In malaria endemic areas, people naturally acquire an age-related immunity to malaria. Part of this immunity involves anti-malarial specific antibodies. Acquisition of these malaria-specific antibodies depends not only on exposure to malaria parasites but also on the human genetic predisposition. CTLA-4 is a costimulatory molecule that delivers an inhibitory signal to suppress T-cell as well as B-cell responses. We investigated associations between malaria-specific antibody levels and CTLA-4 polymorphisms in 189 subjects living in a hyper-endemic area of Papua New Guinea (PNG), where both P. falciparum and P. vivax are prevalent. We determined P. falciparum⁄ P. vivax specific IgG⁄IgE levels (Pf-IgG, Pv-IgG, Pf-IgE, Pv-IgE) and polymorphisms in the CTLA-4 gene at position -1661 promoter region (A⁄G), the +49 exon 1 non-synonymous mutation (A⁄G), and the +6230 3‘-UTR (A⁄G). All quantified antibody levels were significantly higher in subjects > 5 years (n = 150) than in subjects ≤ 5 years of age (n = 39). In children ≤ 5 years old, significant associations were detected between CTLA-4 +49 (GG⁄AG vs. AA) and Pv-IgG (median 18.7 vs. 13.7 Μg⁄ml, P = 0.017) and Pv-IgE (266.6 vs. 146.5 pg⁄ml, P = 0.046). No significant difference was observed in subjects > 5 years old. These results suggest that the CTLA-4+49 polymorphism influenced Pv-IgG and Pv-IgE levels among children less than five years old in the studied population, which may regulate the age- and species-specific clinical outcomes of malaria infection.

OBJECTIVESTo assess trends in smoking prevalence among Japanese adolescents and to analyze possible causal factors for the decrease in smoking prevalence observed in a 2004 survey.

METHODSNationwide cross-sectional surveys were conducted in 1996, 2000 and 2004. Survey schools, both junior and senior high schools, considered to be representative of the whole of Japan were sampled randomly. Enrolled students were asked to complete a self-reporting anonymous questionnaire on smoking behavior. The questionnaires were collected from 115,814 students in 1996, 106,297 in 2000, and 102,451 in 2004. School principals were asked about the policy of their respective school on smoking restrictions.

RESULTSCigarette smoking prevalence (lifetime, current, and daily smoking) in 2004, based on the completed questionnaires, had decreased relative to previous years in both sexes and in all school grades. The most important trends were: a decrease in smoking prevalence among the fathers and older brothers of the students; an increase in the proportion of students who did not have friends; a decrease in the proportion of current smokers who usually bought cigarettes in stores decreased in 2004, in particular for the oldest boys. An association was found between a lower smoking rate at a school and a smoke-free school policy.

CONCLUSIONSJapan has experienced a decrease in the prevalence of smoking among adolescents. A decrease in smoking prevalence among the fathers and older brothers, limitations to minors' access to tobacco, an increase in the proportion of students without friends, and a school policy restricting smoking may have contributed to this decreasing trend.