A critical approach to the hygiene hypothesis
Authors: Ring J. , Krämer U. , Behrendt H. 
Published: February 2005

Background  The prevalence of atopic diseases has increased dramatically during recent decades; the reasons are not known. Among various plausible hypotheses the so‐called hygiene hypothesis (jungle hypothesis) has gained public interest recently. According to this hypothesis improved hygiene leading to a decreased stimulation of the immune system by infections, parasites, vaccinations or contact with immunostimulating agents has led to an immunodeviation with T helper (Th)2‐enhancing effects followed by increased occurrence of IgE‐mediated allergies.

Problems  The hygiene hypothesis is not defined precisely, and some questions remain open: the influence of actual infectious disease or specific vaccinations, the nature of infectious agents (virus, bacteria, fungi, parasites), the definition of the term ‘hygiene’, the nature of other immunostimulating agents and the effects upon different atopic diseases. As arguments in favour of the hygiene hypothesis, the following study results are quoted: children of farmers have less allergies; children from academic parents show an increased risk of atopic diseases; children from anthroposophic families have decreased allergy prevalence rates; effects of endotoxin and CD14 gene polymorphism; and the protective influence of gut flora with high amounts of lactobacilli. The following findings argue against the hygiene hypotheses: parasite infections are associated with an increased risk of urticaria and atopic eczema; some microorganisms e.g. respiratory syncytial virus (RSV), Bordetella pertussis enhance IgE production; patients with active tuberculosis have high Th2 reactions; pertussis vaccination has a protective effect; high allergy prevalences in very poor regions (inner city slums in the United States, Africa, Southern America); germfree conditions prevent the spontaneous outbreak of atopic eczema in certain mouse strains, many other influences (e.g. traffic exhaust exposure) are associated with allergy and sensitization. Comparing the prevalence of atopic diseases and sensitization in East and West German children after reunification there was a striking difference with regard to higher prevalence rates of respiratory atopic diseases in West German children compared to the East, which was not seen for atopic eczema. No single factor has been established to explain this East–West German difference. When differences in pertussis vaccination strategy (in West Germany in the 1980s only about 50% of the children were vaccinated, while in East Germany this was obligatory for everyone) were included in the analysis, it became obvious that 20% of West German children were suffering from pertussis infection compared to 0.5% of East German children and pertussis infection increased the risk for atopic respiratory disease, although not for eczema and sensitization. When pertussis vaccination and infection was included among the confounders to be adjusted for in the multivariate logistic regression, the East–West German difference disappeared for asthma and wheezing, so it can be concluded that pertussis vaccination does prevent pertussis infection and thereby prevents asthma and wheezing independent of atopic sensitization. Furthermore, it has become clear that pollens are not only allergen carriers but also produce proinflammatory mediators of eicosanoid‐like activity. These pollen‐associated lipid mediators (PALMs) − among them pollotrienes − are able to attract neutrophils and activate the innate immune system. They should be regarded together with pollutants and allergens as modulating factors in the determination of allergic disease development.

Conclusions  From a critical evaluation of the evidence it is concluded that the hygiene hypothesis represents an attractive theory and stimulus for further research, particularly the more precise aspect of the jungle hypothesis, with an inverse relationship between parasite infestation and respiratory atopy. It seems that the hygiene hypothesis fits only for atopic respiratory but not for atopic skin disease. Regarding the partly controversial data it is too early to give practical recommendations for allergy prevention based on this hypothesis. There is no rationale to recommend avoidance of vaccinations or adequate body cleaning measures. Effective programmes for primary prevention will be possible only after increased research efforts have elucidated the true causes of increased allergy prevalence.