Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018

The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009–2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012–2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

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Characterizing the countrywide epidemic spread of influenza A(H1N1)pdm09 virus in Kenya between 2009 and 2018

10.1101/2021.03.30.21254587 ◽

2021 ◽

Author(s):

D. Collins Owuor ◽

Zaydah R. de Laurent ◽

Gilbert K. Kikwai ◽

Lillian M. Mayieka ◽

Melvin Ochieng ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Sequence Data ◽

Influenza Viruses ◽

Seasonal Fluctuations ◽

Middle Income ◽

Virus Diversity ◽

Pdm09 Virus ◽

Geographical Regions ◽

Influenza A H1n1

ABSTRACTBackgroundThe spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.MethodsWe isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.ResultsThe transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.ConclusionConsiderable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

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Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza

mSphere ◽

10.1128/msphere.01043-20 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Ikuyo Takayama ◽

Binh Gia Nguyen ◽

Co Xuan Dao ◽

Thach The Pham ◽

Tuan Quoc Dang ◽

...

Keyword(s):

Genetic Diversity ◽

Next Generation Sequencing ◽

Lower Respiratory Tract ◽

Influenza A ◽

Severe Disease ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Host Genetic ◽

Ha Protein ◽

Generation Sequencing

ABSTRACT The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-generation sequencing (NGS) may instead be used to characterize viral populations in an unbiased manner and to measure within-host genetic diversity. In this study, we used NGS analysis to investigate the within-host genetic diversity of influenza A(H1N1)pdm09 virus in the upper and lower respiratory samples from nine patients who were admitted to the intensive care unit (ICU). A total of 47 amino acid substitution positions were found to differ between the upper and lower respiratory tract samples from all patients. However, the D222G/N substitution in hemagglutinin (HA) protein was the only amino acid substitution common to multiple patients. Furthermore, the substitution was detected only in the six samples from the lower respiratory tract. Therefore, it is important to investigate influenza A(H1N1)pdm09 virus populations using multiple paired samples from the upper and lower respiratory tract to avoid overlooking potentially important substitutions, especially in patients with severe disease. IMPORTANCE The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. These results suggest the influenza A(H1N1)pdm09 virus has diversified inside the host owing to differences in tissue specificity. In this study, the within-host genetic diversity of influenza A(H1N1)pdm09 virus was investigated for the first time using next-generation sequencing analysis of the viral whole-genome in samples extracted from the upper and lower respiratory tracts of patients with severe disease.

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Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China

mBio ◽

10.1128/mbio.00909-18 ◽

2018 ◽

Vol 9 (3) ◽

Cited By ~ 17

Author(s):

Ying Chen ◽

Nídia S. Trovão ◽

Guojun Wang ◽

Weifeng Zhao ◽

Ping He ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Southern China ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Potential Threat ◽

Animal Reservoir ◽

Human Contact ◽

Virus Diversity ◽

Zoonotic Risk

ABSTRACTThe capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.IMPORTANCEMammals have emerged as critically underrecognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages. Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as “mixing vessels.” The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats.

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Characterization of influenza A(H1N1)pdm09 viruses in Germany in season 2019-2020 – co-circulation of an antigenic drift variant

10.22541/au.162908014.49850019/v1 ◽

2021 ◽

Author(s):

Marianne Wedde ◽

Djin-Ye Oh ◽

Silke Buda ◽

Andrea Thürmer ◽

Sandra Kaiser ◽

...

Keyword(s):

Influenza A ◽

Influenza Season ◽

Vaccine Virus ◽

Influenza Viruses ◽

Antigenic Drift ◽

Neuraminidase Inhibitors ◽

Pdm09 Virus ◽

Time Period ◽

Influenza A H1n1

Background Influenza A(H1N1)pdm09 virus entered the human population in 2009 and evolved within this population for more than ten years. Despite genetic evolution no remarkable changes in the antigenic reactive pattern of these viruses were observed so far. Methods Primary respiratory samples of the German influenza virological sentinel were investigated by qPCR. Influenza virus-positive samples were characterized genetically and antigenetically. Results In December 2019, a antigenic drift variant characterized by an N156K substitution in the hemagglutinin of influenza A(H1N1)pdm09 virus emerged in Germany, which exhibited a reactivity to ferret antiserum that was an average 6 log2 lower than the vaccine virus A/Brisbane/02/2018 and the other A(H1N1)pdm09 viruses circulating in the influenza season 2019-2020. These viruses accounted for 20% of all A(H1N1)pdm09 viruses characterized in the German influenza sentinel. Patients infected with these viruses had a shorter median time period of medical consultation after onset of symptoms and were more frequently treated with neuraminidase inhibitors in comparison to patients infected with other A(H1N1)pdm09 viruses. Conclusions This parallel circulation of two antigenic variants of A(H1N1)pdm09 viruses which differ remarkably in their antigenic reactive pattern contributes to a greater variability in circulating influenza viruses and challenges vaccination.

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Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe

Journal of General Virology ◽

10.1099/0022-1317-83-4-735 ◽

2002 ◽

Vol 83 (4) ◽

pp. 735-745 ◽

Cited By ~ 83

Author(s):

S. Marozin ◽

V. Gregory ◽

K. Cameron ◽

M. Bennett ◽

M. Valette ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Swine Influenza ◽

Influenza Viruses ◽

Antigenic Drift ◽

H3n2 Virus ◽

Human Populations ◽

Antigenic Variant ◽

Influenza A H1n1 ◽

The Uk

Three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, co-evolve in pigs in Europe. H1N2 viruses isolated from pigs in France and Italy since 1997 were closely related to the H1N2 viruses which emerged in the UK in 1994. In particular, the close relationship of the neuraminidases (NAs) of these viruses to the NA of a previous UK H3N2 swine virus indicated that they had not acquired the NA from H3N2 swine viruses circulating in continental Europe. Moreover, antigenic and genetic heterogeneity among the H1N2 viruses appeared to be due in part to multiple introductions of viruses from the UK. On the other hand, comparisons of internal gene sequences indicated genetic exchange between the H1N2 viruses and co-circulating H1N1 and/or H3N2 subtypes. Most genes of the earlier (1997–1998) H1N2 isolates were more closely related to those of a contemporary French H1N1 isolate, whereas the genes of later (1999–2000) isolates, including the HAs of some H1N2 viruses, were closely related to those of a distinct H1N1 antigenic variant which emerged in France in 1999. In contrast, an H3N2 virus isolated in France in 1999 was closely related antigenically and genetically to contemporary human A/Sydney/5/97-like viruses. These studies reveal interesting parallels between genetic and antigenic drift of H1N1 viruses in pig and human populations, and provide further examples of the contribution of genetic reassortment to the antigenic and genetic diversity of swine influenza viruses and the importance of the complement of internal genes in the evolution of epizootic strains.

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SALIENT FEATURES OF CIRCULATING RESPIRATORY VIRUSES IN THE PRE– AND PANDEMIC INFLUENZA AND COVID–19 SEASONS

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-sfo-1662 ◽

2021 ◽

Author(s):

I. V. Kiseleva ◽

N. V. Larionova ◽

E. P. Grigorieva ◽

A. D. Ksenafontov ◽

M. Al Farroukh ◽

...

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

Influenza Infection ◽

Opportunity To Learn ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Effective Prevention ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Syncytial Virus

Abstract. A wide variety of zoonotic viruses that can cross the interspecies barrier promote the emergence of new, potentially pandemic viruses in the human population that was often accompanied by the disappearance of existing circulating strains. Among the various reasons underlying this phenomenon is the strengthening of populational immunity by expanding the immune layer of the population and improving the means and methods of medical care. However, “Natura abhorret vacuum”, and new pathogens come to replace disappearing pathogens. In the past ten years, there have been two critical events – the pandemic spread of the swine influenza A (H1N1) pdm09 virus in 2009 and the novel SARS–CoV–2 coronavirus in 2019, providing scientists with a unique opportunity to learn more about a relationship between respiratory viruses and their pathogenesis. Together with viruses of pandemic significance, a large number of seasonal respiratory viruses circulate, which contribute to the structure of human morbidity, and co–infections aggravate the condition of the illness. In the conditions of the spread of new viruses with unexplored characteristics, in the absence of means of prevention and therapy, it is especially important to prevent the aggravation of morbidity due to mixed infections. Here we review the mutual involvement of pandemic influenza A(H1N1)pdm09 and SARS–CoV–2 coronavirus and seasonal respiratory viruses in the epidemic process, discuss some issues related to their spread, potential causes affecting the spread and severity of the morbidity. The given facts, testify to the existence of seasonality and temporal patterns of the beginning and end of the circulation of respiratory viruses. Interestingly, the beginning of the circulation of the pandemic influenza A(H1N1)pdm09 virus led to a shift in the timing and intensity of circulation of some respiratory viruses, which is probably caused by the existence of "replication conflicts" between them, and did not affect others. Co–infection with SARS–CoV–2–19 and other respiratory viruses, especially respiratory syncytial virus and rhinoviruses, was quite often observed. At the current stage, no aggravating effect of influenza on the course of COVID–19 in mixed infection has been established. Whether this is due to the mild course of influenza infection in the 2020 epidemic season, or the competitive impact of SARS–CoV–2 on influenza viruses is not yet clear. Experts are still at the stage of accumulating facts and working on creating means of effective prevention and treatment of the new coronavirus infection.

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

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid46440 ◽

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.

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Monitoring Genetic Diversity of Influenza A(H1N1)pdm09 Virus Circulating during the Post-Pandemic Period in Turkey

Japanese Journal of Infectious Diseases ◽

10.7883/yoken.66.299 ◽

2013 ◽

Vol 66 (4) ◽

pp. 299-305 ◽

Cited By ~ 4

Author(s):

Dilek Guldemir ◽

Atila T. Kalaycioglu ◽

A. Basak Altas ◽

Gulay Korukluoglu ◽

Riza Durmaz

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Pdm09 Virus ◽

Influenza A H1n1

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Features of Epidemic Process of Influenza and its Etiology in the Countries of the Northern and Southern Hemispheres in the Period of Circulation of Pandemic Virus A(H1N1)pdm09 (According to WHO)

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2019-18-15-25 ◽

2020 ◽

Vol 18 (6) ◽

pp. 15-25

Author(s):

L. S. Karpova ◽

M. Yu. Pelikh ◽

N. M. Popovtseva ◽

T. P Stolyarova ◽

K. M. Volik

Keyword(s):

Influenza A ◽

The United States ◽

Influenza Viruses ◽

Antigenic Structure ◽

Influenza B ◽

Tropical Countries ◽

Antigenic Variability ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Northern And Southern Hemispheres

Relevance. Influenza is characterized by global distribution and the difference in its seasonality in countries with temperate and tropical climates. The importance of studying antigenic variation of influenza viruses due to the fact that changes in the antigenic structure is an evolutionary mechanism of adaptation of the virus to ensure its survival and cause annual epidemics.Aims. The Aim of this study was to identify the peculiarities of the geographical spread of influenza (seasonal), etiology and the rate of antigenic variability of influenza viruses A and B.Materials and methods. Based on data from WHO Reference research centers, information was collected on circulating influenza virus strains from 1975 A(H3N2), 1977 A(H1N1)pdm09 and type B of the Yamagata and Victoria lines from 1987 to 2019, as well as data on the number of all identified influenza viruses and individual strains circulating in the Northern and Southern hemispheres from 2008 to 2018.Results and discussion. Analysis of the global spread of influenza, its etiology and antigenic variability of viruses, according to WHO, showed that the influenza A(H1N1)pdm09 virus was the main causative agent of epidemics and regional outbreaks in seasons of high influenza activity in all countries except the United States and Canada, where influenza A(H3N2) and B viruses dominated in countries with severe seasonality, the change of season led to a change in the etiology of influenza, and in tropical countries, the A(H1N1)pdm09 virus more often remained dominant in all seasons of the year.Conclusions. The pronounced seasonality of influenza in Northern countries and its absence in tropical countries, where regional outbreaks prevailed in all seasons of the year, were confirmed. Low antigenic variability of influenza A(H1N1)pdm09 strains was confirmed, and the highest – A(H3N2). Among influenza B strains in the Victoria line had less antigenic variability, because the duration of its circulation before the appearance of a new drift variant was longer than that of the Yamagata line. The tendency to increase the total duration of circulation of influenza viruses B/Victoria, A(H1N1)pdm09 and B/Yamagata due to increased circulation before the emergence of new drift variants is shown.

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

Annals of Clinical Chemistry and Laboratory Medicine ◽

10.3126/acclm.v3i2.20737 ◽

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.

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