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Gregory A. Poland, MD, MACP, FIDSA
Mary Lowell Leary Emeritus Professor ofMedicine
Distinguised Mayo In!estigator
Director, Mayo "accine #esearc Grou$
Mayo Clinic #ocester, M%
Editor&in&Cief, "ACCI%E
Obesity and
InfectiousDiseases: A
GlobalHealth and
SecurityIssue
Obesity andInfectiousDiseases: A
GlobalHealth and
SecurityIssue
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The views expressed today are myown and do not necessarily reflect
the opinions of any of the
organizations I am affiliated withincluding the Mayo Clinic, the
Department of Defense, the Defense
Health Board, the dvisoryCommittee on Immunization
!ractices "CDC#, or the $ournal
%CCI&'(
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Levels of Thinking
•At level 1 this talk is about obesity
• At level ! this talk is about ho"obesity a#ects i$$une res%onsesto vaccines and infectious diseases
• At level & this talk is aboutDA'G() * obese %ersons are indanger %ublic health is in dangerand the national security is indanger +
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,y Starting -oints
• Obesity is a signi.cant cause ofincreased severity of infectiousdiseases and their co$%lications *
%articularly in the area of vaccine/%reventable diseases
• Obese %ersons generally res%ondless "ell to vaccines * $aking the$$ore susce%tible to vaccine/%reventable diseases co$%ared tonor$al/"eight individuals
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The 'e" )eality
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Among te many
world ills andtreats'wy
sould o(esitymatter to us)
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%ew #e$ort Finds *(esity Costs +ill
uadru$le *!er te %e-t Decade
+itout Action)The *uture Cost of +esity- &ational and.tate 'stimates of the Impact of +esity on
Direct Health Care 'xpenses,) is the first toestimate oesity prevalence and costs at thestate and national level /0 years from now(The new data shows that if current trends
continue, 12 percent of 3(.( adults will eoese and oesity spending will 4uadruple to5211 illion y 60/7(
&ovemer 6008
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Healthcare 0osts of Obesity
• Obesity is one of the biggestdrivers of %reventable chronicdiseases and healthcare costs inthe nited States2
• Currently, estimates for these costs rangefrom $147 billion to nearly $210 billion peryear. (J Health con 2012!"1#21%
• &ncrease' ob absenteeism ($4." billionannually% )J *cc n+ir e' 2007!4#1"17224-
• o/er pro'ucti+ity at /or ($0" per obesepersonyear% )J *cc n+ir e' 2003!0#"-
• *bese a'ults spen' 42 more on 'irecthealthcare costs )31 higher for 5&640-
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(#ects of Obesity
• Increased risk of a variety ofchronic diseases
• Increased $orbidity and $ortality
• Decreased 3uality of healthcare
• Increased disability
• Decreased 3uality of life
• Increased healthcare costs4individual and societal5
• 'ational Security Issues
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Body9Mass Index andMortality among /(1:Million ;hite dults
& 'ngl < Med 60/0=2:2-66//966/8
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Hu$ans and 'utrition
• Hu$ans are %oorly ada%ted to over/nutrition * the hu$an body is si$%lynot designed for a constant calorie/
rich environ$ent• 'utrition and i$$une syste$ function
are critically linked• *+er; an' un'er;nutrition cause 'ysregulation
of the immune system an' impair immuneprotection against pathogens an' +accines
• Obesity leads to a state ofimmunodeciency
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The 6eight of Obesity on
Infectious Diseases• I$%aired i$$une function
• Leads to increased susce%tibility to:
• uen?a
• Co@sacie+irus
• H. pylori
• ncephalomyocar'itis +irus
• *thers
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Infections in Obese Surgical-atients
>ancet Infect Dis 600:= :- 127?1:
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H1'1 S"ine 7lu
• Obesity is a clear/cut risk factor forsevere infection "ith H1'14children and adults5
•Obesity is a clear/cut risk factor foran increased risk of death fro$H1'140lin Infect Dis !81898:1;
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In?uen@a
• Obesity leads to ecess severe%neu$onia and in?uen@a in $ilitary%o%ulations
• In?uen@a and itBs co$%licationssuch as %neu$onia are $orefre3uent and severe in obese%ersons 40lin Infect Dis !81898:1;
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In?uen@a ACH1'1
• Obese %ersons have an increasedrisk of hos%itali@ation due toin?uen@a ACH1'1 co$%lications 4-LoS
One !8189:e
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-ande$ic H1'1
• Hos%itali@ation due to in?uen@aa$ong %ersons F !8 yCo associated"ith:
•
5& 640 (*A 4.%• Death due to in?uen@a infection
a$ong %ersons F !8 yCo associated"ith:
• 5& 6"0 (*A ".1%• 5& 6 40 (*A 7.B%
• Increased hos%itali@ation or deathnot seen in obese children !/1< yCo
!>o. +ne 60/0=@-e8:81
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6hy
• Hy%oventilation and clearance ofsecretions
• 0onco$itant $etabolic
abnor$alities 4diabetes other5• Obesity induces lo"/grade
in?a$$ation "hich can interfere"ith nor$al i$$une res%onses *resulting in defects in T cell$e$ory cell and dendritic cellfunction needed for %rotectivei$$une res%onses
• (#ects of elevated le tin
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-rotective I$$une
)es%onses• De%ends u%on initiation andamplication of %rotective i$$uneres%onses to a %athogen or vaccine
•Innate sensing of foreign antigen
• &ncrease numbers of innate immune cells
• Aelease of chemical signals
• Sti$ulation of ada%tive i$$uneres%onse
• Humoral (antibo'y%
• Cell;me'iate' immunity
•)ecall $e$ory i$$une
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'xperimental Biology and Medicine 60/0= 62@- /1/6?/161(
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'xperimental Biology and Medicine 60/0= 62@- /1/6?/161(
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Obesity and the I$$une
Syste$• Defective cellular i$$une res%onseto in?uen@a virus 4Obesity !81&9!1:!&EE5
• Decreased 0D= T/cell activation and
$ore ra%id fall in %rotectiveantibody levels 4Int J Obes !81!9&>:18E!5
• 0o$%ro$ised dendritic cell nu$berand function 4Int J Obes !81&9&E:1185
• Obesity i$%airs T cell ho$estasisand antiviral function 4-LoS One!81918:e81!8
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6hy
• Dendritic cells are critical togenerating an i$$une res%onse toviral %athogens
• in innate an' a'apti+e immune systems
• Aecogni?e 'anger signals
• =resent +irus to < cells an' initiate < cell tolerance,memory an' polari?ation
• A$ong $orbidly obese adults 4K,IF85
• ecrease' number of circulating Cs (0.3 +s2.4%
• 100 'ecrease in C3" upregulation (marer of <cell response%
• 2;fol' higher pro'uction of &;10
(immunosuppressi+e%Int < +es 60/2=2A-/@/0
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Le%tin
• A bioche$icalCi$$unologic linkbet"een obesity and %oor vaccineres%onse
• Adi%ocyte/derived cytokine andhor$one
• 'egative e#ects on i$$uneres%onses:
• Dpregulation of naE+e C4F cells
• &nhibition of C4F memory cells
•
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The 0entral )ole of Le%tin
Le%tin / the link bet"een obesity anddecreased vaccine i$$une res%onse
• Obesity can lead to le%tin resistance
• Le%tin resistance adversely a#ects thei$$une res%onse in obese %ersonsincluding to in?uen@a virus 4J I$$unol!81891=;:&1!E9 I$$unology !88:!>=5
• 6e have de$onstrated that S'-s inle%tin and le%tin/related genes areassociated "ith variations in le%tin levelsin?uen@a antibody levels K/cell andgran@y$e K/ (lis%ot and T)(0 4ani$$unosenescence $aker5 accine!81&9&!:==1M
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>ancet Infect Dis 600:= :- 127?1:
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accine )es%onses and
Obesity• He%atitis A
• He%atitis K
•In?uen@a 4children5 inconsistentresultsM
• Tetanus
•
)abies
+at A(out *ter "accines)
%accine 60/@=22-1166
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,agnitude of (#ect
•Decrease in %ercent reaching a%rotective level of antibody by as$uch as 18/>8N 4he%atitis Kvaccine5
• Decreased %ercent %rotected andslo"er rate of develo%$ent ofantibodies 4he%atitis A vaccine5
•
8N decrease in tetanus antibodiesin obese children co$%ared tonor$al "eight children 4Autoi$$unity!88>9&
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7lu accine and Obesity
• 'o di#erence in antibody levelsbet"een obese and non/obesechildren E/1& years old "ith !81;
TI4accine !819&;:>5
• Decreased 0D= T/cell activation ande%ression of functional %roteins4gran@y$e K and I7'/g5 "ith a
greater decline in antibody levels inobese adults co$%ared to non/obese adults "ith !88< TI 4Int J Obes!81!9&>:18E!5
• < cell (C3% importance G limit progressionof 'isease, rapi' +iral clearance, lessen
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7our ,echanis$s
•
7at -ads• ee'le length
• Hypopnea
• ymphatic an' 5loo' Circulation
• 0onco$itant 0onditions• iabetes
• *ther
• nderlying Abnor$alities• eptin le+els
• < cell
• en'ritic cell
• Chronic lo/ le+el in>ammation
• *ther
• Genetic )estrictions
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The oldilocsE Dilemma
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Indirect (#ects of Obesity
• H- infection leads to genital"arts ))-- and a variety ofcancers 4labial vaginal cervical
anal etc25• 1EN of fe$ales 1!/1< yCo and &!N
of fe$ales !8/!< yCo are obese
• Obesity "as found to be aninde%endent risk factor for %oorvaccine schedule adherence
• In one study a ;N decreased
co$%letion rate of & doses of H-;in oun obese fe$ales -LOS O'(
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-ractical I$%lications
• Longer needles for inection
• Develo%$ent of vaccines and vaccinedoses s%eci.cally for obese %ersons
• At the %o%ulation level diPcultyachieving herd i$$unity andcontrolCeradication of vaccine/%reventable diseases
• Higher threshold for concern 4due toelevated risks5 of co$%lications ofvaccine/%reventable diseases
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*5I&
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*(esity A %ational Security Issue
60/0 60/6
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/oo fat, incarcerated, mental
ealt issues, can0t meet
education standards
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/e 1attle of te 1ulge
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Infectobesity
• 0ould obesity be an infectiousdisease
• Ani$al $odels de$onstrate
conversion to obesity afterinfections "ith:• Canine 'istemper +irus
• Aous;associate' +irus 7 (a+ian retro+irus%
• 5orna 'isease +irus• Icrapie agents
• I8;1 a+ian a'eno+irus
• Human a'eno+iruses 8'"B an' 8'"7
• 'ur < !ediatr 60/1=/A2-6@ >ancet Inf Dis 600:=:-127
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+esity is a disease of poverty of mindand pocetoo
disease of low food 4uality, high costand poor availaility
disease of race, geography, mentalhealth, and genetics
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Dr2 -olandBs )ules
• Only eat on the days you eercise4$inor ece%tions5
• Grocery sho% fro$ the %eri%hery ofthe store
• (at out less+far less
• (at food * not too $uch * $ostly%lants
• 7orget unk food * it kills
• Avoid H70S high fat high sugarre.ned foods
• 7ollo" the algorith$
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Should I Workout Today?
2es %o
2es you
sould
Go
+or3out
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6hat ,y -atients See$ ToHear
• He "ants to starve $e todeath+
• If it tastes good * s%it itout
• I $ay not live longer if Ifollo" Dr2 -olandBs rules *
but it "ill sure see$longer
• Is this the rabbit diet
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)eality 0heck
• Obese individuals their fa$iliesand their caretakersdis%ro%ortionally su#er
• Society su#ers through loss of%roductivity inability to controlinfectious diseases anddra$atically elevated healthcare
costs over a lifeti$e
• Obese kids beco$e obese adults"ho raise obese kids+a viciouscycle sustained by the culture andco/cons irators+
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Kotto$ Line
12 6e are beco$ing anation of obesei$$unoco$%ro$ised
elderly %ersons
!2 These issues have%rofoundly negative
synergistic e#ects&2 6e donBt have successful
individual health or%ublic health strategiesto deal "ith this+
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Thank/youQ
%oland2gregoryR$ayo2edu
mailto:[email protected]:[email protected]:[email protected]:[email protected]