Severe Influenza Disease Research Articles

Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease

Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+HLA-DR+PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38+HLA-DR+CD8+ T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38+HLA-DR+CD8+ T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.

Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus.

ABSTRACTInfluenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay (ELISA) was performed on samples from 65 participants challenged with a 2009 H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated with multiple outcome measures to evaluate anti-HA stalk antibody titer as a correlate of protection. Anti-HA stalk antibody titers were present before challenge and rose in response to challenge in 64% of individuals. Those individuals with higher titers at baseline were less likely to develop shedding, but not less likely to develop symptoms. Similar to the hemagglutination inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not independently predict a decrease in the severity of influenza disease, while the antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of protection, the naturally occurring anti-HA stalk antibody titer is predictive of a reduction of certain aspects of disease similar to HAI titer, but the NAI titer is the only identified correlate that is an independent predictor of a reduction of all assessed influenza clinical outcome measures.

Estimating the burden of seasonal influenza in Spain from surveillance of mild and severe influenza disease, 2010-2016.

BackgroundEstimating the national burden of influenza disease is challenging. We aimed to estimate the disease burden of seasonal influenza in Spain, at the primary care and hospital level, over the 6 influenza seasons after 2009 pandemic.MethodsWe used data from the Spanish Influenza Sentinel Surveillance System to estimate weekly influenza rates and the number of influenza‐like illness (ILI) and mild confirmed influenza cases (MCIC). From the surveillance of severe hospitalized confirmed influenza cases (SHCIC), we obtained hospitalization rates and total number of SHCIC, intensive care unit (ICU) admissions and deaths in influenza hospitalized patients. We estimated both mild and severe influenza cases, overall, and by age‐group (<5, 5‐14, 15‐64, and ≥65 years).ResultsThe highest cumulative rates of MCIC were observed in <15 years (1395‐3155 cases/100 000 population in 5‐14 years) and the lowest in ≥65 years (141‐608 cases/100 000 population). SHCIC rates revealed a characteristic U‐shaped distribution, with annual average hospitalization rates of 16.5 and 18.9 SHCIC/100, 000 p in 0‐4 years, and ≥65 years, respectively. We estimated an annual average of 866 868 cases of ILI attended in primary care (55% were MCIC), 3616 SHCIC, 1232 ICU admissions, and 437 deaths in SHCIC. The percentage of ICU admission among SHCIC was highest at 15‐64 years (42%), while the hospitalization fatality rate ranged from 1% in 0‐4 years to 18% in ≥65 years.ConclusionsThe ongoing Spanish Influenza Surveillance System allowed obtaining crucial information regarding the impact of mild and severe influenza in Spain.

Influenza virus replication in macrophages: balancing protection and pathogenesis.

Macrophages are essential for protection against influenza A virus infection, but are also implicated in the morbidity and mortality associated with severe influenza disease, particularly during infection with highly pathogenic avian influenza (HPAI) H5N1 virus. While influenza virus infection of macrophages was once thought to be abortive, it is now clear that certain virus strains can replicate productively in macrophages. This may have important consequences for the antiviral functions of macrophages, the course of disease and the outcome of infection for the host. In this article, we review findings related to influenza virus replication in macrophages and the impact of productive replication on macrophage antiviral functions. A clear understanding of the interactions between influenza viruses and macrophages may lead to new antiviral therapies to relieve the burden of severe disease associated with influenza viruses.

Impact of Influenza A Virus Infection on the Proteomes of Human Bronchoepithelial Cells from Different Donors

Susceptibility to influenza A virus is determined by a balance of viral and host factors. The genetic background of the host contributes to the severity of disease, but the influenza-related proteomes of cells from different individuals have not been compared. We used high-resolution mass spectrometry to identify proteins in normal human bronchial epithelial (NHBE) cells isolated from three different donors. Infection of each NHBE cell culture with influenza A/California/07/2009 (H1N1) resulted in expression of viral proteins and a variety of host proteins, including interferons, interferon-stimulated genes, and secreted chemokines/cytokines. The expression level of viral proteins corresponded to the level of host proteins that support influenza infection (i.e., pro-viral proteins); however, production of infectious virus was inversely related to the levels of antiviral proteins, suggesting that a balance of pro-viral proteins and the antiviral response controls virus replication. In summary, our results demonstrate that expression levels of pro-viral as well as antiviral factors are different for each donor and suggest that relative quantitation of these factors may provide a way to identify individuals or population groups who are susceptible to severe influenza disease.

Seroprevalence of influenza A and B viruses among unvaccinated children in the United Arab Emirates: a cross-sectional study

BackgroundYoung children are at increased risk of severe influenza disease and, thus, are good candidates for receiving annual vaccination. Nevertheless, the influenza vaccine is infrequently given to children in our region. The primary objectives of this study are to monitor the serologic immunities against influenza A and B viruses, and provide pediatric data that support the need for influenza vaccination in the community.MethodsInfluenza A and B virus-specific IgG antibodies were measured in 294 children (median age 4.1 years; range 1.9–12.5 years) between July 2014 and September 2015.ResultsThe percentage of children who were seropositive for influenza A IgG was 15.8%, equivocal 7.4%, and negative 76.8%. The corresponding values for influenza B IgG were 31.3, 9.6, and 59.1%, respectively. There was a higher seropositivity rate for influenza B than for influenza A in all age groups. The percentage of children who were seropositive for either influenza A or B IgG was 27.9% and for both was only 2.7%.ConclusionsMost of the studied children are serologically naïve and, thus, are likely to acquire primary influenza disease. A national policy that endorses childhood influenza vaccination is highly advisable.

Calculated risk: a new single-nucleotide polymorphism linked to severe influenza disease.

Clear links between human genes and susceptibility to influenza disease are scarce. A recent study uncovers a gene variant coupled to severe influenza, and shows how it hampers the expression of an antiviral gene that is key to immune cell survival.

Incidence of influenza virus infection among pregnant women: a systematic review

BackgroundThe World Health Organization (WHO) considers pregnant women to be a risk group for severe influenza disease. We conducted a systematic review to evaluate influenza disease incidence in pregnant women in order to inform estimates of influenza vaccine impact for low-resource countries.MethodsWe performed electronic literature searches, targeting studies on the following outcomes in pregnant women: attack rate, hospitalization rate, intensive care unit admission rate, mortality rate, and disability-adjusted life years lost. Only original studies published in peer-reviewed journals that had laboratory confirmation for influenza virus infection and included population-based incidence rates with denominator data were included. We summarized study characteristics in descriptive tables and outcome-specific Forest plots. We generated summary incidence rates using random effects models and assessed statistical heterogeneity by visual examination of Forest plots, and by χ2 and I2 tests.ResultsWe identified 1543 articles, of which nine articles met the study inclusion criteria. Five were case series, three were cohort studies, and one was a randomized controlled trial. Eight studies were from high-income countries, and one was from an upper middle-income country. Six studies reported results for pandemic influenza, and three reported seasonal influenza. Statistical heterogeneity was high for all outcomes, and methodologies and duration of surveillance varied considerably among studies; therefore, we did not perform meta-analyses.ConclusionsStudy quality was very low according to GRADE criteria. More data on influenza disease incidence in pregnant women, particularly in low- and middle-income countries and for seasonal influenza disease, are needed to inform public health decision-making.

Influenza Virus and Glycemic Variability in Diabetes: A Killer Combination?

Following the 2009 H1N1 influenza virus pandemic, numerous studies identified the striking link between diabetes mellitus and influenza disease severity. Typically, influenza virus is a self-limiting infection but in individuals who have a pre-existing chronic illness, such as diabetes mellitus, severe influenza can develop. Here, we discuss the latest clinical and experimental evidence for the role of diabetes in predisposing the host to severe influenza. We explore the possible mechanisms that underlie this synergy and highlight the, as yet, unexplored role that blood glucose oscillations may play in disease development. Diabetes is one of the world’s fastest growing chronic diseases and influenza virus represents a constant and pervasive threat to human health. It is therefore imperative that we understand how diabetes increases influenza severity in order to mitigate the burden of future influenza epidemics and pandemics.

Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ Tcells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.

Regulatory T cells and IL10 suppress pulmonary host defense during early-life exposure to radical containing combustion derived ultrafine particulate matter

BackgroundExposure to elevated levels of particulate matter (PM) is associated with increased risk of morbidity and mortality due to respiratory tract viral infections in infants. Recent identification of environmentally persistent free radicals (EPFRs) in the PM from a variety of combustion sources suggests its role in the enhancement of disease severity of lower respiratory tract infections (LRTI). Our previous studies demonstrated that acute exposure to EPFRs induces pulmonary immunosuppression allowing for enhanced influenza disease severity. Here, we determine the mechanism of EPFR-induced immunosuppression and its impact on the immune response towards influenza infection.MethodsNeonatal mice (3 days old) were acutely exposed to DCB (combustion derived PM with chemisorbed EPFR) for seven consecutive days. Four days post-exposure (dpe), mice were infected with influenza virus. Pulmonary T cell phenotypes including regulatory T cells (Tregs) were analyzed by flow cytometry. The role of IL10 in EPFR-induced exacerbation of influenza disease severity was determined by administering recombinant IL10 (rIL10) to wild type mice or by using IL10 deficient (IL10−/−) neonatal mice. Mice were assessed for morbidity by measuring percent weight change and pulmonary viral load.ResultsNeonatal mice exposed to EPFRs had a significant increase in pulmonary Tregs and the immunosuppressive cytokine IL10 following influenza infection, which coincided with decreased protective T cell responses to influenza infection at 6 dpi. Depletion of Tregs in EPFR-exposed neonatal mice resulted in increased protective, adaptive T cell responses, whereas adoptive transfer of Tregs from EPFR-exposed neonates to air-exposed neonatal mice suppressed adaptive T cell responses towards influenza infection. Further, treatment with rIL10 could recapitulate EPFR-induced exacerbation of morbidity and pulmonary viral load compared to air exposed and influenza infected mice, whereas, EPFR-exposed IL10−/− neonates exhibited significant reductions in morbidity, pulmonary viral load and adaptive T cell responses following influenza infection.ConclusionsNeonatal exposure to EPFRs induced Tregs and IL10 resulting in suppressed adaptive T cell responses and enhanced influenza disease severity in neonatal mice. Depletion of Tregs increased adaptive T cell responses and deficiency of IL10 reduced morbidity and conferred enhanced protection against influenza virus.

Evaluating Symptom Severity of Influenza Viral Infection Using the Influenza Patient-reported Outcomes Instrument (FLU-PRO) in a Healthy Human Challenge Model

BackgroundTo apply the validated FLU-PRO scoring method to assess influenza symptom severity in a healthy human challenge model.MethodsHealthy adults admitted to the NIH Clinical Center (Day -1) underwent a 9 day inpatient quarantine after intranasal challenge with H1N1pdm (Day 0). Participants completed the 32 item FLU-PRO diary twice daily for 14 days to assess presence and severity of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare severity scores on Day 3 post-challenge by viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers.Results61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of which 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (<40) HAI and NAI titers, respectively. Mean daily FLU-PRO symptom severity domain and total scores are shown in Figure 1. Symptoms were present across all FLU-PRO domains from Day 1 post-challenge. Nose, throat, body, and GI symptoms reached peak severity at Day 3, followed by chest and eye symptoms at Day 4. Subjects with viral shedding had significantly higher mean FLU-PRO scores compared with those without, except for Eye and GI domains (P < .05); mean FLU-PRO scores were significantly higher for subjects with low NAI titer (P < .05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (P < .05) ((high HAI-low NAI (n = 22), low HAI-high NAI (n = 29)).ConclusionThe FLU-PRO can be used to track symptom onset, severity, and recovery from influenza infection in clinical research. In this challenge study, scores were responsive to change even in mild disease and distinguished known clinical subgroups. The use of NAI as an independent predictor of influenza disease severity was also supported.Funded by NCI Contract No. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NIAIDFigure 1.Trajectory of FLU-PRO scores from pre-challenge to Day 10 post-challengeDisclosures J. L. Poon, Evidera: Employee, Salary; R. Yu, Evidera: Employee, Salary; N. K. Leidy, Evidera: Employee, Salary

Efficacy of delayed treatment of China-made Peramivir with repeated intravenous injections in a mouse influenza model: from clinical experience to basal experiment.

BackgroundChina-made Peramivir, an anti-influenza neuraminidase inhibitor drug, is manufactured and widely used in China. Although effective if initiated within 48 h of the onset of symptoms, yet we observed that this drug shows an inconclusive efficacy if treatment is delayed in clinical. Thus we evaluated the efficacy of delayed treatment of China-made Peramivir in a mouse model.MethodsThe mouse model of influenza infection was made and Peramivir was administered intravenously for 5 days following infection, and weight loss, lung index, viral shedding and survival rates were monitored.ResultsPeramivir (60 mg/kg · d, repeated intravenous injections, quaque die (QD) × 5 days) enhanced survival rate and suppressed weight loss when treatment was initiated 24, 36, 48, or even 60 h post-infection (p.i.) (p < 0.01), compared with the virus-untreated group, and efficacy was abolished at 72 h p.i.. However the efficacy of delayed treatment was dose dependent, with the highest dose (90 mg/kg · d) even showing efficacy at 72 h p.i.. Furthermore, Peramivir (60 mg/kg · d, repeated intravenous injections, QD × 5 days) also reduced the lung virus titer 24 and 36 h p.i. on day 5, and even at 48 and 60 h p.i. on day 7 after infection, and the lung index was also improved. What is interesting that the concentration of the drug was maintained in blood after infected.ConclusionsDelayed treatment with China-made Peramivir can reduce the severity of influenza disease, accelerate viral clearance and enhance the survival rate. This drug therefore shows good efficacy and is a promising candidate to control the influenza epidemic in China.

Maternal influenza and birth outcomes: systematic review of comparative studies.

BackgroundAlthough pregnant women are considered at high risk for severe influenza disease, comparative studies of maternal influenza and birth outcomes have not been comprehensively summarised.ObjectiveTo review comparative studies evaluating maternal influenza disease and birth outcomes.Search strategyWe searched bibliographic databases from inception to December 2014.Selection criteriaStudies of preterm birth, small‐for‐gestational‐age (SGA) birth or fetal death, comparing women with and without clinical influenza illness or laboratory‐confirmed influenza infection during pregnancy.Data collection and analysisTwo reviewers independently abstracted data and assessed study quality.Main resultsHeterogeneity across 16 studies reporting preterm birth precluded meta‐analysis. In a subgroup of the highest‐quality studies, two reported significantly increased preterm birth (risk ratios (RR) from 2.4 to 4.0) following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild‐to‐moderate pH1N1 or seasonal influenza found no association. Five studies of SGA birth showed no discernible patterns with respect to influenza disease severity (pooled odds ratio 1.24; 95% CI 0.96–1.59). Two fetal death studies were of sufficient quality and size to permit meaningful interpretation. Both reported an increased risk of fetal death following maternal pH1N1 disease (RR 1.9 for mild‐to‐moderate disease and 4.2 for severe disease).ConclusionsComparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association.Tweetable abstractComparative studies are limited in quality but suggest severe pandemic H1N1 influenza increases preterm birth.

Identification of the immunological parameters that associate with severe influenza disease or recovery in mice

Abstract The severity of influenza virus infection is largely determined by the interplay between the virus and the host. Understanding the pathological drivers of influenza A viruses serves to rapidly characterize the host response to newly emerging influenza viruses and derive prognostic signatures of disease severity. We implemented a differential network approach to uncover novel distinctions between the global transcriptional host response to highly pathogenic and low pathogenic H1N1, H7N9, H7N7, and H5N1 influenza A infections in BALB/c mice. We identified crucial mediators of inflammatory, coagulation, and tissue repair responses that discriminate between disease outcomes. It has been demonstrated that these responses are largely impacted by the immune cell influx into the site of infection. We examined the contribution of resident and lung-infiltrating immune cell quantity and activation state to disease phenotypes by implementing digital cell quantification (DCQ), which allowed us to model the in vivo dynamics of immune cells across viral strains based on time and strain-dependent infected lung transcriptional profiles. Through linear regression modeling, we revealed that distinct monocyte, granulocyte, DC, and T cell populations predict disease morbidity. Additionally, we demonstrated that both the kinetics of CD8+ T cell infiltration and the extent of their activation state, serve as a key predictor of immunopathological consequences of influenza infection. Overall, we provide a multidimensional analysis that delineates how innate immune responses relate to aberrant tissue repair responses and drive subsequent host adaptive immune response that control the severity of influenza virus disease in the murine model.

LAG-3 expressing antigen-specific CD4+ T cells attenuate lung inflammation during acute influenza virus infection

Abstract The host immune system responds to influenza virus infection for eradication of the virus but the immune response associated inflammation causes tissue injury and damage to the host as well. In our antigen-specific mouse model system for influenza virus infection, influenza hemagglutinin antigen-specific CD4+ T cells responded to acute infection with Th1 effector phenotype. A significant proportion of them were also with concurrent expression of LAG-3, CTLA-4, GITR or CD25. Adoptive transfer of purified LAG-3 expressing hemagglutinin antigen-specific CD4+ T cells controlled lung inflammation with acute influenza virus infection, as represented by the activation of co-transferred influenza hemagglutinin antigen-specific CD8+ T cells. Control of the inflammation by LAG-3 expressing antigen-specific Th1 CD4+ T cells was not necessarily associated with impaired capacity of virus eradication. These results reveal, besides effector function for virus eradication, subsets of CD4+ T cells activated by acute influenza virus infection also acquired regulatory function to attenuate inflammation for reducing the damage to the host. These subsets of CD4+ T cells may be employed as the practical handle for management of severe influenza disease.

Regulatory T cells and IL10 suppress pulmonary host defense during early-life exposure to combustion generated radical containing ultrafine particulate matter.

Abstract Exposure to elevated levels of particulate matter (PM) is associated with adverse respiratory health and increased risk of morbidity and mortality due to respiratory tract viral infections in infants. Our previous studies demonstrated combustion derived PM (CDPM) induced immunosuppression allowing for enhanced influenza disease severity and mortality in neonatal mice. Current studies are aimed at understanding the underlying mechanisms. Neonatal mice (3 day old) were acutely exposed to Air or DCB230 (CDPM), and infected with influenza virus (Flu), Air/Flu and DCB/Flu respectively. Pulmonary T cell profile and immunosuppressive cytokines were analyzed. At 10 days-post exposure, a significant increase in pulmonary Tregs and IL10 coinciding with decrease in protective T helper 1 (Th1) and cytotoxic T cell (Tc1) responses was observed in DCB/Flu mice compared to Air/Flu mice. Further, depletion of Tregs (using anti-CD25 antibody) in DCB mice prior to flu infection increased both Th1 and Tc1 cells, whereas adoptive transfer of DCB-induced Tregs into Air mice and later infection with flu suppressed these responses. To elucidate the role of IL10 in DCB/Flu mice, Air exposed neonatal mice were treated with recombinant IL10 (rIL10) and subsequently infected with flu (rIL10/Flu). rIL10/Air/Flu mice had increased morbidity and pulmonary viral load compared to Air/Flu mice, whereas, IL10 deficient DCB/Flu mice exhibited reduction in pulmonary viral load and morbidity compared to wild-type mice indicative of enhanced protection against flu. Together, these studies demonstrate that PM- induced Tregs and their effector cytokine, IL10, suppress adaptive T cell responses leading to increased influenza severity in infected neonatal mice.

Avian Influenza Viruses, Inflammation, and CD8(+) T Cell Immunity.

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed.

Factors associated with a successful expansion of influenza vaccination among pregnant women in Nicaragua

BackgroundPregnant women are at risk of severe influenza disease and are a priority group for influenza vaccination programs. Nicaragua expanded recommendations to include influenza vaccination to all pregnant women in the municipality of Managua in 2013. MethodsWe carried out a survey among 1,807 pregnant women who delivered at public hospitals in the municipality of Managua to evaluate the uptake of influenza vaccination and factors associated with vaccination. ResultsWe observed a high (71%) uptake of influenza vaccination among this population, with no differences observed by age, education or parity of the women. Having four antenatal visits and five or more visits were associated with receipt of influenza vaccination (AORs: 2.58; 95% CI: 1.15, 5.81, and 2.37; 95% CI: 1.12, 5.0, respectively). Also, receipt of influenza vaccination recommendation from a health care provider was positively associated with receipt of influenza vaccination (AOR: 14.22; 95% CI: 10.45, 19.33). ConclusionsThe successful expansion of influenza vaccination among pregnant women in the municipality of Managua may be due to ready access to free medical care and health care providers’ recommendation for vaccination at health care clinics that received influenza vaccine.

Does Influenza Vaccination Modify Influenza Disease Severity? Data on Adults Hospitalized With Influenza During the 2013–14 Season in the United States

Does Influenza Vaccination Modify Influenza Disease Severity? Data on Adults Hospitalized With Influenza During the 2013–14 Season in the United States