The National Influenza Reference Centre Swedish Institute for Infectious Disease Control (SMI) Annual Report September 2000-August 2001

Transkript

1 The National Influenza Reference Centre Swedish Institute for Infectious Disease Control (SMI) Annual Report September 2-August 21 Annika Linde, Camilla Kolmskog, Maria Brytting, Britta Wahren Department of Virology Ingela Berggren Palme, Karl Ekdahl, Johan Lindbäck, Birgitta Runsten, Katarina Skärlund Department of Epidemiology

2 Table: 1. Approximate number of persons/patients forming the basis for reports of absenteeism, ARI at nursing homes and ILI by sentinel doctors County Children at day Schoolchildren Workers Elderly at nursing Sentinels care centers homes AB 42 C D E 29 F 16 G H I K L-M N OPR S T U W X Y 4 Z AC BD Total

3 Activities. 1) Monitoring of influenza activity in Sweden 2) Reports from SMI on influenza activity in Sweden 3) Characterisation of influenza strains 4) Data from the 2-21 season 5) Quality control of laboratory diagnosis of influenza 6) Method Development and Research 1) Monitoring of Influenza activity in Sweden 1:1) Reports of absenteeism from child nurseries, schools, work places and P&I disease in nursery homes for the elderly. Sweden is divided into 21 counties with a County Medical Officer of Communicable Disease Control in each. At a non-statutory basis, these Officers collect information on absence from some child nurseries, schools and work places, and pneumonia and influenza disease (P&I) disease in nurseries for elderly during the influenza season. The counties in Sweden are shown in Fig1:1. The number of children, employees and elderly reported on from each county are presented in Table 1:2. Variations in the basis for the reports occur, due to e.g. holidays and unpredictable factors. Reports on absenteeism during the Christmas and New Year period are not reliable, and thus left unaccounted for. Information on absenteeism has been collected since the season. Mean values for absenteeism were calculated for the period from , and estimated variations (normal, increased, extreme) were used as a reference in diagrams. 1:2) The Sentinel System. During the autumn 1999 a sentinel system with GPs reporting the number of patients with influenza-like disease in relation to the total number of visits was created. The reporting units during the season 2-21 were 62 individual GPs and 39 health units, including 1-4 GPs. The reports encompassed from 4-96 weekly out-patient visits. Sentinel doctors were recruited by the County Medical Officers, and 19/21 counties participated in the system. Date of visit and age and sex of the patients were reported. 1:3) Reports of laboratory verified influenza diagnoses. Influenza isolation is performed at five virus laboratories, placed in University Hospitals and at SMI. The laboratories are relatively evenly distributed with regard to the population in different 2

4 areas. The laboratories also perform influenza serology, antigen detection with immunoflourescense (IF) and by polymerase chain reaction (PCR). Another 15 microbiology laboratories diagnose influenza by IF assays or commercial ELISA KITs. During the influenza season, the 2 laboratories report the number of influenza cases, diagnosed by antigen detection and/or virus isolation weekly. Serology results are not included in these reports. 1:4) Death rates. As soon as available, after the end of the main influenza season, information on the weekly death rate in Sweden is purchased from Statistics, Sweden. Mean death rate for influenza-free weeks during the period has been calculated, and is used as reference for the demonstration of weekly excess mortality. 1:5) Other types of input information from Sweden. During the season, departments of infectious diseases in five cities, the Stockholm County Health Care Information Centre and some other institutions are asked by telephone for their estimation of the influenza activity. 2) Reports from SMI on the influenza activity in Sweden 2:1) Weekly reports to the Swedish Collaborators. Each Friday, all influenza information collected during the week, including the WHO country reports is summarised and sent by fax to the County Medical Officers of Communicable Disease Control, to departments of infectious disease in Sweden, to microbiological laboratories, and to the National Board of Health and Welfare. The information is also available on the SMI homepage ( A summary of the activity during the entire season is distributed towards the end of the summer, when all definitive data are available. 2:2) Other spread of information in Sweden. The media are constantly interested in influenza, and usually contact SMI to get information. In most instances those contacts result in correct and informative articles. The Institute has a monthly journal Smittskydd, and during the influenza season reports on the situation are printed there, when appropriate. An information day for the persons who are active in the surveillance system was arranged in September 2. 2:3) Reports to WHO and other National Influenza centres. Sweden reports to WHO via Flunet, and starts reporting when the first laboratory verified case occurs. Since 2 we have also joined the European Influenza Surveillance Scheme (EISS). 3) Characterisation of influenza strains Influenza strains are sent to SMI from the laboratories performing virus isolation. Isolated virus strains are examined for the type and subtype of virus by (hemagglutination inhibition (HAI); reagents sent by WHO) and IF with monoclonal antibodies (from Laboratories de Virologie, 3

5 Lyon). For 2A strains, HA and NA sequencing was performed, and analysed at SMI. For further characterisation with ferret sera, these strains were also sent to Mill Hill in London. 4) Data from the 2-21 season Summary of the influenza activity in Sweden. The influenza season did not start until January 21, and the total number of laboratory diagnoses was less than 1/3 of what was reported during the previous season. There was no sharp peak of activity, but from week 7 to week 13 there were >5 lab diagnoses reported weekly, and around 2% sentinel visits for influenza-like illness (Fig 4:1). The activity also continued after week 14, when the sentinel surveillance had been stopped for the season. The absenteeism from schools and day-nurseries for children was 2-4% above normal during these weeks, while workplaces and nurseries for elderly were less affected (Fig 4:1). The dominating circulation of Influenza B and A/H1N1 is the likely explanation for the high incidence among children and less impact among elderly, as illustrated from the age distribution of laboratory verified cases (Fig 4:2). These viruses have not been prevalent during recent seasons. An unusual peak of laboratory verified cases at ages 3-4 occurred, not noted during previous years (Fig 4:2). Despite the late and relatively mild season, there was excess mortality from February and onwards (Fig 4:3). In the beginning of the season also some influenza A/H3N2 strains were isolated but thereafter Influenza B and H1N1 dominated. The influenza A/H1N1, A/H3N2 and B viruses were antigenically and genetically closely related to vaccine strains of the year (Table 4:4, Fig 4:5-7). Three of the strains, 1 H1N1 and 2 H3N2 strains, gave reduced ( 4-fold) HI-titres with antisera to the reference strains of the year. The NA sequences were also as expected, and no mutations known to confer resistance to neuraminidase inhibitors were identified. Overall, the results are similar to those obtained with viruses received from other countries during the season. Total number of reported laboratory diagnoses: Influenza A: 274 ( 3/1 6 inhabitants) Influenza B: 412 ( 4/1 6 inhabitants) Tables and diagrams: 4:1) Diagram of weekly reports of absenteeism and P&I in elderly, sentinel reports, and numbers of laboratory verified influenza cases during and :2) Age distribution of laboratory verified cases and 2-21, and sentinel cases compared to laboratory verified cases for :3) Diagram of the weekly number of deaths in Sweden from week 4, 1993 to week 14, 21, and the number of laboratory verified influenza cases during the same periods. (The peak of mortality in September 1994 reflects the Estonia ferry catastrophe). Adjusted mean for corresponding influenza-free weeks is also included. 4:4) Table of isolates for which extended feno- and genotypings were performed. 4

6 4:5) The phylogenetic tree of the amino acid sequences of HA of influenza A/H3 strains isolated in Sweden 2-21 compared to the vaccine strains of the year. Most of the strains are very similar. The isolate Umeå 4/, which differs slightly from the others, is an import case from China. Also Stockholm 9/1, the last H3 isolation is different, but no information on site of infection is available for that patient. 4:6) The phylogenetic tree of the amino acid sequences of HA of influenza A/H1 strains isolated in Sweden 2-21 compared to the vaccine strains of the year. 4:7) The phylogenetic tree of the amino acid sequences of HA of influenza B strains isolated in Sweden 2-21 compared to the vaccine strains of the year 5) Quality control of laboratory diagnosis of influenza. In collaboration with the organisation for External Quality Assessment in Sweden (Equalis), panels for quality control of antigen detection with IF, were sent to laboratories performing this types of diagnostic assays in Sweden. The influenza panel for IF consisted of 8 different acetone fixed preparations of the influenza strains expected for the season, grown in MDCK cells, and mixed with different proportions of uninfected cells from a lymphoblastoid cell line. Most of the 13 participating laboratories answered the panel correctly (118/136 analyses). The results of the External Quality control from related to methods is presented (Table 5:1) 6) Method development and research 6:1) DNA vaccines for influenza: It has been shown by us and others that the vaccination of mice with plasmids containing influenza cdna under the control of CMV promoter may lead to protection from disease, viral shedding and weight loss. We have produced a plasmid handle, into which new hemagglutinin sequences can be inserted by homologous recombination The vaccine has been show to elicit an immune response in mice, and I collaboration with Erasmus Universlity, Rotterdam (Guus Rimmelzwaan) the construct was show also to be immunogenic in ferrets. 6:2) Micro-NT and antiviral assay: A micro-neutralisation assay based on an in situ ELISA detection system for determination of neutralising antiviral antibodies and antiviral resistance in a human fibroblast strain was previously developed. The system has been evaluated as a viral sensitivity assay. In experiments with standard laboratory strains it gives IC5ies to Oseltamivir and Zanamivir similar to those obtained in a plaque assay. 6:3) Lymphocyte proliferation assay using whole blood and FACS: A study was planned to evaluate the protective effect of CMI to influenza in a family study, but could not be performed due to too low influenza activity during the season. 5

7 Contact person for the WHO influenza centre: Annika Linde Dept. of Virology Swedish Institute for Infectious Disease Control SE Solna Sweden Tel: Fax: Annika.Linde@smi.ki.se SMI home page 6

8 Figure 1. Counties in Sweden Area: km 2 Population 1999: AB - Stockholm C - Uppsala D - Sörmland E - Östergötland F - Jönköping G - Kronoberg H - Kalmar I - Gotland K - Blekinge L-M - Skåne N - Halland O-R - V Götaland S - Värmland T - Örebro U - Västmanland W - Dalarna X - Gävleborg Y - Västernorrland Z - Jämtland AC - Västerbotten BD - Norrbotten

9 Table: 1. Approximate number of persons/patients forming the basis for reports of absenteeism, ARI at nursing homes and ILI by sentinel doctors County Children at day Schoolchildren Workers Elderly at nursing Sentinels care centers homes AB 42 C D E 29 F 16 G H I K L-M N OPR S T U W X Y 4 Z AC BD Total

10 Figur 4: Day care centers Extreme Schools Extreme Frånvaro (%) Förhöjd Frånvaro (%) Förhöjd Normal 4 Normal Vecka Vecka 8 Workplaces 6 Nursing homes for elderly Frånvaro (%) Extreme Förhöjd Normal Sjuklighet (%) Extreme Förhöjd Normal Vecka Vecka 5 Labdiagnoser 1 Sentinel 45 9 Antal infl. diagnoser Andel (%) infl. pat. av totalt antal pat Vecka Vecka 1999/2 2/21 Förklaring: De vågräta linjerna i de fyra översta diagrammen anger gräns mellan normal, förhöjd samt mycket förhöjd frånvaro respektive sjuklighet. Gränserna är valda subjektivt utifrån tidigare säsongers nivåer. Veckorna kring jul och nyår fungerar frånvarorapportering inte bra och de har därför lämnats blanka. Aktuell säsong jämförs med föregående säsong.

11 Figure 4:2 3 Age distribution of laboratory verified influenza diagnoses in Sweden during the influenza seasons 1999/2 and 2/21 % of total cases / /2 5 to 5 6 to 1 11 to 2 21 to 3 31 to 4 41 to 5 51 to 6 61 to 7 71 to 8 81 to 9 >9 Age of reported cases Age distribution of 132 cases reported by sentinel doctors related to 596 laboratory diagnoses in Sweden during the 2/21 influenza season 2 % of total cases Sentinel cases Laboratory diagnoses to 5 6 to 1 11 to 2 21 to 3 31 to 4 41 to 5 51 to 6 61 to 7 71 to 8 81 to 9 >9 Age of reported cases

12 Figure 4: 3. Weekly death rates related to number of influenza diagnoses reported from Swedish laboratories week to week Number of deaths Mean number of deaths during weeks without flu Number of diagnoses / / / / / / / /1 14 Number of deaths Number of diagnoses 2 1 Week

13 Figure 4:4 Influenza strains sent to SMI, and results from Mill Hill from the 2-21 season 1. A/Stockholm/9/[H1N1] Antigenically similar to (Gävle, traveller from Bali) A/New Caledoina/2/99[H1N1] 2. A/Stockholm/1/1[H1N1] (Blekinge) 3. A/Stockholm/2/1[H1N1] (Huddinge) 4. A/Stockholm/3/1 (Uppsala) 5. A/Stockholm/4/1[H1N1] (Huddinge) 6. A/Stockholm/5/1[H1N1] (Huddinge) 7. A/Stockholm/6/1[H1N1] (Huddinge) 8. A/Stockholm/7/1[H1N1] (Huddinge) 9. A/Stockholm/8/1[H1N1] (Huddinge) 1. A/Malmö/1/1[H1N1] (Malmö) 11. A/Umeå/4/1[H1N1] (Umeå) 12. A/Umeå/5/1[H1N1] (Umeå) 13. A/Umeå/4/[H3N2] Antigenically similar to (Umeå, traveller from China) A/Moscow/1/99[H3N2] 14. A/Malmö/2/1[H3N2] (Malmö) 15. A/Umeå/1/1[H3N2] (Umeå) 16. A/Umeå/3/1[H3N2] (Umeå) 17. A/Stockholm/9/1[H3N2] (Falun) 18. A/Umeå/2/1[H3N2] Not recovered at Mill Hill (Umeå) 19. A/Umeå/6/1[H3N2] (Umeå) 2. B/Umeå/1/1 Antigenically similar to (Umeå) B/Guangdong/12/ 21. B/Malmö/1/1 Not recovered at Mill Hill (Malmö) 22. B/Stockholm/1/1 (Skövde) 23. B/Göteborg/1/1 (Göteborg)

14 Figure 4:5 Swedish influenza A (H3N2) strains Season Season * Season Season Season Vaccine Stockholm 4/97 Stockholm 1/97 Göteborg 3/97 Stockholm 6/97 Stockholm 7/96 Wuhan 359/95 Stockholm 3/97 Shangdong 9/93 Johannesburg 33/94 Beijing 32/92 Shanghai 16/89 Beijing 353/89 Shanghai 11/87 Stockholm 1/98* 3. Substitutions per 1 amino acids Umeå 1/1 Umeå 2/1 Umeå 3/1 Umeå 6/1 Malmö 2/1 Malmö 2/ Stockholm 12/99 Stockholm 11/99 Stockholm 5/ Stockholm 7/ Stockholm 2/ Umeå 3/ Stockholm 8/ Stockholm 4/ Malmö 1/ Stockholm 3/ Umeå 2/ Umeå 2/99 Malmö 3/98* Malmö 1/99 Malmö 3/99 Göteborg 1/99 Umeå 1/99 Stockholm 13/99 Panama 27/99 Stockholm 9/1 Malmö 2/99 Umeå 4/ Stockholm 3/99 Stockholm 2/99 Stockholm 5/99 Stockholm 1/99 Malmö 14/98* Stockholm 19/98 Göteborg 3/99 Umeå 16/98 Stockholm 1/99 Stockholm 8/99 Stockholm 7/99 Moskva 1/99 Malmö 1/98* Sydney 5/97 Stockholm 6/99 Stockholm 18/99

15 Figure 4:6 Pylogenetic tree - Hemagglutinin gene from influenza A (H1) viruses A/Stockholm/8/1 A/Stockholm/7/1 A/Malmö/1/1 A/Umeå/4/1 Italic, seasons -2 Plain, season 2-21 Underlined, vaccine strains A/Stockholm/9/ A/Umeå/1/ A/Stockholm/4/1 A/Stockholm/1/1 A/Stockholm/5/1 A/Umeå/5/1 A/Stockholm/6/1 A/New Caledonia/2/99 A/Beijing/262/95 A/Umeå/2/91 A/Stockholm/26/9 A/Taiwan/1/86 3. Substitutions per 1 amino acids

16 Figure 4:7 Pylogenetic tree of the influenza B virus hemagglutinin B/Malmö/1/1 Italic, season Plain, season 2-21 Underlined, vaccine strains B/Göteborg/1/1 B/Stockholm/1/1 B/Guangdong/12/ B/Umeå/1/1 B/Stockholm/1/99 B/Stockholm/2/99 B/Beijing/184/93 B/Panama/45/9 B/Yamanashi/16/86 3. Substitutions per 1 amino acids

17 Table 5:1. External Quality Control Assessment in Sweden (Eqalis). Results of panels for influenza antigen detection form The number (%) of reported correct results related to total number of examinations performed with the methods. Influenza A/H1 Influenza A/H3 Influenza B Imagen 97/12 (95%) 83/93 (89%) 89/114 (78%) Chemicon 52/52 (1%) 48/5 (96%) 56/58 (97%) WHO 14/14 (1%) 9/1 (9%) 14/15 (93%) Biosoft/Argene 5/6 (83%) 6/6 (1%) 5/7 (71%) Biotrin 4/4 (1%) 4/4(1%) 4/4(1%)

18 Vårdgivare_namn Vårdgivare Landsting Olofström Vårdcentral Blek Högland Läkare Blek Särna Vårdcentral Dlrn Grängesberg Vårdcentral Dlrn Johnston G (Gagnef) Läkare Dlrn By Vårdcentral Dlrn Långshyttan Vårdcentral Dlrn Lima Vårdcentral Dlrn Ljusne Vårdcentral Gävl Stortorget Vårdcentral Gävl Stål Läkare Gävl Linden Bergvik Vårdcentral Gävl Andersberg Vårdcentral Gävl Johansson Eskil Läkare Hall Andersson Christer Läkare Hall Perkmar Mats Läkare Hall Lars Lingetun Läkare Hall Mattsson Läkare Hall Brydolf, Viktoriaklin Läkare Hall Eksjö(Lindahl) Vårdcentral Jkpg Malm Läkare Jkpg Lindqvist Läkare Jkpg Esplanaden Vårdcentral Kalm Kristineberg Vårdcentral Kalm Borgholm (Staf) Vårdcentral Kalm Vimmerby Vårdcentral Kalm Henriksson Mats Läkare Kron Lenhovda Vårdcentral Kron Överkalix Vårdcentral Nbtn Boström Jörgen Läkare Nbtn Welander,Göinge Läkare Skån Adolfsson Läkare Skån Trönnberg Läkare Skån Eriksson Alsted Läkare Skån Heijbel Läkare Skån (Johansson J) Läkare Skån Fredriksson Läkare Skån Beijersten Läkare Skån Nilsson Gunilla Läkare Skån Bayard Ylva Läkare Skån Marie Läkare Skån Malmberg Läkare Skån Tromberg A Läkare Skån Voss CE (Ödåkra) Läkare Skån Lindgren C (Laröd) Läkare Skån Sjökvist C Läkare Skån Rinkeby Vårdcentral Sthm Johansson Åke Läkare Sthm Divanidij Läkare Sthm Vaxholm Vårdcentral Sthm Eriksson Dahlberg Läkare Sthm Intner RingensVC Läkare Sthm

19 Sissay Läkare Sthm Seon Läkare Sthm HallonbergensVC Läkare Sthm Sorunda Vårdcentral Sthm Lindhé B Läkare Södm Davidsson Lennart Läkare Södm Welff Läkare Södm Lindbom Läkare Södm Reder M Läkare Södm Husläkarakuten Vårdcentral Upps Samanloti Läkare Upps Flogsta Vårdcentral Upps Liljeforstorg Vårdcentral Upps Pepparroten Vårdcentral Upps Westerback Läkare Upps Haag Läkare Upps Björkegren Läkare Upps Holmer T Läkare Vgöt Guldringen 3 Vårdcentral Vgöt Stenstorp Vårdcentral Vgöt Olskroken Vårdcentral Vgöt Olskroken Vårdcentral Vgöt Svanberg Läkare Vgöt Ängabo Vårdcentral Vgöt (Stenstorp) Läkare Vgöt Dotevall Läkare Vgöt Sörqvist Läkare Vgöt Risholm Läkare Vgöt Öhlund Ulla-Karin Läkare Vnrl Näslund K Läkare Vnrl Sunne Vårdcentral Vrml Nordenhäll Barbro Läkare Vrml Sundgren Gudrun Läkare Vrml Asplund Göran Läkare Vrml Drillsnäppan Vårdcentral Vrml Leander Läkare Vrml Sundgren Läkare Vrml Cech Milan Läkare Vrml Ledin Läkare Vrml Elfstrand Läkare Vrml Norberg Vårdcentral Vstm Odensvi Vårdcentral Vstm Bergström Läkare Vtbn Holmsund Vårdcentral Vtbn Skebäck Vårdcentral Öreb Kungsgatan Vårdcentral Östg Vilbergen Vårdcentral Östg Lyckorna Vårdcentral Östg

20 % Inlämnade sentinelrapporter i % av maximalt möjliga fördelat på landsting 2-1 Blek Upps Sthm Hall SödmVgöt Vrml Skån Nbtn Gävl Jkpg Vnrl Öreb Östg Vstm Kron Kalm Dlrn Vtbn

21 Antal rapporterande sentinelenheter per vecka under säsongen 2-21 v42 v43v44 v45 v46v47 v48 v49v5 v51 v52v1 v2 v3v4 v5 v6v7 v8 v9v1 v11 v12v13 %