There is no doubt that millions of lives have been saved through the introduction of vaccination, improved sanitation and the use of antibiotics. Since the identification of disease-causing microbes in the 19th century by Pasteur and Koch, childhood mortality rates have been drastically reduced.
This is an important backdrop to more recent work on the ‘Hygiene Hypothesis’, which is the idea that our current ‘clean’ lifestyle has led to a rise in allergic and autoimmune disease. The hypothesis was first suggested by David P. Strachan to explain a correlation between hay fever and family size in the late 1980s (1). In his study, he found that the youngest children in a family were less likely to develop hay fever than their siblings or only children; the greater the number of older siblings, the lower the chance a child starts sneezing in summer. One explanation for this result is that children tend to be very good at giving each other infections – as any parent is well aware. It also suggests that infections are most protective when they happen in early childhood.
The rise in allergic and autoimmune disease
There is very good evidence that there has been a significant increase in a number of allergic and autoimmune diseases over the last century (2). Approximately 15% of UK children are diagnosed with asthma; atopic dermatitis conditions such as eczema affect 15-30% of children and between 2-10% of adults in industrialised countries, and inflammatory bowel disorders such as Crohn’s disease have also increased (3). For autoimmune disorders such as type 1 diabetes (also known as insulin-dependent or early-onset diabetes), systemic lupus erythematosus and multiple sclerosis the evidence is equally compelling (4).
What links these disorders? They are all caused by an inappropriate immune response; in the case of allergies, immune cells are activated by exposure to normal, harmless factors in the environment; in autoimmune disease, our own body’s tissues are attacked and destroyed. In some cases, it is thought that specific infections may contribute to the development of allergic or autoimmune disorders, but there is far greater evidence that a reduction in exposure to infectious agents may be linked to an increased risk of allergic or autoimmune disease.
The decline in infections
A number of previously common childhood infections have dramatically declined in frequency. These include Hepatitis A virus, gastrointestinal infections that lead to diarrhoea and parasitic infections (such as flukes, pinworms and tapeworms) (2). The decline in these infections in Western countries mirrors the rise in allergic and autoimmune disease. However, this correlation does not prove a causal link, especially as many other environmental factors such as geographical location (a higher incidence in northern versus southern countries) and socio-economic status (the rich are at greater risk than the poor) also predict the probability of developing both allergies and autoimmune diseases.
Experimental models and new therapies
The best evidence for a causative link between a reduced infectious burden and allergic and autoimmune disease comes from experimental animal models. The non-obese diabetic mouse spontaneously develops a disease similar to type 1 diabetes in humans, but this can be completely inhibited by infection with mycobacteria or helminths (4). Specific parasitic infections such as helminths and Schistosomas have been used both in treatment and prevention of inflammatory bowel diseases; exciting new studies aim to identify the factors within the eggs, larvae and extracts from helminths to identify the components that dampen the immune response and alleviate symptoms (5).
There are a number of complicated factors that are likely to contribute to the incidence of allergic and autoimmune diseases. As I mentioned in the opening paragraph, improved sanitation, vaccination and antibiotics are vital in preventing life-threatening infections, but we are learning that our immune system is also trained by the infections that have co-evolved with us. Determining how infection educates the immune system and using this to develop treatments for susceptible individuals is an important aim for those working on the role of infection in susceptibility to allergic and autoimmune disease.
1. Strachan DP (1989). Hay fever, hygiene, and household size. BMJ 299 (6710): 1259–60.
2. Okada H, Kuhn C, Feillet H and Bach J-F (2010). The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin. Exp. Imm. 160: 1-9
3. Swarbrick ET, Farrokhyar F, Irvine EJ. (2001) A critical review of epidemiological studies in inflammatory bowel disease. Scand. J. Gastroenterol 36: 2-15
4. Cooke A (2008). Review series on helminths, immune modulation and the hygiene hypothesis: How might infection modulate the onset of type 1 diabetes? Immunology 126: 12-17
5. Yazdanbakhsh M, Kremsner PG, van Ree R (2002) Allergy, parasites, and the hygiene hypothesis. Science 296: 490–494.
A detailed blog about the hygiene hypothesis and eczema: