obesity and infectious diseases: a global health and national security issue

8/20/2019 Obesity and Infectious Diseases: A Global Health and National Security Issue

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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

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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]

obesity and infectious diseases: a global health and national security issue

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