Performance of case definitions and clinical predictors for influenza surveillance among patients followed in a rural cohort in Senegal

Abstract Background Influenza is a major cause of morbidity and mortality in Africa. However, a lack of epidemiological data remains for this pathology, and the performances of the influenza-like illness (ILI) case definitions used for sentinel surveillance have never been evaluated in Senegal. This study aimed to i) assess the performance of three different ILI case definitions, adopted by the WHO, USA-CDC (CDC) and European-CDC (ECDC) and ii) identify clinical factors associated with a positive diagnosis for Influenza in order to develop an algorithm fitted for the Senegalese context. Methods All 657 patients with a febrile pathological episode (FPE) between January 2013 and December 2016 were followed in a cohort study in two rural villages in Senegal, accounting for 1653 FPE observations with nasopharyngeal sampling and influenza virus screening by rRT-PCR. For each FPE, general characteristics and clinical signs presented by patients were collected. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the three ILI case definitions were assessed using PCR result as the reference test. Associations between clinical signs and influenza infection were analyzed using logistic regression with generalized estimating equations. Sore throat, arthralgia or myalgia were missing for children under 5 years. Results WHO, CDC and ECDC case definitions had similar sensitivity (81.0%; 95%CI: 77.0–85.0) and NPV (91.0%; 95%CI: 89.0–93.1) while the WHO and CDC ILI case definitions had the highest specificity (52.0%; 95%CI: 49.1–54.5) and PPV (32.0%; 95%CI: 30.0–35.0). These performances varied by age groups. In children < 5 years, the significant predictors of influenza virus infection were cough and nasal discharge. In patients from 5 years, cough, nasal discharge, sore throat and asthenia grade 3 best predicted influenza infection. The addition of “nasal discharge” as a symptom to the WHO case definition decreased sensitivity but increased specificity, particularly in the pediatric population. Conclusion In summary, all three definitions studies (WHO, ECDC & CDC) have similar performance, even by age group. The revised WHO ILI definition could be chosen for surveillance purposes for its simplicity. Symptomatic predictors of influenza virus infection vary according the age group.

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Routine blood parameters are helpful for early identification of influenza infection in children

10.21203/rs.3.rs-54705/v2 ◽

2020 ◽

Author(s):

Ronghe Zhu ◽

Cuie Chen ◽

Qiu Wang ◽

Xixi Zhang ◽

Chaosheng Lu ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A Virus ◽

Early Identification ◽

Influenza A ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Cutoff Value ◽

Routine Blood ◽

Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

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Brugada-Like Electrocardiographic Changes during Influenza Infection

Journal of International Medical Research ◽

10.1177/147323000303100313 ◽

2003 ◽

Vol 31 (3) ◽

pp. 244-246 ◽

Cited By ~ 8

Author(s):

K Kusaka ◽

J Yamakawa ◽

K Kawaura ◽

T Itoh ◽

T Takahashi ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Viral Infection ◽

Brugada Syndrome ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Ecg Changes ◽

Early Repolarization ◽

Electrocardiographic Changes

We describe a 32-year-old man with electrocardiographic (ECG) changes consistent with Brugada syndrome and influenza virus infection. The ECG pattern changed after 1 week to one of early repolarization in V1 and V2. This case suggests an association between Brugada syndrome and viral infection.

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Increased Plasma Matrix Metalloproteinase-9 Levels Contribute to Intracerebral Hemorrhage during Thrombolysis after Concomitant Stroke and Influenza Infection

Cerebrovascular Diseases Extra ◽

10.1159/000447750 ◽

2016 ◽

Vol 6 (2) ◽

pp. 50-59 ◽

Cited By ~ 7

Author(s):

Sajjad Muhammad ◽

Oliver Planz ◽

Markus Schwaninger

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Matrix Metalloproteinase ◽

Intracerebral Hemorrhage ◽

Acute Stroke ◽

Plasma Levels ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Concomitant Infection ◽

Metalloproteinase 9

Background: Thrombolysis is the only approved therapy for acute stroke. However, life-threatening complications such as intracerebral hemorrhage (ICH) can develop after intravenous administration of tissue plasminogen activator (tPA). Both infection and thrombolysis during cerebral ischemia disrupt the blood-brain barrier (BBB). tPA can induce matrix metalloproteinase-9 (MMP-9), which is known to be involved in BBB disruption. However, it has still not been investigated whether preexisting influenza virus infection during thrombolysis after acute stroke affects systemic levels of MMP-9 and its inhibitor TIMP-1 and whether increased systemic MMP-9 levels affect ICH. This study aimed to investigate the influence of influenza virus infection on plasma levels of MMP-9 and TIMP-1 after thrombolysis in acute stroke, and to determine whether the infection correlates with intracerebral bleeding. Methods: C57BL/6 mice were infected by administering 1 × 105 plaque-forming units of human influenza (H1N1) virus intranasally. After 3 days of infection the middle cerebral artery was occluded for 45 min and then reperfused. Intravenous tPA (10 mg/kg) treatment was started 10 min after stroke onset. Twenty-four hours after stroke onset, mice were deeply anesthetized with ketamine, venous blood was drawn from the caval vein and centrifuged at 2,000 rpm, and the supernatant was collected and frozen at -80°C. Plasma levels of MMP-9 and TIMP-1 were quantified by using ELISA. Results: After stroke, plasma MMP-9 was significantly increased in mice with a concomitant influenza infection that were treated with tPA (9.99 ± 0.62 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA (4.74 ± 0.48 ng/ml, n = 8). Moreover, plasma levels of TIMP-1, an inhibitor of MMP-9, were also significantly increased in mice treated with tPA after concomitant infection and stroke (42.17 ± 7.02 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA after stroke (20.22 ± 2.12 ng/ml, n = 8). MMP-9 values significantly correlated with intracerebral hemoglobin levels in animals treated with tPA after stroke (p = 0.028, r = 0.76, n = 8) and after concomitant stroke and infection (p = 0.039, r = 0.78, n = 7). Conclusion: Preexisting influenza A virus infection led to increased plasma MMP-9 and TIMP-1 levels in mice undergoing thrombolysis after induced stroke. MMP-9 levels closely correlated with intracerebral bleeding after thrombolysis during concomitant infection and stroke. Thus, our data indicate that thrombolysis may be dangerous during influenza infection. MMP-9 inhibitors might be considered to reduce the side effects of thrombolysis during concomitant infection and stroke.

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Is Influenza an Influenza-Like Illness? Clinical Presentation of Influenza in Hospitalized Patients

Infection Control and Hospital Epidemiology ◽

10.1086/501539 ◽

2006 ◽

Vol 27 (3) ◽

pp. 266-270 ◽

Cited By ~ 86

Author(s):

Hilary M. Babcock ◽

Liana R. Merz ◽

Victoria J. Fraser

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Sore Throat ◽

Clinical Presentation ◽

Ventilatory Support ◽

Influenza Virus Infection ◽

Hospitalized Patients ◽

Series Data ◽

Influenza B ◽

Influenza Like Illness

Background.Early recognition of influenza virus infection in hospitalized patients can prevent nosocomial transmission.Objective.To determine the clinical presentation of influenza in hospitalized patients.Design.Case series. Data were collected retrospectively from medical records and included demographic information, comorbidities, clinical symptoms and signs, microbiologic test results, and outcomes (including pneumonia and intensive care unit [ICU] admission).Setting.A 1,400-bed teaching hospital.Patients.A total of 207 inpatients who received a diagnosis of influenza virus infection during 3 seasons from 2000 to 2003.Results.Over the course of 3 seasons, 207 patients received a diagnosis of influenza (186 were infected with influenza A virus, and 21 were infected with influenza B virus). The most commonly reported symptoms were cough (186 patients [90%]) and subjective fever (137 patients [66%]); 124 patients (60%) had a documented temperature of 37.8°C or greater before influenza was diagnosed. Sore throat was uncommon (44 patients [21%]). Centers for Disease Control and Prevention (CDC) criteria for influenza-like illness (ILI)–temperature 37.8°C or greater and either cough or sore throat–were met by 107 patients (51%). There were no differences in the proportion of patients who met ILI criteria with respect to age, sex, season, influenza virus type, or time to diagnosis in the hospital. Most patients (150 [72%]) received acetaminophen. Only 41 patients (20%) had positive results of clinical cultures; 178 patients (86%) received antibiotic therapy. Fifty-six patients (27%) had pneumonia: 36 (17%) required admission to the ICU, and 25 (12%) required ventilatory support. Patients with pulmonary disease were more likely to require ventilatory support (12 [26%] vs 13 [8%]; P = .003).Conclusions.Only half of hospitalized patients with influenza met CDC criteria for ILI. These criteria may be more appropriate in outpatient settings. A high index of suspicion is needed to recognize influenza in hospitalized patients.

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Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity

Journal of Virology ◽

10.1128/jvi.00395-17 ◽

2017 ◽

Vol 91 (23) ◽

Cited By ~ 2

Author(s):

Ericka Keef ◽

Li Ang Zhang ◽

David Swigon ◽

Alisa Urbano ◽

G. Bard Ermentrout ◽

...

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

Influenza Virus Infection ◽

The Elderly ◽

Morbidity And Mortality ◽

Age Group ◽

Rule Based ◽

Delayed Onset

ABSTRACT Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intrahost immune response to influenza virus infection. The model is fit to experimental data for young and old mice infected with influenza virus. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of the virus. Our models clearly demonstrate differences in these two age groups, particularly in the innate immune responses.

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Low pathogenic avian influenza virus infection retards colon microbiome diversification in two different chicken lines

10.1101/2021.03.15.435422 ◽

2021 ◽

Author(s):

Klaudia Chrzastek ◽

Joy Leng ◽

Mohammad Khalid Zakaria ◽

Dagmara Bialy ◽

Roberto LaRagione ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Rhode Island ◽

Post Infection ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Virus Infectivity ◽

The Impact

A commensal microbiome regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiome population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted. Using 16S rRNA sequencing and subsequent data analysis we found reduced microbiome alpha diversity in the acute period of AIV infection (day 2-3) in both Rhode Island Red and VALO chicken lines. From day 4 post infection a gradual increase in diversity of the colon microbiome was observed, but the diversity did not reach the same level as in uninfected chickens by day 10 post infection, suggesting that AIV infection retards the natural accumulation of colon microbiome diversity, which may further influence chicken health following recovery from infection. Beta diversity analysis indicated differences in diversity between the chicken lines during and following acute influenza infection suggesting the impact of host gut microflora dysbiosis following H9N2 influenza virus infection could differ for different breeds.

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Prevalence of canine parvo virus and canine influenza virus infection in dogs in Dhaka, Mymensingh, Feni and Chittagong districts of Bangladesh

Asian Journal of Medical and Biological Research ◽

10.3329/ajmbr.v2i1.27579 ◽

2016 ◽

Vol 2 (1) ◽

pp. 138-142 ◽

Cited By ~ 1

Author(s):

Soumitra Sen ◽

Md Siddiqur Rahman ◽

Minakshi Nag ◽

Mohummad Muklesur Rahman ◽

Roma Rani Sarker ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Canine Parvovirus ◽

Age Group ◽

Pet Dogs ◽

Canine Influenza Virus ◽

Test Kit ◽

Canine Influenza ◽

Age And Sex

Canine parvovirus (CPV) and canine influenza virus (CIV) are highly contagious virus infecting members of the canine family including dogs, coyotes, foxes and wolves. The research work was carried out to determine the prevalence of CPV and CIV in dogs (stray and pet dogs) in Dhaka, Mymensingh, Feni and Chittagong Districts by using Rapigen CPV and CIV Ag test kit. Fecal samples were collected from 50 dogs of different age and sex from different spots of Dhaka and Chittagong District. Nasal fluid samples were collected from 50 dogs of different age and sex from different spots. The samples were tested with Rapigen canine parvovirus Ag test kit and Rapigen canine influenza Ag test kit. Overall prevalence of CPV in pet dogs was 22% and in stray dogs was 30%. The prevalence of canine parvovirus in relation to age was gradually decreasing with higher age group and the prevalence was 28% in 1-6 months age, 16.66% in 7-12 months age group 11.11%o ver 18 months age group. The prevalence of canine parvovirus was significantly higher in male (24.13%) than that in female (19.04%). All samples showed negative test result for canine influenza virus. Prevalence of canine influenza virus infection were 00.00% in all age groups and sex. Overall prevalence of CIV in all pet and stray dogs were 00.00%.Asian J. Med. Biol. Res. March 2016, 2(1): 138-142

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Association Between the Respiratory Microbiome and Susceptibility to Influenza Virus Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciz968 ◽

2019 ◽

Vol 71 (5) ◽

pp. 1195-1203 ◽

Cited By ~ 8

Author(s):

Tim K Tsang ◽

Kyu Han Lee ◽

Betsy Foxman ◽

Angel Balmaseda ◽

Lionel Gresh ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Fold Increase ◽

Transmission Model ◽

Influenza B ◽

Household Contacts ◽

Index Cases

Abstract Background Previous studies suggest that the nose/throat microbiome may play an important role in shaping host immunity and modifying the risk of respiratory infection. Our aim is to quantify the association between the nose/throat microbiome and susceptibility to influenza virus infection. Methods In this household transmission study, index cases with confirmed influenza virus infection and their household contacts were followed for 9–12 days to identify secondary influenza infections. Respiratory swabs were collected at enrollment to identify and quantify bacterial species via high-performance sequencing. Data were analyzed by an individual hazard-based transmission model that was adjusted for age, vaccination, and household size. Results We recruited 115 index cases with influenza A(H3N2) or B infection and 436 household contacts. We estimated that a 10-fold increase in the abundance in Streptococcus spp. and Prevotella salivae was associated with 48% (95% credible interval [CrI], 9–69%) and 25% (95% CrI, 0.5–42%) lower susceptibility to influenza A(H3N2) infection, respectively. In contrast, for influenza B infection, a 10-fold increase in the abundance in Streptococcus vestibularis and Prevotella spp. was associated with 63% (95% CrI, 17–83%) lower and 83% (95% CrI, 15–210%) higher susceptibility, respectively. Conclusions Susceptibility to influenza infection is associated with the nose/throat microbiome at the time of exposure. The effects of oligotypes on susceptibility differ between influenza A(H3N2) and B viruses. Our results suggest that microbiome may be a useful predictor of susceptibility, with the implication that microbiome could be modulated to reduce influenza infection risk, should these associations be causal.

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Flow Cytometric and Cytokine ELISpot Approaches To Characterize the Cell-Mediated Immune Response in Ferrets following Influenza Virus Infection

Journal of Virology ◽

10.1128/jvi.01001-16 ◽

2016 ◽

Vol 90 (17) ◽

pp. 7991-8004 ◽

Cited By ~ 18

Author(s):

Anthony DiPiazza ◽

Katherine Richards ◽

Frances Batarse ◽

Laura Lockard ◽

Hui Zeng ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Influenza Virus ◽

T Cell ◽

Virus Infection ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Flow Cytometric ◽

Cell Mediated Immune Response ◽

Mhc Locus

ABSTRACTInfluenza virus infections represent a significant socioeconomic and public health burden worldwide. Although ferrets are considered by many to be ideal for modeling human responses to influenza infection and vaccination, efforts to understand the cellular immune response have been severely hampered by a paucity of standardized procedures and reagents. In this study, we developed flow cytometric and T cell enzyme-linked immunosorbent spot (ELISpot) approaches to characterize the leukocyte composition and antigen-specific T cell response within key lymphoid tissues following influenza virus infection in ferrets. Through a newly designed and implemented set of serological reagents, we used multiparameter flow cytometry to directly quantify the frequency of CD4+and CD8+T cells, Ig+B cells, CD11b+myeloid-derived cells, and major histocompatibility complex (MHC) class II-positive antigen-presenting cells (APCs) both prior to and after intranasal infection with A/California/04/09 (H1N1). We found that the leukocyte composition was altered at 10 days postinfection, with notable gains in the frequency of T cells and myeloid cells within the draining lymph node. Furthermore, these studies revealed that the antigen specificity of influenza virus-reactive CD4 and CD8 T cells was very broad, with recognition of the viral HA, NA, M1, NS1, and NP proteins, and that total reactivity to influenza virus postinfection represented approximately 0.1% of the circulating peripheral blood mononuclear cells (PBMC). Finally, we observed distinct patterns of reactivity between individual animals, suggesting heterogeneity at the MHC locus in ferrets within commercial populations, a finding of considerable interest in efforts to move the ferret model forward for influenza vaccine and challenge studies.IMPORTANCEFerrets are an ideal animal model to study transmission, diseases, and vaccine efficacies of respiratory viruses because of their close anatomical and physiological resemblances to humans. However, a lack of reagents has limited our understanding of the cell-mediated immune response following infection and vaccination. In this study, we used cross-reactive and ferret-specific antibodies to study the leukocyte composition and antigen-specific CD4 and CD8 T cell responses following influenza A/California/04/09 (H1N1) virus infection. These studies revealed strikingly distinct patterns of reactivity between CD4 and CD8 T cells, which were overlaid with differences in protein-specific responses between individual animals. Our results provide a first, in-depth look at the T cell repertoire in response to influenza infection and suggest that there is considerable heterogeneity at the MHC locus, which is akin to that in humans and an area of intense research interest.

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Prevention of Murine Influenza a Virus Pneumonitis by Surfactant Nano-Emulsions

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020001100104 ◽

2000 ◽

Vol 11 (1) ◽

pp. 41-49 ◽

Cited By ~ 28

Author(s):

Brian W Donovan ◽

Jon D Reuter ◽

Zhengyi Cao ◽

Andrzej Myc ◽

Kent J Johnson ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Therapeutic Potential ◽

Clinical Signs ◽

Influenza Virus Infection ◽

Initial Study ◽

Ionic Surfactant ◽

Nano Emulsion

Non-ionic surfactant nano-emulsions have extensive anti-microbial activity and are biocompatible with skin and mucous membranes at effective concentrations. Two nano-emulsion formulations (8N8 and 20N10) made from soybean oil, tributyl phosphate and Triton X-100, were tested for their ability to prevent murine influenza virus pneumonia in vivo. In the initial study, CD-1 mice were administered various dilutions of the nano-emulsions intranasally, and safe dosages and concentrations were determined. Non-toxic concentrations of the nano-emulsions were then mixed with influenza virus and applied to the nares of mice. Animals receiving mixtures of two different emulsions (8N8 or 20N10) and a LD50 of virus survived the challenge without evidence of viral infection. To determine if the nano-emulsions could prevent influenza virus infection in vivo when used as a prophylactic treatment, the nano-emulsions (8N8 at 1.0% and 20N10 at 1.0% or 0.2%) were applied to mouse nares 90 min before exposure to 5×105 p.f.u./ml virus by nebulized aerosol. Animals pretreated with the nano-emulsions had significantly decreased clinical signs of infection. Only 26.0% (8N8 at 1.0%), 31.25% (20N10 at 1.0%) and 37.0% (20N10 at 0.2%) of animals pretreated with nano-emulsion died from pneumonitis, whereas >80.0% of mock pretreated animals succumbed to infection ( P<0.005). These findings suggest that non-ionic surfactant nano-emulsions have therapeutic potential for the prevention of influenza virus infection in vivo.

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