It has been hypothesized that micronutrient levels play a role in the immune response to vaccination; however, population-level research on the association between micronutrient levels and immune response to influenza vaccination is needed. In this study, we hypothesized that decreasing levels of nutrients would be associated with decreased hemagglutination inhibition (HAI) responses to influenza vaccination. Therefore, the purpose of this study was to determine whether serum vitamin A, vitamin E, or zinc levels are associated with influenza vaccine response determined by HAI titer in adults 65 years or older. Participants in this study included 205 community-dwelling adults 65 years or older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009. Participants received trivalent influenza vaccine and donated blood samples before and 21 to 28 days after vaccination. Prevaccination levels of serum retinol, α-tocopherol, and zinc as well as prevaccination and postvaccination HAI titer levels were measured. No participants were vitamin A or vitamin E deficient; 20% had low serum zinc levels (<70 μg/dL). Continuous variables and categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not related to prevaccination or postvaccination seroprotection or seroconversion for any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after adjusting for age, sex, body mass index, and prevaccination HAI geometric mean titer. In conclusion, our study population showed no association between variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine response as measured by HAI in adults older than 65 years. Thus, associations between micronutrients and other measures of vaccine response, such as cell-mediated immune parameters, should also be explored.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months. Each season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine in preventing medically attended acute respiratory illness (ARI) associated with laboratory-confirmed influenza. This season, early estimates of influenza vaccine effectiveness are possible because of widespread, early circulation of influenza viruses. By January 3, 2015, 46 states were experiencing widespread flu activity, with predominance of influenza A (H3N2) viruses. This report presents an initial estimate of seasonal influenza vaccine effectiveness at preventing laboratory-confirmed influenza virus infection associated with medically attended ARI based on data from 2,321 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (Flu VE) during November 10, 2014-January 2, 2015. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age, sex, race/ethnicity, self-rated health, and days from illness onset to enrollment) against laboratory-confirmed influenza associated with medically attended ARI was 23% (95% confidence interval [CI] = 8%-36%). Most influenza infections were due to A (H3N2) viruses. This interim VE estimate is relatively low compared with previous seasons when circulating viruses and vaccine viruses were well-matched and likely reflects the fact that more than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014-15 Northern Hemisphere seasonal influenza vaccines. These early, low VE estimates underscore the need for ongoing influenza prevention and treatment measures. CDC continues to recommend influenza vaccination because the vaccine can still prevent some infections with the currently circulating A (H3N2) viruses as well as other viruses that might circulate later in the season, including influenza B viruses. Even when VE is reduced, vaccination still prevents some illness and serious influenza-related complications, including thousands of hospitalizations and deaths. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated, including persons who might already have been ill with influenza this season.

In our prospective cohort study, we compared the performance of nasopharyngeal, oropharyngeal, and nasal swabs for the detection of influenza virus using real-time reverse transcription-PCR assay. Joint consideration of results from oropharyngeal and nasal swabs was as effective as consideration of results from nasopharyngeal swabs alone, as measured by sensitivity and noninferiority analysis.

Early influenza activity during the 2012-13 season enabled estimation of the unadjusted effectiveness of the seasonal influenza vaccine. This report presents updated adjusted estimates based on 2,697 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network during December 3, 2012-January 19, 2013. During this period, overall vaccine effectiveness (VE) (adjusted for age, site, race/ethnicity, self-rated health, and days from illness onset to enrollment) against influenza A and B virus infections associated with medically attended acute respiratory illness was 56%, similar to the earlier interim estimate (62%). VE was estimated as 47% against influenza A (H3N2) virus infections and 67% against B virus infections. When stratified by age group, the point estimates for VE against influenza A (H3N2) and B infections were largely consistent across age groups, with the exception that lower VE against influenza A (H3N2) was observed among adults aged ≥65 years. These adjusted VE estimates indicate that vaccination with the 2012-13 influenza season vaccine reduced the risk for outpatient medical visits resulting from influenza by approximately one half to two thirds for most persons, although VE was lower and not statistically significant among older adults. Antiviral medications should be used as recommended for treatment of suspected influenza in certain patients, including those aged ≥65 years, regardless of their influenza vaccination status.

The clinical manifestations of Lyme disease, caused by Borrelia burgdorferi, vary considerably in different patients, possibly due to infection by strains with varying pathogenicity. Both rRNA intergenic spacer and ospC typing methods have proven to be useful tools for categorizing B. burgdorferi strains that vary in their tendency to disseminate in humans. Neither method, however, is suitable for inferring intraspecific relationships among strains that are important for understanding the evolution of pathogenicity and the geographic spread of disease. In this study, multilocus sequence typing (MLST) was employed to investigate the population structure of B. burgdorferi recovered from human Lyme disease patients. A total of 146 clinical isolates from patients in New York and Wisconsin were divided into 53 sequence types (STs). A goeBURST analysis, that also included previously published STs from the northeastern and upper Midwestern US and adjoining areas of Canada, identified 11 major and 3 minor clonal complexes, as well as 14 singletons. The data revealed that patients from New York and Wisconsin were infected with two distinct, but genetically and phylogenetically closely related, populations of B. burgdorferi. Importantly, the data suggest the existence of B. burgdorferi lineages with differential capabilities for dissemination in humans. Interestingly, the data also indicate that MLST is better able to predict the outcome of localized or disseminated infection than is ospC typing.

Please cite this paper as: Coleman et al. (2013) Evaluation of obesity as an independent risk factor for medically attended laboratory‐confirmed influenza. Influenza and Other Respiratory Viruses 7(2) 160–167. Background The relationship between obesity and susceptibility to influenza infection in humans is unclear. Morbidly obese people were at an increased risk of complications from 2009 pandemic H1N1 influenza [A(H1N1)pdm09]. Objective The goal of this study was to determine whether medically attended, laboratory‐confirmed influenza is independently associated with obesity in adults with acute respiratory illness. Patients/Methods Adults ≥20 years with a medical encounter for acute respiratory illness were recruited from a population cohort during the 2007–2008 ( n = 903), 2008–2009 ( n = 869), and 2009 pandemic ( n = 851) season. Nasopharyngeal swabs were tested for influenza by real‐time reverse‐transcription polymerase chain reaction. Body mass index (BMI) was calculated using data from the electronic medical record. Logistic regression evaluated the association between influenza and obesity, adjusting for gender, vaccination, age, and high‐risk medical condition. Results Influenza was detected in 50% of patients in 2007–2008, 15% in 2008–2009, and 14% during the 2009 pandemic. Predominant seasonal viruses in this population were A/H3N2 in 2007–2008, and A/H1N1 and B in 2008–2009. Mean (±SD) BMI was 30·58 (±7·31) in patients with influenza and 30·93 (±7·55) in test‐negative controls during all seasons. Mean BMI of patients with influenza did not vary by season. After adjusting for confounders, neither obesity nor extreme obesity were associated with influenza by season or for all years combined (OR 0·95: 95% CI 0·75, 1·20 and 1·10: 0·80, 1·52, respectively, for obesity and extreme obesity, all years). Conclusions Obesity was not associated with medically attended influenza among adults with acute respiratory illness in this population.

Objective Examine differences in the detection of influenza by specimen and test type using paired nasal and nasopharyngeal swabs. Design Prospective study Setting Enrollment took place between January and March 2007 in a central Wisconsin population. Participants Adult patients were screened and enrolled by trained research coordinators following medical encounters for acute respiratory illnesses of <10 days duration. Methods Paired nasal and nasopharyngeal swabs were collected from consenting patients and tested by both real-time reverse transcriptase polymerase chain reaction (rRT-PCR) and viral culture. A composite measure of positivity was used as the gold standard; cases included any positive result by rRT-PCR or viral culture from either specimen type. Results Paired samples were collected from 240 adults; 33 (14%) individuals tested positive for influenza by rRT-PCR. Using rRT-PCR, the sensitivity of the nasal swab was 89% (95% CI, 78%-99%) and the sensitivity of the nasopharyngeal swab was 94% (95% CI, 87%-100%), compared to a composite gold standard. Conclusion Test sensitivity did not vary significantly by swab type when using a highly sensitive molecular diagnostic test, but power was limited to detect modest differences.

Please cite this paper as: Irving et al. (2012) Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008. Influenza and Other Respiratory Viruses 6(1), 37–43.Background There are few prospectively collected data comparing illnesses caused by different subtypes of influenza. We compared the clinical presentation and outcomes of subjects with primarily outpatient‐attended influenza A and B infections during four consecutive influenza seasons (2004–2005 through 2007–2008).Methods Patients were prospectively enrolled and tested for influenza following an encounter for acute respiratory illness. Influenza infections were confirmed by culture or reverse transcription polymerase chain reaction; subtype was determined for a sample of influenza A isolates each season. Clinical characteristics of influenza A and B infections were compared across and within individual seasons.Results We identified 901 cases of influenza A and 284 cases of influenza B; 98% of cases were identified through an outpatient medical encounter. Thirty‐six percent of patients with each strain had received seasonal influenza vaccine prior to illness onset. There were no consistent differences in symptoms associated with influenza A and B. Influenza A infection was associated with earlier care seeking compared with influenza B during the 2005–2006 and 2007–2008 seasons, when H3N2 was the dominant type A virus, and in a combined analysis that included all seasons. Twenty‐six (2·2%) of 1185 cases were diagnosed with radiographically confirmed pneumonia, and 59 (5%) of 1185 patients were hospitalized within 30 days of illness onset.Conclusions Over four influenza seasons, aside from shorter intervals from illness onset to clinical encounter for infections with the A(H3N2) subtype, clinical symptoms and outcomes were similar for patients with predominantly outpatient‐attended influenza A and B infections.

Nineteen patients with oseltamivir-resistant seasonal influenza A (H1N1) infections were randomized to receive oseltamivir or placebo. Nasopharyngeal swabs were obtained, and clinical and virologic outcomes were compared, stratified by early or late treatment. Neuraminidase inhibition assay and pyrosequencing for H275Y confirmed resistance. Twelve (63%) patients received oseltamivir; 8 (67%) received late treatment. Seven (37%) patients received placebo; 6 (86%) presented >48 hours after onset. Time to 50% decrease in symptom severity, complete symptom resolution, and first negative culture were shortest among the early treatment group. While sample size prohibits a strong conclusion, future studies should evaluate for similar trends.

BACKGROUND:The continuing epizootic of H5N1 avian influenza (AI) in Asia and subsequent zoonotic transmission has led to heightened concerns about a pandemic and the demand for improved surveillance of poultry in all sectors, including backyard poultry. We conducted a 15-month prospective study to determine the prevalence of AI in backyard poultry and extent of transmission to flock handlers.METHODS:Starting July 2007, registered poultry owners in six counties in central Wisconsin were mailed invitations to participate; household members with poultry exposure were also invited. Premises with < 1000 birds were eligible. Participants completed a baseline interview to characterize poultry exposures. Illness in flocks and flock handlers was monitored using semimonthly telephone interviews and self-report of acute influenza-like symptoms by flock handlers. Participants provided blood at baseline and at the end of the surveillance period for serology and, if ill, nasopharyngeal, eye, and throat swabs for viral testing. Blood was also collected at baseline from a convenience sample of adult poultry.RESULTS:We enrolled 87 flocks and 128 persons who had regular contact with poultry. Influenza-like symptoms were reported by 77 (65%) persons. Swabs were collected from 53 persons at 88 illness episodes. AI was not isolated, but five persons were positive for human influenza. Twenty-one participants (20%) seroconverted to at least one human influenza strain, but there were no seroconversions to AI. Blood samples from all 717 birds tested were seronegative for influenza.CONCLUSION:Despite limited biosecurity there was no evidence of AI infection in participating backyard flocks or flock handlers.

Background: During the 2007-08 influenza season, we reported an interim vaccine effectiveness (VE) estimate of 44% for preventing medically attended influenza. In this analysis we report results for the entire season and compare them with the interim estimate.Methods: Patients with feverishness, chills, or cough <8 days duration were prospectively recruited over 10 weeks and tested for influenza by real-time reverse transcriptase PCR (rRT-PCR). Case-control analyses were performed using data from patients with rRT-PCR confirmed influenza (cases) and ill patients without influenza (test-negative controls). VE was estimated as 100 X (1 - adjusted odds ratio) in a logistic regression model adjusting for age, week, and high risk medical condition. A sample of influenza isolates was antigenically characterized.Results: Influenza was detected by rRT-PCR in 865 (44%) of 1972 patients; 73% were type A and 27% were type B. VE was 37% (95% Cl, 22-49%) overall and 44% (95% Cl, 27-58%) among participants tested 0-3 days after illness onset. VE was 39% (95% Cl, 2-62%) in children 6-59 months old and 37% (95% CI, -2% to 61%) in adults >= 50 years old. VE was 41% (95% Cl, 24-53%) for influenza A and 31% (95% Cl, 3-51%) for influenza B. All 24 characterized influenza A viruses were antigenically matched to the H3N2 vaccine strain, although 14 viruses exhibited mild antigenic drift. There was a lineage mismatch with the vaccine strain for all 39 characterized influenza B viruses.Conclusions: The 2007-08 influenza vaccine provided modest protection against medically attended influenza in this population. The interim estimate of VE after 17 days closely approximated the final season VE, supporting the potential use of interim VE estimates while influenza seasons are still in progress. (C) 2011 Elsevier Ltd. All rights reserved.

The per capita incidence of human Lyme disease in the northeastern United States is more than twice that in the Midwest. However, the prevalence of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the tick vector is nearly identical in the 2 regions. The disparity in human Lyme disease incidence may result from a disparity in the human invasiveness of the bacteria in the Northeast and Midwest caused by fundamentally different evolutionary histories. B. burgdorferi populations in the Northeast and Midwest are geographically isolated, enabling evolutionary divergence in human invasiveness. However, we found that B. burgdorferi populations in the Northeast and Midwest shared a recent common ancestor, which suggests that substantial evolutionary divergence in human invasiveness has not occurred. We propose that differences in either animal ecology or human behavior are the root cause of the differences in human incidence between the 2 regions.

CONTEXT The clinical characteristics of pandemic 2009 influenza A(H1N1) infections have not been compared directly with illnesses caused by other influenza A strains. OBJECTIVE To compare clinical features and outcomes for 2009 H1N1, seasonal H1N1, and H3N2 influenza in a population-based cohort. DESIGN, SETTING, AND PARTICIPANTS Active surveillance with 30-day follow-up for influenza cases among children and adults living in a 14-zip code area in Wisconsin. Patients with subjective fever, chills, or cough of fewer than 8 days' duration were screened for eligibility during an outpatient or inpatient encounter. Consenting patients were interviewed and tested for influenza A during the 2007-2008 and 2008-2009 influenza seasons and from May to November 2009; 6874 patients (70%-86% of eligible patients) agreed to participate. Medical records were reviewed to assess outcomes. MAIN OUTCOME MEASURES Hospital admission, radiographically confirmed pneumonia, and clinical characteristics of influenza A by strain. RESULTS We identified 545 2009 H1N1, 221 seasonal H1N1, and 632 H3N2 infections. The median ages of infected participants were 10, 11, and 25 years, respectively (P < .001). Hospital admission occurred within 30 days for 6 of 395 children with 2009 H1N1 (1.5%; 95% confidence interval [CI], 0.6%-3.1%), 5 of 135 with seasonal H1N1 (3.7%; 95% CI, 1.4%-8.0%), and 8 of 255 with H3N2 (3.1%; 95% CI, 1.5%-5.9%). Among adults, hospital admission occurred in 6 of 150 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 of 86 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 17 of 377 with H3N2 (4.5%; 95% CI, 2.7%-7.0%). Pneumonia occurred in 10 children with 2009 H1N1 (2.5%; 95% CI, 1.3%-4.5%), 2 with seasonal H1N1 (1.5%; 95% CI, 0.2%-5.2%), and 5 with H3N2 (2.0%; 95% CI, 0.7%-4.3%). Among adults, pneumonia occurred in 6 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 4 with H3N2 (1.1%; 95% CI, 0.3%-2.7%). CONCLUSIONS In this population, individuals with 2009 H1N1 infection were younger than those with H3N2. The risk of most serious complications was not elevated in adults or children with 2009 H1N1 compared with recent seasonal strains.

Annual evaluation of influenza vaccine effectiveness (VE) is needed to assess ongoing impact of immunization efforts in the setting of antigenic drift and periodic vaccine reformulation. Optimal methodology for determining VE remains unclear. We compared influenza VE generated from prospective enrollment and rRT-PCR testing (active surveillance group) with VE based on clinician-ordered diagnostic tests (clinical testing group) in a defined population over four seasons. VE was calculated as (1 – adjusted OR) for vaccination in cases vs. test-negative controls. VE based on clinical testing underestimated VE based on active surveillance and testing with rRT-PCR by 5–33% depending on season.

To determine whether poultry contact/consumption predicts colonization with antimicrobial-resistant Escherichia coli, 567 newly hospitalized patients and 100 vegetarians were assessed microbiologically and epidemiologically. Multivariable analysis showed that poultry contact/consumption, other dietary habits, and antimicrobial use did not significantly predict resistance. In contrast, foreign travel significantly predicted both trimethoprim-sulfamethoxazole resistance (prevalence ratio, 2.7 [95% confidence interval, 1.3-5.6]) and "any resistance" (total population), whereas intensive-care-unit exposure predicted any resistance (hospital patients). Thus, most of the individual-level exposures-including poultry contact/consumption-that had been expected to be significant risk factors for infection with antimicrobial-resistant E. coli did not prove to be such. Other exposures, including household-, community-, and population-level effects, may be more important.

Adamantane-resistant influenza A is an emerging problem, but infections caused by resistant and susceptible viruses have not been compared. We identified adamantane resistance in 47% of 152 influenza A virus (H3N2) isolates collected during 2005. Resistant and susceptible viruses caused similar symptoms and illness duration. The prevalence of resistance was highest in children.