Influenza surveillance
Why?
Influenza outbreaks caused by influenza A and/or influenza B viruses occur every winter in Finland. People usually recover from influenza in 1 to 2 weeks, but the elderly and people with underlying diseases, such as chronic disorders of the pulmonary or cardiovascular systems, may develop life-threatening complications after influenza infection. Influenza epidemics are frequently associated with excess mortality and increases in hospital admissions. Due to high morbidity influenza outbreaks also exert great impact in economic terms.
Annual outbreaks are possible, for influenza viruses undergo antigenic drift, a gradual change that enables the virus to evade the immunity developed after previous infections with influenza viruses or in response to vaccinations. In addition to antigenic drift, influenza A viruses occasionally undergo antigenic shift, a more prominent change that results in exceptionally severe epidemics referred to as pandemics.
Due to the rapid evolution of influenza A and B viruses, influenza vaccine must be updated annually to include surface proteins (haemagglutinin and neuraminidase) of the most current influenza virus variants. Vaccination is recommended for high-risk persons every autumn. Influenza surveillance has been launched to monitor the antigenic and genetic changes in influenza viruses to aid in identifying suitable virus strains for inclusion in the new influenza vaccines.
It is also important that when a new virus variant with potential epidemic activity is traced, the health authorities have more time to prepare for the approaching epidemic. Furthermore, it is useful to know whether influenza A or influenza B viruses are circulating, for antiviral drugs (amantadine and rimantadine) are available that are effective against influenza type A but not type B viruses.
How?
The World Health Organization (WHO) established an international network of collaborating national influenza centres with the aim of monitoring changes in influenza viruses whenever and wherever outbreaks of influenza occur. Nowadays this network consists of about 110 national laboratories throughout the world and four collaborating centres (London, Atlanta, Parkville and Tokyo) for reference and research on influenza.
The principal task of the national centres is to undertake virological surveillance by isolating influenza viruses during outbreaks in their homelands, to characterize the isolated strains antigenically and to dispatch a representative collection of isolates to one of the four WHO reference centres, where centralized comparisons of strains from various parts of the world can be made reliable.
Since influenza viruses affecting birds, pigs, horses and other animals may be involved in the emergence of new human pandemic strains, surveillance of these viruses is also important and is one duty of several special laboratories.
Virological surveillance is complemented by serological surveillance. Screening of influenza virus antibodies prior to an approaching epidemic season furnishes information on immunity in various age- groups. Determination of vaccination-induced antibody response is indicative of protection achieved. Furthermore, comparison of antibody levels before and after an outbreak displays the size of the outbreak.
In addition to virological surveillance, useful knowledge on influenza epidemics can be gained by clinical surveillance and use of other nonvirological indicators. These may include morbidity and mortality statistics, monitoring of absenteeism in schools, nursery schools and workplaces and follow-up of drug consumption.
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Our surveillance and reference
functions
- Isolation of influenza viruses from nasopharyngeal aspirates. The specimens arrive from various parts of the country, the majority from military conscripts. Direct detection of viral antigens by time-resolved fluoroimmunoassay is performed in advance in the collaborating laboratory directed by Dr. Marjaana Kleemola, and only specimens positive for influenza virus antigens are inoculated into MDCK cell cultures and embryonated eggs.
- Antigenic typing of influenza virus isolates. Comparisons are performed with reference strains and field strains isolated during previous epidemic seasons in Finland by using HI assays. A panel of antisera produced in rats and ferrets are used.
- Nucleotide sequence analysis of influenza virus isolates. HA1 and NA gene sequences of a collection of field strains isolated in various parts of the country and at different times of the epidemic season are studied. Antigenic changes are considered from the standpoint of amino acid substitutions, and sequence comparisons are performed with vaccine strains from the previous autumn.
- Shipments of new influenza virus isolates to the WHO World Influenza Centre, Mill Hill, London. Virus strains are also exchanged with several WHO National Influenza Centres in Europe and studied in our laboratory antigenically and genetically.
- Serological diagnosis for subtype-determination of influenza A. Paired sera taken during acute and convalescent phases of influenzalike illness are studied for diagnostic rise in HI antibodies against a number of influenza type A and B viruses.
- Determination of pre-epidemic antibody status. Reference strains, current epidemic viruses and a number of recent epidemic strains serve as antigens in HI tests. Estimates are made of individuals in definable population-groups possessing protective antibody levels to the circulating virus variants. This screening has not been performed annually.
- Determining of the size of influenza outbreaks serologically. This is undertaken by applying HI tests and using paired sera collected from the same individuals before and after an outbreak. These studies were performed annually during the 1970s and 1980s, but since they are very laborious with respect to our trained manpower, they are performed infrequently at present.
- Determination of vaccination-induced antibody response. Efforts are made to perform these studies annually in various target groups. HI tests are applied. Vaccine strains and epidemic strains from the previous epidemic seasons serve as antigens. After the epidemic seasons, the antibody response is often measured by using the new virus variants as antigens. The kinetics of antibody formation is monitored occasionally with sequential serum specimens.
- Maintaining collections of influenza virus strains and antisera. In 1997 our virus collection consisted of about 2700 samples of strains isolated in Finland since 1968. The collection of stored antisera prepared against influenza virus strains consisted of about 1300 samples. The virus strains and antisera have been placed at the disposal of our collaborating laboratories participating in influenza surveillance.
- Information service. An information letter, Influenza in Finland, on laboratory findings and epidemic activity is issued weekly during epidemic seasons and mailed to the WHO and more than 20 foreign laboratories participating in influenza surveillance in Europe and the USA. Most of these laboratories regularly send us corresponding information. Our weekly bulletin Influenssa Maailmalla (Influenza in the World; in Finnish), based on this mutual correspondence, is mailed weekly during epidemic seasons or twice weekly to those virological laboratories participating in influenza surveillance in Finland. On request we furnish information to the press, of which this web document forms a part.
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Our major research fields
The aim of our influenza research is to support our surveillance, monitoring and reference activities as the WHO National Influenza Centre. The research is comprised of three topics:
- Seroepidemiology, analysis of vaccination-induced antibody response and determination of vaccination effectiveness.
- Molecular epidemiolgy and evolution of human influenza A and B viruses, especially HA1 and NA genes and their function and significance as determinants of epidemic activity.
- Adaptation and pathogenicity of human influenza viruses in various host systems.
Current problems include:
- The influence of previous antigenic experiences on vaccination-induced antibody response.
- The immunogenic properties of various vaccine products.
- Vaccination-induced antibody response against genetically determined intraepidemic virus variants.
- Genetic and antigenic relationships between epidemic virus and vaccine strains.
- Interepidemic and intraepidemic variation of HA1 and NA genes as well as changes during individual infections.
- Reassortation, intracistronic complementation and convergent development.
- Appearance of relic amino acids from the standpoint of the quasi-species nature of virus populations.
- Amino acid changes of HA1 involved in antigenic drift and receptor-binding properties.
- Evolutionarily significant glycosylation changes in HA1 and NA.
- Amino acid substitutions in HA1 involved in adaptation of the virus to growth in various host systems.
- Influenza virus variants capable to break through vaccination-induced immunity.
Selected publications
- Honkanen P, Läärä E, Pyhälä R, Kivelä S-L,
Mäkelä P. The comparison of two vaccination programs in preventing
influenza-related hospitalisation among the elderly during two consecutive
seasons. Scand J Infect. Dis. (in press).
- Ikonen N, Pyhälä R., Toivonen M, Korpela H. (2005) Influenza A/Fujian/411/02(H3N2)-lineage viruses in Finland: genetic diversity, epidemic activity and vaccination-induced antibody response. - Archives of Virology (in press).
- Ikonen N, Pyhälä R, Axelin T, Kleemola M, Korpela H. (2005) Reappearance of influenza B/Victoria/2/87-lineage viruses: epidemic activity, genetic diversity and vaccination efficacy in the Finnish Defence Forces. - Epidemiology and Infection 133: 263-271.
- Pyhälä R., Visakorpi R., Ikonen N., Kleemola M. (2004) Influence of antigenic drift on the intensity of influenza outbreaks: upper respiratory tract infections of military conscripts in Finland. Journal of Medical Virology 72: 275-280.
- Antonen J.A., Pyhälä R., Hannula P.M., Ala-Houhala I.O., Santanen R., Ikonen N., Saha H.H. (2003) Influenza vaccination of dialysis patients: cross-reactivity of induced haemagglutinating antibodies to H3N2 subtype antigenic variants is comparable with the response of naturally infected young healthy adults. Nephrol Dial Transplant 18: 777-781.
- Pyhälä R., Ikonen N., Haanpää M., Santanen R., Tervahauta R. (2002) Phylogenetic and antigenic analysis of influenza A(H3N2) viruses isolated from conscripts receiving influenza vaccine prior to the epidemic season 1998/1999. Epidemiology and Infection 129: 347-353.
- Machon R.A., Huttunen M.O., Mednick S.A., Sinivuo J., Tanskanen A., Watson J.B., Henriksson M., Pyhälä R. (2002) Adult schizotypal personality characteristics and prenatal influenza in a Finnish birth cohort. Schizophrenia Research 54: 7-16.
- Pyhälä R., Ikonen N., Santanen R., Haanpää M., Jäppinen P., Valle M. (2001). Vaccination-induced HI antibody response to intraepidemic influenza A(H3N2) virus variants of the 1996-1997 epidemic season. Journal of Medical Virology 65; 584-589.
- Pyhälä R., Haanpää M., Kleemola M., Tervahauta R., Visakorpi R., Kinnunen L. (2001). Acceptable protective efficacy of influenza vaccination in young military conscripts under circumstances of incomplete antigenic and genetic match. Vaccine 19; 3253-3260.
- Antonen J., Hannula P., Pyhälä R., Saha H.,
Ala-Houhala I., Pasternack A. (2000). Adequate seroresponse to
influenza vaccination in dialysis patients. Nephron 86: 56-61.
IN FINNISH
- Pyhälä R, Ikonen N, Toivonen
M, Ziegler T, Ruutu P. (2005) Influenssatalvi 2004-2005: veikattiinko
väärää hevosta? Suomen Lääkäril. 60: 3495-3499.
- Pyhälä R. Maailma varautuu
influenssapandemiaan. (2004). Duodecim 120: 2613-1614.
- Pyhälä R, Ikonen N, Korpela
H, Toivonen M, Santanen R, Villberg A, Ziegler T, Ruutu P. (2004). Influenssatalvi
2003-2004 oli A/Fujian/411/02-viruksen läpimurto. Suomen Lääkäril. 59:
3503-3507.
- Pyhälä R. Onnistuuko
lintuinfluenssan juuriminen? (2004). Duodecim 120: 11-12.
- Pyhälä R., Ikonen N., Korpela H., Axelin T.,
Räty R., Ruutu P., Santanen R., Villberg A., Sarjakoski M. (2003).
Influenssatalvi 2002-2003: oikea virus outoon aikaan. Suomen Lääkärilehti
58: 3897-3902.
- Pyhälä R., Ziegler T. (2003).
Influenssavirukset. Teoksessa: Mikrobiologia ja infektiosairaudet. (Toim.:
Huovinen, Meri, Peltola, Vaara, Vaheri & Valtonen). Kustannus Oy
Duodecim. s. 415-428.
- Rapola S., Kuronen T., Hovi T., Pyhälä R.,
Verho J., Kilpi T. (2002). Ikääntyvän influenssa - influenssarokotus
kaikille 65 vuotta täyttäneille. Suomen Lääkärilehti 57: 3731-3736.
- Pyhälä R., Ikonen N., Kleemola M., Korpela
H., Santanen R., Sarjakoski M., Villberg A., Ziegler T. (2002). Talven
2002 influenssaepidemiat: virusten uusimmat yritykset murtaa immuunisuoja.
Suomen Lääkärilehti 57: 3723-3728.
- Hovi T., Jääskeläinen A., Pyhälä R., Ristola
M., Salminen M. (2002). Virusten lääkeresistenssi. Duodecim 118: 911-918.
- Pyhälä R. (2002). Influenssapandemia uhkaa
yhä - mistä rokote? Duodecim 118: 573-577.
- Pyhälä R. (2002). Influenssarokotusten
kohderyhmiä tarkistetaan. Duodecim 118: 73-74.
- Pyhälä R., Tervahauta R., Kleemola M.,
Korpela H., Ikonen N., Sarjakoski M., Saari M., Rostila T. (2001)
Influenssa väisti vanhuksia - talvinen ylikuolleisuus romahti. Suomen
Lääkärilehti 56: 3197-3201.
- Pyhälä R. (2001). Tarvitaanko Suomessa
influenssan kliinistä valvontaa? Suomen Lääkärilehti 56: 1397-1398.
- Pyhälä R. (2000). Hongkongilaisen
influenssaviruksen jälkipolvet Suomessa - 30 vuotta kujanjuoksua ja
perässä pysyttelyä. Duodecim 116: 2483-2488.
- Pyhälä R., Tervahauta R., Korpela H., Haanpää
M., Kleemola M., Rostila T., Saari M., Sarjakoski M. (2000). Influenssassa
uudelle vuosituhannelle. Talven 1999-2000 epidemia ja virukset. Suomen
Lääkärilehti 55: 3695-3701.
Our staff
- Reijo Pyhälä, Ph.D., Docent, Head of the Laboratory
- Niina Ikonen, B.Sc.
- Riitta Santanen, H.N.C. Engineer in Biotechnology
- Anja Villberg, Technician
Collaborating groups
- Jaakko Antonen, M.D., Ph.D. (University of Tampere, Finland)
- Marjaana Kleemola, M.D., Ph.D. (National Public Health Institute, Helsinki, Finland)
- Heikki Korpela, M.D., Ph.D. (Research Institute of Military Medicine, Helsinki, Finland)
- Thedi Ziegler, Ph.D. (National Public Health Institute, Helsinki, Finland)