A Randomized Controlled Trial to Compare Immunogenicity to Cell-Based Versus Live-Attenuated Influenza Vaccines in Children.

BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069.

Effect of mild COVID-19 on health-related quality of life.

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life. Methods: This prospective observational study of symptomatic adults (18-87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6-8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up. Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P < 0.001) and non-COVID cases (3.3 ± 0.32; P < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P < 0.001) and decreased significantly for non-COVID cases (-0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (ß = 1.17; SE = 0.5; P = 0.021), having COVID-19 (ß = 1.99; SE = 0.54; P < 0.001); and non-white race (ß = -2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (ß = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (ß = 2.42; SE = 0.67; P < 0.001). Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6-8 weeks' convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females.

Factors associated with humoral immune response in older adults who received egg-free influenza vaccine.

BACKGROUND: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. METHODS: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. RESULTS: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). CONCLUSION: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.

A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults.

BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.

Agreement among sources of adult influenza vaccination in the age of immunization information systems.

INTRODUCTION: Many vaccination studies rely on self-reported vaccination status, with its inherent biases. Accuracy of influenza vaccination self-report has been evaluated periodically, typically using the medical record as the gold standard. The burgeoning of electronic medical records (EMRs) and immunization information systems (IISs) and the rise of adult vaccine administration in community pharmacies suggest the need for a reevaluation of self-reported vaccination status. METHODS: Vaccination data from self-report, the state IIS, the health system EMR and other sources were compared for participants in outpatient and inpatient influenza vaccine effectiveness studies for four seasons (2016-2017 to 2019-2020). Agreement among the sources was calculated along with sensitivity and specificity. Tests for trend assessed changes in completeness of the Pennsylvania - Statewide IIS (PA-SIIS) data over time. RESULTS: With self-report as the gold standard, agreement with the local EMR, PA-SIIS, and all sources was 62%, 77% and 85%, respectively. Sensitivity of the EMR was 42% (95% CI = 41, 43) and specificity was 91% (90, 92). With PA-SIIS-as the gold standard, agreement with the local EMR and all sources was 77% and 78%, respectively. Sensitivity of all sources combined was 96% (95, 97) and specificity was (63% (62, 64). Capture of influenza vaccinations in the IIS has not consistently improved over time, with a significant increase among children (P = 0.001), no change among working-age adults and a decrease among older adults (P = 0.004). However, PA-SIIS provided the largest percentage of verified vaccines (69.3%) compared with EMR (43.3%) and other sources (12.4%). CONCLUSION: Both self-report and PA-SIIS are good estimates of actual vaccine uptake. When high accuracy data are required, such as for vaccine effectiveness studies, triangulation using multiple sources should be conducted.

The impact of physical frailty on the response to inactivated influenza vaccine in older adults.

Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.

A randomized controlled trial of antibody response to 2018-19 cell-based vs. egg-based quadrivalent inactivated influenza vaccine in children.

BACKGROUND: Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial. METHODS: Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax®]; n = 85); or in egg medium (IIV4 [Fluzone ®]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio ≥ 4 with day 28 titer ≥ 40). Secondary outcomes were elevated titers (day 28 HI titer ≥ 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment. RESULTS: In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients. CONCLUSION: In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses. CLINICAL TRIALS NO: NCT03614975.

Physical health and mental health functional status during and following hospitalization for an acute respiratory illness.

Background: Influenza is a serious respiratory illness causing thousands of hospitalizations annually. This study used the Short Form 12 (SF-12) to evaluate physical and mental health status during and post hospitalization for an acute respiratory illness (ARI). Methods: Adults ≥18 years of age enrolled in the Hospitalized Adult Influenza Vaccine Effectiveness Network study - Pittsburgh site in the 2017-2018 and 2018-2019 influenza seasons with an ARI with cough of ≤10 days' duration were eligible. Enrollees were included regardless of respiratory pathogen identified by respiratory viral panel testing of nasopharyngeal specimens. Respondents completed the SF-12 at enrollment and 3-14 weeks later. Respondents were grouped using discriminant cluster analysis based on SF-12 individual scores and age. Linear regression was used to predict convalescent physical and mental health composite scores. Results: Of 72 enrollees who completed both surveys, 35 were grouped as the high functioning group (HFG), 12 as the low functioning group (LFG) and 25 as the medium functioning group (MFG). At enrollment, the LFG more frequently reported body aches and confusion, lower pre-illness physical activity levels and other measures of physical function than the HFG (P < 0.016). At approximately 5 weeks post enrollment, the HFG reported significant decrements in most SF-12 individual scores and overall physical health (-4.26 ±â€¯8.1; P = 0.017) and mental health (-5.98 ±â€¯10.5; P = 0.011) composite scores. Changes in mental but not physical composite scores from enrollment to convalescence differed significantly (P = 0.016) between HFG and LFG. Conclusions: Although their enrollment and convalescent SF-12 scores were higher, HFG reported larger losses in mental function during an ARI hospitalization than groups with lower enrollment SF-12 scores.

A "Sense"-ational HPV Vaccination Quality Improvement Project in a Family Medicine Residency Practice.

BACKGROUND: Human papillomavirus (HPV) vaccination uptake for adolescents and young adults in the United States remains far from national goals. Using a multi-component intervention aligned with community-wide efforts, we implemented a quality improvement project to increase HPV vaccinations among 9-26 year-old male and female patients in an urban, low income, minority population family medicine residency practice. METHODS: The pre-intervention year was November 2, 2014 to October 31, 2015 and the intervention year was November 1, 2015 to October 31, 2016. Based on community input and published literature, the interventions were creative, practice-specific provider-, patient-, and system-level strategies. To compare pre- and post-intervention vaccinations, HPV vaccination data were extracted from an electronic medical record request for age-eligible patients seen in the practice during the intervention year. Chi-square, McNemar's and 2-tailed, 2-sample Z tests were used to test differences in vaccination initiation (≥1 dose) and completion (3 doses) across groups and over time. RESULTS: Despite high pre-intervention rates (58% and 75%), HPV vaccine initiation significantly increased 12.8 percentage points (PP) for males and 10.6 PP for females from pre- to post-intervention (P < 0.001). HPV vaccine completion also significantly increased 16 PP for males and 10.9 PP for females (P < 0.001). Young adult patients (18-26 years-old) had significant increases in completion rates (9.9 PP; P < 0.001), not observed among adolescents (20 PP; ns). CONCLUSIONS: Consistent and abundant positive HPV vaccination messaging, low-cost sensory rewards, process change, and community, clinician, and nonclinical staff engagement were associated with higher HPV vaccine initiation and completion, especially among young adults.

Influenza Vaccine Intention After a Medically Attended Acute Respiratory Infection.

Background. Little is known about vaccine intention behavior among patients recovering from a medically attended acute respiratory infection. Methods. Adults ≥ 18 years old with an acute respiratory infection in the 2014-2015, 2015-2016, and 2016-2017 influenza seasons were tested for influenza and completed surveys. Across seasons, unvaccinated participants were grouped into those who intended to receive the influenza vaccine in the following season (vaccine intention) and those who did not (no vaccine intention). In 2016-2017, participants were asked the reasons for their vaccination behavior. Results. Of the 837 unvaccinated participants, 308 (37%) intended to be vaccinated the next season. The groups did not differ in demographic or overall health factors. In logistic regression, non-Whites, those reporting wheezing or nasal congestion, and those receiving an antiviral prescription were more likely to be in the vaccine intention group. That group was significantly more likely to cite perceived behavioral control reasons for not being vaccinated (forgot), while the no vaccine intention group was significantly (p < .001) more likely to report knowledge/attitudinal reasons (side effects). Conclusion. Because influenza vaccine is given annually, adults must make a conscious decision to receive the vaccine each year. Understanding the factors related to vaccination behavior and intent can help shape interventions to improve influenza vaccination rates. A medical visit at the time of an acute respiratory illness, especially one in which the provider suspects influenza, as evidenced by an antiviral prescription, is an ideal opportunity to recommend influenza vaccine in the next season, to prevent a similar experience.

The effect of frailty on HAI response to influenza vaccine among community-dwelling adults ≥ 50 years of age.

The immune response to vaccine antigens is less robust in older adults because of changes in the aging immune system. Frailty, the multi-dimensional syndrome marked by losses in function and physiological reserve, is increasingly prevalent with advancing age. Frailty accelerates this immunosenescence but the consequence of frailty on immune response specific to influenza vaccine among older adults, is mixed. An observational, prospective study of 114 adults was conducted in the fall of 2013 to assess the association of physical frailty with immune response to standard dose influenza vaccine in community-dwelling adults ≥ 50 years of age. Participants were stratified by age (<65 years and ≥65 years), and vaccine strain (Influenza A/H1N1, A/H3N2 and B) was analyzed separately adjusting for body mass index (BMI) and baseline log2 hemagglutination inhibition (HAI) titers. Overall, immune responses were lower among those ≥65 years of age than those <65 years. Among those ≥65 years there were no significant differences between frail and non-frail individuals in seroprotection or seroconversion for any influenza strain. Frail individuals <65 years of age compared with non-frail individuals were more likely to be seroprotected and to seroconvert post vaccination. Linear regression models show the same pattern of significant differences between frail and non-frail for those <65 years but no significant differences between frailty groups for those ≥65 years. Additional research may elucidate the reasons for the differences observed between younger frail and non-frail adults.

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains.

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or 'back-boosting' to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre-existing immunity in people of different ages is critical for designing the next-generation of 'universal' or broadly-protective influenza vaccines.

Are children's vitamin D levels and BMI associated with antibody titers produced in response to 2014-2015 influenza vaccine?

BACKGROUND: Vitamin D is an immunomodulating hormone, which has been associated with susceptibility to infectious diseases. METHODS: Serum vitamin D levels in 135 children ages 3-17 y were measured at baseline and hemagglutinin influenza antibody titers were measured pre- and 21 d post influenza vaccination with live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV). Height and weight were derived from the electronic medical record and were used to calculate body mass index (BMI). RESULTS: Thirty-nine percent of children were ages 3-8 years; 75% were black, 34% were obese (BMI ≥ 95th percentile); vitamin D levels were >20 ng/ml in 55%. In linear regression analyses, post vaccination antibody titers for LAIV B lineages (B Brisbane and B Massachusetts) were significantly higher among those with lower vitamin D levels and among younger participants (P < 0.05). No associations between vitamin D levels and responses to LAIV A strains (A/H1N1 and A/H3N2) or to any IIV strains or lineages were found. CONCLUSION: Low vitamin D levels were associated with higher response to LAIV B lineages in the 2014-2015 LAIV, but not related to LAIV A or any IIV strains.

Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination.

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure.

Are plasma mineral levels related to antibody response to influenza vaccination in older adults?

INTRODUCTION: An effective immune response to vaccination may be related to nutritional status. This study examined the association of plasma mineral levels with hemagglutination inhibition (HI) titers produced in response to influenza vaccine in older adults. METHODS: Prior to (Day 0) and 21 (range = 19-28) days after receiving the 2013-14 influenza vaccine, 109 adults ages 51-81 years, provided blood samples. Serum samples were tested for HI activity against the A/H1N1 and A/H3N2 2013-2014 vaccine virus strains. Plasma minerals were collected in zinc-free tubes and assayed by inductively coupled plasma mass spectrometry. HI titers were reported as seroprotection (≥1:40) and seroconversion (≥ 4-fold rise from Day 0 (minimum HI = 1:10) to Day 21). Both HI titers and mineral values were skewed and thus log2 transformed. Magnesium (Mg), phosphorus (P), zinc (Zn), copper (Cu), iron (Fe), potassium (K) and the Cu to Zn ratio were tested. Logistic regression analyses were used to determine the associations between mineral levels and seroconversion and seroprotection of HI titers for each influenza A strain. RESULTS: Participants were 61% white, 28% male, 39% diabetic, and 81% overweight/obese with a mean age of 62.6 y. In logistic regression, Day 21 A/H1N1 seroprotection was associated with P and Zn at Day 21(P < 0.05). Seroconversion of A/H1N1 was associated with Day 21 Cu, P, and Mg (P < 0.03). Day 21 A/H3N2 seroprotection and seroconversion were associated with Day 21 P (P < 0.05). CONCLUSIONS: Phosphorus was associated with seroprotection and seroconversion to influenza A after vaccination; these associations warrant additional studies with larger, more diverse population groups.

Detection of influenza virus infection using two PCR methods.

Rapid, accurate, and cost-effective methods to identify the cause of respiratory tract infections are needed to maximize clinical benefit. Outpatients with acute respiratory illness were tested for influenza using a singleplex reverse transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT-PCR) method tested for influenza and 17 other viruses and was compared with SRT-PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested positive for influenza A and influenza B. This study supports MRT-PCR as a comparable method for detecting influenza among patients seeking outpatient care for acute respiratory illnesses.

Success of the 4 pillars toolkit for influenza and pneumococcal vaccination in adults.

BACKGROUND: Standing order programs (SOPs) allowing nonphysician personnel to assess patients' immunization status and administer vaccines without an individual physician order are a proven method of increasing adult vaccinations, yet they are underutilized by primary care physicians. METHODS: In a before-and-after trial, a pilot-tested and revised SOP toolkit (4 Pillars Toolkit) was implemented in four diverse primary care practices. Changes in influenza and pneumococcal polysaccharide vaccine (PPSV) vaccination rates were measured. The toolkit was evaluated using direct observation, group interviews, and surveys of each practice's staff. RESULTS: Use of the 4 Pillars Toolkit varied across sites. PPSV rates increased significantly overall for high-risk adults (18-64 years; 25% in 2010-2011 vs. 40% in 2011-2012, p = .02) but not for older adults (≥65 years; 44% vs. 52%, p = .26) and in two of four practices among both high-risk and older adults (p < .05). Influenza vaccination rates increased significantly in three of four sites and overall (22% in 2010-2011 vs. 33% in 2011-2012, overall; p < .001). Practices more fully implementing the toolkit demonstrated larger increases in vaccination rates. CONCLUSIONS: The 4 Pillars Toolkit is a promising means of improving primary care practice across diverse settings, with better results observed when strategies were maximally utilized.