Wednesday, May 10, 2006

Hygiene Hypothesis - Part 3 - Evidence

What is the evidence that the decline of exposure to infectious agents is related to an increase of allergies and autoimmune diseases?

The incidence of asthma, allergies and autoimmune diseases has increased dramatically over the last 50 years.

There is a North-South gradient in the incidence of autoimmune diseases. And, this correlates with socio-economic level (Bach, 2002, NEJM). This means that autoimmune diseases are more frequently found at the higher latitudes (closer to the poles) than nearer to the equator. There could be many explanations for this finding but certainly the incidence of worm infection is generally greater the nearer you get to the equator. But even in Europe, the incidence of diabetes and multiple sclerosis is higher in the Scandinavian countries than in Italy, Spain or France.

There is a lower frequency of allergies and autoimmune diseases in populations of lower socio-economic status. For instance, in Europe the prevalence of multiple sclerosis is about 40/100,000 in countries with GNP's less than $14,000 vs 85/100,000 in countries with GNP's greater than $18,000.

Persons that grow up on a farm are less likely to get allergies than persons that do not grow up on a farm.

East Germans (before unification) had lower incidences of asthma and hay fever than West Germans even though East Germany was heavily polluted.

Children in Venezuela, when cured of their worm infections, had an increased incidence in allergies.

Mice (or rats) bred in germ free or pathogen free environments develop autoimmune diseases more frequently than normal mice.

A special mouse strain called non-obese diabetic mice (NOD) rapidly develop diabetes. Diabetes can be prevented if these mice if they are infected with some bacteria or worms. NOD mice have a 40% incidence of diabetes. If the NOD mouse is delivered by cesarian section and raised in a germ-free environment the incidence of diabetes increases to 80%.

Now this evidence is not sufficient to for us to absolutely say that there is a causal relationship between incidence of infections and of allergies and autoimmune diseases. Moreover, infections are also known to result in autoimmune disease in some cases.

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