Northeast Florida Medicine - Fall 2010 - Infectious Diseases

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www . DCMS online . org Northeast Florida Medicine Vol. 61, No. 3 2010 3

Features

11 AnotherSwineFluAffair MobeenH.Rathore,MD,CPE,GuestEditor

12 ChallengesandSuccessesinMothertoChildTransmissionofHIVinFloridaAyeshaMirza,MD

15 MitigatingtheH1N1Pandemic:AYearinReview(CME)TajAzarian,MPHandSaadZaheer,MD,MSPH (Pediatric Perspective by Haidee Custodio, MD)

23 TuberculinSkinTest:LossofanOldFriend?JeffreyLauer,MD(Pediatric Perspective by Ana Alvarez, MD)

31 CommunityAssociatedMethicillinResistantStaphylococcusAureus:AnUpdateNilmarieGuzman,MD(Pediatric Perspective by Nizar Maraqa, MD)

SpecialArticles36 BreastCancerandHIVintheEraofHAART:ACaseReportNaeemLatif,MD,FauziaRana,MDandTroyGuthrie,MD

VOLUME 61, NUMBER 3InfectiousDiseasesFall2010

EDITOR IN CHIEFJoanL.Huffman,MD

MANAGING EDITORLeoraLegacy

ASSOCIATE EDITORSRaedAssar,MDHernanChang,MDStevenCuffe,MDRupleGalani,MDKathyHarris(Alliance)SunilJoshi,MDJamesJoyce,MDNeelKarnani,MDTimothySternberg,MD

Executive Vice PresidentJayW.Millson

DCMS FOUNDATION BOARD OF DIRECTORSBenjaminMoore,MD,PresidentToddL.Sack,MD,VicePresidentKayM.Mitchell,MD,SecretaryJ.EugeneGlenn,MD,TreasurerGuyI.Benrubi,MD,ImmediatePastPresidentMohamedH.Antar,MDRaedAssar,MDAshleyBoothNorse,MDJ.BrackenBurns,DOMalcolmT.Foster,Jr.,MDJeffreyL.Goldhagen,MDJeffreyM.Harris,MDMarkL.Hudak,MDJoanL.Huffman,MDSunilN.Joshi,MDDanielKantor,MDNeelG.Karnani,MDJohnW.KilkennyIII,MDSherryA.King,MDHarryM.Koslowski,MDEliN.Lerner,MDR.StephenLucie,MDJesseP.McRae,MDSenthilR.Meenrajan,MDNathanP.Newman,MDMobeenH.Rathore,MDRonaldJ.Stephens,MDJeffreyH.Wachholz,MDAnneH.Waldron,MDDavidL.Wood,MD

Northeast Florida Medicine is pub-lished by the DCMS Foundation,Jacksonville,Florida,onbehalfoftheCountyMedicalSocietiesofDuval,Clay,Nassau,Putnam,andSt.Johns.Except for official announcementsfromtheCountyMedicalSocieties,nomaterialoradvertisementspublishedinNEFMaretobeseenasrepresent-ingthepolicyorviewsoftheDCMSFoundationoritscolleagueMedicalSocieties.AlladvertisingissubjecttoacceptancebytheEditorinChief.Ad-dresscorrespondenceandadvertisingto:555BishopgateLane,Jacksonville,FL32204(904-355-6561),oremail:[email protected].

COVER: Shot in the Grand Cayman Islands by Dr. Michael Bernhardt - a self confessed “diveaholic.” See photographer’s profile, p.30.

Inside this issue of

Departments4 FromtheEditor’sDesk5 FromthePresident’sDesk8 FMAAnnualMeeting9 DCMSAnnualMeeting-SavetheDate!41 DCMSHistoryBook

Northeast Florida Medicine

4 Vol. 61, No. 3 2010 Northeast Florida Medicine www . DCMS online . org

From the Editor’s Desk

Professionalism“Do all the good you can, by all the means you can, in the ways you can, in all the places you can, to all of the people you can, as long as you ever can.” JohnWesley

What isprofessionalism?To“profess”, i.e.confess; themeaningexpresseshowindividuals/groupsacknowledgetheirownbasicvaluessuchashumanism,altruism,compassionandrespect.Beyondthatcrux,diversetraditions,culturesandprioritiesabound.1

Concernforprofessionalismregressiongrewinthe1980s.TheAmericanMedicalAssociation(AMA),AccreditationCouncilforGraduateMedicalEducation(ACGME),AmericanBoardofMedicine(ABIM)andAmericanCollegeofSurgeons(ACS)statedtheircommitmenttoenhancebehaviorandpersonalinteractionsbetweenpatients,doctors,medicaleducatorsandstudents.2

In 1999, two decades after standards were set, the American Board of Medical Specialties(ABMS)adoptedsixgeneralcompetenciesforBoardCertification.3Theprincipleswereclear,butwerenotformallyintegratedintotheeducationalcurriculumuntil2007whenresidentswerein-troducedtoprofessionalismasoneoftheAGCMEcorecompetencies.Professionalismwasdefinedas“acommitmenttocarryingoutprofessionalresponsibilities,adherencetoethicalprinciples,thedemonstrationofcompassion, integrity,respectforothers;responsivenesstopatientneedsthatsupersedesself-interest;respectforprivacyandautonomy;accountabilitytopatients,societyandtheprofession;andsensitivityandresponsivenesstoadiversepatientpopulation.”4

ManypracticingphysiciansfeltunabletoachievethegoalsofABMSandACGMEduetotheobstaclesthatcomefromtheevolutionfromautonomy,expertopinionandself-interest–toac-

countability,evidence-basedmedicineandsharedresponsibility,therefore,theABIMFoundation,inconcertwiththeAmericanCollegeofPhysicians(ACP)FoundationandtheEuropeanFederation

ofInternalMedicine,drewupaPhysicianCharter,emphasizingthatprofessionalismisthebasisofthemedicine’scontractwithsociety.Thecharterhasbeenendorsedbyover100medicalorganizationsintheU.S.andabroad.

ThefundamentalprinciplesoftheCharterareprimacyofpatientwelfare,patientautonomyandsocialjustice.Thereisalsoasetofprofessionalresponsibilitiesincludingcommitmentto:professionalcompetence,honestywithpatients,patientconfidentiality,maintenanceofappropriaterelationswithpatients,improvementqualityof/accesstocare,ajustdistributionoffiniteresources,scientificknowledge,maintenanceoftrustbymanagingconflictsofinterest,andfinally,professionalresponsibilities.5

Inthisnewmillenniumofcataclysmicchanges,howweexperienceprofessionalismbehaviorofanotherpractitionerisbythewaytheydemonstrate,improveandreassesstheiractions,andchangetheirpersonalculture,andthatoftheirorganization,byattentiontotheirconduct,andself-regulation.TwovaluableresourcestoassisttheflounderingphysicianareDVDsentitled:“MedicalProfessionalismintheNewMillennium”and“ProfessionalisminSurgery,SecondEdition”(availablefromtheACS)whichreviewprofessionalismandpresentvignettesinCMEformat.6

Anotherwaytoheightenprofessionalismisfirsthandexperienceininternationalpatientcareinaustereconditionswithun-derservedpopulations:thiswillinstillanappreciationfortheextentofhumancircumstancesandimbuesincerecompassion,aswellasimplantasenseofrespectanddignityforthoseinneed,andadesirefordedicationtoservice.7

Asourdefinitionofprofessionalismcontinuestotransforminresponsetotechnologyexplosion,disparitiesinhealthcareneeds/availableresources,changingmarketforces,bioterrorismandglobalization,whatarethechallengesyouface,andtheso-lutionsyouhavedevelopedtoengenderpublictrust?Howwillyoumodelprofessionalisminyourpracticeasclinicalsurgeonsand/orsurgicalteachers?Howcanwemoveintothe21stcenturyandinourtransitrevolutionizeprofessionalism?“Sometimes give your services for nothing and if there is an opportunity of serving one who is a stranger, in financial straits, give full assistance to all such, for where there is love of man, there is also love of the art.” Hippocrates

References (web sites accessed on August 2, 2010)

1. dwolfson82.PostAugust20,2009.Inresponseto:Howdoyoudefineprofessionalism?ABIMOnlineCommunity.http://www.abimfoundation.org/Forum/default.aspx?g=posts&t=5

2. LawrenceW.“Isourlevelofprofessionalismwhereitshouldbe?”Bull Am Coll Surg. 2004;89(6):21-25.3. RitchieWP.“Themeasurementofcompetence”.Bull Am Coll Surg. 2001;86(4):10-15.4. CommonProgramRequirements:GeneralCompetencies.ApprovedbytheACGMEBoardFebruary13,2007.http://www.acgme.org/outcome/comp/

GeneralCompetenciesStandards21307.pdf5. “MedicalProfessionalismintheNewMillennium:APhysicianCharter.” Annals of Internal Medicine 2002;136(3):243.6. McGinnis,LS.“PresidentialAddress:Professionalisminthe21stCentury.”Bull Am Coll Surg. 2009;94(12):8-187. SchecterWPandFarmerD.“Surgeryandglobalhealth:Amandatefortraining,researchandservice.”Bull Am Coll Surg.2006;91(5):36-38.

JoanL.Huffman,MD,FACSEditor-in-ChiefNortheast Florida Medicine

http://www.abimfoundation.org/Forum/default.aspx?g=posts&t=5

http://www.abimfoundation.org/Forum/default.aspx?g=posts&t=5

http://www.acgme.org/outcome/comp/GeneralCompetenciesStandards21307.pdf

http://www.acgme.org/outcome/comp/GeneralCompetenciesStandards21307.pdf


From the President’s Desk

Rationing or Reality Check?OnApril19.2010,PresidentObamanominatedDr.DonaldBerwicktobeAdministratoroftheCentersforMedicareand

MedicaidServices,DepartmentofHealthandHumanServices(CMS).Dr.BerwickisPresidentandCEOoftheInstituteforHealthcareImprovement,andisaprofessoratHarvardMedicalSchoolandtheHarvardSchoolofPublicHealth.TherewasimmediateconcernaboutDr.Berwickbeinganavowedproponentofrationedhealthcarewhofavorsagovernment-runsystemcomparabletotheoneinEngland.Ratherthanreflectingyetanotherexampleofpoliticalgrandstanding,thebasisforthisapprehensioncomesfromDr.Berwick’sstatement,“Thedecisionisnotwhetherornotwewillrationcare—thedecisionis

whetherwewillrationwithoureyesopen.”Naturally,whatweasthedispensersofhealthcarehavetobeconcernedwith,iswhose‘openeyes’arebeingconsidered?

TherecessappointmentallowedthePresidenttoinstallBerwickwhiletheSenatewasonvaca-tionovertheJulyFourthholiday,therebybypassingapotentiallylengthyconfirmationprocess.AsdefinedbySenatorMaxBaucus,theDemocraticchairmanoftheSenateFinanceCommittee,theconfirmationprocess“servesasacheckonexecutivepowerandprotects...allAmericansbyensuringthatcrucialquestionsareaskedofthenominee--andanswered.”Circumventingtheproceduralprocesscanalsoimpairthenominee,undermininghislegitimacyaswellasshorteninghistenure.Dr.BerwickcanonlyserveuntilDecember2011,anotablyshortenedtimeframeinwhichtomakeasignificantimpact.

Dr.Berwickisrightfullyrenownedforhisstudiesonhowtoimprovehealthcarewithloweredcosts.Buthehaslefthimselfopentoblisteringcriticismwhenheadvocateshealthcarerationing,whenhesupportshealthcarereformasamatterofredistributingwealth,andwhenheexuberantlylaudstheBritishhealthcaresystem.

Duetoitsmassivesize,theunresolvedissueinthehealth-carereformlegislationisthelackofanydefinedplantoimprovequalityandreducecosts.Theactualformulationofregulationsisstarting,atimeofenormousimportanceforthefutureofourprofession.Butthesheerenormityofourfederalgovernment’sbureaucracyanditsregula-toryagenciesfrequentlyhinderstheireffectiveness.Unfortunately,theirculpabilityhasbeenalltooevidentwithanumberofrecentexigencies:therelationshipoftheMaterialsManagementServiceoftheDept.ofInteriorandtheOilDrillingIndustry;theSecuritiesandExchangeCommission’soversightofournation’sworstfinancialcrisisin80years;andthealltoonumerousintelligencefailures.Nihilisticallythesehavebeendescribedasa‘signofthetimes’withourpervasivesocietallossesofshameandaccountability.Buttheydemonstratewhyweneedtobeallthemorevigilantinknowingwhatourelected,aswellasappointedgovernmentofficialsarethinkinganddoingwhencreatinghealthcareregulationsduringthecomingyear.

Consideringtheprodigiouscomplexityoftheproblemsathand,alongwiththeirproposedsolutions,completetransparencywithreviewandinquirywillbecriticallyvitalandthediametricoppositesoftheconceptofarecessappointment.

Lastyear,Medicarespentover$50billiononthelasttwomonthsofAmerican’slives.Mostofusstatethatwe’dratherdieathome,but75%currentlymeettheirdemiseinahospitalornursinghome.Nearly20%ofourpopulationspendstheirfinaldaysinanICU,wheretheissuesofstaggeringcostandlackofadvanceddirectivesareaconstantconundrum.Howdowebal-ancethecommonlyhelddesiretostayaliveaslongaspossiblewiththeevershrinkingnumbersofdollarstoaccomplishthis?Unlesstherearesomegenerallyacceptedguidelines(ideallydrawnupbyphysicians)regardingthispredicament,noamountofhealthcarereformwillsucceed.Butthereisanunderstandableuneasinessfeltwhenconsideringthecost-effectivenessofkeep-ingtheterminallyillalive.Manybelievethathealthcarerationingalreadyexistsbyvirtueofincomeandinsurancecoverage.Butifwecontinuetoignoretheconcept,theimpendingphysicianshortageandbankruptinghealthcarecostswillemergentlyforcesuchdecisions.

Oursocietyneedstobebetterpreparedtodealwithdeathandthedecisionsthatareimplicitwithit.ThehealthcarereformlegislationpassedinMarchwasdesignedtoslowthegrowthofMedicareexpenses,andtorewardthequalityofcareratherthanthequantity.Afterthefurorcausedbythepoliticallychargedexaggerationsof‘deathpanels’,therewasnoaddressinganyend-of-lifeissues.Incredibly,thelegislationalsotrimsMedicarepaymentsforhospicecare,whichstrivestomaintainqualityoflife,managepain,andofferspiritualguidanceduringthelaststageoflife,inaverycosteffectivefashion.

Now,as theparticularsof theregulationsarebeingcrafted,our inputas thepurveyorsofhealthcare ismostvital. GetReady.

From Donald Berwick’s Speech To Britain’s National Health Service - ‘A Transatlantic Review of the National Health Service at 60’: You could have protected the wealthy and the well, instead of recognizing that sick people tend to be poorer and that poor people tend to be sicker, and that any health care funding plan that is just, equitable, civilized, and humane must – must – redistribute wealth from the richer among us to the poorer and less fortunate.” (July 1, 2008)

John W. Kilkenny III, MD2010 DCMS President


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2010 FMA Annual Meeting

Congratulations to Dr. Miguel Machado, President-Elect of the Florida Medical Association and Shar Donovan,

President of the FMA Alliance

At the FMA Annual Meeting in Orlando, FL, August 13-15, 2010, Miguel Machado, MD, was elected as President-Elect of the Florida Medical Association. He will be FMA President beginning August 2011.

Celebrating the election results are: (L to R)Jennifer Putnam, Dr. Machado’s practice assistant; Lourdes Machado, his daughter; Dr. Machado, and Amaya Munoz, his girlfriend.

Also at the FMA meeting, Mrs. Shar Donovan, an active DCMS Alliance member, was installed as President of the Florida Medical Association Alliance. (see page 41 for more details) Pictured with Mrs. Donovan is her husband, Kevin Donovan, MD (both seated) and their four children (standing, L to R) Luke, Joseph, Troy and Janelle.

DCMS members active on the FMA Board of Governors/BoG (L to R) Eli Lerner, MD, BoG President’s Appointment; Miguel Machado, MD, President-Elect; Ashley Booth-Norse, MD, BoG District B Representative (First female from Duval County to serve in these roles); W. Alan Harmon, MD, Treasurer; and Nitesh Paryani, MD, Resident member elected to the BoG. Special thanks to all the DCMS physicians who served as delegates, reference committee members and in other leadership roles.


You were HERE

Jacksonville Hyatt

The 2010 DCMS Annual Meeting is

DON’T MISS IT! Malcolm Foster, MD, Incoming President

Exhibit Hall & Poster Session

New date & New location!Wednesday, December 1, 2010

5:45 - 9:00 PMHyatt Regency Jacksonville Riverfront

You are going HERE!


THE US DEPT. OF HEALTH AND HUMAN SERVICES SAYS:

“All physicians should stronglyadvise every patient who smokes to quit

because evidence shows that provider advice toquit smoking increases abstinence rates.”

Northeast Florida AHEC offers FREE training to help providers effectively Ask, Advise, and Referpatients to appropriate cessation programs.

TRAININGS ARE AVAILABLE ON-SITE, ATLOCAL/REGIONAL CONFERENCES, AND ON-LINE.In addition, we can help you develop a systemthat will help you identify tobacco-using patients,and then help them QUIT.

The National Cancer Institute projects that if providers assisted even10% of their tobacco-using patients in quitting, the number of tobaccousers in the U.S. would drop by 2 million people annually.

TRAINING TOPICS INCLUDE: • Brief Intervention Training• Motivational Interviewing• NRT Options• Other topics available by

discipline

Northeast Florida AHEC

Search for current workshopsand conferences at:www.ahecregistration.orgSelect Northeast Florida areafor list of local trainings.

CONTACT:NE Florida AHEC Tobacco Training1107 Myra St., Suite 250Jacksonville, FL 32204Ph: (904) 482-0189 • Fax: (904) 482-0196www.northfloridaahec.org www.quitsmokingnowfirstcoast.com

DCMS_QSN/AHEC Ad_July:July 7/9/10 4:07 PM Page 1


This Issue’s Focus: Infectious Diseases

Another Swine Flu AffairThisissueoftheNortheast Florida Medicinejournal(NEFM)isdedicatedtoinfectiousdiseases.Infectionsareanimportantand

prevalentaspectofmedicineandpublichealth,buttheyremainmostlyinthebackgroundofourday-to-daywork.Infectiousdiseasespecialistsconsiderthemselvesmostsuccessfulwhennoonehearsabouttheirspecialty.Whetheritisaddressinginfectionsthroughimmunizations,improvingpublichealth,preventingnosocomialspread,and/orinterveninginperson-to-persontransmission,in-fectiousdiseasespecialistsbelievefirstandforemostinprevention.However,eventslikewereexperiencedlastyearwiththeH1N1pandemiconlyservetoidentifyandhighlightthestrengthsandweaknessesofourpracticeandpreparedness.Itismostimportantthatwelearnfromourexperiencesandtranslatethisknowledgeintoourclinicalandpublichealthpractices.

ItwouldthusbeirresponsiblenottosayafewwordsabouttherecentH1N1pandemic.Inordertolearnfromourexperiencesandimproveourresponseinthefuture,wemustcriticallyscrutinizehowweperformed.Suchre-views,forexample,weredoneaftertheSwinefluscareof1975.1Asanationandstate,ourresponsetothe2009H1N1pandemiccanbebestdescribedas“aptandlucky”.2Withtheprecedentofthe1918and1975epidemicsloominglarge,therewasgreatconcern,buttherewasmuchuncertaintyaboutthepotentialvirulenceoftheH1N1virus.Wewere“lucky”thattheinitialinformationaboutthehighlyvirulentnatureoftheH1N1virusprovedtobemostlyincorrect.But,wewere“aptly”preparedthroughtheproductionoflargeamountsofvaccine.

In2009,manyofthechallengesfacedduring1975withcommunicationandotherissueswereovercome.However,thisdoesn’tprecludetheneedforacriticalanalysisofthe2009H1N1local,regionalandnationalresponse.Wehavealwayslearnedfromourexperienceswithinfectiousdiseases,e.g.,yellowfever,smallpox,polio,malaria,etc.epidemics.Wemustcontinuetolearnfromthe2009H1N1epidemicandcriticallyanalyzeeveryaspectofoursuccessesandfailures.

Oneinterestinglessontobelearnedfromthisepidemicisthechallengeanddifficultyofcom-municationinasysteminwhichthekeyplayersareallfocusedondifferentaspectsofthepandemic.Publichealthagencieswerefocusedonimmunizations;healthcaresystemswerefocusedonpreventingtransmissiontopatientsandprotectingtheirworkforcetoensuretheiravailabilitytomeethealthcare

demands;whilephysicianswererespondingtopatientneedsintheiroffices.Theseincongruentfociresultedinconfusion,concernandineffectiveandinefficientresponsetovariouselementsofthepandemic.Wewereluckythatthepandemicprovednottobeasbadasitcouldhavebeen.Morespecifically,fouraspectsofourresponsetotheepidemicrequireanalysisandimprovement:Communication:Somebelievetherewas“communicationfatigue”aboutthepandemic.Whilethatmaybetrueatthenationallevel;areviewofregionalcommunicationsuggeststhattherewereopportunitiesforimprovedcommunicationatthelocallevel.Thepubliclikestoreceive

informationfromlocal“authorities”and“opinionleaders”withwhomtheycanrelate.Weneedtolearnhowtobettercoordinatecommunicationamongalllevelsoftheprivateandpublicsectors. Guidance: Guidanceprovidedbynationalprofessionalorganiza-tionsandgovernmentalagencieswassometimescontradictory,whichaddedtotheconfusion.Thiswasperhapsthemostdifficultissuefacedbyourhealthcaresystems.Response Systems: Wehaveanexcellentemergencyresponsesystem(ERS)inFlorida,butitisprimarilyfocusedonnaturaldisastersandbioterrorism.PreparationforthesedisastersassumesasingleorseriesofrelatedeventsthatrequirearesponsefromtheERSaftertheeventoccurs.Itisappropriatefortheresponsetobeprimarily“reactive”inthesetypesofdisasters.Infectiousdiseaseepidemicsrequirea“preventiveresponse,”nota“reactive”one.Toquoteanunknownsource,“Itisamarathonandnotasprint.”Infectiouseventscanbeepisodicandcomeinwavesduringepidemics.Adjustmentsmustbemadetodealoptimallywithfutureresponses.Thiswasdoneacenturyagoforyellowfever.3Thiscancertainlybedonetoday.Vaccines: Finally,vaccineprogramsrequiredfortheresponsetoepidemicshavetobepreparedaheadoftimeandmustincludefrontlineproviderswhocandeliverthevaccine.Inthe2009H1N1epidemic,thevaccinesupplywasnotgoodenough,timingwasnotfastenough,deliverywasnotefficientenoughandaccesswasnotequitableenoughThismustbeimprovedbeforethenextepidemichitsusbecausewemaynotbeasluckythenexttime.

Weareastrongandinnovativenationandcanalwaysimproveourresponse,buttodosowemusthavethewillandresources.Thiscanbestbeachievedbyacollaborativeplanbetweenthepublicandprivatesectors.4

IhopeyouenjoythisissueofNEFM.HIV,H1N1,TBandMRSAareamongthemostprevalentinfectiousdiseaseswecontinuetofaceeachday,sothosetopicsareaddressedandwehaveaddeda“PediatricPerspective”forH1N1,TBandMRSA.In“Suc-cessesandChallengesinMothertoChildTransmissionofHIVinFlorida,“ Ayesha Mirza, MD, writesaboutthegreatsuccessinthepreventionofmothertochildtransmissionofHIVandhighlightsthechallengestofaceinthefuture.In“MitigatingtheH1N1Pandemic:AYearinReview,”Taj Azarian, MPH andSaad Zaheer, MD,addressthepublichealthaspectsoftheH1N1epidemic,andHaidee Custodio, MD,providesthe“PediatricPerspective.”ThisisalsotheCMEarticlefortheissue.In“TuberculinSkinTest:LossofanOldFriend?,”Jeffrey Lauer, MD,writesabouttheongoingissueoftuberculosis,and Ana Alvarez, MD,presentsthe“PediatricPerspective”.Andfinally,in“CommunityAssociatedMethicillinResistantStaphylococcusAureus”Nilmarie Guz-man, MD,summarizestheproblemwithMRSAthatallofusaredealingwitheveryday,andNizar Maraqa, MD,providesthe“PediatricPerspective”.Sources: 1.NeustadtREandFineberg,HV.The Swine Flu Affair: Decision-Making on a Slippery Slope.UniversityPressofthePacific,Honolulu,Hawaii.2005;2.McNeil,RonalG.Jr.,“USReactiontoSwineFlu:AptandLucky”.New York TimesJanuary2,2010.http://www.nytimes.com/2010/01/02/health/02flu.html.AccessedJuly2010;3.Oshinsky,DavidM.Polio an American Story.OxfordUniversityPress,NewYork,Ny.2006;4.PierceJohnRandWriterJamesV.Yellow Jack: How Yellow Fever Ravaged America and Walter Reed Discovered Its Deadly Secrets.JohnWiley&Sons,Inc.Hoboken,NJ.

Mobeen H. Rathore, MD, CPEProfessor & Associate Chairman, Chief Pediatric Infectious Diseases & Immu-nology. Wolfson Children’s Hospital & Hospital & General Academic Pediat-rics, University of Florida, Jacksonville, Florida

http://www.nytimes.com/2010/01/02/health/02flu.html

http://www.nytimes.com/2010/01/02/health/02flu.html


Successes and Challenges in Mother toChild Transmission of HIV in Florida

AyeshaMirza,MD

Address Correspondence to: Ayesha Mirza MD, UFCARES,DepartmentofPediatrics,653-1West8thStreet,LRC3rdFloor,Jacksonville,Florida,Ph:904-244-5012,Fax:904-244-5341.Email:[email protected].

Editor’s Note: Due to production constraints, Figure 1 is not printed in the journal. It is available online at www.dcmsonline.org as a web illustration.

Abstract: Most pediatric human immunodeficiency virus (HIV) infec-tions occur through mother to child transmission (MTCT). Significant progress has been made in the United States (US) and other resource rich countries since the start of the HIV epidemic more than 20 years ago. Prior to the institution of highly active antiretroviral therapy (HAART) one in four babies born to an HIV infected mother would be likely to be infected. Significant milestones have been achieved in the prevention of MTCT of HIV in children. Measures contributing to this success include the institution of the 076 Pediatric Aids Clinical Trials Group (PACTG) protocol and zidovudine (ZDV) administra-tion to both mother and baby, availability of HAART for pregnant women, elective caesarian delivery when indicated, avoidance of breast feeding, opt-out testing for pregnant women as well as rapid testing of pregnant women during labor and delivery when results of HIV tests are not available. While Florida has had a high number of MTCT, significant measures have been undertaken to greatly reduce MTCT in the state. These include the passage of laws by the legislature to facilitate HIV testing as well as ‘opt-out’ testing for pregnant women, educational and outreach programs for pregnant and at-risk women, availability of rapid testing at point of care facilities as well as easy access to free rapid tests through various programs. Barriers to care include access to timely care, retention in care as well as institution of appropriate and timely testing of pregnant women in accordance with the 2006 Centers for Disease Control and Prevention (CDC) guidelines. Continuing educa-tion of providers as well as the general public remains the cornerstone of preventive efforts to reduce MTCT.

Overview Incontrasttotheadvancesinthedevelopedworld,pre-

ventionofMTCTisstillamajorpublichealthchallengeinresourcelimitedcountries.AvailabilityoffundingthroughtheUSPresident’sEmergencyPlanforAIDSRelief(PEPFAR),theBillandMelindaGatesFoundation,TheClintonGlobalHealthInitiativeaswellasmultipleothergovernmentalandprivatedonoragencieshavechangedthefaceoftheepidemicsomewhat,butmuchworkstillneedstobedone.3In2008,45%ofHIVinfectedpregnantwomenreceivedantiretroviraldrugstopreventtransmissiontotheirnewbornscomparedwith9%in2004.ThenumberofchildrennewlyinfectedwithHIVinSubSaharanAfricawentfrom460,000in2001to390,000in2008.4Aswouldbeexpected,thereareregionaldifferenceswithsomecountriesdoingbetterthanothersatreducingMTCT.

Comparedtothis,intheUS,thenumbersofnewHIV

infectionsinchildrenare100-200annually,andthesenum-berscontinuetodecrease.Thechallengeswefacehereareofadifferentnature.Approximately25%ofallpeopleinfectedwithHIVdonotknowtheirstatus,thusmanywomenwhoareinfectedwithHIVareunawareoftheirinfection.ThisemphasizestheimportanceofuniversalroutinetestingforHIVaswell as opt-out testing forpregnantwomen.5ThenumbersofwomeninfectedbyHIVhasalsobeengrowingsteadilyand,asisseenacrossthecountry,disproportionatelyaffectsminoritywomen.

One of the most significant achievements of our timesinHIVresearchweretheresultsofthePACTG076whichshowedthatadministrationofZDVtothemotherafterthefirsttrimester,aswellascontinuedadministrationofZDVduring labor and delivery and treatment of the newbornuptosixweeksoflife,resultedinreductioninMTCTbyapproximatelytwo-thirds(from8.3%intheZDVgroupto25.5%intheplacebogroup).1Othersignificantmilestoneshavealsobeenachievedsincethen.TheinstitutionofHAART,caesarian delivery for women with an HIV viral load ≥1000copies/ml,avoidanceofbreastfeedingaswellasusinganopt-outapproachforHIVtestingofpregnantwomenhaveallcontributedtodecreasingtherateofMTCTtolessthan1-2percent.2(Figure 1, www. dcmsonline.org)

Key Florida StatisticsInFloridain1987ofreportedAIDcases,only11%were

women 13 years of age or older. This number increasedto33%in2009.Womenaccountedfor26%oftheHIVcasesreportedin2009.Thefemalepopulationages13+ofFloridain2009was63%whiteand15%black,incontrastthenumbersofwhitewomenaffectedbyHIV/AIDSwas18/15%respectivelycomparedto66/69%forblackwomen.Heterosexualcontactwasthemajormodeofinfection(87-89%).Through2008,1in296women(ages13+)inFloridawerelivingwithHIV/AIDS,including1in64blacks,1in445Hispanics,1in1,153whitesand1in466otherraces.Through2009inFlorida,atotalof28,878womenwereliv-ingwithHIV/AIDS,ofwhich13,842(48%)werewomenofchildbearingage(25-44).Therewere539(2%)femaleswithHIV/AIDSinthe13-19yearagegroupwhichhasnottraditionallybeenconsideredas‘childbearing’age.6

Infectionamongwomenparticularlythoseofchildbear-ing age becomes important since Florida is second onlytoNewYorkState in thenumberofbabiesborn toHIVpositivewomenoverthepast20years.Amongstateswithconfidential name based reporting cumulative through2007,Floridareported541cases(9.3%)ofHIVinfectioninchildrenlessthan13yearsofage,secondonlytoNewYorkwhichreported1765(30.3%)andTexasbeingaclosethird


reporting430cases (7.4%).7-9Floridaalso ranks second inthenumberofcumulativepediatric(AIDS)casesreportedthrough2007,(n=1,544).10HIVreportingwasinitiatedinFloridain1997.

Through 2008, Florida has reported a cumulative totalof2,374HIVandAIDScases.Themajorityofthesecaseswereperinatallyacquired(95%,n=2,250).Theremainder,were acquired through blood transfusion, hemophilia oranotherrisk.11

HIV Challenges in FloridaThe number of perinatally acquired cases has declined

steadilyfromapeakof201casesin1992toonly9sofarin200912.However,missedopportunitiesforinterventioncontinuetooccur.Itrequiresconstantvigilanceonthepartofproviderstomakesurethatpregnantwomenhaveaccesstocare,remainincareandaretestedaccordingtothe2006(CDC)guidelines.13

Accordingtotheseguidelinesforpregnantwomen:• HIVscreeningshouldbeincludedintheroutinepanelof

prenatalscreeningtestsforallpregnantwomen.• HIVscreeningisrecommendedafterthepatientisnotified

that testingwillbeperformedunless thepatientdeclines(opt-outscreening).

• SeparatewrittenconsentforHIVtestingshouldnotbere-quired;generalconsentformedicalcareshouldbeconsideredsufficienttoencompassconsentforHIVtesting.

• Repeatscreeninginthethirdtrimesterisrecommendedincertain jurisdictionswith elevated rates ofHIV infectionamongpregnantwomen

AreviewofMTCTinFloridafrom2002-2009showedthatwhileoverallthenumberofHIVMTCTinFloridais1.5%,whichiswhatisexpectedwithuseofappropriateperinatalpreventionregimensofantiretroviraldrugs(i.e.therewere9(1.5%)perinatallyinfectedchildrenbornto607HIVinfectedwomenin2008),therewereseveralmissedopportunitiesforprevention.14Accesstocareandretentionincarewereseenasthemajorissuesresultinginlesslikelihoodforthehighestriskwomentogettested,especiallyinwomenofcolor.Whilethereasonsforthisaremultifactorial,health-relatedbeliefssuchasavoidanceanddisbeliefofHIVserostatus,conceptionsofillnessandappropriatehealthcare,andnegativeexperienceswith,anddistrustofhealthcareallcontributetodecisionsrelated to access to HIV care. Mental health and stigmaalsoaddsignificantlytotheproblem.Otherfactorssuchasfrequentsexuallytransmittedinfections(STI),intravenousdrugandsubstanceabusehavealsobeenidentifiedasbar-rierstoappropriatecare.Linkagetocareandtheavailabilityofongoingcareiftransferredfromonefacilitytoanotherisalsocrucial.Perhapsmostimportantofall,testingperthe2006CDCguidelines,documentationofmaternaltestingduringboththefirstandthirdtrimesters,statusifknowntobepreviouslyinfected,aswellas,promptrapidtestingduringlaboranddeliveryifstatusisunknownareallcrucialstepsinthepreventionofMTCT.

A retrospective review of HIV exposed infants whosedata was reported to the CDC Enhanced Prevention

SurveillanceSystemfrom1999-2003(n=8115)showedthatforapproximately4%ofexposedinfantswhosedatawasreportedrecognizedmaternalHIVinfectionwasnotdocumentedintheexposedinfants’birthrecord.15AftercontrollingthedataforpotentialconfoundingfactorssuchasprenatalHAARTto themother, HAART to themotherduring labor anddelivery,durationofruptureofmembranes,infantswithoutdocumentationofmaternalHIVinfectionwerefoundtohavehad70%increasedoddsofHIVinfectioncomparedwithinfantswithadequatedocumentation(adjustedOR,1.7;95%CI,1.1-2.6).Thatissimplynotacceptable.Communicationlapsessuchasthisareavoidableandinexcusable.

Addressing the Challenges Florida began to address MTCT in the mid-1990s us-

ing a multi-pronged approach which included educationandinformationcampaignsforbothpregnantwomenandproviders.In1996alaw(FloridaStatutesTitle29§384.31)waspassedthatrequiredproviderstoofferallwomenseeninprenatalcaresettingsanHIVtest.Anotherlawpassedin2005(amendsFloridaStatutesTitle29§381.004)madeitroutinetotestallpregnantwomenforHIVandtoinformthewomanofherrighttorefusetestingunderthe‘opt-out’approach.ItwasalsobroadenedtoincludetestingforotherSTIaswell.16Thislawwasactuallyimplementedin2007.FloridaAdministrativeRule64D-3.042alsostatesthatemer-gencydepartmentsmayfulfillthetestingrequirementsstatedabovebyreferring(inwriting)pregnantwomenwhohavenotreceivedprenatalcaretothelocalhealthdepartmentfortesting.OthermeasuresthathavebeenputinplacebytheFloridaDepartmentofHealth(FDOH)includetheBabyRxPress Program which provides ZDV to HIV exposednewbornsatnocosttothefamilywhentheyhavenoothermeanstopayforthemedication.ThegoalsofthisprogramaretoensurethatnomotherleavesthehospitalwithoutZDVinhandforthebaby.

Inaddition, since2003more thanhalfof thehospitalsinFlorida,includingShandsJacksonville,offerrapidHIVtestingduringlaboranddelivery.DatafromthePregnancyRiskAssessmentMonitoringSystem(PRAMS)indicatethatFlorida’sHIVtestingratesforpregnantwomenhaveincreasedsignificantlyover the last fewyearswith86-90percentofwomensurveyed reporting that theyhaddiscussionswiththeirhealthcareprovideraboutHIVtesting.17

Statewideotherprograms that are available include theTargetedOutreachforPregnantWomenAct(TOPWA)aswell as theAdvancingHIVPreventionalsoknownas theAfrican American Testing Initiative. Both programs offerfreeHIV testing, aswell as outreach andongoing educa-tion.TOPWAisavailableforallhighrisk,aswellasHIVinfectedwomen,andoffersHIVtesting,education,linkagetocareandintensivecasemanagementthroughpregnancyandbeyond.18BothprogramsareavailableinDuvalCountyandatShandsJacksonville

WhileTOPWA initially started in community venues,expansion into jailswas promptedby concerns about thehighHIVprevalenceamongincarceratedwomenaswellasthe lackofadequateprenatalcareamong thosewhowerepregnant.ThereforeinFebruary2002,theFDOHpilotedthefirstTOPWA-fundedjailprograminPalmBeachCountybypartneringwiththelocalSTIprogramwhichhadbeenactive


inthejailsystemforseveralyears.SincethenadditionaljailprogramshavebeenimplementedinOrange,HillboroughandMiami-Dadecounties.TOPWAworkersscreenallfemaleinmatesforprogrameligibility.Theyofferon-sitepregnancyandHIVtestingandcounselingalongwitheducationaboutHIV,STI,substanceabuseanddomesticviolence.Theyalsoensurelinkagetocarebothduringtheperiodofincarcerationaswellasoncethewomanisreleasedfromjail.InadditiontheyworkwithHealthyStartprogramstohelpthemgainaccesstojailstoprovideprenatalcareandrelatedservices.

InadditiontoTOPWA,theFDOHcurrentlyfunds15countyhealthdepartments(includingDuval)toimplementtransitional services in local jails.These jail linkprogramsincludecounselingandtestingforHIV/AIDS,Tuberculosis,hepatitis andotherSTI,preventioneducation,pre-releaseplanningforinmatesandfollow-upservicestoensurethatinmatesarelinkedtocarefollowingrelease.Pre-releaseplan-ningprogramsensurethatinmateshavea30-daysupplyoftheirmedication,anappointmenttobeginmedicalcareneartheirhomeandacopyoftheirmedicalrecordstoexpeditetreatment.19,20

Conclusion Significantmilestoneshavebeenachievedintheprevention

ofMTCTofHIVinchildren.Theinstitutionofthe076PACTGprotocolandZDVadministrationtobothmotherandbaby,availabilityofHAARTforpregnantwomen,elec-tivecaesariandeliverywhenindicated,avoidanceofbreastfeeding,optouttestingforpregnantwomenaswellasrapidtestingofpregnantwomenduringlaboranddeliverywhenresultsofHIVtestsarenotavailablehaveallcontributedtothissuccess.

SignificantmeasureshavealsobeenundertakentoreduceMTCTinFlorida.TheseincludethepassageoflawsbythelegislaturetofacilitateHIVtestingaswellas‘optout’testingforpregnantwomen,educationalandoutreachprogramsforpregnantandatriskwomen,availabilityofrapidtestingatpointofcarefacilitiesaswellaseasyaccesstofreerapidteststhroughvariousprograms.

EffortstopromotepropereducationamonghealthcareprovidersandthecommunityingeneralremaincriticalaswecontinuetostrivetowardstheultimategoalofeliminatingMTCT.Primarycareprovidersneedtohavefrequentandopenconversationswith theirpatients,particularlyyoungwomenabout the importanceof safe sexualpractices andHIVtesting.HIVtestingduringpregnancyisalsocriticalandinjurisdictionswithhighratesofHIVinfection,Floridabeingoneofthem,itisessentialthatthe2006CDCguide-linesbefollowedandprovidersbeawareofandpracticeinaccordancewithstatelaws.InadditioninsituationswhereHIVtestresultsareessentialandunknown,eg.duringlaboranddelivery,rapidtestingatpointofcareinhospitalsandotherhealthcaresettingscanhelpinprovidingquickandtimelyHIVtesting.

References1. Connor EM, Sperling RS, Gelber R et al. Reduction of

maternal-infant transmission of human immunodeficiencyvirus type 1 with zidovudine treatment. N Eng J Med1994;331:1173-80.

2. JamiesonDJ,ClarkJ,KourtisAPetal.Recommendationsfor human immunodeficiency virus screening, prophylaxis

andtreatmentforpregnantwomenintheUnitedStates.Am J Obstet Gynecol2007;197(3Suppl):S26-32.

3. Mofenson LM. Prevention in neglected subpopulations:preventionofmothertochildtransmissionofHIVinfection.Clin Infect Dis2010;Suppl3:S130-48.

4. UNAIDS Data Report 2009. http://data.unaids.org/pub/Report/2009/JC1700_Epi_Update_2009_en.pdf. AccessedMay21,2010.

5. MarksG,CrepazN,JanssenRS.EstimatingsexualtransmissionofHIVfrompersonsawareandunawarethattheyareinfectedwiththevirusintheUSA.AIDS2006;20:1447-1450.

6. HIV/AIDSamongwomen.FloridaFactSheets.http://www.doh.state.fl.us/Disease_ctrl/aids/updates/facts/09Facts/2009_Women_Fact_sheet.pdf.AccessedMay25,2010.

7. Florida: cumulative reported HIV infections (cases).statehealthfacts.org.http://statehealthfacts.org/profileind.jsp?cat=11&sub=122&rgn=11.AccessedNovember24,2009.

8. NewYork:cumulativereportedHIVinfections(cases).statehealthfacts.org.http://statehealthfacts.org/profileind.jsp?cat=11&sub=122&rgn=34.AccessedNovember24,2009.

9. Texas: cumulative reported HIV infections (cases).statehealthfacts.org.http://statehealthfacts.org/profileind. jsp?cat=11&sub=122&rgn=45.AccessedNovember24,2009.

10. Florida: cumulativeAIDScases. statehealthfacts.org.http://statehealthfacts.org/profileind.jsp?cat=11&sub=118&rgn=11.AccessedNovember24,2009.

11. Florida Department of Health, 2008 Fact Sheets. http://www.doh.state.fl.us/Disease_ctrl/aids/updates/facts/2008_Pediatric_Fact_Sheet.pdf.AccessedNovember24,2009.

12. Nita Harrell, Florida Department of Health.PersonalCommunication.September2009.

13. RevisedRecommendationsforHIVtestingofadults,adolescentsand pregnant women in health care settings. MMWR. 2006;55(RR14):1-17. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm.AccessedMay24,2010.

14. MirzaA,CustodioH,HarelleN,RathoreMHetal.AnalysisofperinatalHIVtransmissioninFlorida2002-2009,successandfuturechallenges.Abstract#MOPE0273.InternationalAidsConference,July18-23,2010,Vienna,Austria.

15. Taylor AW, Ruffo N, Griffith J et al. The missinglink: documentation of recognized maternal humanimmunodeficiency virus infection in exposed infant birthrecords, 24 United States jurisdictions, 1999-2003. Am J Obstet Gynecol2007;197(3Suppl):S132-6.

16. The 2005 Florida Statutes.Chapter 384 SexuallyTransmitted Diseases. http://www.leg.state.fl.us/Statutes/index . c fm?App_mode=Di sp l ay_St a tu t e&Sea rch_String=&URL=Ch0384/SEC31.HTM&Title=->2005->Ch0384->Section%2031#0384.31.AccessedMay24,2010.

17.PediatricHIV/AIDSCasesinFlorida,through2007.http://www.doh.state.fl.us/Disease_ctrl/aids/trends/epiprof/epiprof_peds_2007.pdf.AccessedMay24,2010.

18.TOPWA.Informationavailableat:http://www.preventhivflorida.org/Women_Children/TOPWA.htm.AccessedAugust2,2010.

19. Florida DOH Corrections Program. http://www.preventhivflorida.org/Corrections/DOH_Corrections_Programs.htm.AccessedAugust2,2010.

20.ClarkJ,SansomS,SimpsonJB,etal.PromisingstrategiesforpreventingperinatalHIVtransmission:modelprogramsfromthreestates.Matern Child Health J 2006;10:367-373.

http://data.unaids.org/pub/Report/2009/JC1700_Epi_Update_2009_en.pdf

http://data.unaids.org/pub/Report/2009/JC1700_Epi_Update_2009_en.pdf

http://www.doh.state.fl.us/Disease_ctrl/aids/updates/facts/09Facts/2009_Women_Fact_sheet.pdf. Accessed May 25



http://statehealthfacts.org/profileind.jsp?cat=11&sub=122&rgn=11








http://www.doh.state.fl.us/Disease_ctrl/aids/updates/facts/2008_Pediatric_Fact_Sheet.pdf



http://www.doh.state.fl.us/Disease_ctrl/aids/trends/epiprof/epiprof_peds_2007.pdf



http://www.preventhivflorida.org/Women_Children/TOPWA.htm. Accessed August 2

http://www.preventhivflorida.org/Women_Children/TOPWA.htm. Accessed August 2

http://www.preventhivflorida.org/Corrections/DOH_Corrections_Programs.htm. Accessed August 2




Mitigating the H1N1 Pandemic: A Year in Review

Background - Benefits that Matter!TheDuvalCountyMedicalSociety(DCMS)attemptstoprovideitsmemberswiththebenefitsthatconsistentlymeetyourprofes-

sionalneeds.OneexampleofhowthisisbeingaccomplishedisbyprovidingtoDCMSmembersfreeContinuingMedicalEducation(CME)opportunitiesinthesubjectareasmandated/andorsuggestedbytheStateofFloridaBoardofMedicinetoobtainandretainmedicallicensure.TheDCMSwouldliketothanktheSt.Vincent’sHealthcare(SVHC)CommitteeonCMEforreviewingandac-creditingthisactivityincompliancewiththeAccreditationCouncilonContinuingMedicalEducation(ACCME).HelenaKarnani,MD,ChairoftheCMECommittee;BetsyMiller,Director,MedicalStaff,QualityManagement;andCindyWilliamson,CMECo-ordinator,fromSVHCdeservespecialrecognitionfortheirworkonbehalfofDCMS.

ThisissueofNortheast Florida Medicine includesanarticle,“MitigatingtheH1N1Pandemic:AYearinReview”authoredbyTajAzarian,MPHandSaadZaheer,MD,MSPH(see pp. 17-22),whichhasbeenapprovedfor1.0AMAPRACategory1credit(s).™ForafulldescriptionofCMErequirementsforFloridaphysicians(MD/DO),pleasevisittheDCMSwebsite(http://www.dcmsonline.org/cme_requirements.aspx).

Faculty/Credentials: TajAzarian,MPH,worksasaPublicHealthPreparednessandSurveillanceEpidemiologistfortheDuvalCountyHealthDepartmentlocatedinJacksonville,FL.Dr.Zaheer,MD,MSPH,istheProgramDirector,EpidemiologyandBioter-rorismSurveillancefortheDuvalCountyHealthDepartment

Objectives for CME Journal Article1. Describethepublichealthresponsetothe2009InfluenzaA(H1N1)Pandemic2. Identifychallengesandsuccessesoftheresponse3. Generalizethemorbidityandmortalityofthepandemicandtheefficacyofthevaccinationcampaign

Date of Release: September 3, 2010 Date Credit Expires: September 3, 2011 Estimated time to complete: 1 hr.

Methods of Physician Participation in the Learning Process1.Readthe“MitigatingtheH1N1Pandemic:AYearinReview:articleonpages17-22

2.CompletethePostTestandEvaluationonpage16

3.Cutout&faxthePostTestandEvaluationtoDCMS(FAX)904-353-5848ORmembersgotowww.dcmsonline.org&submittestonline

CME Credit EligibilityInordertoreceivefullcreditforthisactivity,aminimumpassinggradeof70%mustbeachieved.Onlyonere-takeopportunitywillbegrantedifapassingscoreisnotmadeonthefirstattempt.DCMSmembersandnon-membershaveoneyeartosubmittheposttestandearnCMEcredit.Acertificateofcredit/completionwillbeemailed,faxedorUSPSmailedwithin4-6weeksofsubmission.Ifyouhaveanyquestions,pleasecontacttheDCMSat355-6561,ext.103,[email protected].

Faculty Disclosure InformationMr.AzarianandDr.Zaheerreportnosignificantrelationshipstodisclose,financialorotherwisewithanycommercialsupporterorproductmanufacturerassociatedwiththisactivity.

Disclosure of Conflicts of InterestSt.Vincent’sHealthcare(SVHC)requiresspeakers,faculty,CMECommittee,andotherindividualswhoareinapositiontocontrolthecontent

ofthiseducationalactivitytodiscloseanyrealorapparentconflictofinteresttheymayhaveasrelatedtothecontentofthisactivity.AllidentifiedconflictsofinterestarethoroughlyevaluatedbySVHCforfairbalance,scientificobjectivityofstudiesmentionedinthepresentationandeducationalmaterialsusedasbasisforcontent,andappropriatenessofpatientcarerecommendations.

Joint Sponsorship Accreditation StatementThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medi-

cal Education through the joint sponsorship of St. Vincent’s Healthcare and the Duval County Medical Society. St. Vincent’s Healthcare is accredited by the Florida Medical Association to provide continuing medical education for physicians.

The St. Vincent’s Healthcare designates this educational activity for a maximum of 1.0 AMA PRA Category 1 credit(s) .TM Physicians should only claim credit commensurate with the extend of their participation in the activity.


1.WhatisthenameoftheFloridaDepartmentofHealth’s syndromicsurveillancesystem? a.NERVSS b.ESSENCE c.NVSNd.ILInet

2.Whichstatewasthefirstonetoreportcasesof2009InfluenzaA(H1N1)intheUnitedStates? a.Floridab.California c.Texas d.NewYork

3.AtwhatphasewastheWHOPandemicAlertLevelwhenFloridaidentifieditsfirstcaseofH1N1? a.Phase3b.Phase4c.Phase5 d.Phase6

4.InFlorida,whichagegroupdemonstratedthehighestrateofinfluenzahospitalizationsduetoH1N1? a.0-4yearsofage b.13-18yearsofagec.25-44yearsofaged.>65yearsofage

MitigatingtheH1N1Pandemic:AYearinReviewCMEQuestions&Answers(CircleCorrectAnswer)Free-DCMSMembers/$50.00chargenon-members*

(Return by September 3, 2011 by FAX: 904-353-5848, by mail: 555 Bishopgate Lane, Jacksonville, FL 32204 OR online: www.dcmsonline.org)

Evaluationquestions&CMECreditInformation(Pleaseevaluatethisarticle.Circleonenumberusingthisscale:1=StronglyAgreeto5=StronglyDisagree)Thearticlemetthestatedobjectives: 1 2 3 4 5Thearticlewasappropriatetomypractice: 1 2 3 4 5Thetopicwascurrentandwellpresented: 1 2 3 4 5Comments:_______________________________________________________________________

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5.WhichpreviouspandemicreplacedthethencirculatingH1N1influenzaviruswithaH2N2virusasthepre-dominantseasonalstrain?

a.1957AsianFluPandemicb.1968HongKongFlu c.1975SwineFlud.1992Fluseason 6.InFlorida,whichagegroupdemonstratedthehighest

rateofinfluenzahospitalizationsduetoH1N1? a.0-4yearsofage b.25-44yearsofagec.50-64yearsofaged.>65yearsofage7.OutsideoftheinitialACIPvaccinationtargetgroups,

which group had the highest estimated vaccinationcoverageinFlorida?

a.Children<6monthsofageb.Childrenaged6months-17yearsofagec.Adults25-64yearsofaged.Elderly>65yearsofage

8.BasedonestimatesfromtheBRFSSandNHFSsurveys,howmanypersonsintheU.S.wereimmunizedforH1N1byFebruary2010?

a.36millionpersons b.72millionpersonsc.86millionpersons d.113millionpersons


AddressCorrespondence to: TajAzarian,MPHDuvalCountyHealth Department, Jacksonville, Florida. Email: [email protected].

Mitigating the H1N1 Pandemic: A Year in ReviewTajAzarian,MPHandSaadZaheer,MD,MSPH

Editor’s Note: Due to production constraints, Figure 2 is not printed in the journal. It is available online at www.dcmsonline.org as a web illustration.

Abstract: In April of 2009, a novel influenza A (H1N1) virus was identified in the United States with the definitive characteristics of a pandemic virus. Within weeks, this virus had spread to every region in the country. In the proceeding months, agencies spanning from the international to county and city levels responded to the rapidly expanding public health emergency. In Duval County, the healthcare and public health community united to mitigate the local effects of the pandemic. This response was marked by myriad challenges that were overcome by pre-event preparedness and planning. These successes were driven by a well developed infrastructure and relationships formed through detailed planning for public health emergencies. These strengths allowed us to address the increase of H1N1 cases in our community, subsequent deaths, and the mass vaccination campaign. Ultimately, the severity of this pandemic was lower than initially predicted; however, the number of hospitalizations and deaths were nonetheless considerable. This experience offers lessons which will facilitate the preparation of future influenza outbreaks and pandemic responses.

OverviewThemonthofApril,2010markedtheoneyearanniversary

oftheemergenceofanovelpandemicinfluenzaviruswithintheUnitedStates.Despitenumerousiterationsofthisvirus’officialtitle,the2009pandemicinfluenzaA(H1N1)viruswillberememberedasoneofthemostreported,documented,studied,anddebatedpublichealtheventsinmodernhistory.Now,overayearaftertheemergenceofthisvirus,wereflectonthechallengesandsuccessesthatoccurred.

Whilevaccinationcampaignsandnumerousstudiesofthe2009influenzapandemicarestillunderway,manyagenciesarereflectingonthelastyeartoevaluatehowtheyresponded.Inthedwindlingdaysofthepandemic,aspredictionsofathirdwaveofillnessbegantofade,membersofthemediawerequicktoposethequestiontothepublichealth(PH)andthemedicalcommunityasawhole,“Howdidwerespond?”Forthosethatexperiencedthepandemicfirsthand;publichealthofficials,healthcareprofessionals,andemergencyrespond-ers,theresponsewasinaccordancewiththeeventwehadplannedforsincethe1918Spanishfluleftadevastatingmarkonmankind.However,asColinPowellsoconciselystated,“Nobattleplansurvivescontactwiththeenemy.”1

Throughoutthecourseoftheresponse,certaintopicspre-dominated.Theseincludedlaboratorytestingandsurveillancemethodologies,infectioncontrolrecommendations,schoolclosures,pandemicalertleveldesignations,andofcourse,thevaccineandimmunizationcampaign.Asaresult,significant

advancementshavealreadybeenmadeinhowtheseareasareaddressedonalocal,state,nationalandinternationalscale,furtherstrengtheningfutureresponsestoPHemergencies.Inaddition,thescientificcommunity’sunderstandingoftheepidemiologyandpathologyof influenzahasgreatlybeenimproved.Subsequently,changes in themedicaldiagnosisand management of influenza patients have positively af-fectedprognoses.Movingforward,wecontinuetoexaminethesetopicsinfinerdetailandprepareforournextencounterwiththeenemy.

The Emergence of a Novel VirusOn April 17, 2009, officials at the Centers for Disease

Control and Prevention (CDC) confirmed two cases ofswine influenza inchildren living inneighboringcountiesinCalifornia.2,3Overthesubsequentweek,reportsoflarge,highmortalityinfluenza-likeillness(ILI)outbreaksinMexicoCityfueledgrowingconcernsthatthetwoCaliforniacaseswereonlythetipoftheiceberg.OnApril24,onlyoneweekaftertheinitialCDCreport,sixadditionalcasesintheUnitedStateswerereportedfromthreestates;California,NewYork,andTexas.Thefollowingday,Dr.MargaretChan,DirectorGeneraloftheWorldHealthOrganization(WHO),declareda“publichealthemergency”inresponsetotheincreaseincasesreportedbytheUnitedStatesandMexico.Twodayslater,WHOraisedthepandemicalertleveltophase4,signifyingverified human-to-human spread of a novel virus. Subse-quently,onApril29,asaresultofincreasedhuman-to-humanspread,WHOraisedthepandemicalertleveltophase5.ThismovecoincidedwiththefirstreporteddeathintheUnitedStatesandsignaledapandemicwasimminent.

A State Responds InthefinaldaysofApril,2009,asthenumberofstates

reportingconfirmedcasesofH1N1begantogrow,theFloridaDepartment of Health (FDOH) prepared in anticipationfortheidentificationofFlorida’sfirstconfirmedcase.Upontheidentificationofanovelinfluenzaviruswithpandemiccapabilities,FDOHenactedresponseplansdelineatedintheBureauofEpidemiology’sPandemicInfluenzaAnnex.Theseplans called for implementation of enhanced surveillanceandcontrolmeasures identified in therapidresponseandcontainmentportionof this two-stageresponse.OnApril27,2009,Florida’sactingstateepidemiologist,Dr.RichardHopkins, addressed the epidemiology staff of the state’s67 county health departments (CHD). This presentationprovidedanoverviewofthecurrentsituationandoutlinedthegoalsoftherapidresponseandcontainmentportionofFlorida’splan.Theprimarygoalatthisstageintheresponse:surveillance.

Two great strengths of FDOH prevailed during theemergenceofthisnovelvirusandthroughoutthepandemic

mailto:[email protected]

mailto:[email protected]


response.Primarily,FDOHhasstrivedtocontinuallyexpandPHsurveillancecapabilities.Electronicsystemsexistforthereceiptoflaboratoryresultsfromlargeprivatelabs,aswellasthestatePHlaboratories.Thesesystemsalsoallowfortheelectronic reporting of investigative case reports from theCHDstothestate.Inaddition,hospitalemergencydepart-ment(ED)syndromicsurveillance(SS)dataaremonitoredthrough the Electronic Surveillance System for the EarlyNotificationofCommunity-basedEpidemics(ESSENCE).Florida’sESSENCESSsystem,whichisimplementedin138Floridahospitals,capturesanestimated75%ofFlorida’sannualEDvisitsandallowsforreal-timepopulation-levelawarenessofPHindicators.ESSENCEwasusedextensivelyduringtheH1N1responsetomonitorlevelsofactivitythroughoutthestate.(Figure 1)Thesesystemsareflexibleandefficient;twoqualities which facilitate effective and timely responses toPHemergencies.Secondly,sincethethreatsofSevereacuterespiratory syndrome (SARS) and H5N1Avian Influenzaraised concerns among health officials, FDOH has beenconductingtrainingsessionstopreparestaffhowtorespond.Thesetrainings,oftenconductedinconjunctionwithcol-laborating state and national agencies, outlined responseplansandforgedinteragencybonds.Ultimately,thesetwooverarchingstrengthsformedtheinfrastructureandlaidthefoundationforthisresponse.

Combinedwiththeearliermentionedsurveillancesystems,theFloridaSentinelInfluenzaSurveillanceProvidersNetwork(ILInet)andtheFloridaPneumoniaandInfluenzaMortalitySurveillanceSystemprovidethebasisformonitoringinfluenza

activityinFloridaannually.CDC’sILInetisthecornerstoneofnationalinfluenzasurveillance.Thisprograminvolvestherecruitmentofsentinel primarycareprovidersthroughouttheUnitedStateswhichreportthenumberofpatientsseenweeklywithILIduringinfluenzaseason.Inaddition,speci-mensarecollectedfromthesepatientsandsenttoaCDCorLaboratoryResponseNetwork(LRN)laboratoryfortestingand strain typing. This surveillance provides a compositeviewofnational influenza activity andcharacterizationofthecirculatinginfluenzaviruses.

AsFDOHrampedupsurveillanceintheearlystagesofthe response, ILInet providers were requested to increasespecimen collection. Health care providers were asked toevaluate patients with ILI and identify individuals withrecenttravelhistorytostatesorcountrieswithdocumentedcases. OnMay1,2009,FDOHCommunicationsOfficereportedtwoCDClaboratoryconfirmedcasesofH1N1inFlorida;an11-year-oldmaleelementaryschoolstudentinLeeCountyanda17-year-oldfemalehighschoolstudentinBrowardCounty.Onthatday,pursuanttoFloridaStatutes,381.00315,GovernorCharlieCristdirectedStateSurgeonGeneralDr.AnaViamonteRostodeclareaPHemergencythatallowedtheStateSurgeonGeneraltotakeanyactionnecessarytoprotectthePH.Atthispointinthepandemicresponse,CDChadreported109confirmedcasesofnovelinfluenzaintheUnitedStates,withonedeathinatwenty-threemonthold.Nationally,anestimated298schoolswereclosed due to cases of H1N1, leaving the issue of schoolclosureswithinFloridaasahighprioritytopic.Withinone

Visits (by Chief Complaint) to Emergency Departments (ED) as a Percentage of ALL ED Visits, Duval County ESSENCE Participating Hospitals (N=8), Week 40, 2006 through Week 24, 2010.

Figure 1 Influenza-like Illness Visits to ED


dayofthisannouncement,sixotherFloridacountieswerereportingcasesofH1N1.

Asthepandemicevolved,thePHsurveillanceandresponseobjectivesevolvedaswell.OnJune11,2009,Dr.Chanan-nouncedthedecisiontoraisethepandemicalertlevelfromphase5to6;stating,“Spreadinseveralcountriescannolongerbetracedtoclearly-definedchainsofhuman-to-humantrans-mission.Furtherspreadisconsideredinevitable”.4Onthatday,nearly30,000confirmedcaseshadbeenreportedin74countries.Thisdesignationindicatedaglobalpandemicwasunderwayandmarkedtheofficialtransitionfromtherapidresponseandcontainmentstrategytocommunitymitigation.BythetimethefirstcasesofH1N1wereidentifiedinFlorida,theWHOpandemicalertwasatphase5.ByMay1,Floridahadalreadyshiftedtoacommunitymitigationstrategy.

A Local County’s ResponseOnApril27,2009,theDuvalCountyHealthDepartment

(DCHD)activatedajointincidentcommandinconjunctionwithJacksonvilleFireandRescuetorespondtothisrapidlyexpandingsituation.Theobjectivesweretocoordinatethelocalresponse,maintainsituationalawareness,andplanfortheidentificationofthecounty’sfirstcase.Immediately,theneed toprovide rapid andaccuratehealth information tohealthcareprofessionalswas identified.Inresponse to thisneed,dailyhealthandmedicalcallswereestablishedtoupdatemembersofthehealthcarecommunity.

DuvalCountyreporteditsfirstconfirmedcaseofH1N1ina25-year-oldfemaleonMay6,2009.ThiswasFlorida’s55thconfirmedcase.Inall,DuvalCountywouldreport67

confirmedhospitalizationsduetoH1N1,including13deaths(asofMay15,2010).Inaddition,DCHDinvestigatedover25ILIoutbreaksinsettingsrangingfromschools,daycares,shelters,militaryfacilities,andfamilyhouseholds.Caseandoutbreakinvestigationswerealsocoupledwithatremendousdemandforpublic information.Callspoured in fromthecommunity:healthcareprovidersreportingcasesandrequest-ingtestingofpatients,concernedcitizenswhohadrecentlyreturnedfromMexico,rumorsofoutbreaks,andinquiriesfromschoolsandbusinesses.AllDCHDepidemiologyandemergencypreparednessstaffwerefocusedontheinfluenzaresponse.

CasesTheidentification,investigation,andreportingofH1N1

caseswasoneofthemostdynamicaspectsoftheresponse.Theinitialobjectivewastoidentify,investigateandreporteach case of influenza.Thiskey factorwas imperative forcharacterizing the pandemic, estimating the severity, andultimatelydeterminingthedetailsofthePHresponse.Sub-sequently,animmediateanddramaticneedforlaboratorytestingemerged.PatientsbegantopresenttoEDswithILIingrowingfrequencies,allrequestingtestingforH1N1.Localprovidersandurgentcarecenterswerealsogreatlyaffectedbyasignificantincreaseinvisitsandaccompanyingtestingdemands.Initially,CDClaboratoriessolelypossessedthecapability to provide confirmatory testing. In Florida, allrequestswereapprovedthroughtheCHDpriortotestingatthestatePHlaboratoryandsubsequentCDCconfirmation.The four FDOH laboratories were quickly overwhelmed.CDCandFDOHissuedclinicianguidanceforthetesting

Figure 3 Number of Specimens Tested

Tested by Florida Bureau of Laboratories and Percent Positive for Influenza - Week 40, 2008 to Week 20, 2010.


ofsuspectH1N1patientsandalleviatedsomeofthedemandfortesting.TheFloridaFluHotlinewasalsoestablishedtoanswerquestionsfromcliniciansandcommunitymembers.Coincidingwiththeincreaseintestingrequests,atremendousdemandforantiviralscausedspotshortagesthroughoutthestate.OnMay7,2009,allFDOHlaboratorieswerevalidatedbyCDCtoprovideconfirmatorytestingfortheofH1N1virus,andbymid-Maymoststateshadacquiredthiscapa-bilityaswell.Duringthepeakofactivity,theselaboratoriesperformedover2200influenzatestsinasingleweek(Figure 2, www.dcmsonline.org and Figure 3, p.19).

InlateMay,CDCupdateditstestingguidancetoplacemoreemphasisonclinicaloutcomesandunderlyingcondi-tions.BetweenthemonthsofApriltoJulyof2009,FDOHreportedalllaboratoryconfirmedcasesofH1N1totheCDC.FromJulyon,FDOH,inaccordancewithupdatedCDCguidance,changedtoreportingcasesmeetingselectcriteria:hospitalizations, including those inpregnantwomen, anddeaths. Anunintended result of the continual change insurveillancecasedefinitionsandcasereportingwasconsider-ableconfusionregardingtheinterpretationofthesefiguresbythemediaandpublic.Thisfactalsohadaneffectonthepublic’sperceptionoftheseverityofthepandemicandthetransparencyofthePHresponse.

In all, Florida reported 1323 hospitalizations betweenJuly28,2009andMay15,2010,including228deaths.Thehighest rateofhospitalizationswasobserved in the00-04agegroup.The50-64year-oldagegroupdemonstratedthehighest rate of deaths. Furthermore, of the total reporteddeaths, 84.2% had an identified underlying condition. Itwas identified early in the pandemic that this virus wassparingolder individuals,contrarytowhat is traditionally

observedwithseasonalinfluenza.Itwouldlaterbeidentifiedthatpeoplebornbefore1957werelesssusceptibletoH1N1thenyounger individuals.Whywas1957 themagicyear?Afteritsfirstappearance,theH1N1viruswhichcausedthe1918pandemicdominatedthecirculatinginfluenzastrainsforalmost40yearsuntilitwasreplacedin1957byaH2N2influenzaviruswhichcausedtheAsianFluPandemic.Whilethepre-1957H1N1viruswassignificantlydifferentthanthe2009virus,enoughantigenic similarityexistedtoprovideindividualsexposedto thepre-1957viruswithprotectionagainstthe2009virus.

FromAugust30,2009,throughMarch27,2010,WHOand National Respiratory and Enteric Virus SurveillanceSystemcollaboratinglaboratoriesintheUnitedStatestested422,648specimens.Ofthese,89,585(21.1%)werepositive:89,298(99.7%)werepositiveforinfluenzaA,andalmostallwere2009H1N1viruses.5DuringAugust30,2009-Mrch27,2010,34statesreportedatotalof41,689hospitalizationsassociatedwithlaboratoryconfirmedinfluenzavirusinfec-tionstoCDC.3Ratesofhospitalizationwerehighestamongchildrenaged0-4years.Atotalof2,096deathsassociatedwithlaboratoryconfirmedinfluenzavirusinfectionswerealsoreportedtoCDCduringthisperiod.Cumulativeinfluenza-associateddeathratessinceAugust30,2009,werehighestamong persons aged 50-64 years and lowest in children.3Basedonthesedata,andstudiesconductedby theCDC,estimatesofmorbidityandmortalitywerecalculatedforthetimeperiodofApril2009throughApril10,2010.6ForthisperiodCDCestimatedbetween43millionand89millioncasesof2009H1N1,betweenabout195,000and403,000H1N1-relatedhospitalizations,andbetweenabout8,870and18,3002009H1N1-relateddeaths.6(Figure 4)

Figure 4 CDC Estimates of 2009 H1N1 Cases in the U.S. by Age Group


The VaccineThemostchallengingcomponentofthePHresponsewas

thevaccinationcampaign.Essentially,allmitigationeffortsareconductedtoslowthespreadofthevirus,providingmoretimeforscientiststodevelopavaccine.Thequickerthevaccineisdevelopedandadministered,thegreaterreductioninthepandemic’smorbidityandmortality.Uponidentificationoftheinfluenzapandemic,severalvaccinemanufacturersbeganworkingonproducingenoughvaccinetomeettheprojecteddemand. Itwas evident thatdespite thismassive effort toproduce sufficient vaccine to rapidly immunize everyone;vaccinewouldmorethanlikelybecomeavailabletostatesinlimitedallocations.InJuly2009,theAdvisoryCommitteeonImmunizationPractices(ACIP)issuedrecommendationsfortheuseofinfluenzaA(H1N1)2009monovalentvaccine.7

Theserecommendationswereintendedtoprovidevaccina-tionprogramsandproviderswith informationtoassist inplanningandtoalertprovidersandthepublicabouttargetgroupscomprisinganestimated159millionpersonswhoarerecommendedtobefirsttoreceivethevaccine.7Whiletheguidingprincipleoftheserecommendationswastovac-cinateasmanypersonsaspossibleandquicklyaspossible,stateandlocalhealthofficialswereleftasthefinaldecisionmakers regardinghow thevaccinewouldbe administeredanddistributed.

Distributionof2009H1N1vaccineintheUnitedStatesbeganonOctober5,usingasystemthatallocatedavailablevaccine to states proportional to their populations. OnOctober14,dosesofvaccinebegantoarriveinsmallamountsto Duval County. Providers and healthcare facilities wererequiredtoordervaccinesthroughanewlycreatedmodulein Florida SHOTS, the state of Florida’s immunization

  % (95% CI)

Children/6 mos to 17 yrs 32.3 (±6.1)

Persons aged ≥18 yrs 16.1 (±2.1)

Person in initial target groups 28 (±4.1)

Persons aged 25--64 yrs at high risk 21.2 (±5.4)

Persons aged 25-64 yrs/not initial target groups  11.2 (±3.1)

Persons aged ≥65 yrs 21.8 (±3.4)

Persons aged ≥6 mos 19.5 (±2.1)

Unweighted Sample Size = 9,442

Table 1 Estimated Florida H1N1 Vaccination Percentages

CDC estimated monovalent vaccination coverage among children and adults, Florida by selected age and priority subgroups - U.S., BRFSS and NHFS, end of January 2010.

H1N1 Pediatric PerspectiveHaideeCustodio,MD,Fellow

Childrenandyoungadultswerefoundparticu-larlysusceptibletothe2009H1N1influenza.1Awidespectrumofillnesswasseenwithmostchildren having mild disease and presentingmainly with fever, cough and rhinorrhea, andalsovomitinganddiarrhea.1,2Ontheotherendofthespectrumwerecriticallyillchildrenmanyofwhomexpiredfromtheillness.3,4The2009H1N1influenza-associatedpediatricdeathsweretwiceasmanyasinthepreviousseason.4

Children with chronic underlying medicalconditions such as pulmonary disease, in par-ticularasthma,werethoughttobeathigherriskforseveredisease.1,2,3Otherriskfactorsincludedneurodevelopmental conditions, cardiovasculardisorders,immunosuppressionandobesity.

Managementofpatientsincludedearlyantivi-raluseandantibioticsincasesofsuperimposedbacterial infections.1,2,3 With H1N1 vaccineavailabilitysinceOctober2009,itishopedthatthemorbidityandmortalitywillbelessamongeventhevulnerablepopulations.

References 1. JainS, etal.”Hospitalizedpatientswith2009

H1N1influenzaintheUnitedStates.”N Engl J MedApril-June,2009;361:1935-1944.

2. Kumar S, et al. ”Clinical and epidemiologicalcharacteristicsofchildrenhospitalizedwith2009pandemicH1N1influenzaAinfection.” Pediatr Infect Dis J. 2010;29:591-594.

3. LockmanJL,etal.“ThecriticallyillchildwithnovelH1N1influenzaA:Acaseseries.”Pediatr Crit Care Med2010;11:173-178.

4. CDC.“Numberofinfluenza-associatedpediatricdeaths.” Available at: http://www.cdc.gov/flu/weekly/.AccessedonJune18,2010.

Address Correspondence to: Haidee Custodio, MD, Fellow, Pediatric Infectious Diseases and Immunology, University of Florida, Jacksonville. Email: [email protected].

http://www.cdc.gov/flu/weekly/

http://www.cdc.gov/flu/weekly/


registry.CHDscouldthenallocatevaccinebasedonpriorityandavailability.Severalmethodswereutilizedtodistributeandadministervaccine. Inaddition to thedistributionofvaccinethroughSHOTS,someCHDsconductedvaccineclinicsmodeledafterpointsofdistribution(PODs)usedinmassprophylaxiscampaigns.Othersfocusedonschool-basedvaccinations.DuvalCountyusedacombinationofPODstargetingfirstrespondersandprioritydistributionofvaccinethroughSHOTStoprovidersservingtargetgroups.VaccinewasalsomadeavailableattheDCHDImmunizationClinic.Vaccineadministrationtrackingprovedanothersurmountabletask.WhileproviderswererequiredtoregisterwithSHOTStoordervaccine, theywerenotrequiredtoenterdoses toadminister.Thismadeitdifficulttodeterminegeographicanddemographicvaccinecoverage.FDOHreliedontrackingofvaccinedosesdistributed,partialentriesofadministereddosesinSHOTS,andsurveysofvaccineadministrationsitestoestimatecoverage.

OnDecember4,2009,countieswereauthorizedtoexpandprovision of the H1N1 flu vaccinations beyond the fiveprioritygroupsbasedonlocalavailabilityofvaccine.DuvalCounty expanded vaccination efforts in mid-December.Atthatpointinthevaccinationeffort,DuvalCountyhaddistributed209,200dosesofH1N1vaccine.AttheendofJanuary,2010,CDCestimatedvaccinationcoverageutilizingtheBehavioralRiskFactorSurveillanceSystem(BRFSS)andNational2009H1N1FluSurvey(NHFS).Approximately61millionpersonshadbeenvaccinatedbytheendof2009.8

ByJanuary29,2010,approximately124milliondoseshadbeendistributed.8AttheendofFebruary,basedondatafromBRFSSandNHFScombined,theestimatedcoverageratewas24.0%,representing72millionpersonsvaccinated.7Incomparisontothenationaldata,Table 1showsFloridaH1N1vaccinationpercentages.9(Table 1, p. 21) FourstatesintheNewEnglandregionhadestimated2009H1N1vaccinationcoverage≥60%.OfthefourNewEnglandstatesachievinghigh coverage in children, three had conducted statewideschoolvaccinationcampaignsthatcoincidedwithaperiodofhighdemandforvaccine.

The RecoveryAftereveryincident,thereisaperiodofrecovery;atimeto

rebuild,assessthelessonslearned,andcontinuetoplanforthenextencounterwiththeenemy.Duringtheseencoun-ters,strengthsandweaknessesquicklybecomeapparent.Theinvestmentthisnationhasmadetostrengtheningprepared-nessandemergencyresponsecapabilitieswereimmediatelyapparent.Theinfrastructure,responseplans,andresourceswereavailabletorespondtothisincident.WithinFDOH,surveillancesystems,training,andstaffdemonstratedtheirability tomeet thedemandsofa largescalePHresponse.Among the local medical community, technology, surgecapacity, and a dedication to care met the needs of thecommunity.Agenciescametogether,realizingthiswasnotjustaPHresponse,itwasacommunityresponse.Withoutcooperationbetweenthesepartners,thepandemiccouldhavetakenamoreseverecourse.

With these strengths, improvements have already beenmadeinseveralotherareas.ThismayhavebeenthefirstPHincidentwhere therewas toomuch information fordeci-sionmakerstoprocess.Continuallymonitoringchangesin

guidancebecameanarduoustaskofitsown.Asaresult,theprocessforupdatingguidance,aswellasthemeansofdis-tributingithasgreatlybeenimproved.Inaddition,effectiveriskcommunicationhasalwaysbeenacrucialcomponentofanyPHresponse.The2009H1N1pandemiccouldnothaveemphasizedthisfactmore.Attimes,thisresponsewasmetwithconfusion,concern,andatsomepoints,doubtbythepublic.Theelectronicagehasrevolutionizedthemeansbywhich individualsobtain information.This, forPH, isadoubleedgedsword.Factsandfalsehoodsarebotheasilydiscoveredontheinternet,andinthatenvironment,itisoftendifficulttodiscernthetwo.Clear,transparentPHmessag-ingatanational,state,andespeciallythelocallevelduringanyemergencymustbestrengthened.EngagingfaithbasedorganizationsandapproachingschoolsprovedsuccessfulincombatingmisinformationduringtheH1N1response.Thesemethodsshouldbeappliedmorebroadly.

SummaryOverall,the2009H1N1PandemicbroughtPHofficials

frombeyondthepublic’ssighttothefrontlineoftheresponse.Asaresult,peoplewereremindedthatwearenotindividu-alsisolatedfromone-another.Weareallinterconnectedinawaywhichallowsavirustocircletheglobeinamatterofweeks.Therippleeffectofthispandemicbeyondinfluenzahassubsequentlyfurtherstrengthenedthewayinwhichthenationrespondstoemergencies.Overthesubsequentyears,officialswillcontinuetostudythepandemic,preparingonceagainforthenextencounterwithanovelvirus.

References1. FormerSecretaryofStateColinPowell,CBS:“FacetheNation,”

Sunday,Feb.21,2010.2. CDC.“SwineinfluenzaA(H1N1)infectionintwochildren

-SouthernCalifornia,”March-April2009.Morb Mortal Wkly Rep 2009;58:400-402.

3. CDC.“Update: infectionswitha swine-origin influenzaA(H1N1)virus-UnitedStatesandothercountries,”April28,2009.Morb Mortal Wkly Rep2009;58:431-433.

4. StatementtothepressbyWHODirector-GeneralDr.MargaretChan,11June2009,“Worldnowatthestartof2009influenzapandemic”.

5. CDC. “Update: Influenza Activity- United States, August30,2009-March27,2010,andCompositionofthe2010-11InfluenzaVaccine,”April16,2010.Morb Mortal Wkly Rep 2010;59(14);423-430.

6. CDC. CDC Estimates of 2009 H1N1 Influenza Cases,HospitalizationsandDeathsintheUnitedStates,April2009–March13,2010,April19,2009.www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm.AccessedJune1,2010.

7. CDC. “Use of influenza A (H1N1) 2009 monovalentvaccine: recommendations of the Advisory Committee onImmunizationPractices(ACIP),”2009.Morb Mortal Wekly Rep2009;58;1-8.

8. CDC. “Interim Results: State-Specific Seasonal InfluenzaVaccinationCoverage-UnitedStates,August2009-January2010.” April 30, 2010. Morb Mortal Wkly Rep 2010;59(16);477-484.

9. CDC.“InterimResults:InfluenzaA(H1N1)2009MonovalentVaccination Coverage - United States, October-December2009.” January 22, 2010. Morb Mortal Wkly Rep 2010;59(02);44-48.


Tuberculin Skin Test: Loss of an Old Friend?JeffreyLauer,MD

AddressCorrespondenceto:JeffLauer,MD,DuvalCountyHealthDepartment, Jacksonville, Florida. Email: [email protected].

Abstract: The tuberculin skin test (TST) has been the only practical and commercially available test approved in the United States up to 2001 for the evaluation of exposure to Mycobacterium (M.) tuberculosis.1 However, with the understanding of the role that interferon gamma (IFN-γ) plays in cell-mediated immune response to M. tuberculosis, there has been the development and growing acceptance of these blood assays for the detection of M. tuberculosis. The strengths and weaknesses of these interferon gamma release assays (IGRAs) are just now beginning to be recognized. Concern for the utility and continued use of the standard TST is coming more into question.

IntroductionTST(alsoknownasPPD)isprobablythemostroutinely

andwidelyusedantigenbycliniciansandimmunologistsandthemainstayforthediagnosisofexposuretoM. tuberculosis.2TheTST was developed from the extract of the tuberclebacillus,theearliestpreparationwhichRobertKochnamed“oldtuberculin”(OT).OTconsistedofconcentratedsterilefiltrateofautolyzed,heat-killedliquidcultureofM. tuber-culosisandbegantobeusedinclinicalandepidemiologicalpracticesforbothveterinaryandhumanmedicinesoonafteritsdevelopment.

The often noted non-specific reactions encountered toOTduetothesharedcross-reactiveantigenswithhosten-counteredenvironmentalantigens,leadFlorenceSeibertin1932tobegindevelopmentofapurifiedturberculoproteinfromOT.3In1942thatpreparationwastermed“tuberculinpurifiedproteinderivative”(PPD)althoughitstillconsistedofamixtureofseverallow-molecular-weightproteinsofM. tuberculosis.TheprevalenceofTBindifferentgroupsdefinedthreecut-pointsrecommendedfordefiningapositivetuber-culinreaction:>5mm,>10mm,and>15mmofinduration.ForpersonswhoareathighestriskfordevelopingactiveTBifinfectedwithM. tuberculosis(i.e.,HIVinfection,immu-nosuppressivetherapyrecipients,recentclosecontactwithinfectiousTB,oranabnormalchestradiographsconsistentwithpriorTB),>5mmofindurationisconsideredpositive.ThoseindividualswithanincreasedriskofrecentinfectionorwithclinicalconditionsthatincreasetheriskforprogressiontoactiveTB,>10mmofindurationareconsideredpositive.Theseincludeinjectiondrugusers,recentimmigrants(i.e.,entryintotheU.Swithinthelast5yrfromhighprevalencecountries),residentsandemployeesofhigh-riskcongregatesettings, health care workers, and persons with clinicalconditionssuchassilicosis,diabetesmellitus,chronicrenalfailure, leukemiasandlymphomas,carcinomaoftheheadorneckandlung,weightlossof>10%idealbodyweight,gastrectomy,andjejunoilealbypass.Childrenyoungerthan

4yrofageorinfants,children,andadolescentsexposedtoadultsinhigh-riskcategoriesalsofallintothiscategory.ForpersonsatlowriskforTB,forwhomtuberculintestingisnotgenerallyindicatedandisnotroutinelyrecommended,>15mmofindurationisconsideredpositive.

AnunderlyingstrategyinthecontrolandeliminationofTBintheU.S.wascontactinvestigationandtreatmentofcontacts with latent TB infection (LTBI).4,5 This strategyhas subsequently developed into “targeted testing” with akeyelement“don’ttestunlessyouintendtotreatanddon’ttreatunlessyouexpecttocompletetherapy”;therefore,don’ttestunlessthereisanexpectationtocompleteappropriatetherapy.6TheculturefiltrateofthePPDvariedintheantigeniccompositionbygrowthcondition,theageofthecultureatthetimeoffiltration,theincubationtemperatureandevenwhengrownundersimilarcultureconditions.7,8Thisvari-abilityandtheknowncross-reactivityreactionofthePPDtootherenvironmentalmycobacterialspeciestakeonincreasedsignificancewiththechangingtuberculosislandscapeintheUnited States. Many countries currently vaccinate theirpopulationswithbacilliCalmétte-Guérin(BCG),avaccineforM. tuberculosis thatcarries cross-reactiveantigensthatarefoundinthecurrentPPD.

BackgroundTuberculosisisamajorcauseofmortalityworldwidewith

anestimatedone-thirdoftheworld’spopulationharboringlatentinfection.9Fiveto10%ofthosewithlatentinfectionwilldevelopactiveM. tuberculosisdiseaseduringtheirlifetimeastheresultofreactivationofthebacillus.Themajorityoftheworld’sresourcesforTBeliminationareusedtodiagnoseand then treat thosewith activediseasewith theDirectlyObservedTherapy(DOTS)programthemainstayofthoseefforts. However, the Global Tuberculosis Report 2008documents the significant lack of culture facilities in thegovernmenthealthsectorinmostdevelopingcountries;the“goldstandard”forTBdiseaseidentificationisgrowthofM. tuberculosis.10Thesignificantpoolofthosealreadyinfectedandvariablelengthuntilreactivationdoesnotlendtoashort-termoreasysolutiontoTBeradicationusingthestrategyofDOTS.ThosewithLTBIoftenaremissedorignoreduntiltheydevelopactivediseaseandthentheycontributetothespreadofTB.

IntheUnitedStates,onaverage,10contactsarelistedforeachpersonwithacaseofinfectiousTB.Approximately20%-30%ofallcontactshaveLTBI,and1%hasTBdisease.OfthosecontactsthatultimatelywillhaveTBdisease,approximatelyhalfacquirediseaseinthefirstyearafterexposure.11Forthesereasons,contactinvestigationsconstituteacrucialpreventionstrategy.TheStopTBpartnershipWorkingGrouponNewTBDiagnosticshasstressedtheimportanceofdevelopingnew


toolsfortheaccurate,rapididentificationofdrug-resistantTBandreliabledetectionoflatentTBinfection.Buttheresourcesneeded1)toinvestigateforthoseexposed(contactinvestiga-tion),2)totreatthosewithproveninfectionbutnodisease,3)providetherapyforanextendedtime-frame(standardofcarerecommendationsarefor9monthsofisoniazid(INH)daily,4)toinsurecompletionofLTBItherapy,5)providecostofmedicationandfinally6)offerthefollow-upcarewithmonitoring,placesanenormousfiscalandmanpowerstrainonresourcepoorcountries.

In 2008, there were an estimated 9.4 (range, 8.9–9.9million)millioncases(equivalentto139casesper100,000population)ofTBglobally.Thisisanincreasefromthe9.3millionTBcasesestimatedtohaveoccurredin2007.Mostoftheestimatednumberofcasesin2008occurredinAsia(55%) andAfrica (30%),with small proportions of casesintheEasternMediterraneanRegion(7%), theEuropeanRegion(5%)andtheRegionoftheAmericas(3%).Twenty-twocountriescontributeto80%oftheworld’sTBcases.ThetopfivecountriesintermsoftotalnumbersofcasesareIndia(1.6–2.4 million), China (1.0–1.6 million), South Africa(0.38–0.57million),Nigeria(0.37–0.55million)andIndo-nesia(0.34–0.52million).IndiaandChinaaloneaccountforanestimated35%ofTBcasesworldwide.9ThosecountriesthatcanleastaffordmeasurestotreatandcontroltuberculosisarethecountriesthathavethehighestTBburden.

TB Prevention and ControlTheUnitedStatesmaintainsaTBeliminationprogram

thatcoversallaspectsofTBcontrolandhaslargelyremainedsuccessfulbecausestateandlocalhealthdepartmentshavelegalresponsibilityforthepreventionandcontrolofTBintheircommunities.11ThreeprioritiesarefundamentaltothepreventionandcontrolofTB.12Thefirstisidentifyingper-sonswhohaveactiveTB,whichentailtreatingandensuringcompletionof appropriate therapy.The secondpriority iscontact investigation todeterminewhether those exposedtoanactivecasehaveinfectionordiseaseandthenprovid-ingthemwithappropriatetreatment.Thethirdpriorityisscreeninghigh-riskpopulations todetectpersonswhoareinfectedandwhocouldbenefitfromtherapytopreventtheinfectionfromprogressingtoTBdisease.Thesecondandthirdprioritieshaveatthecore“targetedtuberculintesting”toidentifypersonswhohavehadrecentinfectionwithM. tuberculosisandthosewhohaveclinicalconditionsthatareassociatedwithanincreasedriskforprogressionofLTBItoactiveTB.

InfectedpersonswhoareconsideredtobeathighriskfordevelopingactiveTBshouldbeofferedtreatmentofLTBIirrespectiveofage.Theriskofan inadequateTBelimina-tionprogramwashighlightedintheU.S.byanincreaseinTBmorbidityby14%from1985through1993.12Severalfactorsattributedtothisincrease,includingthehumanim-munodeficiency virus (HIV) epidemic, the occurrence ofTBinforeign-bornpersonsfromcountriesthathaveahighprevalenceofTBandthetransmissionofM. tuberculosisin

congregate settings (e.g.,health-care facilities, correctionalfacilities, drug-treatment centers, and homeless shelters).Also,manyofthepublichealthTBprogramslackedadequatesupportforTBcontrolastheavailablepublichealthfundsatthefederal,state,andlocallevelshadbeenrestructuredwhenTBcasesweredecliningbefore1985.Thepublichealth-careinfrastructurewassubsequentlyrebuilttomeetthechallengeofthatresurgenceofTBcasesandtheU.S.hasenjoyedacontinueddeclineinTBrates.However,therateofdeclinehasslowed,andthatslowingislikelytheresultofthesamedifficultiesencounteredfrom1985to1993andtothere-activationofLTBIalreadyinthecommunitiesorimportedfromaboardnotpreviouslytreated.12

In1987theCentersforDiseaseControl(CDC)AdvisoryCommitteefortheEliminationofTuberculosiswasestablishedwiththegoaloferadicatingtuberculosisfortheUnitedStatesbytheyear2010.Thatgoalhasnotbeenmet.TheCDCreported12,904activecasesfortheyear2008andacaserateof4.2casesper100,000.Althoughthisrepresentsadeclineof2.9%and3.8%,respectively,comparedto2007thetrendofdecliningannualcaserateshasslowedfrom5.6%for1993through2002toannualdeclineof2.6%for2003through2008.Eighteenstatesreportedincreasedcasecountsfrom2007withCalifornia,Texas,NewYorkandFloridaaccountedfor49%ofthenationalcasetotal.Although2008hasthelowestactivecasereportinthelastseveralyears,theepidemiologyofnewactivecasescontinuesthetrendnotedfrom1993.12Thepercentageofcasesoccurring in foreign-bornpersonscomprises59%ofthenationalcasetotal.In14states,>70%ofTBcasesoccurredamongforeign-bornpersons.Thetopfivecountriesoforiginofforeign-bornpersonswithTBwereMexico,Philippines,Vietnam,IndiaandChina.Whentakentogether,foreign-bornHispanicsandAsiansrepresent80%oftheTBcasesintheforeign-bornpersonsandaccountedfor47%ofthenationalcasetotal.12

Itisapparentthatthereisnotjustaworldeconomybutalsoaworldmedicalcommunityasitrelatestotuberculosis.However,agrowingconcernexistsfordrugresistanceandmulti-drug resistant strains ofTB that exist and are nowcrossingU.S.shores.Onepercent(1.0%)ofreportedcasesin2008hadprimarymultidrugresistance,whichisdefinedasresistancetoatleastisoniazidandrifampinwithnopre-vioushistoryofTBdisease.Thoseareasof theworldthataremaintaining theTBburdenare those thatpossess theleastabilitytofindandtreatthosewithactivediseaseortoconductcontactinvestigationandofferLTBItherapy.TheIGRAs represent anewgenerationof diagnostic tools fordetectingLTBI.

New Generation TestingQuantiFeron–In2001,theQuantiFERON®-TBtest(QFT)

(manufactured by Cellestis Limited, Carnegie, Victoria,Australia)wasapprovedbytheFoodandDrugAdministration(FDA)asanaidfordetectinglatentM. tuberculosisinfection.Thiswasaninvitrodiagnostictestthatmeasuresthequantityof interferon-gamma (IFN-γ) released from sensitized


lymphocytesinwholebloodincubatedovernightwithPPDandcontrolantigens.TheinitiallimitationsofQFTincludetheneedtoprocessthebloodwithin12hoursaftercollectionandthelimitedlaboratoryandclinicalexperiencewiththeassay.ComparedwithTST,QFTresultswere less subjectto readerbias, error anddidnotboost amnestic immuneresponse.ButliketheTST,itassessedresponsetomultipleantigensasitwasincubatedwithPPD.

InaCDC-sponsoredmulticentertrial,concordanceofQFTandTSTwasaffectedbypriorpositiveTST,BCGvaccination,andreactivitytonon-tuberculousmycobacteria(NTM).TheinterpretationofQFTresults,liketheTST,haddifferentcut-offvaluesbasedontheestimatedriskforinfectionwithM. tuberculosis.Thesethreecriteria,neededforthediagnosisofM. tuberculosis: (mitogen--nil)and(tuberculin--nil),areboth>1.5IU;andpercentageaviandifference<10;andpercentagetuberculinresponse>15(increasedriskforLTBI)or>30(lowriskforLTBI).Using15asthepercentagetuberculinresponsecut-offidentifiesapproximatelythesamenumberofpersonsaswithusingaTSTindurationof10mm.Using30asthepercentagecut-offidentifiesapproximatelythesamenumberofpersonsasusingaTSTindurationcut-offof15mm.Thetestisconsiderednegativeif(mitogen--nil)>1.5IUbut(tuberculin--nil)<15%(mitogen--nil).Resultsareconsideredindeterminateif(mitogen--nil)<1.5IU,whichmaybeseenamonganergicpersons.13

QuantiFERON®-TB Gold–OnMay2,2005,anewinvitrotest,QuantiFERON®-TBGold(QFT-G,manufacturedbyCellestisLimited,Carnegie,Victoria,Australia),receivedfinalapprovalfromtheFDA.ThetestistoassistindiagnosingM. tuberculosisinfection,includingbothLTBIandTB.Thisenzyme-linked immunosorbent assay (ELISA) test detectsthe releaseof interferon-gamma(IFN-γ) in freshheparin-izedwholebloodwhenincubatedwithmixturesofsyntheticpeptidessimulatingtwoproteinspresentinM. tuberculosis.Thesetwopeptides:earlysecretoryantigenictarget--6(ESAT-6)andculturefiltrateprotein--10(CFP-10)aresecretedbyM. tuberculosis,pathogenicM. bovisstrains, M. kansasii,M. szulgai,andM. marinum. TheseproteinsareabsentfromallBCGvaccinestrainsandfromothercommonlyencoun-tered NTM. Whole blood from the patient is incubatedwiththesetwopeptidesina24-wellplateovernight.T-cellsthatrecognizetheantigenswillsecreteINF-γ.TheplateiscentrifugedandtheplasmatransferredtoamicrotiterplatewhereantibodiesspecificforIFN-γhavebeencoatedtothebottomofeachwell.Theformedcytokine-boundantibodiesarethendetectedwithanotherantibodyconjugatedtoanenzyme that catalyzes a colorimetric reaction.Theopticaldensityoreachwell ismeasuredandtheconcentrationofIFN-γisdeterminedusingastandardcurve.14

TheoriginalQuantiFERON®-TBtest(QFT)andtheQFT-G,usedifferentantigenstostimulateIFN-γrelease,differentmethodsofmeasurement,anddifferentapproachestotestinterpretation.Likeitspredecessor,QFT-Ginterpretationhasdifferentcut-offvaluestodefinenegative,positiveorindeter-minateandavailablesoftwaresuppliedbythemanufacturer

canbeutilized.CertainlimitationsofQFT-GaresimilartothoseoftheTST,suchasQFT-GandTSTcannotdifferentiateinfectionassociatedwithTBdiseasefromLTBI.QFTwasapprovedasanaidfordiagnosingLTBI,whereasQFT-Gisapprovedasanaid fordiagnosingbothLTBIandTBdisease.TheinitialstudiesusingeitherofIFN-γreleaseassayswereperformedinculture-confirmedorclinicallyhighlyprobablecasesoftuberculosis.WiththedevelopmentandapprovalofQFT-GtheoriginalQuantiFERON®-TBtest(QFT)isnolongercommerciallyavailableandan“infield”versionofQFT-Gwasdeveloped;QuantiFERON-TBInTube(QFT-GIT).Theantigensareinthetubesallowing“infield”mixingandnegatingtherequirementforsampleprocessingwithintwelvehoursofcollection.15

T-Spot TB – T-SPOT.TB is an FDA approved in vitro diagnostic test based on an enzyme-linked immunospot(ELISPOT)methodthatenumeratesthenumberofeffec-torT-cellsrespondingtostimulationbypeptidessimulatingESAT-6 andCFP-10 antigens.Aswith theQFT-Gassay,T-cellsinindividualswithTBinfectionbecomesensitizedtoESAT-6orCFP10invivoandwhentheT-cellsre-encountertheseantigens,exvivointerferon(IFN-γ)-gammacytokineisreleased.WiththeT-Spot.TBthewashedandcountedperipheralbloodmononuclearcells(PBMCs)areseededintofourmicrotiterwellswheretheyareexposedtophytohemag-glutinin, amitotic stimulator indicating cell functionality(positivecontrol),anilcontrol,andtwoseparatepanelsofTBspecificantigens.IFN-γspecificantibodiesinthebaseofthewellattachtosecretedIFN-γandarethendetectedwitha secondantibody linked toacolordetectionagent.EachdarkspotobtainedinthebaseofthewellprovidesameasureoftheabundanceofTBsensitiveeffectorT-cellsintheperipheralblood.TheT-SpotTBassay requiresWBCseparationwhich,althoughmoretechnicallycomplex,allowsforafixednumberofWBCsintheassaywhichisimportantintheimmunosuppressedpopulation.15Forthisarticle,anyofthecurrentlyavailableIFN-γassays(QFT-G,QFT-GIT,orT-SpotTB)willbecollectivelyreferredtoTIGRA’s(Tu-berculosisspecificInterferonGammaReleaseAssay)whendatacanbeusedinterchangeably.Whenaspecificassayisnoted,thetestutilizedwillbeidentified.

Comparison and Utility of TestsEachofthetests(TSTandTIGRA)reliesonadifferent

immuneresponseanddiffersinitsrelativemeasuresofsen-sitivityandspecificity.TheTSTassessesinvivodelayed-typehypersensitivity (Type IV), whereas TIGRA’s measure invitroreleaseofIFN-γ.TheTSTmeasuresresponsetoPPD,apolyvalent antigenicmixture,whereasTIGRA’smeasureresponsetoamixtureofsyntheticpeptidessimulatingtwospecificantigenicproteinspresentinM. tuberculosis.TIGRAsarenotaffectedbypriorBCGvaccinationandareexpectedtobelessinfluencedbypreviousinfectionwithNTM.FortheTST,notallinfectedpersonswillhaveadelayedhypersensi-tivityreactiontoatuberculintest.Alargenumberoffactorshasbeenreportedtocauseadecreasedabilitytorespondtothetuberculintestinthepresenceoftuberculousinfection


includingviralinfection(measles,mumps,chickenpoxandHIV),livevirusvaccinations(measles,mumps,rubella,oralpolio and yellow fever), overwhelming tuberculosis, otherbacterialinfections,drugs(corticosteroidsandmanyotherimmunosuppressiveagents),andmalignancy.16,17Ina2008asystematicreviewbyMadhukaretalidentified22studiesofQFT-G(1369participants),13studiesofTSpotTB(726participants)ofmostlyadultHIV-negativeculturepositivecasesforTB.ThepooledsensitivityfortheQFT-Gstudieswas76%(95%CI,72%to80%)andforTSpotTB90%(CI,86%to93%).Inhead-to-headcomparisonsbetweenQFT-GandTSpotTB,theTSpotTBhadhighersensitivitythantheQFT-G,withdifferencesrangingfrom3%to25%.18

TheoverallconsensusisthatTIGRAtestshaveahigherdiagnosticsensitivitythantheTSTinactivetuberculosisrang-ingfrom83to97%forTB-Spotand70to89%sensitivityforQTF-G.19-22ButliketheTST,a“positive”resultfortheTIGRAsignifiesinfectionandonecannottellactiveTBfromLTBI.TherealutilityofTIGRAsmaybeinidentificationofLTBI.However, the limitationinusingeithertheTSTorTIGRAsisthelackofa“goldstandard”whenevaluatingindividualswithTBinfectionorculturenegativeTBdisease,andthishasleadmostinvestigatorstousesurrogatemarkers,riskfactors(i.e.knownexposuretoactiveinfectiouscaseorendemicarea)orcomparisonwiththeTST,forevaluationofthesetestsinLTBI.Whenusingriskfactorsinlow-endemicregions,thereisahigherTIGRAspositivitythenwithTST.23Whenthesetestswereevaluatedduringcontactinvestigation,bothtestsweremoresensitiveandspecificthantheTST.24-27TheperformanceoftheTIGRAsinnon-immunosuppressedpopulationallowedtheapprovalofthesetestsandtherecom-mendationsfortheiruseinevaluatingselectedgroups.

Performance in Immunosuppressed PersonsAnunknownlimitation is that theTSTandanynewer

tests might not perform the same for detecting LTBI astheydo for detectingM. tuberculosis infectionduringTBdisease.Forexample,reductionofinvivoIFN-γreleasehasbeenattributedtosuppressivecytokinesassociatedwithTBdisease.ThereisalsoasuggestionthatgeneticallydistinctM. tuberculosisstrainsinvokedifferentimmuneresponsesinthedevelopmentofhumantuberculosis.Rakotosaminmanana,etalevaluatedantigen-specificIFN-γproductionresponsesinPBMCfromtwocohortsinMadagascarin2004-2006;notingthat“modern”M.tuberculosisstrainslikeBeijingandCentralAsian(CAS)tendedtogivelowerIFN-γresponsesthan“ancient”strainsliketheEastAfricanIndian(EAI).28ThemajoritystrainintheUnitedStatesistheBeijingstrain.TheperformanceofTIGRAs,inparticularitssensitivityandrateofindeterminateresults,isstillbeingdeterminedinpersonswhoareatriskindevelopingactiveTBbecauseofimpairedimmunefunction.

RecognizedriskfactorsforthedevelopmentofactiveTBare impaired immune function caused by HIV infectionor acquired immunodeficiency syndrome (AIDS), currenttreatment with immunosuppressive drugs including

high-dose corticosteroids, tumor necrosis factor-alpha(TNF-α)antagonists,anddrugsusedformanagingorgantransplantation, selected hematologic disorders (e.g.,myeloproliferative disorders, leukemias, and lymphomas);specific malignancies (e.g., carcinoma of the head, neck,orlung),diabetes,silicosis,andchronicrenalfailure.Theseconditionsortreatmentsareknownorsuspectedtodecreaseresponsiveness to the TST, and they also might decreaseproductionof IFN-γ in theTIGRA’s.29As a result, like a“negative”TST, a negative or indeterminate result in theIFN-γ assays may not accurately reflect M. tuberculosisinfectionintheseimmunosuppressedconditions.TIGRAsrelyonfunctionalCD4TcellsandtheirperformancemightbenegativelyinfluencedbyloworimpairedCD4cellcountsinHIV-infectedindividualsprovidingeitherfalse-negativeorindeterminateresults.

HoffmanandRavnreviewedeightpublishedstudiesevalu-atingthesensitivityofQFT-GinHIV-positiveindividualswithactiveTB,andtheyreportedasensitivityof79%(95%CI73.5-83.5)butwhenthe16.5%ofindeterminateresultswereincluded,thesensitivityfellto66%(95%CI60-17).28InanotherevaluationoftheT-Spot.TBinfourpublishedstudies,theyfoundasimilarsensitivitywhencomparedtoQFT-Gof80.5(95%CI69.5-88)withthe9.5%indeterminateresultsyielding72%(95%CI60-81.5).Whenthesesameauthorsreviewed those studies that comparedTST results in thesamestudieswitheitherQFT-GorT-SpotTB,theyfoundasensitivityofTSTtobe43%(95%CI37-49.5).PossibleexplanationsforthedifferencesbetweenTIGRAsandTSTinknownactiveTBcasesinHIV-infectedindividualsisthetypeofresponsetoeachtestthatisevoked(i.e.atypeIVdelayedhypersensitivity response inTSTcompared to re-sponseofcirculatingTcellsinIGRAstests).30ThreestudiesthatcomparedtheTIGRAssensitivityinHIV-infectedanduninfectedpatientsfoundalowersensitivityinHIV-positivepatientswithactiveTB.21,22,31InHIV-co-infectedindividualsitwouldappearahighersensitivityofTIGRAscomparedwiththeTST,butTIGRAssensitivityremainsimpairedcomparedtohealthycontrols.30

In multivariate analysis, a CD4 count < 200/ ml wasassociatedwithindeterminateQFT-GandTSPOTresults(OR=3.4,95%CI1.5-7.7andOR=3.9,95%CI1.8-8.1,respectively.)Somestudiesindicatedthatnotonlytheabso-luteCD4cellnumberisimportantfortestaccuracybutalsothenadirCD4cellcounts.32,33,34AichelburgetalreportedasignificantassociationbetweennadirCD4cellcountsandthe rate of indeterminateOFT-G IT results.33Unlike theTST,TIGRAsappearrelativelyrobusttoHIVco-infectioninpeoplewithrelativelyhighCD4counts,withatrendtowardmorepositiveresultsbyTSpot.TB.30

Theriskofpulmonarytuberculosis(TB)inrheumatoidarthritis(RA)patientsisincreasedfourfoldcomparedwiththegeneralpopulation.35RApatientstreatedwithtumornecrosisfactor(TNF)inhibitorsareathigherriskofTBinfectionthanthosenotsotreated.Tuberculosisdevelopedin14(0.3%)of5,000RApatients inaJapanesepost-marketingsurvey


ofinfliximab.36TheCDChasrecommendedevaluationfortuberculosisexposurepriortouseofanti-TNFinhibitors.37Ina Japanesecohort,QFT-Gtestinghasbeenassessed in118activepulmonaryTBpatientswithculture-confirmedM. tuberculosiscomparedwith216BCG-vaccinatedadultswithnoidentifiedriskforTB.Withacutofflevelsetat0.35IU/ml,thecommonlyusedpositivecutoffvalue,thesensi-tivitywas89.0%andthespecificitywas98.1%forpatientswithactiveTB,whereassettinga0.1IU/mlcutoff(thelowestleveloftheintermediaterange)resultedinasensitivityandspecificity of 95.8% and 92.0%, respectively. A study byMaeda,T.etalin2009aimedatevaluatingthesensitivityandspecificityofQFT-GinJapaneserheumatoidarthritispatientswithapasthistoryoftuberculosis,recommendedtheuseofacutoffvalueof0.1IU/ml.35UseofthelowercutoffincreasedpositiveQFT-Gresultsfrom13.6%to27.3%inthosewithapasthistoryoftuberculosis.

Childrenarealsointhiscategoryofunclearperformancecharacteristics ofTIGRAs in the determination of LTBI.TherewasnotedintheretrospectivestudybyHausteinetal that35%of the studypopulationof237childrenhadindeterminatetestresultswithQFT-Gwithanoverrepre-sentationofindeterminateresultsinchildrenlessthan5yearsofageandthosewithimmunodeficiencies.38ThesegroupsrepresentchildrenmostatriskfordiseaseprogressionafterTBexposure.Inyoungchildren,TSpotTBappearstohaveahighersensitivitythantheTST,whileQFT-GmayhavelowersensitivitythantheTST.

Ina2010studybyLucasetalevaluatedTIGRAsinhu-manitarianentrantssettlinginWesternAustralia.39Atleast524AfricanandethnicBurmesechildren,ofwhich107under3yearsofage,wereprospectivelyenrolledinacomparisonof theTSpotTBandQFT-GIT. Both testsdemonstratedsimilarratesofpositivityinthissetting(8%TSpotTband10%QFT-IT)butbothhadsignificantfailurerates(15%ofOFT-GITinclusiveresultand14%ofTSpotTbresultswereinclusive).AninadequateTcellresponsetothemitogenwasthepredominantreasonforQFTGITindeterminacywhilethemost common causeof an inconclusive result for theTSpotTBtestwasfailuretoisolatesufficientPBMCs.

ThegrowinglistofdataexistingonreliabilityofTIGRAsinimmunocompromisedpatientsshowthattheprevalenceofindeterminateresultsmayvarydependingonthedegreeofimmunosuppressionandtheTIGRAtestused.40,41Inaddition,phytohemagglutinin(PHA)andrecallantigensusedifferentIFN-γsecretionpathways,whichmaybedifferentiallyaffectedbyimmunosuppressiveconditions.39,42,43

In a study by Lange et al evaluating the indeterminateresultsobtainedinacohortofimmunocompromisedpatientsusingQFT-G-ITdemonstratedthatan indeterminatetestresultwassignificantlyhigherthanthecontrolgroup(similartopreviousstudies)andthattheresultsdiffereddependingof thediseasegroup.43Patientswithautoimmunediseaseshadhigherpercentageofindeterminateresultsthanorgantransplant,7of12systemiclupuserythematosis(SLE)patients

demonstratedindeterminateresultsandhighindeterminateresults were noted in stem cell transplant patients. Alsonotedwerehigherindeterminateresultsinfemalesthaninmalesbeingmostpronouncedinpatientswithautoimmunediseases.Intheirconclusion,differentdiseasestatesareanindependentriskofindeterminateresultsusingQFT-G-IT.AcomparisoninthesegroupswithT-SpotTBhasnotbeenevaluatedandmaynotproducesimilarresults.

Study ConclusionsTheconclusions from thepublished studies todate are

thatTIGRAtestisnotconfoundedbyBCGvaccinationandarethereforemorespecificthantheTST.TIGRAsaremoresensitivethantheTSTinactivetuberculosis,withT.Spot.TBhavinghighersensitivitythanQFT-G.InLTBI,T-Spot.TBprobablyhashighersensitivitythantheTST,whileQFT-GseemstohavesimilarsensitivitytotheTST.IndeterminateresultsarecommonwithQFT-Gandarestronglyassociatedwithimmunosuppression,youngage,andoldage,whilein-determinateresultswithTSpot.TBarerareinallriskgroupsstudiedtodate.30,40

The impactof treatmentonblood test resultshasbeenstudiedforTSpot.TBintuberculosispatientsandinpersonswithLTBI.Ingeneral,theTSpot.TBresponsesdeclinewithtreatmentinbothactivetuberculosisandLTBI.ThisraisesthepossibilityofusingthistesttomonitortreatmentresponseespeciallyinLTBItherapy,forwhichnoparametersexisttodeterminetreatmentsuccess,asa“testofcure”.However,duetotheinterindividualvariationintherateofdeclineandthatonlyaminorityofindividualsbecomenegativeaftercomplet-ingtreatment,thistestasatreatmentmonitorislimited.40Interestingly,TSpot.TBvaluesdeclinedwiththerapyandmayreflectdormantviabletuberclebacilliwhichmayprogresstoactiveTB.ThispromptsaconcernifthedurationoftherapyormediationsusedtotreatTBand/orLTBIbemodifiedtoinsureanegativeTSpot.TBresult.

Guidelines and HighlightsGeneralrecommendationsontheuseofTIGRAaspart

oftheinfectioncontrolprograminhealth-caresettingshavebeenincludedinthemostrecentrevisionoftheTBinfectioncontrolguidelines.TheCDCrecommendstheuseofQFGinallcircumstancesinwhichTSThasformerlybeenusedandrecentlyreleasedguidelinesforusinginterferongammareleaseassayshavejustbecomeavailable.44EuropeanguidelinesadvisethatTIGRAsshouldbeusedtoconfirmthediagnosisofLTBIandasadirectreplacementfortheTSTinpersonswithsuppressedcellularimmunity.44Incountrieswithestablishedmarketeconomies,tuberculinskintestingisstillthemostfrequentlyusedTBtestduetotherelativelylowerratesofTBandhigherpriorityofdetectionandtreatmentoflatentTBinthosesettingscomparedtotheremainingareasoftheworldwithprioritizationtotreatmentofactivecases.

TheresultanditsinterpretationregardlessofthetestusedforadiagnosisofLTBIrequiresthatTBdiseasebeexcludedby medical evaluation, including checking for suggestivesymptomsandsigns,achestradiograph,and,whenindicated,


examination of sputum or other clinical samples for thepresenceofM. tuberculosis.ApositiveTIGRAresultshouldprompt the samepublichealthandmedical interventionsas a positive TST result. As with a negative TST result,negativeTIGRAresultsshouldnotbeusedalonetoexcludeM. tuberculosisinfectioninpersonswithsymptomsorsignssuggestiveofTBdisease.TIGRAassayusuallycanbeusedinplaceof(andnotinadditionto)theTST.InsituationswithserialtestingforM. tuberculosisinfection,initialtwo-steptesting,whichisnecessarywiththeTST,isunnecessarywithQFT-Gandisnotrecommended.45

ThemajorityofhealthyadultswhohavenegativeTIGRAresultsareunlikelytohaveM. tuberculosisinfectionanddonotrequirefurtherevaluationandnoreasonexiststofollowapositiveTIGRAresultwithaTST.However,forpersonswithrecentcontactwithpersonswhohaveinfectiousTB,negativeTIGRAresultsshouldbeconfirmedwitharepeattestperformed8-10weeksaftertheendofexposure,as isrecommendedforanegativeTSTresult.StudiestodeterminethebesttimetoretestcontactswithnegativeTIGRAresultshavenotbeenreported.Untilmoreinformationisavailable,thetimingofTIGRAtestingshouldbethesameasthatusedfor theTST . When “window period” prophylaxis (i.e.,treatmentforpresumedLTBI)isindicatedforcontactsaged<5yearsorseverelyimmunocompromisedpersonswhoareexposedtohighlycontagiousTB,repeattestingforLTBIisrecommended8-10weeks after contacthas ended.A fullcourseoftreatmentshouldbeconsideredevenwithanegativeresultfromeithertestattheendofthewindowperiodwhentherateofM. tuberculosistransmissiontoothercontactswashighorwhenafalse-negativeresultissuspectedbecauseofamedicalcondition.

AnindeterminateTIGRAresultdoesnotprovideusefulin-formationregardingthelikelihoodofM. tuberculosisinfection.TheoptionsaretorepeatTIGRAwithanewlyobtainedbloodspecimen,administeraTST,ordoneither.ForpersonswithanincreasedlikelihoodofM. tuberculosisinfectionwhohaveanindeterminateTIGRAresult,administrationofasecondtest,eitherTIGRAorTST,mightbeprudent.ForpersonswhoareunlikelytohaveM. tuberculosisinfection,nofurthertestsarenecessaryafteranindeterminateTIGRAresult.

TheTIGRAsaddausefultoolinthedevelopedcountiesarmamentariumtowardTBcontrolandelimination,butisnotlikelytoreplacetheTSTespeciallyinlimitedresourceareasoftheworld.ThePPDhasbeenaninvaluableassetsinceitdevelopmentandcontinuesitsusefulnesstothisday.

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12. CDC. Reported tuberculosis in the United States, 2008.Atlanta,GA.U.S.Publicationyear2009;1-131.

13. Mazurek,GHandVillarino,ME.CDC.Guidelinesforusingthe Quantiferon-TB test for diagnosing Mycobacteriumtuberculosisinfection.MMWR 2003;52(No.RR-2)15-8.

14. Mazurek,GH,Jereb,J,LoBue,P.GuidelinesforUsingtheQuantiFERON®-TBGoldTestforDetectingMycobacteriumtuberculosisInfection,UnitedStates December16,2005/54(RR15);49-55.

15. Food and Drug Administration. T-spot.TB-P070006.http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/PMAApproval/ucm102794.htm.AccessedJuly2010.

16. MoriT,ShiozawaK.Suppressionoftuberculinhypersensitivitycausedbyrubellainfection.Am Rev Respir Dis1985;886-890.

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18. Madhukar,P,Zwerling,P,andMenzies,D. SystematicReview:T-Cell–basedAssaysfortheDiagnosisofLatentTuberculosisInfection:AnUpdate. Ann Int Med.2008;149:177-184.

19. Lalvani,A,Pathan,AA,McShane,H,etal.Rapiddetectionof Mycobacterium tuberculosis infection by enumerationof antigen-specific T cells. Am J Respir Crit Care Med2001;163:824-828.

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TST Pediatric PerspectiveAnaM.Alvarez,MD

ThereisenoughpublishedliteraturetosuggestthatIn-terferonGammaReleaseAssays(IGRAs)performaswellinchildrenolderthan5yearsasinadults.However,severallimitationsexisttotheiruseinyoungerchildren,beingtheinsufficient number of published studies in this specificpopulationthemostimportantone.Mostoftheliteratureisonadultpopulationswithsomestudiesincludingchildreninmuchlowernumbers.Additionally,thereportednumberofindeterminateresultsinthepediatricpopulationhasawidevariation,butithasbeenashighas35%.Thishasbeenattributedtoalowmitogenresponseinyoungchildren,anditisprobablyrelatedtoimmunologicimmaturity1,2.

TheAmericanAcademyofPediatricspublishedrecom-mendationsregardingtheuseofIGRAsinchildrenin20093.For immune-competentchildren5yearsof ageorolder,IGRAscanbeusedinplaceofTuberculinSkinTest(TST).However, thesetestsareNOTrecommendedinchildrenyoungerthan5yearsofageorimmunocompromisedchil-dren.Becausethispopulationisathighriskofprogressionandworseoutcomes,someexpertshaverecommendedusingbothtestsinthesechildrenandtointerpretapositiveresultfromeithertestasevidenceofinfection1,4,5.Thispracticehaseconomicalandpracticallimitations.TheTSTcontinuestobethepreferredtestforyoungchildren.

References1. Haustein T, Ridout DA, Hartley JC, et al. The

likelihood of an indeterminate test result from awhole-bloodinterferon-γreleaseassayforthediagnosisof Mycobacterium tuberculosis infection in childrencorrelateswith age and immune status.Pediatr Infect Dis J 2009;28:669-673.

2. ConnellTG,TebrueggeM,RitzN,etal.Indeterminateinterferon-γreleaseassayresultsinchildren.Pediatr Infect Dis J 2010;29:285-286.

3. American Academy of Pediatrics. Tuberculosis. In:PickeringLK,BakerCJ,KimberlinDW,LongSS,eds.RedBook:2009ReportoftheCommitteeonInfectiousDiseases. 28th ed. Elk Grove Village, IL; 2009:680-701.

4. BamfordAR,CrookAM,ClarkJE,etal.Comparisonofinterferon-γreleaseassaysandtuberculinskintestinpredictingactive tuberculosis (TB) inchildren in theUK: a paediatric TB network study. Arch Dis Child 2010;95:180-186.

5. CDC.Updatedguidelinesforusinginterferon-γreleaseassaystodetectMycobacterium tuberculosis infection–UnitedStates,2010.MMWR2010;59:(No.RR-5):1-25.

Address Correspondence to: Ana M. Alvarez, MD, Associ-ate Professor of Pediatrics, Pediatric Infectious Diseases and Immunology,University of Florida\Jacksonville, Email: [email protected]


39. Lucas,M,Nicol,P,McKinnon,E,etal.Aprospectivelarge-scalestudyofmethodsforthedetectionoflatentMycobacterium tuberculosis infection in refugeechildren. Thorax 2010;65:442-448.

40. Connell,TG,Curtis,N,Ranganathan,SC,etal. PerformanceofawholebloodinterferongammaassayfordetectinglatentinfectionwithMycobacterium tuberculosisinchildren. Thorax 2006;61:616-620.

41. Elzi,L,Scheger,M,Weber,R,etal. Reducingtuberculosisincidenceby tuberculin skin testing, preventive treatment,and antiretroviral therapy in an area of low tuberculosistransmission. Clin Infect Dis 2007;44:94-102.

42. StephanC,Wolf,T,Goetsch,U,etal.Comparingquantiferon-tuberculosisgold,T-spottuberculosisandtuberculinskintestinHIV-infectedindividualsfromalowprevalencetuberculosiscountry.AIDS,2008;22(18):2471-9.

43. LangeB,Vavra,M,Kern,WV,etal..Indeterminateresultsof a tuberculosis-specific interferon-gammareleaseassay inimmunocompromisedpatients.Eur Respir J 2010;35:1179-1182.

44. Mazurek,GH,Jereb,J,Vernon,A,etal. UpdatedGuidelinesfor Using Interferon Gamma Release Assays to DetectMycobacterium tuberculosis Infection—UnitedStates,2010.MMWR2010;59(No.RR-5).

45. National Collaborating Centre for Chronic Conditions.Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control.2006;RoyalCollegeofPhysicians,London.pp.27-50.

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Community Associated Methicillin Resistant Staphylococcus Aureus: An Update

NilmarieGuzman,MD

AddressCorrespondence to: NilmarieGuzman,MD,AssistantProfessor,DepartmentofInternalMedicine,UniversityofFlorida,Jacksonville,Florida.Email:[email protected].

Abstract: Community associated methicillin resistant Staphylococcus aureus (CA-MRSA) has been identified for over a decade in previously healthy individuals with no recognized risk factors. It has been recognized in countries around the globe and associated with significant morbidity and mortality. Infections range between mild skin and soft tissue infec-tions to necrotizing pneumonia, endocarditis and osteomyelitis. The rapid spread of this organism in particular populations and evidence of epidemics in several countries suggests that CA-MRSA strains are more virulent than hospital associated strains. Further research has provided invaluable information to understand the emergence, molecular characteristics, diagnostic tools and appropriate treatment options for patients infected with CA-MRSA. Controversy still remains in regards to treatment of choice and ideal prevention strategies. This article intends to present an overview of the epidemiology, pathogenesis and molecular characteristics associated with CA-MRSA as well as recommend treat-ment and prevention modalities.

IntroductionStaphylococcus(S.) aureusisawellrecognizedhumanpatho-

genofworldwidedistribution.Itisacommensalorganismandaleadingcauseofbacterialinfections.Forover50yearsthisorganismhasshownasignificantabilitytodevelopre-sistanceshortlyafterexposuretoantibiotics.OnlytenyearsafterBenzylpenicillinwascommerciallyavailable,itwasnolongereffectiveagainstS. aureus.

In1961,thefirstmethicillinresistantS. aureus isolateswereidentified, just 2 years after methicillin was commerciallyavailable.1Thefollowingfourdecadestheorganismspreadworldwide.Atthebeginningoftheepidemic,infectionswithMRSAwereassociatedwithexposuretohealth-carefacilities.Individuals considered athigh risk forMRSAacquisitionincludedthosewitharecenthospitalization,hemodialysis,illicit drug use or contact with a person diagnosed withMRSAinfection.2

Duringthemid1990s,isolatesofMRSAwereidentifiedfromotherwisehealthyindividualsinthecommunitywithoutpriorexposuretothehealthcaresystem.Furtherevaluationelucidated thatMRSAstrainsacquired in thecommunitydifferfromhospitalassociatedstrainsinepidemiology,na-tureofinfection,andmolecularcharacteristics.Strainsweredenominatedcommunity-associatedMRSAorCA-MRSA.CA-MRSAisnowprevalentandassociatedwithsignificantmortalityandmorbidityrates.

EpidemiologyCA-MRSAS. aureushasbeendefinedasMRSAinfection

inapatientwithoutapriorhistoryofhospitalization,dialysis,

longtermcareresidenceintheprior6-12monthsbeforediseaseonset,absenceofanindwellingline,andacultureobtainedless than 48 hours after admission.3 Between 1997-1999,fourhealthychildrenintheupperMidwesternregionoftheU.S.diedfromsepsisornecrotizingpneumoniasecondarytoMRSA.AnalysisoftheoutbreakconcludedthattheetiologicagentwasCA-MRSA,alsoknownasMW2.MW2andothercloselyrelatedstrains,collectivelyknownaspulse-filledtypeUSA400,multilocussequencetype1strainswerethemostprominentcommunity-associatedstrainsintheU.S.before2001.4,5 Inaddition, in2001-2002,a significant increasewasnoted inCA-MRSA related skin infections especiallyamongpediatricpatientsfromthreedifferentareasincludingAtlanta,BaltimoreandMinnesota.6Subsequently,otherout-breakswereidentifiedinvolvingsportsparticipants,militarypersonnelandprisoners.7-9

In 2003 an alarming increase in CA-MRSA isolates inachildren’shospitalinCorpusChristi,Texaswasreportedfrom1999-2003.In2003MRSAaccountedfor98%ofS. aureus isolates in that institution.10 Further investigationhastranspiredthatCA-MRSAisnowanepidemicinNorthAmerica,mainlyintheU.S.CountriessuchasAustralia,NewZealand,UnitedStates,UK,France,FinlandandCanadawerethefirstonestoreportcasesofCA-MRSA.AnewCA-MRSAcloneknownasUSA300;astrainunrelatedtoMW2/ST1was identified inmostcases in theU.S., revealingarapidreplacementofUSA400inmostareas.

USA300isnowthemostcommoncauseofcommunityassociatedbacterialinfectionsintheU.S.11-14CasesofCA-MRSAhavebeenreportedaroundtheglobe.Duringthepast15years,infectionssecondarytothisorganismhavebecomewidespread.Surveillancereportshavedemonstratedthatthisorganismiseasilytransmissibleinthecommunitybyclosecontacteventootherwisehealthyindividuals.Approximately30%ofindividualswithoutexposuretohealthcarefacilitiesarecolonizedwithS. aureusinthenostrils.15

PopulationsathighriskforCA-MRSAacquisitionincludehousehold contacts, day-care centers, athletes involved incontact sports,prisoners,nativeAmericans,pacific island-ers,children(<2yrs),menwhohavesexwithmen,soldiers,individuals with prior MRSA infection and intravenousdrugusers.Overcrowdedsettingalso representsa risk.16-19TheCentersforDiseaseControlandPrevention(CDC)inAtlantahaveproposedfiveC’sorfactorsofMRSAtransmis-sion:Crowding,frequentskintoskinContact, Compromised skinintegrity,Contaminateditemsandsurfaces,andlackofCleanliness.20


Genetics of CA-MRSABydefinitionmethicillinresistantS. aureusreferstoisolates

thatareresistanttoβ-lactamantibiotics. S. aureusresistancearisesatthemecAgenewhichencodesforalteredpenicillin-binding protein (PBPa). MecA gene is located within theStaphylococcal chromosomal cassette (SCCmec). Strainsof CA-MRSA contain SCCmectype IV and HA-MRSAstrainsharborSCCmectypesIIandIII.ThedifferenceinlocationofmecAgeneexplainsthevariationinantimicrobialsusceptibilitypatternincontrasttohospitalassociatedstrains.

Clinical ManifestationsCA-MRSAisassociatedwithabroadspectrumofclinical

manifestations.TheburdenofstaphylococcalinfectionshasincreasedworldwidesincetheemergenceofCA-MRSA.Skinandsofttissueinfectionsrepresentthemajorityofthecases,about90%.21Skinandsofttissueinfectionsusuallypresentasabscessesorcellulitis,howevertheycanprogresstonecrotiz-ingskininfections.22Otherclinicalmanifestationsincludeendocarditis, septicemia, necrotizing pneumonia, septicthrombophlebitiswithpulmonaryembolization,septicemiawithpurpurafulminans,andboneandjointinfections.23-28TheseverityofCA-MRSAinfectionreliesonhostimmuneresponsesandthepresenceofvirulencefactorssuchasPanton-ValentineLleukocidin(PVL)antigenandothertoxins.

Virulence FactorsS. aureushastheabilityofproducingmultiplefactorsthat

aiminpathogenesisandsurvival.Itiscapableofproducingmoleculesthatinhibitneutrophilrecruitmentandphagocy-tosis.29,30Someofthesemoleculesdegradeandprotectfromneutrophil-derivedreactiveoxygenspeciesandantimicrobialcompounds.S. aureusevadeskillingbyneutrophilsandithasbeenshownthatlysisofneutrophilsoccursmorerapidlyafterphagocytosisofCA-MRSAthanHA-MRSA.31S. aureusproducesavarietyoftoxinsthattargethumanbloodcellssuch as alfa-hemolysis(Hlα), delta, gamma, δ-hemolysin,γ-hemolysis, PVL and alfa-type phenol-soluble modulin(PSMα)peptides.

PVLisacytolytictoxinimplicatedasaS. aureusadher-encemolecule;italsoformsporesinmembranesoftargetleukocytes.32Duetotheabilityofadheringtoextracellularmatrixproteins,PVLhasbeenassociatedwithdevelopmentofnecrotizingpneumonia.33ThepresenceofPVLhasalsobeendescribedinMSSAisolates.PVLpositiveCA-MRSAstrains have been identified in multiple geographic areas with variable prevalence rates.34,35 StrainsassociatedwithskinandsofttissueinfectioninFrancefrom2000-2003was1-3%comparedto>50%inU.S.14

Another key virulence factor is Alfa-hemolysin (H1α).Alfa-hemolysinhaspore-formingactivitytowardlymphocytes,monocytesanderythrocytes.36Expressionofalfa-hemolysinishigherinUSA300isolates.37Researchinmurinemodelsindicate thatHlα isamajorvirulence factorcontributingtopneumoniaandinlightofitsrelativelyhighexpressioninUSA300strains,itcontributestodevelopmentofsevereCA-MRSAinfections.38-39Recently,alfa-typephenolmodulin

peptideshavebeendiscoveredinasearchforvirulencefactorsinUSA300andUSA400strainsthatallowhighvirulence.Theyhaveshownbothinvivo andin vitrocytolyticeffectinhumanneutrophils.PSMαpeptidesareproducedatincreasedlevelsinCA-MRSAstrainscomparedtoHA-MRSAstrains,whichexplainstheenhancedvirulenceassociatedwiththisorganism.40

DiagnosisS. aureuscanbediagnosedbyisolatingtheorganismfrom

culturesoftissue,blood,pusorrespiratoryspecimens.Itwillgrowinanynon-selectivemedium.Ifitisisolatedfrombloodorothersterilesite,thespecificityis100%.Antimicrobialsusceptibilitytestingcanbedonewithdiscdiffusion,brothdilutionorautomatedmethods.AlatexagglutinationtesttoidentifyPBP2aisalsoavailable.41

Molecular typing techniqueshavebeen incorporated todiagnostic testing in order to obtain a prompt diagnosticconfirmationinadditiontoavoidingunnecessaryantibiotics.Molecular typing techniques include toxingeneprofiling,antimicrobialresistancetyping,PulseFilledEletrophoresis,(PFGE)multilocussequencetyping,multilocusrestrictionfragmenttypingandamplifiedfragmentlengthpolymor-phismanalysis.NoveltechniquesusedintheUnitedStatesincludePNA-FISH®orPeptideNucleicAcidFluorescenceInSituHybridizationand theGeneOhm®StaphSRassay,whichisanFDAapprovedmultiplexrealtimePCRassay.CA-MRSA/USA300strainsareusually susceptible toco-trimoxazole, tetracyclines, and clindamycin, however thispatternisnotuniform.42

ManagementMultipletherapeuticoptionsareavailableformanagement

ofMRSA infectioneitherby theoralorparenteral route.Oralagentscommonlyrecommendedincludeclindamycin,tetracyclines,co-trimoxazole,rifampicinandfusidicacid.43-45Clindamycinisactive in vitroin80%oftheisolatesandisalsoactiveagainstgroupAstreptococcus.Sinceresistanceispossible,isolatesmustbetestedforclindamycinresistance,especiallyonisolatesresistanttoerythromycin.Doxycyclineandminocyclinearealsohighlyeffectiveinthemanagementofskinandsofttissueinfections,howevertheyarecontraindicatedduringpregnancyandchildrenyoungerthan8-years-old.

Co-trimoxazoleisactiveagainst90-100%ofCA-MRSAisolates.Disadvantagesincludenephrotoxicpotentialanditisnotrecommendedduringthirdtrimesterofpregnancy.Ri-fampinisnotrecommendedasasingleagentsinceresistanceemergesquickly.Itmustbeusedincombinationwithanotheranti-staphylococcaldrugasadjunctivetherapy.

LinezolidisanotherdrugapprovedforMRSApneumoniaandskinandsofttissueinfections.Itisexpensiveandassociatedwithbonemarrowtoxicityparticularlythrombocytopenia,development of peripheral neuropathy or optic neuritis.Patients taking serotoninuptake inhibitors concomitantlywithlinezolidareatriskofdevelopingserotoninsyndrome.Therefore, linezolidmustbe reserved for caseswereother


MRSA: Pediatric Point of ViewNizar Maraqa, MD

Children have particularly shouldered a big burden ofillnesscausedbytheemergenceoftheMethicillinResistantStaphylococcus aureus (MRSA)pathogeninrecentyears.1Thetendencyforchildrentobeinclosecontactwitheachother,lessmasteryofproperhygiene,aswellastheirparticipationin sporting andother activities linked to the spreadof theorganismhavecontributedtoCommunityAcquiredMRSA(CA-MRSA)becomingthemajorcauseofskinandsofttissueinfectionsseeninpediatricpatients.2

While the virulence of the organism, its pathogenicity,susceptibilitytoantimicrobialagentsandresponsetotherapyhavebeensimilartowhatisseeninadultpatients,certainissuesareuniqueforthepediatricpopulation.Althoughnecrotizingpneumonia, osteoarticular infection, bacteremia and otherinvasiveinfectionshavebeendescribed,byfar,skinabscesseshavebeenthepredominantpresentationofCA-MRSAseeninchildren.Themajorityoftheseseemtoresolvewithspontane-ousorsurgicaldrainage,evenwithoutconcomitantantibiotictherapy,especiallywhentheyareofsmallersize(<=5cmindiameter)occurringinotherwisenormalhosts.3,4

Whenantibioticsaretobeprescribed,pediatricpractitionershave valuable oral options such as clindamycin and co-tri-moxazole(trimethoprim-sulfamethoxazole)availabletotheminliquidandpillformulations.Useofintravenousantibiot-icsfortreatingCA-MRSAinchildrenisusuallyreservedforthesevereorinvasiveinfections.Theintravenousantibioticagentsoffirstchoicearesimilartothoseusedinadults,namelyvancomycinandclindamycin.Fluoroquinolones,daptomy-cinandtigecyclinearenotyetapprovedforuseinchildren.FurtherstudiesinchildrenarerequiredbeforeweareabletousemanyoftheseandotherinvestigationalantibioticsinthefightagainstCA-MRSA.

HandwashingandattentiontohygieneremainscrucialincombatingthespreadofCA-MRSAamongchildrenintheoutpatientand inpatient settings.Decolonizationprotocolshavehadvaryingsuccessinchildrenastheyhavehadinadults.EducatingthepublicandhealthcareforceaboutCA-MRSAiscrucialinlimitingitsspread.

References 1. GerberJS,etal.“Trendsintheincidenceofmethicillin-

resistant Staphylococcus aureus infection in children’shospitals in the United States.” Clin Infect Dis.2009;49(1):65-71.

2. Kaplan S, Huten K, Gonzalez, B,et al. “Three-yearsurveillanceofcommunity-acquiredStaphylococcusaureusinfectionsinchildren.”Clin Infect Dis.2005;40:1785-91.

3. LeeM,Rios,A,Aten,F,etal.“Managementandoutcomeofchildrenwithskinandsofttissueabscessescausedbycommunity-acquiredmethicillin-resistentStaphylococcusaureus.”Pediatr Infect Dis J 2004;23:123-7.

4. MarcinakJ,FrankA.“Treatmentofcommunity-acquiredmethicillin-resistantStaphylococcusaureusinchildren.”Curr Opin Infect Dis.2003;16(3):265-9.

Address correspondence to Nizar Maraqa, MD, Assistant Profes-sor of Pediatrics,Pediatric Infectious Diseases and Immunology, University of Florida, Jacksonville, Florida. Email: [email protected].

drugs are not recommended or contraindicated. Manage-mentofskinabscesses involves incisionanddrainage.Forskinabscesses<5cm,incisionanddrainageusuallysuffices.Inthisscenario,antibioticsarerecommendedinthepresenceofmultiplelesions,severelyimpairedhostdefenses,extensivesurroundingcellulitis,orseveresystemicmanifestationsofinfectionsuchasfever.

Severalintravenousantibioticsareavailableforthemanage-mentofCA-MRSA.Vancomycinremainstobethefirstlineagentrecommended.OtheragentsapprovedareDaptomycin,linezolid,tygecyclineandquinopristin-dalfopristin.46SeveralinvestigationaldrugsareunderstudytoevaluatetheirefficacyforthemanagementCA-MRSAinfections.Theyincludetela-vancin,dalbavancinandoritavancinwhicharederivativesofvancomycin.47-48Theyhavenotshownsuperioritycomparedtostandardtherapiesinclinicaltrials.49Telavancinhasbeenapprovedforthemanagementofskinandsofttissueinfec-tions. Anti-MRSA beta-lactams such as ceftobiprole andceftarolineareunderstudy.Theyhaveshowntobehighlyactiveinrabbitmodelsofendocarditis.50

PreventionSincetheorganismistransmittedbyclosecontact,preven-

tionisfocusedonproperhygiene.Handwashingwithsoapand water or waterless antibacterial gels is recommendedforinfectedpersonsorindividualswhogetindirectcontactwithapatient.Openanddrainingwoundsmustbecovereduntiltheyarehealed.ForthoseindividualswhogetrecurrentMRSAinfections,decolonizationmustbeconsidered.Thiscanbeachievedwithchlorhexidine.Mupirocinointmentisalso recommended,however resistancehasbeen reported.ManagementofCA-MRSAinfectionsrepresentachallengefor clinicians mostly due to multidrug resistance and theorganism’sabilitytoevadetheimmunesystem.Furtherre-searchisneededwithemphasisonnovelpreventionstrategiesandantibioticoptions.

References1. JevonsMP.Celbenin-resistantstaphylococci.BMJ.1961;1:124-125.

2. NaimiTS,LeDEllIndivi,Como-SabettiK,etal.Comparisonofcommunityandhealth-careassociatedmethicillinresistantStaphylococcusaureusinfection. JAMA.2003;290:2976-84.

3. CentersforDiseaseControlandPrevention.Fourpediatricdeaths from community-acquired methicillin-resistantStaphylococcus aureus-Minnesota andNorthDakota,1997-1999JAMA.1999;282:1123–25.

4. Stemper ME, Brady JM, Qutaishat SS, et al.ShiftinStaphylococcus aureus clone linked to an infected tattoo.Emerg Infect Dis. 2006;12:1444-46.

5. FridkinSK,HagemanJC,MorrisonM,et al.Methicillin-resistantStaphylococcus aureus diseaseinthreecommunities.N Engl J Med. 2005;352:1436-44.

6. EllisMW,HospenthalDR,DooleyDP,GrayPJ,MurrayCK.NaturalhistoryofcommunityacquiredMethicillinresistantStaphylococcusaureuscolonizationandinfectioninsoldiers.Clin Infec Dis.2004;39:971-9.


7. Aiello AE, Lowy FD, Wright LN, Larson EL. Methicillinresistant Staphylococcus aureus among US prisoners andmilitarypersonnel:reviewandrecommendationsforfuturestudies.Lancet Infect Dis.2006;6:335-41.

8. Kazakova SV, Hageman JC, Matava M, et al. A clone ofmethicillinresistancestaphylococcusaureusamongprofessionalfootballplayers.N Engl J Med.2005;352:468-75.

9. Purcell,K,FergieJ.EpidemicofCA-MRSAinfections:a14yearstudyatdRiscollChildren’shospital.Arch Pediatr Adolesc Med.2005;159:980.

10. McDougalLK,StewardCD,KillgoreGE,etal.Pulsed-fieldgelelectrophoresistypingofoxacillin-resistantStaphylococcus aureus isolates from the United States: establishing anationaldatabase.J Clin Microbiol. 2003;41:5113-20.

11. MillerLG,DiepBA.Clinicalpractice:colonization,fomites,and virulence: rethinking the pathogenesis of community-associatedmethicillin-resistantStaphylococcus aureus infection.Clin Infect Dis. 2008;46:752-60.

12. Kennedy AD, Otto M, Braughton KR, et al. Epidemiccommunityassociated methicillin-resistant Staphylococcus aureus:recentclonalexpansionanddiversification.Proc Natl Acad Sci USA. 2008;105:1327-32.

13. MoranGJ,KrishnadasanA,GorwitzRJ,etal.Methicillin-resistantS. aureus infectionsamongpatientsintheemergencydepartment.N Engl J Med. 2006;355:666-74.

14. GorwitzRJ,Kruszon-MoranD,McAllisterSK,etal.Changesin the prevalence of nasal colonization with Staphylococcus aureus intheUnitedStates,2001-2004.J Infect Dis. 2008;197:1226-34.

15. DietrichDW,AuldDB,MermelLA.Community-acquiredmethicillin-resistantStaphylococcus aureus in southernNewEnglandchildren.Pediatrics.2004;113(4):e347-e352.

16. GroomAV,WolseyDH,NaimiTS,etal.Community-acquiredmethicillin-resistantStaphylococcus aureus inaruralAmericanIndiancommunity.JAMA.2001;286:1201-5.

17. Castrodale LJ, Beller M, Gessner BD.Over-representationof Samoan/Pacific Islanders with methicillin-resistantStaphylococcus aureus (MRSA) infections at a large familypracticeclinicinAnchorage,Alaska,1996-2000.Alaska Med. 2004;46:88-91.

18. YoungDM,HarrisHW,CharleboisED,etal.Anepidemicof methicillin-resistantStaphylococcus aureus soft tissueinfectionsamongmedicallyunderservedpatients.Arch Surg.2004;139:947-53.

19. CentersforDiseaseControl. www.cdc.gov/niosh/topics/mrsa.AccessedAugust2011.

20. MoranGJ.PrevalenceofCA-MRSAisvariablethroughouttheworld.S. aureus infectionsamongpatientsintheemergencydepartment.N Engl J Med. 2006;355:666-74.

21. DeLeoFR,DiepBA,OttoM:MillerLG,Perdreau-RemingtonF,RiegG,etal.Necrotizingfasciitiscausedbycommunity-associated methicillin-resistant Staphylococcus aureus in LosAngeles.N Engl J Med. 2005;352:1445-53.

22. ArnoldSR,EliasD,BuckinghamSC,etal.Changingpatternsof acute hematogenous osteomyelitis and septic arthritis:emergence of community-associated methicillin-resistantStaphylococcus aureus.J Pediatr Orthop. 2006;26:703-08.

23. BuckJM,Como-SabettiK,HarrimanKH,etal.Community

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25. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonarymanifestations in children with invasive community-acquiredStaphylococcus aureus infection.Clin Infect Dis. 2005;41:583-90.

26. HagemanJC,UyekiTM,FrancisJS,etal.Severecommunity-acquiredpneumoniaduetoStaphylococcus aureus,2003-04influenzaseason.Emerg Infect Dis. 2006;12:894-99.

27. NaimiTS,LeDellKH,Como-SabettiK,etal.Comparisonofcommunity-andhealthcare-associatedmethicillin-resistantStaphylococcus aureus infection.JAMA. 2003;290: 2976-84.

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29. Foster TJ: Immune evasion by staphylococci. Nat Rev Microbiol.2005;3:948-958.

30. Voyich JM, Braughton KR, Sturdevant DE,Whitney AR,Said-SalimB,PorcellaSF,LongRD,DorwardDW,GardnerDJ, Kreiswirth BN et al.: Insights into mechanisms usedby Staphylococcus aureus to avoid destruction by humanneutrophils.J Immunol.2005;175:3907-3919.

31. Tristan A, BenitoY, Montserret R, Boisset S, Dusserre E,Penin F, Ruggiero F, Etienne J, Lortat-Jacob H, Lina Get al.: The signalpeptide of Staphylococcus aureus PantonValentineleukocidin LukS component mediates increasedadhesiontoheparansulfates.PLoS ONE.2009;4:e5042.

32. deBS,TristanA,EtienneJ,BrousseN,VandeneschF,LinaG:StaphylococcusaureusisolatesassociatedwithnecrotizingpneumoniabindtobasementmembranetypeIandIVcollagensandlaminin.J Infect Dis.2004;190:1506-1515.

33. BhakdiS,Tranum-JensenJ:Alpha-toxinofStaphylococcusaureus.Microbiol Rev.1991;55:733-751.

34. VandeneschF,NaimiT,EnrightMC,etal.Community-acquiredmethicillin-resistant Staphylococcus aureus carrying Panton-Valentineleukocidingenes:worldwideemergence.Emerg Infect Dis.2003;9:978-84.

35. TristanA,BesM,MeugnierH,etal.GlobaldistributionofPanton-Valentineleukocidin—positivemethicillin-resistantStaphylococcus aureus,2006.Emerg Infect Dis, 2007;13:594-600.

36. Li M, Diep BA, Villaruz AE, Braughton KR, Jiang X,DeLeo FR,Chambers HF, Lu Y, Otto M: Evolution ofvirulence in epidemic community-associated methicillin-resistantStaphylococcusaureus.Proc Natl Acad Sci U S A. 2009;106:5883-5888.

37. MontgomeryCP,Boyle-VavraS,AdemPV,LeeJC,HusainAN, Clasen J, Daum RS: Comparison of virulence incommunityassociated methicillin-resistant StaphylococcusaureuspulsotypesUSA300andUSA400inaratmodelofpneumonia.J Infect Dis.2008;198:561-570.

38. Burlak C, Hammer CH, Robinson MA, Whitney AR,McGavinMJ,KreiswirthBN,DeLeoFR:Globalanalysisofcommunityassociated methicillin-resistant Staphylococcusaureusexoproteinsrevealsmoleculesproducedinvitroandduringinfection.Cell Microbiol.2007;9:1172-1190.

http://www.cdc.gov/niosh/topics/mrsa


39. WangR,BraughtonKR,KretschmerD,BachTH,QueckSY,LiM,KennedyAD,DorwardDW,KlebanoffSJ,PeschelAetal.:Identificationofnovelcytolyticpeptidesaskeyvirulencedeterminants for community-associated MRSA. Nat Med.2007;13:1510-1514.

40. Shore AC, Rossney AS, O’Connell B, et al. Detectionof SCCmec-associated DNA Segments in multiresistantmethicillinsusceptible Staphylococcus aureus (MSSA) andidentificationofStaphylococcus epidermidis ccrAB4 inbothmethicillin-resistantS. aureus (MRSA)andMSSA.Antimicrob Agents Chemother. 2008;52:4407-19.

41. Van Hal SJ, Stark D, Lockwood B, Marriott D, Harkness J.Methicillin-resistant Staphylococcus aureus (MRSA) detection:comparisonoftwomolecularmethods(IDI-MRSAPCRassayandGenoTypeMRSADirectPCRassay)withthreeselectiveMRSAAgars(MRSAID,MRSASelect,andCHROMagarMRSA)forusewithinfection-controlswabs.J Clin Microbiol. 2007;45: 2486-90.

42. StevensDL,BisnoAL,ChambersHF,etal.Practiceguidelinesfor the diagnosis and management of skin and soft-tissueinfections.Clin Infect Dis. 2005;41:373-406.

43. NathwaniD,MorganM,MastertonRG,etal.GuidelinesforUKpracticeforthediagnosisandmanagementofmethicillin-resistantStaphylococcus aureus (MRSA)infectionspresentinginthecommunity.J Antimicrob Chemother. 2008;61:976-94.

44. Barton MD, Hawkes M, Moore D. Guidelines for theprevention and management of community-acquiredmethicillin-resistantStaphylococcus aureus: aperspective forCanadian health care practitioners. Can J Infect Dis Med Microbiol. 2006;17 (supplC): 4C-24C.

45. Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA, andParticipantsintheCentersforDiseaseControlandPrevention-ConvenedExperts’MeetingonManagementofMRSAintheCommunity.StrategiesforclinicalmanagementofMRSAinthecommunity:summaryofanexperts’meetingconvenedby theCenters forDiseaseControl andPrevention.2006.Availableathttp://www.cdc.gov/ncidod/dhqp/pdf/ar/CAM-RSA_ExpMtgStrategies.pdf.AccessedAugust2010.

46. MicekST.Alternativestovancomycinforthetreatmentofmethicillin-resistantStaphylococcus aureus infections.Clin Infect Dis. 2007;45(Suppl3): S184–S190.

47. PanA,LorenzottiS,ZoncadaA.Registeredandinvestigationaldrugsforthetreatmentofmethicillin-resistantStaphylococcus aureus infection.Recent Patents Anti-Infect Drug Disc. 2008;3:10-33.

48. StryjewskiME,ChambersHF.Skinandsoft-tissueinfectionscaused by community-acquired methicillin-resistantStaphylococcus aureus. Clin Infect Dis. 2008; 46 (suppl 5): S368-S377.

49. ChambersHF.Evaluationofceftobiproleinarabbitmodelofaorticvalveendocarditisduetomethicillin-resistantandvancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 2005;49:884-88.

50. Jacqueline C, Caillon J, Le M, et al. In vivo efficacy ofceftaroline(PPI-0903),anewbroad-spectrumcephalosporin,comparedwithlinezolidandvancomycinagainstmethicillin-resistantandvancomycin-intermediateStaphylococcus aureus inarabbitendocarditismodel.Antimicrob Agents Chemother. 2007;51:3397-400.

© 2010 American Cancer Society, Inc.

In the fight against breast cancer, birthdays are signs of progress – and we want to see more of them. You can help create a world with more birthdays by participating in Making Strides Against Breast Cancer, a noncompetitive walk to raise funds and awareness in support of the fight against breast cancer. Visit cancer.org/stridesonline to join us and help create more birthdays in your community. Together, we’ll stay well, get well, find cures, and fight back.

Saturday, October 16, 2010Registration: 7:30 a.m.Walk Begins: 9:00 a.m.Call today for more information about the August Kick Off

Downtown Jacksonville - San Marco SquareOrange Park - Orange Park Kennel ClubJacksonville Beach - Sea Walk Pavilion

For more information on this or the other events in the First Coast Area, please contact Brandy Robinson at 391-3607 or via email at [email protected]

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Breast Cancer and HIV in the Era of HAART: A Case Report and Review of the Literature

NaeemLatif,MD;FauziaRana,MD;andTroyGuthrie,MD

Special Case Report

Addresscorrespondenceto:NaeemLatif,MD,FellowHematol-ogy/Oncology,UniversityofFlorida,Jacksonville,FL,655W.8thStreet,4N,Pavilion,Jacksonville,FL32209Email:[email protected].

Editor’s Note: Due to production constraints, Figures 1-4 are not printed in the journal. They are available online at www.dcmsonline.org as a web illustration.

Abstract: The incidence of human immunodeficiency virus (HIV) infection is rising in U.S. women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and the use of Highly Active Antiretroviral Therapy (HAART) on the natural history of breast cancer, we are presenting a case of breast cancer in an HIV infected women and reviewing the literature. A literature search was done through Medline by using key words HIV/AIDS, breast cancer and HAART therapy, restricted to English language. There are mostly case reports and only one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response and toxicity associated with treatment were reviewed. Patients with HIV infection present with more advanced stage and aggressive disease and have poor chemotherapy tolerance. A literature review suggests that the incidence of breast cancer is similar or lower in HIV infected patients compared to general population. The impact of HAART therapy on breast cancer incidence in HIV infected patients is still unclear.

IntroductionBreastcanceristhemostcommonlydiagnosedmalignancy

and second leading cause of cancer related death amongwomeninUnitedStates.1TheincidenceofHIVinfectioninwomenisrisinganditcanresultinsuppressionofimmunesystemwhichincreasestheriskofmalignancy.2,3ThenumberofwomenlivingwithAIDSisalsoincreasingduetoHAARTtherapy.Therefore,morewomenwithHIVinfectionareatriskofdevelopingbreast cancer as thepatientpopulationgetsolder.

Theacquiredimmunodeficiency(AIDS)definingneoplasmsareKaposi’ssarcoma,non-Hodgkinlymphoma,andcervicalcancer.4 There are malignancies which are more prevalentinAIDSpatientsthangeneralpopulation.Theyarecallednon-AIDS defining cancers (NADCs) such as Hodgkin’slymphoma,squamouscellcarcinomaofanus,livercancer,head&neckandlungcancer.5,6,7Thedataaboutbreastcan-cerincidenceandprognosisinHIVpatientsislimitedandconflicting.8,9HerewewilldiscussacaseofbreastcancerinanHIVinfectedpatientandreviewtheliteraturetoseeifthereisanyassociationbetweenHIVinfectionandHAARTtherapywithregardstobreastcancerstageatpresentation,responseandtoxicitytotreatment.

Case ReportA 55-year-old African American female presented with

apalpableleftbreastlump.Coreneedlebiopsyofthemassshowed poorly differentiated invasive ductal carcinoma.Thetumorwasestrogenandprogesteronereceptorpositive,Her2neupositive3+byIHCandonelymphnodewasalsopositive for metastasis with extra capsular extension. Thepatientunderwentalumpectomyandauxiliarylymphnodedissection.Shewasstartedonadjuvantchemotherapyconsist-ingofDoxorubicinandCyclophosphamide,butwitheachchemotherapycycleshedevelopedfebrileneutropeniaandrequiredhospitalization.Aftertwocyclesofchemotherapy,shedeclinedtocontinuefurthertreatmentduetopoortoleranceandwasstartedonAromataseinhibitorhormonaltherapy.Sixmonthslatershepresentedwithheadacheandconfusion.AnMRIofthebrainshowed15mmcontrastenhancingrightparietallobemass.(Figures 1 & 2, dcmsonline.org) TheexcisionbiopsyofthemassshowedToxoplasmosiswithnecrosisandmicrocalcification.(Figures 3 & 4, dcmsonline.org) Furtherworkup revealed that the patient was HIV positive withhighviralloadandlowCD4count.ThepatientwasstartedonHAARTtherapyforHIVinfectionandcontinuedwithhormonaltherapyforthebreastcancer.

Afewmonthslaterthepatientdevelopedapericardialandpleuraleffusion,whichwasfoundtobemalignantconsistentwithmetastaticbreastcancer.ShewastreatedwithDocetaxel,Carboplatin,andTrastuzumabwithpegylatedGCSFsup-port. The patient had an excellent response to treatmentwithcompleteresolutionofpericardialandpleuraleffusionwithoutanyepisodesoffebrileneutropenia.

DiscussionIndividualswithHIVinfectionandImmunosuppression

afterallograftorgantransplantationareathigherriskofde-velopingnon–AIDS-definingcancers(NADCs).9,10Howeverthedataaboutbreastcancerincidenceintheseimmunosup-pressedpatientsislimitedandconflicting.3,7AlthoughallthreeAIDS-definingmalignancies(Kaposi’ssarcoma,non-Hodgkinlymphoma,andcervicalcancer)andmanyNADCsareassoci-atedwithaviralpathogenesis,somedonothaveanyknownviraloncogenes,andthereasonsfortheirincreasedincidenceinimmunosuppressedindividualsisunclear.11,12

ThedegreeofimmunesuppressionisdirectlycorrelatedwiththeriskoftwooftheAIDS-definingcancers(Kaposi’ssarcoma and non-Hodgkin’s lymphoma), where the riskincreaseswithdecliningCD4cellcount.7,13,14,15RecentdatahasshownthatalownadirCD4cellcountlessthan200/µLwasassociatedwithincreasedincidenceofanal,lung,liver,


head&neckcancersandHodgkin’slymphoma.10,16However,theassociationbetweenthedegreeofimmunesuppressionandtheriskofNADCs,includingbreastcancer,isunclear.

ThebreastcancerincidenceinHIVpatientsisavailablethrough retrospective registry studies, and the limitationsofthesestudiesareinaccurateandincompletereportingaswellasunderrecognitionofasymptomaticHIVinfectionincancerpatients.17TherearetwolargeregistrystudiesoncancerincidenceintheHIVpopulation.Analysisofthecancerinci-dencefrom1993to2000inacohortofU.S.womenlivingwithandatriskforHIVinfectionrevealedanincidenceof26versus4cancersinHIV-infectedwomenincomparisontothenon-infectedwomen,respectively.However,therewerenocasesofbreastcancerineithercohort.17,18.

Inthesecondstudy,datafromtheAIDS-CancerMatchRegistryStudywasanalyzedtodeterminetherelativeriskofdevelopingcancerduringaperiodextendingfrom60monthspriortothefirstAIDS-definingillnessto27monthsafterAIDSdiagnosis.Thisstudyincluded302,834patients.Therelative risk of developing breast cancer in the pre-AIDSinfection time period was higher than in the post-AIDStimeperiodandthisdifferencewasstatisticallysignificant.18Theoverallriskofbreastcancerinthisgroupwassimilartotheknownriskinthenon-HIVpopulation.Therefore,theincreasedincidenceofbreastcancerearlyinthecourseofHIVinfectionismostlikelyrelatedtoaheightenedrecognitionofbreastcanceratthetimeofHIVdiagnosisduetotheclosermedicalsupervision.

ReportsfromAfricaandWesterncountriessuggestedthatimmunesuppressionwasprotectiveagainstthedevelopmentofbreastcancer.19-23AstatisticallysignificantdecreaseintheincidenceofbreastcancerduringtheAIDSepidemicfromTanzaniaandItalyhasbeenreported.9,24Apossibleexplana-tionfor thisdecrease is thehighmortalityrate inwomenwithHIVinfectionindevelopingAfricancountries.Howeverthereisalsoahypothesisthatthelackofimmuneresponsetobreastcancer isprotective.25-27Theevidencesupportingthe absence of a protective effect of immune suppressiononbreastcancerdevelopment is theunchanged incidencein breast cancer in 5,692 renal transplant patients in theNordic study.28Collectively these reports suggest a similarincidenceofbreastcancerinHIV-infectedwomenandanincreasedincidenceinHIV-infectedmenascomparedtothegeneralpopulation.

The total number of reported cases of breast cancer inHIV-infectedpatientsis48,thefirstcasebeingreportedin1988.18,29TwoofthesecasesofbreastcancerinHIV-infectedpatientsoccurredinyoungmen.30,31Breastcanceratthetimeof diagnosis presented at an advanced stage in two-thirdsofthecasesintheolderseries.Thelargestcaseseriesof20womenwithbreastcancerandHIVisreportedbyHurleyetal,32andincidenceofstageIVbreastcancerwas10%.InanotherseriesbyBasilet,al,20%ofthepatientshadstageIVdisease.18

Chemotherapyisusedinthetreatmentofthemajorityofwomenpresentingwithbreastcancereitherneo-adjuvantorinadjuvantsettings.33TheincidenceofmyelosuppressionwithchemotherapyappearstobesignificantlyhigherintheHIVinfectedpopulation.18Inoneseries,fourofthefivepatientsdevelopedgrade3or4Neutropena18and in another casereportonepatientdiedfromchemotherapyinducedtoxicity.34Hurleyetal.reportedgrade3or4Neutropenainfiveofsevenpatientswithonetreatmentrelatedmortality.Myelosuppres-sionwasseeninbothdoxorubicinbasedregimensaswellaswithlowdoseweeklytaxaneregimens.32

Thepatientwepresented,priortoHIVdiagnosis,didnottoleratechemotherapywellanddevelopedfebrileneutropeniaandrequiredhospitalizationwitheachcycleofAC,possiblyduetolowCD4count.HoweverafterrecognitionofHIVinfectionandtreatmentwithHAARTtherapy,shetoleratedDocetaxel,CarboplatinandTranstruzumabwithpegylatedGCSF(Whitebloodcellstimulant)supportandshedidnotdevelopanyfurtherepisodesoffebrileneutropena.

Datafromthepublishedadjuvanttrialsinbreastcancerdemonstrateanexpectedincidenceofgrade4leukopeniaisabout0.3%,andconsequentlyroutineprophylacticadminis-trationofhematopoieticgrowthfactorsupportisnotrecom-mended.35MyelosuppressionismoreprevalentintheHIVpopulationduetopoorbonemarrowreserveandbecauseofmyelosuppressionfromanti-retroviraltherapysuchaszidovu-dine.Antimetabolites(e.g.,5-fluorouracilandmethotrexate)may synergistically interactwith anti-retroviral nucleosideanalogsandpossiblyotheragentsresultinginmarkedtoxicity.Therefore,prophylacticuseofhematopoieticgrowthfactorsin theHIVpopulation receivingchemotherapy forbreastcancershouldbeconsideredtopreventthemorbidityandmortalityassociatedwithsuchtherapy.

Cytotoxic drugs can potentially suppress immunity inaddition to causing myelosuppression.36-40 In non-HIVinfectedpatients,cytotoxictherapyresultedinreductionofthe lymphocyte counts aswell asNKcell countswithoutaffectingtheabilityofthesecellstolysetargetcells.Ontheotherhand,thenumberandactivityoftheNKandLAKcellswasreducedintheHIVpopulationwithrespecttothenon-infectedhealthypopulationevenwithoutchemotherapy.Therefore, chemotherapy may complicate HIV-inducedimmune suppression and facilitate the worsening of HIVinfectionasreportedbyBasilandHurleyetal.17,31

In conclusion, there is no evidence that breast cancerincidence is higher among HIV-infected women than inthegeneralpopulation.However,itappearsthatthenaturalhistoryofbreastcancer in the settingofHIV infection isworsethaninthegeneralpopulation.Thismayberelatedtoabiologicallymoreaggressivebreastcancercompoundedbytheinabilitytodeliverfulldosesofsystemicanti-cancertherapies in this population of patients. Presence of HIVinfectionmay influence the toxicityof thechemotherapy;howeveritisalsopossiblethatchemotherapymayadverselyimpactthenaturalhistoryofHIVinfectionitself.Thein-creasedincidenceofHIVinfectionsinwomenisexpected


toresultinhigherprevalenceofbreastcancerinthissetting.Therefore,physicianstreatingwomenwithbreastcancerandHIVinfectionmustbeawareofthesepotentialcomplicationsoftherapy.TreatmentplansshouldincludeclosemonitoringoftheCD4count,viralload,chemotherapy-relatedtoxicity,andprophylacticuseofgrowthfactorsupport.

References1. JemalA,ThomasA,MurrayT,etal.Cancerstatics2002.CA

Cancer J Clin2002;52:23-47.

2. PetersBS,BeckEJ,ColemanDG,etal.ChangingdiseasepatternsinpatientswithAIDSinareferralcenterinUnitedKingdom:thechangingfaceofAIDS.BMJ1991;302:203-207.

3. BiggarRJ,RabkinCS.TheepidemiologyofAIDS-relatedneoplasm.Hematol/Oncol Clinic North Amer10:997–1009,1996.

4. RemickSC.Non-AIDS-definingcancers. Hematol/Oncol Clinic North Amer 10:1203–1213,1996.

5. ParkerMS,LevenoDM,CampbellTJ,WorrellJA,CarozzaSE.AIDS-relatedbronchogenic carcinoma: factorfiction?Chest113:154–161,1998.

6. Chung M, Chang HR, Bland KI, Wanebo HJ. Youngerwomenwithbreastcarcinomahaveapoorerprognosisthanolderwomen.Cancer 77:97–103,1996.

7. GrulichAE,VanLeeuwenMT,etal.IncidenceofcancerinpeoplewithHIV/AIDScomparedwithimmunosuppressedtransplantrecipients:Ameta-analysis.Lancet 370:59-67,2007.

8. FrischM,BiggarRJ,EngelsEA,etal.Associationofcancerwith AIDS-related immunosuppression in adults. JAMA285:1736-1745,2001.

9. M.Intra,V.Ripamonti,JournalofSurgicalOncologyetal.Journal of surgical oncology2005;91:141-142.

10. ThomasP,DavidR.HighlyActiveAntiretroviralTherapyandtheIncidenceofNon–AIDS-DefiningCancersinPeoplewithHIVInfection.JCO 27:884-890,2009.

11. BowerM,PowlesT,NelsonM,etal.HIV-relatedlungcancerintheeraofhighlyactiveantiretroviraltherapy.Aids17:371-375,2003.

12. Kirk GD, Merlo C, O’Driscoll P, et al. HIV infection isassociatedwithanincreasedriskforlungcancer,independentofsmoking.Clin Infect Dis45:103-110,2007.

13. InternationalCollaborationonHIVCancer.Highlyactiveantiretroviral therapy and incidence of cancer in humanimmunodeficiencyvirus-infectedadults. J Natl Cancer Inst92:1823-1830,2000.

14. CliffordGM,PoleselJ,RickenbachM,etal.CancerriskintheSwissHIVCohortStudy:Associationswithimmunodeficiency,smoking,andhighlyactiveantiretroviraltherapy.J Natl Cancer Inst 97:425-432,2005.

15. Stebbing J, Gazzard B, Mandalia S, et al. AntiretroviraltreatmentregimensandimmuneparametersinthepreventionofsystemicAIDS-relatednon-Hodgkin’slymphoma. J Clin Oncol 22:2177-2183,2004.

16. PatelP,HansonDL,SullivanPS,etal.IncidenceoftypesofcanceramongHIV-infectedpersonscomparedwiththegeneralpopulationintheUnitedStates,1992-2003. Ann Intern Med 148:728-736,2008.

17. PhelpsRM,SmithDK,GardnerLI,CarpenterCCJ,KleinRS,JamiesonD,VlahovD,SchumanP,HolmbergSD.Cancer

incidenceinwomenwithoratriskforHIVinfection. Int J Cancer94(5):753-757,200.

18. BasilF.El-Rayeset,al.Breastcancerinwomenwithhumanimmunodeficiencyvirusinfection:implicationfordiagnosisandtherapy.Breast Cancer Research and Treatment76:111-116,2002.

19. SpielmannM,KitschkeHJ,TietjeK.Cellularimmunityinbreastcancerpatient.Onkologie 5(suppl):42-45,1982

20. LeeYT,SheikhKM,QuismorioFP,FriouGJ.Circulatinganti-tumorandautoantibodiesinbreastcarcinoma:relationshiptostageandprognosis.Breast Cancer Res Treat 6:57-65,1985.

21. Rotstein S, Blomgren H, Petrini B,Wasserman J, NilssonB,BaralE.Bloodlymphocytecountswithsubsetanalysisinoperablebreastcancer:relationtotheextentoftumordiseaseandprognosis.Cancer 56:1413-1419,1985.

22. HeadJF,ElliottRL,McCoyJL.Evaluationof lymphocyteimmunityinbreastcancerpatients.BreastCancer Res Treat26:77-88,1993.

23. Stewart T, Grayson H, Tsai SJ, Henderson R, Opezl G.Incidence of de novo breast cancer in women chronicallyimmunosuppressedafterorgantransplantation. Lancet346:796-798,1995.

24. AmirH,KaayaEE,KwesigaboG,etal.BreastCancerbeforeandduringtheAIDSepidemicinwomenandmen:AstudyofTanzanianCancerRegistryData1968to1996.J Natl Med Assoc2000;92:301-305.

25. Pantanowitz L,DezubeBJ.BreastCancer inwomenwithHIV/AIDS.JAMA2001;285:3090-3091.

26. HeadJF,ElliottRL,McCoyJL.Evaluationof lymphocyteimmunityinbreastcancerpatients.Breast Cancer Res Treat 1993;26:77-88.

27. PantanowitzL,at.al.BreastCancerandAIDS. J Natl Med Assoc2001;93:40-41.

28. BirkelandSA,StormHH,LammLU,BarlowL,BlohmeI,ForsbergB,EklundB,FjeldborgO,FriedbergM,FrodinL.CancerriskafterrenaltransplantationintheNordiccountries,1964–1986.Int J Cancer60(2):183-189,1995.

29. Lake-LewinD,ArkelYS.SpectrumofmalignanciesinHIVpositive individuals. Proc Am Soc Clin Oncol 7: 5, 1987(abstract).

30. MyersAM,McCartyE,AbernathyC,MooreGE.BreastcancerinamanwithHIVinfection. AIDS6:1218-1220,1992.

31. WidrickP,BoguniewiczA,NazeerT,RemickSC.Breastcancerinamanwithhumanimmunodeficiencyvirusinfection.Mayo Clinic Proc72:761-764,1997.

32. HurleyJ,FrancoS,Gomez-FernandezC,ReisI,VelezP,DolinyP,HarringtonJrW,WilkinsonJ,KanhoushR,LeeY.Breastcancerandhumanimmunodeficiencyvirus:areportof20cases.Clin Breast Cancer2:215-220,2001.

33. HarrisJMorrow,NortonL.“Malignanttumorsofthebreast.”DevitaVT,HellmanS,RosenbergSA.Cancer: Principal and Practice of Oncology. 8thed,Philadelphia:LippincottWilliams&Wilkins.

34. Garcia-Tejedor et al. Breast cancer and HIV-The adverseeffectsofchemotherapy: The Breast Journal,Vol13Number6:616-623,2007.

continued to page 40


Shar Donovan Installed as New FMA Alliance President

SharDonovan,spouseofDr.KevinDonovan,andapastpresi-dentoftheDCMSAlliance,(DCMSA)wasinstalledAugust14,2010astheFloridaMedicalAssociationAlliance’s(FMAA)83rdPresident.(see p.8)

ShehasbeenamemberoftheFMAABoardofDirectorssince2002.Dr.&Mrs.DonovanandtheirfourchildrenhavelivedinJacksonville,FLsince1999.DuringtheseyearsMrs.DonovanhasbeenactiveintheDCMSA,servingaspresidentin2003,andtheFMAA;shewaspresident-electlastyear.

AboutbeingFMAAPresident,Mrs.Donovansays,“Iamcom-mitted to working throughout the state, reaching out to eachcountytoenablemorecountyleaderstobecomestateleaders.IlookforwardtosharingtheFMAAlliance’svisionofsupportingthefamilyofmedicinethroughourhealthprojectsandlegislativeadvocacy.”


35. OzerH,ArmitageJO,BennettCL,CrawfordJ,etal.2000updateofrecommendationfortheuseofhematopoieticcolony-stimulatingfactors:evidence-based,clinicalpracticeguidelines.AmericanSocietyofClinicalOncologyGrowthFactorsExpertPanel.J Clin Oncol 18(20):3558-3585,2000.

36. BrennerBG,FriedmanG,MargoleseRG.Therelationshipofclinicalandtherapeuticmodalitytonaturalkillercellactivityinhumanbreastcancer.Cancer 56:1543-1548,1985.

37. Zielinski CC, Muller C, Kubista E, Staffen A, Eibl MM.Effectsofadjuvantchemotherapyonspecificandnon-specificimmunemechanisms.Acta Med Austriaca17:11-14,1990.

38. SewellHF,HalbertCF,RobinsRA,GalvinA,ChanS,BiameyRW.Chemotherapy-induceddifferentialchangesinlymphocytesubsetsandnatural-killer-cellfunctioninpatientswithadvancedbreastcancer.IntJCancer55:735-738,1993.

39. BeitschP,LotzovaE,HortobayiG,PollockR.Naturalimmunityinbreastcancerpatientsduringneoadjuvantchemotherapyandaftersurgery. Surg Oncol3:211-219,1994.

40. SpinaM,NastiG,SimonelliC,BertolaG,RossiC,TirelliU.BreastcancerinawomanwithHIVinfection:acasereport. Ann Oncol5:661-662,1994.

For more information, contact Shelly Hakes, Director of Society Relations at (800) 741-3742, Ext. 3294.

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Find it on the Website

Looking for the Post Test for the CME article in this issue or for other CME courses to complete?

Go to the DCMS website atwww.dcmsonl ine.org. Cl ick“NEFM”,“CurrentIssue”,andthen“Table of Contents”. The currentCME article is listed there (witha PostTest link) OR click “CMEArticles” under “NEFM” and seea list of all the CME articles stillavailableforcredit.

See the digital version of the journal! (followdirectionsabove)

continued from page 38


September is Women in Medicine MonthIn honor of Women in Medicine month, the DCMS is pleased to highlight the legacies of a few of the female physicians

who have impacted our medical community.Patricia Cowdery, MD was instrumental in growing the public health outreach clinics while she served as Duval County Health Unit Director in the 1960’s. Dr. Cowdery also served as Director of the Department of Health, Welfare, and Bio-environmental Services from 1972 to 1988.

Gladys Soler, MD served as Director of the Pediatric Clinic at University Medical Center from 1964 until her retirement in 1992. In this role, she was “The Pediatri-cian” to the indigent children of Jacksonville for over a

quarter century. She also played a major role in teaching general pediatrics to residents and students.

Doris Carson, MD practiced obstetrics and gynecology for almost 40 years, including a period as Pres-ident of the Medical Staff at Baptist Medical Center, the first woman to hold that position. She was the

founder of Planned Parenthood of Northeast Florida and worked with many organizations dealing with adolescent health issues.

Kay Gilmour, MD was the first female President of the DCMS in 1992. She was a private practice cardiolo-gist, with a special interest in Emergency Preparedness, especially for those with special needs in the event of a natural disaster or community wide emergency.

The impact of these physicians (and many others) on the DCMS and surrounding area will be forgotten and lost unless the DCMS updates its published history. So 157 years of medicine is being chronicled in a coffee table book. Two thirds of the book will include significant events that left a lasting impression on our medical community. The remainder of the book will feature physician and practice histories and profiles, purchased by physicians, families, and groups who want to chronicle their legacy in Jacksonville’s medical history.

Do you have a legacy to share with our

medical community?

Patricia Cowdery, MD Gladys Soler, MD

Doris Carson, MD Kay Gilmour, MD

Contact Mr. John Compton, Publisher

at 904-355-6561 x110 [email protected]


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DCMS Membership Applications

Thesephysicians’applicationsformember-ship in the Duval County Medical Societyarenowbeingprocessed.AnyinformationoropinionsyoumayhaveconcerningtheeligibilityoftheapplicantslistedheremaybedirectedtoAshleyBoothNorse,MD,DCMSMembershipCommitteeChair (904-244-4106orBarbaraBraddock, Membership Director (904-355-6561x107).

Michael J. Boyle, MDSurgery/SurgicalOncology21stCenturyOncology7551BaymeadowsRd.Medical Degree: National University ofIrelandResidency: IndianaUniversitySchoolofMedicineFellowship:UniversityofMiamiCollegeofMedicine/JacksonNominated by: Scot Ackerman, MD;RobertJoyce,MD;AlanMarks,MD

Kevin M. Comar, MDGastroenterologyBorland-GrooverClinicPA14546St.AugustineRd.#101MedicalDegree:NortheasternOhioUni-versitiesCollegeofMedicineResidency/Fellowship:VirginiaCommon-wealthUniversityMedicalSchoolNominatedby:MarieReid,MD;DanielKohm,MD;BradfordJoseph,MD

Michael L. Freeman, MDReproductiveEndocrinology/InfertilityFloridaInstituteforReproductiveMedicine836PrudentialDr.#902Medical Degree: University of FloridaCollegeofMedicineResidency:BayfrontMedicalCenterFellowship: Detroit Medical Center &WayneStateUniversityNominatedby:KevinWinslow,MD;Ken-nethSekine,MD;ScottSegel,MD

Jennifer Anne Glassman, MDFamilyMedicineFamilyCarePartners6484Ft.CarolineRd.MedicalDegree:UniversityofConnecticutSchoolofMedicineResidency:St.AnthonyFamilyMedicineResidencyNominatedby:JuliusGorospe,MD;Wil-liamCarriere,MD;DuaneBork,MD

Gary A. Glicksteen, MDInternalMedicineInternalMedicalGroup8614BaymeadowsWay#100MedicalDegree:UniversityofCincinnatiCollegeofMedicineResidency:RiversideMethodistHospitalNominatedby:RichardGlock,MD;JosephStepp,MD;RichardGrochmal,MD

Kevin M. Kaplan, MDSportsMedicine/AdvancedArthroscopyJacksonvilleOrthopaedicInstitute1325SanMarcoBlvd.#200Medical Degree: New York UniversityMedicalSchoolResidency:NewYorkUniversityHospitalforJointDiseasesFellowship: Kerlan Jobe OrthopaedicClinicNominatedby:SteveLucie,MD;CarlosTandron,MD;WilliamPujadas,MD

Gregory M. Lewis, MD

Ophthalmology(Retina)RetinaAssociatesPA2ShircliffWay#715MedicalDegree:UniversityofTennesseeSchoolofMedicineResidency:MedicalCollegeofVirginiaFellowship:UniversityofAlabamaSchoolofMedicineNominatedby:FredLambrou,Jr.,MD;WalterGilbert,Jr.,MD;JanetBetchkal,MD

Frank W. McDonald, MDOphthalmology/CorneaLevensonEyeAssociates,Inc.751OakSt.#200Medical Degree: University of AlabamaSchoolofMedicineResidency:UniversityofMississippiMedi-calCenterFellowship:Cornea&RefractiveSurgeryNominated:JeffreyLevenson,MD;RonaldSingal,MD;SheldonSingal,MD

Elizabeth Anne Moran, MDPediatricOrthopaedicsNemoursChildren’sClinic807Children’sWayMedicalDegree:BostonUniversitySchoolofMedicineResidency:NationalNavalMedicalCenterBethesdaFellowship:NemoursChildren’sClinicNominated by: John Mazur, MD; EricLoveless,MD;KevinNeal,MD

Florence Marie-Louise O’Connell, MDDermatologyJacksonvilleDermatologyAssociatesPL8075GateParkwayW.#201Medical Degree: University of FloridaCollegeofMedicineResidency:UniversityofFloridaCollegeofMedicineNominated by: Tricia Andrews, MD;AshleyBoothNorse,MDBrad Douglas Talley, MDDiagnosticRadiologyDrs.MoriBean&BrooksPA3599UniversityBlvd.S.Bldg.300MedicalDegree:DukeUniversitySchoolofMedicineResidency: Harvard Medical School/

Brigham&Women’sHospitalFellowship:UniversityofFloridaCollegeofMedicineNominatedby:BrettGratz,MD;DennisWulfeck,MD;JohnMcKenzie,MD

RESIDENTS/FELLOWSMayo Clinic Jacksonville

Abdominal Transplant SurgeryCynthiaL.Leaphart,MD

AnesthesiologyPereneV.Patel,MD

DermatologyTandyS.Repass,MD

EndocrinologyAnaMariaChindris,MD

Family MedicineSaraFilmalter,MDAmitJ.Grover,MDJoshuaM.Henry,MDHeidiHepp,MDAunnaPourang,MD

Internal MedicineChristopherAustin,MDJenniferCrozier,MDJimmyMoss,MDWilliamPalmer,MDRyanPeck,MDPatressAnnPersons,MDGregoryL.Repass,MDPhilipTran,MD

NeurologyRebeccaHurst,MDGlenT.Robinson,MD

NeurosurgeryWilsonP.Daugherty,MD

Palliative CareAlvaRoche’-Green,MD

Radiation OncologyRichardLee,MD

RadiologyMadhuraDesai,MDJohnFeldman,MDJamieGiesbrandt,MDKirkGiesbrandt,MDAndrewGinzel,MDJonathanMalone,MDMatthewMorris,MD

TRANSITIONAL YEARKristinM.Eller,MD(Neurology)SheenaGurwara,MDYunSunLee,MDJohnathanR.Renew,MD(Anesthesiology)MelissaA.Saad,MD


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JSMP 2010 Athletic Screenings

The Jacksonville Sports Medicine Program’s (JSMP) 2010 athletic screenings were conducted August 7 for high school athletes and August 14 for middle school athletes (Boys at Nemours Children’s Clinic and girls at Wolfson Children’s Hos-pital). At least 1,000 student athletes were given free pre-participation athletic screenings by nearly 500 volunteer health professionals. (Physicians, PAs, and allied health professionals) The physician and PA volunteers were coordinated through the Duval County Medical Society. The screenings are not intended to replace annual physical exams by pediatricians and primary care physicians, so students are referred to individual physicians for follow-up care.

Pictured: (Top L to R) DCMS members Dr. Ruple Galani and Dr. George Arm-strong, Jr.; Mary McCormack, Nemours’ Volunteer Coordinator; and Robert Sefcik, JSMP Executive Director; DCMS member Dr. Kevin Kaplan with a student athlete. (Left, middle) Athletes line up for their screenings; (Left, bottom, L to R) Dr. Armstrong, Dr. Irene Malesic and Jim Mackie, health athletic trainer for Trinity Christian High School.


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Duval County Medical Society Foundation555 Bishopgate LaneJacksonville, FL 32204

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Documents

Northeast Florida Medicine - Fall 2010 - Infectious Diseases