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Is there scientific evidence that suppression of acute diseases in childhood induce chronic diseases in the future?
Abstract
Seeking to understand the individual in his symptomatic totality has been an aim of homeopathy since its beginning. Throughout its history, homeopaths have been concerned that inadequate treatment of acute diseases in childhood may lead to future chronic diseases. Hahnemann cautioned that by treating acute diseases with allopathic medicine, with strong doses of drugs, or suppressing local symptoms of those diseases, would increase the risk of future chronic diseases. Burnett proposed the theory of vaccinosis and warned of chronic manifestations subsequent to smallpox vaccination. French homeopaths, seeking the physiopathological origin of chronic diseases, correlated it to the abnormal reaction of the reticuloendothelial system (RES). Through the study of experimental pathology, Maffei attributed symptomatic manifestations to the imbalance between the immunological phenomena of allergy and immunity. He termed the sensitizing and pathogenic effects of medications and vaccines, 'metallergy' and 'parallergy', respectively. The hygiene hypothesis is based on evidence that the imbalance of immunological response in childhood, specifically among the Th1 and Th2 lymphocyte subpopulations, is responsible for the development of some allergic and chronic diseases in the future. The deranging factor for the predisposition to future allergic response (Th2) is the obstruction of natural manifestations of infectious diseases (Th1 response) in young children. Homeopathic treatment aims to equilibrate vital reaction, corresponding to an integrative physiological response, it may regulate Th1/Th2 imbalance. However, clinical trials to support this hypothesis are lacking.
... According to previous studies, homeopathic medications might be of help in alleviating the immune depression that may follow vaccinations or other stressors (Schuberth et al., 2002;Teixeira, 2002). ...
... The observation that administration of Thuja in goats can prevent the impairment of lymphoblastogenesis following vaccination against BTV is novel. However, our results support the hypothesis that homeopathic medications may be of help in alleviating side effects of vaccinations (Teixeira, 2002). ...
This preliminary study was realized to assess the effects of Thuya occidentalis in homeopathic dilution (200 centesimal dilution) on nonspecific lymphoblastogenesis of goats vaccinated against bluetongue virus serotype 2 (BTV). Twenty Saanen goats were treated as follows: six goats were vaccinated with a live attenuated vaccine against BTV, four goats were vaccinated and injected with 1 ml of an alcoholic solution containing Thuya occidentalis, six goats were neither vaccinated nor given thuya, the remaining four goats were not vaccinated, but treated with thuya. Administration of thuya prevented depression of nonspecific lymphoblastogenesis, which followed vaccination.
... Suppressing the symptoms of a disease often causes adverse effects on the body. The suppressed disease tends to affect deeper structures and settles in healthier tissues and organs [20][21]. The consolidated theory on disease constitutes a valuable source of information and understanding of the natural history of a disease, since it also allows for the analysis of symptoms as well as the pathophysiological behavior of the human body. ...
... Not only do homeopathic treatments present a low risk of adverse reactions, the low cost of homeopathic preparations is low and they distinction from the concept of placebo [29,34]. In contrast, chronic use of chemical medicines can be interpreted from a homeopathic view as a phenomenon of "symptom suppression," given that patients may develop terminal kidney failure [20]. In addition, it is well documented that a vast number of antimicrobial medicines administered for the treatment of urinary tract infections also cause nephrotoxicity . ...
Background: Chronic diseases are illnesses or health conditions that are persistent and have long-term effects on the physical status of the human body. The manifestation of a chronic disease is the result of coexistence of multiple chronic diseases. Especially, the chronic kidney disease (CKD) is a representative chronic syndrome of multifactorial affair, characterized by a gradual progression.
Methods: This study considered 81 patients with CKD and investigated the correlation between the disease and the patients' demographics, anamnesis, and clinical presentation, as well as the potential relationship between the disease and other illnesses.
Results: A signifiant number of diseases can lead to the manifestation of CKD, and notably, many of them are idiopathic. However, despite the rapid development in medical science and pharmaceutical technology and a plethora of research trials, there is a lack of ability to identify and analyze the causes and pathophysiologic mechanisms that are responsible for the manifestation of CKD.
Conclusions: This retrospective study investigates the factors that may play a role in the manifestation of CKD through the knowledge and research of both conventional medicine and homeopathy.
... It identifies the cause of such phenomena as the imbalance of lymphocytic immunological response, secondary to the inhibition of manifestations of infectious diseases. [3] As per Dr. Hahnemann, the susceptibility to different acute diseases is an outcome of the combined effect of the chronic miasm and accessory circumstances of the patient. [4] As psora is the mother of all acute diseases, removal of the predisposition to acute diseases depends on the removal of chronic miasm through anti-miasmatic treatment. ...
... A pesar de lo enormes beneficios de los programas de inmunización convencional realizados en la esfera de la salud pública, también se han podido documentar reacciones adversas y agravaciones de enfermedades crónicas cuando sus efectos son evaluados, con base en patrones de susceptibilidad individual. Apoyados en razones científicas bien justificadas 74,75 , los médicos homeópatas tienen derecho a contraindicar cualquier vacuna para evitar mayores daños en la salud del paciente. ...
La Homeopatía puede utilizarse para la prevención de enfermedades epidêmicas (homeoprofilaxis) siempre que los medicamentos sean escogidos individualmente, de acuerdo al ‘principio de semejanza sintomática’ y a la totalidad de los sintomas característicos de una epidemia dada (remedio del ‘genio epidémico’), como demuestran un gran número de ejemplos en la literatura. El uso de nosodes para prevención de epidemias (isoprofilaxis), es decir, escogidos en función del ‘principio de identidad etiológica’, con total omisión de la individualización sintomática y los estudios patogenésicos, no tiene fundamento en el modelo epistemológico homeopático. Hasta que no se disponga de evidencias científicas confiables que atestigüen su eficacia y seguridad, no es posible indicar el remplazo de las vacunas tradicionales por una ‘inmunización isopática’, pues representaría una contravención de los principios bioéticos de ‘beneficencia’ y ‘no-maleficencia’. Aunque es cierto que muchos homeópatas indican sistemáticamente tal remplazo, este es criticado por instituciones homeopáticas de todo el mundo. En este artículo, discuto más extensamente aspectos epistemológicos, éticos y científicos de estas modalidades de profilaxis que abordé someramente en una revisión anterior.
... Pautando estas observações em dezenas de estudos epidemiológicos que confirmavam a teoria imunológica da "hipótese higiênica", este artigo é a tradução literal de artigo de revisão publicado em 2002 na Homeopathy (Is there scientific evidence that suppression of acute diseases in childhood induce chronic diseases in the future? [39]), tendo sido contestado em 2005 por revisão composta por estudos contrários à "hipótese higiênica" [40]. No mesmo ano, na edição seguinte da Homeopathy, publicamos outra revisão atualizada com centenas de novos estudos que confirmavam a referida teoria [41], sendo contestada novamente [42], perpetuando-se o debate sobre a referida proposta até os dias atuais [43]. ...
Founded in 1936 to divulgate studies on homeopathy and related fields, Revista de Homeopatia, edited by the São Paulo Medical Homeopathic Association, is one of the oldest homeopathic scientific publications in the world, and is currently included in several databases and digital libraries. Initially published in printed format, starting 2008 it became an open-access electronic journal “to facilitate the access to this ield of medical-scientific studies”. Based on that same ideal, I recently made a collection of articles ublished in this journal, as well as in Revista de Homeopatia, edited by the Brazilian Medical Homeopathic Association, available online. To facilitate the initial immersion in the wide-scoped content of these “Homeopathic studies, in this article I present a synthesis of the results and conclusions of articles published over 20 years, with some additional reflections on the relevance of those publications for my clinical practice, as well as for the elaboration of other varieties of scientific productions.
RESUMO: Inaugurada em 1936, com o intuito de difundir estudos relacionados à homeopatia e áreas afins, a Revista de Homeopatia da Associação Paulista de Homeopatia (APH) é uma das mais antigas publicações científicas homeopáticas, estando incluída em diversos bancos de dados e bibliotecas virtuais. Inicialmente editada na forma impressa, passou a ser disponibilizada na forma online por acesso aberto a partir de 2008, facilitando o “acesso ao saber construído nesta área de estudos médicos científicos”. Compartilhando esse mesmo ideal, disponibilizei recentemente, em formato digital de livre acesso, uma coletânea de artigos publicados na forma impressa da revista, juntamente com estudos publicados na Revista de Homeopatia da Associação Médica Homeopática Brasileira (AMHB). Objetivando facilitar o contato de todos ao vasto conteúdo destes “Estudos homeopáticos”, elaborei neste artigo uma síntese dos resultados e conclusões destes 20 anos de publicações na Revista de Homeopatia (São Paulo), acrescentando algumas reflexões sobre a importância das mesmas na minha prática clínica e na elaboração de outras produções científicas.
... In spite of the enormous benefits that conventional immunization programs afford in the public health sphere, adverse reactions and aggravation of chronic diseases might be found, when their effects are evaluated based on patterns of individual susceptibility. Based on well-justified clinical and scientific reasons [68,69], homeopathic doctors are entitled to contraindicate any vaccine to avoid further impairment of the patient's health. ...
Homeopathy might be employed for the prevention of epidemic diseases (homeoprophylaxis) provided remedies are selected on an individual basis in compliance with the ‘principle of symptom-based similitude’ and according to the totality of symptoms peculiar to a given epidemic (remedy of the ‘epidemic genius’ or ‘genus epidemicus’), as countless examples in the literature show. The use of nosodes for the prevention of epidemic diseases (isoprophylaxis), i.e., selected based on the ‘principle of etiological identity’ with full neglect of symptom-based individualization and pathogenetic trials, is not supported by the homeopathic epistemological model. As long as there are no reliable scientific evidences attesting to its efficacy and safety, ‘isopathic immunization’ might not be indicated as a regular replacement of classical immunization, as it would mean a transgression of the bioethical principles of ‘beneficence’ and ‘non-maleficence’. Although many homeopathic practitioners systematically indicate that practice, it is condemned by homeopathic institutions worldwide. In this article, I elaborate on epistemological, ethical and scientific features of these disparate approaches to prophylaxis, which I had summarily addressed in a previous review.
http://www.feg.unesp.br/~ojs/index.php/ijhdr/article/view/707/687
... A narrative review has cited the hygiene hypothesis and its immunological theory as the 'scientific basis' to endorse the following observations, 'empirically cited over the centuries' by 'homeopathic physicians': suppression of natural manifestation of acute diseases can cause future chronic diseases, suppressing the manifestation of acute disease, vaccines can subsequently induce chronic diseases, with predominantly allergic symptoms (dermatitis, rhinitis, sinusitis, bronchitis, etc). 14 The objective of this article is to evaluate the validity of these claims, and specifically the following: Do infections in infancy protect against atopy? Is immunisation (suppressing 'benign' infections of infancy) a risk factor for the development of atopy? ...
The 'hygiene hypothesis' has been used to justify a belief common among homeopaths, that the suppression of childhood infections and immunisation may lead to the development of chronic atopic diseases.
To analyse the influence of childhood infections and immunisation on the development of atopy.
Qualitative systematic review of direct epidemiological evidence (Medline 1993-2004) concerning the influence of childhood infections and immunisation on the development of atopy and discussion based on homeopathy.
(1) Childhood infections do not protect against atopy; on the contrary, they increase the risk of allergic diseases, in agreement to Hahnemann's observations, which included epidemic diseases among the factors capable of stimulating the development of chronic diseases. (2) Vaccination is not a risk factor for atopy, notwithstanding the allergenic effect of some vaccines.
... At the end of 2002, I published an article that related 'the clinical observation, empirically cited over the centuries', that 'inhibition of acute disease manifestation in childhood can predispose to future chronic diseases', according to distinct lines from medical thought: homeopathy (Hahnemann, Burnett, French school), anthroposophic medicine, experimental pathology (Maffei). 1 This theory assumed a modern scientific guise in the 'hygiene hypothesis', suggesting 'an inverse relationship between atopic diseases and an environment that leads to increased pathogen exposure'. ...
... In a theoretical study 16 relations have been suggested between the homeopathic theory of chronic disease, the Th1-Th2 balance (other Th cells are also implicated), and the hygiene hypothesis to explain the development of atopy. The possible protective effect of childhood infections against atopy and the role of vaccination as a risk factor for atopy have been systematically analysed 17 and not confirmed. ...
Vaccine hesitancy–the reluctance to receive recommended vaccination because of concerns and doubts about vaccines–is recognized as a significant threat to the success of vaccination programs and has been associated with recent major outbreaks of vaccine-preventable diseases. Moreover, the association between complementary and alternative medicine (CAM) use and vaccine hesitancy and/or refusal has been frequently reported in the literature. To date, significant gaps persist in our understanding of contemporary Canadian CAM providers’ beliefs regarding vaccination and how socio-professional influences may shape their vaccine-related attitudes and behaviours. To address the latter gap, the current study aims to explore the content of professional guidelines, recommendations and other discourses among CAM providers as they concern vaccination by analyzing both academic, peer-reviewed literature and Canadian organizational webpages prepared by and/or for practicing chiropractors, naturopaths and homeopaths. In the academic literature, we identified a number of complex and diverging views on vaccination that spanned topics of effectiveness; safety; theoretical, empirical, and ethical soundness; political justifiability; and compatibility with CAM philosophy and professional boundaries. However, in its current state the CAM literature cannot be described in broad strokes as being either pro- or anti-vaccination without considering finer areas of disagreement. Compared to the academic literature, which focuses more on the conceptual and evidentiary basis of vaccination, a greater proportion of vaccine-related content on Canadian CAM organizations’ webpages seems to be dedicated to offering specific directives and prescriptions to providers. Guidelines and standards of practice address a number of issues, including vaccine administration, counsel, education and marketing. As CAM organizations further evolve in Canada and elsewhere as part of a broader “professionalization” initiative, greater attention will need to be directed at their role in shaping providers’ beliefs and practices that both support and undermine vaccine promotion efforts.
Homeopathy might be employed for the prevention of epidemic diseases (homeoprophylaxis) provided remedies are selected on an individual basis in compliance with the 'principle of symptom-based similitude' and according to the totality of symptoms peculiar to a given epidemic (remedy of the 'epidemic genius' or 'genus epidemicus'), as countless examples in the literature show. The use of nosodes for the prevention of epidemic diseases (isoprophylaxis), i.e., selected based on the 'principle of etiological identity' with full neglect of symptom-based individualization and pathogenetic trials, is not supported by the homeopathic epistemological model. As long as there are no reliable scientific evidences attesting to its efficacy and safety, 'isopathic immunization' might not be indicated as a regular replacement of classical immunization, as it would mean a transgression of the bioethical principles of 'beneficence' and 'non-maleficence'. Although many homeopathic practitioners systematically indicate that practice, it is condemned by homeopathic institutions worldwide. In this article, I elaborate on epistemological, ethical and scientific features of these disparate approaches to prophylaxis, which I had summarily addressed in a previous review.
Available at: http://highdilution.org/index.php/ijhdr/article/view/707
Autoimmune and neuroimmune diseases prevalence rates are rising enormously. It would be difficult to explain with genetic and environmental factors. Noteworthy, this rising maybe related with childhood vaccine programs. There is also a lack of information about this topic in pediatric and family medicine practice in some countries like Turkey. Prevention and treatment of these diseases is possible if pathogenesis could be well understood. We attempt to review this topic in immunological and neurological perspectives for this purpose. We searched Pubmed from year 2000 to date with neuroimmune, autoimmune, measles and vaccine link keywords in some combinations and related topics. The obtained information from this search dealt with some important subheadings. There is a need for further investigations of neuroimmune disease and the possible vaccine link.
Although the academic and classic scientific class exigencies for well elaborated homeopathic clinical tests (double-blind, randomized), which prove the effectiveness of the homeopathic treatment against the placebo and other therapeutics, the Brazilian scientific homeopathic class hasn’t done its best efforts to produce this kind of work, getting farther and farther from the universities research centers. In order to approach this academic environment, we have been trying to suit the conventional model of clinical research to the homeopathic model, enabling the clinical research with homeopathy to be performed and accepted by the modern scientific current, considering the modification of some basic premises.
RESUMO: Apesar da exigência do meio acadêmico e científico clássico por ensaios clínicos homeopáticos bem elaborados (duplo-cego, randomizado), que evidenciem a eficácia do tratamento homeopático frente ao placebo e demais terapêuticas, a classe científica homeopática brasileira não tem se empenhado em produzir este tipo de trabalho, afastando-se cada vez mais dos centros de pesquisa universitários. No intuito de nos aproximarmos deste meio acadêmico, buscamos adaptar o modelo de pesquisa clínica convencional ao modelo homeopático, possibilitando que a pesquisa clínica com homeopatia possa ser realizada e aceita pelo pensamento científico moderno, desde que algumas premissas básicas sejam modificadas.
Objective: To investigate the association between early childhood infections and subsequent development of asthma.
Design: Longitudinal birth cohort study.
Setting: Five children's hospitals in five German cities.
Participants: 1314 children born in 1990 followed from birth to the age of 7 years.
Main outcome measures: Asthma and asthmatic symptoms assessed longitudinally by parental questionnaires; atopic sensitisation assessed longitudinally by determination of IgE concentrations to various allergens; bronchial hyperreactivity assessed by bronchial histamine challenge at age 7 years.
Results: Compared with children with 1 episode of runny nose before the age of 1 year, those with 2 episodes were less likely to have a doctor's diagnosis of asthma at 7 years old (odds ratio 0.52 (95% confidence interval 0.29 to 0.92)) or to have wheeze at 7 years old (0.60 (0.38 to 0.94)), and were less likely to be atopic before the age of 5 years. Similarly, having 1 viral infection of the herpes type in the first 3 years of life was inversely associated with asthma at age 7 (odds ratio 0.48 (0.26 to 0.89)). Repeated lower respiratory tract infections in the first 3 years of life showed a positive association with wheeze up to the age of 7 years (odds ratio 3.37 (1.92 to 5.92) for 4 infections v 3 infections).
Conclusion: Repeated viral infections other than lower respiratory tract infections early in life may reduce the risk of developing asthma up to school age.
During 1979-82 hospital discharge rates after emergency admission for acute appendicitis were higher in Eire (17.4 per 10,000 population) than in England (10.3), Scotland (11.1), or Wales (12.3). Comparison of food consumption between the four countries, and between the health board areas of Eire and regions of Scotland, shows that appendicitis rates are highest in communities that consume more potatoes, sugar, and cereals, and less non-potato vegetables and fruit. The rates are also related to mortality from enteric and respiratory infections, to general practice consultations for infective disease, and to postneonatal mortality. This is evidence in favour of the hygiene hypothesis for the aetiology of appendicitis.
Allergic asthma is characterized by airway hyperresponsiveness and pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the expression of Th2 cytokines and their associated responses, including eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have previously shown in a murine model that antigen-induced increases in airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell dependent. We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression. Sensitized A/J mice developed airway hyperresponsiveness and increased numbers of BAL eosinophils and other inflammatory cells after single or repeated intratracheal challenges with sheep red blood cell antigen. Pulmonary mRNA and protein levels of the Th2 cytokines IL-4 and IL-5 were increased after antigen challenge. Administration of IL-12 (1 microgram/d x 5 d) at the time of a single antigen challenge abolished the airway hyperresponsiveness and pulmonary eosinophilia and promoted an increase in interferon (IFN) gamma and decreases in IL-4 and IL-5 expression. The effects of IL-12 were partially dependent on IFN-gamma, because concurrent treatment with IL-12 and anti-IFN-gamma monoclonal antibody partially reversed the inhibition of airway hyperresponsiveness and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation. These data show that antigen-induced airway hyperresponsiveness and inflammation can be blocked by IL-12, which suppresses Th2 cytokine expression. Local administration of IL-12 may provide a novel immunotherapy for the treatment of pulmonary allergic disorders such as atopic asthma.
Commitment of T helper 1 (Th1) or Th2 populations developing during an immune response to a pathogen, or an inappropriate immune response to an allergen or autoantigen, may determine the difference between health and chronic disease. We show that strongly polarized Th1 and Th2 populations assessed by immunoassay are heterogeneous using flow cytometry to detect single cells producing interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Th1 populations arising after 1 wk of stimulation in IL-12 plus anti-IL-4 antibodies could convert to Th2 cells when restimulated in IL-4. Th2 populations resulting from stimulation for 1 wk in IL-4 could give rise to Th1 cells upon restimulation in IL-12 plus anti-IL-4. In contrast, the cytokine profiles of long-term Th1 and Th2 populations arising originally from repeated stimulation in IL-12 or IL-4 appeared more homogeneous and were not reversible, although IL-4 dramatically reduced the number of IFN-gamma-producing Th1 cells. This may explain previous reports that Th1 cells can be converted to Th2 cells.
In a study of 58 children under the age of 16 with insulin dependent diabetes (IDDM) and 172 matched non-diabetic controls, infection during the first year of life was associated with a reduction in diabetes risk (odds ratio 0.81, 95% confidence interval 0.67 to 0.98, per infective episode). Decreased exposure to common infections during infancy may be linked with subsequent IDDM.
The balance between interferon gamma (IFN gamma) and interleukin 4 (IL4) producing T cells (T1 and T2 cells) seems to be of importance in many (auto)immune disorders. In general, T1 cell activity is important in cellular immunity whereas T2 cell activity plays a part in humoral responses. T1 cell activity predominates in joints of patients with rheumatoid arthritis (RA) whereas T2 cell activity is characteristic of atopic syndromes. This study investigated whether the prevalence of hay fever in RA is low and if severity of RA (T1 cell activity) can be influenced by the concomitant occurrence of a T2 cell mediated disease (hay fever).
The prevalence of hay fever was assessed in 643 consecutive (RA and non-RA) patients seen in our outpatient clinic and confirmed by skin test and specific IgE. Of this group the 12 RA patients with hay fever were compared with RA patients without hay fever (matched for age, sex, and disease duration).
The prevalence of hay fever in RA patients is lower than in non-RA patients (4% versus 8%), and yields a relative risk for RA patients to develop hay fever of 0.48. RA patients with hay fever showed a lower disease activity (erythrocyte sedimentation rate, C reactive protein, Thompson joint score, and radiographic joint damage (Sharp) score) than RA patients without hay fever. The clinical data were related to peripheral blood T1/T2 cell balance: a lower IFN gamma/IL4 ratio was observed for RA patients with hay fever, indicating a comparatively increased T2 cell activity in RA patients with hay fever.
These results argue in favour of the exploration of treatments aimed at regulation of a possible imbalance in T1/T2 cell activity in RA.
Allergic asthma is thought to be regulated by Th2 cells, and inhibiting this response is a promising mode of intervention. Many studies have focused on differentiation of Th cells to the Th1 or Th2 subset in vitro. IL-4 is essential for Th2 development, while IL-12 induces Th1 development, which can be enhanced by IL-18. In the present study, we investigated whether IL-12 and IL-18 were able to interfere in Th2 development and the associated airway symptoms in a mouse model of allergic asthma. Mice were sensitized with OVA using a protocol that induces IgE production. Repeated challenges by OVA inhalation induced elevated serum levels of IgE, airway hyperresponsiveness, and a predominantly eosinophilic infiltrate in the bronchoalveolar lavage concomitant with the appearance of Ag-specific Th2-like cells in lung tissue and lung-draining lymph nodes. Whereas treatments with neither IL-12 nor IL-18 during the challenge period were effective, combined treatment of IL-12 and IL-18 inhibited Ag-specific Th2-like cell development. This inhibition was associated with an absence of IgE up-regulation, airway hyperresponsiveness, and cellular infiltration in the lavage. These data show that, in vivo, the synergistic action of IL-12 and IL-18 is necessary to prevent Th2-like cell differentiation, and consequently inhibits the development of airway symptoms in a mouse model of allergic asthma.
To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies.
Retrospective case-control study.
240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24.
Air force school in Caserta, Italy.
Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis.
Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18% v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0. 70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus).
Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.
The timing of events leading to allergic sensitisation has become a very important area in the attempt to halt the dramatic increase in the prevalence of diseases such as asthma, eczema and hay fever. Recent research has demonstrated that events taking place during the gestational period may well play a role in determining whether or not a genetic susceptibility becomes translated into disease processes. Maternal atopy seems to have an important effect on the developing immune response of the infant and increases the chances of the child developing allergy in later life. Maternal IgE, IgG and amniotic fluid cytokines, combined with the presence of allergen in the feto–maternal environment are all possible factors involved in the ultimate outcome in terms of infants Th-1/Th-2 responses to common environmental antigens. Immune modulation at this stage of development may, in the future, be a way forward in the prevention of allergy.
Background-Atopy is of complex origins but the recent rise in atopic diseases in westernised communities points to the action of important environmental effects. One candidate mechanism is the changing pattern of microbial exposure in childhood. This epidemiological study investigated the relationship between childhood infections and subsequent atopic disease, taking into account a range of social and medical variables. Methods-A total of 1934 subjects representing a retrospective 1975-84 birth group at a family doctor practice in Oxfordshire were studied. Public health and practice records were reviewed; temporal records were made of all diagnoses of infections and their treatments, all immunisations, and diagnoses of asthma, hay fever and eczema; maternal atopy and a number of other variables were documented. Results-Logistic regression analysis identified three statistically significant predictors of subsequent atopic disease: maternal atopy (1.97, 95% CI 1.46 to 2.66, p<0.0001), immunisation with whole-cell pertussis vaccine (1.76, 95% CI 1.39 to 2.23, p<0.0001), and treatment with oral antibiotics in the first two years of life (2.07, 95% CI 1.64 to 2.60, p<0.0001). There was no significant association found for maternal smoking, bottle feeding, sib-ship size, or social class. Conclusions-The prediction of atopic disease by maternal atopy mainly reflects the effect of acknowledged genetic factors. Interpretation of the prediction of atopic disorders by immunisation with whole-cell pertussis vaccine and treatment with oral antibiotics needs to be very cautious because of the possibilities of confounding effects and reverse causation. However, plausible immune mechanisms are identifiable for the promotion of atopic disorders by both facta,rs and further investigation of these associations is warranted.
Any system or device containing computers should be assumed to have Year 2000 problems. Date defects in the intensive care environment might be harmful to patients or lead to allegations of harm. Year 2000 problems will not only be when the date changes to 1 January 2000 but may occur before and after. The NHS has given sound advice about addressing Year 2000 problems and intensive care units might be well advised to take steps of their own. It is important to take Year 2000 problems seriously, it is also necessary to maintain balance. Prepared staff with realistic contingency plans should be able to cope with any reasonably anticipated problems arising in intensive care.
Allergic asthma is characterized by airway hyperresponsiveness and pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the expression of Th2 cytokines and their associated responses, including eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have previously shown in a murine model that antigen-induced increases in airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell dependent. We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression. Sensitized A/J mice developed airway hyperresponsiveness and increased numbers of BAL eosinophils and other inflammatory cells after single or repeated intratracheal challenges with sheep red blood cell antigen. Pulmonary mRNA and protein levels of the Th2 cytokines IL-4 and IL-5 were increased after antigen challenge. Administration of IL-12 (1 microgram/d x 5 d) at the time of a single antigen challenge abolished the airway hyperresponsiveness and pulmonary eosinophilia and promoted an increase in interferon (IFN) gamma and decreases in IL-4 and IL-5 expression. The effects of IL-12 were partially dependent on IFN-gamma, because concurrent treatment with IL-12 and anti-IFN-gamma monoclonal antibody partially reversed the inhibition of airway hyperresponsiveness and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation. These data show that antigen-induced airway hyperresponsiveness and inflammation can be blocked by IL-12, which suppresses Th2 cytokine expression. Local administration of IL-12 may provide a novel immunotherapy for the treatment of pulmonary allergic disorders such as atopic asthma.
We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic imm;notherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p=0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p=0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?
Commitment of T helper 1 (Th1) or Th2 populations developing during an immune response to a pathogen, or an inappropriate immune response to an allergen or autoantigen, may determine the difference between health and chronic disease. We show that strongly polarized Th1 and Th2 populations assessed by immunoassay are heterogeneous using flow cytometry to detect single cells producing interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Th1 populations arising after 1 wk of stimulation in IL-12 plus anti-IL-4 antibodies could convert to Th2 cells when restimulated in IL-4. Th2 populations resulting from stimulation for 1 wk in IL-4 could give rise to Th1 cells upon restimulation in IL-12 plus anti-IL-4. In contrast, the cytokine profiles of long-term Th1 and Th2 populations arising originally from repeated stimulation in IL-12 or IL-4 appeared more homogeneous and were not reversible, although IL-4 dramatically reduced the number of IFN-gamma-producing Th1 cells. This may explain previous reports that Th1 cells can be converted to Th2 cells.
Background: We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined.Objectives: We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies.Methods: Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was quantitated by a sensitive reverse transcription, competitive PCR.Results: IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90 ± 0.18 vs 1.24 ± 0.19 log10 fmol/μL for individuals with allergies) (P = .02). Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant.Conclusions: IL-12 production in individuals with MS is much greater than in individuals with allergies. Because IL-12 induces TH1 cytokine synthesis and reduces the production of TH2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system. (J Allergy Clin Immunol 1998;102:428-35.)
This work suggests that it is possible to study some key issues relevant to homoeopathy using standard trial designs. Further the results of this pilot study appear to demonstrate a difference in effect between a 30c potency and a placebo. A larger definitive study is under way to examine the reproducibility of these results
Background There is increasing evidence that the T-cell reactivity to environmental allergens underlying expression of allergic disease in adulthood, develops initially during childhood. However, there is little information available on the kinetics of these early responses, or on the patterns of cytokine production during this period.
Objective The purpose of this study was twofold: to obtain further information on the reported differences between responses to food versus inhalant allergens during early childhood, and to ascertain the age-range over which T-cell responses to inhalant allergens become polarized towards the TH2 cytokine profile, in potentially atopic children.
Methods In vitro cytokine responses to house dust mite (HDM) and egg (OVA) were assessed by semiquantitative RT-PCR in panels of 2- and 5-year-old children and adults; lymphoproliferative responses to OVA were subjected to epitope analysis.
Results At age 2 years IL-4/IL-5 responses to HDM grouped with positive atopic family history, and by age 5 years cytokine responses correlated strongly with individual SPT reactivity to HDM. In contrast, OVA responses were restricted to weak and transient IL-5 signals in the 2-year-old family history positive group. Lymphoproliferation assays performed in parallel indicate a log-scale greater postnatal expansion of T-cell reactivity to the inhalant allergen; preliminary epitope analysis of OVA responses indicate that the number of OVA epitopes recognised decrease during early childhood.
Conclusions Inhalant allergen-specific in vitro cytokine production associated with positive skin-prick test (SPT) reactions, one of the hallmarks of adult atopy, manifests in children at or before 5 years of age; additionally, cytokine responses in SPT negative 5 year-olds are restricted to IFNγ, as per normal adults. In contrast, T-cell responses to a typical food allergen appear to be deleted during early childhood.
BackgroundReversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in Western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy).MethodsIn a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint.FindingsAtopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0·51 [95% Cl 0·32–0·84]). The number needed to treat was 4·5 (95% Cl 2·6–15·6).InterpretationsLactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.
There is controversy regarding immunization. This paper concentrates on measles although the evidence is more broadly based. Both mortality and morbidity figures strongly suggest that despite a few casualties the campaign has saved many lives and much suffering, even though its goal of eliminating measles has not yet been achieved. Unfortunately the immunizing effect of the vaccine has a shorter duration of action than the disease itself, and this has led to outbreaks of measles amongst older age-groups immunized as babies. Morbidity and mortality are higher when measles is contracted at older ages. A revaccination campaign is under way. Side effects from revaccination are less frequent than with primary vaccination.
The incidence of a variety of chronic diseases, some of which are related to the immune system, has risen concurrently with the various immunization programmes. Opponents fear that the two phenomena are connected, and that by proceeding with immunization we are fundamentally damaging the race. While the evidence for such a connection is weak, it cannot entirely be dismissed as it is equally hard to disprove. We should remain alert to the possibility and research it honestly while continuing with the campaign, since abandoning it would undoubtedly result in much more loss of life and permanent disability.
We evaluated the allergy status of 134 immigrants from Asia, Africa, the Middle East and South America, who were referred to our clinic during the past 10 years. Fifty Swedish patients were used for comparison. When the atopy state was not taken into account, no significant difference was found between the two groups with respect to total IgE levels. However, IgE levels of non-atopic immigrants were significantly higher than the IgE levels of non-atopic Swedes. While there was no significant difference in IgE levels between atopic and non-atopic immigrants, this difference was significant in Swedish patients. In general, IgE levels of immigrants showed a decline with time and reached approximately the same levels as for the Swedish patients in 10.5 years. In the immigrant group atopic women had a considerably lower IgE level than the atopic men. Among the atopics there were no differences between sexes. In Swedes and immigrants pollen was the most common group of allergens. The spectrum of allergy in the immigrant group changed with time in Sweden, and gradually became more similar to the Swedish spectrum. Skin and/or RAST positivity to birch increased from 16% within 2.5 years to 53% after more than 10.5 years in Sweden. Our data indicate that environmental factors rather than hereditary differences determine the IgE state. Within a few years the immunologic status of immigrants adapts to the new environment.
In human beings, as in mice, two distinct patterns of cytokine secretion have been defined among CD4+ helper T-cell clones. Human type 1 helper (Th1), but not type 2 helper (Th2), cells produce interleukin-2 (IL-2), gamma-interferon (IFN-gamma), and tumor necrosis factor-beta, whereas Th2, but not Th1, cells secrete IL-4 and IL-5, but not IL-2 or IFN-gamma. Other cytokines, such as IL-3, IL-6, GM-CSF, or TNF-alpha, are produced by both Th1 and Th2 cells. Th0 cells, a third Th subset, show combined production of Th1- and Th2-type cytokines. The different cytokine patterns are associated with different functions. In general, Th2 cells provide an excellent helper function for B-cell antibody production, particularly of the IgE class. On the other hand, Th1 cells are responsible for delayed type hypersensitivity reactions and are cytolytic for autologous antigen-presenting cells, including B cells. Most allergen- or helminth-antigen-specific human CD4+ T-cell clones exhibit a Th2 phenotype, whereas most clones specific for bacterial antigens show a Th1 profile. Allergen-specific Th2 cells seem to play a crucial role in atopy. These cells induce IgE production via IL-4 and favor the proliferation, differentiation, and activation of eosinophils via IL-5. In addition, Th2-derived IL-3 and IL-4 are mast-cell growth factors that act in synergy, at least in vitro. Recent evidence indicates that allergen-specific Th2 cells are selectively enriched in tissues affected by allergic inflammation, such as the bronchial mucosa of subjects with allergic asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects exerted on the in vitro development of purified protein derivative (PPD)-specific or Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines (TCL) and T cell clones (TCC) by IL-4 or IFN-gamma addition or neutralization in human PBMC cultures were examined. PBMC from two normal individuals, which were stimulated with PPD and then cultured in IL-2 alone, developed into PPD-specific TCL and TCC able to produce IFN-gamma and IL-2 but not IL-4 and IL-5 (Th1-like). IFN-gamma or anti-IL-4 antibody addition in bulk cultures before cloning did not influence the PPD-specific TCL profile of cytokine production. In contrast, the addition of IL-4 resulted in the development of PPD-specific TCL and TCC able to produce not only IFN-gamma and IL-2 but also IL-4 and IL-5. PBMC from one atopic Der p I-sensitive patient, which were stimulated with Der p I and then cultured in IL-2 alone, developed into Der p I-specific TCL and TCC able to produce IL-5 and large amounts of IL-4 but no IFN-gamma (Th2-like). The addition in bulk cultures, before cloning, of either IFN-gamma or anti-IL-4 antibody markedly inhibited the development of Der p I-specific T cells into IL-4- and IL-5-producing TCL. Accordingly, the development into Der p I-specific Th2-like TCC was significantly reduced by the addition of IFN-gamma in bulk culture and was virtually suppressed by the presence of both IFN-gamma and anti-IL-4 antibody. These data suggest that the presence or the absence of IL-4 and IFN-gamma in bulk cultures of PBMC before cloning may have strong regulatory effects on the in vitro development of human CD4+ T cells into Th1 or Th2 clones.
Appendicitis was rare in the past and still is in traditional Third World populations. It began to increase a century ago, peaked about 1950, and has now fallen to about half its previous incidence. As to causation, dietetically, it was contended that the increase was promoted primarily by an associated fall in dietary fiber intake. The recently advanced hygiene hypothesis considers the increase to have stemmed from improvements in hygiene, generally; these limited exposure to enteric infections and modified response to virus infections, thereby triggering appendicitis. Major uncertainties still prevail over the promotive and precipitating factors of the disease. It is doubtful whether individuals can take any action to avoid appendicitis.
Hay fever has been described as a "post industrial
revolution epidemic,"' and successive morbidity
surveys from British general practice suggest that its
prevalence has continued to increase over the past 30
years.) Other evidence suggests a recent increase in the
prevalence of asthma2 and childhood eczema.3 This
paper suggests a possible explanation for these trends
over time.
The hypothesis that homoeopathic potencies are placebos was tested in a randomised, double-blind, placebo-controlled trial. The study model chosen compared the effects of a homoeopathic preparation of mixed grass pollens with placebo in 144 patients with active hayfever. The homoeopathically treated patients showed a significant reduction in patient and doctor assessed symptom scores. The significance of this response was increased when results were corrected for pollen count and the response was associated with a halving of the need for antihistamines. An initial aggravation of symptoms was noted more often in patients receiving the potency and was followed by an improvement in that group. No evidence emerged to support the idea that placebo action fully explains the clinical responses to homoeopathic drugs.
The mechanisms regulating the onset of atopic sensitization in human beings are not yet fully clarified. We assessed the capacity of mitogen-stimulated umbilical and peripheral blood mononuclear cells to produce interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) at birth and at 9 months of age in 159 infants. Mononuclear cell production of both IFN-gamma and IL-2 at 9 months, but not at birth, was found to be inversely related to parental immediate skin test reactivity to seven local aeroallergens. Skin test reactivity at the age of 6 years was also inversely related to IFN-gamma and IL-2 production at 9 months of age. However, no relationship was evident between total serum IgE levels at 6 years and production of these cytokines at 9 months. The proportions of circulating lymphocytes and CD4+ or CD8+ cells were also unrelated to skin test reactivity at the age of 6 years. These data suggest that mechanisms regulating skin test reactivity to inhaled allergens may involve deficient IFN-gamma production, deficient IL-2 production, or both during or preceding the time of initial sensitization and that additional mechanisms are involved in regulating total serum IgE level.
A large body of evidence suggests the existence of polarized human T cell responses, reminiscent of Th1 and Th2 subsets described for mouse T cells. Human Th1-like cells preferentially develop during infections by intracellular bacteria, protozoa, and viruses, whereas Th2-like cells predominate during helminthic infestations and in response to common environmental allergens. The cytokine profile of “natural immunity” evoked by different offending agents in the context of different host genetic backgrounds appears to be a critical factor in determining the phenotype of the subsequent specific response.
Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, they can also promote different immunopathological reactions. Th1-type responses appear to be involved in organ specific autoimmunity, in contact dermatitis, and in some chronic inflammatory disorders of unknown etiology. In contrast, in genetically predisposed hosts, Th2-type responses against common environmental allergens are responsible for triggering of allergic atopic disorders. Altered profiles of lymphokine production may account for immune dysfunctions in some primary or acquired immunodeficiency syndromes. The role of lymphokines produced by T cells in the pathogenesis of systemic autoimmune disorders is less clear. Further work is also required to better clarify the role of T cell-derived lymphokines in protecting against tumors or in favoring their development.
The development of restricted cytokine profiles by subsets of CD4+ T cells is a pivotal point in the regulation of immune responses. T cells producing Th1 cytokines (IL-2 and interferon-gamma) induce cell-mediated immunity, whereas T cells producing Th2 cytokines (IL-4, IL-5, and IL-10) play a prominent role in the induction of humoral immunity. We examined a group of patients with multiple sclerosis, a disease caused by excess production of Th1 cytokines in myelin-reactive T cells, and control patients with noninflammatory neuroconvulsive disorders, for the presence of allergic disease, which is caused by excess production of Th2 cytokines in allergen-specific T cells. The patients with multiple sclerosis had significantly fewer allergic symptoms, a lower number of positive allergen-specific IgE test results, and lower composite allergy indexes than control subjects. These results demonstrate that the prevalence of IgE-mediated allergic disease is decreased in a group of patients with multiple sclerosis and support the hypothesis that genetic factors that promote susceptibility to Th1-mediated inflammatory disease in human beings protect against the development of Th2-mediated disease.
The increase in atopic diseases may be partly explicable by a decline of certain infectious diseases, or changes in childhood vaccination programmes, or both. We investigated whether BCG vaccination against tuberculosis influences the development of atopy.
We did a retrospective cohort study of 216 children with atopic heredity, born in Stockholm between 1989 and 1992, who received BCG vaccination when they were younger than 6 months, and 358 age-matched controls who had not been vaccinated. Both groups attended Sachs' Children's Hospital, Stockholm, Sweden, during 1995-96 for assessment of atopic history and clinical signs of atopic disease. All children also underwent skin-prick testing (SPT) and serum was analysed for allergen-specific IgE antibodies. Serum from parents was also analysed for IgE antibodies.
77 (36%) children in the BCG group and 145 (41%) in the control group had a positive history or clinical signs of atopic disease. In the vaccinated group, 26 (12%) children had one or more positive SPT, and 61 (31%) had circulating allergen-specific IgE antibodies, whereas in the control group, the numbers were 35 (10%) and 84 (27%) respectively. Atopy was confirmed by serology in parents of almost two-thirds of the children in each group. Other risk factors for atopic disease were evenly distributed between the two groups.
Early BCG vaccination in children with atopic heredity does not seem to affect the development of atopic disease before school age.
There is increasing evidence that the T-cell reactivity to environmental allergens underlying expression of allergic disease in adulthood, develops initially during childhood. However, there is little information available on the kinetics of these early responses, or on the patterns of cytokine production during this period.
The purpose of this study was twofold: to obtain further information on the reported differences between responses to food versus inhalant allergens during early childhood, and to ascertain the age-range over which T-cell responses to inhalant allergens become polarized towards the TH2 cytokine profile, in potentially atopic children.
In vitro cytokine responses to house dust mite (HDM) and egg (OVA) were assessed by semiquantitative RT-PCR in panels of 2- and 5-year-old children and adults; lymphoproliferative responses to OVA were subjected to epitope analysis.
At age 2 years IL-4/IL-5 responses to HDM grouped with positive atopic family history, and by age 5 years cytokine responses correlated strongly with individual SPT reactivity to HDM. In contrast, OVA responses were restricted to weak and transient IL-5 signals in the 2-year-old family history positive group. Lymphoproliferation assays performed in parallel indicate a log-scale greater postnatal expansion of T-cell reactivity to the inhalant allergen; preliminary epitope analysis of OVA responses indicate that the number of OVA epitopes recognised decrease during early childhood.
Inhalant allergen-specific in vitro cytokine production associated with positive skin-prick test (SPT) reactions, one of the hallmarks of adult atopy, manifests in children at or before 5 years of age; additionally, cytokine responses in SPT negative 5 year-olds are restricted to IFNgamma, as per normal adults. In contrast, T-cell responses to a typical food allergen appear to be deleted during early childhood.
The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents.
Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates.
We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children.
The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies).
We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined.
We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies.
Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was quantitated by a sensitive reverse transcription, competitive PCR.
IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90+/-0.18 vs 1.24+/-0.19 log10 fmol/microL for individuals with allergies) (P = .02). Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant.
IL-12 production in individuals with MS is much greater than in individuals with allergies. Because IL-12 induces TH1 cytokine synthesis and reduces the production of TH2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system.
Atopy is of complex origins but the recent rise in atopic diseases in westernized communities points to the action of important environmental effects. One candidate mechanism is the changing pattern of microbial exposure in childhood. This epidemiological study investigated the relationship between childhood infections and subsequent atopic disease, taking into account a range of social and medical variables.
A total of 1934 subjects representing a retrospective 1975-84 birth group at a family doctor practice in Oxfordshire were studied. Public health and practice records were reviewed; temporal records were made of all diagnoses of infections and their treatments, all immunisations, and diagnoses of asthma, hay fever and eczema; maternal atopy and a number of other variables were documented.
Logistic regression analysis identified three statistically significant predictors of subsequent atopic disease: maternal atopy (1.97, 95% CI 1.46 to 2.66, p < 0.0001), immunisation with whole-cell pertussis vaccine (1.76, 95% CI 1.39 to 2.23, p < 0.0001), and treatment with oral antibiotics in the first two years of life (2.07, 95% CI 1.64 to 2.60, p < 0.0001). There was no significant association found for maternal smoking, bottle feeding, sibship size, or social class.
The prediction of atopic disease by maternal atopy mainly reflects the effect of acknowledged genetic factors. Interpretation of the prediction of atopic disorders by immunisation with wholecell pertussis vaccine and treatment with oral antibiotics needs to be very cautious because of the possibilities of confounding effects and reverse causation. However, plausible immune mechanisms are identifiable for the promotion of atopic disorders by both factors and further investigation of these association is warranted.
Recent decades have seen a significant shift in the main causes of illness among infants and young children. Until the 1950s and 196Os, acute infectious diseases affecting the gastrointestinal tract were the most common conditions requiring medical attention. This pattern of morbidity persists to this day in the poorest regions of the world and still claims the lives of millions of children. In developed countries, however, and also in developing countries where successful programmes of vaccination and prevention have been established, chronic, recurrent illnesses of the respiratory tract have taken the place of acute diarrhoea. A very high proportion of children (up to half in populations of northern European origin) are affected by allergies, and the prevalence of asthma and other forms of recurrent airway obstruction is rising.’ Paradoxically, the increases seem most striking in areas where the quality of outdoor air has significantly improved’ and where good sanitation and nutrition prevail. Some years ago we separately proposed3,* similar hypotheses to explain these findings. This so-called “hygiene hypothesis” was an immunological extension of a concept introduced by Strachan.5 Its cornerstone is that changes in the type and level of stimulation from the microbial environment associated with improvements in public health and hygiene may have indirectly influenced the postnatal development of immune function(s), so as to increase predisposition to chronic allergic conditions during childhood. These changes involve both a general decrease in infectious burden during early life (in particular, respiratory infections) and variations in gastrointestinal flora. In this paper, we review how recent advances in understanding of the way immune responses develop in early life support the hygiene hypothesis.