TCR Alpha Beta and CD19+ Depleted Haploidentical Peripheral Stem Cell Transplantation Using Reduced Toxicity Conditioning Regimen with Pharmacokinetics Guided Busulfan, Fludarabine, Thiotepa and Thymoglobulin Offers Durable Donor Engraftment in Children with Primary Immune Deficiency Disorders

Background: Allogeneic hematopoietic cell transplantation (HCT) with ex vivo T cell receptor (TCR) alphabeta+ T cell and CD19+ B cell depletion is an effective approach for children with primary immune deficiency disorders (PIDD) as it combines advantages of high CD34+ cell dose facilitating rapid engraftment with low risk of Graft Versus Host Disease (GVHD). The ideal pre-conditioning regimen that facilitates robust donor engraftment without increasing risk of transplant related mortality has not been well defined with this approach. Method(s): We report the outcomes of 4 pediatric subjects: Chronic Granulomatous Disease (CGD) (2), Wiskott Aldrich Syndrome (WAS) (1), and RAC2 deficient Severe Combined Immunodeficiency (1) who underwent haploidentical HCT with TCRalphabeta+ T cell/CD19+ depletion at Johns Hopkins All Children's Hospital/Moffitt Cancer Center from 2020-2022 (NCT04414046). Pre-conditioning regimen consisted of distal thymoglobulin (7.5 mg/kg), fludarabine (175 mg/m2), thiotepa (10 mg/kg) and pharmacokinetic guided busulfan targeting a cumulative area under curve (cAUC) (65-75 mgxhr/L). Rituximab (200 mg/m2) was administered on day +1. Result(s): The median age at HCT was 51 months (range 10-163 months). All patients received mobilized peripheral blood stem cells from HLA- haploidentical donors (paternal=1, maternal=1 sibling=2). Median busulfan cAUC for all patients was 69 mgxhr/L (range 65-76). Median CD34 and TCR alphabeta T cell dose was 9.13x106 cells/kg (range 7.0-18.9x106) and 0.7x105 cells/kg (range 0.09-1.0x105). Median times to neutrophil and platelet engraftment were 11 days (9-12) and 11 days (range 8-15), respectively. All 4 patients are alive with median follow-up of 19.5 months (range 7-24). One patient developed late VOD without organ dysfunction that resolved with defibrotide. At last follow up, peripheral T and myeloid chimerisms exceeded 90% in all 4 patients. Average time to CD4 recovery (> 200x106/L) was 142 days. Pre-existing inflammatory bowel disease in CGD (n=1) and WAS (n=1) patients resolved immediately following transplant. There was no graft failure, and none developed Grade III-IV acute or extensive chronic GVHD. Patient with WAS developed recurrent autoimmune cytopenias requiring corticosteroids, rituximab, sirolimus and daratumumab, and ultimately resolved. Viral reactivations included EBV (n= 1), adeno (n= 1), HHV6 (n= 2), BK (n=1), norovirus (n=1), and late HSV (n=1), all responded to antivirals without disease. All patients acquired SARS-Cov-2 after transplant and recovered without sequelae. Conclusion(s): TCR alphabeta+ and CD19+ depleted haploidentical transplantation using a reduced toxicity conditioning regimen with pharmacokinetic guided busulfan, fludarabine, thiotepa and thymoglobulin is well-tolerated in young children with PIDD that results in rapid, durable engraftment with low likelihood of GVHD and graft rejection.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Rapid Virucidal Activity of Japanese Saxifraga Species-Derived Condensed Tannins against SARS-CoV-2, Influenza A Virus, and Human Norovirus Surrogate Viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus are global threats to human health. The application of effective virucidal agents, which contribute to the inactivation of viruses on hands and environmental surfaces, is important to facilitate robust virus infection control measures. Naturally derived virucidal disinfectants have attracted attention owing to their safety and eco-friendly properties. In this study, we showed that multiple Japanese Saxifraga species-derived fractions demonstrated rapid, potent virucidal activity against the SARS-CoV-2 ancestral strain and multiple variant strains, IAV, and two human norovirus surrogates: feline calicivirus (FCV) and murine norovirus (MNV). Condensed tannins were identified as active chemical constituents that play a central role in the virucidal activities of these fractions. At a concentration of 25 µg/mL, the purified condensed tannin fraction Sst-2R induced significant reductions in the viral titers of the SARS-CoV-2 ancestral strain, IAV, and FCV (reductions of ≥3.13, ≥3.00, and 2.50 log10 50% tissue culture infective doses [TCID50]/mL, respectively) within 10 s of reaction time. Furthermore, at a concentration of 100 µg/mL, Sst-2R induced a reduction of 1.75 log10 TCID50/mL in the viral titers of MNV within 1 min. Western blotting and transmission electron microscopy analyses revealed that Sst-2R produced structural abnormalities in viral structural proteins and envelopes, resulting in the destruction of viral particles. Furthermore, Saxifraga species-derived fraction-containing cream showed virucidal activity against multiple viruses within 10 min. Our findings indicate that Saxifraga species-derived fractions containing condensed tannins can be used as disinfectants against multiple viruses on hands and environmental surfaces. IMPORTANCE SARS-CoV-2, IAV, and norovirus are highly contagious pathogens. The use of naturally derived components as novel virucidal/antiviral agents is currently attracting attention. We showed that fractions from extracts of Saxifraga species, in the form of a solution as well as a cream, exerted potent, rapid virucidal activities against SARS-CoV-2, IAV, and surrogates of human norovirus. Condensed tannins were found to play a central role in this activity. The in vitro cytotoxicity of the purified condensed tannin fraction at a concentration that exhibited some extent of virucidal activity was lower than that of 70% ethanol or 2,000 ppm sodium hypochlorite solution, which are popular virucidal disinfectants. Our study suggests that Saxifraga species-derived fractions containing condensed tannins can be used on hands and environmental surfaces as safe virucidal agents against multiple viruses.

Food as a transmitter of viruses: A review

Viruses have been present throughout human history, causing diseases due to infections and food poisoning;they have caused frequent public health problems worldwide. These illnesses are usually mild, moderate, or severe in nature. The personal hygiene of food handlers and processing processes should be checked periodically. Virus detection protocols and safety measures should be continually reviewed as viruses change their mode of infection. The objective of this review was to discuss the possible routes of virus transmission to humans through food. Important topics have been reviewed such as: definition of food viruses, presence, and types of viruses in food, enteric viruses, zoonotic viruses, water as a means of transmission, risks of infection, other non-conventional foods as potential transmitters of viruses and food safety, in addition to current and future challenges, research work on viruses more resistant to heat treatments in food should be sought. Also, future work on survival time of active viruses on food surfaces. In addition, studies that determine the mechanisms of virus mutation in relation to the conditions of food handling and processing.

Study of asymptomatic norovirus infection in kitchen workers in key places in Tongzhou district, Beijing, 2019-2021

Objective: To investigate the prevalence of asymptomatic norovirus infections status in kitchen workers in schools, child care settings, and catering service units and other key places in Tongzhou district of Beijing from 2019 to 2021, and provide evidence for scientific prevention and control of norovirus infection. Methods: The simple random sampling method was used to select the kitchen workers, especially the kitchen workers preparing cold dish, from catering service units, schools, childcare settings, construction sites, hotels as study subjects, and their anal swabs or stool samples were collected for norovirus nucleic acid detection by fluorescence quantitative PCR. Descriptive method was used to analyze the asymptomatic norovirus infection status of the kitchen workers. Results: A total of 3880 samples were collected from 552 units, and 15 norovirus positive cases were detected, including 1 sample positive for GI and 14 samples positive for GII. The asymptomatic norovirus infection rate was 0.39% (15/3880), in which 0.30% (5/1656) in man, and 0.45% (10/2224) in women. No asymptomatic infections were detected in age groups < 18 years and > 60 years, and 2055 cases were detected in age group 19- years, with a positive rate of 0.34% (7/2055), and 1637 cases were detected in age group 46- years, with a positive rate of 0.49% (8/1637). In 2019 when no COVID-19 epidemic occurred, the asymptomatic norovirus infection rate was 1.00% (1/100), but the asymptomatic norovirus infection rate was 0.39% (11/2805)in 2020 and 0.31%(3/975)in 2021 in the context of COVID-19 epidemic. Conclusion: The asymptomatic norovirus infection rate in kitchen workers in key places in Tongzhou was similar to the average level in Beijing during the same period. In COVID-19 epidemic period, the asymptomatic norovirus infection rate was lower than that before the epidemic.

Epidemiological and etiological analysis of a case cluster caused by norovirus in a nursing home in Lanzhou

Objective: To understand the epidemiology and etiology of a cluster of cases with gastroenteritis in a nursing home in Anning district of Lanzhou, and to provide a scientific evidence for the prevention and control of norovirus diarrhea in community nursing centers. Methods: From January 28 to February 4 2021, an epidemiological investigation was conducted on all diarrhea cases, nursing staff and chefs in a nursing home in Anning district, Lanzhou city. Samples of patients' anal swabs, feces, vomitus were collected for norovirus detection by real-time fluorescent PCR. ORF1/ORF2 junction region of norovirus in some selected positive samples(Ct value 25) was sequenced. MEGA-X software was used to construct a phylogenetic tree for genetic evolution analysis using the neighboring method. Results: The first case was confirmed on January20,2021, and the number of cases peaked during January 25and 29.A total of 58 clinically diagnosed cases were reported,57were older people, with an incidence of(57/360,15.83%). Diarrhea(50/58,86.21%),vomiting(35/58,60.34%),nausea(13/58,22.41%)and abdominal pain(6/58,10.34%)were common symptoms, all cases were mild. Fifty-three asymptomatic cases were detected among chefs, housekeepers and nurses.A total of 163specimens were tested, the positive rate of norovirus GII was 49.08%(80/163). The positive rate of fecal samples collected from nurses, chefs and housekeepers was 48.62%(53/109), and was11.11%(2/18)in environmental surface swabs. The possibility of other pathogenic infections such as SARS-CoV-2was ruled out by further tests. Thirteen positive samples were selected for sequencing, and 9were successfully sequenced, they were all recombinant GII.4Sydney_2012 [P16]genotypes, forming an independent cluster, while in a large evolutionary branch with the 2020GII.10 [P16]and 2019GII.2 [P16]virus strains in Lanzhou city, showing a relative close genetic connection. Conclusions: GII .4Sydney_2012[P16]genotype of norovirus is found to be causative pathogen of this outbreak, and close contact is the main reason of the outbreak and persistence of the infection,so asymptomatic infections of norovirus play an important role in the disease spreading. Therefore, public health management in nursing homes and other centralized nursing facilities should be strengthened especially for asymptomatic workers in order to prevent virus transmission.

Predicting norovirus and rotavirus resurgence in the United States following the COVID-19 pandemic: a mathematical modelling study.

BACKGROUND: To reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed. METHODS: We fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012-2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022-2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels. RESULTS: We found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70-90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70-90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection. CONCLUSIONS: These results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses.

Virus Infections in Older People.

Older people are more prone to viral infections, and often have worse outcomes. This was well demonstrated during the COVID-19 pandemic, where a disproportionate number of deaths occurred in the oldest and frailest people. The assessment of the older person with a viral infection is complicated by the high prevalence of multiple comorbidities and sensory or cognitive impairment. They often present with common geriatric syndromes such as falls or delirium, rather than the more typical features of a viral illness in younger people. Comprehensive geriatric assessment by a specialist multidisciplinary team is the gold standard of management, as viral illness is unlikely to present in isolation of other healthcare needs. We discuss the presentation, diagnosis, prevention, and management of common viral infections-respiratory syncytial virus, coronavirus, norovirus, influenza, hepatitis, herpes, and dengue viruses-with special consideration of infections in the older patient.

Incidence of acute intestinal infections in Saint Petersburg during COVID-19 pandemic.

The results of a study of modern epidemiological and characteristics of acute intestinal infections against the backdrop of the COVID-19 pandemic are presented. The article reflects current trends in the frequency of detection of acute intestinal infections of viral and bacterial etiology, in particular, the growing prevalence of norovirus infection is shown. Particular attention is paid to the increase in the incidence of salmonellosis and campylobacteriosis. An increase in the incidence of salmonellosis in 2019 by 25.7% is shown, which is higher than the average long-term incidence rate by 28.1%. Age features of the incidence of viral and bacterial intestinal infections among children have been established. Given the widespread use of antibiotics or other drugs that change the intestinal microbial landscape (cytostatics, chemotherapy drugs), as well as a significant increase in the number of hospitalizations of patients, there is a high risk of developing antibiotic-associated diarrhea. Undoubted attention requires the problem of registration, diagnosis of clostridium infections, which make it difficult to obtain data on the prevalence of infection caused by Clostridium difficile in the Russian Federation and St. Petersburg. The article discusses in detail the possibilities for further improvement of measures to prevent the transmission of acute intestinal infections.Copyright © 2022 Authors. All rights reserved.

Incidence of acute intestinal infections in Saint Petersburg during COVID-19 pandemic.

The results of a study of modern epidemiological and characteristics of acute intestinal infections against the backdrop of the COVID-19 pandemic are presented. The article reflects current trends in the frequency of detection of acute intestinal infections of viral and bacterial etiology, in particular, the growing prevalence of norovirus infection is shown. Particular attention is paid to the increase in the incidence of salmonellosis and campylobacteriosis. An increase in the incidence of salmonellosis in 2019 by 25.7% is shown, which is higher than the average long-term incidence rate by 28.1%. Age features of the incidence of viral and bacterial intestinal infections among children have been established. Given the widespread use of antibiotics or other drugs that change the intestinal microbial landscape (cytostatics, chemotherapy drugs), as well as a significant increase in the number of hospitalizations of patients, there is a high risk of developing antibiotic-associated diarrhea. Undoubted attention requires the problem of registration, diagnosis of clostridium infections, which make it difficult to obtain data on the prevalence of infection caused by Clostridium difficile in the Russian Federation and St. Petersburg. The article discusses in detail the possibilities for further improvement of measures to prevent the transmission of acute intestinal infections.Copyright © 2022 Authors. All rights reserved.

Acute Diarrhea in Adults

Acute diarrheal disease accounts for 179 million outpatient visits annually in the United States. Diarrhea can be categorized as inflammatory or noninflammatory, and both types have infectious and noninfectious causes. Infectious noninflammatory diarrhea is often viral in etiology and is the most common presentation;however, bacterial causes are also common and may be related to travel or foodborne illness. History for patients with acute diarrhea should include onset and frequency of symptoms, stool character, a focused review of systems including fever and other symptoms, and evaluation of exposures and risk factors. The physical examination should include evaluation for signs of dehydration, sepsis, or potential surgical processes. Most episodes of acute diarrhea in countries with adequate food and water sanitation are uncomplicated and self-limited, requiring only an initial evaluation and supportive treatment. Additional diagnostic evaluation and management may be warranted when diarrhea is bloody or mucoid or when risk factors are present, including immunocompromise or recent hospitalization. Unless an outbreak is suspected, molecular studies are preferred over traditional stool cultures. In all cases, management begins with replacing water, electrolytes, and nutrients. Oral rehydration is preferred;however, signs of severe dehydration or sepsis warrant intravenous rehydration. Antidiarrheal agents can be symptomatic therapy for acute watery diarrhea and can help decrease inappropriate antibiotic use. Empiric antibiotics are rarely warranted, except in sepsis and some cases of travelers' or inflammatory diarrhea. Targeted antibiotic therapy may be appropriate following microbiologic stool assessment. Hand hygiene, personal protective equipment, and food and water safety measures are integral to preventing infectious diarrheal illnesses.Copyright © 2022 American Academy of Family Physicians.

Virucidal efficacy of household dishwashers

Not only since SARS-CoV-2, have transmission routes of viruses been of interest. Noroviruses e.g., can be transmitted via smear infection, are relatively stable in the environment and very resistant to chemical disinfection. Some studies determined the virucidal efficacy of laundering processes, but few studies focused on the virucidal efficacy of dishwashing processes. Here, especially consumer related conditions are of interest. Households for example are a hotspot of norovirus infection and thus a sufficient reduction of these and other viruses from dishes must be insured to avoid an infection via this route. The likelihood of such an event should not be underestimated, since it was shown that the washing machine can be a reservoir for the transmission of extended spectrum beta-lactamase producing bacteria in newborns. Although viruses do not replicate in these devices a transmission via contaminated cutlery e.g., cannot be excluded. Using a consumer related approach to determine the virucidal efficacy of dishwashers, we found a combination of a bleach containing dishwasher detergent, a cleaning temperature of 45 C for 45 min and a rinsing temperature of 50 C, to be sufficient to reduces viral titer of bovine corona virus, murine norovirus and modified vaccinia virus by 4.8, 4.2 and 3.8 logarithmic stages respectively.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Analysis of epidemic characteristics and related factors of norovirus in diarrhea patients in Guangxi, 2015-2020

To analyze the epidemiological characteristics and related factors of norovirus in Guangxi from 2015 to 2020, and to provide scientific recommendations for norovirus prevention and control. Methods The foodborne diseases surveillance data were collected from 11 sentinel hospitals through the National Foodborne Disease Monitoring and Reporting System from 2015 to 2020. R software with version 4.0.3 was used for descriptive and statistical analysis, including epidemic curve, chi-square test, and trend chi-square and so on. Logistic regression was used to analyze norovirus-related factors, OR values and 95% confidence intervals were calculated respectively with the statistical test level of P < 0.05. Results There were 1 008 norovirus cases detected, with a detection rate of 12.75% (1 008/7 903). Children with age less than 5 years (OR=1.43, 95%CI: 1.13-1.82) and patients at age 20-45 (OR=1.45, 95%CI: 1.13-1.87) were high risk population. The detection rate was higher in autumn (OR=1.29, 95%CI: 1.08-1.53) but lower in summer (OR=0.67, 95%CI: 0.55-0.80). In addition, the tourist area (Guilin City) presented a higher detection rate than other areas (OR=1.41, 95%CI: 1.10-1.80). Aquatic products (OR=1.40, 95%CI: 1.03-1.91), meat and dairy products (OR=1.31, 95%CI: 1.06-1.61) were high-risk foods for norovirus infection. The prevention and control policies of COVID-19 can reduce the possibility of norovirus by 61% (OR=0.39, 95%CI: 0.31-0.49) showed a declining trend (Trend X2=85.33, P < 0.001). In addition, prolonged visit time can lead to 19%-23% decrease in the detection rate of norovirus (OR24-48 hours=0.81, 95%CI: 0.70-0.95;OR>48 hours=0.77, 95%CI: 0.63-0.93). Conclusions The epidemic of norovirus presented seasonal and regional distribution in Guangxi with a declining detection rate trend in diarrhea patients during recent 6 years. Young children were high-risk population in infection norovirus. The intake of seafood can increase the risk of norovirus infection. The prevention and control policies of COVID-19 can sharply decrease the possibility of infection norovirus. The monitoring of key foods such as seafood should be strengthened, and the early screening of suspected cases should be taken. The norovirus monitoring should be improved to ensure the health of the population.

An Investigation into the Presence of Pathogens on Inanimate Surfaces in the Hospital Environment

Background The hospital environment is understood to play an important role in the transmission of nosocomial pathogens, with inanimate surfaces facilitating pathogen movement and persistence in the environment. The majority of studies of surface contamination have been carried out in outbreak conditions or on high-dependency wards. Current surface cleaning guidance only requires surfaces to be visually clean. Microbiological standards for cleanliness have been proposed however they are not widely adopted and little implementation guidance is available. Evidence-based surface sampling protocols are required for the transmission risk surfaces pose to be adequately quantified and addressed. Methods Environmental surface samples will be collected in a number of in- and outpatient settings staff and public areas, such as waiting rooms. This will be done before and after cleaning. Pathogens associated with nosocomial infection (e.g., ESKAPE pathogens Clostridioides difficile and Candida auris) will be identified through culture methods and MALDI-ToF mass spectrometry. Antimicrobial susceptibility profiles of isolates will be determined following EUCAST protocols. Realtime PCR will be utilized to identify viral pathogens (including norovirus adenovirus influenza and SARS-CoV-2) present. Following this samples will be collected for community composition sequencing allowing for non-culturable microorganisms to be identified. Whole genome sequencing will be performed on any pathogens of interest isolated during this investigation. Results and Conclusion Fewer microorganisms are expected to be isolated after cleaning than prior and samples from inpatient environments will have higher proportions of pathogens. The hospital microbiome has rarely been investigated outside of outbreak conditions. This study presents a novel, systematic approach to assess the microorganisms present in the hospital environment and how they are impacted by current cleaning measures. This will build a comprehensive picture of the hospital microflora and provide an evidence base for the development of surface sampling protocols helping inform clinical risk assessments and subsequently improving patient outcomes.

Emergent variant modeling of the serological repertoire to norovirus in young children.

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens.

Seasonal Trends in the Prevalence and Incidence of Viral Encephalitis in Korea (2015-2019).

Viral infections are a common cause of encephalitis. This study investigated the relationship between the incidence of encephalitis and that of respiratory and enteric viral infections in all age groups from 2015 to 2019, using the Health Insurance Review and Assessment (HIRA) Open Access Big Data Platform. We identified monthly incidence patterns and seasonal trends using the autoregressive integrated moving average (ARIMA). The Granger causality test was used to analyze correlations between encephalitis incidence and the positive detection rate (PDR) at 1-month intervals. A total of 42,775 patients were diagnosed with encephalitis during the study period. The incidence of encephalitis was highest in the winter (26.8%). The PDRs for respiratory syncytial virus (HRSV) and coronavirus (HCoV) were associated with the trend in encephalitis diagnosis in all age groups, with a 1-month lag period. In addition, an association with norovirus was observed in patients aged over 20 years, and with influenza virus (IFV) in patients aged over 60 years. This study found that HRSV, HCoV, IFV, and norovirus tended to precede encephalitis by 1 month. Further research is required to confirm the association between these viruses and encephalitis.

Real-world practice of the Egyptian Kelleni's protocol amid changing tropism of SARS-CoV-2 omicron BA.5.2.1.7, XBB 1.5 and CH.1.1 subvariants: a multi-purpose protocol.

The Egyptian immune-modulatory Kelleni's protocol, including nitazoxanide as an integral component, is being safely and effectively practiced to manage SARS-CoV-2, RSV, influenza infections in pediatric, adult and pregnant patients with negligible requirements for the relatively expensive diagnostic molecular tests. Most recently, Kelleni's protocol is being likewise used to manage potential norovirus infection which is currently confused with SARS-CoV-2 Omicron new enterotropic subvariants and the antihistaminic loratadine has been co-administered in selected patients. Notably, Africa has the least mandates, restrictions and SARS-CoV-2 vaccination rates and yet the least COVID-19 mortality.

Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus.

Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus (IV). Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection; however, poor immunogenicity greatly hinders their application. The protruding (P) domain of the norovirus (NoV), which can self-assemble into a 24-mer particle called the NoV P particle, offers an ideal antigen presentation platform. In this study, a multiepitope nanovaccine displaying influenza epitopes (HMN-PP) was constructed based on the NoV P particle nanoplatform. Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form. Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin (HA)-specific neutralizing antibodies, and the antibodies could persist for at least three months after the last immunization. Furthermore, HMN-PP induced matrix protein 2 extracellular domain (M2e)-specific antibody-dependent cell-mediated cytotoxicity, CD4+ and CD8+ T-cell responses, and a nucleoprotein (NP)-specific cytotoxic T lymphocyte (CTL) response. These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s12274-023-5395-6.

Expanding the Pathogen Panel in Wastewater Epidemiology to Influenza and Norovirus.

Since the start of the 2019 pandemic, wastewater-based epidemiology (WBE) has proven to be a valuable tool for monitoring the prevalence of SARS-CoV-2. With methods and infrastructure being settled, it is time to expand the potential of this tool to a wider range of pathogens. We used over 500 archived RNA extracts from a WBE program for SARS-CoV-2 surveillance to monitor wastewater from 11 treatment plants for the presence of influenza and norovirus twice a week during the winter season of 2021/2022. Extracts were analyzed via digital PCR for influenza A, influenza B, norovirus GI, and norovirus GII. Resulting viral loads were normalized on the basis of NH4-N. Our results show a good applicability of ammonia-normalization to compare different wastewater treatment plants. Extracts originally prepared for SARS-CoV-2 surveillance contained sufficient genomic material to monitor influenza A, norovirus GI, and GII. Viral loads of influenza A and norovirus GII in wastewater correlated with numbers from infected inpatients. Further, SARS-CoV-2 related non-pharmaceutical interventions affected subsequent changes in viral loads of both pathogens. In conclusion, the expansion of existing WBE surveillance programs to include additional pathogens besides SARS-CoV-2 offers a valuable and cost-efficient possibility to gain public health information.

Norovirus and Coronavirus Risks in Food Service Settings: A Systematic Review for Future Research

This study discusses norovirus- and coronavirus-related health risks, foodborne illnesses, and outbreak risks associated with food and personal hygiene in the food service industry. Norovirus and coronavirus are global concerns. Employing a systematic review, the study focuses on the epidemiology of the viruses, including risk factors, possible transmission stages, and food safety regulations and practices. It is clear that the health risks related to norovirus have not received much attention from food service and hospitality management scholars. However, coronavirus risks and transmission route are well acknowledged by public and food service industry due to the current global pandemic. This study is one of the first studies that presents scholarly research results and discussions on the norovirus and coronavirus risks in food service settings providing implications and suggestions for future research. © 2021 Taylor & Francis.