scholarly journals Oseltamivir susceptibility in south-western France during the 2007-8 and 2008-9 influenza epidemics and the ongoing influenza pandemic 2009

2009 ◽  
Vol 14 (38) ◽  
Author(s):  
S Burrel ◽  
L Roncin ◽  
M E Lafon ◽  
H Fleury

The recent emergence of seasonal influenza A(H1N1) strains resistant to oseltamivir makes it necessary to monitoring carefully the susceptibility of human influenza viruses to neuraminidase inhibitors. We report the prevalence of the oseltamivir resistance among influenza A viruses circulating in south-western France over the past three years: seasonal influenza A(H1N1), seasonal influenza A(H3N2), and the influenza A(H1N1)v viruses associated with the ongoing 2009 pandemic. The main result of the study is the absence of oseltamivir resistance in the pandemic H1N1 strains studied so far (n=129).

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Aneta Nitsch-Osuch ◽  
Lidia Bernadeta Brydak

Neuraminidase inhibitors (NAIs) are antiviral drugs for treatment and prophylaxis of influenza. By blocking the activity of the enzyme neuraminidase, NAIs prevent new viral particles from being released. The increasing use of NAIs brings into focus the risk of drug resistance arising to the class. There are three levels of antiviral resistance according to the way that resistance can be detected or inferred: genotypic, phenotypic and clinical resistance. For many years seasonal influenza viruses resistance to NAIs was low (0.33%). Recently, there has been described an increasing number of resistant seasonal influenza strains to oseltamivir (2% in adults, 5-18% in children). In 2007 there were published data describing 14% resistant to oseltamivir strains of influenza A/H1N1/ in Europe. Approximately 0.5-1.0% of influenza A/H1N1/pdm09 isolates are currently resistant to oseltamivir. The established markers of the resistance to oseltamivir were found in 2.4% of human and 0.8% of avian isolates of influenza A/H5N1/. It has been not observed a cross resistance among oseltamivir and zanamivir. NAIs resistance in influenza viruses is relative and despite its presence patients with resistant viruses may still benefit from receiving these antivirals. The response to treatment with antivirals remains the most important proof of antiviral effectiveness. The rational use of NAIs is essential to preserve the best choice for treatment and prophylaxis of seasonal, avian and pandemic influenza.


2014 ◽  
Vol 9 (6) ◽  
pp. 628-633
Author(s):  
Dawid Nidzworski ◽  
Joanna Dobkowska ◽  
Marcin Hołysz ◽  
Beata Gromadzka ◽  
Bogusław Szewczyk

AbstractInfluenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.


2009 ◽  
Vol 14 (20) ◽  
Author(s):  
D Vicente ◽  
G Cilla ◽  
M Montes ◽  
J Mendiola ◽  
E Pérez-Trallero

A worldwide increase of adamantane-resistant influenza A(H3N2) and oseltamivir-resistant influenza A(H1N1) viruses has been observed in recent years. The aim of this study was to analyse the prevalence of antiviral drug-resistant influenza A in a region of northern Spain. Resistance to adamantanes was detected in 45.3% (68/150) of influenza AH3 viruses analysed for the period from 2000-1 to 2008-9. Adamantane-resistance was absent in our region during the 2000-1 to 2002-3 influenza seasons. However, after the first adamantane-resistant virus (characterised as A/Fujian/411/2002) was detected in the 2003-4 season, a rapid increase in the proportion of resistant strains was observed (4.9% [2/41], 80% [8/10] and 100% [53/53] in the 2004-5, 2006-7 and 2008-9 seasons, respectively). Four of the first five adamantane-resistant AH3 viruses detected were isolated from adult patients, but the subsequent spread was observed mainly among children. No resistance to adamantanes was detected among the 65 influenza AH1 viruses analysed throughout the study period. Among the 172 influenza A (76 AH1 and 96 AH3) viruses analysed, five strains (AH1 with mutation H274Y) showed oseltamivir resistance, and all were detected in the last season. Amantadine use was very scarce in our region, and oseltamivir was not used at all; therefore the increase of resistance was attributed to imported drug-resistant influenza viruses.


2011 ◽  
Vol 16 (3) ◽  
Author(s):  
A C Hurt ◽  
Y M Deng ◽  
J Ernest ◽  
N Caldwell ◽  
L Leang ◽  
...  

During the first year of the influenza A(H1N1)2009 pandemic, unprecedented amounts of the neuraminidase inhibitors, predominantly oseltamivir, were used in economically developed countries for the treatment and prophylaxis of patients prior to the availability of a pandemic vaccine. Due to concerns about the development of resistance, over 1,400 influenza A(H1N1)2009 viruses isolated from the Asia-Pacific region during the first year of the pandemic (March 2009 to March 2010) were analysed by phenotypic and genotypic assays to determine their susceptibility to the neuraminidase inhibitors. Amongst viruses submitted to the World Health Organization Collaborating Centre for Reference and Research in Melbourne, Australia, oseltamivir resistance was detected in 1.3% of influenza A(H1N1)2009 strains from Australia and 3.1% of strains from Singapore, but none was detected in specimens received from other countries in Oceania or south-east Asia, or in east Asia. The overall frequency of oseltamivir resistance in the Asia-Pacific region was 16 of 1,488 (1.1%). No zanamivir-resistant viruses were detected. Of the 16 oseltamivir-resistant isolates detected, nine were from immunocompromised individuals undergoing oseltamivir treatment and three were from immunocompetent individuals undergoing oseltamivir treatment. Importantly, four oseltamivir-resistant strains were from immunocompetent individuals who had not been treated with oseltamivir, demonstrating limited low-level community transmission of oseltamivir-resistant strains. Even with increased use of oseltamivir during the pandemic, the frequency of resistance has been low, with little evidence of community-wide spread of the resistant strains. Nevertheless, prudent use of the neuraminidase inhibitors remains necessary, as does continued monitoring for drug-resistant influenza viruses.


2010 ◽  
Vol 88 (4) ◽  
pp. 575-587 ◽  
Author(s):  
Christine Korteweg ◽  
Jiang Gu

The 2009 H1N1 and H5N1 influenza viruses are newly (re-) emerged influenza A viruses (2009 A(H1N1) and A(H5N1), respectively) that have recently posed tremendous health threats in many regions worldwide. With the 2009 outbreak of H1N1 influenza A, the world witnessed the first influenza pandemic of the 21st century. The disease has rapidly spread across the entire globe, and has resulted in hundreds of thousands of cases with confirmed infection. Although characterized by high transmissibility, the virulence and fatality of the 2009 A(H1N1) influenza virus have thus far remained relatively low. The reverse holds true for A(H5N1) influenza; at a fatality rate that exceeds 60%, it is known to cause severe damage to the human respiratory system, but is not presently capable of efficient transmission from human to human. Apart from the clear differences between the two types of influenza, there are some significant similarities that warrant attention. In particular, the more severe and fatal 2009 A(H1N1) influenza cases have shown symptoms similar to those reported in cases of A(H5N1) influenza. Histopathological findings for these cases, to the extent available, also appear to have similarities for both diseases in terms of damage and severity. Here we review important recent publications in this area, and we discuss some of the key commonalities and contrasts between the two influenza A types in terms of their biology, origins, clinical features, pathology and pathogenesis, and receptors and transmissibility.


2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.


mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.


2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.


2015 ◽  
Vol 144 (8) ◽  
pp. 1579-1583
Author(s):  
J. Y. WONG ◽  
P. WU ◽  
E. H. Y. LAU ◽  
T. K. TSANG ◽  
V. J. FANG ◽  
...  

SUMMARYDuring the early stage of an epidemic, timely and reliable estimation of the severity of infections are important for predicting the impact that the influenza viruses will have in the population. We obtained age-specific deaths and hospitalizations for patients with laboratory-confirmed H1N1pdm09 infections from June 2009 to December 2009 in Hong Kong. We retrospectively obtained the real-time estimates of the hospitalization fatality risk (HFR), using crude estimation or allowing for right-censoring for final status in some patients. Models accounting for right-censoring performed better than models without adjustments. The risk of deaths in hospitalized patients with confirmed H1N1pdm09 increased with age. Reliable estimates of the HFR could be obtained before the peak of the first wave of H1N1pdm09 in young and middle-aged adults but after the peak in the elderly. In the next influenza pandemic, timely estimation of the HFR will contribute to risk assessment and disease control.


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