Turtles Book - English References
Turtles Book - English References
Turtles
All
The
Way
Down
Vaccine Science and Myth
*
References
Contents
1-20
1 Page Name:
Vaccine Product Approval Process
Website: Archive:
FDA website http://archive.is/eyQNd
http://www.fda.gov/biologicsbloodvaccines/developmentap
provalprocess/biologicslicenseapplicationsblaprocess/ucm1
33096.htm
Page Name:
Inside Clinical Trials: Testing Medical Products in People
Website: Archive:
FDA website https://web.archive.org/web/2018082517511
http://www.fda.gov/Drugs/ResourcesForYo 3/https://www.fda.gov/Drugs/ResourcesFor
u/Consumers/ucm143531.htm You/Consumers/ucm143531.htm
2 Document Name:
ICH Harmonised Tripartite Guideline
Choice Of Control Group And Related Issues In Clinical Trials E10
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Ste
p4/E10_Guideline.pdf
Author/Year: Archive:
ICH Expert Working https://drive.google.com/open?id=1IrAW9UYSFvIA8npBLKsA
Group, 2008 UZxft53cmhml
P 28:
It should be appreciated, however, that subjects receiving a new treatment are not receiving
standard therapy (just as a placebo control group is not) and may be receiving an ineffective
or harmful drug.
Archive:
http://archive.is/RfO2H
For instance:
(Reuters) - An influential U.S. medical advisory panel on Wednesday recommended that
people 65 and older be given Pfizer Inc’s blockbuster Prevnar 13 vaccine to protect against
pneumococcal bacteria that can cause pneumonia and other infections.
[…]
Prevnar 13 and an older version of the vaccine known as Prevnar 7 have combined annual
sales of almost $4.5 billion, making them Pfizer’s second-biggest franchise. Prevnar 13 is
approved for children 6 weeks through 17 years of age, and for adults 50 and older.
6 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
6 Document Name:
ICH Harmonised Tripartite Guideline
Choice Of Control Group And Related Issues In Clinical Trials E10
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Ste
p4/E10_Guideline.pdf
Author/Year: Archive:
ICH Expert Working https://drive.google.com/open?id=1IrAW9UYSFvIA8npBLKsA
Group, 2000 UZxft53cmhml
P 19:
When a new treatment is tested for a condition for which no effective treatment is known,
there is usually no ethical problem with a study comparing the new treatment to placebo.
Document Name:
Expert consultation on the use of placebos in vaccine trials
http://apps.who.int/iris/bitstream/handle/10665/94056/9789241506250_eng.pdf
Author/Year: Archive:
WHO, 2013 https://drive.google.com/open?id=1yLHGu4pO0K2xUZmNsE4
RyxrbUtkq382y
P 9:
A common model for the evaluation and deployment of a new vaccine, against a disease for
which there is no existing vaccine, is that it is first tested in a placebo-controlled trial.
P 12:
As a general rule, research subjects in the control group of a trial of a diagnostic,
therapeutic, or preventive intervention should receive an established effective intervention.
In some circumstances it may be ethically acceptable to use an alternative comparator, such
as placebo or ‘‘no treatment’’.
7 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
7 Document Name:
Expert consultation on the use of placebos in vaccine trials
http://apps.who.int/iris/bitstream/handle/10665/94056/9789241506250_eng.pdf
Author/Year: Archive:
WHO, 2013 https://drive.google.com/open?id=1yLHGu4pO0K2xUZmNsE4Ry
xrbUtkq382y
P 12-13:
…there is uniformity on the use of placebos, i.e. that if a proven effective intervention
exists, the trial intervention should generally be tested against it. Failure to do so deprives
participants in the “control” arm of an intervention that is likely to benefit them.
8 Document Name:
ICH Harmonised Tripartite Guideline
Choice Of Control Group And Related Issues In Clinical Trials E10
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Ste
p4/E10_Guideline.pdf
Author/Year: Archive:
ICH Expert Working https://drive.google.com/open?id=1IrAW9UYSFvIA8npBLKsAUZ
Group, 2000 xft53cmhml
P 18:
A useful approach to the assessment of assay sensitivity in active control trials and in
placebo-controlled trials is the three-arm trial, including both placebo and a known active
treatment, a trial design with several advantages.
Article Name: PMID:
Alternatives to Placebo-Controlled Trials 17469680
https://www.cambridge.org/core/services/aop-
cambridge-
core/content/view/28A722D8EF2C2FCABB3A1 Archive:
AC2477DFBB8/S0317167100005540a.pdf/altern https://drive.google.com/open?id=1uSP
dSiRKhZex8QwuHiOmLjgxD3_Fi7vE
atives_to_placebocontrolled_trials.pdf
Lead Author/Year: Journal:
David L. Streiner, 2007 The Canadian Journal Of Neurological
Sciences
P 5:
My recommendation would be that, when an existing therapy exists, and if certain
conditions apply:
* Studies should consist of three arms: the new drug, the existing drug, and a placebo
group..
9 Document Name:
ICH Harmonised Tripartite Guideline
Choice Of Control Group And Related Issues In Clinical Trials E10
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Ste
p4/E10_Guideline.pdf
8 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
Author/Year: Archive:
ICH Expert Working Group, 2000 https://drive.google.com/open?id=1IrAW9UYSFvIA
8npBLKsAUZxft53cmhml
Section 2.5.2:
It is always difficult, and in many cases impossible, to establish comparability of the
treatment and control groups and thus to fulfill the major purpose of a control group (see
section 1.2). The groups can be dissimilar with respect to a wide range of factors, other than
use of the study treatment, that could affect outcome, including demographic characteristics,
diagnostic criteria, stage or severity of disease, concomitant treatments, and observational
conditions (such as methods of assessing outcome, investigator expectations). Such
dissimilarities can include important but unrecognized prognostic factors that have not been
measured. Blinding and randomization are not available to minimize bias when external
controls are used.
[…]
Control groups in a randomized study need to meet certain criteria to be entered into the
study, criteria that are generally more stringent and identify a less sick population than is
typical of external control groups. An external control group is often identified
retrospectively, leading to potential bias in its selection.
10 Document Name:
HAVRIX, Package Insert
https://drive.google.com/open?id=1XGppC-tPGSWvEZNGK8kRY15nGz76lxSA
Section 5.6.1:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical
trials of another vaccine, and may not reflect the rates observed in practice.
11 Document Name:
Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations
http://pediatrics.aappublications.org/content/pediatrics/60/1/91.full.pdf
Author/Year: Archive:
AAP, 1977 https://drive.google.com/open?id=1sjvo_5OLgRv8ZCkh7lic-
1Kih1gV1zEF
P 1-2:
The publication of these general guidelines and their implications for future drug
development led the
FDA to request that the Academy’s Committee on Drugs advise it about standards of ethical
research which could be recommended to assure that children, and society in general, are
served appropriately by studies carried out in pediatric populations without undue hazard or
discomfort.
[…]
The Committee believes that it is unethical to adhere to a system which forces physicians to
use therapeutic agents in an uncontrolled experimental situation virtually every time they
prescribe for children. Furthermore, it is not only ethical but also imperative that new drugs
to be used in children be studied in children under controlled circumstances so the benefits
of therapeutic advances will become available to all who may need them.
12 Document Name:
Ethical Considerations in Conducting Pediatric Research
Book chapter from:
Pediatric Clinical Pharmacology
https://www.springer.com/gp/book/9783642201943
Lead Author/Year:
Michelle Roth-Cline, 2011
9 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
P 221:
A fundamental pillar of pediatric research is the ethical principle of “scientific necessity.”
This principle holds that children should not be enrolled in a clinical investigation unless
necessary to achieve an important scientific and/or public health objective concerning the
health and welfare of children. An “important scientific question” may be one that generates
information that is necessary and timely for establishing the appropriate pediatric use of
investigational therapeutics. A corollary is that children should not be enrolled in studies
that are duplicative or unlikely to yield important knowledge applicable to children about the
product or condition under investigation.
13 Document Name:
Ethical Considerations in Conducting Pediatric Research
Book chapter from:
Pediatric Clinical Pharmacology
https://www.springer.com/gp/book/9783642201943
Lead Author/Year:
Michelle Roth-Cline, 2011
P 222,224:
First, the risks to which children would be exposed must be low if there is no prospect of
direct therapeutic benefit (PDB) to the enrolled children. Second, children should not be
placed at a disadvantage by being enrolled in a clinical trial, either through exposure to
excessive risks or by failing to get necessary health care. Consequently, the data necessary
to initiate a pediatric investigation must demonstrate either an acceptably low risk of the
experimental intervention or a sufficient PDB to justify the risks of the intervention.
[…]
Investigations involving children that pose more than low risk cannot be justified by the
importance of anticipated knowledge. In pediatric studies, the allowable risk exposure for an
intervention or procedure not offering a PDB must be restricted to low risk.
Doucment Name:
MMR II Clinical Trials – DFA FOIA
https://drive.google.com/open?id=1GKahQSNG8LvCAnEG7SGNyYPUEiSJwfd8
An example from a form filled by investigators in vaccine trial in the late 1970s.
P 103:
B. Describe the benefit to the subject or advancment of knowledge that will balance the risk
involved.
C. Indicate measures proposed to minimize risk […]
14 Document Name:
Ethical Considerations in Conducting Pediatric Research
Book chapter from:
Pediatric Clinical Pharmacology
https://www.springer.com/gp/book/9783642201943
Lead Author/Year:
Michelle Roth-Cline, 2011
10 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
P 226-228:
FDA regulations also include a classification of “minor increase over minimal risk” (21 CFR
50.53, 2011). An intervention or procedure approved under this category must also involve
“experiences to subjects that are reasonably commensurate with those inherent in their
actual or expected… situations” and be “likely to yield generalizable knowledge about the
subjects’ disorder or condition that is of vital importance for the understanding or
amelioration of the subjects’ disorder or condition.”
[…]
In assessing whether an intervention or procedure presents no more than a minor increase
over minimal risk, there must be sufficient data that any research-related pain, discomfort or
stress will not be severe and that any potential harms will be transient and reversible (Fisher
et al. 2007). Even if the average risk associated with an intervention or procedure is thought
to be low, if the risk estimate is unknown, reflects a large degree of variability, or has not
been adequately characterized, then the risks of an intervention or procedure cannot be
considered only a minor increase over minimal risk.
15 Document Name:
VAQTA Package Insert
https://drive.google.com/open?id=1LuPKwCve8Pguo-GJOzbOm1b9Hgu0Zn15
P 7:
In a double-blind, placebo-controlled efficacy trial (i.e. The Monroe Efficacy Study), 1037
healthy children and adolescents 2 through 16 years of age.were randomized to receive a
primary dose of 25U of VAQTA and a booster dose of VAQTA 6, 12, or 18 months later, or
placebo (alum diluent)… There were no significant differences in the rates of any adverse
events or adverse reactions between vaccine and placebo recipients after Dose 1.
16 Document Name:
DAPTACEL Clinical Review
https://drive.google.com/open?id=1CFrePXwN-q5ywCnuflnwLjUwScsLPvBU
P 61, Table 50:
Rates for all hospitalizations, hospitalizations for acute otitis media, suspected
bacterial respiratory infection, lower respiratory infection – no antibiotics, upper
respiratory infection – no antibiotics, viral infection, gastroenteritis, urinary tract infection,
seizures, trauma/intoxication, surgery were similar among vaccine groups.
Streiner notes this problem in the context of measuring trial efficacy, but it's clear
the same problem exists with the safety aspect, p 5:
However, there are many methodological problems when the comparison group consists of
an active treatment: […] (b) when the two arms yield comparable results, there is no
guarantee that either one was effective in that particular trial;
18 Document Name:
Recommended Child and Adolescent Immunization Schedule
for ages 18 years or younger
https://drive.google.com/open?id=1Bcb5L30zbAB4FGtzItrzUs_g1yJCy4lt
Author/Year:
CDC, 2020
19 Document Name:
Pediarix Package Insert
https://drive.google.com/open?id=1rY3q-bXZDxIErcWTvm2th3hGm4zBRPAk
P 5, 6, 8
20 Document Name:
Kinrix Package Insert
https://drive.google.com/open?id=1Ulz5HRP4ROFm49kQniiuqQ2vsRIFNH61
P4
21-40
21 Document Name:
INFANRIX Package Insert
https://drive.google.com/open?id=1fUUkPH8gHd5fiBFhyZhGBl56fwLtmcCf
P 10:
Selected adverse events reported from a double-blind, randomized Italian clinical efficacy
trial involving 4,696 children administered INFANRIX or 4,678 children administered
whole-cell DTP vaccine (DTwP) (manufactured by Connaught Laboratories, Inc.) as a 3-
dose primary series are shown in Table 4.
[…]
In a German safety study that enrolled 22,505 infants (66,867 doses of INFANRIX
administered as a 3-dose primary series at 3, 4, and 5 months of age), all subjects were
monitored for unsolicited adverse events that occurred within 28 days following vaccination
using report cards.
22 Document Name:
The Immunological Basis for Immunization Series - Pertussis
http://apps.who.int/iris/bitstream/10665/44311/1/9789241599337_eng.pdf
23 Document Name:
Adverse Effects of Pertussis and Rubella Vaccines
http://www.nap.edu/read/1815/chapter/4#38
Author/Year:
IOM 1991
12 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
P 38:
In fact, since the first reports of serious adverse events following administration of pertussis
and rubella vaccines (Madsen, 1933; Modlin et al., 1975), virtually no placebo-controlled or
other experimental studies in humans of the adverse events covered in this report have been
published.
24 Document Name:
Adverse Effects of Pertussis and Rubella Vaccines
http://www.nap.edu/read/1815/chapter/4#39
Author/Year:
IOM 1991
P 39:
A number of early studies of pertussis vaccine in the United States and the United Kingdom
did include unexposed controls, but these studies were primarily concerned with efficacy
and not with adverse events.
25 Search link:
https://www.clinicaltrials.gov/ct2/results?term=Infanrix+safety&recr=Closed&rslt=&type=
&cond=&intr=&titles=&outc=&spons=&lead=GlaxoSmithKline&id=&state1=&cntry1=&st
ate2=&cntry2=&state3=&cntry3=&locn=&gndr=&age=0&phase=2&phase=3&rcv_s=&rcv
_e=&lup_s=&lup_e=
or
https://drive.google.com/open?id=14MfvK7yfw9M092-JHj3RB5_x7mjiPT_E
26 Document Name:
Pentacel Package Insert
https://drive.google.com/open?id=1SB8zUchU9xp_j0eQTHent-znyta_oHec
P 10(11)
27 Document Name:
Pentacel Safety Review
https://drive.google.com/open?id=1u4ugyQjcQWZ43AMSop6-zSYugykHLoDK
P 75-76
28 Document Name:
Quadracel Package Insert
https://drive.google.com/open?id=1qIjY0SVED2Q8WxXhJj8DAXDJ725F6NVa
P 5(6)
29 Document Name:
DAPTACEL Package Insert
https://drive.google.com/open?id=1mD_GBQsmiGMO-VFpdRMqEdX6yMLVfFwn
P 10, 16-17, 21-22
30 Document Name:
DAPTACEL Clinical Review
https://drive.google.com/open?id=1CFrePXwN-q5ywCnuflnwLjUwScsLPvBU
P 57, 61:
The Swedish trial (1992-1995) compared 4 groups: one of Infanrix by SmithKline Beecham
(GSK), one CDPT (DAPTACEL) by Aventis-Pasteur (Sanofi), and one DTPwc – old
generation vaccine by Aventis-Pasteur. The control group received a DT vaccine.
13 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
31 Document Name:
Hiberix Package Insert
https://drive.google.com/open?id=1epLW5onHsW93NI2_qNxH-KaMvkcvATdc
P 4, 14
32 Document Name:
ActHIB Package Insert
https://drive.google.com/open?id=1MeKZaNrIaVRjy_2VmtvBQ98t6syrVM14
P 19-21
33 Document Name:
PedvaxHIB Package Insert
https://drive.google.com/open?id=10rwMmdmZ_H3FE9v1oPPiByLqGbFegngS
P7
34 Document Name:
IPOL Package Insert
https://drive.google.com/open?id=1sWAblyncNXw-78rh8LtzkIKAmQfAkOK2
35 Document Name:
IPOL FOIA FDA 2018
https://drive.google.com/open?id=1V7zf1YPJF2_V2KRRf-wUz-dCeKxMaUvz
P 90-93, 13-15
36 Document Name:
PREVNAR-13 Package Insert
https://drive.google.com/open?id=1_iI7Np-BfDmUwkQzuJWp46rkSBZ-ow5i
P 6:
The safety of Prevnar 13 was evaluated in 13 clinical trials in which 4,729 infants (6 weeks
through 11 months of age) and toddlers (12 months through 15 months of age) received at
least one dose of Prevnar 13 and 2,760 infants and toddlers received at least one dose of
Prevnar active control.
37 Document Name:
PREVNAR-13 Package Insert
https://drive.google.com/open?id=1_iI7Np-BfDmUwkQzuJWp46rkSBZ-ow5i
P 6:
Serious adverse events reported following vaccination in infants and toddlers occurred in
8.2% among Prevnar 13 recipients and 7.2% among Prevnar recipients.
[…]
The most commonly reported serious adverse events were in the ‘Infections and
infestations’ system organ class including bronchiolitis (0.9%, 1.1%), gastroenteritis, (0.9%,
0.9%), and pneumonia (0.9%, 0.5%) for Prevnar 13 and Prevnar respectively.
38 Document Name:
PREVNAR Package Insert
https://drive.google.com/open?id=1VLR6NluMGK0E4yXUZM18IpUpi_MI7-MP
P 3, 5, 15, 21
14 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
40 Document Name:
PREVNAR Package Insert
https://drive.google.com/open?id=1VLR6NluMGK0E4yXUZM18IpUpi_MI7-MP
P 2, 21:
Efficacy was assessed in a randomized, double-blinded clinical trial in a multiethnic
population at Northern California Kaiser Permanente (NCKP) from October 1995 through
August 20, 1998, in which 37,816 infants were randomized to receive either Prevnar® or a
control vaccine (an investigational meningococcal group C conjugate vaccine [MnCC]) at 2,
4, 6, and 12-15 months of age.
[…]
The majority of the safety experience with Prevnar® comes from the NCKP Efficacy Trial
in which 17,066 infants received 55,352 doses of Prevnar®, along with other routine
childhood vaccines through April 1998.
41-60
41 Document Name:
ENGERIX Package Insert
https://drive.google.com/open?id=1aZ1MtPiO58lE6Pjg0Ee_PZZ10c4iLjUs
P 7:
Based on clinical trial symptom sheet data, the incidence of local side effects is 24% and of
systemic side effects 8%; both local and systemic side effects occurred in approximately
13% of subjects. The incidence of local and systemic reactions was comparable to those of
plasma derived hepatitis B vaccines.
42 Document Name:
ENGERIX Package Insert
https://drive.google.com/open?id=1aZ1MtPiO58lE6Pjg0Ee_PZZ10c4iLjUs
P 7:
In a comparative trial in subjects from 11 years up to and including 15 years of age, the
incidence of local and general solicited symptoms reported after a two-dose regimen of
ENGERIX-B 20 μg was overall similar to that reported after the standard three-dose
regimen of ENGERIX-B 10 μg.
15 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
43 Document Name:
TWINRIX Package Insert
https://drive.google.com/open?id=1K0vRj8CXuYtdhYUys4EPj2cG_niylk0I
P 4:
In a US study, 773 subjects (aged 18 to 70 years) were randomized 1:1 to receive TWINRIX
(0-, 1-, and 6-month schedule) or concurrent administration of ENGERIX-B (0-, 1-, and 6-
month schedule) and HAVRIX (0- and 6-month schedule).
44 Document Name:
Recombivax-HB Package Insert
https://drive.google.com/open?id=1LHJU_WAhXqewxvZJwWpRCRT7f4pHFaPk
45 Document Name:
HAVRIX Package Insert
https://drive.google.com/open?id=1XGppC-tPGSWvEZNGK8kRY15nGz76lxSA
P 5, 10
46 Document Name:
VAQTA Clinical Review
https://drive.google.com/open?id=1IASUdLYQ1eUDFb8vXgFH61ZhJ9rJAfRd
P 12, 22
47 Document Name:
VAQTA Package Insert
https://drive.google.com/open?id=1LuPKwCve8Pguo-GJOzbOm1b9Hgu0Zn15
P 11, paragraph 11. Description of the vaccine adjuvant. P 7 Table 5 (and table comments) –
using the control group.
49 Document Name:
Varivax Package Insert
https://drive.google.com/open?id=1NnEIia3vR_01iqYnq2wNDRWz_ZcvPo48
P5
16 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
52 Document Name:
ProQuad Package Insert
https://drive.google.com/open?id=13MxSgUKzQwZ59M2YZ_9Hwtc_2l7tSQVh
P 6, 8, 9-11.
53 Document Name:
MMR II Package Insert
https://drive.google.com/open?id=1IFm340mDs4z_GUMRASgVUWK8mzQnNpXx
54 Document Name:
MMR II FOIA FDA
https://drive.google.com/open?id=1GKahQSNG8LvCAnEG7SGNyYPUEiSJwfd8
55 Document Name:
MMR FOIA FDA
https://drive.google.com/open?id=16qovZioEkWxDF739XeUdwvAyRk7unWm5
56 Document Name:
Federal Register / Vol. 78, No. 142
https://drive.google.com/open?id=1Dml_DhOUJWX5LlKr-9gM7olmHwlQVwFQ
Author/Year:
Federal Register, 2013
P 3-4
17 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
58 Document Name:
Rotarix Clinical Review
https://drive.google.com/open?id=1LNjfqQDrsaQEdaZ0MYNkc_YfIrOz2kto
P 24:
The placebo consisted of all components of Rotarix, but without any RV particles.
59 Document Name:
Rotateq Clinical Review
https://drive.google.com/open?id=1T5ZQZYINtJhdrYGHrwSZ1M5HWFKf4dK8
P 37
61-70
61 Article Name: PMID:
Safety and Efficacy of an Attenuated 16394298
Vaccine against Severe Rotavirus
Gastroenteritis Archive:
https://drive.google.com/open?id=1BFeBU
https://www.nejm.org/doi/full/10.1056/NEJ
KyHVq9msLCtJLdY3bHJsIIQ4pS3
Moa052434
Lead Author/Year: Journal:
Guillermo M. Ruiz-Palacios, 2006 The New England Journal of Medicine
P 15-17
P 28-30 (6-8)
18 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
63 Document Name:
ROTARIX Package Insert
https://drive.google.com/open?id=1b1rURgJfPiXgg3HGZtYzhpKnjv7ZW-P0
P 5:
No increased risk of intussusception was observed in this clinical trial following
administration of ROTARIX when compared with placebo
65 Document Name:
Ethical Considerations in Conducting Pediatric Research
Book chapter from:
Pediatric Clinical Pharmacology
https://www.springer.com/gp/book/9783642201943
Author/Year:
Michelle Roth-Cline, 2011
P 228:
In assessing whether an intervention or procedure presents no more than a minor increase
over minimal risk, there must be sufficient data that any research-related pain, discomfort or
stress will not be severe and that any potential harms will be transient and reversible.
66 Document Name:
Declaration Of Helsinki – Ethical Principles For Medical Research Involving Human
Subjects
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-
medical-research-involving-human-subjects/
Author/Year: Archive:
WMA, 1964 http://archive.is/4r8lC
Paragraph 18:
19 | Chapter 1: Turtles All The Way Down – Vaccine Clinical Trials
18. Physicians may not be involved in a research study involving human subjects unless they
are confident that the risks have been adequately assessed and can be satisfactorily managed.
When the risks are found to outweigh the potential benefits or when there is conclusive
proof of definitive outcomes, physicians must assess whether to continue, modify or
immediately stop the study
Paragraph 18:
26. For a potential research subject who is incapable of giving informed consent, the
physician must seek informed consent from the legally authorised representative. These
individuals must not be included in a research study that has no likelihood of benefit for
them unless it is intended to promote the health of the group represented by the potential
subject, the research cannot instead be performed with persons capable of providing
informed consent, and the research entails only minimal risk and minimal burden.
67 Document Name:
The Nuremberg Code
"Trials of War Criminals before the Nuremberg Military Tribunals under Control Council
Law No. 10"
https://drive.google.com/open?id=1zCEx9tvA_1vs4KycwYUU9uQ1GHC0mXp6
Author/Year:
U.S. Government, 1949
P 1 item 4:
The experiment should be so conducted as to avoid all unnecessary physical and mental
suffering and injury.
68 Document Name:
Expert consultation on the use of placebos in vaccine trials
http://apps.who.int/iris/bitstream/handle/10665/94056/9789241506250_eng.pdf
Author/Year: Archive:
WHO, 2013 https://drive.google.com/open?id=1yLHGu4pO0K2
xUZmNsE4RyxrbUtkq382y
P 12:
The research must have a risk–benefit profile judged to be favourable, based on sufficient
evidence from previous clinical and non-clinical studies (i.e. the expected benefits of
conducting the research must outweigh any associated potential risks). There is an ethical
obligation to introduce measures to reduce the risks to all trial participants.
69 Document Name:
DAPTACEL Clinical Review
https://drive.google.com/open?id=1CFrePXwN-q5ywCnuflnwLjUwScsLPvBU
P 61 Table 50
1-20
1 Document Name:
Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism
http://nationalacademies.org/hmd/reports/2001/immunization-safety-review-measles-
mumps-rubella-vaccine-and-autism.aspx
Author/Year:
IOM, 2011
2 Document Name:
Immunization Safety Review: Thimerosal - Containing Vaccines and Neurodevelopmental
Disorders
http://www.nationalacademies.org/hmd/reports/2001/Immunization-Safety-Review-
Thimerosal---Containing-Vaccines-and-Neurodevelopmental-Disorders.aspx
Author/Year:
IOM, 2001
3 Document Name:
Immunization Safety Review: Vaccinations and Sudden Unexpected Death in Infancy
http://www.nationalacademies.org/hmd/Reports/2003/Immunization-Safety-Review-
Vaccinations-and-Sudden-Unexpected-Death-in-Infancy.aspx
Author/Year:
IOM, 2003
4 Document Name:
Immunization Safety Review Vaccines and Autism
https://www.nap.edu/catalog/10997/immunization-safety-review-vaccines-and-autism
Author/Year:
IOM, 20041
5 Document Name:
Childhood Immunization Schedule and Safety: Stakeholder Concerns, Scientific Evidence,
and Future Studies
http://nationalacademies.org/hmd/reports/2013/the-childhood-immunization-schedule-and-
safety.aspx
Author/Year:
IOM, 2013
6 Document Name:
Adverse Effects of Vaccines: Evidence and Causality
http://nationalacademies.org/hmd/reports/2011/adverse-effects-of-vaccines-evidence-and-
causality.aspx
Author/Year:
IOM, 2011
7 Document Name:
Adverse Effects of Vaccines: Evidence and Causality
21 | Chapter 2: The Science of Adverse Events - A Missing Link and an Empty Toolbox
http://nationalacademies.org/hmd/reports/2011/adverse-effects-of-vaccines-evidence-and-
causality.aspx
Author/Year:
IOM, 2011
P 30 (59):
In 2009 HRSA requested that the IOM convene a committee of experts to review the
epidemiological, clinical, and biological evidence regarding adverse health events associated
with specific vaccines covered by the VICP. The committee was charged with developing a
consensus report with conclusions on the evidence bearing on causality and the evidence
regarding the biological mechanisms that underlie specific theories for how a specific
vaccine is related to a specific adverse event.
8 Short Name:
IOM 2011
P IX (10):
Following in this tradition, the task of this committee was to assess dispassionately the
scientific evidence about whether eight different vaccines cause adverse events (AE), a total
of 158 vaccine-AE pairs, the largest study undertaken to date, and the first comprehensive
review since 1994.
9 Short Name:
IOM 2011
P 18 (47):
The committee concluded the evidence convincingly supports 14 specific vaccine–adverse
event relationships. In all but one of these relationships, the conclusion was based on strong
mechanistic evidence with the epidemiologic evidence rated as either limited confidence or
insufficient.
[…]
The committee concluded the evidence favors acceptance of four specific vaccine–adverse
event relationships.
10 Short Name:
IOM 2011
P 23 (52):
The committee concluded the evidence favors rejection of five vaccine–adverse event
relationships.
[…]
The vast majority of causality conclusions in the report are that the evidence was inadequate
to accept or reject a causal relationship.
11 Short Name:
IOM 2011
P 19-21 (48-50)
12 Short Name:
IOM 2011
P 630-632 (659-661)
22 | Chapter 2: The Science of Adverse Events - A Missing Link and an Empty Toolbox
Archive:
http://archive.is/q82UH
Bernadine Healy, a former top official in US Public Health bodies, told CBS News in
2008:
Healy goes on to say public health officials have intentionally avoided researching whether
subsets of children are "susceptible" to vaccine side effects - afraid the answer will scare the
public.
"You're saying that public health officials have turned their back on a viable area of research
largely because they're afraid of what might be found?" Attkisson asked.
Healy said: "There is a completely expressed concern that they don't want to pursue a
hypothesis because that hypothesis could be damaging to the public health community at
large by scaring people.
15 Short Name:
IOM 2011
P 28 (57):
The overwhelming safety and effectiveness of vaccines in current use in preventing serious
disease has allowed them to gain their preeminent role in the routine protection of health.
23 | Chapter 2: The Science of Adverse Events - A Missing Link and an Empty Toolbox
16 Short Name:
IOM 2011
P 49 (78):
It is important to note that mechanistic evidence can only support causation. Epidemiologic
evidence, by contrast, can support (“favors acceptance of”) a causal association or can
support the absence of (“favors rejection of”) a causal association in the general population
and in various subgroups that can be identified and investigated, unless or until supportive
mechanistic evidence is discovered or a rare, susceptible subgroup can be identified and
investigated.
17 Short Name:
IOM 2011
P X (11):
Many of the case reports the committee reviewed simply cited a temporal relation between
vaccine administration and an adverse event.
18 Short Name:
IOM 2011
P 440-442 (469-471)
19 Short Name:
IOM 2011
P 154-156 (183-185)
20 Page Name:
Acute Disseminated Encephalomyelitis (ADEM)
Website:
WEBMD
https://www.webmd.com/brain/acute-disseminated-encephalomyelitis-adem#1
Archive:
http://archive.is/8u53v
ADEM seems to be an autoimmune disease. That means your immune system attacks your
body's own cells and tissues as if they were outside bacteria or viruses. Experts don't know
exactly what triggers it, but it could be an overreaction to an infection. Most of the time, the
attack happens when a child is getting over some common illness, like a cold or stomach
bug.
ADEM sometimes follows an immunization, particularly certain rabies shots and
the vaccine for measles, mumps, and rubella. No direct connection has been made though.
Other times, nothing out of the ordinary happens before symptoms appear.
21-34
21 Page Name:
Optic neuritis
Website:
Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/optic-neuritis/symptoms-causes/syc-
20354953
Archive:
http://archive.is/A9RBl
The exact cause of optic neuritis is unknown.
24 | Chapter 2: The Science of Adverse Events - A Missing Link and an Empty Toolbox
22 Page Name:
Guillain-Barre syndrome
Website:
Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms-
causes/syc-20362793
Archive:
http://archive.is/2IgLm
The exact cause of Guillain-Barre syndrome isn't known.
23 Page Name:
What is Transverse Myelitis?
Website:
Johns Hopkins Medicine
http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/transverse_myelit
is/about-tm/what-is-transverse-myelitis.html
Archive:
http://archive.is/CiqdA
The cause of 60% of TM cases may remain unknown despite the presence of inflammatory
mechanisms. However, the remaining 40% is associated with autoimmune disorders such as
multiple sclerosis, neuromyelitis optica, systemic lupus erythematous, Sjogren’s syndrome
and sarcoidosis among others. The term idiopathic — meaning the cause is unknown- has
been used in the past in situations in which the cause cannot be determined. However, the
lack of demonstration of a causative disorder, mechanism or agent may be the result of
failure of an early diagnosis or the result of causative factors that disappears quickly such as
in cases of viral infections or post-infectious disorders.
24 Page Name:
Lupus
Website:
Mayo Clinic
http://www.mayoclinic.org/diseases-conditions/lupus/basics/causes/con-20019676
Archive:
http://archive.is/SY0oG
Lupus occurs when your immune system attacks healthy tissue in your body (autoimmune
disease). It's likely that lupus results from a combination of your genetics and your
environment.
It appears that people with an inherited predisposition for lupus may develop the disease
when they come into contact with something in the environment that can trigger lupus. The
cause of lupus in most cases, however, is unknown.
25 Page Name:
Vasculitis
Website:
Mayo Clinic
http://www.mayoclinic.org/diseases-conditions/vasculitis/basics/causes/con-20026049
Archive:
http://archive.fo/DMh6g
The exact cause of vasculitis isn't fully understood. Some types are related to a person's
genetic makeup. Others result from the immune system attacking blood vessel cells by
mistake.
25 | Chapter 2: The Science of Adverse Events - A Missing Link and an Empty Toolbox
26 Page Name:
Type 1 diabetes in children
Website:
Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/type-1-diabetes-in-children/symptoms-
causes/syc-20355306
Archive:
http://archive.fo/TqdgF
The exact cause of type 1 diabetes is unknown. But in most people with type 1 diabetes, the
body's immune system — which normally fights harmful bacteria and viruses — mistakenly
destroys insulin-producing (islet) cells in the pancreas. Genetics and environmental factors
appear to play a role in this process.
27 Short Name:
IOM 2011
P 13 (43)
28 Short Name:
IOM 2011
P XI (12):
Although the committee is optimistic that more can and will be known about vaccine safety
in the future…
29 Document Name:
Varivax Product Sheet
https://drive.google.com/open?id=1NnEIia3vR_01iqYnq2wNDRWz_ZcvPo48
P4
Vaccine-related adverse reactions reported during clinical trials were assessed by the study
investigators to be possibly, probably, or definitely vaccine-related and are summarized
below.
30 Document Name:
Engerix Clinical Review
https://drive.google.com/open?id=1lt2scepRp3pTpbB4HQ3cYtE5bU3twD6o
P 15:
Of 55 SAEs reported during the active phase of the protocol and 12 reported during the 180
day extended safety follow-up, none were considered to be vaccine related.
31 Document Name:
PEDIACEL Package Insert
https://drive.google.com/open?id=18Bb7jBpmRTQHDJ_JAYb7v1fpCK9-NboP
P 10:
The following additional adverse events have been spontaneously reported during the
postmarketing use of PEDIACEL® worldwide. Because these events are reported
voluntarily from a population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to vaccine exposure.
Document Name:
HAVRIX, Package Insert
https://drive.google.com/open?id=1XGppC-tPGSWvEZNGK8kRY15nGz76lxSA
P 6:
In addition to reports in clinical trials, worldwide voluntary reports of adverse events
received 136 for HAVRIX since market introduction of this vaccine are listed below. This
list includes serious 137 adverse events or events which have a suspected causal connection
to components of HAVRIX 138 or other vaccines or drugs. Because these events are
reported voluntarily from a population of 139 uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal 140 relationship to the vaccine.
Document Name:
ENGERIX Package Insert
https://drive.google.com/open?id=1aZ1MtPiO58lE6Pjg0Ee_PZZ10c4iLjUs
P 87:
The following adverse events have been reported following widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances the causal relationship to the vaccine
has not been established.
Website: Archive:
https://www.ynet.co.il/articles/0,7340,L-4590167,00.html http://archive.is/AbUmZ
In spite of all the intensive tests he has undergone, both hospitals have not been able to find
out why the sudden and dramatic liver collapse. It is a rare condition. Once or twice a year,
we have such a condition of a child with liver failure even though they are completely
healthy.
"In this condition, they undergo tests to detect infectious, autoimmune or metabolic diseases,
and often the cause is not found," explains Dr. Michael Gurevich, senior physician at the
Schneider hospital transplant system, who was one of the surgeons.
One of the causes of the collapse, which was tested and ruled out is the flu vaccine he
received the day before. "The medical literature does not describe a case where the flu
vaccine caused liver inflammation or liver failure," Dr. Gurevich emphasizes. The mother
also denies the possibility.
"The source of the problem is unknown and will probably never be known. All the
possibilities were checked, all the tests were done, and do not know. We were told that it is a
very rare condition for a child fully healthy to undergo a liver collapse. The best infectious
disease specialists have said that if the child turned yellow within a day, then he was
probably already sick. "
34 Short Name:
IOM 2011
P 28(57):
The overwhelming safety and effectiveness of vaccines in current use in preventing serious
disease has allowed them to gain their preeminent role in the routine protection of health.
Chapter 3: Defective by Design - Vaccine
Adverse Event Reporting Systems
1-20
1 Article Name: PMID:
Understanding vaccine safety information from the Vaccine 15071280
Adverse Event Reporting System
Lead Author/Year: Journal:
Fredrick Varricchio, 2004 The Pediatric Infectious Disease Journal
P 2:
Clinical trials of new vaccines have typically involved a relatively small number of
individuals (usually fewer than 10 000) and thus cannot usually detect uncommon adverse
events.
Lead Author/Year:
Ross Lazarus, 2011
P 6:
New surveillance methods for drug and vaccine adverse effects are needed. Barriers to
reporting include a lack of clinician awareness, uncertainty about when and what to report,
as well as the burdens of reporting: reporting is not part of clinicians’ usual workflow, takes
time, and is duplicative.
Lead Author/Year:
NIH/FDA, 1998
P 1-2:
Thus, when the product leaves the controlled study environment of clinical trials and is put
into general clinical use by practitioners, the ability to determine the actual incidence of
adverse events is questionable.
P 4:
Therefore because VAERS functions primarily as a voluntary reporting system, reporting
occurs for only a proportion of suspected adverse events, and this proportion varies
depending on the vaccine and the type of event.
Lead Author/Year:
David A. Kessler, 1993
David Kessler, former head of FDA -
P 1:
Only about 1% of serious events are reported to the FDA, according to one study.
Lead Author/Year:
Ross Lazarus, 2011
P 6:
Adverse events from drugs and vaccines are common, but underreported. Although 25% of
ambulatory patients experience an adverse drug event, less than 0.3% of all adverse drug
events and 1-13% of serious events are reported to the Food and Drug Administration
(FDA). Likewise, fewer than 1% of vaccine adverse events are reported.
21-40
21 Abbreviated Name: Archive:
Slade 2009 https://drive.google.com/open?id=1MQIcFiM-
5POt66gfIdLaASCdgY9EZcDF
P 7:
AEFI reporting rates also need cautious interpretation, because vaccine distribution data do
not allow calculation of age-specific reporting rates and do not provide the numbers of doses
actually administered
24 Documnet Name:
GARDASIL Package Insert
https://drive.google.com/open?id=1u3cOmn6ehXdR21bNuUQ7He3q6e2jFFxx
P 8, Table 9
33 | Chapter 3: Defective by Design - Vaccine Adverse Event Reporting Systems
Archive:
http://archive.is/tIPgl
Website:
NPR (Bational Public Radio)
https://www.npr.org/templates/story/story.php?storyId=112035659?storyId=112035659
It still appears that the vaccine is safe and that the benefits outweigh the risks.
Article Name: Date:
HPV shot found safe, but some experts question Aug 18, 2009
its benefits
Archive:
http://archive.fo/lOJ2M
Website:
CNN
http://edition.cnn.com/2009/HEALTH/08/18/hpv.vaccine.safety/index.html?iref=24hours
"This continues to be a safe vaccine," says lead researcher Dr. Barbara A. Slade, a medical
officer at the CDC.
35 | Chapter 3: Defective by Design - Vaccine Adverse Event Reporting Systems
Website:
CDC website
https://vaers.hhs.gov/resources/infoproviders.html
Author/Year:
GACVS, 2013
P3
41-50
41 Abbreviated Name: Archive:
Lazarus 2011 https://drive.google.com/open?id=1Uih_BuqrRJoaj4o3otgqZiW
iYgeBIH9H
P 3-4
P 3:
Aim 3. Comprehensively evaluate ESP:VAERS performance in a randomized trial, and in
comparison to existing VAERS and Vaccine Safety Datalink data.
P 5:
The draft was then widely circulated as an initial / working draft for comment by relevant
staff in the CDC and among our clinical colleagues at Atrius. In addition to review by the
internal CDC Brighton Collaboration liaison, this protocol has also received review &
comment via the CDC’s Clinical Immunization Safety Assessment (CISA) Network.
On the other hand, more serious and unexpected medical events are probably more likely to
be reported than minor ones, especially when they occur soon after vaccination, even if they
may be coincidental and related to other causes.
38 | Chapter 3: Defective by Design - Vaccine Adverse Event Reporting Systems
48 Page Name:
Vaccine Safety Datalink
Archive:
http://archive.is/TKFoj
Website:
HCSRN website
http://www.hcsrn.org/en/Collaboration/Consortia/vsd.html
PI: Frank DeStefano, MD of the CDC Immunization Safety Office
Funding agency: Centers for Disease Control and Prevention (CDC)
Website:
CDC website
https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/data-sharing-
guidelines.html
50 Document Name:
Vaccine Safety Research, Data Access, and Public Trust
https://www.nap.edu/catalog/11234/vaccine-safety-research-data-access-and-public-trust
Author/Year:
IOM 2005
P 96:
One of the key goals of the Vaccine Safety Datalink (VSD) data sharing program should be
maintenance of public trust in the use of the VSD to draw scientific conclusions about vaccine safety.
Because of the contentious nature of some of the issues surrounding the VSD and the strained
relationship between the Centers for Disease Control and Prevention (CDC) and some people who
have been critical of CDC’s vaccine safety activities, the committee recognizes that there may be
public concerns about the role of CDC in reviewing proposals to use VSD data and in setting the VSD
research agenda. A perception of bias in the VSD proposal-review process and in the priorities
established for the VSD research plan could jeopardize public confidence in VSD activities. There are
legitimate reasons for public concern about the independence and fairness of the review of VSD data
sharing proposals and of determinations about when and how to release preliminary findings of VSD
analyses. The lack of transparency of some of those processes affects the trust relationship between the
National Immunization Program (NIP) and some members of the general public.
P 97-98:
The limitations of the VSD data sharing program and the limited ability of independent external
researchers to conduct high-quality corroboration studies or studies of new hypotheses create a special
need to involve the public in the priority-setting process for the VSD research plan. Only NIP-
affiliated or MCO-affiliated researchers have access to VSD data for events before and after January 1,
2001, for corroboration studies and studies of new hypotheses, so independent external researchers
may not be able to conduct studies that members of the public consider to have high priority.
[…]
In view of the limited ability of independent researchers to conduct high-quality VSD studies of new
hypotheses and the limited ability of the public to provide input on which VSD studies should be
39 | Chapter 3: Defective by Design - Vaccine Adverse Event Reporting Systems
pursued with federal tax dollars, there needs to be greater opportunity for input into the setting of
priorities in the VSD research plan and greater transparency of the priority-setting process.
Chapter 4: Epidemiology 101
1-20
1 Article Name: PMID:
The history of the discovery of the cigaretteelung 22345227
cancer link: evidentiary traditions, corporate
denial, global toll Archive:
https://tobaccocontrol.bmj.com/content/tobaccoco https://drive.google.com/open?id=1YA
ntrol/21/2/87.full.pdf WDfVhDNWb1O-
SiwIRQDk9lF1jC7IUw
Lead Author/Year: Journal:
Robert N Proctor, 2012 Tobacco Control
P 1:
Lung cancer was still a very rare disease; so rare, in fact, that medical professors when
confronted with a case sometimes told their students they might never see another.
research director Helmut Wakeham put it in 1961, carcinogens were found in ‘practically
every class of compounds in cigarette smoke’.
Website:
Australian Bureau of Statistics
http://www.abs.gov.au/websitedbs/a3121120.nsf/home/statistical+language+-
+correlation+and+causation
Correlation is a statistical measure (expressed as a number) that describes the size and
direction of a relationship between two or more variables. A correlation between variables,
however, does not automatically mean that the change in one variable is the cause of the
change in the values of the other variable.
Causation indicates that one event is the result of the occurrence of the other event; i.e. there
is a causal relationship between the two events. This is also referred to as cause and effect.
Website:
emedicinehealth
http://www.emedicinehealth.com/emphysema/article_em.htm
http://www.emedicinehealth.com/emphysema/page2_em.htm
The importance of cigarette smoking as a risk factor for developing emphysema cannot be
overemphasized. Cigarette smoke contributes to this disease process in two ways. It destroys
lung tissue, which results in the obstruction of air flow, and it causes inflammation and
irritation of airways that can add to air flow obstruction.
Website:
E X T O X N E T
Extension Toxicology Network
http://pmep.cce.cornell.edu/profiles/extoxnet/TIB/epidemiology.html
Epidemiological studies can never prove causation; that is, it cannot prove that a specific
risk factor actually causes the disease being studied. Epidemiological evidence can only
show that this risk factor is associated (correlated) with a higher incidence of disease in the
population exposed to that risk factor. The higher the correlation the more certain the
association, but it cannot prove the causation
43 | Chapter 4: Epidemiology 101
The single most effective action that parents and caregivers can take to lower a baby's risk of
SIDS is to place the baby to sleep on his or her back for naps and at night.
Compared with back sleeping, stomach sleeping carries between 1.7 and 12.9 times the risk
of SIDS. The mechanisms by which stomach sleeping might lead to SIDS are not entirely
known. Studies suggest that stomach sleeping may increase SIDS risk through a variety of
mechanisms, including:
Increasing the probability that the baby re-breathes his or her own exhaled breath, leading to
carbon dioxide buildup and low oxygen levels; Causing upper airway obstruction;
Interfering with body heat dissipation, leading to overheating.
Whatever the mechanism, evidence from numerous countries—including New Zealand,
Sweden, and the United States—suggests that placing babies on their backs to sleep results
in a substantial decline in the SIDS rate compared to placing babies on their stomachs to
sleep.
Retrospective study:
a study in which a search is made for a relationship between one (usually current) phenomen
on or condition and another that occurred in the past. An example is
a study of the family histories of young women diagnosed as having clear cell
adenomas of the vagina, which yielded a relationship between the administration of diethy
lstilbestrol to the mothers of the women during pregnancy and
the development of the condition in the daughters.
21-29
21 Document Name:
Reference Manual on Scientific Evidence
https://www.nap.edu/read/13163/chapter/12#583
Lead Author/Year:
Federal Judicial Center
National Research Council, 2011
P 583:
The second major reason for an invalid outcome in epidemiologic studies is systematic error
or bias. Bias may arise in the design or conduct of a study, data collection, or data analysis.
The meaning of scientific bias differs from conventional (and legal) usage, in which bias
refers to a partisan point of view. When scientists use the term bias, they refer to anything
that results in a systematic (nonrandom) error in a study result and thereby compromises its
validity. Two important categories of bias are selection bias (inappropriate methodology for
selection of study subjects) and information bias (a flaw in measuring exposure or disease in
the study groups).
Archive:
25 Document Name:
https://drive.google.com/open?id=
Adverse Effects of Vaccines: Evidence and Causality
http://nationalacademies.org/hmd/reports/2011/adverse 1nl18cdV_y3TtQBzoCq0tSiuYm
-effects-of-vaccines-evidence-and-causality.aspx HF1_yYQ
Author/Year:
IOM, 2011
P 17 (46):
Epidemiologic analyses also cannot identify with certainty which individual in a population
at risk will develop a given condition.
1-20
Document Name:
1 DPT Vaccine Roulette 1982
https://www.youtube.com/watch?v=qpUsg4bDH5w
or
https://www.youtube.com/watch?v=VtOh6vFnWg4
Website: Archive:
The Atlantic hhttp://archive.is/uOhEJ
http://www.theatlantic.com/health/archive/2014/10/how-anti-
vaccine-fear-takes-hold/381355/
For example –
Jacklyn Smoot, a 26 year-old new mother from Orange, California, feels torn. Her son’s
pediatrician and the Centers for Disease Control and Prevention assure her that vaccines are
safe and effective. Smoot hears personal stories from vaccine skeptics like her mother, some
friends, and Internet bloggers, however, who warn that vaccines can cause injury or death.
She wonders who is right.
Smoot’s struggle began when she got a flu shot in December 2012. Her mother’s reaction
surprised her. “She said, ‘What? But you’re pregnant!’ She scared me,” Smoot says. “I
found myself online for three hours trying to figure out if it was a good idea that I had gotten
the flu shot while I was pregnant.”
Then she got on the Internet.
Smoot downloaded the recommended immunization schedule from the CDC website. She
looked up each vaccine on the schedule. Although she says she tried to look at a variety of
trustworthy websites, she can only remember reading any information supporting
vaccination on the CDC website. Smoot, however, says she does not trust doctors and
scientists. “I know they’re just going to tell me they’re safe, and they’re recommended, and
this is what you’re supposed to do,” she says.
Dr. Neal Halsey is a professor at the Johns Hopkins Bloomberg School of Public Health and
the School of Medicine. He runs the Institute for Vaccine Safety, providing independent
assessment of and education on vaccine safety. “The vaccines we have available that are
recommended for routine use in children are very safe vaccines,” he says.
Dr. Diane Griffin, a virologist and chair of the molecular biology and immunology
department at Johns Hopkins, agrees. “Oh, yes, vaccines are very safe,” she says.
According to the CDC, vaccines in the United States are the most safe and effective
immunizations in history. The CDC’s website says severe reactions to vaccines “occur so
rarely that the risk is difficult to calculate.”
“I probably find more information that says vaccines aren’t safe,” she says. “I think it’s only
because …” She pauses. “Well, I don’t really know. It could be maybe what I’m paying
attention to more.”
Document Name:
Talking with Parents about Vaccines for Infants
https://www.cdc.gov/vaccines/hcp/patient-ed/conversations/downloads/talk-infants-color-
office.pdf
49 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
Author/Year: Archive:
CDC, 2012 https://drive.google.com/open?id=1CmLPr0
40TWioZcFMuyqifdm9GT9rsctH
10 Document Name:
Addressing Common Concerns of Vaccine-Hesitant Parents
https://www.aap.org/en-us/Documents/immunization_vaccine-hesitant%20parent_final.pdf
Author/Year: Archive:
American Academy of Pediatrics, 2013 https://drive.google.com/open?id=1-
EzjdlPKRJgqy02o6xR_WypH7unz6fq6
The document contains examples of "parental concerns" ans studies who answer them.
Website: Archive:
USA TODAY http://archive.is/ixi6Z
http://usatoday30.usatoday.com/news/health/story/2012-04-
09/researchers-autism-causes/54129282/1
More than $1 billion has been spent over the past decade searching for the causes of autism.
In some ways, the research looks like a long-running fishing expedition, with a focus on
everything from genetics to the age of the father, the weight of the mother, and how close a
child lives to a freeway.[…] The lion's share of money for finding a cause has been spent on
genetics. […]
But even genetics enthusiasts acknowledge that genes are only part of the answer. Studies of
identical twins have shown that autism can occur in one and not the other, meaning
something outside a child's DNA is triggering the disorder in many cases. Some cases may
be entirely due to other causes, Dawson said.
That broad "other" category means "environmental" influences — not necessarily chemicals,
but a grab bag of outside factors that include things like the age of the father at conception
and illnesses and medications the mother had while pregnant.
Website: Archive:
Scientific American http://archive.is/jftAe
Large genetic studies have ruled out the idea that the malfunction of a universal gene or set
of genes causes autism. And the new papers, which assessed the genomes of about 1,000
families that had only one autistic child, revealed that the genetic mutations that are likely
responsible for the disorder are exceedingly rare—sometimes almost unique to an individual
patient. Even some of the most common point of mutations were found in only about 1
percent of autistic children.
Website: Archive:
CNN http://archive.is/qGAsI
http://edition.cnn.com/2008/HEALTH/conditions/03/06/vacci
nes.autism/index.html
Numerous studies have shown no link between illness and the vaccines, public health
officials have long contended.
16 Document Name:
Responsible Science, Volume I
https://www.nap.edu/catalog/1864/responsible-science-volume-i-ensuring-the-integrity-of-
the-research
51 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
Author/Year: Archive:
NAS, 1992 https://drive.google.com/open?id=1782CN
gkLfXgxmkd3NtBj0diDm8PJjBb5
P 36:
Until the past decade, scientists, research institutions, and government agencies relied solely
on a system of self-regulation based on shared ethical principles and generally accepted
research practices to ensure integrity in the research process. Among the very basic
principles that guide scientists, as well as many other scholars, are those expressed as
respect for the integrity of knowledge, collegiality, honesty, objectivity, and openness.
These principles are at work in the fundamental elements of the scientific method, such as
formulating a hypothesis, designing an experiment to test the hypothesis, and collecting and
interpreting data. In addition, more particular principles characteristic of specific scientific
disciplines influence the methods of observation; the acquisition, storage, management, and
sharing of data; the communication of scientific knowledge and information; and the
training of younger scientists. How these principles are applied varies considerably among
the several scientific disciplines, different research organizations, and individual
investigators.
17 Document Name:
Responsible Science, Volume I
https://www.nap.edu/catalog/1864/responsible-science-volume-i-ensuring-the-integrity-of-
the-research
Author/Year: Archive:
NAS, 1992 https://drive.google.com/open?id=1782CNg
kLfXgxmkd3NtBj0diDm8PJjBb5
P 95:
Regardless of the incidence, the panel emphasizes that even infrequent cases of misconduct
in science are serious matters. The number of confirmed incidents of misconduct in science,
together with the possibility of underreporting and the results presented in some preliminary
studies, indicate that misconduct in science is a problem that cannot be ignored. The
consequences of even infrequent cases of misconduct in science require that attention be
given to appropriate methods of treatment and prevention.
Archive:
19 Page Name:
http://archive.is/QP9Wz
Budget
Website:
NIH website
https://www.nih.gov/about-nih/what-we-do/budget
Within the Federal budget, there should be an overall strategy for research, with areas of
increased and areas of decreased emphasis… To ensure the most effective use of Federal
discretionary funding it is essential that agreement be reached on which fields and which
investment strategies hold the greatest promise for new knowledge that will contribute most
effectively to better health, greater equity and social justice, improved living standards, a
sustainable environment, a secure national defense, and to extending our understanding of
nature.
Website: Archive:
Huffington Post http://archive.is/Mz2fY
https://www.huffingtonpost.com/david-katz-md/research-
funding-when-is-_b_5493613.html
All research starts with biased funders and researchers — because in the absence of such
bias, it would be research no one would bother doing. I don’t think anyone runs studies in
the absence of hopes and preferences pertaining to the outcomes.
[…]
So, too, do all funders. While the NIH does not generally manufacture and sell the
interventions it studies, it certainly does care about the outcomes. NIH, too, must justify its
existence, and budget — just not to shareholders. NIH and all federal agencies are
accountable to Congress, and by extension to us, in our tax-paying multitudes. NIH
competes in the federal budget with other societal priorities (and, no doubt, pork-barrel
boondoggles); and perhaps more intensely, the various institutes compete with one another
for slices of the common pie. Too many negative study results tend to suggest that an
institute is not spending money all that well and wisely — and affect the outcome of that
competition. Even NIH program officers are biased about study outcomes.
21-40
21 Article Name: Date:
Follow the Funding May 1, 2015
Website: Archive:
The Scientist http://archive.is/Wpcec
http://www.the-
scientist.com/?articles.view/articleNo/42799/title/Follow-the-
Funding/
A few years ago, David Sinclair’s lab was slipping through his fingers. With grant money
running dry and the outlook for overall federal research budgets bleak, the Harvard
geneticist was losing lab members because he couldn’t support them with funding from the
National Institutes of Health (NIH), as he had done in years past. Sinclair says his 18-
person-strong group dwindled to just four or five people. “And that was painful,” he recalls.
“I had to let people go for lack of money.”
And Sinclair says he’s not alone. “Even at a place like Harvard, I know [other] labs that
have downsized dramatically and even closed down,” he says. “So it’s hit across the board.”
53 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
22 A few articles from the scientific literature, demonstrating the high importance of submitting
a research proposal.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133061#pone.0133061.ref
012
Archive :http://archive.is/B5y7y
http://www.bmj.com/content/317/7173/1647
Archive :http://archive.is/ao0fc
http://www.apa.org/gradpsych/2016/01/research-funding.aspx
Archive :http://archive.is/R4iUH
23 Dr. Boyd Hally desribes how the NIH stopped funding his research on Alzheimer disease
when he wanted to investigate mercury exposure as a possible cause.
https://www.youtube.com/watch?v=8AQxkIcXrt0
25 Document Name:
Financing Vaccines in the 21st Century: Assuring Access and Availability
https://www.nap.edu/catalog/10782/financing-vaccines-in-the-21st-century-assuring-access-
and-availability
Author/Year: Archive:
IOM, 2004 https://drive.google.com/open?id=15_AilgxcXk
feOJaNbCgScTr2MbeuMTuD
P 196:
The major contributors to vaccine research in the United States are companies conducting
industrial research, government agencies (the National Institutes of Health [NIH] and the
Department of Defense [DoD]), and the academic institutions they fund.
statistics in ways that make their own drugs look better than they are. If troubling signs
about a drug arise, they can steer clear of further exploration.
Website: Archive:
Sceintific American http://archive.is/gFzXa
http://www.scientificamerican.com/article/straight-talk-about-
vaccination/
This sad state of affairs exists because parents have been persistently and insidiously misled
by information in the press and on the Internet and because the health care system has not
effectively communicated the counterarguments, which are powerful.
[…]
The key facts parents need to know, though, are that vaccines prevent potentially fatal
diseases, that vaccines have a high degree of safety, and that their safety is constantly
evaluated and reevaluated in a system operating independently from the pharmaceutical
companies that make vaccines.
Website:
AAP, 2013
https://www.aap.org/en-us/Documents/immunization_vaccine_studies.pdf
Document Name:
Information Sheet Observed Rate Of Vaccine Reactions Measles, Mumps And Rubella
Vaccines
Author/Year: Archive:
WHO, 2014 https://drive.google.com/open?id=12JQo
http://www.who.int/vaccine_safety/initiative/too DTvzr3qlbq93QChZP8a_vhOSn9J5
ls/MMR_vaccine_rates_information_sheet.pdf
P 3, 9
36 Document Name:
Adverse Effects of Vaccines: Evidence and Causality
http://nationalacademies.org/hmd/reports/2011/adverse-effects-of-vaccines-evidence-and-
causality.aspx
Author/Year: Archive:
https://drive.google.com/open?id=1nl18cdV_y3TtQBz
IOM, 2011
oCq0tSiuYmHF1_yYQ
P 145(174)
Website: Archive:
Atlanta Business Chronicle https://web.archive.org/web/201
http://www.bizjournals.com/atlanta/news/2011/04/13/da 80919220752/https://webcache.
ne-indicted-for-defrauding-cdc.html googleusercontent.com/search?q
=cache:sU81j6AiPG8J:https://w
ww.bizjournals.com/atlanta/new
s/2011/04/13/dane-indicted-for-
defrauding-
cdc.html+&cd=1&hl=en&ct=cl
nk&gl=il&client=firefox-b
58 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
Thorsen worked in the 1990s as a visiting scientist at the CDC Division of Birth Defects and
Developmental Disabilities, when the CDC was soliciting grant applications for research
related to infant disabilities. Thorsen promoted the idea of awarding the grant to Denmark
and provided input and guidance for the research. From 2000 to 2009, the CDC awarded
more than $11 million to two governmental agencies in Denmark to study the relationship
between autism and exposure to vaccines…
Page Name:
Fugitive Profiles
Website: Archive:
Office of Inspector General, HHS http://archive.is/wip/4qVfg
https://oig.hhs.gov/fraud/fugitives/profiles.asp#other-
fugitives
41-60
41 Page Name: Archive:
Vaccines Do Not Cause Autism http://archive.is/SCAqJ
59 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
Website:
CDC website
http://www.cdc.gov/vaccinesafety/concerns/autism.html
There is no link between vaccines and autism
42 Document Name:
Adverse Effects of Vaccines: Evidence and Causality
http://nationalacademies.org/hmd/reports/2011/adverse-effects-of-vaccines-evidence-and-
causality.aspx
Author/Year: Archive:
https://drive.google.com/open?id=1nl18cdV_y3TtQBz
IOM, 2011
oCq0tSiuYmHF1_yYQ
P 50 (79):
Epidemiologic analyses are usually unable to detect an increased or decreased risk that is
small, unless the study population is very large or the difference between the groups (e.g.,
vaccinated vs. unvaccinated) at risk is very high… These studies also can fail to detect risks
that affect a small subset of the population.
Study Title P 1:
Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is
Not Associated with Risk of Autism
Few examples –
51 No link between vaccines and autism
https://www.ncbi.nlm.nih.gov/pubmed/17928818
No link between Type 1 diabetes and vaccines of the childhood program
https://www.ncbi.nlm.nih.gov/pubmed/11731639
No link between vaccines and asthma
https://www.ncbi.nlm.nih.gov/pubmed/12182372
No link between thimerosal in vaccines and neurological disabilities
https://www.ncbi.nlm.nih.gov/pubmed/14595043
Influenza and H1N1 vaccines are safe
https://www.ncbi.nlm.nih.gov/pubmed/21767718
52 Archive:
http://archive.is/bh8oL
Website: Archive:
CBS News http://archive.is/TKUmJ
http://www.cbsnews.com/news/no-link-found-between-
autism-and-number-of-vaccines/
61-80
61 Abbreviated Name: Archive:
DeStefano 2013 https://drive.google.com/open?id=1LVEHpSumks-
XGbdd7DujwX2hDOP4ltVl
P 4:
Admittedly, this approach assumes that all proteins and polysaccharides in a vaccine evoke
equivalent immune responses, whereas some proteins actually may be more likely than
others to stimulate an immune response. Moreover, the calculations do not take into account
the number of epitopes per antigen or the immunologic strength of each epitope.
72 Document Name:
MMWR Vol. 63, No. 5
https://www.cdc.gov/mmwr/pdf/rr/rr6305.pdf
Author/Year: Archive:
https://drive.google.com/open?id=1KF2xY
CDC, 2014
aHnQs8NrjCW1owte8XUM_-s2NOM
P 28 (30)
73 Document Name:
HPV Vaccine is Safe — (Gardasil)
https://www.cdc.gov/vaccinesafety/pdf/data-summary-hpv-gardasil-vaccine-is-safe.pdf
Author/Year: Archive:
https://drive.google.com/open?id=1HxmM
CDC, 2016
kj_j9UedaLjabAkHNH05f2Ma9fF-
P2
66 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
As of July 2020.
74 http://onlinelibrary.wiley.com/doi/10.1111/joim.12155/citedby
http://ajph.aphapublications.org/doi/pdf/10.2105/ https://drive.google.com/open?id=13b5
AJPH.94.6.985 r3JluMRXKcXVsouZfPpCDPsnDqkqI
Lead Author/Year: Journal:
Tricia M. McKeever, 2004 American Journal of Public Health
81-100
81 Page Name: Archive:
School of Medicine - School staff listing http://archive.is/Hhsw2
Website:
University of Nottingham
https://www.nottingham.ac.uk/medicine/people/tricia.mckeever
Website: Archive:
MEDPAGE TODAY http://archive.is/NWRZ5
http://www.medpagetoday.com/infectiousdisease/vaccines/36
69
As the mercury-containing preservative thimerosal was removed from vaccines, and as
fewer children received the mumps-measles-rubella vaccine, the rates of autism and related
disorders rose among Canadian school children.
In a study of nearly 28,000 children born between 1987 and 1998, the prevalence of
pervasive developmental disorders was greater in those children vaccinated after the
mercury-containing compound thimerosal was completely eliminated from vaccines in
Canada, reported Eric Fombonne, M.D., of McGill University in Montreal, and colleagues.
Article Name: Date:
Vaccines And Autism July 6, 2006
Website: Archive:
CBS http://archive.is/mPFH3
http://www.cbsnews.com/news/vaccines-and-autism/
New research from Canada may not end the debate about childhood vaccines and autism —
but it offers more evidence that vaccines are not to blame for the dramatic rise in reported
cases of the developmental disorder.
Article Name: Date:
Study: Vaccines Don't Cause Autism July 6, 2006
Website: Archive:
WEBMD http://archive.is/4Dsbb
http://www.webmd.com/children/vaccines/news/20060706/stu
dy-vaccines-dont-cause-autism
New research from Canada may not end the debate about childhood vaccines and autism,
but it offers more evidence that vaccines are not to blame for the dramatic rise in reported
cases of the developmental disorder.
The study examined outcomes among 28,000 children in Quebec, exposed to different
dosages of the measles, mumps, rubella (MMR) vaccine[…]
As of July 2020
95 https://pediatrics.aappublications.org/content/118/1/e139/tab-article-info
70 | Chapter 5: Purposefully Biased Science - Epidemiology and Vaccine Safety
97 Document Name:
The Childhood Immunization Schedule and Safety
Stakeholder Concerns, Scientific Evidence, and Future Studies
http://www.nap.edu/catalog/13563/the-childhood-immunization-schedule-and-safety-
stakeholder-concerns-scientific-evidence
Author/Year: Archive:
https://drive.google.com/open?id=1no7T_
IOM, 2013
Zx03ToHXlEMGix9miyZMhiRIVtW
P 86 (103):
The initial literature search identified 32 papers on the relationship between immunizations
or vaccines and pervasive developmental disorder… each of the other four papers might
help with a study of the schedule.
[…]
This was an ecological study, but the data were interpreted carefully and the differences in
appropriate trends were noted
98 Document Name:
Adverse Effects of Vaccines: Evidence and Causality
http://nationalacademies.org/hmd/reports/2011/adverse-effects-of-vaccines-evidence-and-
causality.aspx
Author/Year: Archive:
https://drive.google.com/open?id=1nl18cdV_y3Tt
IOM, 2011
QBzoCq0tSiuYmHF1_yYQ
P 145 (174):
[it was] not considered in the weight of epidemiologic evidence because they provided… an
ecological comparison study lacking individual-level data.
101-114
101 Article Name: Date:
A Tale of Two Cities: Flawed Epidemiology Mar 7, 2007
Author: Archive:
F. Edward Yazbak http://archive.is/253mj
Author: Archive:
F. Edward Yazbak http://archive.is/253mj
As a note, I believe the evidence of no link between MMR and Autism is sufficient. It's not
worth publishing more on this subject. We will not be publishing this exchange of
correspondence.
Website: Archive:
TOHE http://archive.is/OUeBu
https://www.timeshighereducation.com/news/should-
academics-be-paid-for-peer-review
As the number of papers needing review increases, journals are thinking of replacing a
voluntary system with cash rewards
1-20
1 Page Name: Archive:
The Journey of Your Child's Vaccine htthttp://archive.is/uuJeo
Website:
CDC website
http://www.cdc.gov/vaccines/parents/infographics/journey-of-child-vaccine.html
2 Document Name:
The Childhood Immunization Schedule and Safety
Stakeholder Concerns, Scientific Evidence, and Future Studies
http://www.nap.edu/catalog/13563/the-childhood-immunization-schedule-and-safety-
stakeholder-concerns-scientific-evidence
Author/Year: Archive:
https://drive.google.com/open?id=1no7T_Zx03To
IOM, 2013
HXlEMGix9miyZMhiRIVtW
P 40 (57):
…the sample sizes in prelicensing clinical trials may not have been adequate to detect rare
adverse events, the prelicensing study population may not have been monitored for long-
term adverse events, and populations may not have been heterogeneous
Document Name:
Compulsory Vaccination Briefly Considered
Author/Year: Archive:
https://drive.google.com/open?id=1_bol5t6Zyrnej
John Gibbs, 1856
9goXH9P2fmoTQYrMI8X
P 10-11:
The main question for the consideration of science is not whether vaccination be a
protection against one form of disease, but what is its general influence upon the
constitution?
[…]
What is the percentage of deaths before a given age, from all epidemics, amongst the
vaccinated, as compared with the unvaccinated? What is the percentage respectively of cases
of disease of the respiratory organs, of skin diseases, of scrofula, and of convulsions? What
is the average duration of life amongst the vaccinated and amongst the unvaccinated? Of a
thousand children vaccinated within a given time after birth, and of a thousand
unvaccinated, the whole two thousand being placed as nearly as possible in like
circumstances, what percentage in each thousand attain the age of puberty? These are
statistics with which the advocates of vaccination have never grappled.
15 Document Name:
Olmsted, who worked in news agency UPI, published the series on UPI's website. The series
was later removed from the site. It can be read here:
https://drive.google.com/open?id=1BCJfmWLMrjSuZ8vRYa6LL4slSnhXdfk3
21-40
21 Page Name:
Why Is Autism Rate So High For Somalis In Minn.
Website:
YouTube
https://www.youtube.com/watch?v=xUf4L6UQhbk
79 | Chapter 6: The Studies That Will Never be Done
unvaccinated, vaccine-delayed and vaccinated children and report back to the NVAC”
[…]
The National Vaccine Program Office of HHS asked the IOM to convene a diverse
committee of experts in pediatrics, neurology, medical ethics, immunology, statistics,
epidemiology, and public health to identify study designs feasible to address questions about
the safety of the United States’ childhood immunization schedule.
41-60
41 Abbreviated Name: Archive:
IOM 2013 https://drive.google.com/open?id=1no7T_Zx03ToHXlEMGix9
miyZMhiRIVtW
P 106 (123):
…any child, even the child of a parent who staunchly rejects vaccination, who is randomized
to a no-vaccination arm is essentially consigned to an elevated risk of severe illness and
even possible death should the child contract a vaccine-preventable disease.
P 107 (124)
The ethics of human experimentation always trump scientific and other considerations, and
no study that needlessly endangers children is acceptable.
42 Document Name:
National, State, and Local Area Vaccination Coverage Among Children Aged 19–35
Months — United States, 2012
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6236a1.htm
Author/Year: Archive:
CDC, 2013 http://archive.is/UtX6r
Table 1, Vaccine coverage data 2008-2012:
Children who received no vaccinations: 2011 - 0.8%, 2012 – 0.8%
43 Document Name:
National vaccine objection (conscientious objection) data 1999 to 2015
https://beta.health.gov.au/resources/publications/national-vaccine-objection-conscientious-
objection-data-1999-to-2015
Author/Year: Archive:
AIR, 2018 https://drive.google.com/open?id=1U7VlgPAzdcEE1SRg12T-
00WlWRj27fo5
Data on conscientious objection for the period 2010-2015, P 2.
83 | Chapter 6: The Studies That Will Never be Done
Website: Archive:
USA TODAY http://archive.is/ixi6Z
http://usatoday30.usatoday.com/news/health/story/2012-04-
09/researchers-autism-causes/54129282/1
More than $1 billion has been spent over the past decade searching for the causes of autism
85 | Chapter 6: The Studies That Will Never be Done
In addition, the committee state that the VSD can be used for vaccinated-
Unvaccinated studies., P 116 (135):
To date, the data obtained from VSD have already been used to study health outcomes of
children with incomplete immunizations or who may follow alternative schedules, as
described above. In addition, the VSD system has a large enough proportion of unvaccinated
children to investigate differences in health outcomes of unvaccinated and vaccinated
children.
61-73
61 Abbreviated Name: Archive:
IOM 2013 https://drive.google.com/open?id=1no7T_Zx03ToHXlEMGix9
miyZMhiRIVtW
P 20 (37):
The NVAC report stated that “the strongest study design, a randomized clinical trial that
includes a study arm receiving no vaccine or vaccine not given in accord with the current
recommended schedule, is not ethical, would not pass Institutional Review Board (IRB)
review, and cannot be done”… Furthermore, it may be impossible to draw unbiased results
from an observational study of this issue because of potential differences in baseline health
and social characteristics of populations and subgroups.
1-20
1 Document Name: Author/Year:
Recommended Child and Adolescent Immunization CDC, 2020
Schedule, for ages 18 years or younger
https://drive.google.com/file/d/11tcxNEPzYibSrwe
2RbnDnD2epCfnZlXo
P 2, table 1.
Certain combinations of medicines (prescription or otherwise) cause side effects that do not
arise when the individual substances are taken alone. Studies published over the past two
decades suggest that such “drug interactions” cause more than 30 percent of side effects
from medications.
Each millilitre of blood contains ten million B cells, the white blood cells that are associated
with the immune response. It is estimated that this would be enough to cope with thousands
of vaccines at a time, meaning that a baby’s immune system is not stretched at all by
receiving several vaccines at once.
Page Name (from Hebrew): Archive:
Common Questions http://archive.is/t2klK
Website:
“Vaccines” website of Wolfson Hospital
http://chisunim.co.il/Claim.aspx?cat=1&id=3&l=1
“Another common claim is that vaccines cause an unbearable burden on the immune system.
The addition of new vaccines only increases this concern. In reality, a baby's immune
system can respond to about 100,000 different organisms (bacteria, viruses, etc.). Therefore,
vaccinating against 10 organisms will use 0.01% of the active immune capacity."
93 | Chapter 7: Unsubstantiated Guidelines
20 Document Name:
INFANRIX-IPV-HIB Package Insert
https://drive.google.com/open?id=1L7FcWdJOT8-h8m4na4uSVtKuagBdK1gA
P 3.
21-31
21 Document Name:
Vaccines When Your Child Is Sick
https://www.cdc.gov/vaccines/hcp/patient-ed/conversations/downloads/fs-child-sick.pdf
Author/Year: Archive:
CDC, 2014 https://drive.google.com/open?id=1rqg7CK6-
Y8kXI_JWEQmKYEsLXNpKWr9z
P 1:
vaccines do not make a mild illness worse
P 2:
Vaccines are safe and effective when given to children with mild illness
22 Document Name:
Vaccines When Your Child Is Sick
https://www.cdc.gov/vaccines/hcp/patient-ed/conversations/downloads/fs-child-sick.pdf
Author/Year: Archive:
CDC, 2014 https://drive.google.com/open?id=1rqg7CK6-
Y8kXI_JWEQmKYEsLXNpKWr9z
P 1:
There is no health benefit to waiting to vaccinate your child if he or she has a mild illness.
It’s important that children get their vaccines on time—even if they don’t feel well—so
they’re protected against serious diseases.
94 | Chapter 7: Unsubstantiated Guidelines
There is no confirmation in the study that any of the children were actually ill at the time of
immunization, and no way of knowing whether these children had taken antipyretic
medications to appear to have only mild illness.
P 3:
Finally, Canadian immunization guidelines indicate that children are to be vaccinated
between 12 and 15 months of age. This study took patients between 15 and 23 months.
Although 40% of the patients were 15 months old, most were older.
Participants in the study will be monitored by telephone contacts on days 7, 14, and 42 after
each dose and within 48 to 72 hours of each dose of the rotavirus vaccine regarding any
serious adverse events.
Or, influenza vaccine trial - Archive:
Page Name: http://archive.is/zIgcr
Immunogenicity and Safety of a Trivalent Inactivated
Influenza Vaccine, Formulation 2010-2011, in Healthy
Subjects Aged Over 6 Months Old to 18 Years Old
Website:
clinicaltrials.gov
https://clinicaltrials.gov/ct2/show/NCT01356342
All participants will be followed, either by clinical visit or by telephone contact, for 6
months after the first vaccination for safety reasons.
Chapter 8: The Disappearance Of Disease
1-20
1 Article Name: Archive:
The Importance of Social Intervention in Britain's https://drive.google.com/open
Mortality Decline c.1850-1914: a Re-interpretation of the ?id=1c8AaRwdKf2O1On-
Role of Public Health VT0pI34G8xCEBWOIj
https://pdfs.semanticscholar.org/a350/8f97eff18b8cffb5ccd
8c87feda108895c58.pdf
3 Article Name:
Reasons for the Decline of Mortality in England and Wales during the Nineteenth Century
https://www.jstor.org/stable/2173119
Lead Author/Year: Journal:
Thomas McKeown , 1962 Population Investigation Committee
P 7:
Since 1837 knowledge of the birth rate and the death rate of England and Wales has been
available from national sources.
98 | Chapter 8: The Disappearance Of Disease
4 Article Name:
An Interpretation of the Modern Rise of Population in Europe
https://www.jstor.org/stable/2173815
Lead Author/Year: Journal:
Thomas McKeown , 1972 Population Investigation Committee
P 6:
The nature of infectious disease was not understood before 1850; infectious organisms
affecting man were not identified until the last quarter of the nineteenth century, and specific
prevention or treatment is unlikely to have had much influence on the national death rate
before the introduction of chemotherapy in the nineteen thirties.
7 Article Name:
An Interpretation of the Decline of Mortality in England and Wales during the Twentieth
Century
http://www.jstor.org/stable/2173935
20 Colgrove 2002 (see reference 88 of this chapter) details the arguments made
against McKeown's work, especially p 3. Szreter also (Szreter 1988 p 6 and 11)
does not criticize the quality of McKeown's data.
21-40
21 Abbreviated Name: Archive:
Szreter 1988 https://drive.google.com/open?id=1c8AaRwdKf2O1On-
VT0pI34G8xCEBWOIj
P 2-3:
It should be stressed at the outset that this achievement of McKeown's work, in deflating the
historical claims of one particular section of the medical profession and its 'high tech'
invasive and biochemical medicine, remains unaffected by the arguments set out below.
McKeown's unanswerable point is precisely that this modern kind of applied medical
science virtually did not exist during the period addressed here.
and P 9:
The chapter then proceeded to demonstrate for each of the major diseases in turn that, with
the exception of smallpox and diphtheria, the dates at which either effective immunization
procedures or scientific medical treatments first became available were often far too late in
time to be able to account for all but the last few percentage points of the overall decline of
the disease. This was certainly true of respiratory tuberculosis, measles, and scarlet fever;
and broadly true for whooping cough and the bronchitis, pneumonia, and influenza group.
All had been declining very considerably in incidence long before effective chemotherapy or
other scientific techniques had become available.
Lead Author/Year:
CDC, 1980
P 5:
In 1893, an act provided for collection of information on a weekly basis… It was not until
1925, however, that that all states began to report regularly.
Website:
NHS
http://www.nhs.uk/conditions/diphtheria/pages/introduction.aspx
Before a vaccination programme was introduced in 1940, diphtheria was a very common
condition and one of the leading causes of death in children.
41-60
41 Page Name: Archive:
Notifiable diseases: historic annual totals http://archive.is/2zzwJ
Cases of infectious diseases: annual total figures from 1912 to
2017
https://www.gov.uk/government/publications/notifiable-diseases-
historic-annual-totals
Website:
GOV.UK
42 See official morbidity data - US (note 39) and UK (note 41). Typhoid fever also
appears in the table under the names Paratyphoid fevers and Enteric fever.
43 Book Title:
Vaccines (6th edition)
Published by Elsevier Saunders
https://www.elsevier.com/books/vaccines/plotkin/978-1-4557-
0090-5
Lead Author/Year:
Stanley Plotkin, 2013
P 789:
There probably is no other widely used vaccine that is as controversial as BCG. Its effects in
extremely large, randomized, controlled, and case-control studies have been widely
disparate, in some cases demonstrating a great degree of protection and in others offering no
benefit.
46 Book Title:
Vaccines (6th edition)
Published by Elsevier Saunders
https://www.elsevier.com/books/vaccines/plotkin/978-1-4557-
0090-5
Lead Author/Year:
Stanley Plotkin, 2013
P 789:
The bacille Calmette-Gurin (BCG) vaccines […] have been used routinely since the 1960s
in almost all countries of the world except the United States and the Netherlands.
Website:
Public Health England
51 Book Title:
Corn and Capitalism: How a Botanical Bastard Grew to Global Dominance
https://books.google.co.il/books?id=cRnjAQAAQBAJ&pg=PA172#v=onepage&q&f=false
Lead Author/Year:
Arturo Warman, 2003
P 171-172:
In 1915 the number of the stricken was estimated at between 75,000 and 160,000.
[…]
The tendency for the number of those affected by pellagra to climb turned the corner during
the same period. In 1940 pellagra sufferers were estimated at fewer than 50,000 and their
numbers fell by half over the next five years. In the 19505 pellagra became a clinical
curiosity, a disease of the past.
52 Book Title:
Vaccines (6th edition)
Published by Elsevier Saunders
https://www.elsevier.com/books/vaccines/plotkin/978-1-4557-
0090-5
Lead Author/Year:
Stanley Plotkin, 2013
P 1407:
There is little doubt that the introduction of routine tetanus toxoid vaccination in the 1940s
had an impact on trends and patterns of the disease. However, because the incidence of
tetanus was declining prior to widespread vaccination, as a result of decreasing exposure
(fewer people in contact with soil and animal feces, which are the main reservoirs of the
tetanus bacillus), and because of the widespread use of tetanus toxoid in wound
management, it is difficult to assess the extent to which routine prophylactic vaccination
contributed to the decline in tetanus morbidity.
61-80
61 Abbreviated Name: Archive:
Burian 2000 https://drive.google.com/open?id=1VPeNmgPhp0L2lxxWa33z
YdLHx3Mx8-fY
P 8:
In the United States, repeated cholera epidemics and other disease outbreaks gradually
influenced municipalities to improve sanitation practices. Between 1832 and 1873,
numerous American cities were afflicted with major outbreaks of disease, including cholera
in 1832, 1849, and 1866 and typhoid in 1848. The causes of the outbreaks were attributed to
a variety of reasons including unsanitary conditions and punishment from God. The
experience gained from the epidemics improved the understanding of cholera and other
diseases and their corresponding etiology.
P 14:
At the end of the nineteenth century, the basic techniques of urban wastewater collection
were established, the sewer technologies were mostly developed, and the necessary
construction materials and equipment were available. By that time, most major U.S. cities
had also constructed some form of a sewer system.
62 Article Name:
The role of public health improvements in health advances: The twentieth-century United
States
https://link.springer.com/article/10.1353/dem.2005.0002
63 Article Name:
The role of public health improvements in health advances: The twentieth-century United
States
https://link.springer.com/article/10.1353/dem.2005.0002
Lead Author/Year: Journal:
David Cutler, 2005 Demography
P 15-16:
A striking finding is that clean water technologies appear to have reduced typhoid fever by
26% initially and by another 65% after five years, leading to its near-eradication by 1936.
P 1:
Manure piles also produced huge numbers of flies, in reality a much more serious vector for
infectious diseases such as typhoid fever than odors. By the turn of the century public health
officials had largely accepted the bacterial theory of disease and had identified the “queen of
the dung-heap” or fly, as a major source. Inventors and city officials devised improved
methods of street cleaning and street sweeping became a major urban expense.
P 2:
If the horse created many problems for the city, it was also true that urban life was
extremely hard on the horse. The average streetcar horse had a life expectancy of about four
years... In 1880, New York City removed 15,000 dead horses from its streets, and late as
1916 Chicago carted away 9,202 horse carcasses. Special trucks were devised to remove
dead horses.
75 Article Name:
Food in 19th-Century American Cities
http://americanhistory.oxfordre.com/view/10.1093/acrefore/978019932
9175.001.0001/acrefore-9780199329175-e-281
P 6:
The summer months were most abundant and diverse, with stone fruits, berries, apples,
tomatoes, watermelons, lettuces, and other warm-weather produce crowding the tables under
the market-house roofs. Food also spoiled quickest in these months, and observers noted the
rapidity with which meat spoiled and vegetables wilted.
P 12:
As for fresh vegetables, they were not commonly consumed in the 1800s, though the diet
expanded to incorporate them by the second half of the century… Fruits also were more
commonly eaten in stewed and dessert forms rather than fresh.
P 3:
The new transportation networks also improved the quality of food entering American
cities… Foods that previously had perished during travel along rudimentary roads now
endured long distances without spoiling. Railroads carried milk from rural areas to far-off
cities, oysters from New York City to Buffalo, wild game from Iowa to Baltimore, salmon
from Maine to Philadelphia, even lobster from the East Coast to Chicago.
81-100
81 Page Name:
About FDA - Part I: The 1906 Food and Drugs Act and Its Enforcement
Archive:
http://archive.is/A0SeF
Website:
FDA
https://www.fda.gov/AboutFDA/History/FOrgsHistory/EvolvingPowers/ucm054819.htm
116 | Chapter 8: The Disappearance Of Disease
101-120
101 Article Name: PMID:
Dynamics of Obesity and Chronic Health 20159870
Conditions Among Children and Youth
https://jamanetwork.com/journals/jama/fullarticl Archive:
e/185391 https://drive.google.com/open?id=1aO
ddhiCdNzVF9PStJPMYU-
8lmuyhLDRY
Lead Author/Year: Journal:
Jeanne Van Cleave, 2010 JAMA
P4
Website: Archive:
Wall Street Journal http://archive.is/IGY7m
https://www.wsj.com/articles/SB10001424052970203731004
576046073896475588
Website: Archive:
Reuters http://archive.is/I3rfR
http://www.reuters.com/article/medco-children-
idUSN1924289520100519
121 | Chapter 8: The Disappearance Of Disease
Lead Author/Year:
Israeli Department of Health, 2011
P 236 (Translated from Hebrew):
"In a 2008 survey, 7.9 percent of eighth-graders reported having asthma or spastic
bronchitis at present, and 13.9 percent of Jewish and Arab students reported ever having
asthma or spastic bronchitis."
Lead Author/Year:
Knesset [Israeli Parliamnet] Research Center, 2013
P 2 (from Hebrew):
"Our examination revealed that the education system does not have data on the number of
students diagnosed with ADHD or patients taking Ritalin or its alternatives. The Ministry
of Education publishes general guidelines regarding Ritalin treatment among students in
schools, but emphasizes that this issue is the responsibility of the Ministry of Health. The
Ministry of Health does not have accurate information on the number of students
diagnosed with ADHD or on the number of students treated with Ritalin.”
Lead Author/Year:
Israeli Ministry of Health, 2010
Slide 7:
1,044 children up to the age of 18 were hospitalized for a food allergic reaction in 2008
124 | Chapter 8: The Disappearance Of Disease
121-125
121 Article Name: Date:
CDC: Measles Outbreak a 'Wake-Up Call' Jan 29, 2015
Archive:
http://archive.is/5sLoj
Website:
Medpagetoday
http://www.medpagetoday.com/primarycare/vaccines/49786
Anne Schuchat, MD, director of the CDC's National Center for Immunization and
Respiratory Diseases, told reporters on a conference call that 84 people in 14 states have
been diagnosed with measles so far in 2015 and, of them, 67 are linked to the Disneyland
outbreak
[…]
The Disneyland-centered outbreak is "a wake-up call" for Americans to be vaccinated so
that future imported cases don't spread.
126 | Chapter 8: The Disappearance Of Disease
P 4:
Additionally, growing public awareness of these conditions coupled with advances in
screening in health care and school settings may identify mildly affected children who in
previous years may have gone undiagnosed, accounting for some of the rapid increase in
overall prevalence.
P 3:
However, premature infants of higher birthweight experience much less longterm
morbidity than in years past, and the absolute numbers of extremely low-birthweight
infants are small (less than 1 percent of all births). Advances in prenatal and newborn
screening for genetic and infectious conditions have also prevented a significant
proportion of intellectual disabilities.
Chapter 9: Herd Immunity
1-20
1 Book Title:
Vaccines (6th edition)
Published by Elsevier Saunders
https://www.elsevier.com/books/vaccines/plotkin/978-1-4557-0090-5
Lead Author/Year:
Stanley Plotkin, 2013
P 1395:
…the concept of herd immunity… refers to the prevalence or proportion of immune persons
in a population… which, if achieved, should lead to the elimination of an infection from a
population.
2 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
Lead Author/Year:
Stanley Plotkin, 2013
P 1395:
herd immunity, a term that refers to… indirect protection of nonimmune persons,
attributable to the presence and proximity of immune persons.
3 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
Lead Author/Year:
Stanley Plotkin, 2013
P 1396:
if an infection or vaccine induces some degree of immunity against infection, then some
nonimmune people will be protected indirectly, by the presence and proximity of immune
persons, and transmission should stop in a population prior to the infection of all susceptible
individuals.
4 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
For example, exposure to the measles virus results in lifelong immunity.
P 1403:
One of the remarkable observations about measles is that immunity induced by natural
infection appears to remain strong for life: thus, Panum observed that individuals exposed to
measles in 1781 in the Faroe Islands were still immune when the virus was next introduced,
65 years later, in 1846.
128 | Chapter 9: Herd Immunity
5 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
For example, immunity to the Hib bacterium, P 1406:
The absence of disease in the neonatal period is a result of maternal antibody, passed to the
infant either transplacentally or via breast milk. As infant antibody levels fall, susceptibility
rises…
6 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1397-1398.
7 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1406:
If a vaccine were to protect only against disease, and not at all against infection, then it
would have no influence on infection transmission in the community and there would be no
indirect protection (vaccination of one person would have no influence on any others in the
community). It would be possible to reduce disease with such a vaccine but not to eradicate
the infection.
8 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 748:
The most common source of environmental exposure to C. tetani bacilli and spores is soil,
where the organism is widely but variably distributed.
9 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 756:
Immunization histories were reported for 986 (49%) of the tetanus cases reported from 1972
to 2009 (Centers for Disease Control and Prevention, unpublished data). Of those 986 cases,
163 (16%) had received at least a three-dose primary series of tetanus toxoid before onset of
tetanus; 62 (6%) reported that the last dose of tetanus toxoid was received less than 10 years
before the illness.
10 Page Name:
Notifiable diseases: historic annual totals
Website:
GOV.UK
https://www.gov.uk/government/publications/notifiable-diseases-historic-annual-totals
For example, in the UK, an average of 5 cases of tetanus were recorded each year in 2001-
2015. Official UK (England-Wales) morbidity data on the UK Ministry of Health website.
Document Name: Archive:
Infectious diseases requiring notification in https://drive.google.com/open?id=1QEXa9
Israel ZV_xDKvAdsUhN4ByWAfc7FbMjsH
Author/Year:
Israeli Ministry of Health, 2012
P 56:
In Israel, less than one case per year was recorded between 1990-2010.
129 | Chapter 9: Herd Immunity
11 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1396:
The focal point of much of the theoretical work on community immunity has been the
recognition that, if an infection or vaccine induces some degree of immunity against
infection, then some nonimmune people will be protected indirectly, by the presence and
proximity of immune persons, and transmission should stop in a population prior to the
infection of all susceptible individuals.
13 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1395:
The social benefits of such indirect protection have important policy implications, including
provision of a rationale for mandating immunization.
Website:
Daily Mail
https://www.dailymail.co.uk/wires/ap/article-4739388/Italy-approves-hotly-contested-
vaccine-program.html
Under Italy’s new requirements, parents must present proof of vaccinations to gain
admission into preschools, while parents of children of mandatory school age face fines of
up to 500 euros ($588) for noncompliance. The requirements cover 10 vaccinations,
including diphtheria, tetanus, measles, mumps, rubella and chicken pox.
Page Name: Archive:
The 11 vaccines set to become compulsory in France and why http://archive.is/XRzRu
French doctors are firmly in favour
Website:
TheLocal.fr
https://www.thelocal.fr/20170705/these-are-the-eleven-vaccines-that-will-be-compulsory-
in-france-from-2018
Three vaccines: diptheria, tetanus and polio are already obligatory but from 2018 these will
be joined by eight more: whooping cough, measles, mumps, rubella, hepatitus B, influenza,
pneumonia and meningitis C.
Website:
Vaccines
http://chisunim.co.il/Article.aspx?id=28
In the State of Israel, there is no legal obligation to vaccinate. Until a few years ago, it
seemed that there was no need for such legislation due to the high rate of immunization of
children in Israel, which was among the highest in the world.
However, due to an increase in the rate of those who oppose vaccines, this issue is expected
to come up.
17 Document Name:
PREVNAR Package Insert
https://drive.google.com/open?id=1VLR6NluMGK0E4yXUZM18IpUpi_MI7-MP
Number of participants in the clinical trial - p. 3. Number of cases avoided (of all
strains) - Table 1, p. 4 (per protocol).
18 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1396:
The focal point of much of the theoretical work on community immunity has been the
recognition that, if an infection or vaccine induces some degree of immunity against
infection, then some nonimmune people will be protected indirectly, by the presence and
proximity of immune persons, and transmission should stop in a population prior to the
infection of all susceptible individuals. This insight encourages the estimation of threshold
numbers or proportions of immune persons necessary for this cessation to occur.
19 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 400:
The elegant theory just summarized is built on extreme assumptions: that all individuals mix
at random, that individuals are either fully susceptible or fully immune, and that the
population is uniform (ie, that all individuals behave the same way and all infected
individuals are equally infectious). These assumptions are unlikely to hold for any infection
in any human population.
20 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1401.
21-40
21 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1403:
Published estimates of herd immunity thresholds required to eradicate measles have ranged
from 55% to 96%, depending on the modeling approach and the assumptions employed (eg,
whether age or seasonality of transmission was included). The logic and the flaws
underlying the various estimates have been discussed elsewhere.
22 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1405:
Published estimates of a crude herd immunity threshold for diphtheria have ranged from
50% to 90%.
132 | Chapter 9: Herd Immunity
23 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1404:
Several investigations have concluded that, for the incidence of CRS to decrease in the long
term, the minimal vaccination coverage that must be achieved and maintained in young
children of both sexes is in the region of 50% to 80%.
24 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1411:
The herd immunity threshold concept provides an epidemiologic attribute with which to
characterize particular infections. Although precision may not be possible because of
population heterogeneities or because of variability in the immune status of individuals—the
crude thresholds are naively optimistic in practice—even crude estimates can be of use in
giving a rough guideline for predicting the impact of a vaccination program and at least a
hint as to the potential for eradication.
25 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1402:
If a vaccine were to protect only against disease, and not at all against infection, then it
would have no influence on infection transmission in the community and there would be no
indirect protection (vaccination of one person would have no influence on any others in the
community). It would be possible to reduce disease with such a vaccine but not to eradicate
the infection.
26 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 746:
Tetanus is unique among vaccine-preventable diseases in that it is not communicable.
Clostridium tetani, the causative agent of tetanus, is widespread in the environment; many
animals in addition to humans can harbor and excrete the organism and its spores. When
spores of C. tetani are introduced into the anaerobic conditions found in devitalized tissue or
punctures, they germinate to vegetative bacilli that elaborate toxin. The clinical presentation
results from the actions of this toxin on the central nervous system (CNS). Many animal
species besides humans are susceptible to the disease.
27 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 752-754:
A decline in tetanus incidence in industrialized countries began in the early 1900s. By the
mid-1930s, many European countries had tetanus mortality rates of less than 1 per 100,000
Factors that contributed to the decline included urbanization, mechanization of agriculture,
adoption of aseptic surgical and medical techniques, hygienic childbirth and wound care
practices, use of prophylactic tetanus antitoxin, and, ultimately, use of antibiotics.
[…]
Historically, tetanus was a dreaded consequence of war, with incidence rates on the order of
two cases per 1,000 injured troops;
[…]
In 1947, when national reporting began, the incidence of reported cases was 0.39 per
100,000.
133 | Chapter 9: Herd Immunity
28 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1407:
Clostridium tetani is not communicable between human hosts, and thus vaccination cannot
lead to indirect protection in the sense implied in many definitions of herd immunity.
Certainly there is no threshold proportion of immune persons, below 100%, that can ensure
total absence of tetanus from a community.
29 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1407:
It appears that wild-type polioviruses ceased to circulate in most of the United States by
1970, at which time only some 65% of children were receiving a complete course of OPV.
However, given the complex history of previous IPV and then OPV programs in the
country, and the propensity of OPV—let alone wild—viruses to circulate in the community,
the actual level of immunity in the population at that time is unknown.
It is also possible that the disappearance of wild-type polioviruses from the United States
and other countries employing OPV has resulted not only from the achievement of some
herd immunity threshold, but also from the competition for ecologic space between the wild-
type viruses and the constantly introduced vaccine strains.
31 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1407:
…there is good epidemiologic evidence for indirect protection by IPVs. Countries that have
used only IPV (eg, Sweden, Finland, and the Netherlands) experienced elimination of
circulating wild-type polioviruses for long periods of time.
134 | Chapter 9: Herd Immunity
32 Document Name:
Polio - The Beginning Of The End
Author/Year: Archive:
WHO, 1997 https://drive.google.com/open?id=1r0R4dlS
UiB6jOtNta-FvrKDD-gFlzW9h
P 20:
Inactivated polio vaccine (IPV) works by producing protective antibodies in the blood—thus
preventing the spread of poliovirus to the central nervous system. However, it induces only
very low- level immunity to poliovirus inside the gut. As a result, it provides individual
protection against polio paralysis but only marginally reduces the spread of wild poliovirus.
In a person immunized with IPV, wild virus can still multiply inside the intestines and be
shed in stools. Because of this, IPV could not be used to eradicate polio.
33 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 631:
Continued use of OPV will induce effective intestinal immunity, thereby enhancing
community resistance to transmission of imported wild poliovirus.
34 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1407:
…live poliovirus vaccine virus is excreted in the feces and by the oropharynx in sufficient
quantities for it to be transmitted to contacts. This unique attribute of OPV provides a
special mechanism for indirect protection of non-vaccinees—in effect by vaccinating them
surreptitiously.
Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 492:
Humans are the only reservoir for pertussis, and chronic carriage is not known to occur. In
principle, then, pertussis can be eradicated.
41-60
41 Abbreviated Name: Archive:
Warfel 2014 https://drive.google.com/open?id=1XSP3srb
YjgMOiC1TtGMRMQpl2SQDHRDr
P 2:
To assess the ability of vaccination to prevent pertussis infection by transmission, two aP-
vaccinated animals and one unvaccinated animal were cohoused with a directly challenged,
unvaccinated animal. Similar to our previous findings (18), all animals became colonized 7–
10 d after cohousing with the infected animal.
immunologic surrogate by which to bridge these vaccine classes. Had carriage studies been
conducted in parallel with wP introductions, then this might have provided supportive
evidence that infections were being blocked. But carriage studies were not done. Rather, it
was assumed that because wP vaccines appeared to confer herd immunity, they therefore
blocked carriage.
54 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 471-472.
55 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1405:
It is hoped thereby to prevent infection transmission to young infants, in whom the disease is
most severe. This has been extended to selective vaccination of parents and others in contact
with young infants, a strategy known as cocooning, yet another approach to manipulating
the community distribution of immunity.
A: […] Since pertussis spreads so easily, vaccine protection decreases over time, and
acellular pertussis vaccines may not prevent colonization (carrying the bacteria in your body
without getting sick) or spread of the bacteria, we can't rely on herd immunity to protect
people from pertussis.
60 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 155:
The entire operon is under the control of a repressor gene, dtxR, which in the presence of
iron binds to and inhibits the tox gene; toxin is produced only under low-iron conditions.
61-80
Author/Year:
61 Document Name:
CDC Pink Book - Diphtheria CDC, 2011
https://drive.google.com/file/d/1RHDvQU2YyPDfIcv-
qiEC9LPBMM22GEwo/view?usp=sharing
P 75:
Only toxigenic strains can cause severe disease.
62 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 154:
…the frequency of these various complications appears to vary considerably between
epidemics, for which no clear explanation is available.
63 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 157:
The precise microbial events responsible for the transmission of diphtheria remain unclear.
141 | Chapter 9: Herd Immunity
Author/Year:
64 Document Name:
CDC Pink Book - Diphtheria CDC, 2011
https://drive.google.com/file/d/1RHDvQU2YyPDfIcv-
qiEC9LPBMM22GEwo/view?usp=sharing
P 81.
65 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1405:
The protection against disease imparted by diphtheria toxoid vaccines has never been
evaluated in formal trials, although observational studies provide estimates ranging from
55% to 90%.
Journal: Archive:
British Journal of Nursing https://drive.google.com/open?id=1INU0IsP
giT4WVNMXUMKj7cT9ZmPtzcnM
P 1:
Immunisation affords a good degree of protection, though not complete protection, against
an attack of diphtheria. It affords a very high degree of protection indeed against the risk of
death from diphtheria. Immunised people, if they get diphtheria, nearly always get it very
lightly.
[…]
A child who has been immunised is about four times less likely to catch diphtheria, and
about 25 times less likely to die from it than one who has not.
Author/Year:
67 Document Name:
CDC Pink Book - Diphtheria CDC, 2011
https://drive.google.com/file/d/1RHDvQU2YyPDfIcv-
qiEC9LPBMM22GEwo/view?usp=sharing
P 78.
68 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 156:
Although diphtheria antitoxin is the mainstay of diphtheria therapy, penicillin or,
alternatively, erythromycin should be given to hasten clearance of the organism, prevent
transmission, and cease further production of diphtheria toxin… Before the development of
antibiotic therapy, convalescent carriage of toxigenic organisms was a major problem. Up to
50% and 25% of patients continued to harbor the organism 2 and 4 weeks after onset,
respectively. As late as 2 months after onset, reported carriage rates varied between 1% and
8%.
Author/Year:
69 Document Name:
CDC Pink Book - Diphtheria CDC, 2011
https://drive.google.com/file/d/1RHDvQU2YyPDfIcv-
qiEC9LPBMM22GEwo/view?usp=sharing
P 79, 84.
142 | Chapter 9: Herd Immunity
71 Abbreviated Name:
Miller 1972
P 3:
In 1936, Frost et al alluded to a paucity of observations on record concerning antitoxic
immunity and the carrier state. Nonetheless, he stated that the limited data suggested that
there is little, if any, difference between those individuals with and those without antitoxic
immunity in their risk of becoming infected. […] The findings in Elgin corroborate the
assumptions of Frost et al and show that there is no difference in the risk of diphtheria
acquisition among those with full, lapsed, inadequate, and no immunizations.
72 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1406:
Given that diphtheria toxin is not a constituent of Corynebacterium diphtheriae per se, but
exists as a consequence of bacteriophage infection, the immunity induced by toxoid
vaccination may not provide protection against infection at all. However, toxoid vaccines do
protect against toxin mediated disease, and transmission of the diphtheria bacillus is more
efficient from clinical patients than from subclinical carriers - thus the toxoid vaccines may
protect against infectiousness and infection transmission, but not (or more than) against
infection receipt… This may have been an important contributor to the disappearance of
diphtheria in vaccinated populations.
73 Article Name:
The Epidemiological Importance Of Diphtheria Carriers
https://academic.oup.com/aje/article-abstract/5/4/508/149362?redirectedFrom=fulltext
P 20:
After making necessary allowance for differences in age-distribution of the two groups of
contacts, it is a conservative estimate to state that the risk of attack is ten times as great for
family contacts of cases as for those in similar association with known bacillus carriers.
74 Abbreviated Name:
Doull 1925
P 1:
…and as carriers are much more numerous than clinically recognizable cases, and are for the
most part subject to no restriction of their intercourse with the general public, it is
reasonable to infer that they may be, in the aggregate, the most frequent sources of clinical
infection.
75 Abbreviated Name:
Doull 1925
P 2:
A similar conclusion is indicated by the results of attempts to trace the sources of infection
of recognized cases. For example, in a study of some 500 cases reported in a limited section
of Baltimore, investigators from this school have been able to find evidence of prior
association with recognized or even suspected cases of clinical diphtheria in only about 20
per cent, of the cases investigated. Making all due allowance for the imperfections of such
an investigation, it still appears that a large proportion of the cases investigated must have
contracted their infections from unrecognized clinical cases or from carriers.
76 Abbreviated Name:
Doull 1925
P 20:
It seems impossible to explain the general distribution of diphtheria and the usual absence of
traceable lines of contact from clinical cases on any other hypothesis except that infection is
spread largely by carriers.
77 Abbreviated Name:
Miller 1972
P 2:
Throat cultures were done on 306 children and staff; toxigenic C diphtheriae, gravis type,
was isolated from 104 (34%). Fifteen of these (14%) were cases, and 89 (86%) were
carriers. There was no statistical difference in the risk of diphtheria infection among those
with full, lapsed, inadequate, or no previous diphtheria immunization.
78 Abbreviated Name:
Miller 1972
P 3:
Recent epidemics in Austin and Elgin Texas, provided ample evidence that carriers continue
to play a very important role in the transmission of diphtheria.
79 Abbreviated Name:
Miller 1972
P 3:
However, diphtheria outbreaks have been described in populations with as much as 94% of
the people being previously immunized. These outbreaks, the known importance of carriers
in the spread of diphtheria, and the demonstrated failure of toxoid to prevent the carrier state
144 | Chapter 9: Herd Immunity
lead us to conclude that the concept of herd immunity is not applicable in the prevention of
diphtheria
81-100
81 Abbreviated Name:
Chen 1985
P 3:
The decline in diphtheria incidence in the United States during 1971-81 occurred despite
serologic studies during the 1970s showing subprotective serum diphtheria antitoxin levels
in approximately 25 per cent of the children and 75 per cent of the adults tested in three US
cities.
Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 165:
Despite the relatively low levels of immunity among adults in many countries, diphtheria
has remained well controlled in most countries with effective childhood immunization
programs… Serologic studies in Europe and the United States have demonstrated that many
adults in these countries remain susceptible to diphtheria.
145 | Chapter 9: Herd Immunity
82 Abbreviated Name:
Chen 1985
P 3:
The frequency of diphtheria carriage in the United States is not known accurately.
83 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 1405:
Estimates aside, the proportion of the population actually immune to diphtheria today is
elusive. Vaccine coverage is difficult to define because it has varied over time, and because
at least three doses are recommended, although one or two provide some protection.
85 Abbreviated Name:
Karelitz 1947
P 10:
Patients with faucial diphtheria treated with antitoxin and penicillin… were rendered
diphtheria negative more rapidly than were the patients who received antitoxin and no
penicillin. Carriers of virulent C. diphtheria were likewise rendered free of the bacteria by
treatment with penicillin.
86 Abbreviated Name:
Zalma 1970
P 4:
Fourteen of 142 treated carriers (9.9%) were not cleared of C diphtheriae after treatment
with procaine penicillin, administered intramuscularly, 600,000 to 2,000,000 units a day for
seven to ten days, and most were given a course of erythromycin, which eradicated the
organism in every patient.
Abbreviated Name:
Miller 1972
P 3:
At the first appearance of a diphtheria case, control activities should be directed toward
identifying, isolating, and treating carriers, as well as toward immunizing persons with less
than full immunization status. This dual approach will reduce or eliminate the spread of
infection by reducing the number of carriers, and it will reduce the number of cases by
improving the immunization status of exposed individuals.
Author/Year:
87 Document Name:
CDC Pink Book - Diphtheria CDC, 2011
https://drive.google.com/file/d/1RHDvQU2YyPDfIcv-
qiEC9LPBMM22GEwo/view?usp=sharing
P 78-79.
146 | Chapter 9: Herd Immunity
Persons with suspected diphtheria should be given antibiotics and antitoxin in adequate
dosage and placed in isolation after the provisional clinical diagnosis is made and
appropriate cultures are obtained.
[…]
The disease is usually not contagious 48 hours after antibiotics are instituted. Elimination of
the organism should be documented by two consecutive negative cultures after therapy is
completed.
88 Abbreviated Name:
Chen 1985
P 4:
The Rumanian experience lends support for this hypothesis; improved immunization led to a
sharp decline in diphtheria morbidity disproportionate to the actual number of persons with
Schick-proven immunity, and surveillance cultures in epidemic and nonepidemic
communities showed a concomitant drop in the percentage of toxigenic strains from 86 per
cent in 1955-66 to 5 per cent in 1977.
89 Article Name:
Corynebacterium diphtheriae: Microbiological Methods Used in Clinical and
Epidemiological Investigations
https://www.sciencedirect.com/science/article/pii/S058095170870374X
Lead Author/Year:
Alice Saragea, 1979
P 165 (also in the chart on p 166:
1. Epidemiological methods
[…]
(g) Diagnosis, isolation and treatment of contacts (treatment by antibiotics).
91 Abbreviated Name:
Markina 2000
P 2.
92 Abbreviated Name:
Markina 2000
P 7:
The Soviet and Russian experience has been that of persistent circulation of toxigenic strains
of C. diphtheriae and at least two resurgences of diphtheria despite fairly high levels of
vaccine coverage among most childhood age groups.
147 | Chapter 9: Herd Immunity
94 Abbreviated Name:
Vitek 2000
P 2:
Soviet public health officials believed that this tightly controlled system of laboratory and
clinical surveillance would identify individuals needing treatment sufficiently early to avoid
the need for prophylactic antibiotic treatment.
95 Abbreviated Name:
Vitek 2000
P 4:
Prophylactic antibiotics were not given to close contacts of cases or carriers of diphtheria in
a school or work place.
96 Abbreviated Name:
Markina 2000
P 7:
Toxigenic C. diphtheriae continues to circulate throughout the Russian Federation, and
interruption of circulation in most areas is unlikely in the near future.
97 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 260.
98 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 274-279
99 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 292:
However, although it might be assumed that high vaccine coverage in communities would
lead to reduced community transmission and to reductions in severe influenza-related
outcomes, no large prospective study has yet convincingly demonstrated that vaccinating
entire populations, or epidemiologically important subpopulations such as school-age
children, will provide significant protection against influenza-related complications (eg,
death or hospitalization) for other groups.
148 | Chapter 9: Herd Immunity
101-120
101 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 183-188.
Archive:
105 Document Name (in Hebrew):
https://drive.google.com/ope
National Hepatitis Prevention Programs
n?id=1jWjwQsaeXHiqagzxr
http://fs.knesset.gov.il/globaldocs/MMM/40c28d55-f7f7-
2SZXJq6KuBeu78U
e411-80c8-00155d010977/2_40c28d55-f7f7-e411-80c8-
00155d010977_11_7600.pdf
Author/Year:
Flora Koch Davidovich, Knesset Research Center, 2014
Vaccine coverage data and examination of age-specific incidence trends indicate that
incidence declines have occurred with modest levels of coverage and in unvaccinated age
groups, suggesting a strong herd immunity effect.
Author/Year:
108 Document Name:
CDC Pink Book – Hepatitis B CDC, 2011
https://drive.google.com/file/d/1PeVszIcp5GNIES278_QQX
Y8tDo-Vnf3t/view?usp=sharing
P 116-117.
Author/Year:
110 Document Name:
CDC Pink Book – Hepatitis B CDC, 2011
https://drive.google.com/file/d/1PeVszIcp5GNIES278_QQX
Y8tDo-Vnf3t/view?usp=sharing
P 119:
The virus is transmitted by parenteral or mucosal exposure to HBsAg-positive body fluids
from persons who have acute or chronic HBV infection. The highest concentrations of
virus are in blood and serous fluids; lower titers are found in other fluids, such as saliva
and semen. Saliva can be a vehicle of transmission through bites; however, other types of
exposure to saliva, including kissing, are unlikely modes of transmission. There appears to
be no transmission of HBV via tears, sweat, urine, stool, or droplet nuclei.
Archive:
114 Page Name:
http://archive.is/XZzZs
Recommendations of the Immunization Practices Advisory
Committee Prevention of Perinatal Transmission of
Hepatitis B Virus: Prenatal Screening of all Pregnant
Women for Hepatitis B Surface Antigen
Website:
CDC website
https://www.cdc.gov/Mmwr/preview/mmwrhtml/00000036.htm?fref=gc
The estimate is based on pre-vaccine CDC data - below. (Plotkin 2013 mentions
an estimate of 0.6 percent).
Screening the approximately 3.5 million pregnant women per year for HBsAg would
identify 16,500 positive women and allow treatment that would prevent about 3,500
infants from becoming HBV carriers.
Archive:
116 Page Name:
http://archive.is/oOPwj
Hepatitis B virus
Website:
HSE website
http://www.hse.gov.uk/biosafety/blood-borne-viruses/hepatitis-b.htm
The UK is a low prevalence area, with a carriage rate of 0.1-0.5%, although rates may vary
between individual communities.
Archive:
117 Document Name (in Hebrew):
https://drive.google.com/ope
National Hepatitis Prevention Programs
n?id=1jWjwQsaeXHiqagzxr
http://fs.knesset.gov.il/globaldocs/MMM/40c28d55-f7f7-
2SZXJq6KuBeu78U
e411-80c8-00155d010977/2_40c28d55-f7f7-e411-80c8-
00155d010977_11_7600.pdf
Author/Year:
Flora Koch Davidovich, Knesset Research Center, 2014
P 2.
Author/Year:
119 Document Name:
CDC Pink Book – Hepatitis B CDC, 2011
https://drive.google.com/file/d/1PeVszIcp5GNIES278_QQX
Y8tDo-Vnf3t/view?usp=sharing
P 115:
The first recorded cases of “serum hepatitis,” or hepatitis B, are thought to be those that
followed the administration of smallpox vaccine containing human lymph to shipyard
workers in Germany in l883.
121-140
121 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 215:
Infants born to mothers with chronic HBV infection can acquire perinatal HBV infection,
which usually occurs at the time of birth; in utero transmission of HBV is relatively rare
(accounting for < 2% of infections transmitted from mother to infant), and the virus is not
transmitted through breastfeeding.
Website: Archive:
PBS http://archive.is/Z26jo
http://www.pbs.org/newshour/rundown/self-destructing-
syringes-force-safer-injection-practices/
About 40 percent of all injections are given with unsterilized, reused syringes and needles,
reports the World Health Organization. An estimated 1.3 million deaths — and 21.7
million new Hepatitis B infections — occur each year as a result of the unsafe practice.
Archive:
127 Page Name:
http://archive.is/kccin
Hepatitis B Virus: A Comprehensive Strategy for
Eliminating Transmission in the United States Through
Universal Childhood Vaccination: Recommendations of
the Immunization Practices Advisory Committee (ACIP)
Website:
CDC website
https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm?fref=gc
Section: EPIDEMIOLOGY AND PREVENTION OF HEPATITIS B
VIRUS INFECTION
Infections among Infants and Children
Archive:
130 Document Name:
https://drive.google.com/open?id=
Unusual Cases of Hepatitis B Virus Transmission in
the Community 1tNQw80K3IY-
http://www.immunize.org/catg.d/p2100.pdf FNOoaAcxrDe2oVmt0bb5p
Author/Year:
Immunize.org
Author/Year:
132 Document Name:
CDC Pink Book – Rotavirus CDC, 2011
https://drive.google.com/file/d/17oSPucPglFR3-
n79hEokf30r1Rtr4-PT/view?usp=sharing
P 244-246.
Author/Year:
133 Document Name:
CDC Pink Book – Rotavirus CDC, 2011
https://drive.google.com/file/d/17oSPucPglFR3-
n79hEokf30r1Rtr4-PT/view?usp=sharing
P 265.
Author/Year:
134 Document Name:
CDC Pink Book – Rotavirus CDC, 2011
https://drive.google.com/file/d/17oSPucPglFR3-
n79hEokf30r1Rtr4-PT/view?usp=sharing
P 264:
After a single natural infection, 38% of children are protected against any subsequent
rotavirus infection, 77% are protected against rotavirus diarrhea, and 87% are protected
against severe diarrhea. Reinfection can occur at any age.
[…]
The first infection after 3 months of age is generally the most severe.
P 270:
In addition, infants may experience multiple episodes of rotavirus diarrhea because the
initial infection may provide only partial immunity.
Author/Year:
135 Document Name:
CDC Pink Book – Rotavirus CDC, 2011
https://drive.google.com/file/d/17oSPucPglFR3-
n79hEokf30r1Rtr4-PT/view?usp=sharing
P 266:
154 | Chapter 9: Herd Immunity
Rotavirus infection is not nationally notifiable in the United States. Estimates of incidence
and disease burden are based on special surveys, cohort studies, and hospital discharge
data. In the prevaccine era an estimated 3 million rotavirus infections occurred every year
in the United States and 95% of children experienced at least one rotavirus infection by
age 5 years. The incidence of rotavirus is similar in developed and developing countries,
suggesting that improved sanitation alone is not sufficient to prevent the infection.
Author/Year:
136 Document Name:
CDC Pink Book – Rotavirus CDC, 2011
https://drive.google.com/file/d/17oSPucPglFR3-
n79hEokf30r1Rtr4-PT/view?usp=sharing
P 266.
Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 674:
These estimates, prior to the use of rotavirus vaccines, indicated that by the end of the
second or third year of life, 60% to 80% of all children developed a rotaviral diarrheal
illness (approximately 2.7 million episodes per year), 1 in 6.5 sought medical attention, 1
in 70 (55,000 to 70,000 patients) were hospitalized, and 1 in 66,000 to 1 in 200,000 (20 to
60 children) died as a result of the rotavirus.
Archive:
138 Page Name (Hebrew):
http://archive.is/lpSxT
Rotavirus
Website:
Israeli Ministry of Health
https://www.health.gov.il/Subjects/pregnancy/Childbirth/Vaccination_of_infants/Pages/Ro
ta_Virus.aspx
The history of the disease in Israel
Before the vaccine existed, the virus caused 4,400 hospitalizations of children a year in
Israel. Death from this virus is common in developing countries and very rare in developed
countries and in Israel.
Several countries that have introduced rotavirus vaccines in their national childhood
immunization programs have already seen remarkable declines in severe rotavirus
gastroenteritis after vaccine introduction.
141-160
141 Article Name:
Rotavirus vaccination and herd immunity: an evidence-based review
https://www.dovepress.com/rotavirus-vaccination-and-herd-immunity-an-evidence-based-
review-peer-reviewed-article-PHMT
assumption may need reassessment. Studies in a variety of settings have shown evidence
of greater than expected declines in rotavirus disease.
Author/Year:
154 Document Name:
CDC Pink Book – Pneumococcal Disease CDC, 2011
https://drive.google.com/file/d/17nHF95iC1QlRcMYqUT-
j5b6ThstrdL2d/view?usp=sharing
P 233, 237.
Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 506-507.
158 | Chapter 9: Herd Immunity
Author/Year:
158 Document Name:
CDC Pink Book – Pneumococcal Disease CDC, 2011
https://drive.google.com/file/d/17nHF95iC1QlRcMYqUT-
j5b6ThstrdL2d/view?usp=sharing
P 238-240.
161-180
161 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 529:
Thus, as for direct effect of PCV7s on carriage, an overall reduction of carriage of VT
serotypes can be attributed to PCVs, with a parallel increase in non-VT serotypes (termed
replacement). This phenomenon is expected to be of great magnitude, resulting in herd
immunity against vaccine serotype disease on the one hand, but a potential for replacement
disease on the other hand.
Author/Year:
163 Document Name:
CDC Pink Book – Pneumococcal Disease CDC, 2011
https://drive.google.com/file/d/17nHF95iC1QlRcMYqUT-
j5b6ThstrdL2d/view?usp=sharing
P 239:
In 2010 a 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United
States. It contains the 7 serotypes of S pneumonia as PCV7 plus serotypes 1, 3, 5, 6A, 7F
and 19A… ABCs data indicate that in 2008, a total of 61% of invasive pneumococcal
disease cases among children younger than 5 years were attributable to the serotypes
included in PCV13…
Author/Year:
165 Document Name (Hebrew):
Immunization Guide Israeli Ministry of Health, 2015
https://drive.google.com/open?id=1db5nqObGNR
g8QwTaOUuTARsisHlPrf4U
P 10.
P 4:
In 2011, PCV13 coverage reached nearly 90% on a national basis... The hospitalization
rates for pneumococcal pneumonia and the incidence rates of invasive disease in the
elderly population have remained stable or increased over the past decade, suggesting that
the indirect benefit of routine infant vaccination did not occur in this age group Not yet
published preliminary analyses by Martinelli et al. seem to indicate that in Italy more than
65% of pneumococcal pneumonia cases in older adults were caused by the serotypes
targeted by PCV13.
Denmark and UK - PMID:
Article Name: 28032483
Indirect Effects of Pneumococcal Conjugate Vaccines
Archive:
in National Immunization Programs for Children on
https://drive.google.com/open?i
Adult Pneumococcal Disease
d=1UmSJwz1som0iOzgCG0xX
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52040 UVBJ_WipDBsH
04/pdf/ic-48-257.pdf
Lead Author/Year: Journal:
Young Keun Kim , 2016 Infection & Chemotherapy
P 4.
P 4:
The hospitalization rates for pneumococcal pneumonia and the incidence rates of invasive
disease in the elderly population have remained stable or increased over the past decade,
suggesting that the indirect benefit of routine infant vaccination did not occur in this age
group.
[…]
In Italy, even after pediatric vaccination with PCVs, vaccine serotypes are still responsible
for most pneumonia and invasive diseases in the elderly population.
vaccinated carriers, which will influence the success of current vaccine strategies and must
be taken into account when future strategies are developed.
Author/Year:
176 Document Name:
CDC Pink Book – Haemophilus influenzae type b CDC, 2011
https://drive.google.com/file/d/1WJ4IgC2gyzbnSvpmr6I5p
OZMPGnuFj-V/view?usp=sharing
P 88-91.
Author/Year:
178 Document Name:
CDC Pink Book – Haemophilus influenzae type b CDC, 2011
https://drive.google.com/file/d/1WJ4IgC2gyzbnSvpmr6I5p
OZMPGnuFj-V/view?usp=sharing
P 88-90.
Author/Year:
179 Document Name:
CDC Pink Book – Haemophilus influenzae type b CDC, 2011
https://drive.google.com/file/d/1WJ4IgC2gyzbnSvpmr6I5p
OZMPGnuFj-V/view?usp=sharing
P 91.
164 | Chapter 9: Herd Immunity
181-200
Author/Year:
181 Document Name:
CDC Pink Book – Haemophilus influenzae type b CDC, 2011
https://drive.google.com/file/d/1WJ4IgC2gyzbnSvpmr6I5p
OZMPGnuFj-V/view?usp=sharing
P 91, 93.
Archive:
187 Page Name:
https://web.archive.org/web/20180907094136/
Chickenpox Prevention and Treatment
https://www.cdc.gov/chickenpox/about/preven
tion-treatment.html
Website:
CDC
https://www.cdc.gov/chickenpox/about/prevention-treatment.html
Use non-aspirin medications, such as acetaminophen, to relieve fever from chickenpox.
Do not use aspirin or aspirin-containing products to relieve fever from chickenpox. The
use of aspirin in children with chickenpox has been associated with Reye’s syndrome, a
severe disease that affects the liver and brain and can cause death.
Author/Year:
200 Document Name:
CDC Pink Book – Rubella CDC, 2011
https://drive.google.com/file/d/11JSySIkEL9HODpfuTATai
JQwWXlIwJyK/view?usp=sharing
P 275-279.
201-220
Author/Year:
201 Document Name:
CDC Pink Book – Rubella CDC, 2011
https://drive.google.com/file/d/11JSySIkEL9HODpfuTATai
JQwWXlIwJyK/view?usp=sharing
P 276-277.
Author/Year:
202 Document Name:
CDC Pink Book – Rubella CDC, 2011
https://drive.google.com/file/d/11JSySIkEL9HODpfuTATai
JQwWXlIwJyK/view?usp=sharing
P 279.
Author/Year:
208 Document Name:
CDC Pink Book – Rubella CDC, 2011
https://drive.google.com/file/d/11JSySIkEL9HODpfuTATai
JQwWXlIwJyK/view?usp=sharing
P 281:
Follow-up studies indicate that one dose of vaccine confers long-term, probably lifelong,
protection.
Author/Year:
209 Document Name:
CDC Pink Book – Rubella CDC, 2011
https://drive.google.com/file/d/11JSySIkEL9HODpfuTATai
JQwWXlIwJyK/view?usp=sharing
P 276:
Prevention of CRS is the main objective of rubella vaccination programs in the United
States.
Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 710:
The goal of rubella vaccination programs is the prevention of the intrauterine infection that
causes CRS, and, incidentally, the occasional complication of the disease in adults
169 | Chapter 9: Herd Immunity
221-240
221 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 437-438.
171 | Chapter 9: Herd Immunity
Author/Year:
227 Document Name:
CDC Pink Book – Measles CDC, 2011
https://drive.google.com/file/d/1Yh8xUeOHSeX78GGs8Dd
WDFCm-hiKlSDz/view?usp=sharing
P 177-178.
Archive:
231 Page Name:
http://archive.is/cTbrj
Complications of measles
Website:
CDC
https://www.cdc.gov/measles/about/complications.html
For every 1,000 children who get measles, one or two will die from it.
Archive:
232 Page Name:
http://archive.is/8YVzg
Measles notifications and deaths in England and Wales:
1940 to 2016
https://www.gov.uk/government/publications/measles-
deaths-by-age-group-from-1980-to-2013-ons-
data/measles-notifications-and-deaths-in-england-and-
wales-1940-to-2013
Website:
Public Health England
Birth data of the National Bureau of Statistics Archive:
http://archive.is/i0yx9
Page Name:
Trends in births and deaths over the last century
http://visual.ons.gov.uk/birthsanddeaths/
Website:
UK Office for National statistics
Archive:
233 Page Name (Hebrew):
http://archive.is/yCIfs
Birth data in Israel
Website:
https://tinyurl.com/y8z7v573
Document Name: Archive:
Infectious diseases requiring notification in https://drive.google.com/open?id=1QEXa9
Israel ZV_xDKvAdsUhN4ByWAfc7FbMjsH
https://www.health.gov.il/PublicationsFiles/
Disease1951_2010.pdf
Author/Year:
Israeli Ministry of Health, 2012
Measles mortality data on p 123.
P 6:
For measles, the contribution to the all-cause mortality burden reduced steadily over the
prevaccination period, so once vaccination was introduced in 1976, the mortality burden
was already too low to note a clear effect of vaccination.
P 365:
Measles vaccine provides both personal immunity to prevent disease when exposed to
measles virus and population immunity through decreased intensity of transmission as the
proportion of immune persons in a population increases. The population immunity effect
decreases the risk of measles among immunized as well as unimmunized persons.
241-253
241 Article Name: PMID:
18558875
Correlates of Vaccine-Induced Immunity
P 1:
Pertussis decreased in non-vaccinated infants (2003 to 2012, p < 0.001), indicating herd
immunity, both in those too young to be vaccinated and those older than three months.
It is therefore likely that there has been under-reporting of pertussis cases following the
introduction of aP vaccination in Sweden, and the degree of under-reporting within the
country may vary.
1-20
1 Article Name: PMID:
From Emergence to Eradication: The Epidemiology of Poliomyelitis 20978089
Deconstructed
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991634/pdf/kwq320.pdf
2 http://archive.is/L7Mv5
4 Book Title:
Vaccines (6th edition)
Published by Elsevier Saunders
https://www.elsevier.com/books/vaccines/plotkin/978-1-4557-0090-5
Lead Author/Year:
Stanley Plotkin, 2013
P 573:
Fortunately, in 1908 Karl Landsteiner and Eric Popper isolated the virus of poliomyelitis,
and scientific study of the agent began.
P 1:
Notwithstanding the intensive studies of investigators, very little information of practical
value has been added to our knowledge of poliomyelitis during the past forty years.
P 1:
…the main problem in the epidemiology of poliomyelitis concerns the cause or causes of the
sudden appearance in certain parts of the world of large numbers of paralytic cases.
Abbreviated Name: PMID:
Nathanson 2010 20978089
P 2:
Beginning around 1880, a series of outbreaks of infantile paralysis were reported from
several Scandinavian countries and the United States... Most remarkable is the almost
simultaneous appearance of outbreaks in European countries and the United States.
P 1:
the bulk of the evidence suggests that the epidemic outbursts, of the type which have
occurred especially in the United States and a few other countries in the past thirty to forty
years, are events that could not readily have been missed in the past.
P:
Why did paralytic poliomyelitis become an epidemic disease only a little more than fifty
years ago, and as such why does it seem to be affecting more and more the countries in
which sanitation and hygiene, along with the general standard of living, are presumably
making the greatest advances, while other large parts of the world, regardless of latitude, are
still relatively unaffected?
P 6:
.China, the Fiji Islands, Africa and certain other regions, in which only sporadic cases but no
epidemics were known to occur…
P 1:
…cities like Peiping, Tientsin and Shanghai, occupying approximately the same latitude in
China, in which only rare sporadic cases have been recorded thus far, despite the presence in
these cities for many years now of excellent western trained physicians who could not have
missed such outbreaks in the native population if they had occurred.
21-40
21 Article Name: PMID:
The Epidemiology Of Poliomyelitis 20242791
Problems at Home and Among the Armed Forces Abroad
Lead Author/Year: Journal:
Albert B. Sabin, 1947 JAMA
P 6-7.
181 | Chapter 10: The Mysteries of Polio
P 6:
Poliomyelitis has occurred among American troops in certain foreign countries, especially
the Middle East, the Philippine Islands and during the past summer Japan and North China,
in numbers and under circumstances that raise puzzling questions.
23 Article Name:
Poliomyelitis In British And American Troops In The Middle East: The
Isolation Of VirusFrom Human Faeces
https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2284416&blo
btype=pdf
Lead Author/Year: Journal:
John R. Paul, 1944 BMJ
P 1:
In 1941 a total of 74 cases were notified as acute poliomyelitis or encephalitis in the M.E.F.,
and of these 19 were fatal; in 1942 there were 32 cases, with 14 deaths. The rate among
American soldiers stationed in the Middle East (during the first 10 months of 1943) has been
more than 10 times that recorded in the United States for a similar period of time.
P 7:
This past summer I had occasion to observe an outbreak of poliomyelitis among American
marines stationed in the Tientsin area of North China. Four men died, 1 was severely
paralyzed and at least 25 others had nonparalytic attacks. There was no evidence of an
outbreak of poliomyelitis in the native population at the time, and Dr. Grice, a British
physician in practice in Tientsin for twenty-five years, informed me that while he not
infrequently saw paralytic poliomyelitis in children in the foreign colony he rarely saw the
disease among the Chinese.
26 Article Name:
Epidemiology Of Acute Poliomyelitis
In India Command
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(45)90883-
X/fulltext?code=lancet-site
Lead Author/Year: Journal:
Douglas McAlpine, 1945 Lancet
P 1, Table 1.
182 | Chapter 10: The Mysteries of Polio
27 Article Name:
Epidemiology Of Acute Poliomyelitis
In India Command
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(45)90883-
X/fulltext?code=lancet-site
Lead Author/Year: Journal:
Douglas McAlpine, 1945 Lancet
P 1, Table 3.
28 Article Name:
Epidemiology Of Acute Poliomyelitis
In India Command
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(45)90883-
X/fulltext?code=lancet-site
Lead Author/Year: Journal:
Douglas McAlpine, 1945 Lancet
P 1, Table 1 and 3. In addition:
British Army at Home: For 1943 and 1944 the incidence of acute poliomyelitis was 0 02 per
1000.
29 Article Name:
Poliomyelitis
https://jamanetwork.com/journals/jama/article-abstract/296121
Lead Author/Year: Journal:
Hart E. Van Riper, 1947 JAMA
P 1:
The period of evolution from sporadic to epidemic poliomyelitis corresponds roughly with
the institution of widespread measures for improved sanitation. This interesting coincidence
has led to the hypothesis that the virus is more widespread in areas where the sporadic
disease predominates, making possible frequent exposures of the young infant to virus
during the time when he still retains a high titer of passive immunity from his mother.
Exposure to the virus under these conditions would surely stimulate further resistance to
poliomyelitis and only occasionally result in the production of the frank disease. This theory
might explain the infrequent cases of poliomyelitis in young children as they occurred in the
early history of the disease in Europe and the United States. But, in regions where epidemics
predominate, people are exposed to the virus less frequently and at a later period in life,
when they have lost all or most of the passive immunity acquired from the mother. Thus
there results a greater chance for the development of frank disease among older age groups
rather than an increased resistance.
31 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 31:
Polioviruses probably circulated in an uninterrupted endemic manner for many centuries,
infecting new cohorts of susceptible infants continuously, almost all early in life, when
maternally derived antibody transferred from mother to newborn still provided some
protection.
A change from endemic transmission to periodic epidemics was first observed in some
temperate-climate countries (eg, Norway, Sweden, and the United States) late in the 19th
century and at the beginning of the 20th century… The generally accepted explanation,
supported by numerous studies, is that, in a temperate-zone climate with increased economic
development and correspondingly improved resources for community sanitation and
household hygiene, exposure to polioviruses was postponed to later in life.
37 Page Name:
Vaccines and Immunization - Polio
Website: Archive:
Museum of Healthcare http://archive.is/VR6Aa
http://www.museumofhealthcare.ca/explore/exhibits/vaccinati
ons/polio.html
Thus, over time, a growing percentage of children, as well as young adults, particularly
among the more hygienic middle class in small towns and new suburban areas during the
postwar “baby boom,” were vulnerable to the poliovirus, which had a greater chance of
invading the nervous system and causing paralytic damage.
38 Book Title:
Dirt and Disease: Polio Before FDR
https://www.amazon.com/Dirt-Disease-Medicine-American-
Society/dp/0813517869/ref=sr_1_1?s=books&ie=UTF8&qid=1476620110&sr=1-
1&keywords=9780813517865
Lead Author/Year: Publisher:
Naomi Rogers, 1992 Rutgers University Press
185 | Chapter 10: The Mysteries of Polio
39 Book Title:
Dirt and Disease: Polio Before FDR
https://www.amazon.com/Dirt-Disease-Medicine-American-
Society/dp/0813517869/ref=sr_1_1?s=books&ie=UTF8&qid=1476620110&sr=1-
1&keywords=9780813517865
Lead Author/Year: Publisher:
Naomi Rogers, 1992 Rutgers University Press
P 165:
During the 1920s and 1930s the public and the scientific community developed a new image
of polio. Until then polio, seen as a children's illness that rarely attached adults, was
associated with immigrants and urban slums.
40 Book Title:
Dirt and Disease: Polio Before FDR
https://www.amazon.com/Dirt-Disease-Medicine-American-
Society/dp/0813517869/ref=sr_1_1?s=books&ie=UTF8&qid=1476620110&sr=1-
1&keywords=9780813517865
Lead Author/Year: Publisher:
Naomi Rogers, 1992 Rutgers University Press
P 9-10:
The scenes show narrow streets lined with dirty and unsanitary pushcarts, the latter filled
with fly-specked cakes and candy and decaying fruit... all are touched by many hands before
they are finally eaten; there are uncovered garbage cans near which cats and children play
and squabble over crusts of bread and other tid-bits.
41-60
41 Article Name: Date:
In Reaction to Zika Outbreak, Echoes of Polio Aug 29, 2016
Website: Archive:
NYTIMES http://archive.is/qp0YD
http://www.nytimes.com/2016/08/30/health/zika-outbreak-
echoes-of-polio.html
The first child to be paralyzed lived in a modest Italian neighborhood east of the Gowanus in
Brooklyn. Polio soon jumped to Pigtown, a gritty pig-farming area, and most of the first 20
cases were in Italian children.
43 Book Title:
Murderous Contagion: A Human History of Disease
https://www.amazon.com/Murderous-Contagion-Human-History-Disease/dp/1782069437
Lead Author/Year: Publisher:
Mary Dobson , 2015 Quercus Publishing
But in the summer of 1916 it became clear that the epidemic, while striking hardest at the
young, affected both rich and poor, long-time residents as well as recent immigrants.
44 Book Title:
Dirt and Disease: Polio Before FDR
https://www.amazon.com/Dirt-Disease-Medicine-American-
Society/dp/0813517869/ref=sr_1_1?s=books&ie=UTF8&qid=1476620110&sr=1-
1&keywords=9780813517865
Lead Author/Year: Publisher:
Naomi Rogers, 1992 Rutgers University Press
P 10:
Poliomyelitis paralyzed infants and children. Their economic or sanitary conditions seemed
to make little difference; rich or poor, clean or dirty, no child seemed immune.
45 Article Name:
Notes Of An Epidemic Of Acute Anterior Poliomyelitis
https://jamanetwork.com/journals/jama/article-abstract/458738
Lead Author/Year: Journal:
Charles S. Caverly, 1896 JAMA
P 1:
That the general sanitary surroundings and methods of living were in anywise responsible
for the outbreak is also more than doubtful, since the disease showed no partiality to that
class of the population whose habits and surroundings are the most unsanitary. The so-called
laboring classes were oftenest affected, but not out of proportion to their numbers. These
classes here, whether among the farming population or in the mills and quarries, have
usually pure air, food and water. Hence, general sanitary conditions did not seem to have
any influence on the epidemic.
46 Article Name:
The Occurrence Of Infantile Paralysis In Massachusetts In 1907
https://archive.org/details/b22431779
Lead Author/Year: Journal:
Robert W. Lovett, 1908 Boston Medical and Surgical Journal
P 6-7:
The reports on the conditions of the house in which the patients lived are of interest. One
hundred and fifteen lived in detached houses; 110 in tenements. As to the influence of
dampness, 99 lived on the first floor; 65 on the second; 12 on the third; and 6 in the upper
stories; 20 occupied the whole house. Sanitary conditions were described as exceptionally
good in 21. Good, in 123. Fair, in 55. Poor or bad, in 23… The house was screened in 133
cases, and not screened or insufficiently so in 80… Analyzing these data for what they are
worth, it would seem that it was not an affection confined to the lower classes.
187 | Chapter 10: The Mysteries of Polio
47 Article Name:
An Epidemic Of Infantile Paralysis In Western Massachusetts In 1908
https://archive.org/details/bostonmedicalsur1611mass
Lead Author/Year: Journal:
Herbert C. Emerson, 1909 Boston Medical and Surgical Journal
P 118:
Investigation of the home conditions of each case shows that sanitary conditions were found
to be excellent in 4 cases, good in 17, fair in 31 and bad in 17. Forty-one of the cases lived
in detached houses, 17 in two-tenement and 3 in three-tenement houses, while but 8 lived in
houses having four or more tenements…
The sanitary arrangements in the houses showed that 23 houses had water closets connected
with the sewer and 46 had earth closets; that the sink water from 30 houses was carried into
the sewer and in 39 cases it was disposed of in various ways on the land nearby or in pipes
to the nearest brook, pond, etc.
48 Book Title:
Preventive Medicine and Hygiene
https://drive.google.com/open?id=1ONdl0AG5blbj8mJM0vMupllqgVoL0T4D
Lead Author/Year: Publisher:
Milton J. Rosenau, 1918 D Appleton and Company
P 340:
From the standpoint of prevention it is important to note that social and hygienic conditions
apparently have no influence whatever in determining the infection. All classes are affected
in about equal proportion.
50 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 35:
This indicated the presence of an almost constantly moderate endemicity (Levenstein K,
1937) that varied between 1.7 and 0.3 per 100,000 population during the whole reporting
period. An exception were the epidemic years 1928, 1929, 1934 and 1939, when the attack
rates ranged between 2.1 and 4.1 per 100,000.
51 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 43, Figure 4.1
188 | Chapter 10: The Mysteries of Polio
52 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 39:
This pattern, common to the other countries in the geopolitical area, was the result of poor
sanitation which favored the community transmission of infection in a slowly growing
population, and to a low level of family hygiene which supported the intrafamilial spread of
fecal-oral transmitted infectious diseases. The result was infection in early life, which led to
immunity to polio in the majority of the population. This maintained an endemic state which
prevented massive spread.
53 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 41:
This population was severely affected by the disease, as expressed by an exceedingly high
attack rate of 271.0 per 100,000, recorded in the year following immigration, as compared
with 122.0 per 100,000 in the veteran Israeli residents.
54 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 118:
There were high attack rates, which ranged between 268.0 per 100,000 in kibbutz
settlements and 107.0 per 100,000 in towns, respectively. Quite strikingly, similarly high
rates occurred in kibbutz and immigrant camp populations, in spite of the marked
differences in terms of housing, sanitation and nutrition.
55 Article Name:
The Epidemiology of Polio in Israel - An Historical Perspective
Lead Author/Year: Journal:
Tiberio A. Swartz, 2008 Israel Center for Disease Control (ICDC), Ministry of Health
P 52-54.
57 Abbreviated Name:
Plotkin 2013 - Vaccines (6th edition)
P 606:
Lower socioeconomic status has been shown to be a risk for paralytic poliomyelitis in
developing countries, probably because children belonging to the lower socioeconomic
group experience more intense exposure to poliovirus (ie, a higher virus inoculum, which
has been shown in experimental studies to be a risk factor for paralytic disease).
58 Document Name:
Poliovirus infection case definition summary
https://www.health.gov.au/internet/main/publishing.nsf/Content/cda-phlncd-
polio.htm/$FILE/polio.pdf
Lead Author/Year: Archive:
Public Health Laboratory Network https://drive.google.com/open?id=1RCX0f4JIg
(Australia), 2000 DWhu4Ypvf55CUPB8b1FJg3f
P 1:
The risk of infection is directly correlated with poor hygiene and poor sanitation and
overcrowding, typically among inadequately vaccinated populations. This is a major health
problem in the developing world causing mortality and morbidity among thousands of
children annually.
P 3:
High population densities and poor sanitation therefore appear to explain the persistence of
polio. These factors act to facilitate the transmission not only of poliovirus but also of other
enteroviruses and diarrhea…
61-80
61 Article Name: PMID:
The Poliomyelitis Story: A Scientific Hegira 2994307
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589894/pdf/yjbm00092-
0018.pdf
190 | Chapter 10: The Mysteries of Polio
P 5:
It is frequently stated that no two cases of poliomyelitis are exactly alike
69 Article Name:
Acute Poliomyelitis With Special Reference To Early Symptomatology And
Contact Histories
https://www.jstor.org/stable/25361797?
Lead Author/Year: Journal:
Douglas McAlpine, 1947 BMJ
P 1, 3.
71 Article Name:
Report Of A Possibly Milk-Born Epidemic Of Infantile Paralysis
Lead Author/Year: Journal:
John C. Dingman, 1916 New York State Journal of Medicine
192 | Chapter 10: The Mysteries of Polio
72 Article Name:
An Outbreak Of Poliomyelitis Apparently Milk Borne
https://jamanetwork.com/journals/jama/article-abstract/242504
73 Article Name:
An Institutional Outbreak Of Poliomyelitis Apparently Due To A Streptococcus In Milk
https://www.jstor.org/stable/30083744
Lead Author/Year: Journal:
Edward C. Rosenow, 1932 Journal of Infectious Diseases
74 Book Title:
Poliomyelitis In All Its Aspects
Lead Author/Year: Publisher:
John Ruhrah , 1917 LEA & FEBIGER
P 57:
The fact [is] that the disease seems to spread radially from an infected center so that the
most recent cases are generally found to be the farthest away from the center geographically.
Book Title:
Acute Poliomyelitis (Heine-Medin's Disease)
Lead Author/Year: Publisher:
Ivar Wickman, 1913 The Journal of Nervous and Mental Disease Publishing
Company
P 112:
The Swedish epidemic of 1905 thus demonstrated that the mode in which the disease
spreads both within the large epidemic centers and within the individual components which
constitutes them, so far as it was possible to determine, was essentially analogous to that
established for a number of other infectious diseases, in which transmission takes place from
person to person.
75 Article Name:
Dangers In The Manufacture Of Paris Green And Scheele's Green
https://www.jstor.org/stable/41829377
Year: Journal:
1917 Monthly Review of the U.S. Bureau of Labor Statistics
76 Book Title:
Before Silent Spring: Pesticides and Public Health in Pre-DDT America
Lead Author/Year: Publisher:
James Whorton, 1974 Princeton University Press
P 39-40:
An incomplete list of arsenic-tinted items compiled by the Medical Society of London in the
early 18805, for example, enumerated paper, fancy and surface coloured, in sheets for
covering cardboard boxes; for labels of all kinds; for advertisement cards, playing cards,
wrappers for sweetmeats, cosaques, etc.; for the ornamentation of children's toys; for
covering-children's and other books; for lamp shades, paperhangings for walls and other
purposes; artificial leaves and flowers; wax ornaments for Christmas trees and other
purposes; printed or woven fabrics intended for use as garments; printed or woven fabrics
intended for use as curtains or coverings for furniture; children's toys, particularly inflated
india-rubber balls with dry colour inside, painted india-rubber dolls, stands and rockers of
193 | Chapter 10: The Mysteries of Polio
rocking-horses and the like, glass balls (hollow); distemper colour for decorative purposes;
oil paint for the same; lithographer's colour printing; decorated tin plates, including painted
labels used by butchers and others to advertise the price of provisions; japanned goods
generally; Venetian and other blinds; American or leather cloth; printed table baizes;
carpets, floorcloth, linoleum, book cloth and fancy bindings. To this list may be added
coloured soaps, sweetmeats and false malachite. Arsenic is also used in the preparation of
skins for stuffing and of some preservatives used by anatomists." Other lists, though less
lengthy, often turned up additional arsenical products. The renowned British toxicologist
Robert Christison observed that not only was Scheele's green used to make sweetmeats more
appetizing, but that it was also added to preserves and to apple tarts, and that several
children had been made ill by the latter.‘ Others‘ pointed out that the green cakes in water
color sets generally contained arsenic, as did dental fillings, and that people had been injured
by arsenical stockings, veils, cosmetics, concert tickets, fly papers, stuffed animals, even
money.
77 Book Title:
Before Silent Spring: Pesticides and Public Health in Pre-DDT America
Lead Author/Year: Publisher:
James Whorton, 1974 Princeton University Press
P 49-51:
The respect in which Fowler's solution was held can be best appreciated by an enumeration
of the conditions for which it was regularly prescribed. These included anemia, headache,
dyspepsia, eczema, psoriasis, all other chronic skin diseases, neuralgia, chorea, epilepsy,
whooping cough, asthma, bronchitis, emphysema, pulmonary tuberculosis, malaria, and
cancer. In addition, Fowler's solution was suggested, at one time or another, for cholera,
yellow fever, syphilis, diabetes, angina pectoris, tic douloureux, gout, arthritis, rheumatism,
constipation, morning sickness, melancholia, impotence, fits of sneezing, warts, boils, and,
for the careless traveler in the Orient, cobra bites.
78 Book Title:
Before Silent Spring: Pesticides and Public Health in Pre-DDT America
Lead Author/Year: Publisher:
James Whorton, 1974 Princeton University Press
P 41:
The real leadership of the campaign against arsenical manufactures was assumed by the
physicians of Massachusetts, most prominent among these Yankee meddlers being a
foursome of Bostonians: Frank Winthrop Draper, medical examiner (coroner) of Boston and
lecturer at Harvard Medical School; James Jackson Putnam, professor of neurology at
Harvard; Frederick Cheever Shattuck, professor of clinical medicine; and William Barker
Hills, the medical school's chemistry professor. With a diligence befitting Harvard men,
these four delivered lectures and published papers on the dangers of arsenic in the
household, with the express purpose of informing the citizenry, through their physicians, of
products to be avoided.
79 Article Name:
On The Character Of The Evidence As To The Injuriousness Of Arsenic As
A Domestic Poison
https://jamanetwork.com/journals/jama/article-abstract/466612
Lead Author/Year: Journal:
James J. Putnam, 1891 JAMA
P 3.
194 | Chapter 10: The Mysteries of Polio
80 Article Name:
On The Character Of The Evidence As To The Injuriousness Of Arsenic As
A Domestic Poison
https://jamanetwork.com/journals/jama/article-abstract/466612
Lead Author/Year: Journal:
James J. Putnam, 1891 JAMA
P 2:
These results conclusively show: first, that the community is exposed to arsenical
contamination on a very large scale.
81-100
81 Book Title:
Encyclopedia of Pest Management
https://books.google.co.il/books?id=ytFoAcwI4sQC&pg=PA377&lpg=PA377#v=onepage&
q&f=false
Lead Author/Year: Publisher:
David Pimentel, 2013 CRC Press
P 377:
The Colorado potato beetle, provides a prime example. It appeared as a devastating pest of
potato in Iowa and Nebraska in 1861, having transferred from a native weed to an
introduced relative, the potato. The beetle spread rapidly eastward, reaching the Atlantic
coast in 1874, despite the use of traditional nonchemical means of control. In 1867, farmers
in the west discovered that the Colorado potato beetle could be controlled with Paris green,
an arsenical. Paris green was in general use by 1880 and became the first widely used
pesticide in North America.
82 Book Title:
War on Bugs
https://www.amazon.com/War-Bugs-Will-Allen/dp/1933392460
Lead Author/Year: Publisher:
Will Allen, 2007 CRC Press
Chapter 14.
83 Book Title:
Before Silent Spring: Pesticides and Public Health in Pre-DDT America
Lead Author/Year: Publisher:
James Whorton, 1974 Princeton University Press
P 23:
This decline did not leave the field uncontested to Paris green, for shortly before 1900 the
most effective arsenical insecticide of all had been discovered, during the campaign against
the gypsy moth. A leaf-eating insect native to Europe, the moth was first brought to the New
World by Leopold Trouvelot, a French-born Harvard astronomer with a side-interest in
silkworm breeding. Some experiments dealing with the latter subject seemed to Trouvelot to
require gypsy moths, and so in 1869 he imported a number of gypsy moth eggs and cared
for them until the insects reached maturity. The moths wasted little time asserting their
independence, and soon escaped from Trouvelot's home in Medford, Massachusetts. Twenty
years later, in 1889, their descendants, in the form of caterpillars, returned to Medford, in
numbers that "were so enormous that the trees were completely stripped of their leaves, the
crawling caterpillars covered the sidewalks, the trunks of the shade trees, the fences and the
sides of the houses, entering the houses and getting into the food and into the beds. They
195 | Chapter 10: The Mysteries of Polio
were killed in countless numbers by the inhabitants who swept them up into piles, poured
kerosene over them and set them on fire. Thousands upon thousands were crushed under the
feet of pedestrians, and a pungent and filthy stench arose from their decaying bodies. The
numbers were so great that in the still, summer nights the sound of their feeding could
plainly be heard, while the pattering of the excremental pellets on the ground sounded like
rain.
86 Article Name:
Is Acute Poliomyelitis Unusually Prevalent This Season?
Lead Author/Year: Journal:
James J. Putnam, 1893 Boston Medical and Surgical Journal
P 2.
88 Article Name:
Is Acute Poliomyelitis Unusually Prevalent This Season?
Lead Author/Year: Journal:
James J. Putnam, 1893 Boston Medical and Surgical Journal
P 2:
…that the patients did not come to any extent, from any one locality, but from different parts
of the large area of the suburbs of Boston... Very few of the patients came from Boston
proper;
89 Article Name:
Notes Of An Epidemic Of Acute Anterior Poliomyelitis
https://jamanetwork.com/journals/jama/article-abstract/458738
Lead Author/Year: Journal:
Charles S. Caverly, 1896 JAMA
P 1:
The epidemic, as I have indicated, invaded our valley in the early summer of 1894. It
prevailed with increasing severity during July, apparently reached its climax about the first
of August, and steadily declined until about the first of October, the last case occurring early
in that month.
91 Page Name:
Vermont Seasonality Calendar
Website: Archive:
Vermont Agency of Agriculture http://archive.is/EDfEH
http://agriculture.vermont.gov/buy_local/harvest_calendar
92 Document Name:
ATSDR - Arsenic Toxicity
Archive:
https://drive.google.com/open?id=17
http://www.atsdr.cdc.gov/csem/arsenic/docs/arsenic uL_KUUCnrOv-
.pdf zfAP9QUkh_zOoInWjXQ
Author/Year:
CDC, 2009
P 47.
Document Name: Archive:
ATSDR - Lead Toxicity https://drive.google.com/open?id=1K
http://www.atsdr.cdc.gov/csem/lead/docs/lead.pdf D8Gzk2wKXPT4UG8mpyjCvhtBk
WbaiHx
197 | Chapter 10: The Mysteries of Polio
Author/Year:
CDC, 2009
P. 45.
93 Article Name:
On The Character Of The Evidence As To The Injuriousness Of Arsenic As
A Domestic Poison
https://jamanetwork.com/journals/jama/article-abstract/466612
Lead Author/Year: Journal:
James J. Putnam, 1891 JAMA
P 3.
94 Article Name:
The Occurrence Of Infantile Paralysis In Massachusetts In 1907
https://archive.org/details/b22431779
Lead Author/Year: Journal:
Robert W. Lovett, 1908 Boston Medical and Surgical Journal
P 3:
Vulpian produced, experimentally, paralysis of the extensors and lesions resembling those of
poliomyelitis in a dog by lead poisoning, and in a case of lead poisoning found pronounced
poliomyelitis with colloid degeneration arid cell atrophy. Phillippe and Gauthard report a
case of anterior poliomyelitis from lead poisoning and Obrastoff one from arsenical
poisoning. Onuf reported the case of a painter with flaccid paralysis of both legs, in whom
autopsy showed lesions characteristic of the disease.
95 Article Name:
Report Of An Unusual Case Of Lead Paralysis With Autopsy
.https://ia800201.us.archive.org/21/items/journalofnervous27ameruoft/journ
alofnervous27ameruoft.pdf
Lead Author/Year: Journal:
B. Onof, 1900 Journal of Nervous and Mental Disease
P 155-156.
101-120
101 Article Name:
The History of Lead Arsenate Use in Apple Production: Comparison of its Impact in
Virginia with Other States
Lead Author/Year: Journal:
Michael J. Weaver, 2008 Journal of Pesticide Safety Education
P 12:
The search for substitutes for LA began in earnest when it was discovered in 1919 that
contemporary practices for washing produce were failing to adequately remove As
residues (Shepard, 1939). Unfortunately, all of the tested alternative materials were found
to provide less effective insect control or were more toxic to plants and animals. No
adequate substitutes were found until 1947, when the synthetic organic insecticide
dichlorodiphenyltrichloroethane (DDT) was introduced.
199 | Chapter 10: The Mysteries of Polio
PMID:
104 Article Name:
19750602
‘Do Not Eat Those Apples; They’ve Been On The Ground!’: Polio
Epidemics And Preventive Measures, Sweden 1880s-1940s
Lead Author/Year: Journal:
Per Axelsson, 2009 Asclepio. Revista de Historia de la Medicina y de la Ciencia
P 8:
Medin considered polio to be an acute infectious disease, affecting the nervous system,
that could cause epidemics, but he did not consider it to be contagious.
PMID:
105 Article Name:
19750602
‘Do Not Eat Those Apples; They’ve Been On The Ground!’: Polio
Epidemics And Preventive Measures, Sweden 1880s-1940s
Lead Author/Year: Journal:
Per Axelsson, 2009 Asclepio. Revista de Historia de la Medicina y de la Ciencia
P 7:
As late as 1911 some physicians in Sweden still argued that polio was a disease caused by
miasma. The theory of miasma implied that disease was not caused by contagions but by
putrefaction, i.e. «bad air» and should be combated with cleaner environments which often
meant improved hygiene and sanitation.
suggests that the disease is but mildly contagious to say the most. A large number of
children were in intimate contact with those that were sick, and of these children an
insignificant minority developed the disease… the circumstances were particularly
favorable to the investigation of points of contact between sick and well and of the
detection of contagion.
118 Cases from the medical literature of paralysis as a result of spoiled PMID:
or poisoned food - 14771968
Article Name:
Poisoning as The Cause of Poliomyelitis
Lead Author/Year: Journal:
Ralph R. Scobey, 1950 Archives of Pediatrics
P 7-17.
121-140
121 Article Name: PMID:
Jamaica Ginger Paralysis 666613
Forty-seven-Year Follow-up
Lead Author/Year: Journal:
John P. Morgan, 1978 Archives of Neurology
Article Name: PMID:
The Jamaica ginger paralysis 6750161
Lead Author/Year: Journal:
John P. Morgan, 1982 JAMA
conditions showed that dissemination must be due to the busy traffic which permitted
more frequent communication between the people.
141-160
141 Book Title:
Infantile Paralysis In Vermont
https://archive.org/details/infantileparalys00cave
Lead Author/Year: Publisher:
Charles S. Caverly, 1925 Burlington, Vermont
State Department Of Public Health
Referring to the polio epidemic in Vermont in 1912, p 88:
This once more emphasizes the rather slight contagiousness of the disease
Referring to the polio epidemic in Vermont in 1916-17, p 150:
While, therefore, contact infection seems to be increasingly traceable, it must still be
considered a disease of rather low contagiousness.
And p. 167:
These figures corroborate the statement made before that while the disease is a
communicable disease, it is one of low contagiousness.
And this, even though he is well aware of Wickman's theory, p. 158:
Infantile Paralysis is generally recognized as a contagious disease and one that may be
spread innocently by persons who have no clinical symptoms, in other words, by "abortive
cases" or “healthy carriers."
161-180
161 Article Name:
Sewage as a carrier and disseminator of Poliomyelitis Virus
Lead Author/Year: Journal:
C. Kling, 1942 Acta Medica Scandinavica
211 | Chapter 10: The Mysteries of Polio
P 32:
…we know also the vehicle where the infectious agent, while the epidemic is going on and
for some time after its end, dwells, i. e. the sewage.
Article Name:
173 The Polioviruses Of Man
Lead Author/Year: Journal:
Stanley A. Plotkin, 1962 Annals of New York Academy of Sciences
P 13, Table 10.
Page Name:
Pink Book - Polio
213 | Chapter 10: The Mysteries of Polio
Website: Archive:
CDC http://archive.is/yvRRU
https://www.cdc.gov/vaccines/pubs/pinkbook/polio.html
Humans are the only known reservoir of poliovirus, which is transmitted most frequently
by persons with inapparent infections.
181-200
181 Article Name:
The Occurrence Of Infantile Paralysis
In Massachusetts In 1910
Lead Author/Year: Journal:
Robert W. Lovett, 1911 Boston Medical and Surgical Journal
P 4:
Total, 34 homes out of 110 had illness, paralysis or death in 82 animals near the time of
the human paralysis.
Article Name:
187 The Occurrence Of Infantile Paralysis In Massachusetts In 1908
Lead Author/Year: Journal:
Robert W. Lovett, 1909 Boston Medical and Surgical Journal
P 1:
It was noted by Wickman that in the Swedish epidemic of 1903 dogs were apparently
affected in many instances with the children, but he was not convinced of the identity of
the two affections.
216 | Chapter 10: The Mysteries of Polio
201-220
201 Document Name:
Green Book - Poliomyelitis
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/148141/Gre
en-Book-Chapter-26-Polio-updated-18-January-2013.pdf
Author/Year: Archive:
NHS, 2013 https://drive.google.com/open?id=15wYdgB3upwPEHYP7XZkU
VxQEAOXe1Lnb
P 2, chart 26.1
221-240
221 Article Name: PMID:
From Emergence to Eradication: The Epidemiology of Poliomyelitis 20978089
Deconstructed
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991634/pdf/kwq320.pdf
P 4:
…it is remarkable that, unlike certain other infections of childhood, the epidemics of
paralysis occur during the very months when the children are away from school.
factor in the production of epidemics, because the age incidence was not found to vary
materially from year to year, even during epidemics which occurred after a number of
years of comparative freedom from the disease. Twenty years later, I showed that
Aycock's observation was still valid, despite the fact that age selection patterns had
changed over the years in certain communities.
among the Nazis: "Geigy maintained particularly good relations Claus Ungewitter, the
Reich commissioner for chemicals ...
The report also singled out Geigy and Roche for using forced labour at their plants in
Germany .
It said at least 33 Dutch and French labourers were forced to work for Geigy between 1943
and 1945, while at least 61 prisoners-of-war and 150 foreign labourers were forced to
work at the Roche plant...
It said the companies' claims that they were cut off from their subsidiaries in Germany
were patently false: "senior managers at the parent company in Switzerland were aware
that forced labour was being used... As a rule they were not worried or uneasy about the
situation, and as long as production was maintained they had no thoughts of intervening.
241-260
241 Article Name:
DDT Poisonins and the Elusive "Virus X:" A New Cause for Gastro-Enteritis
Lead Author/Year: Journal:
Morton S. Biskind, 1949 American Journal of Digestive Diseases
P 1:
Not only is it used in households with reckless abandon, so that sprays and aerosols are
inhaled, the solutions are permitted to contaminate the skin, bedding and other textiles are
saturated, and food and food utensils are contaminated, but DDT is also widely used in
restaurants and food processing establishments and as an insecticide on crops. Cattle,
sheep and other food animals are extensively dusted with it and large areas are
indiscriminately sprayed from airplanes for mosquito control.
Pictures of DDT spraying:
https://www.gettyimages.com/photos/spray-ddt
Unfortunately, today contamination of food is virtually universal. Even if the farmer does
not use the new insecticides (and few do not), it is a rare food that escapes contact with
insecticides in storage, shipment, processing plants, warehouses and stores. Dendy, for
instance, bought milk and meat on the open market in Texas, from July through December.
Every specimen of these staples was found to contain DDT, from less than 0.5 p. p. m. to
13.8 p. p. m. in milk and from 3.1 p. p. m. in lean meat to 68.5 p. p. m. in fat meat.
261-280
261 Document Name:
Pharmacologic And Toxicologic Aspects Of DDT
Lead Author/Year: Archive:
231 | Chapter 10: The Mysteries of Polio
P 2:
DDT is a "cerebrospinal" poison which acts primarily on the central nervous system in
man and higher animals as contrasted with its apparent peripheral action in insects. The
principal systemic effects in higher animals are disturbances of the central nervous system
characterized by hyperexcitability, generalized tremors, spastic or flaccid paralysis and
convulsions.
281-300
281 Article Name:
The Epidemiology of Poliomyelitis in Africa
Lead Author/Year: Archive:
James Gear, 1958 https://drive.google.com/open?id=1F-IcUN-b22YEghe-
3I4Pldwk4vwDA3xe
P 5:
The systemic spraying of villages and towns with DDT, BHC and similar long-acting
insecticides has not hastened the end of an epidemic, nor indeed has it prevented the onset
of an epidemic.
animals and man). One after another new compounds were introduced, the total list being
very long indeed.
P 2:
This statement pointed out that the toxicity of DDT for man "has been given full
consideration in making recommendations for its use. There is no evidence that the use of
DDT in accordance with the recommendations of the various federal agencies has ever
caused human sickness due to DDT itself... "Statements that DDT is responsible for
causing the so-called 'virus X disease' of man and 'X disease' of cattle are totally without
foundation. Both of these diseases were recognized before the utilization of DDT as an
insecticide."
P 1:
Although flies have been found to be contaminated with virus, there has been no reliable
evidence of spread by insects, water, food or sewage…
301-320
301 Article Name: PMID:
Transmission Of Poliomyelitis Virus 14889394
Lead Author/Year: Journal:
Albert B. Sabin, 1951 Journal of Pediatrics
P 5:
If the introduction of the virus into the mouth by means of the hands or other materials is
of basic importance in the transmission of poliomyelitis, can we regard the period of
communicability as being for only a few days before and a few days to a week after onset
of symptoms, when, by our present methods, the virus is still readily demonstrable in the
stools of approximately 50 per cent of individuals during the third and fourth weeks? How
much reliance should we place on the epidemiological observations which place the
"infectious period" at four to five days before and after onset of symptoms, when it is
realized that these conclusions are based on tracing extrafamilial secondary cases to
presumably single contacts with patients who became sick and had to go to bed?
P 4:
The main portal of exit is the intestinal tract, and large quantities of virus can be found in
the feces often for many weeks and occasionally for many months… Epidemiologic
evidence indicates that a case is most infectious during the early phase of infection,
sometime before onset of symptoms or in the first few days of the clinical disease.
Article Name:
Present Concepts And Recent Advances In Acute Poliomyelitis
Lead Author/Year: Journal:
John R. Paul, 1952 AMA Archive of Internal Medicine
P 3:
In these recent discoveries it is possible that we have witnessed the end of what might be
termed "the monkey era" in poliomyelitis research. This is no great loss, for the expense of
maintaining monkey colonies for poliomyelitis research has been great. Also it is
heartening to realize that the way is now open for many laboratories to engage in certain
clinical and epidemiological investigations on poliomyelitis which have been denied to
them in the past because of expense and other difficulties. Scores of new investigators can
now enter the poliomyelitis field, and new impetus can be given to such work all over the
world. All this stems from the discovery that a tissue-culture tube may be substituted for a
monkey.
These children comprised essentially the only population group that received vaccine
during the spring and summer of 1955.
321-340
321 For instance - PMID:
Article Name: 13571484
The Influence Of Natural And Artificially Induced Immunity On
Alimentary Infections With Polioviruses
244 | Chapter 10: The Mysteries of Polio
332 In Israel –
Article Name:
An Outbreak Of Poliomyelitis In Israel In 1961 And The Use Of Attenuated Type 1
Vaccine In Its Control
Article Name:
A Survey of Immunization Levels After an Oral Poliovaccine Program in Cleveland
Lead Author/Year: Journal:
Martha L. Lepow, 1964 JAMA
P 5, table 3:
Vaccination operation in the Cleveland area, Ohio, in 1962. Similarly, the vast majority of
Sabin vaccinees were previously vaccinated with the Salk vaccine.
Article Name:
336 Laboratory Data On The Detroit Poliomyelitis Epidemic - 1958
Lead Author/Year: Journal:
Gordon C. Brown, 1960 JAMA
P 1:
Virological laboratory tests were carried out on 1,060 persons, probably the greatest
percentage of victims of a large epidemic of poliomyelitis ever to be subjected to
laboratory investigation.
Article Name:
337 Laboratory Data On The Detroit Poliomyelitis Epidemic - 1958
Lead Author/Year: Journal:
Gordon C. Brown, 1960 JAMA
P 2, tables 1 and 2.
Article Name:
338 Laboratory Data On The Detroit Poliomyelitis Epidemic - 1958
Lead Author/Year: Journal:
Gordon C. Brown, 1960 JAMA
P 1:
248 | Chapter 10: The Mysteries of Polio
Specimens from paralytic patients were retested if the findings had been negative for virus
on the first attempt.
Article Name:
339 Preliminary Report And Observations On The 1956 Poliomyelitis Outbreak In Chicago
Lead Author/Year: Journal:
Herman N. Bundesen, 1957 JAMA
P 1:
Of the 1,111 cases, virology reports have been received on 651. Of these 651 cases, a
poliomyelitis virus has been successfully isolated from 412.
Article Name:
340 Effectiveness of Salk Vaccine
Analysis of Virologically Confirmed Cases of
Paralytic and Nonparalytic Poliomyelitis
Lead Author/Year: Journal:
Joseph L. Melnick, 1961 JAMA
P 1:
Of the 126 cases which were diagnosed clinically as paralytic poliomyelitis, 102 yielded a
virus in monkey kidney cultures. Of the viruses isolated, all but 2 were polioviruses… In
the same period, 125 cases diagnosed as aseptic meningitis were studied… Of these, only
23 were polioviruses…
341-360
341 Article Name: PMID:
Nonpolioviruses and Paralytic Disease 14468369
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575072/pdf/califmed001
57-0049.pdf
Lead Author/Year: Journal:
Robert L. Magoffin, 1962 California Medicine
P 4:
In etiologic studies of clinical paralytic poliomyelitis in California, poliovirus was
recovered from about 80 per cent of the patients under five years of age, as compared with
60 to 65 per cent of older children and adults.
P 9:
In contrast, inapparent infection, either natural or oral vaccine induced, does result in a
marked degree of resistance to intestinal multiplication of virus, although in neither case is
this resistance absolute.
Article Name:
353 The Influence Of Natural And Artificially Induced Immunity On
PMID:
13571484
Alimentary Infections With Polioviruses
Lead Author/Year: Journal:
John P. Fox, 1958 American Journal of Public Health
P 9:
At that time, no evidence could be found that primary vaccination had influenced either
the occurrence or course of alimentary infections in any way, whereas it was already clear
that immunity resulting from natural infection did exert a significantly limiting effect.
Article Name:
354 The Influence Of Natural And Artificially Induced Immunity On
PMID:
13571484
Alimentary Infections With Polioviruses
Lead Author/Year: Journal:
John P. Fox, 1958 American Journal of Public Health
P 11:
Infected but vaccinated children appeared to be just as effective sources for intrahousehold
spread of virus as did unvaccinated children.
Article Name:
355 The Influence Of Natural And Artificially Induced Immunity On
PMID:
13571484
Alimentary Infections With Polioviruses
Lead Author/Year: Journal:
John P. Fox, 1958 American Journal of Public Health
P 9:
Among children without natural immunity there was little variation in the duration of
excretion in relation to vaccination… Rather surprisingly, however, tests for the amount of
virus present in the first virus-positive specimen revealed nearly as much virus (4.2 mean
long infectivity) in stools from children with prior natural immunity as in those, whether
vaccinated or not, without natural immunity (4.0 to 4.9 mean log infectivity).
Article Name:
356 The Influence Of Natural And Artificially Induced Immunity On
PMID:
13571484
Alimentary Infections With Polioviruses
Lead Author/Year: Journal:
John P. Fox, 1958 American Journal of Public Health
P 11:
…it is concluded that widespread use of Salk vaccine should not by any reasonable
mechanism influence poliovirus dissemination.
Article Name:
357 Influence Of Vaccination With Formalin Inactivated Vaccine Upon
PMID:
14415906
Gastrointestinal Infection With Polioviruses
Lead Author/Year: Journal:
Martha Lipson Lepow, 1960 American Journal of Public Health
P 9:
The results of this study would indicate that the prior administration of one or two doses of
inactivated poliomyelitis vaccine does not reduce the susceptibility of the lower
252 | Chapter 10: The Mysteries of Polio
gastrointestinal tract of man to poliovirus infection. These results are in accord with those
of Fox, Davis, Koprowski, and Sabin… Vaccination cannot be expected to decrease
significantly the number of persons in the community suffering from inapparent poliovirus
infections. Therefore, the opportunities of becoming infected will be the same as before
vaccine was used, although paralytic disease can be expected to be less frequent.
Article Name:
358 Influence Of Vaccination With Formalin Inactivated Vaccine Upon
PMID:
14415906
Gastrointestinal Infection With Polioviruses
Lead Author/Year: Journal:
Martha Lipson Lepow, 1960 American Journal of Public Health
P 10:
The observations of Koprowski and Sabin with avirulent viruses, and Fox with natural
infection provide more direct evidence concerning this question. They indicate that
antibody, either acquired passively from the mother or resulting from vaccination with
killed vaccine, has no effect upon the susceptibility of the bowel.
Article Name:
359 Influence Of Vaccination With Formalin Inactivated Vaccine Upon
PMID:
14415906
Gastrointestinal Infection With Polioviruses
Lead Author/Year: Journal:
Martha Lipson Lepow, 1960 American Journal of Public Health
P 11:
It is concluded that immunization with killed poliomyelitis vaccines cannot be expected to
decrease the numbers of persons in the community with alimentary poliovirus infection.
Thus, vaccination, while of value to the persons immunized, is unlikely to provide
protection to those not vaccinated.
361-380
361 Article Name:
Exit Poliomyelitis-What Next?
Lead Author/Year: Journal:
Sven Gard, 1961 Yale Journal Of Biology And Medicine
P 8:
In any event, Salk was inclined to regard the reduced attack rates as an effect of the
vaccination, reasoning as follows. If oropharyngeal secretions are more important for
transmission of virus in communities where contact with sewage or feces is less likely, and
if vaccination has little or no effect upon fecal virus but does have a significant effect upon
253 | Chapter 10: The Mysteries of Polio
pharyngeal virus, then it is conceivable that spread of virus may be diminished by effective
vaccination...
381-400
381 Book Title:
Patenting The Sun: Polio and the Salk Vaccine
https://www.amazon.com/Patenting-Sun-Polio-Salk-
Vaccine/dp/0688094945
DDT was sufficiently cheap and effective to open up new possibilities for insecticide use
that has previously been technically and economically impossible.
after exposure to DDT sprays and after consuming food contaminated with this poison.
Children and infants especially are much more susceptible to poisoning than adults.
401-420
401 Page Name:
Select Committee to Investigate the Use of Chemicals in Food and Cosmetics (1950-52)
Website:
Archives.GOV
https://www.archives.gov/legislative/guide/house/chapter-22-select-food-and-
cosmetics.html
The committee was authorized to inquire into the extent and the effect of the use of
chemicals, synthetics, pesticides, and insecticides in the production and preparation of
food products and to determine the effects of such use on the public and upon agricultural
stability.
For, although virtual control of paralytic poliomyelitis has been achieved in large
geographical areas, in others (particularly tropical and sub-tropical ones) the disease is
only now beginning to appear for the first time in epidemic form.
421-440
421 Article Name: PMID:
Differential Diagnosis of Acute Flaccid Paralysis and Its Role in 11218380
Poliomyelitis Surveillance
Lead Author/Year: Journal:
Arthur Marx, 2000 Epidemiologic Reviews
P 11:
Exposure (often agricultural or industrial) to chemicals such as lead, arsenic… may cause
peripheral motor neuropathy… Arsenic-containing compounds such as melarsoprol are
still being used in developing countries for the treatment of African trypanosomiasis
(sleeping sickness) and may cause Guillain-Barre syndrome-like AFP.
P 11:
Exposure (often agricultural or industrial) to chemicals such as lead, arsenic… may cause
peripheral motor neuropathy… Arsenic-containing compounds such as melarsoprol are
still being used in developing countries for the treatment of African trypanosomiasis
(sleeping sickness) and may cause Guillain-Barre syndrome-like AFP.
formulated from active ingredients imported from regional sources having chemicals
synthesizing capabilities. Many of these chemicals have been banned or their use severely
restricted in ‘western’ nations but are freely available on the world market.
P 1:
Current eradication strategies recommended by the World Health Organization include
national mass campaigns administering oral polio vaccine to all children under 5 years of
age, enhanced surveillance to detect cases of acute flaccid paralysis, creating a network of
269 | Chapter 10: The Mysteries of Polio
laboratories for viral diagnosis, and targeted immunization to areas and populations where
poliovirus transmission is likely to persist.
P 14:
In 1992, the officially reported figure was 15,406 cases (figure 3) an 8% increase from the
14,199 reported the previous year but a 52% fall from the 32,419 reported in 1988.
In its defense, the World Health Organization claimed that the number PMID:
of reported cases was much lower than its actual rate - 15932011
Article Name:
Polio Eradication Initiative In India: Deconstructing The GPEI
Lead Author/Year: Journal:
C. Sathyamala, 2005 International Journal of Health Services
P 18:
In 1988, when the WHO launched the global eradication program, the total number of
paralytic poliomyelitis cases reported worldwide was 32,419. However, the WHO
increased the figure 10-fold to justify the claim that paralytic poliomyelitis was a major
problem of public health importance. Thus, post facto, the number of polio cases
worldwide artificially rose from about 35,000 to 350,000 for 1988. The WHO’s argument
was that the reported cases were an underestimate and that they were at least ten times
more.
P 1:
Acute flaccid paralysis (AFP) is a clinical syndrome characterized by rapid onset of
weakness, including (less frequently) =weakness of the muscles of respiration and
swallowing, progressing to maximum severity within several days to weeks.
P 1:
A cause-and-effect relation between exposure to insecticides and subsequent development
of polyneuropathy is very difficult to prove even when strongly suspected… Our two
patients… might have been considered to be suffering from a sporadic form of the
Guillain-Barre' syndrome of cryptogenic origin had not the close association between
exposure to insecticide and neurologic manifestations made an etiologic relationship
probable.
P 1:
A syndrome identical to polio is caused by other enteroviruses, notably enterovirus 71, and
some atypical cases may be difficult to differentiate clinically from Guillain-Barre
syndrome. A definitive diagnosis requires laboratory confirmation, and virus isolation
from stools is the most reliable test.
441-447
272 | Chapter 10: The Mysteries of Polio