natural treatment for the disease yellow fever in adults

if we can move along now. i stand corrected.this is the session on yellow fever. and ifdr. bocchini can introduce then dr. staples.>> thank you for not allowing anybody to take a break.it could shorten the discussion period for this session.so today the yellow fever vaccines work group will presentfollow-up information related to yellow fever vaccine inanticipation of an acip vote. these are the members of thework group and i want to thank

everyone for theirparticipation, especially dr. staples for her work as thecds cd lead for this work group. so just as a quick reminder foreveryone, in april 2013 the world health organization'sstrategic advisory group of experts concluded that a singledose of yellow fever vaccine is sufficient to promote lifelongprotection and booster doses were no longer needed.additional data, however, was indicated by world healthorganization for identifying specific risk groups which mightbenefit from second dose or

booster dose.since 1965, international health regulations allow countries torequire yellow fever vaccine dose within the past ten yearsfor entry. in june of 2014, the worldhealth organization, world health assembly adopted anamendment to the ihr that extend yellow fever protection to thelife of the person vaccinated. this new change will take effectin june of 2016, so there will no longer be a requirement forcountries to maintain that ten-year interval.so because of those changes, the

je vaccine work group wasreformed to include yellow fever vaccine in october 2013.we've met multiple times to discuss the booster doses, and iwon't go through the data, but as you know, we've had threeprevious presentations to acip on this topic, including apresentation of grade in june 2014.and we presented the initial set of recommendations.we received feedback from the acip and subsequently continuedto meet to address the issues raised by acip.so overall at the june meeting,

there was general support toremove booster dose requirement, but questions were raised aboutgroups for whom additional doses would be considered.fist was some discussion about the immune response a inchildren, the interval between doses in certain group, and whatconstitutes high-risk settings for exposure to yellow fever.the issue related to children, we worked with the committee oninfectious diseases, a presentation was made at thenovember meeting, an updated analysis on immune response ofchildren was discussed, and in

addition whether children'simmune response to yellow fever vaccine was different fromadults. dr. staples will discussresults of the further analysis and the acip recommendations.the work group discussed time interval for additional doses inpregnant women, stem cell transplant recipient,hiv-infected individuals and further clarified high-risksettings for exposure for the wild type yellow fever virus.today dr. staples will present a summary of the grade review,consideration for special

population, proposedrecommendations for consideration by acip.and we look forward to discussion and a vote.>> thank you for staying and, and i won't be long because istand between you and lunch. i want to start by summarizinggrade, booster doses before presenting new data that addressissues that were raised during the june acip meeting, andfinally conclude about presenting about the proposedlanguage for yellow fever vaccine booster vaccine doses.just to remind people, the

primary policy question at thatthe work group started for grade was should booster doses ofyellow fever vaccine every ten years continue to be recommendedfor healthy travelers and laboratory workers.the intervention would be to remove current recommendationversus the current option would be to continue the currentrecommendation for booster doses.the grade evaluation, there were four benefits that the workgroup considered to be critical, namely vaccine efficacy, seraprotection, vaccine

effectiveness, and seropositivity. however, there are no data onthe vaccine efficacy or sera protection.there were three harms considered by the work group tobe critical, including serious adverse events and two specifictypes of yellow fever adverse events.i'll now review is main findings of each critical outcomestarting with vaccine effectiveness, which wasdescribed as a lack of vaccine failures.there have been 18 vaccine

failures identified among over540 million doses of yellow fever vaccine that have beendelivered. only two or 11% of the 18vaccine al failures occurred more than ten years from thelast dose of vaccine, namely as 20 and 27 years.for the sera positivity data at ten or more years withvaccination, there were 13 observational studies with datafor 1,137 persons. the estimate of sera positivityis 92% using a random effect model.switching to 20 years, there's

three observational studies with immunogenicity data for 164persons at 20 or more years post vaccination, and the estimatefor sera positivity for this group is 80% using the randomeffects model. moving to the harms, there werenine observational studies that had data on 333 million doses ofthe vaccine distributed. there was 1,255 subjects whoreported a serious adverse event following vaccination.of the 201 subjects where the dose type was known, 7% occurredfollowing a booster dose of

yellow fever vaccine.the data were similar for yellow fever vaccine associatedneurologic and viscerotropic. this slide is to remindeverybody about the various evidence you've heard about, onebeing the highest level of confidence in the estimated effect on the outcome and four being the lowest.so for the five critical outcomes access for yellow fevervaccine booster doses, the quality of evidence for each wasfour, as it only included observational studies withimportant limitations typically

related to bias andindirectness. so the overall quality ofevidence was four. there was an additional policyquestion created to address persons who were considered bythe work group not to belong to healthy travelers and laboratoryworkers. and that specific question isshould booster doses of yellow fever vaccine every ten yearscontinue to be recommended for travelers and laboratory workerswho have precautions for vaccinations that may have negatively impacted their immune

response to primary dose ofyellow fever vaccine such as pregnancy, asymptomatic hiv, oryoung age. in next slide, i'll go over theevidence for four special populations that were consideredby the work group related to this additional policy questionand also address concerns raised in june.there are two observational studies that provide immunogeni-city data for pregnant women. in the first study 39% ofpregnant women vaccinated during third trimester zero convertedin comparison to 94% of the

general population to receivethe vaccine at the same time in nigeria as part of an outbreakresponse. in the second study conducted inbrazil, 98% of pregnant women vaccinated primarily duringtheir first trimester, sera converted and developed yellowfever virus-specific antibodies. from these two studies we canconclude that the proportion of pregnant women who developantibody titers following yellow fever vaccination is variable,but day that indicate a lack of initial sera conversion for somepregnant women.

given this, the work groupsuggested revaccinating women who received their initial dose of yellow fever vaccine while pregnant one time prior to theirnext travel at risk. i'm sorry.at-risk travel. there is no immunogenicity datafor recipient, but the data suggest most recipients becomesera negative to antigens on transplantation.guidelines recommend readministering live viralvaccines, specifically mmr, post transplant when the recipient isno longer immunnosuppressed.

the work group suggestrevaccinating one time before their next at-risk travel aslong as they're immunocompetent. three studies compare. this is comparison to 74% in ageand nutritionally matched children.in the second study, 83% of hiv-infected travelers hadyellow fever virus-specific antibodies one year postvaccination and began comparisons of 97% unaffectedcontrol. in the last study, 77% of hivinfected travelers had yellow

fever virus specific antibodiesat one to ten years post vaccination, and this is incomparison to 88% of unaffected control.to summarize the data, the data indicate that hiv infectedpersons are less likely to have sustained yellow fever virusspecific antibody fighters following vaccination.given this, the work group suggests continuing doses ofyellow fever vaccine every ten years for persons who receiveyellow fever vaccine while infected with hiv.now, moving to young children,

which was a particular area ofdiscussion following the gene presentation, there are 12studies with immunogenicity data on 4,675 children aged 4 monthsto 10 years in endemic areas at least one to two months postvaccination. the estimate sera conversionrate is 93% with a 95% confidence interval with 88% to96% using a random effects model.we also looked at differences in sera conversion rates amongdifferent pediatric age groups because the study irrigated theresult base age, there were two

age groups that could be readilyexplored. the top table shows you the seroconversion rate for children 9 months and older compared tochildren aged less than 9 months.the estimated sera conversion rates were similar at 92% and95% with overlapping confidence intervals.the bottom table shows data for children 9 months and oldercompared to children aged less than 12 months and the seraconversion rates again are not different, at 89% for childrenolder -- 12 months and older and

93% for children less than 12months. again, with overlappingconfidence intervals. to summarize the pediatric dataand note other considerations, the estimate for pediatric seraconversion rate was 93%, and uningested seroconversion ratefor adults at the same time point is 98% for all populationsand 97% for endemic populations, an just a remind the pediatricdata came from -- when these data were presentedand discussed with aap's committee on infectious diseasesor coid, they concluded that

young children were notimmunologically different from adults in their response toyellow fever vaccine. the work group finallyconsidered persons who were considered to be at higher riskfor yellow fever virus exposure based on season, location,activity, and duration of their exposure.there were three situations where a person was considered tobe at higher risk location for yellow fever virus exposure.these include west africa during peak transmission season wherethe disease risk is estimated to

be about ten times higher thansouth america. also arias with ongoingoutbreaks and finally regular exposure to wild type yes, ma'amyell virus in a laboratory. then finally travel for longperiods of time was also to likely increase the risk ofdisease. now i'd like to summarize thedata and considerations related to yellow fever vaccine boosterdoses from the vaccine effectiveness data, very fewvaccine failures noted to cur following yellow fever vaccineadministration.

most or 92% of vaccinerecipients are sero positive ten or more years post vaccination.serious adverse events are uncommon following booster dosesof yellow fever vaccine. a high value was placed by thework group on preventing serious disease with no treatment andpoor outcome. and finally the currentstatement in the recommendations will no longer be relevant wheni remember health regulations are updated in june of 2016.given these data and considerations the work groupconcluded that a single dose of

yellow fever vaccine provideslong lasting protection in most travelers.and therefore the work group would no longer recommendbooster doses of yellow fever vaccine for those travelers.however, the work group would recommend yellow fever vaccinebooster doses for persons whose immune response to the previousdose may have been compromise and consider booster doses inpersons at higher risk settings for exposure to yellow fevervirus. this finally leads me to therecommendations that the work

group is proposing for acip'sconsideration and vote. the recommendation for mosttravelers would be a single dose of yellow fever vaccine provideslong lasting protection and is adequate for most travelers.this is a category a recommendation.for certain populations noted below, the recommendation wouldbe additional doses of yellow fever vaccine are recommendedfor certain travelers including women pregnant when they receivetheir initial dose of yellow fever vaccine should receive oneadditional dose of yellow fever

vaccine prior to their nexttravel that puts them at risk for yellow fever virusinfection. individual who is received stemcell transplants after receiving a dose of yellow fever vaccineand who are sufficiently immunocompetent to be safelyvaccinated should be revaccinated prior to their nexttravel that puts them at risk for individuals hiv infectedwhen they received their last dose of yellow fever vaccine,they should receive a dose every ten years if they continue to beat risk for yellow fever virus

infection. for this group, we wanted toknow that persons should be considered for the additionaldoses should be assessed for contraindications andprecautions. that would be a category arecommendation. for persons in higher risksettings the recommendation would be a booster dose may beconsidered for travelers who received their last dose ofyellow fever vaccine at least ten years previously and whowill be at a higher risk setting

based on season, location,activity, and their -- duration of travel. this would include travelersspending long times in highly endemic areas or traveling tothose arias such as rural west africa during peak season orthose with ongoing outbreak. this is a category brecommendation. finally for laboratory workersin higher risk settings recommendation would belaboratory worker who is routinely handle wild typeyellow fever virus should have

yellow fever virus specificantibody neutralizing titers measured at least every tenyears to determine if they need additional doses.for those unable to have those measured, vaccine should given as long as they remain at risk. this is a category arecommendation. i would like to now turn it overthe dr. tempte to walk us through the next step.thank you. thank you very much for,again, a very nice presentation with limited time.but, i think you picked up all

the issues that had beenpreviously raised by the group so i appreciate this from theworking group. dr. reingold.>> quick question about pregnant women.the data you showed suggests it's women only vaccinated inthe third trimester who need an extra dose.all pregnant women just because you don't think women will knowwhich trimester they were vaccinated in?>> i think it's more the fact it's only derived from twostudies that that i think that's

insufficient to say withcertainty it's the third trimester.what about the second trimester. we don't know exactly what thatis. we are being perhaps a littlemore conservative and just suggesting if you're vaccinatedduring pregnancy you should receive another dose if you'reable to. doctor?>> for the laboratory workers you suggested antibody titers.did you consider that possibility for the other groupsthat you're considering

revaccinating as an option?you did have some sera conversion among all thosegroups. given the adverse reactions thatcan happen with the vaccine and the seriousness of it, i'm justwondering if you considered antibody titers first and theninsufficient revaccination. we did discuss antibodiestiter, and currently the only place to get those performed isat cdc and our facility. sometimes it's logisticallychallenged and it's done through a test that takes about fourweeks to get the results.

at least from our travelpractitioners in the group they didn't think it was verypractical, particularly if people are rushing in the doorto get their vaccines and they won't have an answer.but cdc traditionally does do antibody testing for many of thehigh-risk groups we highlighted here, risk groups that would beconcerned. that's something already goingon and could be maintained. number of laboratory workersthat really handle wild type yellow fever virus on a regularbasis is quite small, and they

obviously would be aware andshould be able to channel through and use thatneutralization testing. miss pellegrini.>> if i'm remembering our fall conversation correctly when wediscussed children, there was some question about whethertravelers who were vaccinated as children would, indeed, havelife-long protection. was the work group able to findany data that would help clarify that?>> yes. we looked at the pediatric dataand i showed you pretty much

all of the data that that was for the initial sera conversion. there's only one study out thereand the data are not primarily dealing withyellow fever. it was dealing with looking atchirp that had received yellow fever vaccine because they'regoing to give them that -- vaccine.they looked at those children based on age cohorts and some ofthose children had been revaccinated so the results arevery confusing and not -- unfortunately not helpful.it is something that when we

discuss with aap they said itwould be great to get more data. i didn't have an opportunity dueto the time to present future studies, but it is one of thestudies we've highlighted for future work.>> and dr. atkinson at the microphone.>> i'm william atkinson. i'm a messenger.i'm delivering a -- i'm asking a question on behalf of dr. stanplotkin, who is not here because of the southern severethunderstorm. dr. plotkin would like toinquire about the study just

published in "vaccine" showing17% zero negative 5 nine years post vaccination in normalpeople. i would have to seespecifically -- there's been several yellow fever vaccinestudies published in the last six months but i'm not sure thedata behind that one. and i think the issue that we'vealso had in the work group is knowing exactly what seroprotection they used because there are different cutoffs fordetectable antibodies. sometimes comparing one studywithout those results, it would

be hard to make further commenton that. are there other questions orcomments? okay.again, thanks for a very nice presentation.i think our next step is to move on and see emotion for approval.again, i think the questions that were raised in the pasthave been addressed nicely by the work groups.i will entertain a motion from dr. ruben.make a motion to approve recommendation.>> other further comment.

the not, dr. karen, we'll startwith you and go arnold to your right.>> karen, yes. reilly, yes.>> okini, yes. vasquez, yes.>> campsockhalt, yes. ron gold, yes.>> pellegrini, yes. tempte, yes.>> ruben, yes. romero, yes.>> harriman, yes. harrison, yes.>> bollange, yes. the motion carries 13-4.no votes against.

so thankfully there is no vfcresolution needed for this vote. and we're able towish dr. harrison a good trip home.dr. bennett and dr. kemp have already had flight delays.i'm just going to move long very quickly with public comment.we have one more public comment here.but warfare we get to that, i want to express our appreciationfirst of all to everybody in this room who adapted plans,made do with nothing going on yesterday, and still showed uphere today.

we also appreciate the workgroups who greatly and rapidly changed presentations to try andcondense them down into the time available because we did havethese four things we felt very important to get through.that being said, we did put off discussion and volts oninfluenza h5n1, smallpox and recommendations plus otherconsiderations for meningococcal b and hpv until the junemeeting. so keep posted on those.but, again, thanks to the work groups for adapting to this verylimited time period we had.

that being said, is sallylongberg here? and if you can come up to themicrophone? hi.i'm sally greenberg and i'm executive director of thenational consumers league. i'm here to support the routineschedule of meningitis b. my organization's been aroundsince 1899. we are the oldest consumerorganization. and we also survey consumers ontheir attitudes about vaccines. and what we find in our latestsurvey was that 87% of parents

want to get there and supportgetting their children vaccinated and the disease theyfear most that vaccinating can prevent is meningitis.so i'm here also to support the many parents and families whocame out of their -- at their own expense.we -- i come to this both as a consumer advocate and wearingseveral other hats. one is that i had an uncle whohad polio, got it the year before the polio vaccine cameout, and i watched my family suffer with a -- he clung tolife in an iron lung for two

years then went on to be aquadriplegic. one year later he could havebeen -- this tragic condition could have been prevented.but i'm also the parent of a college-age kid who is abaseball player and lives in the dorms.as i meet with a lot of the meningitis victims, we take avery strong stand in favor and in support of safe and effectivevaccines. i'm finding it very difficult toaccess that vaccine for him. it would be wonderful if thisvaccine became part of the

routine schedule.and it's -- they have to order it, they're not sure which onethey want to order. there's a will the of confusion.i've had maybe ten phone calls and we still haven't figured outhow to get this vaccine. so it really isn't fair for myson to be the only guy to get it on his campus, which he probablywill be, but, you know, i really feel so strongly that when youhave something that's safe and effective and thanks to all ofyou for the critically important work that you do, but there'sjust no reason why this

shouldn't be part of the routineschedule. so i'm really here with lotsof hats on. but i think most importantly tosupport all these families, the parents who came forward withthese devastating conditions as a result of contractingmeningitis b and something that's totally preventable.so thank you for giving me the chance to speak, and appreciateit. i thank you for yourpatience, too, waiting until the end here.before i finish up, i'm just

going to for the record say --because i don't have time to read all these and we have fouradditional letters that the letters have been provided tothe members, and the letters will also be placed in theirtotality into the minutes from this meeting.but the first letter is from the national consumers league.and actually, the letter by sally greenberg, who just spoke.so that will be in. we have a letter from lesliemeyer speaking to the routine recommendation for sera group bin the meningococcal vaccines.

and she is on the board ofdirectors of the national meningitis association.so that will be in. we have an additional letterfrom the american for consumer institute center for citizens research. and, again, making their pleafor a universal routine recommendation for meningococcalb. and finally from the nationalhispanic medical association, a letter, again, requestingconsideration for routine recommendation, meningococcal bvaccine.

so we have a lot of work aheadof us coming up. but i think we have come to theend of our agenda. i'm just going to see if there'sany additional comment from members here or dr. shuchat oranyone else? and seeing none -- and, again,before we leave, just one more mention of our appreciation todr. pickering for his nine years of service to acip and our bestwishes as he moves on from here. so with that, thank you verymuch, and travel well. thank you.[ applause ]