Publications by authors named "Rachel Truscon"

14 Publications

  • Page 1 of 1

Distinct influenza surveillance networks and their agreement in recording regional influenza circulation: Experience from Southeast Michigan.

Influenza Other Respir Viruses 2021 Nov 25. Epub 2021 Nov 25.

Michigan Influenza Center, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Introduction: In Southeast Michigan, active surveillance studies monitor influenza activity in hospitals, ambulatory clinics, and community households. Across five respiratory seasons, we assessed the contribution of data from each of the three networks towards improving our overall understanding of regional influenza circulation.

Methods: All three networks used case definitions for acute respiratory illness (ARI) and molecularly tested for influenza from research-collected respiratory specimens. Age- and network-stratified epidemic curves were created for influenza A and B. We compared stratified epidemic curves visually and by centering at seasonal midpoints.

Results: Across all seasons (from 2014/2015 through 2018/2019), epidemic curves from each of the three networks were comparable in terms of both timing and magnitude. Small discrepancies in epidemics recorded by each network support previous conclusions about broader characteristics of particular influenza seasons.

Conclusion: Influenza surveillance systems based in hospital, ambulatory clinic, and community household settings appear to provide largely similar information regarding regional epidemic activity. Together, multiple levels of influenza surveillance provide a detailed view of regional influenza epidemics, but a single surveillance system-regardless of population subgroup monitored-appears to be sufficient in providing vital information regarding community influenza epidemics.
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http://dx.doi.org/10.1111/irv.12944DOI Listing
November 2021

Effectiveness of Influenza Vaccines in the HIVE Household Cohort Over 8 Years: Is There Evidence of Indirect Protection?

Clin Infect Dis 2021 10;73(7):1248-1256

University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, Michigan, USA.

Background: The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (ie, indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Methods: Using longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.

Results: The pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8) and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (-6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccination coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VE was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.

Conclusions: Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. Although there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.
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http://dx.doi.org/10.1093/cid/ciab395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492146PMC
October 2021

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population.

Vaccine 2019 02 7;37(10):1284-1292. Epub 2019 Feb 7.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, United States.

Background: Influenza vaccines are important for prevention of influenza-associated hospitalization. However, the effectiveness of influenza vaccines can vary by year and influenza type and subtype and mechanisms underlying this variation are incompletely understood. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness in hospitalized populations.

Methods: We enrolled adults hospitalized for treatment of acute respiratory illnesses during the 2014-2015 and 2015-2016 influenza seasons whose symptoms began <10 days prior to enrollment. Influenza infection status was determined by RT-PCR. Influenza vaccination status was defined by self-report and medical record/registry documentation. Serum specimens collected at hospital admission were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated how well antibody measured in these specimens represented pre-infection immune status, and measured associations between antibody and influenza vaccination and infection.

Results: Serum specimens were retrieved for 315 participants enrolled during the 2014-2015 season and 339 participants during the 2015-2016 season. Specimens were collected within 3 days of illness onset from 65% of participants. Geometric mean titers (GMTs) did not vary by the number of days from illness onset to specimen collection among influenza positive participants suggesting that measured antibody was representative of pre-infection immune status rather than a de novo response to infection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016.

Conclusions: Serum collected shortly after illness onset at hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2019.01.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595494PMC
February 2019

The Household Influenza Vaccine Effectiveness Study: Lack of Antibody Response and Protection Following Receipt of 2014-2015 Influenza Vaccine.

Clin Infect Dis 2017 Oct;65(10):1644-1651

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Antigenically drifted A(H3N2) viruses circulated extensively during the 2014-2015 influenza season. Vaccine effectiveness (VE) was low and not significant among outpatients but in a hospitalized population was 43%. At least one study paradoxically observed increased A(H3N2) infection among those vaccinated 3 consecutive years.

Methods: We followed a cohort of 1341 individuals from 340 households. VE against laboratory-confirmed influenza was estimated. Hemagglutination-inhibition and neuraminidase-inhibition antibody titers were determined in subjects ≥13 years.

Results: Influenza A(H3N2) was identified in 166 (12%) individuals and B(Yamagata) in 34 (2%). VE against A(H3N2) was -3% (95% confidence interval [CI]: -55%, 32%) and similarly ineffective between age groups; increased risk of infection was not observed among those vaccinated in 2 or 3 previous years. VE against influenza B(Yamagata) was 57% (95% CI: -3%, 82%) but only significantly protective in children <9 years (87% [95% CI: 43%, 97%]). Less than 20% of older children and adults had ≥4-fold antibody titer rise against influenza A(H3N2) and B antigens following vaccination; responses were surprisingly similar for antigens included in the vaccine and those similar to circulating viruses. Antibody against A/Hong Kong/4801/14, similar to circulating 2014-2015 A(H3N2) viruses and included in the 2016-2017 vaccine, did not significantly predict protection.

Conclusions: Absence of VE against A(H3N2) was consistent with circulation of antigenically drifted viruses; however, generally limited antibody response following vaccination is concerning even in the context of antigenic mismatch. Although 2014-2015 vaccines were not effective in preventing A(H3N2) infection, no increased susceptibility was detected among the repeatedly vaccinated.
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http://dx.doi.org/10.1093/cid/cix608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850544PMC
October 2017

Vaccination has minimal impact on the intrahost diversity of H3N2 influenza viruses.

PLoS Pathog 2017 01 31;13(1):e1006194. Epub 2017 Jan 31.

Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.

While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus' rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity of influenza A virus and to define the impact of vaccine-induced immunity on within-host populations. Importantly, this study design allowed us to isolate the impact of vaccination while still studying natural infection. We used pre-season hemagglutination inhibition and neuraminidase inhibition titers to quantify vaccine-induced immunity directly and to assess its impact on intrahost populations. We identified 166 cases of H3N2 influenza over 3 seasons and 5119 person-years. We obtained whole genome sequence data for 119 samples and used a stringent and empirically validated analysis pipeline to identify intrahost single nucleotide variants at ≥1% frequency. Phylogenetic analysis of consensus hemagglutinin and neuraminidase sequences showed no stratification by pre-season HAI and NAI titer, respectively. In our study population, we found that the vast majority of intrahost single nucleotide variants were rare and that very few were found in more than one individual. Most samples had fewer than 15 single nucleotide variants across the entire genome, and the level of diversity did not significantly vary with day of sampling, vaccination status, or pre-season antibody titer. Contrary to what has been suggested in experimental systems, our data indicate that seasonal influenza vaccination has little impact on intrahost diversity in natural infection and that vaccine-induced immunity may be only a minor contributor to antigenic drift at local scales.
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http://dx.doi.org/10.1371/journal.ppat.1006194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302840PMC
January 2017

Modest Waning of Influenza Vaccine Efficacy and Antibody Titers During the 2007-2008 Influenza Season.

J Infect Dis 2016 10 19;214(8):1142-9. Epub 2016 Apr 19.

Department of Epidemiology.

Background: Antibody titers decrease with time following influenza vaccination, raising concerns that vaccine efficacy might wane. However, the relationship between time since vaccination and protection is unclear.

Methods: Time-varying vaccine efficacy (VE[t]) was examined in healthy adult participants (age range, 18-49 years) in a placebo-controlled trial of inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) performed during the 2007-2008 influenza season. Symptomatic respiratory illnesses were laboratory-confirmed as influenza. VE(t) was estimated by fitting a smooth function based on residuals from Cox proportional hazards models. Subjects had blood samples collected immediately prior to vaccination, 30 days after vaccination, and at the end of the influenza season for testing by hemagglutination inhibition and neuraminidase inhibition assays.

Results: Overall efficacy was 70% (95% confidence interval [CI], 50%-82%) for IIV and 38% (95% CI, 5%-59%) for LAIV. Statistically significant waning was detected for IIV (P = .03) but not LAIV (P = .37); however, IIV remained significantly efficacious until data became sparse at the end of the season. Similarly, antibody titers against influenza virus hemagglutinin and neuraminidase significantly decreased over the season among IIV recipients.

Conclusions: Both vaccines were efficacious but LAIV less so. IIV efficacy decreased slowly over time, but the vaccine remained significantly efficacious for the majority of the season.
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http://dx.doi.org/10.1093/infdis/jiw105DOI Listing
October 2016

Substantial Influenza Vaccine Effectiveness in Households With Children During the 2013-2014 Influenza Season, When 2009 Pandemic Influenza A(H1N1) Virus Predominated.

J Infect Dis 2016 Apr 23;213(8):1229-36. Epub 2015 Nov 23.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: We examined the influenza vaccine effectiveness (VE) during the 2013-2014 influenza season, in which 2009 pandemic influenza A(H1N1) virus (influenza A[H1N1]pdm09) predominated. In 2 previous years when influenza A(H3N2) virus predominated, the VE was low and negatively affected by prior year vaccination.

Methods: We enrolled and followed 232 households with 1049 members, including 618 children; specimens were collected from subjects with acute respiratory illnesses. The VE in preventing laboratory-confirmed influenza A(H1N1)pdm09 infection was estimated in adjusted models. Preseason hemagglutination-inhibition and neuraminidase-inhibition antibody titers were determined to assess susceptibility.

Results: Influenza A(H1N1)pdm09 was identified in 25 households (10.8%) and 47 individuals (4.5%). Adjusted VE against infection with influenza A(H1N1)pdm09 was 66% (95% confidence interval [CI], 23%-85%), with similar point estimates in children and adults, and against both community-acquired and household-acquired infections. VE did not appear to be different for live-attenuated and inactivated vaccines among children aged 2-8 years, although numbers were small. VE was similar for subjects vaccinated in both current and prior seasons and for those vaccinated in the current season only; susceptibility titers were consistent with this observation.

Conclusions: Findings, including substantial significant VE and a lack of a negative effect of repeated vaccination on VE, were in contrast to those seen in prior seasons in which influenza A(H3N2) virus predominated.
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http://dx.doi.org/10.1093/infdis/jiv563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799665PMC
April 2016

Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination.

J Infect Dis 2015 Dec 26;212(12):1914-22. Epub 2015 May 26.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Antibody titers to influenza hemagglutinin (HA) and neuraminidase (NA) surface antigens increase in the weeks after infection or vaccination, and decrease over time thereafter. However, the rate of decline has been debated.

Methods: Healthy adults participating in a randomized placebo-controlled trial of inactivated (IIV) and live-attenuated (LAIV) influenza vaccines provided blood specimens immediately prior to vaccination and at 1, 6, 12, and 18 months postvaccination. Approximately half had also been vaccinated in the prior year. Rates of hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titer decline in the absence of infection were estimated.

Results: HAI and NAI titers decreased slowly over 18 months; overall, a 2-fold decrease in antibody titer was estimated to take >600 days for all HA and NA targets. Rates of decline were fastest among IIV recipients, explained in part by faster declines with higher peak postvaccination titer. IIV and LAIV recipients vaccinated 2 consecutive years exhibited significantly lower HAI titers following vaccination in the second year, but rates of persistence were similar.

Conclusions: Antibody titers to influenza HA and NA antigens may persist over multiple seasons; however, antigenic drift of circulating viruses may still necessitate annual vaccination. Vaccine seroresponse may be impaired with repeated vaccination.
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http://dx.doi.org/10.1093/infdis/jiv313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655854PMC
December 2015

Comparative efficacy of inactivated and live attenuated influenza vaccines.

N Engl J Med 2009 Sep;361(13):1260-7

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Background: The efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines.

Methods: We carried out a randomized, double-blind, placebo-controlled trial of licensed inactivated and live attenuated influenza vaccines in healthy adults during the 2007-2008 influenza season and estimated the absolute and relative efficacies of the two vaccines.

Results: A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine.

Conclusions: In the 2007-2008 season, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (ClinicalTrials.gov number, NCT00538512.)
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http://dx.doi.org/10.1056/NEJMoa0808652DOI Listing
September 2009

Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines.

J Infect Dis 2008 Aug;198(3):312-7

University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, Michigan 48109, USA.

Background: The efficacy of influenza vaccines may vary annually. In 2004-2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so.

Methods: In 2005-2006, we continued our trial, examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza.

Results: A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%), respectively.

Conclusions: With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine, but not statistically greater than that of the placebo.
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http://dx.doi.org/10.1086/589885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613648PMC
August 2008

Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines.

N Engl J Med 2006 Dec;355(24):2513-22

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor 48109, USA.

Background: The efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine.

Methods: We carried out a randomized, double-blind, placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004-2005 influenza season and estimated both absolute and relative efficacies.

Results: A total of 1247 persons were vaccinated between October and December 2004. Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A (H3N2) virus, the A/California/07/2004-like strain, and of type B viruses from two lineages. The absolute efficacy of the inactivated vaccine against both types of virus was 77% (95% confidence interval [CI], 37 to 92) as measured by isolating the virus in cell culture, 75% (95% CI, 42 to 90) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction, and 67% (95% CI, 16 to 87) as measured by either isolating the virus or observing a rise in the serum antibody titer. The absolute efficacies of the live attenuated vaccine were 57% (95% CI, -3 to 82), 48% (95% CI, -7 to 74), and 30% (95% CI, -57 to 67), respectively. The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses.

Conclusions: In the 2004-2005 season, in which most circulating viruses were dissimilar to those included in the vaccine, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (ClinicalTrials.gov number, NCT00133523.)
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http://dx.doi.org/10.1056/NEJMoa061850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614682PMC
December 2006

Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets.

J Infect Dis 2004 Nov 28;190(9):1627-30. Epub 2004 Sep 28.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.

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.
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http://dx.doi.org/10.1086/424572DOI Listing
November 2004

Detection and control of influenza outbreaks in well-vaccinated nursing home populations.

Clin Infect Dis 2004 Aug 2;39(4):459-64. Epub 2004 Aug 2.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA.

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 2000-2001, 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.
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http://dx.doi.org/10.1086/422646DOI Listing
August 2004

Assessment of development of resistance to antivirals in the ferret model of influenza virus infection.

J Infect Dis 2003 Nov 17;188(9):1355-61. Epub 2003 Oct 17.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.

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.
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http://dx.doi.org/10.1086/379049DOI Listing
November 2003
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