. . . a state of allergic response, mediated by IgE, to largely innocuous, common environmental antigens . . . it underlies the clinical diseases of asthma, hay fever, and eczema. (Shirakawa et al 1997, p 77)
Statistics from many studies demonstrate that the prevalence and severity of atopy and associated allergic diseases has risen world-wide in the last few decades (see for example, Burney, Chinn & Rona 1990; Burr et al 1989; Chadwick & Cardew 1997; Cookson & Moffatt 1997; Prescott et al 1999; Shaheen et al 1995; Taylor et al 1984). Increases have even been recorded in areas such as Africa and Asia where atopic diseases like asthma were previously rare. In North America and Europe, allergic diseases currently affect more than 15% of children and adults (Plaut, Dickler & Rotrosen 1998).
It is necessary to be mindful that some of the apparent statistical increases may be due to external factors that influence recording methods. These may include detection bias as a result of increased publicity and awareness of the conditions, and changes in diagnostic criteria. There are also difficulties in drawing conclusions about long-term trends when extensive data has only been available in many areas for a decade or so (Chadwick & Cardew 1997).
However, the currently available data suggest that atopic conditions are increasing world-wide, notably in children and young adults. For example studies have shown that asthma diagnosis for 8-11 year olds in Australia increased from 12.9% in 1982 to 29.7% in 1992. In Scotland, for 8-13 year olds it increased from 4.1% to 19.6% between 1964 and 1994. For Taiwan the figure for current asthma in 7-15 year olds
has risen from 1.3% in 1974 to 10.8% in 1994 (In Woolcock & Peat 1997, p 123).
So far the environmental changes that have been suggested as contributing to this rise in atopy include:
air pollution.
increased environmental toxins such as pesticides, herbicides and fungicides.
increased indoor exposure to dust mite antigens.
dietary changes.
(Henderson et al 1999, Shirakawa et al 1997).
There is also concern expressed by some parents (Australian Vaccination Network 1997; James 1988, p 11-19; Taycare 1997), health professionals (Blomfield 1998; Golden 1997, p 11; Kalokerinos 1974, p 59; Mendelsohn 1984; Rose 1997; Sinclair 1992, p 40-43; Smith 1994; Taycare 1997) and scientists (Henderson et al 1999; Kemp et al 1997; Odelram et al 1994; Odent, Culpin & Kimmel 1994; Rook & Zumla 1997) that immunisation may be a contributing factor. Its widespread use, accompanied by the decline of many infectious diseases in Western countries, is certainly temporally associated with the rise in atopy.
While it has been shown that some vaccines, such as measles and BCG may have long-term benefits and help prevent the development of atopic conditions, other vaccines, particularly DTP, have been associated with the exacerbation of atopic conditions. So also has the practice of administering multiple vaccines at the one time (Rook & Zumla 1997; Shoenfeld, Aharon-Maor & Sherer 2000). This will be discussed in detail in Sections 7.5.3.
Statistics (as reported in Chadwick & Cardew 1997; Peat et al 1994) show that allergic respiratory diseases, and particularly atopic asthma have increased progressively since the early 1960’s. This is synchronistic with the introduction of widespread mass immunisation of children for pertussis, diphtheria and polio was
widely implemented during the 1950’s. Measles immunisation was introduced during the 1960’s.
There is evidence that childhood infections play a part in the development of the immune system, by “either mobilizing general defense mechanisms or ‘teaching’ a lesson in how to handle other infections” (Aaby 1995, p 683) and that their
immunisation-induced decline means this developmental role may now be lacking (Cookson & Moffatt 1997; Kramer 1999; Shaheen 1996; Shirakawa et al 1997; Strachan, Taylor & Carpenter 1996). It is possible that the link may be stronger. The actual process of immunisation may be directly causative, or at least a triggering mechanism in the development of atopy in some children.
7.5.2 EVIDENCE OF CONCERN ABOUT A POSSIBLE LINK BETWEEN
IMMUNISATION AND ATOPY 7.5.2.1 Comments from parents:
These comments are from parents who have been motivated to write detailed accounts of their experiences of immunising their children for publication by the Australian Vaccination Network (AVN). These, and other accounts in the book
Vaccination Roulette (AVN 1998) have two common themes. They express a
concern about the perceived effects of immunisation on the health of their children, and dissatisfaction with the response of their local immunisation providers,
particularly their failure to acknowledge their concerns and provide of adequate relevant information.
There are many other children and babies in this area that are suffering similar reactions [asthma and eczema] and we are all being told that it is purely coincidental. (Hawkins 1998, p 140)
Fourteen days [after her second DTP shot], our baby developed eczema . . . She also began to have ear drainage problems and later
developed numerous food allergies, with one doctor describing the quantity of these as ‘over the top’. (Klotz 1998, p 157)
I [was] told . . . that he had to have his vaccinations, so I dutifully took him to the doctor and had it done. Not a thought entered my head to ask a
question about the procedure and indeed not a word was ever mentioned about adverse reactions or anything. (Messenger 1998, p 88)
7.5.2.2 Comments from health practitioners:
These comments reflect the experiences of a variety of health practitioners: a general practitioner, a nurse and a paediatrician. Although the official stance of their professions is that vaccines are safe and effective, these individuals are representative of a section of health professionals who have expressed concern about unrecognised and long term effects. Speaking out publicly against
immunisation as a medical practitioner carries with it the threat (Cosford in Taycare 1997), and sometimes the reality (McFarlane 1995) of being “debarred” from the profession. These quotes have been obtained from the publications and videos of natural health practitioners or immunisation information awareness groups such as the Australian Vaccination Network.
Many parents report that their children become increasingly intolerant of certain foods after vaccination. Griffin - medical practitioner, PhD. (1998, p 97)
I find a lot of people who had a problem with pertussis vaccine when they were children. They end up with a lot of respiratory problems. They get the sinus, the chest problems, the glue-ear . . . Rose - nurse specialising in allergies (In Taycare 1997)
There may be a relationship between immunization as a stress and the onset of some of the devastating array of [atopic] symptoms I am seeing all the time in younger and younger children. Paediatrician (In Sinclair 1992, p 41)
(See also AVN, 1998. pp 59, 85, 115, 188, 306; Taycare 1997, and more
detailed discussion in Chapter 14of this thesis.)
7.5.2.3 Comments from scientific journals:
Scientific studies on the association between atopy and childhood immunisation have provided confusing results. Pertussis is the main vaccine that has been studied in relation to atopic conditions, and some studies do show a link (Kemp et al 1997 [cohort study]; Odent, Culpin & Kimmel 1994 [population-based cross- sectional study]; Odelram et al 1994 [randomised double-blind control trial];
Schuster, Hoffman & Reinhardt 1993 [prospective study]), while others don’t (Butler et al 1982 [longitudinal cohort study]; Nilsson et al 1996 [randomised double-blind control trial]; Wjst et al 1994 [population-based cross-sectional study]). An
important point to note here is that some studies examined pertussis vaccines only, while other studies used the combination DTP vaccine, so direct comparisons are difficult. However, there is evidence that the administration of multiple vaccines may be associated with the development of atopic states (see Section 7.5.3; Rook & Zumla 1997; Shoenfeld, Ahron-Maor & Sherer 2000).
The comments below provide a summary of the findings of scientific studies reported in respected journals that show a statistically significant link between immunisation and childhood diagnosis of atopic conditions such as asthma and allergies. They all conclude that the link is significant enough to warrant further investigation.
. . . in Christchurch, New Zealand, the Wellington Asthma Research Group studied 1265 children aged 10 years and found that none of the 23 children who had not received diphtheria, pertussis, and tetanus or polio
immunisations had recorded consultations for asthma or other allergic illnesses whereas 23% of the immunised children had had episodes of asthma and 30% had consultations for other allergic illnesses. [This report and the one by Odent, Culpin & Kimmel 1994] point a strong finger of suspicion at childhood immunisation being the cause of the remarkable increase in childhood asthma and allergies over the past few decades. (Blomfield 1998, p 205; for full report see Kemp et al 1997 [longitudinal study])
The surprise came when we classified the questionnaire according to pertussis vaccination. Among 243 immunised children . . . 26 were
diagnosed as having asthma (10.69%), compared with four (1.97%) of the 203 children . . . who had not been immunised. . . Up to now we have not been able to detect any confounding factors explaining such differences . . . Therefore the focus should be on pertussis. (Odent, Clupin & Kimmel 1994, p 593 [population-based cross-sectional study])
The correlation between total IgE and PT-IgE [pertussis toxin - immunoglobulin E], which was most prominent in children with atopy, indicates that the role of immunization for the development of allergy merits further studies. (Odelram et al 1994 [randomised double-blind control trial])
7.5.3 MECHANISMS BY WHICH IMMUNISATION MAY INFLUENCE THE
DEVELOPMENT OF ATOPIC CONDITIONS
It is only recently that research into the development of the child’s immune system has begun to clarify the processes by which atopic states develop and persist in young children. Studies suggest that “the first three years of life may be important for the acquisition of atopy” (Van Asperan, Kemp & Mukhi 1990, in Woolcock & Peat 1997, p 128). These studies have focused primarily on the role of T cells and their associated cytokines. They offer hope that some of the immune imbalances that predispose to atopy may be avoided, or rectified if they arise (Bleeker, Postma & Meyers 1997; Holt et al 1997; Prescott et al 1999; Shirakawa et al 1997; Warner et al 1997). However, to use this research to its full potential, a clear understanding must be gained of the operation of environmental factors on the developing
immune system, so that exacerbating conditions can be minimized.
The current understanding of the development of the infant’s immune system does make plausible a connection between immunisation and atopy. The key issue is the balance between the two types of T helper cells, Th1 and Th2, and the respective roles they play in different types of immune response (for further discussion of Th1 and Th2 responses, see Sections 2.6; 4.2.1 and 5.3).
Atopy in adults is associated with the long-term expression of allergen- specific immunity, characterised by production of T-helper 2 (Th2) cytokines such as interleukin-4 and interleukin-5, which promote IgE production and eosinophilia. By contrast, non-atopic people show mainly T-helper 1 (Th1) immunity characterised by production of interferon-, which inhibits the growth of Th2 cells. (Prescott 1999, p 196)
Normally a predominance of Th2 type immunity is indication of pathology,
. . . except during pregnancy, when it develops naturally. This is because control mechanisms . . . limit capacity for intrauterine induction of Th1 responses, especially responses involving interferon-, which is highly toxic to the placenta. (Prescott 1999, p 200)
If this shift to a predominately Th2 type of immunity does not occur, then there is an increased risk of miscarriage, but as a consequence, both in the womb and after birth, a child’s immunity is predominately Th2 (Björkstén 1999).
Studies have shown that fetal and neonatal T cells have a much lower capacity to produce the Th1 cytokine, interferon-, than do adult T cells. The ability to mount an effective Th1 type immune response develops gradually, with production of
interferon- increasing progressively from birth until about five to seven years (Holt 1995).
The period from birth to six months is a particularly critical time. The ability to rapidly increase the production of interferon-in the months after birth is a crucial factor that differentiates non-atopic from atopic children. This is because
interferon- inhibits the production and maturation of Th2 cells, and if it is not present in sufficient amounts early enough, Th2 memory cells (those able to “remember” an antigen encounter and respond very quickly on subsequent
exposure) are able to proliferate. A balance between Th1 and Th2 responses, and
(Prescott 1999).
. . . absence of an effective Th2 inhibitory signal at this time may permit early expansion and maturation of Th2 memory cells, such that negative control via competing Th1 cells cannot be readily achieved. (Prescott 1999, p 200)
A study by Holt et al (1992) found evidence that the postnatal development of immune competence is slower in children who are genetically at high risk for atopy. They found a
. . . markedly reduced frequency of immunocompetent T cell precursors in the blood of high risk children . . . and moreover demonstrated lower production of IL-4 and (particularly) IFN-in cloned cells from this group. This finding has been confirmed [by other researchers including Martinez et al 1995 & 1997], . . . indicating that children at greatest risk for development of allergic disease are those with the lowest capacity for IFN- production, which may limit the efficiency of Th cell switching to Th1. (Holt et al 1997, p 44)
Identifying children who are genetically at risk of developing atopy is possible, as there is an identified hereditary pattern. Research shows that 50% of children with one allergic parent and 80% of children with two allergic parents become atopic. Also development of atopy is more significantly linked with allergic mothers than with allergic fathers, as it is not only passed on at the chromosomal level, but also by the conditions experienced by the fetus in utero (Warner et al 1997, p 221).
Many studies acknowledge the role that microbial exposure and early childhood infections play in aiding the development of a more effective Th1 type immune response (eg Björkstén 1999; Martinez 1994; Prescott 1999; Romagnani 1992; Rook & Stanford 1998; Shaheen 1996; Strachan, Taylor & Carpenter 1996). This is because
the production of interferon- and interleukin-2 cytokines that selectively enhance the development of Th1-type lymphocytes, and suppress Th2-type differentiation. (Strachan, Taylor & Carpenter 1996, p 422)
To summarise, the current understanding of childhood immunity holds that infants are born with a dominant Th2 type (atopy related) immune profile. In the first six
months of life a normal infant should rapidly increase its production of interferon- as it develops the ability to mount appropriate mature Th1 type immune responses. This transition continues gradually for the next five to seven years, with the
assistance of exposure to various bacterial and viral infections, until an “adult-type” balance between Th1 and Th2 type immunity is achieved. If this transition is not successfully achieved and the child retains a predominately Th2 type profile, it is prone to atopic disease. For a child with a family history of atopy it is likely that this transition, especially in the important initial stages, will be slower and less effective than average.
There is evidence that immunisation influences the Th1/Th2 cytokine balance.
Vaccinations or infections can exert a long-lasting systemic effect, and non- specifically increase or reduce the Th1 to Th2 cytokine balance of the response to other unrelated antigens. This systemic effect influences survival from unrelated diseases. (Rook & Zumla 1997, p 1831)
DTP induces a Th2 cytokine response, as does the simultaneous administration of multiple vaccines (Rook & Zumla 1997; Shoenfeld, Ahron-Maor & Sherer 2000).
The current paediatric immunisation schedules, in most nations, call for the simultaneous administration of multiple vaccines. It is recommended that at two, four and six months of age, an infant simultaneously receive:
DTP (Diphtheria, Tetanus, Pertussis)
Poliomyelitis – 3 strains
Haemophilus Influenzae type B Hepatitis B (NHMRC 2000a)
This administration of multiple vaccines may influence the natural development of a balance between the initial Th2 and the evolving Th1 types of immunity, particularly in children genetically at risk of atopy for whom this maturation process is slower than average.
7.5.4 TH2 AND THE CHILDHOOD IMMUNISATION SCHEDULE
For reasons that are possibly erroneous, and which have been discussed in
sections 5.2 and 5.3, the infant dose of tetanus, pertussis, and polio vaccines is the same as the adult dose, and therefore, in effect, several times the adult dose on a per kilogram basis. For diphtheria it is considerably higher, 30 Lf [limit of
flocculation] for infants compared to 2 Lf for adults. This is in contrast to the dose per weight schedule that is usual for nearly all other drugs and supplements. The administration of a higher dose to infants is based on the theory of neonatal tolerance, the validity of which is increasingly being questioned (see Chapter 5).
Simultaneous administration of these doses of DTP, OPV (which carries three strains of attenuated polio virus), Hib and HBV, in an infant, would therefore constitute a considerable antigenic load, particularly as DTP, Hib and HBV are injected, thus bypassing the body’s normal defense mechanisms. Even the
scheduling at two, four and six months would constitute a concentrated exposure to these antigens. Further to this, the use of aluminium compounds as vaccine
Section 4.4 and Kovarik & Seigrist 1998), especially in children with atopy (Odelram et al 1994). Aluminium compounds are employed as adjuvants in the DTP, Hib and HBV vaccines.
Significantly, infants are exposed to all these atopy inducing factors at the same time as their developing immune systems are required to significantly increase
production of interferon-, and make a natural shift from Th2 to Th1 type immunity. Obviously the majority of infants manage this transition to Th1 type immunity despite the immunological obstacles presented, however
. . . the reduction in Th1 function is much greater in individuals genetically at risk of atopy. (Prescott 1999, p 199)
For infants prone to atopy, who are already at a disadvantage in making the normal Th2 to Th1 shift, the early childhood immunisation program could feasibly be a major contributing factor to the
. . . persistence of the fetal Th2 responses during early childhood in atopic individuals and subsequent expression of disease. (Prescott 1999, p 196)
Of the adverse reactions to vaccines reported to the Vaccine Adverse Event Reporting System (VAERS) in the United States during 1991-94, 75.7% of the 38,787 reports followed the administration of multiple vaccines (Braun & Ellenberg 1997). The studies done by Odent, Culpin & Kimmel (1994) and Kemp et al (1997) both showed significantly lower rates of asthmatic and atopic conditions in
unimmunised children. It is also interesting that several studies on atopy, and particularly on asthma, have noted that the prevalence of allergies and asthma is lower in the younger children of large families than children higher in the birth order, (eg Cookson & Moffatt 1997; von Mutius et al 1997; Shaheen 1996; Shirakawa 1997; Strachan 1989) and this is usually, and feasibly, interpreted as
“indirect evidence that infection early in childhood may prevent allergic disease.” (Shaheen 1996) However, it is also recognised that larger family size is associated with lower immunisation rates for the younger children (Forrest, Burgess &
McIntyre 2000; Ponsonby et al 1997) simply because the mother often becomes too busy to remain as conscientious about immunisation as she was with the older children. Further studies could usefully examine this link.
7.5.5 SUMMARY OF FINDINGS ON IMMUNISATION AND ATOPY
Infants are born with a predominately Th2 cytokine profile. During the first five to seven years, and particularly in the first six months of life, they develop the Th1 cytokine profile that is an important part of the body’s defence against infectious diseases. The maintenance of a predominately Th2 profile has been linked with the