Infectious Disease, Autoimmunity and

the Hygiene Hypothesis

The Hygiene Hypothesis suggests that parasites and microbes have been important for shaping and tuning the evolution of the human immune system. According to this hypothesis, the immune system is in a state of preparedness, primed to repel the pathogen assaults that characterized the lot of humanity for most of its existence. In developed countries industrialization has strongly contributed to human migration from rural areas to the cities. One of the consequences of resettlement has been the removal of people from the pathogen-replete ecosystems in which their immune systems had adapted since prehistory. Sanitation, and access to clean food and water became a common life standard for most individuals in the developed world. Additionally, following the Second World War the use of antibiotics became commonplace, dramatically altering exposure to bacterial pathogens. The fact that infections were no longer prevalent has led to the emergence of autoimmune inflammatory diseases. This suggests that parasites, if not actually preventing autoimmunity per se, at least divert the immune system to the more productive cause of limiting tissue pathology. Parasites themselves wield an astonishing array of mechanisms to evade the ravages of the host's immune system and in so doing ameliorate the more self-destructive aspects of a response.

Figure 1. Inverse correlation between Type 1 Diabetes (T1D) and ‘neglected infectious diseases’. Red delineates areas which harbour six or more of the low mortality neglected diseases (filariasis, leprosy, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma). Yellow delineates areas where there are relatively high incidences of T1D (> 8 per 100 000/year). Non coloured areas delineate where T1D < 8 per 100 000/year and where the ‘neglected diseases’ are not endemic.

Industrialized countries are indeed experiencing an increase in autoimmune diseases. A very different picture is present in developing countries. Because of limited economic resources, health aid organizations tend to focus more on the three so-called ‘Big Killer Diseases’; HIV, malaria and tuberculosis. As a consequence, six neglected infectious diseases with low mortality rates such as filariasis, leprosy, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma, are still widespread yet autoimmune inflammatory diseases are virtually absent (WHO and International Diabetes Federation databases) (see Figure 1). Loss of parasite colonization in those individuals living in developed countries has had a unique impact on our immune response and, together with genetic predisposition, is probably the pre-eminent factor contributing to the development of autoimmune disease.

T1D occurs equally among males and females and is more common in whites than in non-whites. Data from the IDF (International Diabetes Federation) database indicate that T1D is rare in most African and Asian populations. Conversely, some northern European (Finland and Sweden) and northern American countries, have high rates of T1D. Over a million people worldwide have MS and this incidence also appears to be increasing. Onset of symptoms typically occurs between the ages of 15 and 40 years, with a peak incidence in people in their 20s and 30s, and women are affected twice as often as men. MS occurs worldwide but is most common in Caucasian people of northern European origin. It is extremely rare among Asians and Africans. Crohn's disease also occurs most frequently among North Europeans and North Americans. Although the disorder can begin at any age, its onset principally occurs between 15 and 30 years of age. There appears to be a familial aggregation of patients with Crohn's disease such that 20–30% of patients with Crohn's disease have a family history of inflammatory bowel disease.