scholarly journals Antiviral resistance of influenza A (H3N2) strains isolated in northern Greece between 2004 and 2007

2009 ◽  
Vol 14 (4) ◽  
Author(s):  
A Melidou ◽  
V Kyriazopoulou ◽  
E Diza ◽  
S Alexiou ◽  
Y Pierroutsakos
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Antiviral Drugs ◽  
Resistance Mutations ◽  
Northern Greece ◽  
Ha Gene ◽  
Global Trend ◽  
Resistant Strains ◽  
Na Sequences ◽  
And Control

The prevention and control of influenza with vaccines and antiviral drugs is of great importance. M2 inhibitors, amantadine and rimantadine have been extensively used in some countries. The next generation of antiviral drugs, neuraminidase (NA) inhibitors oseltamivir and zanamivir, are being stockpiled for a potential influenza pandemic. The emergence of resistant strains is thus an important issue. The purpose of this study was to examine the sensitivity to M2 and NA inhibitors of Greek influenza A(H3N2) strains isolated during three influenza seasons between 2004 and 2008 and to determine the phylogenetic clades of those strains. M2 and NA sequences of 34 patient isolates were checked for known resistance mutations. In addition, haemagglutinin (HA) sequences were used to determine the phylogenetic relationship between resistant and sensitive strains. All influenza A(H3N2) strains isolated during the season 2004-5 were found susceptible to adamantanes, bearing the S31N mutation, compared to 88% of the strains isolated in 2005-6 and 75% of the strains isolated in 2006-7. Molecular analysis of the HA gene showed a correlation of the mutants with specific phylogenetic clades. No known mutations in the NA or HA gene that have been implicated in resistance to NA inhibitors were found in the A(H3N2) strains isolated in the three influenza seasons. Despite the fact that amantadine is the only drug approved for prophylaxis in Greece, it has not been extensively used. So it seems that resistant strains circulating in the area after 2005 followed the global trend of replacement of susceptible strains by resistant ones. Oseltamivir and zanamivir are currently approved only for therapeutic use in Greece and has not been extensively used either.

scholarly journals Multiple Influenza A (H3N2) Mutations Conferring Resistance to Neuraminidase Inhibitors in a Bone Marrow Transplant Recipient

2014 ◽  
Vol 58 (12) ◽  
pp. 7188-7197 ◽  
Author(s):  
Alireza Eshaghi ◽  
Sarah Shalhoub ◽  
Paul Rosenfeld ◽  
Aimin Li ◽  
Rachel R. Higgins ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Therapy ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Marrow Transplant ◽  
Viral Fitness ◽  
H3n2 Virus ◽  
Resistance Mutations ◽  
Depth Analysis ◽  
Resistant Strains

ABSTRACTImmunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Δ245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.

scholarly journals Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Stephen Baker ◽  
Pham Thanh Duy ◽  
Tran Vu Thieu Nga ◽  
Tran Thi Ngoc Dung ◽  
Voong Vinh Phat ◽  
...  
Keyword(s):  
Target Genes ◽  
Systemic Infection ◽  
Critical Factor ◽  
Selective Advantage ◽  
Salmonella Typhi ◽  
Antimicrobial Treatment ◽  
Resistance Mutations ◽  
Resistant Strains ◽  
And Control

Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced.

scholarly journals Community transmission of influenza A (H1N1)v virus at a rock festival in Belgium, 2-5 July 2009

2009 ◽  
Vol 14 (31) ◽  
Author(s):  
I Gutiérrez ◽  
A Litzroth ◽  
S Hammadi ◽  
H Van Oyen ◽  
C Gérard ◽  
...  
Keyword(s):  
Surveillance System ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Control Measures ◽  
Influenza Like Illness ◽  
Health Authorities ◽  
Influenza A H1n1 ◽  
Community Transmission ◽  
And Control

On 6 July 2009 the Belgian enhanced surveillance system for influenza-like illness among travellers returning from influenza A(H1N1)v affected areas detected a case linked to a rock festival which took place on 2-5 July. The health authorities implemented communication and control measures leading to the detection of aditional cases. This paper describes the outbreak and its impact on the management of the influenza pandemic in Belgium.

scholarly journals Oseltamivir-Resistant Influenza A Viruses Are Transmitted Efficiently among Guinea Pigs by Direct Contact but Not by Aerosol

2008 ◽  
Vol 82 (20) ◽  
pp. 10052-10058 ◽  
Author(s):  
Nicole M. Bouvier ◽  
Anice C. Lowen ◽  
Peter Palese
Keyword(s):  
Influenza Virus ◽  
Guinea Pigs ◽  
Direct Contact ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Transmission Model ◽  
Resistance Mutations ◽  
In Ovo ◽  
Oseltamivir Resistance

ABSTRACT Influenza viruses resistant to the neuraminidase (NA) inhibitor oseltamivir arise under drug selection pressure both in vitro and in vivo. Several mutations in the active site of the viral NA are known to confer relative resistance to oseltamivir, and influenza viruses with certain oseltamivir resistance mutations have been shown to transmit efficiently among cocaged ferrets. However, it is not known whether NA mutations alter aerosol transmission of drug-resistant influenza virus. Here, we demonstrate that recombinant human influenza A/H3N2 viruses without and with oseltamivir resistance mutations (in which NA carries the mutation E119V or the double mutations E119V I222V) have similar in ovo growth kinetics and infectivity in guinea pigs. These viruses also transmit efficiently by the contact route among cocaged guinea pigs, as in the ferret model. However, in an aerosol transmission model, in which guinea pigs are caged separately, the oseltamivir-resistant viruses transmit poorly or not at all; in contrast, the oseltamivir-sensitive virus transmits efficiently even in the absence of direct contact. The present results suggest that oseltamivir resistance mutations reduce aerosol transmission of influenza virus, which could have implications for public health measures taken in the event of an influenza pandemic.

Variation in the HA antigenicity of A(H1N1)pdm09-related swine influenza viruses

2021 ◽  
Author(s):  
Ahmed Magdy Khalil ◽  
Reiko Yoshida ◽  
Tatsunori Masatani ◽  
Ayato Takada ◽  
Makoto Ozawa
Keyword(s):  
Genetic Diversity ◽  
Amino Acid ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Gene Segment ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Single Amino Acid ◽  
Ha Gene ◽  
The Impact

Since the influenza pandemic in 2009, the causative agent ‘A(H1N1)pdm09 virus’, has been circulating in both human and swine populations. Although phylogenetic analyses of the haemagglutinin (HA) gene segment have revealed broader genetic diversity of A(H1N1)pdm09-related swine influenza A viruses (swIAVs) compared with human A(H1N1)pdm09 viruses, it remains unclear whether the genetic diversity reflects the antigenic differences in HA. To assess the impact of the diversity of the HA gene of A(H1N1)pdm09-related swIAVs on HA antigenicity, we characterized 12 swIAVs isolated in Japan from 2013 to 2018. We used a ferret antiserum and a panel of anti-HA mouse monoclonal antibodies (mAbs) raised against an early A(H1N1)pdm09 isolate. The neutralization assay with the ferret antiserum revealed that five of the 12 swIAVs were significantly different in their HA antigenicity from the early A(H1N1)pdm09 isolate. The mAbs also showed differential neutralization patterns depending on the swIAV strains. In addition, the single amino acid substitution at position 190 of HA, which was found in one of the five antigenically different swIAVs but not in human isolates, was shown to be one of the critical determinants for the antigenic difference of swIAV HAs. Two potential N-glycosylation sites at amino acid positions 185 and 276 of the HA molecule were identified in two antigenically different swIAVs. These results indicated that the genetic diversity of HA in the A(H1N1)pdm09-related swIAVs is associated with their HA antigenic variation. Our findings highlighted the need for surveillance to monitor the emergence of swIAV antigenic variants with public health importance.

scholarly journals Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards

2015 ◽  
Vol 81 (7) ◽  
pp. 2378-2383 ◽  
Author(s):  
Anna Gillman ◽  
Shaman Muradrasoli ◽  
Hanna Söderström ◽  
Fredrik Holmberg ◽  
Neus Latorre-Margalef ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Sewage Treatment ◽  
Wild Birds ◽  
Viral Fitness ◽  
Wild Type Virus ◽  
Resistance Mutations ◽  
Drug Pressure ◽  
Influenza A H1n1 ◽  
H274y Mutation

ABSTRACTInfluenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In thisin vivomallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.

scholarly journals Assessment of exposure to influenza A viruses in pigs between weaning and market age

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Juliana Bonin Ferreira ◽  
Zvonimir Poljak ◽  
Robert Friendship ◽  
Éva Nagy ◽  
Greg Wideman ◽  
...  
Keyword(s):  
Influenza A ◽  
Production Systems ◽  
Influenza A Viruses ◽  
Ha Gene ◽  
Testing Strategies ◽  
Common Causes ◽  
Nasal Swabs ◽  
Antibody Titers ◽  
2009 H1n1 ◽  
Low Prevalence

AbstractInfluenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.

scholarly journals Attaching Zanamivir to a Polymer Markedly Enhances Its Activity Against Drug-resistant Strains of Influenza a Virus

2011 ◽  
Vol 100 (3) ◽  
pp. 831-835 ◽  
Author(s):  
Alisha K. Weight ◽  
Jayanta Haldar ◽  
Luis Álvarez de Cienfuegos ◽  
Larisa V. Gubareva ◽  
Terrence M. Tumpey ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Optimal Control of an SIR Model with Delay in State and Control Variables

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Mohamed Elhia ◽  
Mostafa Rachik ◽  
Elhabib Benlahmar
Keyword(s):  
Optimal Control ◽  
Influenza A ◽  
Optimization Strategy ◽  
Sir Epidemic Model ◽  
Optimal Control Strategy ◽  
Control Variables ◽  
Sir Epidemic ◽  
Influenza A H1n1 ◽  
Using Data ◽  
And Control

We will investigate the optimal control strategy of an SIR epidemic model with time delay in state and control variables. We use a vaccination program to minimize the number of susceptible and infected individuals and to maximize the number of recovered individuals. Existence for the optimal control is established; Pontryagin’s maximum principle is used to characterize this optimal control, and the optimality system is solved by a discretization method based on the forward and backward difference approximations. The numerical simulation is carried out using data regarding the course of influenza A (H1N1) in Morocco. The obtained results confirm the performance of the optimization strategy.

scholarly journals A large outbreak of influenza A and B on a cruise ship causing widespread morbidity

2003 ◽  
Vol 130 (2) ◽  
pp. 263-271 ◽  
Author(s):  
J. M. L. BROTHERTON ◽  
V. C. DELPECH ◽  
G. L. GILBERT ◽  
S. HATZI ◽  
P. D. PARASKEVOPOULOS ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Influenza A ◽  
Surveillance Systems ◽  
Cruise Ship ◽  
Influenza Like Illness ◽  
Antiviral Therapies ◽  
Intervention Measures ◽  
Large Outbreak ◽  
And Control ◽  
Control Study

In September 2000 an outbreak of influenza-like illness was reported on a cruise ship sailing between Sydney and Noumea with over 1100 passengers and 400 crew on board. Laboratory testing of passengers and crew indicated that both influenza A and B had been circulating on the ship. The cruise coincided with the peak influenza period in Sydney. Morbidity was high with 40 passengers hospitalized, two of whom died. A questionnaire was sent to passengers 3 weeks after the cruise and 836 of 1119 (75%) responded. A total of 310 passengers (37%) reported suffering from an influenza-like illness (defined as cough, fever, myalgia and weakness) and 528 (63%) had seen a doctor for illness related to the cruise. One-third of passengers reported receipt of influenza vaccination in 2000; however neither their rates of influenza-like illness nor hospitalization were significantly different from those in unvaccinated passengers. A case–control study also found no significant protective effect of influenza vaccination. With the increasing popularity of cruise vacations, such outbreaks are likely to affect increasing numbers of people. Whilst influenza vaccination of passengers and crew may afford some protection, uptake and effectiveness may not be sufficient to prevent outbreaks. Surveillance systems and early intervention measures, such as antiviral therapies, should be considered to detect and control such outbreaks.

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