ratio and NoV capsid protein concentration. Specifically, in a buffer system, this linearity (R2 = 0.9026) was observed over a 0-32 ng/µL range with a limit of detection (LOD) of 9.65 ng/µL. Similarly, for NoV spiked into stool suspensions, a strong linear correlation (R2 = 0.9170) was found across a 0-100 ng/µL range, with an LOD of 37.11 ng/µL. Evaluation with real stool samples yielded 77% sensitivity and 65% specificity. Notably, the assay demonstrated the highest sensitivity towards NoV GII.2 (100%), followed by GII.4 (78%). Scanning transmission electron microscopy confirmed the underlying aggregation and dispersion patterns of the aptamer-functionalized AuNPs. This colorimetric assay provides a simple, rapid, and visual method for NoV detection. Nevertheless, further enhancements are necessary to improve its performance in the direct testing of complex specimens, paving the way for future on-site detection applications, especially in resource-limited settings.

Resveratrol Mitigates Inflammation by Modulating Tumor Necrosis Factor-Alpha Receptors (TNFRs) in a 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-Induced Rat Model of Colitis

2025-06-16

Médea Veszelka , József Hegyközi , Nikoletta Almási +7 more | International Journal of Molecular Sciences

Several substances with antioxidant and anti-inflammatory properties are currently being investigated as potential adjunctive or standalone treatments for inflammatory bowel disease (IBD). One such substance is resveratrol (RES), also known … Several substances with antioxidant and anti-inflammatory properties are currently being investigated as potential adjunctive or standalone treatments for inflammatory bowel disease (IBD). One such substance is resveratrol (RES), also known as 3,5,4'-trihydroxy-trans-stilbene, a natural dietary polyphenol with diverse health-promoting effects. In this study, male Wistar-Hannover rats received oral RES supplementation at doses of 5, 10, or 20 mg/kg/day for 28 days. On day 25 colitis was induced using intracolonic administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Based on histological and planimetric analysis, the 10 mg/kg dose significantly reduced colonic ulceration and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) expression compared to the TNBS group. Immunohistochemistry also revealed that RES at this dose attenuated the intensity of TNF-α receptors, namely TNFR1 and TNFR2. Furthermore, the concentration of lipocalin-2 (Lcn-2) was significantly elevated in TNBS-induced colitis. In conclusion, our findings suggest that RES may exert its protective effects partly through the modulation of TNF receptor signaling in TNBS-induced colitis.

Full genome characterization of a Kenyan G8P[14] rotavirus strain suggests artiodactyl-to-human zoonotic transmission

2025-06-16

Ernest Apondi Wandera , Yuki Akari , Carlene Sang +7 more | Tropical Medicine and Health

Abstract Background Rotavirus infections are a major cause of severe gastroenteritis in children. Human rotavirus strains with the unconventional G8P[14] genotype have sporadically been detected in diarrheic patients in different … Abstract Background Rotavirus infections are a major cause of severe gastroenteritis in children. Human rotavirus strains with the unconventional G8P[14] genotype have sporadically been detected in diarrheic patients in different parts of the world. However, full genomes of only two human G8P[14] strains from Africa (North Africa) have been sequenced, and the origin and evolutionary patterns of African G8P[14] strains remain to be elucidated. Methods In this study, we sequenced the full genome of an African G8P[14] strain (RVA/Human-wt/KEN/A75/2000/G8P[14]) identified in archival stool samples from a diarrheic child in Kenya. Results Full genome-based analysis of strain A75 revealed a unique genogroup constellation, G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3, with the I2-R2-C2-M2-A11-N2-T6-E2-H3 part being common among rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis showed that all the 11 genomic segments of strain A75 are closely related to segments found in artiodactyl rotavirus strains, and likely strain A75 derived from spillover transmission of an artiodactyl rotavirus strain to humans. Conclusion This is the first report on a full genome-based characterization of a human G8P[14] strain from East Africa. This study demonstrates the diversity of human G8P[14] strains in Africa and contributes to the elucidation of their spreading and evolution, which includes zoonotic transmission from artiodactyls.

Anti-vaccine antibodies against measles, rubella, parotitis and hepatitis B in children with inflammatory bowel disease and healthy controls

2025-06-16

Elizaveta Makarova , О. В. Голева , Tatiana Gabrusskaya +7 more | World Journal of Clinical Pediatrics

BACKGROUND Patients with inflammatory bowel diseases (IBD) often miss the scheduled vaccines and have a higher risk of infection susceptibility, including vaccine-prevented diseases. AIM To evaluate the vaccine coverage and … BACKGROUND Patients with inflammatory bowel diseases (IBD) often miss the scheduled vaccines and have a higher risk of infection susceptibility, including vaccine-prevented diseases. AIM To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles, mumps, rubella, and hepatitis B in children with IBD. METHODS Total 98 patients: 46 females (47.2%) and 52 males (52.8%) with IBD (Crohn’s disease-75% and ulcerative colitis-25%) with disease onset age-11.0 (6.0; 14.0) years whom clinical data, vaccination status and levels of the post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, measured with ELISA were prospectively evaluated. The control group consisted of 88 healthy peers from the biobank data. RESULTS Patients with IBD had lower levels of measles, rubella, and hepatitis B, except mumps, compared to controls. Incomplete vaccination/non-protective titer of the antibodies against measles, mumps rubella, and hepatitis B had 33 (33.7%)/52.3%, 21 (21.4%)/50.4%, 26 (25.8)/25.6% and 26 (25.8%)/55.2%, respectively. Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines. The age of the IBD diagnosis ≤ 6 years was the predictor of incomplete vaccination for measles [odds ratio (OR) = 4.6, P = 0.001], mumps (OR = 5.0, P = 0.001), rubella (OR = 5.4, P = 0.0005) and hepatitis B (OR = 5.4, P = 0.0005) and corticosteroid treatment for measles (OR = 2.2, P = 0.074) and mumps (OR = 3.0, P = 0.047) vaccines. Incomplete vaccination was the predictor of non-protective titer of antibodies against rubella (OR = 6.8, 95%CI: 2.3-19.9, P = 0.0002)/mumps (OR = 7.0, 95%CI: 2.4-20.8; P = 0.0002). CONCLUSION Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles, rubella, and hepatitis B. Nearly half of the IBD patients require revaccination.

FREQUENCY OF HYPERNATREMIA SECONDARY TO ACUTE GASTROENTERITIS IN CHILDREN UNDER FIVE YEARS OF AGE

2025-06-15

Haanieh Nasiraei Mir , Amir Sharon , Ali Jahan +3 more | Pakistan Journal of Intensive Care Medicine

Background: Acute gastroenteritis remains a leading cause of morbidity and mortality among children under five years of age in developing countries. Electrolyte imbalances, particularly hypernatremia, can complicate its clinical course … Background: Acute gastroenteritis remains a leading cause of morbidity and mortality among children under five years of age in developing countries. Electrolyte imbalances, particularly hypernatremia, can complicate its clinical course and may significantly increase the risk of adverse outcomes if not promptly identified and managed. Objective: To determine the frequency and severity of hypernatremia secondary to acute gastroenteritis in children under five years of age. Study Design: Cross-sectional study. Setting: Pediatric Department, Northwest General Hospital, Peshawar, Pakistan. Duration of Study: Three months, from February 7, 2025, to May 7, 2025. Methods: A total of 121 children under the age of five years presenting with acute gastroenteritis were enrolled using a consecutive sampling technique. Serum sodium levels were measured upon admission. Hypernatremia was categorized into three levels of severity: mild (146–149 mmol/L), moderate (150–169 mmol/L), and severe (≥170 mmol/L). Data were analyzed using SPSS version 25.0. Descriptive statistics were used to calculate frequencies, percentages, means, and standard deviations. Results: The mean age of the participants was 2.50 ± 1.17 years. Of the 121 children, 57.0% were male and 43.0% were female. Hypernatremia was observed in 21 patients (17.4%). Among those with hypernatremia, 14.3% had mild, 52.4% had moderate, and 33.3% had severe hypernatremia. Conclusion: Hypernatremia was present in 17.4% of children under five years of age with acute gastroenteritis, with the majority presenting in the moderate severity category. Early detection and appropriate management of electrolyte imbalances are critical to improving clinical outcomes in pediatric gastroenteritis cases.

Development and Evaluation of a Polyclonal Antibody-Based Lateral Flow Immunoassay Test Strip for Rapid Detection of Rotavirus in Faecal Samples

2025-06-15

Tien Hoang Ngo , Van-Dao Tran , Tram Thi Ngoc Ngo +2 more | Applied Biochemistry and Microbiology

The transmission dynamics of Norovirus in England: a genotype-specific modelling study

2025-06-14

Juan F. Vesga , Amy Douglas , Cristina Celma +3 more | medRxiv (Cold Spring Harbor Laboratory)

Background Norovirus is the leading cause of acute gastroenteritis cases in England and worldwide, with diverse co-circulating genotypes. Recent surveillance in England shows GII.17 surpassing GII.4 in prevalence among reported … Background Norovirus is the leading cause of acute gastroenteritis cases in England and worldwide, with diverse co-circulating genotypes. Recent surveillance in England shows GII.17 surpassing GII.4 in prevalence among reported cases, and vaccine candidates targeting multiple genotypes are advancing. However, most transmission models still focus on single-strain dynamics, limiting their ability to assess the role of co-circulating strains on population burden. Methods We developed an age structured multistrain transmission model that integrates norovirus genotype diversity, waning immunity, and cross-protection within genogroups. We calibrate to case and genotyping surveillance time-series from UKHSA with community-wide age structured incidence estimates and cross-sectional seroprevalence among English children to capture the transmission dynamics of the main co-circulating Norovirus strains in England. Using a calibrated model, we examine the case of an emerging GII.4 variant under different scenarios of transmissibility. Results We found that on average the current GII.4 strain has an R0 of ~3.6. We estimate the average number of lifetime Norovirus-caused AGE cases per person to be between 3 and 4, with 60% of children in England experiencing at least one symptomatic episode by the age of four. Our inference analysis suggests that cross-protection within genogroups (between strains of the same genogroup, like GII.4 with other GII), is very limited at conferring protection. Importantly, our modelling suggests that a potential emerging variant would only cause a larger epidemic season if such variant was more transmissible, while equally transmissible new variants would create a re-distribution of co-circulating strains but maintaining the same epidemic size overall. Conclusions This approach addresses key limitations of single-strain frameworks and offers a more comprehensive understanding of norovirus dynamics, improving the capacity to assess the potential population-level effects of upcoming multivalent vaccine strategies.

Structure and stabilization of the antigenic glycoprotein building blocks of the New World mammarenavirus spike complex

2025-06-13

Guido C. Paesen , Weng M. Ng , Simon Kimuda +3 more | mBio

ABSTRACT The spillover of New World (NW) arenaviruses from rodent reservoirs into human populations poses a continued risk to human health. NW arenaviruses present a glycoprotein (GP) complex on the … ABSTRACT The spillover of New World (NW) arenaviruses from rodent reservoirs into human populations poses a continued risk to human health. NW arenaviruses present a glycoprotein (GP) complex on the envelope surface of the virion, which orchestrates host cell entry and is a key target of the immune response arising from infection and immunization. Each protomer of the trimeric GP is composed of a stable signal peptide, a GP1 attachment glycoprotein, and a GP2 fusion glycoprotein. To glean insights into the architecture of this key therapeutic target, we determined the crystal structures of NW GP1−GP2 heterodimeric complexes from Junín virus and Machupo virus. Due to the metastability of the interaction between GP1 and GP2, structural elucidation required the introduction of a disulfide bond at the GP1−GP2 complex interface, but no other stabilizing modifications were required. While the overall assembly of NW GP1−GP2 is conserved with that presented by Old World (OW) arenaviruses, including Lassa virus and lymphocytic choriomeningitis virus, NW GP1−GP2 complexes are structurally distinct. Indeed, we note that when compared to the OW GP1−GP2 complex, the globular portion of NW GP1 undergoes limited structural alterations upon detachment from its cognate GP2. We further demonstrate that our engineered GP1−GP2 heterodimers are antigenically relevant and recognized by neutralizing antibodies. These data provide insights into the distinct assemblies presented by NW and OW arenaviruses, as well as provide molecular-level blueprints that may guide vaccine development. IMPORTANCE Although the emergence of New World (NW) hemorrhagic fever mammarenaviruses poses an unceasing threat to human health, there is a paucity of reagents capable of protecting against the transmission of these pathogens from their natural rodent reservoirs. This is, in part, attributed to our limited understanding of the structure and function of the NW glycoprotein spike complex presented on the NW arenavirus surface. Here, we provide a detailed molecular-level description of how the two major components of this key therapeutic target assemble to form a key building block of the NW arenaviral spike complex. The insights gleaned from this work provide a framework for guiding the structure-based development of NW arenaviral vaccines.

Trimming the fat: a brief review of lipids at the host-pathogen interface

2025-06-13

F.T. Korkmaz | Infection and Immunity

ABSTRACT Microbial-derived lipids and the host receptors that bind them are collectively critical for immune regulation on the host side and for a multitude of biological functions on the microbial … ABSTRACT Microbial-derived lipids and the host receptors that bind them are collectively critical for immune regulation on the host side and for a multitude of biological functions on the microbial side, including membrane structure, energy generation, resistance to stress, and, importantly, virulence. Bacteria, viruses, fungi, and eukaryotic microorganisms comprise common and unique lipid species that can be modified to avoid immune detection and aid in antimicrobial resistance. Moreover, the host receptors that interact with lipids are equally diverse in their structure and function, driving both beneficial and pathogenic responses depending on the location, strength, and duration of signaling. The following review will discuss all the aforementioned aspects of lipids at the host-pathogen interface, which should be expanded upon in future studies to develop novel therapeutics that consider lipids as distinct immune modulators.

Intravenous Rehydration for Severe Acute Malnutrition with Gastroenteritis

2025-06-13

Kathryn Maitland , Maurice Ouattara , Hadiza Alhaji Sainna +7 more | New England Journal of Medicine

International recommendations advise against the use of intravenous rehydration therapy in children with severe acute malnutrition because of the concern about fluid overload, but evidence to support this concern is … International recommendations advise against the use of intravenous rehydration therapy in children with severe acute malnutrition because of the concern about fluid overload, but evidence to support this concern is lacking. Given the high mortality associated with the current recommendations, the adoption of intravenous rehydration strategies might improve outcomes. We conducted a factorial, open-label superiority trial in four countries in Africa. Children 6 months to 12 years of age with severe acute malnutrition with gastroenteritis and dehydration underwent randomization in a 2:1:1 ratio to one of three rehydration strategies: oral rehydration, plus intravenous boluses for shock; a rapid intravenous strategy that consisted of lactated Ringer's solution (100 ml per kilogram of body weight) administered over a period of 3 to 6 hours, with boluses for shock; or a slow intravenous strategy that consisted of the same solution administered over a period of 8 hours, with no boluses. The primary end point was death at 96 hours. A total of 272 children underwent randomization; 138 were assigned to the oral strategy, 67 to the rapid intravenous strategy, and 67 to the slow intravenous strategy. Participants were followed for 28 days. A nasogastric tube was used for oral rehydration in 126 of 135 participants (93%) in the oral group and in 82 of 126 (65%) in the intravenous groups. Intravenous boluses were administered at admission in 12 participants (9%) in the oral group, 7 (10%) in the rapid intravenous group, and none in the slow intravenous group. At 96 hours, 11 participants (8%) in the oral group and 9 (7%) in the intravenous groups (5 in the rapid group and 4 in the slow group) had died (risk ratio, 1.02; 95% confidence interval [CI], 0.41 to 2.52; P = 0.69). At 28 days, 17 participants (12%) in the oral group and 14 (10%) in the intravenous groups had died (hazard ratio, 0.85; 95% CI, 0.41 to 1.78). Serious adverse events occurred in 32 participants (23%) in the oral group, 14 (21%) in the rapid intravenous group, and 10 (15%) in the slow intravenous group. No evidence of pulmonary edema, heart failure, or fluid overload was noted. Among children with severe acute malnutrition and gastroenteritis, no evidence of a difference in mortality at 96 hours was noted between oral and intravenous rehydration strategies. (Funded by the Joint Global Health Trials scheme and others; GASTROSAM Current Controlled Trials number, ISRCTN76149273.).

Multiplex detection of respiratory RNA viruses without amplification based on CRISPR-Cas13a immunochromatographic test strips

2025-06-12

Quan Wang , Wenqian Jiang , Zhiqing Huang +3 more | Virology Journal

Acute respiratory infections, caused by RNA viruses like respiratory syncytial virus, influenza, rhinovirus, and coronavirus, are major global health threats. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) is the … Acute respiratory infections, caused by RNA viruses like respiratory syncytial virus, influenza, rhinovirus, and coronavirus, are major global health threats. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) is the gold standard for detecting these viruses but is time-consuming, complex, and requires specialized equipment. There is a need for rapid, convenient, and multi-target detection methods to improve disease prevention and control. This study developed a multi-target immunochromatographic detection method using LbuCas13a protein and "band elimination" test strips for detecting SARS-CoV-2 and influenza virus. The method's performance was evaluated by testing known 5 positive and 4 negative samples for SARS-CoV-2 and comparing results with fluorescent PCR and colloidal gold methods. Detection sensitivity was quantified using digital PCR and qPCR. The immunochromatographic test strips showed 100% concordance with fluorescent PCR and colloidal gold methods in initial clinical SARS-CoV-2 detection. Subsequently, we used dual-target immunochromatographic test strips to detect 9 SARS-CoV-2 positive samples and 9 H3N2 positive samples. However, false negatives were observed in dual-target detection of SARS-CoV-2 and H3N2 samples, likely due to low sample concentration or sample degradation. The method had a minimum detection limit of 381.75 copies/µL, as determined by digital PCR and qPCR. The developed multi-target immunochromatographic detection method offers a rapid, low-cost, and simple approach for detecting both SARS-CoV-2 and influenza viruses. With high sensitivity, specificity, and reliability, this method holds promise as a practical tool for RNA virus diagnosis and improving public health response to respiratory infections.

Nanomaterial Applications in Prevention and Treatment Strategies of Virus: A Review

2025-06-12

Gao Xin , Chong Zhang , Jinyang Ni +3 more | Bioconjugate Chemistry

Virus infections pose significant threats to human health and have profound implications for the global economy. Traditional vaccines and antiviral drugs have several limitations in the management of viral infections. … Virus infections pose significant threats to human health and have profound implications for the global economy. Traditional vaccines and antiviral drugs have several limitations in the management of viral infections. For example, the efficacy of vaccines diminishes following viral mutations, while antiviral medications are susceptible to the development of drug resistance. In recent years, nanomaterials have attracted considerable attention in antiviral research due to their physicochemical properties and biocompatibility. This article provides a systematic overview of the advancements in the antiviral application of nanomaterials. We provide a comprehensive overview of the antiviral effects of nanomaterials in various applications, including the enhancement of immune responses as vaccine carriers, improved sensitivity in virus detection, inhibition of viral infection by direct antiviral activity, enhancement of drug efficacy as drug delivery carriers, interruption of virus transmission by surface coating, and virus tracing to assist in the study of viral mechanisms. Challenges of nanomaterials in the antiviral research are also discussed.

A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen

2025-06-12

Maria Letizia Di Martino , Laura Jenniches , Anjeela Bhetwal +7 more | Nature Genetics

Abstract Studying the pathogenesis of human-adapted microorganisms is challenging, since small animal models often fail to recapitulate human physiology. Hence, the comprehensive genetic and regulatory circuits driving the infection process … Abstract Studying the pathogenesis of human-adapted microorganisms is challenging, since small animal models often fail to recapitulate human physiology. Hence, the comprehensive genetic and regulatory circuits driving the infection process of principal human pathogens such as Shigella flexneri remain to be defined. We combined large-scale Shigella infections of enteroids and colonoids with transposon-directed insertion sequencing and Bayesian statistical modeling to address infection bottlenecks, thereby establishing the comprehensive genome-wide map of Shigella genes required to infect human intestinal epithelium. This revealed the Shigella virulence effectors essential for epithelial cell colonization across geometries and intestinal segments, identified over 100 chromosomal genes involved in the process and uncovered a post-transcriptional mechanism whereby tRNA-modification enzymes and differential codon usage exert global control of a bacterial virulence program. Our findings provide a broadly applicable framework for combining advanced organotypic tissue culture with functional genomics and computational tools to map human–microorganism interactions at scale.