scholarly journals A Review of Clinical Influenza A and B Infections With Reduced Susceptibility to Both Oseltamivir and Zanamivir

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Yacine Abed ◽  
Guy Boivin
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Cross Resistance ◽  
Influenza B ◽  
Neuraminidase Inhibitors ◽  
Resistance Phenotype ◽  
Clinical Concern ◽  
Severe Influenza ◽  
Clinical Cases

Abstract Anti-influenza drugs play major roles in the management of severe influenza infections. Neuraminidase inhibitors (NAIs), which are active against all influenza A subtypes and the 2 major influenza B lineages, constitute the only class of antivirals recommended for the control of influenza epidemics and eventual pandemics. Thus, the emergence of NAI resistance could be a major clinical concern. Although most currently circulating influenza A and B strains are susceptible to NAIs, clinical cases of influenza viruses harboring single or multiple NA substitutions or deletions conferring a cross-resistance phenotype to the 2 main NAIs (oseltamivir and zanamivir) have been reported, mostly in immunocompromised individuals. Moreover, such events seem to be more frequent in A(H1N1)pdm09 viruses containing the H274Y substitution together with other NA changes (I222R, E119D/G). This review summarizes the therapeutic regimens leading to the emergence of NAI cross-resistant influenza A and B viruses as well as the virologic properties of such variants.

scholarly journals Antiviral drug resistance in seasonal and pandemic influenza

2011 ◽  
Vol 32 (1) ◽  
pp. 26
Author(s):  
Aeron C Hurt
Keyword(s):  
Drug Resistance ◽  
Human Population ◽  
Influenza A ◽  
Antiviral Drug ◽  
Influenza Viruses ◽  
Antiviral Resistance ◽  
Influenza B ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses ◽  
Antiviral Drug Resistance

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.

scholarly journals In Vitro Properties and Virulence of Contemporary Recombinant Influenza B Viruses Harboring Mutations of Cross-Resistance to Neuraminidase Inhibitors

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 6 ◽  
Author(s):  
Clément Fage ◽  
Yacine Abed ◽  
Liva Checkmahomed ◽  
Marie-Christine Venable ◽  
Guy Boivin
Keyword(s):  
Influenza A ◽  
Mdck Cells ◽  
Viral Fitness ◽  
World Health ◽  
Cross Resistance ◽  
Influenza B ◽  
Neuraminidase Inhibitors ◽  
Clinical Markers ◽  
The Impact

Three neuraminidase inhibitors (NAIs: Oseltamivir, zanamivir and peramivir) are currently approved in many countries for the treatment of influenza A and B infections. The emergence of influenza B viruses (IBVs) containing mutations of cross-resistance to these NAIs constitutes a serious clinical threat. Herein, we used a reverse genetics system for the current B/Phuket/3073/2013 vaccine strain to investigate the impact on in vitro properties and virulence of H136N, R152K, D198E/N, I222T and N294S NA substitutions (N2 numbering), reported by the World Health Organization (WHO) as clinical markers of reduced or highly-reduced inhibition (RI/HRI) to multiple NAIs. Recombinant viruses were tested by NA inhibition assays. Their replicative capacity and virulence were evaluated in ST6GalI-MDCK cells and BALB/c mice, respectively. All NA mutants (excepted D198E/N) showed RI/HRI phenotypes against ≥ 2 NAIs. These mutants grew to comparable titers of the recombinant wild-type (WT) IBV in vitro, and some of them (H136N, I222T and N294S mutants) induced more weight loss and mortality in BALB/c mice in comparison to the recombinant WT IBV. These results demonstrate that, in contemporary IBVs, some NA mutations may confer RI/HRI phenotypes to existing NAIs without altering the viral fitness. This reinforces the need for development of novel antiviral strategies with different mechanisms of action.

scholarly journals Report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2017

2019 ◽  
Vol 43 ◽  
Author(s):  
Merryn Roe ◽  
Matthew Kaye ◽  
Pina Iannello ◽  
Hilda Lau ◽  
Iwona Buettner ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Vaccine Virus ◽  
Influenza Viruses ◽  
World Health ◽  
Influenza Surveillance ◽  
Influenza B ◽  
Neuraminidase Inhibitors ◽  
Response System ◽  
Surveillance And Response

As part of its role in the World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a record total of 5866 human influenza positive samples during 2017. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and were propagated in qualified cells and hens’ eggs for use as potential seasonal influenza vaccine virus candidates. In 2017, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 54% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2017. However, phylogenetic analysis indicated that the majority of circulating A(H3) viruses had undergone genetic drift relative to the WHO recommended vaccine strain for 2017. Of 3733 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, only two A(H1)pdm09 viruses and one A(H3) virus showed highly reduced inhibition by oseltamivir, while just one A(H1)pdm09 virus showed highly reduced inhibition by zanamivir.

scholarly journals Influenza viruses resistant to neuraminidase inhibitors.

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Aneta Nitsch-Osuch ◽  
Lidia Bernadeta Brydak
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Response To Treatment ◽  
Cross Resistance ◽  
Published Data ◽  
Neuraminidase Inhibitors ◽  
Viral Particles ◽  
Clinical Resistance ◽  
Influenza A H1n1

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.

scholarly journals Sensitivity of influenza viruses to specific drugs in Russia during 2017−2020. The rare finds and perspective antivirals

2020 ◽  
Vol 25 (2) ◽  
pp. 65-77
Author(s):  
Natalia V. Breslav ◽  
Kirill G. Krasnoslobotsev ◽  
Evgeniya A. Mukasheva ◽  
Elena S. Kirillova ◽  
Alexandra G. Rosatkevich ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Epidemiological Surveillance ◽  
Influenza B Virus ◽  
Influenza B ◽  
Neuraminidase Inhibitors ◽  
Chemotherapy Drugs ◽  
Pdm09 Virus ◽  
Severe Acute Respiratory Infection ◽  
Influenza A H1n1

BACKGROUND: The article presents the results of studying the effectiveness of anti-influenza drugs in Russia in the period 20172020. The sensitivity of circulating strains of influenza viruses A(H1N1)pdm09, A(H3N2) and B to neuraminidase inhibitors oseltamivir, zanamivir and rimantadine was determined. The analysis of scientific articles by both domestic and foreign researchers on new promising chemotherapy drugs for influenza viruses was carried out. AIMS: study of the sensitivity of influenza viruses circulating strains to specific anti-influenza drugs in the framework of monitoring in the period 20172020. MATERIALS AND METHODS: The study was conducted within the framework of epidemiological surveillance of the influenza viruses circulation using the collection of the influenza etiology and epidemiology laboratory with the following criteria for selecting strains isolated from pregnant women, patients with complicated flu infection and severe acute respiratory infection (SARI), lethal outcomes, as well as patients undergoing treatment with specific drugs. Virological, immunological, and molecular genetic methods were used in the study, and following drugs substances were used: oseltamivir carboxylate, zanamivir, and rimantadine. RESULTS: For the period 20172020, the sensitivity of 541 influenza A and B viruses epidemic strains to anti-influenza drugs was studied. Most of the studied strains remained sensitive to neuraminidase inhibitors. The exceptions were: in 2017/2018 5 strains of the influenza A(H1N1)pdm09 virus resistant to oseltamivir and 2 strains of the influenza B virus, one with reduced sensitivity to oseltamivir, the second to zanamivir; in 2019/2020 influenza A(H1N1)pdm09 virus strain with reduced sensitivity to both drugs. In the 2018/2019 season, an influenza A/Moscow/246/2018 A(H1N1)pdm09 strain was found to be sensitive to rimantadine. CONCLUSIONS: The main and most common genetic markers of influenza viruses resistance to specific drugs are: for oseltamivir substitution H274Y in the influenza A(H1N1)pdm09 virus NA; for rimantadine substitution S31N in the influenza A(H1N1)pdm09 and A(H3N2) viruses M2 protein. Taking into account the low frequency of strains with reduced sensitivity to drugs with antineuraminidase activity, can confidently approve that they remain the drugs of choice for the treatment and prevention of influenza infection.

scholarly journals An evaluation of the InDevR FluChip-8G insight microarray assay in characterizing influenza a viruses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Emily S. Bailey ◽  
Xinye Wang ◽  
Mai-juan Ma ◽  
Guo-lin Wang ◽  
Gregory C. Gray
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Time Range ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Laboratory Methods ◽  
Duke University ◽  
Multiple Viral Strains ◽  
Rapid Characterization

AbstractInfluenza viruses are an important cause of disease in both humans and animals, and their detection and characterization can take weeks. In this study, we sought to compare classical virology techniques with a new rapid microarray method for the detection and characterization of a very diverse, panel of animal, environmental, and human clinical or field specimens that were molecularly positive for influenza A alone (n = 111), influenza B alone (n = 3), both viruses (n = 13), or influenza negative (n = 2) viruses. All influenza virus positive samples in this study were first subtyped by traditional laboratory methods, and later evaluated using the FluChip-8G Insight Assay (InDevR Inc. Boulder, CO) in laboratories at Duke University (USA) or at Duke Kunshan University (China). The FluChip-8G Insight multiplexed assay agreed with classical virologic techniques 59 (54.1%) of 109 influenza A-positive, 3 (100%) of the 3 influenza B-positive, 0 (0%) of 10 both influenza A- and B-positive samples, 75% of 24 environmental samples including those positive for H1, H3, H7, H9, N1, and N9 strains, and 80% of 22 avian influenza samples. It had difficulty with avian N6 types and swine H3 and N2 influenza specimens. The FluChip-8G Insight assay performed well with most human, environmental, and animal samples, but had some difficulty with samples containing multiple viral strains and with specific animal influenza strains. As classical virology methods are often iterative and can take weeks, the FluChip-8G Insight Assay rapid results (time range 8 to 12 h) offers considerable time savings. As the FluChip-8G analysis algorithm is expected to improve over time with addition of new subtypes and sample matrices, the FluChip-8G Insight Assay has considerable promise for rapid characterization of novel influenza viruses affecting humans or animals.

scholarly journals Influenza: An Emerging and Re-emerging Public Health Threat in Nepal

2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Winter Season ◽  
Emerging Infectious Diseases ◽  
Influenza Viruses ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
New Variant ◽  
Seasonal Epidemics

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.

scholarly journals Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 977
Author(s):  
Kobporn Boonnak ◽  
Chayasin Mansanguan ◽  
Dennis Schuerch ◽  
Usa Boonyuen ◽  
Hatairat Lerdsamran ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Antigenic Drift ◽  
Influenza B ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

2021 ◽  
Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Severe Influenza ◽  
B Virus

scholarly journals Clinical Investigations. Comparison of Directigen Flu A+B with Real Time PCR in the Diagnosis of Influenza / Сравнение Иммунохроматографического Метода (Directigen Flu A+B) И Теста RT-PCR При Инфекциях Гриппа

Folia Medica ◽  
2015 ◽  
Vol 57 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Golubinka Bosevska ◽  
Nikola Panovski ◽  
Elizabeta Janceska ◽  
Vladimir Mikik ◽  
Irena Kondova Topuzovska ◽  
...  
Keyword(s):  
Real Time ◽  
Influenza A Virus ◽  
Real Time Pcr ◽  
Influenza A ◽  
Age Groups ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Nose And Throat

AbstractEarly diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. MATERIALS AND METHODS: One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0 - 4 yrs, 5 - 9 yrs, 10 - 14 yrs, 15 - 19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. RESULTS: Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. CONCLUSION: Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.

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