Rpid communictions Estimting the impct of the influenz pndemic on mortlity in the elderly in Nvrre, Spin J Cstill (jcstilc@nvrr.es) 1, J Etxeberri 1, E Ardnz 1, Y Floristán 1, R López Escudero 1, M Guevr 1 1. Public Helth Institute of Nvrre nd Centro de Investigción Biomédic en Red de Epidemiologí y Slud Públic (CIBERESP, Biomedicl Reserch Network of Epidemiology nd Public Helth), Pmplon, Spin Cittion style for this rticle: Cittion style for this rticle: Cstill J, Etxeberri J, Ardnz E, Floristán Y, López Escudero R, Guevr M. Estimting the impct of the influenz pndemic on mortlity in the elderly in Nvrre, Spin. Euro Surveill. 2010;15(5):pii=19481. Avilble online: http:///viewarticle. spx?articleid=19481 This rticle hs been published on 4 Februry 2010 We nlysed mortlity mong people ged 65 yers or older in Nvrre, Spin in nd compred it with the men for the sme period of time in the previous three yers. In the pndemic weeks 24 to 52 we observed 4.9% more deths thn expected (p=0.0268). Excess mortlity occurred during the circultion of sesonl influenz (8.0%, p=0.0367) nd the first wve of pndemic influenz (9.9%, p=0.0079). In the second wve of pndemic influenz there ws non-significnt excess of deths (5.2%, p=0.1166). Surveillnce of lbortory-confirmed severe influenz cses detected only one deth in this ge group. Introduction Influenz hs usully been ssocited with incresed mortlity in the elderly [1-4]. However, the lrge mjority of influenz cses re not lbortory-confirmed, nd only smll prt of the excess deths occurring in periods when influenz virus is circulting re registered s deths cused by influenz [5]. The influenz pndemic coincided with incresed use of lbortory techniques to confirm influenz cses, lthough confirmtion ws limited to only smll proportion of ll possible cses [6]. In Spin, s in other developed countries, influenz testing hs been systemticlly incorported for ll ptients hospitlised with cute respirtory disese [7]. From the stndpoint of epidemiologicl surveillnce, this ws interpreted to men tht the lrge mjority of severe cses nd of deths from the influenz virus cn now be confirmed [8]. Bsed on this informtion, the pndemic influenz virus hs been relted to reltively low number of deths in ptients with lbortory-confirmed results, smll proportion of which occurred in elderly people [9-11]. The objective of this study ws to evlute the possible repercussions of the circultion of the pndemic influenz on mortlity in dults ged 65 yers nd older. Methods The study ws crried out in Nvrre, Spin ( region of 620,000 inhbitnts). Influenz surveillnce in this region is bsed on utomtic reporting of cses of influenz-like illness dignosed in primry helthcre nd hospitls. Virologicl surveillnce includes weekly reports from ll three lbortories tht perform influenz tests to confirm the custive gent. Through sentinel network composed of representtive smple of 76 generl prctitioners nd primry helthcre peditricins covering 18% of the popultion, nsophryngel swbs were tken from systemticlly selected ptients with influenz-like illness, fter receiving informed consent from the ptients or their prents. Hospitlised ptients with cute respirtory disese were swbbed for influenz virus testing in ccordnce with hospitl protocols until week 20 of. Swbbing ws subsequently extended to ll ptients who were treted in emergency rooms or hospitlised with cute severe respirtory disese possibly cused by influenz. Swbs were processed in the lbortory by reverse trnscription polymerse chin rection (RT-PCR) nd virus culture. Positive smples were chrcterised for influenz A (subtypes H1 nd H3) nd influenz B virus using immunofluorescence nd RT-PCR. Strting in June, rel-time RT-PCR for detection of the influenz H1N1 virus ws performed on ll swbs. Bsed on the incidence of reported influenz-like illness nd the type of influenz virus in circultion in the region, we distinguished six periods in. Between weeks 1 nd 8, wve of sesonl influenz ws identified, with 94% of the circulting strins corresponding to type A(H3N2). From week 9 to 15, there ws only spordic circultion of influenz B, with very low incidence. Between weeks 16 nd 23, no influenz virus ws detected (inter-sesonl period). From week 24 to 35, influenz ctivity re-emerged with ll 98 positive swbs corresponding to the pndemic influenz virus (first wve of pndemic influenz). From week 36 to 39, spordic detection of this strin continued, with low incidence of influenz-like illness (pndemic remission period). From week 40 to 49 there ws lrge wve of influenz with high incidence nd ll circulting strins corresponding to the pndemic influenz virus (second wve of pndemic influenz). Finlly, from week 50 to 52 there ws new remission 1
period with low incidence nd only spordic detection of pndemic influenz. In the present study we used informtion from computerised mortlity registers, which cover pproximtely 70% of the popultion (76,201 dults ged 65 yers or older) nd of the deths in the region nd provide informtion in rel time. We nlysed ll deths reported in dults ged 65 yers or older in nd compred them with the expected number of deths, clculted s the verge of deths for the sme periods of the three preceding yers (2006, 2007 nd 2008). For comprison we used the periods defined ccording to the incidence nd the type of influenz virus in circultion in Nvrre in. Poisson distribution ws used to compre observed nd expected deths. Rtes were clculted with the popultion covered by the computerised registers on 1 Jnury of ech yer tken s the denomintor. Stndrdised mortlity rtios were obtined using the popultion on 1 Jnury s the reference popultion. Avilble ge groups were 65-69, 70-74, 75-79, 80-84 nd 85 yers. Results Active epidemiologicl nd virologicl surveillnce of influenz detected the first lbortory-confirmed cse of pndemic influenz in Nvrre in week 24 of. Between tht dte nd the end of, 3,190 swbs were tested for influenz, nd 933 cses of lbortory-confirmed pndemic influenz were detected. The number of cses of influenz-like illness tht received medicl ttention reched 37 cses per 1,000 popultion (n=22,374). During, 223 ptients dignosed with pndemic influenz in Nvrre required hospitlistion, 17 of them required dmission to intensive cre units, nd four died. In dults ged 65 yers nd older, 829 tests for influenz were performed, 28 ptients with confirmed pndemic influenz required hospitl dmission, two in intensive cre units, nd one person died. The Figure shows the number of deths per week observed in persons ged 65 yers or older compred with the number of expected deths, nd indictes the periods with influenz ctivity in nd in the reference yers. In the pndemic period (weeks 24 to 52) 1,671 deths were registered in persons ged 65 yers or older, 4.9% more thn expected (p=0.0268). In contrst, in the weeks without circultion of pndemic virus (weeks 1 to 23), there ws no significnt difference between observed nd expected deths (Tble 1). Tble 2 shows the mortlity in short periods bsed on incidence of influenz-like illness nd the type of virus circulting in the region. Sttisticlly significnt excess mortlity mong dults ged 65 yers or older Figure Number of deths per week registered nd expected (men of the three previous yers) in the popultion ged 65 yers or older covered by computerised deth registers, Nvrre, 100 Sesonl influenz 2008 - First pndemic wve in Second pndemic wve in 80 Number of deths 60 40 20 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 Week Observed deths Expected deths with influenz ctivity in the three yers of reference The dt represented re moving verges clculted over three vlues with weights 0.25, 0.5, 0.25. 2
Tble 1 Mortlity mong dults ged 65 yers or older in the popultion covered by computerised deth registers in Nvrre, 2006- Non-pndemic period weeks 1 to 23 Pndemic period weeks 24 to 52 Expected deths (nnul verge for 2006-2008) 1,390 1,593 Observed deths in 1,410 1,671 Percentge of chnge +1.4% +4.9% P vlue 0.2993 0.0268 Annul verge mortlity rte for 2006-2008 4,255 3,867 Mortlity rte in 4,198 3,946 Percentge of chnge -1.3% +2.0% P vlue 0.6785 0.4753 Stndrdised mortlity rtio 0.96 1.00 ws observed in periods with circultion of sesonl or pndemic influenz virus, but not in periods when influenz ctivity ws low or bsent. There ws n excess mortlity of 8.0% (p=0.0367) in the sesonl influenz period compred with the expected number of deths. There ws lso n excess mortlity of 9.9% (p=0.0079) coinciding with the first wve of pndemic influenz, nd gin n excess mortlity of 5.2% in the second wve, lthough the ltter did not rech sttisticl significnce (p=0.1166) (Tble 2). During the study there were no other known cuses tht could explin the excess mortlity observed. In the summer of, the het lert threshold (minimum temperture of 21.5 ºC) ws not exceeded t ny time in Nvrre, nd the dys with highest mortlity did not coincide with the hottest dys. When we repeted the comprisons, tking s the reference the men number of deths in the sme period in the previous five yers, the min study findings were not ffected. Rtes per 100,000 person-yers. Tble 2 Epidemiologicl nd virologicl surveillnce of influenz in ll ges, nd mortlity in the popultion ged 65 yers or older, in six periods with circultion of different influenz viruses, Nvrre, 1 to 8 9 to 15 16 to 23 24 to 35 36 to 39 40 to 49 50 to 52 Mediclly-ttended influenz-like illness Number of cses 6,683 680 182 2,495 1,385 17,578 1,175 Incidence rte per 1,000 inhbitnts 10.9 1.1 0.3 4.1 2.3 28.2 1.9 Lbortory-confirmed influenz in sentinel network Swbs from sentinel network ptients 107 19 27 245 64 419 62 Number of lbortory-confirmed cses (%) 57 (53%) 12 (63%) 0 (0%) Circulting influenz strins A(H3N2) B None 98 (39%) 2 (3%) 213 (51%) 14 (23%) Lbortory-confirmed influenz mong hospitlised ptients Hospitlised ptients 12 3 0 52 14 143 14 Intensive cre units 2 0 0 6 3 7 1 Deths 0 0 0 0 0 4 0 Deths in popultion ged 65 yers or older Expected number (nnul verge for 2006-2008 period) 528 432 431 612 216 569 197 Observed number in 570 395 445 673 207 598 193 Percentge of chnge +8.0% -8.6% +3.3% +9.9% -4.0% +5.2% -1.9% P vlue 0.0367 0.0346 0.2563 0.0079 0.2748 0.1166 0.6217 Mortlity rtes in popultion ged 65 or older Annul verge mortlity rte for 2006-2008 period** 5,305 4,344 3,789 3,591 3,795 4,002 4,614 Mortlity rte in b 5,576 3,864 3,809 3,840 3,544 4,095 4,405 Percentge of chnge +5.1% -11.0% +0.5% +6.9% -6.6% +2.3% -4.5% Stndrdised mortlity rtio 1.03 0.87 0.98 1.05 0.91 1.00 0.93 Influenz A(H3N2): 94%; sesonl influenz : 2%; influenz B: 4%. b Rte per 100,000 person-yers. 3
Discussion Our results suggest excess mortlity ffecting older dults tht coincided with the time when the pndemic influenz ws in circultion. Similr excess mortlity hs lso been observed to coincide with circultion of the sesonl influenz virus, but not in periods with little or no influenz ctivity. Most of the excess deths in our study were not identified s influenz deths, despite systemtic testing during the pndemic period of cses with cute respirtory disese requiring hospitl dmission, s well s substntil number of ptients in primry nd emergency cre. By focusing concern on deths occurring in persons with lbortory-confirmed pndemic influenz [8-11] this dditionl mortlity my not be detected. It is possible tht some of these deths occurred outside the hospitl, or tht the influenz ws hidden by nother underlying pthology. Previous studies hve suggested tht influenz cn trigger or excerbte non-infectious pthologies such s crdiovsculr diseses [12]. Our study ws ecologicl in design; therefore cuses other thn the influenz pndemic could explin the detected excess mortlity. However, the fct tht the excess mortlity coincided with periods of virl circultion, whether sesonl or pndemic, lends some strength to this hypothesis. Moreover, we reviewed nd ruled out other cuses tht re most frequently ssocited with excess mortlity in the older popultion. Crrying out the study in reltively smll geogrphic re llowed us to discriminte between periods of cler influenz ctivity nd those in which influenz ws bsent. This mde it possible to estblish more precisely the temporl coincidence between influenz circultion nd excess deths, n ssocition tht my be diluted when lrger geogrphic res re nlysed. Some possible bises hve to be considered. The popultion ged 65 yers or older incresed by 3% from the period between 2006 nd 2008 to, nd the popultion ged 85 yers nd over incresed by 10%. This explins the differences between the results in bsolute numbers nd rtes, with predominnce of generl upwrd trends in the bsolute number of deths nd downwrd trends in crude nd djusted mortlity rtes. These chnges in the popultion produce greter number of deths, regrdless of other fctors, but do not ffect djusted mortlity rtes. On the contrry, if the influenz hs produced n increse in mortlity, it my be prtilly hidden by the descending seculr trend in the generl mortlity. Therefore, similr comprisons of observed versus expected mortlity in periods with nd without influenz ctivity llow us to estimte the impct of the influenz on mortlity, voiding the mentioned bises. The source of mortlity dt represents lrge nd stble proportion of the popultion of Nvrre. The registers include deths occurring in the mjor municiplities, but do not include deths in the Nvrre popultion tht hve occurred outside these municiplities. This probbly hs little consequence when nlysing the popultion ged 65 yers or older, given their low geogrphic mobility. In ny cse, it seems pproprite to evlute the ssocition between influenz circultion (cute disese) nd deths occurring in the sme plce, regrdless of whether or not it is the usul residence. The method of nlysis used probbly does not llow us to show the impct of influenz on mortlity in ll its mgnitude. Other fctors ffecting mortlity could hve been present in the reference periods of the previous three yers, which would tend to ttenute the excess mortlity shown in. For exmple, wves of sesonl influenz lso occurred in the reference yers, which ffected the periods between the first fifteen nd lst six weeks in the yer (Figure). This could explin why the deths coinciding with the summer wve of pndemic influenz were clerly shown s excess mortlity, wheres excess mortlity during the times of the yer when influenz is usully present my hve been prtilly hidden by including in the reference periods weeks in which sesonl virus ws circulting in previous yers. In conclusion, these results suggest tht the pndemic influenz my hve been ccompnied by incresed mortlity in older persons, which would not hve been detected by looking for cses of cute respirtory disese in hospitls, either becuse the deth could hve occurred outside the hospitl or becuse influenz infection ws not suspected. Acknowledgements This work ws supported in prt by the Fondo de Investigción Snitri, Instituto de Slud Crlos III (PI061346). References 1. Glezen WP. Serious morbidity nd mortlity ssocited with influenz epidemics. Epidemiol Rev. 1982;4:25-44. 2. Thompson WW, Shy DK, Weintrub E, Brmmer L, Cox N, Anderson LJ, et l. 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