SummaryEpidemiological data have indicated that some infections are associated with a low risk of allergic diseases, thus supporting the idea (hygiene hypothesis) that the microbial load is an important environmental factor conferring protection against the development of allergies. We set out to test the hygiene hypothesis in a unique epidemiological setting in two socio-economically and culturally markedly different, although genetically related, populations living in geographically adjacent areas. The study cohorts included 266 schoolchildren from the Karelian Republic in Russia and 266 schoolchildren from Finland. The levels of total IgE and allergen-specific IgE for birch, cat and egg albumen were measured. Microbial antibodies were analysed against enteroviruses (coxsackievirus B4), hepatitis A virus, Helicobacter pylori and Toxoplasma gondii. Although total IgE level was higher in Russian Karelian children compared to their Finnish peers, the prevalence of allergen-specific IgE was lower among Russian Karelian children. The prevalence of microbial antibodies was, in turn, significantly more frequent in the Karelian children, reflecting the conspicuous difference in socio-economic background factors. Microbial infections were associated with lower risk of allergic sensitization in Russian Karelian children, enterovirus showing the strongest protective effect in a multivariate model. The present findings support the idea that exposure to certain infections, particularly in childhood, may protect from the development of atopy. Enterovirus infections represent a new candidate to the list of markers of such a protective environment. However, possible causal relationship needs to be confirmed in further studies.

Kondrashova A, Seiskari T, Ilonen J, Knip M, Hyo¨ty H. The 'Hygiene hypothesis' and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland. APMIS 2013; 121: 478-93. Autoimmune and allergic diseases have become a major health problem in the Western world during past decades. The hygiene hypothesis suggests that decreased microbial exposure in childhood leads to increasing prevalence of these diseases. This review summarizes epidemiological evidence and current immunological knowledge concerning the hygiene hypothesis. Recent results from Russian Karelia and Finland imply that environmental factors have greatly contributed to the increasing prevalence of immune-mediated disorders. Infections, or lack of them, may indeed be strongly involved in the development of both autoimmune and allergic diseases.Key words: Hygiene hypothesis; infections; autoimmune diseases; allergy; Finland; Russian Karelia.Anita Kondrashova, Department of Virology, School of Medicine, University of Tampere, Biokatu 10, Tampere 33520, Finland. e-mail: anita.kondrashova@uta. fiThe rapid increase in allergic and other atopic diseases in the industrialized world is usually considered to have started between 1960 and 1970 with a progressive rate during the 1980s and 1990s. The prevalence of asthma has increased about 1% per year from around 1980. The increase in asthma has been documented over the last 10 years in both developed and developing countries.Prevalence greater than 15% has been reported from UK and Australia and more than 10% from Peru, Costa Rica, and Brazil. UK studies show that atopic, rather than non-atopic, asthma is responsible for a large proportion of the rise (1, 2). The incidence and prevalence of atopy generally remain at a considerable, low level in many, but not all of the developing regions of the world. The International Study of Asthma and Allergies in Childhood (ISAAC) showed that the prevalence of self-reported asthma ranged from 2-3% in developing countries to 20-40% in developed countries. The prevalence of other atopic diseases showed similar wide variation with resembling but not identical rankings (3). In addition, the prevalence of atopic dermatitis has doubled or tripled in industrialized countries during the past three decades,

Rannikko ). Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality. J Intern Med 2019; 286: 553-561.Conclusion. Proprotein convertase subtilisin/kexin type 9 is upregulated in blood culture-positive infections. Plasma PCSK9 resembles acute-phase proteins; its expression is induced during an infection, reduced in liver disease and correlates positively with CRP level. We have shown that PCSK9 levels are lower in patients with a fatal prognosis.

Underlying diseases were found to have a considerable role in the death of patients suffering from blood culture-positive sepsis in an ED of a developed country, as only 16% of the deaths by day 90 occurred where death was sepsis-related and the patient had a life-expectancy of more than 6 months. Improving the outcome of sepsis with new treatments is thus challenging. It is possible that day 7+day 28 mortality is a more appropriate endpoint than day 90 mortality when studying the outcome of sepsis, as this time-span includes most of the patients whose death was related to sepsis.

The prevalence of thyroid autoimmunity is lower in Russian Karelia than in Finland. This difference was not related to ethnic background or HLA-DQ alleles. The results support the idea that the Russian Karelian environment, which is characterized by inferior prosperity and standard of hygiene, may provide protection against thyroid autoimmunity.