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Rapid Responses: Rapid Responses published:
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Type I diabetes and the hygiene hypothesis
- Wendy J A Anderson, Lorna Watson (25 February 2001)
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IFH Response to 'The Protective Effect of Childhood Infections' article
- Silvia Pellegrini (1 March 2001)
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Saturation of IgE response by parasites and the aetiology and treatment of atopy
- Sam Shuster (12 March 2001)
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Hygiene is still good
- Wasim Maziak (16 March 2001)
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Small family may promote development of asthma
- S K Agarwal (23 March 2002)
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Wendy J A Anderson, Consultant Respiratory Physician, SpR in Public Health Medicine Antrim Hospital, 45 Bush Road, Antrim, N. Ireland. Lothian Health, 148 Pleasance, Edinburgh, EH8 6RE, Lorna Watson
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EDITOR- Johnston and Openshaw (Editorial 17th February) state that children are born with strong interleukin 4 based, type 2 immune responses and mature to interferon gamma based, type 1 responses, and that this process is under genetic and environmental influence. They go on to state that asthma and atopy are rising in prevalence and that having older siblings and being exposed to infections promotes the normal maturation of the immune system towards a type 1 response.(1) This argument fails to take account of the evidence from insulin dependent diabetes, which is an interferon gamma based, type 1 mediated, disease. Insulin dependent diabetes is rising in incidence in children from western societies, is commoner in first born children and in the children of the well off.(2,3,4) While it remains possible that infection may have a role in the changing epidemiology of disease, the evidence above contradicts the suggestion that this is due to a failure of normal immune development, towards a type 1 immune response. Further, whilst consistent with current dogma, the conclusion that we should attempt to mimic the effect of childhood infection on the immune system is at least premature, if not totally flawed, on two counts. Firstly, association, not causation, has been demonstrated (5) and, secondly, the proposed mechanism of action is inconsistent with available evidence. (1) Johnston SL, Openshaw PJM. The protective effect of childhood infection. BMJ 2001;322:376-7. (2) Patterson CC, Carson DJ, Hadden DR. Epidemiology of childhood IDDM in Northern Ireland 1989-1994: low incidence in areas with highest population density and most household crowding. Northern Ireland Diabetes Study Group. Diabetologia 1996; 39(9):1063-9. (3) Bingley P, Douek I, Rogers C, Gale E. Influence of maternal age at delivery and birth order on risk of type1 diabetes in childhood:prospective population based family study. BMJ 2000; 321:420-4 (4) Green A, Gale E, Patterson C. Incidence of childhood-onset insulin dependent diabetes mellitus: the EURODIAB ACE study. Lancet 1992; 339:905- 909. (5) Hill’s Criteria of Causation in Last JM. (Ed) A Dictionary of Epidemiology. 3rd Edition, Oxford University Press 1995. |
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Silvia Pellegrini, Secretartiat IFH
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Dear Sir / Madam I am contacting you on behalf of the Scientific Advisory Board of the International Scientific Forum on Home Hygiene (IFH) in response to the article that was published in the British Medical Journal on Friday 16 February 2001 regarding the rise in the prevalence of asthma and atopic disease. The ‘Hygiene Hypothesis’ contends that, if we are not exposed to infectious agents, the immune system becomes imbalanced in favour of allergic response, thereby increasing susceptibility to atopic disease1. This has promoted assumptions that this is in some way related to our “too clean” modern lifestyles. What is often not clearly explained is that reduced exposure to microbes in our modern world could just as well be down to vaccines and antibiotics, sanitation, pure drinking water and clean food – as to domestic hygiene – and that any protective effect of microbial exposure may be confined to certain microbes (eg mycobacteria), at certain times (eg infancy), for certain individuals. Some scientists have good evidence suggesting that the trend in allergies is nothing to do with microbial exposure but relates to dietary changes occurring in recent years. It is the opinion of the IFH that the link between hygiene and atopic disease is by no means established and that, in view of the fact that infectious disease remains a significant concern and that prevention through hygiene is a cornerstone in our defence against infection, there is a real need to communicate a more balanced view to the public in order to ensure that hygiene standards are maintained. As part of its work, the IFH has developed an evidence-based approach to home hygiene which seeks to distinguish hygiene from cleaning. A key feature of this approach is the concept of targeted hygiene or “hot spot” hygiene in which the risky situations in the home, and the procedures required to reduce those risks, are identified. This approach to home hygiene is already well accepted and enforced in public health, food manufacturing etc as the most cost effective means of infection control in hospital and community settings. Responsible targeted hygiene enables us to fight infectious disease in the most effective manner, whilst upsetting the natural balance of our human and natural environment as little as possible. As part of this work, the IFH has produced guidelines for preventing infectious disease within the home. For copies of the guidelines or further information, please contact the IFH Secretariat at secretariat@ifh-homehygiene.org. Yours sincerely Silvia Pellegrini IFH Secretariat 1 Rook GAW, Stanford JL. Give us this day our daily germs. Immunology Today 1998;19: 113-116 |
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Sam Shuster, retired
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Sir, Your recent editorial1 asks how the apparent protective effect of childhood infections2 can be used to prevent atopic diseases. I have a simple suggestion, based on a somewhat different explanation of the "allergy epidemic". I have long considered that the IgE system evolved for control of parasitic diseases, atopy being the consequent "disorder of this primary mechanism" 3. That this consequence had come about from loss of gut parasites from the 19C onwards, occurred to me during a departmental seminar on the emergence of hay fever, and was subsequently included an historical account4 . My idea was that in past times the IgE system was too "saturated" by common parasitic allergens to react to atopic allergens. As gut allergen load decreased in developing societies, IgE recognition occurred to previously marginalised allergens, such as the air -borne grass pollen and house dust mite, with their response of hay- fever, asthma and eczema in the nose, lung and skin, and the anaphylactic response to absorbed foods, as in peanut allergy. Suitable historical records of gut parasites may exist, but it seemed possible that Jewish people, with their obsessive dietary rules, might have experienced atopy sooner than others. But while I found a description of a common and unique disorder called "miliary", but which is clearly an eczema, in Le Jau's account (most accessible in summary5) of diseases of Jews in an 18C French town, he also noted infestation with worms. Thus the evidence that hay fever occurred in Jews as early as Talmudic times6 may be more significant for my hypothesis, as is the recently demonstrated7relationship of gut parasites and IgE response. Direct proof would be oral immunisation with a gut worm antigen, which my idea predicts should prevent atopy in children, if not treat it in adults (whether there is an age difference for immune, as for endocrine responses8, should be tested, not assumed1). From mid 80's I tried to persuade industry to provide a gut worm allergen, but failed, even though the proposed end-point of clinical response and decreased wealing from atopic antigens is simple9 and would provide a patent, that industrial nirvana. Since retiring, I have tried to get a company to take the project over - one is still sitting on the proposal, after more than a year! I believe the idea that loss of parasitic allergens (mainly helminthic) has allowed the development of an IgE response to air-borne allergens such as house dust mite, pollens, food and other "atopic" allergens, provides a testable explanation of the development of atopy. Perhaps more importantly, it offers a simple means of prevention and treatment, by abrogating the response to atopic allergens by saturation of the IgE system by oral immunisation with an helminthic or similar allergen. Perhaps, with the greater contemporary interest, industry can at last be persuaded to provide such an allergen. Sam Shuster, 1. Johnston SL, Openshaw JM. The protective effect of childhood infections. The next challenge is to mimic safely this protection against allergy and asthma. BMJ 2001; 322: 377-388 2. Strachan DP. Hay fever, hygiene and household size. BMJ 1989; 299: 1259 -60 3 Shuster 1978. Dermatology in Internal Medicine OUP, Oxford 1978, ISBN 0-19-261142-9, p34. 4 Emanuel MB. Hay fever, a post industrial revolution epidemic: a history of its growth during the 19th century. Clin Allergy 1988; 18: 295-304. 5 Mitchell H, Kottek SS. An eighteenth-century view of the diseases of the jews in northeastern France: medical anthropology and the politics of jewish emancipation. Bull Hist Med 1993; 67: 248-281 6 Rosen Z. Nasal allergy in biblical and talmudic times. Annals of Allergy 1971; 29: 261-262. 7 van den Buggekaarm AHJ, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, Yazdanbakhsh M. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interlukin-10. Lancet 2000; 356: 1723-1727. 8 Thody AJ, Shuster S. Control and function of sebaceous glands. Physiol Rev 1989; 69: 383-416. 9 Humphreys F, Shuster S. The effect of indomethacin on the kinetics of histamine, 48/80 and antigen wealing. Br J Clin Pharmacol; 1990: 29: 195- 199 |
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Wasim Maziak, Georg Forster Fellow Institute of Epidemiology and Social Medicine, Muenster, Germany
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Editor In a recent editorial related to a newly published study showing a protective effect of upper respiratory tract infections on the occurrence of asthma in children [1], Johnston and Openshaw suggest that we should find “ways of reproducing the protective effects of early childhood infections, while at the same time reducing the burden of serious infectious diseases” [1]. Given the current epidemiology of the relation between childhood infections and asthma or allergy in general, such suggestion looks rather hasty to me. A protective effect of childhood infections on allergy was first suggested by David Strachan as an explanation for the protective effect of sibship size on atopic disease [2]. Subsequently Holt and Martinez provided a theoretical backup for the hygiene hypothesis by applying the Th1-Th2 paradigm to the study of allergy and infection [3]. Indeed the effect of siblings and day care attendance, as surrogate markers of childhood infections, has been repeatedly shown to provide some protection against the development of asthma. However, when studies looked directly at this relation there was more conflict than agreement. The relentless efforts of scientists to make sense out of these inconsistencies, by grouping infections according to the type of pathogen, location of infection, time of infection, or by identifying different syndromes within childhood asthma, did not produce a clearer picture. As a result, in an excellent review of all studies looking at the infection-allergy relationship, David Strachan, the father of the hygiene hypothesis, states that: “The totality of current evidence from cross sectional and longitudinal studies of common specific and non- specific infectious illnesses in infancy and childhood offers no support for the hygiene hypothesis” [4]. The uncertainty surrounding the hygiene hypothesis involves even the basic assumption that the protective effect of sibship size is due to enhanced exposure to infections, as Nafstad and colleagues recently found that asthma was inversely related to the presence of older siblings, while early respiratory infections increase, rather than decrease, the risk of developing asthma [5]. We ought to be very careful about rushing to premature conclusions considering the hygiene hypothesis, owing to the great potential of misinterpretation of such hypothesis by the public. Not only that most of recent improvement in our health and life expectancy was due to simple sanitation and hygiene measures, but as Paul Ewald suggests, good hygiene forces microorganisms to adopt a less virulent forms by breaking their transmission. Wasim Maziak PhD
References 1. Johnston SL, Openshaw PJM. The protective effect of childhood infections (Editorial). BMJ 2001;322:376-377. 2. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299:1259- 60. 3. Martinez FD, Holt PG. Role of microbial burden in aetiology of allergy and asthma. Lancet 1999;354(suppl II):1215-21. 4. Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 2000;55(Suppl 1):S2-S10). 5. Nafstad P, Magnus P, Jaakkola JJ. Early respiratory infections and childhood asthma. Pediatrics 2000 Sep;106(3):E38. |
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S K Agarwal, Head, Department of Chest Diseases, Institute of Medical Sciences, BHU, Varanasi
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Living in a small family group in hygienic conditions and taking antibiotics in early life may promote the development of asthma. Many common viral infections induce a strong protective host response dominated by the production of interferon (IFN ). This type 1 response is more effective at eliminating viruses than the alternative type 2 response (characterized by the production of interleukin 4 and interleukin 5), which promotes IgE production, eosinophilia, atopy, and asthma. Children are born with strong type 2 responses but mature their type 1 responses in the first year or so of life under environmental influence, mainly that of common childhood infections. There are “good” and “bad” germs that must be identified to prevent bad ones from harming us, and to take advantage of the good ones to properly booster our immune responses. Increased exposure to microbial agents, either through the infecting pathway or exposure to its products has been shown to substantially reduce the risk of atopic and nonatopic asthma. |
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