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Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroenteritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internalizes, and induces disease. [ABSTRACT FROM AUTHOR]

University administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies. [ABSTRACT FROM AUTHOR]

Concern has grown that children vaccinated against rotavirus in developing countries may be vulnerable to rotavirus diarrhea in the second year of life due to waning immunity. Adding a booster dose of rotavirus vaccine at 9 or 12 months of age with measles vaccine has been suggested as a strategy to address this. We evaluated the hypothetical potential benefits of a booster dose on reduction of rotavirus mortality. The projected number of deaths averted were calculated using national level full series vaccination coverage, estimated national rotavirus deaths by week of age, and VE at <12 months of age and ≥12 months of age derived from the published literature. We assumed three functional forms of waning based on the VE estimates: stepwise, linear, and logarithmic. We modeled three potential boosting scenarios: (a) reduced VE waning in the second year of life by 50%, (b) reestablished second year of life VE to the levels in the first year of life, and (c) boosted first year VE by 50% of the difference between VE in the first and second years. To express uncertainty resulting from the parameters, each of the nine models were run 1000 times using a random sample of input values. Across all WHO regions, with the stepwise models we estimated a median of 9800 (95%CI: 9400, 10,200), 19,600 (95%CI: 18,800, 20,400), and 29,400 (95%CI: 28,200, 30,700) additional rotavirus deaths averted in the reduced VE waning, reestablished VE, and boosted VE scenarios. These estimates were highly sensitive to the assumed functional form of waning with approximately 65–80% fewer deaths averted if immunity waned in a linear or logarithmic fashion compared to the stepwise model. While these projections will benefit from improved input data points, our results inform consideration of booster doses of rotavirus vaccine. [ABSTRACT FROM AUTHOR]

The article presents the discussion on epidemiology of endemic pathogens being essential for managing the potential for resurgence of common infections and reenergizing control efforts. Topics include influenza, measles, and norovirus continuing affecting the age distribution, severity, and typical seasonal patterns; and returning to workplaces and the resumption of in-person schooling, social activities, and large gatherings.

Background: Norovirus is the most common cause of outbreaks of acute gastroenteritis in National Health Service hospitals in the United Kingdom. Wards (units) are often closed to new admissions to stop the spread of the virus, but there is limited evidence describing the cost-effectiveness of ward closure.Methods: An economic analysis based on the results from a large, prospective, active-surveillance study of gastroenteritis outbreaks in hospitals and from an epidemic simulation study compared alternative ward closure options evaluated at different time points since first infection, assuming different efficacies of ward closure.Results: A total of 232 gastroenteritis outbreaks occurring in 14 hospitals over a 1-year period were analyzed. The risk of a new outbreak in a hospital is significantly associated with the number of admission, general medical, and long-stay wards that are concurrently affected but is less affected by the level of community transmission. Ward closure leads to higher costs but reduces the number of new outbreaks by 6%-56% and the number of clinical cases by 1%-55%, depending on the efficacy of the intervention. The incremental cost per outbreak averted varies from £10 000 ($14 000) to £306 000 ($428 000), and the cost per case averted varies from £500 ($700) to £61 000 ($85 000). The cost-effectiveness of ward closure decreases as the efficacy of the intervention increases, and the cost-effectiveness increases with the timing of the intervention. The efficacy of ward closure is critical from a cost-effectiveness perspective.Conclusions: Ward closure may be cost-effective, particularly if targeted to high-throughput units. [ABSTRACT FROM AUTHOR]

Background. Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. Methods. We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. Results. Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). Conclusions. GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children. [ABSTRACT FROM AUTHOR]

Summary Background Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. Methods We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. Findings In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80–98) against homotypic strains, 71% (39–86) against partly heterotypic strains, and 87% (76–93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36–73), 72% (58–81), and 47% (28–61). In high-income countries, RV5 vaccine effectiveness was 83% (78–87) against homotypic strains, 82% (70–89) against single-antigen vaccine type strains, 82% (70–89) against partly heterotypic strains, and 75% (47–88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58–78) against single-antigen vaccine type strains, 37% (10–56) against partly heterotypic strains, and 87% (38–97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P[4] (2198 of 4428, 50%) and G1P[8] (953, 22%), and those in countries using RV5 were G1P[8] (1280 of 3875, 33%) and G2P[4] (1169, 30%). Sustained predominance of a single strain was not recorded. Interpretation RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. Funding None. [ABSTRACT FROM AUTHOR]

Serum antibodies play an important role in natural protection from rotavirus infection and disease, but conflicting estimates of association have emerged from epidemiological studies in different geographical settings. In this study, we aim to assess the relationship between pre-existing serum immunoglobulin (Ig)G and IgA titers with protection against rotavirus infection and disease in a birth cohort of Indian children. Children were recruited at birth and followed up for 36 months. Stool samples were collected every 2 weeks and during episodes of diarrhea and serum samples were obtained at least every 6 months. The incidence rate of rotavirus infection and diarrhea was 0.9 (95% CI: 0.88, 0.99) and 0.2 (95% CI: 0.19, 0.25) episodes per child year, respectively. The risk of rotavirus infection and diarrhea decreased with age, while antibody titers (IgG and IgA) increased with age. After adjusting for age and number of previous infections, higher levels of IgG and IgA were independently associated with reduced risk of rotavirus infection. However, we did not find a clear association of IgG or IgA with rotavirus diarrhea risk or a threshold level of protection. The study supports a correlation of serum antibodies in reducing the risk of rotavirus infections, however the potential of serum antibody titer as a correlate of protection is not clear for children in lower income settings. [ABSTRACT FROM AUTHOR]

The pathogenicity of norovirus is definitively established. However, norovirus is frequently detected in the stool of healthy individuals. To gain understanding of the apparent high prevalence of asymptomatic infection, we analyzed a dynamic transmission model of norovirus infection, disease, and immunity. We simulated norovirus epidemiology in low- and high-transmission settings by varying the basic reproduction number (R0). We predicted annual disease incidence values in children aged 0–4 years of 25% with a low R0 and 29% with a high R0. However, the point prevalence of asymptomatic infection rose sharply from 3% to 48% from the low to high R0 settings. Among older children and adults, the models projected that incidence of disease would rise from 6% to 16% from the low to high R0 settings, whereas asymptomatic infection prevalence was lower in this age group. Asymptomatic prevalence of norovirus can change dramatically with small changes in R0. The ratio of prevalence in cases to controls could be high in a developed country and close to or even less than 1 in a high-exposure setting, despite similar disease incidence. These findings highlight an important limitation of case-control studies for pathogens for which there is suboptimal diagnostic specificity. [ABSTRACT FROM PUBLISHER]

Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570--800 deaths, 56,000--71,000 hospitalizations, 400,000 emergency department visits, 1.7--1.9 million outpatient visits, and 19--21 million total illnesses per year. Persons ≥65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease. [ABSTRACT FROM AUTHOR]

Background: We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era. Methods: Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (household-contact characteristics). Results: Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was <18 months and had vomiting, with household contact <10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission. Conclusion: Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees. [ABSTRACT FROM AUTHOR]

Following the introduction of rotavirus vaccination in the United States, rotavirus and cause-unspecified gastroenteritis discharges significantly decreased in 2008 in the 0-4, 5-14, and 15-24-year age groups, with significant reductions observed in March, the historic peak rotavirus month, in all age groups. We estimate that 15% of the total 66 000 averted hospitalizations and 20% of the $204 million in averted direct medical costs attributable to the vaccination program were among unvaccinated 5-24 year-olds. This study demonstrates a previously unrecognized burden of severe rotavirus in the population >5 years and the primacy of very young children in the transmission of rotavirus. [ABSTRACT FROM AUTHOR]

Background. Diarrhea remains an important cause of morbidity, but until the mid 1990s, hospital admissions for diarrhea in the US adult population were declining. We aimed to describe recent trends in gastroenteritis hospitalizations and to determine the contribution of norovirus. Methods. We analyzed all gastroenteritis-associated hospital discharges during 1996-2007 from a nationally representative data set of hospital inpatient stays. Annual rates of discharges by age were calculated. Time-series regression models were fitted using cause-specified discharges as explanatory variables; model residuals were analyzed to estimate norovirus- and rotavirus-associated discharges. We then calculated the annual hospital charges for norovirus-associated discharges. Results. Sixty-nine percent of all gastroenteritis discharges were cause-unspecified and rates increased by⩾50% in all adult and elderly age groups (⩾18 years of age) from 1996 through 2007. We estimate an annual mean of 71,000 norovirus-associated hospitalizations, costing $493 million per year, with surges to nearly 110,000 hospitalizations per year in epidemic seasons. We also estimate 24,000 rotavirus hospitalizations annually among individuals aged ⩾5 years. Conclusions. Gastroenteritis hospitalizations are increasing, and we estimate that norovirus is the cause of 10% of cause-unspecified and 7% of all-cause gastroenteritis discharges. Norovirus should be routinely considered as a cause of gastroenteritis hospitalization. [ABSTRACT FROM AUTHOR]

Rotavirus is a major cause of infectious intestinal disease in young children; a substantial prevalence of asymptomatic infection has been reported across all age groups. In this study, the authors determined characteristics of asymptomatic rotavirus infection and potential risk factors for infection. Healthy persons were recruited at random from the general population of England during the Study of Infectious Intestinal Disease in England (1993–1996). Rotavirus infection was identified using reverse-transcription polymerase chain reaction. Multivariable logistic regression was used to compare exposures reported by participants with rotavirus infection with those of participants who tested negative. Multiple imputation was used to account for missing responses in the data set. The age-adjusted prevalence of asymptomatic rotavirus infection was 11%; prevalence was highest in children under age 18 years. Attendance at day care was a risk factor for asymptomatic rotavirus infection in children under age 5 years; living in a household with a baby that was still in diapers was a risk factor in older adults. The results suggest that asymptomatic rotavirus infection is transmitted through the same route as rotavirus infectious intestinal disease: person-to-person contact. More work is needed to understand the role of asymptomatic infections in transmission leading to rotavirus disease. [ABSTRACT FROM PUBLISHER]

Abstract: Two rotavirus vaccines are currently recommended for inclusion in routine childhood immunization programmes. We developed a deterministic age-structured model of rotavirus transmission and disease to investigate the population-level effects of vaccination in England and Wales. The model explicitly captures the natural history of infection and uses realistic population mixing patterns. The model accurately reproduces the strong seasonal pattern and age distribution of rotavirus disease observed in England and Wales. We predict vaccination will provide both direct and indirect protection within the population. If coverage levels comparable to other childhood vaccines are achieved, we predict that vaccination will reduce rotavirus disease incidence by 61% resulting in a potential fall in burden on health-care services. [Copyright &y& Elsevier]

Norovirus, the most commonly identified cause of both sporadic cases and outbreaks of infectious diarrhoea in developed countries, exhibits a complex epidemiology and has a strong wintertime seasonality. Viral populations are dynamic and evolve under positive selection pressure. Methods: Time series-adapted Poisson regression models were fitted to daily counts of laboratory reports of norovirus in England and Wales from 1993 to 2006. Findings: Inverse linear associations with daily temperature over the previous seven weeks (rate ratio (RR) = 0.85; 95% CI: 0.83 to 0.86 for every 1°C increase) and relative humidity over the previous five weeks (RR = 0.980; 95% CI: 0.973 to 0.987 for every 1% increase) were found, with temperature having a greater overall effect. The emergence of new norovirus variants (RR = 1.16; 95% CI: 1.10 to 1.22) and low population immunity were also associated with heightened norovirus activity. Temperature and humidity, which may be localised, had highly consistent effects in each region of England and Wales. Conclusions: These results point to a complex interplay between host, viral and climatic factors driving norovirus epidemic patterns. Increases in norovirus are associated with cold, dry temperature, low population immunity and the emergence of novel genogroup 2 type 4 antigenic variants. [ABSTRACT FROM AUTHOR]

Abstract: Background: The use of RT-PCR for diagnosis of group A rotaviruses is increasing, but up to 14% of healthy individuals may be positive by RT-PCR. If RT-PCR is not well correlated with disease, rotavirus A may not always be the cause of illness in RT-PCR positive patients with infectious intestinal disease (IID). Objectives: To describe the differences in faecal viral load between ELISA positive IID cases, RT-PCR positive cases and healthy controls. To develop a cut-off in faecal viral load for attributing illness to rotavirus A in RT-PCR positive IID cases. Study design: Faecal viral load was measured, using real time RT-PCR, in 118 community IID cases and 65 healthy controls, previously tested by ELISA. Cycle threshold (Ct) values from the real-time RT-PCR were used as a proxy measure of viral load. A cut-off for attributing illness to rotavirus A was selected, using ROC analysis. Results: There was little overlap in viral load between ELISA positive IID cases (median Ct 17) and healthy controls (median Ct 37), but ELISA negative, RT-PCR positive IID cases (median Ct 37) had viral loads similar to healthy controls, indicating that RT-PCR is not detecting extra cases of group A rotavirus associated IID, only sub-clinical infections. The optimal cut-off in the real time RT-PCR was at Ct value 24–27. Conclusion: ELISA is the best method for the laboratory diagnosis of rotavirus A associated IID. If RT-PCR is used, it is advisable to use a real time platform and to use a viral load cut-off equivalent to the detection limit of ELISA. [Copyright &y& Elsevier]

Background: Reverse transcription-polymerase chain reaction (RT-PCR) is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID). However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case. Methods: Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct) values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC) analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases. Results: One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories. Conclusion: We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to define in-house cut-offs for their assays, to provide the best possible diagnostic service to clinicians and public health workers. Other clinical and epidemiological information should also be considered for patients with Ct values close to the cut-off, for the most accurate diagnosis of IID aetiology. [ABSTRACT FROM AUTHOR]

HIV prevalence has recently begun to decline in Zimbabwe, a result of both high levels of AIDS mortality and a reduction in incident infections. An important component in understanding the dynamics in HIV prevalence is knowledge of past trends in incidence, such as when incidence peaked and at what level. However, empirical measurements of incidence over an extended time period are not available from Zimbabwe or elsewhere in sub-Saharan Africa. Using mortality data, we use a back-calculation technique to reconstruct historic trends in incidence. From AIDS mortality data, extracted from death registration in Harare, together with an estimate of survival post-infection, HIV incidence trends were reconstructed that would give rise to the observed patterns of AIDS mortality. Models were fitted assuming three parametric forms of the incidence curve and under nine different assumptions regarding combinations of trends in non-AIDS mortality and patterns of survival post-infection with HIV. HIV prevalence was forward-projected from the fitted incidence and mortality curves. Models that constrained the incidence pattern to a cubic spline function were flexible and produced well-fitting, realistic patterns of incidence. In models assuming constant levels of non-AIDS mortality, annual incidence peaked between 4 and 5% between 1988 and 1990. Under other assumptions the peak level ranged from 3 to 8% per annum. However, scenarios assuming increasing levels of non-AIDS mortality resulted in implausibly low estimates of peak prevalence (11%), whereas models with decreasing underlying crude mortality could be consistent with the prevalence and mortality data. HIV incidence is most likely to have peaked in Harare between 1988 and 1990, which may have preceded the peak elsewhere in Zimbabwe. This finding, considered alongside the timing and location of HIV prevention activities, will give insight into the decline of HIV prevalence in Zimbabwe. [ABSTRACT FROM AUTHOR]

Objective To compare alternative methods to vital registration systems for estimating adult mortality, and describe patterns of mortality in Manicaland, Zimbabwe, which has been severely affected by HIV. Methods We compared estimates of adult mortality from (1) a single question on household mortality, (2) repeated household censuses, and (3) an adult cohort study with linked HIV testing from Manicaland, with a mathematical model fitted to local age-specific HIV prevalence (1998-2000). Findings The crude death rate from the single question (29 per 1000 person-years) was roughly consistent with that from the mathematical model (22-25 per 1000 person-years), but much higher than that from the household censuses (12 per 1000 person-years). Adult mortality in the household censuses (males 0.65; females 0.51) was lower than in the cohort study (males 0.77; females 0.57), while mathematical models gave a much higher estimate, especially for females (males 0.80-0.83; females 0.75-0.80). The population attributable fraction of adult deaths due to HIV was 0.61 for men and 0.70 for women, with life expectancy estimated to be 34.3 years for males and 38.2 years for females. Conclusion Each method for estimating adult mortality had limitations in terms of loss to follow-up (cohort study), under-ascertainment (household censuses), transparency of underlying processes (single question), and sensitivity to parameterization (mathematical model). However, these analyses make clear the advantages of longitudinal cohort data, which provide more complete ascertainment than household censuses, highlight possible inaccuracies in model assumptions, and allow direct quantification of the impact of HIV. [ABSTRACT FROM AUTHOR]

Background: Noroviruses are highly infectious pathogens that cause gastroenteritis in the community and in semi-closed institutions such as hospitals. During outbreaks, multiple units within a hospital are often affected, and a major question for control programs is: are the affected units part of the same outbreak or are they unrelated transmission events? In practice, investigators often assume a transmission link based on epidemiological observations, rather than a systematic approach to tracing transmission. Here, we present a combined molecular and statistical method for assessing: 1) whether observed clusters provide evidence of local transmission and 2) the probability that anecdotally∣linked outbreaks truly shared a transmission event. Methods: 76 healthcare associated outbreaks were observed in an active and prospective surveillance scheme of 15 hospitals in the county of Avon, England from April 2002 to March 2003. Viral RNA from 64 out of 76 specimens from distinct outbreaks was amplified by reverse transcription-PCR and was sequenced in the polymerase (ORF 1) and capsid (ORF 2) regions. The genetic diversity, at the nucleotide level, was analysed in relation to the epidemiological patterns. Results: Two out of four genetic and epidemiological clusters of outbreaks were unlikely to have occurred by chance alone, thus suggesting local transmission. There was anecdotal epidemiological evidence of a transmission link among 5 outbreaks pairs. By combining this epidemiological observation with viral sequence data, the evidence of a link remained convincing in 3 of these pairs. These results are sensitive to prior beliefs of the strength of epidemiological evidence especially when the outbreak strains are common in the background population. Conclusion: The evidence suggests that transmission between hospitals units does occur. Using the proposed criteria, certain hypothesized transmission links between outbreaks were supported while others were refuted. The combined molecular/epidemiologic approach presented here could be applied to other viral populations and potentially to other pathogens for a more thorough view of transmission. [ABSTRACT FROM AUTHOR]

Background It has recently been argued that unsafe medical injections are a major transmission route of HIV infection in the generalised epidemics of sub-Saharan Africa. Methods and Findings We have analysed the pattern of injections in relation to HIV incidence in a population cohort in Manicaland in a rural area of Zimbabwe. In Poisson regression models, injections were not found to be associated with HIV in males (rate ratio = 0.33; 95% confidence interval: 0.07 to 1.46) or females (rate ratio = 1.04; 95% confidence interval: 0.59 to 1.85). Conclusion It is important that unsafe medical injections can be confidently excluded as a major source of HIV infection. In rural Zimbabwe the evidence is that they can. [ABSTRACT FROM AUTHOR]

Healthcare-associated outbreaks of gastroenteritis are an increasingly recognized problem, but detailed knowledge of the epidemiology of these events is lacking. We actively monitored three hospital systems in England for outbreaks of gastroenteritis in 2002 to 2003. A total of 2,154 patients (2.21 cases/1,000 hospital-days) and 1,360 health-care staff (0.47 cases/1,000 hospital-days) were affected in 227 unit outbreaks (1,33 outbreaks/unit-year). Norovirus, detected in 63% of outbreaks, was the predominant etiologic agent. Restricting new admissions to affected units resulted in 5,443 lost bed-days. The cost of bed-days lost plus staff absence was calculated to be £635,000 (U.S.$ 1.01 million) per 1,000 beds. By our extrapolation, gastroenteritis outbreaks likely cost the English National Health Service £115 million (U.S,$ 184 million) in 2002 to 2003. Outbreaks were contained faster (7,9 vs. 15.4 days, p = 0.0023) when units were rapidly dosed to new admissions (<4 days). Implementing control measures rapidly may be effective in controlling outbreaks. [ABSTRACT FROM AUTHOR]

Noroviruses are generally believed to cause relatively mild gastroenteritis of short duration in otherwise healthy adults. However, outbreaks in health care settings are common and affect vulnerable populations. During 2002-2003, a total of 4 major hospitals, 11 community hospitals, and 135 nursing homes in the county of Avon, England, were prospectively monitored for outbreaks of gastroenteritis. For 482 hospital staff, 166 nursing home staff, and 266 nursing home residents, the median duration of norovirus gastroenteritis was 2 days, with 75% achieving complete recovery within 3 days. The median duration of norovirus gastroenteritis for 730 hospital patients was 3 days (75% of the patients achieved complete recovery within 5 days), which was significantly longer than that for all other groups (P< .001). Therefore, infection in hospitalized persons may be more severe than that in other groups in the community at large. This increased duration of acute illness should be considered when implementing measures to prevent transmission in hospital settings. [ABSTRACT FROM AUTHOR]

To gain understanding of surveillance and epidemiology of viral gastroenteritis outbreaks in Europe, we compiled data from 10 surveillance systems in the Foodborne Viruses in Europe network. Established surveillance systems found Norovirus to be responsible for >85% (N =3,714) of all nonbacterial outbreaks of gastroenteritis reported from 1995 to 2000. However, the absolute number and population-based rates of viral gastroenteritis outbreaks differed markedly among European surveillance systems. A wide range of estimates of the importance of foodborne transmission were also found. We review these differences within the context of the sources of outbreak surveillance information, clinical definitions, and structures of the outbreak surveillance systems. [ABSTRACT FROM AUTHOR]

Background: Noroviruses are the most common cause of gastroenteritis outbreaks in industrialised countries. Gastroenteritis caused by Norovirus infection has been described as a highly seasonal syndrome, often referred to as "winter vomiting disease". Methods: The Public Health Laboratory Service Communicable Disease Surveillance Centre has systematically collected reports of laboratory confirmed cases of Norovirus-gastroenteritis since 1995. We analysed these data for annual and seasonal trends and age distribution. Results: A mid-summer peak in reported cases of Norovirus was observed in 2002, unlike all six previous years when there was a marked summer decline. Total reports from 2002 have also been higher than all previous years. From the first 10 months of 2002, a total of 3029 Norovirus diagnoses were reported compared the previous peak in 1996 of 2437 diagnoses for the whole 12-month period. The increase in 2002 was most marked in the 65 and older age group. Conclusion: This surveillance data challenges the view that Noroviruses infections exclusively have wintertime seasonality. [ABSTRACT FROM AUTHOR]

The authors explore the importance of birth cohorts in understanding norovirus infection, epidemiology and immunity. They note on the importance of birth cohort studies in understanding the acquisition of protective immunity against a pathogen. They mention a birth cohort study in Mexico which showed that severe disease is restricted to the first 2 infections, that each infection reduces future disease risk.

The authors discuss the implications of a new study that presents compelling data to show that norovirus evolution is driven by immune selection pressure. [ABSTRACT FROM AUTHOR]

Presents the response of the authors to comments on their study regarding the association between injections and HIV incidence. Investigation of the hypothesised importance of medical injections in the transmission of HIV in Africa; Difficulty in collecting data for the study; Problems in generating reliable responses to questions about sexual behavior.

In this first special theme issue, Emerging Themes in Epidemiology publishes a collection of articles on the theme of Epidemiology in conflict. Violent conflict is an issue of great sensitivity within public health, but more structured research and reasoned discussion will allow us to better mitigate the public health impacts of war, and place the public health community in a more informed position in discussions about possible interventions in future conflicts. [ABSTRACT FROM AUTHOR]

Emerging Themes in Epidemiology is a new, online Open Access journal. This editorial — which coincides with the Journal's launch — describes its unique review and publication model. The editorial board and review process of ETE will be managed by research degree students and will therefore be a training ground for students (though final editorial control rests with senior faculty Associate Editors). With our mix of Open Access publishing and the strong involvement of students in editing and reviewing, we believe that Emerging Themes in Epidemiology will be a progressive medium for promoting new ideas in epidemiology. [ABSTRACT FROM AUTHOR]

Background While prior studies have suggested a role for norovirus gastroenteritis in contributing to severe morbidity and mortality, the importance of norovirus as a causal pathogen for hospitalization and mortality remains poorly understood. We estimated the effect of laboratory-confirmed norovirus infection on hospitalization and mortality among a national cohort of veterans who sought care within the Veterans Affairs health care system. Methods We analyzed electronic health record data from a cohort study of adults who were tested for norovirus within the Veterans Affairs system between 1 January 2010 and 31 December 2018. Adjusted risk ratios (aRRs) for hospitalization and mortality were estimated using log-binomial regression models, adjusting for age, Clostridioides difficile , underlying medical conditions, and nursing home residence. Results In total, 23 196 veterans had 25 668 stool samples tested for norovirus; 2156 samples (8.4%) tested positive. Testing positive for norovirus infection, compared with testing negative, was associated with a slight increased risk of hospitalization (aRR, 1.13 [95% confidence interval, 1.06–1.21]) and a significant increased risk of mortality within 3 days after the norovirus test (2.14 [1.10–4.14]). The mortality aRR within 1 week and 1 month were reduced to 1.40 (95% confidence interval,.84–2.34) and 0.97 (.70–1.35), respectively. Conclusions Older veterans with multiple comorbid conditions were at a slight increased risk of hospitalization and significant increased risk of mortality in the 3 days after a norovirus-positive test, compared with those testing negative. Clinicians should be aware of these risks and can use these data to inform clinical management for veterans with norovirus. [ABSTRACT FROM AUTHOR]

Norovirus is the leading cause of acute gastroenteritis and foodborne disease in the United States. The Food and Drug Administration recommends that food workers infected with norovirus be excluded from the workplace while symptomatic and for 48 hours after their symptoms subside. Compliance with this recommendation is not ideal, and the population-level impacts of changes in food-worker compliance have yet to be quantified. We aimed to assess the population impacts of varying degrees of compliance with the current recommendation through the use of a compartmental model. We modeled the number and proportion of symptomatic norovirus cases averted annually in the US population (using data from 1983–2014) in specific age groups (children aged <5 years, children aged 5–17 years, adults aged 18–64 years, and adults aged ≥65 years) under various scenarios of food-worker exclusion (i.e. proportion compliant and days of postsymptomatic exclusion) in comparison with a referent scenario which assumed that 66. 6 ¯ % of norovirus-symptomatic food workers and 0% of postsymptomatic food workers were excluded from work. Overall, we estimated that 6.0 million cases of norovirus have already been avoided annually under the referent scenario and that 6.7 million (28%) more cases might be avoided through 100% compliance with the current recommendations. Substantial population-level benefits were predicted from improved compliance in exclusion of norovirus-infected food workers from the workplace—benefits that may be realized through policies or programs incentivizing self-exclusion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Indirect protection and indirect measures of protection from rotavirus in adults," by E.J. Anderson, S. Reddy, B.Z. Katz and G. Noskin in the 2012 issue.

The author focuses on environmental transmission of norovirus due to vomiting on aircraft. He mentions that public vomiting in direct transmission can spread norovirus and can lead to outbreaks and from the time of vomiting norovirus occurs a week later. He also mentions that the use of sodium hypochlorite can least prevent the outbreak and he suggests for an additional study to find the needed disinfectants or sanitizer that are safe and effective when norovirus outbreak occur.

The article comments the study on the re-evaluation of epidemiological criteria for keying out outbreaks of acute gastroenteritis due to norovirus in the U.S. The author stressed that the data used in the study is limited that do not clearly reflect the overall occurrence of the outbreak. He asserted that the result of the study therefore fall short in providing the basic information about norovirus epidemiology.

Essential food workers experience elevated risks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to prolonged occupational exposures in food production and processing areas, shared transportation (car or bus), and employerprovided shared housing. Our goal was to quantify the daily cumulative risk of SARS-CoV-2 infection for healthy susceptible produce workers and to evaluate the relative reduction in risk attributable to food industry interventions and vaccination. We simulated daily SARSCoV- 2 exposures of indoor and outdoor produce workers through six linked quantitative microbial risk assessment (QMRA) model scenarios. For each scenario, the infectious viral dose emitted by a symptomatic worker was calculated across aerosol, droplet, and fomitemediated transmission pathways. Standard industry interventions (2-m physical distancing, handwashing, surface disinfection, universal masking, ventilation) were simulated to assess relative risk reductions from baseline risk (no interventions, 1-m distance). Implementation of industry interventions reduced an indoor worker's relative infection risk by 98.0% (0.020; 95% uncertainty interval [UI], 0.005 to 0.104) from baseline risk (1.00; 95% UI, 0.995 to 1.00) and an outdoor worker's relative infection risk by 94.5% (0.027; 95% UI, 0.013 to 0.055) from baseline risk (0.487; 95% UI, 0.257 to 0.825). Integrating these interventions with twodose mRNA vaccinations (86 to 99% efficacy), representing a worker's protective immunity to infection, reduced the relative infection risk from baseline for indoor workers by 99.9% (0.001; 95% UI, 0.0002 to 0.005) and outdoor workers by 99.6% (0.002; 95% UI, 0.0003 to 0.005). Consistent implementation of combined industry interventions, paired with vaccination, effectively mitigates the elevated risks from occupationally acquired SARS-CoV-2 infection faced by produce workers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Vital registration and cause of death reporting is incomplete in the countries in which the HIV epidemic is most severe. A reliable tool that is independent of HIV status is needed for measuring the frequency of AIDS deaths and ultimately the impact of antiretroviral therapy on mortality.Methods and Findings: A verbal autopsy questionnaire was administered to caregivers of 381 adults of known HIV status who died between 1998 and 2003 in Manicaland, eastern Zimbabwe. Individuals who were HIV positive and did not die in an accident or during childbirth (74%; n = 282) were considered to have died of AIDS in the gold standard. Verbal autopsies were randomly allocated to a training dataset (n = 279) to generate classification criteria or a test dataset (n = 102) to verify criteria. A rule-based algorithm created to minimise false positives had a specificity of 66% and a sensitivity of 76%. Eight predictors (weight loss, wasting, jaundice, herpes zoster, presence of abscesses or sores, oral candidiasis, acute respiratory tract infections, and vaginal tumours) were included in the algorithm. In the test dataset of verbal autopsies, 69% of deaths were correctly classified as AIDS/non-AIDS, and it was not necessary to invoke a differential diagnosis of tuberculosis. Presence of any one of these criteria gave a post-test probability of AIDS death of 0.84.Conclusions: Analysis of verbal autopsy data in this rural Zimbabwean population revealed a distinct pattern of signs and symptoms associated with AIDS mortality. Using these signs and symptoms, demographic surveillance data on AIDS deaths may allow for the estimation of AIDS mortality and even HIV prevalence. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Paying for bmj.com," by Delamonthe T. Smith in the August 2, 2003 issue.

Background: Although effective against hepatitis B virus (HBV) infection, hepatitis B (HepB) vaccination is only recommended for infants, children, and adults at higher risk. We conducted an economic evaluation of universal HepB vaccination among US adults.Methods: Using a decision analytic model with Markov disease progression, we compared current vaccination recommendations (baseline) with either 3-dose or 2-dose universal HepB vaccination (intervention strategies). In simulated modeling of 1 million adults distributed by age and risk groups, we quantified health benefits (quality-adjusted life years, QALYs) and costs for each strategy. Multivariable probabilistic sensitivity analyses identified key inputs. All costs reported in 2019 US dollars.Results: With incremental base-case vaccination coverage up to 50% among persons at lower risk and 0% increment among persons at higher risk, each of 2 intervention strategies averted nearly one-quarter of acute HBV infections (3-dose strategy, 24.8%; 2-dose strategy, 24.6%). Societal incremental cost per QALY gained of $152 722 (interquartile range, $119 113-$235 086) and $155 429 (interquartile range, $120 302-$242 226) were estimated for 3-dose and 2-dose strategies, respectively. Risk of acute HBV infection showed the strongest influence.Conclusions: Universal adult vaccination against HBV may be an appropriate strategy for reducing HBV incidence and improving resulting health outcomes. [ABSTRACT FROM AUTHOR]

Background Vaccines may play a role in controlling the spread of antibiotic resistance. However, it is unknown if rotavirus vaccination affects antibiotic use in the United States (US). Methods Using data from the IBM MarketScan Commercial Database, we conducted a retrospective cohort of US children born between 2007 and 2018 who were continuously enrolled for the first 8 months of life (N = 2 136 136). We followed children through 5 years of age and compared children who completed a full rotavirus vaccination series by 8 months of age to children who had not received any doses of rotavirus vaccination. We evaluated antibiotic prescriptions associated with an acute gastroenteritis (AGE) diagnosis and defined the switching of antibiotics as the prescription of a second, different antibiotic within 28 days. Using a stratified Kaplan-Meier approach, we estimated the cumulative incidence for each study group, adjusted for receipt of pneumococcal conjugate vaccine, provider type, and urban/rural status. Results Overall, 0.8% (n = 17 318) of participants received an antibiotic prescription following an AGE diagnosis. The 5-year adjusted relative cumulative incidence of antibiotic prescription following an AGE diagnosis was 0.793 (95% confidence interval [CI],.761–.827) among children with complete rotavirus vaccination compared to children without rotavirus vaccination. Additionally, children with complete vaccination were less likely to switch antibiotics (0.808 [95% CI,.743–.887]). Rotavirus vaccination has averted an estimated 67 045 (95% CI, 53 729–80 664) antibiotic prescriptions nationally among children born between 2007 and 2018. Conclusions These results demonstrate that rotavirus vaccines reduce antibiotic prescribing for AGE, which could help reduce the growth of antibiotic resistance. [ABSTRACT FROM AUTHOR]

The article discusses the changing epidemiology and understanding of the complex and varying dynamics of severe acute respiratory syndrome coronavirus 2, the virus that causes the COVID-19 pandemic. The researchers retraced the steps through the questions that the community faced as the pandemic unfolded. It highlights the key roles of mathematical modeling and quantitative analyses of empirical data in addressing the questions and to better understand and control the pandemic.

We have come a long way since the start of the COVID-19 pandemicÑfrom hoarding toilet paper and wiping down groceries to sending our children back to school and vaccinating billions. Over this period, the global community of epidemiologists and evolutionary biologists has also come a long way in understanding the complex and changing dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. In this Review, we retrace our steps through the questions that this community faced as the pandemic unfolded. We focus on the key roles that mathematical modeling and quantitative analyses of empirical data have played in allowing us to address these questions and ultimately to better understand and control the pandemic. [ABSTRACT FROM AUTHOR]

Background Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. Methods We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months–17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012–2013 to 2016–2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 – adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. Results We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7–10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012–2013 to 2016–2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. Conclusions Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons. [ABSTRACT FROM AUTHOR]

Understanding how immunity shapes the dynamics of multistrain pathogens is essential in determining the selective pressures imposed by vaccines. There is currently much interest in elucidating the strain dynamics of rotavirus to determine whether vaccination may lead to the replacement of vaccine-type strains. In developed countries, G1P[8] strains constitute the majority of rotavirus infections most years, but occasionally other genotypes dominate for reasons that are not well understood. We developed a mathematical model to examine the interaction of five common rotavirus genotypes. We explored a range of estimates for the relative strength of homotypic vs. heterotypic immunity and compared model predictions against observed genotype patterns from six countries. We then incorporated vaccination in the model to examine its impact on rotavirus incidence and the distribution of strains. Our model can explain the coexistence and cyclical pattern in the distribution of genotypes observed in most developed countries. The predicted frequency of cycling depends on the relative strength of homotypic vs. heterotypic immunity. Vaccination that provides strong protection against G1 and weaker protection against other strains will likely lead to an increase in the relative prevalence of non-G1 strains, whereas a vaccine that provides equally strong immunity against all strains may promote the continued predominance of G1. Overall, however, disease incidence is expected to be substantially reduced under both scenarios and remain below prevaccination levels despite the possible emergence of new strains. Better understanding of homotypic vs. heterotypic immunity, both natural and vaccine-induced, will be critical in predicting the impact of vaccination. [ABSTRACT FROM AUTHOR]