Obesity

Obesity and
and
Infectious
Infectious
Diseases:
Diseases: A
A
Global
Global
Health
Health and
and
Gregory A. Poland, MD, MACP, FIDSA
Security
Mary Lowell Leary Emeritus Professor
of
Security
Medicine
Distinguished Mayo Investigator Issue
Issue
Director, Mayo Vaccine Research Group
Mayo Clinic Rochester, MN
Editor-in-Chief, VACCINE

The views expressed today are my

own and do not necessarily reflect
the opinions of any of the
organizations I am affiliated with
including the Mayo Clinic, the
Department of Defense, the Defense
Health Board, the Advisory
Committee on Immunization
Practices (CDC), or the journal
VACCINE.

Levels of Thinking
At level 1, this talk is about obesity
At level 2, this talk is about how
obesity affects immune responses
to vaccines and infectious diseases

At level 3, this talk is about

DANGER obese persons are in

danger, public health is in danger,
and the national security is in
danger

My Starting Points
Obesity is a significant cause of

increased severity of infectious

diseases and their complications
particularly in the area of vaccinepreventable diseases

Obese persons generally respond

less well to vaccines making them

more susceptible to vaccinepreventable diseases compared to
normal-weight individuals

The New Reality

Among the many

world ills and
threatswhy
should obesity
matter to us?

New Report Finds Obesity Costs Will

Quadruple Over the Next Decade
Without Action
"The Future Cost of Obesity: National and
State Estimates of the Impact of Obesity on
Direct Health Care Expenses," is the first to
estimate obesity prevalence and costs at the
state and national level 10 years from now.
The new data shows that if current trends
continue, 43 percent of U.S. adults will be
obese and obesity spending will quadruple to
$344 billion by 2018.
November 2009

Healthcare Costs of Obesity

Obesity is one of the biggest

drivers of preventable chronic

diseases and healthcare costs in
the United States.
Currently, estimates for these costs range

from $147 billion to nearly $210 billion per

year. (J Health Econ 2012;31:219)
Increased job absenteeism ($4.3 billion
annually) [J Occ Envir Med 2007;49:1317224]
Lower productivity at work ($503 per obese
person/year) [J Occ Envir Med 2008;50:39]
Obese adults spend 42% more on direct
healthcare costs [81% higher for BMI>40]

Effects of Obesity
Increased risk of a variety of
chronic diseases

Increased morbidity and mortality

Decreased quality of healthcare
Increased disability
Decreased quality of life
Increased healthcare costs
(individual and societal)

National Security Issues

Body-Mass Index and

Mortality among 1.46
Million White Adults
N Engl J Med 2010;
363:2211-2219

Humans and Nutrition

Humans are poorly adapted to over-

nutrition the human body is simply

not designed for a constant calorierich environment

Nutrition and immune system function

are critically linked
Over- and under-nutrition cause dysregulation
of the immune system and impair immune
protection against pathogens and vaccines

Obesity leads to a state of

immunodeficiency

The Weight of Obesity on

Infectious Diseases
Impaired immune function
Leads to increased susceptibility to:

TB
Pneumonia
Influenza
Coxsackievirus
H. pylori
Encephalomyocarditis virus
Others

Infections in Obese Surgical

Patients

Lancet Infect Dis 2006; 6: 43846

H1N1 Swine Flu

Obesity is a clear-cut risk factor for
severe infection with H1N1
(children and adults)

Obesity is a clear-cut risk factor for

an increased risk of death from
H1N1(Clin Infect Dis 2010;50:1498 and PLoS
One 2010:e9694)

Influenza
Obesity leads to excess severe

pneumonia and influenza in military

populations

Influenza and its complications

such as pneumonia are more

frequent and severe in obese
persons (Clin Infect Dis 2010;50:1498 and
PLoS One 2010:e9694)

Obesity is a risk factor for severe

pandemic H1N1 infection and

complications in both children and
adults (Epi and Infect 2015;143:2939)

Influenza A/H1N1
Obese persons have an increased
risk of hospitalization due to
influenza A/H1N1 complications
One 2010;5:e9694)

(PLoS

Obese persons have a higher death

and complication rate following
influenza A infections including
A/H1N1 (Prev Med 2013;56:118; Infl Other
Resp Viruses 2012;6:313; PLoS One
2012;7:e47540)

Pandemic H1N1
Hospitalization due to influenza

among persons > 20 y/o associated

with:
BMI >40 (OR 4.9)

Death due to influenza infection

among persons > 20 y/o associated

with:
BMI >30 (OR 3.1)
BMI > 40 (OR 7.6)

Increased hospitalization or death

not seen PLoS

in obese
children 2-19 y/o
One 2010;5:e9694

Why?
Hypoventilation and clearance of
secretions

Concomitant metabolic

abnormalities (diabetes, other)

Obesity induces low-grade

inflammation which can interfere

with normal immune responses
resulting in defects in T cell,
memory cell, and dendritic cell
function needed for protective
immune responses

Effects of elevated leptin

Protective Immune
Responses

Depends upon initiation and

amplification of protective immune

responses to a pathogen or vaccine

Innate sensing of foreign antigen

Increase numbers of innate immune cells
Release of chemical signals

Stimulation of adaptive immune

response
Humoral (antibody)
Cell-mediated immunity

Recall memory immune

Experimental Biology and Medicine 2010; 235: 14121424.

Experimental Biology and Medicine 2010; 235: 14121424.

Obesity and the Immune

System
Defective cellular immune response
to influenza virus

(Obesity 2013;21:2377)

Decreased CD8 T-cell activation and

more rapid fall in protective
antibody levels (Int J Obes 2012;36:1072)

Compromised dendritic cell number

and function

(Int J Obes 2013;37:1510)

Obesity impairs T cell homestasis

and antiviral function
2015;10:e0120918)

(PLoS One

Why?
Dendritic cells are critical to

generating an immune response to

viral pathogens
Link innate and adaptive immune systems
Recognize danger signals
Present virus to T cells and initiate T cell tolerance,
memory and polarization

Among morbidly obese adults (BMI>50)

Decreased number of circulating DCs (0.8% vs

2.4%)
100% decrease in CD83 upregulation (marker of T
cell response)
2-fold higher production of IL-10
(immunosuppressive)
Int J Obes 2013;37:1510

Leptin
A biochemical/immunologic link

between obesity and poor vaccine

response

Adipocyte-derived cytokine and

hormone

Negative effects on immune

responses:
Upregulation of nave CD4+ cells
Inhibition of CD4+ memory cells
Th1 cell differentiation blocked
Decreased cytokine production

The Central Role of Leptin

Leptin - the link between obesity and
decreased vaccine immune response

Obesity can lead to leptin resistance

Leptin resistance adversely affects the
immune response in obese persons,
including to influenza virus (J Immunol
2010;184:3127; Immunology 2009;126:268)

We have demonstrated that SNPs in

leptin and leptin-related genes are

associated with variations in leptin levels,
influenza antibody levels, B-cell and
granzyme B- Elispot, and TREC (an
immunosenescence maker) [Vaccine
2013;32:881]

Lancet Infect Dis 2006; 6: 43846

Vaccine Responses and

Obesity
Hepatitis A
Hepatitis B
Influenza (children) [inconsistent
results]

Tetanus
Rabies
What About Other Vaccines?
Vaccine 2015;33:4422

Magnitude of Effect
Decrease in percent reaching a

protective level of antibody by as

much as 10-60% (hepatitis B
vaccine)

Decreased percent protected and

slower rate of development of
antibodies (hepatitis A vaccine)

50% decrease in tetanus antibodies

in obese children compared to
normal weight children (Autoimmunity
2006;39:137)

20% decrease in 4-fold rise of

Vaccine
2015;33:4422
influenza H3N2
antibodies
in obese

Flu Vaccine and Obesity

No difference in antibody levels

between obese and non-obese

children 7-13 years old with 2014
TIV (Vaccine 2015;34:56)

Decreased CD8 T-cell activation and

expression of functional proteins

(granzyme B and IFN-g), with a
greater decline in antibody levels in
obese adults compared to nonobese adults with 2009 TIV (Int J Obes
2012;36:1072)

T cell (CD8) importance limit progression

of disease, rapid viral clearance, lessen

Four Mechanisms
Fat Pads
Needle length
Hypopnea
Lymphatic and Blood Circulation

Concomitant Conditions
Diabetes
Other

Underlying Abnormalities

Leptin levels
T cell
Dendritic cell
Chronic low level inflammation
Other

Genetic Restrictions

The Goldilocks Dilemma

Indirect Effects of Obesity

HPV infection leads to genital

warts, RRPP, and a variety of

cancers (labial, vaginal, cervical,
anal, etc.)

17% of females 12-19 y/o, and 32%

of females 20-29 y/o are obese

Obesity was found to be an

independent risk factor for poor

vaccine schedule adherence

In one study a 45% decreased

completion rate of 3 doses of HPV4

in young obese females [PLOS ONE

Practical Implications
Longer needles for injection
Development of vaccines and vaccine
doses specifically for obese persons

At the population level, difficulty

achieving herd immunity and
control/eradication of vaccinepreventable diseases

Higher threshold for concern (due to

elevated risks) of complications of
vaccine-preventable diseases

OBESITY
A National Security Issue

Obesity A National Security Issue

2010

2012

Too fat, incarcerated, mental

health issues, cant meet
education standards

The Battle of the Bulge

Infectobesity
Could obesity be an infectious
disease?

Animal models demonstrate

conversion to obesity after

infections with:
Canine distemper virus
Rous-associated virus 7 (avian retrovirus)
Borna disease virus
Scrapie agents
SMAM-1 avian adenovirus
Human adenoviruses Ad36 and Ad37

Eur J Pediatr 2014;173:25

Lancet Inf Dis 2006;6:438

Obesity is a disease of poverty of mind

and pocketbook
A disease of low food quality, high cost
and poor availability
A disease of race, geography, mental
health, and genetics

Dr. Polands Rules

Only eat on the days you exercise
(minor exceptions)

Grocery shop from the periphery of

the store

Eat out lessfar less

Eat food not too much mostly
plants

Forget junk food it kills

Avoid HFCS, high fat, high sugar,
refined foods

Follow the algorithm

Should I Workout Today?

Yes
Go
Workout

No
Yes you
should

What My Patients Seem To

Hear
He wants to starve me to
death

If it tastes good spit it

out

I may not live longer if I

follow Dr. Polands rules

but it will sure seem
longer

Is this the rabbit diet?

Reality Check
Obese individuals, their families,
and their caretakers
disproportionally suffer

Society suffers through loss of

productivity, inability to control

infectious diseases, and
dramatically elevated healthcare
costs over a lifetime

Obese kids become obese adults

who raise obese kidsa vicious

cycle sustained by the culture and
co-conspirators

Bottom Line
1. We are becoming a
nation of obese,
immunocompromised,
elderly persons
2. These issues have
profoundly negative
synergistic effects
3. We dont have successful
individual health or
public health strategies
to deal with this

Thank-you!
poland.gregor
y@mayo.edu

Truth holding a mirror and a serpent