Globally, norovirus is associated with approximately one-fifth of all diarrhea cases, with similar prevalence in both children and adults, and is estimated to cause over 200,000 deaths annually in ...developing countries. Norovirus is an important pathogen in a number of high-priority domains: it is the most common cause of diarrheal episodes globally, the principal cause of foodborne disease outbreaks in the United States, a key health care-acquired infection, a common cause of travel-associated diarrhea, and a bane for deployed military troops. Partly as a result of this ubiquity and burden across a range of different populations, identifying target groups and strategies for intervention has been challenging. And, on top of the breadth of this public health problem, there remain important gaps in scientific knowledge regarding norovirus, especially with respect to disease in low-income settings. Many pathogens can cause acute gastroenteritis. Historically, rotavirus was the most common cause of severe disease in young children globally. Now, vaccines are available for rotavirus and are universally recommended by the World Health Organization. In countries with effective rotavirus vaccination programs, disease due to that pathogen has decreased markedly, but norovirus persists and is now the most common cause of pediatric gastroenteritis requiring medical attention. However, the data supporting the precise role of norovirus in low- and middle-income settings are sparse. With vaccines in the pipeline, addressing these and other important knowledge gaps is increasingly pressing. We assembled an expert group to assess the evidence for the global burden of norovirus and to consider the prospects for norovirus vaccine development. The group assessed the evidence in the areas of burden of disease, epidemiology, diagnostics, disease attribution, acquired immunity, and innate susceptibility, and the group considered how to bring norovirus vaccines from their current state of development to a viable product that will benefit global health.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Noroviruses are the most common cause of acute gastroenteritis across all ages worldwide. These pathogens are generally understood to exhibit a wintertime seasonality, though a systematic assessment ...of seasonal patterns has not been conducted in the era of modern diagnostics.
We conducted a systematic review of the Pubmed Medline database for articles published between 1997 and 2011 to identify and extract data from articles reporting on monthly counts of norovirus. We conducted a descriptive analysis to document seasonal patterns of norovirus disease, and we also constructed multivariate linear models to identify factors associated with the strength of norovirus seasonality.
The searched identified 293 unique articles, yielding 38 case and 29 outbreak data series. Within these data series, 52.7% of cases and 41.2% of outbreaks occurred in winter months, and 78.9% of cases and 71.0% of outbreaks occurred in cool months. Both case and outbreak studies showed an earlier peak in season-year 2002-03, but not in season-year 2006-07, years when new genogroup II type 4 variants emerged. For outbreaks, norovirus season strength was positively associated with average rainfall in the wettest month, and inversely associated with crude birth rate in both bivariate and multivariate analyses. For cases, none of the covariates examined was associated with season strength. When case and outbreaks were combined, average rainfall in the wettest month was positively associated with season strength.
Norovirus is a wintertime phenomenon, at least in the temperate northern hemisphere where most data are available. Our results point to possible associations of season strength with rain in the wettest month and crude birth rate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate ...vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus.
We developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses.
Globally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2-5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4-83.4 billion) in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4 billion for all other age groups combined. Costs per norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84-99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons), high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs), while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days).
The total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large costs overwhelmingly are from productivity losses resulting from acute illness. Low, middle, and high income countries all have a considerable economic burden, suggesting that norovirus gastroenteritis is a truly global economic problem. Our findings can help identify which age group(s) and/or geographic regions may benefit the most from interventions.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Despite substantial decreases in recent decades, acute gastroenteritis causes the second greatest burden of all infectious diseases worldwide. Noroviruses are a leading cause of ...sporadic cases and outbreaks of acute gastroenteritis across all age groups. We aimed to assess the role of norovirus as a cause of endemic acute gastroenteritis worldwide. Methods We searched Embase, Medline, and Global Health databases from Jan 1, 2008, to March 8, 2014, for studies that used PCR diagnostics to assess the prevalence of norovirus in individuals with acute gastroenteritis. We included studies that were done continuously for 1 year or more from a specified catchment area (geographical area or group of people), enrolled patients who presented with symptoms of acute gastroenteritis, and used PCR-based diagnostics for norovirus on all stool specimens from patients with acute gastroenteritis. The primary outcome was prevalence of norovirus among all cases of gastroenteritis. We generated pooled estimates of prevalence by fitting linear mixed-effect meta-regression models. Findings Of 175 articles included, the pooled prevalence of norovirus in 187 336 patients with acute gastroenteritis was 18% (95% CI 17–20). Norovirus prevalence tended to be higher in cases of acute gastroenteritis in community (24%, 18–30) and outpatient (20%, 16–24) settings compared with inpatient (17%, 15–19, p=0·066) settings. Prevalence was also higher in low-mortality developing (19%, 16–22) and developed countries (20%, 17–22) compared with high-mortality developing countries (14%, 11–16; p=0·058). Patient age and whether the study included years of novel strain emergence were not associated with norovirus prevalence. Interpretation Norovirus is a key gastroenteritis pathogen associated with almost a fifth of all cases of acute gastroenteritis, and targeted intervention to reduce norovirus burden, such as vaccines, should be considered. Funding The Foodborne Disease Burden Epidemiology Reference Group (FERG) of WHO and the Government of the Netherlands on behalf of FERG.
Background. Norovirus and rotavirus are prominent enteric viruses responsible for severe acute gastroenteritis disease burden around the world. Both viruses recognize and bind to histo-blood group ...antigens, which are expressed by the fucosyltransferase 2 (FUT2) gene. Individuals with a functional FUT2 gene are termed "secretors." FUT2 polymorphisms may influence viral binding patterns and, therefore, may influence host susceptibility to infection by these viruses. Methods. We performed a systematic review of the published literature on this topic. Data were abstracted and compiled for descriptive analyses and metaanalyses. We estimated pooled odds ratios (ORs) for infection using random-effects models. Results. We found that secretors were 9.9 times (95% confidence interval CI, 3.9–24.8) as likely to be infected with genogroup II.4 noroviruses and 2.2 times as likely to be infected with genogroup II non-4 noroviruses (95% CI, 1.2–4.2) compared with nonsecretors. Secretors were also 26.6 times more susceptible to infections from P8-type rotaviruses compared with nonsecretors (95% CI, 8.3–85.0). Conclusions. Our analyses indicate that host genetic susceptibility to norovirus and rotavirus infection may be strain specific. As strain distribution and the proportion of genetic phenotypes vary in different countries, future studies should focus on differences in susceptibility among various ethnicities. Knowledge of innate susceptibility to rotavirus and norovirus can lead to improved under-standing of both vaccine performance and individual risk of disease.
Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young ...children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed.
Abstract
In April 2020, the incidence of norovirus outbreaks reported to the National Outbreak Reporting System dramatically declined. We used regression models to determine if this decline was best ...explained by underreporting, seasonal trends, or reduced exposure due to nonpharmaceutical interventions (NPIs) implemented for severe acute respiratory syndrome coronavirus 2 using data from 9 states from July 2012 to July 2020. The decline in norovirus outbreaks was significant for all 9 states, and underreporting and/or seasonality are unlikely to be the primary explanation for these findings. These patterns were similar across a variety of settings. NPIs appear to have reduced incidence of norovirus, a nonrespiratory pathogen.
The incidence of norovirus declined in spring 2020 in the United States, at the same time that nonpharmaceutical interventions for severe acute respiratory syndrome coronavirus 2 were introduced. Nonpharmaceutical interventions appear to be an important driver of these patterns.
Vaccination with the primary series was strongly associated with reduction in COVID-19 mortality at state level in the Alpha, Delta, and Omicron wave. This effect did not vary by the state-level ...seroprevalence or estimated proportion of the population ever infected.
Abstract
Background
Immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be induced by natural infection or vaccination or both. Interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied.
Methods
We used regression models to evaluate whether the impact of coronavirus disease 2019 (COVID-19) vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for 3 evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy for the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state.
Results
COVID-19 mortality decreased as coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or proportion of the total population ever infected. Seroprevalence and proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods.
Conclusions
COVID-19 vaccination was associated with a sustained reduction in mortality at state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.
Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. Such studies are now underway amid the ongoing rollout of SARS-CoV-2 vaccines globally. ...Although traditional case-control and test-negative design studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here, we review the theoretical basis for estimation of vaccine direct effects under traditional case-control and test-negative design frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, nonspecific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The traditional case-control design may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The test-negative design reduces but may not eliminate this confounding, for instance, if individuals who receive vaccination seek care or testing for less-severe illness. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.
Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons ...for reduced efficacy in these settings could identify strategies to improve vaccine performance.
We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.
Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.
The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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