CDC Influenza Technical Key Points February 15, 2018

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CDC Influenza Technical Key Pints In this dcument: Summary Key Pints U.S. Vaccine Effectiveness U.S. Flu Activity Update Summary Key Pints On Thursday, tw influenza-related reprts appeared in the Mrbidity and Mrtality Weekly Reprt (MMWR): Interim Estimates f 2017-18 Seasnal Influenza Vaccine Effectiveness United States, February 2018 and Update: Influenza Activity United States, Octber 1, 2017 February 3, 2018 This flu seasn started early and has been intense, with recrd-breaking levels f influenza-like illness and hspitalizatin rates. As f February 3, flu activity was high and widespread acrss mst f the cuntry and significant activity is expected t cntinue fr several weeks. CDC estimates that U.S. flu vaccines this seasn were 36% effective verall against all influenza A and B viruses. This means that this seasn s vaccine reduced a vaccinated persn's risk f getting sick and having t g t the dctr fr flu by abut ne-third. Estimates shwed that effectiveness varied by virus type, subtype and even by the age f the peple being vaccinated in sme cases. As expected, effectiveness against the mst cmmn H3N2 virus was lwer (25%) while effectiveness against H1N1 (67%) and influenza B viruses (42%) was higher. A ntable exceptin t lwer VE against H3N2 viruses was that it ffered gd prtectin (51%) fr children 6 mnths t 8 years. This seasn s vaccine perfrmed as we expected and ffers prtectin fr many peple wh received it. These findings als underscre the need fr better flu vaccines, and the scientific data t help guide effrts t imprve flu vaccines. CDC cntinues t recmmend getting a flu vaccine. While flu vaccine varies in hw well it wrks, it is the best available way t prevent influenza and can reduce illnesses, dctr's visits and hspitalizatins. While flu vaccine effectiveness can vary, CDC recmmends an annual flu vaccine as the best way t prevent seasnal flu. CDC als recmmends rapid treatment f seriusly ill and high-risk suspect flu patients with influenza antiviral drugs. U.S. Flu Vaccine Effectiveness Estimates Tpline Messages On February 15, CDC published a Mrbidity and Mrtality Weekly Reprt (MMWR) entitled Interim Estimates f 2017-18 Seasnal Influenza Vaccine Effectiveness United States, February 2018. This reprt is available nline at https://www.cdc.gv/mmwr/index.html. During each flu seasn since 2004-2005, CDC has estimated the effectiveness f seasnal flu vaccines t prevent labratry-cnfirmed flu illness resulting in a dctr s visit.*

CDC Influenza Technical Key Pints *Clinically what is being measured is labratry cnfirmed influenza assciated with medically attended acute respiratry illness (ARI). This reprt uses data frm 4,562 children and adults enrlled in the U.S. Influenza Vaccine Effectiveness Netwrk (U.S. Flu VE Netwrk) during Nvember 2, 2017 February 3, 2018. During this perid, verall adjusted vaccine effectiveness (VE) against influenza A and B virus infectin was 36% (95% CI: 27% t 44%). This means that CDC s early 2017-2018 estimates shw the flu vaccine has perfrmed similarly t what CDC expected at the beginning f the seasn with A(H3N2) viruses driving the majrity f flu activity. Overall, the seasnal flu vaccine has reduced the risk f getting sick and having t g t the dctr frm flu by abut ne third. Influenza A(H3N2) viruses were respnsible fr mst (69%) f the flu infectins reprted in this study, and as expected, VE was lwer against influenza A(H3N2) viruses. VE was 25% (95% CI: 13% 36%) against illness caused specifically by influenza A(H3N2) viruses. Of nte: VE was much higher in children 6 mnths thrugh 8 years f age: verall VE against influenza A and B viruses was 59% (95% CI: 44% 69%) in this age grup. Children in this age grup als had higher VE specifically against A(H3N2). VE against A(H3N2) viruses was 51% (95% CI: 29% 66%) in children 6 mnths thrugh 8 years f age. This means the risk fr A(H3N2) illness that required a dctr s visit was reduced by mre than half amng this grup f vaccinated children. VE against ther flu viruses, including against influenza A(H1N1) and influenza B viruses, als was higher than against A(H3N2). VE was 67% (CI:54% 76%) against influenza A(H1N1)pdm09 viruses VE was 42% (CI: 25% 56%) against influenza B viruses, prviding a mderate level f prtectin. These interim VE estimates reflect the nging challenges with creating effective flu vaccines against influenza A(H3N2) viruses. (H3N2 viruses have prven prblematic since the 2011 12 seasn.) The interim estimate f 25% VE against A(H3N2) viruses this seasn shws that seasnal flu vaccines are prviding sme prtectin, in cntrast t recently reprted, nn-significant interim estimates f 17% frm Canada and 10% frm Australia. These results als are similar t the final U.S. VE estimates f 32% against A(H3N2) viruses reprted last seasn (2016-2017). Hwever, there is rm fr imprvement. There are many pssible reasns fr lwer effectiveness against H3N2 viruses, and it s imprtant t get mre data t help develp better flu vaccines.

CDC Influenza Technical Key Pints Several hyptheses fr why flu vaccines prvide less benefit against H3N2 viruses culd include the fllwing: Hst factrs, such as hw a persn s unique immune system respnds t vaccinatin r previus flu infectins. Nte: sme existing science suggests that the flu viruses peple are expsed t early in life will affect the way their immune systems respnd t flu infectin r vaccinatin later in life a prcess called imprinting r riginal antigenic sin. Anther factr culd be the unique characteristics f circulating H3N2 viruses and changes that ccur in H3N2 viruses ver time. And lastly, the egg-adapted changes that ccur with greater frequency in H3N2 viruses when they are grwn in eggs as part f the flu vaccine manufacturing prcess. Nte: A(H3N2) viruses are particularly difficult t grw in eggs. While these pints represent factrs that public health scientists and fficials must study and better understand in the future, these early VE estimates als underscre the need fr nging influenza preventin and treatment measures nw. CDC cntinues t recmmend flu vaccinatin because the flu vaccine can still prevent sme infectins with flu viruses that are expected t cntinue circulating fr several weeks. Vaccine effectiveness pint estimates fr influenza B and A (H1N1) indicate that 2017-2018 flu vaccines will reduce peple s risk f flu illness assciated with influenza B r A(H1N1) viruses that results in a dctr s visit by 42% t 67%. Als, even with vaccine effectiveness f 25% against H3N2 viruses, flu vaccinatin will still prevent a substantial amunt f illness due t this virus. Flu vaccinatin has prevented thusands f hspitalizatins during previus seasns when A(H3N2) viruses were predminant, including during the 2014 15 seasn when interim VE estimates were similar t thse reprted here. In the United States, annual vaccinatin against seasnal flu is recmmended fr all peple 6 mnths f age and lder. In additin, apprpriate use f flu antiviral medicatins fr treatment f severely ill peple r peple at high risk fr cmplicatins frm the flu wh develp flu symptms is imprtant, especially amng lder adults, wh currently have the highest hspitalizatin rates. The VE estimates being reprted tday are interim estimates fr the 2017-2018 seasn, and the final VE estimates will be published after the seasn is ver. The final seasn VE estimates may differ frm these interim estimates, and based n previus end f seasn estimates, they may be a little lwer than the interim estimates. CDC will cntinue t mnitr vaccine effectiveness thrugh the rest f the seasn. Yearly mnitring f vaccine effectiveness is critical t identifying vaccine issues that need t be understd and crrected.

CDC Influenza Technical Key Pints Methds At five study sites, patients 6 mnths f age and lder seeking utpatient medical care fr ARI with cugh within 7 days f illness nset were enrlled. The five study sites f the U.S. Flu VE Netwrk are lcated in the fllwing states: Wiscnsin, Michigan, Washingtn Pennsylvania, and Texas. Participants were interviewed t cllect demgraphic data, infrmatin n general and current health status, and symptms, and 2017-2018 vaccinatin status. (Nte: a limitatin f this current data is that vaccinatin status included self-reprt at fur f five sites. Self-reprting can bias results twards higher vaccinatin rates.) Nasal and rpharyngeal swabs (r nasal swabs) were cllected t btain respiratry specimens. Specimens were tested at U.S. Flu VE Netwrk labratries using CDC s rrt-pcr prtcl. VE against all influenza virus types cmbined and against viruses by type/subtype were estimated as 100% x (1 dds rati). Estimates were adjusted fr study site, age grup, sex, race/ethnicity, self-rated general health, number f days frm illness nset t enrllment, and week f illness. Results Interim VE estimates fr the 2017-18 seasn were based n patients enrlled thrugh February 3, 2018. Amng the 4,562 children and adults with ARI enrlled at the five study sites frm Nvember 2, 2017 thrugh February 3, 2018, a ttal f 1,712 (38%) tested psitive fr influenza by rrt-pcr, including 1,392 (81%) influenza A viruses and 323 (19%) influenza B viruses. Amng 1,340 subtyped influenza A viruses, 1,143 (85%) were A/(H3N2) viruses and 208 (16%) were A(H1N1)pdm09 viruses. Mst (98%) f influenza B viruses belnged t the B/Yamagata lineage. The prprtin f patients with influenza differed by study site, sex, age grup, race/ethnicity, self-rated health status, and interval frm illness nset t enrllment. The percentage f patients wh were vaccinated ranged frm 45% t 59% amng study sites and differed by sex, age grup, race/ethnicity, and self-rated health status.

CDC Influenza Technical Key Pints Amng ARI patient participants, 43% f thse with influenza had received the 2017-2018 seasnal influenza vaccine, cmpared with 53% f influenza negative participants. VE During this perid, verall adjusted vaccine effectiveness (VE) against influenza A and B virus infectin assciated with medically attended ARI was 36% (95% CI: 27% t 44%). Mst (69%) f influenza infectins were caused by influenza A(H3N2) viruses. VE was estimated t be 25% (95% CI: 13% 36%) against illness caused by influenza A(H3N2) viruses Of nte: statistically significant prtectin against medically attended influenza was fund amng children 6 mnths thrugh 8 years f age: VE was 59% (95% CI: 44% 69%). VE was estimated t be 67% (CI:54% 76%) against A(H1N1)pdm09 viruses VE was estimated t be 42% (CI: 25% 56%) against influenza B viruses. As f February 3, 2018, a ttal f 257 influenza A(H3N2) viruses frm U.S. Flu VE Netwrk participants had been characterized by CDC. 240 (93%) belnged t either genetic grup 3C.2a (226 viruses) r t the related subgrup 3C.2a1 (14), whereas 17 (7%) belnged t grup 3C.3a. Genetic grup 3C.2a includes the A/Hng Kng/4801/2014 reference virus representing the A(H3N2) cmpnent f the 2017-2018 Nrthern Hemisphere influenza vaccines. Backgrund Each seasn, CDC studies hw well flu vaccines wrk by cllecting data thrugh the U.S. VE netwrk f five sites acrss the United States. Flu vaccine effectiveness can vary each year based n a number f factrs, including the match between vaccine viruses and circulating viruses, what viruses are circulating, and the age and immune factrs f the persn being vaccinated. CDC will cntinue t publish influenza labratry and disease surveillance data weekly in FluView. Updated VE estimates will be prvided as warranted and final VE estimates will be published after the seasn ends. Final seasn VE estimates may differ frm the interim estimates, and may be a little lwer than the interim estimates. U.S. Flu Activity Update MMWR: Influenza Activity Influenza Activity United States, Octber 1, 2017 February 3, 2018 Seasnal Flu Update: The MMWR reprt is available n CDC s website at: https://www.cdc.gv/mmwr/index.html. Influenza illness during the 2017-2018 seasn has been substantial thus far, with sme f the highest levels f ILI and hspitalizatin rates in recent years and elevated activity ccurring in mst f the cuntry simultaneusly.

CDC Influenza Technical Key Pints Clinical labratries tested 666,493 specimens fr influenza virus, and 124,316 (18.7%) tested psitive. The percentage f specimens testing psitive fr influenza A viruses peaked at 21.8% during the week ending January 13; the percentage testing psitive fr influenza B viruses has cntinued t increase and was 8.1% during the week ending February 3. Public health labratries tested 51,014 specimens fr influenza virus, and 27,669 tested psitive. This includes 23,257 (84.1%) fr influenza A and 4,412 (15.9%) fr influenza B viruses. Nearly all the influenza viruses characterized during this perid were genetically r antigenically similar t the cell grwn reference viruses representing vaccine cmpnents recmmended fr prductin in the 2017 18 Nrthern Hemisphere influenza vaccines. Fr the A(H3N2) viruses, 98.1% were antigenically similar t the cell-prpagated reference virus representing the vaccine cmpnent but nly 64.4% were antigenically similar t the egg-prpagated reference virus representing the vaccine cmpnent. Fur viruses (all A(H1N1pdm09 viruses) cllected in the U.S. this seasn were fund t be resistant t seltamivir and peramivir. N antiviral resistance t seltamivir, zanamivir, r peramivir has been identified amng influenza A(H3N2) r influenza B viruses cllected since Octber 1, 2017. Influenza-like Illness The weekly percentage f utpatient visits t heath care prviders participating in ILINet fr ILI ranged frm 1.3% t 7.7%. The percentage first exceeded the natinal baseline level f 2.2% during the week ending Nvember 25, 2017 (week 47) and has remained at r abve the baseline fr 11 cnsecutive weeks. Frm the week ending December 23, 2017, (week 51), thrugh the week ending February 3, 2018, (week 5), all 10 HHS regins reprted a percentage f utpatient visits fr ILI at r abve their regin-specific baseline levels. Since the week ending December 30, 2017, mre than half f the 53 jurisdictins (50 states, District f Clumbia, New Yrk City, and Puert Ric) experienced high ILI activity each week, with the largest number f jurisdictins (46, 87%) experiencing high ILI activity during the week ending February 3, 2018. During the past five seasns, the largest number f jurisdictins experiencing high ILI activity in a single week ranged frm 16 (30%) during the 2015 16 seasn t 31 (58%) during the 2012 13 and 2014 15 seasns. Gegraphic Spread: During the 2017 18 seasn, the peak number f jurisdictins reprting widespread activity in a single week was 50 (93%); this ccurred fr the 3 cnsecutive weeks (weeks ending January 6, January 13, and January 20, 2018).

CDC Influenza Technical Key Pints During the previus five influenza seasns, the peak number f jurisdictins reprting widespread activity in a single week during each seasn has ranged frm 41 (76%) in the 2015 16 seasn t 48 (89%) during the 2012 13 seasn. Hspitalizatins: Frm Octber 1, 2017 February 3, 2018, 17,101 labratry-cnfirmed influenza-related hspitalizatins were reprted, representing a cumulative incidence amng all age grups f 59.9 per 100,000 ppulatin. The cumulative influenza hspitalizatin rates per 100,000 ppulatin during Octber 1, 2017 February 3, 2018, fr persns aged 0 4 years, 5 17 years, 18 49 years, 50 64 years, and 65 years were 40.0, 10.3, 18.3, 63.1, and 263.6, respectively. Persns aged 65 years had the highest rate and accunted fr 59% f reprted influenza-assciated hspitalizatins. Amng all hspitalizatins, 14,770 (86.4%) were assciated with influenza A virus infectin. The remaining hspitalizatins included 2,251 (13.2%) with influenza B virus infectin, 43 (0.3%) with influenza A virus and influenza B virus cinfectin, and 37 (0.2%) with influenza virus infectin fr which the type was nt determined. Amng the 3,841 patients fr whm influenza A subtype infrmatin was available, 3,308 (86.1%) were infected with influenza A(H3N2) viruses and 533 (13.9%) with influenza A(H1N1)pdm09 viruses. Amng hspitalized persns aged 0 64 years fr whm influenza A subtype infrmatin was available, 23.6% were infected with influenza A(H1N1)pdm09 viruses, cmpared with nly 7.0% f thse aged 65 years. Infrmatin n underlying medical cnditins was available fr 2,147 (12.6%) hspitalized patients with labratry-cnfirmed influenza as f February 3, 2018. Amng 1,955 hspitalized adults with infrmatin n underlying medical cnditin available, 1,325 (67.8%) had at least ne underlying medical cnditin that placed them at high risk fr influenza-assciated cmplicatins. The mst cmmnly reprted medical cnditins were cardivascular disease (35.5%), metablic disrders (33.0%), besity (25.2%), and chrnic lung disease (23.6%). Amng 192 hspitalized children with infrmatin n underlying medical cnditins available, 97 (50.5%) had at least ne underlying medical cnditin. The mst cmmnly reprted cnditins were asthma (22.8%), neurlgic disrders (14.4%), and besity (10.1%). Amng 151 hspitalized wmen aged 15 44 years with infrmatin n pregnancy status, 36 (23.8%) were pregnant.

CDC Influenza Technical Key Pints Pneumnia and Influenza-Attributed Deaths: CDC tracks pneumnia and influenza (P&I) attributed deaths thrugh the Natinal Center fr Health Statistics (NCHS) Mrtality Reprting System. Accrding t this CDC surveillance system: Frm Octber 1, 2017, t January 20, 2018, the weekly percentage f deaths attributed t P&I has ranged frm 5.8% t 10.1% and has exceeded the epidemic threshld fr 5 cnsecutive weeks. P&I percentages fr recent weeks are likely t be artificially lw because f a delay in manual cding fr deaths ccurring in 2018. The percentage f deaths caused by P&I is higher amng manually cded death certificates than amng machine-cded death certificates. The percentage f deaths caused by P&I will likely increase as mre data becme available. Pediatric Deaths: As f February 3, 2018, (week 5), 63 labratry-cnfirmed influenza-assciated pediatric deaths ccurring during the 2017 18 seasn were reprted t CDC. Of the 63 deaths: Fifteen deaths were assciated with an influenza A(H1N1)pdm09 virus infectin Sixteen were assciated with an influenza A(H3N2) virus infectin Furteen were assciated with infectin with an influenza A virus fr which n subtyping was perfrmed, and 18 were assciated with an influenza B virus infectin. Amng the children fr whm medical histry is knwn, 54% were therwise healthy. Of the children wh were eligible fr vaccinatin ( 6 mnths f age) and fr whm vaccinatin status was knwn, 26% received at least 1 dse f influenza vaccine befre nset f illness. Since influenza-assciated pediatric mrtality became a natinally ntifiable cnditin in 2004, the number f influenza-assciated pediatric deaths per seasn has ranged frm 37 t 171, excluding the 2009 pandemic, when there were 358 pediatric deaths during April 15, 2009 Octber 2, 2010 were reprted t CDC. Flu Severity: With several mre weeks f elevated influenza activity anticipated this seasn, it is t early t assess verall severity f the seasn. Hwever, estimates f the burden f influenza disease frm the 2012 13 and 2014 15 seasns prvide an indicatin f what might be anticipated fr the 2017 18 seasn. CDC estimated that during each f thse seasns influenza accunted fr as many as 35.6 millin illnesses, 16.6 millin medically attended visits, 710,000 hspitalizatins and 56,000 deaths. CDC Discussin/Recmmendatins:

CDC Influenza Technical Key Pints Influenza A(H3N2) is the predminant influenza virus circulating this seasn. Past A(H3N2) virus predminant seasns such as the 2012 13 and 2014 15 seasns had increased numbers f influenza related infectins, hspitalizatins, and deaths cmpared with A(H1N1)pdm09 virus-predminant seasns. With several mre weeks f elevated influenza activity expected, an increasing prprtin f influenza A(H1N1)pdm09 and influenza B viruses, and the ptential t prevent significant illness thrugh influenza vaccinatin, CDC cntinues t recmmend influenza vaccinatin at this time. In the United States, annual vaccinatin against seasnal flu is recmmended fr all peple 6 mnths f age and lder. During influenza seasns with increased severity, influenza antiviral medicatins fr treatment f influenza are an even mre imprtant adjunct t vaccinatin. Three neuraminidase inhibitr antiviral medicatins are apprved and recmmended fr use in the United States during the 2017 18 influenza seasn: Oral seltamivir (available as a generic r under the trade name Tamiflu), Inhaled zanamivir Intravenus peramivir Treatment with influenza antiviral medicatins initiated as clse t the nset f illness as pssible is recmmended fr patients with cnfirmed r suspected influenza wh have severe, cmplicated, r prgressive illness. Clinical benefit f antiviral treatment is greatest when treatment begins within 48 hurs after symptm nset; hwever, antiviral treatment initiated later than 48 hurs after illness nset can still be beneficial fr sme patients. A CDC health advisry released n December 27, 2017, regarding treatment with antiviral medicatins is available at https://emergency.cdc.gv/han/han00409.asp. Fr cmplete CDC antiviral guidelines, please see https://www.cdc.gv/flu/prfessinals/antivirals/index.htm. Nvel Influenza A Viruses: Six human infectins with nvel influenza A viruses were reprted t CDC during Octber 1, 2017 February 3, 2018. All f these were variant virus infectins (human infectins with influenza viruses that nrmally circulate in swine). Five f these infectins were previusly described. The sixth human infectin with a nvel influenza A virus was caused by an influenza A(H3N2) variant (A[H3N2]v) virus in Iwa in an adult patient with nset f respiratry symptms in Nvember 2017. This patient reprted expsure t swine during the week preceding illness nset, was nt hspitalized, and has fully recvered. N sustained human-t-human transmissin was identified. Fr mre infrmatin:

CDC Influenza Technical Key Pints Influenza surveillance reprts fr the United States are psted nline weekly (https://www.cdc.gv/flu/weekly). Additinal infrmatin regarding influenza viruses, influenza surveillance, influenza vaccine, influenza antiviral medicatins, and nvel influenza A infectins in humans is available nline (https://www.cdc.gv/flu).