Influenza activity in Czechoslovakia and the USSR, 1980-1985

Between 1980 and 1985, Czechoslovakia had experienced 4 and the USSR 3 major influenza outbreaks. Of the 3 epidemic outbreaks in the USSR, 2 were associated with influenza B virus (in the 1980/81 and 1983/84 seasons) and 1 with influenza A virus of the H3N2 subtype. In the USSR, influenza A (H1N1) virus never predominated as a cause of epidemic during the 5 years period. In Czechoslovakia, 2 epidemics (in the 1980/81 and 1983/84 seasons) were due to influenza A (H1N1) virus. The epidemic in the 1981/82 season had two waves of unequal heights and a mixed type B and subtype A (H3N2) etiology; a two-wave epidemic associated with isolates of influenza A (H1N1) and influenza B viruses was also recorded in the 1983/84 season. The influenza A (H3N2) epidemic in 1983 was of explosive character. All influenza viruses circulating in the two countries between 1980 and 1985 were of the same antigenic profile, but were isolated from the epidemics that occurred in different influenza seasons. The virological surveillance revealed strains of virus closely related to drift variants detected from outbreaks in 1977-1979 and the new variants A/Chile 1/83, A/Philippines 2/82, A/Caen 1/84 and B/USSR 100/83.     

The clinico-epidemiological characteristics of the course of a mixed epidemic of influenza and respiratory syncytial infection in Novoshakhtinsk in the summer of 1986

In the summer of 1986 the epidemic, whose etiological agents were influenza viruses A (H1N1) and respiratory syncytial virus, was registered among the population of Novoshakhtinsk. In a number of mines 15.3-16.7% of the employees were affected. Influenza viruses A (H1N1) proved to be closely related in their antigenic and biological properties to viruses isolated in the USSR in March-June 1986, as well as to viruses A (H1N1), the etiological agents of the epidemic which developed in the USSR in October-December 1986.     

The etiological structure of the morbidity from influenza and other ARDs on the territory of Russia in the season of 1997-1998

The antigenic properties of 51 strains of influenza virus A(H1N1), isolated in different cities of Russia during the epidemic of 1998, were studied. Most of these strains (49) proved to be similar to virus A/Bern/07/95 in the antigenic structure of hemagglutinin, but 2 strains isolated in Ulan-Ude were found to be closely related to new antigenic variants of this virus: A/Beijing/262/95 and A/Fukuoka/c7/98. The analysis of the antigenic structure of influenza-like diseases (ILD) in different cities of Russia revealed that adenoviruses causing up to 10.9-14.6% of all acute respiratory virus infections dominated at the pre- and post-epidemic periods. RS-viruses, parainfluenza viruses of types 2 and 3 circulated during the whole season (their proportion was 5.1-6.6%). The intensity of the circulation of influenza viruses A(H1N1) and A(H3N2) increased, starting from January, and continued till April 1998; its peak was observed in February-March in most of the cities of Russia (up to 37.5-41.6% according to the results of immunofluorescent diagnostics and 53-73% of ILD according to the results of the hemagglutination inhibition test). The occurrence of influenza B during this season was very low.     

Evolutionary dynamics of local pandemic H1N1/2009 influenza virus lineages revealed by whole-genome analysis

Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.     

Phylogenetic and genetic characterization of a 2017 clinical isolate of H7N9 virus in Guangzhou,China during the fifth epidemic wave

Pathogenic H7N9 influenza viruses continue to pose a public health concern. The H7N9 virus has caused five outbreak waves of human infections in China since 2013. In the present study, a novel H7N9 strain (A/Guangdong/8H324/2017) was isolated from a female patient with severe respiratory illness during the fifth wave of the 2017 H7N9 epidemic. Phylogenetic analysis showed that the H7N9 viruses collected during the fifth wave belong to two different lineages: the Pearl River Delta lineage and the Yangtze River Delta lineage. The novel isolate is closely related to the Pearl River Delta H7N9 viruses, which were isolated from patients in Guangdong Province. The novel H7N9 isolate has an insertion of three basic amino acids in the cleavage site of hemagglutinin (HA), which may enhance virulence in poultry. The 2017 isolate also possesses an R292K substitution in the neuraminidase (NA) protein, which confers oseltamivir resistance. This study highlights the pandemic potential of the novel H7N9 virus in mammals; thus, future characterization and surveillance is warranted.     

辽宁省2016‒2017年H3N2亚型流感病毒 HA1基因特征分析

摘要：目的 了解2016?2017年辽宁省H3N2亚型流感病毒基因变异情况及流行株与疫苗株的匹配情况。方法 采用逆转录聚合酶链反应（RT-PCR）对分离得到的H3N2亚型流感毒株的HA1基因进行扩增,扩增片段经测序与近年来WHO推荐的北半球疫苗株进行比对和基因特征分析。结果 进化分析表明,2016?2017年H3N2亚型流感病毒与近三年的疫苗株均不在同一分支上;基因特性分析中,所有病毒均在A、B抗原决定簇上发生了两处以上的变异;19株病毒的受体结合位点131位氨基酸发生了新的变异;20株病毒中有1株突变产生了新的半胱氨酸,提示可能有新的二硫键产生;糖基化位点并未检测到新的突变。结论 2016?2017年辽宁省H3N2亚型流感病毒的抗原性及基因特性均发生了一定的变化,但变异程度不大,应密切关注疫苗株对流感病毒的免疫效果及流感毒株的变异情况。     

The laboratory epidemiological study of the joint circulation of the influenza virus A subtypes A/H1N1/ and A/H3N2/ in Bulgaria]

The National Influenza Center of Bulgaria made the epidemiological analysis of the spread of influenza virus, type A, for the period of 11 years on the basis of mass laboratory investigations. Subtype A (H1N1) was found to be the main factor of epidemics in 1978 and 1982, while the epidemics of 1980, 1983, 1985, 1986, 1987 and 1988 were mainly caused by subtype A (H3N2). The data of laboratory and epidemiological studies indicated that after 20-year absence influenza virus A, subtype A (H1N1), was found again to circulate among the population of Bulgaria, and in 1978-1988 circulated simultaneously with the previous subtype A (H3N2). The simultaneous circulation of two subtypes of influenza virus was of great importance for the frequency, spread and duration of influenza epidemics.     

Minor changes in the hemagglutinin of influenza A(H1N1)2009 virus alter its antigenic properties

Background

The influenza A(H1N1)2009 virus has been the dominant type of influenza A virus in Finland during the 2009–2010 and 2010–2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1)2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination.

Methods/Results

Based on the HA sequences of influenza A(H1N1)2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009–2010 and 2010–2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1)2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20^th century.

Conclusions

According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1)2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1)2009 viruses.     

Evolutionary pattern of the hemagglutinin gene of influenza B viruses isolated in Japan: cocirculating lineages in the same epidemic season.

The unexpectedly low efficacy of influenza vaccine during school outbreaks of influenza B virus in the spring of 1987 in Japan was probably attributable to a poor antibody response of vaccinees to the epidemic viruses. An antigenic analysis of the causative B viruses isolated in 1987 and 1988 showed much variation in hemagglutination inhibition patterns. The nucleotide sequences that code for the HA1 domain of B/Fukuoka/c-27/81, B/Ibaraki/2/85, B/Nagasaki/1/87, and B/Yamagata/16/88 viruses were determined and compared with those of the previously reported hemagglutinin genes. The nucleotide sequences of the hemagglutinin gene of a new variant, B/Yamagata/16/88, had only 93.4% homology with those of two other viruses from the same epidemic. An analysis of nucleotide and amino acid substitutions of the hemagglutinin genes of influenza B viruses revealed that new and some old variants could cocirculate in the same epidemic. A phylogenetic tree constructed by the neighbor-joining method allowed estimation of an evolutionary rate of 2.3 x 10(-3) synonymous (silent) substitutions per nucleotide site per year in the hemagglutinin gene.     

Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe

In the early 1970s, a human influenza A/Port Chalmers/1/73 (H3N2)-like virus colonized the European swine population. Analyses of swine influenza A (H3N2) viruses isolated in The Netherlands and Belgium revealed that in the early 1990s, antigenic drift had occurred, away from A/Port Chalmers/1/73, the strain commonly used in influenza vaccines for pigs. Here we show that Italian swine influenza A (H3N2) viruses displayed antigenic and genetic changes similar to those observed in Northern European viruses in the same period. We used antigenic cartography methods for quantitative analyses of the antigenic evolution of European swine H3N2 viruses and observed a clustered virus evolution as seen for human viruses. Although the antigenic drift of swine and human H3N2 viruses has followed distinct evolutionary paths, potential cluster-differentiating amino acid substitutions in the influenza virus surface protein hemagglutinin (HA) were in part the same. The antigenic evolution of swine viruses occurred at a rate approximately six times slower than the rate in human viruses, even though the rates of genetic evolution of the HA at the nucleotide and amino acid level were similar for human and swine H3N2 viruses. Continuous monitoring of antigenic changes is recommended to give a first indication as to whether vaccine strains may need updating. Our data suggest that humoral immunity in the population plays a smaller role in the evolutionary selection processes of swine H3N2 viruses than in human H3N2 viruses.     

Antigenic and genetic evolution of equine influenza A (H3N8) virus from 1968 to 2007

Equine influenza virus is a major respiratory pathogen in horses, and outbreaks of disease often lead to substantial disruption to and economic losses for equestrian industries. The hemagglutinin (HA) protein is of key importance in the control of equine influenza because HA is the primary target of the protective immune response and the main component of currently licensed influenza vaccines. However, the influenza virus HA protein changes over time, a process called antigenic drift, and vaccine strains must be updated to remain effective. Antigenic drift is assessed primarily by the hemagglutination inhibition (HI) assay. We have generated HI assay data for equine influenza A (H3N8) viruses isolated between 1968 and 2007 and have used antigenic cartography to quantify antigenic differences among the isolates. The antigenic evolution of equine influenza viruses during this period was clustered: from 1968 to 1988, all isolates formed a single antigenic cluster, which then split into two cocirculating clusters in 1989, and then a third cocirculating cluster appeared in 2003. Viruses from all three clusters were isolated in 2007. In one of the three clusters, we show evidence of antigenic drift away from the vaccine strain over time. We determined that a single amino acid substitution was likely responsible for the antigenic differences among clusters.     

The epidemic spread of the influenza A and B viruses in the USSR in 1985-1986

The data on the spread of influenza A and B in the autumn and winter of 1985-1986 are given. Three epidemics caused by all presently circulating viruses, B, A (H3N2) and A (H1N1), were registered in the USSR. Of these, the greatest one was the epidemic of influenza B; morbidity rate among the adult population during this epidemic was at the level with the morbidity rate characteristic of the epidemics registered at the period of 1962-1972, and morbidity rate among children, especially school children, was even higher.     

Establishment and lineage replacement of H6 influenza viruses in domestic ducks in southern China

Domestic ducks in southern China act as an important reservoir for influenza viruses and have also facilitated the establishment of multiple H6 influenza virus lineages. To understand the continuing evolution of these established lineages, 297 H6 viruses isolated from domestic ducks during 2006 and 2007 were genetically and antigenically analyzed. Phylogenetic analyses showed that group II duck H6 viruses had replaced the previously predominant group I lineage and extended their geographic distribution from coastal to inland regions. Group II H6 virus showed that the genesis and development of multiple types of deletions in the neuraminidase (NA) stalk region could occur in the influenza viruses from domestic ducks. A gradual replacement of the N2 NA subtype with N6 was observed. Significant antigenic changes occurred within group II H6 viruses so that they became antigenically distinguishable from group I and gene pool viruses. Gene exchange between group II H6 viruses and the established H5N1, H9N2, or H6N1 virus lineages in poultry in the region was very limited. These findings suggest that domestic ducks can facilitate significant genetic and antigenic changes in viruses established in this host and highlight gaps in our knowledge of influenza virus ecology and even the evolutionary behavior of this virus family in its aquatic avian reservoirs.     

Epidemiological analysis of acute respiratory disease (ARD) and characteristics of the influenza epidemic in Bohemia during the season 1986/1987

The authors analyze the findings of epidemiological and virological surveillance of ARD in Bohemia during the season 1986/1987. In all, 57.5% of the Czech population was affected by acute respiratory disease (ARD). There were 5,950,832 cases reported, 124,444 complications (2.1% of the overall morbidity rate) and 5,374 deaths due to influenza, bronchitis, pneumonia and chronic pulmonary affection. The influenza epidemic commenced during the 48-th calendary week (CW) and lasted 5 weeks till the 52-nd CW. The epidemic was due to an influenza virus strain of the subtype A(H1N1) antigenically related to the drift variant A (Singapore) 6/86. Within an extremely short period of the epidemic, 1,094,865 influenza cases were reported and 22,313 cases of complications. 10.7% of the CSR population were affected during the epidemic in whose etiology noninfluenza respiratory viruses were significantly implicated, especially adenoviruses (41.7%) and the RS virus (26.9%). There was no excessive mortality in the course of the epidemic. The authors discuss the atypical nature of this particular influenza epidemic and the etiological role of respiratory viruses.     

Influenza A/H1N1 2009 Pandemic and Respiratory Virus Infections,Beijing, 2009–2010

To determine the role of the pandemic influenza A/H1N1 2009 (A/H1N1 2009pdm) in acute respiratory tract infections (ARTIs) and its impact on the epidemic of seasonal influenza viruses and other common respiratory viruses, nasal and throat swabs taken from 7,776 patients with suspected viral ARTIs from 2006 through 2010 in Beijing, China were screened by real-time PCR for influenza virus typing and subtyping and by multiplex or single PCR tests for other common respiratory viruses. We observed a distinctive dual peak pattern of influenza epidemic during the A/H1N1 2009pdm in Beijing, China, which was formed by the A/H1N1 2009pdm, and a subsequent influenza B epidemic in year 2009/2010. Our analysis also shows a small peak formed by a seasonal H3N2 epidemic prior to the A/H1N1 2009pdm peak. Parallel detection of multiple respiratory viruses shows that the epidemic of common respiratory viruses, except human rhinovirus, was delayed during the pandemic of the A/H1N1 2009pdm. The H1N1 2009pdm mainly caused upper respiratory tract infections in the sampled patients; patients infected with H1N1 2009pdm had a higher percentage of cough than those infected with seasonal influenza or other respiratory viruses. Our findings indicate that A/H1N1 2009pdm and other respiratory viruses except human rhinovirus could interfere with each other during their transmission between human beings. Understanding the mechanisms and effects of such interference is needed for effective control of future influenza epidemics.     

Exploring the Molecular Epidemiology and Evolutionary Dynamics of Influenza A Virus in Taiwan

The evolution and population dynamics of human influenza in Taiwan is a microcosm of the viruses circulating worldwide, which has not yet been studied in detail. We collected 343 representative full genome sequences of human influenza A viruses isolated in Taiwan between 1979 and 2009. Phylogenetic and antigenic data analysis revealed that H1N1 and H3N2 viruses consistently co-circulated in Taiwan, although they were characterized by different temporal dynamics and degrees of genetic diversity. Moreover, influenza A viruses of both subtypes underwent internal gene reassortment involving all eight segments of the viral genome, some of which also occurred during non-epidemic periods. The patterns of gene reassortment were different in the two subtypes. The internal genes of H1N1 viruses moved as a unit, separately from the co-evolving HA and NA genes. On the other hand, the HA and NA genes of H3N2 viruses tended to segregate consistently with different sets of internal gene segments. In particular, as reassortment occurred, H3HA always segregated as a group with the PB1, PA and M genes, while N2NA consistently segregated with PB2 and NP. Finally, the analysis showed that new phylogenetic lineages and antigenic variants emerging in summer were likely to be the progenitors of the epidemic strains in the following season. The synchronized seasonal patterns and high genetic diversity of influenza A viruses observed in Taiwan make possible to capture the evolutionary dynamic and epidemiological rules governing antigenic drift and reassortment and may serve as a “warning” system that recapitulates the global epidemic.     

Evolutional analysis of human influenza A virus N2 neuraminidase genes based on the transition of the low-pH stability of sialidase activity

The 1957 and 1968 human pandemic influenza A virus strains as well as duck viruses possess sialidase activity under low-pH conditions, but human H3N2 strains isolated after 1968 do not possess such activity. We investigated the transition of avian (duck)-like low-pH stability of sialidase activities with the evolution of N2 neuraminidase (NA) genes in human influenza A virus strains. We found that the NA genes of H3N2 viruses isolated from 1971 to 1982 had evolved from the side branches of NA genes of H2N2 epidemic strains isolated in 1968 that were characterized by the low-pH-unstable sialidase activities, though the NA genes of the 1968 pandemic strains preserved the low-pH-stable sialidase. These findings suggest that the prototype of the H3N2 epidemic influenza strains isolated after 1968 probably acquired the NA gene from the H2N2 low-pH-unstable sialidase strain by second genetic reassortment in humans.     

Research progress in human infection with avian influenza H7N9 virus

Since the identification of the novel reassortant avian influenza A (H7N9) virus in China in 2013, until Jun 30, 2017, the virus has caused five epidemic waves leading to a total of 1,552 human infections, with a fatality rate of about 40%. In the spring of 2017, highly pathogenic avian influenza (HPAI) H7N9 virus emerged and has caused 25 human infections. The HPAI H7N9 virus has some biological differences from the LPAI one, such as its multiple basic amino acid residues on HA leading to its independence on trypsin for replication. The pathogenicity of the HPAI H7N9 virus to experimental animals or humans is still unclear. A(H7N9) vaccine development for pandemic preparedness is ongoing, including the reassortment (H7N9/PR8) reverse genetic based vaccine, the virus like particle (VLP) vaccine, the intranasal live attenuated influenza vaccine (LAIV), the non-adjuvant Vero cell culture-derived inactivated whole-virus vaccine, the MDCK culture-derived vaccine, the H7 DNA vaccine and the recombinant replicative H7N9 virus (H7N9-53TM) vaccine. Five neuramidinase resistant sites of A(H7N9) virus isolated from patients have been reported. Some alternative drugs have been studied, such as DAS181 (Fludase), ribavirin, troglitazone and minocycline. Persistent surveillance and enhanced global control are essential to fight against human infections with A(H7N9) virus.     

Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations in major antigenic sites of the hemagglutinin molecule analogous to those for human influenza virus

H5N1 highly pathogenic avian influenza virus has been endemic in poultry in Egypt since 2008, notwithstanding the implementation of mass vaccination and culling of infected birds. Extensive circulation of the virus has resulted in a progressive genetic evolution and an antigenic drift. In poultry, the occurrence of antigenic drift in avian influenza viruses is less well documented and the mechanisms remain to be clarified. To test the hypothesis that H5N1 antigenic drift is driven by mechanisms similar to type A influenza viruses in humans, we generated reassortant viruses, by reverse genetics, that harbored molecular changes identified in genetically divergent viruses circulating in the vaccinated population. Parental and reassortant phenotype viruses were antigenically analyzed by hemagglutination inhibition (HI) test and microneutralization (MN) assay. The results of the study indicate that the antigenic drift of H5N1 in poultry is driven by multiple mutations primarily occurring in major antigenic sites at the receptor binding subdomain, similarly to what has been described for human influenza H1 and H3 subtype viruses.     

Impact of the 2009 H1N1 Pandemic on Age-Specific Epidemic Curves of Other Respiratory Viruses: A Comparison of Pre-Pandemic,Pandemic and Post-Pandemic Periods in a Subtropical City

Background

The 2009 H1N1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical Hong Kong. This study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses.

Methods

Weekly laboratory-confirmed cases of influenza A (subtypes seasonal A(H1N1), A(H3N2), pandemic virus A(H1N1)pdm09), influenza B, respiratory syncytial virus (RSV), adenovirus and parainfluenza were obtained from 2004 to 2013. Age-specific epidemic curves of viruses other than A(H1N1)pdm09 were compared between the pre-pandemic (May 2004 – April 2009), pandemic (May 2009 – April 2010) and post-pandemic periods (May 2010 – April 2013).

Results

There were two peaks of A(H1N1)pdm09 in Hong Kong, the first in September 2009 and the second in February 2011. The infection rate was found highest in young children in both waves, but markedly fewer cases in school children were recorded in the second wave than in the first wave. Positive proportions of viruses other than A(H1N1)pdm09 markedly decreased in all age groups during the first pandemic wave. After the first wave of the pandemic, the positive proportion of A(H3N2) increased, but those of B and RSV remained slightly lower than their pre-pandemic proportions. Changes in seasonal pattern and epidemic peak time were also observed, but inconsistent across virus-age groups.

Conclusion

Our findings provide some evidence that age distribution, seasonal pattern and peak time of other respiratory viruses have changed since the pandemic. These changes could be the result of immune interference and changing health seeking behavior, but the mechanism behind still needs further investigations.