n engl j med 372;10nejm.orgmarch 5, 2015PERSPECTI VE899HHS
Efforts to Improve U.S. Health Careadverse events while
hospitalized, andmanypeopledonotreceive care that they should
receive, while others receive care that does not
benefitthem.Growthofhealth care spending is at historic lows:
Medicarespendingperbenefi-ciaryincreasedbyapproximately
2%peryearfrom2010to2014 a rate far below both histori-cal averages
and the growth rate ofthegrossdomesticproduct.4 Survey data show
that more than 7in10peoplewhosignedup forinsuranceinthenewhealth
insurancemarketplacelastyear saythequalityoftheircoverage is
excellent or good.5 However, it will take additional effort to
sus-tainandaugmentthepositive changes we have seen so far.We are
dedicated to using in-centivesforhigher-valuecare, fostering
greater integration and
coordinationofcareandatten-tiontopopulationhealth,and
providingaccesstoinformation thatcanenablecliniciansand patients to
make better-informed choices. We believe that, by work-ing in
partnership across the pub-lic and private sectors, we can
ac-celeratetheseimprovementsand integratethemintothefabricof the
U.S. health system.Disclosure forms provided by the author are
available with the full text of this article at NEJM.orgMs. Burwell
is the U.S. Secretary of Health and Human
Services.ThisarticlewaspublishedonJanuary26, 2015, at
NEJM.org.1.RajkumarR,ConwayPH,TavennerM.
CMSengagingmultiplepayersinpay-ment reform. JAMA
2014;311:1967-8.2.BrennanN,OelschlaegerA,CoxC, Tavenner M.
Leveraging the big-data
revolu-tion:CMSisexpandingcapabilitiestospur
healthsystemtransformation.HealthAff (Millwood)
2014;33:1195-202.3.OfficeoftheNationalCoordinatorfor
HealthInformationTechnology.Reportto Congress, October 2014
(http://www.healthit
.gov/sites/default/files/rtc_adoption_and_exchange9302014.pdf
).4.Chappel A, Misra A, Sheingold S. ASPE
is-suebrief:Medicaresbendingcostcurve.
July28,2014(http://aspe.hhs.gov/health/
reports/2014/MedicareCost/ib_medicost .pdf
).5.NewportF.Newlyinsuredthroughex-changes give coverage good
marks. Gallup. November 14, 2014
(http://www.gallup.com/poll/179396/newly-insured-exchanges-give
-coverage-good-marks.aspx).DOI: 10.1056/NEJMp1500445Copyright 2015
Massachusetts Medical Society.Making Hepatitis E a
Vaccine-Preventable DiseaseEyasu Teshale, M.D., and John W. Ward,
M.D.Related article, p. 914InthisissueoftheJournal, Zhang and
colleagues provide dataobtainedfrommorethan
110,000healthyparticipants16 to65yearsofageconfirming
thathepatitisEcanbeprevent-edbyvaccination(pages914922).Initialresultsfromthis
cohortstudyrevealedthatthe vaccine candidate is safe and
ef-ficacious(95%efficacyoverthe 12-monthperiodaftervaccina-tion).1
The current report further shows that Hecolin (the hepatitis
EvaccinelicensedinChinain 2011)remainsimmunogenicand efficacious at
least 4.5 years after completionofthethree-dose schedule
administered at 0, 1, and 6 months.SinceZhangetal.conducted their
study in China, they found protection mainly against hepati-tis E
virus (HEV) genotype 4, the viral strain that is most common
inthatcountry(seemap).Addi-tionalstudiesareneeded,how-ever,toestablishthevaccines
efficacy in areas where the other three HEV genotypes predominate.
InSouthAsiaandcertainareas inAfrica,HEVgenotype1isa
leadingcauseofacutehepatitis, infecting millions of people each
yearandcausinganestimated 70,000 deaths annually.2 Although
hepatitisEisoftenamilddis-ease, HEV infection can cause
ful-minanthepatitisanddeath.As many as 20% of pregnant women
whodevelophepatitisEduring thethirdtrimestermaydiefrom
thediseaseoritscomplications. LargeepidemicscausedbyHEV genotype 1
are common, particu-larlyamongpeoplelivingin
crowded,unsanitaryconditions, suchascampsforrefugees,and
internallydisplacedpeople.In suchsettings,whereHEVinfec-tion is
mainly transmitted by the fecaloralroute,improvements
insanitationandprovisionof
safedrinkingwatercannottypi-callybeprovidedatalevelthat
haltstransmission,soepidemics canbeprolonged.HepatitisE vaccination
could be a useful ad-junct in these settings.Although hepatitis E
is known tobeaproblemintheseareas,
theabsenceofprecisedatare-garding the burden of hepatitis E disease
and related deaths is a ma-jor barrier to defining the
clini-calandpublichealthapplica-tions of a hepatitis E vaccine. For
example, in Bangladesh, a study inwhichstandardizedinterviews The
New England Journal of Medicine Downloaded from nejm.org on August
3, 2015. For personal use only. No other uses without permission.
Copyright 2015 Massachusetts Medical Society. All rights reserved.
PERSPECTI VEn engl j med 372;10nejm.orgmarch 5, 2015900were
conducted with family mem-bersandcaregiverstoassessthe cause of
maternal deaths revealed thatoneinfivewasrelatedto jaundice;
although published data suggestthatabouthalfthose deaths could be
related to hepa-titis E, limited capacity for research hampered
efforts to identify HEV as the cause.3 Furthermore, epide-miologic
information on infection anddiseaseduringchildhoodis lacking.
Prospective studies based on accurate HEV testing are
need-edtoreliablyestimatetheinci-denceofhepatitisEandrelated
mortality among pregnant women, their newborns, and children.The
gaps in data extend to the United States, where the lack of highly
sensitive and specific tests approvedbytheFoodandDrug
Administrationandtheabsence ofsurveillancecasedefinitions limit
definitive diagnosis and re-portingofhepatitisE.Despite these
limitations, laboratory test-ing conducted by the Centers for
DiseaseControlandPrevention (CDC)attherequestofhealth
authoritiesandcliniciansiden-tifiedcasesofhepatitisEthat
occurredasaresultofautoch-thonoustransmissionofHEV genotype 3 in
the United States.4 HEVgenotype 3 infection in
hu-mansisthoughttobeafood-bornezoonosisresultingfrom
consumptionofraworunder-cookedmeatandoffalofHEV-infectedpigs,boars,anddeer,
although data that would conclu-sively establish a cause are often
lacking.SomecasesofHEVge-notype 3 have occurred in recipi-ents of
solid-organ transplants, a populationatriskforchronic hepatitis
E.In2014,theCDCawarded funds to two U.S. national
labo-ratoriesforsharingdeidentified
datafromhepatitistesting,in-cludingtestsforHEVantibody
orHEVRNA.Epidemiologic studies, guided by enhanced
sur-veillance,areneededtoidentify the populations that have a
bur-denofHEVinfectionandmay
thereforebenefitfromvaccina-tion.Inthemeantime,U.S.cli-niciansshouldincludehepatitis
Einthedifferentialdiagnosis ofhepatitis,particularlyforpa-tients
with a history of travel to areas where hepatitis E is endem-ic or
when other more common causesofhepatitishavebeen ruled
out.IftheefficacyofthisHEV
vaccineisdeterminedtobepan-genotypic,severalpublichealth questions
must be answered,
in-cludingwhoshouldbevaccinat-ed,whentovaccinate,andthe
cost-effectivenessofvaccination asapreventiontool.Additional data
regarding the safety, immu-nogenicity,andefficacyofthe
hepatitisEvaccineinpregnant women,personswithchronic liver disease,
and other
vulnera-blepopulationsareneeded.Be-forehepatitisEvaccinationcan
beconsideredasanadditionto the childhood vaccination
sched-ule,safetyandefficacydataare needed for children less than 16
yearsofage,includingdataon howthisvaccineinteractswith other
vaccines when given simul-Making Hepatitis E a Vaccine-Preventable
DiseaseGeographic Distribution of HEV Genotypes in Locally Acquired
HEV Infection. The map shows the predominant locally acquired human
genotype in each country. Data are from the Division of Viral
Hepatitis, Centers for Disease Control and Prevention.The New
England Journal of Medicine Downloaded from nejm.org on August 3,
2015. For personal use only. No other uses without permission.
Copyright 2015 Massachusetts Medical Society. All rights reserved.
n engl j med 372;10nejm.orgmarch 5, 2015PERSPECTI
VE901taneously.Finally,fieldtrialsare neededtoestablishaneffective
vaccinationseries.Although studiesofthevaccinesuggest
thattwodosesmayeffectively
preventhepatitisE,awell-de-signedevaluationoftheeffec-tivenessoffewerdosesand
shorterdosingschedulesisre-quired.TheWorldHealthOrganiza-tionsStrategicAdvisoryGroup
of Experts (SAGE) on immuniza-tionrecentlycitedtheneedfor
additional data regarding the in-cidenceofHEVinfectionand
diseaseandthesafetyandeffi-cacyofthevaccinebeforerec-ommendingroutinehepatitisE
vaccinationincountrieswhere hepatitisEishighlyendemic
(www.who.int/wer/2014/wer8950 .pdf ).YetSAGErecognizedthat
thecurrentlackofdatashould not preclude the use of this vac-cine in
special situations,
empha-sizingthatitshouldbeconsid-eredforcontrollinghepatitisE
outbreaks.Dataonthediseaseburden will help to build a case for
hep-atitis E vaccination in both high-income and low-income
settings. Robustdatafrompublichealth
surveillanceandsurveyscanin-formtheseefforts,helpingto stimulate
industry interest in vac-cine development and production. Other
hepatitis E vaccines are in development. However, an earlier
promising candidate did not prog-ress to licensure and production,
presumablybecauseofthelack of a well-defined market and
in-dicationsforvaccination.5To date, only the vaccine studied by
Zhangetal.hasprogressedbe-yond a phase 2 clinical trial.A hepatitis
E vaccine could be-come a powerful new tool in the
preventionandcontrolofHEV transmissionanddisease.Most immediately,
it can have a role in curbingoutbreaksofhepatitisE in humanitarian
crises. The bene-fits of broad adoption of hepati-tis E vaccine
could be far-reaching, ifstudiesrevealthatvaccination
protectsagainstallHEVgeno-typesandissafeandeffective
whenusedinpeopleathighest risk for hepatitis E-related illness
anddeath,includingpregnant women. Given the sustained pro-tection
afforded by hepatitis E vac-cination reported by Zhang et al., now
is the time to answer these remainingquestionsandestab-lish the
public health applications of a hepatitis E
vaccine.Theviewsexpressedinthisarticleare those of the authors and
do not necessarily represent the official position of the Cen-ters
for Disease Control and Prevention.Disclosure forms provided by the
authors are available with the full text of this article at
NEJM.org.FromtheDivisionofViralHepatitis,Cen-tersforDiseaseControlandPrevention,
Atlanta.1.Zhu FC, Zhang J, Zhang XF, et al. Efficacy and safety of
a recombinant hepatitis E vac-cine in healthy adults: a
large-scale, random-ised, double-blind placebo-controlled, phase 3
trial. Lancet 2010;376:895-902.2.Rein DB, Stevens GA, Theaker J,
Witten-bornJS,WiersmaST.Theglobalburdenof hepatitis E virus
genotypes 1 and 2 in 2005. Hepatology 2012;55:988-97.3.Gurley ES,
Halder AK, Streatfield PK, et al.Estimatingtheburdenofmaternaland
neonatal deaths associated with jaundice in Bangladesh: possible
role of hepatitis E in-fection. Am J Public Health
2012;102:2248-54.4.Drobeniuc J, Greene-Montfort T, Le NT, et al.
Laboratory-based surveillance for hep-atitis E virus infection,
United States, 2005-2012. Emerg Infect Dis
2013;19:218-22.5.ShresthaMP,ScottRM,JoshiDM,etal. Safety and
efficacy of a recombinant hepa-titis E vaccine. N Engl J Med
2007;356:895-903.DOI: 10.1056/NEJMp1415240Copyright 2015
Massachusetts Medical Society.Making Hepatitis E a
Vaccine-Preventable DiseaseOn Taking Notice Learning Mindfulness
from (Boston) BrahminsMichael W. Kahn, M.D.I
wasaharried,greenresident busilyreadyinganelderlypa-tient call her
Margaret for hospital discharge when her face unexpectedly began
glowing with pleasure. Looking me intently in
theeye,sheexclaimed,Ido hopeyouknowDr.Edgecomb!
ButbeforeIcouldrespond,she continued,Doyouknowwhat he told me when
I left his office last time? Now you just be sure
tonoticethecrocusesbythe
doorwayonyourwayout,Mar-garet;theyrelovelythisyear. Thats just the
kind of person he is...andhewassoright about the crocuses.Isnt that
nice! I replied,
dis-creetlyrollingmyeyesandcon-tinuingtowriteprescriptions. How
quaint it seemed: the elderly doctor, possibly taught by Oslers
students,tryingtodoaslittle harmaspossiblewithhishoary
knowledge;hiselderlypatient, evidentlydelightedtoreceive
crocus-basedmedicine.Though IdidntknowDr.Edgecomb
(alsoapseudonym)personally,I The New England Journal of Medicine
Downloaded from nejm.org on August 3, 2015. For personal use only.
No other uses without permission. Copyright 2015 Massachusetts
Medical Society. All rights reserved.
