Association of BCG
Running head: DRAFT OF RESEARCH PROPOSAL
Association of BCG vaccine and allergic diseases
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Association of BCG
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Abstract
The generalizability of the apparent decreased risk of allergic and atopic diseases associated with
BCG vaccination will be investigated by examining data available from previously published
studies. Statistical reanalysis of these studies will be done to confirm this association.
Association of BCG
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Association of BCG vaccine and allergic diseases
Introduction
Statement of the problem:
Each year more than 50 million Americans suffer from allergic diseases.
Allergies are the 6th leading cause of chronic disease in the United States, costing the
health care system $18 billion annually. Two estimates of allergy prevalence in the
United States are 9 percent and 16 percent. The prevalence of allergic rhinitis has
increased substantially over the past 15 years. Approximately 16.7 million office visits
to health care providers each year are attributed to allergic rhinitis. Estimates of the
prevalence of allergy to latex allergens in the general population vary widely, from less
than 1 percent to 6 percent. Certain individuals, including health care workers who
wear latex gloves and children with spina bifida who have had multiple surgical
procedures, are at particularly high risk for allergic reactions to latex. Atopic individuals
(those with allergies) are at an increased risk of developing latex allergy. Based on
1988 to 1993 data, 220 cases of anaphylaxis and 3 deaths per year are due to latex
allergy [1, 2].
Atopic dermatitis is one of the most common skin diseases, particularly in infants
and children. The estimated prevalence in the United States is 9 percent. The prevalence of
atopic dermatitis appears to be increasing. Health care provider visits for contact dermatitis and
other eczemas, which include atopic dermatitis, are 7 million per year [1, 2].
Chronic sinusitis is the most commonly reported chronic disease, affecting 12.6
percent of people (approximately 38 million) in the United States in 1996 [2]. In 1996, estimated
U.S. health care expenditures attributable to sinusitis were more than $5.8 billion [1, 2].
Association of BCG
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Penicillin is a common cause of drug allergy. Anaphylactic reactions to penicillin cause
400 deaths annually among Americans, making penicillin allergy a more common cause of death
than food allergy [2].
Acute urticaria (hives) is common, affecting 10 to 20 percent of the population at
some time in their lives. Half of those affected continue to have symptoms for more than
6 months [1].
Allergy to venom of stinging insects (honeybees, wasps, hornets, yellow jackets,
and fire ants) is relatively common, with prevalence of systemic reactions in American
adults of 3.3 percent [2]. Between 40 and 100 Americans have been reported to die
annually from anaphylaxis to insects, although this number may be markedly underestimated [2].
Statement of the Purpose
The increase of allergic diseases in the industrialized world has often been explained
by a decline in infections during childhood. The immunological explanation has been put into the
context of the functional T cell subsets known as Th1 and Th2 that display polarized cytokine
profiles. It has been argued that bacterial and viral infections during early life direct the maturing
immune system towards Th1, which in turn counterbalance pro-allergic Th2 responses. Thus a
reduction in the overall microbial burden will result in weak Th1 imprinting, and unrestrained
Th2 responses that allow an increase in allergy.
One theory of immune regulation involves homeostasis between T- helper 1(Th1) and Thelper 2 (Th2) activity. The Th1/Th2 hypothesis arose from 1986 research suggesting mouse Thelper cells expressed differing cytokine patterns. This hypothesis was adapted to human
immunity, with Th1- and Th2-helper cells directing different immune response pathways. Th1
cells drive the type-1 pathway ("cellular immunity") to fight viruses and other intracellular
Association of BCG
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pathogens, eliminate cancerous cells, and stimulate delayed-type hypersensitivity (DTH) skin
reactions. Th2 cells drive the type-2 pathway ("humoral immunity") and up-regulate antibody
production to fight extracellular organisms; type 2 dominance is credited with tolerance of
xenografts and of the fetus during pregnancy. Over-activation of either pattern can cause disease,
and either pathway can down-regulate the other.
This study seeks to elaborate this theory further and tries to answer if children exposed to
BCG (infectious challenge) have decreased risk for developing atopy plus allergic reactions due
to less polarization of Th1-Th2 immune response.
Statement of research question
Clean Environment Theory: Is increased hygiene and a lack of exposure to various
microorganisms affecting the immune systems of many populations particularly in highly
developed countries like the US - to the degree that individuals are losing their bodily
ability to fight off certain diseases?
This is a fairly new school of thought that argues that rising incidence of asthma,
inflammatory bowel disease, multiple sclerosis and perhaps several other diseases may
be, at least in part, the result of lifestyle and environmental changes that have made us too
"clean" for our own good.
Statement of the hypothesis
Is there an association of BCG vaccination with risk of development for atopy and other
allergic reactions?
Association of BCG
Method
Procedure: Potential studies for analysis will be identified by searching the MEDLINE
data base for the time period of January 1966 (the earliest MEDLINE reference date) to the
latest. References will be identified from the intersection of the medical subject headings: ‘BCG
vaccine’, ‘atopic and allergic diseases’ and ‘Th1 and Th2 immune response’.
Statistical Analysis:
For each study meeting the inclusion criteria, the odds ratio will be utilized as a method
of association due to its comparability across different sampling methods and its 95%
confidence interval (CI) will be calculated to decrease bias. The association of BCG
vaccination and development of atopic and allergic diseases will be seen.
Limitation of the study:
One criticism of the Meta-analytical statistical evaluation of published reports is that studies
with non-significant results fail to be published; thus published studies may be a biased
sample of data analyses conducted for the hypothesis under examination.
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Association of BCG
References
1. American Academy of Allergy, Asthma and Immunology (AAAAI). The Allergy
Report: Science Based Findings on the Diagnosis & Treatment of Allergic Disorders,
1996-2001.
2. CDC. Fast Stats A-Z, Vital and Health Statistics, Series 10, no.200, Table 57. 1996.
Web: http://www.cdc.gov/nchs/data/series/sr_10/sr10_200.pdf.
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