Technology transfer of an oil-in-water vaccine-adjuvant for strengthening pandemic influenza preparedness in Indonesia.

With the current enzootic circulation of highly pathogenic avian influenza viruses, the ability to increase global pandemic influenza vaccine production capacity is of paramount importance. This has been highlighted by, and is one of the main pillars of, the WHO Global Action Plan for Influenza Vaccines (GAP). Such capacity expansion is especially relevant in developing countries. The Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia's state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. This paper describes the experience acquired and lessons learnt from this technology transfer project.

Sterblichkeit während Grippeepidemien in der Schweiz 1969-1985. [Mortality in influenza epidemics in Switzerland 1969-1985].

In Switzerland from 1969-1985, 9 out of 11 influenza epidemics were associated with a statistically significant increase in mortality. A total of 12,202 excess deaths from all causes was identified. Expected deaths were forecast for each epidemic period separately for 4 age groups using Fourier and Arima modeling. 75.7% of all-cause excess deaths occurred in age group 70 to 89 and 5.1% in age group 1-59. In the 70-89 years old group the excess mortality risk during influenza epidemics was 271.6 per 100,000, whereas in age group 1-59 it was only 1.7 per 100,000. Only 40% of all excess deaths had been ascribed to acute respiratory conditions. Influenza viruses A H3N2 were the most frequently identified agents. In some instances mortality increased before the morbidity reports of the Swiss practitioners indicated the occurrence of an epidemic. Also, morbidity reporting decreased over successive years. A decrease in mortality following the epidemics was not observed. A more complete vaccination of high risk patients in Switzerland is desirable.

The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.

UNLABELLED: Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivityin vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection ofTmprss2knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion ofTmprss4alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virusin vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously thatTmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2andTmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza virusesin vivo.

Hepatitis E virus: a zoonosis adapting to humans.

Hepatitis E virus (HEV) infection is gaining global attention, not only because of the increasing burden of the disease in low endemicity countries, in terms of morbidity and mortality rates, but also due to recent advances in the molecular virology and epidemiology of this emerging pathogen. HEV infection spread can be described as the evolution of a zoonosis towards an established human infection. As known from other viruses, such as the human immunodeficiency virus or the influenza viruses, crossing the species barriers from animals to humans is a recurrent phenomenon. Albeit slow at the beginning, once the virus has adapted to humans, the person-to-person spread can proceed very quickly. Although an optimal cell culture system for HEV is not yet available, outstanding progress has been made with the in vitro expression of HEV-like particles. These new tools have fostered new research to understand the molecular, structural and immunological aspects of human HEV infection. Although some promising data from Phase II vaccine trials are available, recent discoveries will certainly open new avenues for HEV-specific prophylaxis and therapy.

Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

Oseltamivir in seasonal, avian H5N1 and pandemic 2009 A/H1N1 influenza: pharmacokinetic and pharmacodynamic characteristics.

Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza and the recent pandemic 2009 A/H1N1 influenza, reducing both the duration and severity of the illness. It is also effective when used preventively. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of possible therapeutic drug monitoring. According to the currently available literature, the pharmacokinetics of oseltamivir carboxylate after oral administration of oseltamivir are characterized by mean ± SD bioavailability of 79 ± 12%, apparent clearance of 25.3 ± 7.0 L/h, an elimination half-life of 7.4 ± 2.5 hours and an apparent terminal volume of distribution of 267 ± 122 L. A maximum plasma concentration of 342 ± 83 μg/L, a time to reach the maximum plasma concentration of 4.2 ± 1.1 hours, a trough plasma concentration of 168 ± 32 μg/L and an area under the plasma concentration-time curve from 0 to 24 hours of 6110 ± 1330 μg · h/L for a 75 mg twice-daily regimen were derived from literature data. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Interpatient variability is moderate (28% in apparent clearance and 46% in the apparent central volume of distribution); there is no indication of significant erratic or limited absorption in given patient subgroups. The in vitro pharmacodynamics of oseltamivir carboxylate reveal wide variation in the concentration producing 50% inhibition of influenza A and B strains (range 0.17-44 μg/L). A formal correlation between systemic exposure to oseltamivir carboxylate and clinical antiviral activity or tolerance in influenza patients has not yet been demonstrated; thus no formal therapeutic or toxic range can be proposed. The pharmacokinetic parameters of oseltamivir carboxylate after oseltamivir administration (bioavailability, apparent clearance and the volume of distribution) are fairly predictable in healthy subjects, with little interpatient variability outside the effect of renal function in all patients and bodyweight in children. Thus oseltamivir carboxylate exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics. However, there is a lack of clinical study data on naturally infected patients. In addition, the therapeutic margin of oseltamivir carboxylate is poorly defined. The usefulness of systematic therapeutic drug monitoring in patients therefore appears to be questionable; however, studies are still needed to extend the knowledge to particular subgroups of patients or dosage regimens.

Prevalence of respiratory viruses among febrile children with or without acute respiratory symptoms in Tanzania

Background Respiratory viruses are the most frequent cause of febrile illnesses in infants and young children but few investigations have assessed their impact and epidemiology in Africa . We investigated their rate in febrile outpatient children attending in Tanzania. Methods Children aged 2 months -10 years with fever >38 _C were recruited prospectively between April and December 2008. Medical history and clinical examination were recorded in a standardized fashion and nasopharyngeal swabs analyzed for the presence of 12 viruses by real-time PCR (FLUAV, FLUBV, RSV, MPV, HPIV-1/3, four types of HCoV, HBoV, PIC and HAdV). Ct values were used to provide semi-quantitative viral loads.Results Of 1005 febrile children enrolled, 623 (62%) had respiratory symptoms (URTI in 66%, bronchiolitis in 7% and clinical pneumonia in 27%); 156 (16%) had febrile illness that remained of unspecified etiology and 226 (22%) had other infectious diseases and no ARI (62 malaria, 56 gastroenteritis, 36 urinary tract and 72 others). The proportions of patients with at least one respiratory virus were 70%, 61% and 47% (Pvalue < 0.001) in these three groups. When excluding picornavirus and adenovirus these proportions were 48%, 24% and 26% (P-value < 0.001). Apart from picornavirus and adenovirus, influenza A and B viruses were the most frequent followed by coronavirus and RSV. The proportion of children with presumably high viral titers (Ct < 25) was higher in the group with respiratory symptoms (31%) than in the two other groups (21% and 16%). Influenza genotyping revealed strains that were similar to the ones circulating elsewhere in the world.Conclusion In African children with febrile illness, the prevalence of respiratory viruses, especially influenza A and B, is high particularly in the presence of respiratory symptoms, but also, although less so, in those with unspecified etiology or other infectious diseases. This highlights that these viruses are commonly circulating in Tanzanian children.

A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients.

BACKGROUND: Community-acquired respiratory viral infections (RVIs) are common in lung transplant patients and may be associated with acute rejection and bronchiolitis obliterans syndrome (BOS). The use of sensitive molecular methods that can simultaneously detect a large panel of respiratory viruses may help better define their effects. METHODS: Lung transplant recipients undergoing serial surveillance and diagnostic bronchoalveolar lavages (BALs) during a period of 3 years were enrolled. BAL samples underwent multiplex testing for a panel of 19 respiratory viral types/subtypes using the Luminex xTAG respiratory virus panel assay. RESULTS: Demographics, symptoms, and forced expiratory volume in 1 sec were prospectively collected for 93 lung transplant recipients enrolled. Mean number of BAL samples was 6.2+/-3.1 per patient. A respiratory virus was isolated in 48 of 93 (51.6%) patients on at least one BAL sample. Of 81 positive samples, the viruses isolated included rhinovirus (n=46), parainfluenza 1 to 4 (n=17), coronavirus (n=11), influenza (n=4), metapneumovirus (n=4), and respiratory syncytial virus (n=2). Biopsy-proven acute rejection (> or =grade 2) or decline in forced expiratory volume in 1 sec > or =20% occurred in 16 of 48 (33.3%) patients within 3 months of RVI when compared with 3 of 45 (6.7%) RVI-negative patients within a comparable time frame (P=0.001). No significant difference was seen in incidence of acute rejection between symptomatic and asymptomatic patients. Biopsy-proven obliterative bronchiolitis or BOS was diagnosed in 10 of 16 (62.5%) patients within 1 year of infection. CONCLUSION: Community-acquired RVIs are frequently detected in BAL samples from lung transplant patients. In a significant percentage of patients, symptomatic or asymptomatic viral infection is a trigger for acute rejection and obliterative bronchiolitis/BOS.

Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses.

Hepatic natural killer (NK) cells mediate antigen-specific contact hypersensitivity (CHS) in mice deficient in T cells and B cells. We report here that hepatic NK cells, but not splenic or naive NK cells, also developed specific memory of vaccines containing antigens from influenza, vesicular stomatitis virus (VSV) or human immunodeficiency virus type 1 (HIV-1). Adoptive transfer of virus-sensitized NK cells into naive recipient mice enhanced the survival of the mice after lethal challenge with the sensitizing virus but not after lethal challenge with a different virus. NK cell memory of haptens and viruses depended on CXCR6, a chemokine receptor on hepatic NK cells that was required for the persistence of memory NK cells but not for antigen recognition. Thus, hepatic NK cells can develop adaptive immunity to structurally diverse antigens, an activity that requires NK cell-expressed CXCR6.

Who knew? Awareness of being recommended for influenza vaccination among US adults

Please cite this paper as: Maurer et al. (2012) Who knew? Awareness of being recommended for influenza vaccination among US adults. Influenza and Other Respiratory Viruses 6(4), 284-290. Background  Starting with the 2010-2011 influenza season, the Advisory Committee on Immunization Practices at the US Centers for Disease Control and Prevention recommends annual influenza vaccination to all people aged 6 months and older unless contraindicated. Objectives  To measure perceived influenza vaccination recommendation status among US adults (n = 2122) and its association with socio-demographic characteristics and recommendation status during the 2009-2010 pandemic influenza season. Methods  We analyze nationally representative data from longitudinal Internet surveys of US adults conducted in November-December 2009 and September-October 2010. Results  During the 2010-2011 vaccination season, 46·2 percent (95%-CI: 43·3-49·1%) of US adults correctly reported to be covered by a government recommendation for influenza vaccination. Awareness of being covered by a government influenza vaccination recommendation was statistically significantly higher among non-working adults and adults who had been recommended for seasonal vaccination or both seasonal and H1N1 vaccination during the 2009-2010 pandemic influenza vaccination season. Conclusion  Our results highlight that a majority of US adults do not know that they are recommended for annual influenza vaccination by the government. The fraction of adults who are unaware of their recommendation status is especially large among newly recommended healthy young adults. The universal vaccination recommendations will only be successful if they reach both patients and physicians and lead to changing vaccination practices. The universal nature of the new recommendation simplifies vaccination-related outreach and compliance with government vaccination guidelines considerably, as it does not require any identification of specific recommendation groups based on complex personal or health risk factors.

Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection.

OBJECTIVE: To assess the incidence and epidemiological pattern of respiratory viruses in HIV-infected patients and to evaluate their potential clinical impact. DESIGN AND METHODS: A prospective population-based cohort study was conducted at three Swiss university hospitals. Study participants were HIV-infected patients who underwent a bronchoalveolar lavage to rule out an opportunistic event. All bronchoalveolar lavage specimens were screened using a set of real-time reverse transcriptase-polymerase chain reaction assays targeting 17 different respiratory viruses. RESULTS: Between November 2003 and November 2006, 59 bronchoalveolar episodes from 55 HIV-infected patients were analysed. Eleven of 59 episodes (18.6%) were positive for at least one respiratory virus. Coronavirus OC43 was identified in three cases (27.3%) followed by influenza A in two (18.2%). Parainfluenza virus (PIV) 2, PIV 3, PIV 4, bocavirus, human rhinovirus A and human metapneumovirus were each identified in one case (9%). In the majority of these cases (63.6%) no other concomitant microorganism was isolated. CONCLUSIONS: Clinical investigation of respiratory viral infections in HIV-infected patients should not be restricted to prototype viruses and also need to target all the different family of viruses as it seems likely that these viruses contribute to pulmonary complications and morbidity in this population.

Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults.

BACKGROUND: The epidemiology of respiratory viruses and their potential clinical impact when recovered in lower respiratory specimens has not been established in the hospital setting. A study was performed to investigate the association between positive viral detection and respiratory infection in an at-risk population. METHODS: 299 adult patients who underwent bronchoalveolar lavage (BAL) procedures were enrolled in a hospital-based prospective cohort study. Descriptive epidemiology is presented of 17 different respiratory viruses detected by reverse transcription-polymerase chain reaction assays in BAL fluid specimens. Multivariate analysis was conducted to identify the clinical characteristics independently associated with the presence of virus. RESULTS: Of 522 BAL fluid specimens analysed, 81% were collected in adult transplant recipients or other immunocompromised patients. Overall, PCR assays identified viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus-positive BAL fluid were found in the different subpopulations studied (p = 0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis using mixed models showed that respiratory viral infections were associated with a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung transplant recipients in whom a respiratory infection was suspected, the respiratory viral detection rate was 24.4% compared with 13.8% overall in other patients (p = 0.02). CONCLUSIONS: In this cohort of hospitalised adults, respiratory viruses detected in BAL fluid specimens were associated with respiratory symptoms, absence of radiological infiltrates and a poor response to antibiotic therapy.

Influenza surveillance using data from a telemedicine centre.

OBJECTIVES: This study aimed at investigating whether data from medical teleconsultations may contribute to influenza surveillance. METHODS: International Classification of Primary Care 2nd Edition (ICPC-2) codes were used to analyse the proportion of teleconsultations due to influenza-related symptoms. Results were compared with the weekly Swiss Sentinel reports. RESULTS: When using the ICPC-2 code for fever we could reproduce the seasonal influenza peaks of the winter seasons 07/08, 08/09 and 09/10 as depicted by the Sentinel data. For the pandemic influenza 09/10, we detected a much higher first peak in summer 2009 which correlated with a potential underreporting in the Sentinel system. CONCLUSIONS: ICPC-2 data from medical teleconsultations allows influenza surveillance in real time and correlates very well with the Swiss Sentinel system.

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

Rapport de synthèse: Enjeux de la recherche : La pneumonie communautaire chez l'enfant est un problème de santé publique considérable. Elle est responsable de 2 millions de mort par année, 70% survenant dans les pays en voie de développement. Sous nos latitudes son incidence est de 40/1000 enfants par année, ce qui représente une morbidité importante. Deux difficultés surviennent lorsqu'on cherche à diagnostiquer une pneumonie. La première est de distinguer une pneumonie bactérienne d'une virale, particulièrement chez les petits enfants où les infections virales des voies respiratoires inférieures sont fréquentes. L'OMS a définit la pneumonie selon des critères exclusivement cliniques et une étude effectuée à Lausanne en 2000 a montré que ces critères peuvent être utilisés dans nos contrées. La seconde difficulté est de définir l'agent causal de la pneumonie, ceci pour plusieurs raisons : L'aspiration endotrachéale, seul examen fiable, ne peut être obtenue de routine chez l'enfant vu son caractère invasif, la culture des secrétions nasopharyngées reflète la flore physiologique de la sphère ORL et une bactériémie n'est présente que dans moins de 10% des pneumonies. L'étiologie de la pneumonie reste souvent inconnue, et de ce fait plusieurs enfants reçoivent des antibiotiques pour une infection non bactérienne ce qui contribue au développement de résistances. L'objectif de cette étude était d'effectuer une recherche extensive de l'agent causal de la pneumonie et de déterminer quels facteurs pourraient aider le clinicien à différencier une pneumonie virale de bactérienne, en corrélant l'étiologie avec la sévérité clinique et les marqueurs de l'inflammation. Contexte de la recherche : II s'agissait d'une étude prospective, multicentrique, incluant les enfants âgés de 2 mois à 5 ans hospitalisés pour une pneumonie, selon les critères de l'OMS, dans le service de pédiatrie de Lausanne et Genève entre mars 2003 et Décembre 2005, avant l'implantation de la vaccination antipneumococcique de routine. Chaque enfant, en plus des examens usuels, bénéficiait d'une recherche étiologique extensive : Culture virale et bactérienne, PCR (Mycoplasma Pneumoniae, Chlamydia Pneumoniae, Virus Influenza A et B, RSV A et B, Rhinovirus, Parainfluenza 1-3, enterovirus, human metapneumovirus, coronavirus OC43, E229 ; et NL 63) et détection d'AG viraux dans les sécrétions nasopharyngées ; sérologies virales et bactériennes à l'entrée et 3 semaines après la sortie (AG Influenza A et B, Parainfluenza 1,2 et 3, RSV, Adenovirus, M.Pneumoniae et S.Pneumoniae). Conclusions : Un agent pathogène a été découvert chez 86% des 99 patients retenus confirmant le fait que plus la recherche étiologique est étendue plus le pourcentage d'agent causal trouvé est élevé. Une infection bactérienne a été découverte chez 53% des patients dont 45% avaient une infection à S. Pneumoniae confirmant l'importance d'une vaccination antipneumococcique de routine. La déshydratation et les marqueurs de l'inflammation tels que la C-Reactive Protein et la Procalcitonine étaient significativement plus élevés dans les pneumonies bactériennes. Aucune corrélation n'a été trouvée entre le degré de sévérité de la pneumonie et l'étiologie. L'étude a confirmé la haute prévalence d'infections virales (67%) et de co-infection (33%) dans la pneumonie de l'enfant sans que l'on connaisse le rôle réel du virus dans la pathogenèse de la pneumonie. Perspectives : d'autres études à la suite de celle-ci devraient être effectuées en incluant les patients ambulatoires afin de déterminer, avec un collectif plus large de patient, une éventuelle corrélation entre sévérité clinique et étiologie. Abstract : Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.

The use of classification and regression trees to predict the likelihood of seasonal influenza.

Background Individual signs and symptoms are of limited value for the diagnosis of influenza. Objective To develop a decision tree for the diagnosis of influenza based on a classification and regression tree (CART) analysis. Methods Data from two previous similar cohort studies were assembled into a single dataset. The data were randomly divided into a development set (70%) and a validation set (30%). We used CART analysis to develop three models that maximize the number of patients who do not require diagnostic testing prior to treatment decisions. The validation set was used to evaluate overfitting of the model to the training set. Results Model 1 has seven terminal nodes based on temperature, the onset of symptoms and the presence of chills, cough and myalgia. Model 2 was a simpler tree with only two splits based on temperature and the presence of chills. Model 3 was developed with temperature as a dichotomous variable (≥38°C) and had only two splits based on the presence of fever and myalgia. The area under the receiver operating characteristic curves (AUROCC) for the development and validation sets, respectively, were 0.82 and 0.80 for Model 1, 0.75 and 0.76 for Model 2 and 0.76 and 0.77 for Model 3. Model 2 classified 67% of patients in the validation group into a high- or low-risk group compared with only 38% for Model 1 and 54% for Model 3. Conclusions A simple decision tree (Model 2) classified two-thirds of patients as low or high risk and had an AUROCC of 0.76. After further validation in an independent population, this CART model could support clinical decision making regarding influenza, with low-risk patients requiring no further evaluation for influenza and high-risk patients being candidates for empiric symptomatic or drug therapy.