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Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of influenza antivirals. A controlled trial examining baloxavir treatment efficacy to reduce transmission, including the risk of transmitting virus with reduced baloxavir susceptibility, is currently in progress. If reduced transmission risk is confirmed, modeling studies indicate that early treatment could have major epidemiologic benefits in seasonal and pandemic influenza., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Oseltamivir has been used to treat children with influenza for nearly 2 decades, with treatment currently approved for infants aged ≥2 weeks. However, efficacy and safety remain controversial. Newer randomized, placebo-controlled trials (RCTs), not included in previous meta-analyses, can add to the evidence base., Methods: We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a 2-stage, random-effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RMST) by treatment group. We also examined complications and safety., Results: We identified 5 trials that included 2561 patients in the intention-to-treat (ITT) and 1598 in the intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference, -17.6 hours; 95% confidence interval [CI], -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours; 95% CI, -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group., Conclusions: Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.

Background: Influenza causes millions of illnesses annually; certain groups are at higher risk for complications. Early antiviral treatment can reduce the risk of complications and is recommended for outpatients at increased risk. We describe antiviral prescribing among high-risk outpatients for 5 influenza seasons and explore factors that may influence prescribing., Methods: We analyzed antiviral prescription and clinical data for high-risk outpatients aged ≥6 months with an acute respiratory illness (ARI) and enrolled in the US Influenza Vaccine Effectiveness Network during the 2011-2012 through 2015-2016 influenza seasons. We obtained clinical information from interviews and electronic medical records and tested all enrollees for influenza with real-time reverse-transcription polymerase chain reaction (rRT-PCR). We calculated the number of patients with ARI that must be treated to treat 1 patient with influenza., Results: Among high-risk outpatients with ARI who presented to care within 2 days of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication, including 472 of 1292 (37%) of those with rRT-PCR-confirmed influenza. Forty percent of high-risk outpatients with influenza presented to care early. Earlier presentation was associated with antiviral treatment (odds ratio [OR], 4.1; 95% confidence interval [CI], 3.5-4.8), as was fever (OR, 3.2; 95% CI, 2.7-3.8), although 25% of high-risk outpatients with influenza were afebrile. Empiric treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with influenza., Conclusions: Influenza antiviral medications were infrequently prescribed for high-risk outpatients with ARI who would benefit most. Efforts to increase appropriate antiviral prescribing are needed to reduce influenza-associated complications.

Background and Objectives: The Influenza Resistance Information Study (IRIS) was initiated in 2008 to study the emergence of neuraminidase inhibitor (NAI) resistance and the clinical course of influenza in immunocompetent treated and untreated patients., Methods: Patients had throat/nose swabs collected on days 1, 3, 6 and 10 for analyses of influenza type, subtype and virus susceptibility to NAIs. RT-PCR-positive samples were cultured and tested for NAI resistance by specific RT-PCR and phenotypic testing. Scores for influenza symptoms were recorded on diary cards (Days 1-10). This study focuses on influenza A-infected cases only., Results: Among 3230 RT-PCR-positive patients, 2316 had influenza A of whom 1216 received oseltamivir monotherapy within 2 days of symptom onset (9 seasonal H1N1; 662 H3N2; 545 H1N1pdm2009). Except for 9 patients with naturally resistant seasonal H1N1 (2008/9), no resistance was detected in Day 1 samples. Emergence of resistance (post-Day 1) was detected in 43/1207 (3.56%) oseltamivir-treated influenza A-infected patients, with a higher frequency in 1- to 5-year-olds (11.8%) vs >5-year-olds (1.4%). All N1- and N2-resistant viruses had H275Y (n = 27) or R292K (n = 16) substitutions, respectively. For 43 patients, virus clearance was significantly delayed vs treated patients with susceptible viruses (8.1 vs 10.9 days; P < .0001), and 11 (23.2%) remained RT-PCR positive for influenza at Day 10. However, their symptoms resolved by Day 6 or earlier., Conclusions: Oseltamivir resistance was only detected during antiviral treatment, with the highest incidence occurring among 1- to 5-year-olds. Resistance delayed viral clearance, but had no impact on symptom resolution., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

During the 2013-2014 influenza season, we analyzed data from 6004 outpatients aged ≥6 months with acute respiratory illness (ARI). Among the 2786 ARI patients at higher risk for influenza complications, 835 (30%) presented to care ≤2 days from symptom onset; among those, 126 (15%) were prescribed an antiviral medication., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety., Methods: We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes., Findings: We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0·79, 95% CI 0·74-0·85; p<0·0001). The median times to alleviation were 97·5 h for oseltamivir and 122·7 h for placebo groups (difference -25·2 h, 95% CI -36·2 to -16·0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0·85) but remained highly significant (median difference -17·8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0·56, 95% CI 0·42-0·75; p=0·0001; 4·9% oseltamivir vs 8·7% placebo, risk difference -3·8%, 95% CI -5·0 to -2·2) and also fewer admittances to hospital for any cause (RR 0·37, 95% CI 0·17-0·81; p=0·013; 0·6% oseltamivir, 1·7% placebo, risk difference -1·1%, 95% CI -1·4 to -0·3). Regarding safety, oseltamivir increased the risk of nausea (RR 1·60, 95% CI 1·29-1·99; p<0·0001; 9·9% oseltamivir vs 6·2% placebo, risk difference 3·7%, 95% CI 1·8-6·1) and vomiting (RR 2·43, 95% CI 1·83-3·23; p<0·0001; 8·0% oseltamivir vs 3·3% placebo, risk difference 4·7%, 95% CI 2·7-7·3). We recorded no effect on neurological or psychiatric disorders or serious adverse events., Interpretation: Our findings show that oseltamivir in adults with influenza accelerates time to clinical symptom alleviation, reduces risk of lower respiratory tract complications, and admittance to hospital, but increases the occurrence of nausea and vomiting., Funding: Multiparty Group for Advice on Science (MUGAS) foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Seasonal influenza causes >200 000 annual hospitalizations in the United States. Current antiviral treatment options are limited to oral or inhaled agents. There is an urgent unmet need for intravenous antiviral treatments., Methods: Patients hospitalized with suspected influenza were randomized to 5-day treatment with intravenous peramivir (600 mg once daily) or placebo; all received the institution's standard of care (SOC) treatment. Time to clinical resolution and change in viral shedding in nasopharyngeal specimens were the primary and key secondary end points., Results: Influenza infection was confirmed in 338 of 405 enrolled patients. At the time of a preplanned interim analysis, the primary efficacy analysis population comprised 121 patients who did not receive a concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir versus 49.5 (40.0-61.9) hours for placebo (P = .97). A larger treatment effect was observed in patients with history of symptoms <48 hours or admitted to an intensive care unit. Greater reductions in viral shedding, based on median tissue culture infective dose, were observed in patients who received peramivir than in placebo recipients, although this difference was not statistically significant. The incidence and severity of adverse events and laboratory abnormalities were similar between the 2 treatment groups. The study was terminated for futility after a preplanned interim analysis., Conclusions: A significant clinical benefit was not demonstrated for peramivir plus SOC compared with placebo plus SOC. Peramivir was generally safe and well tolerated. These findings highlight the challenges in designing studies to evaluate influenza antiviral agents in a hospitalized setting. Clinical Trials Registration. NCT00958776., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Early antiviral treatment (≤2 days since illness onset) of influenza reduces the probability of influenza-associated complications. Early empiric antiviral treatment is recommended for those with suspected influenza at higher risk for influenza complications regardless of their illness severity. We describe antiviral receipt among outpatients with acute respiratory illness (ARI) and antibiotic receipt among patients with influenza., Methods: We analyzed data from 5 sites in the US Influenza Vaccine Effectiveness Network Study during the 2012-2013 influenza season. Subjects were outpatients aged ≥6 months with ARI defined by cough of ≤7 days' duration; all were tested for influenza by polymerase chain reaction (PCR). Medical history and prescription information were collected by medical and pharmacy records. Four sites collected prescribing data on 3 common antibiotics (amoxicillin-clavulanate, amoxicillin, and azithromycin)., Results: Of 6766 enrolled ARI patients, 509 (7.5%) received an antiviral prescription. Overall, 2366 (35%) had PCR-confirmed influenza; 355 (15%) of those received an antiviral prescription. Among 1021 ARI patients at high risk for influenza complications (eg, aged <2 years or ≥65 years or with ≥1 chronic medical condition) presenting to care ≤2 days from symptom onset, 195 (19%) were prescribed an antiviral medication. Among participants with PCR-confirmed influenza and antibiotic data, 540 of 1825 (30%) were prescribed 1 of 3 antibiotics; 297 of 1825 (16%) were prescribed antiviral medications., Conclusions: Antiviral treatment was prescribed infrequently among outpatients with influenza for whom therapy would be most beneficial; in contrast, antibiotic prescribing was more frequent. Continued efforts to educate clinicians on appropriate antibiotic and antiviral use are essential to improve healthcare quality., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Following emergence of naturally occurring oseltamivir-resistant influenza A(H1N1) viruses, a global observational investigation, the Influenza Resistance Information Study (IRIS; NCT00884117), was initiated in 2008 to study neuraminidase inhibitor (NAI) resistance and clinical outcome., Methods: Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by semiquantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) for influenza type and subtype and NAI resistance. RT-qPCR-positive specimens were cultured, sequenced, and phenotypically tested for NAI resistance. Treatment was at the physician's discretion., Results: Of 1799 influenza-positive (RT-qPCR) patients, 1281 had influenza A (47 seasonal H1N1; 335 H3N2; 899 H1N1pdm2009) and 518 had influenza B. Antivirals were administered to 1041 (58%) patients (26, 245, 514, and 256, respectively). All seasonal H1N1 strains were genotypically (H275Y) and phenotypically resistant to oseltamivir. No genotypic resistance was detected in the day 1 samples of any other viral subtypes. Mutation-specific (MS) RT-PCR detected resistance to oseltamivir in 19 patients postbaseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292K]), 14 of whom were children aged ≤5 years. In 12 of 19 patients, viral loads were too low to permit cell culture and 14 of 19 were RT-qPCR negative by day 10. In 1 other H1N1pdm2009 patient, H275Y was detected by sequencing but not by MS RT-PCR. No emergent resistance was found in influenza B infections., Conclusions: In years 1-3 of IRIS, emergent resistance to oseltamivir in influenza viruses during treatment was uncommon (2.2%) and mostly found in patients aged 1-5 years. Viral loads were low in many cases and viral clearance rapid.

Antivirals are effective in prophylaxis and therapy for influenza and are likely to be active against a new pandemic variant. They can be divided into the M2 inhibitors, adamantane and rimantadine, and the neuraminidase inhibitors (NAIs), zanamivir and oseltamivir. The former are limited in activity to type A viruses, whereas the latter are also active against type B viruses. Both classes of drugs appear similarly efficacious in prophylaxis at approximately 70-90%. However, use of M2 inhibitors (adamantanes) in therapy is limited by side effects, more common with amantadine, and also by production of antiviral resistance and lack of demonstrated prevention of complications. The NAIs prevent both types of seasonal influenza, shorten duration of illness, and reduce complications. As such, their use for seasonal influenza treatment has been increasing. They are active against A(H5N1) but oseltamivir has been most extensively stockpiled because the infection in humans may be disseminated. Resistance does emerge, but not at the same frequency as with the M2 inhibitors. Resistant viruses also appear less fit and thus less able to spread. However, as use increases, resistance needs to be carefully monitored.

Four household-based, randomized clinical trials, two each of zanamivir and oseltamivir, were designed primarily to estimate the effect of postexposure prophylaxis on preventing influenza illness in household contacts. However, the effect of influenza antivirals on infectiousness as well as on the ability of the virus to cause disease--the pathogenicity--have important public health consequences. The authors show how such studies can provide estimates of pathogenicity, antiviral efficacy for pathogenicity, and the antiviral effect on infectiousness. Analysis of the four studies confirmed the high prophylactic efficacy against illness of both zanamivir (75%, 95% confidence interval (CI): 54, 86) and oseltamivir (81%, 95% CI: 35, 94). The effect on reducing infectiousness was 19% (95% CI: -160, 75) for zanamivir and 80% (95% CI: 43, 93) for oseltamivir. Pathogenicity in controls ranged from 44% (95% CI: 33, 55) to 66% (95% CI: 48, 72). Efficacy in reducing pathogenicity for zanamivir was 52% (95% CI: 19, 72) and 56% (95% CI: 14, 77) in the two studies; for oseltamivir, it was 56% (95% CI: 10, 73) and 79% (95% CI: 45, 92). Studies of influenza antivirals in transmission units would be improved if randomization schemes were used that allow estimation of the antiviral effect on infectiousness from individual studies.

Neuraminidase inhibitors (NAIs) are antivirals designed to target conserved residues at the neuraminidase (NA) enzyme active site in influenza A and B viruses. The conserved residues that interact with NAIs are under selective pressure, but only a few have been linked to resistance. In the A/Wuhan/359/95 (H3N2) recombinant virus background, we characterized seven charged, conserved NA residues (R118, R371, E227, R152, R224, E276, and D151) that directly interact with the NAIs but have not been reported to confer resistance to NAIs. These NA residues were replaced with amino acids that possess side chains having similar properties to maintain their original charge. The NA mutations we introduced significantly decreased NA activity compared to that of the A/Wuhan/359/95 recombinant wild-type and R292K (an NA mutation frequently reported to confer resistance) viruses, which were analyzed for comparison. However, the recombinant viruses differed in replication efficiency when we serially passaged them in vitro; the growth of the R118K and E227D viruses was most impaired. The R224K, E276D, and R371K mutations conferred resistance to both zanamivir and oseltamivir, while the D151E mutation reduced susceptibility to oseltamivir only (approximately 10-fold) and the R152K mutation did not alter susceptibility to either drug. Because the R224K mutation was genetically unstable and the emergence of the R371K mutation in the N2 subtype is statistically unlikely, our results suggest that only the E276D mutation is likely to emerge under selective pressure. The results of our study may help to optimize the design of NAIs.

Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) develops at a low level following drug treatment, and person-to-person transmission of resistant virus has not been recognized to date. The Neuraminidase Inhibitor Susceptibility Network (NISN) was established to follow susceptibility of isolates and occurrence of NAI resistance at a population level in various parts of the world. Isolates from the WHO influenza collaborating centers were screened for susceptibilities to oseltamivir and zanamivir by a chemiluminescent enzyme inhibition assay, and those considered potentially resistant were analyzed by sequence analysis of the neuraminidase genes. During the first 3 years of NAI use (1999 to 2002), 2,287 isolates were tested. Among them, eight (0.33%) viruses had a >10-fold decrease in susceptibility to oseltamivir, one (0.22%) in 1999 to 2000, three (0.36%) in 2000 to 2001, and four (0.41%) in 2001 to 2002. Six had unique changes in the neuraminidase gene compared to neuraminidases of the same subtype in the influenza sequence database. Although only one of the mutations had previously been recognized in persons receiving NAIs, none were from patients who were known to have received the drugs. During the 3 years preceding NAI use, no resistant variants were detected among 1,054 viruses. Drug use was relatively stable during the period, except for an approximate 10-fold increase in oseltamivir use in Japan during the third year. The frequency of variants with decreased sensitivity to the NAIs did not increase significantly during this period, but continued surveillance is required, especially in regions with higher NAI use.

While measures such as closing schools and social distancing may slow the effects of pandemic influenza, only vaccines and antiviral drugs are clearly efficacious in preventing infection or treating illness. Unless the pandemic strain closely resembles one already recognized, vaccine will not be available early. However, studies can be conducted beforehand to address questions concerning vaccine dose, frequency of inoculation, and need for adjuvants. In contrast, antiviral drugs, particularly the neuraminidase inhibitors, will be effective for treatment and available if stockpiling takes place. Special questions need to be answered if a highly lethal virus, such as influenza A (H5N1), produces the pandemic. Both vaccines and antiviral drugs will be required for a coordinated strategy.

The outbreak of H5N1 avian influenza in Asia has reignited concerns about an influenza pandemic. It is clear that influenza vaccine will be in short supply (or nonexistent) early in an influenza pandemic. Without vaccine, the role of antiviral agents, especially oseltamivir, in treatment and prophylaxis is of paramount importance. Unfortunately, the government cannot possibly stockpile enough oseltamivir to provide long-term prophylaxis or treatment for every healthcare worker in the United States. We think that hospitals should consider stockpiling oseltamivir, and we provide a strategy for doing so at a reasonable cost.

Background: Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in the pandemic.METHODS. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; the first dose was given 4 h before inoculation with H5N1 A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens were evaluated.RESULTS. Oseltamivir produced a dose-dependent antiviral effect against VN1203/04 in vivo (P<.01). The 5-day regimen at 10 mg/kg/day protected 50% of mice; deaths in this treatment group were delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively (P<.05). Overall, the efficacy of the 5- and 8-day regimens differed significantly (death hazard ratio, 2.658; P<.01). The new H5N1 antigenic variant VN1203/04 was more pathogenic in mice than was A/HK/156/97 virus, and a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect.CONCLUSIONS. Oseltamivir prophylaxis is efficacious against lethal challenge with VN1203/04 virus in mice. Viral virulence may affect the antiviral treatment schedule.

Three type A influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. Previously, in the ferret model, an R292K mutant of a type A (H3N2) virus was not transmitted under conditions in which the wild-type virus was transmitted. This model was used to investigate whether the E119V mutant of a type A (H3N2) virus and the H274Y mutant of a type A (H1N1) virus would be transmitted under similar circumstances. Both mutant viruses were transmitted, although the H274Y mutant required a 100-fold-higher dose for infection of donor ferrets and was transmitted more slowly than was the wild type. Both the mutant and the wild-type viruses retained their genotypic characteristics.

We attempted to develop in vivo resistance of influenza virus to amantadine and to zanamivir, by use of the ferret model of influenza virus infection. Resistance of influenza virus A/LosAngeles/1/87 (H3N2) to amantadine was generated within 6 days, during a single course of treatment, and mutations in the M2 gene that are characteristic of human infections were observed. In contrast, during an identical single course of treatment with zanamivir, no evidence of reduced susceptibility was demonstrated. Pooled virus shed by zanamivir-treated ferrets was used to infect another group of ferrets. Twenty virus clones grew in plaque assays containing zanamivir, indicating possible reduced susceptibility; however, none exhibited reduced susceptibility to zanamivir in neuraminidase (NA) inhibition assays. Sequencing of the NA gene of these clones revealed only a noncoding nucleotide mutation at position 685. Sequencing of the hemagglutinin gene revealed mutations at positions 53, 106, 138, 145, 166, and 186. Similar to the situation in humans, amantadine use in ferrets rapidly produces antiviral resistance, but zanamivir use does not, although nucleotide changes were observed.

Antivirals are effective in the prophylaxis and therapy of influenza and are likely to be active against a new pandemic variant. They can be divided into the M2 inhibitors, amantadine and rimantadine, and the neuraminidase inhibitors (NIs), zanamivir and oseltamivir. The former are limited in activity to type A viruses, while the latter are also active against type B viruses. Both classes of drugs are approximately 70-90% efficacious when used as prophylaxis. However, the use of M2 inhibitors in therapy is frequently limited by side effects, more common with amantadine, by the emergence of antiviral resistance and by the lack of demonstrated prevention of complications. In contrast, the NIs are better tolerated, antiviral resistance has not emerged as a significant problem and limited evidence suggests they may reduce the frequency of influenza complications. Antiviral agents have not been widely used for either prophylaxis or treatment of annual influenza epidemics. During the early months of the next pandemic they will be the only specific agents that could be used for prevention and treatment. Their availability will depend entirely on the creation of stockpiles of these agents well in advance of the arrival of the pandemic.

A double-blind, randomized study of inhaled zanamivir for the prevention of influenza in families was conducted. Once a person with a suspected case of influenza was identified (index patient), treatment of all other household members (contacts) > or =5 years old was initiated. Contacts received either 10 mg zanamivir or placebo inhaled once daily for 10 days. Index patients received relief medication only. In total, 487 households (242 placebo and 245 zanamivir) were enrolled, with 1291 contacts randomly assigned to receive prophylaxis. Four percent of zanamivir versus 19% of placebo households (P<.001) had at least 1 contact who developed symptomatic, laboratory-confirmed influenza, representing 81% protective efficacy (95% confidence interval, 64%-90%). Protective efficacy was similarly high for individuals (82%) and against both influenza types A and B (78% and 85%, respectively, for households). Zanamivir was well tolerated and was effective in preventing influenza types A and B within households where the index patient was not treated.

Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures formitigating pandemic influenza. Our objectivewas to examine if the use of facemasks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007-2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survivalmodels using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with amaximumreduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These nonpharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic. [ABSTRACT FROM AUTHOR]

The second annual Seasonal and Pandemic Influenza Conference, which took place in February 2007 in Arlington, Virginia, focused on recent progress in basic and clinical research regarding preparedness for outbreaks of influenza. Sporadic outbreaks of avian influenza A in Asia and the Middle East remind us that the threat of another influenza pandemic remains real. Although the exact mechanisms underlying avian influenza A human pathogenicity remain unclear, preclinical studies in animal models provide insights into the mechanisms of avian influenza A virus infection and transmission from bird to human and, rarely, from human to human. With regard to prevention, developmental studies of adjuvant-supplemented vaccines indicate promising immunogenicity and cross-reactivity. The pipeline of new antiviral agents in development is also increasing, including a new neuraminidase inhibitor and agents aimed at completely new targets. Global strategic planning efforts focus on assuring sufficient stocks of vaccines and antiviral agents, as well as timely nonpharmacological interventions to potentially delay or contain spread of an outbreak. These initiatives will also help control outbreaks of seasonal influenza. [ABSTRACT FROM AUTHOR]

Background. influenza outbreaks continue to occur in nursing homes despite high vaccination coverage among residents. Recommendations for outbreak control in institutions such as nursing homes advises use of antiviral drugs to reduce influenza transmission. Methods. influenza surveillance was performed among elderly residents of nursing homes in Michigan during 2 influenza seasons. The antiviral drug oseltamivir was used for outbreak control at the discretion of nursing home staff once influenza transmission was confirmed by virus isolation or rapid antigen detection. Results. During 2000-200 1, influenza was not confirmed in any of the 28 participating homes, despite transmission of types A (H1N1) and B in the community. During 2001-2002, influenza type A (H3N2) transmission was confirmed in 8 (26%) of 31 participating homes; influenza vaccine coverage among residents was 57%- 98% in outbreak-associated homes. Oseltamivir was used in all homes with influenza transmission; outbreak control varied according to the rapidity of outbreak recognition and the extent of antiviral use. Reported adverse events were primarily gastrointestinal reactions and rashes. Analysis of the usefulness of rapid antigen detection tests for outbreak recognition indicated a sensitivity of only 77% (specificity, 92%). Conclusions. Oseltamivir was reasonably well tolerated, and its use, along with continued promotion of vaccination coverage among nursing home residents and staff, should be a valuable addition to institutional outbreak-control strategies. [ABSTRACT FROM AUTHOR]

To create a clinical prediction index that aids in the diagnosis of picornavirus respiratory infections, we analyzed patients from 5 clinical trials designed to evaluate the efficacy of an antiviral treatment for respiratory infections. Logistic regression was used to determine which baseline symptoms and patient characteristics best predicted picornavirus infection. Parameter estimates were then used to create a predictive index for estimating the probability of picornavirus infection on the basis of cold symptoms. The presence at baseline of rhinorrhea (odds ratio [OR], 2.73), nasal congestion (OR, 1.63), and sore throat (OR, 1.37) increased the likelihood of picornavirus infection; the presence of myalgia (OR, 0.71) and fever (OR, 0.59) decreased the likelihood. The positive and negative predictive values of the model were 61.5% and 64.4%, respectively. The model was simplified for clinical use by creating a whole-number index: the lowest possible score (-3) indicates a 15% chance of picornavirus infection and the highest (7) indicates a 69% chance of picornavirus infection. [ABSTRACT FROM AUTHOR]

The author comments on the study by N. Sugaya and colleagues which compares the effectiveness of oseltamivir and zanamivir against influenza virus infection in children, published within the issue. He remarks that the longest duration of type B influenza illness for patients treated with both drugs is a finding that could be related to the higher inhibitory concentration values. He notes that study confirms that the drugs were similarly effective in terms of clinical outcomes.