Influence of Pediatric Vaccines on Social Behavior in the Infant Rhesus Monkey
Britni
1Washington
1
Curtis ,
Kelly
1
Morrisroe ,
Vernon
1
Yutuc ,
Clayton
1
Ferrier ,
Gene
1
Sackett ,
Laura
2
Hewitson
National Primate Research Center, Center for Human Development & Disability, Seattle, WA; 2 Johnson Center for Child Health & Development, Austin, TX
Abstract
Pediatric vaccines have been controversial due to presumed
negative effects on development, particularly impaired social
interaction and communication, hyperactivity, and repetitive
stereotyped behaviors that are characteristic of autism spectrum
disorder (ASD) . Some reports suggest that exposure to ethyl
mercury (EtHg) in the form of thimerosal in pediatric vaccines may
play a causative role in such negative effects (Austin et al., 2008).
Nursery raised male infant rhesus macaques (n=79) were assigned
at birth to one of six vaccine study groups. Subjects began
socializing in a playroom at approximately 25 days of age and were
socialized 5 days per week in unchanging 4-monkey play groups
until 11-12 months of age. Playroom behavior data were collected
by observers using a computer system measuring the duration and
frequency of all nonsocial and social activities. Data were analyzed
using repeated measure ANOVAs. No significant overall group
differences in nonsocial or social behavior were found when
comparing the vaccine groups to saline controls. The data provide
no evidence of abnormal social behavior in rhesus macaques
exposed to low-dose thimerosal or other vaccine combinations,
contrary to the proposed negative affects of vaccines on the social
behavior of developing children.
Table 1. Experimental study groups based upon the vaccines
administered, presence or absence of thimerosal or MMR (mumpsmeasles-rubella), vs. saline placebo.
Group
Group 1
Code
Control
N
16
Vaccines administered
None, all saline placebos
Group 2
TCV only
12
Thimerosal only
Group 3
MMR
15
MMR only
Group 4
Group 5
Group 6
1990s - Primate
1990’s - Pediatric
2008
Code
Behavior
0
Passive
1
2
3
4
Our goal was to look for potential behavioral effects of a variety
of vaccine regimens in a primate model using infant male rhesus
macaques. We were interested to see if groups of animals
exposed to thimerosal containing vaccines showed any difference
in behaviors from animals on placebo or non-thimerosal vaccines.
In particular we were looking for an effect between groups in the
negative behaviors associated with autism spectrum disorders.
5
6
7
8
Materials & Methods
Data were collected from 20-25 days through 12 months of age
by experienced testers observing focal monkey behaviors in a
playroom. The five minute observations on each play group
member were made 3 times per week during weekday 30-45
minute playroom sessions. The 4 monkeys in each unchanging
play group were from the same vaccine condition. A digital code
recorded the duration, frequency, and sequence of the focal
animal’s social and nonsocial behaviors.
12
12
1990’s vaccines on primate schedule
1990’s vaccines on human pediatric schedule
Vaccine regimen recommended in 2008
Table 2. Focal monkey behavior codes scored on a laptop computer
during playroom social behavior sessions. Behaviors can be either
interactive with other monkeys or individual nonsocial activity.
Description
No intense interaction with other monkeys, self, or objects. Can include a
slow visual scanning component, social contact such as huddling or proximity
within one foot, and occurs without locomotion.
Explore
Visual and/or tactual inspection of monkeys, self, or objects, with or without
locomotion.
Withdraw Retreat from an animal or object creating increased distance by locomotion,
with no fear behaviors.
FearFear display involving submissive posture, retraction of lips cooing,
Disturbance screeching, convulsive jerking, 3 successive hoots, with or without
withdrawal or locomotion.
RockStrong clasping-grasping of another monkey without play behavior, or selfHuddleclasping with arms, legs, hands, or feet, without locomotion and no active
Selfclasp
inspection of own or other’s body.
Stereotypy Repetitive body movements, with or without locomotion, requiring three or
more consecutive repetitive movements.
Play
Behaviors with greater physical intensity than explore, involving “ears backmouth puckering” expression, open mouth without teeth exposure or ears
back, chasing, wrestling, bouncing, running or jumping, rolling, biting without
injury, or “tug-of-war” with an object.
Sex
Presenting rear area, inspection of genitalia, masturbation, with thrusting
toward a monkey or tester, mounting and thrusting a monkey or object.
Aggression “Stiff” stance, piloerection, open-mouth threat, back, rolling and hitting with
or without injury.
Materials & Methods
Introduction
12
Results
Table 3: Overall mean duration and frequency of all non-social or
social behaviors. Overall means (N=790) and 95% Confidence Intervals
(bootstrapped from 1000 samples).
FOCAL
CATEGORY
NONSOCIAL
Duration
BEHAVIORS
Frequency
SOCIAL
Duration
BEHAVIORS
Frequency
Passive
0.56
0.30-0.86
194.1
192.1-195.9
0
0.03
0.02-004
30.4
30.0-30.9
0
2.6
2.3-2.8
1.3
1.2-1.4
0.04
0.02-0.05
0.44
0.34-0.55
0.60
.16-1.15
0
0.6
0.55-0.64
0.46
0.42-0.49
0.014
0.019-0.02
011
0.09-0.13
0.02
0.01-0.04
0
17.0
16.3-17.8
1.6
1.3-1.8
0.04
0.02-0.05
5.2
5.1-5.4
0.28
0.25-0.32
0.01
0.007-0.016
Mean
CI
Explore
Mean
CI
FearMean
Withdrawal
CI
Disturbed
Mean
CI
Rock-Huddle-Self Mean
Clasp
CI
Stereotypy
Mean
CI
Play
Mean
CI
Sex
Mean
CI
Aggress-Threat
Mean
CI
6.0
4.8-7.3
0.13
0.03-0.26
0.001
0-0.004
13.4
12.9-13.9
0.0001
00-.001
0.0001
0-0.001
1.0
0.9-1.2
0.01
0-0.001
0.0002
00-.001
10.5
10.2-10.8
0.0001
0-0.0004
0.001
0-0.0003
Figure 1: Duration (top graphs) and frequency (bottom graphs) of observed nonsocial positive (left) and social positive (right) behaviors between two and eleven
months of age for each study group. These data suggest that the animals in the
vaccinated groups did not behave significantly differently than control animals.
Table 4: Repeated measure Analyses of Variance: Group is an
uncorrelated variable, 30-day month and Group X Month are
correlated variables.
* Uses Greenhouse-Geisser Sphericity correction to df
** Composite of categories 2, 3, 4, and 5 (see table 3)
*** Composite of categories 6, 7, and 8
Nonsocial Behavior
Passive
Explore
Negative**
Positive***
Month
df=9/657
F
P*
2.63
0.005
12.64
<0.001
32.27
<0.001
44.06
<0.001
Group
df=5/73
F
P
1.69
0.15
1.79
0.13
1.34
0.26
2.01
0.09
Mn X Gr
df=45/657
F
P*
1.28
0.11
1.56
0.06
1.01
0.44
3.58
<0.001
Social Behavior
Passive
Explore
Negative**
Positive***
Month
df=9/657
F
P*
5.94
<0.001
20.07
<0.001
1.87
0.16
5.36
<0.001
Group
df=5/73
F
P
1.02
0.41
1.13
0.35
0.87
0.50
1.35
0.25
Mn X Gr
df=45/657
F
P*
1.24
0.21
0.94
0.54
1.56
0.12
1.63
0.02
Conclusions
No significant differences were found between vaccine and control
groups in either social or non-social behavior. Negative behaviors of
Fear, Withdraw, Stereotypy, and Aggression were rarely exhibited,
such that we did not have adequate numbers in those behaviors to
make any comparisons in either social or non-social categories.
There was an interesting spike in group 4 non-social positive
behavior between 8 & 10 months, and in groups 4 & 5 in social
positive behavior at month 10 but by month 12, all groups were
showing similar behavior trends.
Acknowledgements
We would like to thank the staff of the WaNPRC IPRL. We are very
grateful for funding from the following sources:
Christopher Johnson
The 1964 Robert Wood Johnson Charitable Trust
The Ted Lindsay Foundation
SafeMinds
National Autism Association
NIH grant RR00166
CHDD grant HD02274