Rezultatele investigatiilor de laborator pentru gripa realizate in sezonul particularitati

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1 IC Rezultatele investigatiilor de laborator pentru gripa realizate in sezonul particularitati Intâlnirea de lucru cu tema Rezultatele supravegherii infectiilor respiratorii acute, a gripei si a SARI in sezonul si lansarea Metodologiei de supraveghere pentru sezonul Bucuresti, noiembrie 2016

2 NIC - Algorithm Sample ILI/SARI RRT-PCR for influenza virus type A and type B SARI negative for influenza virus Type A positive Type B positive >10% of positive influenza virus Subtype: A/H1N1pdm 09 and A/H3 SNP Oseltamivir (RRT-PCR) Genetic lineage (RRT-PCR ) Isolation (MDCK, MDCK Siat) Other respiratory viruses MERS CoV (screening and confirmation) HA/NA genes sequencing - genetic characterization - relevant mutations for antiviral resistance - HI assay (antigenic characterization) - Phenotypic test for antiviral sensitivity

3 Supravegherea virologica a activitatii gripale in Romania sezon 2015/16 Primul virus gripal din sistemul santinela a fost detectat in saptamana 42/2015, un virus A(H1N1)pdm09 (GL/12/004), al doilea in saptamana 51/2015, un virus A(H3N2) (INBI Prof.Matei Bals) dar detectii constante au inceput in saptamana 3 din Cel mai mare numar de specimene positive detectate s-a inregistrat in saptamanile 5-9.

4 # Activitatea gripei a fost caracterizata prin dominanta virusului gripal A(H1N1) pdm09, dar virusuri A(H3N2) si tip B au fost detectate pe tot parcursul sezonului. 200 Fig. 1. Weekly distribution of influenza virus detection in in ILI sentinel and nonsentinel Romania H3 B H1pdm09 Neg week

5 Total probe ILI Distributia detectiilor de virus gripal pe tip/subtip la pacientii cu ILI N = 1905 (%) Sistem santinela N = 449 (23.6%) Sistem non-santinela N = 1456 (76.4%) Pozitive 835 (43.8) 166 (37.0) 669 (45.9) - tip A: 729 (87.3) 144 (86.7) 585 (87.4) A/H1pdm (91.1) 124 (86.1 ) 540 (92.3) A/H3 65 (8.9) 20 (13.9) 45 (7.7) - tip B 106 (12.7) 22 (13.3) 84 (12.6) Alte virusuri 13 (0.7) 0 13 (0.9) Negative 1057 (55.5) 283 (63.0) 774 (53.2) 98 dintre detectiile de virus B (ILI si SARI) testate pentru linii genetice: 97 au fost B(Vic)-lineage si 1 B(Yam)-lineage.

6 SARI in sistemul santinela si non-santinela: 646 specimene testate Pozitive virus gripal 309 (47.8%): 107 cazuri fatale: 101 H1 pdm09 (94.4%) Tip A: 299 (96.8%): 5 H3 H1N1 pdm09: 283 (94.6%) 1 tip B H3N2: 16 (5.4%) Tip B: 10 (3.2 %) Alte 3 cazuri fatale pozitive pentru virus Respirator Syncytial (SB/01/04, 5 luni, IS/03/089, 59 ani, SPH001, 82 ani)

7 Fig 2. Distributia virusurilor respiratorii in probe ILI 12% 8% 2% Fig 3. Distributia virusurilor respiratorii in probe SARI 3% 6% 3% 5% 78% 83% IV H1pdm09 IV H3 IV type B Other respiratory viruses IV H1pdm09 IV H3 IV type B RSV Other respiratory viruses 30 specimene pozitive pentru alte virusuri respiratorii: 19 RSV, 1hMPV, 2 Coronavirus 229E/NL63, 1 Adenovirus, 2 Rhinovirus, 5 Bocavirus.

8 Number of antigenic (AG) and genetic (GEN) characterisations reported, by country in the influenza season 2015/ antigenic and 3056 genetic characterisations were reported to TESSy Sursa: TESSy_Virus characterisation summary_wk wk

9 2015/16

10 Caracterizarea antigenica a virusului gripal in sezonul 2015/16 (N = 177) % 7% 10 A/H3N2: A/Switzerland/ /2013 A/H3N2: Hong Kong/4801/2014 A/H3N2: AH3 NOCAT 83% 2 A/H1N1 pdm09 A/H3N2 B 15 B/Phuket/3073/2013 BYam B/Brisbane/60/2008 B/Vic

11 Sensibilitatea la antivirale prin metoda fenotipica H3 10 BC; BB; CL; CT; GL; GR B/Vic 3 BB; CT; DJ B/Yam 1 BB H1 65 BB; BZ; CL; CT; DB; DJ; GL; IS, MS, OT; TM; VN Total 79 Toate tulpinile au arătat o inhibare normală. In plus, toate virusurile gripale N1 testate pentru detectarea mutatiei H275Y s-au dovedit a fi sensibile la oseltamivir.

12 Caracterizarea genetica a virusului gripal in sezonul 2015/16 (N = 137) 2 A/H1N1 pdm09 A/H3N2 B 13% 12% 16 genah3/switzerland/ /2013 genah3/hong Kong/4801/ % 15 B/Phuket/3073/2013 BYam B/Brisbane/60/2008 B/Vic

13 2015/16

14 Compararea filogenetica a genelor HA ale virusurilor gripale A/H1N1pdm09 circulante in sezonul 2015/16 cu tulpina vaccinala Albastru: ILI; Rosu: SARI; Bold: Deces

15 Substitution D222G toti pacientii spitalizati * Coinfection H1 pdm09 and type B Record ID A/Timis/134705/2013 A/Iasi/138230/2013 A/Cluj/178247/2015 A/Cluj/192516/2016 A/Bacau/194305/2016 A/Suceava/194312/2016 Collecti on 02/ / / / / /2016 AV Age/ Gender Vacc Immunocompro mised/comorbidit ies Complic. Outcom e No 31/F No Pregnancy, obesity Pneumonia Alive No 54/F No Severe idiopathic pancytopenia Pneumonia* Died Yes 62/F No Unknown Pneumonia Died Yes 38/M No Unknown Pneumonia Died No 32/F No Pregnancy, obesity Pneumonia Died No 40/M No Unknown Pneumonia Died

16 Compararea filogenetica a genelor HA ale virusurilor gripale A/H3N2 circulante in sezonul 2015/16 cu tulpina vaccinala

17 Compararea filogenetica a genelor HA ale virusurilor gripale tip B, circulante in sezonul 2015/16 cu tulpinile vaccinale

18 Concluzii 2015/16 Virusurile A(H1N1)pdm09 au dominat sezonul si au fost antigenic similare cu componenta vaccinului. Intre virusurile tip B, linia Victoria a fost dominanta si neinclusa in vaccinul trivalent. Majoritatea virusurilor A(H3N2) nu au putut fi caracterizate antigenic datorita reducerii capacitatii de aglutinare a eritrocitelor de cobai/curcan chiar si in prezenta de oseltamivir. Nu au fost dovezi ale reducerii inhibarii virusurilor gripale A si B la inhibitori ai neuraminidazei. O mai bună diagnosticare a gripei, dar si a altor infectii acute respiratorii, in spitale ar putea îmbunătăti măsurile de control al acestora si prescrierea adecvata de medicamente antivirale.

19 Detectia moleculara a virusului gripal (VG) si a altor virusuri respiratorii in sezonul 2016/17 Laborator INSP CRSP Timisoara VG tip VG subtip INSP CRSP Iasi INBI M.Bals Bucuresti Sp.Clin.B.Inf. Constanta VG - tip si RSV Sp.Clin.B.Inf. Cluj VG - tip si nongripale CNG Cantacuzino

20 Transferul probelor biologice pozitive pentru virus gripal de la laboratoarele Centrelor Regionale la CNG Cantacuzino Cinci probe per tip, per saptamana, sau majoritatea, dacã detectiile sunt sub cinci/sãptãmânã. Toate detectiile de virus gripal tip A nesubtipabil. Frecventa transportului poate varia, saptamanal sau la doua saptamani, sau ori de cate ori este nevoie.

21 Transferul probelor biologice pozitive pentru virus gripal de la TOATE laboratoarele la CNG Cantacuzino Pe langa aceasta "cotă" solicitam probe de la cazuri speciale, care pot fi boli grave sau atipice, circumstante epidemiologice speciale (de exemplu, suspiciune de infectie zoonotica, suspiciune de MERS-CoV) sau suspiciune de "esec vaccinal" / rezistenta la antivirale. CNG asteapta primele prelevate pozitive. Este important sa se cunoasca daca sunt asemanatoare cu tulpinile vaccinale si sa se observe eventuala aparitie de noi grupuri filogenetice. Toate detectiile pozitive pentru mai multe gene de tipuri/subtipuri diferite (posibilele coinfectii care trebuie confirmate prin metode alternative).

22 FluNet 14 November 2016 Source: Global Influenza Surveillance and Response System (GISRS) National Influenza Centres (NICs) and other national influenza laboratories from 85 countries, areas or territories reported data to FluNet: 84.2% influenza A: 5.3% A(H1N1)pdm % A(H3N2) 15.8% influenza B 30% B-Yamagata lineage 70% B-Victoria lineage. Romania 1 pozitiv tip B, B/Victoria lineage, ca si tulpina vaccinala, import din America de Sud, SJU Boli Infectioase Ploiesti 1 pozitiv tip A, subtip H3N2, grup genetic A/Bolzana/7/2016 clade 3C.2a1, ca si tulpina vaccinala (3C.2a), Sp.Clin.Boli Inf. Si Tropicale Dr.V.Babes 1 pozitiv tip A (transfer de la INBI Prof.Matei Bals ), subtip H3N2.

23 Case-control study hospital based (N = 166) Cases Controls IMOVE + si IMOVE Case-control study primary care based (N = 152) Cases Controls Vaccinated 6 (9.1%) 6 (6%) Unvaccinated Total We provided data for pooled analysis to measure VE among the elderly. Vaccinated 3 (4.2%) 10 (12.5%) Unvaccinated Total The adjusted VE for age group, chronic condition and onset month is 64.5% (95%CI: ). The low number of specimens for VE analysis resulted in broad confidence intervals in the VE analysis.

24 Acknowledgements WHO Collaborating Centre for Reference and Research on Influenza Crick Worldwide Influenza Centre, The Francis Crick Institute, Mill Hill Laboratory London for the excellent scientific and technical support. WHO EURO funding part of our work through the IMOVE study. Special thanks to Odette Popovici, MD, senior epidemiologist, National Institute of Public Health, focal point for SARI surveillance and Rodica Popescu, MD, senior epidemiologist, National Institute of Public Health, focal point for ILI surveillance. We acknowledge the hard work performed by physicians and their patients, epidemiologists and other contributors in influenza surveillance. Technical work performed by our colleagues George Necula and Sorin Dinu, Luiza Ustea, Emilia Dobre and Mirela Ene. Report prepared by: Alina Elena Ivanciuc, Mihaela Lazãr, Cristina Tecu, Maria Elena Mihai, Carmen Maria Cherciu, Daniela Pitigoi and Emilia Lupulescu

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