scholarly journals Rapid spread of drug-resistant influenza A viruses in the Basque Country, northern Spain, 2000-1 to 2008-9

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.

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).


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.


2011 ◽  
Vol 32 (1) ◽  
pp. 26
Author(s):  
Aeron C Hurt

Two classes of anti-influenza drugs are currently available for the treatment or prophylaxis of influenza. These are the adamantanes (amantadine and rimantadine), which block the activity of the M2 ion channel of influenza A viruses (but not influenza B viruses), and the neuraminidase inhibitors (NAIs), which act by binding to the enzymatic site of the influenza neuraminidase (NA) thereby preventing progeny virions from being released from the host cell during viral replication. Antiviral resistance can occur in influenza viruses and render the drug ineffective for the treatment of patients. Virtually all influenza A viruses currently circulating in the human population are resistant to the adamantanes, while in comparison these viruses remain susceptible to the NAIs. In particular, very low NAI resistance has been observed in pandemic A(H1N1) 2009 viruses, even though unprecedented amounts of these drugs were used.


2014 ◽  
Vol 58 (9) ◽  
pp. 5220-5228 ◽  
Author(s):  
Mélanie Samson ◽  
Yacine Abed ◽  
François-Marc Desrochers ◽  
Stephanie Hamilton ◽  
Angela Luttick ◽  
...  

ABSTRACTNeuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstratedin vitroactivity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses underin vitrolaninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant.In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistancein vitro.


2011 ◽  
Vol 9 (3) ◽  
pp. 434-442 ◽  
Author(s):  
Leo Heijnen ◽  
Gertjan Medema

The role of the water cycle in spreading human pathogenic influenza viruses is poorly studied and is not considered to be significant. However, gastrointestinal symptoms developed in a large proportion of influenza A (H1N1) 2009 virus infected people during the pandemic in 2009 and fecal shedding was reported. This fecal route could potentially play a role in the entry of human pathogenic influenza viruses in to the water cycle. Monitoring of influenza viruses in sewage and surface water during the pandemic in 2009 showed that influenza A viruses were detected in sewage and surface water. However, the pandemic influenza A (H1N1) 2009 virus was not detected. These findings imply that the water cycle did not play a relevant role in spreading the pandemic influenza virus during the epidemic in the Netherlands in 2009. Analyses of deliberately contaminated water samples confirmed the ability of quantitative RT-PCR to detect influenza viruses in sewage samples whereas the analysis of large volumes of surface water was strongly hampered by the presence of PCR-inhibiting substances.


1991 ◽  
Vol 106 (2) ◽  
pp. 383-395 ◽  
Author(s):  
S. Nakajima ◽  
K. Nakamura ◽  
F. Nishikawa ◽  
K. Nakajima

SUMMARYFrom January 1985 to March 1989, off-season viruses of H1N1 and H3N2 subtypes of influenza A viruses were isolated on five occasions in Japan. The HA gene sequences of the influenza A(H1N1) and A(H3N2) viruses isolated in Japan from 1985–9 were analysed and the phylogenetic tree for each subtype virus was constructed to determine any genetic relationship between viruses isolated in off-seasons and the epidemic viruses of the following influenza seasons. In one instance with H1N1 viruses in 1986 and in two instances with H3N2 viruses in 1985 and 1987, the spring isolates were genetically close to some of the winter isolates and were considered to be the parental viruses of the following influenza seasons. However, even in these cases, influenza viruses of the same subtype with different lineages co-circulated in Japan.


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.


2005 ◽  
Vol 49 (2) ◽  
pp. 556-559 ◽  
Author(s):  
Yacine Abed ◽  
Nathalie Goyette ◽  
Guy Boivin

ABSTRACT The emergence of resistance to amantadine in influenza A viruses has been shown to occur rapidly during treatment as a result of single-amino-acid substitutions at position 26, 27, 30, 31, or 34 within the transmembrane domain of the matrix-(M)-2 protein. In this study, reverse genetics was used to generate and characterize recombinant influenza A (H1N1) viruses harboring L26F, V27A, A30T, S31N, G34E, and V27A/S31N mutations in the M2 gene. In plaque reduction assays, all mutations conferred amantadine resistance, with drug concentrations resulting in reduction of plaque number by 50% (IC50s) 154- to 3,300-fold higher than those seen for the wild type (WT). M2 mutants had no impairment in their replicative capacities in vitro on the basis of plaque size and replication kinetics experiments. In addition, all mutants were at least as virulent as the WT in experimentally infected mice, with the highest mortality rate being obtained with the recombinant harboring a double V27A/S31N mutation. These findings could help explain the frequent emergence and transmission of amantadine-resistant influenza viruses during antiviral pressure in the clinical setting.


2021 ◽  
Author(s):  
Saptarshi Banerjee ◽  
Aratrika De ◽  
Nandita Kedia ◽  
Lin-Fa Wang ◽  
Arindam Mondal

Bat influenza A viruses (H17N10 and H18N11) are genetically distant from conventional influenza A viruses and replicates poorly in non-bat hosts species. However, the reason behind the lower replication fitness of these viruses are yet to be elucidated. In this work, we have identified species-specific signature residues, present in viral PB2 protein, which is a major determinant of polymerase fitness in human, avian and bat cell lines. Through extensive sequence and structural comparison between the bat and non-bat influenza virus RNA polymerases, we have identified a previously uncharacterized PB2-282 residue, which is serine in bat virus PB2 protein but harbours highly conserved glutamic acid in conventional influenza A viruses. Introduction of these bat specific signatures in the polymerase of a human adapted strain of influenza A/H1N1 virus drastically reduces its polymerase activity and replication efficiency in cell lines of human, bat and canine origin. In contrast, introduction of the human-specific signatures in bat virus PB2 (H17N10), significantly enhances its function in the context of a chimeric RNA polymerase. Interestingly, the PB2-282 resides within an evolutionary conserved 'S-E-S' motif present across different genera of influenza viruses but is replaced with a 'S-S-T' motif in bat influenza viruses, indicating that this E to S transition may serve as a species-specific adaptation signature that modulates the activity of bat virus polymerase in other host species.


2021 ◽  
Vol 11 (4) ◽  
pp. 723-736
Author(s):  
O. G. Kurskaya ◽  
A. V. Anoshina ◽  
N. V. Leonova ◽  
O. A. Simkina ◽  
T. V. Komissarova ◽  
...  

Influenza and other acute respiratory viral infections lead to a substantial incidence of severe cases and hospitalizations and so remain a global health problem. Within the frame of the Global Influenza Hospital Surveillance Network (GIHSN), we assessed the contribution of influenza and other respiratory viruses to severe cases of influenzalike diseases in patients hospitalized to the Novosibirsk infectious hospitals in the years 2018–2019. We analyzed 484 nasopharyngeal swabs collected from patients admitted to the hospitals with acute respiratory infections (ARI) using real-time polymerase chain reaction commercial kits. We confirmed viral etiology of ARI in 69.8% cases. Influenza viruses were detected in 47.1% cases, wherein concomitant circulation of influenza A(H1N1)pdm09 and A(H3N2) viruses was observed in 20.7% and 26% of patients, respectively, whereas influenza B virus was detected only in one sample. All analyzed influenza A viruses were antigenically similar to vaccine strains. Genetically, the Novosibirsk strains were closely related to influenza A viruses distributed in Russia and worldwide. Influenza A(H1N1)pdm09 virus was detected in all patients aged 0 to 14 years and required intensive care. Other respiratory viruses were detected in 36.4% of children and 5.8% of adults, and 8.3% of children had viral coinfection, whereas no cases of coinfection were detected in adults. The most common viruses in children were metapneumovirus — 12.8%, rhinovirus — 9.3% and respiratory syncytial virus — 8.0%. In adults, metapneumovirus, adenovirus, parainfluenza virus and rhinovirus were detected with a detection rate no exceeding 2%. In this study, we found no differences in the detection rate of the influenza virus due to concomitant chronic diseases, pregnancy, or smoking habits. At the same time, the detection rate of other respiratory viruses in non-smokers vs. smokers was significantly lower than in smokers and former smokers (26.15%, 66.67% and 62.50%, respectively). In addition, the level of detection of respiratory viruses in children with vs. without chronic pathology was significantly higher (55.3% and 38.7%, respectively). Thus, our and similar studies are important for monitoring and control of the infection.


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